Comparing interventions and exploring neural mechanisms of exercise in Parkinson disease: a study protocol for a randomized controlled trial.

PubMed

Earhart, Gammon M; Duncan, Ryan P; Huang, John L; Perlmutter, Joel S; Pickett, Kristen A

2015-02-05

Effective treatment of locomotor dysfunction in Parkinson disease (PD) is essential, as gait difficulty is an early and major contributor to disability. Exercise is recommended as an adjunct to traditional treatments for improving gait, balance, and quality of life. Among the exercise approaches known to improve walking, tango and treadmill training have recently emerged as two promising therapies for improving gait, disease severity and quality of life, yet these two interventions have not been directly compared to each other. Prior studies have been helpful in identifying interventions effective in improving gait function, but have done little to elucidate the neural mechanisms underlying functional improvements. The primary objective of the proposed work is to compare the effects of three community-based exercise programs, tango, treadmill training and stretching, on locomotor function in individuals with PD. In addition, we aim to determine whether and how these interventions alter functional connectivity of locomotor control networks in the brain. One hundred and twenty right-handed individuals with idiopathic PD who are at least 30 years of age will be assigned in successive waves to one of three community-based exercise groups: tango dancing, treadmill training or stretching (control). Each group will receive three months of exercise training with twice weekly one-hour group classes. Each participant will be evaluated at three time points: pre-intervention (baseline), post-intervention (3 months), and follow-up (6 months). All evaluations will include assessment of gait, balance, disease severity, and quality of life. Baseline and post-intervention evaluations will also include task-based functional magnetic resonance imaging (fMRI) and resting state functional connectivity MRI. All MRI and behavioral measures will be conducted with participants OFF anti-Parkinson medication, with behavioral measures also assessed ON medication. This study will provide important insights regarding the effects of different modes of exercise on locomotor function in PD. The protocol is innovative because it: 1) uses group exercise approaches for all conditions including treadmill training, 2) directly compares tango to treadmill training and stretching, 3) tests participants OFF medication, and 4) utilizes two distinct neuroimaging approaches to explore mechanisms of the effects of exercise on the brain. ClinicalTrials.gov NCT01768832 .

Development of a Countermeasure to Mitigate Postflight Locomotor Dysfunction

NASA Technical Reports Server (NTRS)

Bloomberg, J. J.; Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Richards, J. T.; Miller, C. A.; Brady, R.; Warren, L. E.; Ruttley, T. M.

2006-01-01

Astronauts returning from space flight experience locomotor dysfunction following their return to Earth. Our laboratory is currently developing a gait adaptability training program that is designed to facilitate recovery of locomotor function following a return to a gravitational environment. The training program exploits the ability of the sensorimotor system to generalize from exposure to multiple adaptive challenges during training so that the gait control system essentially learns to learn and therefore can reorganize more rapidly when faced with a novel adaptive challenge. Evidence for the potential efficacy of an adaptive generalization gait training program can be obtained from numerous studies in the motor learning literature which have demonstrated that systematically varying the conditions of training enhances the ability of the performer to learn and retain a novel motor task. These variable practice training approaches have been used in applied contexts to improve motor skills required in a number of different sports. The central nervous system (CNS) can produce voluntary movement in an almost infinite number of ways. For example, locomotion can be achieved with many different combinations of joint angles, muscle activation patterns and forces. The CNS can exploit these degrees of freedom to enhance motor response adaptability during periods of adaptive flux like that encountered during a change in gravitational environment. Ultimately, the functional goal of an adaptive generalization countermeasure is not necessarily to immediately return movement patterns back to normal. Rather the training regimen should facilitate the reorganization of available sensory and motor subsystems to achieve safe and effective locomotion as soon as possible after long duration space flight. Indeed, this approach has been proposed as a basic feature underlying effective neurological rehabilitation. We have previously confirmed that subjects participating in an adaptive generalization training program using a variety of visuomotor distortions and throwing as the dependent measure can learn to enhance their ability to adapt to a novel sensorimotor environment (Roller et al., 2001). Importantly, this increased adaptability was retained even one month after completion of the training period. Adaptive generalization has been observed in a variety of other tasks requiring sensorimotor transformations including manual control tasks and reaching (Bock et al., 2001, Seidler, 2003) and obstacle avoidance during walking (Lam and Dietz, 2004). Taken together, the evidence suggests that a training regimen exposing crewmembers to variation in locomotor conditions, with repeated transitions among states, may enhance their ability to learn how to reassemble appropriate locomotor patterns upon return from microgravity. We believe exposure to this type of training will extend crewmembers locomotor behavioral repertoires, facilitating the return of functional mobility after long duration space flight. In other words, our proposed training protocol will compel subjects to develop new behavioral solutions under varying sensorimotor demands. Over time subjects will learn to create appropriate locomotor solution more rapidly enabling acquisition of mobility sooner after long-duration space flight. A gait adaptability training program can be superimposed on nominal treadmill exercise activities thus ensuring that no additional crew time is required to perform this type of training regimen and that it can be implemented with current in-flight exercise systems available on the International Space Station.

Early life stress induces attention-deficit hyperactivity disorder (ADHD)-like behavioral and brain metabolic dysfunctions: functional imaging of methylphenidate treatment in a novel rodent model.

PubMed

Bock, J; Breuer, S; Poeggel, G; Braun, K

2017-03-01

In a novel animal model Octodon degus we tested the hypothesis that, in addition to genetic predisposition, early life stress (ELS) contributes to the etiology of attention-deficit hyperactivity disorder-like behavioral symptoms and the associated brain functional deficits. Since previous neurochemical observations revealed that early life stress impairs dopaminergic functions, we predicted that these symptoms can be normalized by treatment with methylphenidate. In line with our hypothesis, the behavioral analysis revealed that repeated ELS induced locomotor hyperactivity and reduced attention towards an emotionally relevant acoustic stimulus. Functional imaging using ( 14 C)-2-fluoro-deoxyglucose-autoradiography revealed that the behavioral symptoms are paralleled by metabolic hypoactivity of prefrontal, mesolimbic and subcortical brain areas. Finally, the pharmacological intervention provided further evidence that the behavioral and metabolic dysfunctions are due to impaired dopaminergic neurotransmission. Elevating dopamine in ELS animals by methylphenidate normalized locomotor hyperactivity and attention-deficit and ameliorated brain metabolic hypoactivity in a dose-dependent manner.

Targeting L-Selectin to Improve Neurologic and Urologic Function After Spinal Cord Injury

DTIC Science & Technology

2015-10-01

demonstrated locomotor recovery in mice receiving 40mg/kg DFA up to 3 hours following spinal cord injury -We demonstrated improved locomotor recovery...health, as evaluated by body weight -We identified no added locomotor recovery due to multiple, successive doses of DFA. Moreover, additional doses...bladder function Significance: We have identified robust locomotor recovery in both mild and severe spinal cord injured mice that received DFA up

Acetylcholinesterase inhibition and locomotor function after motor-sensory cortex impact injury.

PubMed

Holschneider, Daniel P; Guo, Yumei; Roch, Margareth; Norman, Keith M; Scremin, Oscar U

2011-09-01

Traumatic brain injury (TBI) induces transient or persistent dysfunction of gait and balance. Enhancement of cholinergic transmission has been reported to accelerate recovery of cognitive function after TBI, but the effects of this intervention on locomotor activity remain largely unexplored. The hypothesis that enhancement of cholinergic function by inhibition of acetylcholinesterase (AChE) improves locomotion following TBI was tested in Sprague-Dawley male rats after a unilateral controlled cortical impact (CCI) injury of the motor-sensory cortex. Locomotion was tested by time to fall on the constant speed and accelerating Rotarod, placement errors and time to cross while walking through a horizontal ladder, activity monitoring in the home cages, and rearing behavior. Assessments were performed the 1st and 2nd day and the 1st, 2nd, and 3rd week after TBI. The AChE inhibitor physostigmine hemisulfate (PHY) was administered continuously via osmotic minipumps implanted subcutaneously at the rates of 1.6-12.8 μmol/kg/day. All measures of locomotion were impaired by TBI and recovered to initial levels between 1 and 3 weeks post-TBI, with the exception of the maximum speed achievable on the accelerating Rotarod, as well as rearing in the open field. PHY improved performance in the accelerating Rotarod at 1.6 and 3.2 μmol/kg/day (AChE activity 95 and 78% of control, respectively), however, higher doses induced progressive deterioration. No effect or worsening of outcomes was observed at all PHY doses for home cage activity, rearing, and horizontal ladder walking. Potential benefits of cholinesterase inhibition on locomotor function have to be weighed against the evidence of the narrow range of useful doses.

A Comparison of Locomotor Therapy Interventions: Partial-Body Weight-Supported Treadmill, Lokomat, and G-EO Training in People With Traumatic Brain Injury.

PubMed

Esquenazi, Alberto; Lee, Stella; Wikoff, Amanda; Packel, Andrew; Toczylowski, Theresa; Feeley, John

2017-09-01

Literature in the application of gait training techniques in persons with traumatic brain injury (TBI) is limited. Current techniques require multiple staff and are physically demanding. The use of a robotic locomotor training may provide improved training capacity for this population. To examine the impact of 3 different modes of locomotor therapy on gait velocity and spatiotemporal symmetry using an end effector robot (G-EO); a robotic exoskeleton (Lokomat), and manual assisted partial-body weight-supported treadmill training (PBWSTT) in participants with traumatic brain injury. Randomized, prospective study. Tertiary rehabilitation hospital. A total of 22 individuals with ≥12 months chronic TBI with hemiparetic pattern able to walk overground without assistance at velocities between 0.2 and 0.6 m/s. Eighteen sessions of 45 minutes of assigned locomotor training. Overground walking self-selected velocity (SSV), maximal velocity (MV), spatiotemporal asymmetry ratio, 6-Minute Walk Test (6MWT), and mobility domain of Stroke Impact Scale (MSIS). Severity in walking dysfunction was similar across groups as determined by walking velocity data. At baseline, participants in the Lokomat group had a baseline velocity that was slightly slower compared with the other groups. Training elicited a statistically significant median increase in SSV for all groups compared with pretraining (Lokomat, P = .04; G-EO, P = .03; and PBWSTT, P = .02) and MV excluding the G-EO group (Lokomat, P = .04; PBWSTT, P = .03 and G-EO, P = .15). There were no pre-post significant differences in swing time, stance time, and step length asymmetry ratios at SSV or MV for any of the interventions. Mean rank in the change of SSV and MV was not statistically significantly different between groups. Participants in the G-EO and PBWSTT groups significantly improved their 6MWT posttraining (P = .04 and .03, respectively). The MSIS significantly improved only for the Lokomat group (P = .04 and .03). The data did not elicit between-groups significant differences for 6MWT and MSIS. There was less use of staff for Lokomat than G-EO. Locomotor therapy using G-EO, Lokomat, or PBWSTT in individuals with chronic TBI increased SSV and MV without significant changes in gait symmetry. Staffing needed for therapy provision was the least for the Lokomat. A larger study may further elucidate changes in gait symmetry and other training parameters. II. Copyright © 2017 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Mito-Apocynin Prevents Mitochondrial Dysfunction, Microglial Activation, Oxidative Damage, and Progressive Neurodegeneration in MitoPark Transgenic Mice.

PubMed

Langley, Monica; Ghosh, Anamitra; Charli, Adhithiya; Sarkar, Souvarish; Ay, Muhammet; Luo, Jie; Zielonka, Jacek; Brenza, Timothy; Bennett, Brian; Jin, Huajun; Ghaisas, Shivani; Schlichtmann, Benjamin; Kim, Dongsuk; Anantharam, Vellareddy; Kanthasamy, Arthi; Narasimhan, Balaji; Kalyanaraman, Balaraman; Kanthasamy, Anumantha G

2017-11-10

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive motor deficits and degeneration of dopaminergic neurons. Caused by a number of genetic and environmental factors, mitochondrial dysfunction and oxidative stress play a role in neurodegeneration in PD. By selectively knocking out mitochondrial transcription factor A (TFAM) in dopaminergic neurons, the transgenic MitoPark mice recapitulate many signature features of the disease, including progressive motor deficits, neuronal loss, and protein inclusions. In the present study, we evaluated the neuroprotective efficacy of a novel mitochondrially targeted antioxidant, Mito-apocynin, in MitoPark mice and cell culture models of neuroinflammation and mitochondrial dysfunction. Oral administration of Mito-apocynin (10 mg/kg, thrice a week) showed excellent central nervous system bioavailability and significantly improved locomotor activity and coordination in MitoPark mice. Importantly, Mito-apocynin also partially attenuated severe nigrostriatal degeneration in MitoPark mice. Mechanistic studies revealed that Mito-apo improves mitochondrial function and inhibits NOX2 activation, oxidative damage, and neuroinflammation. The properties of Mito-apocynin identified in the MitoPark transgenic mouse model strongly support potential clinical applications for Mito-apocynin as a viable neuroprotective and anti-neuroinflammatory drug for treating PD when compared to conventional therapeutic approaches. Collectively, our data demonstrate, for the first time, that a novel orally active apocynin derivative improves behavioral, inflammatory, and neurodegenerative processes in a severe progressive dopaminergic neurodegenerative model of PD. Antioxid. Redox Signal. 27, 1048-1066.

Zebrafish Locomotor Responses Demonstrate Irritant Effects of Fine Particulate Matter Sources and a Role for TRPA1

EPA Science Inventory

Fine particulate matter (PM) air pollution is a complex mixture of chemicals, the composition of which is determined by contributing sources, and has been linked to cardiopulmonary dysfunction. These effects stem in part from the irritating properties of PM constituents, which ...

Reduced Activity of AMP-Activated Protein Kinase Protects against Genetic Models of Motor Neuron Disease

PubMed Central

Lim, M. A.; Selak, M. A.; Xiang, Z.; Krainc, D.; Neve, R. L.; Kraemer, B. C.; Watts, J. L.

2012-01-01

A growing body of research indicates that amyotrophic lateral sclerosis (ALS) patients and mouse models of ALS exhibit metabolic dysfunction. A subpopulation of ALS patients possesses higher levels of resting energy expenditure and lower fat-free mass compared to healthy controls. Similarly, two mutant copper zinc superoxide dismutase 1 (mSOD1) mouse models of familial ALS possess a hypermetabolic phenotype. The pathophysiological relevance of the bioenergetic defects observed in ALS remains largely elusive. AMP-activated protein kinase (AMPK) is a key sensor of cellular energy status and thus might be activated in various models of ALS. Here, we report that AMPK activity is increased in spinal cord cultures expressing mSOD1, as well as in spinal cord lysates from mSOD1 mice. Reducing AMPK activity either pharmacologically or genetically prevents mSOD1-induced motor neuron death in vitro. To investigate the role of AMPK in vivo, we used Caenorhabditis elegans models of motor neuron disease. C. elegans engineered to express human mSOD1 (G85R) in neurons develops locomotor dysfunction and severe fecundity defects when compared to transgenic worms expressing human wild-type SOD1. Genetic reduction of aak-2, the ortholog of the AMPK α2 catalytic subunit in nematodes, improved locomotor behavior and fecundity in G85R animals. Similar observations were made with nematodes engineered to express mutant tat-activating regulatory (TAR) DNA-binding protein of 43 kDa molecular weight. Altogether, these data suggest that bioenergetic abnormalities are likely to be pathophysiologically relevant to motor neuron disease. PMID:22262909

Training to Facilitate Adaptation to Novel Sensory Environments

NASA Technical Reports Server (NTRS)

Bloomberg, J. J.; Peters, B. T.; Mulavara, A. P.; Brady, R. A.; Batson, C. D.; Ploutz-Snyder, R. J.; Cohen, H. S.

2010-01-01

After spaceflight, the process of readapting to Earth s gravity causes locomotor dysfunction. We are developing a gait training countermeasure to facilitate adaptive responses in locomotor function. Our training system is comprised of a treadmill placed on a motion-base facing a virtual visual scene that provides an unstable walking surface combined with incongruent visual flow designed to train subjects to rapidly adapt their gait patterns to changes in the sensory environment. The goal of our present study was to determine if training improved both the locomotor and dual-tasking ability responses to a novel sensory environment and to quantify the retention of training. Subjects completed three, 30-minute training sessions during which they walked on the treadmill while receiving discordant support surface and visual input. Control subjects walked on the treadmill without any support surface or visual alterations. To determine the efficacy of training, all subjects were then tested using a novel visual flow and support surface movement not previously experienced during training. This test was performed 20 minutes, 1 week, and 1, 3, and 6 months after the final training session. Stride frequency and auditory reaction time were collected as measures of postural stability and cognitive effort, respectively. Subjects who received training showed less alteration in stride frequency and auditory reaction time compared to controls. Trained subjects maintained their level of performance over 6 months. We conclude that, with training, individuals became more proficient at walking in novel discordant sensorimotor conditions and were able to devote more attention to competing tasks.

The upright posture improves plantar stepping and alters responses to serotonergic drugs in spinal rats.

PubMed

Sławińska, Urszula; Majczyński, Henryk; Dai, Yue; Jordan, Larry M

2012-04-01

Recent studies on the restoration of locomotion after spinal cord injury have employed robotic means of positioning rats above a treadmill such that the animals are held in an upright posture and engage in bipedal locomotor activity. However, the impact of the upright posture alone, which alters hindlimb loading, an important variable in locomotor control, has not been examined. Here we compared the locomotor capabilities of chronic spinal rats when placed in the horizontal and upright postures. Hindlimb locomotor movements induced by exteroceptive stimulation (tail pinching) were monitored with video and EMG recordings. We found that the upright posture alone significantly improved plantar stepping. Locomotor trials using anaesthesia of the paws and air stepping demonstrated that the cutaneous receptors of the paws are responsible for the improved plantar stepping observed when the animals are placed in the upright posture.We also tested the effectiveness of serotonergic drugs that facilitate locomotor activity in spinal rats in both the horizontal and upright postures. Quipazine and (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) improved locomotion in the horizontal posture but in the upright posture either interfered with or had no effect on plantar walking. Combined treatment with quipazine and 8-OH-DPAT at lower doses dramatically improved locomotor activity in both postures and mitigated the need to activate the locomotor CPG with exteroceptive stimulation. Our results suggest that afferent input from the paw facilitates the spinal CPG for locomotion. These potent effects of afferent input from the paw should be taken into account when interpreting the results obtained with rats in an upright posture and when designing interventions for restoration of locomotion after spinal cord injury.

The upright posture improves plantar stepping and alters responses to serotonergic drugs in spinal rats

PubMed Central

Sławińska, Urszula; Majczyński, Henryk; Dai, Yue; Jordan, Larry M

2012-01-01

Recent studies on the restoration of locomotion after spinal cord injury have employed robotic means of positioning rats above a treadmill such that the animals are held in an upright posture and engage in bipedal locomotor activity. However, the impact of the upright posture alone, which alters hindlimb loading, an important variable in locomotor control, has not been examined. Here we compared the locomotor capabilities of chronic spinal rats when placed in the horizontal and upright postures. Hindlimb locomotor movements induced by exteroceptive stimulation (tail pinching) were monitored with video and EMG recordings. We found that the upright posture alone significantly improved plantar stepping. Locomotor trials using anaesthesia of the paws and air stepping demonstrated that the cutaneous receptors of the paws are responsible for the improved plantar stepping observed when the animals are placed in the upright posture. We also tested the effectiveness of serotonergic drugs that facilitate locomotor activity in spinal rats in both the horizontal and upright postures. Quipazine and (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) improved locomotion in the horizontal posture but in the upright posture either interfered with or had no effect on plantar walking. Combined treatment with quipazine and 8-OH-DPAT at lower doses dramatically improved locomotor activity in both postures and mitigated the need to activate the locomotor CPG with exteroceptive stimulation. Our results suggest that afferent input from the paw facilitates the spinal CPG for locomotion. These potent effects of afferent input from the paw should be taken into account when interpreting the results obtained with rats in an upright posture and when designing interventions for restoration of locomotion after spinal cord injury. PMID:22351637

Activation of the unfolded protein response promotes axonal regeneration after peripheral nerve injury.

PubMed

Oñate, Maritza; Catenaccio, Alejandra; Martínez, Gabriela; Armentano, Donna; Parsons, Geoffrey; Kerr, Bredford; Hetz, Claudio; Court, Felipe A

2016-02-24

Although protein-folding stress at the endoplasmic reticulum (ER) is emerging as a driver of neuronal dysfunction in models of spinal cord injury and neurodegeneration, the contribution of this pathway to peripheral nerve damage remains poorly explored. Here we targeted the unfolded protein response (UPR), an adaptive reaction against ER stress, in mouse models of sciatic nerve injury and found that ablation of the transcription factor XBP1, but not ATF4, significantly delay locomotor recovery. XBP1 deficiency led to decreased macrophage recruitment, a reduction in myelin removal and axonal regeneration. Conversely, overexpression of XBP1s in the nervous system in transgenic mice enhanced locomotor recovery after sciatic nerve crush, associated to an improvement in key pro-regenerative events. To assess the therapeutic potential of UPR manipulation to axonal regeneration, we locally delivered XBP1s or an shRNA targeting this transcription factor to sensory neurons of the dorsal root ganglia using a gene therapy approach and found an enhancement or reduction of axonal regeneration in vivo, respectively. Our results demonstrate a functional role of specific components of the ER proteostasis network in the cellular changes associated to regeneration and functional recovery after peripheral nerve injury.

Activation of the unfolded protein response promotes axonal regeneration after peripheral nerve injury

PubMed Central

Oñate, Maritza; Catenaccio, Alejandra; Martínez, Gabriela; Armentano, Donna; Parsons, Geoffrey; Kerr, Bredford; Hetz, Claudio; Court, Felipe A.

2016-01-01

Although protein-folding stress at the endoplasmic reticulum (ER) is emerging as a driver of neuronal dysfunction in models of spinal cord injury and neurodegeneration, the contribution of this pathway to peripheral nerve damage remains poorly explored. Here we targeted the unfolded protein response (UPR), an adaptive reaction against ER stress, in mouse models of sciatic nerve injury and found that ablation of the transcription factor XBP1, but not ATF4, significantly delay locomotor recovery. XBP1 deficiency led to decreased macrophage recruitment, a reduction in myelin removal and axonal regeneration. Conversely, overexpression of XBP1s in the nervous system in transgenic mice enhanced locomotor recovery after sciatic nerve crush, associated to an improvement in key pro-regenerative events. To assess the therapeutic potential of UPR manipulation to axonal regeneration, we locally delivered XBP1s or an shRNA targeting this transcription factor to sensory neurons of the dorsal root ganglia using a gene therapy approach and found an enhancement or reduction of axonal regeneration in vivo, respectively. Our results demonstrate a functional role of specific components of the ER proteostasis network in the cellular changes associated to regeneration and functional recovery after peripheral nerve injury. PMID:26906090

Abdominal Manual Therapy Repairs Interstitial Cells of Cajal and Increases Colonic c-Kit Expression When Treating Bowel Dysfunction after Spinal Cord Injury

PubMed Central

Zhang, Wenyi; Zhu, Zhaojin; Xie, Bin; Yu, Jun

2017-01-01

Background This study aimed to evaluate the therapeutic effects of abdominal manual therapy (AMT) on bowel dysfunction after spinal cord injury (SCI), investigating interstitial cells of Cajal (ICCs) and related c-kit expression. Methods Model rats were divided as SCI and SCI with drug treatment (intragastric mosapride), low-intensity (SCI + LMT; 50 g, 50 times/min), and high-intensity AMT (SCI + HMT; 100 g, 150 times/min). After 14 days of treatment, weight, improved Basso-Beattie-Bresnahan (BBB) locomotor score, and intestinal movement were evaluated. Morphological structure of spinal cord and colon tissues were examined. Immunostaining, RT-PCR, and western blot were used to assess c-kit expression. Results In SCI rats, AMT could not restore BBB, but it significantly increased weight, shortened time to defecation, increased feces amounts, and improved fecal pellet traits and colon histology. AMT improved the number, distribution, and ultrastructure of colonic ICCs, increasing colonic c-kit mRNA and protein levels. Compared with the SCI + Drug and SCI + LMT groups, the SCI + HMT group showed better therapeutic effect in improving intestinal transmission function and promoting c-kit expression. Conclusions AMT is an effective therapy for recovery of intestinal transmission function. It could repair ICCs and increase c-kit expression in colon tissues after SCI, in a frequency-dependent and pressure-dependent manner. PMID:29349063

Further Evidence of Complex Motor Dysfunction in Drug Naive Children with Autism Using Automatic Motion Analysis of Gait

ERIC Educational Resources Information Center

Nobile, Maria; Perego, Paolo; Piccinini, Luigi; Mani, Elisa; Rossi, Agnese; Bellina, Monica; Molteni, Massimo

2011-01-01

In order to increase the knowledge of locomotor disturbances in children with autism, and of the mechanism underlying them, the objective of this exploratory study was to reliably and quantitatively evaluate linear gait parameters (spatio-temporal and kinematic parameters), upper body kinematic parameters, walk orientation and smoothness using an…

Voluntary wheel running improves recovery from a moderate spinal cord injury.

PubMed

Engesser-Cesar, Christie; Anderson, Aileen J; Basso, D Michele; Edgerton, V R; Cotman, Carl W

2005-01-01

Recently, locomotor training has been shown to improve overground locomotion in patients with spinal cord injury (SCI). This has triggered renewed interest in the role of exercise in rehabilitation after SCI. However, there are no mouse models for voluntary exercise and recovery of function following SCI. Here, we report voluntary wheel running improves recovery from a SCI in mice. C57Bl/10 female mice received a 60-kdyne T9 contusion injury with an IH impactor after 3 weeks of voluntary wheel running or 3 weeks of standard single housing conditions. Following a 7-day recovery period, running mice were returned to their running wheels. Weekly open-field behavior measured locomotor recovery using the Basso, Beattie and Bresnahan (BBB) locomotor rating scale and the Basso Mouse Scale (BMS) locomotor rating scale, a scale recently developed specifically for mice. Initial experiments using standard rung wheels show that wheel running impaired recovery, but subsequent experiments using a modified flat-surface wheel show improved recovery with exercise. By 14 days post SCI, the modified flat-surface running group had significantly higher BBB and BMS scores than the sedentary group. A repeated measures ANOVA shows locomotor recovery of modified flat-surface running mice was significantly improved compared to sedentary animals (p < 0.05). Locomotor assessment using a ladder beam task also shows a significant improvement in the modified flat-surface runners (p < 0.05). Finally, fibronectin staining shows no significant difference in lesion size between the two groups. These data represent the first mouse model showing voluntary exercise improves recovery after SCI.

(-)Epigallocatechin-3-gallate prevents the reserpine-induced impairment of short-term social memory in rats.

PubMed

Tseng, Hsiang-Chien; Wang, Mao-Hsien; Soung, Hung-Sheng; Chang, Yi; Chang, Kuo-Chi

2015-12-01

Reserpine has been confirmed to induce cognitive dysfunction and increase brain neural oxidative stress. Green tea catechins, particularly (-)epigallocatechin-3-gallate (EGCG), have strong antioxidative properties and can protect against numerous oxidative damages. In this study, we examined the possible protective effects of EGCG on reserpine-induced impairment of short-term memory in rats. Reserpine (1 mg/kg, intraperitoneal)-induced memory impairment was assessed using the social recognition task method; locomotor activity and the olfactory discrimination ability were not altered as measured by an open-field test and an olfactory discrimination test, respectively. EGCG treatment (100 and 300 mg/kg, intraperitoneal, for 7 days, starting 6 days before the reserpine injection) could improve the worsened social memory of reserpine-treated rats. Also, EGCG treatment reduced reserpine-induced lipid peroxidation and enhanced the antioxidation power in the hippocampi of reserpine-treated rats. These results suggest a protective effect of EGCG in treating reserpine-induced impairment of memory, most probably through its powerful antioxidative activities. Accordingly, EGCG may hold a clinically relevant value in preventing reserpine-induced cognitive dysfunction.

Sodium Butyrate Improves Locomotor Impairment and Early Mortality in a Rotenone-Induced Drosophila Model of Parkinson’s Disease

PubMed Central

St. Laurent, Robyn; O’Brien, Liam M.; Ahmad, S. Tariq

2013-01-01

Parkinson’s disease (PD) is a neurodegenerative disorder primarily affecting the dopaminergic neurons in the nigrastriatal pathway resulting in debilitating motor impairment in both familial and sporadic cases. Histone deacetylase (HDAC) inhibitors have been recently implicated as a therapeutic candidate because of their ability to correct the disrupted HDAC activity in PD and other neurodegenerative diseases. Sodium butyrate (SB), an HDAC inhibitor, reduces degeneration of dopaminergic neurons in a mutant alpha-synuclein Drosophila transgenic model of familial PD. Chronic exposure to the pesticide rotenone also causes selective degeneration of dopaminergic neurons and causes locomotor impairment and early mortality in a Drosophila model of chemically-induced PD. This study investigated the effects of sodium butyrate on locomotor impairment and early mortality in a rotenone-induced PD model. We show that treatment with 10 mM SB-supplemented food rescued the rotenone-induced locomotor impairment and early mortality in flies. Additionally, flies with the genetic knockdown of HDAC activity through Sin3A loss-of-function mutation (Sin3Alof) were resistant to rotenone-induced locomotor impairment and early mortality. Furthermore, SB-supplemented Sin3Alof flies had a modest additive effect for improving locomotor impairment. We also show SB-mediated improvement of rotenone-induced locomotor impairment was associated with elevated dopamine levels in the brain. However, the possibility of SB-mediated protective role through mechanisms independent from dopamine system is also discussed. These findings demonstrate that HDAC inhibitors like SB can ameliorate locomotor impairment in a rotenone-induced PD model. PMID:23623990

Relating ranging ecology, limb length, and locomotor economy in terrestrial animals.

PubMed

Pontzer, Herman

2012-03-07

Ecomorphological analyses have identified a number of important evolutionary trends in vertebrate limb design, but the relationships between daily travel distance, locomotor ecology, and limb length in terrestrial animals remain poorly understood. In this paper I model the net rate of energy intake as a function of foraging efficiency, and thus of locomotor economy; improved economy leads to greater net energy intake. However, the relationship between locomotor economy and net intake is highly dependent on foraging efficiency; only species with low foraging efficiencies experience strong selection pressure for improved locomotor economy and increased limb length. Examining 237 terrestrial species, I find that nearly all taxa obtain sufficiently high foraging efficiencies that selection for further increases in economy is weak. Thus selection pressures for increased economy and limb length among living terrestrial animals may be relatively weak and similar in magnitude across ecologically diverse species. The Economy Selection Pressure model for locomotor economy may be useful in investigating the evolution of limb design in early terrestrial taxa and the coevolution of foraging ecology and locomotor anatomy in lineages with low foraging efficiencies. Copyright © 2011 Elsevier Ltd. All rights reserved.

Pedunculopontine network dysfunction in Parkinson's disease with postural control and sleep disorders.

PubMed

Gallea, Cecile; Ewenczyk, Claire; Degos, Bertrand; Welter, Marie-Laure; Grabli, David; Leu-Semenescu, Smaranda; Valabregue, Romain; Berroir, Pierre; Yahia-Cherif, Lydia; Bertasi, Eric; Fernandez-Vidal, Sara; Bardinet, Eric; Roze, Emmanuel; Benali, Habib; Poupon, Cyril; François, Chantal; Arnulf, Isabelle; Lehéricy, Stéphane; Vidailhet, Marie

2017-05-01

The objective of this study was to investigate pedunculopontine nucleus network dysfunctions that mediate impaired postural control and sleep disorder in Parkinson's disease. We examined (1) Parkinson's disease patients with impaired postural control and rapid eye movement sleep behavior disorder (further abbreviated as sleep disorder), (2) Parkinson's disease patients with sleep disorder only, (3) Parkinson's disease patients with neither impaired postural control nor sleep disorder, and (4) healthy volunteers. We assessed postural control with clinical scores and biomechanical recordings during gait initiation. Participants had video polysomnography, daytime sleepiness self-evaluation, and resting-state functional MRIs. Patients with impaired postural control and sleep disorder had longer duration of anticipatory postural adjustments during gait initiation and decreased functional connectivity between the pedunculopontine nucleus and the supplementary motor area in the locomotor network that correlated negatively with the duration of anticipatory postural adjustments. Both groups of patients with sleep disorder had decreased functional connectivity between the pedunculopontine nucleus and the anterior cingulate cortex in the arousal network that correlated with daytime sleepiness. The degree of dysfunction in the arousal network was related to the degree of connectivity in the locomotor network in all patients with sleep disorder, but not in patients without sleep disorder or healthy volunteers. These results shed light on the functional neuroanatomy of pedunculopontine nucleus networks supporting the clinical manifestation and the interdependence between sleep and postural control impairments in Parkinson's disease. © 2016 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

Initiation of bladder voiding with epidural stimulation in paralyzed, step trained rats.

PubMed

Gad, Parag N; Roy, Roland R; Zhong, Hui; Lu, Daniel C; Gerasimenko, Yury P; Edgerton, V Reggie

2014-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury.

Initiation of Bladder Voiding with Epidural Stimulation in Paralyzed, Step Trained Rats

PubMed Central

Gad, Parag N.; Roy, Roland R.; Zhong, Hui; Lu, Daniel C.; Gerasimenko, Yury P.; Edgerton, V. Reggie

2014-01-01

The inability to control timely bladder emptying is one of the most serious challenges among the several functional deficits that occur after a complete spinal cord injury. Having demonstrated that electrodes placed epidurally on the dorsum of the spinal cord can be used in animals and humans to recover postural and locomotor function after complete paralysis, we hypothesized that a similar approach could be used to recover bladder function after paralysis. Also knowing that posture and locomotion can be initiated immediately with a specific frequency-dependent stimulation pattern and that with repeated stimulation-training sessions these functions can improve even further, we reasoned that the same two strategies could be used to regain bladder function. Recent evidence suggests that rats with severe paralysis can be rehabilitated with a multisystem neuroprosthetic training regime that counteracts the development of neurogenic bladder dysfunction. No data regarding the acute effects of locomotion on bladder function, however, were reported. In this study we show that enabling of locomotor-related spinal neuronal circuits by epidural stimulation also influences neural networks controlling bladder function and can play a vital role in recovering bladder function after complete paralysis. We have identified specific spinal cord stimulation parameters that initiate bladder emptying within seconds of the initiation of epidural stimulation. The clinical implications of these results are substantial in that this strategy could have a major impact in improving the quality of life and longevity of patients while simultaneously dramatically reducing ongoing health maintenance after a spinal cord injury. PMID:25264607

Depression is an early disease manifestation in lupus-prone MRL/lpr mice.

PubMed

Gao, Hua-Xin; Campbell, Sean R; Cui, Min-Hui; Zong, Pu; Hee-Hwang, Jong; Gulinello, Maria; Putterman, Chaim

2009-02-15

Many lupus patients develop neuropsychiatric manifestations, including cognitive dysfunction, depression, and anxiety. However, it is not clear if neuropsychiatric lupus is a primary disease manifestation, or is secondary to non-CNS disease. We found that MRL/lpr lupus-prone mice exhibited significant depression-like behavior already at 8 weeks of age, despite normal visual working memory, locomotor coordination and social preference. Moreover, depression was significantly correlated with titers of autoantibodies against DNA, NMDA receptors and cardiolipin. Our results indicate that lupus mice develop depression and CNS dysfunction very early in the course of disease, in the absence of substantial pathology involving other target organs.

Locomotor training improves premotoneuronal control after chronic spinal cord injury.

PubMed

Knikou, Maria; Mummidisetty, Chaithanya K

2014-06-01

Spinal inhibition is significantly reduced after spinal cord injury (SCI) in humans. In this work, we examined if locomotor training can improve spinal inhibition exerted at a presynaptic level. Sixteen people with chronic SCI received an average of 45 training sessions, 5 days/wk, 1 h/day. The soleus H-reflex depression in response to low-frequency stimulation, presynaptic inhibition of soleus Ia afferent terminals following stimulation of the common peroneal nerve, and bilateral EMG recovery patterns were assessed before and after locomotor training. The soleus H reflexes evoked at 1.0, 0.33, 0.20, 0.14, and 0.11 Hz were normalized to the H reflex evoked at 0.09 Hz. Conditioned H reflexes were normalized to the associated unconditioned H reflex evoked with subjects seated, while during stepping both H reflexes were normalized to the maximal M wave evoked after the test H reflex at each bin of the step cycle. Locomotor training potentiated homosynaptic depression in all participants regardless the type of the SCI. Presynaptic facilitation of soleus Ia afferents remained unaltered in motor complete SCI patients. In motor incomplete SCIs, locomotor training either reduced presynaptic facilitation or replaced presynaptic facilitation with presynaptic inhibition at rest. During stepping, presynaptic inhibition was modulated in a phase-dependent manner. Locomotor training changed the amplitude of locomotor EMG excitability, promoted intralimb and interlimb coordination, and altered cocontraction between knee and ankle antagonistic muscles differently in the more impaired leg compared with the less impaired leg. The results provide strong evidence that locomotor training improves premotoneuronal control after SCI in humans at rest and during walking. Copyright © 2014 the American Physiological Society.

Influence of basal ganglia on upper limb locomotor synergies. Evidence from deep brain stimulation and L-DOPA treatment in Parkinson's disease.

PubMed

Crenna, P; Carpinella, I; Lopiano, L; Marzegan, A; Rabuffetti, M; Rizzone, M; Lanotte, M; Ferrarin, M

2008-12-01

Clinical evidence of impaired arm swing while walking in patients with Parkinson's disease suggests that basal ganglia and related systems play an important part in the control of upper limb locomotor automatism. To gain more information on this supraspinal influence, we measured arm and thigh kinematics during walking in 10 Parkinson's disease patients, under four conditions: (i) baseline (no treatment), (ii) therapeutic stimulation of the subthalamic nucleus (STN), (iii)L-DOPA medication and (iv) combined STN stimulation and L-DOPA. Ten age-matched controls provided reference data. Under baseline conditions the range of patients' arm motion was severely restricted, with no correlation with the excursion of the thigh. In addition, the arm swing was abnormally coupled in time with oscillation of the ipsilateral thigh. STN stimulation significantly increased the gait speed and improved the spatio-temporal parameters of arm and thigh motion. The kinematic changes as a function of gait speed changes, however, were significantly smaller for the upper than the lower limb, in contrast to healthy controls. Arm motion was also less responsive after L-DOPA. Simultaneous deep brain stimulation and L-DOPA had additive effects on thigh motion, but not on arm motion and arm-thigh coupling. The evidence that locomotor automatisms of the upper and lower limbs display uncorrelated impairment upon dysfunction of the basal ganglia, as well as different susceptibility to electrophysiological and pharmacological interventions, points to the presence of heterogeneously distributed, possibly partially independent, supraspinal control channels, whereby STN and dopaminergic systems have relatively weaker influence on the executive structures involved in the arm swing and preferential action on those for lower limb movements. These findings might be considered in the light of phylogenetic changes in supraspinal control of limb motion related to primate bipedalism.

Efficacy of Stochastic Vestibular Stimulation to Improve Locomotor Performance in a Discordant Sensory Environment

NASA Technical Reports Server (NTRS)

Temple, D. R.; De Dios, Y. E.; Layne, C. S.; Bloomberg, J. J.; Mulavara, A. P.

2016-01-01

Astronauts exposed to microgravity face sensorimotor challenges incurred when readapting to a gravitational environment. Sensorimotor Adaptability (SA) training has been proposed as a countermeasure to improve locomotor performance during re-adaptation, and it is suggested that the benefits of SA training may be further enhanced by improving detection of weak sensory signals via mechanisms such as stochastic resonance when a non-zero level of stochastic white noise based electrical stimulation is applied to the vestibular system (stochastic vestibular stimulation, SVS). The purpose of this study was to test the efficacy of using SVS to improve short-term adaptation in a sensory discordant environment during performance of a locomotor task.

Changes in motor function, cognition, and emotion-related behavior after right hemispheric intracerebral hemorrhage in various brain regions of mouse.

PubMed

Zhu, Wei; Gao, Yufeng; Wan, Jieru; Lan, Xi; Han, Xiaoning; Zhu, Shanshan; Zang, Weidong; Chen, Xuemei; Ziai, Wendy; Hanley, Daniel F; Russo, Scott J; Jorge, Ricardo E; Wang, Jian

2018-03-01

Intracerebral hemorrhage (ICH) is a detrimental type of stroke. Mouse models of ICH, induced by collagenase or blood infusion, commonly target striatum, but not other brain sites such as ventricular system, cortex, and hippocampus. Few studies have systemically investigated brain damage and neurobehavioral deficits that develop in animal models of ICH in these areas of the right hemisphere. Therefore, we evaluated the brain damage and neurobehavioral dysfunction associated with right hemispheric ICH in ventricle, cortex, hippocampus, and striatum. The ICH model was induced by autologous whole blood or collagenase VII-S (0.075 units in 0.5 µl saline) injection. At different time points after ICH induction, mice were assessed for brain tissue damage and neurobehavioral deficits. Sham control mice were used for comparison. We found that ICH location influenced features of brain damage, microglia/macrophage activation, and behavioral deficits. Furthermore, the 24-point neurologic deficit scoring system was most sensitive for evaluating locomotor abnormalities in all four models, especially on days 1, 3, and 7 post-ICH. The wire-hanging test was useful for evaluating locomotor abnormalities in models of striatal, intraventricular, and cortical ICH. The cylinder test identified locomotor abnormalities only in the striatal ICH model. The novel object recognition test was effective for evaluating recognition memory dysfunction in all models except for striatal ICH. The tail suspension test, forced swim test, and sucrose preference test were effective for evaluating emotional abnormality in all four models but did not correlate with severity of brain damage. These results will help to inform future preclinical studies of ICH outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of locomotor training in completely spinalized cats previously submitted to a spinal hemisection.

PubMed

Martinez, Marina; Delivet-Mongrain, Hugo; Leblond, Hugues; Rossignol, Serge

2012-08-08

After a spinal hemisection in cats, locomotor plasticity occurring at the spinal level can be revealed by performing, several weeks later, a complete spinalization below the first hemisection. Using this paradigm, we recently demonstrated that the hemisection induces durable changes in the symmetry of locomotor kinematics that persist after spinalization. Can this asymmetry be changed again in the spinal state by interventions such as treadmill locomotor training started within a few days after the spinalization? We performed, in 9 adult cats, a spinal hemisection at thoracic level 10 and then a complete spinalization at T13, 3 weeks later. Cats were not treadmill trained during the hemispinal period. After spinalization, 5 of 9 cats were not trained and served as control while 4 of 9 cats were trained on the treadmill for 20 min, 5 d a week for 3 weeks. Using detailed kinematic analyses, we showed that, without training, the asymmetrical state of locomotion induced by the hemisection was retained durably after the subsequent spinalization. By contrast, training cats after spinalization induced a reversal of the left/right asymmetries, suggesting that new plastic changes occurred within the spinal cord through locomotor training. Moreover, training was shown to improve the kinematic parameters and the performance of the hindlimb on the previously hemisected side. These results indicate that spinal locomotor circuits, previously modified by past experience such as required for adaptation to the hemisection, can remarkably respond to subsequent locomotor training and improve bilateral locomotor kinematics, clearly showing the benefits of locomotor training in the spinal state.

Asymmetric pedunculopontine network connectivity in parkinsonian patients with freezing of gait

PubMed Central

Fling, Brett W.; Cohen, Rajal G.; Mancini, Martina; Nutt, John G.; Fair, Damian A.

2013-01-01

Freezing of gait is one of the most debilitating symptoms in Parkinson’s disease as it causes falls and reduces mobility and quality of life. The pedunculopontine nucleus is one of the major nuclei of the mesencephalic locomotor region and has neurons related to anticipatory postural adjustments preceding step initiation as well as to the step itself, thus it may be critical for coupling posture and gait to avoid freezing. Because freezing of gait and postural impairments have been related to frontal lesions and frontal dysfunction such as executive function, we hypothesized that freezing is associated with disrupted connectivity between midbrain locomotor regions and medial frontal cortex. We used diffusion tensor imaging to quantify structural connectivity of the pedunculopontine nucleus in patients with Parkinson’s disease with freezing of gait, without freezing, and healthy age-matched controls. We also included behavioural tasks to gauge severity of freezing of gait, quantify gait metrics, and assess executive cognitive functions to determine whether between-group differences in executive dysfunction were related to pedunculopontine nucleus structural network connectivity. Using seed regions from the pedunculopontine nucleus, we were able to delineate white matter connections between the spinal cord, cerebellum, pedunculopontine nucleus, subcortical and frontal/prefrontal cortical regions. The current study is the first to demonstrate differences in structural connectivity of the identified locomotor pathway in patients with freezing of gait. We report reduced connectivity of the pedunculopontine nucleus with the cerebellum, thalamus and multiple regions of the frontal cortex. Moreover, these structural differences were observed solely in the right hemisphere of patients with freezing of gait. Finally, we show that the more left hemisphere-lateralized the pedunculopontine nucleus tract volume, the poorer the performance on cognitive tasks requiring the initiation of appropriate actions and/or the inhibition of inappropriate actions, specifically within patients with freezing. These results support the notion that freezing of gait is strongly related to structural deficits in the right hemisphere’s locomotor network involving prefrontal cortical areas involved in executive inhibition function. PMID:23824487

Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress.

PubMed

Mehta, Vineet; Parashar, Arun; Udayabanu, Malairaman

2017-03-15

It is now evident that chronic stress is associated with anxiety, depression and cognitive dysfunction and very few studies have focused on identifying possible methods to prevent these stress-induced disorders. Previously, we identified abundance of quercetin in Urtica dioica extract, which efficiently attenuated stress related complications. Therefore, current study was designed to investigate the effect of quercetin on chronic unpredicted stress (CUS) induced behavioral dysfunction, oxidative stress and neuroinflammation in the mouse hippocampus. Animals were subjected to unpredicted stress for 21days, during which 30mg/kg quercetin was orally administered to them. Effect of CUS and quercetin treatment on animal behavior was assessed between day 22-26. Afterward, the hippocampus was processed to evaluate neuronal damage, oxidative and inflammatory stress. Results revealed that stressed animals were highly anxious (Elevated Plus Maze and Open Field), showed depressive-like behavior (sucrose preference task), performed poorly in short-term and long-term associative memory task (passive avoidance step-through task) and displayed reduced locomotion (open field). Quercetin alleviated behavioral dysfunction in chronically stressed animals. Compared to CUS, quercetin treatment significantly reduced anxiety, attenuated depression, improved cognitive dysfunction and normalized locomotor activity. Further, CUS elevated the levels of oxidative stress markers (TBARS, nitric oxide), lowered antioxidants (total thiol, catalase), enhanced expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β and COX-2) in the hippocampus and damaged hippocampal neurons. Quercetin treatment significantly lowered oxidative and inflammatory stress and prevented neural damage. In conclusion, quercetin can efficiently prevent stress induced neurological complications by rescuing brain from oxidative and inflammatory stress. Copyright © 2017 Elsevier Inc. All rights reserved.

Sensory-evoked perturbations of locomotor activity by sparse sensory input: a computational study

PubMed Central

Brownstone, Robert M.

2015-01-01

Sensory inputs from muscle, cutaneous, and joint afferents project to the spinal cord, where they are able to affect ongoing locomotor activity. Activation of sensory input can initiate or prolong bouts of locomotor activity depending on the identity of the sensory afferent activated and the timing of the activation within the locomotor cycle. However, the mechanisms by which afferent activity modifies locomotor rhythm and the distribution of sensory afferents to the spinal locomotor networks have not been determined. Considering the many sources of sensory inputs to the spinal cord, determining this distribution would provide insights into how sensory inputs are integrated to adjust ongoing locomotor activity. We asked whether a sparsely distributed set of sensory inputs could modify ongoing locomotor activity. To address this question, several computational models of locomotor central pattern generators (CPGs) that were mechanistically diverse and generated locomotor-like rhythmic activity were developed. We show that sensory inputs restricted to a small subset of the network neurons can perturb locomotor activity in the same manner as seen experimentally. Furthermore, we show that an architecture with sparse sensory input improves the capacity to gate sensory information by selectively modulating sensory channels. These data demonstrate that sensory input to rhythm-generating networks need not be extensively distributed. PMID:25673740

Body-weight-supported treadmill rehabilitation after stroke.

PubMed

Duncan, Pamela W; Sullivan, Katherine J; Behrman, Andrea L; Azen, Stanley P; Wu, Samuel S; Nadeau, Stephen E; Dobkin, Bruce H; Rose, Dorian K; Tilson, Julie K; Cen, Steven; Hayden, Sarah K

2011-05-26

Locomotor training, including the use of body-weight support in treadmill stepping, is a physical therapy intervention used to improve recovery of the ability to walk after stroke. The effectiveness and appropriate timing of this intervention have not been established. We stratified 408 participants who had had a stroke 2 months earlier according to the extent of walking impairment--moderate (able to walk 0.4 to <0.8 m per second) or severe (able to walk <0.4 m per second)--and randomly assigned them to one of three training groups. One group received training on a treadmill with the use of body-weight support 2 months after the stroke had occurred (early locomotor training), the second group received this training 6 months after the stroke had occurred (late locomotor training), and the third group participated in an exercise program at home managed by a physical therapist 2 months after the stroke (home-exercise program). Each intervention included 36 sessions of 90 minutes each for 12 to 16 weeks. The primary outcome was the proportion of participants in each group who had an improvement in functional walking ability 1 year after the stroke. At 1 year, 52.0% of all participants had increased functional walking ability. No significant differences in improvement were found between early locomotor training and home exercise (adjusted odds ratio for the primary outcome, 0.83; 95% confidence interval [CI], 0.50 to 1.39) or between late locomotor training and home exercise (adjusted odds ratio, 1.19; 95% CI, 0.72 to 1.99). All groups had similar improvements in walking speed, motor recovery, balance, functional status, and quality of life. Neither the delay in initiating the late locomotor training nor the severity of the initial impairment affected the outcome at 1 year. Ten related serious adverse events were reported (occurring in 2.2% of participants undergoing early locomotor training, 3.5% of those undergoing late locomotor training, and 1.6% of those engaging in home exercise). As compared with the home-exercise group, each of the groups receiving locomotor training had a higher frequency of dizziness or faintness during treatment (P=0.008). Among patients with severe walking impairment, multiple falls were more common in the group receiving early locomotor training than in the other two groups (P=0.02). Locomotor training, including the use of body-weight support in stepping on a treadmill, was not shown to be superior to progressive exercise at home managed by a physical therapist. (Funded by the National Institute of Neurological Disorders and Stroke and the National Center for Medical Rehabilitation Research; LEAPS ClinicalTrials.gov number, NCT00243919.).

Visual and kinesthetic locomotor imagery training integrated with auditory step rhythm for walking performance of patients with chronic stroke.

PubMed

Kim, Jin-Seop; Oh, Duck-Won; Kim, Suhn-Yeop; Choi, Jong-Duk

2011-02-01

To compare the effect of visual and kinesthetic locomotor imagery training on walking performance and to determine the clinical feasibility of incorporating auditory step rhythm into the training. Randomized crossover trial. Laboratory of a Department of Physical Therapy. Fifteen subjects with post-stroke hemiparesis. Four locomotor imagery trainings on walking performance: visual locomotor imagery training, kinesthetic locomotor imagery training, visual locomotor imagery training with auditory step rhythm and kinesthetic locomotor imagery training with auditory step rhythm. The timed up-and-go test and electromyographic and kinematic analyses of the affected lower limb during one gait cycle. After the interventions, significant differences were found in the timed up-and-go test results between the visual locomotor imagery training (25.69 ± 16.16 to 23.97 ± 14.30) and the kinesthetic locomotor imagery training with auditory step rhythm (22.68 ± 12.35 to 15.77 ± 8.58) (P < 0.05). During the swing and stance phases, the kinesthetic locomotor imagery training exhibited significantly increased activation in a greater number of muscles and increased angular displacement of the knee and ankle joints compared with the visual locomotor imagery training, and these effects were more prominent when auditory step rhythm was integrated into each form of locomotor imagery training. The activation of the hamstring during the swing phase and the gastrocnemius during the stance phase, as well as kinematic data of the knee joint, were significantly different for posttest values between the visual locomotor imagery training and the kinesthetic locomotor imagery training with auditory step rhythm (P < 0.05). The therapeutic effect may be further enhanced in the kinesthetic locomotor imagery training than in the visual locomotor imagery training. The auditory step rhythm together with the locomotor imagery training produces a greater positive effect in improving the walking performance of patients with post-stroke hemiparesis.

Supplementation of Spirulina (Arthrospira platensis) Improves Lifespan and Locomotor Activity in Paraquat-Sensitive DJ-1βΔ93 Flies, a Parkinson's Disease Model in Drosophila melanogaster.

PubMed

Kumar, Ajay; Christian, Pearl K; Panchal, Komal; Guruprasad, B R; Tiwari, Anand K

2017-09-03

Spirulina (Arthrospira platensis) is a cyanobacterium (blue-green alga) consumed by humans and other animals because of its nutritional values and pharmacological properties. Apart from high protein contents, it also contains high levels of antioxidant and anti-inflammatory compounds, such as carotenoids, β-carotene, phycocyanin, and phycocyanobilin, indicating its possible pharmaco-therapeutic utility. In the present study using DJ-1β Δ93 flies, a Parkinson's disease model in Drosophila, we have demonstrated the therapeutic effect of spirulina and its active component C-phycocyanin (C-PC) in the improvement of lifespan and locomotor behavior. Our findings indicate that dietary supplementation of spirulina significantly improves the lifespan and locomotor activity of paraquat-fed DJ-1β Δ93 flies. Furthermore, supplementation of spirulina and C-PC individually and independently reduced the cellular stress marked by deregulating the expression of heat shock protein 70 and Jun-N-terminal kinase signaling in DJ-1β Δ93 flies. A significant decrease in superoxide dismutase and catalase activities in spirulina-fed DJ-1β Δ93 flies tends to indicate the involvement of antioxidant properties associated with spirulina in the modulation of stress-induced signaling and improvement in lifespan and locomotor activity in Drosophila DJ-1β Δ93 flies. Our results suggest that antioxidant boosting properties of spirulina can be used as a nutritional supplement for improving the lifespan and locomotor behavior in Parkinson's disease.

Neurological Dysfunction in Early Maturity of a Model for Niemann-Pick C1 Carrier Status.

PubMed

Hung, Ya Hui; Walterfang, Mark; Churilov, Leonid; Bray, Lisa; Jacobson, Laura H; Barnham, Kevin J; Jones, Nigel C; O'Brien, Terence J; Velakoulis, Dennis; Bush, Ashley I

2016-07-01

Autosomal recessive inheritance of NPC1 with loss-of-function mutations underlies Niemann-Pick disease, type C1 (NP-C1), a lysosomal storage disorder with progressive neurodegeneration. It is uncertain from limited biochemical studies and patient case reports whether NPC1 haploinsufficiency can cause a partial NP-C1 phenotype in carriers. In the present study, we examined this possibility in heterozygotes of a natural loss-of-function mutant Npc1 mouse model. We found partial motor dysfunction and increased anxiety-like behavior in Npc1 (+/-) mice by 9 weeks of age. Relative to Npc1 (+/+) mice, Npc1 (+/-) mice failed to show neurodevelopmental improvements in motor coordination and balance on an accelerating Rotarod. In the open-field test, Npc1 (+/-) mice showed an intermediate phenotype in spontaneous locomotor activity compared with Npc1 (+/+) and Npc1 (-/-) mice, as well as decreased center tendency. Together with increased stride length under anxiogenic conditions on the DigiGait treadmill, these findings are consistent with heightened anxiety. Our findings indicate that pathogenic NPC1 allele carriers, who represent about 0.66 % of humans, could be vulnerable to motor and anxiety disorders.

Developmental kinesiology: three levels of motor control in the assessment and treatment of the motor system.

PubMed

Kobesova, Alena; Kolar, Pavel

2014-01-01

Three levels of sensorimotor control within the central nervous system (CNS) can be distinguished. During the neonatal stage, general movements and primitive reflexes are controlled at the spinal and brain stem levels. Analysis of the newborn's spontaneous general movements and the assessment of primitive reflexes is crucial in the screening and early recognition of a risk for abnormal development. Following the newborn period, the subcortical level of the CNS motor control emerges and matures mainly during the first year of life. This allows for basic trunk stabilization, a prerequisite for any phasic movement and for the locomotor function of the extremities. At the subcortical level, orofacial muscles and afferent information are automatically integrated within postural-locomotor patterns. Finally, the cortical (the highest) level of motor control increasingly becomes activated. Cortical control is important for the individual qualities and characteristics of movement. It also allows for isolated segmental movement and relaxation. A child with impaired cortical motor control may be diagnosed with developmental dyspraxia or developmental coordination disorder. Human ontogenetic models, i.e., developmental motor patterns, can be used in both the diagnosis and treatment of locomotor system dysfunction. Copyright © 2013 Elsevier Ltd. All rights reserved.

Role of spared pathways in locomotor recovery after body-weight-supported treadmill training in contused rats.

PubMed

Singh, Anita; Balasubramanian, Sriram; Murray, Marion; Lemay, Michel; Houle, John

2011-12-01

Body-weight-supported treadmill training (BWSTT)-related locomotor recovery has been shown in spinalized animals. Only a few animal studies have demonstrated locomotor recovery after BWSTT in an incomplete spinal cord injury (SCI) model, such as contusion injury. The contribution of spared descending pathways after BWSTT to behavioral recovery is unclear. Our goal was to evaluate locomotor recovery in contused rats after BWSTT, and to study the role of spared pathways in spinal plasticity after BWSTT. Forty-eight rats received a contusion, a transection, or a contusion followed at 9 weeks by a second transection injury. Half of the animals in the three injury groups were given BWSTT for up to 8 weeks. Kinematics and the Basso-Beattie-Bresnahan (BBB) test assessed behavioral improvements. Changes in Hoffmann-reflex (H-reflex) rate depression property, soleus muscle mass, and sprouting of primary afferent fibers were also evaluated. BWSTT-contused animals showed accelerated locomotor recovery, improved H-reflex properties, reduced muscle atrophy, and decreased sprouting of small caliber afferent fibers. BBB scores were not improved by BWSTT. Untrained contused rats that received a transection exhibited a decrease in kinematic parameters immediately after the transection; in contrast, trained contused rats did not show an immediate decrease in kinematic parameters after transection. This suggests that BWSTT with spared descending pathways leads to neuroplasticity at the lumbar spinal level that is capable of maintaining locomotor activity. Discontinuing training after the transection in the trained contused rats abolished the improved kinematics within 2 weeks and led to a reversal of the improved H-reflex response, increased muscle atrophy, and an increase in primary afferent fiber sprouting. Thus continued training may be required for maintenance of the recovery. Transected animals had no effect of BWSTT, indicating that in the absence of spared pathways this training paradigm did not improve function.

Effects of Dietary Vitamin E Supplementation in Bladder Function and Spasticity during Spinal Cord Injury

PubMed Central

Cordero, Kathia; Coronel, Gemma G.; Serrano-Illán, Miguel; Cruz-Bracero, Jennifer

2018-01-01

Traumatic spinal cord injury (SCI) results in debilitating autonomic dysfunctions, paralysis and significant sensorimotor impairments. A key component of SCI is the generation of free radicals that contributes to the high levels of oxidative stress observed. This study investigates whether dietary supplementation with the antioxidant vitamin E (alpha-tocopherol) improves functional recovery after SCI. Female adult Sprague-Dawley rats were fed either with a normal diet or a dietary regiment supplemented with vitamin E (51 IU/g) for eight weeks. The rats were subsequently exposed either to a contusive SCI or sham operation, and evaluated using standard functional behavior analysis. We report that the rats that consumed the vitamin E-enriched diet showed an accelerated bladder recovery and significant improvements in locomotor function relative to controls, as determined by residual volumes and Basso, Beatie, and Bresnaham BBB scores, respectively. Interestingly, the prophylactic dietary intervention did not preserve neurons in the ventral horn of injured rats, but it significantly increased the numbers of oligodendrocytes. Vitamin E supplementation attenuated the depression of the H-reflex (a typical functional consequence of SCI) while increasing the levels of supraspinal serotonin immunoreactivity. Our findings support the potential complementary use of vitamin E to ameliorate sensory and autonomic dysfunctions associated with spinal cord injury, and identified promising new cellular and functional targets of its neuroprotective effects. PMID:29495419

Quercetin ameliorates chronic unpredicted stress-induced behavioral dysfunction in male Swiss albino mice by modulating hippocampal insulin signaling pathway.

PubMed

Mehta, Vineet; Singh, Tiratha Raj; Udayabanu, Malairaman

2017-12-01

Chronic stress is associated with impaired neurogenesis, neurodegeneration and behavioral dysfunction, whereas the mechanism underlying stress-mediated neurological complications is still not clear. In the present study, we aimed to investigate whether chronic unpredicted stress (CUS) mediated neurological alterations are associated with impaired hippocampal insulin signaling or not, and studied the effect of quercetin in this scenario. Male Swiss albino mice were subjected to 21day CUS, during which 30mg/kg quercetin treatment was given orally. After 21days, behavioral functions were evaluated in terms of locomotor activity (Actophotometer), muscle coordination (Rota-rod), depression (Tail Suspension Test (TST), Forced Swim Test (FST)) and memory performance (Passive-avoidance step-down task (PASD)). Further, hippocampal insulin signaling was evaluated in terms of protein expression of insulin, insulin receptor (IR) and glucose transporter 4 (GLUT-4) and neurogenesis was evaluated in terms of doublecortin (DCX) expression. 21day CUS significantly impaired locomotion and had no effect on muscle coordination. Stressed animals were depressed and showed markedly impaired memory functions. Quercetin treatment significantly improvement stress-mediated behavior dysfunction as indicated by improved locomotion, lesser immobility time and greater frequency of upward turning in TST and FST and increased transfer latency on the day 2 (short-term memory) and day 5 (long-term memory) in PASD test. We observed significantly higher IR expression and significantly lower GLUT-4 expression in the hippocampus of stressed animals, despite of nonsignificant difference in insulin levels. Further, chronic stress impaired hippocampal neurogenesis, as indicated by the significantly reduced levels of hippocampal DCX expression. Quercetin treatment significantly lowered insulin and IR expression and significantly enhanced GLUT-4 and DCX expression in the hippocampus, when compared to CUS. In conclusion, quercetin treatment efficiently alleviated stress mediated behavioral dysfunction by modulating hippocampal insulin signaling and neurogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

A cable-driven locomotor training system for restoration of gait in human SCI.

PubMed

Wu, Ming; Hornby, T George; Landry, Jill M; Roth, Heidi; Schmit, Brian D

2011-02-01

A novel cable-driven robotic locomotor training system was developed to provide compliant assistance/resistance forces to the legs during treadmill training in patients with incomplete spinal cord injury (SCI). Eleven subjects with incomplete SCI were recruited to participate in two experiments to test the feasibility of the robotic gait training system. Specifically, 10 subjects participated in one experimental session to test the characteristics of the robotic gait training system and one subject participated in repeated testing sessions over 8 weeks with the robotic device to test improvements in locomotor function. Limb kinematics were recorded in one experiment to evaluate the system characteristics of the cable-driven locomotor trainer and the overground gait speed and 6 min walking distance were evaluated at pre, 4 and 8 weeks post treadmill training of a single subject as well. The results indicated that the cable driven robotic gait training system improved the kinematic performance of the leg during treadmill walking and had no significant impact on the variability of lower leg trajectory, suggesting a high backdrivability of the cable system. In addition, results from a patient with incomplete SCI indicated that prolonged robotic gait training using the cable robot improved overground gait speed. Results from this study suggested that a cable driven robotic gait training system is effective in improving leg kinematic performance, yet allows variability of gait kinematics. Thus, it seems feasible to improve the locomotor function in human SCI using this cable driven robotic system, warranting testing with a larger group of patients. Copyright © 2010 Elsevier B.V. All rights reserved.

Balance and ambulation improvements in individuals with chronic incomplete spinal cord injury using locomotor training-based rehabilitation.

PubMed

Harkema, Susan J; Schmidt-Read, Mary; Lorenz, Douglas J; Edgerton, V Reggie; Behrman, Andrea L

2012-09-01

To evaluate the effects of intensive locomotor training on balance and ambulatory function at enrollment and discharge during outpatient rehabilitation after incomplete SCI. Prospective observational cohort. Seven outpatient rehabilitation centers from the Christopher and Dana Reeve Foundation NeuroRecovery Network (NRN). Patients (N=196) with American Spinal Injury Association Impairment Scale (AIS) grade C or D SCI who received at least 20 locomotor training treatment sessions in the NRN. Intensive locomotor training, including step training using body-weight support and manual facilitation on a treadmill followed by overground assessment and community integration. Berg Balance Scale; Six-Minute Walk Test; 10-Meter Walk Test. Outcome measures at enrollment showed high variability between patients with AIS grades C and D. Significant improvement from enrollment to final evaluation was observed in balance and walking measures for patients with AIS grades C and D. The magnitude of improvement significantly differed between AIS groups for all measures. Time since SCI was not associated significantly with outcome measures at enrollment, but was related inversely to levels of improvement. Significant variability in baseline values of functional outcome measures is evident after SCI in individuals with AIS grades C and D and significant functional recovery can continue to occur even years after injury when provided with locomotor training. These results indicate that rehabilitation, which provides intensive activity-based therapy, can result in functional improvements in individuals with chronic incomplete SCI. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Locomotor activity, emotionality, sensori-motor gating, learning and memory in the APPswe/PS1dE9 mouse model of Alzheimer's disease.

PubMed

O'Leary, Timothy P; Hussin, Ahmed T; Gunn, Rhian K; Brown, Richard E

2018-06-02

The APPswe/PS1dE9 mouse (line 85) is a double transgenic model of Alzheimer's disease (AD) with familial amyloid precursor protein and presenilin-1 mutations. These mice develop age-related behavioral changes reflective of the neuropsychiatric symptoms (altered anxiety-like behaviour, hyperactivity) and cognitive dysfunction (impaired learning and memory) observed in AD. The APPswe/PS1dE9 mouse has been used to examine the efficacy of therapeutic interventions on behaviour, despite previous difficulties in replicating behavioural phenotypes. Therefore, the purpose of this study was to establish the reliability of these phenotypes by further characterizing the behaviour of male APPswe/PS1dE9 and wild-type mice between 7 and 14 months of age. Mice were tested on the open-field over 5-days to examine emotionality, locomotor activity and inter-session habituation. Mice were also tested on the repeated-reversal water maze task and spontaneous alternation on the Y-maze to assess working memory. Sensori-motor gating was examined with acoustic startle and pre-pulse inhibition. Lastly contextual and cued (trace) memory was assessed with fear conditioning. The results show that among non-cognitive behaviours, APPswe/PS1dE9 mice have normal locomotor activity, anxiety-like behavior, habituation and sensori-motor gating. However, APPswe/PS1dE9 mice show impaired working memory on the repeated-reversal water-maze and impaired memory in contextual but not trace-cued fear conditioning. These results indicate that the APPswe/PS1dE9 (line 85) mice have deficits in some types of hippocampal-dependent learning and memory and, at the ages tested, APPswe/PS1dE9 mice model cognitive dysfunction but not neuropsychiatric symptoms. Copyright © 2018. Published by Elsevier Inc.

Ethnic Differences in Disability Prevalence and Their Determinants Studied over a 20-Year Period: A Cohort Study

PubMed Central

Williams, Emily D.; Tillin, Therese; Whincup, Peter; Forouhi, Nita G.; Chaturvedi, Nishi

2012-01-01

Background To compare disability prevalence rates in the major ethnic groups in the UK and understand the risk factors contributing to differences identified. It was hypothesised that Indian Asian and African Caribbean people would experience higher rates of disability compared with Europeans. Methods Data was collected from 888 European, 636 Indian Asian and 265 African Caribbean men and women, aged 58–88 years at 20-year follow-up of community-based cohort study, based in West London. Disability was measured using a performance-based locomotor function test and self-reported questionnaires on functional limitation, and instrumental (IADL) and basic activities of daily living (ADL). Results The mean (SD) age of participants at follow-up was 69.6 (6.2) years. Compared with Europeans, Indian Asian people were significantly more likely to experience all of the disability outcomes than Europeans; this persisted after adjustment for socioeconomic, behavioural, adiposity and chronic disease risk factors measured at baseline (locomotor dysfunction: adjusted odds ratio (OR) 2.20, 95% CI 1.56–3.11; functional limitation: OR 2.77, 2.01–3.81; IADL impairment: OR 3.12, 2.20–4.41; ADL impairment: OR 1.58, 1.11–2.24). In contrast, a modest excess risk of disability was observed in African Caribbeans, which was abolished after adjustment (e.g. locomotor dysfunction: OR 1.37, 0.90–1.91); indeed a reduced risk of ADL impairment appeared after multivariable adjustment (OR from 0.99, 0.68–1.45 to 0.59, 0.38–0.93), compared with Europeans. Conclusions Substantially elevated risk of disability was observed among Indian Asian participants, unexplained by known factors. A greater understanding of determinants of disability and normative functional beliefs of healthy aging is required in this population to inform intervention efforts to prevent disability. PMID:23029128

The Development of an Accelerometer System for Measuring Pelvic Motion During Walking.

DTIC Science & Technology

1979-01-01

9. PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT, PROJECT, T ASK AFIT STUDENT AT: University of Oxford CONTROLLING OFFICE NAME AND...bones, joints or muscles and physiotherapy to improve the functioning of impaired lower limbs. When irreparable damage occurs, the normal locomotor system...restoring near normal functioning of the locomotor system. Any improvement in surgical procedures, physiotherapy techniques, orthoses or prostheses

Development of a Countermeasure to Enhance Postflight Locomotor Adaptability

NASA Technical Reports Server (NTRS)

Bloomberg, Jacob J.

2006-01-01

Astronauts returning from space flight experience locomotor dysfunction following their return to Earth. Our laboratory is currently developing a gait adaptability training program that is designed to facilitate recovery of locomotor function following a return to a gravitational environment. The training program exploits the ability of the sensorimotor system to generalize from exposure to multiple adaptive challenges during training so that the gait control system essentially learns to learn and therefore can reorganize more rapidly when faced with a novel adaptive challenge. We have previously confirmed that subjects participating in adaptive generalization training programs using a variety of visuomotor distortions can enhance their ability to adapt to a novel sensorimotor environment. Importantly, this increased adaptability was retained even one month after completion of the training period. Adaptive generalization has been observed in a variety of other tasks requiring sensorimotor transformations including manual control tasks and reaching (Bock et al., 2001, Seidler, 2003) and obstacle avoidance during walking (Lam and Dietz, 2004). Taken together, the evidence suggests that a training regimen exposing crewmembers to variation in locomotor conditions, with repeated transitions among states, may enhance their ability to learn how to reassemble appropriate locomotor patterns upon return from microgravity. We believe exposure to this type of training will extend crewmembers locomotor behavioral repertoires, facilitating the return of functional mobility after long duration space flight. Our proposed training protocol will compel subjects to develop new behavioral solutions under varying sensorimotor demands. Over time subjects will learn to create appropriate locomotor solution more rapidly enabling acquisition of mobility sooner after long-duration space flight. Our laboratory is currently developing adaptive generalization training procedures and the associated flight hardware to implement such a training program during regular inflight treadmill operations. A visual display system will provide variation in visual flow patterns during treadmill exercise. Crewmembers will be exposed to a virtual scene that can translate and rotate in six-degrees-of freedom during their regular treadmill exercise period. Associated ground based studies are focused on determining optimal combinations of sensory manipulations (visual flow, body loading and support surface variation) and training schedules that will produce the greatest potential for adaptive flexibility in gait function during exposure to challenging and novel environments. An overview of our progress in these areas will be discussed during the presentation.

Effects of caffeine on locomotor activity in streptozotocin-induced diabetic rats.

PubMed

Bădescu, S V; Tătaru, C P; Kobylinska, L; Georgescu, E L; Zahiu, D M; Zăgrean, A M; Zăgrean, L

2016-01-01

Diabetes mellitus modifies the expression of adenosine receptors in the brain. Caffeine acts as an antagonist of A1 and A2A adenosine receptors and was shown to have a dose-dependent biphasic effect on locomotion in mice. The present study investigated the link between diabetes and locomotor activity in an animal model of streptozotocin-induced diabetes, and the effects of a low-medium dose of caffeine in this relation. The locomotor activity was investigated by using Open Field Test at 6 weeks after diabetes induction and after 2 more weeks of chronic caffeine administration. Diabetes decreased locomotor activity (total distance moved and mobility time). Chronic caffeine exposure impaired the locomotor activity in control rats, but not in diabetic rats. Our data suggested that the medium doses of caffeine might block the A2A receptors, shown to have an increased density in the brain of diabetic rats, and improve or at least maintain the locomotor activity, offering a neuroprotective support in diabetic rats. Abbreviations : STZ = streptozotocin, OFT = Open Field Test.

Sustained increase of alpha7 nicotinic receptors and choline-induced improvement of learning deficit in STOP knock-out mice.

PubMed

Bouvrais-Veret, Caroline; Weiss, Stéphanie; Andrieux, Annie; Schweitzer, Annie; McIntosh, J Michael; Job, Didier; Giros, Bruno; Martres, Marie-Pascale

2007-06-01

Mice deficient in the microtubule stabilizing protein STOP (stable tubule only polypeptide) show synaptic plasticity anomalies in hippocampus, dopamine hyper-reactivity in the limbic system and severe behavioral deficits. Some of these disturbances are alleviated by long-term antipsychotic treatment. Therefore, this mouse line represents a pertinent model for some aspects of schizophrenia symptomatology. Numerous data support dysfunction of nicotinic neurotransmission in schizophrenia and epidemiological studies show increased tobacco use in schizophrenic patients, in whom nicotine has been reported to improve cognitive deficits and impairment in sensory gating. In this study, we examined potential alterations in cholinergic (ACh) and nicotinic components and functions in STOP mutant mice. STOP KO mice displayed no variation of the density of ACh esterase and beta2* nicotinic receptors (nAChRs), large reductions in the density of vesicular ACh transporter and alpha6* nAChRs and marked increases in the density of alpha7 nAChRs, in some brain areas. STOP KO mice were hypersensitive to the stimulating locomotor effect of nicotine and, interestingly, their impaired performance in learning the cued version of the water maze were improved by administration of the preferential alpha7 nAChR agonist choline. Altogether, our data show that the deletion of the ubiquitous STOP protein elicited restricted alterations in ACh components. They also suggest that nicotinic neurotransmission can be deficient in STOP KO mice and that mutant mice can represent a meaningful model to study some nicotinic dysfunctions and therapeutic treatments.

A Review on Locomotor Training after Spinal Cord Injury: Reorganization of Spinal Neuronal Circuits and Recovery of Motor Function

PubMed Central

2016-01-01

Locomotor training is a classic rehabilitation approach utilized with the aim of improving sensorimotor function and walking ability in people with spinal cord injury (SCI). Recent studies have provided strong evidence that locomotor training of persons with clinically complete, motor complete, or motor incomplete SCI induces functional reorganization of spinal neuronal networks at multisegmental levels at rest and during assisted stepping. This neuronal reorganization coincides with improvements in motor function and decreased muscle cocontractions. In this review, we will discuss the manner in which spinal neuronal circuits are impaired and the evidence surrounding plasticity of neuronal activity after locomotor training in people with SCI. We conclude that we need to better understand the physiological changes underlying locomotor training, use physiological signals to probe recovery over the course of training, and utilize established and contemporary interventions simultaneously in larger scale research studies. Furthermore, the focus of our research questions needs to change from feasibility and efficacy to the following: what are the physiological mechanisms that make it work and for whom? The aforementioned will enable the scientific and clinical community to develop more effective rehabilitation protocols maximizing sensorimotor function recovery in people with SCI. PMID:27293901

Hyperactivity and depression-like traits in Bax KO mice

PubMed Central

Krahe, Thomas E.; Medina, Alexandre E.; Lantz, Crystal L.; Filgueiras, Cláudio C.

2018-01-01

The Bax gene is a member of the Bcl-2 gene family and its pro-apoptotic Bcl-associated X (Bax) protein is believed to be crucial in regulating apoptosis during neuronal development as well as following injury. With the advent of mouse genomics, mice lacking the pro-apoptotic Bax gene (Bax KO) have been extensively used to study how cell death helps to determine synaptic circuitry formation during neurodevelopment and disease. Surprisingly, in spite of its wide use and the association of programmed neuronal death with motor dysfunctions and depression, the effects of Bax deletion on mice spontaneous locomotor activity and depression-like traits are unknown. Here we examine the behavioral characteristics of Bax KO male mice using classical paradigms to evaluate spontaneous locomotor activity and depressive-like responses. In the open field, Bax KO animals exhibited greater locomotor activity than their control littermates. In the forced swimming test, Bax KO mice displayed greater immobility times, a behavior despair state, when compared to controls. Collectively, our findings corroborate the notion that a fine balance between cell survival and death early during development is critical for normal brain function later in life. Furthermore, it points out the importance of considering depressive-like and hyperactivity behavioral phenotypes when conducting neurodevelopmental and other studies using the Bax KO strain. PMID:26363094

Imaging: what can it tell us about parkinsonian gait?

PubMed Central

Bohnen, Nicolaas I.; Jahn, Klaus

2013-01-01

Functional neuroimaging has provided new tools to study cerebral gait control in Parkinson disease (PD). First, imaging of blood flow functions has identified a supraspinal locomotor network that includes the (frontal) cortex, basal ganglia, brainstem tegmentum and the cerebellum. These studies emphasize also the cognitive and attentional dependency of gait in PD. Furthermore, gait in PD and related syndromes like progressive supranuclear palsy may be associated with dysfunction of the indirect, modulatory prefrontal–subthalamic–pedunculopontine loop of locomotor control. The direct, stereotyped locomotor loop from the primary motor cortex to the spinal cord with rhythmic cerebellar input appears preserved and may contribute to the unflexible gait pattern in parkinsonian gait. Second, neurotransmitter and proteinopathy imaging studies are beginning to unravel novel mechanisms of parkinsonian gait and postural disturbances. Dopamine displacement imaging studies have shown evidence for a mesofrontal dopaminergic shift from a depleted striatum in parkinsonian gait. This may place additional burden on other brain systems mediating attention functions to perform previously automatic motor tasks. For example, our preliminary cholinergic imaging studies suggest significant slowing of gait speed when additional forebrain cholinergic denervation occurs in PD. Cholinergic denervation of the pedunculopontine nucleus and its thalamic projections have been associated with falls and impaired postural control. Deposition of β-amyloid may represent another non-dopaminergic correlate of gait disturbance in PD. These findings illustrate the emergence of dopamine non-responsive gait problems to reflect the transition from a predominantly hypodopaminergic disorder to a multisystem neurodegenerative disorder involving non-dopaminergic locomotor network structures and pathologies. PMID:24132837

Gradual training reduces practice difficulty while preserving motor learning of a novel locomotor task.

PubMed

Sawers, Andrew; Hahn, Michael E

2013-08-01

Motor learning strategies that increase practice difficulty and the size of movement errors are thought to facilitate motor learning. In contrast to this, gradual training minimizes movement errors and reduces practice difficulty by incrementally introducing task requirements, yet remains as effective as sudden training and its large movement errors for learning novel reaching tasks. While attractive as a locomotor rehabilitation strategy, it remains unknown whether the efficacy of gradual training extends to learning locomotor tasks and their unique requirements. The influence of gradual vs. sudden training on learning a locomotor task, asymmetric split belt treadmill walking, was examined by assessing whole body sagittal plane kinematics during 24 hour retention and transfer performance following either gradual or sudden training. Despite less difficult and less specific practice for the gradual cohort on day 1, gradual training resulted in equivalent motor learning of the novel locomotor task as sudden training when assessed by retention and transfer a day later. This suggests that large movement errors and increased practice difficulty may not be necessary for learning novel locomotor tasks. Further, gradual training may present a viable locomotor rehabilitation strategy avoiding large movement errors that could limit or impair improvements in locomotor performance. Copyright © 2013 Elsevier B.V. All rights reserved.

Dose-Response Outcomes Associated with Different Forms of Locomotor Training in Persons with Chronic Motor-Incomplete Spinal Cord Injury.

PubMed

Sandler, Evan B; Roach, Kathryn E; Field-Fote, Edelle C

2017-05-15

Outcomes of training are thought to be related to the amount of training (training dose). Although various approaches to locomotor training have been used to improve walking function in persons with spinal cord injury (SCI), little is known about the relationship between dose of locomotor training and walking outcomes. This secondary analysis aimed to identify the relationship between training dose and improvement in walking distance and speed associated with locomotor training in participants with chronic motor-incomplete spinal cord injury (MISCI). We compared the dose-response relationships associated with each of four different locomotor training approaches. Participants were randomized to either: treadmill-based training with manual assistance (TM = 17), treadmill-based training with stimulation (TS = 18), overground training with stimulation (OG = 15), and treadmill-based training with locomotor robotic device assistance (LR = 14). Subjects trained 5 days/week for 12 weeks, with a target of 60 training sessions. The distance-dose and time-dose were calculated based on the total distance and total time, respectively, participants engaged in walking over all sessions combined. Primary outcome measures included walking distance (traversed in 2 min) and walking speed (over 10 m). Only OG training showed a good correlation between distance-dose and change in walking distance and speed walked over ground (r = 0.61, p = 0.02; r = 0.62, p = 0.01). None of the treadmill-based training approaches were associated with significant correlations between training dose and improvement of functional walking outcome. The findings suggest that greater distance achieved over the course of OG training is associated with better walking outcomes in the studied population. Further investigation to identify the essential elements that determine outcomes would be valuable for guiding rehabilitation.

Alterations in Aerobic Exercise Performance and Gait Economy Following High-Intensity Dynamic Stepping Training in Persons With Subacute Stroke.

PubMed

Leddy, Abigail L; Connolly, Mark; Holleran, Carey L; Hennessy, Patrick W; Woodward, Jane; Arena, Ross A; Roth, Elliot J; Hornby, T George

2016-10-01

Impairments in metabolic capacity and economy (O2cost) are hallmark characteristics of locomotor dysfunction following stroke. High-intensity (aerobic) training has been shown to improve peak oxygen consumption in this population, with fewer reports of changes in O2cost. However, particularly in persons with subacute stroke, inconsistent gains in walking function are observed with minimal associations with gains in metabolic parameters. The purpose of this study was to evaluate changes in aerobic exercise performance in participants with subacute stroke following high-intensity variable stepping training as compared with conventional therapy. A secondary analysis was performed on data from a randomized controlled trial comparing high-intensity training with conventional interventions, and from the pilot study that formed the basis for the randomized controlled trial. Participants 1 to 6 months poststroke received 40 or fewer sessions of high-intensity variable stepping training (n = 21) or conventional interventions (n = 12). Assessments were performed at baseline (BSL), posttraining, and 2- to 3-month follow-up and included changes in submaximal (Equation is included in full-text article.)O2 ((Equation is included in full-text article.)O2submax) and O2cost at fastest possible treadmill speeds and peak speeds at BSL testing. Significant improvements were observed in (Equation is included in full-text article.)O2submax with less consistent improvements in O2cost, although individual responses varied substantially. Combined changes in both (Equation is included in full-text article.)O2submax and (Equation is included in full-text article.)O2 at matched peak BSL speeds revealed stronger correlations to improvements in walking function as compared with either measure alone. High-intensity stepping training may elicit significant improvements in (Equation is included in full-text article.)O2submax, whereas changes in both peak capacity and economy better reflect gains in walking function. Providing high-intensity training to improve locomotor and aerobic exercise performance may increase the efficiency of rehabilitation sessions.Video Abstract available for more insights from the authors (see Supplemental Digital Content, http://links.lww.com/JNPT/A142).

Pharmacological Modulation of 5-HT2C Receptor Activity Produces Bidirectional Changes in Locomotor Activity, Responding for a Conditioned Reinforcer, and Mesolimbic DA Release in C57BL/6 Mice.

PubMed

Browne, Caleb J; Ji, Xiaodong; Higgins, Guy A; Fletcher, Paul J; Harvey-Lewis, Colin

2017-10-01

Converging lines of behavioral, electrophysiological, and biochemical evidence suggest that 5-HT 2C receptor signaling may bidirectionally influence reward-related behavior through an interaction with the mesolimbic dopamine (DA) system. Here we directly test this hypothesis by examining how modulating 5-HT 2C receptor activity affects DA-dependent behaviors and relate these effects to changes in nucleus accumbens (NAc) DA release. In C57BL/6 mice, locomotor activity and responding for a conditioned reinforcer (CRf), a measure of incentive motivation, were examined following treatment with three 5-HT 2C receptor ligands: the agonist CP809101 (0.25-3 mg/kg), the antagonist SB242084 (0.25-1 mg/kg), or the antagonist/inverse agonist SB206553 (1-5 mg/kg). We further tested whether doses of these compounds that changed locomotor activity and responding for a CRf (1 mg/kg CP809101, 0.5 mg/kg SB242084, or 2.5 mg/kg SB206553) also altered NAc DA release using in vivo microdialysis in anesthetized mice. CP809101 reduced locomotor activity, responding for a CRf, and NAc DA release. In contrast, both SB242084 and SB206553 enhanced locomotor activity, responding for a CRf, and NAc DA release, although higher doses of SB206553 produced opposite behavioral effects. Pretreatment with the non-selective DA receptor antagonist α-flupenthixol prevented SB242084 from enhancing responding for a CRf. Thus blocking tonic 5-HT 2C receptor signaling can release serotonergic inhibition of mesolimbic DA activity and enhance reward-related behavior. The observed bidirectional effects of 5-HT 2C receptor ligands may have important implications when considering the 5-HT 2C receptor as a therapeutic target for psychiatric disorders, particularly those presenting with motivational dysfunctions.

Urtica dioica leaves modulates muscarinic cholinergic system in the hippocampus of streptozotocin-induced diabetic mice.

PubMed

Patel, Sita Sharan; Parashar, Arun; Udayabanu, Malairaman

2015-06-01

Diabetes mellitus is a chronic metabolic disorder and has been associated with cognitive dysfunction. In our earlier study, chronic Urtica dioica (UD) treatment significantly ameliorated diabetes induced associative and spatial memory deficit in mice. The present study was designed to explore the effect of UD leaves extract on muscarinic cholinergic system, which has long been known to be involved in cognition. Streptozotocin (STZ) (50 mg/kg, i.p., consecutively for 5 days) was used to induce diabetes followed by treatment with UD extract (50 mg/kg, oral) or rosiglitazone (5 mg/kg, oral) for 8 weeks. STZ-induced diabetic mice showed significant reduction in hippocampal muscarinic acetylcholine receptor-1 and choline acetyltransferase expressions. Chronic diabetes significantly up-regulated the protein expression of acetylcholinesterase associated with oxidative stress in hippocampus. Besides, STZ-induced diabetic mice showed hypolocomotion with up-regulation of muscarinic acetylcholine receptor-4 expression in striatum. Chronic UD treatment significantly attenuated the cholinergic dysfunction and oxidative stress in the hippocampus of diabetic mice. UD had no effect on locomotor activity and muscarinic acetylcholine receptor-4 expression in striatum. In conclusion, UD leaves extract has potential to reverse diabetes mediated alteration in muscarinic cholinergic system in hippocampus and thereby improve memory functions.

Dual spinal lesion paradigm in the cat: evolution of the kinematic locomotor pattern.

PubMed

Barrière, Grégory; Frigon, Alain; Leblond, Hugues; Provencher, Janyne; Rossignol, Serge

2010-08-01

The recovery of voluntary quadrupedal locomotion after an incomplete spinal cord injury can involve different levels of the CNS, including the spinal locomotor circuitry. The latter conclusion was reached using a dual spinal lesion paradigm in which a low thoracic partial spinal lesion is followed, several weeks later, by a complete spinal transection (i.e., spinalization). In this dual spinal lesion paradigm, cats can express hindlimb walking 1 day after spinalization, a process that normally takes several weeks, suggesting that the locomotor circuitry within the lumbosacral spinal cord had been modified after the partial lesion. Here we detail the evolution of the kinematic locomotor pattern throughout the dual spinal lesion paradigm in five cats to gain further insight into putative neurophysiological mechanisms involved in locomotor recovery after a partial spinal lesion. All cats recovered voluntary quadrupedal locomotion with treadmill training (3-5 days/wk) over several weeks. After the partial lesion, the locomotor pattern was characterized by several left/right asymmetries in various kinematic parameters, such as homolateral and homologous interlimb coupling, cycle duration, and swing/stance durations. When no further locomotor improvement was observed, cats were spinalized. After spinalization, the hindlimb locomotor pattern rapidly reappeared, but left/right asymmetries in swing/stance durations observed after the partial lesion could disappear or reverse. It is concluded that, after a partial spinal lesion, the hindlimb locomotor pattern was actively maintained by new dynamic interactions between spinal and supraspinal levels but also by intrinsic changes within the spinal cord.

Improved walking ability and reduced therapeutic stress with an electromechanical gait device.

PubMed

Freivogel, Susanna; Schmalohr, Dieter; Mehrholz, Jan

2009-09-01

To evaluate the effectiveness of repetitive locomotor training using a newly developed electromechanical gait device compared with treadmill training/gait training with respect to patient's ambulatory motor outcome, necessary personnel resources, and discomfort experienced by therapists and patients. Randomized, controlled, cross-over trial. Sixteen non-ambulatory patients after stroke, severe brain or spinal cord injury sequentially received 2 kinds of gait training. Study intervention A: 20 treatments of locomotor training with an electromechanical gait device; control intervention B: 20 treatments of locomotor training with treadmill or task-oriented gait training. The primary variable was walking ability (Functional Ambulation Category). Secondary variables included gait velocity, Motricity-Index, Rivermead-Mobility-Index, number of therapists needed, and discomfort and effort of patients and therapists during training. Gait ability and the other motor outcome related parameters improved for all patients, but without significant difference between intervention types. However, during intervention A, significantly fewer therapists were needed, and they reported less discomfort and a lower level of effort during training sessions. Locomotor training with or without an electromechanical gait trainer leads to improved gait ability; however, using the electromechanical gait trainer requires less therapeutic assistance, and therapist discomfort is reduced.

Improved gait after repetitive locomotor training in children with cerebral palsy.

PubMed

Smania, Nicola; Bonetti, Paola; Gandolfi, Marialuisa; Cosentino, Alessandro; Waldner, Andreas; Hesse, Stefan; Werner, Cordula; Bisoffi, Giulia; Geroin, Christian; Munari, Daniele

2011-02-01

The aim of this study was to evaluate the effectiveness of repetitive locomotor training with an electromechanical gait trainer in children with cerebral palsy. In this randomized controlled trial, 18 ambulatory children with diplegic or tetraplegic cerebral palsy were randomly assigned to an experimental group or a control group. The experimental group received 30 mins of repetitive locomotor training with an applied technology (Gait Trainer GT I) plus 10 mins of passive joint mobilization and stretching exercises. The control group received 40 mins of conventional physiotherapy. Each subject underwent a total of 10 treatment sessions over a 2-wk period. Performance on the 10-m walk test, 6-min walk test, WeeFIM scale, and gait analysis was evaluated by a blinded rater before and after treatment and at 1-mo follow-up. The experimental group showed significant posttreatment improvement on the 10-m walk test, 6-min walk test, hip kinematics, gait speed, and step length, all of which were maintained at the 1-mo follow-up assessment. No significant changes in performance parameters were observed in the control group. Repetitive locomotor training with an electromechanical gait trainer may improve gait velocity, endurance, spatiotemporal, and kinematic gait parameters in patients with cerebral palsy.

Effects of caffeine on locomotor activity in streptozotocin-induced diabetic rats

PubMed Central

Bădescu, SV; Tătaru, CP; Kobylinska, L; Georgescu, EL; Zahiu, DM; Zăgrean, AM; Zăgrean, L

2016-01-01

Diabetes mellitus modifies the expression of adenosine receptors in the brain. Caffeine acts as an antagonist of A1 and A2A adenosine receptors and was shown to have a dose-dependent biphasic effect on locomotion in mice. The present study investigated the link between diabetes and locomotor activity in an animal model of streptozotocin-induced diabetes, and the effects of a low-medium dose of caffeine in this relation. The locomotor activity was investigated by using Open Field Test at 6 weeks after diabetes induction and after 2 more weeks of chronic caffeine administration. Diabetes decreased locomotor activity (total distance moved and mobility time). Chronic caffeine exposure impaired the locomotor activity in control rats, but not in diabetic rats. Our data suggested that the medium doses of caffeine might block the A2A receptors, shown to have an increased density in the brain of diabetic rats, and improve or at least maintain the locomotor activity, offering a neuroprotective support in diabetic rats. Abbreviations: STZ = streptozotocin, OFT = Open Field Test PMID:27974933

Establishment of a novel experimental protocol for drug-induced seizure liability screening based on a locomotor activity assay in zebrafish.

PubMed

Koseki, Naoteru; Deguchi, Jiro; Yamashita, Akihito; Miyawaki, Izuru; Funabashi, Hitoshi

2014-08-01

As drug-induced seizures have severe impact on drug development, evaluating seizure induction potential of candidate drugs at the early stages of drug discovery is important. A novel assay system using zebrafish has attracted interest as a high throughput toxicological in vivo assay system, and we tried to establish an experimental method for drug-induced seizure liability on the basis of locomotor activity in zebrafish. We monitored locomotor activity at high-speed movement (> 20 mm/sec) for 60 min immediately after exposure, and assessed seizure liability potential in some drugs using locomotor activity. However this experimental procedure was not sufficient for predicting seizures because the potential of several drugs with demonstrated seizure potential in mammals was not detected. We, therefore, added other parameters for locomotor activity such as extending exposure time or conducting flashlight stimulation (10 Hz) which is a known seizure induction stimulus, and these additional parameters improved seizure potential detection in some drugs. The validation study using the improved methodology was used to assess 52 commercially available drugs, and the prediction rate was approximately 70%. The experimental protocol established in this present study is considered useful for seizure potential screening during early stages of drug discovery.

Study of behavioral parameters during learning of rats in an operant feeding task and evaluation of biochemical indexes after dietary consumption of the phytoecdysteroid extract.

PubMed

Murtazina, E P; Sidorova, Yu S; Zhuravlev, B V; Mazo, V K; Zorin, S N; Volodin, V V

2014-11-01

Experiments on rats were performed to study the process of operant feeding learning, locomotor activity, oxygen consumption, and concentrations of corticosterone, β-endorphin, and prostaglandin E in blood serum after dietary treatment with the phytoecdysteroid extract. Administration of phytoecdysteroids was followed by the improvement of learning and increase in oxygen consumption and locomotor activity. Locomotor activity and oxygen consumption in the majority of control rats and phytoecdysteroid-treated animals were shown to be interrelated with the total locomotor activity and goal-directed operant behavior, respectively. No significant differences were found in the concentration of hormones in blood serum from animals of the control and treatment groups.

A single exercise bout and locomotor learning after stroke: physiological, behavioural, and computational outcomes.

PubMed

Charalambous, Charalambos C; Alcantara, Carolina C; French, Margaret A; Li, Xin; Matt, Kathleen S; Kim, Hyosub E; Morton, Susanne M; Reisman, Darcy S

2018-05-15

Previous work demonstrated an effect of a single high-intensity exercise bout coupled with motor practice on the retention of a newly acquired skilled arm movement, in both neurologically intact and impaired adults. In the present study, using behavioural and computational analyses we demonstrated that a single exercise bout, regardless of its intensity and timing, did not increase the retention of a novel locomotor task after stroke. Considering both present and previous work, we postulate that the benefits of exercise effect may depend on the type of motor learning (e.g. skill learning, sensorimotor adaptation) and/or task (e.g. arm accuracy-tracking task, walking). Acute high-intensity exercise coupled with motor practice improves the retention of motor learning in neurologically intact adults. However, whether exercise could improve the retention of locomotor learning after stroke is still unknown. Here, we investigated the effect of exercise intensity and timing on the retention of a novel locomotor learning task (i.e. split-belt treadmill walking) after stroke. Thirty-seven people post stroke participated in two sessions, 24 h apart, and were allocated to active control (CON), treadmill walking (TMW), or total body exercise on a cycle ergometer (TBE). In session 1, all groups exercised for a short bout (∼5 min) at low (CON) or high (TMW and TBE) intensity and before (CON and TMW) or after (TBE) the locomotor learning task. In both sessions, the locomotor learning task was to walk on a split-belt treadmill in a 2:1 speed ratio (100% and 50% fast-comfortable walking speed) for 15 min. To test the effect of exercise on 24 h retention, we applied behavioural and computational analyses. Behavioural data showed that neither high-intensity group showed greater 24 h retention compared to CON, and computational data showed that 24 h retention was attributable to a slow learning process for sensorimotor adaptation. Our findings demonstrated that acute exercise coupled with a locomotor adaptation task, regardless of its intensity and timing, does not improve retention of the novel locomotor task after stroke. We postulate that exercise effects on motor learning may be context specific (e.g. type of motor learning and/or task) and interact with the presence of genetic variant (BDNF Val66Met). © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Developmental Deltamethrin Exposure Causes Persistent Changes in Dopaminergic Gene Expression, Neurochemistry, and Locomotor Activity in Zebrafish.

PubMed

Kung, Tiffany S; Richardson, Jason R; Cooper, Keith R; White, Lori A

2015-08-01

Pyrethroids are commonly used insecticides that are considered to pose little risk to human health. However, there is an increasing concern that children are more susceptible to the adverse effects of pesticides. We used the zebrafish model to test the hypothesis that developmental exposure to low doses of the pyrethroid deltamethrin results in persistent alterations in dopaminergic gene expression, neurochemistry, and locomotor activity. Zebrafish embryos were treated with deltamethrin (0.25-0.50 μg/l), at concentrations below the LOAEL, during the embryonic period [3-72 h postfertilization (hpf)], after which transferred to fresh water until the larval stage (2-weeks postfertilization). Deltamethrin exposure resulted in decreased transcript levels of the D1 dopamine (DA) receptor (drd1) and increased levels of tyrosine hydroxylase at 72 hpf. The reduction in drd1 transcripts persisted to the larval stage and was associated with decreased D2 dopamine receptor transcripts. Larval fish, exposed developmentally to deltamethrin, had increased levels of homovanillic acid, a DA metabolite. Since the DA system is involved in locomotor activity, we measured the swim activity of larval fish following a transition to darkness. Developmental exposure to deltamethrin significantly increased larval swim activity which was attenuated by concomitant knockdown of the DA transporter. Acute exposure to methylphenidate, a DA transporter inhibitor, increased swim activity in control larva, while reducing swim activity in larva developmentally exposed to deltamethrin. Developmental exposure to deltamethrin causes locomotor deficits in larval zebrafish, which is likely mediated by dopaminergic dysfunction. This highlights the need to understand the persistent effects of low-dose neurotoxicant exposure during development. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Developmental Deltamethrin Exposure Causes Persistent Changes in Dopaminergic Gene Expression, Neurochemistry, and Locomotor Activity in Zebrafish

PubMed Central

Kung, Tiffany S.; Richardson, Jason R.; Cooper, Keith R.; White, Lori A.

2015-01-01

Pyrethroids are commonly used insecticides that are considered to pose little risk to human health. However, there is an increasing concern that children are more susceptible to the adverse effects of pesticides. We used the zebrafish model to test the hypothesis that developmental exposure to low doses of the pyrethroid deltamethrin results in persistent alterations in dopaminergic gene expression, neurochemistry, and locomotor activity. Zebrafish embryos were treated with deltamethrin (0.25–0.50 μg/l), at concentrations below the LOAEL, during the embryonic period [3–72 h postfertilization (hpf)], after which transferred to fresh water until the larval stage (2-weeks postfertilization). Deltamethrin exposure resulted in decreased transcript levels of the D1 dopamine (DA) receptor (drd1) and increased levels of tyrosine hydroxylase at 72 hpf. The reduction in drd1 transcripts persisted to the larval stage and was associated with decreased D2 dopamine receptor transcripts. Larval fish, exposed developmentally to deltamethrin, had increased levels of homovanillic acid, a DA metabolite. Since the DA system is involved in locomotor activity, we measured the swim activity of larval fish following a transition to darkness. Developmental exposure to deltamethrin significantly increased larval swim activity which was attenuated by concomitant knockdown of the DA transporter. Acute exposure to methylphenidate, a DA transporter inhibitor, increased swim activity in control larva, while reducing swim activity in larva developmentally exposed to deltamethrin. Developmental exposure to deltamethrin causes locomotor deficits in larval zebrafish, which is likely mediated by dopaminergic dysfunction. This highlights the need to understand the persistent effects of low-dose neurotoxicant exposure during development. PMID:25912032

Loss of NCB5OR in the cerebellum disturbs iron pathways, potentiates behavioral abnormalities, and exacerbates harmaline-induced tremor in mice.

PubMed

Stroh, Matthew A; Winter, Michelle K; Swerdlow, Russell H; McCarson, Kenneth E; Zhu, Hao

2016-08-01

Iron dyshomeostasis has been implicated in many diseases, including a number of neurological conditions. Cytosolic NADH cytochrome b5 oxidoreductase (NCB5OR) is ubiquitously expressed in animal tissues and is capable of reducing ferric iron in vitro. We previously reported that global gene ablation of NCB5OR resulted in early-onset diabetes and altered iron homeostasis in mice. To further investigate the specific effects of NCB5OR deficiency on neural tissue without contributions from known phenotypes, we generated a conditional knockout (CKO) mouse that lacks NCB5OR only in the cerebellum and midbrain. Assessment of molecular markers in the cerebellum of CKO mice revealed changes in pathways associated with cellular and mitochondrial iron homeostasis. (59)Fe pulse-feeding experiments revealed cerebellum-specific increased or decreased uptake of iron by 7 and 16 weeks of age, respectively. Additionally, we characterized behavioral changes associated with loss of NCB5OR in the cerebellum and midbrain in the context of dietary iron deprivation-evoked generalized iron deficiency. Locomotor activity was reduced and complex motor task execution was altered in CKO mice treated with an iron deficient diet. A sucrose preference test revealed that the reward response was intact in CKO mice, but that iron deficient diet consumption altered sucrose preference in all mice. Detailed gait analysis revealed locomotor changes in CKO mice associated with dysfunctional proprioception and locomotor activation independent of dietary iron deficiency. Finally, we demonstrate that loss of NCB5OR in the cerebellum and midbrain exacerbated harmaline-induced tremor activity. Our findings suggest an essential role for NCB5OR in maintaining both iron homeostasis and the proper functioning of various locomotor pathways in the mouse cerebellum and midbrain.

Effects of chronic prenatal MK-801 treatment on object recognition, cognitive flexibility, and drug-induced locomotor activity in juvenile and adult rat offspring.

PubMed

Gallant, S; Welch, L; Martone, P; Shalev, U

2017-06-15

Patients with schizophrenia display impaired cognitive functioning and increased sensitivity to psychomimetic drugs. The neurodevelopmental hypothesis of schizophrenia posits that disruption of the developing brain predisposes neural networks to lasting structural and functional abnormalities resulting in the emergence of such symptoms in adulthood. Given the critical role of the glutamatergic system in early brain development, we investigated whether chronic prenatal exposure to the glutamate NMDA receptor antagonist, MK-801, induces schizophrenia-like behavioural and neurochemical changes in juvenile and adult rats. Pregnant Long-Evans rats were administered saline or MK-801 (0.1mg/kg; s.c.) at gestation day 7-19. Object recognition memory and cognitive flexibility were assessed in the male offspring using a novel object preference task and a maze-based set-shifting procedure, respectively. Locomotor-activating effects of acute amphetamine and MK-801 were also assessed. Adult, but not juvenile, prenatally MK-801-treated rats failed to show novel object preference after a 90min delay, suggesting that object recognition memory may have been impaired. In addition, the set-shifting task revealed impaired acquisition of a new rule in adult prenatally MK-801-treated rats compared to controls. This deficit appeared to be driven by regression to the previously learned behaviour. There were no significant differences in drug-induced locomotor activity in juvenile offspring or in adult offspring following acute amphetamine challenges. Unexpectedly, MK-801-induced locomotor activity in adult prenatally MK-801-treated rats was lower compared to controls. Glutamate transmission dysfunction during early development may modify behavioural parameters in adulthood, though these parameters do not appear to model deficits observed in schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

Loss of NCB5OR in the cerebellum disturbs iron pathways, potentiates behavioral abnormalities, and exacerbates harmaline-induced tremor in mice

PubMed Central

Stroh, Matthew A.; Winter, Michelle K.; Swerdlow, Russell H.; McCarson, Kenneth E.; Zhu, Hao

2018-01-01

Iron dyshomeostasis has been implicated in many diseases, including a number of neurological conditions. Cytosolic NADH cytochrome b5 oxidoreductase (NCB5OR) is ubiquitously expressed in animal tissues and is capable of reducing ferric iron in vitro. We previously reported that global gene ablation of NCB5OR resulted in early-onset diabetes and altered iron homeostasis in mice. To further investigate the specific effects of NCB5OR deficiency on neural tissue without contributions from known phenotypes, we generated a conditional knockout (CKO) mouse that lacks NCB5OR only in the cerebellum and midbrain. Assessment of molecular markers in the cerebellum of CKO mice revealed changes in pathways associated with cellular and mitochondrial iron homeostasis. 59Fe pulse-feeding experiments revealed cerebellum-specific increased or decreased uptake of iron by 7 weeks and 16 weeks of age, respectively. Additionally, we characterized behavioral changes associated with loss of NCB5OR in the cerebellum and midbrain in the context of dietary iron deprivation-evoked generalized iron deficiency. Locomotor activity was reduced and complex motor task execution was altered in CKO mice treated with an iron deficient diet. A sucrose preference test revealed that the reward response was intact in CKO mice, but that iron deficient diet consumption altered sucrose preference in all mice. Detailed gait analysis revealed locomotor changes in CKO mice associated with dysfunctional proprioception and locomotor activation independent of dietary iron deficiency. Finally, we demonstrate that loss of NCB5OR in the cerebellum and midbrain exacerbated harmaline-induced tremor activity. Our findings suggest an essential role for NCB5OR in maintaining both iron homeostasis and the proper functioning of various locomotor pathways in the mouse cerebellum and midbrain. PMID:27188291

Locomotor training and virtual reality-based balance training for an individual with multiple sclerosis: a case report.

PubMed

Fulk, George D

2005-03-01

Impaired walking ability, balance, and fatigue are common problems for people with multiple sclerosis (MS). The purpose of this case report is to describe the use of plan of care that included locomotor training using both a body weight support (BWS) with a treadmill (TM) and overground walking as well as a virtual reality (VR)-based balance intervention to improve walking ability, balance, and endurance for an individual with MS. The client was a 48-year-old female with a 10-year history of MS. Her main goals were to improve walking ability, balance, and endurance. She presented with impaired gait, balance, motor function, and increased fatigue. Locomotor training using a BWS/TM system and overground and VR-based balance interventions were implemented 2 days a week for 12 weeks. The client demonstrated improvements in gait speed, gait endurance, and balance postintervention and maintained the improvements at a 2-month follow up. This case report is the first to report on the use of locomotor training with BWS/TM system and overground and VR-based balance interventions for a client with MS. The plan of care was formulated based on the patient's goals and the available literature on the use of the interventions with other patients with neurologic conditions to provide an intervention that was task-oriented, skilled, and intensive.

Electromechanical gait training with functional electrical stimulation: case studies in spinal cord injury.

PubMed

Hesse, S; Werner, C; Bardeleben, A

2004-06-01

Single case studies. To describe the technique of intensive locomotor training on an electromechanical gait trainer (GT) combined with functional electrical stimulation (FES). Neurological Rehabilitation Clinic, Berlin, Germany. Four spinal cord-injured (SCI) patients, one tetraparetic, two paraparetic, and one patient with an incomplete cauda syndrome, more than 3 months postinjury, who were unable to walk at all, or with two therapists. They received 25 min of locomotor training on the GT plus FES daily for 5 weeks in addition to the regular therapy. The patients tolerated the programme well, and therapists rated the programme less strenuous compared to manually assisted treadmill training. Gait ability improved in all four patients; three patients could walk independently on the floor with the help of technical aids, and one required the help of one therapist after therapy; gait speed and endurance more than doubled, and the gastrocnemius activity increased in the patients with a central paresis. This combined technique allows intensive locomotor therapy in SCI subjects with reduced effort from the therapists. The patients' improved walking ability confirmed the potential of locomotor therapy in SCI subjects.

Early application of tail nerve electrical stimulation-induced walking training promotes locomotor recovery in rats with spinal cord injury.

PubMed

Zhang, S-X; Huang, F; Gates, M; Shen, X; Holmberg, E G

2016-11-01

This is a randomized controlled prospective trial with two parallel groups. The objective of this study was to determine whether early application of tail nerve electrical stimulation (TANES)-induced walking training can improve the locomotor function. This study was conducted in SCS Research Center in Colorado, USA. A contusion injury to spinal cord T10 was produced using the New York University impactor device with a 25 -mm height setting in female, adult Long-Evans rats. Injured rats were randomly divided into two groups (n=12 per group). One group was subjected to TANES-induced walking training 2 weeks post injury, and the other group, as control, received no TANES-induced walking training. Restorations of behavior and conduction were assessed using the Basso, Beattie and Bresnahan open-field rating scale, horizontal ladder rung walking test and electrophysiological test (Hoffmann reflex). Early application of TANES-induced walking training significantly improved the recovery of locomotor function and benefited the restoration of Hoffmann reflex. TANES-induced walking training is a useful method to promote locomotor recovery in rats with spinal cord injury.

Schwann Cells Transplantation Improves Locomotor Recovery in Rat Models with Spinal Cord Injury: a Systematic Review and Meta-Analysis.

PubMed

Yang, Lei; Ge, Yingbin; Tang, Jian; Yuan, Jinxia; Ge, Dawei; Chen, Hongtao; Zhang, Hongxiu; Cao, Xiaojian

2015-01-01

Schwann cells (SCs) which were demonstrated to be responsible for axonal myelination and ensheathing are widely studied and commonly used for cell transplantation to treat spinal cord injury (SCI). We performed this meta-analysis to summarize the effects of SCs versus controls for locomotor recovery in rat models of traumatic SCI. Studies of the BBB scores after transplantation of SCs were searched out from Pubmed, Cochrane Library Medline databases and analyzed by Review Manager 5.2.5. Thirteen randomized controlled animal trials were selected with 283 rats enrolled. The studies were divided to different subgroups by different models of SCI, different cell doses for transplantation, different sources of SCs and different transplantation ways. The pooled results of this meta-analysis suggested that SCs transplantation cannot significantly improve the locomotor recovery at a short time after intervention (1 week after transplantation) in both impacted and hemi-sected SCI models. However, at a longer time after intervention (3, 5-7 and over 8 weeks after transplantation), significant improvement of BBB score emerged in SCs groups compared with control groups. Subgroup analyses revealed that SCs transplantation can significantly promote locomotor recovery regardless of in high or low doses of cells, from different sources (isolated from sciatic nerves or differentiated from bone marrow stromal cells(BMSCs)) and with or without scaffolding. SCs seem to demonstrate substantial beneficial effects on locomotor recovery in a widely-used animal models of SCI. © 2015 The Author(s) Published by S. Karger AG, Basel.

Effects of optokinetic stimulation induced by virtual reality on locomotion: a preliminary study.

PubMed

Ohyama, Seizo; Nishiike, Suetaka; Watanabe, Hiroshi; Matsuoka, Katsunori; Takeda, Noriaki

2008-11-01

Exposure to a virtual environment for 20 min was sufficient to cause adaptive changes in locomotion in healthy subjects, suggesting that virtual environments might improve locomotor deviation in patients with unilateral labyrinthine defects. Postural and locomotor control in patients with unilateral labyrinthine defects deviates towards the lesion side. The aim of this study was to examine whether active locomotion within a virtual environment can increase the functionality of rehabilitation. We examined the effects of optokinetic stimulation produced by a virtual reality environment on ocular movement and locomotor tracks in 10 healthy subjects. During the 20 min experiment, the mean locomotor deviation and the mean frequency and mean amplitude of optokinetic nystagmus during the last period of the experiment were significantly higher than those during the initial period.

Effect and reporting bias of RhoA/ROCK-blockade intervention on locomotor recovery after spinal cord injury: a systematic review and meta-analysis.

PubMed

Watzlawick, Ralf; Sena, Emily S; Dirnagl, Ulrich; Brommer, Benedikt; Kopp, Marcel A; Macleod, Malcolm R; Howells, David W; Schwab, Jan M

2014-01-01

Blockade of small GTPase-RhoA signaling pathway is considered a candidate translational strategy to improve functional outcome after spinal cord injury (SCI) in humans. Pooling preclinical evidence by orthodox meta-analysis is confounded by missing data (publication bias). To conduct a systematic review and meta-analysis of RhoA/Rho-associated coiled-coil containing protein kinase (ROCK) blocking approaches to (1) analyze the impact of bias that may lead to inflated effect sizes and (2) determine the normalized effect size of functional locomotor recovery after experimental thoracic SCI. We conducted a systematic search of PubMed, EMBASE, and Web of Science and hand searched related references. Studies were selected if they reported the effect of RhoA/ROCK inhibitors (C3-exoenzmye, fasudil, Y-27632, ibuprofen, siRhoA, and p21) in experimental spinal cord hemisection, contusion, or transection on locomotor recovery measured by the Basso, Beattie, and Bresnahan score or the Basso Mouse Scale for Locomotion. Two investigators independently assessed the identified studies. Details of individual study characteristics from each publication were extracted and effect sizes pooled using a random effects model. We assessed risk for bias using a 9-point-item quality checklist and calculated publication bias with Egger regression and the trim and fill method. A stratified meta-analysis was used to assess the impact of study characteristics on locomotor recovery. Thirty studies (725 animals) were identified. RhoA/ROCK inhibition was found to improve locomotor outcome by 21% (95% CI, 16.0-26.6). Assessment of publication bias by the trim and fill method suggested that 30% of experiments remain unpublished. Inclusion of these theoretical missing studies suggested a 27% overestimation of efficacy, reducing the overall efficacy to a 15% improvement in locomotor recovery. Low study quality was associated with larger estimates of neurobehavioral outcome. Taking into account publication bias, RhoA/ROCK inhibition improves functional outcome in experimental SCI by 15%. This is a plausible strategy for the pharmacological augmentation of neurorehabilitation after human SCI. These findings support the necessity of a systematic analysis to identify preclinical bias before embarking on a clinical trial.

NeuroRecovery Network provides standardization of locomotor training for persons with incomplete spinal cord injury.

PubMed

Morrison, Sarah A; Forrest, Gail F; VanHiel, Leslie R; Davé, Michele; D'Urso, Denise

2012-09-01

To illustrate the continuity of care afforded by a standardized locomotor training program across a multisite network setting within the Christopher and Dana Reeve Foundation NeuroRecovery Network (NRN). Single patient case study. Two geographically different hospital-based outpatient facilities. This case highlights a 25-year-old man diagnosed with C4 motor incomplete spinal cord injury with American Spinal Injury Association Impairment Scale grade D. Standardized locomotor training program 5 sessions per week for 1.5 hours per session, for a total of 100 treatment sessions, with 40 sessions at 1 center and 60 at another. Ten-meter walk test and 6-minute walk test were assessed at admission and discharge across both facilities. For each of the 100 treatment sessions percent body weight support, average, and maximum treadmill speed were evaluated. Locomotor endurance, as measured by the 6-minute walk test, and overground gait speed showed consistent improvement from admission to discharge. Throughout training, the patient decreased the need for body weight support and was able to tolerate faster treadmill speeds. Data indicate that the patient continued to improve on both treatment parameters and walking function. Standardization across the NRN centers provided a mechanism for delivering consistent and reproducible locomotor training programs across 2 facilities without disrupting training or recovery progression. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

[Differential diagnosis of polyarthritis pain syndrome of the locomotor apparatus].

PubMed

Menninger, H

1998-02-28

Widespread pain syndromes of the musculoskeletal system present to general practitioners, internists, neurologists and orthopedic surgeons every day. The syndromes may result both from organic diseases (inflammatory joint diseases, rheumatic manifestations of organ diseases) as well as dysfunctional syndromes, the latter including mainly biomechanically induced syndromes and fibromyalgia. The approach is predominantly clinically oriented and requires laboratory means or technical procedures only in a limited extend. The duration of history, the recognition of synovitis and of myofascial trigger points or of integumental tender points allow in most patients to achieve appropriate diagnostic criteria.

[Complex stimulation of the locomotor and psycholingual develop- ment of children with perinatal lesions of the central nervous system].

PubMed

Skvortsov, I A; Khavkhun, L A; Ustinova, E V; I'lin, L B

1989-01-01

In 121 children with perinatal CNS damage a combined therapy was performed including, besides routine drug treatment, imitation stimulation of age-matched posture-++-tonic attitudes and motor skills, metameric reflexotherapy aimed at the CNS region lesioned, magnetotherapy, electric laser puncture targeted at correction of dysfunctioning brain structures. Treatment efficiency was controlled by the brain "development profile" derived from formalized neurological and neuropsychological investigations, and electroneuromyography. The efficiency of the therapy was considerably decreased by the 3rd semester of life.

Kynurenine 3-monooxygenase is implicated in antidepressants-responsive depressive-like behaviors and monoaminergic dysfunctions.

PubMed

Tashiro, Tomoyuki; Murakami, Yuki; Mouri, Akihiro; Imamura, Yukio; Nabeshima, Toshitaka; Yamamoto, Yasuko; Saito, Kuniaki

2017-01-15

l-Tryptophan (TRP) is metabolized via serotonin and kynurenine pathways (KP). Several studies have demonstrated that abnormality of both pathways is involved in the pathogenesis of major depressive disorder (MDD). Kynurenine 3-monooxygenase (KMO), a pivotal enzyme in the KP, has been suggested to play major roles in physiological and pathological events mediated by bioactive kynurenine metabolites. In this study, we investigated the role of KMO in the emotional and cognitive functions by using KMO knockout (KO) mice. We measured contents of TRP and monoamines and their metabolites in the serum and hippocampus of KMO KO mice. Further, we investigated whether antidepressants improved the depressive-like behaviors in KMO KO mice. KMO KO mice showed depressive-like behaviors such as decreased sucrose preference and increased immobility in the forced swimming test and high anxiety by decreased time spent in the center area of open field. But, there was no difference in spontaneous alternation in Y-maze test, counts of rearing or locomotor activity. Higher contents of TRP metabolites such as kynurenine (KYN), kynurenic acid (KA), anthranilic acid (AA), and 3-hydroxykynurenine (3-HK) in the serum and hippocampus and decreased serotonin turnover and higher content of normetanephrine (NM) in the hippocampus were observed in the KMO KO mice. Although both antidepressant attenuated increase of immobility, sertraline but not imipramine improved decrease of sucrose preference in the KMO KO mice. These findings suggested that KMO KO mice show antidepressants-responsive depressive-like behaviors and monoaminergic dysfunctions via abnormality of kynurenine metabolism with good validities as MDD model. Copyright © 2016 Elsevier B.V. All rights reserved.

Novel multi-system functional gains via task specific training in spinal cord injured male rats.

PubMed

Ward, Patricia J; Herrity, April N; Smith, Rebecca R; Willhite, Andrea; Harrison, Benjamin J; Petruska, Jeffrey C; Harkema, Susan J; Hubscher, Charles H

2014-05-01

Locomotor training (LT) after spinal cord injury (SCI) is a rehabilitative therapy used to enhance locomotor recovery. There is evidence, primarily anecdotal, also associating LT with improvements in bladder function and reduction in some types of SCI-related pain. In the present study, we determined if a step training paradigm could improve outcome measures of locomotion, bladder function, and pain/allodynia. After a T10 contusive SCI trained animals (adult male Wistar rats), trained animals began quadrupedal step training beginning 2 weeks post-SCI for 1 h/day. End of study experiments (3 months of training) revealed significant changes in limb kinematics, gait, and hindlimb flexor-extensor bursting patterns relative to non-trained controls. Importantly, micturition function, evaluated with terminal transvesical cystometry, was significantly improved in the step trained group (increased voiding efficiency, intercontraction interval, and contraction amplitude). Because both SCI and LT affect neurotrophin signaling, and neurotrophins are involved with post-SCI plasticity in micturition pathways, we measured bladder neurotrophin mRNA. Training regulated the expression of nerve growth factor (NGF) but not BDNF or NT3. Bladder NGF mRNA levels were inversely related to bladder function in the trained group. Monitoring of overground locomotion and neuropathic pain throughout the study revealed significant improvements, beginning after 3 weeks of training, which in both cases remained consistent for the study duration. These novel findings, improving non-locomotor in addition to locomotor functions, demonstrate that step training post-SCI could contribute to multiple quality of life gains, targeting patient-centered high priority deficits.

Tamoxifen and estradiol improved locomotor function and increased spared tissue in rats after spinal cord injury: their antioxidant effect and role of estrogen receptor alpha.

PubMed

Mosquera, Laurivette; Colón, Jennifer M; Santiago, José M; Torrado, Aranza I; Meléndez, Margarita; Segarra, Annabell C; Rodríguez-Orengo, José F; Miranda, Jorge D

2014-05-02

17β-Estradiol is a multi-active steroid that imparts neuroprotection via diverse mechanisms of action. However, its role as a neuroprotective agent after spinal cord injury (SCI), or the involvement of the estrogen receptor-alpha (ER-α) in locomotor recovery, is still a subject of much debate. In this study, we evaluated the effects of estradiol and of Tamoxifen (an estrogen receptor mixed agonist/antagonist) on locomotor recovery following SCI. To control estradiol cyclical variability, ovariectomized female rats received empty or estradiol filled implants, prior to a moderate contusion to the spinal cord. Estradiol improved locomotor function at 7, 14, 21, and 28 days post injury (DPI), when compared to control groups (measured with the BBB open field test). This effect was ER-α mediated, because functional recovery was blocked with an ER-α antagonist. We also observed that ER-α was up-regulated after SCI. Long-term treatment (28 DPI) with estradiol and Tamoxifen reduced the extent of the lesion cavity, an effect also mediated by ER-α. The antioxidant effects of estradiol were seen acutely at 2 DPI but not at 28 DPI, and this acute effect was not receptor mediated. Rats treated with Tamoxifen recovered some locomotor activity at 21 and 28 DPI, which could be related to the antioxidant protection seen at these time points. These results show that estradiol improves functional outcome, and these protective effects are mediated by the ER-α dependent and independent-mechanisms. Tamoxifen׳s effects during late stages of SCI support the use of this drug as a long-term alternative treatment for this condition. Copyright © 2014 Elsevier B.V. All rights reserved.

Grafting of fetal brainstem 5-HT neurons into the sublesional spinal cord of paraplegic rats restores coordinated hindlimb locomotion.

PubMed

Sławińska, Urszula; Miazga, Krzysztof; Cabaj, Anna M; Leszczyńska, Anna N; Majczyński, Henryk; Nagy, James I; Jordan, Larry M

2013-09-01

In rodent models of spinal cord injury, there is increasing evidence that activation of the locomotor central pattern generator (CPG) below the site of injury with 5-hydroxytryptamine (5-HT) agonists improves locomotor recovery and restores coordination. A promising means of replacing 5-HT control of locomotion is to graft brainstem 5-HT neurons into the spinal cord below the level of the spinal cord injury. However, it is not known whether this approach improves limb coordination because recovery of coordinated stepping has not been documented in detail in previous studies employing this transplantation strategy. Here, adult rats with complete spinal cord transections at the T9/10 level were grafted with E14 fetal neurons from the medulla at the T10/11 vertebra level one month after injury. The B1, B2 and B3 fetal anlagen of brainstem 5-HT neurons, a grouping that included the presumed precursors of recently described 5-HT locomotor command neurons, were used in these grafts. EMG and video recordings of treadmill locomotion evoked by tail stimulation showed full recovery of inter- and intralimb coordination in the grafted rats. We showed, using systemically applied antagonists, that 5-HT₂ and 5-HT₇ receptors mediate the improved locomotion after grafting, but through actions on different populations of spinal locomotor neurons. Specifically, 5-HT₂ receptors control CPG activation as well as motoneuron output, while 5-HT₇ receptors contribute primarily to activity of the locomotor CPG. These results are consistent with the roles for these receptors during locomotion in intact rodents and in rodent brainstem-spinal cord in vitro preparations. Copyright © 2013 Elsevier Inc. All rights reserved.

Locomotor Dysfunction after Spaceflight: Characterization and Countermeasure Development

NASA Technical Reports Server (NTRS)

Mulavara, A. P.; Cohen, H. S.; Peters, B. T.; Miller, C. A.; Brady, R.; Bloomberg, Jacob J.

2007-01-01

Astronauts returning from space flight show disturbances in locomotor control manifested by changes in various sub-systems including head-trunk coordination, dynamic visual acuity, lower limb muscle activation patterning and kinematics (Glasauer, et al., 1995; Bloomberg, et al., 1997; McDonald, et al., 1996; 1997; Layne, et al., 1997; 1998, 2001, 2004; Newman, et al., 1997; Bloomberg and Mulavara, 2003). These post flight changes in locomotor performance, due to neural adaptation to the microgravity conditions of space flight, affect the ability of crewmembers especially after a long duration mission to egress their vehicle and perform extravehicular activities soon after landing on Earth or following a landing on the surface of the Moon or Mars. At present, no operational training intervention is available pre- or in- flight to mitigate post flight locomotor disturbances. Our laboratory is currently developing a gait adaptability training program that is designed to facilitate recovery of locomotor function following a return to a gravitational environment. The training program exploits the ability of the sensorimotor system to generalize from exposure to multiple adaptive challenges during training so that the gait control system essentially "learns to learn" and therefore can reorganize more rapidly when faced with a novel adaptive challenge. Ultimately, the functional goal of an adaptive generalization countermeasure is not necessarily to immediately return movement patterns back to "normal". Rather the training regimen should facilitate the reorganization of available sensorimotor sub-systems to achieve safe and effective locomotion as soon as possible after space flight. We have previously confirmed that subjects participating in adaptive generalization training programs, using a variety of visuomotor distortions and different motor tasks from throwing to negotiating an obstacle course as the dependent measure, can learn to enhance their ability to adapt to a novel sensorimotor environment (Roller et al., 2001; Cohen et al. 2005). Importantly, this increased adaptability is retained even one month after completion of the training period. Our laboratory is currently developing adaptive generalization training procedures and the associated flight hardware to implement such a training program, using variations of visual flow, subject loading, and treadmill speed; during regular in-flight treadmill operations.

Astrocyte atrophy and immune dysfunction in self-harming macaques.

PubMed

Lee, Kim M; Chiu, Kevin B; Sansing, Hope A; Inglis, Fiona M; Baker, Kate C; MacLean, Andrew G

2013-01-01

Self-injurious behavior (SIB) is a complex condition that exhibits a spectrum of abnormal neuropsychological and locomotor behaviors. Mechanisms for neuropathogenesis could include irregular immune activation, host soluble factors, and astrocyte dysfunction. We examined the role of astrocytes as modulators of immune function in macaques with SIB. We measured changes in astrocyte morphology and function. Paraffin sections of frontal cortices from rhesus macaques identified with SIB were stained for glial fibrillary acidic protein (GFAP) and Toll-like receptor 2 (TLR2). Morphologic features of astrocytes were determined using computer-assisted camera lucida. There was atrophy of white matter astrocyte cell bodies, decreased arbor length in both white and gray matter astrocytes, and decreased bifurcations and tips on astrocytes in animals with SIB. This was combined with a five-fold increase in the proportion of astrocytes immunopositive for TLR2. These results provide direct evidence that SIB induces immune activation of astrocytes concomitant with quantifiably different morphology.

Locomotor Dysfunction after Long-Duration Space Flight and Development of Countermeasures to Facilitate Faster Recovery

NASA Technical Reports Server (NTRS)

Mulavara, A. P.; Wood, S. J.; Cohen, H. S.; Bloomberg, J. J.

2012-01-01

Exposure to the microgravity conditions of space flight induces adaptive modification in sensorimotor function allowing astronauts to operate in this unique environment. This adaptive state, however, is inappropriate for a 1-g environment. Consequently astronauts must spend time readapting to Earth s gravity following their return to Earth. During this readaptation period, alterations in sensorimotor function cause various disturbances in astronaut gait during postflight walking. They often rely more on vision for postural and gait stability and many report the need for greater cognitive supervision of motor actions that previous to space flight were fully automated. Over the last several years our laboratory has investigated postflight astronaut locomotion with the aim of better understanding how adaptive changes in underlying sensorimotor mechanisms contribute to postflight gait dysfunction. Exposure to the microgravity conditions of space flight induces adaptive modification in the control of vestibularly-mediated reflexive head movement during locomotion after space flight. Furthermore, during motor learning, adaptive transitions are composed of two main mechanisms: strategic and plastic. Strategic mechanisms represent immediate and transitory modifications in control to deal with changes in the prevailing environment that, if prolonged, induce plastic mechanisms designed to automate new behavioral responses. The goal of the present study was to examine the contributions of sensorimotor subsystems such as the vestibular and body load sensing (BLS) somatosensory influences on head movement control during locomotion after long-duration space flight. Further we present data on the two motor learning processes during readaptation of locomotor function after long-duration space flight.

S-phenylpiracetam, a selective DAT inhibitor, reduces body weight gain without influencing locomotor activity.

PubMed

Zvejniece, Liga; Svalbe, Baiba; Vavers, Edijs; Makrecka-Kuka, Marina; Makarova, Elina; Liepins, Vilnis; Kalvinsh, Ivars; Liepinsh, Edgars; Dambrova, Maija

2017-09-01

S-phenylpiracetam is an optical isomer of phenotropil, which is a clinically used nootropic drug that improves physical condition and cognition. Recently, it was shown that S-phenylpiracetam is a selective dopamine transporter (DAT) inhibitor that does not influence norepinephrine (NE) or serotonin (5-HT) receptors. The aim of the present study was to study the effects of S-phenylpiracetam treatment on body weight gain, blood glucose and leptin levels, and locomotor activity. Western diet (WD)-fed mice and obese Zucker rats were treated daily with peroral administration of S-phenylpiracetam for 8 and 12weeks, respectively. Weight gain and plasma metabolites reflecting glucose metabolism were measured. Locomotor activity was detected in an open-field test. S-phenylpiracetam treatment significantly decreased body weight gain and fat mass increase in the obese Zucker rats and in the WD-fed mice. In addition, S-phenylpiracetam reduced the plasma glucose and leptin concentration and lowered hyperglycemia in a glucose tolerance test in both the mice and the rats. S-phenylpiracetam did not influence locomotor activity in the obese Zucker rats or in the WD-fed mice. The results demonstrate that S-phenylpiracetam reduces body weight gain and improves adaptation to hyperglycemia without stimulating locomotor activity. Our findings suggest that selective DAT inhibitors, such as S-phenylpiracetam, could be potentially useful for treating obesity in patients with metabolic syndrome with fewer adverse health consequences compared to other anorectic agents. Copyright © 2017. Published by Elsevier Inc.

Mutation of zebrafish dihydrolipoamide branched-chain transacylase E2 results in motor dysfunction and models maple syrup urine disease

PubMed Central

Friedrich, Timo; Lambert, Aaron M.; Masino, Mark A.; Downes, Gerald B.

2012-01-01

SUMMARY Analysis of zebrafish mutants that demonstrate abnormal locomotive behavior can elucidate the molecular requirements for neural network function and provide new models of human disease. Here, we show that zebrafish quetschkommode (que) mutant larvae exhibit a progressive locomotor defect that culminates in unusual nose-to-tail compressions and an inability to swim. Correspondingly, extracellular peripheral nerve recordings show that que mutants demonstrate abnormal locomotor output to the axial muscles used for swimming. Using positional cloning and candidate gene analysis, we reveal that a point mutation disrupts the gene encoding dihydrolipoamide branched-chain transacylase E2 (Dbt), a component of a mitochondrial enzyme complex, to generate the que phenotype. In humans, mutation of the DBT gene causes maple syrup urine disease (MSUD), a disorder of branched-chain amino acid metabolism that can result in mental retardation, severe dystonia, profound neurological damage and death. que mutants harbor abnormal amino acid levels, similar to MSUD patients and consistent with an error in branched-chain amino acid metabolism. que mutants also contain markedly reduced levels of the neurotransmitter glutamate within the brain and spinal cord, which probably contributes to their abnormal spinal cord locomotor output and aberrant motility behavior, a trait that probably represents severe dystonia in larval zebrafish. Taken together, these data illustrate how defects in branched-chain amino acid metabolism can disrupt nervous system development and/or function, and establish zebrafish que mutants as a model to better understand MSUD. PMID:22046030

A Toll-Like Receptor 9 Antagonist Improves Bladder Function and White Matter Sparing in Spinal Cord Injury

PubMed Central

David, Brian T.; Sampath, Sujitha; Dong, Wei; Heiman, Adee; Rella, Courtney E.; Elkabes, Stella

2014-01-01

Abstract Spinal cord injury (SCI) affects motor, sensory, and autonomic functions. As current therapies do not adequately alleviate functional deficits, the development of new and more effective approaches is of critical importance. Our earlier investigations indicated that intrathecal administration of a toll-like receptor 9 (TLR9) antagonist, cytidine-phosphate-guanosine oligodeoxynucleotide 2088 (CpG ODN 2088), to mice sustaining a severe, mid-thoracic contusion injury diminished neuropathic pain but did not alter locomotor deficits. These changes were paralleled by a decrease in the pro-inflammatory response at the injury epicenter. Using the same SCI paradigm and treatment regimen, the current studies investigated the effects of the TLR9 antagonist on bladder function. We report that the TLR9 antagonist decreases SCI-elicited urinary retention and ameliorates bladder morphopathology without affecting kidney function. A significant improvement in white matter sparing was also observed, most likely due to alterations in the inflammatory milieu. These findings indicate that the TLR9 antagonist has beneficial effects not only in reducing sensory deficits, but also on bladder dysfunction and tissue preservation. Thus, modulation of innate immune receptor signaling in the spinal cord can impact the effects of SCI. PMID:24936867

A toll-like receptor 9 antagonist improves bladder function and white matter sparing in spinal cord injury.

PubMed

David, Brian T; Sampath, Sujitha; Dong, Wei; Heiman, Adee; Rella, Courtney E; Elkabes, Stella; Heary, Robert F

2014-11-01

Spinal cord injury (SCI) affects motor, sensory, and autonomic functions. As current therapies do not adequately alleviate functional deficits, the development of new and more effective approaches is of critical importance. Our earlier investigations indicated that intrathecal administration of a toll-like receptor 9 (TLR9) antagonist, cytidine-phosphate-guanosine oligodeoxynucleotide 2088 (CpG ODN 2088), to mice sustaining a severe, mid-thoracic contusion injury diminished neuropathic pain but did not alter locomotor deficits. These changes were paralleled by a decrease in the pro-inflammatory response at the injury epicenter. Using the same SCI paradigm and treatment regimen, the current studies investigated the effects of the TLR9 antagonist on bladder function. We report that the TLR9 antagonist decreases SCI-elicited urinary retention and ameliorates bladder morphopathology without affecting kidney function. A significant improvement in white matter sparing was also observed, most likely due to alterations in the inflammatory milieu. These findings indicate that the TLR9 antagonist has beneficial effects not only in reducing sensory deficits, but also on bladder dysfunction and tissue preservation. Thus, modulation of innate immune receptor signaling in the spinal cord can impact the effects of SCI.

DEVELOPMENT OF AN INFLIGHT COUNTERMEASURE TO MITIGATE POSTFLIGHT GAIT DYSFUNCTION

NASA Technical Reports Server (NTRS)

Bloomberg, J. J.; Mulavara, A. P.; Cohen, H. S.; Richards, J. T.; Miller, C. A.

2005-01-01

Following spaceflight crewmembers experience gait and postural instabilities due to inflight adaptive alterations in sensorimotor function. These changes can pose a risk to crew safety if nominal or emergency vehicle egress is required immediately following long-duration spaceflight. At present, no operational countermeasure is available to mitigate postflight locomotor disturbances. Therefore, the goal of this study is to develop an inflight training regimen that facilitates the recovery of locomotor function after long-duration spaceflight. The countermeasure we are developing is based on the concept of variable practice. During this type of training the subject gains experience producing the appropriate adaptive motor behavior under a variety of sensory conditions and response constraints. This countermeasure is built around current ISS treadmill exercise activities. Crewmembers will conduct their nominal inflight treadmill exercise while being exposed to variations in visual flow patterns. These variations will challenge the postural and locomotor systems repeatedly, thereby promoting adaptive reorganization in locomotor behavior. As a result of this training a subject learns to solve a class of motor problems, rather than a specific motor solution to one problem, Le., the subject learns response generalizability or the ability to "learn to learn" under a variety of environmental constraints. We anticipate that this training will accelerate recovery of postural and locomotor function during readaptation to gravitational environments following spaceflight facilitating neural adaptation to unit (Earth) and partial (Mars) gravity after long-duration spaceflight. The study calls for one group of subjects to perform the inflight treadmill training regimen while a control group of subjects performs only the nominal exercise procedures. Locomotor function in both groups is assessed before and after spaceflight using two tests of gait function: The Integrated Treadmill Locomotion Test (ITLT) and the Functional Mobility Test (FMT). The ITLT characterizes alterations in the integrated function of multiple sensorimotor subsystems responsible for the control of locomotion. This test calls for subjects to walk on a motorized treadmill while we assess changes in dynamic postural stability, head-trunk coordination, short-latency head stabilization responses, dynamic visual acuity, lower limb coordination strategies and gait cycle timing. To make these assessments we measure the following parameters while subjects walk on the treadmill: 1) full body 3-dimensional kinematics using a motion capture system (Motion Analysis Corp., Santa Rosa, CA); 2) the shock-wave transmitted from heel-strike to the head using triaxial accelerometers placed on the tibia and head (Entran, Fairfield, NJ); 3) vertical forces using an instrumented treadmill (Kistler Instrument Corp., Amherst, NY); 4) Dynamic visual acuity using Landolt Cs presented on a laptop computer located 4m from the eyes and 5) Gait cycle timing using foot-switches (Motion Lab Systems, Inc., Baton Rouge, LA) attached to the plantar surface of each shoe at the heel and toe. The FMT evaluates a subject's ability to perform challenging locomotor maneuvers similar to those encountered during an egress from a space vehicle. Subjects step over and duck under obstacles along with negotiating a series of pylons set up on a base of 10 cm thick medium density foam. The dependent measures for the FMT are time to complete the course and the number of obstacles touched. To date, we have collected pre and postflight locomotion data from Expeditions 5-9 who will serve as part of the control group for this study. Preliminary results comparing the recovery rates in gait control sub-systems obtained from the ITLT and FMT performance showed two recovery patterns: 1) a concordant recovery trend between gait control parameters and FMT performance indicating a restitution pattern of recovery and 2) gait controecovery that lagged recovery in FMT performance suggesting that improvement in locomotor function was attained through a pattern of substitution. These data suggest that recovery of postflight locomotor function may occur through adaptive mechanisms that lead to either restitution or substitution of function. Understanding the modes of postflight readaptation has implications for countermeasure development and testing and in astronaut postflight rehabilitation.

Development of an Inflight Countermeasure to Mitigate Postflight Gait Dysfunction

NASA Technical Reports Server (NTRS)

Bloomberg, J. J.; Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Richards, J. T.; Miller, C. A.; Brady, R.; Warren, L. E.

2005-01-01

Following spaceflight crewmembers experience gait and postural instabilities due to inflight adaptive alterations in sensorimotor function. These changes can pose a risk to crew safety if nominal or emergency vehicle egress is required immediately following long-duration spaceflight. At present, no operational countermeasure is available to mitigate postflight locomotor disturbances. Therefore, the goal of this study is to develop an inflight training regimen that facilitates the recovery of locomotor function after long-duration spaceflight. The countermeasure we are developing is based on the concept of variable practice. During this type of training the subject gains experience producing the appropriate adaptive motor behavior under a variety of sensory conditions and response constraints. This countermeasure is built around current ISS treadmill exercise activities. Crewmembers will conduct their nominal inflight treadmill exercise while being exposed to variations in visual flow patterns. These variations will challenge the postural and locomotor systems repeatedly, thereby promoting adaptive reorganization in locomotor behavior. As a result of this training a subject learns to solve a class of motor problems, rather than a specific motor solution to one problem, Le., the subject learns response generalizability or the ability to "learn to learn" under a variety of environmental constraints. We anticipate that this training will accelerate recovery of postural and locomotor function during readaptation to gravitational environments following spaceflight facilitating neural adaptation to unit (Earth) and partial (Mars) gravity after long-duration spaceflight. The study calls for one group of subjects to perform the inflight treadmill training regimen while a control group of subjects performs only the nominal exercise procedures. Locomotor function in both groups is assessed before and after spaceflight using two tests of gait function: The Integrated Treadmill Locomotion Test (ITLT) and the Functional Mobility Test (FMT). The ITLT characterizes alterations in the integrated function of multiple sensorimotor subsystems responsible for the control of locomotion. This test calls for subjects to walk on a motorized treadmill while we assess changes in dynamic postural stability, head-trunk coordination, short-latency head stabilization responses, dynamic visual acuity, lower limb coordination strategies and gait cycle timing. To make these assessments we measure the following parameters while subjects walk on the treadmill: 1) full body 3-dimensional kinematics using a motion capture system (Motion Analysis Corp., Santa Rosa, CA); 2) the shock-wave transmitted from heel-strike to the head using triaxial accelerometers placed on the tibia and head (Entran, Fairfield, NJ); 3) vertical forces using an instumented treadmill (Kistler Instrument Corp., Amherst, NY); 4) Dynamic visual acuity using Landolt Cs presented on a laptop computer located 4m from the eyes and 5) Gait cycle timing using foot-switches (Motion Lab Systems, Inc., Baton Rouge, LA) attached to the plantar surface of each shoe at the heel and toe. The FMT evaluates s. subject's ability to perform challenging locomotor maneuvers similar to those encountered during an egress from a space vehicle. Subjects step over and duck under obstacles along with negotiating a series of pylons set up on a base of 10 cm thick medium density foam. The dependent measures for the FMT are time to complete the course and the number of obstacles touched. To date, we have collected pre and postflight locomotion data from Expeditions 5-9 who will serve as part of the control group for this study. Preliminary results comparing the recovery rates in gait control sub-systems obtained from the ITLT and FMT performance showed two recovery patterns: 1) a concordant recovery trend between gait control parameters and FMT performance indicating a restitution pattern of recovery and 2) gait controecovery that lagged recovery in FMT performance suggesting that improvement in locomotor function was attained through a pattern of substitution. These data suggest that recovery of postflight locomotor function may occur through adaptive mechanisms that lead to either restitution or substitution of function. Understanding the modes of postflight readaptation has implications for countermeasure development and testing and in astronaut postflight rehabilitation.

A stochastic locomotor control model for the nurse shark, Ginglymostoma cirratum.

PubMed

Gerald, K B; Matis, J H; Kleerekoper, H

1978-06-12

The locomotor behavior of the nurse shark (Ginglymostoma cirratum) is characterized by 17 variables (frequency and ratios of left, right, and total turns; their radians; straight paths (steps); distance travelled; and velocity) Within each of these variables there is an internal time dependency the structure of which was elaborated together with an improved statistical model predicting their behavior within 90% confidence limits. The model allows for the sensitive detection of subtle locomotor response to sensory stimulation as values of variables may exceed the established confidence limits within minutes after onset of the stimulus. The locomotor activity is well described by an autoregression time series model and can be predicted by only seven variables. Six of these form two independently operating clusters. The first one consists of: the number of right turns, the distance travelled and the mean velocity; the second one of: the mean size of right turns, of left turns, and of all turns. The same clustering is obtained independently by a cluster analysis of cross-sections of the seven time series. It is apparent that, among a total of 17 locomotor variables, seven behave as individually independent agents, presumably controlled by seven separate and independent centers. The output of each center can only be predicted by its own behavior. In spite of the individual of the seven variables, their internal structure is similar in important aspects which may result from control by a common command center. The shark locomotor model differs in important aspects from the previously constructed for the goldfish. The interdependence of the locomotor variables in both species may be related to the control mechanisms postulated by von Holst for the coordination of rhythmic fin movements in fishes. A locomotor control model for the nurse shark is proposed.

Neurochemical excitation of propriospinal neurons facilitates locomotor command signal transmission in the lesioned spinal cord.

PubMed

Zaporozhets, Eugene; Cowley, Kristine C; Schmidt, Brian J

2011-06-01

Previous studies of the in vitro neonatal rat brain stem-spinal cord showed that propriospinal relays contribute to descending transmission of a supraspinal command signal that is capable of activating locomotion. Using the same preparation, the present series examines whether enhanced excitation of thoracic propriospinal neurons facilitates propagation of the locomotor command signal in the lesioned spinal cord. First, we identified neurotransmitters contributing to normal endogenous propriospinal transmission of the locomotor command signal by testing the effect of receptor antagonists applied to cervicothoracic segments during brain stem-induced locomotor-like activity. Spinal cords were either intact or contained staggered bilateral hemisections located at right T1/T2 and left T10/T11 junctions designed to abolish direct long-projecting bulbospinal axons. Serotonergic, noradrenergic, dopaminergic, and glutamatergic, but not cholinergic, receptor antagonists blocked locomotor-like activity. Approximately 73% of preparations with staggered bilateral hemisections failed to generate locomotor-like activity in response to electrical stimulation of the brain stem alone; such preparations were used to test the effect of neuroactive substances applied to thoracic segments (bath barriers placed at T3 and T9) during brain stem stimulation. The percentage of preparations developing locomotor-like activity was as follows: 5-HT (43%), 5-HT/N-methyl-D-aspartate (NMDA; 33%), quipazine (42%), 8-hydroxy-2-(di-n-propylamino)tetralin (20%), methoxamine (45%), and elevated bath K(+) concentration (29%). Combined norepinephrine and dopamine increased the success rate (67%) compared with the use of either agent alone (4 and 7%, respectively). NMDA, Mg(2+) ion removal, clonidine, and acetylcholine were ineffective. The results provide proof of principle that artificial excitation of thoracic propriospinal neurons can improve supraspinal control over hindlimb locomotor networks in the lesioned spinal cord.

Administration of low dose estrogen attenuates persistent inflammation, promotes angiogenesis, and improves locomotor function following chronic spinal cord injury in rats.

PubMed

Samantaray, Supriti; Das, Arabinda; Matzelle, Denise C; Yu, Shan P; Wei, Ling; Varma, Abhay; Ray, Swapan K; Banik, Naren L

2016-05-01

Spinal cord injury (SCI) causes loss of neurological function and, depending upon the severity of injury, may lead to paralysis. Currently, no FDA-approved pharmacotherapy is available for SCI. High-dose methylprednisolone is widely used, but this treatment is controversial. We have previously shown that low doses of estrogen reduces inflammation, attenuates cell death, and protects axon and myelin in SCI rats, but its effectiveness in recovery of function is not known. Therefore, the goal of this study was to investigate whether low doses of estrogen in post-SCI would reduce inflammation, protect cells and axons, and improve locomotor function during the chronic phase of injury. Injury (40 g.cm force) was induced at thoracic 10 in young adult male rats. Rats were treated with 10 or 100 μg 17β-estradiol (estrogen) for 7 days following SCI and compared with vehicle-treated injury and laminectomy (sham) controls. Histology (H&E staining), immunohistofluorescence, Doppler laser technique, and Western blotting were used to monitor tissue integrity, gliosis, blood flow, angiogenesis, the expression of angiogenic factors, axonal degeneration, and locomotor function (Basso, Beattie, and Bresnahan rating) following injury. To assess the progression of recovery, rats were sacrificed at 7, 14, or 42 days post injury. A reduction in glial reactivity, attenuation of axonal and myelin damage, protection of cells, increased expression of angiogenic factors and microvessel growth, and improved locomotor function were found following estrogen treatment compared with vehicle-treated SCI rats. These results suggest that treatment with a very low dose of estrogen has significant therapeutic implications for the improvement of locomotor function in chronic SCI. Experimental studies with low dose estrogen therapy in chronic spinal cord injury (SCI) demonstrated the potential for multi-active beneficial outcomes that could ameliorate the degenerative pathways in chronic SCI as shown in (a). Furthermore, the alterations in local spinal blood flow could be significantly alleviated with low dose estrogen therapy. This therapy led to the preservation of the structural integrity of the spinal cord (b), which in turn led to the improved functional recovery as shown (c). © 2016 International Society for Neurochemistry.

Conditional Sox9 ablation improves locomotor recovery after spinal cord injury by increasing reactive sprouting.

PubMed

McKillop, William M; York, Elisa M; Rubinger, Luc; Liu, Tony; Ossowski, Natalie M; Xu, Kathy; Hryciw, Todd; Brown, Arthur

2016-09-01

The absence of axonal regeneration after spinal cord injury (SCI) has been attributed to the up-regulation of axon-repelling molecules, such as chondroitin sulfate proteoglycans (CSPGs) present in the glial scar that forms post-SCI. We previously identified the transcription factor SOX9 as a key up-regulator of CSPG production and also demonstrated that conditional Sox9 ablation leads to decreased CSPG levels and improved recovery of hind limb function after SCI. We herein demonstrate increased neural input onto spinal neurons caudal to the lesion in spinal cord injured Sox9 conditional knock out mice as indicated by increased levels of the presynaptic markers synaptophysin and vesicular glutamate transporter 1 (VGLUT1) compared to controls. Axonal sparing, long-range axonal regeneration and reactive sprouting were investigated as possible explanations for the increase in neural inputs caudal to the lesion and for the improved locomotor outcomes in spinal cord-injured Sox9 conditional knock out mice. Whereas retrograde tract-tracing studies failed to reveal any evidence for increased axonal sparing or for long-range regeneration in the Sox9 conditional knock out mice, anterograde tract-tracing experiments demonstrated increased reactive sprouting caudal to the lesion after SCI. Finally we demonstrate that application of a broad spectrum MMP inhibitor to reduce CSPG degradation in Sox9 conditional knock out mice prevents the improvements in locomotor recovery observed in untreated Sox9 conditional knock out mice. These results suggest that improved recovery of locomotor function in Sox9 conditional knock out mice after SCI is due to increased reactive sprouting secondary to reduced CSPG levels distal to the lesion. Copyright © 2016 Elsevier Inc. All rights reserved.

Locomotor training with body weight support in SCI: EMG improvement is more optimally expressed at a low testing speed.

PubMed

Meyns, P; Van de Crommert, H W A A; Rijken, H; van Kuppevelt, D H J M; Duysens, J

2014-12-01

Case series. To determine the optimal testing speed at which the recovery of the EMG (electromyographic) activity should be assessed during and after body weight supported (BWS) locomotor training. Tertiary hospital, Sint Maartenskliniek, Nijmegen, The Netherlands. Four participants with incomplete chronic SCI were included for BWS locomotor training; one AIS-C and three AIS-D (according to the ASIA (American Spinal Injury Association) Impairment Scale or AIS). All were at least 5 years after injury. The SCI participants were trained three times a week for a period of 6 weeks. They improved their locomotor function in terms of higher walking speed, less BWS and less assistance needed. To investigate which treadmill speed for EMG assessment reflects the functional improvement most adequately, all participants were assessed weekly using the same two speeds (0.5 and 1.5 km h(-1), referred to as low and high speed, respectively) for 6 weeks. The change in root mean square EMG (RMS EMG) was assessed in four leg muscles; biceps femoris, rectus femoris, gastrocnemius medialis and tibialis anterior. The changes in RMS EMG occurred at similar phases of the step cycle for both walking conditions, but these changes were larger when the treadmill was set at a low speed (0.5 km h(-1)). Improvement in gait is feasible with BWS treadmill training even long after injury. The EMG changes after treadmill training are more optimally expressed using a low rather than a high testing treadmill speed.

High Throughput Measurement of Locomotor Sensitization to Volatilized Cocaine in Drosophila melanogaster.

PubMed

Filošević, Ana; Al-Samarai, Sabina; Andretić Waldowski, Rozi

2018-01-01

Drosophila melanogaster can be used to identify genes with novel functional roles in neuronal plasticity induced by repeated consumption of addictive drugs. Behavioral sensitization is a relatively simple behavioral output of plastic changes that occur in the brain after repeated exposures to drugs of abuse. The development of screening procedures for genes that control behavioral sensitization has stalled due to a lack of high-throughput behavioral tests that can be used in genetically tractable organism, such as Drosophila . We have developed a new behavioral test, FlyBong, which combines delivery of volatilized cocaine (vCOC) to individually housed flies with objective quantification of their locomotor activity. There are two main advantages of FlyBong: it is high-throughput and it allows for comparisons of locomotor activity of individual flies before and after single or multiple exposures. At the population level, exposure to vCOC leads to transient and concentration-dependent increase in locomotor activity, representing sensitivity to an acute dose. A second exposure leads to further increase in locomotion, representing locomotor sensitization. We validate FlyBong by showing that locomotor sensitization at either the population or individual level is absent in the mutants for circadian genes period (per) , Clock (Clk) , and cycle (cyc) . The locomotor sensitization that is present in timeless (tim) and pigment dispersing factor (pdf) mutant flies is in large part not cocaine specific, but derived from increased sensitivity to warm air. Circadian genes are not only integral part of the neural mechanism that is required for development of locomotor sensitization, but in addition, they modulate the intensity of locomotor sensitization as a function of the time of day. Motor-activating effects of cocaine are sexually dimorphic and require a functional dopaminergic transporter. FlyBong is a new and improved method for inducing and measuring locomotor sensitization to cocaine in individual Drosophila . Because of its high-throughput nature, FlyBong can be used in genetic screens or in selection experiments aimed at the unbiased identification of functional genes involved in acute or chronic effects of volatilized psychoactive substances.

High Throughput Measurement of Locomotor Sensitization to Volatilized Cocaine in Drosophila melanogaster

PubMed Central

Filošević, Ana; Al-samarai, Sabina; Andretić Waldowski, Rozi

2018-01-01

Drosophila melanogaster can be used to identify genes with novel functional roles in neuronal plasticity induced by repeated consumption of addictive drugs. Behavioral sensitization is a relatively simple behavioral output of plastic changes that occur in the brain after repeated exposures to drugs of abuse. The development of screening procedures for genes that control behavioral sensitization has stalled due to a lack of high-throughput behavioral tests that can be used in genetically tractable organism, such as Drosophila. We have developed a new behavioral test, FlyBong, which combines delivery of volatilized cocaine (vCOC) to individually housed flies with objective quantification of their locomotor activity. There are two main advantages of FlyBong: it is high-throughput and it allows for comparisons of locomotor activity of individual flies before and after single or multiple exposures. At the population level, exposure to vCOC leads to transient and concentration-dependent increase in locomotor activity, representing sensitivity to an acute dose. A second exposure leads to further increase in locomotion, representing locomotor sensitization. We validate FlyBong by showing that locomotor sensitization at either the population or individual level is absent in the mutants for circadian genes period (per), Clock (Clk), and cycle (cyc). The locomotor sensitization that is present in timeless (tim) and pigment dispersing factor (pdf) mutant flies is in large part not cocaine specific, but derived from increased sensitivity to warm air. Circadian genes are not only integral part of the neural mechanism that is required for development of locomotor sensitization, but in addition, they modulate the intensity of locomotor sensitization as a function of the time of day. Motor-activating effects of cocaine are sexually dimorphic and require a functional dopaminergic transporter. FlyBong is a new and improved method for inducing and measuring locomotor sensitization to cocaine in individual Drosophila. Because of its high-throughput nature, FlyBong can be used in genetic screens or in selection experiments aimed at the unbiased identification of functional genes involved in acute or chronic effects of volatilized psychoactive substances. PMID:29459820

Locomotor function after long-duration space flight: effects and motor learning during recovery.

PubMed

Mulavara, Ajitkumar P; Feiveson, Alan H; Fiedler, James; Cohen, Helen; Peters, Brian T; Miller, Chris; Brady, Rachel; Bloomberg, Jacob J

2010-05-01

Astronauts returning from space flight and performing Earth-bound activities must rapidly transition from the microgravity-adapted sensorimotor state to that of Earth's gravity. The goal of the current study was to assess locomotor dysfunction and recovery of function after long-duration space flight using a test of functional mobility. Eighteen International Space Station crewmembers experiencing an average flight duration of 185 days performed the functional mobility test (FMT) pre-flight and post-flight. To perform the FMT, subjects walked at a self selected pace through an obstacle course consisting of several pylons and obstacles set up on a base of 10-cm-thick, medium-density foam for a total of six trials per test session. The primary outcome measure was the time to complete the course (TCC, in seconds). To assess the long-term recovery trend of locomotor function after return from space flight, a multilevel exponential recovery model was fitted to the log-transformed TCC data. All crewmembers exhibited altered locomotor function after space flight, with a median 48% increase in the TCC. From the fitted model we calculated that a typical subject would recover to 95% of his/her pre-flight level at approximately 15 days post-flight. In addition, to assess the early motor learning responses after returning from space flight, we modeled performance over the six trials during the first post-flight session by a similar multilevel exponential relation. We found a significant positive correlation between measures of long-term recovery and early motor learning (P < 0.001) obtained from the respective models. We concluded that two types of recovery processes influence an astronaut's ability to re-adapt to Earth's gravity environment. Early motor learning helps astronauts make rapid modifications in their motor control strategies during the first hours after landing. Further, this early motor learning appears to reinforce the adaptive realignment, facilitating re-adaptation to Earth's 1-g environment on return from space flight.

Post-stroke unilateral spatial neglect: virtual reality-based navigation and detection tasks reveal lateralized and non-lateralized deficits in tasks of varying perceptual and cognitive demands.

PubMed

Ogourtsova, Tatiana; Archambault, Philippe S; Lamontagne, Anouk

2018-04-23

Unilateral spatial neglect (USN), a highly prevalent and disabling post-stroke impairment, has been shown to affect the recovery of locomotor and navigation skills needed for community mobility. We recently found that USN alters goal-directed locomotion in conditions of different cognitive/perceptual demands. However, sensorimotor post-stroke dysfunction (e.g. decreased walking speed) could have influenced the results. Analogous to a previously used goal-directed locomotor paradigm, a seated, joystick-driven navigation experiment, minimizing locomotor demands, was employed in individuals with and without post-stroke USN (USN+ and USN-, respectively) and healthy controls (HC). Participants (n = 15 per group) performed a seated, joystick-driven navigation and detection time task to targets 7 m away at 0°, ±15°/30° in actual (visually-guided), remembered (memory-guided) and shifting (visually-guided with representational updating component) conditions while immersed in a 3D virtual reality environment. Greater end-point mediolateral errors to left-sided targets (remembered and shifting conditions) and overall lengthier onsets in reorientation strategy (shifting condition) were found for USN+ vs. USN- and vs. HC (p < 0.05). USN+ individuals mostly overshot left targets (- 15°/- 30°). Greater delays in detection time for target locations across the visual spectrum (left, middle and right) were found in USN+ vs. USN- and HC groups (p < 0.05). USN-related attentional-perceptual deficits alter navigation abilities in memory-guided and shifting conditions, independently of post-stroke locomotor deficits. Lateralized and non-lateralized deficits in object detection are found. The employed paradigm could be considered in the design and development of sensitive and functional assessment methods for neglect; thereby addressing the drawbacks of currently used traditional paper-and-pencil tools.

Locomotor adaptation is modulated by observing the actions of others

PubMed Central

Patel, Mitesh; Roberts, R. Edward; Riyaz, Mohammed U.; Ahmed, Maroof; Buckwell, David; Bunday, Karen; Ahmad, Hena; Kaski, Diego; Arshad, Qadeer

2015-01-01

Observing the motor actions of another person could facilitate compensatory motor behavior in the passive observer. Here we explored whether action observation alone can induce automatic locomotor adaptation in humans. To explore this possibility, we used the “broken escalator” paradigm. Conventionally this involves stepping upon a stationary sled after having previously experienced it actually moving (Moving trials). This history of motion produces a locomotor aftereffect when subsequently stepping onto a stationary sled. We found that viewing an actor perform the Moving trials was sufficient to generate a locomotor aftereffect in the observer, the size of which was significantly correlated with the size of the movement (postural sway) observed. Crucially, the effect is specific to watching the task being performed, as no motor adaptation occurs after simply viewing the sled move in isolation. These findings demonstrate that locomotor adaptation in humans can be driven purely by action observation, with the brain adapting motor plans in response to the size of the observed individual's motion. This mechanism may be mediated by a mirror neuron system that automatically adapts behavior to minimize movement errors and improve motor skills through social cues, although further neurophysiological studies are required to support this theory. These data suggest that merely observing the gait of another person in a challenging environment is sufficient to generate appropriate postural countermeasures, implying the existence of an automatic mechanism for adapting locomotor behavior. PMID:26156386

Slow Versus Fast Robot-Assisted Locomotor Training After Severe Stroke: A Randomized Controlled Trial.

PubMed

Rodrigues, Thais Amanda; Goroso, Daniel Gustavo; Westgate, Philip M; Carrico, Cheryl; Batistella, Linamara R; Sawaki, Lumy

2017-10-01

Robot-assisted locomotor training on a bodyweight-supported treadmill is a rehabilitation intervention that compels repetitive practice of gait movements. Standard treadmill speed may elicit rhythmic movements generated primarily by spinal circuits. Slower-than-standard treadmill speed may elicit discrete movements, which are more complex than rhythmic movements and involve cortical areas. Compare effects of fast (i.e., rhythmic) versus slow (i.e., discrete) robot-assisted locomotor training on a bodyweight-supported treadmill in subjects with chronic, severe gait deficit after stroke. Subjects (N = 18) were randomized to receive 30 sessions (5 d/wk) of either fast or slow robot-assisted locomotor training on a bodyweight-supported treadmill in an inpatient setting. Functional ambulation category, time up and go, 6-min walk test, 10-m walk test, Berg Balance Scale, and Fugl-Meyer Assessment were administered at baseline and postintervention. The slow group had statistically significant improvement on functional ambulation category (first quartile-third quartile, P = 0.004), 6-min walk test (95% confidence interval [CI] = 1.8 to 49.0, P = 0.040), Berg Balance Scale (95% CI = 7.4 to 14.8, P < 0.0001), time up and go (95% CI = -79.1 to 5.0, P < 0.0030), and Fugl-Meyer Assessment (95% CI = 24.1 to 45.1, P < 0.0001). The fast group had statistically significant improvement on Berg Balance Scale (95% CI = 1.5 to 10.5, P = 0.02). In initial stages of robot-assisted locomotor training on a bodyweight-supported treadmill after severe stroke, slow training targeting discrete movement may yield greater benefit than fast training.

Inducing hindlimb locomotor recovery in adult rat after complete thoracic spinal cord section using repeated treadmill training with perineal stimulation only

PubMed Central

Alluin, Olivier; Delivet-Mongrain, Hugo

2015-01-01

Although a complete thoracic spinal cord section in various mammals induces paralysis of voluntary movements, the spinal lumbosacral circuitry below the lesion retains its ability to generate hindlimb locomotion. This important capacity may contribute to the overall locomotor recovery after partial spinal cord injury (SCI). In rats, it is usually triggered by pharmacological and/or electrical stimulation of the cord while a robot sustains the animals in an upright posture. In the present study we daily trained a group of adult spinal (T7) rats to walk with the hindlimbs for 10 wk (10 min/day for 5 days/wk), using only perineal stimulation. Kinematic analysis and terminal electromyographic recordings revealed a strong effect of training on the reexpression of hindlimb locomotion. Indeed, trained animals gradually improved their locomotion while untrained animals worsened throughout the post-SCI period. Kinematic parameters such as averaged and instant swing phase velocity, step cycle variability, foot drag duration, off period duration, and relationship between the swing features returned to normal values only in trained animals. The present results clearly demonstrate that treadmill training alone, in a normal horizontal posture, elicited by noninvasive perineal stimulation is sufficient to induce a persistent hindlimb locomotor recovery without the need for more complex strategies. This provides a baseline level that should be clearly surpassed if additional locomotor-enabling procedures are added. Moreover, it has a clinical value since intrinsic spinal reorganization induced by training should contribute to improve locomotor recovery together with afferent feedback and supraspinal modifications in patients with incomplete SCI. PMID:26203108

Advancing Measurement of Locomotor Rehabilitation Outcomes to Optimize Interventions and Differentiate between Recovery versus Compensation

PubMed Central

Bowden, Mark G.; Behrman, Andrea L.; Woodbury, Michelle; Gregory, Chris M.; Velozo, Craig A.; Kautz, Steven A.

2017-01-01

Progress in locomotor rehabilitation has created an increasing need to understand the factors that contribute to motor behavior, to determine whether these factors are modifiable, and if so, to determine how best to modify them in a way that promotes improved function. Currently available measures do not have the capacity to distinguish between neuromotor recovery and compensation for impaired underlying body structure/functions. The purpose of this Special Interest article is to examine the state of outcomes measurement in physical therapy in regards outcomes to locomotor rehabilitation, and to suggest approaches that may improve assessment of recovery and clinical decision-making capabilities. We examine historical approaches to measurement of locomotor rehabilitation outcomes including rating scales, timed movement tasks, and laboratory-based outcome measures, and we discuss the emerging use of portable technology to assess walking in a free living environment. The ability to accurately measure outcomes of rehabilitation, both in and away from the laboratory setting, allows assessment of skill acquisition, retention, and long-term carryover in a variety of environments. Accurate measurement allows behavioral changes to be observed and assessments to be made, not only regarding an individual's ability to adapt during interventions, but also their ability to incorporate new skills into a real-world behavior. The result of such an approach to assessment may be that interventions truly translate from laboratory to real-world environments. Future locomotor measurement tools must be based on a theoretical framework that can guide their use to accurately quantify treatment effects and provide a basis upon which to develop and refine therapeutic interventions. PMID:22333921

Oral erlotinib, but not rapamycin, causes modest acceleration of bladder and hindlimb recovery from spinal cord injury in rats.

PubMed

Kjell, J; Pernold, K; Olson, L; Abrams, M B

2014-03-01

Erlotinib and Rapamycin are both in clinical use and experimental inhibition of their respective molecular targets, EGFR and mTORC1, has improved recovery from spinal cord injury. Our aim was to determine if daily Erlotinib or Rapamycin treatment started directly after spinal contusion injury in rats improves locomotion function or recovery of bladder function. Stockholm, Sweden. Rats were subjected to contusion injuries and treated during the acute phase with either Erlotinib or Rapamycin. Recovery of bladder function was monitored by measuring residual urine volume and hindlimb locomotion assessed by open-field observations using the BBB rating scale as well as by automated registration of gait parameters. Body weights were monitored. To determine whether Erlotinib and Rapamycin inhibit the same signaling pathway, a cell culture system and western blots were used. Erlotinib accelerated locomotor recovery and slightly improved bladder recovery; however, we found no long-term improvements of locomotor function. Rapamycin did neither improved locomotor function nor bladder recovery. In vitro studies confirmed that Erlotinib and Rapamycin both inhibit the EGFR-mTORC1 signaling pathway. We conclude that none of these two drug regimes improved long-term functional outcome in our current model of spinal cord injury. Nevertheless, oral treatment with Erlotinib may offer modest temporary advantages, whereas treatment with Rapamycin does not.

Paraquat affects mitochondrial bioenergetics, dopamine system expression, and locomotor activity in zebrafish (Danio rerio).

PubMed

Wang, Xiao H; Souders, Christopher L; Zhao, Yuan H; Martyniuk, Christopher J

2018-01-01

The dipyridyl herbicide paraquat induces oxidative stress in cells and is implicated in adult neurodegenerative diseases. However, less is known about paraquat toxicity in early stages of vertebrate development. To address this gap, zebrafish (Danio rerio) embryos were exposed to 1, 10 and 100 μM paraquat for 96 h. Paraquat did not induce significant mortality nor deformity in embryos and larvae, but it did accelerate time to hatch. To evaluate whether mitochondrial respiration was related to earlier hatch times, oxygen consumption rate was measured in whole embryos. Maximal respiration of embryos exposed to 100 μM paraquat for 24 h was reduced by more than 70%, suggesting that paraquat negatively impacts mitochondrial bioenergetics in early development. Based upon this evidence for mitochondrial dysfunction, transcriptional responses of oxidative stress- and apoptosis-related genes were measured. Fish exposed to 1 μM paraquat showed higher expression levels of superoxide dismutase 2, heat shock protein 70, Bcl-2-associated X protein, and B-cell CLL/lymphoma 2a compared to control fish. No differences among groups were detected in larvae exposed to 10 and 100 μM paraquat, suggesting a non-monotonic response. We also measured endpoints related to larval behavior and dopaminergic signaling as paraquat is associated with degeneration of dopamine neurons. Locomotor activity was stimulated with 100 μM paraquat and dopamine transporter and dopamine receptor 3 mRNA levels were increased in larvae exposed to 1 μM paraquat, interpreted to be a compensatory response at lower concentrations. This study improves mechanistic understanding into the toxic actions of paraquat on early developmental stages. Copyright © 2017 Elsevier Ltd. All rights reserved.

Low-energy extracorporeal shock wave therapy promotes vascular endothelial growth factor expression and improves locomotor recovery after spinal cord injury.

PubMed

Yamaya, Seiji; Ozawa, Hiroshi; Kanno, Haruo; Kishimoto, Koshi N; Sekiguchi, Akira; Tateda, Satoshi; Yahata, Kenichiro; Ito, Kenta; Shimokawa, Hiroaki; Itoi, Eiji

2014-12-01

Extracorporeal shock wave therapy (ESWT) is widely used for the clinical treatment of various human diseases. Recent studies have demonstrated that low-energy ESWT upregulates the expression of vascular endothelial growth factor (VEGF) and promotes angiogenesis and functional recovery in myocardial infarction and peripheral artery disease. Many previous reports suggested that VEGF produces a neuroprotective effect to reduce secondary neural tissue damage after spinal cord injury (SCI). The purpose of the present study was to investigate whether low-energy ESWT promotes VEGF expression and neuroprotection and improves locomotor recovery after SCI. Sixty adult female Sprague-Dawley rats were randomly divided into 4 groups: sham group (laminectomy only), sham-SW group (low-energy ESWT applied after laminectomy), SCI group (SCI only), and SCI-SW group (low-energy ESWT applied after SCI). Thoracic spinal cord contusion injury was inflicted using an impactor. Low-energy ESWT was applied to the injured spinal cord 3 times a week for 3 weeks. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan (BBB) Scale (open field locomotor score) at different time points over 42 days after SCI. Hematoxylin and eosin staining was performed to assess neural tissue damage in the spinal cord. Neuronal loss was investigated by immunostaining for NeuN. The mRNA expressions of VEGF and its receptor, Flt-1, in the spinal cord were assessed using real-time polymerase chain reaction. Immunostaining for VEGF was performed to evaluate VEGF protein expression in the spinal cord. In both the sham and sham-SW groups, no animals showed locomotor impairment on BBB scoring. Histological analysis of H & E and NeuN stainings in the sham-SW group confirmed that no neural tissue damage was induced by the low-energy ESWT. Importantly, animals in the SCI-SW group demonstrated significantly better locomotor improvement than those in the SCI group at 7, 35, and 42 days after injury (p < 0.05). The number of NeuN-positive cells in the SCI-SW group was significantly higher than that in the SCI group at 42 days after injury (p < 0.05). In addition, mRNA expressions of VEGF and Flt-1 were significantly increased in the SCI-SW group compared with the SCI group at 7 days after injury (p < 0.05). The expression of VEGF protein in the SCI-SW group was significantly higher than that in the SCI group at 7 days (p < 0.01). The present study showed that low-energy ESWT significantly increased expressions of VEGF and Flt-1 in the spinal cord without any detrimental effect. Furthermore, it significantly reduced neuronal loss in damaged neural tissue and improved locomotor function after SCI. These results suggested that low-energy ESWT enhances the neuroprotective effect of VEGF in reducing secondary injury and leads to better locomotor recovery following SCI. This study provides the first evidence that low-energy ESWT can be a safe and promising therapeutic strategy for SCI.

Ankle voluntary movement enhancement following robotic-assisted locomotor training in spinal cord injury.

PubMed

Varoqui, Deborah; Niu, Xun; Mirbagheri, Mehdi M

2014-03-31

In incomplete spinal cord injury (iSCI), sensorimotor impairments result in severe limitations to ambulation. To improve walking capacity, physical therapies using robotic-assisted locomotor devices, such as the Lokomat, have been developed. Following locomotor training, an improvement in gait capabilities-characterized by increases in the over-ground walking speed and endurance-is generally observed in patients. To better understand the mechanisms underlying these improvements, we studied the effects of Lokomat training on impaired ankle voluntary movement, known to be an important limiting factor in gait for iSCI patients. Fifteen chronic iSCI subjects performed twelve 1-hour sessions of Lokomat training over the course of a month. The voluntary movement was qualified by measuring active range of motion, maximal velocity peak and trajectory smoothness for the spastic ankle during a movement from full plantar-flexion (PF) to full dorsi-flexion (DF) at the patient's maximum speed. Dorsi- and plantar-flexor muscle strength was quantified by isometric maximal voluntary contraction (MVC). Clinical assessments were also performed using the Timed Up and Go (TUG), the 10-meter walk (10MWT) and the 6-minute walk (6MWT) tests. All evaluations were performed both before and after the training and were compared to a control group of fifteen iSCI patients. After the Lokomat training, the active range of motion, the maximal velocity, and the movement smoothness were significantly improved in the voluntary movement. Patients also exhibited an improvement in the MVC for their ankle dorsi- and plantar-flexor muscles. In terms of functional activity, we observed an enhancement in the mobility (TUG) and the over-ground gait velocity (10MWT) with training. Correlation tests indicated a significant relationship between ankle voluntary movement performance and the walking clinical assessments. The improvements of the kinematic and kinetic parameters of the ankle voluntary movement, and their correlation with the functional assessments, support the therapeutic effect of robotic-assisted locomotor training on motor impairment in chronic iSCI.

Glucosamine-containing supplement improves locomotor functions in subjects with knee pain: a randomized, double-blind, placebo-controlled study

PubMed Central

Kanzaki, Noriyuki; Ono, Yoshiko; Shibata, Hiroshi; Moritani, Toshio

2015-01-01

Background The aim of this study was to investigate the ability of a glucosamine-containing supplement to improve locomotor functions in subjects with knee pain. Methods A randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted for 16 weeks in 100 Japanese subjects (age, 51.8±0.8 years) with knee pain. Subjects were randomly assigned to one of the two supplements containing 1) 1,200 mg of glucosamine hydrochloride, 60 mg of chondroitin sulfate, 45 mg of type II collagen peptides, 90 mg of quercetin glycosides, 10 mg of imidazole peptides, and 5 μg of vitamin D per day (GCQID group, n=50) or 2) a placebo (placebo group, n=50). Japanese Knee Osteoarthritis Measure, visual analog scale score, normal walking speed, and knee-extensor strength were measured to evaluate the effects of the supplement on knee-joint functions and locomotor functions. Results In subjects eligible for efficacy assessment, there was no significant group × time interaction, and there were improvements in knee-joint functions and locomotor functions in both groups, but there was no significant difference between the groups. In subjects with mild-to-severe knee pain at baseline, knee-extensor strength at week 8 (104.6±5.0% body weight vs 92.3±5.5% body weight, P=0.030) and the change in normal walking speed at week 16 (0.11±0.03 m/s vs 0.05±0.02 m/s, P=0.038) were significantly greater in the GCQID group than in the placebo group. Further subgroup analysis based on Kellgren–Lawrence (K–L) grade showed that normal walking speed at week 16 (1.36±0.05 m/s vs 1.21±0.02 m/s, P<0.05) was significantly greater in the GCQID group than in the placebo group in subjects with K–L grade I. No adverse effect of treatment was identified in the safety assessment. Conclusion In subjects with knee pain, GCQID supplementation was effective for relieving knee pain and improving locomotor functions. PMID:26604721

Glucosamine-containing supplement improves locomotor functions in subjects with knee pain: a randomized, double-blind, placebo-controlled study.

PubMed

Kanzaki, Noriyuki; Ono, Yoshiko; Shibata, Hiroshi; Moritani, Toshio

2015-01-01

The aim of this study was to investigate the ability of a glucosamine-containing supplement to improve locomotor functions in subjects with knee pain. A randomized, double-blind, placebo-controlled, parallel-group comparative study was conducted for 16 weeks in 100 Japanese subjects (age, 51.8±0.8 years) with knee pain. Subjects were randomly assigned to one of the two supplements containing 1) 1,200 mg of glucosamine hydrochloride, 60 mg of chondroitin sulfate, 45 mg of type II collagen peptides, 90 mg of quercetin glycosides, 10 mg of imidazole peptides, and 5 μg of vitamin D per day (GCQID group, n=50) or 2) a placebo (placebo group, n=50). Japanese Knee Osteoarthritis Measure, visual analog scale score, normal walking speed, and knee-extensor strength were measured to evaluate the effects of the supplement on knee-joint functions and locomotor functions. In subjects eligible for efficacy assessment, there was no significant group × time interaction, and there were improvements in knee-joint functions and locomotor functions in both groups, but there was no significant difference between the groups. In subjects with mild-to-severe knee pain at baseline, knee-extensor strength at week 8 (104.6±5.0% body weight vs 92.3±5.5% body weight, P=0.030) and the change in normal walking speed at week 16 (0.11±0.03 m/s vs 0.05±0.02 m/s, P=0.038) were significantly greater in the GCQID group than in the placebo group. Further subgroup analysis based on Kellgren-Lawrence (K-L) grade showed that normal walking speed at week 16 (1.36±0.05 m/s vs 1.21±0.02 m/s, P<0.05) was significantly greater in the GCQID group than in the placebo group in subjects with K-L grade I. No adverse effect of treatment was identified in the safety assessment. In subjects with knee pain, GCQID supplementation was effective for relieving knee pain and improving locomotor functions.

GABA-BZD Receptor Modulating Mechanism of Panax quinquefolius against 72-h Sleep Deprivation Induced Anxiety like Behavior: Possible Roles of Oxidative Stress, Mitochondrial Dysfunction and Neuroinflammation

PubMed Central

Chanana, Priyanka; Kumar, Anil

2016-01-01

Rationale: Panax quinquefolius (American Ginseng) is known for its therapeutic potential against various neurological disorders, but its plausible mechanism of action still remains undeciphered. GABA (Gamma Amino Butyric Acid) plays an important role in sleep wake cycle homeostasis. Thus, there exists rationale in exploring the GABA-ergic potential of Panax quinquefolius as neuroprotective strategy in sleep deprivation induced secondary neurological problems. Objective: The present study was designed to explore the possible GABA-ergic mechanism in the neuro-protective effect of Panax quinquefolius against 72-h sleep deprivation induced anxiety like behavior, oxidative stress, mitochondrial dysfunction, HPA-axis activation and neuroinflammation. Materials and Methods: Male laca mice were sleep deprived for 72-h by using Grid suspended over water method. Panax quinquefolius (American Ginseng 50, 100, and 200 mg/kg) was administered alone and in combination with GABA modulators (GABA Cl− channel inhibitor, GABA-benzodiazepine receptor inhibitor and GABAA agonist) for 8 days, starting 5 days prior to 72-h sleep deprivation period. Various behavioral (locomotor activity, mirror chamber test), biochemical (lipid peroxidation, reduced glutathione, catalase, nitrite levels), mitochondrial complexes, neuroinflammation marker (Tumor Necrosis Factor, TNF-alpha), serum corticosterone, and histopathological sections of brains were assessed. Results: Seventy two hours sleep deprivation significantly impaired locomotor activity, caused anxiety-like behavior, conditions of oxidative stress, alterations in mitochondrial enzyme complex activities, raised serum corticosterone levels, brain TNFα levels and led to neuroinflammation like signs in discrete brain areas as compared to naive group. Panax quinquefolius (100 and 200 mg/kg) treatment restored the behavioral, biochemical, mitochondrial, molecular and histopathological alterations. Pre-treatment of GABA Cl− channel inhibitor as well as GABA-benzodiazepine receptor inhibitor, significantly reversed the protective effect of P. quinquefolius (100 mg/kg) in 72-h sleep deprived animals (P < 0.05). However, pretreatment with GABAA agonist, potentiated Panax quinquefolius's protective effect which was significant as compared to their effect per se (p < 0.05). Conclusion: GABA-ergic mechanism could be involved in the neuroprotective effect of P.quinquefolius against sleep deprivation induced anxiety-like behavior, oxidative stress, mitochondrial dysfunction, HPA axis activation and neuroinflammation. PMID:27013946

Brain and spinal cord interaction: a dietary curcumin derivative counteracts locomotor and cognitive deficits after brain trauma.

PubMed

Wu, Aiguo; Ying, Zhe; Schubert, David; Gomez-Pinilla, Fernando

2011-05-01

In addition to cognitive dysfunction, locomotor deficits are prevalent in traumatic brain injured (TBI) patients; however, it is unclear how a concussive injury can affect spinal cord centers. Moreover, there are no current efficient treatments that can counteract the broad pathology associated with TBI. The authors have investigated potential molecular basis for the disruptive effects of TBI on spinal cord and hippocampus and the neuroprotection of a curcumin derivative to reduce the effects of experimental TBI. The authors performed fluid percussion injury (FPI) and then rats were exposed to dietary supplementation of the curcumin derivative (CNB-001; 500 ppm). The curry spice curcumin has protective capacity in animal models of neurodegenerative diseases, and the curcumin derivative has enhanced brain absorption and biological activity. The results show that FPI in rats, in addition to reducing learning ability, reduced locomotor performance. Behavioral deficits were accompanied by reductions in molecular systems important for synaptic plasticity underlying behavioral plasticity in the brain and spinal cord. The post-TBI dietary supplementation of the curcumin derivative normalized levels of BDNF, and its downstream effectors on synaptic plasticity (CREB, synapsin I) and neuronal signaling (CaMKII), as well as levels of oxidative stress-related molecules (SOD, Sir2). These studies define a mechanism by which TBI can compromise centers related to cognitive processing and locomotion. The findings also show the influence of the curcumin derivative on synaptic plasticity events in the brain and spinal cord and emphasize the therapeutic potential of this noninvasive dietary intervention for TBI.

Objective measures of motor dysfunction after compression spinal cord injury in adult rats: correlations with locomotor rating scores.

PubMed

Semler, Joerg; Wellmann, Katharina; Wirth, Felicitas; Stein, Gregor; Angelova, Srebrina; Ashrafi, Mahak; Schempf, Greta; Ankerne, Janina; Ozsoy, Ozlem; Ozsoy, Umut; Schönau, Eckhard; Angelov, Doychin N; Irintchev, Andrey

2011-07-01

Precise assessment of motor deficits after traumatic spinal cord injury (SCI) in rodents is crucial for understanding the mechanisms of functional recovery and testing therapeutic approaches. Here we analyzed the applicability to a rat SCI model of an objective approach, the single-frame motion analysis, created and used for functional analysis in mice. Adult female Wistar rats were subjected to graded compression of the spinal cord. Recovery of locomotion was analyzed using video recordings of beam walking and inclined ladder climbing. Three out of four parameters used in mice appeared suitable: the foot-stepping angle (FSA) and the rump-height index (RHI), measured during beam walking, and for estimating paw placement and body weight support, respectively, and the number of correct ladder steps (CLS), assessing skilled limb movements. These parameters, similar to the Basso, Beattie, and Bresnahan (BBB) locomotor rating scores, correlated with lesion volume and showed significant differences between moderately and severely injured rats at 1-9 weeks after SCI. The beam parameters, but not CLS, correlated well with the BBB scores within ranges of poor and good locomotor abilities. FSA co-varied with RHI only in the severely impaired rats, while RHI and CLS were barely correlated. Our findings suggest that the numerical parameters estimate, as intended by design, predominantly different aspects of locomotion. The use of these objective measures combined with BBB rating provides a time- and cost-efficient opportunity for versatile and reliable functional evaluations in both severely and moderately impaired rats, combining clinical assessment with precise numerical measures.

Too Little and Too Much: Hypoactivation and Disinhibition of Medial Prefrontal Cortex Cause Attentional Deficits

PubMed Central

McGarrity, Stephanie; Mason, Rob; Fone, Kevin C.

2014-01-01

Attentional deficits are core symptoms of schizophrenia, contributing strongly to disability. Prefrontal dysfunction has emerged as a candidate mechanism, with clinical evidence for prefrontal hypoactivation and disinhibition (reduced GABAergic inhibition), possibly reflecting different patient subpopulations. Here, we tested in rats whether imbalanced prefrontal neural activity impairs attention. To induce prefrontal hypoactivation or disinhibition, we microinfused the GABA-A receptor agonist muscimol (C4H6N2O2; 62.5, 125, 250 ng/side) or antagonist picrotoxin (C30H34O13; 75, 150, 300 ng/side), respectively, into the medial prefrontal cortex. Using the five-choice serial reaction time (5CSRT) test, we showed that both muscimol and picrotoxin impaired attention (reduced accuracy, increased omissions). Muscimol also impaired response control (increased premature responses). In addition, muscimol dose dependently reduced open-field locomotor activity, whereas 300 ng of picrotoxin caused locomotor hyperactivity; sensorimotor gating (startle prepulse inhibition) was unaffected. Therefore, infusion effects on the 5CSRT test can be dissociated from sensorimotor effects. Combining microinfusions with in vivo electrophysiology, we showed that muscimol inhibited prefrontal firing, whereas picrotoxin increased firing, mainly within bursts. Muscimol reduced and picrotoxin enhanced bursting and both drugs changed the temporal pattern of bursting. Picrotoxin also markedly enhanced prefrontal LFP power. Therefore, prefrontal hypoactivation and disinhibition both cause attentional deficits. Considering the electrophysiological findings, this suggests that attention requires appropriately tuned prefrontal activity. Apart from attentional deficits, prefrontal disinhibition caused additional neurobehavioral changes that may be relevant to schizophrenia pathophysiology, including enhanced prefrontal bursting and locomotor hyperactivity, which have been linked to psychosis-related dopamine hyperfunction. PMID:24899715

Potential contributions of training intensity on locomotor performance in individuals with chronic stroke.

PubMed

Holleran, Carey L; Rodriguez, Kelly S; Echauz, Anthony; Leech, Kristan A; Hornby, T George

2015-04-01

Many interventions can improve walking ability of individuals with stroke, although the training parameters that maximize recovery are not clear. For example, the contribution of training intensity has not been well established and may contribute to the efficacy of many locomotor interventions. The purpose of this preliminary study was to evaluate the effects of locomotor training intensity on walking outcomes in individuals with gait deficits poststroke. Using a randomized cross-over design, 12 participants with chronic stroke (>6-month duration) performed either high-intensity (70%-80% of heart rate reserve; n = 6) or low-intensity (30%-40% heart rate reserve; n = 6) locomotor training for 12 or fewer sessions over 4 to 5 weeks. Four weeks following completion, the alternate training intervention was performed. Training intensity was manipulated by adding loads or applying resistance during walking, with similar speeds, durations, and amount of stepping practice between conditions. Greater increases in 6-Minute Walk Test performance were observed following high-intensity training compared with low-intensity training. A significant interaction of intensity and order was also observed for 6-Minute Walk Test and peak treadmill speed, with the largest changes in those who performed high-intensity training first. Moderate correlations were observed between locomotor outcomes and measures of training intensity. This study provides the first evidence that the intensity of locomotor practice may be an important independent determinant of walking outcomes poststroke. In the clinical setting, the intensity of locomotor training can be manipulated in many ways, although this represents only 1 parameter to consider.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A90).

Effects of Overground Locomotor Training on Walking Performance in Chronic Cervical Motor Incomplete Spinal Cord Injury: A Pilot Study.

PubMed

Gollie, Jared M; Guccione, Andrew A; Panza, Gino S; Jo, Peter Y; Herrick, Jeffrey E

2017-06-01

To determine the effects of a novel overground locomotor training program on walking performance in people with chronic cervical motor incomplete spinal cord injury (iSCI). Before-after pilot study. Human performance research laboratory. Adults (N=6, age >18y) with chronic cervical iSCI with American Spinal Injury Association Impairment Scale grades C and D. Overground locomotor training included two 90-minute sessions per week for 12 to 15 weeks. Training sessions alternated between uniplanar and multiplanar stepping patterns. Each session was comprised of 5 segments: joint mobility, volitional muscle activation, task isolation, task integration, and activity rehearsal. Overground walking speed, oxygen consumption (V˙o 2 ), and carbon dioxide production (V˙co 2 ). Overground locomotor training increased overground walking speed (.36±.20 vs .51±.24 m/s, P<.001, d=.68). Significant decreases in V˙o 2 (6.6±1.3 vs 5.7±1.4mL·kg·min, P=.038, d=.67) and V˙co 2 (753.1±125.5 vs 670.7±120.3mL/min, P=.036, d=.67) during self-selected constant work rate treadmill walking were also noted after training. The overground locomotor training program used in this pilot study is feasible and improved both overground walking speed and walking economy in a small sample of people with chronic cervical iSCI. Future studies are necessary to establish the efficacy of this overground locomotor training program and to differentiate among potential mechanisms contributing to enhanced walking performance in people with iSCI after overground locomotor training. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Fiber atrophy and hypertrophy in skeletal muscles of late middle-aged Fischer 344 x Brown Norway F1-hybrid rats.

PubMed

Hepple, Russell T; Ross, Karen D; Rempfer, Amanda B

2004-02-01

We examined young adult and late middle-aged male rats to test the hypothesis that gastrocnemius (a locomotor muscle) demonstrates reduced fiber size with aging, whereas soleus (a postural muscle) demonstrates atrophy of some fibers and compensatory hypertrophy in other fibers. Although body mass was greater in late middle-aged animals, mass was reduced in gastrocnemius but not soleus muscle. In another group of animals, physical activity was reduced by 34% in late middle-aged animals. Whereas mean fiber size was lower in gastrocnemius of late middle-aged animals, it was not different in soleus. Histograms revealed atrophied fibers (/=8000 micro m(2)) in soleus with aging. Atrophied fibers often demonstrated no subsarcolemmal mitochondrial staining, suggesting denervation, whereas hypertrophied fibers often demonstrated cytochrome oxidase deficiency, suggesting mitochondrial dysfunction. These results underscore the divergent influences (e.g., physical inactivity, denervation, mitochondrial dysfunction) affecting fiber size with aging.

Recovery of locomotion in the cat following spinal cord lesions.

PubMed

Rossignol, S; Bouyer, L; Barthélemy, D; Langlet, C; Leblond, H

2002-10-01

In most species, locomotor function beneath the level of a spinal cord lesion can be restored even if the cord is completely transected. This suggests that there is, within the spinal cord, an autonomous network of neurons capable of generating a locomotor pattern independently of supraspinal inputs. Recent studies suggest that several physiological and neurochemical changes have to occur in the neuronal networks located caudally to the lesion to allow the expression of spinal locomotion. Some evidence of this plasticity will be addressed in this review. In addition, original data on the functional organisation of the lumbar spinal cord will also be presented. Recent works in our lab show that segmental responsiveness of the spinal cord of the cat to locally micro-injected drugs in different lumbar segments, in combination with complete lesions at various level of the spinal cord, suggest a rostro-caudal organisation of spinal locomotor control. Moreover, the integrity of midlumbar segments seems to be crucial for the expression of spinal locomotion. These data suggest that the regions of critical importance for locomotion can be confined to a restricted portion of the spinal cord. Later, these midlumbar segments could be targeted by electrical stimulation or grafts to improve recovery of function. Understanding the changes in spinal cord neurophysiology and neurochemistry after a lesion is of critical importance to the improvement of treatments for locomotor rehabilitation in spinal-cord-injured patients.

An infrared system for monitoring Drosophila motility during microgravity

NASA Technical Reports Server (NTRS)

Miller, Mark S.; Fortney, Michael D.; Keller, Tony S.

2002-01-01

Presently, the precise mechanisms of the aging process are unknown. Examination and comprehension of the aging process in other species could lead to significant advances in the understanding of human aging. Drosophila melanogaster (fruit fly), commonly used for aging studies, is a widely studied organism in terms of behavior, development, and genetics. Previous microgravity experiments have shown a significant decrease in the life span of young male Drosophila after microgravity exposure. This decrease in lifespan may be related to locomotor activity, a convenient measure of overall physiological performance. This study describes the design and performance of a Drosophila Infrared Motility Monitoring System (DIMMS). The DIMMS uses a unique design of two infrared (IR) beams per fly to measure the locomotor activity of 240 flies. Locomotor activity is measured in terms of number of IR crossings per unit time, instantaneous velocity, and continuous velocity. Ground-based results using the DIMMS equipment agree well with previous values for Drosophila locomotor velocity. DIMMS is an improvement over equipment previously used due to its ability to continuously monitor locomotor activity throughout short-duration microgravity exposure. DIMMS is also lightweight, compact, and power efficient. DIMMS has been flight tested onboard NASA's KC-135 reduced gravity research aircraft and a Nike-Orion sounding rocket.

An infrared system for monitoring Drosophila motility during microgravity.

PubMed

Miller, Mark S; Fortney, Michael D; Keller, Tony S

2002-12-01

Presently, the precise mechanisms of the aging process are unknown. Examination and comprehension of the aging process in other species could lead to significant advances in the understanding of human aging. Drosophila melanogaster (fruit fly), commonly used for aging studies, is a widely studied organism in terms of behavior, development, and genetics. Previous microgravity experiments have shown a significant decrease in the life span of young male Drosophila after microgravity exposure. This decrease in lifespan may be related to locomotor activity, a convenient measure of overall physiological performance. This study describes the design and performance of a Drosophila Infrared Motility Monitoring System (DIMMS). The DIMMS uses a unique design of two infrared (IR) beams per fly to measure the locomotor activity of 240 flies. Locomotor activity is measured in terms of number of IR crossings per unit time, instantaneous velocity, and continuous velocity. Ground-based results using the DIMMS equipment agree well with previous values for Drosophila locomotor velocity. DIMMS is an improvement over equipment previously used due to its ability to continuously monitor locomotor activity throughout short-duration microgravity exposure. DIMMS is also lightweight, compact, and power efficient. DIMMS has been flight tested onboard NASA's KC-135 reduced gravity research aircraft and a Nike-Orion sounding rocket.

FES-assisted Cycling Improves Aerobic Capacity and Locomotor Function Postcerebrovascular Accident.

PubMed

Aaron, Stacey E; Vanderwerker, Catherine J; Embry, Aaron E; Newton, Jennifer H; Lee, Samuel C K; Gregory, Chris M

2018-03-01

After a cerebrovascular accident (CVA) aerobic deconditioning contributes to diminished physical function. Functional electrical stimulation (FES)-assisted cycling is a promising exercise paradigm designed to target both aerobic capacity and locomotor function. This pilot study aimed to evaluate the effects of an FES-assisted cycling intervention on aerobic capacity and locomotor function in individuals post-CVA. Eleven individuals with chronic (>6 months) post-CVA hemiparesis completed an 8-wk (three times per week; 24 sessions) progressive FES-assisted cycling intervention. V˙O2peak, self-selected, and fastest comfortable walking speeds, gait, and pedaling symmetry, 6-min walk test (6MWT), balance, dynamic gait movements, and health status were measured at baseline and posttraining. Functional electrical stimulation-assisted cycling significantly improved V˙O2peak (12%, P = 0.006), self-selected walking speed (SSWS, 0.05 ± 0.1 m·s, P = 0.04), Activities-specific Balance Confidence scale score (12.75 ± 17.4, P = 0.04), Berg Balance Scale score (3.91 ± 4.2, P = 0.016), Dynamic Gait Index score (1.64 ± 1.4, P = 0.016), and Stroke Impact Scale participation/role domain score (12.74 ± 16.7, P = 0.027). Additionally, pedal symmetry, represented by the paretic limb contribution to pedaling (paretic pedaling ratio [PPR]) significantly improved (10.09% ± 9.0%, P = 0.016). Although step length symmetry (paretic step ratio [PSR]) did improve, these changes were not statistically significant (-0.05% ± 0.1%, P = 0.09). Exploratory correlations showed moderate association between change in SSWS and 6-min walk test (r = 0.74), and moderate/strong negative association between change in PPR and PSR. These results support FES-assisted cycling as a means to improve both aerobic capacity and locomotor function. Improvements in SSWS, balance, dynamic walking movements, and participation in familial and societal roles are important targets for rehabilitation of individuals after CVA. Interestingly, the correlation between PSR and PPR suggests that improvements in pedaling symmetry may translate to a more symmetric gait pattern.

Evaluation of stomatognathic problems in children with osteogenesis imperfecta (osteogenesis imperfecta - oi) - preliminary study.

PubMed

Smoląg, Danuta; Kulesa-Mrowiecka, Małgorzata; Sułko, Jerzy

2017-01-01

According to epidemiological data, muscular dysfunctions of the masticatory system occur in 15-23% of the population. Preventive examinations of functional disorders of the stomatognathic system are, therefore, of particular importance. A distinct group of patients exposed to dysfunctions in the area of the masticatory organ locomotor apparatus comprises those with genetic diseases characterised by disorders in collagen formation. One of such diseases is osteogenesis imperfecta (OI) and dentinogenesis imperfecta that usually goes together with the former. The objective of this work was to evaluate the frequency with which particular disorders of the masticatory organ locomotor apparatus occur within the group of patients with osteogenesis imperfecta. The study was performed on patients of the Orthopaedic Clinic of the Polish-American Paediatric Institute in Kraków. The mean age of the children was 7.9 years. In all the cases, a genetic diagnosis of OI has been confirmed. The research methods were based on an in-depth interview on family diseases, pregnancy, postnatal period, feeding, subjective assessment of dysfunctions in the stomatognathic system. An examination of the deformations in the stomatognathic system and the skeleton was conducted, as well as an examination of the trauma and tone of the jaw. The relationship between breastfeeding and swallowing and speech disorders was also evaluated. The impact of intubation on mandibular ranges was investigated. The results obtained were subjected to statistical analysis on the basis of which conclusions were drawn concerning disorders in the stomatognathic system which tend to occur in children with OI. The renunciation of breastfeeding significantly contributes to sucking and swallowing disorders, rumen disorders, as well as biomechanical disorders in the temporomandibular joint. A significant dependence between breastfeeding and swallowing problems was found, whereas there was no such dependence with respect to speech impediments. The results of the research conducted led to the following conclusions: 1. Among pediatric patients with OI there are disorders in the stomatognathic system. The most common dysfunctions are: abdominal, swallowing and sucking disorders, abnormal muscle structure of the rumen and biomechanical disorders in the temporomandibular joints. Breastfeeding significantly contributes to swallowing disorders. 2. The therapeutic process involving children with OI requires the cooperation of specialists in orthopedics, pediatrics, physiotherapy, orthodontics and neurologopedics to carry out comprehensive diagnostics and treatment tailored to the individual needs of the patient. 3. In order to draw final conclusions, there is a need for more research by means of objective tools, such as EMG and a condensate recorder.

Evaluation of the clinical efficacy of meloxicam in cats with painful locomotor disorders.

PubMed

Lascelles, B D; Henderson, A J; Hackett, I J

2001-12-01

The ability of two non-steroidal anti-inflammatory drugs to modify the clinical manifestations of pain associated with locomotor disease was assessed. Sixty-nine cats with acute or chronic locomotor disorders were recruited from 14 first opinion UK veterinary practices and randomly allocated to one of two treatment groups. Group A received meloxicam drops (0.3 mg/kg orally on day 1 followed by 0.1 mg/kg daily for four more consecutive days) and group B received ketoprofen tablets (1.0 mg/kg orally once daily for five days). Each cat underwent a full clinical examination before treatment, 24 hours after initiation of treatment and 24 hours after completion of treatment. General clinical parameters (demeanour and feed intake) and specific locomotor parameters (weightbearing, lameness, local inflammation and pain on palpation) were scored using a discontinuous scale scoring system. The two groups did not differ in terms of age, weight, gender distribution or duration of clinical signs; nor did they differ in terms of general clinical or specific locomotor scores pretreatment. Both treatment regimens resulted in a significant improvement in demeanour, feed intake and weightbearing, and a significant reduction in lameness, pain on palpation and inflammation. No significant difference was observed between the two treatment groups with respect to any of the parameters measured and both treatments were associated with minimal observed side effects. Meloxicam and ketoprofen were found to be effective analgesics and well tolerated in cats with acute or chronic locomotor disorders when administered for short-term treatment (five days) in such cases. However, meloxicam was assessed to be significantly more palatable than ketoprofen.

Serotonin receptor and dendritic plasticity in the spinal cord mediated by chronic serotonergic pharmacotherapy combined with exercise following complete SCI in the adult rat.

PubMed

Ganzer, Patrick D; Beringer, Carl R; Shumsky, Jed S; Nwaobasi, Chiemela; Moxon, Karen A

2018-06-01

Severe spinal cord injury (SCI) damages descending motor and serotonin (5-HT) fiber projections leading to paralysis and serotonin depletion. 5-HT receptors (5-HTRs) subsequently upregulate following 5-HT fiber degeneration, and dendritic density decreases indicative of atrophy. 5-HT pharmacotherapy or exercise can improve locomotor behavior after SCI. One might expect that 5-HT pharmacotherapy acts on upregulated spinal 5-HTRs to enhance function, and that exercise alone can influence dendritic atrophy. In the current study, we assessed locomotor recovery and spinal proteins influenced by SCI and therapy. 5-HT, 5-HT 2A R, 5-HT 1A R, and dendritic densities were quantified both early (1 week) and late (9 weeks) after SCI, and also following therapeutic interventions (5-HT pharmacotherapy, bike therapy, or a combination). Interestingly, chronic 5-HT pharmacotherapy largely normalized spinal 5-HTR upregulation following injury. Improvement in locomotor behavior was not correlated to 5-HTR density. These results support the hypothesis that chronic 5-HT pharmacotherapy can mediate recovery following SCI, despite acting on largely normal spinal 5-HTR levels. We next assessed spinal dendritic plasticity and its potential role in locomotor recovery. Single therapies did not normalize the loss of dendritic density after SCI. Groups displaying significantly atrophied dendritic processes were rarely able to achieve weight supported open-field locomotion. Only a combination of 5-HT pharmacotherapy and bike therapy enabled significant open-field weigh-supported stepping, mediated in part by restoring spinal dendritic density. These results support the use of combined therapies to synergistically impact multiple markers of spinal plasticity and improve motor recovery. Copyright © 2018 Elsevier Inc. All rights reserved.

Ankle voluntary movement enhancement following robotic-assisted locomotor training in spinal cord injury

PubMed Central

2014-01-01

Background In incomplete spinal cord injury (iSCI), sensorimotor impairments result in severe limitations to ambulation. To improve walking capacity, physical therapies using robotic-assisted locomotor devices, such as the Lokomat, have been developed. Following locomotor training, an improvement in gait capabilities—characterized by increases in the over-ground walking speed and endurance—is generally observed in patients. To better understand the mechanisms underlying these improvements, we studied the effects of Lokomat training on impaired ankle voluntary movement, known to be an important limiting factor in gait for iSCI patients. Methods Fifteen chronic iSCI subjects performed twelve 1-hour sessions of Lokomat training over the course of a month. The voluntary movement was qualified by measuring active range of motion, maximal velocity peak and trajectory smoothness for the spastic ankle during a movement from full plantar-flexion (PF) to full dorsi-flexion (DF) at the patient’s maximum speed. Dorsi- and plantar-flexor muscle strength was quantified by isometric maximal voluntary contraction (MVC). Clinical assessments were also performed using the Timed Up and Go (TUG), the 10-meter walk (10MWT) and the 6-minute walk (6MWT) tests. All evaluations were performed both before and after the training and were compared to a control group of fifteen iSCI patients. Results After the Lokomat training, the active range of motion, the maximal velocity, and the movement smoothness were significantly improved in the voluntary movement. Patients also exhibited an improvement in the MVC for their ankle dorsi- and plantar-flexor muscles. In terms of functional activity, we observed an enhancement in the mobility (TUG) and the over-ground gait velocity (10MWT) with training. Correlation tests indicated a significant relationship between ankle voluntary movement performance and the walking clinical assessments. Conclusions The improvements of the kinematic and kinetic parameters of the ankle voluntary movement, and their correlation with the functional assessments, support the therapeutic effect of robotic-assisted locomotor training on motor impairment in chronic iSCI. PMID:24684813

[Focal cerebral ischemia in rats with estrogen deficiency and endothelial dysfunction].

PubMed

Litvinov, A A; Volotova, E V; Kurkin, D V; Logvinova, E O; Darmanyan, A P; Tyurenkov, I N

2017-01-01

To assess an effect of ovariectomy (OE) on the cerebral blood flow, endothelium-dependent vasodilation, neurological, cognitive and locomotor deficit as markers of brain damage after focal ischemia in rats. The study was conducted in 48 female Wistar rats. Ovariectomy was performed with ovaries and uterine body extirpation, cerebral ischemia was performed by middle cerebral artery occlusion (MCAO) in rats. To assess brain damage, Combs and Garcia scores, 'open field' test (OFT), 'extrapolatory escape test' (EET), 'passive avoidance test' (PAT), 'beam-walking test' were used. Cerebral blood flow was measured using ultrasonic flowmetry. After 7 days of MCAO, the cerebral blood flow in ovarioectomized animals was reduced by 20% compared to sham-ovariectomized animals. Ovariectomized animals with MCAO showed a three-fold endothelium-dependent vasodilation reduction (the reaction of cerebral vessels to the introduction of acetylcholine and N-L-arginine), indicating the presence of severe endothelial dysfunction. In ovarioectomized animals, the cerebral blood flow was reduced by 34% compared to sham-operated animals. MCAO and OE taken together resulted in more than 2-fold increase in neurological, motor disturbances, 3-fold decrease in motor activity of the animals in the OP test. Focal ischemia in ovarioectomized animals with endothelial dysfunction led to memory decrease by 1/5 fold in PAT and by 2-fold in EET.

Cannabis-induced Moto-Cognitive Dysfunction in Wistar Rats: Ameliorative Efficacy of Nigella Sativa.

PubMed

Imam, Aminu; Ajao, Moyosore Saliu; Amin, Abdulbasit; Abdulmajeed, Wahab Imam; Ibrahim, Abdulmumin; Olajide, Olayemi Joseph; Ajibola, Musa Iyiola; Alli-Oluwafuyi, Abdulmusawir; Balogun, Wasiu Gbolahan

2016-09-01

Cannabis is a widely used illicit drug with various threats of personality syndrome, and Nigella sativa has been widely implicated as having therapeutic efficacy in many neurological diseases. The present study investigates the ameliorative efficacy of Nigella sativa oil (NSO) on cannabis-induced moto-cognitive defects. Scopolamine (1 mg/kg i.p.) was given to induce dementia as a standard base line for cannabis (20 mg/kg)-induced cognitive impairment, followed by an oral administration of NSO (1 ml/kg) for 14 consecutive days. The Morris water maze (MWM) paradigm was used to assess the memory index, the elevated plus maze was used for anxiety-like behaviour, and the open field test was used for locomotor activities; thereafter, the rats were sacrificed and their brains were removed for histopathologic studies. Cannabis-like Scopolamine caused memory impairment, delayed latency in the MWM, and anxiety-like behaviour, coupled with alterations in the cerebello-hippocampal neurons. The post-treatment of rats with NSO mitigated cannabis-induced cognitive dysfunction as with scopolamine and impaired anxiety-like behaviour by increasing open arm entry, line crossing, and histological changes. The observed ameliorative effects of NSO make it a promising agent against moto-cognitive dysfunction and cerebelo-hippocampal alterations induced by cannabis.

Cannabis-induced Moto-Cognitive Dysfunction in Wistar Rats: Ameliorative Efficacy of Nigella Sativa

PubMed Central

Imam, Aminu; Ajao, Moyosore Saliu; Amin, Abdulbasit; Abdulmajeed, Wahab Imam; Ibrahim, Abdulmumin; Olajide, Olayemi Joseph; Ajibola, Musa Iyiola; Alli-Oluwafuyi, Abdulmusawir; Balogun, Wasiu Gbolahan

2016-01-01

Background Cannabis is a widely used illicit drug with various threats of personality syndrome, and Nigella sativa has been widely implicated as having therapeutic efficacy in many neurological diseases. The present study investigates the ameliorative efficacy of Nigella sativa oil (NSO) on cannabis-induced moto-cognitive defects. Methods Scopolamine (1 mg/kg i.p.) was given to induce dementia as a standard base line for cannabis (20 mg/kg)-induced cognitive impairment, followed by an oral administration of NSO (1 ml/kg) for 14 consecutive days. The Morris water maze (MWM) paradigm was used to assess the memory index, the elevated plus maze was used for anxiety-like behaviour, and the open field test was used for locomotor activities; thereafter, the rats were sacrificed and their brains were removed for histopathologic studies. Results Cannabis-like Scopolamine caused memory impairment, delayed latency in the MWM, and anxiety-like behaviour, coupled with alterations in the cerebello-hippocampal neurons. The post-treatment of rats with NSO mitigated cannabis-induced cognitive dysfunction as with scopolamine and impaired anxiety-like behaviour by increasing open arm entry, line crossing, and histological changes. Conclusions The observed ameliorative effects of NSO make it a promising agent against moto-cognitive dysfunction and cerebelo-hippocampal alterations induced by cannabis. PMID:27904421

Functional and physiological effects of treadmill training induced by buspirone, carbidopa, and L-DOPA in clenbuterol-treated paraplegic mice.

PubMed

Ung, Roth-Visal; Rouleau, Pascal; Guertin, Pierre A

2012-05-01

Chronic spinal cord injury may be complicated by weight loss, muscle atrophy, and bone loss. The authors identified a combination pharmacotherapy using buspirone, carbidopa, and L-DOPA (BCD) that elicits bouts of locomotor-like movements in spinal cord-transected (Tx) mice. They then evaluated the effects of 8 weeks of treadmill training in Tx mice that received BCD or BCD + clenbuterol, a monoaminergic agent with anabolic properties, on locomotor function, muscle atrophy, adipose tissue loss, and bone density measures. Induced locomotor movement, adipose tissue, skeletal muscle, and femoral bone properties were compared in unoperated control mice, operated controls (untreated, untrained Tx mice), and 2 groups of treated, trained Tx mice (Tx + BCD, Tx + BCD + clenbuterol) that also received training. BCD- and BCD + clenbuterol-treated mice showed comparable levels of locomotor movements that significantly improved over time. Soleus muscle mass and soleus and extensor digitorum longus cross-sectional area significantly increased in both groups of BCD-treated mice, with greater effects in BCD + clenbuterol-treated animals. Fiber type conversion, adipose tissues, bone mineral density, and content were reduced in all Tx groups compared with unoperated control mice. These findings suggest that locomotor movement and muscle properties can be restored to near-normal levels after several weeks of BCD treatment, regular training, and clenbuterol in completely paraplegic animals.

Involvement of decreased muscarinic receptor function in prepulse inhibition deficits in mice reared in social isolation

PubMed Central

Koda, K; Ago, Y; Yano, K; Nishimura, M; Kobayashi, H; Fukada, A; Takuma, K; Matsuda, T

2011-01-01

BACKGROUND AND PURPOSE We have previously reported that galantamine, a weak acetylcholinesterase inhibitor, improves prepulse inhibition (PPI) deficits in mice reared in social isolation. ACh receptors are involved in the underlying mechanism of PPI, but whether rearing in social isolation causes dysfunction of the cholinergic system is unknown. In this study, we examined the involvement of muscarinic receptors in the improvement of PPI deficits induced by galantamine, and whether the cholinergic system is altered in mice reared in isolation. EXPERIMENTAL APPROACH Three-week-old male ddY mice were housed in isolated cages for 6 weeks before the initiation of experiments to create PPI deficits. Cholinergic functions were determined by measuring the behavioural and neurochemical responses to nicotinic and muscarinic receptor agonists. KEY RESULTS The improvement by galantamine of social isolation-induced PPI deficits was blocked by scopolamine, a non-selective muscarinic antagonist, and telenzepine, a preferential M1 receptor antagonist. Activation of M1 receptors improved social isolation-induced PPI deficits. Social isolation did not affect choline acetyltransferase and acetylcholinesterase activities in the prefrontal cortex and hippocampus, but it reduced the locomotor-suppressive response to muscarinic agonist oxotremorine, but not to nicotine. The isolation also attenuated the M1 receptor agonist N-desmethylclozapine-induced increase in prefrontal dopamine release. CONCLUSIONS AND IMPLICATIONS Galantamine improves PPI deficits of mice reared in social isolation via activation of M1 receptors. Social isolation reduces the muscarinic, especially M1, receptor function and this is involved in PPI deficits. PMID:20958289

Agmatine improves locomotor function and reduces tissue damage following spinal cord injury.

PubMed

Yu, C G; Marcillo, A E; Fairbanks, C A; Wilcox, G L; Yezierski, R P

2000-09-28

Clinically effective drug treatments for spinal cord injury (SCI) remain unavailable. Agmatine, an NMDA receptor antagonist and inhibitor of nitric oxide synthase (NOS), is an endogenous neuromodulator found in the brain and spinal cord. Evidence is presented that agmatine significantly improves locomotor function and reduces tissue damage following traumatic SCI in rats. The results suggest the importance of future therapeutic strategies encompassing the use of single drugs with multiple targets for the treatment of acute SCI. The therapeutic targets of agmatine (NMDA receptor and NOS) have been shown to be critically linked to the pathophysiological sequelae of CNS injury and this, combined with the non-toxic profile, lends support to agmatine being considered as a potential candidate for future clinical applications.

Unexpected recovery after robotic locomotor training at physiologic stepping speed: a single-case design.

PubMed

Spiess, Martina R; Jaramillo, Jeffrey P; Behrman, Andrea L; Teraoka, Jeffrey K; Patten, Carolynn

2012-08-01

To investigate the effect of walking speed on the emergence of locomotor electromyogram (EMG) patterns in an individual with chronic incomplete spinal cord injury (SCI), and to determine whether central pattern generator activity during robotic locomotor training (RLT) transfers to volitional EMG activity during overground walking. Single-case (B-A-B; experimental treatment-withdrawal-experimental treatment) design. Freestanding rehabilitation research center. A 50-year-old man who was nonambulatory for 16 months after incomplete SCI (sub-T11). The participant completed two 6-week blocks of RLT, training 4 times per week for 30 minutes per session at walking speeds up to 5km/h (1.4m/s) over continuous bouts lasting up to 17 minutes. Surface EMG was recorded weekly during RLT and overground walking. The Walking Index for Spinal Cord Injury (WISCI-II) was assessed daily during training blocks. During week 4, reciprocal, patterned EMG emerged during RLT. EMG amplitude modulation revealed a curvilinear relationship over the range of walking speeds from 1.5 to 5km/h (1.4m/s). Functionally, the participant improved from being nonambulatory (WISCI-II 1/20), to walking overground with reciprocal stepping using knee-ankle-foot orthoses and a walker (WISCI-II 9/20). EMG was also observed during overground walking. These functional gains were maintained greater than 4 years after locomotor training (LT). Here we report an unexpected course of locomotor recovery in an individual with chronic incomplete SCI. Through RLT at physiologic walking speeds, it was possible to activate the central pattern generator even 16 months postinjury. Further, to a certain degree, improvements from RLT transferred to overground walking. Our results suggest that LT-induced changes affect the central pattern generator and allow supraspinal inputs to engage residual spinal pathways. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Locomotor activity modulates associative learning in mouse cerebellum.

PubMed

Albergaria, Catarina; Silva, N Tatiana; Pritchett, Dominique L; Carey, Megan R

2018-05-01

Changes in behavioral state can profoundly influence brain function. Here we show that behavioral state modulates performance in delay eyeblink conditioning, a cerebellum-dependent form of associative learning. Increased locomotor speed in head-fixed mice drove earlier onset of learning and trial-by-trial enhancement of learned responses that were dissociable from changes in arousal and independent of sensory modality. Eyelid responses evoked by optogenetic stimulation of mossy fiber inputs to the cerebellum, but not at sites downstream, were positively modulated by ongoing locomotion. Substituting prolonged, low-intensity optogenetic mossy fiber stimulation for locomotion was sufficient to enhance conditioned responses. Our results suggest that locomotor activity modulates delay eyeblink conditioning through increased activation of the mossy fiber pathway within the cerebellum. Taken together, these results provide evidence for a novel role for behavioral state modulation in associative learning and suggest a potential mechanism through which engaging in movement can improve an individual's ability to learn.

Effects of repeated walking in a perturbing environment: a 4-day locomotor learning study.

PubMed

Blanchette, Andreanne; Moffet, Helene; Roy, Jean-Sébastien; Bouyer, Laurent J

2012-07-01

Previous studies have shown that when subjects repeatedly walk in a perturbing environment, initial movement error becomes smaller, suggesting that retention of the adapted locomotor program occurred (learning). It has been proposed that the newly learned locomotor program may be stored separately from the baseline program. However, how locomotor performance evolves with repeated sessions of walking with the perturbation is not yet known. To address this question, 10 healthy subjects walked on a treadmill on 4 consecutive days. Each day, locomotor performance was measured using kinematics and surface electromyography (EMGs), before, during, and after exposure to a perturbation, produced by an elastic tubing that pulled the foot forward and up during swing, inducing a foot velocity error in the first strides. Initial movement error decreased significantly between days 1 and 2 and then remained stable. Associated changes in medial hamstring EMG activity stabilized only on day 3, however. Aftereffects were present after perturbation removal, suggesting that daily adaptation involved central command recalibration of the baseline program. Aftereffects gradually decreased across days but were still visible on day 4. Separation between the newly learned and baseline programs may take longer than suggested by the daily improvement in initial performance in the perturbing environment or may never be complete. These results therefore suggest that reaching optimal performance in a perturbing environment should not be used as the main indicator of a completed learning process, as central reorganization of the motor commands continues days after initial performance has stabilized.

Stimulation of the mesencephalic locomotor region for gait recovery after stroke.

PubMed

Fluri, Felix; Malzahn, Uwe; Homola, György A; Schuhmann, Michael K; Kleinschnitz, Christoph; Volkmann, Jens

2017-11-01

One-third of all stroke survivors are unable to walk, even after intensive physiotherapy. Thus, other concepts to restore walking are needed. Because electrical stimulation of the mesencephalic locomotor region (MLR) is known to elicit gait movements, this area might be a promising target for restorative neurostimulation in stroke patients with gait disability. The present study aims to delineate the effect of high-frequency stimulation of the MLR (MLR-HFS) on gait impairment in a rodent stroke model. Male Wistar rats underwent photothrombotic stroke of the right sensorimotor cortex and chronic implantation of a stimulating electrode into the right MLR. Gait was assessed using clinical scoring of the beam-walking test and video-kinematic analysis (CatWalk) at baseline and on days 3 and 4 after experimental stroke with and without MLR-HFS. Kinematic analysis revealed significant changes in several dynamic and static gait parameters resulting in overall reduced gait velocity. All rats exhibited major coordination deficits during the beam-walking challenge and were unable to cross the beam. Simultaneous to the onset of MLR-HFS, a significantly higher walking speed and improvements in several dynamic gait parameters were detected by the CatWalk system. Rats regained the ability to cross the beam unassisted, showing a reduced number of paw slips and misses. MLR-HFS can improve disordered locomotor function in a rodent stroke model. It may act by shielding brainstem and spinal locomotor centers from abnormal cortical input after stroke, thus allowing for compensatory and independent action of these circuits. Ann Neurol 2017;82:828-840. © 2017 American Neurological Association.

Olanzapine treatment and metabolic dysfunction: a dose response study in female Sprague Dawley rats.

PubMed

Weston-Green, Katrina; Huang, Xu-Feng; Deng, Chao

2011-03-01

Second generation antipsychotics are commonly prescribed for the treatment of schizophrenia, however some can induce metabolic dysfunction side-effects such as weight gain, obesity and diabetes. Clinical reports suggest olanzapine alters satiety signals, although findings appear conflicting. Previous animal model studies have utilised a range of olanzapine dosages, however the dosage that better mimics the human scenario of olanzapine-induced weight gain is unclear. Female Sprague-Dawley rats were treated orally, three times daily with olanzapine (0.25mg/kg, 0.5mg/kg, 1.0mg/kg, 2.0mg/kg), self-administered in a sweet cookie dough pellet at eight-hourly intervals) or vehicle (n=12/group) for 14-days. Olanzapine orally self-administered in multiple doses (eight-hourly intervals) may circumvent a drop in plasma drug concentration and ensure the maintenance of a consistently high olanzapine level in the rat. Olanzapine increased body weight (0.5mg/kg, 1.0mg/kg, 2.0mg/kg), food intake (2.0mg/kg) and feeding efficiency (0.5-2.0mg/kg), with no effect on water intake. Subcutaneous inguinal (1.0mg/kg, 2.0mg/kg) and intra-abdominal perirenal fat were increased (2.0mg/kg), but not interscapula brown adipose tissue. Olanzapine increased circulating ghrelin and cholecystokinin, but had no effect on peptide YY((3-36)). Olanzapine decreased insulin (0.25-2.0mg/kg) and locomotor activity in the open field arena (0.5-2.0mg/kg). A low dosage of 0.25mg/kg olanzapine had no effect on most parameters measured. Olanzapine-induced weight gain is associated with hyperphagia, enhanced feeding efficiency and adiposity, decreased locomotor activity and altered satiety signaling. The animal model used in the present study of self-administered oral olanzapine treatment (t.i.d.) at a dosage range of 0.5-2.0mg/kg (but not 0.25mg/kg) mimics aspects of the clinic. Copyright © 2010 Elsevier B.V. All rights reserved.

GLYX-13 Ameliorates Schizophrenia-Like Phenotype Induced by MK-801 in Mice: Role of Hippocampal NR2B and DISC1

PubMed Central

Zhou, Dongsheng; Lv, Dan; Wang, Zhen; Zhang, Yanhua; Chen, Zhongming; Wang, Chuang

2018-01-01

Background: Evidence supports that the hypofunction of N-methyl-D-aspartate receptor (NMDAR) and downregulation of disrupted-in-schizophrenia 1 (DISC1) contribute to the pathophysiology of schizophrenia. N-Methyl D-aspartate receptor subtype 2B (NR2B)-containing NMDAR are associated with cognitive dysfunction in schizophrenia. GLYX-13 is an NMDAR glycine-site functional partial agonist and cognitive enhancer that does not induce psychotomimetic side effects. However, it remains unclear whether NR2B plays a critical role in the GLYX-13-induced alleviation of schizophrenia-like behaviors in mice. Methods: The effect of GLYX-13 was tested by observing changes in locomotor activity, novel object recognition ability, and prepulse inhibition (PPI) induced by dizocilpine (known as MK-801) in mice. Lentivirus-mediated NR2B knockdown in the hippocampus was assessed to confirm the role of NR2B in GLYX-13 pathophysiology, using Western blots and immunohistochemistry. Results: The systemic administration of GLYX-13 (0.5 and 1 mg/kg, i.p.) ameliorates MK-801 (0.5 mg/kg, i.p.)-induced hyperlocomotion, deficits in memory, and PPI in mice. Additionally, GLYX-13 normalized the MK-801-induced alterations in signaling molecules, including NR2B and DISC1 in the hippocampus. Furthermore, we found that NR2B knockdown produced memory and PPI deficits without any changes in locomotor activity. Notably, DISC1 levels significantly decreased by NR2B knockdown. However, the effective dose of GLYX-13 did not alleviate the memory and PPI dysfunctions or downregulation of DISC1 induced by NR2B knockdown. Conclusion: Our results suggest GLYX-13 as a candidate for schizophrenia treatment, and NR2B and DISC1 in the hippocampus may account for the molecular mechanisms of GLYX-13. PMID:29695955

Pantethine rescues a Drosophila model for pantothenate kinase–associated neurodegeneration

PubMed Central

Rana, Anil; Seinen, Erwin; Siudeja, Katarzyna; Muntendam, Remco; Srinivasan, Balaji; van der Want, Johannes J.; Hayflick, Susan; Reijngoud, Dirk-Jan; Kayser, Oliver; Sibon, Ody C. M.

2010-01-01

Pantothenate kinase–associated neurodegeneration (PKAN), a progressive neurodegenerative disorder, is associated with impairment of pantothenate kinase function. Pantothenate kinase is the first enzyme required for de novo synthesis of CoA, an essential metabolic cofactor. The pathophysiology of PKAN is not understood, and there is no cure to halt or reverse the symptoms of this devastating disease. Recently, we and others presented a PKAN Drosophila model, and we demonstrated that impaired function of pantothenate kinase induces a neurodegenerative phenotype and a reduced lifespan. We have explored this Drosophila model further and have demonstrated that impairment of pantothenate kinase is associated with decreased levels of CoA, mitochondrial dysfunction, and increased protein oxidation. Furthermore, we searched for compounds that can rescue pertinent phenotypes of the Drosophila PKAN model and identified pantethine. Pantethine feeding restores CoA levels, improves mitochondrial function, rescues brain degeneration, enhances locomotor abilities, and increases lifespan. We show evidence for the presence of a de novo CoA biosynthesis pathway in which pantethine is used as a precursor compound. Importantly, this pathway is effective in the presence of disrupted pantothenate kinase function. Our data suggest that pantethine may serve as a starting point to develop a possible treatment for PKAN. PMID:20351285

Anti-Parkinson Activity of Petroleum Ether Extract of Ficus religiosa (L.) Leaves

PubMed Central

Bhangale, Jitendra O.; Acharya, Sanjeev R.

2016-01-01

In the present study, we evaluated anti-Parkinson's activity of petroleum ether extract of Ficus religiosa (PEFRE) leaves in haloperidol and 6 hydroxydopamine (6-OHDA) induced experimental animal models. In this study, effects of Ficus religiosa (100, 200, and 400 mg/kg, p.o.) were studied using in vivo behavioral parameters like catalepsy, muscle rigidity, and locomotor activity and its effects on neurochemical parameters (MDA, CAT, SOD, and GSH) in rats. The experiment was designed by giving haloperidol to induce catalepsy and 6-OHDA to induce Parkinson's disease-like symptoms. The increased cataleptic scores (induced by haloperidol) were significantly (p < 0.001) found to be reduced, with the PEFRE at a dose of 200 and 400 mg/kg (p.o.). 6-OHDA significantly induced motor dysfunction (muscle rigidity and hypolocomotion). 6-OHDA administration showed significant increase in lipid peroxidation level and depleted superoxide dismutase, catalase, and reduced glutathione level. Daily administration of PEFRE (400 mg/kg) significantly improved motor performance and also significantly attenuated oxidative damage. Thus, the study proved that Ficus religiosa treatment significantly attenuated the motor defects and also protected the brain from oxidative stress. PMID:26884755

Adipose-derived Stem Cells Stimulated with n-Butylidenephthalide Exhibit Therapeutic Effects in a Mouse Model of Parkinson's Disease.

PubMed

Chi, Kang; Fu, Ru-Huei; Huang, Yu-Chuen; Chen, Shih-Yin; Hsu, Ching-Ju; Lin, Shinn-Zong; Tu, Chi-Tang; Chang, Li-Hsun; Wu, Ping-An; Liu, Shih-Ping

2018-03-01

Parkinson's disease (PD) causes motor dysfunction and dopaminergic cell death. Drug treatments can effectively reduce symptoms but often cause unwanted side effects. Stem cell therapies using cell replacement or indirect beneficial secretomes have recently emerged as potential therapeutic strategies. Although various types of stem cells have been proposed as possible candidates, adipose-derived stem cells (ADSCs) are easily obtainable, more abundant, less ethically disputed, and able to differentiate into multiple cell lineages. However, treatment of PD using adult stem cells is known to be less efficacious than neuron or embryonic stem cell transplantation. Therefore, improved therapies are urgently needed. n-Butylidenephthalide (BP), which is extracted from Angelica sinensis, has been shown to have anti-inflammatory and neuroprotective effects. Indeed, we previously demonstrated that BP treatment of ADSCs enhances the expression of neurogenesis and homing factors such as nuclear receptor related 1 protein, stromal-derived factor 1, and brain-derived neurotrophic factor. In the present study, we examined the ability of BP-pretreated ADSC transplantation to improve PD motor symptoms and protect dopamine neurons in a mouse model of PD. We evaluated the results using neuronal behavior tests such as beam walking, rotarod, and locomotor activity tests. ADSCs with or without BP pretreatment were transplanted into the striatum. Our findings demonstrated that ADSC transplantation improved motor abilities with varied efficacies and that BP stimulation improved the therapeutic effects of transplantation. Dopaminergic cell numbers returned to normal in ADSC-transplanted mice after 22 d. In summary, stimulating ADSCs with BP improved PD recovery efficiency. Thus, our results provide important new strategies to improve stem cell therapies for neurodegenerative diseases in future studies.

Locomotor Adaptation Improves Balance Control, Multitasking Ability and Reduces the Metabolic Cost of Postural Instability

NASA Technical Reports Server (NTRS)

Bloomberg, J. J.; Peters, B. T.; Mulavara, A. P.; Brady, R. A.; Batson, C. D.; Miller, C. A.; Ploutz-Snyder, R. J.; Guined, J. R.; Buxton, R. E.; Cohen, H. S.

2011-01-01

During exploration-class missions, sensorimotor disturbances may lead to disruption in the ability to ambulate and perform functional tasks during the initial introduction to a novel gravitational environment following a landing on a planetary surface. The overall goal of our current project is to develop a sensorimotor adaptability training program to facilitate rapid adaptation to these environments. We have developed a unique training system comprised of a treadmill placed on a motion-base facing a virtual visual scene. It provides an unstable walking surface combined with incongruent visual flow designed to enhance sensorimotor adaptability. Greater metabolic cost incurred during balance instability means more physical work is required during adaptation to new environments possibly affecting crewmembers? ability to perform mission critical tasks during early surface operations on planetary expeditions. The goal of this study was to characterize adaptation to a discordant sensory challenge across a number of performance modalities including locomotor stability, multi-tasking ability and metabolic cost. METHODS: Subjects (n=15) walked (4.0 km/h) on a treadmill for an 8 -minute baseline walking period followed by 20-minutes of walking (4.0 km/h) with support surface motion (0.3 Hz, sinusoidal lateral motion, peak amplitude 25.4 cm) provided by the treadmill/motion-base system. Stride frequency and auditory reaction time were collected as measures of locomotor stability and multi-tasking ability, respectively. Metabolic data (VO2) were collected via a portable metabolic gas analysis system. RESULTS: At the onset of lateral support surface motion, subj ects walking on our treadmill showed an increase in stride frequency and auditory reaction time indicating initial balance and multi-tasking disturbances. During the 20-minute adaptation period, balance control and multi-tasking performance improved. Similarly, throughout the 20-minute adaptation period, VO2 gradually decreased following an initial increase after the onset of support surface motion. DISCUSSION: Resu lts confirmed that walking in discordant conditions not only compromises locomotor stability and the ability to multi-task, but comes at a quantifiable metabolic cost. Importantly, like locomotor stability and multi-tasking ability, metabolic expenditure while walking in discordant sensory conditions improved during adaptation. This confirms that sensorimotor adaptability training can benefit multiple performance parameters central to the successful completion of critical mission tasks.

Improvements in bladder, bowel and sexual outcomes following task-specific locomotor training in human spinal cord injury.

PubMed

Hubscher, Charles H; Herrity, April N; Williams, Carolyn S; Montgomery, Lynnette R; Willhite, Andrea M; Angeli, Claudia A; Harkema, Susan J

2018-01-01

Locomotor training (LT) as a therapeutic intervention following spinal cord injury (SCI) is an effective rehabilitation strategy for improving motor outcomes, but its impact on non-locomotor functions is unknown. Given recent results of our labs' pre-clinical animal SCI LT studies and existing overlap of lumbosacral spinal circuitries controlling pelvic-visceral and locomotor functions, we addressed whether LT can improve bladder, bowel and sexual function in humans at chronic SCI time-points (> two years post-injury). Prospective cohort study; pilot trial with small sample size. Eight SCI research participants who were undergoing 80 daily one-hour sessions of LT on a treadmill using body-weight support, or one-hour of LT and stand training on alternate days, as part of another research study conducted at the Kentucky Spinal Cord Injury Research Center, University of Louisville, were enrolled in this pilot trial. Urodynamic assessments were performed and International Data Set questionnaire forms completed for bladder, bowel and sexual functions at pre-and post-training time points. Four usual care (non-trained; regular at-home routine) research participants were also enrolled in this study and had the same assessments collected twice, at least 3 months apart. Filling cystometry documented significant increases in bladder capacity, voiding efficiency and detrusor contraction time as well as significant decreases in voiding pressure post-training relative to baseline. Questionnaires revealed a decrease in the frequency of nocturia and urinary incontinence for several research participants as well as a significant decrease in time required for defecation and a significant increase in sexual desire post-training. No significant differences were found for usual care research participants. These results suggest that an appropriate level of sensory information provided to the spinal cord, generated through task-specific stepping and/or loading, can positively benefit the neural circuitries controlling urogenital and bowel functions. ClinicalTrials.gov NCT03036527.

Improvements in bladder, bowel and sexual outcomes following task-specific locomotor training in human spinal cord injury

PubMed Central

Williams, Carolyn S.; Montgomery, Lynnette R.; Willhite, Andrea M.; Angeli, Claudia A.; Harkema, Susan J.

2018-01-01

Objective Locomotor training (LT) as a therapeutic intervention following spinal cord injury (SCI) is an effective rehabilitation strategy for improving motor outcomes, but its impact on non-locomotor functions is unknown. Given recent results of our labs’ pre-clinical animal SCI LT studies and existing overlap of lumbosacral spinal circuitries controlling pelvic-visceral and locomotor functions, we addressed whether LT can improve bladder, bowel and sexual function in humans at chronic SCI time-points (> two years post-injury). Study design Prospective cohort study; pilot trial with small sample size. Methods Eight SCI research participants who were undergoing 80 daily one-hour sessions of LT on a treadmill using body-weight support, or one-hour of LT and stand training on alternate days, as part of another research study conducted at the Kentucky Spinal Cord Injury Research Center, University of Louisville, were enrolled in this pilot trial. Urodynamic assessments were performed and International Data Set questionnaire forms completed for bladder, bowel and sexual functions at pre-and post-training time points. Four usual care (non-trained; regular at-home routine) research participants were also enrolled in this study and had the same assessments collected twice, at least 3 months apart. Results Filling cystometry documented significant increases in bladder capacity, voiding efficiency and detrusor contraction time as well as significant decreases in voiding pressure post-training relative to baseline. Questionnaires revealed a decrease in the frequency of nocturia and urinary incontinence for several research participants as well as a significant decrease in time required for defecation and a significant increase in sexual desire post-training. No significant differences were found for usual care research participants. Conclusions These results suggest that an appropriate level of sensory information provided to the spinal cord, generated through task-specific stepping and/or loading, can positively benefit the neural circuitries controlling urogenital and bowel functions. Trial registration ClinicalTrials.gov NCT03036527 PMID:29385166

Examination of the Combined Effects of Chondroitinase ABC, Growth Factors and Locomotor Training following Compressive Spinal Cord Injury on Neuroanatomical Plasticity and Kinematics

PubMed Central

Alluin, Olivier; Fehlings, Michael G.; Rossignol, Serge; Karimi-Abdolrezaee, Soheila

2014-01-01

While several cellular and pharmacological treatments have been evaluated following spinal cord injury (SCI) in animal models, it is increasingly recognized that approaches to address the glial scar, including the use of chondroitinase ABC (ChABC), can facilitate neuroanatomical plasticity. Moreover, increasing evidence suggests that combinatorial strategies are key to unlocking the plasticity that is enabled by ChABC. Given this, we evaluated the anatomical and functional consequences of ChABC in a combinatorial approach that also included growth factor (EGF, FGF2 and PDGF-AA) treatments and daily treadmill training on the recovery of hindlimb locomotion in rats with mid thoracic clip compression SCI. Using quantitative neuroanatomical and kinematic assessments, we demonstrate that the combined therapy significantly enhanced the neuroanatomical plasticity of major descending spinal tracts such as corticospinal and serotonergic-spinal pathways. Additionally, the pharmacological treatment attenuated chronic astrogliosis and inflammation at and adjacent to the lesion with the modest synergistic effects of treadmill training. We also observed a trend for earlier recovery of locomotion accompanied by an improvement of the overall angular excursions in rats treated with ChABC and growth factors in the first 4 weeks after SCI. At the end of the 7-week recovery period, rats from all groups exhibited an impressive spontaneous recovery of the kinematic parameters during locomotion on treadmill. However, although the combinatorial treatment led to clear chronic neuroanatomical plasticity, these structural changes did not translate to an additional long-term improvement of locomotor parameters studied including hindlimb-forelimb coupling. These findings demonstrate the beneficial effects of combined ChABC, growth factors and locomotor training on the plasticity of the injured spinal cord and the potential to induce earlier neurobehavioral recovery. However, additional approaches such as stem cell therapies or a more adapted treadmill training protocol may be required to optimize this repair strategy in order to induce sustained functional locomotor improvement. PMID:25350665

The "beneficial" effects of locomotor training after various types of spinal lesions in cats and rats.

PubMed

Rossignol, Serge; Martinez, Marina; Escalona, Manuel; Kundu, Aritra; Delivet-Mongrain, Hugo; Alluin, Olivier; Gossard, Jean-Pierre

2015-01-01

This chapter reviews a number of experiments on the recovery of locomotion after various types of spinal lesions and locomotor training mainly in cats. We first recall the major evidence on the recovery of hindlimb locomotion in completely spinalized cats at the T13 level and the role played by the spinal locomotor network, also known as the central pattern generator, as well as the beneficial effects of locomotor training on this recovery. Having established that hindlimb locomotion can recover, we raise the issue as to whether spinal plastic changes could also contribute to the recovery after partial spinal lesions such as unilateral hemisections. We found that after such hemisection at T10, cats could recover quadrupedal locomotion and that deficits could be improved by training. We further showed that, after a complete spinalization a few segments below the first hemisection (at T13, i.e., the level of previous studies on spinalization), cats could readily walk with the hindlimbs within hours of completely severing the remaining spinal tracts and not days as is usually the case with only a single complete spinalization. This suggests that neuroplastic changes occurred below the first hemisection so that the cat was already primed to walk after the spinalization subsequent to the hemispinalization 3 weeks before. Of interest is the fact that some characteristic kinematic features in trained or untrained hemispinalized cats could remain after complete spinalization, suggesting that spinal changes induced by training could also be durable. Other studies on reflexes and on the pattern of "fictive" locomotion recorded after curarization corroborate this view. More recent work deals with training cats in more demanding situations such as ladder treadmill (vs. flat treadmill) to evaluate how the locomotor training regimen can influence the spinal cord. Finally, we report our recent studies in rats using compressive lesions or surgical complete spinalization and find that some principles of locomotor recovery in cats also apply to rats when adequate locomotor training is provided. © 2015 Elsevier B.V. All rights reserved.

Chronic choline supplementation improves cognitive and motor performance via modulating oxidative and neurochemical status in rats.

PubMed

Tabassum, Saiqa; Haider, Saida; Ahmad, Saara; Madiha, Syeda; Parveen, Tahira

2017-08-01

Choline, an essential nutrient, accounts for multiple functions in the body and brain. While its beneficial effects on healthy adults are not clear, choline supplementation is important during pregnancy for brain development, in elderly patients for support of cognitive performance and in patients with neurological disorders to reduce memory deficits. Thus, the aim of this study is to investigate whether choline administration in healthy adult rats beneficially impacts cognitive and locomotor performance, and associated oxidative and neurochemical outcomes. Two groups, control and choline, received tap water and choline bitartrate, respectively at the dose equivalent to adequate intake for five weeks. Food intake and body weight were monitored daily. Behavioral analysis comprising assessment of cognitive performance (by novel object recognition, passive avoidance and Morris Water Maze test) and locomotor performance (by Open field, Kondziela's inverted screen and beam walking test) were performed. Following testing, rats were decapitated and brain samples were collected for estimation of acetylcholine, redox profile and monoamine measurements. The results showed that chronic choline administration significantly improves cognitive and locomotor performance accompanied by a reduction in oxidative stress, enhanced cholinergic neurotransmission and monoamine levels in the brain of healthy adult rats. Hence, chronic choline intake was found to improve behavioral, oxidative and neurochemical outcomes in the normal population, so it can be suggested that choline tablets can be used as a safe and effective supplement for improving the neurological health of normal individuals and that they might also be beneficial in preventing cognitive and motor disorders later in life. Copyright © 2017 Elsevier Inc. All rights reserved.

Circadian rhythm resynchronization improved isoflurane-induced cognitive dysfunction in aged mice.

PubMed

Song, Jia; Chu, Shuaishuai; Cui, Yin; Qian, Yue; Li, Xiuxiu; Xu, Fangxia; Shao, Xueming; Ma, Zhengliang; Xia, Tianjiao; Gu, Xiaoping

2018-04-13

Postoperative cognitive dysfunction (POCD) is a common clinical phenomenon characterized by cognitive deficits in patients after anesthesia and surgery. Advanced age is a significant independent risk factor for POCD. We previously reported that in young mice, sleep-wake rhythm is involved in the isoflurane-induced memory impairment. In present study, we sought to determine whether advanced age increased the risk of POCD through aggravated and prolonged post-anesthetic circadian disruption in the elderly. We constructed POCD model by submitting the mice to 5-h 1.3% isoflurane anesthesia from Zeitgeber Time (ZT) 14 to ZT19. Under novel object recognition assay (NOR) and Morris water maze (MWM) test, We found 5-h isoflurane anesthesia impaired the cognition of young mice for early 3 days after anesthesia but damaged the aged for at least 1 week. With Mini-Mitter continuously monitoring, a 3.22 ± 0.75 h gross motor activity acrophase delay was manifested in young mice on D1, while in the aged mice, the gross motor activity phase shift lasted for 3 days, consistent with the body temperature rhythm trends of change. Melatonin has been considered as an effective remedy for circadian rhythm shift. In aged mice, melatonin was pretreated intragastrically at the dose of 10 mg/kg daily for 7 consecutive days before anesthesia. We found that melatonin prevented isoflurane-induced cognitive impairments by restoring the locomotor activity and temperature circadian rhythm via clock gene resynchronization. Overall, these results indicated that Long-term isoflurane anesthesia induced more aggravated and prolonged memory deficits and circadian rhythms disruption in aged mice. Melatonin could prevent isoflurane-induced cognitive impairments by circadian rhythm resynchronization. Copyright © 2018. Published by Elsevier Inc.

Perturbation schedule does not alter retention of a locomotor adaptation across days.

PubMed

Hussain, Sara J; Morton, Susanne M

2014-06-15

Motor adaptation in response to gradual vs. abrupt perturbation schedules may involve different neural mechanisms, potentially leading to different levels of motor memory. However, no study has investigated whether perturbation schedules alter memory of a locomotor adaptation across days. We measured adaptation and retention (memory) of altered interlimb symmetry during walking in two groups of participants over 2 days. On day 1, participants adapted to either a single, large perturbation (abrupt schedule) or a series of small perturbations that increased in size over time (gradual schedule). Retention was examined on day 2. On day 1, initial swing time and foot placement symmetry error sizes differed between groups but overall adaptation magnitudes were similar. On day 2, participants in both groups showed similar retention, readaptation, and aftereffect sizes, although there were some trends for improved memory in the abrupt group. These results conflict with previous data but are consistent with newer studies reporting no behavioral differences following adaptation using abrupt vs. gradual schedules. Although memory levels were very similar between groups, we cannot rule out the possibility that the neural mechanisms underlying this memory storage differ. Overall, it appears that adaptation of locomotor patterns via abrupt and gradual perturbation schedules produces similar expression of locomotor memories across days. Copyright © 2014 the American Physiological Society.

A longitudinal study on gross motor development in children with learning disorders.

PubMed

Westendorp, Marieke; Hartman, Esther; Houwen, Suzanne; Huijgen, Barbara C H; Smith, Joanne; Visscher, Chris

2014-02-01

This longitudinal study examined the development of gross motor skills, and sex-differences therein, in 7- to 11-years-old children with learning disorders (LD) and compared the results with typically developing children to determine the performance level of children with LD. In children with LD (n=56; 39 boys, 17 girls), gross motor skills were assessed with the Test of Gross Motor Development-2 and measured annually during a 3-year period. Motor scores of 253 typically developing children (125 boys, 112 girls) were collected for references values. The multilevel analyses showed that the ball skills of children with LD improved with age (p<.001), especially between 7 and 9 years, but the locomotor skills did not (p=.50). Boys had higher ball skill scores than girls (p=.002) and these differences were constant over time. Typically developing children outperformed the children with LD on the locomotor skills and ball skills at all ages, except the locomotor skills at age 7. Children with LD develop their ball skills later in the primary school-period compared to typically developing peers. However, 11 year-old children with LD had a lag in locomotor skills and ball skills of at least four and three years, respectively, compared to their peers. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Group 2 Metabotropic Glutamate Receptor Agonist LY379268 Rescues Neuronal, Neurochemical and Motor Abnormalities in R6/2 Huntington’s Disease Mice

PubMed Central

Reiner, A.; Lafferty, D.C.; Wang, H.B.; Del Mar, N.; Deng, Y.P.

2012-01-01

Excitotoxic injury to striatum by dysfunctional cortical input or aberrant glutamate uptake may contribute to Huntington’s Disease (HD) pathogenesis. Since corticostriatal terminals possess mGluR2/3 autoreceptors, whose activation dampens glutamate release, we tested the ability of the mGluR2/3 agonist LY379268 to improve the phenotype in R6/2 HD mice with 120–125 CAG repeats. Daily subcutaneous injection of a maximum tolerated dose (MTD) of LY379268 (20mg/kg) had no evident adverse effects in WT mice, and diverse benefits in R6/2 mice, both in a cohort of mice tested behaviorally until the end of R6/2 lifespan and in a cohort sacrificed at 10 weeks of age for blinded histological analysis. MTD LY379268 yielded a significant 11% increase in R6/2 survival, an improvement on rotarod, normalization and/or improvement in locomotor parameters measured in open field (activity, speed, acceleration, endurance, and gait), a rescue of a 15–20% cortical and striatal neuron loss, normalization of SP striatal neuron neurochemistry, and to a lesser extent enkephalinergic striatal neuron neurochemistry. Deficits were greater in male than female R6/2 mice, and drug benefit tended to be greater in males. The improvements in SP striatal neurons, which facilitate movement, are consistent with the improved movement in LY379268-treated R6/2 mice. Our data indicate that mGluR2/3 agonists may be particularly useful for ameliorating the morphological, neurochemical and motor defects observed in HD. PMID:22472187

[Application of locomotor activity test to evaluate functional injury after global cerebral ischemia in C57BL/6 mice].

PubMed

Zhang, Li-quan; Xu, Jia-ni; Wang, Zhen-zhen; Zeng, Li-jun; Ye, Yi-lu; Zhang, Wei-ping; Wei, Er-qing; Zhang, Qi

2014-05-01

To evaluate the application of locomotor activity test in functional injury after global cerebral ischemia (GCI) in C57BL/6 mice. GCI was induced by bilateral carotid arteries occlusion for 30 min in C57BL/6 mice. Mice were divided into sham group, GCI group and minocycline group. Saline or minocycline (45 mg/kg) was i.p. injected once daily for 6 d after ischemia. At Day 6 after ischemia, locomotor activity was recorded for 1 h in open field test. Total distance, central distance, central distance ratio, periphery distance, periphery distance ratio, central time and periphery time were used to evaluate the behavior characteristics of locomotor activity in C57BL/6 mice after ischemia. The survival neuron density was detected by Nissl staining in hippocampus, cortex and striatum. Compared with sham group, total distance, central distance and central time increased and periphery time decreased in C57BL/6 mice after GCI (Ps<0.05). However, minocycline significantly reduced the central distance and central time and increased the periphery time (Ps<0.05). Neurons were damaged in hippocampus, cortex and striatum after GCI, which manifested by decreased neurons and the most serious damage in hippocampal CA1 region. Minocycline significantly improved the neuron appearance and increased the neuron number in hippocampus and striatum (P<0.001 or P<0.05). Locomotor activity in open field test can objectively evaluate the behavior injury after GCI in mice. Central distance and central time can be used as indexes of quantitative assessment.

Cannabidiol-treated rats exhibited higher motor score after cryogenic spinal cord injury.

PubMed

Kwiatkoski, Marcelo; Guimarães, Francisco Silveira; Del-Bel, Elaine

2012-04-01

Cannabidiol (CBD), a non-psychoactive constituent of cannabis, has been reported to induce neuroprotective effects in several experimental models of brain injury. We aimed at investigating whether this drug could also improve locomotor recovery of rats submitted to spinal cord cryoinjury. Rats were distributed into five experimental groups. Animals were submitted to laminectomy in vertebral segment T10 followed or not by application of liquid nitrogen for 5 s into the spinal cord at the same level to cause cryoinjury. The animals received injections of vehicle or CBD (20 mg/kg) immediately before, 3 h after and daily for 6 days after surgery. The Basso, Beattie, and Bresnahan motor evaluation test was used to assess motor function post-lesion one day before surgery and on the first, third, and seventh postoperative days. The extent of injury was evaluated by hematoxylin-eosin histology and FosB expression. Cryogenic lesion of the spinal cord resulted in a significant motor deficit. Cannabidiol-treated rats exhibited a higher Basso, Beattie, and Bresnahan locomotor score at the end of the first week after spinal cord injury: lesion + vehicle, day 1: zero, day 7: four, and lesion + Cannabidiol 20 mg/kg, day 1: zero, day 7: seven. Moreover, at this moment there was a significant reduction in the extent of tissue injury and FosB expression in the ventral horn of the spinal cord. The present study confirmed that application of liquid nitrogen to the spinal cord induces reproducible and quantifiable spinal cord injury associated with locomotor function impairments. Cannabidiol improved locomotor functional recovery and reduced injury extent, suggesting that it could be useful in the treatment of spinal cord lesions.

Effects of serotonergic medications on locomotor performance in humans with incomplete spinal cord injury.

PubMed

Leech, Kristan A; Kinnaird, Catherine R; Hornby, T George

2014-08-01

Incomplete spinal cord injury (iSCI) often results in significant motor impairments that lead to decreased functional mobility. Loss of descending serotonergic (5HT) input to spinal circuits is thought to contribute to motor impairments, with enhanced motor function demonstrated through augmentation of 5HT signaling. However, the presence of spastic motor behaviors in SCI is attributed, in part, to changes in spinal 5HT receptors that augment their activity in the absence of 5HT, although data demonstrating motor effects of 5HT agents that deactivate these receptors are conflicting. The effects of enhancement or depression of 5HT signaling on locomotor function have not been thoroughly evaluated in human iSCI. Therefore, the aim of the current study was to investigate acute effects of 5HT medications on locomotion in 10 subjects with chronic (>1 year) iSCI. Peak overground and treadmill locomotor performance, including measures of gait kinematics, electromyographic (EMG) activity, and oxygen consumption, were assessed before and after single-dose administration of either a selective serotonin reuptake inhibitor (SSRI) or a 5HT antagonist using a double-blinded, randomized, cross-over design. Results indicate that neither medication led to improvements in locomotion, with a significant decrease in peak overground gait speed observed after 5HT antagonists (from 0.8±0.1 to 0.7±0.1 m/s; p=0.01). Additionally, 5-HT medications had differential effects on EMG activity, with 5HT antagonists decreasing extensor activity and SSRIs increasing flexor activity. Our data therefore suggest that acute manipulation of 5HT signaling, despite changes in muscle activity, does not improve locomotor performance after iSCI.

Continuous tamoxifen delivery improves locomotor recovery 6h after spinal cord injury by neuronal and glial mechanisms in male rats.

PubMed

Colón, Jennifer M; González, Pablo A; Cajigas, Ámbar; Maldonado, Wanda I; Torrado, Aranza I; Santiago, José M; Salgado, Iris K; Miranda, Jorge D

2018-01-01

No treatment is available for patients with spinal cord injury (SCI). Patients often arrive to the hospital hours after SCI suggesting the need of a therapy that can be used on a clinically relevant window. Previous studies showed that Tamoxifen (TAM) treatment 24h after SCI benefits locomotor recovery in female rats. Tamoxifen exerts beneficial effects in male and female rodents but a gap of knowledge exists on: the therapeutic window of TAM, the spatio-temporal mechanisms activated and if this response is sexually dimorphic. We hypothesized that TAM will favor locomotor recovery when administered up-to 24h after SCI in male Sprague-Dawley rats. Rats received a thoracic (T10) contusion using the MACSIS impactor followed by placebo or TAM (15mg/21days) pellets in a therapeutic window of 0, 6, 12, or 24h. Animals were sacrificed at 2, 7, 14, 28 or 35days post injury (DPI) to study the molecular and cellular changes in the acute and chronic stages. Immediate or delayed therapy (t=6h) improved locomotor function, increased white matter spared tissue, and neuronal survival. TAM reduced reactive gliosis during chronic stages and increased the expression of Olig-2. A significant difference was observed in estrogen receptor alpha between male and female rodents from 2 to 28 DPI suggesting a sexually dimorphic characteristic that could be related to the behavioral differences observed in the therapeutic window of TAM. This study supports the use of TAM in the SCI setting due to its neuroprotective effects but with a significant sexually dimorphic therapeutic window. Copyright © 2017 Elsevier Inc. All rights reserved.

Cholinergic mechanisms in spinal locomotion—potential target for rehabilitation approaches

PubMed Central

Jordan, Larry M.; McVagh, J. R.; Noga, B. R.; Cabaj, A. M.; Majczyński, H.; Sławińska, Urszula; Provencher, J.; Leblond, H.; Rossignol, Serge

2014-01-01

Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Tests of these suggestions, however, reveal that the spinal cholinergic system plays little if any role in the induction of locomotion, because MLR-evoked locomotion in decerebrate cats is not prevented by cholinergic antagonists. Furthermore, it is not required for the development of stepping movements after spinal cord injury, because cholinergic agonists do not facilitate the appearance of locomotion after spinal cord injury, unlike the dramatic locomotion-promoting effects of clonidine, a noradrenergic α-2 agonist. Furthermore, cholinergic antagonists actually improve locomotor activity after spinal cord injury, suggesting that plastic changes in the spinal cholinergic system interfere with locomotion rather than facilitating it. Changes that have been observed in the cholinergic innervation of motoneurons after spinal cord injury do not decrease motoneuron excitability, as expected. Instead, the development of a “hyper-cholinergic” state after spinal cord injury appears to enhance motoneuron output and suppress locomotion. A cholinergic suppression of afferent input from the limb after spinal cord injury is also evident from our data, and this may contribute to the ability of cholinergic antagonists to improve locomotion. Not only is a role for the spinal cholinergic system in suppressing locomotion after SCI suggested by our results, but an obligatory contribution of a brainstem cholinergic relay to reticulospinal locomotor command systems is not confirmed by our experiments. PMID:25414645

The origin of bipedality as the result of a developmental by-product: The case study of the olive baboon (Papio anubis).

PubMed

Druelle, François; Aerts, Peter; Berillon, Gilles

2017-12-01

In this paper, we point to the importance of considering infancy in the emergence of new locomotor modes during evolution, and particularly when considering bipedal walking. Indeed, because infant primates commonly exhibit a more diverse posturo-locomotor repertoire than adults, the developmental processes of locomotion represent an important source of variation upon which natural selection may act. We have had the opportunity to follow the development of locomotion in captive individuals of a committed quadrupedal primate, the olive baboon (Papio anubis). We observed six infants at two different stages of their development. In total, we were able to analyze the temporal parameters of 65 bipedal steps, as well as their behavioral components. Our results show that while the basic temporal aspects of the bipedal walking gait (i.e., duty factor, dimensionless frequency, and hind lag) do not change during development, the baboon is able to significantly improve the coordination pattern between hind limbs. This probably influences the bout duration of spontaneous bipedal walking. During the same developmental stage, the interlimb coordination in quadrupedal walking is improved and the proportion of quadrupedal behaviors increases significantly. Therefore, the quadrupedal pattern of primates does not impede the developmental acquisition of bipedal behaviors. This may suggest that the same basic mechanism is responsible for controlling bipedal and quadrupedal locomotion, i.e., that in non-human primates, the neural networks for quadrupedal locomotion are also employed to perform (occasional) bipedal walking. In this context, a secondary locomotor mode (e.g., bipedalism) experienced during infancy as a by-product of locomotor development may lead to evolutionary novelties when under appropriate selective pressures. Copyright © 2017 Elsevier Ltd. All rights reserved.

Timing of Locomotor Recovery from Anoxia Modulated by the white Gene in Drosophila

PubMed Central

Xiao, Chengfeng; Robertson, R. Meldrum

2016-01-01

Locomotor recovery from anoxia follows the restoration of disordered ion distributions and neuronal excitability. The time taken for locomotor recovery after 30 sec anoxia (around 10 min) is longer than the time for the propagation of action potentials to be restored (<1 min) in Drosophila wild type. We report here that the white (w) gene modulates the timing of locomotor recovery. Wild-type flies displayed fast and consistent recovery of locomotion from anoxia, whereas mutants of w showed significantly delayed and more variable recovery. Genetic analysis including serial backcrossing revealed a strong association between the w locus and the timing of locomotor recovery, and haplo-insufficient function of w+ in promoting fast recovery. The locomotor recovery phenotype was independent of classic eye pigmentation, although both are associated with the w gene. Introducing up to four copies of mini-white (mw+) into w1118 was insufficient to promote fast and consistent locomotor recovery. However, flies carrying w+ duplicated to the Y chromosome showed wild-type-like fast locomotor recovery. Furthermore, Knockdown of w by RNA interference (RNAi) in neurons but not glia delayed locomotor recovery, and specifically, knockdown of w in subsets of serotonin neurons was sufficient to delay the locomotor recovery. These data reveal an additional role for w in modulating the timing of locomotor recovery from anoxia. PMID:27029736

Distinct sets of locomotor modules control the speed and modes of human locomotion

PubMed Central

Yokoyama, Hikaru; Ogawa, Tetsuya; Kawashima, Noritaka; Shinya, Masahiro; Nakazawa, Kimitaka

2016-01-01

Although recent vertebrate studies have revealed that different spinal networks are recruited in locomotor mode- and speed-dependent manners, it is unknown whether humans share similar neural mechanisms. Here, we tested whether speed- and mode-dependence in the recruitment of human locomotor networks exists or not by statistically extracting locomotor networks. From electromyographic activity during walking and running over a wide speed range, locomotor modules generating basic patterns of muscle activities were extracted using non-negative matrix factorization. The results showed that the number of modules changed depending on the modes and speeds. Different combinations of modules were extracted during walking and running, and at different speeds even during the same locomotor mode. These results strongly suggest that, in humans, different spinal locomotor networks are recruited while walking and running, and even in the same locomotor mode different networks are probably recruited at different speeds. PMID:27805015

Satisfaction and perceptions of long-term manual wheelchair users with a spinal cord injury upon completion of a locomotor training program with an overground robotic exoskeleton.

PubMed

Gagnon, Dany H; Vermette, Martin; Duclos, Cyril; Aubertin-Leheudre, Mylène; Ahmed, Sara; Kairy, Dahlia

2017-12-19

The main objectives of this study were to quantify clients' satisfaction and perception upon completion of a locomotor training program with an overground robotic exoskeleton. A group of 14 wheelchair users with a spinal cord injury, who finished a 6-8-week locomotor training program with the robotic exoskeleton (18 training sessions), were invited to complete a web-based electronic questionnaire. This questionnaire encompassed 41 statements organized around seven key domains: overall satisfaction related to the training program, satisfaction related to the overground robotic exoskeleton, satisfaction related to the program attributes, perceived learnability, perceived health benefits and risks and perceived motivation to engage in physical activity. Each statement was rated using a visual analogue scale ranging from "0 = totally disagree" to "100 = completely agree". Overall, respondents unanimously considered themselves satisfied with the locomotor training program with the robotic exoskeleton (95.7 ± 0.7%) and provided positive feedback about the robotic exoskeleton itself (82.3 ± 6.9%), the attributes of the locomotor training program (84.5 ± 6.9%) and their ability to learn to perform sit-stand transfers and walk with the robotic exoskeleton (79.6 ± 17%). Respondents perceived some health benefits (67.9 ± 16.7%) and have reported no fear of developing secondary complications or of potential risk for themselves linked to the use of the robotic exoskeleton (16.7 ± 8.2%). At the end of the program, respondents felt motivated to engage in a regular physical activity program (91.3 ± 0.1%). This study provides new insights on satisfaction and perceptions of wheelchair users while also confirming the relevance to continue to improve such technologies, and informing the development of future clinical trials. Implications for Rehabilitation All long-term manual wheelchair users with a spinal cord injury who participated in the study are unanimously satisfied upon completion of a 6-8-week locomotor training program with the robotic exoskeleton and would recommend the program to their peers. All long-term manual wheelchair users with a spinal cord injury who participated in the study offered positive feedback about the robotic exoskeleton itself and feel it is easy to learn to perform sit-stand transfers and walk with the robotic exoskeleton. All long-term manual wheelchair users with a spinal cord injury who participated in the study predominantly perceived improvements in their overall health status, upper limb strength and endurance as well as in their sleep and psychological well-being upon completion of a 6-8-week locomotor training program with the robotic exoskeleton. All long-term manual wheelchair users with a spinal cord injury who participated in the study unanimously felt motivated to engage in a regular physical activity program adapted to their condition and most of them do plan to continue to participate in moderate-to-strenuous physical exercise. Additional research on clients' perspectives, especially satisfaction with the overground exoskeleton and locomotor training program attributes, is needed.

Recovery of forward stepping in spinal cord injured patients does not transfer to untrained backward stepping.

PubMed

Grasso, Renato; Ivanenko, Yuri P; Zago, Myrka; Molinari, Marco; Scivoletto, Giorgio; Lacquaniti, Francesco

2004-08-01

Six spinal cord injured (SCI) patients were trained to step on a treadmill with body-weight support for 1.5-3 months. At the end of training, foot motion recovered the shape and the step-by-step reproducibility that characterize normal gait. They were then asked to step backward on the treadmill belt that moved in the opposite direction relative to standard forward training. In contrast to healthy subjects, who can immediately reverse the direction of walking by time-reversing the kinematic waveforms, patients were unable to step backward. Similarly patients were unable to perform another untrained locomotor task, namely stepping in place on the idle treadmill. Two patients who were trained to step backward for 2-3 weeks were able to develop control of foot motion appropriate for this task. The results show that locomotor improvement does not transfer to untrained tasks, thus supporting the idea of task-dependent plasticity in human locomotor networks.

(-)Epigallocatechin-3-gallate decreases the stress-induced impairment of learning and memory in rats.

PubMed

Soung, Hung-Sheng; Wang, Mao-Hsien; Tseng, Hsiang-Chien; Fang, Hsu-Wei; Chang, Kuo-Chi

2015-08-18

Stress induces reactive oxygen species (ROS) and causes alterations in brain cytoarchitecture and cognition. Green tea has potent antioxidative properties especially the tea catechin (-) epigallocatechin-3-gallate (EGCG). These powerful antioxidative properties are able to protect against various oxidative damages. In this study we investigated the impact of stress on rats' locomotor activity, learning and memory. Many tea catechins, including EGCG, were examined for their possible therapeutic effects in treating stress-induced impairment. Our results indicated that locomotor activity was decreased, and the learning and memory were impaired in stressed rats (SRs). EGCG treatment was able to prevent the decreased locomotor activity as well as improve the learning and memory in SRs. EGCG treatment was also able to reduce the increased oxidative status in SRs' hippocampi. The above results suggest a therapeutic effect of EGCG in treating stress-induced impairment of learning and memory, most likely by means of its powerful antioxidative properties. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Body size and predatory performance in wolves: is bigger better?

PubMed

MacNulty, Daniel R; Smith, Douglas W; Mech, L David; Eberly, Lynn E

2009-05-01

1. Large body size hinders locomotor performance in ways that may lead to trade-offs in predator foraging ability that limit the net predatory benefit of larger size. For example, size-related improvements in handling prey may come at the expense of pursuing prey and thus negate any enhancement in overall predatory performance due to increasing size. 2. This hypothesis was tested with longitudinal data from repeated observations of 94 individually known wolves (Canis lupus) hunting elk (Cervus elaphus) in Yellowstone National Park, USA. Wolf size was estimated from an individually based sex-specific growth model derived from body mass measurements of 304 wolves. 3. Larger size granted individual wolves a net predatory advantage despite substantial variation in its effect on the performance of different predatory tasks; larger size improved performance of a strength-related task (grappling and subduing elk) but failed to improve performance of a locomotor-related task (selecting an elk from a group) for wolves > 39 kg. 4. Sexual dimorphism in wolf size also explained why males outperformed females in each of the three tasks considered (attacking, selecting, and killing). 5. These findings support the generalization that bigger predators are overall better hunters, but they also indicate that increasing size ultimately limits elements of predatory behaviour that require superior locomotor performance. We argue that this could potentially narrow the dietary niche of larger carnivores as well as limit the evolution of larger size if prey are substantially more difficult to pursue than to handle.

Body size and predatory performance in wolves: Is bigger better?

USGS Publications Warehouse

MacNulty, D.R.; Smith, D.W.; Mech, L.D.; Eberly, L.E.

2009-01-01

Large body size hinders locomotor performance in ways that may lead to trade-offs in predator foraging ability that limit the net predatory benefit of larger size. For example, size-related improvements in handling prey may come at the expense of pursuing prey and thus negate any enhancement in overall predatory performance due to increasing size. 2. This hypothesis was tested with longitudinal data from repeated observations of 94 individually known wolves (Canis lupus) hunting elk (Cervus elaphus) in Yellowstone National Park, USA. Wolf size was estimated from an individually based sex-specific growth model derived from body mass measurements of 304 wolves. 3. Larger size granted individual wolves a net predatory advantage despite substantial variation in its effect on the performance of different predatory tasks; larger size improved performance of a strength-related task (grappling and subduing elk) but failed to improve performance of a locomotor-related task (selecting an elk from a group) for wolves > 39 kg. 4. Sexual dimorphism in wolf size also explained why males outperformed females in each of the three tasks considered (attacking, selecting, and killing). 5. These findings support the generalization that bigger predators are overall better hunters, but they also indicate that increasing size ultimately limits elements of predatory behaviour that require superior locomotor performance. We argue that this could potentially narrow the dietary niche of larger carnivores as well as limit the evolution of larger size if prey are substantially more difficult to pursue than to handle. ?? 2009 British Ecological Society.

Effects of nicergoline on age-related decrements in radial maze performance and acetylcholine levels.

PubMed

McArthur, R A; Carfagna, N; Banfi, L; Cavanus, S; Cervini, M A; Fariello, R; Post, C

1997-01-01

The effects of chronic oral administration of nicergoline (5.0 mg/kg; bid) on locomotor activity, eight-arm radial maze performance plus striatal, cortical, and hippocampal acetylcholine (ACh) levels were examined in young and aged Wistar rats. Chronic nicergoline administration did not modify either the locomotor activity or radial maze learning in young rats. Young rats learned the radial maze procedure rapidly and improved their performance throughout the successive training sessions. Radial maze performance in young rats was characterised by very few arm reentries. Aged rats were hypoactive and did not explore or enter the radial maze arms, and consequently performed poorly in the radial maze throughout the training sessions. Nicergoline treatment did not significantly modify locomotor activity in aged rats. Aged rats treated with nicergoline also performed poorly initially but improved with repeated training in the radial maze. This improvement was associated with an increasing number of arms being entered and very few arm reentries. Reduced acetylcholine (ACh) levels were also associated with age. Aged rats had significantly reduced levels of ACh in the straitum and cortex, but not the hippocampus as compared to young rats. Nicergoline treatment did not change ACh levels in young rats, but substantially restored the reduced ACh levels in aged rats. These results indicate that nicergoline is an effective cognitive enhancer in a learning model of age-related deficits and that these results may be related to changes in the cholinergic system.

Integrated Locomotor Function Tests for Countermeasure Evaluation

NASA Technical Reports Server (NTRS)

Bloomberg, J. J.; Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Landsness, E. C.; Black, F. O.

2005-01-01

Following spaceflight crewmembers experience locomotor dysfunction due to inflight adaptive alterations in sensorimotor function. Countermeasures designed to mitigate these postflight gait alterations need to be assessed with a new generation of tests that evaluate the interaction of various sensorimotor sub-systems central to locomotor control. The goal of the present study was to develop new functional tests of locomotor control that could be used to test the efficacy of countermeasures. These tests were designed to simultaneously examine the function of multiple sensorimotor systems underlying the control of locomotion and be operationally relevant to the astronaut population. Traditionally, gaze stabilization has been studied almost exclusively in seated subjects performing target acquisition tasks requiring only the involvement of coordinated eye-head movements. However, activities like walking involve full-body movement and require coordination between lower limbs and the eye-head-trunk complex to achieve stabilized gaze during locomotion. Therefore the first goal of this study was to determine how the multiple, interdependent, full-body sensorimotor gaze stabilization subsystems are functionally coordinated during locomotion. In an earlier study we investigated how alteration in gaze tasking changes full-body locomotor control strategies. Subjects walked on a treadmill and either focused on a central point target or read numeral characters. We measured: temporal parameters of gait, full body sagittal plane segmental kinematics of the head, trunk, thigh, shank and foot, accelerations along the vertical axis at the head and the shank, and the vertical forces acting on the support surface. In comparison to the point target fixation condition, the results of the number reading task showed that compensatory head pitch movements increased, peak head acceleration was reduced and knee flexion at heel-strike was increased. In a more recent study we investigated the adaptive remodeling of the full-body gaze control systems following exposure to visual-vestibular conflict. Subjects walked on a treadmill before and after a 30- minute exposure to 0.5X minifying during which self-generated sinusoidal vertical head rotations were performed while seated. Following exposure to visual-vestibular conflict subjects showed a restriction in compensatory head movements, increased knee and ankle flexion after heel-strike and a decrease in the rate of body loading during the rapid weight transfer phase after the heel strike event. Taken together, results from both studies provide evidence that the full body contributes to gaze stabilization during locomotion, and that different functional elements are responsive to changes in visual task constraints and are subject to adaptive alterations following exposure to visual-vestibular conflict. This information provides the basis for the design of a new generation of integrative tests that incorporate the evaluation of multiple neural control systems relevant to astronaut operational performance.

Locomotor activity: A distinctive index in morphine self-administration in rats.

PubMed

Zhang, Jian-Jun; Kong, Qingyao

2017-01-01

Self-administration of addictive drugs is a widely used tool for studying behavioral, neurobiological, and genetic factors in addiction. However, how locomotor activity is affected during self-administration of addictive drugs has not been extensively studied. In our present study, we tested the locomotor activity levels during acquisition, extinction and reinstatement of morphine self-administration in rats. We found that compared with saline self-administration (SA), rats that trained with morphine SA had higher locomotor activity. Rats that successfully acquired SA also showed higher locomotor activity than rats that failed in acquiring SA. Moreover, locomotor activity was correlated with the number of drug infusions but not with the number of inactive pokes. We also tested the locomotor activity in the extinction and the morphine-primed reinstatement session. Interestingly, we found that in the first extinction session, although the number of active pokes did not change, the locomotor activity was significantly lower than in the last acquisition session, and this decrease can be maintained for at least six days. Finally, morphine priming enhanced the locomotor activity during the reinstatement test, regardless of if the active pokes were significantly increased or not. Our results clearly suggest that locomotor activity, which may reflect the pharmacological effects of morphine, is different from drug seeking behavior and is a distinctive index in drug self-administration.

Mirtazapine attenuates the expression of nicotine-induced locomotor sensitization in rats.

PubMed

Barbosa-Méndez, Susana; Jurado, Noé; Matus-Ortega, Maura; Martiñon, Susana; Heinze, Gerardo; Salazar-Juárez, Alberto

2017-10-05

Nicotine is the primary psychoactive component of tobacco. Many addictive nicotinic actions are mediated by an increase in the activity of the serotonin (5-HT) system. Some studies show that the 5-HT 2A , 5-HT 2C , and 5-HT 3 receptors have a central role in the induction and expression of nicotine-induced locomotor sensitization. Mirtazapine, an antagonist of the α 2- adrenergic receptors, the 5-HT 2A/C , and the 5-HT 3 receptors, has proven effective in reducing behavioral effects induced by drugs like cocaine and methamphetamines in human and animal. In this study, we evaluated the effect of mirtazapine on the locomotor activity and on the expression of nicotine-induced locomotor sensitization. We used the nicotine locomotor sensitization paradigm to assess the effects of mirtazapine on nicotine-induced locomotor activity and locomotor sensitization. Mirtazapine (30mg/kg, i.p.) was administered during extinction. Our study found that mirtazapine attenuated the expression of locomotor sensitization induced by different nicotine doses, decreased the duration of locomotor effects and locomotor activity induced by binge administration of nicotine. In addition, our study revealed that treatment with mirtazapine for 60 days produced an enhanced attenuation of nicotine-induced locomotor activity during the expression phase of behavioral sensitization, compared to that obtained when mirtazapine was administered for 30 days. This suggests that use of mirtazapine in controlled clinical trials may be a useful therapy to maintain abstinence for long periods. Copyright © 2017 Elsevier B.V. All rights reserved.

Locomotor Performance During Rehabilitation of People With Lower Limb Amputation and Prosthetic Nonuse 12 Months After Discharge.

PubMed

Roffman, Caroline E; Buchanan, John; Allison, Garry T

2016-07-01

It is recognized that multifactorial assessments are needed to evaluate balance and locomotor function in people with lower limb amputation. There is no consensus on whether a single screening tool could be used to identify future issues with locomotion or prosthetic use. The purpose of this study was to determine whether different tests of locomotor performance during rehabilitation were associated with significantly greater risk of prosthetic abandonment at 12 months postdischarge. This was a retrospective cohort study. Data for descriptive variables and locomotor tests (ie, 10-Meter Walk Test [10MWT], Timed "Up & Go" Test [TUGT], Six-Minute Walk Test [6MWT], and Four Square Step Test [FSST]) were abstracted from the medical records of 201 consecutive participants with lower limb amputation. Participants were interviewed and classified as prosthetic users or nonusers at 12 months postdischarge. The Mann-Whitney U test was used to analyze whether there were differences in locomotor performance. Receiver operating characteristic curves were generated to determine performance thresholds, and relative risk (RR) was calculated for nonuse. At 12 months postdischarge, 18% (n=36) of the participants had become prosthetic nonusers. Performance thresholds, area under the curve (AUC), and RR of nonuse (95% confidence intervals [CI]) were: for the 10MWT, if walking speed was ≤0.44 ms(-1) (AUC=0.743), RR of nonuse=2.76 (95% CI=1.83, 3.79; P<.0001); for the TUGT, if time was ≥21.4 seconds (AUC=0.796), RR of nonuse=3.17 (95% CI=2.17, 4.14; P<.0001); for the 6MWT, if distance was ≤191 m (AUC=0.788), RR of nonuse=2.84, (95% CI=2.05, 3.48; P<.0001); and for the FSST, if time was ≥36.6 seconds (AUC=0.762), RR of nonuse=2.76 (95% CI=1.99, 3.39; P<.0001). Missing data, potential recall bias, and assessment times that varied were limitations of the study. Locomotor performance during rehabilitation may predict future risk of prosthetic nonuse. It may be implied that the 10MWT has the greatest clinical utility as a single screening tool for prosthetic nonuse, given the highest proportion of participants were able to perform this test early in rehabilitation. However, as locomotor skills improve, other tests (in particular, the 6MWT) have specific clinical utility. To fully enable implementation of these locomotor criteria for prosthetic nonuse into clinical practice, validation is warranted. © 2016 American Physical Therapy Association.

Hyperactivity in the Gunn rat model of neonatal jaundice: age-related attenuation and emergence of gait deficits

PubMed Central

Stanford, John A.; Shuler, Jeffrey M.; Fowler, Stephen C.; Stanford, Kimberly G.; Ma, Delin; Bittel, Douglas C.; Le Pichon, Jean-Baptiste; Shapiro, Steven M.

2014-01-01

Background Neonatal jaundice resulting from elevated unconjugated bilirubin (UCB) occurs in 60–80% of newborn infants. Although mild jaundice is generally considered harmless, little is known about its long-term consequences. Recent studies have linked mild bilirubin-induced neurological dysfunction (BIND) with a range of neurological syndromes, including attention deficit-hyperactivity disorder. The goal of this study was to measure BIND across the lifespan in the Gunn rat model of BIND. Methods Using a sensitive force plate actometer, we measured locomotor activity and gait in jaundiced (jj) Gunn rats versus their non-jaundiced (Nj) littermates. Data were analyzed for young adult (3–4 months), early middle-aged (9–10 months), and late middle-aged (17–20 months) male rats. Results jj rats exhibited lower body weights at all ages and a hyperactivity that resolved at 17–20 months of age. Increased propulsive force and gait velocity accompanied hyperactivity during locomotor bouts at 9–10 months in jj rats. Stride length did not differ between the two groups at this age. Hyperactivity normalized and gait deficits, including decreased stride length, propulsive force, and gait velocity, emerged in the 17–20-month-old jj rats. Conclusions These results demonstrate that, in aging, hyperactivity decreases with the onset of gait deficits in the Gunn rat model of BIND. PMID:25518009

Post-weaning social isolation increases activity in a novel environment but decreases defensive burying and subchronic MK-801 enhances the activity but not the burying effect in rats.

PubMed

Simpson, Sarah M; Menard, Janet L; Reynolds, James N; Beninger, Richard J

2010-03-01

Subchronic treatment with a non-competitive glutamate NMDA-receptor antagonist [e.g., MK-801 or phencyclidine] or social isolation (SI) from weaning (age 21 days) to adulthood (age 56 days) produce deficits similar to some of the positive and negative symptoms of schizophrenia. Few studies have evaluated the effects of these treatments on emotional behavior. We hypothesized that subchronic MK-801, post-weaning SI or the two in combination would alter activity in a novel environment, anxiety-like behaviors in the elevated plus-maze, coping responses in the defensive burying paradigm and social behavior. In experiment 1, SI rats (n=17) showed increased locomotor activity when exposed to a novel environment, no change in plus-maze behavior and decreased defensive burying when compared to group housed rats (n=16). Subchronic MK-801 enhanced the increase in activity but not the decrease in burying in SI rats. Experiment 2 evaluated the effects on social behavior of post-weaning SI. The locomotor and burying results of experiment 1 were replicated and SI rats (n=9) were found to decrease orientation towards a novel conspecific social target when compared to group housed rats (n=8). The behavioral abnormalities of SI rats may be a manifestation of GABAergic dysfunction that has recently become evident in schizophrenia. (c) 2009 Elsevier Inc. All rights reserved.

The CB1 receptor is required for the establishment of the hyperlocomotor phenotype in developmentally-induced hypothyroidism in mice.

PubMed

Giné, Elena; Echeverry-Alzate, Victor; Lopez-Moreno, Jose Antonio; Rodriguez de Fonseca, Fernando; Perez-Castillo, Ana; Santos, Angel

2017-04-01

Alterations in motor functions are well-characterized features observed in humans and experimental animals with thyroid hormone dysfunctions during development. We have previously suggested the implication of the endocannabinoid system in the hyperlocomotor phenotype observed in developmentally induced hypothyroidism in rats. In this work we have further analyzed the implication of endocannabinoids in the effect of hypothyroidism on locomotor activity. To this end, we evaluated the locomotor activity in adult mice lacking the cannabinoid receptor type 1 (CB1R -/- ) and in their wild type littermates (CB1R +/+ ), whose hypothyroidism was induced in day 12 of gestation and maintained during the experimental period. Our results show that hypothyroidism induced a hyperlocomotor phenotype only in CB1R +/+ , but not in CB1R -/- mice. In contrast with our previous results in rats, the expression of CB1R in striatum and the motor response to the cannabinoid agonist HU210 was unaltered in hypothyroid CB1R +/+ mice suggesting that the cannabinoid system is not altered by hypothyroidism. Also, no effect of HU210 was observed in locomotion of CB1R -/- mice. Finally, since the dopaminergic system plays a major role in the control of locomotor activity we studied its function in hypothyroid wild type and knockout animals. Our results show no alteration in the behavioral response induced by the dopamine D1 receptor agonist SKF38393. However we observed a decreased response to the dopamine D2 receptor antagonist haloperidol only in hypothyroid CB1R +/+ mice, which might indicate potential alterations in D2R signaling in these animals. In conclusion, our data suggest that the cannabinoid system is necessary for the induction of hyperlocomotor phenotype in mice with developmentally induced hypothyroidism. Copyright © 2016 Elsevier Ltd. All rights reserved.

Subchronic MK-801 treatment and post-weaning social isolation in rats: differential effects on locomotor activity and hippocampal long-term potentiation.

PubMed

Ashby, Donovan M; Habib, Diala; Dringenberg, Hans C; Reynolds, James N; Beninger, Richard J

2010-09-01

Subchronic NMDA receptor antagonist treatment and post-weaning social isolation are two animal models of schizophrenia symptoms. However, behavioral and physiological changes following a combination of these two procedures have not been investigated. Thus, we examined effects of a novel, "double hit" model combining these two treatments, comparing them to standard models involving only NMDA antagonist treatment or social isolation. Male, Sprague-Dawley rats were either group-housed or maintained in social isolation (starting at postnatal day [PD] 21 and continuing throughout the study). Each housing condition was further subdivided into two groups, receiving either subchronic treatment with either saline or MK-801 (0.5mg/kg, i.p., 2xday for seven days starting at PD 56). Post-weaning social isolation increased locomotor activity (assessed at PD 70) in response to a novel environment and an acute amphetamine injection, while subchronic MK-801 increased only amphetamine induced locomotor activity. Subsequent electrophysiological experiments (under urethane anesthesia) assessing changes in plasticity of hippocampal synapses showed that subchronic MK-801 treatment resulted in an increase in long-term potentiation in area CA1 in response to high frequency stimulation of the contralateral CA3 area, while housing condition had no effect. No other changes in hippocampal electrophysiology (input-output curves, paired-pulse facilitation) were observed. These data are the first to demonstrate an enhancement in hippocampal long-term plasticity in vivo following subchronic MK-801 administration, an effect that may be related to the well-characterized changes in glutamatergic and GABAergic systems seen after subchronic NMDA receptor blockade. That lack of additive or synergistic effects in the "double hit model" suggests that combining isolation and subchronic MK-801 treatment does not necessarily produce greater behavioral or physiological dysfunction than that seen with either treatment alone. Copyright 2010 Elsevier B.V. All rights reserved.

Differential housing and novelty response: Protection and risk from locomotor sensitization

PubMed Central

Garcia, Erik J.; Haddon, Tara N.; Saucier, Donald A.; Cain, Mary E.

2017-01-01

High novelty seeking increases the risk for drug experimentation and locomotor sensitization. Locomotor sensitization to psychostimulants is thought to reflect neurological adaptations that promote the transition to compulsive drug taking. Rats reared in enrichment (EC) show less locomotor sensitization when compared to rats reared in isolation (IC) or standard conditions (SC). The current research study was designed to test if novelty response contributed locomotor sensitization and more importantly, if the different housing environments could change the novelty response to protect against the development of locomotor sensitization in both adolescence and adulthood. Experiment 1: rats were tested for their response to novelty using the inescapable novelty test (IEN) and pseudorandomly assigned to enriched (EC), isolated (IC), or standard (SC) housing conditions for 30 days. After housing, they were tested with IEN. Rats were then administered amphetamine (0.5 mg/kg) or saline and locomotor activity was measured followed by a sensitization test 14 days later. Experiment 2: rats were tested in the IEN test early adulthood and given five administrations of amphetamine (0.3 mg/kg) or saline and then either stayed in or switched housing environments for 30 days. Rats were then re-tested in the IEN test in late adulthood and administered five more injections of their respective treatments and tested for locomotor sensitization. Results indicate that IC and SC increased the response to novelty. EC housing decreased locomotor response to amphetamine and saline, and SC housing increased the locomotor response to amphetamine. Mediation results indicated that the late adult novelty response fully mediates the locomotor response to amphetamine and saline, while the early adulthood novelty response did not. Conclusions Differential housing changes novelty and amphetamine locomotor response. Novelty response is altered into adulthood and provides evidence that enrichment can be used to reduce drug vulnerability. PMID:28108176

Quantification of locomotor activity in larval zebrafish: considerations for the design of high-throughput behavioral studies.

PubMed

Ingebretson, Justin J; Masino, Mark A

2013-01-01

High-throughput behavioral studies using larval zebrafish often assess locomotor activity to determine the effects of experimental perturbations. However, the results reported by different groups are difficult to compare because there is not a standardized experimental paradigm or measure of locomotor activity. To address this, we investigated the effects that several factors, including the stage of larval development and the physical dimensions (depth and diameter) of the behavioral arena, have on the locomotor activity produced by larval zebrafish. We provide evidence for differences in locomotor activity between larvae at different stages and when recorded in wells of different depths, but not in wells of different diameters. We also show that the variability for most properties of locomotor activity is less for older than younger larvae, which is consistent with previous reports. Finally, we show that conflicting interpretations of activity level can occur when activity is assessed with a single measure of locomotor activity. Thus, we conclude that although a combination of factors should be considered when designing behavioral experiments, the use of older larvae in deep wells will reduce the variability of locomotor activity, and that multiple properties of locomotor activity should be measured to determine activity level.

Temperature and population density effects on locomotor activity of Musca domestica (Diptera: Muscidae).

PubMed

Schou, T M; Faurby, S; Kjærsgaard, A; Pertoldi, C; Loeschcke, V; Hald, B; Bahrndorff, S

2013-12-01

The behavior of ectotherm organisms is affected by both abiotic and biotic factors. However, a limited number of studies have investigated the synergistic effects on behavioral traits. This study examined the effect of temperature and density on locomotor activity of Musca domestica (L.). Locomotor activity was measured for both sexes and at four densities (with mixed sexes) during a full light and dark (L:D) cycle at temperatures ranging from 10 to 40°C. Locomotor activity during daytime increased with temperature at all densities until reaching 30°C and then decreased. High-density treatments significantly reduced the locomotor activity per fly, except at 15°C. For both sexes, daytime activity also increased with temperature until reaching 30 and 35°C for males and females, respectively, and thereafter decreased. Furthermore, males showed a significantly higher and more predictable locomotor activity than females. During nighttime, locomotor activity was considerably lower for all treatments. Altogether the results of the current study show that there is a significant interaction of temperature and density on daytime locomotor activity of M. domestica and that houseflies are likely to show significant changes in locomotor activity with change in temperature.

Locomotor activity: A distinctive index in morphine self-administration in rats

PubMed Central

Kong, Qingyao

2017-01-01

Self-administration of addictive drugs is a widely used tool for studying behavioral, neurobiological, and genetic factors in addiction. However, how locomotor activity is affected during self-administration of addictive drugs has not been extensively studied. In our present study, we tested the locomotor activity levels during acquisition, extinction and reinstatement of morphine self-administration in rats. We found that compared with saline self-administration (SA), rats that trained with morphine SA had higher locomotor activity. Rats that successfully acquired SA also showed higher locomotor activity than rats that failed in acquiring SA. Moreover, locomotor activity was correlated with the number of drug infusions but not with the number of inactive pokes. We also tested the locomotor activity in the extinction and the morphine-primed reinstatement session. Interestingly, we found that in the first extinction session, although the number of active pokes did not change, the locomotor activity was significantly lower than in the last acquisition session, and this decrease can be maintained for at least six days. Finally, morphine priming enhanced the locomotor activity during the reinstatement test, regardless of if the active pokes were significantly increased or not. Our results clearly suggest that locomotor activity, which may reflect the pharmacological effects of morphine, is different from drug seeking behavior and is a distinctive index in drug self-administration. PMID:28380023

Panic disorder and locomotor activity

PubMed Central

Sakamoto, Noriyuki; Yoshiuchi, Kazuhiro; Kikuchi, Hiroe; Takimoto, Yoshiyuki; Kaiya, Hisanobu; Kumano, Hiroaki; Yamamoto, Yoshiharu; Akabayashi, Akira

2008-01-01

Background Panic disorder is one of the anxiety disorders, and anxiety is associated with some locomotor activity changes such as "restlessness". However, there have been few studies on locomotor activity in panic disorder using actigraphy, although many studies on other psychiatric disorders have been reported using actigraphy. Therefore, the aim of the present study was to investigate the relationship between panic disorder and locomotor activity pattern using a wrist-worn activity monitor. In addition, an ecological momentary assessment technique was used to record panic attacks in natural settings. Methods Sixteen patients with panic disorder were asked to wear a watch-type computer as an electronic diary for recording panic attacks for two weeks. In addition, locomotor activity was measured and recorded continuously in an accelerometer equipped in the watch-type computer. Locomotor activity data were analyzed using double cosinor analysis to calculate mesor and the amplitude and acrophase of each of the circadian rhythm and 12-hour harmonic component. Correlations between panic disorder symptoms and locomotor activity were investigated. Results There were significant positive correlations between the frequency of panic attacks and mesor calculated from double cosinor analysis of locomotor activity (r = 0.55) and between HAM-A scores and mesor calculated from double cosinor analysis of locomotor activity (r = 0.62). Conclusion Panic disorder patients with more panic attacks and more anxiety have greater objectively assessed locomotor activity, which may reflect the "restlessness" of anxiety disorders. PMID:19017383

Locomotor Treadmill Training Promotes Soleus Trophism by Mammalian Target of Rapamycin Pathway in Paraplegic Rats.

PubMed

do Espírito Santo, Caroline Cunha; Secco, Daniela Dal; Meireles, Anamaria; de Freitas, Gabriel Ribeiro; Bobinski, Franciane; Cunha, Mauricio Peña; Rodrigues, Ana Lúcia Severo; Swarowsky, Alessandra; Santos, Adair Roberto Soares; Ilha, Jocemar

2018-06-01

Assisted-treadmill training, may be helpful in promoting muscle mass preservation after incomplete spinal cord injury (SCI). However, biological mechanism involved in this process is still not fully understood. This study investigated the effects of locomotor treadmill training on muscle trophism mediated by protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (p70S6K) in paraplegic rats. Adult female Wistar rats underwent an incomplete thoracic SCI induced by compression using an aneurysm clip. After 7 days, injured animals started a 3-week locomotor treadmill training with body weight-support and manual step help. Soleus trophism was measured by muscle weight and transverse myofiber cross-sectional area (CSA). An enzyme-linked immunosorbent assay (ELISA) and western blot analysis were used to detect brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB), Akt, mTOR and p70S6K in paretic soleus. Trained animals did not show locomotor improved, but present an increase in muscle weight and myofiber CSA. Furthermore, the levels of Akt, p70S6K phosphorylation, mTOR and TrkB receptor were increased by training in soleus. In contrast, muscle BDNF levels were significantly reduced after training. The results suggest locomotor treadmill training partially reverts/prevents soleus muscle hypotrophy in rats with SCI. Furthermore, this study provided the first evidence that morphological muscle changes were caused by Akt/mTOR/p70S6K signaling pathway and TrkB up-regulation, which may increase the sensitivity of muscle, reducing autocrine signaling pathway demand of BDNF for cell growth.

High-Intensity Locomotor Exercise Increases Brain-Derived Neurotrophic Factor in Individuals with Incomplete Spinal Cord Injury.

PubMed

Leech, Kristan A; Hornby, T George

2017-03-15

High-intensity locomotor exercise is suggested to contribute to improved recovery of locomotor function after neurological injury. This may be secondary to exercise-intensity-dependent increases in neurotrophin expression demonstrated previously in control subjects. However, rigorous examination of intensity-dependent changes in neurotrophin levels is lacking in individuals with motor incomplete spinal cord injury (SCI). Therefore, the primary aim of this study was to evaluate the effect of locomotor exercise intensity on peripheral levels of brain-derived neurotrophic factor (BDNF) in individuals with incomplete SCI. We also explored the impact of the Val66Met single-nucleotide polymorphism (SNP) on the BDNF gene on intensity-dependent changes. Serum concentrations of BDNF and insulin-like growth factor-1 (IGF-1), as well as measures of cardiorespiratory dynamics, were evaluated across different levels of exercise intensity achieved during a graded-intensity, locomotor exercise paradigm in 11 individuals with incomplete SCI. Our results demonstrate a significant increase in serum BDNF at high, as compared to moderate, exercise intensities (p = 0.01) and 15 and 30 min post-exercise (p < 0.01 for both), with comparison to changes at low intensity approaching significance (p = 0.05). Serum IGF-1 demonstrated no intensity-dependent changes. Significant correlations were observed between changes in BDNF and specific indicators of exercise intensity (e.g., rating of perceived exertion; R = 0.43; p = 0.02). Additionally, the data suggest that Val66Met SNP carriers may not exhibit intensity-dependent changes in serum BDNF concentration. Given the known role of BDNF in experience-dependent neuroplasticity, these preliminary results suggest that exercise intensity modulates serum BDNF concentrations and may be an important parameter of physical rehabilitation interventions after neurological injury.

High-Intensity Locomotor Exercise Increases Brain-Derived Neurotrophic Factor in Individuals with Incomplete Spinal Cord Injury

PubMed Central

Leech, Kristan A.

2017-01-01

Abstract High-intensity locomotor exercise is suggested to contribute to improved recovery of locomotor function after neurological injury. This may be secondary to exercise-intensity–dependent increases in neurotrophin expression demonstrated previously in control subjects. However, rigorous examination of intensity-dependent changes in neurotrophin levels is lacking in individuals with motor incomplete spinal cord injury (SCI). Therefore, the primary aim of this study was to evaluate the effect of locomotor exercise intensity on peripheral levels of brain-derived neurotrophic factor (BDNF) in individuals with incomplete SCI. We also explored the impact of the Val66Met single-nucleotide polymorphism (SNP) on the BDNF gene on intensity-dependent changes. Serum concentrations of BDNF and insulin-like growth factor-1 (IGF-1), as well as measures of cardiorespiratory dynamics, were evaluated across different levels of exercise intensity achieved during a graded-intensity, locomotor exercise paradigm in 11 individuals with incomplete SCI. Our results demonstrate a significant increase in serum BDNF at high, as compared to moderate, exercise intensities (p = 0.01) and 15 and 30 min post-exercise (p < 0.01 for both), with comparison to changes at low intensity approaching significance (p = 0.05). Serum IGF-1 demonstrated no intensity-dependent changes. Significant correlations were observed between changes in BDNF and specific indicators of exercise intensity (e.g., rating of perceived exertion; R = 0.43; p = 0.02). Additionally, the data suggest that Val66Met SNP carriers may not exhibit intensity-dependent changes in serum BDNF concentration. Given the known role of BDNF in experience-dependent neuroplasticity, these preliminary results suggest that exercise intensity modulates serum BDNF concentrations and may be an important parameter of physical rehabilitation interventions after neurological injury. PMID:27526567

Neuroprotection of locomotor networks after experimental injury to the neonatal rat spinal cord in vitro.

PubMed

Margaryan, G; Mattioli, C; Mladinic, M; Nistri, A

2010-02-03

Treatment to block the pathophysiological processes triggered by acute spinal injury remains unsatisfactory as the underlying mechanisms are incompletely understood. Using as a model the in vitro spinal cord of the neonatal rat, we investigated the feasibility of neuroprotection of lumbar locomotor networks by the glutamate antagonists 6-cyano-7-nitroquinoxaline-2, 3-dione (CNQX) and aminophosphonovalerate (APV) against acute lesions induced by either a toxic solution (pathological medium (PM) to mimic the spinal injury hypoxic-dysmetabolic perturbation) or excitotoxicity with kainate. The study outcome was presence of fictive locomotion 24 h after the insult and its correlation with network histology. Inhibition of fictive locomotion by PM was contrasted by simultaneous and even delayed (1 h later) co-application of CNQX and APV with increased survival of ventral horn premotoneurons and lateral column white matter. Neither CNQX nor APV alone provided neuroprotection. Kainate-mediated excitotoxicity always led to loss of fictive locomotion and extensive neuronal damage. CNQX and APV co-applied with kainate protected one-third of preparations with improved motoneuron and dorsal horn neuronal counts, although they failed with delayed application. Our data suggest that locomotor network neuroprotection was possible when introduced very early during the pathological process of spinal injury, but also showed how the borderline between presence or loss of locomotor activity was a very narrow one that depended on the survival of a certain number of neurons or white matter elements. The present report provides a model not only for preclinical testing of novel neuroprotective agents, but also for estimating the minimal network membership compatible with functional locomotor output. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Low-energy extracorporeal shock wave therapy for promotion of vascular endothelial growth factor expression and angiogenesis and improvement of locomotor and sensory functions after spinal cord injury.

PubMed

Yahata, Kenichiro; Kanno, Haruo; Ozawa, Hiroshi; Yamaya, Seiji; Tateda, Satoshi; Ito, Kenta; Shimokawa, Hiroaki; Itoi, Eiji

2016-12-01

OBJECTIVE Extracorporeal shock wave therapy (ESWT) is widely used to treat various human diseases. Low-energy ESWT increases expression of vascular endothelial growth factor (VEGF) in cultured endothelial cells. The VEGF stimulates not only endothelial cells to promote angiogenesis but also neural cells to induce neuroprotective effects. A previous study by these authors demonstrated that low-energy ESWT promoted expression of VEGF in damaged neural tissue and improved locomotor function after spinal cord injury (SCI). However, the neuroprotective mechanisms in the injured spinal cord produced by low-energy ESWT are still unknown. In the present study, the authors investigated the cell specificity of VEGF expression in injured spinal cords and angiogenesis induced by low-energy ESWT. They also examined the neuroprotective effects of low-energy ESWT on cell death, axonal damage, and white matter sparing as well as the therapeutic effect for improvement of sensory function following SCI. METHODS Adult female Sprague-Dawley rats were divided into the SCI group (SCI only) and SCI-SW group (low-energy ESWT applied after SCI). Thoracic SCI was produced using a New York University Impactor. Low-energy ESWT was applied to the injured spinal cord 3 times a week for 3 weeks after SCI. Locomotor function was evaluated using the Basso, Beattie, and Bresnahan open-field locomotor score for 42 days after SCI. Mechanical and thermal allodynia in the hindpaw were evaluated for 42 days. Double staining for VEGF and various cell-type markers (NeuN, GFAP, and Olig2) was performed at Day 7; TUNEL staining was also performed at Day 7. Immunohistochemical staining for CD31, α-SMA, and 5-HT was performed on spinal cord sections taken 42 days after SCI. Luxol fast blue staining was performed at Day 42. RESULTS Low-energy ESWT significantly improved not only locomotion but also mechanical and thermal allodynia following SCI. In the double staining, expression of VEGF was observed in NeuN-, GFAP-, and Olig2-labeled cells. Low-energy ESWT significantly promoted CD31 and α-SMA expressions in the injured spinal cords. In addition, low-energy ESWT significantly reduced the TUNEL-positive cells in the injured spinal cords. Furthermore, the immunodensity of 5-HT-positive axons was significantly higher in the animals treated by low-energy ESWT. The areas of spared white matter were obviously larger in the SCI-SW group than in the SCI group, as indicated by Luxol fast blue staining. CONCLUSIONS The results of this study suggested that low-energy ESWT promotes VEGF expression in various neural cells and enhances angiogenesis in damaged neural tissue after SCI. Furthermore, the neuroprotective effect of VEGF induced by low-energy ESWT can suppress cell death and axonal damage and consequently improve locomotor and sensory functions after SCI. Thus, low-energy ESWT can be a novel therapeutic strategy for treatment of SCI.

The Lesioned Spinal Cord Is a “New” Spinal Cord: Evidence from Functional Changes after Spinal Injury in Lamprey

PubMed Central

Parker, David

2017-01-01

Finding a treatment for spinal cord injury (SCI) focuses on reconnecting the spinal cord by promoting regeneration across the lesion site. However, while regeneration is necessary for recovery, on its own it may not be sufficient. This presumably reflects the requirement for regenerated inputs to interact appropriately with the spinal cord, making sub-lesion network properties an additional influence on recovery. This review summarizes work we have done in the lamprey, a model system for SCI research. We have compared locomotor behavior (swimming) and the properties of descending inputs, locomotor networks, and sensory inputs in unlesioned animals and animals that have received complete spinal cord lesions. In the majority (∼90%) of animals swimming parameters after lesioning recovered to match those in unlesioned animals. Synaptic inputs from individual regenerated axons also matched the properties in unlesioned animals, although this was associated with changes in release parameters. This suggests against any compensation at these synapses for the reduced descending drive that will occur given that regeneration is always incomplete. Compensation instead seems to occur through diverse changes in cellular and synaptic properties in locomotor networks and proprioceptive systems below, but also above, the lesion site. Recovery of locomotor performance is thus not simply the reconnection of the two sides of the spinal cord, but reflects a distributed and varied range of spinal cord changes. While locomotor network changes are insufficient on their own for recovery, they may facilitate locomotor outputs by compensating for the reduction in descending drive. Potentiated sensory feedback may in turn be a necessary adaptation that monitors and adjusts the output from the “new” locomotor network. Rather than a single aspect, changes in different components of the motor system and their interactions may be needed after SCI. If these are general features, and where comparisons with mammalian systems can be made effects seem to be conserved, improving functional recovery in higher vertebrates will require interventions that generate the optimal spinal cord conditions conducive to recovery. The analyses needed to identify these conditions are difficult in the mammalian spinal cord, but lower vertebrate systems should help to identify the principles of the optimal spinal cord response to injury. PMID:29163065

Abnormality of circadian rhythm accompanied by an increase in frontal cortex serotonin in animal model of autism.

PubMed

Tsujino, Naohisa; Nakatani, Yasushi; Seki, Yoshinari; Nakasato, Akane; Nakamura, Michiko; Sugawara, Michiya; Arita, Hideho

2007-02-01

Several clinical reports have indicated that autistic patients often show disturbance of the circadian rhythm, which may be related to dysfunction of the serotonergic system in the brain. Using rats exposed prenatally to valproic acid (VPA) as an animal model of autism, we examined locomotor activity and feeding under a reversed 12-h light/dark cycle, and found disturbance of the circadian rhythm characterized by frequent arousal during the light/sleep phase. In addition, measurement of brain serotonin (5-HT) level using in vivo microdialysis showed that the brain 5-HT level in VPA-exposed rats was significantly higher than that in control rats. These results suggest that a higher brain 5-HT level might be responsible for the irregular sleep/awake rhythm in autism.

Increased phencyclidine-induced hyperactivity following cortical cholinergic denervation.

PubMed

Mattsson, Anna; Lindqvist, Eva; Ogren, Sven Ove; Olson, Lars

2005-11-07

Altered cholinergic function is considered as a potential contributing factor in the pathogenesis of schizophrenia. We hypothesize that cortical cholinergic denervation may result in changes in glutamatergic activity. Therefore, we lesioned the cholinergic corticopetal projections by local infusion of 192 IgG-saporin into the nucleus basalis magnocellularis of rats. Possible effects of this lesion on glutamatergic systems were examined by phencyclidine-induced locomotor activity, and also by N-methyl-D-aspartate receptor binding. We find that cholinergic lesioning of neocortex leads to enhanced sensitivity to phencyclidine in the form of a dramatic increase in horizontal activity. Further, N-methyl-D-aspartate receptor binding is unaffected in denervated rats. These results suggest that aberrations in cholinergic function might lead to glutamatergic dysfunctions, which might be of relevance for the pathophysiology for schizophrenia.

Human embryonic stem cell-derived oligodendrocyte progenitor cell transplants remyelinate and restore locomotion after spinal cord injury.

PubMed

Keirstead, Hans S; Nistor, Gabriel; Bernal, Giovanna; Totoiu, Minodora; Cloutier, Frank; Sharp, Kelly; Steward, Oswald

2005-05-11

Demyelination contributes to loss of function after spinal cord injury, and thus a potential therapeutic strategy involves replacing myelin-forming cells. Here, we show that transplantation of human embryonic stem cell (hESC)-derived oligodendrocyte progenitor cells (OPCs) into adult rat spinal cord injuries enhances remyelination and promotes improvement of motor function. OPCs were injected 7 d or 10 months after injury. In both cases, transplanted cells survived, redistributed over short distances, and differentiated into oligodendrocytes. Animals that received OPCs 7 d after injury exhibited enhanced remyelination and substantially improved locomotor ability. In contrast, when OPCs were transplanted 10 months after injury, there was no enhanced remyelination or locomotor recovery. These studies document the feasibility of predifferentiating hESCs into functional OPCs and demonstrate their therapeutic potential at early time points after spinal cord injury.

Assessment of learning, memory, and attention in developmental neurotoxicity regulatory studies: synthesis, commentary, and recommendations.

PubMed

Vorhees, Charles V; Makris, Susan L

2015-01-01

Cognitive tests of learning and memory (L&M) have been required by U.S. Environmental Protection Agency (EPA) developmental neurotoxicity test (DNT) guidelines for more than two decades. To evaluate the utility of these guidelines, the EPA reviewed 69 pesticide DNT studies. This review found that the DNT provided or could provide the point-of-departure for risk assessment by showing the Lowest Observable Adverse Effect Level (LOAEL) in 28 of these studies in relation to other reported end points. Among the behavioral tests, locomotor activity and auditory/acoustic startle provided the most LOAELs, and tests of cognitive function and the Functional Observational Battery (FOB) the fewest. Two issues arose from the review: (1) what is the relative utility of cognitive tests versus tests of unconditioned behavior, and (2) how might cognitive tests be improved? The EPA sponsored a symposium to address this. Bushnell reviewed studies in which both screening (locomotor activity, FOB, reflex ontogeny, etc.) and complex tests (those requiring training) were used within the same study; he found relatively little evidence that complex tests provided a LOAEL lower than screening tests (with exceptions). Levin reviewed reasons for including cognitive tests in regulatory studies and methods and evidence for the radial arm maze and its place in developmental neurotoxicity assessments. Driscoll and Strupp reviewed the value of serial reaction time operant methods for assessing executive function in developmental neurotoxicity studies. Vorhees and Williams reviewed the value of allocentric (spatial) and egocentric cognitive tests and presented methods for using the Morris water maze for spatial and the Cincinnati water maze for egocentric cognitive assessment. They also reviewed the possible use of water radial mazes. The relatively lower impact of cognitive tests in previous DNT studies in the face of the frequency of human complaints of chemical-induced cognitive dysfunction indicates that animal cognitive tests need improvement. The contributors to this symposium suggest that if the guidelines are updated, they be made more specific by recommending preferred tests and providing greater detail on key characteristics of such tests. Additionally, it is recommended that guidance be developed to address important issues with cognitive tests and to provide the information needed to improve the design, conduct, and interpretation of tests of higher function within a regulatory context. These steps will maximize the value of cognitive tests for use in hazard evaluation and risk assessment. Copyright © 2015 Elsevier Inc. All rights reserved.

Effects of the root bark of Paeonia suffruticosa on mitochondria-mediated neuroprotection in an MPTP-induced model of Parkinson's disease.

PubMed

Kim, Hyo Geun; Park, Gunhyuk; Piao, Ying; Kang, Min Seo; Pak, Youngmi Kim; Hong, Seon-Pyo; Oh, Myung Sook

2014-03-01

Parkinson's disease (PD) is generally characterized by the progressive loss of dopaminergic neurons projecting from the substantia nigra pars compacta (SNpc) to the striatum that results in movement dysfunction, but also entails mitochondrial dysfunction. The purpose of this study is to evaluate the protective effects of Moutan Cortex Radicis (MCE, Moutan peony) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD-like symptoms and to elucidate the underlying mechanisms of action, with a focus on mitochondrial function. In a rat primary mesencephalic culture system, MCE significantly protected dopaminergic neurons from the neurotoxic effects of 1-methyl-4-phenylpyridinium (MPP(+)), an active form of MPTP. Additionally, in a subacute mouse model of MPTP-induced PD, MCE resulted in enhanced recovery from PD-like motor symptoms, including increased locomotor activity and reduced bradykinesia. MCE increased dopamine availability and protected against MPTP-induced dopaminergic neuronal damage. Moreover, MCE inhibited MPTP-induced mitochondrial dysfunction and resulted in increased expression of phosphorylated Akt, ND9, mitochondrial transcription factor A, and H2AX in the SNpc. Mitochondria-mediated apoptosis was also inhibited, via the regulation of B-cell lymphoma family proteins and the inhibition of cytochrome C release and caspase-3 activation. These results indicate that MCE has neuroprotective effects in PD models and may be useful for preventing or treating PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

Quantification of locomotor activity in larval zebrafish: considerations for the design of high-throughput behavioral studies

PubMed Central

Ingebretson, Justin J.; Masino, Mark A.

2013-01-01

High-throughput behavioral studies using larval zebrafish often assess locomotor activity to determine the effects of experimental perturbations. However, the results reported by different groups are difficult to compare because there is not a standardized experimental paradigm or measure of locomotor activity. To address this, we investigated the effects that several factors, including the stage of larval development and the physical dimensions (depth and diameter) of the behavioral arena, have on the locomotor activity produced by larval zebrafish. We provide evidence for differences in locomotor activity between larvae at different stages and when recorded in wells of different depths, but not in wells of different diameters. We also show that the variability for most properties of locomotor activity is less for older than younger larvae, which is consistent with previous reports. Finally, we show that conflicting interpretations of activity level can occur when activity is assessed with a single measure of locomotor activity. Thus, we conclude that although a combination of factors should be considered when designing behavioral experiments, the use of older larvae in deep wells will reduce the variability of locomotor activity, and that multiple properties of locomotor activity should be measured to determine activity level. PMID:23772207

White - cGMP Interaction Promotes Fast Locomotor Recovery from Anoxia in Adult Drosophila

PubMed Central

2017-01-01

Increasing evidence indicates that the white (w) gene in Drosophila possesses extra-retinal functions in addition to its classical role in eye pigmentation. We have previously shown that w+ promotes fast and consistent locomotor recovery from anoxia, but how w+ modulates locomotor recovery is largely unknown. Here we show that in the absence of w+, several PDE mutants, especially cyclic guanosine monophosphate (cGMP)-specific PDE mutants, display wildtype-like fast locomotor recovery from anoxia, and that during the night time, locomotor recovery was light-sensitive in white-eyed mutant w1118, and light-insensitive in PDE mutants under w1118 background. Data indicate the involvement of cGMP in the modulation of recovery timing and presumably, light-evoked cGMP fluctuation is associated with light sensitivity of locomotor recovery. This was further supported by the observations that w-RNAi-induced delay of locomotor recovery was completely eliminated by upregulation of cGMP through multiple approaches, including PDE mutation, simultaneous overexpression of an atypical soluble guanylyl cyclase Gyc88E, or sildenafil feeding. Lastly, prolonged sildenafil feeding promoted fast locomotor recovery from anoxia in w1118. Taken together, these data suggest that a White-cGMP interaction modulates the timing of locomotor recovery from anoxia. PMID:28060942

Alternate pathways of body shape evolution translate into common patterns of locomotor evolution in two clades of lizards.

PubMed

Bergmann, Philip J; Irschick, Duncan J

2010-06-01

Body shape has a fundamental impact on organismal function, but it is unknown how functional morphology and locomotor performance and kinematics relate across a diverse array of body shapes. We showed that although patterns of body shape evolution differed considerably between lizards of the Phrynosomatinae and Lerista, patterns of locomotor evolution coincided between clades. Specifically, we found that the phrynosomatines evolved a stocky phenotype through body widening and limb shortening, whereas Lerista evolved elongation through body lengthening and limb shortening. In both clades, relative limb length played a key role in locomotor evolution and kinematic strategies, with long-limbed species moving faster and taking longer strides. In Lerista, the body axis also influenced locomotor evolution. Similar patterns of locomotor evolution were likely due to constraints on how the body can move. However, these common patterns of locomotor evolution between the two clades resulted in different kinematic strategies and levels of performance among species because of their morphological differences. Furthermore, we found no evidence that distinct body shapes are adaptations to different substrates, as locomotor kinematics did not change on loose or solid substrates. Our findings illustrate the importance of studying kinematics to understand the mechanisms of locomotor evolution and phenotype-function relationships.

Daily rhythms of locomotor and demand-feeding activities in Schizothorax pelzami (Kessler, 1870).

PubMed

Ebrahimi, Ehsan; Kamrani, Ehsan; Heydarnejad, Mohammad Saeed; Safari, Omid

2017-01-01

A study was carried out to investigate the daily rhythms of locomotor and feeding activity of Khajoo, Schizothorax pelzami, a candidate species for freshwater aquaculture. Using self-feeder juvenile Khajoo were exposed to a 12/12 LD cycle to determine the rhythms of locomotor and feeding activity. The effects of feeding on locomotor and feeding activity of fish were also examined. Finally, the endogenous rhythmicity under different lighting condition tested. Fish displayed a strictly diurnal feeding and locomotor activities with 98% and 84% of the total activity occurred in the photophase, respectively. In scheduled feeding, both the L-group (fed in light) and the D-group (fed in the dark) showed a diurnal locomotor activity pattern. However, the L-group had a peak of locomotor activity near the feeding time, but the D-group had a scarce locomotor activity in the scatophase with no significant change at the mealtime. Most of the individuals display free-running rhythms when exposed to different lighting condition including, constant darkness, ultradian 45:45 min LD cycle and reversed DL photo cycle. Taken together the results of this study showed that both locomotor and feeding activity have diurnal rhythms in Khajoo S. pelzami, even fish feeding had taken place at night. Additionally, the free-running locomotor activity of the fish in the absence of external light stimuli, suggests the existence of an endogenous timing mechanism in this fish species.

Differential housing and novelty response: Protection and risk from locomotor sensitization.

PubMed

Garcia, Erik J; Haddon, Tara N; Saucier, Donald A; Cain, Mary E

2017-03-01

High novelty seeking increases the risk for drug experimentation and locomotor sensitization. Locomotor sensitization to psychostimulants is thought to reflect neurological adaptations that promote the transition to compulsive drug taking. Rats reared in enrichment (EC) show less locomotor sensitization when compared to rats reared in isolation (IC) or standard conditions (SC). The current research study was designed to test if novelty response contributed locomotor sensitization and more importantly, if the different housing environments could change the novelty response to protect against the development of locomotor sensitization in both adolescence and adulthood. Experiment 1: rats were tested for their response to novelty using the inescapable novelty test (IEN) and pseudorandomly assigned to enriched (EC), isolated (IC), or standard (SC) housing conditions for 30days. After housing, they were tested with IEN. Rats were then administered amphetamine (0.5mg/kg) or saline and locomotor activity was measured followed by a sensitization test 14days later. Experiment 2: rats were tested in the IEN test early adulthood and given five administrations of amphetamine (0.3mg/kg) or saline and then either stayed in or switched housing environments for 30days. Rats were then re-tested in the IEN test in late adulthood and administered five more injections of their respective treatments and tested for locomotor sensitization. Results indicate that IC and SC increased the response to novelty. EC housing decreased locomotor response to amphetamine and saline, and SC housing increased the locomotor response to amphetamine. Mediation results indicated that the late adult novelty response fully mediates the locomotor response to amphetamine and saline, while the early adulthood novelty response did not. Differential housing changes novelty and amphetamine locomotor response. Novelty response is altered into adulthood and provides evidence that enrichment can be used to reduce drug vulnerability. Copyright © 2017 Elsevier Inc. All rights reserved.

Caffeine-supplemented diet modulates oxidative stress markers and improves locomotor behavior in the lobster cockroach Nauphoeta cinerea.

PubMed

da Silva, Cícera Simoni; de Cássia Gonçalves de Lima, Rita; Elekofehinti, Olusola Olalekan; Ogunbolude, Yetunde; Duarte, Antonia Eliene; Rocha, João Batista Teixeira; Alencar de Menezes, Irwin Rose; Barros, Luiz Marivando; Tsopmo, Appolinaire; Lukong, Kiven Erique; Kamdem, Jean Paul

2018-02-25

The effects of caffeine supplementation is well documented in conventional animal models, however, in the lobster cockroaches Nauphoeta cinerea, they have not been reported. Thus, the aim of this study was to investigate the locomotor behavior and biochemical endpoints in the head of the nymphs of N. cinerea following 60 days exposure to food supplemented with 0, 0.5, 1.0, 2.5, 5.0 and 10.0 mg of caffeine/g of diet. The analysis of the locomotor behavior using the video-tracking software, Any-maze, for 12 min revealed that caffeine supplementation caused significant behavioral improvement. There was increase in distance travelled, velocity, frequency of rotation and turn angle (stereotypical behavior such as circling movements), and this was supported by the representative track plots of the path travelled by cockroaches in the open-field arena. In addition, caffeine supplementation markedly increased total thiol and non-protein thiol glutathione (GSH) levels in the heads of cockroaches, and this was in parallel with significant reduction of lipid peroxidation and free Fe(II) content. Taking together, our results indicate that long-term caffeine supplementation may exert preventive effects against oxidative stress and support the use of N. cinerea as an efficient alternative model to assess the efficacy of food molecules. Copyright © 2018 Elsevier B.V. All rights reserved.

Spinal cord injury: overview of experimental approaches used to restore locomotor activity.

PubMed

Fakhoury, Marc

2015-01-01

Spinal cord injury affects more than 2.5 million people worldwide and can lead to paraplegia and quadriplegia. Anatomical discontinuity in the spinal cord results in disruption of the impulse conduction that causes temporary or permanent changes in the cord's normal functions. Although axonal regeneration is limited, damage to the spinal cord is often accompanied by spontaneous plasticity and axon regeneration that help improve sensory and motor skills. The recovery process depends mainly on synaptic plasticity in the preexisting circuits and on the formation of new pathways through collateral sprouting into neighboring denervated territories. However, spontaneous recovery after spinal cord injury can go on for several years, and the degree of recovery is very limited. Therefore, the development of new approaches that could accelerate the gain of motor function is of high priority to patients with damaged spinal cord. Although there are no fully restorative treatments for spinal injury, various rehabilitative approaches have been tested in animal models and have reached clinical trials. In this paper, a closer look will be given at the potential therapies that could facilitate axonal regeneration and improve locomotor recovery after injury to the spinal cord. This article highlights the application of several interventions including locomotor training, molecular and cellular treatments, and spinal cord stimulation in the field of rehabilitation research. Studies investigating therapeutic approaches in both animal models and individuals with injured spinal cords will be presented.

Step training with body weight support: effect of treadmill speed and practice paradigms on poststroke locomotor recovery.

PubMed

Sullivan, Katherine J; Knowlton, Barbara J; Dobkin, Bruce H

2002-05-01

To investigate the effect of practice paradigms that varied treadmill speed during step training with body weight support in subjects with chronic hemiparesis after stroke. Randomized, repeated-measures pilot study with 1- and 3-month follow-ups. Outpatient locomotor laboratory. Twenty-four individuals with hemiparetic gait deficits whose walking speeds were at least 50% below normal. Participants were stratified by locomotor severity based on initial walking velocity and randomly assigned to treadmill training at slow (0.5mph), fast (2.0mph), or variable (0.5, 1.0, 1.5, 2.0mph) speeds. Participants received 20 minutes of training per session for 12 sessions over 4 weeks. Self-selected overground walking velocity (SSV) was assessed at the onset, middle, and end of training, and 1 and 3 months later. SSV improved in all groups compared with baseline (P<.001). All groups increased SSV in the 1-month follow-up (P<.01) and maintained these gains at the 3-month follow-up (P=.77). The greatest improvement in SSV across training occurred with fast training speeds compared with the slow and variable groups combined (P=.04). Effect size (ES) was large between fast compared with slow (ES=.75) and variable groups (ES=.73). Training at speeds comparable with normal walking velocity was more effective in improving SSV than training at speeds at or below the patient's typical overground walking velocity. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

Therapeutic effects of an anti-gravity locomotor training (AlterG) on postural balance and cerebellum structure in children with Cerebral Palsy.

PubMed

Rasooli, A H; Birgani, P M; Azizi, Sh; Shahrokhi, A; Mirbagheri, M M

2017-07-01

We evaluated the therapeutic effects of anti-gravity locomotor treadmill (AlterG) training on postural stability in children with Cerebral Palsy (CP) and spasticity, particularly in the lower extremity. AlterG can facilitate walking by reducing the weight of CP children by up to 80%; it can also help subjects maintain an appropriate posture during the locomotor AlterG training. Thus, we hypothesized that AlterG training, for a sufficient period of time, has a potential to produce cerebellum neuroplasticity, and consequently result in an effective permanent postural stability. AlterG training was given for 45 minutes, three times a week for two months. Postural balance was evaluated using posturography. The parameters of the Romberg based posturography were extracted to quantify the Center of Balance (CoP). The neuroplasticity of Cerebellum was evaluated using a Diffusion Tensor Imaging (DTI). The evaluations were done pre- and post-training. The Fractional Anisotropy (FA) feature was used for quantifying structural changes in the cerebellum. The results showed that AlterG training resulted in an increase in average FA value of the cerebellum white matter following the training. The results of the posturography evaluations showed a consistent improvement in postural stability. These results were consistent in all subjects. Our findings indicated that the improvement in the posture was accompanied with the enhancement of the cerebellum white matter structure. The clinical implication is that AlterG training can be considered a therapeutic tool for an effective and permanent improvement of postural stability in CP children.

A Review of the Pedunculopontine Nucleus in Parkinson's Disease.

PubMed

French, Isobel T; Muthusamy, Kalai A

2018-01-01

The pedunculopontine nucleus (PPN) is situated in the upper pons in the dorsolateral portion of the ponto-mesencephalic tegmentum. Its main mass is positioned at the trochlear nucleus level, and is part of the mesenphalic locomotor region (MLR) in the upper brainstem. The human PPN is divided into two subnuclei, the pars compacta (PPNc) and pars dissipatus (PPNd), and constitutes both cholinergic and non-cholinergic neurons with afferent and efferent projections to the cerebral cortex, thalamus, basal ganglia (BG), cerebellum, and spinal cord. The BG controls locomotion and posture via GABAergic output of the substantia nigra pars reticulate (SNr). In PD patients, GABAergic BG output levels are abnormally increased, and gait disturbances are produced via abnormal increases in SNr-induced inhibition of the MLR. Since the PPN is vastly connected with the BG and the brainstem, dysfunction within these systems lead to advanced symptomatic progression in Parkinson's disease (PD), including sleep and cognitive issues. To date, the best treatment is to perform deep brain stimulation (DBS) on PD patients as outcomes have shown positive effects in ameliorating the debilitating symptoms of this disease by treating pathological circuitries within the parkinsonian brain. It is therefore important to address the challenges and develop this procedure to improve the quality of life of PD patients.

A Review of the Pedunculopontine Nucleus in Parkinson's Disease

PubMed Central

French, Isobel T.; Muthusamy, Kalai A.

2018-01-01

The pedunculopontine nucleus (PPN) is situated in the upper pons in the dorsolateral portion of the ponto-mesencephalic tegmentum. Its main mass is positioned at the trochlear nucleus level, and is part of the mesenphalic locomotor region (MLR) in the upper brainstem. The human PPN is divided into two subnuclei, the pars compacta (PPNc) and pars dissipatus (PPNd), and constitutes both cholinergic and non-cholinergic neurons with afferent and efferent projections to the cerebral cortex, thalamus, basal ganglia (BG), cerebellum, and spinal cord. The BG controls locomotion and posture via GABAergic output of the substantia nigra pars reticulate (SNr). In PD patients, GABAergic BG output levels are abnormally increased, and gait disturbances are produced via abnormal increases in SNr-induced inhibition of the MLR. Since the PPN is vastly connected with the BG and the brainstem, dysfunction within these systems lead to advanced symptomatic progression in Parkinson's disease (PD), including sleep and cognitive issues. To date, the best treatment is to perform deep brain stimulation (DBS) on PD patients as outcomes have shown positive effects in ameliorating the debilitating symptoms of this disease by treating pathological circuitries within the parkinsonian brain. It is therefore important to address the challenges and develop this procedure to improve the quality of life of PD patients. PMID:29755338

Predictive Measures of Locomotor Performance on an Unstable Walking Surface

NASA Technical Reports Server (NTRS)

Bloomberg, J. J.; Peters, B. T.; Mulavara, A. P.; Caldwell, E. E.; Batson, C. D.; De Dios, Y. E.; Gadd, N. E.; Goel, R.; Wood, S. J.; Cohen, H. S.;

[Effects of nootropic drugs on behavior of BALB/c and C57BL/6 mice in the exploratory cross-maze test].

PubMed

Vasil'eva, E V; Salimov, R M; Kovalev, G I

2012-01-01

Exploratory behavior, locomotor activity, and anxiety in inbred mice of C57BL/6 and BALB/c strains subchronically treated with placebo or various types of nootropic (cognition enhancing) drugs (piracetam, phenotropil, noopept, semax, pantogam, nooglutil) have been evaluated using the exploratory cross-maze test. It was found that BALB/c mice in comparison to C57BL/6 mice are characterized by greater anxiety and lower efficiency of exploratory behavior in the previously unfamiliar environment. All tested drugs clearly improved the exploratory behavior in BALB/c mice only. In BALB/c mice, piracetam, phenotropil, noopept, and semax also reduced anxiety, while phenotropil additionally increased locomotor activity. Thus, the nootropic drugs displayed clear positive modulation of spontaneous orientation in the mice strain with initially low exploratory efficiency (BALB/c) in the cross-maze test. Some drugs (pantogam, nooglutil) exhibited only nootropic properties, while the other drugs exhibited both nootropic effects on the exploratory activity and produced modulation of the anxiety level (piracetam, fenotropil, noopept, semax) and locomotor activity (fenotropil).

Spermidine promotes stress resistance in Drosophila melanogaster through autophagy-dependent and -independent pathways.

PubMed

Minois, N; Carmona-Gutierrez, D; Bauer, M A; Rockenfeller, P; Eisenberg, T; Brandhorst, S; Sigrist, S J; Kroemer, G; Madeo, F

2012-10-11

The naturally occurring polyamine spermidine (Spd) has recently been shown to promote longevity across species in an autophagy-dependent manner. Here, we demonstrate that Spd improves both survival and locomotor activity of the fruit fly Drosophila melanogaster upon exposure to the superoxide generator and neurotoxic agent paraquat. Although survival to a high paraquat concentration (20 mM) was specifically increased in female flies only, locomotor activity and survival could be rescued in both male and female animals when exposed to lower paraquat levels (5 mM). These effects are dependent on the autophagic machinery, as Spd failed to confer resistance to paraquat-induced toxicity and locomotor impairment in flies deleted for the essential autophagic regulator ATG7 (autophagy-related gene 7). Spd treatment did also protect against mild doses of another oxidative stressor, hydrogen peroxide, but in this case in an autophagy-independent manner. Altogether, this study establishes that the protective effects of Spd can be exerted through different pathways that depending on the oxidative stress scenario do or do not involve autophagy.

Progression of multiple behavioral deficits with various ages of onset in a murine model of Hurler syndrome.

PubMed

Pan, Dao; Sciascia, Anthony; Vorhees, Charles V; Williams, Michael T

2008-01-10

Mucopolysaccharidosis type I (MPS I) is one of the most common lysosomal storage diseases with progressive neurological dysfunction. To characterize the chronological behavioral profiles and identify the onset of functional deficits in a MPS I mouse model (IDUA(-/-)), we evaluated anxiety, locomotor behavior, startle, spatial learning and memory with mice at 2, 4, 6 and 8 months of age. In automated open-field test, IDUA(-/-) mice showed hypoactivity as early as 2 months of age and altered anxiety starting from 6 months of age during the initial exploratory phase, even though normal habituation was observed at all ages. In the marble-burying task, the anxiety-like compulsive behavior was normal in IDUA(-/-) mice at almost all tested ages, but significantly reduced in 8-month old male IDUA(-/-) mice which coincided with the rapid death of IDUA(-/-) males starting from 7 months of age. In the Morris water maze, IDUA(-/-) mice exhibited impaired proficient learning only at 4 months of age during the acquisition phase. Spatial memory deficits were observed in IDUA(-/-) mice during both 1 and 7 days probe trials at 4 and 8 months of age. The IDUA(-/-) mice performed normally in a novel object recognition task at younger ages until 8 months old when reduced visual cognitive memory retention was noted in the IDUA(-/-) mice. In addition, 8-month-old IDUA(-/-) mice failed to habituate to repeated open-field exposure, suggesting deficits in non-aversive and non-associative memory. In acoustic startle assessment, significantly more non-responders were found in IDUA(-/-) mice, but normal performance was seen in those that did show a response. These results presented a temporal evaluation of phenotypic behavioral dysfunctions in IDUA(-/-) mice from adolescence to maturity, indicating the impairments, with different ages of onset, in locomotor and anxiety-like compulsive behaviors, spatial learning and memory, visual recognition and short-term non-associative memory retention. This study would also provide guidelines for the experimental designs of behavioral evaluation on innovative therapies for the treatment of MPS type I.

Agmatine blocks ethanol-induced locomotor hyperactivity in male mice.

PubMed

Ozden, Onder; Kayir, Hakan; Ozturk, Yusuf; Uzbay, Tayfun

2011-05-20

Ethanol-induced locomotor activity is associated to rewarding effects of ethanol and ethanol dependence. Agmatine is a novel endogenous ligand at α2-adrenoceptors, imidazoline and N-methyl-d-aspartate (NMDA) receptors, as well as a nitric oxide synthase (NOS) inhibitor. There is no evidence presented for the relationship between the acute locomotor stimulating effect of ethanol and agmatine. Thus, the present study investigated the effects of agmatine on acute ethanol-induced locomotor hyperactivity in mice. Adult male Swiss-Webster mice (26-36g) were used as subjects. Locomotor activity of the mice was recorded for 30min immediately following intraperitoneal administration of ethanol (0.5, 1 and 2g/kg) or saline (n=8 for each group). Agmatine (5, 10 and 20mg/kg) or saline was administered intraperitoneally to another four individual groups (n=8 for each group) of the mice 20min before the ethanol injection. In these groups, locomotor activity was also recorded immediately following ethanol (0.5g/kg) injection for 30min. Ethanol (0.5g/kg) produced some significant increases in locomotor activity of the mice. Agmatine (5-20mg/kg) significantly blocked the ethanol (0.5g/kg)-induced locomotor hyperactivity. These doses of agmatine did not affect the locomotor activity in naive mice when they were administered alone. Our results suggest that agmatine has an important role in ethanol-induced locomotor hyperactivity in mice. There may be a relationship between the addictive psychostimulant effects of the ethanol and central agmatinergic system. Copyright © 2011 Elsevier B.V. All rights reserved.

Locomotor Behaviour of Blattella germanica Modified by DEET

PubMed Central

Sfara, Valeria; Mougabure-Cueto, Gastón A.; Zerba, Eduardo N.; Alzogaray, Raúl A.

2013-01-01

N,N-diethyl-3-methylbenzamide (DEET) is the active principle of most insect repellents used worldwide. However, its toxicity on insects has not been widely studied. The aim of this work is to study the effects of DEET on the locomotor activity of Blattella germanica. DEET has a dose-dependent repellent activity on B. germanica. Locomotor activity was significantly lower when insects were pre-exposed to 700 µg/cm2 of DEET for 20 or 30 minutes, but it did not change when pre-exposure was shorter. Locomotor activity of insects that were pre-exposed to 2.000 µg/cm2 of DEET for 10 minutes was significantly lower than the movement registered in controls. No differences were observed when insects were pre-exposed to lower concentrations of DEET. A 30-minute pre-exposure to 700 µg/cm2 of DEET caused a significant decrease in locomotor activity. Movement was totally recovered 24 h later. The locomotor activity measured during the exposure to different concentrations of DEET remained unchanged. Insects with decreased locomotor activity were repelled to the same extent than control insects by the same concentration of DEET. We demonstrated that the repellency and modification of locomotor activity elicited by DEET are non-associated phenomena. We also suggested that the reduction in locomotor activity indicates toxicity of DEET, probably to insect nervous system. PMID:24376701

Locomotor behaviour of Blattella germanica modified by DEET.

PubMed

Sfara, Valeria; Mougabure-Cueto, Gastón A; Zerba, Eduardo N; Alzogaray, Raúl A

2013-01-01

N,N-diethyl-3-methylbenzamide (DEET) is the active principle of most insect repellents used worldwide. However, its toxicity on insects has not been widely studied. The aim of this work is to study the effects of DEET on the locomotor activity of Blattella germanica. DEET has a dose-dependent repellent activity on B. germanica. Locomotor activity was significantly lower when insects were pre-exposed to 700 µg/cm(2) of DEET for 20 or 30 minutes, but it did not change when pre-exposure was shorter. Locomotor activity of insects that were pre-exposed to 2.000 µg/cm(2) of DEET for 10 minutes was significantly lower than the movement registered in controls. No differences were observed when insects were pre-exposed to lower concentrations of DEET. A 30-minute pre-exposure to 700 µg/cm(2) of DEET caused a significant decrease in locomotor activity. Movement was totally recovered 24 h later. The locomotor activity measured during the exposure to different concentrations of DEET remained unchanged. Insects with decreased locomotor activity were repelled to the same extent than control insects by the same concentration of DEET. We demonstrated that the repellency and modification of locomotor activity elicited by DEET are non-associated phenomena. We also suggested that the reduction in locomotor activity indicates toxicity of DEET, probably to insect nervous system.

Sex differences in the acute locomotor response to methamphetamine in BALB/c mice.

PubMed

Ohia-Nwoko, Odochi; Haile, Colin N; Kosten, Therese A

2017-06-01

Women use methamphetamine more frequently than men and are more vulnerable to its negative psychological effects. Rodent models have been an essential tool for evaluating the sex-dependent effects of psychostimulants; however, evidence of sex differences in the behavioral responses to methamphetamine in mice is lacking. In the present study, we investigated acute methamphetamine-induced (1mg/kg and 4mg/kg) locomotor activation in female and male BALB/c mice. We also evaluated whether basal locomotor activity was associated with the methamphetamine-induced locomotor response. The results indicated that female BALB/c mice displayed enhanced methamphetamine-induced locomotor activity compared to males, while basal locomotor activity was positively correlated with methamphetamine-induced activity in males, but not females. This study is the first to show sex-dependent locomotor effects of methamphetamine in BALB/c mice. Our observations emphasize the importance of considering sex when assessing behavioral responses to methamphetamine. Copyright © 2017 Elsevier B.V. All rights reserved.

Potential of adult mammalian lumbosacral spinal cord to execute and acquire improved locomotion in the absence of supraspinal input

NASA Technical Reports Server (NTRS)

Edgerton, V. R.; Roy, R. R.; Hodgson, J. A.; Prober, R. J.; de Guzman, C. P.; de Leon, R.

1992-01-01

The neural circuitry of the lumbar spinal cord can generate alternating extension and flexion of the hindlimbs. The hindlimbs of adult cats with complete transection of the spinal cord at a low thoracic level (T12-T13) can perform full weight-supporting locomotion on a treadmill belt moving at a range of speeds. Some limitations in the locomotor capacity can be associated with a deficit in the recruitment level of the fast extensors during the stance phase and the flexors during the swing phase of a step cycle. The level of locomotor performance, however, can be enhanced by daily training on a treadmill while emphasizing full weight-support stepping and by providing appropriately timed sensory stimulation, loading, and/or pharmacologic stimulation of the hindlimb neuromuscular apparatus. Furthermore, there appears to be an interactive effect of these interventions. For example, the maximum treadmill speed that a spinal adult cat can attain and maintain is significantly improved with daily full weight-supporting treadmill training, but progressive recruitment of fast extensors becomes apparent only when the hindlimbs are loaded by gently pulling down on the tail during the stepping. Stimulation of the sural nerve at the initiation of the flexion phase of the step cycle can likewise markedly improve the locomotor capability. Administration of clonidine, in particular in combination with an elevated load, resulted in the most distinct and consistent alternating bursts of electromyographic activity during spinal stepping. These data indicate that the spinal cord has the ability to execute alternating activation of the extensor and flexor musculature of the hindlimbs (stepping) and that this ability can be improved by several interventions such as training, sensory stimulation, and use of some pharmacologic agents. Thus, it appears that the spinal cord, without supraspinal input, is highly plastic and has the potential to "learn," that is, to acquire and improve its ability to execute full weight-supporting locomotion on a treadmill belt.

Ankle Training With a Robotic Device Improves Hemiparetic Gait After a Stroke

PubMed Central

Forrester, Larry W.; Roy, Anindo; Krebs, Hermano Igo; Macko, Richard F.

2013-01-01

Background Task-oriented therapies such as treadmill exercise can improve gait velocity after stroke, but slow velocities and abnormal gait patterns often persist, suggesting a need for additional strategies to improve walking. Objectives To determine the effects of a 6-week visually guided, impedance controlled, ankle robotics intervention on paretic ankle motor control and gait function in chronic stroke. Methods This was a single-arm pilot study with a convenience sample of 8 stroke survivors with chronic hemiparetic gait, trained and tested in a laboratory. Subjects trained in dorsiflexion–plantarflexion by playing video games with the robot during three 1-hour training sessions weekly, totaling 560 repetitions per session. Assessments included paretic ankle ranges of motion, strength, motor control, and overground gait function. Results Improved paretic ankle motor control was seen as increased target success, along with faster and smoother movements. Walking velocity also increased significantly, whereas durations of paretic single support increased and double support decreased. Conclusions Robotic feedback training improved paretic ankle motor control with improvements in floor walking. Increased walking speeds were comparable with reports from other task-oriented, locomotor training approaches used in stroke, suggesting that a focus on ankle motor control may provide a valuable adjunct to locomotor therapies. PMID:21115945

To 3D or Not to 3D, That Is the Question: Do 3D Surface Analyses Improve the Ecomorphological Power of the Distal Femur in Placental Mammals?

PubMed Central

Gould, Francois D. H.

2014-01-01

Improvements in three-dimensional imaging technologies have renewed interest in the study of functional and ecological morphology. Quantitative approaches to shape analysis are used increasingly to study form-function relationships. These methods are computationally intensive, technically demanding, and time-consuming, which may limit sampling potential. There have been few side-by-side comparisons of the effectiveness of such approaches relative to more traditional analyses using linear measurements and ratios. Morphological variation in the distal femur of mammals has been shown to reflect differences in locomotor modes across clades. Thus I tested whether a geometric morphometric analysis of surface shape was superior to a multivariate analysis of ratios for describing ecomorphological patterns in distal femoral variation. A sample of 164 mammalian specimens from 44 genera was assembled. Each genus was assigned to one of six locomotor categories. The same hypotheses were tested using two methods. Six linear measurements of the distal femur were taken with calipers, from which four ratios were calculated. A 3D model was generated with a laser scanner, and analyzed using three dimensional geometric morphometrics. Locomotor category significantly predicted variation in distal femoral morphology in both analyses. Effect size was larger in the geometric morphometric analysis than in the analysis of ratios. Ordination reveals a similar pattern with arboreal and cursorial taxa as extremes on a continuum of morphologies in both analyses. Discriminant functions calculated from the geometric morphometric analysis were more accurate than those calculated from ratios. Both analysis of ratios and geometric morphometric surface analysis reveal similar, biologically meaningful relationships between distal femoral shape and locomotor mode. The functional signal from the morphology is slightly higher in the geometric morphometric analysis. The practical costs of conducting these sorts of analyses should be weighed against potentially slight increases in power when designing protocols for ecomorphological studies. PMID:24633081

Actions of incretin metabolites on locomotor activity, cognitive function and in vivo hippocampal synaptic plasticity in high fat fed mice.

PubMed

Porter, David; Faivre, Emilie; Flatt, Peter R; Hölscher, Christian; Gault, Victor A

2012-05-01

The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) improve markers of cognitive function in obesity-diabetes, however, both are rapidly degraded to their major metabolites, GLP-1(9-36)amide and GIP(3-42), respectively. Therefore, the present study investigated effects of GLP-1(9-36)amide and GIP(3-42) on locomotor activity, cognitive function and hippocampal synaptic plasticity in mice with diet-induced obesity and insulin resistance. High-fat fed Swiss TO mice treated with GLP-1(9-36)amide, GIP(3-42) or exendin(9-39)amide (twice-daily for 60 days) did not exhibit any changes in bodyweight, non-fasting plasma glucose and plasma insulin concentrations or glucose tolerance compared with high-fat saline controls. Similarly, locomotor and feeding activity, O(2) consumption, CO(2) production, respiratory exchange ratio and energy expenditure were not altered by chronic treatment with incretin metabolites. Administration of the truncated metabolites did not alter general behavior in an open field test or learning and memory ability as recorded during an object recognition test. High-fat mice exhibited a significant impairment in hippocampal long-term potentiation (LTP) which was not affected by treatment with incretin metabolites. These data indicate that incretin metabolites do not influence locomotor activity, cognitive function and hippocampal synaptic plasticity when administered at pharmacological doses to mice fed a high-fat diet. Copyright © 2012 Elsevier Inc. All rights reserved.

Locomotor training improves reciprocal and nonreciprocal inhibitory control of soleus motoneurons in human spinal cord injury

PubMed Central

Smith, Andrew C.; Mummidisetty, Chaithanya K.

2015-01-01

Pathologic reorganization of spinal networks and activity-dependent plasticity are common neuronal adaptations after spinal cord injury (SCI) in humans. In this work, we examined changes of reciprocal Ia and nonreciprocal Ib inhibition after locomotor training in 16 people with chronic SCI. The soleus H-reflex depression following common peroneal nerve (CPN) and medial gastrocnemius (MG) nerve stimulation at short conditioning-test (C-T) intervals was assessed before and after training in the seated position and during stepping. The conditioned H reflexes were normalized to the unconditioned H reflex recorded during seated. During stepping, both H reflexes were normalized to the maximal M wave evoked at each bin of the step cycle. In the seated position, locomotor training replaced reciprocal facilitation with reciprocal inhibition in all subjects, and Ib facilitation was replaced by Ib inhibition in 13 out of 14 subjects. During stepping, reciprocal inhibition was decreased at early stance and increased at midswing in American Spinal Injury Association Impairment Scale C (AIS C) and was decreased at midstance and midswing phases in AIS D after training. Ib inhibition was decreased at early swing and increased at late swing in AIS C and was decreased at early stance phase in AIS D after training. The results of this study support that locomotor training alters postsynaptic actions of Ia and Ib inhibitory interneurons on soleus motoneurons at rest and during stepping and that such changes occur in cases with limited or absent supraspinal inputs. PMID:25609110

A disparity between locomotor economy and territory-holding ability in male house mice.

PubMed

Morris, Jeremy S; Ruff, James S; Potts, Wayne K; Carrier, David R

2017-07-15

Both economical locomotion and physical fighting are important performance traits to many species because of their direct influence on components of Darwinian fitness. Locomotion represents a substantial portion of the total daily energy budget of many animals. Fighting performance often determines individual reproductive fitness through the means of resource control, social dominance and access to mates. However, phenotypic traits that improve either locomotor economy or fighting ability may diminish performance in the other. Here, we tested for a predicted disparity between locomotor economy and competitive ability in wild-derived house mice ( Mus musculus ). We used 8 week social competition trials in semi-natural enclosures to directly measure male competitive ability through territorial control and female occupancy within territories. We also measured oxygen consumption during locomotion for each mouse using running trials in an enclosed treadmill and open-flow respirometry. Our results show that territory-holding males have higher absolute and mass-specific oxygen consumption when running (i.e. reduced locomotor economy) compared with males that do not control territories. This relationship was present both before and after 8 week competition trials in semi-natural enclosures. This disparity between physical competitive ability and economical locomotion may impose viability costs on males in species for which competition over mates is common and may constrain the evolution of behavioral and phenotypic diversity, particularly in natural settings with environmental and resource variability. © 2017. Published by The Company of Biologists Ltd.

Use of trunk stabilization and locomotor training in an adult with cerebellar ataxia: a single system design.

PubMed

Freund, Jane E; Stetts, Deborah M

2010-10-01

The purpose of this study is to describe the effects of trunk stabilization training and locomotor training (LT) using body-weight support on a treadmill (BWST) and overground walking on balance, gait, self-reported function, and trunk muscle performance in an adult with severe ataxia secondary to brain injury. There are no studies on the effectiveness of these combined interventions in persons with ataxia. The subject was a 23-year-old male who had a traumatic brain injury 13 months prior. An A-B-A withdrawal single-system design was used. Outcome measures were Berg Balance Test (BBT), timed unsupported stance, Functional Ambulation Category (FAC), 10-meter walk test (10-MWT), Outpatient Physical Therapy Improvement in Movement Assessment Log (OPTIMAL), transverse abdominis (TrA) thickness, and isometric trunk endurance tests. Performance on the BBT, timed unsupported stance, FAC, 10-MWT, and OPTIMAL each improved after 10 weeks of intervention. In additions, TrA symmetry at rest improved as did right side-bridge endurance time. LT, using BWST and overground walking, and trunk stabilization training may be effective in improving balance, gait, function, and trunk performance in individuals with severe ataxia. Further research with additional subjects is indicated.

Use of quadrupedal step training to re-engage spinal interneuronal networks and improve locomotor function after spinal cord injury.

PubMed

Shah, Prithvi K; Garcia-Alias, Guillermo; Choe, Jaehoon; Gad, Parag; Gerasimenko, Yury; Tillakaratne, Niranjala; Zhong, Hui; Roy, Roland R; Edgerton, V Reggie

2013-11-01

Can lower limb motor function be improved after a spinal cord lesion by re-engaging functional activity of the upper limbs? We addressed this issue by training the forelimbs in conjunction with the hindlimbs after a thoracic spinal cord hemisection in adult rats. The spinal circuitries were more excitable, and behavioural and electrophysiological analyses showed improved hindlimb function when the forelimbs were engaged simultaneously with the hindlimbs during treadmill step-training as opposed to training only the hindlimbs. Neuronal retrograde labelling demonstrated a greater number of propriospinal labelled neurons above and below the thoracic lesion site in quadrupedally versus bipedally trained rats. The results provide strong evidence that actively engaging the forelimbs improves hindlimb function and that one likely mechanism underlying these effects is the reorganization and re-engagement of rostrocaudal spinal interneuronal networks. For the first time, we provide evidence that the spinal interneuronal networks linking the forelimbs and hindlimbs are amenable to a rehabilitation training paradigm. Identification of this phenomenon provides a strong rationale for proceeding toward preclinical studies for determining whether training paradigms involving upper arm training in concert with lower extremity training can enhance locomotor recovery after neurological damage.

Elevations of Endogenous Kynurenic Acid Produce Spatial Working Memory Deficits

PubMed Central

Chess, Amy C.; Simoni, Michael K.; Alling, Torey E.; Bucci, David J.

2007-01-01

Kynurenic acid (KYNA) is a tryptophan metabolite that is synthesized and released by astrocytes and acts as a competitive antagonist of the glycine site of N-methyl-D-aspartate receptors at high concentrations and as a noncompetitive antagonist of the α7-nicotinic acetylcholine receptor at low concentrations. The discovery of increased cortical KYNA levels in schizophrenia prompted the hypothesis that elevated KYNA concentration may underlie the working memory dysfunction observed in this population that has been attributed to altered glutamatergic and/or cholinergic transmission. The present study investigated the effect of elevated endogenous KYNA on spatial working memory function in rats. Increased KYNA levels were achieved with intraperitoneal administration of kynurenine (100 mg/kg), the precursor of KYNA synthesis. Rats were treated with either kynurenine or a vehicle solution prior to testing in a radial arm maze task at various delays. Elevations of endogenous KYNA resulted in increased errors in the radial arm maze. In separate experiments, assessment of locomotor activity in an open field and latency to retrieve food reward from one of the maze arms ruled out the possibility that deficits in the maze were attributable to altered locomotor activity or motivation to consume food. These results provide evidence that increased KYNA levels produce spatial working memory deficits and are among the first to demonstrate the influence of glia-derived molecules on cognitive function. The implications for psychopathological conditions such as schizophrenia are discussed. PMID:16920787

Consequences of Developmental Exposure to Concentrated Ambient Ultrafine Particle Air Pollution Combined with the Adult Paraquat and Maneb Model of the Parkinson’s Disease Phenotype in Male Mice

PubMed Central

Allen, Joshua L; Liu, Xiufang; Weston, Douglas; Conrad, Katherine; Oberdörster, Günter; Cory-Slechta, Deborah A

2014-01-01

Current evidence suggests suceptibility of both the substantia nigra and striatum to exposure to components of air pollution. Further, air pollution has been associated with increased risk of PD diagnsosis in humans or PD-like pathology in animals. This study examined whether exposure of mice to concentrated ambient ultrafine particles (CAPS; <100 nm diameter) during the first two weeks of life would alter susceptibility to induction of the Parkinson’s disease phenyotype (PDP) in a pesticide-based paraquat and maneb (PQ+MB) model during adulthood utilizing i.p. injections of 10 mg/kg PQ and 30 mg/kg MB 2× per week for 6 weeks. Evidence of CAPS-induced enhancement of the PQ+MB PDP was limited primarily to delayed recovery of locomotor activity 24 post injection of PQ+MB that could be related to alterations in striatal GABA inhibitory function. Absence of more extensive interactions might also reflect the finding that CAPS and PQ+MB appeared to differentially target the nigrostriatal dopamine and amino acid systems, with CAPS impacting striatum and PQ+MB impacting dopamine-glutamate function in midbrain; both CAPS and PQ+MB elevated glutamate levels in these specific regions, consistent with potential excitotoxicity. These findings demonstrate the ability of postnatal CAPS to produce locomotor dysfunction and dopaminergic and glutamateric changes, independent of PQ+MB, in brain regions involved in the PDP. PMID:24486957

Impaired contextual fear-conditioning in MAM rodent model of schizophrenia.

PubMed

Gill, Kathryn M; Miller, Sarah A; Grace, Anthony A

2018-05-01

The methylazoxymethanol acetate (MAM) rodent neurodevelopmental model of schizophrenia exhibits aberrant dopamine system activation attributed to hippocampal dysfunction. Context discrimination is a component of numerous behavioral and cognitive functions and relies on intact hippocampal processing. The present study explored context processing behaviors, along with dopamine system activation, during fear learning in the MAM model. Male offspring of dams treated with MAM (20mg/kg, i.p.) or saline on gestational day 17 were used for electrophysiological and behavioral experiments. Animals were tested on the immediate shock fear conditioning paradigm, with either different pre-conditioning contexts or varying amounts of context pre-exposure (0-10 sessions). Amphetamine-induced locomotor activity and dopamine neural activity was measured 1-week after fear conditioning. Saline, but not MAM animals, demonstrated enhanced fear responses following a single context pre-exposure in the conditioning context. One week following fear learning, saline rats with 2 or 7min of context pre-exposure prior to fear conditioning also demonstrated enhanced amphetamine-induced locomotor response relative to MAM animals. Dopamine neuron recordings showed fear learning-induced reductions in spontaneous dopamine neural activity in MAM rats that was further reduced by amphetamine. Apomorphine administration confirmed that reductions in dopamine neuron activity in MAM animals resulted from over excitation, or depolarization block. These data show a behavioral insensitivity to contextual stimuli in MAM rats that coincide with a less dynamic dopamine response after fear learning. Copyright © 2017 Elsevier B.V. All rights reserved.

Locomotor problems among rural elderly population in a District of Aligarh, North India.

PubMed

Maroof, Mohd; Ahmad, Anees; Khalique, Najam; Ansari, M Athar

2017-01-01

Locomotor functions decline with the age along with other physiological changes. This results in deterioration of the quality of life with decreased social and economic role in the society, as well as increased dependency, for the health care and other basic services. The demographic transition resulting in increased proportion of elderly may pose a burden to the health system. To find the prevalence of locomotor problems among the elderly population, and related sociodemographic factors. The study was a community-based cross-sectional study done at field practice area of Rural Health Training Centre, JN Medical College, AMU, Aligarh, Uttar Pradesh, India. A sample of 225 was drawn from 1018 elderly population aged 60 years and above using systematic random sampling with probability proportionate to size. Sociodemographic characteristics were obtained using pretested and predesigned questionnaire. Locomotor problems were assessed using the criteria used by National Sample Survey Organization. Data were analyzed using SPSS version 20. Chi-square test was used to test relationship of locomotor problems with sociodemographic factors. P <0.05 was considered statistically significant. The prevalence of locomotor problems among the elderly population was 25.8%. Locomotor problems were significantly associated with age, gender, and working status whereas no significant association with literacy status and marital status was observed. The study concluded that approximately one-fourth of the elderly population suffered from locomotor problems. The sociodemographic factors related to locomotor problems needs to be addressed properly to help them lead an independent and economically productive life.

Identification of potential therapeutic compounds for Parkinson's disease using Drosophila and human cell models.

PubMed

Sanz, Francisco José; Solana-Manrique, Cristina; Muñoz-Soriano, Verónica; Calap-Quintana, Pablo; Moltó, María Dolores; Paricio, Nuria

2017-07-01

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. It is caused by a loss of dopaminergic neurons in the substantia nigra pars compacta, leading to a decrease in dopamine levels in the striatum and thus producing movement impairment. Major physiological causes of neurodegeneration in PD are oxidative stress (OS) and mitochondrial dysfunction; these pathophysiological changes can be caused by both genetic and environmental factors. Although most PD cases are sporadic, it has been shown that 5-10% of them are familial forms caused by mutations in certain genes. One of these genes is the DJ-1 oncogene, which is involved in an early-onset recessive PD form. Currently, PD is an incurable disease for which existing therapies are not sufficiently effective to counteract or delay the progression of the disease. Therefore, the discovery of alternative drugs for the treatment of PD is essential. In this study we used a Drosophila PD model to identify candidate compounds with therapeutic potential for this disease. These flies carry a loss-of-function mutation in the DJ-1β gene, the Drosophila ortholog of human DJ-1, and show locomotor defects reflected by a reduced climbing ability. A pilot modifier chemical screen was performed, and several candidate compounds were identified based on their ability to improve locomotor activity of PD model flies. We demonstrated that some of them were also able to reduce OS levels in these flies. To validate the compounds identified in the Drosophila screen, a human cell PD model was generated by knocking down DJ-1 function in SH-SY5Y neuroblastoma cells. Our results showed that some of the compounds were also able to increase the viability of the DJ-1-deficient cells subjected to OS, thus supporting the use of Drosophila for PD drug discovery. Interestingly, some of them have been previously proposed as alternative therapies for PD or tested in clinical trials and others are first suggested in this study as potential drugs for the treatment of this disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Antagonistic Serotonergic and Octopaminergic Neural Circuits Mediate Food-Dependent Locomotory Behavior in Caenorhabditis elegans

PubMed Central

McCloskey, Richard J.; Peters, Emily

2017-01-01

Biogenic amines are conserved signaling molecules that link food cues to behavior and metabolism in a wide variety of organisms. In the nematode Caenorhabditis elegans, the biogenic amines serotonin (5-HT) and octopamine regulate a number of food-related behaviors. Using a novel method for long-term quantitative behavioral imaging, we show that 5-HT and octopamine jointly influence locomotor activity and quiescence in feeding and fasting hermaphrodites, and we define the neural circuits through which this modulation occurs. We show that 5-HT produced by the ADF neurons acts via the SER-5 receptor in muscles and neurons to suppress quiescent behavior and promote roaming in fasting worms, whereas 5-HT produced by the NSM neurons acts on the MOD-1 receptor in AIY neurons to promote low-amplitude locomotor behavior characteristic of well fed animals. Octopamine, produced by the RIC neurons, acts via SER-3 and SER-6 receptors in SIA neurons to promote roaming behaviors characteristic of fasting animals. We find that 5-HT signaling is required for animals to assume food-appropriate behavior, whereas octopamine signaling is required for animals to assume fasting-appropriate behavior. The requirement for both neurotransmitters in both the feeding and fasting states enables increased behavioral adaptability. Our results define the molecular and neural pathways through which parallel biogenic amine signaling tunes behavior appropriately to nutrient conditions. SIGNIFICANCE STATEMENT Animals adjust behavior in response to environmental changes, such as fluctuations in food abundance, to maximize survival and reproduction. Biogenic amines, such as like serotonin, are conserved neurotransmitters that regulate behavior and metabolism in relation to energy status. Disruptions of biogenic amine signaling contribute to human neurological diseases of mood, appetite, and movement. In this study, we investigated the roles of the biogenic amines serotonin and octopamine in regulating locomotion behaviors associated with feeding and fasting in the roundworm Caenorhabditis elegans. We identified neural circuits through which these signals work to govern behavior. Understanding the molecular pathways through which biogenic amines function in model organisms may improve our understanding of dysfunctions of appetite and behavior found in mammals, including humans. PMID:28698386

Possible involvement of GABAergic mechanism in protective effect of melatonin against sleep deprivation-induced behaviour modification and oxidative damage in mice.

PubMed

Kumar, Anil; Singh, Anant

2009-08-01

Sleep is an important physiological process responsible for the maintenance of physical, mental and emotional health of a living being. Sleep deprivation is considered risky for several pathological diseases such as anxiety and motor and cognitive dysfunctions. Sleep deprivation has recently been reported to cause oxidative damage. This study has been designed to explore the possible involvement of the GABAergic mechanism in protective effects of melatonin against 72-h sleep deprivation-induced behaviour modification and oxidative damage in mice. Mice were sleep-deprived for a period of 72 h using the grid over water suspended method. Animals were divided into groups of 6-8 animals each. Melatonin (5 and 10 mg/kg), flumazenil (0.5 mg/kg), picrotoxin (0.5 mg/kg) and muscimol (0.05 mg/kg) were administered for 5 days starting 2 days before 72-h sleep deprivation. Various behavioural tests (plus maze, zero maze, mirror chamber, actophotometer) and body weight assessment followed by oxidative stress parameters (malondialdehyde level, glutathione, catalase, nitrite and protein) were carried out. The 72-h sleep deprivation caused significant anxiety-like behaviour, weight loss, impaired locomotor activity and oxidative damage as compared with naïve (without sleep deprivation). Treatment with melatonin (5 mg/kg and 10 mg/kg, ip) significantly improved locomotor activity, weight loss and antianxiety effect as compared with control (sleep-deprived). Biochemically, melatonin treatment significantly restored reduced glutathione, catalase activity, attenuated lipid peroxidation and nitrite level as compared with control animals (72-h sleep-deprived). Flumazenil (0.5 mg/kg) and picrotoxin (0.5 mg/kg) pretreatments with a lower dose of melatonin (5 mg/kg) significantly antagonized the protective effect of melatonin. However, muscimol (0.05 mg/kg) pretreatment with melatonin (5 mg/kg, ip) potentiated the protective effect of melatonin which was significant as compared with their effect per se. This study suggests that GABAergic modulation is involved in the protective action of melatonin against sleep deprivation-induced anxiety-like behaviour and associated oxidative damage.

Vertebral telangiectatic osteosarcoma in a dog.

PubMed

Brellou, G; Papaioannou, N; Patsikas, M; Polizopoulou, Z; Vlemmas, I

2004-01-01

Telangiectatic osteosarcoma (TOS) affecting the seventh cervical vertebra (C7) was diagnosed in a 4-year-old male dog with signs of locomotor dysfunction. Bone lysis and an extradural-extramedullary mass were observed in radiographs and occipital myelograms. The diagnosis was confirmed by histopathologic and immunohistochemical examination of the mass. The tumor was composed of large blood-filled cavities lined by anaplastic stromal cells (malignant osteoblasts). Around the cavities were characteristic tumor giant cells ("bizarre cells"). Immunohistochemically the tumor cells were positive for proliferating cell nuclear antigen. The lining cells of the cysts were negative for von Willebrand factor. The histologic findings in this case of TOS involving C7 were similar to those seen in other cases of TOS in dogs and in people. Immunohistochemistry was a useful tool for assessing malignancy and for ruling out other differential diagnoses.

Heptachlor induced nigral dopaminergic neuronal loss and Parkinsonism-like movement deficits in mice

PubMed Central

Hong, Seokheon; Hwang, Joohyun; Kim, Joo Yeon; Shin, Ki Soon; Kang, Shin Jung

2014-01-01

Epidemiological studies have suggested an association between pesticide exposure and Parkinson's disease. In this study, we examined the neurotoxicity of an organochlorine pesticide, heptachlor, in vitro and in vivo. In cultured SH-SY5Y cells, heptachlor induced mitochondria-mediated apoptosis. When injected into mice intraperitoneally on a subchronic schedule, heptachlor induced selective loss of dopaminergic neurons in the substantia nigra pars compacta. In addition, the heptachlor injection induced gliosis of microglia and astrocytes selectively in the ventral midbrain area. When the general locomotor activities were monitored by open field test, the heptachlor injection did not induce any gross motor dysfunction. However, the compound induced Parkinsonism-like movement deficits when assessed by a gait and a pole test. These results suggest that heptachlor can induce Parkinson's disease-related neurotoxicities in vivo. PMID:24577234

The Effects of Sex-Ratio and Density on Locomotor Activity in the House Fly, Musca domestica

PubMed Central

Bahrndorff, Simon; Kjærsgaard, Anders; Pertoldi, Cino; Loeschcke, Volker; Schou, Toke M.; Skovgård, Henrik; Hald, Birthe

2012-01-01

Although locomotor activity is involved in almost all behavioral traits, there is a lack of knowledge on what factors affect it. This study examined the effects of sex—ratio and density on the circadian rhythm of locomotor activity of adult Musca domestica L. (Diptera: Muscidae) using an infra—red light system. Sex—ratio significantly affected locomotor activity, increasing with the percentage of males in the vials. In accordance with other studies, males were more active than females, but the circadian rhythm of the two sexes was not constant over time and changed during the light period. There was also an effect of density on locomotor activity, where males at intermediate densities showed higher activity. Further, the predictability of the locomotor activity, estimated as the degree of autocorrelation of the activity data, increased with the number of males present in the vials both with and without the presence of females. Overall, this study demonstrates that locomotor activity in M. domestica is affected by sex—ratio and density. Furthermore, the predictability of locomotor activity is affected by both sex—ratio, density, and circadian rhythm. These results add to our understanding of the behavioral interactions between houseflies and highlight the importance of these factors when designing behavioral experiments using M. domestica.

Amelioration of motor/sensory dysfunction and spasticity in a rat model of acute lumbar spinal cord injury by human neural stem cell transplantation

PubMed Central

2013-01-01

Introduction Intraspinal grafting of human neural stem cells represents a promising approach to promote recovery of function after spinal trauma. Such a treatment may serve to: I) provide trophic support to improve survival of host neurons; II) improve the structural integrity of the spinal parenchyma by reducing syringomyelia and scarring in trauma-injured regions; and III) provide neuronal populations to potentially form relays with host axons, segmental interneurons, and/or α-motoneurons. Here we characterized the effect of intraspinal grafting of clinical grade human fetal spinal cord-derived neural stem cells (HSSC) on the recovery of neurological function in a rat model of acute lumbar (L3) compression injury. Methods Three-month-old female Sprague–Dawley rats received L3 spinal compression injury. Three days post-injury, animals were randomized and received intraspinal injections of either HSSC, media-only, or no injections. All animals were immunosuppressed with tacrolimus, mycophenolate mofetil, and methylprednisolone acetate from the day of cell grafting and survived for eight weeks. Motor and sensory dysfunction were periodically assessed using open field locomotion scoring, thermal/tactile pain/escape thresholds and myogenic motor evoked potentials. The presence of spasticity was measured by gastrocnemius muscle resistance and electromyography response during computer-controlled ankle rotation. At the end-point, gait (CatWalk), ladder climbing, and single frame analyses were also assessed. Syrinx size, spinal cord dimensions, and extent of scarring were measured by magnetic resonance imaging. Differentiation and integration of grafted cells in the host tissue were validated with immunofluorescence staining using human-specific antibodies. Results Intraspinal grafting of HSSC led to a progressive and significant improvement in lower extremity paw placement, amelioration of spasticity, and normalization in thermal and tactile pain/escape thresholds at eight weeks post-grafting. No significant differences were detected in other CatWalk parameters, motor evoked potentials, open field locomotor (Basso, Beattie, and Bresnahan locomotion score (BBB)) score or ladder climbing test. Magnetic resonance imaging volume reconstruction and immunofluorescence analysis of grafted cell survival showed near complete injury-cavity-filling by grafted cells and development of putative GABA-ergic synapses between grafted and host neurons. Conclusions Peri-acute intraspinal grafting of HSSC can represent an effective therapy which ameliorates motor and sensory deficits after traumatic spinal cord injury. PMID:23710605

Improved clinical status, quality of life, and walking capacity in Parkinson's disease after body weight-supported high-intensity locomotor training.

PubMed

Rose, Martin H; Løkkegaard, Annemette; Sonne-Holm, Stig; Jensen, Bente R

2013-04-01

To evaluate the effect of body weight-supported progressive high-intensity locomotor training in Parkinson's disease (PD) on (1) clinical status; (2) quality of life; and (3) gait capacity. Open-label, fixed sequence crossover study. University motor control laboratory. Patients (N=13) with idiopathic PD (Hoehn and Yahr stage 2 or 3) and stable medication use. Patients completed an 8-week (3 × 1h/wk) training program on a lower-body positive-pressure treadmill. Body weight support was used to facilitate increased intensity and motor challenges during treadmill training. The training program contained combinations of (1) running and walking intervals, (2) the use of sudden changes (eg, in body weight support and speed), (3) different types of locomotion (eg, chassé, skipping, and jumps), and (4) sprints at 50 percent body weight. The Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Parkinson's Disease Questionnaire-39 items (PDQ-39), and the six-minute walk test were conducted 8 weeks before and pre- and posttraining. At the end of training, statistically significant improvements were found in all outcome measures compared with the control period. Total MDS-UPDRS score changed from (mean ± 1SD) 58±18 to 47±18, MDS-UPDRS motor part score changed from 35±10 to 29±12, PDQ-39 summary index score changed from 22±13 to 13±12, and the six-minute walking distance changed from 576±93 to 637±90m. Body weight-supported progressive high-intensity locomotor training is feasible and well tolerated by patients with PD. The training improved clinical status, quality of life, and gait capacity significantly. Copyright © 2013 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Locomotor impact of beneficial or nonbeneficial H-reflex conditioning after spinal cord injury

PubMed Central

Chen, Yi; Chen, Lu; Liu, Rongliang; Wang, Yu; Wolpaw, Jonathan R.

2013-01-01

When new motor learning changes neurons and synapses in the spinal cord, it may affect previously learned behaviors that depend on the same spinal neurons and synapses. To explore these effects, we used operant conditioning to strengthen or weaken the right soleus H-reflex pathway in rats in which a right spinal cord contusion had impaired locomotion. When up-conditioning increased the H-reflex, locomotion improved. Steps became longer, and step-cycle asymmetry (i.e., limping) disappeared. In contrast, when down-conditioning decreased the H-reflex, locomotion did not worsen. Steps did not become shorter, and asymmetry did not increase. Electromyographic and kinematic analyses explained how H-reflex increase improved locomotion and why H-reflex decrease did not further impair it. Although the impact of up-conditioning or down-conditioning on the H-reflex pathway was still present during locomotion, only up-conditioning affected the soleus locomotor burst. Additionally, compensatory plasticity apparently prevented the weaker H-reflex pathway caused by down-conditioning from weakening the locomotor burst and further impairing locomotion. The results support the hypothesis that the state of the spinal cord is a “negotiated equilibrium” that serves all the behaviors that depend on it. When new learning changes the spinal cord, old behaviors undergo concurrent relearning that preserves or improves their key features. Thus, if an old behavior has been impaired by trauma or disease, spinal reflex conditioning, by changing a specific pathway and triggering a new negotiation, may enable recovery beyond that achieved simply by practicing the old behavior. Spinal reflex conditioning protocols might complement other neurorehabilitation methods and enhance recovery. PMID:24371288

Nucleus accumbens deep-brain stimulation efficacy in ACTH-pretreated rats: alterations in mitochondrial function relate to antidepressant-like effects

PubMed Central

Kim, Y; McGee, S; Czeczor, J K; Walker, A J; Kale, R P; Kouzani, A Z; Walder, K; Berk, M; Tye, S J

2016-01-01

Mitochondrial dysfunction has a critical role in the pathophysiology of mood disorders and treatment response. To investigate this, we established an animal model exhibiting a state of antidepressant treatment resistance in male Wistar rats using 21 days of adrenocorticotropic hormone (ACTH) administration (100 μg per day). First, the effect of ACTH treatment on the efficacy of imipramine (10 mg kg−1) was investigated alongside its effect on the prefrontal cortex (PFC) mitochondrial function. Second, we examined the mood-regulatory actions of chronic (7 day) high-frequency nucleus accumbens (NAc) deep-brain stimulation (DBS; 130 Hz, 100 μA, 90 μS) and concomitant PFC mitochondrial function. Antidepressant-like responses were assessed in the open field test (OFT) and forced swim test (FST) for both conditions. ACTH pretreatment prevented imipramine-mediated improvement in mobility during the FST (P<0.05). NAc DBS effectively improved FST mobility in ACTH-treated animals (P<0.05). No improvement in mobility was observed for sham control animals (P>0.05). Analyses of PFC mitochondrial function revealed that ACTH-treated animals had decreased capacity for adenosine triphosphate production compared with controls. In contrast, ACTH animals following NAc DBS demonstrated greater mitochondrial function relative to controls. Interestingly, a proportion (30%) of the ACTH-treated animals exhibited heightened locomotor activity in the OFT and exaggerated escape behaviors during the FST, together with general hyperactivity in their home-cage settings. More importantly, the induction of this mania-like phenotype was accompanied by overcompensative increased mitochondrial respiration. Manifestation of a DBS-induced mania-like phenotype in imipramine-resistant animals highlights the potential use of this model in elucidating mechanisms of mood dysregulation. PMID:27327257

Object recognition impairment in Fmr1 knockout mice is reversed by amphetamine: involvement of dopamine in the medial prefrontal cortex.

PubMed

Ventura, R; Pascucci, T; Catania, M V; Musumeci, S A; Puglisi-Allegra, S

2004-09-01

Fragile X syndrome is an X-linked form of mental retardation including, among others, symptoms such as stereotypic behaviour, hyperactivity, hyperarousal, and cognitive deficits. We hypothesized that hyperactivity and/or compromised attentional, cognitive functions may lead to impaired performance in cognitive tasks in Fmr1 knockout mice, the most widely used animal model of fragile X syndrome, and suggested that psychostimulant treatment may improve performance by acting on one or both components. Since hyperactivity and cognitive functions have been suggested to depend on striatal and prefrontal cortex dopaminergic dysfunction, we assessed whether amphetamine produced beneficial, positive effects by acting on dopaminergic corticostriatal systems. Our results show that Fmr1 knockout mice are not able to discriminate between a familiar object and a novel one in the object recognition test, thus showing a clear-cut cognitive impairment that, to date, has been difficult to demonstrate in other cognitive tasks. Amphetamine improved performance of Fmr1 knockout mice, leading to enhanced ability to discriminate novel versus familiar objects, without significantly affecting locomotor activity. In agreement with behavioural data, amphetamine produced a greater increase in dopamine release in the prefrontal cortex of Fmr1 knockout compared with the wild-type mice, while a weak striatal dopaminergic response was observed in Fmr1 knockout mice. Our data support the view that the psychostimulant ameliorates performance in Fmr1 knockout mice by improving merely cognitive functions through its action on prefrontal cortical dopamine, irrespective of its action on motor hyperactivity. These results indicate that prefrontal cortical dopamine plays a major role in cognitive impairments characterizing Fmr1 knockout mice, thus pointing to an important aetiological factor in the fragile X syndrome.

Robot-assisted vs. sensory integration training in treating gait and balance dysfunctions in patients with multiple sclerosis: a randomized controlled trial

PubMed Central

Gandolfi, Marialuisa; Geroin, Christian; Picelli, Alessandro; Munari, Daniele; Waldner, Andreas; Tamburin, Stefano; Marchioretto, Fabio; Smania, Nicola

2014-01-01

Background: Extensive research on both healthy subjects and patients with central nervous damage has elucidated a crucial role of postural adjustment reactions and central sensory integration processes in generating and “shaping” locomotor function, respectively. Whether robotic-assisted gait devices might improve these functions in Multiple sclerosis (MS) patients is not fully investigated in literature. Purpose: The aim of this study was to compare the effectiveness of end-effector robot-assisted gait training (RAGT) and sensory integration balance training (SIBT) in improving walking and balance performance in patients with MS. Methods: Twenty-two patients with MS (EDSS: 1.5–6.5) were randomly assigned to two groups. The RAGT group (n = 12) underwent end-effector system training. The SIBT group (n = 10) underwent specific balance exercises. Each patient received twelve 50-min treatment sessions (2 days/week). A blinded rater evaluated patients before and after treatment as well as 1 month post treatment. Primary outcomes were walking speed and Berg Balance Scale. Secondary outcomes were the Activities-specific Balance Confidence Scale, Sensory Organization Balance Test, Stabilometric Assessment, Fatigue Severity Scale, cadence, step length, single and double support time, Multiple Sclerosis Quality of Life-54. Results: Between groups comparisons showed no significant differences on primary and secondary outcome measures over time. Within group comparisons showed significant improvements in both groups on the Berg Balance Scale (P = 0.001). Changes approaching significance were found on gait speed (P = 0.07) only in the RAGT group. Significant changes in balance task-related domains during standing and walking conditions were found in the SIBT group. Conclusion: Balance disorders in patients with MS may be ameliorated by RAGT and by SIBT. PMID:24904361

Transcranial direct current stimulation improves short-term memory in an animal model of attention-deficit/hyperactivity disorder.

PubMed

Leffa, Douglas Teixeira; de Souza, Andressa; Scarabelot, Vanessa Leal; Medeiros, Liciane Fernandes; de Oliveira, Carla; Grevet, Eugenio Horacio; Caumo, Wolnei; de Souza, Diogo Onofre; Rohde, Luis Augusto Paim; Torres, Iraci L S

2016-02-01

Attention deficit hyperactivity disorder (ADHD) is characterized by impairing levels of hyperactivity, impulsivity and inattention. However, different meta-analyses have reported disruptions in short and long-term memory in ADHD patients. Previous studies indicate that mnemonic dysfunctions might be the result of deficits in attentional circuits, probably due to ineffective dopaminergic modulation of hippocampal synaptic plasticity. In this study we aimed to evaluate the potential therapeutic effects of a neuromodulatory technique, transcranial direct current stimulation (tDCS), in short-term memory (STM) deficits presented by the spontaneous hypertensive rats (SHR), the most widely used animal model of ADHD. Adult male SHR and Wistar Kyoto rats (WKY) were subjected to a constant electrical current of 0.5 mA intensity applied on the frontal cortex for 20 min/day during 8 days. STM was evaluated with an object recognition test conducted in an open field. Exploration time and locomotion were recorded, and brain regions were dissected to determine dopamine and BDNF levels. SHR spent less time exploring the new object when compared to WKY, and tDCS improved object recognition deficits in SHR without affecting WKY performance. Locomotor activity was higher in SHR and it was not affected by tDCS. After stimulation, dopamine levels were increased in the hippocampus and striatum of both strains, while BDNF levels were increased only in the striatum of WKY. These findings suggest that tDCS on the frontal cortex might be able to improve STM deficits present in SHR, which is potentially related to dopaminergic neurotransmission in the hippocampus and striatum of those animals. Copyright © 2016. Published by Elsevier B.V.

Gait Adaptability Training Improves Both Postural Stability and Dual-Tasking Ability

NASA Technical Reports Server (NTRS)

Brady, Rachel A.; Batson, Crystal D.; Peters, Brian T.; Ploutz-Snyder, Robert J.; Mulavara, Ajitkumar P.; Bloomberg, Jacob J.

2010-01-01

After spaceflight, the process of readapting to Earth's gravity commonly presents crewmembers with a variety of locomotor challenges. Our recent work has shown that the ability to adapt to a novel discordant sensorimotor environment can be increased through preflight training, so one focus of our laboratory has been the development of a gait training countermeasure to expedite the return of normal locomotor function after spaceflight. We used a training system comprising a treadmill mounted on a motion base facing a virtual visual scene that provided a variety of sensory challenges. As part of their participation in a larger retention study, 10 healthy adults completed 3 training sessions during which they walked on a treadmill at 1.1 m/s while receiving discordant support-surface and visual manipulations. After a single training session, subjects stride frequencies improved, and after 2 training sessions their auditory reaction times improved, where improvement was indicated by a return toward baseline values. Interestingly, improvements in reaction time came after stride frequency improvements plateaued. This finding suggests that postural stability was given a higher priority than a competing cognitive task. Further, it demonstrates that improvement in both postural stability and dual-tasking can be achieved with multiple training exposures. We conclude that, with training, individuals become more proficient at walking in discordant sensorimotor conditions and are able to devote more attention to competing tasks.

Hybrid gait training with an overground robot for people with incomplete spinal cord injury: a pilot study.

PubMed

Del-Ama, Antonio J; Gil-Agudo, Angel; Pons, José L; Moreno, Juan C

2014-01-01

Locomotor training has proved to provide beneficial effect in terms of mobility in incomplete paraplegic patients. Neuroprosthetic technology can contribute to increase the efficacy of a training paradigm in the promotion of a locomotor pattern. Robotic exoskeletons can be used to manage the unavoidable loss of performance of artificially driven muscles. Hybrid exoskeletons blend complementary robotic and neuro-prosthetic technologies. The aim of this pilot study was to determine the effects of hybrid gait training in three case studies with persons with incomplete spinal cord injury (iSCI) in terms of locomotion performance during assisted gait, patient-robot adaptations, impact on ambulation and assessment of lower limb muscle strength and spasticity. Participants with iSCI received interventions with a hybrid bilateral exoskeleton for 4 days. Assessment of gait function revealed that patients improved the 6 min and 10 m walking tests after the intervention, and further improvements were observed 1 week after the intervention. Muscle examination revealed improvements in knee and hip sagittal muscle balance scores and decreased score in ankle extensor balance. It is concluded that improvements in biomechanical function of the knee joint after the tested overground hybrid gait trainer are coherent with improvements in gait performance.

Hybrid gait training with an overground robot for people with incomplete spinal cord injury: a pilot study

PubMed Central

del-Ama, Antonio J.; Gil-Agudo, Ángel; Pons, José L.; Moreno, Juan C.

2014-01-01

Locomotor training has proved to provide beneficial effect in terms of mobility in incomplete paraplegic patients. Neuroprosthetic technology can contribute to increase the efficacy of a training paradigm in the promotion of a locomotor pattern. Robotic exoskeletons can be used to manage the unavoidable loss of performance of artificially driven muscles. Hybrid exoskeletons blend complementary robotic and neuro-prosthetic technologies. The aim of this pilot study was to determine the effects of hybrid gait training in three case studies with persons with incomplete spinal cord injury (iSCI) in terms of locomotion performance during assisted gait, patient-robot adaptations, impact on ambulation and assessment of lower limb muscle strength and spasticity. Participants with iSCI received interventions with a hybrid bilateral exoskeleton for 4 days. Assessment of gait function revealed that patients improved the 6 min and 10 m walking tests after the intervention, and further improvements were observed 1 week after the intervention. Muscle examination revealed improvements in knee and hip sagittal muscle balance scores and decreased score in ankle extensor balance. It is concluded that improvements in biomechanical function of the knee joint after the tested overground hybrid gait trainer are coherent with improvements in gait performance. PMID:24860478

Locomotor Training and Strength and Balance Exercises for Walking Recovery After Stroke: Response to Number of Training Sessions.

PubMed

Rose, Dorian K; Nadeau, Stephen E; Wu, Samuel S; Tilson, Julie K; Dobkin, Bruce H; Pei, Qinglin; Duncan, Pamela W

2017-11-01

Evidence-based guidelines are needed to inform rehabilitation practice, including the effect of number of exercise training sessions on recovery of walking ability after stroke. The objective of this study was to determine the response to increasing number of training sessions of 2 interventions-locomotor training and strength and balance exercises-on poststroke walking recovery. This is a secondary analysis of the Locomotor Experience Applied Post-Stroke (LEAPS) randomized controlled trial. Six rehabilitation sites in California and Florida and participants' homes were used. Participants were adults who dwelled in the community (N=347), had had a stroke, were able to walk at least 3 m (10 ft) with assistance, and had completed the required number of intervention sessions. Participants received 36 sessions (3 times per week for 12 weeks), 90 minutes in duration, of locomotor training (gait training on a treadmill with body-weight support and overground training) or strength and balance training. Talking speed, as measured by the 10-Meter Walk Test, and 6-minute walking distance were assessed before training and following 12, 24, and 36 intervention sessions. Participants at 2 and 6 months after stroke gained in gait speed and walking endurance after up to 36 sessions of treatment, but the rate of gain diminished steadily and, on average, was very low during the 25- to 36-session epoch, regardless of treatment type or severity of impairment. Results may not generalize to people who are unable to initiate a step at 2 months after stroke or people with severe cardiac disease. In general, people who dwelled in the community showed improvements in gait speed and walking distance with up to 36 sessions of locomotor training or strength and balance exercises at both 2 and 6 months after stroke. However, gains beyond 24 sessions tended to be very modest. The tracking of individual response trajectories is imperative in planning treatment. Published by Oxford University Press on behalf of American Physical Therapy Association 2017.

Robot-assisted gait training versus treadmill training in patients with Parkinson's disease: a kinematic evaluation with gait profile score.

PubMed

Galli, M; Cimolin, V; De Pandis, M F; Le Pera, D; Sova, I; Albertini, G; Stocchi, F; Franceschini, M

2016-01-01

The purpose of this study was to quantitatively compare the effects, on walking performance, of end-effector robotic rehabilitation locomotor training versus intensive training with a treadmill in Parkinson's disease (PD). Fifty patients with PD were randomly divided into two groups: 25 were assigned to the robot-assisted therapy group (RG) and 25 to the intensive treadmill therapy group (IG). They were evaluated with clinical examination and 3D quantitative gait analysis [gait profile score (GPS) and its constituent gait variable scores (GVSs) were calculated from gait analysis data] at the beginning (T0) and at the end (T1) of the treatment. In the RG no differences were found in the GPS, but there were significant improvements in some GVSs (Pelvic Obl and Hip Ab-Add). The IG showed no statistically significant changes in either GPS or GVSs. The end-effector robotic rehabilitation locomotor training improved gait kinematics and seems to be effective for rehabilitation in patients with mild PD.

Inclusive intervention to enhance the fundamental movement skills of children without hearing: a preliminary study.

PubMed

Gursel, Ferda

2014-02-01

The purpose of this study was to assess an intervention program on the fundamental movement skill of students with and without hearing impairment, using the Test of Gross Motor Development-2 (TGMD-2) standardized Turkish norm. Preschool children with and without hearing impairment participated in this study. At the beginning of the study, most of the children with hearing impairment demonstrated developmental delay on the Locomotor subscale (6/7), as did about one-third (4/11) of the children without hearing impairment. For the Object control subscale, 4/7 of children with hearing impairment and none without hearing impairment showed developmental delay prior to the intervention program. After the intervention program, 3/7 children with hearing impairment had developmental delay on the Locomotor subscale. On the Object control subscale, 2/7 children with hearing impairment and none without hearing impairment showed developmental delay. The six-week intervention program improved TGMD-2 scores of children with hearing impairment, yet did not yield statistically significant improvement of fundamental movement skills.

Effects of locomotor skill program on minority preschoolers' physical activity levels.

PubMed

Alhassan, Sofiya; Nwaokelemeh, Ogechi; Ghazarian, Manneh; Roberts, Jasmin; Mendoza, Albert; Shitole, Sanyog

2012-08-01

This pilot study examined the effects of a teacher-taught, locomotor skill (LMS)-based physical activity (PA) program on the LMS and PA levels of minority preschooler-aged children. Eight low-socioeconomic status preschool classrooms were randomized into LMS-PA (LMS-oriented lesson plans) or control group (supervised free playtime). Interventions were delivered for 30 min/day, five days/week for six months. Changes in PA (accelerometer) and LMS variables were assessed with MANCOVA. LMS-PA group exhibited a significant reduction in during-preschool (F (1,16) = 6.34, p = .02, d = 0.02) and total daily (F (1,16) = 9.78, p = .01, d = 0.30) percent time spent in sedentary activity. LMS-PA group also exhibited significant improvement in leaping skills, F (1, 51) = 7.18, p = .01, d = 0.80). No other, significant changes were observed. The implementation of a teacher-taught, LMS-based PA program could potentially improve LMS and reduce sedentary time of minority preschoolers.

Post-treatment with cotinine improved memory and decreased depressive-like behavior after chemotherapy in rats.

PubMed

Iarkov, Alexandre; Appunn, Doreen; Echeverria, Valentina

2016-11-01

Most cancer patients treated with systemic adjuvant chemotherapy endure long-lasting side effects including decrease in concentration, forgetfulness and slower thinking, which are globally termed "chemobrain." Cotinine, the main derivative of nicotine, improved visual and spatial working memory and decreased depressive-like behavior in an animal model of chemotherapy-induced cognitive impairment. In this study, we investigated the effect of cotinine on weight gain, locomotor activity, cognitive abilities and depressive-like behavior in rats treated with the chemotherapy mix, cyclophosphamide, methotrexate and 5-fluorouracil. Locomotor activity and depressive-like behavior were assessed using the rotarod and Porsolt's tests, respectively. Changes in cognitive abilities were determined using the novel place recognition test. Female rats treated with cotinine after chemotherapy, recovered weight faster, showed superior cognitive abilities and lower levels of depressive-like behavior than chemotherapy, vehicle-treated rats. This evidence suggests that treatment with cotinine may facilitate the recovery and diminish the cognitive consequences of chemotherapy.

Differential regulation of NMDA receptors by d-serine and glycine in mammalian spinal locomotor networks

PubMed Central

Acton, David

2017-01-01

Activation of N-methyl-d-aspartate receptors (NMDARs) requires the binding of a coagonist, either d-serine or glycine, in addition to glutamate. Changes in occupancy of the coagonist binding site are proposed to modulate neural networks including those controlling swimming in frog tadpoles. Here, we characterize regulation of the NMDAR coagonist binding site in mammalian spinal locomotor networks. Blockade of NMDARs by d(−)-2-amino-5-phosphonopentanoic acid (d-APV) or 5,7-dichlorokynurenic acid reduced the frequency and amplitude of pharmacologically induced locomotor-related activity recorded from the ventral roots of spinal-cord preparations from neonatal mice. Furthermore, d-APV abolished synchronous activity induced by blockade of inhibitory transmission. These results demonstrate an important role for NMDARs in murine locomotor networks. Bath-applied d-serine enhanced the frequency of locomotor-related but not disinhibited bursting, indicating that coagonist binding sites are saturated during the latter but not the former mode of activity. Depletion of endogenous d-serine by d-amino acid oxidase or the serine-racemase inhibitor erythro-β-hydroxy-l-aspartic acid (HOAsp) increased the frequency of locomotor-related activity, whereas application of l-serine to enhance endogenous d-serine synthesis reduced burst frequency, suggesting a requirement for d-serine at a subset of synapses onto inhibitory interneurons. Consistent with this, HOAsp was ineffective during disinhibited activity. Bath-applied glycine (1–100 µM) failed to alter locomotor-related activity, whereas ALX 5407, a selective inhibitor of glycine transporter-1 (GlyT1), enhanced burst frequency, supporting a role for GlyT1 in NMDAR regulation. Together these findings indicate activity-dependent and synapse-specific regulation of the coagonist binding site within spinal locomotor networks, illustrating the importance of NMDAR regulation in shaping motor output. NEW & NOTEWORTHY We provide evidence that NMDARs within murine spinal locomotor networks determine the frequency and amplitude of ongoing locomotor-related activity in vitro and that NMDARs are regulated by d-serine and glycine in a synapse-specific and activity-dependent manner. In addition, glycine transporter-1 is shown to be an important regulator of NMDARs during locomotor-related activity. These results show how excitatory transmission can be tuned to diversify the output repertoire of spinal locomotor networks in mammals. PMID:28202572

Elimination of Left-Right Reciprocal Coupling in the Adult Lamprey Spinal Cord Abolishes the Generation of Locomotor Activity

PubMed Central

Messina, J. A.; St. Paul, Alison; Hargis, Sarah; Thompson, Wengora E.; McClellan, Andrew D.

2017-01-01

The contribution of left-right reciprocal coupling between spinal locomotor networks to the generation of locomotor activity was tested in adult lampreys. Muscle recordings were made from normal animals as well as from experimental animals with rostral midline (ML) spinal lesions (~13%→35% body length, BL), before and after spinal transections (T) at 35% BL. Importantly, in the present study actual locomotor movements and muscle burst activity, as well as other motor activity, were initiated in whole animals by descending brain-spinal pathways in response to sensory stimulation of the anterior head. For experimental animals with ML spinal lesions, sensory stimulation could elicit well-coordinated locomotor muscle burst activity, but with some significant differences in the parameters of locomotor activity compared to those for normal animals. Computer models representing normal animals or experimental animals with ML spinal lesions could mimic many of the differences in locomotor activity. For experimental animals with ML and T spinal lesions, right and left rostral hemi-spinal cords, disconnected from intact caudal cord, usually produced tonic or unpatterned muscle activity. Hemi-spinal cords sometimes generated spontaneous or sensory-evoked relatively high frequency “burstlet” activity that probably is analogous to the previously described in vitro “fast rhythm”, which is thought to represent lamprey locomotor activity. However, “burstlet” activity in the present study had parameters and features that were very different than those for lamprey locomotor activity: average frequencies were ~25 Hz, but individual frequencies could be >50 Hz; burst proportions (BPs) often varied with cycled time; “burstlet” activity usually was not accompanied by a rostrocaudal phase lag; and following ML spinal lesions alone, “burstlet” activity could occur in the presence or absence of swimming burst activity, suggesting the two were generated by different mechanisms. In summary, for adult lampreys, left and right hemi-spinal cords did not generate rhythmic locomotor activity in response to descending inputs from the brain, suggesting that left-right reciprocal coupling of spinal locomotor networks contributes to both phase control and rhythmogenesis. In addition, the present study indicates that extreme caution should be exercised when testing the operation of spinal locomotor networks using artificial activation of isolated or reduced nervous system preparations. PMID:29225569

Recovery of bimodal locomotion in the spinal-transected salamander, Pleurodeles waltlii.

PubMed

Chevallier, Stéphanie; Landry, Marc; Nagy, Frédéric; Cabelguen, Jean-Marie

2004-10-01

Electromyographic (EMG) analysis was used to provide an assessment of the recovery of locomotion in spinal-transected adult salamanders (Pleurodeles waltlii). EMG recordings were performed during swimming and overground stepping in the same animal before and at various times (up to 500 days) after a mid-trunk spinalization. Two-three weeks after spinalization, locomotor EMG activity was limited to the forelimbs and the body rostral to the transection. Thereafter, there was a return of the locomotor EMG activity at progressively more caudal levels below the transection. The animals reached stable locomotor patterns 3-4 months post-transection. Several locomotor parameters (cycle duration, burst duration, burst proportion, intersegmental phase lag, interlimb coupling) measured at various recovery times after spinalization were compared with those in intact animals. These comparisons revealed transient and long-term alterations in the locomotor parameters both above and below the transection site. These alterations were much more pronounced for swimming than for stepping and revealed differences in adaptive plasticity between the two locomotor networks. Recovered locomotor activity was immediately abolished by retransection at the site of the original spinalization, suggesting that the spinal cord caudal to the transection was reinnervated by descending brain and/or propriospinal axons, and that this regeneration contributed to the restoration of locomotor activity. Anatomical studies conducted in parallel further demonstrated that some of the regenerated axons came from glutamatergic and serotoninergic immunoreactive cells within the reticular formation.

Use of electronic games by young children and fundamental movement skills?

PubMed

Barnett, Lisa M; Hinkley, Trina; Okely, Anthony D; Hesketh, Kylie; Salmon, Jo

2012-06-01

This study investigated associations between pre-school children's time spent playing electronic games and their fundamental movement skills. In 2009, 53 children had physical activity (Actigraph accelerometer counts per minute), parent proxy-report of child's time in interactive and non-interactive electronic games (min./week), and movement skill (Test of Gross Motor Development-2) assessed. Hierarchical linear regression, adjusting for age (range = 3-6 years), sex (Step 1), and physical activity (cpm; M=687, SD=175.42; Step 2), examined the relationship between time in (a) non-interactive and (b) interactive electronic games and locomotor and object control skill. More than half (59%, n=31) of the children were female. Adjusted time in interactive game use was associated with object control but not locomotor skill. Adjusted time in non-interactive game use had no association with object control or locomotor skill. Greater time spent playing interactive electronic games is associated with higher object control skill proficiency in these young children. Longitudinal and experimental research is required to determine if playing these games improves object control skills or if children with greater object control skill proficiency prefer and play these games.

The tarsal-metatarsal complex of caviomorph rodents: Anatomy and functional-adaptive analysis.

PubMed

Candela, Adriana M; Muñoz, Nahuel A; García-Esponda, César M

2017-06-01

Caviomorph rodents represent a major adaptive radiation of Neotropical mammals. They occupy a variety of ecological niches, which is also reflected in their wide array of locomotor behaviors. It is expected that this radiation would be mirrored by an equivalent disparity of tarsal-metatarsal morphology. Here, the tarsal-metatarsal complex of Erethizontidae, Cuniculidae, Dasyproctidae, Caviidae, Chinchillidae, Octodontidae, Ctenomyidae, and Echimyidae was examined, in order to evaluate its anatomical variation and functional-adaptive relevance in relation to locomotor behaviors. A qualitative study in functional morphology and a geometric morphometric analysis were performed. We recognized two distinct tarsal-metatarsal patterns that represent the extremes of anatomical variation in the foot. The first, typically present in arboreal species, is characterized by features that facilitate movements at different levels of the tarsal-metatarsal complex. The second pattern, typically present in cursorial caviomorphs, has a set of features that act to stabilize the joints, improve the interlocking of the tarsal bones, and restrict movements to the parasagittal plane. The morphological disparity recognized in this study seems to result from specific locomotor adaptations to climb, dig, run, jump and swim, as well as phylogenetic effects within and among the groups studies. © 2017 Wiley Periodicals, Inc.

Zinc-containing yeast extract promotes nonrapid eye movement sleep in mice.

PubMed

Cherasse, Yoan; Saito, Hitomi; Nagata, Nanae; Aritake, Kosuke; Lazarus, Michael; Urade, Yoshihiro

2015-10-01

Zinc is an essential trace element for humans and animals, being located, among other places, in the synaptic vesicles of cortical glutamatergic neurons and hippocampal mossy fibers in the brain. Extracellular zinc has the potential to interact with and modulate many different synaptic targets, including glutamate and GABA receptors. Because of the central role of these neurotransmitters in brain activity, we examined in this study the sleep-promoting activity of zinc by monitoring locomotor activity and electroencephalogram after its administration to mice. Zinc-containing yeast extract (40 and 80 mg/kg) dose dependently increased the total amount of nonrapid eye movement sleep and decreased the locomotor activity. However, this preparation did not change the amount of rapid eye movement sleep or show any adverse effects such as rebound of insomnia during a period of 24 h following the induction of sleep; whereas the extracts containing other divalent cations (manganese, iron, and copper) did not decrease the locomotor activity. This is the first evidence that zinc can induce sleep. Our data open the way to new types of food supplements designed to improve sleep. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Role of the 5-HT₂A receptor in the locomotor hyperactivity produced by phenylalkylamine hallucinogens in mice.

PubMed

Halberstadt, Adam L; Powell, Susan B; Geyer, Mark A

2013-07-01

The 5-HT₂A receptor mediates the effects of serotonergic hallucinogens and may play a role in the pathophysiology of certain psychiatric disorders, including schizophrenia. Given these findings, there is a need for animal models to assess the behavioral effects of 5-HT₂A receptor activation. Our previous studies demonstrated that the phenylalkylamine hallucinogen and 5-HT₂A/₂C agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) produces dose-dependent effects on locomotor activity in C57BL/6J mice, increasing activity at low to moderate doses and reducing activity at high doses. DOI did not increase locomotor activity in 5-HT₂A knockout mice, indicating the effect is a consequence of 5-HT₂A receptor activation. Here, we tested a series of phenylalkylamine hallucinogens in C57BL/6J mice using the Behavioral Pattern Monitor (BPM) to determine whether these compounds increase locomotor activity by activating the 5-HT₂A receptor. Low doses of mescaline, 2,5-dimethoxy-4-ethylamphetamine (DOET), 2,5-dimethoxy-4-propylamphetamine (DOPR), 2,4,5-trimethoxyamphetamine (TMA-2), and the conformationally restricted phenethylamine (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine (TCB-2) increased locomotor activity. By contrast, the non-hallucinogenic phenylalkylamine 2,5-dimethoxy-4-tert-butylamphetamine (DOTB) did not alter locomotor activity at any dose tested (0.1-10 mg/kg i.p.). The selective 5-HT₂A antagonist M100907 blocked the locomotor hyperactivity induced by mescaline and TCB-2. Similarly, mescaline and TCB-2 did not increase locomotor activity in 5-HT₂A knockout mice. These results confirm that phenylalkylamine hallucinogens increase locomotor activity in mice and demonstrate that this effect is mediated by 5-HT₂A receptor activation. Thus, locomotor hyperactivity in mice can be used to assess phenylalkylamines for 5-HT₂A agonist activity and hallucinogen-like behavioral effects. These studies provide additional support for the link between 5-HT₂A activation and hallucinogenesis. Copyright © 2013 Elsevier Ltd. All rights reserved.

A new model of the spinal locomotor networks of a salamander and its properties.

PubMed

Liu, Qiang; Yang, Huizhen; Zhang, Jinxue; Wang, Jingzhuo

2018-05-22

A salamander is an ideal animal for studying the spinal locomotor network mechanism of vertebrates from an evolutionary perspective since it represents the transition from an aquatic to a terrestrial animal. However, little is known about the spinal locomotor network of a salamander. A spinal locomotor network model is a useful tool for exploring the working mechanism of the spinal networks of salamanders. A new spinal locomotor network model for a salamander is built for a three-dimensional (3D) biomechanical model of the salamander using a novel locomotion-controlled neural network model. Based on recent experimental data on the spinal circuitry and observational results of gaits of vertebrates, we assume that different interneuron sets recruited for mediating the frequency of spinal circuits are also related to the generation of different gaits. The spinal locomotor networks of salamanders are divided into low-frequency networks for walking and high-frequency networks for swimming. Additionally, a new topological structure between the body networks and limb networks is built, which only uses the body networks to coordinate the motion of limbs. There are no direct synaptic connections among limb networks. These techniques differ from existing salamander spinal locomotor network models. A simulation is performed and analyzed to validate the properties of the new spinal locomotor networks of salamanders. The simulation results show that the new spinal locomotor networks can generate a forward walking gait, a backward walking gait, a swimming gait, and a turning gait during swimming and walking. These gaits can be switched smoothly by changing external inputs from the brainstem. These properties are consistent with those of a real salamander. However, it is still difficult for the new spinal locomotor networks to generate highly efficient turning during walking, 3D swimming, nonrhythmic movements, and so on. New experimental data are required for further validation.

Thoracic Hemisection in Rats Results in Initial Recovery Followed by a Late Decrement in Locomotor Movements, with Changes in Coordination Correlated with Serotonergic Innervation of the Ventral Horn

PubMed Central

Leszczyńska, Anna N.; Majczyński, Henryk; Wilczyński, Grzegorz M.; Sławińska, Urszula; Cabaj, Anna M.

2015-01-01

Lateral thoracic hemisection of the rodent spinal cord is a popular model of spinal cord injury, in which the effects of various treatments, designed to encourage locomotor recovery, are tested. Nevertheless, there are still inconsistencies in the literature concerning the details of spontaneous locomotor recovery after such lesions, and there is a lack of data concerning the quality of locomotion over a long time span after the lesion. In this study, we aimed to address some of these issues. In our experiments, locomotor recovery was assessed using EMG and CatWalk recordings and analysis. Our results showed that after hemisection there was paralysis in both hindlimbs, followed by a substantial recovery of locomotor movements, but even at the peak of recovery, which occurred about 4 weeks after the lesion, some deficits of locomotion remained present. The parameters that were abnormal included abduction, interlimb coordination and speed of locomotion. Locomotor performance was stable for several weeks, but about 3–4 months after hemisection secondary locomotor impairment was observed with changes in parameters, such as speed of locomotion, interlimb coordination, base of hindlimb support, hindlimb abduction and relative foot print distance. Histological analysis of serotonergic innervation at the lumbar ventral horn below hemisection revealed a limited restoration of serotonergic fibers on the ipsilateral side of the spinal cord, while on the contralateral side of the spinal cord it returned to normal. In addition, the length of these fibers on both sides of the spinal cord correlated with inter- and intralimb coordination. In contrast to data reported in the literature, our results show there is not full locomotor recovery after spinal cord hemisection. Secondary deterioration of certain locomotor functions occurs with time in hemisected rats, and locomotor recovery appears partly associated with reinnervation of spinal circuitry by serotonergic fibers. PMID:26606275

Electrolytic lesions of the nucleus accumbens core (but not the medial shell) and the basolateral amygdala enhance context-specific locomotor sensitization to nicotine in rats.

PubMed

Kelsey, John E; Gerety, Lyle P; Guerriero, Rejean M

2009-06-01

We previously demonstrated that lesions of the nucleus accumbens (NAc) core enhanced locomotion and locomotor sensitization to repeated injections of nicotine in rats (Kelsey & Willmore, 2006). In this study, we compared the effects of separate lesions of the NAc core, NAc medial shell, and basolateral amygdala on context-specific locomotor sensitization to repeated injections of 0.4 mg/kg nicotine. Electrolytic lesions of the NAc core increased locomotion, and lesions of the core (but not the shell) and the basolateral amygdala enhanced context-specific locomotor sensitization by enhancing the development of sensitization in paired rats and decreasing expression in unpaired rats relative to sham-operated rats when challenged with an injection of 0.4 mg/kg nicotine in the locomotor chambers. These data are consistent with findings that the NAc core and the basolateral amygdala share a variety of behavioral functions and anatomical connections. The findings that lesions of these structures enhance context-specific locomotor sensitization while typically impairing other reward-related behaviors also indicate that the processes underlying locomotor sensitization and reward are not identical. Copyright (c) 2009 APA, all rights reserved.

Development of Testing Methodologies to Evaluate Postflight Locomotor Performance

NASA Technical Reports Server (NTRS)

Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Richards, J. T.; Miller, C. A.; Brady, R.; Warren, L. E.; Bloomberg, J. J.

2006-01-01

Crewmembers experience locomotor and postural instabilities during ambulation on Earth following their return from space flight. Gait training programs designed to facilitate recovery of locomotor function following a transition to a gravitational environment need to be accompanied by relevant assessment methodologies to evaluate their efficacy. The goal of this paper is to demonstrate the operational validity of two tests of locomotor function that were used to evaluate performance after long duration space flight missions on the International Space Station (ISS).

Direct effects of tadalafil on lower urinary tract symptoms versus indirect effects mediated through erectile dysfunction symptom improvement: integrated data analyses from 4 placebo controlled clinical studies.

PubMed

Brock, Gerald B; McVary, Kevin T; Roehrborn, Claus G; Watts, Steven; Ni, Xiao; Viktrup, Lars; Wong, David G; Donatucci, Craig

2014-02-01

Tadalafil has regulatory approval for the treatment of men with signs/symptoms of benign prostatic hyperplasia with and without erectile dysfunction. We assessed whether the effects of treatment with tadalafil for lower urinary tract symptoms/benign prostatic hyperplasia are independent of improvements in erectile dysfunction. Four separate analyses used integrated data from 4 randomized, double-blind, placebo controlled studies in men with lower urinary tract symptoms/benign prostatic hyperplasia with and without erectile dysfunction to test whether total I-PSS (International Prostate Symptom Score) improvement was due to improvement in IIEF-EF (International Index of Erectile Function-Erectile Function domain score). Unidirectional and bidirectional path analysis models determined direct and indirect treatment effects mediated by improvements in lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction symptoms. A total of 1,496 men, of whom 77% had erectile dysfunction, received at least 1 dose of tadalafil 5 mg once daily or placebo. The placebo adjusted treatment effect for men with erectile dysfunction was represented by a mean decrease of -2.3 (p <0.0001) in total I-PSS vs -2.2 (p = 0.0007) for men without erectile dysfunction. The correlation between change from baseline in total I-PSS and IIEF-EF was weak (r(2) = 0.08, p <0.0001). The unidirectional path analysis model suggested that the total treatment effect on total I-PSS score improvement (2.25) was derived from a direct treatment effect of 1.57 (70%, p <0.001) and an indirect treatment effect of 0.67 (30% via IIEF-EF improvement, p <0.001). Bidirectional path analysis showed that total I-PSS improvement was largely attributed to direct (92.5%, p <0.001) vs indirect (7.5%, p = 0.32) treatment effects via IIEF-EF improvement. Regardless of the analytical approach, self-reported erectile dysfunction status did not appreciably influence tadalafil treatment response in men with lower urinary tract symptoms/benign prostatic hyperplasia, supporting the dual action of tadalafil on lower urinary tract symptoms/benign prostatic hyperplasia and erectile dysfunction. Copyright © 2014. Published by Elsevier Inc.

Dissociation of corticotropin-releasing factor receptor subtype involvement in sensitivity to locomotor effects of methamphetamine and cocaine.

PubMed

Giardino, William J; Mark, Gregory P; Stenzel-Poore, Mary P; Ryabinin, Andrey E

2012-02-01

Enhanced sensitivity to the euphoric and locomotor-activating effects of psychostimulants may influence an individual's predisposition to drug abuse and addiction. While drug-induced behaviors are mediated by the actions of several neurotransmitter systems, past research revealed that the corticotropin-releasing factor (CRF) system is important in driving the acute locomotor response to psychostimulants. We previously reported that genetic deletion of the CRF type-2 receptor (CRF-R2), but not the CRF type-1 receptor (CRF-R1) dampened the acute locomotor stimulant response to methamphetamine (1 mg/kg). These results contrasted with previous studies implicating CRF-R1 in the locomotor effects of psychostimulants. Since the majority of previous studies focused on cocaine, rather than methamphetamine, we set out to test the hypothesis that these drugs differentially engage CRF-R1 and CRF-R2. We expanded our earlier findings by first replicating our previous experiments at a higher dose of methamphetamine (2 mg/kg), and by assessing the effects of the CRF-R1-selective antagonist CP-376,395 (10 mg/kg) on methamphetamine-induced locomotor activity. Next, we used both genetic and pharmacological tools to examine the specific components of the CRF system underlying the acute locomotor response to cocaine (5-10 mg/kg). While genetic deletion of CRF-R2 dampened the locomotor response to methamphetamine (but not cocaine), genetic deletion and pharmacological blockade of CRF-R1 dampened the locomotor response to cocaine (but not methamphetamine). These findings highlight the differential involvement of CRF receptors in acute sensitivity to two different stimulant drugs of abuse, providing an intriguing basis for the development of more targeted therapeutics for psychostimulant addiction.

Feedback and feedforward locomotor adaptations to ankle-foot load in people with incomplete spinal cord injury.

PubMed

Gordon, Keith E; Wu, Ming; Kahn, Jennifer H; Schmit, Brian D

2010-09-01

Humans with spinal cord injury (SCI) modulate locomotor output in response to limb load. Understanding the neural control mechanisms responsible for locomotor adaptation could provide a framework for selecting effective interventions. We quantified feedback and feedforward locomotor adaptations to limb load modulations in people with incomplete SCI. While subjects airstepped (stepping performed with kinematic assistance and 100% bodyweight support), a powered-orthosis created a dorisflexor torque during the "stance phase" of select steps producing highly controlled ankle-load perturbations. When given repetitive, stance phase ankle-load, the increase in hip extension work, 0.27 J/kg above baseline (no ankle-load airstepping), was greater than the response to ankle-load applied during a single step, 0.14 J/kg (P = 0.029). This finding suggests that, at the hip, subjects produced both feedforward and feedback locomotor modulations. We estimate that, at the hip, the locomotor response to repetitive ankle-load was modulated almost equally by ongoing feedback and feedforward adaptations. The majority of subjects also showed after-effects in hip kinetic patterns that lasted 3 min in response to repetitive loading, providing additional evidence of feedforward locomotor adaptations. The magnitude of the after-effect was proportional to the response to repetitive ankle-foot load (R(2) = 0.92). In contrast, increases in soleus EMG amplitude were not different during repetitive and single-step ankle-load exposure, suggesting that ankle locomotor modulations were predominately feedback-based. Although subjects made both feedback and feedforward locomotor adaptations to changes in ankle-load, between-subject variations suggest that walking function may be related to the ability to make feedforward adaptations.

Poststroke Hemiparesis Impairs the Rate but not Magnitude of Adaptation of Spatial and Temporal Locomotor Features

PubMed Central

Savin, Douglas N.; Tseng, Shih-Chiao; Whitall, Jill; Morton, Susanne M.

2015-01-01

Background Persons with stroke and hemiparesis walk with a characteristic pattern of spatial and temporal asymmetry that is resistant to most traditional interventions. It was recently shown in nondisabled persons that the degree of walking symmetry can be readily altered via locomotor adaptation. However, it is unclear whether stroke-related brain damage affects the ability to adapt spatial or temporal gait symmetry. Objective Determine whether locomotor adaptation to a novel swing phase perturbation is impaired in persons with chronic stroke and hemiparesis. Methods Participants with ischemic stroke (14) and nondisabled controls (12) walked on a treadmill before, during, and after adaptation to a unilateral perturbing weight that resisted forward leg movement. Leg kinematics were measured bilaterally, including step length and single-limb support (SLS) time symmetry, limb angle center of oscillation, and interlimb phasing, and magnitude of “initial” and “late” locomotor adaptation rates were determined. Results All participants had similar magnitudes of adaptation and similar initial adaptation rates both spatially and temporally. All 14 participants with stroke and baseline asymmetry temporarily walked with improved SLS time symmetry after adaptation. However, late adaptation rates poststroke were decreased (took more strides to achieve adaptation) compared with controls. Conclusions Mild to moderate hemiparesis does not interfere with the initial acquisition of novel symmetrical gait patterns in both the spatial and temporal domains, though it does disrupt the rate at which “late” adaptive changes are produced. Impairment of the late, slow phase of learning may be an important rehabilitation consideration in this patient population. PMID:22367915

Short-Term Genetic Selection for Adolescent Locomotor Sensitivity to Delta9-Tetrahydrocannabinol (THC).

PubMed

Kasten, Chelsea R; Zhang, Yanping; Mackie, Ken; Boehm, Stephen L

2018-05-01

Cannabis use is linked to positive and negative outcomes. Identifying genetic targets of susceptibility to the negative effects of cannabinoid use is of growing importance. The current study sought to complete short-term selective breeding for adolescent sensitivity and resistance to the locomotor effects of a single 10 mg/kg THC dose in the open field. Selection for THC-locomotor sensitivity was moderately heritable, with the greatest estimates of heritability seen in females from the F2 to S3 generations. Selection for locomotor sensitivity also resulted in increased anxiety-like activity in the open field. These results are the first to indicate that adolescent THC-locomotor sensitivity can be influenced via selective breeding. Development of lines with a genetic predisposition for THC-sensitivity or resistance to locomotor effects allow for investigation of risk factors, differences in consequences of THC use, identification of correlated behavioral responses, and detection of genetic targets that may contribute to heightened cannabinoid sensitivity.

A feasibility study on the design and walking operation of a biped locomotor via dynamic simulation

NASA Astrophysics Data System (ADS)

Wang, Mingfeng; Ceccarelli, Marco; Carbone, Giuseppe

2016-06-01

A feasibility study on the mechanical design and walking operation of a Cassino biped locomotor is presented in this paper. The biped locomotor consists of two identical 3 degrees-of-freedom tripod leg mechanisms with a parallel manipulator architecture. Planning of the biped walking gait is performed by coordinating the motions of the two leg mechanisms and waist. A threedimensional model is elaborated in SolidWorks® environment in order to characterize a feasible mechanical design. Dynamic simulation is carried out in MSC.ADAMS® environment with the aims of characterizing and evaluating the dynamic walking performance of the proposed design. Simulation results show that the proposed biped locomotor with proper input motions of linear actuators performs practical and feasible walking on flat surfaces with limited actuation and reaction forces between its feet and the ground. A preliminary prototype of the biped locomotor is built for the purpose of evaluating the operation performance of the biped walking gait of the proposed locomotor.

V3 spinal neurons establish a robust and balanced locomotor rhythm during walking.

PubMed

Zhang, Ying; Narayan, Sujatha; Geiman, Eric; Lanuza, Guillermo M; Velasquez, Tomoko; Shanks, Bayle; Akay, Turgay; Dyck, Jason; Pearson, Keir; Gosgnach, Simon; Fan, Chen-Ming; Goulding, Martyn

2008-10-09

A robust and well-organized rhythm is a key feature of many neuronal networks, including those that regulate essential behaviors such as circadian rhythmogenesis, breathing, and locomotion. Here we show that excitatory V3-derived neurons are necessary for a robust and organized locomotor rhythm during walking. When V3-mediated neurotransmission is selectively blocked by the expression of the tetanus toxin light chain subunit (TeNT), the regularity and robustness of the locomotor rhythm is severely perturbed. A similar degeneration in the locomotor rhythm occurs when the excitability of V3-derived neurons is reduced acutely by ligand-induced activation of the allatostatin receptor. The V3-derived neurons additionally function to balance the locomotor output between both halves of the spinal cord, thereby ensuring a symmetrical pattern of locomotor activity during walking. We propose that the V3 neurons establish a regular and balanced motor rhythm by distributing excitatory drive between both halves of the spinal cord.

MK-801 increases locomotor activity in a context-dependent manner in zebrafish.

PubMed

Tran, Steven; Muraleetharan, Arrujyan; Fulcher, Niveen; Chatterjee, Diptendu; Gerlai, Robert

2016-01-01

Zebrafish have become a popular animal model for behavioral neuroscience with an increasing number of studies examining the effects of pharmacological compounds targeting the brain. Exposure to MK-801, a non-competitive N-methyl-d-aspartate receptor antagonist has been shown to increase locomotor activity in zebrafish. However, others have failed to replicate this finding as several contradicting studies report no changes in locomotor activity following exposure to similar doses. In the current study we reconcile these behavioral reports by demonstrating that zebrafish do not exhibit changes in locomotor activity during exposure to non-sedative doses of MK-801. Interestingly, zebrafish do exhibit significant increases in locomotion if pre-treated with MK-801 followed by subsequent testing in a novel environment, which suggests the effects of MK-801 are context-dependent. In addition, we examine the potential role of the dopaminergic system in mediating MK-801's locomotor stimulant effect by quantifying the levels of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the brains of zebrafish following a 30 min exposure to 10 μM of MK-801 (the dose found to induce the largest increase in locomotor activity). Our findings indicate that the MK-801-induced increase in locomotor activity is not accompanied by changes in whole-brain levels of dopamine or DOPAC. Overall, our results suggest that MK-801's context-dependent locomotor stimulant effect may be independent of whole-brain dopaminergic activation. Copyright © 2015 Elsevier B.V. All rights reserved.

Mitochondrial pyruvate carrier regulates autophagy, inflammation, and neurodegeneration in experimental models of Parkinson's disease.

PubMed

Ghosh, Anamitra; Tyson, Trevor; George, Sonia; Hildebrandt, Erin N; Steiner, Jennifer A; Madaj, Zachary; Schulz, Emily; Machiela, Emily; McDonald, William G; Escobar Galvis, Martha L; Kordower, Jeffrey H; Van Raamsdonk, Jeremy M; Colca, Jerry R; Brundin, Patrik

2016-12-07

Mitochondrial and autophagic dysfunction as well as neuroinflammation are involved in the pathophysiology of Parkinson's disease (PD). We hypothesized that targeting the mitochondrial pyruvate carrier (MPC), a key controller of cellular metabolism that influences mTOR (mammalian target of rapamycin) activation, might attenuate neurodegeneration of nigral dopaminergic neurons in animal models of PD. To test this, we used MSDC-0160, a compound that specifically targets MPC, to reduce its activity. MSDC-0160 protected against 1-methyl-4-phenylpyridinium (MPP + ) insult in murine and cultured human midbrain dopamine neurons and in an α-synuclein-based Caenorhabditis elegans model. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, MSDC-0160 improved locomotor behavior, increased survival of nigral dopaminergic neurons, boosted striatal dopamine levels, and reduced neuroinflammation. Long-term targeting of MPC preserved motor function, rescued the nigrostriatal pathway, and reduced neuroinflammation in the slowly progressive Engrailed1 (En1 +/- ) genetic mouse model of PD. Targeting MPC in multiple models resulted in modulation of mitochondrial function and mTOR signaling, with normalization of autophagy and a reduction in glial cell activation. Our work demonstrates that changes in metabolic signaling resulting from targeting MPC were neuroprotective and anti-inflammatory in several PD models, suggesting that MPC may be a useful therapeutic target in PD. Copyright © 2016, American Association for the Advancement of Science.

Neuroprotective Effects of Platonin, a Therapeutic Immunomodulating Medicine, on Traumatic Brain Injury in Mice after Controlled Cortical Impact.

PubMed

Yen, Ting-Lin; Chang, Chao-Chien; Chung, Chi-Li; Ko, Wen-Chin; Yang, Chih-Hao; Hsieh, Cheng-Ying

2018-04-06

Traumatic brain injury (TBI) is one of the leading causes of mortality worldwide and leads to persistent cognitive, sensory, motor dysfunction, and emotional disorders. TBI-caused primary injury results in structural damage to brain tissues. Following the primary injury, secondary injuries which are accompanied by neuroinflammation, microglial activation, and additional cell death subsequently occur. Platonin, a cyanine photosensitizing dye, has been used to treat trauma, ulcers, and some types of acute inflammation. In the present study, the neuroprotective effects of platonin against TBI were explored in a controlled cortical impact (CCI) injury model in mice. Treatment with platonin (200 µg/kg) significantly reduced the neurological severity score, general locomotor activity, and anxiety-related behavior, and improved the rotarod performance of CCI-injured mice. In addition, platonin reduced lesion volumes, the expression of cleaved caspase-3, and microglial activation in TBI-insulted brains. Platonin also suppressed messenger (m)RNA levels of caspase-3, caspase-1, cyclooxygenase-2, tumor necrosis factor-α, interleukin-6, and interleukin-1β. On the other hand, free radical production after TBI was obviously attenuated in platonin-treated mice. Treatment with platonin exhibited prominent neuroprotective properties against TBI in a CCI mouse model through its anti-inflammatory, anti-apoptotic, and anti-free radical capabilities. This evidence collectively indicates that platonin may be a potential therapeutic medicine for use with TBIs.

Targeting L-Selectin to Improve Neurologic and Urologic Function After Spinal Cord Injury

DTIC Science & Technology

2013-10-01

locomotor recovery. When cystometry was performed at the end of the study, 29/34 (~85%) of mice exhibited partial or complete voluntary bladder...0.05). Following euthanasia , bladders were removed, weighed, and normalized to total bodyweight (Figure 11C). One-way ANOVA demonstrated no

The Role of Acid Sensing Ion Channels in Spinal Cord Injury

DTIC Science & Technology

2012-10-01

ASIC1a is localized to the cell bodies and dendrites of neurons [4]. Pathological cerebral acidosis activates these channels which, in turn, kill...Tripathi, P. Wei, and A.T. Lash, The PPAR gamma agonist Pioglitazone improves anatomical and locomotor recovery after rodent spinal cord injury. Exp Neurol

Drosophila Models of Parkinson's Disease: Discovering Relevant Pathways and Novel Therapeutic Strategies

PubMed Central

Muñoz-Soriano, Verónica; Paricio, Nuria

2011-01-01

Parkinson's disease (PD) is the second most common neurodegenerative disorder and is mainly characterized by the selective and progressive loss of dopaminergic neurons, accompanied by locomotor defects. Although most PD cases are sporadic, several genes are associated with rare familial forms of the disease. Analyses of their function have provided important insights into the disease process, demonstrating that three types of cellular defects are mainly involved in the formation and/or progression of PD: abnormal protein aggregation, oxidative damage, and mitochondrial dysfunction. These studies have been mainly performed in PD models created in mice, fruit flies, and worms. Among them, Drosophila has emerged as a very valuable model organism in the study of either toxin-induced or genetically linked PD. Indeed, many of the existing fly PD models exhibit key features of the disease and have been instrumental to discover pathways relevant for PD pathogenesis, which could facilitate the development of therapeutic strategies. PMID:21512585

Improvement in motor performance of Weaver mutant mice following lesions of the cerebellum.

PubMed

Grüsser, C; Grüsser-Cornehls, U

1998-12-01

In Weaver mutants (B6CBA wv/wv) cerebellar granule cells degenerate almost completely postnatally. A partial loss of Purkinje cells (PC) and a degeneration of dopaminergic cells in the substantia nigra have also been found. Weaver mice suffer from striking motor symptoms, including difficulty in walking without toppling over. In an attempt to influence the poor motor performance, the cerebellum in young animals was removed, thus eliminating the faulty output of surviving PCs, demonstrated electrophysiologically. Unoperated Weaver, lesioned wildtypes and one sham mouse were used as controls. Before and after operation, a battery of behavioural tests was performed. In Weaver mice, tumbling to the side (t) and the relation of t to the motor activity (k) while traversing an open-field matrix, (t/k), improved considerably, as did manoeuvring on a slanted wire mesh, but keeping balance on a wooden bench did not to the same degree. Locomotor activity alone improved in some animals. In wildtypes no significant changes occurred after operation, with the exception of a strong reduction in locomotor activity. The experiments demonstrate that the motor performance in Weaver mutant mice benefits from removal of their cerebellum.

Cocaine locomotor activation, sensitization and place preference in six inbred strains of mice

PubMed Central

2011-01-01

Background The expanding set of genomics tools available for inbred mouse strains has renewed interest in phenotyping larger sets of strains. The present study aims to explore phenotypic variability among six commonly-used inbred mouse strains to both the rewarding and locomotor stimulating effects of cocaine in a place conditioning task, including several strains or substrains that have not yet been characterized for some or all of these behaviors. Methods C57BL/6J (B6), BALB/cJ (BALB), C3H/HeJ (C3H), DBA/2J (D2), FVB/NJ (FVB) and 129S1/SvImJ (129) mice were tested for conditioned place preference to 20 mg/kg cocaine. Results Place preference was observed in most strains with the exception of D2 and 129. All strains showed a marked increase in locomotor activity in response to cocaine. In BALB mice, however, locomotor activation was context-dependent. Locomotor sensitization to repeated exposure to cocaine was most significant in 129 and D2 mice but was absent in FVB mice. Conclusions Genetic correlations suggest that no significant correlation between conditioned place preference, acute locomotor activation, and locomotor sensitization exists among these strains indicating that separate mechanisms underlie the psychomotor and rewarding effects of cocaine. PMID:21806802

The kinematic recovery process of rhesus monkeys after spinal cord injury.

PubMed

Wei, Rui-Han; Zhao, Can; Rao, Jia-Sheng; Zhao, Wen; Zhou, Xia; Tian, Peng-Yu; Song, Wei; Ji, Run; Zhang, Ai-Feng; Yang, Zhao-Yang; Li, Xiao-Guang

2018-05-16

After incomplete spinal cord injury (SCI), neural circuits may be plastically reconstructed to some degree, resulting in extensive functional locomotor recovery. The present study aimed to observe the post-SCI locomotor recovery of rhesus monkey hindlimbs and compare the recovery degrees of different hindlimb parts, thus revealing the recovery process of locomotor function. Four rhesus monkeys were chosen for thoracic hemisection injury. The hindlimb locomotor performance of these animals was recorded before surgery, as well as 6 and 12 weeks post-lesion. Via principal component analysis, the relevant parameters of the limb endpoint, pelvis, hindlimb segments, and joints were processed and analyzed. Twelve weeks after surgery, partial kinematic recovery was observed at the limb endpoint, shank, foot, and knee joints, and the locomotor performance of the ankle joint even recovered to the pre-lesion level; the elevation angle of the thigh and hip joints showed no obvious recovery. Generally, different parts of a monkey hindlimb had different spontaneous recovery processes; specifically, the closer the part was to the distal end, the more extensive was the locomotor function recovery. Therefore, we speculate that locomotor recovery may be attributed to plastic reconstruction of the motor circuits that are mainly composed of corticospinal tract. This would help to further understand the plasticity of motor circuits after spinal cord injury.

Oxytocin decreases cocaine taking, cocaine seeking, and locomotor activity in female rats

PubMed Central

Leong, Kah-Chung; Zhou, Luyi; Ghee, Shannon M.; See, Ronald E.; Reichel, Carmela M.

2015-01-01

Oxytocin has been shown to decrease cocaine taking and seeking in male rats, suggesting potential treatment efficacy for drug addiction. In the present study, we extended these findings to the assessment of cocaine seeking and taking in female rats. Further, we made direct comparisons of oxytocin’s impact on cocaine induced locomotor activity in both males and females. In females, systemic oxytocin (0.3, 1.0, 3.0 mg/kg) attenuated lever pressing for cocaine during self-administration and oxytocin (1.0 mg/kg) attenuated cue-induced cocaine seeking following extinction. Cocaine increased baseline locomotor activity to a greater degree in females relative to males. Oxytocin (0.1, 0.3, 1.0, and 3.0 mg/kg) reduced cocaine-induced locomotor activity in females, but not significantly in males. These data illustrate sex similarities in oxytocin’s attenuation of cocaine seeking, but sex differences in cocaine-induced locomotor effects. While reductions in cocaine seeking cannot be attributed to a reduction in locomotor activity in males, attenuation of locomotor function cannot be entirely ruled out as an explanation for a decrease in cocaine seeking in females suggesting that oxytocin’s effect on cocaine seeking may be mediated by different mechanisms in male and females. PMID:26523890

[Assessing the treatment for sacroiliac joint dysfunction, piriformis syndrome and tarsal tunnel syndrome associated with lumbar degenerative disease].

PubMed

Morimoto, Daijiro; Isu, Toyohiko; Shimoda, Yuusuke; Hamauchi, Shuuji; Sasamori, Tooru; Sugawara, Atsushi; Kim, Kyongsong; Matsumoto, Ryouji; Isobe, Masanori

2009-09-01

Sacroiliac joint (SIJ) dysfunction, piriformis syndrome (PFS) and tarsal tunnel syndrome (TTS) produce symptoms similar to lumbar degenerative disease (LDD). Patients who have these diseases plus LDD sometimes experience residual symptoms after surgery for LDD. We therefore assessed the results of treatment of SIJ dysfunction, PFS and TTS associated with LDD. We assessed 25 patients who underwent surgery for LDD and were affected with SIJ dysfunction (12 patients), PFS (7 patients) or TTS (6 patients). SIJ dysfunction was treated with rest, drugs, pelvic band and sacroiliac joint block. PFS was treated with rest, drugs, physical exercise, injection of local anesthetic into the piriformis muscle, and surgical resection of the piriformis muscle. TTS was treated with drugs and tarsal tunnel opening. We analyzed the improvement score and recovery rate (JOA score) for both LDD surgery and the treatment of SIJ dysfunction, PFS and TTS. Symptom improvement was observed in all patients with SIJ dysfunction and PFS and in 4 patients with TTS. The improvement score and recovery rate of treatments for SIJ dysfunction, PFS and TTS were lower than those of surgery for LDD. The improvement score and recovery rate of treatment for SIJ dysfunction, PFS and TTS were not as high as those for LDD. To enhance patient satisfaction, it is important to consider these complicating diseases when designing treatments for LDD.

The recovery of running ability in an adolescent male after traumatic brain injury: a case study.

PubMed

Moriello, Gabriele; Frear, Matthew; Seaburg, Kristin

2009-06-01

The purpose of this case study was to document outcomes after a rehabilitation program in an adolescent male after traumatic brain injury. Three years after sustaining an injury in a skiing accident, a 17-year-old boy participated in a rehabilitation program with the goal of acquiring the ability to run one mile with his peers. On initial evaluation, the individual had significant left lower extremity weakness, impaired standing balance, limited endurance, and running limitations. He was able to run 10 m wearing a plastic ankle-foot orthosis on the left side but required supervision for safety. The intervention included strength training once weekly for 17 weeks, body weight-supported, treadmill-based locomotor training once weekly for 15 weeks followed by a combination of overground locomotor training and strengthening exercise once weekly for six weeks. After the intervention, muscle strength of the lower extremities increased and the individual was able to run one mile independently. The quality of his running improved, with better mechanics to absorb forces at impact during the absorption phase and increased lower extremity extension during the propulsion phase. A rehabilitation program consisting of strengthening and locomotor training improved running speed, quality, and endurance in an adolescent male after traumatic brain injury. He was able to progress to a less restrictive carbon fiber brace as a result of gains in lower extremity strength. This change in ability allowed him to participate in physical education by running on a track and playing softball with his peers.

The effects of locomotor training in children with spinal cord injury: a systematic review.

PubMed

Donenberg, Jennifer Glenna; Fetters, Linda; Johnson, Robert

2018-06-19

Discuss the effectiveness of locomotor training (LT) in children following spinal cord injury (SCI). This intervention was assessed following an exhaustive search of the literature using the Preferred Reporting Items for Systematic Reviews and Meta- Analyses: The PRISMA Statement as a guideline. Six databases were searched including PubMed, PEDro, CINAHL, Cochrane, PsycINFO, and Web of Knowledge in January 2016 and November 2016, without date restrictions. Inclusion criteria were: studies in English and peer-reviewed and journal articles with a primary intervention of LT in children following SCI. Twelve articles, reporting eleven studies, were included. A systematic review assessing locomotor training in children with SCI published in April 2016 was also included. Participants were ages 15 months to 18 years old. Forms of LT included body-weight supported treadmill or over ground training, functional electrical stimulation, robotics, and virtual reality. Protocols differed in set-up and delivery mode, with improvements seen in ambulation for all 41 participants following LT. Children might benefit from LT to develop or restore ambulation following SCI. Age, completeness, and level of injury remain the most important prognostic factors to consider with this intervention. Additional benefits include improved bowel/ bladder management and control, bone density, cardiovascular endurance, and overall quality of life. Looking beyond the effects LT has just on ambulation is crucial because it can offer benefits to all children sustaining a SCI, even if restoration or development of walking is not the primary goal. Further rigorous research is required to determine the overall effectiveness of LT.

Locomotor Recovery in Spinal Cord Injury: Insights Beyond Walking Speed and Distance.

PubMed

Awai, Lea; Curt, Armin

2016-08-01

Recovery of locomotor function after incomplete spinal cord injury (iSCI) is clinically assessed through walking speed and distance, while improvements in these measures might not be in line with a normalization of gait quality and are, on their own, insensitive at revealing potential mechanisms underlying recovery. The objective of this study was to relate changes of gait parameters to the recovery of walking speed while distinguishing between parameters that rather reflect speed improvements from factors contributing to overall recovery. Kinematic data of 16 iSCI subjects were repeatedly recorded during in-patient rehabilitation. The responsiveness of gait parameters to walking speed was assessed by linear regression. Principal component analysis (PCA) was applied on the multivariate data across time to identify factors that contribute to recovery after iSCI. Parameters of gait cycle and movement dynamics were both responsive and closely related to the recovery of walking speed, which increased by 96%. Multivariate analysis revealed specific gait parameters (intralimb shape normality and consistency) that, although less related to speed increments, loaded highly on principal component one (PC1) (58.6%) explaining the highest proportion of variance (i.e., recovery of outcome over time). Interestingly, measures of hip, knee, and ankle range of motion showed varying degrees of responsiveness (from very high to very low) while not contributing to gait recovery as revealed by PCA. The conjunct application of two analysis methods distinguishes gait parameters that simply reflect increased walking speed from parameters that actually contribute to gait recovery in iSCI. This distinction may be of value for the evaluation of interventions for locomotor recovery.

Continuous delivery of ropinirole reverses motor deficits without dyskinesia induction in MPTP-treated common marmosets.

PubMed

Stockwell, K A; Virley, D J; Perren, M; Iravani, M M; Jackson, M J; Rose, S; Jenner, P

2008-05-01

L-DOPA treatment of Parkinson's disease induces a high incidence of motor complications, notably dyskinesia. Longer acting dopamine agonists, e.g. ropinirole, are thought to produce more continuous dopaminergic stimulation and less severe dyskinesia. However, standard oral administration of dopamine agonists does not result in constant plasma drug levels, therefore, more continuous drug delivery may result in both prolonged reversal of motor deficits and reduced levels of dyskinesia. Therefore, we compared the effects of repeated oral administration of ropinirole to constant subcutaneous infusion in MPTP-treated common marmosets. Animals received oral administration (0.4 mg/kg, BID) or continuous infusion of ropinirole (0.8 mg/kg/day) via osmotic minipumps for 14 days (Phase I). The treatments were then switched and continued for a further 14 days (Phase II). In Phase I, locomotor activity was similar between treatment groups but reversal of motor disability was more pronounced in animals receiving continuous infusion. Dyskinesia intensity was low in both groups however there was a trend suggestive of less marked dyskinesia in those animals receiving continuous infusion. In Phase II, increased locomotor activity was maintained but animals switched from oral to continuous treatment showing an initial period of enhanced locomotor activity. The reversal of motor disability was maintained in both groups, however, motor disability tended towards greater improvement following continuous infusion. Importantly, dyskinesia remained low in both groups suggesting that constant delivery of ropinirole neither leads to priming nor expression of dyskinesia. These results suggest that a once-daily controlled-release formulation may provide improvements over existing benefits with standard oral ropinirole in Parkinson's disease patients.

OSO paradigm--A rapid behavioral screening method for acute psychosocial stress reactivity in mice.

PubMed

Brzózka, M M; Unterbarnscheidt, T; Schwab, M H; Rossner, M J

2016-02-09

Chronic psychosocial stress is an important environmental risk factor for the development of psychiatric diseases. However, studying the impact of chronic psychosocial stress in mice is time consuming and thus not optimally suited to 'screen' increasing numbers of genetically manipulated mouse models for psychiatric endophenotypes. Moreover, many studies focus on restraint stress, a strong physical stressor with limited relevance for psychiatric disorders. Here, we describe a simple and a rapid method based on the resident-intruder paradigm to examine acute effects of mild psychosocial stress in mice. The OSO paradigm (open field--social defeat--open field) compares behavioral consequences on locomotor activity, anxiety and curiosity before and after exposure to acute social defeat stress. We first evaluated OSO in male C57Bl/6 wildtype mice where a single episode of social defeat reduced locomotor activity, increased anxiety and diminished exploratory behavior. Subsequently, we applied the OSO paradigm to mouse models of two schizophrenia (SZ) risk genes. Transgenic mice with neuronal overexpression of Neuregulin-1 (Nrg1) type III showed increased risk-taking behavior after acute stress exposure suggesting that NRG1 dysfunction is associated with altered affective behavior. In contrast, Tcf4 transgenic mice displayed a normal stress response which is in line with the postulated predominant contribution of TCF4 to cognitive deficits of SZ. In conclusion, the OSO paradigm allows for rapid screening of selected psychosocial stress-induced behavioral endophenotypes in mouse models of psychiatric diseases. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of 6-hydroxydopamine exposure on motor activity and biochemical expression in zebrafish (Danio rerio) larvae.

PubMed

Feng, Chien-Wei; Wen, Zhi-Hong; Huang, Shi-Ying; Hung, Han-Chun; Chen, Chun-Hong; Yang, San-Nan; Chen, Nan-Fu; Wang, Hui-Min; Hsiao, Chung-Der; Chen, Wu-Fu

2014-06-01

Parkinson's disease (PD) is a neurodegenerative disease that is characterized by the progressive loss of dopaminergic (DA) neurons in the substantia nigra. However, current treatments for PD are mainly palliative. Recently, researchers discovered that neurotoxins can induce Parkinsonian-like symptoms in zebrafish. No study to date has investigated the characteristics of PD, such as neuroinflammation factors, oxidative stress, or ubiquitin dysfunction, in this model. Therefore, the current study was aimed at utilizing commonly used clinical drugs, minocycline, vitamin E, and Sinemet, to test the usefulness of this model. Previous studies had indicated that DA cell loss was greater with 6-hydroxydopamine (6-OHDA) than with other neurotoxins. Thus, we first challenged zebrafish with 6-OHDA immersion and found a significant reduction in zebrafish locomotor activity; we then reversed the locomotor disruptions by treatment with vitamin E, Sinemet, or minocycline. The present study also analyzed the mRNA expression of parkin, pink1, and cd-11b, because the expression of these molecular targets has been shown to result in attenuation in mammalian models of PD. Vitamin E, Sinemet, and minocycline significantly reversed 6-OHDA-induced changes of parkin, pink1, and cd-11b mRNA expression in zebrafish. Moreover, we assessed tyrosine hydroxylase (TH) expression to confirm the therapeutic effects of vitamin E tested on this PD model and established that vitamin E reversed the 6-OHDA-induced damage on TH expression. Our results provide some support for the validity of this in vivo Parkinson's model, and we hope that this model will be more widely used in the future.

Monosodium glutamate, a food additive, induces depressive-like and anxiogenic-like behaviors in young rats.

PubMed

Quines, Caroline B; Rosa, Suzan G; Da Rocha, Juliana T; Gai, Bibiana M; Bortolatto, Cristiani F; Duarte, Marta Maria M F; Nogueira, Cristina W

2014-06-27

Monosodium glutamate (MSG) has been the target of research due to its toxicological effects. We investigated the depressive- and anxiogenic-like behaviors in rats exposed to neonatal subcutaneous injection of MSG. The involvement of the serotonergic system, by measuring [(3)H] serotonin (5-HT) uptake in cerebral cortices, and the hypothalamic pituitary adrenal (HPA) axis, by determining serum adrenocorticotropic hormone (ACTH) and corticosterone levels, was also examined. Male and female newborn Wistar rats were divided into control and MSG groups, which received, respectively, a daily subcutaneous injection of saline (0.9%) or MSG (4 g/kg/day) from the 1st to 5th postnatal day. The behavioral tests [spontaneous locomotor activity, contextual fear conditioning, and forced swimming test (FST)] were performed from the 60th to 64th postnatal day. MSG-treated animals showed alteration in the spontaneous locomotor activity, an increase in the number of fecal pellets and the number of animal's vocalizations and urine occurrence, and a decrease in the grooming time. The MSG exposure increased the immobility time in the FST and the freezing reaction in the contextual fear conditioning. Additionally, MSG treatment increased the [(3)H]5-HT uptake in the cerebral cortices of rats and induced a deregulation of HPA axis function (by increasing serum ACTH and corticosterone levels). In conclusion MSG-treated rats are more susceptible to develop anxiogenic- and depressive-like behaviors, which could be related to a dysfunction in the serotonergic system. Copyright © 2014 Elsevier Inc. All rights reserved.

Dopamine-dependent periadolescent maturation of corticostriatal functional connectivity in mouse.

PubMed

Galiñanes, Gregorio L; Taravini, Irene R E; Murer, M Gustavo

2009-02-25

Altered corticostriatal information processing associated with early dopamine systems dysfunction may contribute to attention deficit/hyperactivity disorder (ADHD). Mice with neonatal dopamine-depleting lesions exhibit hyperactivity that wanes after puberty and is reduced by psychostimulants, reminiscent of some aspects of ADHD. To assess whether the maturation of corticostriatal functional connectivity is altered by early dopamine depletion, we examined preadolescent and postadolescent urethane-anesthetized mice with or without dopamine-depleting lesions. Specifically, we assessed (1) synchronization between striatal neuron discharges and oscillations in frontal cortex field potentials and (2) striatal neuron responses to frontal cortex stimulation. In adult control mice striatal neurons were less spontaneously active, less responsive to cortical stimulation, and more temporally tuned to cortical rhythms than in infants. Striatal neurons from hyperlocomotor mice required more current to respond to cortical input and were less phase locked to ongoing oscillations, resulting in fewer neurons responding to refined cortical commands. By adulthood some electrophysiological deficits waned together with hyperlocomotion, but striatal spontaneous activity remained substantially elevated. Moreover, dopamine-depleted animals showing normal locomotor scores exhibited normal corticostriatal synchronization, suggesting that the lesion allows, but is not sufficient, for the emergence of corticostriatal changes and hyperactivity. Although amphetamine normalized corticostriatal tuning in hyperlocomotor mice, it reduced horizontal activity in dopamine-depleted animals regardless of their locomotor phenotype, suggesting that amphetamine modified locomotion through a parallel mechanism, rather than that modified by dopamine depletion. In summary, functional maturation of striatal activity continues after infancy, and early dopamine depletion delays the maturation of core functional capacities of the corticostriatal system.

Dopamine-dependent periadolescent maturation of corticostriatal functional connectivity in mouse

PubMed Central

Galiñanes, Gregorio L.; Taravini, Irene R.E.; Murer, M. Gustavo

2009-01-01

Altered corticostriatal information processing associated with early dopamine systems dysfunction may contribute to attention deficit/hyperactivity disorder (ADHD). Mice with neonatal dopamine-depleting lesions exhibit hyperactivity that wanes after puberty and is reduced by psychostimulants, reminiscent of some aspects of ADHD. To assess whether the maturation of corticostriatal functional connectivity is altered by early dopamine depletion, we examined pre- and post-adolescent urethane-anesthetized mice with or without dopamine-depleting lesions. Specifically, we assessed (1) synchronization between striatal neuron discharges and oscillations in frontal cortex field potentials and (2) striatal neuron responses to frontal cortex stimulation. In adult control mice striatal neurons were less spontaneously active, less responsive to cortical stimulation and more temporally tuned to cortical rhythms than in infants. Striatal neurons from hyperlocomotor mice required more current to respond to cortical input and were less phase-locked to ongoing oscillations, resulting in fewer neurons responding to refined cortical commands. By adulthood some electrophysiological deficits waned together with hyperlocomotion, but striatal spontaneous activity remained substantially elevated. Moreover, dopamine-depleted animals showing normal locomotor scores exhibited normal corticostriatal synchronization, suggesting that the lesion allows, but is not sufficient, for the emergence of corticostriatal changes and hyperactivity. Although amphetamine normalized corticostriatal tuning in hyperlocomotor mice, it reduced horizontal activity in dopamine-depleted animals irrespective of their locomotor phenotype, suggesting that amphetamine modified locomotion through a parallel mechanism, rather than that modified by dopamine depletion. In summary, functional maturation of striatal activity continues after infancy, and early dopamine depletion delays the maturation of core functional capacities of the corticostriatal system. PMID:19244524

The endocannabinoid gene faah2a modulates stress-associated behavior in zebrafish

PubMed Central

Lee, Han B.; El Khoury, Louis Y.; Sigafoos, Ashley N.; Petersen, Morgan O.; Clark, Karl J.

2018-01-01

The ability to orchestrate appropriate physiological and behavioral responses to stress is important for survival, and is often dysfunctional in neuropsychiatric disorders that account for leading causes of global disability burden. Numerous studies have shown that the endocannabinoid neurotransmitter system is able to regulate stress responses and could serve as a therapeutic target for the management of these disorders. We used quantitative reverse transcriptase-polymerase chain reactions to show that genes encoding enzymes that synthesize (abhd4, gde1, napepld), enzymes that degrade (faah, faah2a, faah2b), and receptors that bind (cnr1, cnr2, gpr55-like) endocannabinoids are expressed in zebrafish (Danio rerio). These genes are conserved in many other vertebrates, including humans, but fatty acid amide hydrolase 2 has been lost in mice and rats. We engineered transcription activator-like effector nucleases to create zebrafish with mutations in cnr1 and faah2a to test the role of these genes in modulating stress-associated behavior. We showed that disruption of cnr1 potentiated locomotor responses to hyperosmotic stress. The increased response to stress was consistent with rodent literature and served to validate the use of zebrafish in this field. Moreover, we showed for the first time that disruption of faah2a attenuated the locomotor responses to hyperosmotic stress. This later finding suggests that FAAH2 may be an important mediator of stress responses in non-rodent vertebrates. Accordingly, FAAH and FAAH2 modulators could provide distinct therapeutic options for stress-aggravated disorders. PMID:29304078

Hyperalgesia, low-anxiety, and impairment of avoidance learning in neonatal caffeine-treated rats.

PubMed

Pan, Hong-Zhen; Chen, Hwei-Hsien

2007-03-01

The nonselective adenosine receptor antagonist caffeine is used clinically to treat apnea in preterm infants. The brain developmental stage of preterm infants is usually at a period of rapid brain growth, referred as brain growth spurt, which occurs during early postnatal life in rats and is highly sensitive to central nervous system (CNS) acting drugs. The aim of this work was to study whether caffeine treatment during brain growth spurt produces long-term effects on the adenosine receptor-regulated behaviors including nociception, anxiety, learning, and memory. Neonatal male and female Sprague-Dawley rats were administered either deionized water or caffeine (15-20 mg kg(-1) day(-1)) through gavage (0.05 ml/10 g) over postnatal days (PN) 2-6. The hot-plate test, elevated plus-maze, dark-light transition test, and step-through inhibitory avoidance learning task were examined in juvenile rats. Furthermore, the responses to adenosine A(1) receptor agonist N(6)-cyclopentyladenosine (CPA)-induced hypothermia and A(2A) receptor agonist CGS21680-induced locomotor depression were also compared. Caffeine-treated rats showed hyperalgesia in hot-plate test, less anxiety than controls in the elevated plus-maze and dark-light transition, and impairment in step-through avoidance learning test. Moreover, the responses to CPA-induced hypothermia and CGS21680-induced locomotor depression were enhanced in caffeine-treated rats. These results indicate that caffeine exposure during brain growth spurt alters the adenosine receptor-regulated behaviors and the responsiveness to adenosine agonists, suggesting the risk of adenosine receptor-related behavioral dysfunction may exist in preterm newborns treated for apnea with caffeine.

Behavioural and cognitive abnormalities in an imprinting centre deletion mouse model for Prader-Willi syndrome.

PubMed

Relkovic, Dinko; Doe, Christine M; Humby, Trevor; Johnstone, Karen A; Resnick, James L; Holland, Anthony J; Hagan, Jim J; Wilkinson, Lawrence S; Isles, Anthony R

2010-01-01

The genes in the imprinted cluster on human chromosome 15q11-q13 are known to contribute to psychiatric conditions such as schizophrenia and autism. Major disruptions of this interval leading to a lack of paternal allele expression give rise to Prader-Willi syndrome (PWS), a neurodevelopmental disorder with core symptoms of a failure to thrive in infancy and, on emergence from infancy, learning disabilities and over-eating. Individuals with PWS also display a number of behavioural problems and an increased incidence of neuropsychiatric abnormalities, which recent work indicates involve aspects of frontal dysfunction. To begin to examine the contribution of genes in this interval to relevant psychological and behavioural phenotypes, we exploited the imprinting centre (IC) deletion mouse model for PWS (PWS-IC(+/-)) and the five-choice serial reaction time task (5-CSRTT), which is primarily an assay of visuospatial attention and response control that is highly sensitive to frontal manipulations. Locomotor activity, open-field behaviour and sensorimotor gating were also assessed. PWS-IC(+/-) mice displayed reduced locomotor activity, increased acoustic startle responses and decreased prepulse inhibition of startle responses. In the 5-CSRTT, the PWS-IC(+/-) mice showed deficits in discriminative response accuracy, increased correct reaction times and increased omissions. Task manipulations confirmed that these differences were likely to be due to impaired attention. Our data recapitulate several aspects of the PWS clinical condition, including findings consistent with frontal abnormalities, and may indicate novel contributions of the imprinted genes found in 15q11-q13 to behavioural and cognitive function generally.

Differential Adaptations of the Musculoskeletal System after Spinal Cord Contusion and Transection in Rats.

PubMed

Lin, Ching-Yi; Androjna, Charlie; Rozic, Richard; Nguyen, Bichtram; Parsons, Brett; Midura, Ronald J; Lee, Yu-Shang

2018-04-05

Spinal cord injury (SCI) causes impaired neuronal function with associated deficits in the musculoskeletal system, which can lead to permanent disability. Here, the impact of SCI on in vivo musculoskeletal adaptation was determined by studying deficits in locomotor function and analyzing changes that occur in the muscle and bone compartments within the rat hindlimb after contusion or transection SCI. Analyses of locomotor patterns, as assessed via the Basso, Beattie, and Bresnahan (BBB) rating scale, revealed that transection animals showed significant deficits, while the contusion group had moderate deficits, compared with naïve groups. Muscle myofiber cross-sectional areas (CSA) of both the soleus and tibialis anterior muscles were significantly decreased three months after contusion SCI. Such decreases in CSA were even more dramatic in the transection SCI group, suggesting a dependence on muscle activity, which is further validated by the correlation analyses between BBB score and myofiber CSA. Bone compartment analyses, however, revealed that transection animals showed the most significant deficits, while contusion animals showed no significant differences in the trabecular bone content within the proximal tibia compartment. In general, values of bone volume per total bone volume (BV/TV) were similar across the SCI groups. Significant decreases were observed, however, in the transection animals for bone mineral content, bone mineral density, and three-dimensional trabecular structure parameters (trabecular number, thickness, and spacing) compared with the naïve and contusion groups. Together, these findings suggest an altered musculoskeletal system can be correlated directly to motor dysfunctions seen after SCI.

Role of the 5-HT2A receptor in the locomotor hyperactivity produced by phenylalkylamine hallucinogens in mice

PubMed Central

Halberstadt, Adam L.; Powell, Susan B.; Geyer, Mark A.

2014-01-01

The 5-HT2A receptor mediates the effects of serotonergic hallucinogens and may play a role in the pathophysiology of certain psychiatric disorders, including schizophrenia. Given these findings, there is a need for animal models to assess the behavioral effects of 5-HT2A receptor activation. Our previous studies demonstrated that the phenylalkylamine hallucinogen and 5-HT2A/2C agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) produces dose-dependent effects on locomotor activity in C57BL/6J mice, increasing activity at low to moderate doses and reducing activity at high doses. DOI did not increase locomotor activity in 5-HT2A knockout mice, indicating the effect is a consequence of 5-HT2A receptor activation. Here, we tested a series of phenylalkylamine hallucinogens in C57BL/6J mice using the Behavioral Pattern Monitor (BPM) to determine whether these compounds increase locomotor activity by activating the 5-HT2A receptor. Low doses of mescaline, 2,5-dimethoxy-4-ethylamphetamine (DOET), 2,5-dimethoxy-4-propylamphetamine (DOPR), 2,4,5-trimethoxyamphetamine (TMA-2), and the conformationally restricted phenethylamine (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine (TCB-2) increased locomotor activity. By contrast, the non-hallucinogenic phenylalkylamine 2,5-dimethoxy-4-tert-butylamphetamine (DOTB) did not alter locomotor activity at any dose tested (0.1-10 mg/kg i.p.). The selective 5-HT2A antagonist M100907 blocked the locomotor hyperactivity induced by mescaline and TCB-2. Similarly, mescaline and TCB-2 did not increase locomotor activity in 5-HT2A knockout mice. These results confirm that phenylalkylamine hallucinogens increase locomotor activity in mice and demonstrate that this effect is mediated by 5-HT2A receptor activation. Thus, locomotor hyperactivity in mice can be used to assess phenylalkylamines for 5-HT2A agonist activity and hallucinogen-like behavioral effects. These studies provide additional support for the link between 5-HT2A activation and hallucinogenesis. PMID:23376711

Locomotor Expertise Predicts Infants' Perseverative Errors

ERIC Educational Resources Information Center

Berger, Sarah E.

2010-01-01

This research examined the development of inhibition in a locomotor context. In a within-subjects design, infants received high- and low-demand locomotor A-not-B tasks. In Experiment 1, walking 13-month-old infants followed an indirect path to a goal. In a control condition, infants took a direct route. In Experiment 2, crawling and walking…

Locomotor Status and the Development of Spatial Search Skills.

ERIC Educational Resources Information Center

Bai, Dina L.; Bertenthal, Bennett I.

1992-01-01

Investigated the possibility that previous reports of a relation between locomotor status and stage-4 object permanence performance could be generalized to performance on an object localization task. Findings suggest that the effects of locomotor experience on infants' search performance are quite specific and mediated by a variety of factors that…

Motoneurons regulate the central pattern generator during drug-induced locomotor-like activity in the neonatal mouse

PubMed Central

Falgairolle, Melanie; Puhl, Joshua G; Pujala, Avinash; Liu, Wenfang; O’Donovan, Michael J

2017-01-01

Motoneurons are traditionally viewed as the output of the spinal cord that do not influence locomotor rhythmogenesis. We assessed the role of motoneuron firing during ongoing locomotor-like activity in neonatal mice expressing archaerhopsin-3 (Arch), halorhodopsin (eNpHR), or channelrhodopsin-2 (ChR2) in Choline acetyltransferase neurons (ChAT+) or Arch in LIM-homeodomain transcription factor Isl1+ neurons. Illumination of the lumbar cord in mice expressing eNpHR or Arch in ChAT+ or Isl1+ neurons, depressed motoneuron discharge, transiently decreased the frequency, and perturbed the phasing of the locomotor-like rhythm. When the light was turned off motoneuron firing and locomotor frequency both transiently increased. These effects were not due to cholinergic neurotransmission, persisted during partial blockade of gap junctions and were mediated, in part, by AMPAergic transmission. In spinal cords expressing ChR2, illumination increased motoneuron discharge and transiently accelerated the rhythm. We conclude that motoneurons provide feedback to the central pattern generator (CPG) during drug-induced locomotor-like activity. DOI: http://dx.doi.org/10.7554/eLife.26622.001 PMID:28671548

Modular diversification of the locomotor system in damselfishes (Pomacentridae).

PubMed

Aguilar-Medrano, Rosalía; Frédérich, Bruno; Barber, Paul H

2016-05-01

As fish move and interact with their aquatic environment by swimming, small morphological variations of the locomotor system can have profound implications on fitness. Damselfishes (Pomacentridae) have inhabited coral reef ecosystems for more than 50 million years. As such, habitat preferences and behavior could significantly constrain the morphology and evolvability of the locomotor system. To test this hypothesis, we used phylogenetic comparative methods on morphometric, ecological and behavioral data. While body elongation represented the primary source of variation in the locomotor system of damselfishes, results also showed a diverse suite of morphological combinations between extreme morphologies. Results show clear associations between behavior, habitat preferences, and morphology, suggesting ecological constraints on shape diversification of the locomotor system. In addition, results indicate that the three modules of the locomotor system are weakly correlated, resulting in versatile and independent characters. These results suggest that Pomacentridae is shape may result from the interaction between (1) integrated parts of morphological variation that maintain overall swimming ability and (2) relatively independent parts of the morphology that facilitate adaptation and diversification. © 2016 Wiley Periodicals, Inc.

Osteological postcranial traits in hylid anurans indicate a morphological continuum between swimming and jumping locomotor modes.

PubMed

Soliz, Mónica; Tulli, Maria J; Abdala, Virginia

2017-03-01

Anurans exhibit a particularly wide range of locomotor modes that result in wide variations in their skeletal structure. This article investigates the possible correlation between morphological aspects of the hylid postcranial skeleton and their different locomotor modes and habitat use. To do so, we analyzed 18 morphometric postcranial variables in 19 different anuran species representative of a variety of locomotor modes (jumper, hopper, walker, and swimmer) and habitat uses (arboreal, bush, terrestrial, and aquatic). Our results show that the evolution of the postcranial hylid skeleton cannot be explained by one single model, as for example, the girdles suggest modular evolution while the vertebral column suggests other evolutionary modules. In conjunction with data from several other studies, we were able to show a relationship between hylid morphology and habitat use; offering further evidence that the jumper/swimmer and walker/hopper locomotor modes exhibit quite similar morphological architecture. This allowed us to infer that new locomotor modalities are, in fact, generated along a morphological continuum. J. Morphol. 278:403-417, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Central command dysfunction in rats with heart failure is mediated by brain oxidative stress and normalized by exercise training.

PubMed

Koba, Satoshi; Hisatome, Ichiro; Watanabe, Tatsuo

2014-09-01

Sympathoexcitation elicited by central command, a parallel activation of the motor and autonomic neural circuits in the brain, has been shown to become exaggerated in chronic heart failure (CHF). The present study tested the hypotheses that oxidative stress in the medulla in CHF plays a role in exaggerating central command-elicited sympathoexcitation, and that exercise training in CHF suppresses central command-elicited sympathoexcitation through its antioxidant effects in the medulla. In decerebrate rats, central command was activated by electrically stimulating the mesencephalic locomotor region (MLR) after neuromuscular blockade. The MLR stimulation at a current intensity greater than locomotion threshold in rats with CHF after myocardial infarction (MI) evoked larger (P < 0.05) increases in renal sympathetic nerve activity and arterial pressure than in sham-operated healthy rats (Sham) and rats with CHF that had completed longterm (8–12 weeks) exercise training (MI + TR). In the Sham and MI + TR rats, bilateral microinjection of a superoxide dismutase (SOD) mimetic Tempol into the rostral ventrolateral medulla (RVLM) had no effects on MLR stimulation-elicited responses. By contrast, in MI rats, Tempol treatment significantly reduced MLR stimulation-elicited responses. In a subset of MI rats, treatment with Tiron, another SOD mimetic, within the RVLM also reduced responses. Superoxide generation in the RVLM, as evaluated by dihydroethidium staining, was enhanced in MI rats compared with that in Sham and MI + TR rats. Collectively, these results support the study hypotheses. We suggest that oxidative stress in the medulla in CHF mediates central command dysfunction, and that exercise training in CHF is capable of normalizing central command dysfunction through its antioxidant effects in the medulla.

Zebrafish as a Model for Epilepsy-Induced Cognitive Dysfunction: A Pharmacological, Biochemical and Behavioral Approach

PubMed Central

Kundap, Uday P.; Kumari, Yatinesh; Othman, Iekhsan; Shaikh, Mohd. Farooq

2017-01-01

Epilepsy is a neuronal disorder allied with distinct neurological and behavioral alterations characterized by recurrent spontaneous epileptic seizures. Impairment of the cognitive performances such as learning and memory is frequently observed in epileptic patients. Anti-epileptic drugs (AEDs) are efficient to the majority of patients. However, 30% of this population seems to be refractory to the drug treatment. These patients are not seizure-free and frequently they show impaired cognitive functions. Unfortunately, as a side effect, some AEDs could contribute to such impairment. The major problem associated with conducting studies on epilepsy-related cognitive function is the lack of easy, rapid, specific and sensitive in vivo testing models. However, by using a number of different techniques and parameters in the zebrafish, we can incorporate the unique feature of specific disorder to study the molecular and behavior basis of this disease. In the view of current literature, the goal of the study was to develop a zebrafish model of epilepsy induced cognitive dysfunction. In this study, the effect of AEDs on locomotor activity and seizure-like behavior was tested against the pentylenetetrazole (PTZ) induced seizures in zebrafish and epilepsy associated cognitive dysfunction was determined using T-maze test followed by neurotransmitter estimation and gene expression analysis. It was observed that all the AEDs significantly reversed PTZ induced seizure in zebrafish, but had a negative impact on cognitive functions of zebrafish. AEDs were found to modulate neurotransmitter levels, especially GABA, glutamate, and acetylcholine and gene expression in the drug treated zebrafish brains. Therefore, combination of behavioral, neurochemical and genenetic information, makes this model a useful tool for future research and discovery of newer and safer AEDs. PMID:28824436

Resveratrol suppresses neuroinflammation in the experimental paradigm of autism spectrum disorders.

PubMed

Bhandari, Ranjana; Kuhad, Anurag

2017-02-01

Neuronal dysfunction caused by neuroinflammation triggered by the stimulation of matrix metalloproteinases and the subsequent release of pro-inflammatory cytokines, as a result of oxidative stress and mitochondrial dysfunction, is one of the probable mechanisms involved in the pathogenesis of autism spectrum disorders (ASD). The aim of the present study was to explore the ameliorative potential of resveratrol on neuroinflammation in the experimental paradigm of neuroinflammatory model of ASD in rats. 1M Propanoic acid (PPA) (4 μl) was infused over 10 min into the anterior portion of the lateral ventricle to induce ASD like symptoms in rats. Resveratrol (5, 10 and 15 mg/kg) was administered starting from the 2nd day of the surgery and continued upto 28th day. Rats were tested for various behavioural paradigms such as social interaction, stereotypy, locomotor activity, anxiety, novelty, depression, spatial learning, memory, repetitive and pervasive behaviour between the 7th day and 28th day. In addition, biochemical tests for oxidative stress, mitochondrial complexes, TNF-α and MMP-9 were also assessed. Treatment with resveratrol for four weeks restored, significantly and dose dependently, all the neurological, sensory, behavioural, biochemical and molecular deficits in PPA induced autistic phenotype in rats. The major finding of the study is that resveratrol restored the core and associated symptoms of autistic phenotype by suppressing oxidative-nitrosative stress, mitochondrial dysfunction, TNF-α and MMP-9 expression in PPA induced ASD in rats. Therefore, resveratrol might serve as an adjunct potential therapeutic agent for amelioration of neurobehavioural and biochemical deficits associated with autism spectrum disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Disruption of Locomotion in Response to Hindlimb Muscle Stretch at Acute and Chronic Time Points after a Spinal Cord Injury in Rats.

PubMed

Keller, Anastasia V P; Wainwright, Grace; Shum-Siu, Alice; Prince, Daniella; Hoeper, Alyssa; Martin, Emily; Magnuson, David S K

2017-02-01

After spinal cord injury (SCI) muscle contractures develop in the plegic limbs of many patients. Physical therapists commonly use stretching as an approach to avoid contractures and to maintain the extensibility of soft tissues. We found previously that a daily stretching protocol has a negative effect on locomotor recovery in rats with mild thoracic SCI. The purpose of the current study was to determine the effects of stretching on locomotor function at acute and chronic time points after moderately severe contusive SCI. Female Sprague-Dawley rats with 25 g-cm T10 contusion injuries received our standard 24-min stretching protocol starting 4 days (acutely) or 10 weeks (chronically) post-injury (5 days/week for 5 or 4 weeks, respectively). Locomotor function was assessed using the BBB (Basso, Beattie, and Bresnahan) Open Field Locomotor Scale, video-based kinematics, and gait analysis. Locomotor deficits were evident in the acute animals after only 5 days of stretching and increasing the perceived intensity of stretching at week 4 resulted in greater impairment. Stretching initiated chronically resulted in dramatic decrements in locomotor function because most animals had BBB scores of 0-3 for weeks 2, 3, and 4 of stretching. Locomotor function recovered to control levels for both groups within 2 weeks once daily stretching ceased. Histological analysis revealed no apparent signs of overt and persistent damage to muscles undergoing stretching. The current study extends our observations of the stretching phenomenon to a more clinically relevant moderately severe SCI animal model. The results are in agreement with our previous findings and further demonstrate that spinal cord locomotor circuitry is especially vulnerable to the negative effects of stretching at chronic time points. While the clinical relevance of this phenomenon remains unknown, we speculate that stretching may contribute to the lack of locomotor recovery in some patients.

Afferent control of central pattern generators: experimental analysis of locomotion in the decerebrate cat.

PubMed

Baev, K V; Esipenko, V B; Shimansky YuP

1991-01-01

Changes in the motor activity of the spinal locomotor generator evoked by tonic and phasic peripheral afferent signals during fictitious locomotion of both slow and fast rhythms were analysed in the cat. The tonic afferent inflow was conditioned by the position of the hindlimb. The phasic afferent signals were imitated by electrical stimulation of hindlimb nerves. The correlation between the kinematics of hindlimb locomotor movement and sensory inflow was investigated during actual locomotion. Reliable correlations between motor activity parameters during fictitious locomotion were revealed in cases of both slow and fast "locomotor" rhythms. The main difference between these cases was that correlations "duration-intensity" were positive in the first and negative in the second case. The functional role of "locomotor" pattern dependence on tonic sensory inflow consisted of providing stability for planting the hindlimb on the ground. For any investigated afferent input the phase moments in the "locomotor" cycle were found, in which an afferent signal caused no rearrangement in locomotor generator activity. These moments corresponded to the transitions between "flexion" and "extension" phases and to the bursts of integral afferent activity observed during real locomotion. The data obtained are compared with the results previously described for the scratching generator. The character of changes in "locomotor" activity in response to tonic and phasic sensory signals was similar to that of such changes in "scratching" rhythm in the case of fast "locomotion". Intensification of the "flexion" phase caused by phasic high-intensity stimulation of cutaneous afferents during low "locomotor" rhythm was changed to inhibition (such as observed during "scratching") when this rhythm was fast. It is concluded that the main regularities of peripheral afferent control for both the locomotor and scratching generators are the same. Moreover, these central pattern generators are just working regimes of a general spinal motor optimal control system containing the intrinsic model of limb movement dynamics. The consequences of this concept and ways of further research are discussed.

Interferon β induces clearance of mutant ataxin 7 and improves locomotion in SCA7 knock-in mice.

PubMed

Chort, Alice; Alves, Sandro; Marinello, Martina; Dufresnois, Béatrice; Dornbierer, Jean-Gabriel; Tesson, Christelle; Latouche, Morwena; Baker, Darren P; Barkats, Martine; El Hachimi, Khalid H; Ruberg, Merle; Janer, Alexandre; Stevanin, Giovanni; Brice, Alexis; Sittler, Annie

2013-06-01

We showed previously, in a cell model of spinocerebellar ataxia 7, that interferon beta induces the expression of PML protein and the formation of PML protein nuclear bodies that degrade mutant ataxin 7, suggesting that the cytokine, used to treat multiple sclerosis, might have therapeutic value in spinocerebellar ataxia 7. We now show that interferon beta also induces PML-dependent clearance of ataxin 7 in a preclinical model, SCA7(266Q/5Q) knock-in mice, and improves motor function. Interestingly, the presence of mutant ataxin 7 in the mice induces itself the expression of endogenous interferon beta and its receptor. Immunohistological studies in brains from two patients with spinocerebellar ataxia 7 confirmed that these modifications are also caused by the disease in humans. Interferon beta, administered intraperitoneally three times a week in the knock-in mice, was internalized with its receptor in Purkinje and other cells and translocated to the nucleus. The treatment induced PML protein expression and the formation of PML protein nuclear bodies and decreased mutant ataxin 7 in neuronal intranuclear inclusions, the hallmark of the disease. No reactive gliosis or other signs of toxicity were observed in the brain or internal organs. The performance of the SCA7(266Q/5Q) knock-in mice was significantly improved on two behavioural tests sensitive to cerebellar function: the Locotronic® Test of locomotor function and the Beam Walking Test of balance, motor coordination and fine movements, which are affected in patients with spinocerebellar ataxia 7. In addition to motor dysfunction, SCA7(266Q/5Q) mice present abnormalities in the retina as in patients: ataxin 7-positive neuronal intranuclear inclusions that were reduced by interferon beta treatment. Finally, since neuronal death does not occur in the cerebellum of SCA7(266Q/5Q) mice, we showed in primary cell cultures expressing mutant ataxin 7 that interferon beta treatment improves Purkinje cell survival.

Loss of VGLUT3 Produces Circadian-Dependent Hyperdopaminergia and Ameliorates Motor Dysfunction and l-Dopa-Mediated Dyskinesias in a Model of Parkinson's Disease

PubMed Central

Divito, Christopher B.; Steece-Collier, Kathy; Case, Daniel T.; Williams, Sean-Paul G.; Stancati, Jennifer A.; Zhi, Lianteng; Rubio, Maria E.; Sortwell, Caryl E.; Collier, Timothy J.; Sulzer, David; Edwards, Robert H.; Zhang, Hui

2015-01-01

The striatum is essential for many aspects of mammalian behavior, including motivation and movement, and is dysfunctional in motor disorders such as Parkinson's disease. The vesicular glutamate transporter 3 (VGLUT3) is expressed by striatal cholinergic interneurons (CINs) and is thus well positioned to regulate dopamine (DA) signaling and locomotor activity, a canonical measure of basal ganglia output. We now report that VGLUT3 knock-out (KO) mice show circadian-dependent hyperlocomotor activity that is restricted to the waking cycle and is due to an increase in striatal DA synthesis, packaging, and release. Using a conditional VGLUT3 KO mouse, we show that deletion of the transporter from CINs, surprisingly, does not alter evoked DA release in the dorsal striatum or baseline locomotor activity. The mice do, however, display changes in rearing behavior and sensorimotor gating. Elevation of DA release in the global KO raised the possibility that motor deficits in a Parkinson's disease model would be reduced. Remarkably, after a partial 6-hydroxydopamine (6-OHDA)-mediated DA depletion (∼70% in dorsal striatum), KO mice, in contrast to WT mice, showed normal motor behavior across the entire circadian cycle. l-3,4-dihydroxyphenylalanine-mediated dyskinesias were also significantly attenuated. These findings thus point to new mechanisms to regulate basal ganglia function and potentially treat Parkinson's disease and related disorders. SIGNIFICANCE STATEMENT Dopaminergic signaling is critical for both motor and cognitive functions in the mammalian nervous system. Impairments, such as those found in Parkinson's disease patients, can lead to severe motor deficits. Vesicular glutamate transporter 3 (VGLUT3) loads glutamate into secretory vesicles for neurotransmission and is expressed by discrete neuron populations throughout the nervous system. Here, we report that the absence of VGLUT3 in mice leads to an upregulation of the midbrain dopamine system. Remarkably, in a Parkinson's disease model, the mice show normal motor behavior. They also show fewer abnormal motor behaviors (dyskinesias) in response to l-3,4-dihydroxyphenylalanine, the principal treatment for Parkinson's disease. The work thus suggests new avenues for the development of novel treatment strategies for Parkinson's disease and potentially other basal-ganglia-related disorders. PMID:26558771

Neurochemical factors underlying individual differences in locomotor activity and anxiety-like behavioral responses in zebrafish.

PubMed

Tran, Steven; Nowicki, Magda; Muraleetharan, Arrujyan; Chatterjee, Diptendu; Gerlai, Robert

2016-02-04

Variation among individuals may arise for several reasons, and may have diverse underlying mechanisms. Individual differences have been studied in a variety of species, but recently a new model organism has emerged in this field that offers both sophistication in phenotypical characterization and powerful mechanistic analysis. Recently, zebrafish, one of the favorites of geneticists, have been shown to exhibit consistent individual differences in baseline locomotor activity. In the current study, we further explore this finding and examine whether individual differences in locomotor activity correlate with anxiety-like behavioral measures and with levels of dopamine, serotonin and the metabolites of these neurotransmitters. In addition, we examine whether individual differences in locomotor activity are also associated with reactivity to the locomotor stimulant effects of and neurochemical responses to acute ethanol exposure (30min long, 1% v/v ethanol bath application). Principal component analyses revealed a strong association among anxiety-like responses, locomotor activity, serotonin and dopamine levels. Furthermore, ethanol exposure was found to abolish the locomotion-dependent anxiety-like behavioral and serotonergic responses suggesting that this drug also engages a common underlying pathway. Overall, our results provide support for an important role of the serotonergic system in mediating individual differences in anxiety-like responses and locomotor activity in zebrafish and for a minor modulatory role of the dopaminergic system. Copyright © 2015 Elsevier Inc. All rights reserved.

Mephedrone interactions with cocaine: prior exposure to the 'bath salt' constituent enhances cocaine-induced locomotor activation in rats.

PubMed

Gregg, Ryan A; Tallarida, Christopher S; Reitz, Allen B; Rawls, Scott M

2013-12-01

Concurrent use of mephedrone (4-methylmethcathinone; MEPH) and established drugs of abuse is now commonplace, but knowledge about interactions between these drugs is sparse. The present study was designed to test the hypothesis that prior MEPH exposure enhances the locomotor-stimulant effects of cocaine and methamphetamine (METH). For cocaine experiments, rats pretreated with saline, cocaine (15 mg/kg), or MEPH (15 mg/kg) for 5 days were injected with cocaine after 10 days of drug absence. For METH experiments, rats pretreated with saline, METH (2 mg/kg), or MEPH (15 mg/kg) were injected with METH after 10 days of drug absence. Cocaine challenge produced greater locomotor activity after pretreatment with cocaine or MEPH than after pretreatment with saline. METH challenge produced greater locomotor activity after METH pretreatment than after saline pretreatment; however, locomotor activity in rats pretreated with MEPH or saline and then challenged with METH was not significantly different. The locomotor response to MEPH (15 mg/kg) was not significantly affected by pretreatment with cocaine (15 mg/kg) or METH (0.5, 2 mg/kg). The present demonstration that cocaine-induced locomotor activation is enhanced by prior MEPH exposure suggests that MEPH cross-sensitizes to cocaine and increases cocaine efficacy. Interestingly, MEPH cross-sensitization was not bidirectional and did not extend to METH, suggesting that the phenomenon is sensitive to specific psychostimulants.

Locomotor play drives motor skill acquisition at the expense of growth: A life history trade-off

PubMed Central

Berghänel, Andreas; Schülke, Oliver; Ostner, Julia

2015-01-01

The developmental costs and benefits of early locomotor play are a puzzling topic in biology, psychology, and health sciences. Evolutionary theory predicts that energy-intensive behavior such as play can only evolve if there are considerable benefits. Prominent theories propose that locomotor play is (i) low cost, using surplus energy remaining after growth and maintenance, and (ii) beneficial because it trains motor skills. However, both theories are largely untested. Studying wild Assamese macaques, we combined behavioral observations of locomotor play and motor skill acquisition with quantitative measures of natural food availability and individual growth rates measured noninvasively via photogrammetry. Our results show that investments in locomotor play were indeed beneficial by accelerating motor skill acquisition but carried sizable costs in terms of reduced growth. Even under moderate natural energy restriction, investment in locomotor play accounted for up to 50% of variance in growth, which strongly contradicts the current theory that locomotor play only uses surplus energy remaining after growth and maintenance. Male immatures played more, acquired motor skills faster, and grew less than female immatures, leading to persisting size differences until the age of female maturity. Hence, depending on skill requirements, investment in play can take ontogenetic priority over physical development unconstrained by costs of play with consequences for life history, which strongly highlights the ontogenetic and evolutionary importance of play. PMID:26601237

Locomotor play drives motor skill acquisition at the expense of growth: A life history trade-off.

PubMed

Berghänel, Andreas; Schülke, Oliver; Ostner, Julia

2015-08-01

The developmental costs and benefits of early locomotor play are a puzzling topic in biology, psychology, and health sciences. Evolutionary theory predicts that energy-intensive behavior such as play can only evolve if there are considerable benefits. Prominent theories propose that locomotor play is (i) low cost, using surplus energy remaining after growth and maintenance, and (ii) beneficial because it trains motor skills. However, both theories are largely untested. Studying wild Assamese macaques, we combined behavioral observations of locomotor play and motor skill acquisition with quantitative measures of natural food availability and individual growth rates measured noninvasively via photogrammetry. Our results show that investments in locomotor play were indeed beneficial by accelerating motor skill acquisition but carried sizable costs in terms of reduced growth. Even under moderate natural energy restriction, investment in locomotor play accounted for up to 50% of variance in growth, which strongly contradicts the current theory that locomotor play only uses surplus energy remaining after growth and maintenance. Male immatures played more, acquired motor skills faster, and grew less than female immatures, leading to persisting size differences until the age of female maturity. Hence, depending on skill requirements, investment in play can take ontogenetic priority over physical development unconstrained by costs of play with consequences for life history, which strongly highlights the ontogenetic and evolutionary importance of play.

Cilnidipine, an L/N-type calcium channel blocker prevents acquisition and expression of ethanol-induced locomotor sensitization in mice.

PubMed

Bhutada, Pravinkumar; Mundhada, Yogita; Patil, Jayshree; Rahigude, Anand; Zambare, Krushna; Deshmukh, Prashant; Tanwar, Dhanshree; Jain, Kishor

2012-04-11

Several evidences indicated the involvement of L- and N-type calcium channels in behavioral effects of drugs of abuse, including ethanol. Calcium channels are implicated in ethanol-induced behaviors and neurochemical responses. Calcium channel antagonists block the psychostimulants induced behavioral sensitization. Recently, it is demonstrated that L-, N- and T-type calcium channel blockers attenuate the acute locomotor stimulant effects of ethanol. However, no evidence indicated the role of calcium channels in ethanol-induced psychomotor sensitization. Therefore, present study evaluated the influence of cilnidipine, an L/N-type calcium channel blocker on acquisition and expression of ethanol-induced locomotor sensitization. The results revealed that cilnidipine (0.1 and 1.0μg/mouse, i.c.v.) attenuates the expression of sensitization to locomotor stimulant effect of ethanol (2.0g/kg, i.p.), whereas pre- treatment of cilnidipine (0.1 and 1.0μg/mouse, i.c.v.) during development of sensitization blocks acquisition and attenuates expression of sensitization to locomotor stimulant effect of ethanol. Cilnidipine per se did not influence locomotor activity in tested doses. Further, cilnidipine had no influence on effect of ethanol on rotarod performance. These results support the hypothesis that neuroadaptive changes in calcium channels participate in the acquisition and the expression of ethanol-induced locomotor sensitization. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Cerebellar contribution to locomotor behavior: A neurodevelopmental perspective.

PubMed

Sathyanesan, Aaron; Gallo, Vittorio

2018-04-30

The developmental trajectory of the formation of cerebellar circuitry has significant implications for locomotor plasticity and adaptive learning at later stages. While there is a wealth of knowledge on the development of locomotor behavior in human infants, children, and adolescents, pre-clinical animal models have fallen behind on the study of the emergence of behavioral motifs in locomotor function across postnatal development. Since cerebellar development is protracted, it is subject to higher risk of genetic or environmental disruption, potentially leading to abnormal behavioral development. This highlights the need for more sophisticated and specific functional analyses of adaptive cerebellar behavior within the context of whole-body locomotion across the entire span of postnatal development. Here we review evidence on cerebellar contribution to adaptive locomotor behavior, highlighting methodologies employed to quantify and categorize behavior at different developmental stages, with the ultimate goal of following the course of early behavioral alterations in neurodevelopmental disorders. Since experimental paradigms used to study cerebellar behavior are lacking in both specificity and applicability to locomotor contexts, we highlight the use of the Erasmus Ladder - an advanced, computerized, fully automated system to quantify adaptive cerebellar learning in conjunction with locomotor function. Finally, we emphasize the need to develop objective, quantitative, behavioral tasks which can track changes in developmental trajectories rather than endpoint measurement at the adult stage of behavior. Copyright © 2018 Elsevier Inc. All rights reserved.

Enhanced locomotor adaptation aftereffect in the “broken escalator” phenomenon using anodal tDCS

PubMed Central

Kaski, D.; Quadir, S.; Patel, M.; Yousif, N.

2012-01-01

The everyday experience of stepping onto a stationary escalator causes a stumble, despite our full awareness that the escalator is broken. In the laboratory, this “broken escalator” phenomenon is reproduced when subjects step onto an obviously stationary platform (AFTER trials) that was previously experienced as moving (MOVING trials) and attests to a process of motor adaptation. Given the critical role of M1 in upper limb motor adaptation and the potential for transcranial direct current stimulation (tDCS) to increase cortical excitability, we hypothesized that anodal tDCS over leg M1 and premotor cortices would increase the size and duration of the locomotor aftereffect. Thirty healthy volunteers received either sham or real tDCS (anodal bihemispheric tDCS; 2 mA for 15 min at rest) to induce excitatory effects over the primary motor and premotor cortex before walking onto the moving platform. The real tDCS group, compared with sham, displayed larger trunk sway and increased gait velocity in the first AFTER trial and a persistence of the trunk sway aftereffect into the second AFTER trial. We also used transcranial magnetic stimulation to probe changes in cortical leg excitability using different electrode montages and eyeblink conditioning, before and after tDCS, as well as simulating the current flow of tDCS on the human brain using a computational model of these different tDCS montages. Our data show that anodal tDCS induces excitability changes in lower limb motor cortex with resultant enhancement of locomotor adaptation aftereffects. These findings might encourage the use of tDCS over leg motor and premotor regions to improve locomotor control in patients with neurological gait disorders. PMID:22323638

Mesenchymal stem cells improve locomotor recovery in traumatic spinal cord injury: systematic review with meta-analyses of rat models.

PubMed

Oliveri, Roberto S; Bello, Segun; Biering-Sørensen, Fin

2014-02-01

Traumatic spinal cord injury (SCI) is a devastating event with huge personal and societal costs. A limited number of treatments exist to ameliorate the progressive secondary damage that rapidly follows the primary mechanical impact. Mesenchymal stem or stromal cells (MSCs) have anti-inflammatory and neuroprotective effects and may thus reduce secondary damage after administration. We performed a systematic review with quantitative syntheses to assess the evidence of MSCs versus controls for locomotor recovery in rat models of traumatic SCI, and identified 83 eligible controlled studies comprising a total of 1,568 rats. Between-study heterogeneity was large. Fifty-three studies (64%) were reported as randomised, but only four reported adequate methodologies for randomisation. Forty-eight studies (58%) reported the use of a blinded outcome assessment. A random-effects meta-analysis yielded a difference in behavioural Basso-Beattie-Bresnahan (BBB) locomotor score means of 3.9 (95% confidence interval [CI] 3.2 to 4.7; P<0.001) in favour of MSCs. Trial sequential analysis confirmed the findings of the meta-analyses with the upper monitoring boundary for benefit being crossed by the cumulative Z-curve before reaching the diversity-adjusted required information size. Only time from intervention to last follow-up remained statistically significant after adjustment using multivariate random-effects meta-regression modelling. Lack of other demonstrable explanatory variables could be due to insufficient meta-analytic study power. MSCs would seem to demonstrate a substantial beneficial effect on locomotor recovery in a widely-used animal model of traumatic SCI. However, the animal results should be interpreted with caution concerning the internal and external validity of the studies in relation to the design of future clinical trials. © 2013.

Decoding bipedal locomotion from the rat sensorimotor cortex.

PubMed

Rigosa, J; Panarese, A; Dominici, N; Friedli, L; van den Brand, R; Carpaneto, J; DiGiovanna, J; Courtine, G; Micera, S

2015-10-01

Decoding forelimb movements from the firing activity of cortical neurons has been interfaced with robotic and prosthetic systems to replace lost upper limb functions in humans. Despite the potential of this approach to improve locomotion and facilitate gait rehabilitation, decoding lower limb movement from the motor cortex has received comparatively little attention. Here, we performed experiments to identify the type and amount of information that can be decoded from neuronal ensemble activity in the hindlimb area of the rat motor cortex during bipedal locomotor tasks. Rats were trained to stand, step on a treadmill, walk overground and climb staircases in a bipedal posture. To impose this gait, the rats were secured in a robotic interface that provided support against the direction of gravity and in the mediolateral direction, but behaved transparently in the forward direction. After completion of training, rats were chronically implanted with a micro-wire array spanning the left hindlimb motor cortex to record single and multi-unit activity, and bipolar electrodes into 10 muscles of the right hindlimb to monitor electromyographic signals. Whole-body kinematics, muscle activity, and neural signals were simultaneously recorded during execution of the trained tasks over multiple days of testing. Hindlimb kinematics, muscle activity, gait phases, and locomotor tasks were decoded using offline classification algorithms. We found that the stance and swing phases of gait and the locomotor tasks were detected with accuracies as robust as 90% in all rats. Decoded hindlimb kinematics and muscle activity exhibited a larger variability across rats and tasks. Our study shows that the rodent motor cortex contains useful information for lower limb neuroprosthetic development. However, brain-machine interfaces estimating gait phases or locomotor behaviors, instead of continuous variables such as limb joint positions or speeds, are likely to provide more robust control strategies for the design of such neuroprostheses.

Intermittent fasting alleviates the neuropathic phenotype in a mouse model of Charcot-Marie-Tooth disease

PubMed Central

Madorsky, Irina; Opalach, Katherine; Waber, Amanda; Verrier, Jonathan D.; Solmo, Chelsea; Foster, Thomas; Dunn, William A; Notterpek, Lucia

2009-01-01

Charcot-Marie-Tooth type 1A (CMT1A) neuropathies linked to the misexpression of peripheral myelin protein 22 (PMP22) are progressive demyelinating disorders of the peripheral nervous system. In this study we asked whether dietary restriction by intermittent fasting (IF) could alleviate the neuropathic phenotype in the Trembler J (TrJ) mouse model of CMT1A. Our results show that neuropathic mice kept on a five month long IF regimen had improved locomotor performance compared to ad libitum (AL) fed littermates. The functional benefits of this dietary intervention are associated with an increased expression of myelin proteins combined with a thicker myelin sheath, less redundant basal lamina, and a reduction in aberrant Schwann cell proliferation. These morphological improvements are accompanied by a decrease in PMP22 protein aggregates, and enhanced expression of cytosolic chaperones and constituents of the autophagy-lysosomal pathway. These results indicate that dietary restriction is beneficial for peripheral nerve function in TrJ neuropathic mice, as it promotes the maintenance of locomotor performance. PMID:19320048

Locomotor Adaptation to an Asymmetric Force on the Human Pelvis Directed Along the Right Leg.

PubMed

Vashista, Vineet; Martelli, Dario; Agrawal, Sunil

2015-09-11

In this work, we study locomotor adaptation in healthy adults when an asymmetric force vector is applied to the pelvis directed along the right leg. A cable-driven Active Tethered Pelvic Assist Device (A-TPAD) is used to apply an external force on the pelvis, specific to a subject's gait pattern. The force vector is intended to provide external weight bearing during walking and modify the durations of limb supports. The motivation is to use this paradigm to improve weight bearing and stance phase symmetry in individuals with hemiparesis. An experiment with nine healthy subjects was conducted. The results show significant changes in the gait kinematics and kinetics while the healthy subjects developed temporal and spatial asymmetry in gait pattern in response to the applied force vector. This was followed by aftereffects once the applied force vector was removed. The adaptation to the applied force resulted in asymmetry in stance phase timing and lower limb muscle activity. We believe this paradigm, when extended to individuals with hemiparesis, can show improvements in weight bearing capability with positive effects on gait symmetry and walking speed.

Robot-assisted gait training versus treadmill training in patients with Parkinson’s disease: a kinematic evaluation with gait profile score

PubMed Central

Galli, Manuela; Cimolin, Veronica; De Pandis, Maria Francesca; Le Pera, Domenica; Sova, Ivan; Albertini, Giorgio; Stocchi, Fabrizio; Franceschini, Marco

2016-01-01

Summary The purpose of this study was to quantitatively compare the effects, on walking performance, of end-effector robotic rehabilitation locomotor training versus intensive training with a treadmill in Parkinson’s disease (PD). Fifty patients with PD were randomly divided into two groups: 25 were assigned to the robot-assisted therapy group (RG) and 25 to the intensive treadmill therapy group (IG). They were evaluated with clinical examination and 3D quantitative gait analysis [gait profile score (GPS) and its constituent gait variable scores (GVSs) were calculated from gait analysis data] at the beginning (T0) and at the end (T1) of the treatment. In the RG no differences were found in the GPS, but there were significant improvements in some GVSs (Pelvic Obl and Hip Ab-Add). The IG showed no statistically significant changes in either GPS or GVSs. The end-effector robotic rehabilitation locomotor training improved gait kinematics and seems to be effective for rehabilitation in patients with mild PD. PMID:27678210

An in vivo study of low back pain and shock absorption in the human locomotor system.

PubMed

Voloshin, A; Wosk, J

1982-01-01

In this second of three papers, the principles of a non-invasive in vivo method to quantitatively evaluate the shock absorbing capacity of the human musculoskeletal system and the correlation of this shock absorbing capacity with low back pain (LPB) symptoms are presented. The experiments involved patients suffering from low back pain (as well as other degenerative joint diseases) and healthy patients. The obtained results reveal that low back pain correlates with the reduced capacity of the human musculoskeletal system between the femoral condyle and the forehead to attenuate incoming shock waves. Examination of the absolute values of the amplitude of the propagated waves leads to the conclusion that the human locomotor system, which possesses reduced attenuation capacity, tries to prevent overloading of the head from insufficiently attenuated shock waves. Results of the present investigation support the idea that the repetitive loading resulting from gait generates intermittent waves that propagate through the entire human musculoskeletal system from the heel up to the head. These waves are gradually attenuated along this course by the natural shock absorbers (bone and soft tissues). Contemporary methods for examination of the human musculoskeletal system may by improved by using the proposed non-invasive in vivo technique for quantitative characterization of the locomotor system's shock absorbing capacity.

Can the mammalian lumbar spinal cord learn a motor task?

PubMed

Hodgson, J A; Roy, R R; de Leon, R; Dobkin, B; Edgerton, V R

1994-12-01

Progress toward restoring locomotor function in low thoracic spinal transected cats and the application of similar techniques to patients with spinal cord injury is reviewed. Complete spinal cord transection (T12-T13) in adult cats results in an immediate loss of locomotor function in the hindlimbs. Limited locomotor function returns after several months in cats that have not received specific therapies designed to restore hindlimb stepping. Training transected cats to step on a treadmill for 30 min.d-1 and 5 d.wk-1 greatly improves their stepping ability. The most successful outcome was in cats where training began early, i.e., 1 wk after spinal transection. Cats trained to stand instead of stepping had great difficulty using the hindlimbs for locomotion. These effects were reversible over a 20-month period such that cats unable to step as a result of standing training could be trained to step and, conversely, locomotion in stepping-trained cats could be abolished by standing training. These results indicate that the spinal cord is capable of learning specific motor tasks. It has not been possible to elicit locomotion in patients with clinically complete spinal injuries, but appropriately coordinated EMG activity has been demonstrated in musculature of the legs during assisted locomotion on a treadmill.

(−)-Epicatechin Prevents Blood Pressure Increase and Reduces Locomotor Hyperactivity in Young Spontaneously Hypertensive Rats

PubMed Central

Berenyiova, A.; Drobna, M.; Lukac, S.

2016-01-01

This study investigated the effects of subchronic (−)-epicatechin (Epi) treatment on locomotor activity and hypertension development in young spontaneously hypertensive rats (SHR). Epi was administered in drinking water (100 mg/kg/day) for 2 weeks. Epi significantly prevented the development of hypertension (138 ± 2 versus 169 ± 5 mmHg, p < 0.001) and reduced total distance traveled in the open-field test (22 ± 2 versus 35 ± 4 m, p < 0.01). In blood, Epi significantly enhanced erythrocyte deformability, increased total antioxidant capacity, and decreased nitrotyrosine concentration. In the aorta, Epi significantly increased nitric oxide (NO) synthase (NOS) activity and elevated the NO-dependent vasorelaxation. In the left heart ventricle, Epi increased NOS activity without altering gene expressions of nNOS, iNOS, and eNOS. Moreover, Epi reduced superoxide production in the left heart ventricle and the aorta. In the brain, Epi increased nNOS gene expression (in the brainstem and cerebellum) and eNOS expression (in the cerebellum) but had no effect on overall NOS activity. In conclusion, Epi prevented the development of hypertension and reduced locomotor hyperactivity in young SHR. These effects resulted from improved cardiovascular NO bioavailability concurrently with increased erythrocyte deformability, without changes in NO production in the brain. PMID:27885334

Longitudinal Change in the Relationship between Fundamental Motor Skills and Perceived Competence: Kindergarten to Grade 2

PubMed Central

Naylor, Patti-Jean

2017-01-01

As children transition from early to middle childhood, the relationship between motor skill proficiency and perceptions of physical competence should strengthen as skills improve and inflated early childhood perceptions decrease. This study examined change in motor skills and perceptions of physical competence and the relationship between those variables from kindergarten to grade 2. Participants were 250 boys and girls (Mean age = 5 years 8 months in kindergarten). Motor skills were assessed using the Test of Gross Motor Development-2 and perceptions were assessed using a pictorial scale of perceived competence. Mixed-design analyses of variance revealed there was a significant increase in object-control skills and perceptions from kindergarten to grade 2, but no change in locomotor skills. In kindergarten, linear regression showed that locomotor skills and object-control skills explained 10% and 9% of the variance, respectively, in perceived competence for girls, and 7% and 11%, respectively, for boys. In grade 2, locomotor skills predicted 11% and object-control skills predicted 19% of the variance in perceptions of physical competence, but only among the boys. Furthermore, the relationship between motor skills and perceptions of physical competence strengthened for boys only from early to middle childhood. However, it seems that forces other than motor skill proficiency influenced girls’ perceptions of their abilities in grade 2.

Objective and quantitative equilibriometric evaluation of individual locomotor behaviour in schizophrenia: Translational and clinical implications.

PubMed

Haralanov, Svetlozar; Haralanova, Evelina; Milushev, Emil; Shkodrova, Diana; Claussen, Claus-Frenz

2018-04-17

Psychiatry is the only medical specialty that lacks clinically applicable biomarkers for objective evaluation of the existing pathology at a single-patient level. On the basis of an original translational equilibriometric method for evaluation of movement patterns, we have introduced in the everyday clinical practice of psychiatry an easy-to-perform computerized objective quantification of the individual locomotor behaviour during execution of the Unterberger stepping test. For the last 20 years, we have gradually collected a large database of more than 1000 schizophrenic patients, their relatives, and matched psychiatric, neurological, and healthy controls via cross-sectional and longitudinal investigations. Comparative analyses revealed transdiagnostic locomotor similarities among schizophrenic patients, high-risk schizotaxic individuals, and neurological patients with multiple sclerosis and cerebellar ataxia, thus suggesting common underlying brain mechanisms. In parallel, intradiagnostic dissimilarities were revealed, which allow to separate out subclinical locomotor subgroups within the diagnostic categories. Prototypical qualitative (dysmetric and ataxic) locomotor abnormalities in schizophrenic patients were differentiated from 2 atypical quantitative ones, manifested as either hypolocomotion or hyperlocomotion. Theoretical analyses suggested that these 3 subtypes of locomotor abnormalities could be conceived as objectively measurable biomarkers of 3 schizophrenic subgroups with dissimilar brain mechanisms, which require different treatment strategies. Analogies with the prominent role of locomotor measures in some well-known animal models of mental disorders advocate for a promising objective translational research in the so far over-subjective field of psychiatry. Distinctions among prototypical, atypical, and diagnostic biomarkers, as well as between neuromotor and psychomotor locomotor abnormalities, are discussed. Conclusions are drawn about the translational and clinical implications of the new approach and its future perspectives. © 2018 John Wiley & Sons, Ltd.

The effects of the novel DA D3 receptor antagonist SR 21502 on cocaine reward, cocaine seeking and cocaine-induced locomotor activity in rats.

PubMed

Galaj, E; Ananthan, S; Saliba, M; Ranaldi, Robert

2014-02-01

There is a focus on developing D3 receptor antagonists as cocaine addiction treatments. We investigated the effects of a novel selective D3 receptor antagonist, SR 21502, on cocaine reward, cocaine-seeking, food reward, spontaneous locomotor activity and cocaine-induced locomotor activity in rats. In Experiment 1, rats were trained to self-administer cocaine under a progressive ratio (PR) schedule of reinforcement and tested with vehicle or one of three doses of SR 21502. In Experiment 2, animals were trained to self-administer cocaine under a fixed ratio schedule of reinforcement followed by extinction of the response. Then, animals were tested with vehicle or one of the SR 21502 doses on cue-induced reinstatement of responding. In Experiment 3, animals were trained to lever press for food under a PR schedule and tested with vehicle or one dose of the compound. In Experiments 4 and 5, in separate groups of animals, the vehicle and three doses of SR 21502 were tested on spontaneous or cocaine (10 mg/kg, IP)-induced locomotor activity, respectively. SR 21502 produced significant, dose-related (3.75, 7.5 and 15 mg/kg) reductions in breakpoint for cocaine self-administration, cue-induced reinstatement (3.75, 7.5 and 15 mg/kg) and cocaine-induced locomotor activity (3.75, 7.5 and 15 mg/kg) but failed to reduce food self-administration and spontaneous locomotor activity. SR 21502 decreases cocaine reward, cocaine-seeking and locomotor activity at doses that have no effect on food reward or spontaneous locomotor activity. These data suggest SR 21502 may selectively inhibit cocaine's rewarding, incentive motivational and stimulant effects.

Locomotor activity and gait in aged mice deficient for type IX collagen

PubMed Central

Costello, Kerry E.; Guilak, Farshid; Griffin, Timothy M.

2010-01-01

Osteoarthritis (OA) is a risk factor for physical inactivity and impaired mobility, but it is not well understood how these locomotor behaviors are affected by the age of onset of OA and disease severity. Male mice homozygous for a Col9a1 gene inactivation (Col9a1−/−) develop early onset knee OA, increased tactile pain sensitivity, and gait alterations by 9 mo of age. We hypothesized that aged Col9a1−/− mice would reduce joint pain by adopting locomotor behaviors that reduce both the magnitude and daily frequency of joint loading. We tested this hypothesis by evaluating gait and spontaneous locomotor activity in 15- to 17-mo-old male Col9a1−/− (n = 5) and Col9a1+/+(WT) (n = 5) mice using well-controlled measures of voluntary activity in overground and running wheel conditions, as well as studies of gait in a velocity-controlled treadmill. We found no difference due to genotype in freely chosen locomotor velocity, stride frequency, hindfoot duty factor, dark phase activity time, or dark-phase travel distance during overground, running wheel, or speed-matched treadmill locomotion. Interpretation of these findings is potentially confounded by the observation that WT mice have greater knee OA than Col9a1−/− mice in the lateral tibial plateau by 17 mo of age. When accounting for individual differences in knee OA, functional locomotor impairments in aged Col9a1−/− and WT mice are manifested as reductions in total locomotor activity levels (e.g., both distance traveled and time active), particularly for wheel running. These results support the concept that current disease status, rather than age of disease onset, is the primary determinant of impaired locomotor activity with aging. PMID:20360435

SGLT2 inhibition via dapagliflozin improves generalized vascular dysfunction and alters the gut microbiota in type 2 diabetic mice.

PubMed

Lee, Dustin M; Battson, Micah L; Jarrell, Dillon K; Hou, Shuofei; Ecton, Kayl E; Weir, Tiffany L; Gentile, Christopher L

2018-04-27

Type 2 diabetes (T2D) is associated with generalized vascular dysfunction characterized by increases in large artery stiffness, endothelial dysfunction, and vascular smooth muscle dysfunction. Sodium glucose cotransporter 2 inhibitors (SGLT2i) represent the most recently approved class of oral medications for the treatment of T2D, and have been shown to reduce cardiovascular and overall mortality. Although it is currently unclear how SGLT2i decrease cardiovascular risk, an improvement in vascular function is one potential mechanism. The aim of the current study was to examine if dapagliflozin, a widely prescribed STLT2i, improves generalized vascular dysfunction in type 2 diabetic mice. In light of several studies demonstrating a bi-directional relation between orally ingested medications and the gut microbiota, a secondary aim was to determine the effects of dapagliflozin on the gut microbiota. Male diabetic mice (Db, n = 24) and control littermates (Con; n = 23) were randomized to receive either a standard diet or a standard diet containing dapagliflozin (60 mg dapagliflozin/kg diet; 0.006%) for 8 weeks. Arterial stiffness was assessed by aortic pulse wave velocity; endothelial function and vascular smooth muscle dysfunction were assessed by dilatory responses to acetylcholine and sodium nitroprusside, respectively. Compared to untreated diabetic mice, diabetic mice treated with dapagliflozin displayed significantly lower arterial stiffness (Db = 469 cm/s vs. Db + dapa = 435 cm/s, p < 0.05), and improvements in endothelial dysfunction (area under the curve [AUC] Db = 57.2 vs. Db + dapa = 117.0, p < 0.05) and vascular smooth muscle dysfunction (AUC, Db = 201.7 vs. Db + dapa = 285.5, p < 0.05). These vascular improvements were accompanied by reductions in hyperglycemia and circulating markers of inflammation. The microbiota of Db and Con mice were distinctly different, and dapagliflozin treatment was associated with minor alterations in gut microbiota composition, particularly in Db mice, although these effects did not conclusively mediate the improvements in vascular function. Dapagliflozin treatment improves arterial stiffness, endothelial dysfunction and vascular smooth muscle dysfunction, and subtly alters microbiota composition in type 2 diabetic mice. Collectively, the improvements in generalized vascular function may represent an important mechanism underlying the cardiovascular benefits of SGLT2i treatment.

Complex rehabilitation and the clinical condition of working rheumatoid arthritis patients: does cryotherapy always overtop traditional rehabilitation?

PubMed

Księżopolska-Orłowska, Krystyna; Pacholec, Anna; Jędryka-Góral, Anna; Bugajska, Joanna; Sadura-Sieklucka, Teresa; Kowalik, Katarzyna; Pawłowska-Cyprysiak, Karolina; Łastowiecka-Moras, Elżbieta

2016-01-01

Rehabilitation slows the progress of rheumatoid arthritis (RA) and prevents progression of disability. This study aimed to compare the impact of two rehabilitation programmes on pain, disease activity, locomotor function, global health and work ability forecast in RA patients. Sixty-four employed women aged 24-65 years participated in the study. All patients underwent individual and instrumental kinesiotherapy. Thirty-two patients underwent cryogenic chamber therapy and local cryotherapy as well as non-weight-bearing, instrumental and individual kinesiotherapy. The remaining 32 patients received traditional rehabilitation in the form of electromagnetic and instrumental therapy, individual and pool-based non-weight-bearing kinesiotherapy. Rehabilitation lasted 3 weeks. Patients were examined three times: prior to rehabilitation, after 3 weeks of therapy and 3 months after completion of rehabilitation. The following study instruments were used: to assess disease activity: DAS-28; functional impairment: HAQ-DI; pain severity: VAS; patients' overall well-being: a scale from 0 to 100 (Global Health Index); and patients' own prognosis of fitness for work: the 6th question from Work Ability Index (WAI). Statistical analysis of data was performed using the STATISTICA 8.0 package. Mixed-design two-way analysis of variance was used for hypothesis testing. All patients improved after rehabilitation. The group of patients those who underwent cryotherapy had improved DAS-28, HAQ-DI, VAS and global health scores immediately following the 3-week rehabilitation programme (p < 0.001, p = 0.001, p = 0.007 and p < 0.001, respectively), as well as at the 3-month follow-up (p < 0.001, p < 0.001, p = 0.009 and p < 0.001, respectively). Rehabilitation using cryotherapy resulted in greater improvement in disease activity DAS-28 [F(2,105) = 5.700; p = 0.007; η(2) = 0.084] and HAQ-DI locomotor function scores [F(2,109) = 6.771; p = 0.003; η(2) = 0.098] compared to traditional rehabilitation. The impact of both forms of rehabilitation on patients' own prognosis of work ability in the next 2 years was not significant. Results of patients who underwent traditional approach showed decreased disease activity following the initial 3-week period; however, this improvement did not sustain to the end of follow-up, 3 months later. Complex rehabilitation in RA has a positive effect on patients' clinical condition. The rehabilitation programme that includes cryotherapy overtops traditional rehabilitation, particularly as regards improvement in locomotor function, disease activity and sustaining willingness to continue working and exerts long-lasting effect. Rehabilitation using cryotherapy is more effective in improving locomotor function, decreasing disease activity and sustaining willingness to continue working compared to traditional rehabilitation. Rehabilitation using cryotherapy significantly reduces the intensity of pain experienced by patients with RA, and this positive effect is maintained at 3 months post-rehabilitation. Complex rehabilitation, particularly treatment using cryotherapy, improves patients' subjective assessment of their overall well-being and perception of their disease. Complex rehabilitation in rheumatoid arthritis has a positive effect on patients' clinical condition.

The putative role of oxidative stress and inflammation in the pathophysiology of sleep dysfunction across neuropsychiatric disorders: Focus on chronic fatigue syndrome, bipolar disorder and multiple sclerosis.

PubMed

Morris, Gerwyn; Stubbs, Brendon; Köhler, Cristiano A; Walder, Ken; Slyepchenko, Anastasiya; Berk, Michael; Carvalho, André F

2018-04-04

Sleep and circadian abnormalities are prevalent and burdensome manifestations of diverse neuro-immune diseases, and may aggravate the course of several neuropsychiatric disorders. The underlying pathophysiology of sleep abnormalities across neuropsychiatric disorders remains unclear, and may involve the inter-play of several clinical variables and mechanistic pathways. In this review, we propose a heuristic framework in which reciprocal interactions of immune, oxidative and nitrosative stress, and mitochondrial pathways may drive sleep abnormalities across potentially neuroprogressive disorders. Specifically, it is proposed that systemic inflammation may activate microglial cells and astrocytes in brain regions involved in sleep and circadian regulation. Activated glial cells may secrete pro-inflammatory cytokines (for example, interleukin-1 beta and tumour necrosis factor alpha), nitric oxide and gliotransmitters, which may influence the expression of key circadian regulators (e.g., the Circadian Locomotor Output Cycles Kaput (CLOCK) gene). Furthermore, sleep disruption may further aggravate oxidative and nitrosative, peripheral immune activation, and (neuro) inflammation across these disorders in a vicious pathophysiological loop. This review will focus on chronic fatigue syndrome, bipolar disorder, and multiple sclerosis as exemplars of neuro-immune disorders. We conclude that novel therapeutic targets exploring immune and oxidative & nitrosative pathways (p.e. melatonin and molecular hydrogen) hold promise in alleviating sleep and circadian dysfunction in these disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

The rare DAT coding variant Val559 perturbs DA neuron function, changes behavior, and alters in vivo responses to psychostimulants.

PubMed

Mergy, Marc A; Gowrishankar, Raajaram; Gresch, Paul J; Gantz, Stephanie C; Williams, John; Davis, Gwynne L; Wheeler, C Austin; Stanwood, Gregg D; Hahn, Maureen K; Blakely, Randy D

2014-11-04

Despite the critical role of the presynaptic dopamine (DA) transporter (DAT, SLC6A3) in DA clearance and psychostimulant responses, evidence that DAT dysfunction supports risk for mental illness is indirect. Recently, we identified a rare, nonsynonymous Slc6a3 variant that produces the DAT substitution Ala559Val in two male siblings who share a diagnosis of attention-deficit hyperactivity disorder (ADHD), with other studies identifying the variant in subjects with bipolar disorder (BPD) and autism spectrum disorder (ASD). Previously, using transfected cell studies, we observed that although DAT Val559 displays normal total and surface DAT protein levels, and normal DA recognition and uptake, the variant transporter exhibits anomalous DA efflux (ADE) and lacks capacity for amphetamine (AMPH)-stimulated DA release. To pursue the significance of these findings in vivo, we engineered DAT Val559 knock-in mice, and here we demonstrate in this model the presence of elevated extracellular DA levels, altered somatodendritic and presynaptic D2 DA receptor (D2R) function, a blunted ability of DA terminals to support depolarization and AMPH-evoked DA release, and disruptions in basal and psychostimulant-evoked locomotor behavior. Together, our studies demonstrate an in vivo functional impact of the DAT Val559 variant, providing support for the ability of DAT dysfunction to impact risk for mental illness.

The rare DAT coding variant Val559 perturbs DA neuron function, changes behavior, and alters in vivo responses to psychostimulants

PubMed Central

Mergy, Marc A.; Gowrishankar, Raajaram; Gresch, Paul J.; Gantz, Stephanie C.; Williams, John; Davis, Gwynne L.; Wheeler, C. Austin; Stanwood, Gregg D.; Hahn, Maureen K.; Blakely, Randy D.

2014-01-01

Despite the critical role of the presynaptic dopamine (DA) transporter (DAT, SLC6A3) in DA clearance and psychostimulant responses, evidence that DAT dysfunction supports risk for mental illness is indirect. Recently, we identified a rare, nonsynonymous Slc6a3 variant that produces the DAT substitution Ala559Val in two male siblings who share a diagnosis of attention-deficit hyperactivity disorder (ADHD), with other studies identifying the variant in subjects with bipolar disorder (BPD) and autism spectrum disorder (ASD). Previously, using transfected cell studies, we observed that although DAT Val559 displays normal total and surface DAT protein levels, and normal DA recognition and uptake, the variant transporter exhibits anomalous DA efflux (ADE) and lacks capacity for amphetamine (AMPH)-stimulated DA release. To pursue the significance of these findings in vivo, we engineered DAT Val559 knock-in mice, and here we demonstrate in this model the presence of elevated extracellular DA levels, altered somatodendritic and presynaptic D2 DA receptor (D2R) function, a blunted ability of DA terminals to support depolarization and AMPH-evoked DA release, and disruptions in basal and psychostimulant-evoked locomotor behavior. Together, our studies demonstrate an in vivo functional impact of the DAT Val559 variant, providing support for the ability of DAT dysfunction to impact risk for mental illness. PMID:25331903

Predictive and Reactive Locomotor Adaptability in Healthy Elderly: A Systematic Review and Meta-Analysis.

PubMed

Bohm, Sebastian; Mademli, Lida; Mersmann, Falk; Arampatzis, Adamantios

2015-12-01

Locomotor adaptability is based on the implementation of error-feedback information from previous perturbations to predictively adapt to expected perturbations (feedforward) and to facilitate reactive responses in recurring unexpected perturbations ('savings'). The effect of aging on predictive and reactive adaptability is yet unclear. However, such understanding is fundamental for the design and application of effective interventions targeting fall prevention. We systematically searched the Web of Science, MEDLINE, Embase and Science Direct databases as well as the reference lists of the eligible articles. A study was included if it addressed an investigation of the locomotor adaptability in response to repeated mechanical movement perturbations of healthy older adults (≥60 years). The weighted average effect size (WAES) of the general adaptability (adaptive motor responses to repeated perturbations) as well as predictive (after-effects) and reactive adaptation (feedback responses to a recurring unexpected perturbation) was calculated and tested for an overall effect. A subgroup analysis was performed regarding the factor age group [i.e., young (≤35 years) vs. older adults]. Furthermore, the methodological study quality was assessed. The review process yielded 18 studies [1009 participants, 613 older adults (70 ± 4 years)], which used various kinds of locomotor tasks and perturbations. The WAES for the general locomotor adaptability was 1.21 [95% confidence interval (CI) 0.68-1.74, n = 11] for the older and 1.39 (95% CI 0.90-1.89, n = 10) for the young adults with a significant (p < 0.05) overall effect for both age groups and no significant subgroup differences. Similar results were found for the predictive (older: WAES 1.10, 95% CI 0.37-1.83, n = 8; young: WAES 1.54, 95% CI 0.11-2.97, n = 7) and reactive (older: WAES 1.09, 95% CI 0.22-1.96, n = 5; young: WAES 1.35, 95% CI 0.60-2.09, n = 5) adaptation featuring significant (p < 0.05) overall effects without subgroup differences. The average score of the methodological quality was 67 ± 8 %. The present meta-analysis provides elaborate statistical evidence that locomotor adaptability in general and predictive and reactive adaptation in particular remain highly effective in the elderly, showing only minor, not statistically significant age-related deficits. Consequently, interventions which use adaptation and learning paradigms including the application of the mechanisms responsible for an effective predictive and reactive dynamic stability control may progressively improve older adults' recovery performance and, thus, reduce their risk of falling.

Locomotor Tests Predict Community Mobility in Children and Youth with Cerebral Palsy

ERIC Educational Resources Information Center

Ferland, Chantale; Moffet, Helene; Maltais, Desiree

2012-01-01

Ambulatory children and youth with cerebral palsy have limitations in locomotor capacities and in community mobility. The ability of three locomotor tests to predict community mobility in this population (N = 49, 27 boys, 6-16 years old) was examined. The tests were a level ground walking test, the 6-min-Walk-Test (6MWT), and two tests of advanced…

Locomotor exercise in weightlessness

NASA Technical Reports Server (NTRS)

Thornton, W.; Whitmore, H.

1991-01-01

The requirements for exercise in space by means of locomotion are established and addressed with prototype treadmills for use during long-duration spaceflight. The adaptation of the human body to microgravity is described in terms of 1-G locomotor biomechanics, the effects of reduced activity, and effective activity-replacement techniques. The treadmill is introduced as a complement to other techniques of force replacement with reference given to the angle required for exercise. A motor-driven unit is proposed that can operate at a variety of controlled speeds and equivalent grades. The treadmills permit locomotor exercise as required for long-duration space travel to sustain locomotor and cardiorespiratory capacity at a level consistent with postflight needs.

Effects of edaravone on muscle atrophy and locomotor function in patients with ischemic stroke: a randomized controlled pilot study.

PubMed

Naritomi, Hiroaki; Moriwaki, Hiroshi; Metoki, Norifumi; Nishimura, Hiroyuki; Higashi, Yasuto; Yamamoto, Yasumasa; Yuasa, Hiroyuki; Oe, Hiroshi; Tanaka, Kortaro; Saito, Kozue; Terayama, Yasuo; Oda, Tadafumi; Tanahashi, Norio; Kondo, Hisao

2010-01-01

Stroke patients with severe leg paralysis are often bedridden in the acute and subacute phase, which increases the risk of disuse muscle atrophy in the chronic phase. The evidence to date indicates that oxidative stress plays an important role in the mechanism of disuse muscle atrophy. Therefore, the aim of this study was to determine if long-term radical scavenger treatment with edaravone following an acute stroke prevents the progression of disuse muscle atrophy and improves leg locomotor function in the chronic phase. This randomized controlled pilot study was conducted at 19 acute stroke and rehabilitation centers across Japan. Forty-seven ischemic stroke patients with at least leg motor weakness admitted within 24 hours of onset were randomly assigned to receive continuous intravenous infusions of edaravone 30 mg twice daily for 3 days (short-term group) or 10-14 days (long-term group). The primary endpoints of the study included the degree of leg disuse muscle atrophy, as measured by the percentage change from baseline in femoral muscle circumference 15 cm above the knee, and the improvement in leg locomotor function, as assessed by the maximum walking speed over 10 m, 3 months after the onset of stroke. Three-month follow-up was completed by a total of 41 patients (21 in the short-term group and 20 in the long-term group). On admission, there was no significant difference in the severity of stroke or the grade of leg paresis between the two treatment groups. The grade of disuse muscle atrophy and incidence of gait impairment 3 weeks after stroke onset were also similar between the short- and long-term groups. However, disuse muscle atrophy of the paretic and non-paretic legs was significantly less severe in the long-term versus the short-term treatment group (3.6 ± 5.9% and 1.5 ± 6.0% vs 8.3 ± 5.2% and 5.7 ± 6.4%; p < 0.01 and p < 0.05) 3 months after stroke onset. Additionally, the maximum walking speed over a distance of 10 m was significantly greater in the long-term group (98 ± 67 vs 54 ± 55 cm/sec; p < 0.05). Edaravone treatment for up to 14 days suppresses the progression of disuse muscle atrophy and improves leg locomotor function to a greater extent than shorter-term treatment in acute stroke patients. This suggests that the management of stroke may be improved with long-term edaravone therapy by providing myoprotective effects that ameliorate functional outcome in the chronic phase.

Effects of sex pheromones and sexual maturation on locomotor activity in female sea lamprey (Petromyzon marinus)

USGS Publications Warehouse

Walaszczyk, Erin J.; Johnson, Nicholas S.; Steibel, Juan Pedro; Li, Weiming

2013-01-01

Synchronization of male and female locomotor rhythmicity can play a vital role in ensuring reproductive success. Several physiological and environmental factors alter these locomotor rhythms. As sea lamprey, Petromyzon marinus, progress through their life cycle, their locomotor activity rhythm changes multiple times. The goal of this study was to elucidate the activity patterns of adult female sea lamprey during the sexual maturation process and discern the interactions of these patterns with exposure to male pheromones. During these stages, preovulated and ovulated adult females are exposed to sex pheromone compounds, which are released by spermiated males and attract ovulated females to the nest for spawning. The locomotor behavior of adult females was monitored in a natural stream with a passive integrated tag responder system as they matured, and they were exposed to a sex pheromone treatment (spermiated male washings) or a control (prespermiated male washings). Results showed that, dependent on the hour of day, male sex pheromone compounds reduce total activity (p < 0.05) and cause increases in activity during several daytime hours in preovulated and ovulated females. These results are one of the first examples of how sex pheromones modulate a locomotor rhythm in a vertebrate, and they suggest that the interaction between maturity stage and sex pheromone exposure contributes to the differential locomotor rhythms found in adult female sea lamprey. This phenomenon may contribute to the reproductive synchrony of mature adults, thus increasing reproductive success in this species.

Either brain-derived neurotrophic factor or neurotrophin-3 only neurotrophin-producing grafts promote locomotor recovery in untrained spinalized cats.

PubMed

Ollivier-Lanvin, Karen; Fischer, Itzhak; Tom, Veronica; Houlé, John D; Lemay, Michel A

2015-01-01

Background. Transplants of cellular grafts expressing a combination of 2 neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) have been shown to promote and enhance locomotor recovery in untrained spinalized cats. Based on the time course of recovery and the absence of axonal growth through the transplants, we hypothesized that recovery was due to neurotrophin-mediated plasticity within the existing locomotor circuitry of the lumbar cord. Since BDNF and NT-3 have different effects on axonal sprouting and synaptic connectivity/strengthening, it becomes important to ascertain the contribution of each individual neurotrophins to recovery. Objective. We studied whether BDNF or NT-3 only producing cellular grafts would be equally effective at restoring locomotion in untrained spinal cats. Methods. Rat fibroblasts secreting one of the 2 neurotrophins were grafted into the T12 spinal transection site of adult cats. Four cats in each group (BDNF alone or NT-3 alone) were evaluated. Locomotor recovery was tested on a treadmill at 3 and 5 weeks post-transection/grafting. Results. Animals in both groups were capable of plantar weight-bearing stepping at speed up to 0.8 m/s as early as 3 weeks and locomotor capabilities were similar at 3 and 5 weeks for both types of graft. Conclusions. Even without locomotor training, either BDNF or NT-3 only producing grafts promote locomotor recovery in complete spinal animals. More clinically applicable delivery methods need to be developed. © The Author(s) 2014.

Effect of Environmental Conditions and Toxic Compounds on the Locomotor Activity of Pediculus humanus capitis (Phthiraptera: Pediculidae).

PubMed

Ortega-Insaurralde, I; Toloza, A C; Gonzalez-Audino, P; Mougabure-Cueto, G A; Alvarez-Costa, A; Roca-Acevedo, G; Picollo, M I

2015-09-01

In this work, we evaluated the effect of environmental variables such as temperature, humidity, and light on the locomotor activity of Pediculus humanus capitis. In addition, we used selected conditions of temperature, humidity, and light to study the effects of cypermethrin and N,N-diethyl-3-methylbenzamide (DEET) on the locomotor activity of head lice. Head lice increased their locomotor activity in an arena at 30°C compared with activity at 20°C. When we tested the influence of the humidity level, the locomotor activity of head lice showed no significant differences related to humidity level, both at 30°C and 20°C. Concerning light influence, we observed that the higher the intensity of light, the slower the movement of head lice. We also demonstrated that sublethal doses of toxics may alter locomotor activity in adults of head lice. Sublethal doses of cypermethrin induced hyperactivated responses in adult head lice. Sublethal doses of DEET evocated hypoactivated responses in head lice. The observation of stereotyped behavior in head lice elicited by toxic compounds proved that measuring locomotor activity in an experimental set-up where environmental conditions are controlled would be appropriate to evaluate compounds of biological importance, such as molecules involved in the host-parasite interaction and intraspecific relationships. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Lumbar muscle inflammation alters spinally mediated locomotor recovery induced by training in a mouse model of complete spinal cord injury.

PubMed

Jeffrey-Gauthier, Renaud; Piché, Mathieu; Leblond, Hugues

2017-09-17

Locomotor networks after spinal cord injury (SCI) are shaped by training-activated proprioceptive and cutaneous inputs. Nociception from injured tissues may alter these changes but has largely been overlooked. The objective of the present study was to ascertain whether lumbar muscle inflammation hinders locomotion recovery in a mouse model of complete SCI. Lower limb kinematics during treadmill training was assessed before and after complete SCI at T8 (2, 7, 14, 21 and 28days post-injury). Locomotor recovery was compared in 4 groups of CD1 mice: control spinal mice; spinal mice with daily locomotor training; spinal mice with lumbar muscle inflammation (Complete Freund's Adjuvant (CFA) injection); and spinal mice with locomotor training and CFA. On day 28, H-reflex excitability and its inhibition at high-frequency stimulation (frequency-dependent depression: FDD) were compared between groups, all of which showed locomotor recovery. Recovery was enhanced by training, whereas lumbar muscle inflammation hindered these effects (knee angular excursion and paw drag: p's<0.05). In addition, lumbar muscle inflammation impaired hind limb coupling during locomotion (p<0.05) throughout recovery. Also, H-reflex disinhibition was prevented by training, with or without CFA injection (p's<0.05). Altogether, these results indicate that back muscle inflammation modulates spinally mediated locomotor recovery in mice with complete SCI, in part, by reducing adaptive changes induced by training. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Crocin improved locomotor function and mechanical behavior in the rat model of contused spinal cord injury through decreasing calcitonin gene related peptide (CGRP).

PubMed

Karami, Masoume; Bathaie, S Zahra; Tiraihi, Taqi; Habibi-Rezaei, Mehran; Arabkheradmand, Jalil; Faghihzadeh, Soghrat

2013-12-15

Various approaches have been offered to alleviate chronic pain resulting from spinal cord injuries (SCIs). Application of herbs and natural products, with potentially lower adverse effects, to cure diseases has been recommended in both traditional and modern medicines. Here, the effect of crocin on chronic pain induced by spinal cord contusion was investigated in an animal model. Female Wistar rats were randomly divided into five groups (5 rats in each); three groups were contused at the L1 level. One group was treated with crocin (150mg/kg) two weeks after spinal cord injury; the second group, control, was treated with vehicle only; and the third group was treated with ketoprofen. Two normal groups were also considered with or without crocin treatment. The mechanical behavioral test, the locomotor recovery test and the thermal behavioral test were applied weekly to evaluate the injury and recovery of rats. Significant improvements (p<0.05) in mechanical behavioral and locomotor recovery tests were seen in the rats treated with crocin. Thermal behavioral test did not show any significant changes due to crocin treatment. Plasma concentration of calcitonin-gene related peptide (CGRP) changed from 780.2±2.3 to 1140.3±4.5pg/ml due to SCI and reached 789.1±2.7pg/ml after crocin treatment. These changes were significant at the level of p<0.05. The present study shows the beneficial effects of crocin treatment on chronic pain induced by SCI, through decreasing CGRP as an important mediator of inflammation and pain. Copyright © 2013 Elsevier GmbH. All rights reserved.

Longitudinal Recovery and Reduced Costs After 120 Sessions of Locomotor Training for Motor Incomplete Spinal Cord Injury.

PubMed

Morrison, Sarah A; Lorenz, Douglas; Eskay, Carol P; Forrest, Gail F; Basso, D Michele

2018-03-01

To determine the impact of long-term, body weight-supported locomotor training after chronic, incomplete spinal cord injury (SCI), and to estimate the health care costs related to lost recovery potential and preventable secondary complications that may have occurred because of visit limits imposed by insurers. Prospective observational cohort with longitudinal follow-up. Eight outpatient rehabilitation centers that participate in the Christopher & Dana Reeve Foundation NeuroRecovery Network (NRN). Individuals with motor incomplete chronic SCI (American Spinal Injury Association Impairment Scale C or D; N=69; 0.1-45y after SCI) who completed at least 120 NRN physical therapy sessions. Manually assisted locomotor training (LT) in a body weight-supported treadmill environment, overground standing and stepping activities, and community integration tasks. International Standards for Neurological Classification of Spinal Cord Injury motor and sensory scores, orthostatic hypotension, bowel/bladder/sexual function, Spinal Cord Injury Functional Ambulation Inventory (SCI-FAI), Berg Balance Scale, Modified Functional Reach, 10-m walk test, and 6-minute walk test. Longitudinal outcome measure collection occurred every 20 treatments and at 6- to 12-month follow-up after discharge from therapy. Significant improvement occurred for upper and lower motor strength, functional activities, psychological arousal, sensation of bowel movement, and SCI-FAI community ambulation. Extended training enabled minimal detectable changes at 60, 80, 100, and 120 sessions. After detectable change occurred, it was sustained through 120 sessions and continued 6 to 12 months after treatment. Delivering at least 120 sessions of LT improves recovery from incomplete chronic SCI. Because walking reduces rehospitalization, LT delivered beyond the average 20-session insurance limit can reduce rehospitalizations and long-term health costs. Copyright © 2018 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Ongoing Walking Recovery 2 Years After Locomotor Training in a Child With Severe Incomplete Spinal Cord Injury

PubMed Central

Fox, Emily J.; Tester, Nicole J.; Phadke, Chetan P.; Nair, Preeti M.; Senesac, Claudia R.; Howland, Dena R.

2010-01-01

Background and Purpose The authors previously reported on walking recovery in a nonambulatory child with chronic, severe, incomplete cervical spinal cord injury (SCI) after 76 sessions of locomotor training (LT). Although clinical measures did not predict his recovery, reciprocal patterned leg movements developed, affording recovery of independent walking with a reverse rolling walker. The long-term functional limitations and secondary complications often associated with pediatric-onset SCI necessitate continued follow-up of children with SCI. Therefore, the purpose of this case report is to describe this child's walking function and musculoskeletal growth and development during the 2 years since his participation in an LT program and subsequent walking recovery. Case Description Following LT, the child attended elementary school as a full-time ambulator. He was evaluated 1 month (baseline), 1 year, and 2 years after LT. Examination of walking function included measures of walking independence, gait speed and spatiotemporal parameters, gait kinematics, and daily step activity. Growth and development were assessed by tracking his height, weight, incidence of musculoskeletal complications, and gross motor task performance. Outcomes Over the 2 years, the child continued to ambulate independently with a reverse rolling walker, increasing his fastest gait speed. Spatiotemporal and kinematic features of his walking improved, and daily step activity increased. Height and weight remained on their preinjury trajectory and within age-appropriate norms. The child experienced only minor musculoskeletal complications. Additionally, he gained the ability to use reciprocal patterned leg movements during locomotor tasks such as assisted stair climbing and independent tricycle pedaling. Conclusions Two years after recovery of walking, this child with incomplete SCI had maintained and improved his walking function and experienced age-appropriate growth and development. PMID:20299409

Ongoing walking recovery 2 years after locomotor training in a child with severe incomplete spinal cord injury.

PubMed

Fox, Emily J; Tester, Nicole J; Phadke, Chetan P; Nair, Preeti M; Senesac, Claudia R; Howland, Dena R; Behrman, Andrea L

2010-05-01

The authors previously reported on walking recovery in a nonambulatory child with chronic, severe, incomplete cervical spinal cord injury (SCI) after 76 sessions of locomotor training (LT). Although clinical measures did not predict his recovery, reciprocal patterned leg movements developed, affording recovery of independent walking with a reverse rolling walker. The long-term functional limitations and secondary complications often associated with pediatric-onset SCI necessitate continued follow-up of children with SCI. Therefore, the purpose of this case report is to describe this child's walking function and musculoskeletal growth and development during the 2 years since his participation in an LT program and subsequent walking recovery. Following LT, the child attended elementary school as a full-time ambulator. He was evaluated 1 month (baseline), 1 year, and 2 years after LT. Examination of walking function included measures of walking independence, gait speed and spatiotemporal parameters, gait kinematics, and daily step activity. Growth and development were assessed by tracking his height, weight, incidence of musculoskeletal complications, and gross motor task performance. Over the 2 years, the child continued to ambulate independently with a reverse rolling walker, increasing his fastest gait speed. Spatiotemporal and kinematic features of his walking improved, and daily step activity increased. Height and weight remained on their preinjury trajectory and within age-appropriate norms. The child experienced only minor musculoskeletal complications. Additionally, he gained the ability to use reciprocal patterned leg movements during locomotor tasks such as assisted stair climbing and independent tricycle pedaling. Two years after recovery of walking, this child with incomplete SCI had maintained and improved his walking function and experienced age-appropriate growth and development.

Cognitive and locomotor/exploratory behavior after chronic exercise in the olfactory bulbectomy animal model of depression.

PubMed

Van Hoomissen, Jacqueline; Kunrath, Julie; Dentlinger, Renee; Lafrenz, Andrew; Krause, Mark; Azar, Afaf

2011-09-12

Despite the evidence that exercise improves cognitive behavior in animal models, little is known about these beneficial effects in animal models of pathology. We examined the effects of activity wheel (AW) running on contextual fear conditioning (CFC) and locomotor/exploratory behavior in the olfactory bulbectomy (OBX) model of depression, which is characterized by hyperactivity and changes in cognitive function. Twenty-four hours after the conditioning session of the CFC protocol, the animals were tested for the conditioned response in a conditioned and a novel context to test for the effects of both AW and OBX on CFC, but also the context specificity of the effect. OBX reduced overall AW running behavior throughout the experiment, but increased locomotor/exploratory behavior during CFC, thus demonstrating a context-dependent effect. OBX animals, however, displayed normal CFC behavior that was context-specific, indicating that aversively conditioned memory is preserved in this model. AW running increased freezing behavior during the testing session of the CFC protocol in the control animals but only in the conditioned context, supporting the hypothesis that AW running improves cognitive function in a context-specific manner that does not generalize to an animal model of pathology. Blood corticosterone levels were increased in all animals at the conclusion of the testing sessions, but levels were higher in AW compared to sedentary groups indicating an effect of exercise on neuroendocrine function. Given the differential results of AW running on behavior and neuroendocrine function after OBX, further exploration of the beneficial effects of exercise in animal models of neuropathology is warranted. Copyright © 2011 Elsevier B.V. All rights reserved.

Objective assessment of movement competence in children using wearable sensors: An instrumented version of the TGMD-2 locomotor subtest.

PubMed

Bisi, Maria Cristina; Pacini Panebianco, G; Polman, R; Stagni, R

2017-07-01

Movement competence (MC) is defined as the development of sufficient skill to assure successful performance in different physical activities. Monitoring children MC during maturation is fundamental to detect early minor delays and define effective intervention. To this purpose, several MC assessment batteries are available. When evaluating movement strategies, with the aim of identifying specific skill components that may need improving, widespread MC assessment is limited by high time consumption for scoring and the need for trained operators to ensure reliability. This work aims to facilitate and support the assessment by designing, implementing and validating an instrumented version of the TGMD-2 locomotor subtest based on Inertial Measurement Units (IMUs) to quantify MC in children rapidly and objectively. 45 typically developing children, aged 6-10, performed the TGMD-2 locomotor subtest (six skills). During the tests, children wore five IMUs mounted on lower back, on ankles and on wrists. Sensor and video recordings of the tests were collected. Three expert evaluators performed the standard assessment of TGMD-2. Using theoretical and modelling approaches, algorithms were implemented to automatically score children tests based on IMUs' data. The automatic assessment, compared to the standard one, showed an agreement higher than 87% on average on the entire group for each skill and a reduction of time for scoring from 15 to 2min per participant. Results support the use of IMUs for MC assessment: this approach will allow improving the usability of MC assessment, supporting objectively evaluator decisions and reducing time requirement for the evaluation of large groups. Copyright © 2017 Elsevier B.V. All rights reserved.

Fenbendazole improves pathological and functional recovery following traumatic spinal cord injury.

PubMed

Yu, C G; Singh, R; Crowdus, C; Raza, K; Kincer, J; Geddes, J W

2014-01-03

During a study of spinal cord injury (SCI), mice in our colony were treated with the anthelmintic fenbendazole to treat pinworms detected in other mice not involved in the study. As this was not part of the original experimental design, we subsequently compared pathological and functional outcomes of SCI in female C57BL/6 mice who received fenbendazole (150 ppm, 8 mg/kg body weight/day) for 4 weeks prior to moderate contusive SCI (50 kdyn force) as compared to mice on the same diet without added fenbendazole. The fenbendazole-treated mice exhibited improved locomotor function, determined using the Basso mouse scale, as well as improved tissue sparing following contusive SCI. Fenbendazole may exert protective effects through multiple possible mechanisms, one of which is inhibition of the proliferation of B lymphocytes, thereby reducing antibody responses. Autoantibodies produced following SCI contribute to the axon damage and locomotor deficits. Fenbendazole pretreatment reduced the injury-induced CD45R-positive B cell signal intensity and IgG immunoreactivity at the lesion epicenter 6 weeks after contusive SCI in mice, consistent with a possible effect on the immune response to the injury. Fenbendazole and related benzimadole antihelmintics are FDA approved, exhibit minimal toxicity, and represent a novel group of potential therapeutics targeting secondary mechanisms following SCI. Copyright © 2013. Published by Elsevier Ltd.

Fenbendazole improves pathological and functional recovery following traumatic spinal cord injury

PubMed Central

Yu, Chen Guang; Singh, Ranjana; Crowdus, Carolyn; Raza, Kashif; Kincer, Jeanie; Geddes, James W.

2014-01-01

During a study of spinal cord injury (SCI), mice in our colony were treated with the anthelmintic fenbendazole to treat pinworms detected in other mice not involved in the study. As this was not part of the original experimental design, we subsequently compared pathological and functional outcomes of SCI in female C57BL/6 mice who received fenbendazole (150 ppm, 8 mg/kg body weight/day) for four weeks prior to moderate contusive SCI (50 kdyn force) as compared to mice on the same diet without added fenbendazole. The fenbendazole-treated mice exhibited improved locomotor function, determined using the Basso mouse scale, as well as improved tissue sparing following contusive SCI. Fenbendazole may exert protective effects through multiple possible mechanisms, one of which is inhibition of the proliferation of B lymphocytes, thereby reducing antibody responses. Autoantibodies produced following SCI contribute to the axon damage and locomotor deficits. Fenbendazole pretreatment reduced the injury-induced CD45R-positive B cell signal intensity and IgG immunoreactivity at the lesion epicenter six weeks after contusive SCI in mice, consistent with a possible effect on the immune response to the injury. Fenbendazole and related benzimadole antihelmintics are FDA approved, exhibit minimal toxicity, and represent a novel group of potential therapeutics targeting secondary mechanisms following SCI. PMID:24183965

Differences in the locomotor-activating effects of indirect serotonin agonists in habituated and non-habituated rats.

PubMed

Halberstadt, Adam L; Buell, Mahálah R; Price, Diana L; Geyer, Mark A

2012-07-01

The indirect serotonin (5-HT) agonist 3,4-methylenedioxymethamphetamine (MDMA) produces a distinct behavioral profile in rats consisting of locomotor hyperactivity, thigmotaxis, and decreased exploration. The indirect 5-HT agonist α-ethyltryptamine (AET) produces a similar behavioral profile. Using the Behavioral Pattern Monitor (BPM), the present investigation examined whether the effects of MDMA and AET are dependent on the novelty of the testing environment. These experiments were conducted in Sprague-Dawley rats housed on a reversed light cycle and tested during the dark phase of the light/dark cycle. We found that racemic MDMA (RS-MDMA; 3 mg/kg, SC) increased locomotor activity in rats tested in novel BPM chambers, but had no effect on locomotor activity in rats habituated to the BPM chambers immediately prior to testing. Likewise, AET (5 mg/kg, SC) increased locomotor activity in non-habituated animals but not in animals habituated to the test chambers. These results were unexpected because previous reports indicate that MDMA has robust locomotor-activating effects in habituated animals. To further examine the influence of habituation on MDMA-induced locomotor activity, we conducted parametric studies with S-(+)-MDMA (the more active enantiomer) in habituated and non-habituated rats housed on a standard or reversed light cycle. Light cycle was included as a variable due to reported differences in sensitivity to serotonergic ligands during the dark and light phases. In confirmation of our initial studies, rats tested during the dark phase and habituated to the BPM did not show an S-(+)-MDMA (3 mg/kg, SC)-induced increase in locomotor activity, whereas non-habituated rats did. By contrast, in rats tested during the light phase, S-(+)-MDMA increased locomotor activity in both non-habituated and habituated rats, although the response in habituated animals was attenuated. The finding that habituation and light cycle interact to influence MDMA- and AET-induced hyperactivity demonstrates that there are previously unrecognized complexities associated with the behavioral effects of these drugs. Copyright © 2012 Elsevier Inc. All rights reserved.

Sexual dysfunction and male infertility.

PubMed

Lotti, Francesco; Maggi, Mario

2018-05-01

Infertility affects up to 12% of all men, and sexual dysfunction occurs frequently in men of reproductive age, causing infertility in some instances. In infertile men, hypoactive sexual desire and lack of sexual satisfaction are the most prevalent types of sexual dysfunction, ranging from 8.9% to 68.7%. Erectile dysfunction and/or premature ejaculation, evaluated with validated tools, have a prevalence of one in six infertile men, and orgasmic dysfunction has a prevalence of one in ten infertile men. In addition, infertile men can experience a heavy psychological burden. Infertility and its associated psychological concerns can underlie sexual dysfunction. Furthermore, general health perturbations can lead to male infertility and/or sexual dysfunction. Erectile dysfunction and male infertility are considered proxies for general health, the former underlying cardiovascular disorders and the latter cancerous and noncancerous conditions. The concept that erectile dysfunction in infertile men might be an early marker of poor general health is emerging. Finally, medications used for general health problems can cause sperm abnormalities and sexual dysfunction. The treatment of some causes of male infertility might improve semen quality and reverse infertility-related sexual dysfunction. In infertile men, an investigation of sexual, general, and psychological health status is advisable to improve reproductive problems and general health.

SKIPing to Motor Competence: The Influence of Project Successful Kinesthetic Instruction for Preschoolers on Motor Competence of Disadvantaged Preschoolers

ERIC Educational Resources Information Center

Altunsöz, Irmak Hürmeriç; Goodway, Jacqueline D.

2016-01-01

Background: Preschool children who are at risk have been shown to demonstrate developmental delays in their fundamental motor skills. The body of research on motor skill development of children indicates that these children, when provided with motor skill instruction, significantly improved their locomotor and object control (OC) skill…

Pilates training improves 5-km run performance by changing metabolic cost and muscle activity in trained runners

PubMed Central

Finatto, Paula; Silva, Edson Soares Da; Okamura, Alexandre B.; Almada, Bruna P.; Oliveira, Henrique B.

2018-01-01

Purpose Strength training improves distance running economy and performance. This finding is based predominantly on maximal and explosive strength programmes applied to locomotor muscles, particularly on the lower limbs. It is not certain whether a minimization of metabolic cost (Cmet) and an improvement in running performance is feasible with strength training of the postural and trunk muscles. Methods Using kinematic, neuromuscular and metabolic measurements of running at two different speeds before and after a 12-week Pilates training programme, we tested the hypothesis that core training might improve the running Cmet and performance of trained runners. Thirty-two individuals were randomly assigned to the control group (CG, n = 16) or the Pilates group (PG, n = 16). Results Confirming our hypothesis, a significant improvement (p<0.05) was observed for running performance in the PG (pre: 25.65±0.4 min; post: 23.23±0.4 min) compared to the CG (pre: 25.33±0.58 min; post: 24.61±0.52 min). Similarly, the PG (4.33±0.07 J.kg-1.m-1) had better responses than the CG (4.71±0.11 J.kg-1.m-1) during post-training for Cmet. These findings were accompanied by decreased electromyographic activity of the postural muscles at submaximal running intensities in the PG. Conclusions Overall, these results provide a rationale for selecting strength training strategies that target adaptations on specific postural and locomotor muscles for trained distance runners. PMID:29561907

Pilates training improves 5-km run performance by changing metabolic cost and muscle activity in trained runners.

PubMed

Finatto, Paula; Silva, Edson Soares Da; Okamura, Alexandre B; Almada, Bruna P; Oliveira, Henrique B; Peyré-Tartaruga, Leonardo A

2018-01-01

Strength training improves distance running economy and performance. This finding is based predominantly on maximal and explosive strength programmes applied to locomotor muscles, particularly on the lower limbs. It is not certain whether a minimization of metabolic cost (Cmet) and an improvement in running performance is feasible with strength training of the postural and trunk muscles. Using kinematic, neuromuscular and metabolic measurements of running at two different speeds before and after a 12-week Pilates training programme, we tested the hypothesis that core training might improve the running Cmet and performance of trained runners. Thirty-two individuals were randomly assigned to the control group (CG, n = 16) or the Pilates group (PG, n = 16). Confirming our hypothesis, a significant improvement (p<0.05) was observed for running performance in the PG (pre: 25.65±0.4 min; post: 23.23±0.4 min) compared to the CG (pre: 25.33±0.58 min; post: 24.61±0.52 min). Similarly, the PG (4.33±0.07 J.kg-1.m-1) had better responses than the CG (4.71±0.11 J.kg-1.m-1) during post-training for Cmet. These findings were accompanied by decreased electromyographic activity of the postural muscles at submaximal running intensities in the PG. Overall, these results provide a rationale for selecting strength training strategies that target adaptations on specific postural and locomotor muscles for trained distance runners.

Resveratrol improves prostate fibrosis during progression of urinary dysfunction in chronic prostatitis.

PubMed

He, Yi; Zeng, Hui-Zhi; Yu, Yang; Zhang, Jia-Shu; Duan, Xingping; Zeng, Xiao-Na; Gong, Feng-Tao; Liu, Qi; Yang, Bo

2017-09-01

We investigated whether prostate fibrosis was associated with urinary dysfunction in chronic prostatitis (CP) and whether resveratrol improved urinary dysfunction and the underlying molecular mechanism. Rat model of CP was established via subcutaneous injections of DPT vaccine and subsequently treated with resveratrol. Bladder pressure and volume tests investigated the effect of resveratrol on urinary dysfunction in CP rats. Western blotting and immunohistochemical staining examined the expression level of C-kit/SCF and TGF-β/Wnt/β-catenin. Compared to the control group, the maximum capacity of the bladder, residual urine volume and maximum voiding pressure, the activity of C-kit/SCF and TGF-β/Wnt/β-catenin pathways were increased significantly in the CP group. Resveratrol treatment significantly improved these factors. CP induced significantly prostate fibrosis, which exhibits a close relationship with urinary dysfunction. Resveratrol improved fibrosis, which may be associated with the suppression of C-kit/SCF and TGF-β/Wnt/β-catenin pathway. Copyright © 2017 Elsevier B.V. All rights reserved.

Acupuncture does not ameliorate metabolic disturbances in the P450 aromatase inhibitor-induced rat model of polycystic ovary syndrome.

PubMed

Maliqueo, Manuel; Benrick, Anna; Marcondes, Rodrigo Rodrigues; Johansson, Julia; Sun, Miao; Stener-Victorin, Elisabet

2017-01-01

What is the central question of this study? The effectiveness of low-frequency electroacupuncture in the treatment of metabolic disorders associated with polycystic ovary syndrome (PCOS), an endocrine-metabolic disorder characterized by an imbalance in sex steroid production, is controversial. What is the main finding and its importance? In a rat model of PCOS induced by the inhibition of P450 aromatase, low-frequency electroacupuncture increased low-density lipoprotein-cholesterol but did not improve the insulin resistance or the adipose tissue dysfunction, suggesting that a balance of sex steroids is needed to restore the metabolic function in this rat model of PCOS. Low-frequency electroacupuncture restores sex steroid synthesis and sympathetic activity in women with polycystic ovary syndrome, which may ameliorate its metabolic disturbances, probably by modulating sympathetic nerve activity or sex steroid synthesis. We investigated whether low-frequency electroacupuncture regulates the metabolic function to the same extent as treatment with estradiol or β-adrenergic blocking in a rat model of polycystic ovary syndrome induced by a P450 aromatase inhibitor (letrozole). Letrozole (200 μg day -1 ) or placebo pellets were implanted in prepubertal Wistar rats. Six weeks thereafter, rats were treated for 5-6 weeks with the following: low-frequency electroacupuncture (5 days per week); a β-adrenergic blocker (propranolol hydrochloride, 0.1 mg kg -1 , 5 days per week); or 17β-estradiol (2.0 μg) every fourth day. Body weight development, body composition, locomotor activity, insulin sensitivity, tissue-specific glucose uptake, lipid profile, adipocyte size, serum concentrations of adiponectin and insulin, and gene expression in inguinal fat were measured. All treatments increased circulating levels of low-density lipoprotein-cholesterol. Estradiol treatment restored locomotor activity and increased insulin sensitivity but did not modify the glucose uptake in muscle and fat. An upregulation of genes related to insulin sensitivity and downregulation of genes related to adipogenesis were observed in subcutaneous adipose tissue from rats exposed to letrozole. Only estradiol treatment normalized the expression of these genes. In conclusion, low-frequency electroacupuncture increased low-density lipoprotein-cholesterol without affecting insulin sensitivity or adipose tissue function, which could suggest effects on hepatic lipid regulation, probably mediated by the action of estradiol or the β-adrenergic pathway. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Flavanol-rich cocoa ameliorates lipemia-induced endothelial dysfunction.

PubMed

Westphal, Sabine; Luley, Claus

2011-09-01

Consumption of flavanols improves chronic endothelial dysfunction. We investigated whether it can also improve acute lipemia-induced endothelial dysfunction. In this randomized, placebo-controlled, double-blind, crossover trial, 18 healthy subjects received a fatty meal with cocoa either rich in flavanols (918 mg) or flavanol-poor. Flow-mediated dilation (FMD), triglycerides, and free fatty acids were then determined over 6 h. After the flavanol-poor fat loading, the FMD deteriorated over 4 h. The consumption of flavanol-rich cocoa, in contrast, improved this deterioration in hours 2, 3, and 4 without abolishing it completely. Flavanols did not have any influence on triglycerides or on free fatty acids. Flavanol-rich cocoa can alleviate the lipemia-induced endothelial dysfunction, probably through an improvement in endothelial NO synthase.

Evaluation of harmonic direction-finding systems for detecting locomotor activity

USGS Publications Warehouse

Boyarski, V.L.; Rodda, G.H.; Savidge, J.A.

2007-01-01

We conducted a physical simulation experiment to test the efficacy of harmonic direction finding for remotely detecting locomotor activity in animals. The ability to remotely detect movement helps to avoid disturbing natural movement behavior. Remote detection implies that the observer can sense only a change in signal bearing. In our simulated movements, small changes in bearing (<5.7??) were routinely undetectable. Detectability improved progressively with the size of the simulated animal movement. The average (??SD) of reflector tag movements correctly detected for 5 observers was 93.9 ?? 12.8% when the tag was moved ???11.5??; most observers correctly detected tag movements ???20.1??. Given our data, one can assess whether the technique will be effective for detecting movements at an observation distance appropriate for the study organism. We recommend that both habitat and behavior of the organism be taken into consideration when contemplating use of this technique for detecting locomotion.

Muscle spindle feedback directs locomotor recovery and circuit reorganization after spinal cord injury.

PubMed

Takeoka, Aya; Vollenweider, Isabel; Courtine, Grégoire; Arber, Silvia

2014-12-18

Spinal cord injuries alter motor function by disconnecting neural circuits above and below the lesion, rendering sensory inputs a primary source of direct external drive to neuronal networks caudal to the injury. Here, we studied mice lacking functional muscle spindle feedback to determine the role of this sensory channel in gait control and locomotor recovery after spinal cord injury. High-resolution kinematic analysis of intact mutant mice revealed proficient execution in basic locomotor tasks but poor performance in a precision task. After injury, wild-type mice spontaneously recovered basic locomotor function, whereas mice with deficient muscle spindle feedback failed to regain control over the hindlimb on the lesioned side. Virus-mediated tracing demonstrated that mutant mice exhibit defective rearrangements of descending circuits projecting to deprived spinal segments during recovery. Our findings reveal an essential role for muscle spindle feedback in directing basic locomotor recovery and facilitating circuit reorganization after spinal cord injury. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparative limb proportions reveal differential locomotor morphofunctions of alligatoroids and crocodyloids

NASA Astrophysics Data System (ADS)

Iijima, Masaya; Kubo, Tai; Kobayashi, Yoshitsugu

2018-03-01

Although two major clades of crocodylians (Alligatoroidea and Crocodyloidea) were split during the Cretaceous period, relatively few morphological and functional differences between them have been known. In addition, interaction of multiple morphofunctional systems that differentiated their ecology has barely been assessed. In this study, we examined the limb proportions of crocodylians to infer the differences of locomotor functions between alligatoroids and crocodyloids, and tested the correlation of locomotor and feeding morphofunctions. Our analyses revealed crocodyloids including Gavialis have longer stylopodia (humerus and femur) than alligatoroids, indicating that two groups may differ in locomotor functions. Fossil evidence suggested that alligatoroids have retained short stylopodia since the early stage of their evolution. Furthermore, rostral shape, an indicator of trophic function, is correlated with limb proportions, where slender-snouted piscivorous taxa have relatively long stylopodia and short overall limbs. In combination, trophic and locomotor functions might differently delimit the ecological opportunity of alligatoroids and crocodyloids in the evolution of crocodylians.

The Role of Storage Lipids in the Relation between Fecundity, Locomotor Activity, and Lifespan of Drosophila melanogaster Longevity-Selected and Control Lines

PubMed Central

Nasiri Moghadam, Neda; Holmstrup, Martin; Manenti, Tommaso; Brandt Mouridsen, Marie; Pertoldi, Cino; Loeschcke, Volker

2015-01-01

The contribution of insect fat body to multiple processes, such as development, metamorphosis, activity, and reproduction results in trade-offs between life history traits. In the present study, age-induced modulation of storage lipid composition in Drosophila melanogaster longevity-selected (L) and non-selected control (C) lines was studied and the correlation between total body fat mass and lifespan assessed. The trade-offs between fecundity, locomotor activity, and lifespan were re-evaluated from a lipid-related metabolic perspective. Fewer storage lipids in the L lines compared to the C lines supports the impact of body fat mass on extended lifespan. The higher rate of fecundity and locomotor activity in the L lines may increase the lipid metabolism and enhance the lipolysis of storage lipids, reducing fat reserves. The correlation between neutral lipid fatty acids and fecundity, as well as locomotor activity, varied across age groups and between the L and C lines. The fatty acids that correlated with egg production were different from the fatty acids that correlated with locomotor activity. The present study suggests that fecundity and locomotor activity may positively affect the lifespan of D. melanogaster through the inhibition of fat accumulation. PMID:26115349

Pre-existing differences in motivation for food and sensitivity to cocaine-induced locomotion in obesity-prone rats.

PubMed

Vollbrecht, Peter J; Nobile, Cameron W; Chadderdon, Aaron M; Jutkiewicz, Emily M; Ferrario, Carrie R

2015-12-01

Obesity is a significant problem in the United States, with roughly one third of adults having a body mass index (BMI) over thirty. Recent evidence from human studies suggests that pre-existing differences in the function of mesolimbic circuits that mediate motivational processes may promote obesity and hamper weight loss. However, few preclinical studies have examined pre-existing neurobehavioral differences related to the function of mesolimbic systems in models of individual susceptibility to obesity. Here, we used selectively bred obesity-prone and obesity-resistant rats to examine 1) the effect of a novel "junk-food" diet on the development of obesity and metabolic dysfunction, 2) over-consumption of "junk-food" in a free access procedure, 3) motivation for food using instrumental procedures, and 4) cocaine-induced locomotor activity as an index of general mesolimbic function. As expected, eating a sugary, fatty, "junk-food" diet exacerbated weight gain and increased fasted insulin levels only in obesity-prone rats. In addition, obesity-prone rats continued to over-consume junk-food during discrete access testing, even when this same food was freely available in the home cage. Furthermore, when asked to press a lever to obtain food in an instrumental task, rates of responding were enhanced in obesity-prone versus obesity-resistant rats. Finally, obesity-prone rats showed a stronger locomotor response to 15 mg/kg cocaine compared to obesity-resistant rats prior to any diet manipulation. This enhanced sensitivity to this dose of cocaine is indicative of basal differences in the function of mesolimbic circuits in obesity-prone rats. We speculate that pre-existing differences in motivational systems may contribute to over-consumption and enhanced motivation in susceptible individuals. Copyright © 2015 Elsevier Inc. All rights reserved.

Adult brain and behavioral pathological markers of prenatal immune challenge during early/middle and late fetal development in mice.

PubMed

Meyer, Urs; Nyffeler, Myriel; Yee, Benjamin K; Knuesel, Irene; Feldon, Joram

2008-05-01

Maternal infection during pregnancy increases the risk for neurodevelopmental disorders such as schizophrenia and autism in the offspring. This association appears to be critically dependent on the precise prenatal timing. However, the extent to which distinct adult psychopathological and neuropathological traits may be sensitive to the precise times of prenatal immune activation remains to be further characterized. Here, we evaluated in a mouse model of prenatal immune challenge by the viral mimic, polyriboinosinic-polyribocytidilic acid (PolyIC), whether prenatal immune activation in early/middle and late gestation may influence the susceptibility to some of the critical cognitive, pharmacological, and neuroanatomical dysfunctions implicated in schizophrenia and autism. We revealed that PolyIC-induced prenatal immune challenge on gestation day (GD) 9 but not GD17 significantly impaired sensorimotor gating and reduced prefrontal dopamine D1 receptors in adulthood, whereas prenatal immune activation specifically in late gestation impaired working memory, potentiated the locomotor reaction to the NMDA-receptor antagonist dizocilpine, and reduced hippocampal NMDA-receptor subunit 1 expression. On the other hand, potentiation of the locomotor reaction to the dopamine-receptor agonist amphetamine and reduction in Reelin- and Parvalbumin-expressing prefrontal neurons emerged independently of the precise times of prenatal immune challenge. Our findings thus highlight that prenatal immune challenge during early/middle and late fetal development in mice leads to distinct brain and behavioral pathological symptom clusters in adulthood. Further examination and evaluation of in utero immune challenge at different times of gestation may provide important new insight into the neuroimmunological and neuropathological mechanisms underlying the segregation of different symptom clusters in heterogeneous neuropsychiatric disorders such as schizophrenia and autism.

Behavioral abnormalities in female mice following administration of aluminum adjuvants and the human papillomavirus (HPV) vaccine Gardasil.

PubMed

Inbar, Rotem; Weiss, Ronen; Tomljenovic, Lucija; Arango, Maria-Teresa; Deri, Yael; Shaw, Christopher A; Chapman, Joab; Blank, Miri; Shoenfeld, Yehuda

2017-02-01

Vaccine adjuvants and vaccines may induce autoimmune and inflammatory manifestations in susceptible individuals. To date most human vaccine trials utilize aluminum (Al) adjuvants as placebos despite much evidence showing that Al in vaccine-relevant exposures can be toxic to humans and animals. We sought to evaluate the effects of Al adjuvant and the HPV vaccine Gardasil versus the true placebo on behavioral and inflammatory parameters in female mice. Six-week-old C57BL/6 female mice were injected with either, Gardasil, Gardasil + pertussis toxin (Pt), Al hydroxide, or, vehicle control in amounts equivalent to human exposure. At 7.5 months of age, Gardasil and Al-injected mice spent significantly more time floating in the forced swimming test (FST) in comparison with vehicle-injected mice (Al, p = 0.009; Gardasil, p = 0.025; Gardasil + Pt, p = 0.005). The increase in floating time was already highly significant at 4.5 months of age for the Gardasil and Gardasil + Pt group (p ≤ 0.0001). No significant differences were observed in the number of stairs climbed in the staircase test which measures locomotor activity. These results indicate that differences observed in the FST were unlikely due to locomotor dysfunction, but rather due to depression. Moreover, anti-HPV antibodies from the sera of Gardasil and Gardasil + Pt-injected mice showed cross-reactivity with the mouse brain protein extract. Immunohistochemistry analysis revealed microglial activation in the CA1 area of the hippocampus of Gardasil-injected mice. It appears that Gardasil via its Al adjuvant and HPV antigens has the ability to trigger neuroinflammation and autoimmune reactions, further leading to behavioral changes.

ER Stress Induced by Tunicamycin Triggers α-Synuclein Oligomerization, Dopaminergic Neurons Death and Locomotor Impairment: a New Model of Parkinson's Disease.

PubMed

Cóppola-Segovia, Valentín; Cavarsan, Clarissa; Maia, Flavia G; Ferraz, Anete C; Nakao, Lia S; Lima, Marcelo Ms; Zanata, Silvio M

2017-10-01

Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive death of dopaminergic neurons of the substantia nigra pars compacta (SNpc), leading to the major clinical abnormalities that characterize this disease. Although PD's etiology is unknown, α-synuclein aggregation plays a pivotal role in PD pathogenesis, which could be associated to some pathological processes such as oxidative stress, endoplasmic reticulum (ER) stress, impaired protein degradation, and mitochondrial dysfunction. Increasing experimental evidence indicates that ER stress is involved in PD, however most of the described results employed cultured cell lines and genetically modified animal models. In this study, we developed a new ER stress rat model employing the well-known ER stressor tunicamycin (Tm). To evaluate if ER stress was able to induce PD features, we performed an intranigral injection of Tm (0.1 μg/cerebral hemisphere) and animals (male Wistar rats) were analyzed 7 days post injection. The classical 6-OHDA neurotoxin model (1 μg/cerebral hemisphere) was used as an established positive control for PD. We show that Tm injection induced locomotor impairment, dopaminergic neurons death, and activation of astroglia. In addition, we observed an extensive α-synuclein oligomerization in SNpc of Tm-injected animals when compared with DMSO-injected controls. Finally, both Tm and 6-OHDA treated animals presented increased levels of ER stress markers. Taken together, these findings show for the first time that the ER stressor Tm recapitulates some of the phenotypic characteristics observed in rodent models of PD, reinforcing the concept that ER stress could be an important contributor to the pathophysiology of PD. Therefore, we propose the intranigral Tm injection as a new ER stress-based model for the study of PD in vivo.

HIV-1 TAT protein enhances sensitization to methamphetamine by affecting dopaminergic function.

PubMed

Kesby, James P; Najera, Julia A; Romoli, Benedetto; Fang, Yiding; Basova, Liana; Birmingham, Amanda; Marcondes, Maria Cecilia G; Dulcis, Davide; Semenova, Svetlana

2017-10-01

Methamphetamine abuse is common among humans with immunodeficiency virus (HIV). The HIV-1 regulatory protein TAT induces dysfunction of mesolimbic dopaminergic systems which may result in impaired reward processes and contribute to methamphetamine abuse. These studies investigated the impact of TAT expression on methamphetamine-induced locomotor sensitization, underlying changes in dopamine function and adenosine receptors in mesolimbic brain areas and neuroinflammation (microgliosis). Transgenic mice with doxycycline-induced TAT protein expression in the brain were tested for locomotor activity in response to repeated methamphetamine injections and methamphetamine challenge after a 7-day abstinence period. Dopamine function in the nucleus accumbens (Acb) was determined using high performance liquid chromatography. Expression of dopamine and/or adenosine A receptors (ADORA) in the Acb and caudate putamen (CPu) was assessed using RT-PCR and immunohistochemistry analyses. Microarrays with pathway analyses assessed dopamine and adenosine signaling in the CPu. Activity-dependent neurotransmitter switching of a reserve pool of non-dopaminergic neurons to a dopaminergic phenotype in the ventral tegmental area (VTA) was determined by immunohistochemistry and quantified with stereology. TAT expression enhanced methamphetamine-induced sensitization. TAT expression alone decreased striatal dopamine (D1, D2, D4, D5) and ADORA1A receptor expression, while increasing ADORA2A receptors expression. Moreover, TAT expression combined with methamphetamine exposure was associated with increased adenosine A receptors (ADORA1A) expression and increased recruitment of dopamine neurons in the VTA. TAT expression and methamphetamine exposure induced microglia activation with the largest effect after combined exposure. Our findings suggest that dopamine-adenosine receptor interactions and reserve pool neuronal recruitment may represent potential targets to develop new treatments for methamphetamine abuse in individuals with HIV. Copyright © 2017 Elsevier Inc. All rights reserved.

Motor neurons and glia exhibit specific individualized responses to TDP-43 expression in a Drosophila model of amyotrophic lateral sclerosis.

PubMed

Estes, Patricia S; Daniel, Scott G; McCallum, Abigail P; Boehringer, Ashley V; Sukhina, Alona S; Zwick, Rebecca A; Zarnescu, Daniela C

2013-05-01

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by complex neuronal and glial phenotypes. Recently, RNA-based mechanisms have been linked to ALS via RNA-binding proteins such as TDP-43, which has been studied in vivo using models ranging from yeast to rodents. We have developed a Drosophila model of ALS based on TDP-43 that recapitulates several aspects of pathology, including motor neuron loss, locomotor dysfunction and reduced survival. Here we report the phenotypic consequences of expressing wild-type and four different ALS-linked TDP-43 mutations in neurons and glia. We show that TDP-43-driven neurodegeneration phenotypes are dose- and age-dependent. In motor neurons, TDP-43 appears restricted to nuclei, which are significantly misshapen due to mutant but not wild-type protein expression. In glia and in the developing neuroepithelium, TDP-43 associates with cytoplasmic puncta. TDP-43-containing RNA granules are motile in cultured motor neurons, although wild-type and mutant variants exhibit different kinetic properties. At the neuromuscular junction, the expression of TDP-43 in motor neurons versus glia leads to seemingly opposite synaptic phenotypes that, surprisingly, translate into comparable locomotor defects. Finally, we explore sleep as a behavioral readout of TDP-43 expression and find evidence of sleep fragmentation consistent with hyperexcitability, a suggested mechanism in ALS. These findings support the notion that although motor neurons and glia are both involved in ALS pathology, at the cellular level they can exhibit different responses to TDP-43. In addition, our data suggest that individual TDP-43 alleles utilize distinct molecular mechanisms, which will be important for developing therapeutic strategies.

Pre-existing differences in motivation for food and sensitivity to cocaine-induced locomotion in obesity-prone rats

PubMed Central

Vollbrecht, Peter J.; Nobile, Cameron W.; Chadderdon, Aaron M.; Jutkiewicz, Emily M.; Ferrario, Carrie R.

2015-01-01

Obesity is a significant problem in the United States, with roughly one third of adults having a body mass index (BMI) over thirty. Recent evidence from human studies suggests that pre-existing differences in the function of mesolimbic circuits that mediate motivational processes may promote obesity and hamper weight loss. However, few preclinical studies have examined pre-existing neurobehavioral differences related to the function of mesolimbic systems in models of individual susceptibility to obesity. Here, we used selectively bred obesity-prone and obesity-resistant rats to examine 1) the effect of a novel “junk-food” diet on the development of obesity and metabolic dysfunction, 2) over-consumption of “junk-food” in a free access procedure, 3) motivation for food using instrumental procedures, and 4) cocaine-induced locomotor activity as an index of general mesolimbic function. As expected, eating a sugary, fatty, “junk-food” diet exacerbated weight gain and increased fasted insulin levels only in obesity-prone rats. In addition, obesity-prone rats continued to over-consume junk-food during discrete access testing, even when this same food was freely available in the home cage. Furthermore, when asked to press a lever to obtain food in an instrumental task, rates of responding were enhanced in obesity-prone versus obesity-resistant rats. Finally, obesity-prone rats showed a stronger locomotor response to 15 mg/kg cocaine compared to obesity-resistant rats prior to any diet manipulation. This enhanced sensitivity to this dose of cocaine is indicative of basal differences in the function of mesolimbic circuits in obesity-prone rats. We speculate that pre-existing differences in motivational systems may contribute to over-consumption and enhanced motivation in susceptible individuals. PMID:26423787

Developmental exposure to acetaminophen does not induce hyperactivity in zebrafish larvae.

PubMed

Reuter, Isabel; Knaup, Sabine; Romanos, Marcel; Lesch, Klaus-Peter; Drepper, Carsten; Lillesaar, Christina

2016-08-01

First line pain relief medication during pregnancy relies nearly entirely on the over-the-counter analgesic acetaminophen, which is generally considered safe to use during gestation. However, recent epidemiological studies suggest a risk of developing attention-deficit/hyperactivity disorder (ADHD)-like symptoms in children if mothers use acetaminophen during pregnancy. Currently, there are no experimental proofs that prenatal acetaminophen exposure causes developmental brain alterations of progeny. Exposure to high acetaminophen concentrations causes liver toxicity, which is well investigated in different model organisms. However, sub-liver-toxic concentrations have not been experimentally investigated with respect to ADHD endophenotypes such as hyperactivity. We used zebrafish to investigate the potential impact of acetaminophen exposure on locomotor activity levels, and compared it to the established zebrafish Latrophilin 3 (Lphn3) ADHD-model. We determined the sub-liver-toxic concentration of acetaminophen in zebrafish larvae and treated wild-type and lphn3.1 knockdown larvae with increasing concentrations of acetaminophen. We were able to confirm that lphn3.1 knockdown alone causes hyperactivity, strengthening the implication of Lphn3 dysfunction as an ADHD risk factor. Neither acute nor chronic exposure to acetaminophen at sub-liver-toxic concentrations in wild-type or lphn3.1 knock-downs increases locomotor activity levels. Together our findings show that embryonic to larval exposure to acetaminophen does not cause hyperactivity in zebrafish larvae. Furthermore, there are no additive and/or synergistic effects of acetaminophen exposure in a susceptible background induced by knock-down of lphn3.1. Our experimental study suggests that there is, at least in zebrafish larvae, no direct link between embryonic acetaminophen exposure and hyperactivity. Further work is necessary to clarify this issue in humans.

Dysfunction in endoplasmic reticulum-mitochondria crosstalk underlies SIGMAR1 loss of function mediated motor neuron degeneration.

PubMed

Bernard-Marissal, Nathalie; Médard, Jean-Jacques; Azzedine, Hamid; Chrast, Roman

2015-04-01

Mutations in Sigma 1 receptor (SIGMAR1) have been previously identified in patients with amyotrophic lateral sclerosis and disruption of Sigmar1 in mouse leads to locomotor deficits. However, cellular mechanisms underlying motor phenotypes in human and mouse with disturbed SIGMAR1 function have not been described so far. Here we used a combination of in vivo and in vitro approaches to investigate the role of SIGMAR1 in motor neuron biology. Characterization of Sigmar1(-/-) mice revealed that affected animals display locomotor deficits associated with muscle weakness, axonal degeneration and motor neuron loss. Using primary motor neuron cultures, we observed that pharmacological or genetic inactivation of SIGMAR1 led to motor neuron axonal degeneration followed by cell death. Disruption of SIGMAR1 function in motor neurons disturbed endoplasmic reticulum-mitochondria contacts, affected intracellular calcium signalling and was accompanied by activation of endoplasmic reticulum stress and defects in mitochondrial dynamics and transport. These defects were not observed in cultured sensory neurons, highlighting the exacerbated sensitivity of motor neurons to SIGMAR1 function. Interestingly, the inhibition of mitochondrial fission was sufficient to induce mitochondria axonal transport defects as well as axonal degeneration similar to the changes observed after SIGMAR1 inactivation or loss. Intracellular calcium scavenging and endoplasmic reticulum stress inhibition were able to restore mitochondrial function and consequently prevent motor neuron degeneration. These results uncover the cellular mechanisms underlying motor neuron degeneration mediated by loss of SIGMAR1 function and provide therapeutically relevant insight into motor neuronal diseases. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Developmental exposure to a complex PAH mixture causes persistent behavioral effects in naive Fundulus heteroclitus (killifish) but not in a population of PAH-adapted killifish.

PubMed

Brown, D R; Bailey, J M; Oliveri, A N; Levin, E D; Di Giulio, R T

2016-01-01

Acute exposures to some individual polycyclic aromatic hydrocarbons (PAHs) and complex PAH mixtures are known to cause cardiac malformations and edema in the developing fish embryo. However, the heart is not the only organ impacted by developmental PAH exposure. The developing brain is also affected, resulting in lasting behavioral dysfunction. While acute exposures to some PAHs are teratogenically lethal in fish, little is known about the later life consequences of early life, lower dose subteratogenic PAH exposures. We sought to determine and characterize the long-term behavioral consequences of subteratogenic developmental PAH mixture exposure in both naive killifish and PAH-adapted killifish using sediment pore water derived from the Atlantic Wood Industries Superfund Site. Killifish offspring were embryonically treated with two low-level PAH mixture dilutions of Elizabeth River sediment extract (ERSE) (TPAH 5.04 μg/L and 50.4 μg/L) at 24h post fertilization. Following exposure, killifish were raised to larval, juvenile, and adult life stages and subjected to a series of behavioral tests including: a locomotor activity test (4 days post-hatch), a sensorimotor response tap/habituation test (3 months post hatch), and a novel tank diving and exploration test (3months post hatch). Killifish were also monitored for survival at 1, 2, and 5 months over 5-month rearing period. Developmental PAH exposure caused short-term as well as persistent behavioral impairments in naive killifish. In contrast, the PAH-adapted killifish did not show behavioral alterations following PAH exposure. PAH mixture exposure caused increased mortality in reference killifish over time; yet, the PAH-adapted killifish, while demonstrating long-term rearing mortality, had no significant changes in mortality associated with ERSE exposure. This study demonstrated that early embryonic exposure to PAH-contaminated sediment pore water caused long-term locomotor and behavioral alterations in killifish, and that locomotor alterations could be observed in early larval stages. Additionally, our study highlights the resistance to behavioral alterations caused by low-level PAH mixture exposure in the adapted killifish population. Furthermore, this is the first longitudinal behavioral study to use killifish, an environmentally important estuarine teleost fish, and this testing framework can be used for future contaminant assessment. Copyright © 2015 Elsevier Inc. All rights reserved.

Anxiolytic-Like Effects and Increase in Locomotor Activity Induced by Infusions of NMDA into the Ventral Hippocampus in Rat: Interaction with GABAergic System.

PubMed

Bina, Payvand; Rezvanfard, Mehrnaz; Ahmadi, Shamseddin; Zarrindast, Mohammad Reza

2014-10-01

In this study, we investigated the role of N-Methyl-D-Aspartate (NMDA) receptors in the ventral hippocampus (VH) and their possible interactions with GABAA system on anxiety-like behaviors. We used an elevated-plus maze test (EPM) to assess anxiety-like behaviors and locomotor activity in male Wistar rats. The results showed that intra-VH infusions of different doses of NMDA (0.25 and 0.5 μg/rat) increased locomotor activity, and also induced anxiolytic-like behaviors, as revealed by a tendency to increase percentage of open arm time (%OAT), and a significant increase in percentage of open arm entries (%OAE). The results also showed that intra-VH infusions of muscimol (0.5 and 1 μg/rat) or bicuculline (0.5 and 1 μg/rat) did not significantly affect anxiety-like behaviors, but bicuculline at dose of 1 μg/rat increased locomotor activity. Intra-VH co-infusions of muscimol (0.5 μg/rat) along with low doses of NMDA (0.0625 and 0.125 μg/rat) showed a tendency to increase %OAT, %OAE and locomotor activity; however, no interaction was observed between the drugs. Interestingly, intra-VH co-infusions of bicuculline (0.5 μg/rat) along with effective doses of NMDA (0.25 and 0.5 μg/rat) decreased %OAT, %OAE and locomotor activity, and a significant interaction between two drugs was observed. It can be concluded that GABAergic system may mediate the anxiolytic-like effects and increase in locomotor activity induced by NMDA in the VH.

Levamisole enhances the rewarding and locomotor-activating effects of cocaine in rats.

PubMed

Tallarida, Christopher S; Tallarida, Ronald J; Rawls, Scott M

2015-04-01

The Drug Enforcement Agency estimates that 80% of cocaine seized in the United States contains the veterinary pharmaceutical levamisole (LVM). One problem with LVM is that it is producing life-threatening neutropenia in an alarming number of cocaine abusers. The neuropharmacological profile of LVM is also suggestive of an agent with modest reinforcing and stimulant effects that could enhance cocaine's addictive effects. We tested the hypothesis that LVM (ip) enhances the rewarding and locomotor stimulant effects of cocaine (ip) using rat conditioned place preference (CPP) and locomotor assays. Effects of LVM by itself were also tested. LVM (0-10 mg/kg) produced CPP at 1mg/kg (P<0.05) and locomotor activation at 5mg/kg (P < 0.05). For CPP combination experiments, a statistically inactive dose of LVM (0.1 mg/kg) was administered with a low dose of cocaine (2.5 mg/kg). Neither agent produced CPP compared to saline (P > 0.05); however, the combination of LVM and cocaine produced enhanced CPP compared to saline or either drug by itself (P < 0.01). For locomotor experiments, the same inactive dose of LVM (0.1mg/kg, ip) was administered with low (10 mg/kg) and high doses (30 mg/kg) of cocaine. LVM (0.1 mg/kg) enhanced locomotor activation produced by 10mg/kg of cocaine (P < 0.05) but not by 30 mg/kg (P>0.05). LVM can enhance rewarding and locomotor-activating effects of low doses of cocaine in rats while possessing modest activity of its own. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Locomotor adaptability in persons with unilateral transtibial amputation.

PubMed

Darter, Benjamin J; Bastian, Amy J; Wolf, Erik J; Husson, Elizabeth M; Labrecque, Bethany A; Hendershot, Brad D

2017-01-01

Locomotor adaptation enables walkers to modify strategies when faced with challenging walking conditions. While a variety of neurological injuries can impair locomotor adaptability, the effect of a lower extremity amputation on adaptability is poorly understood. Determine if locomotor adaptability is impaired in persons with unilateral transtibial amputation (TTA). The locomotor adaptability of 10 persons with a TTA and 8 persons without an amputation was tested while walking on a split-belt treadmill with the parallel belts running at the same (tied) or different (split) speeds. In the split condition, participants walked for 15 minutes with the respective belts moving at 0.5 m/s and 1.5 m/s. Temporal spatial symmetry measures were used to evaluate reactive accommodations to the perturbation, and the adaptive/de-adaptive response. Persons with TTA and the reference group of persons without amputation both demonstrated highly symmetric walking at baseline. During the split adaptation and tied post-adaptation walking both groups responded with the expected reactive accommodations. Likewise, adaptive and de-adaptive responses were observed. The magnitude and rate of change in the adaptive and de-adaptive responses were similar for persons with TTA and those without an amputation. Furthermore, adaptability was no different based on belt assignment for the prosthetic limb during split adaptation walking. Reactive changes and locomotor adaptation in response to a challenging and novel walking condition were similar in persons with TTA to those without an amputation. Results suggest persons with TTA have the capacity to modify locomotor strategies to meet the demands of most walking conditions despite challenges imposed by an amputation and use of a prosthetic limb.

Long-term imaging of circadian locomotor rhythms of a freely crawling C. elegans population

PubMed Central

Winbush, Ari; Gruner, Matthew; Hennig, Grant W.; van der Linden, Alexander M.

2016-01-01

Background Locomotor activity is used extensively as a behavioral output to study the underpinnings of circadian rhythms. Recent studies have required a populational approach for the study of circadian rhythmicity in Caenorhabditis elegans locomotion. New method We describe an imaging system for long-term automated recording and analysis of locomotion data of multiple free-crawling C. elegans animals on the surface of an agar plate. We devised image analysis tools for measuring specific features related to movement and shape to identify circadian patterns. Results We demonstrate the utility of our system by quantifying circadian locomotor rhythms in wild-type and mutant animals induced by temperature cycles. We show that 13 °C:18 °C (12:12 h) cycles are sufficient to entrain locomotor activity of wild-type animals, which persist but are rapidly damped during 13 °C free-running conditions. Animals with mutations in tax-2, a cyclic nucleotide-gated (CNG) ion channel, significantly reduce locomotor activity during entrainment and free-running. Comparison with existing method(s) Current methods for measuring circadian locomotor activity is generally restricted to recording individual swimming animals of C. elegans, which is a distinct form of locomotion from crawling behavior generally observed in the laboratory. Our system works well with up to 20 crawling adult animals, and allows for a detailed analysis of locomotor activity over long periods of time. Conclusions Our population-based approach provides a powerful tool for quantification of circadian rhythmicity of C. elegans locomotion, and could allow for a screening system of candidate circadian genes in this model organism. PMID:25911068

Effects of Sodium Butyrate on Methamphetamine-Sensitized Locomotor Activity

PubMed Central

Harkness, John H.; Hitzemann, Robert J.; Edmunds, Stephanie; Phillips, Tamara J.

2012-01-01

Neuroadaptations associated with behavioral sensitization induced by repeated exposure to methamphetamine (MA) appear to be involved in compulsive drug pursuit and use. Increased histone acetylation, an epigenetic effect resulting in altered gene expression, may promote sensitized responses to psychostimulants. The role of histone acetylation in the expression and acquisition of MA-induced locomotor sensitization was examined by measuring the effect of histone deacetylase inhibition by sodium butyrate (NaB). For the effect on expression, vehicle or NaB (630 mg/kg, intraperitoneally) was administered 30 min prior to MA challenge in mice treated repeatedly with MA (10 days of 2 mg/kg MA) or saline (10 days), and then locomotor response to MA challenge was measured. NaB treatment increased the locomotor response to MA in both acutely MA treated and sensitized animals. For acquisition, NaB was administered 30 min prior to each MA exposure (10 days of 1 or 2 mg/kg), but not prior to the MA challenge test. Treatment with NaB during the sensitization acquisition period significantly increased locomotor activation by MA in sensitized mice only. NaB alone did not significantly alter locomotor activity. Acute NaB or MA, but not the combination, appeared to increase striatal acetylation at histone H4. Repeated treatment with MA, but not NaB or MA plus NaB, increased striatal acetylation at histone H3. Although increased histone acetylation may alter the expression of genes involved in acute locomotor response to MA and in the acquisition of MA-induced sensitization, results for acetylation at H3 and H4 showed little correspondence with behavior. PMID:23137698

Asymmetric Operation of the Locomotor Central Pattern Generator in the Neonatal Mouse Spinal Cord

PubMed Central

Endo, Toshiaki; Kiehn, Ole

2008-01-01

The rhythmic voltage oscillations in motor neurons (MNs) during locomotor movements reflect the operation of the pre-MN central pattern generator (CPG) network. Recordings from MNs can thus be used as a method to deduct the organization of CPGs. Here, we use continuous conductance measurements and decomposition methods to quantitatively assess the weighting and phase tuning of synaptic inputs to different flexor and extensor MNs during locomotor-like activity in the isolated neonatal mice lumbar spinal cord preparation. Whole cell recordings were obtained from 22 flexor and 18 extensor MNs in rostral and caudal lumbar segments. In all flexor and the large majority of extensor MNs the extracted excitatory and inhibitory synaptic conductances alternate but with a predominance of inhibitory conductances, most pronounced in extensors. These conductance changes are consistent with a “push–pull” operation of locomotor CPG. The extracted excitatory and inhibitory synaptic conductances varied between 2 and 56% of the mean total conductance. Analysis of the phase tuning of the extracted synaptic conductances in flexor and extensor MNs in the rostral lumbar cord showed that the flexor-phase–related synaptic conductance changes have sharper locomotor-phase tuning than the extensor-phase–related conductances, suggesting a modular organization of premotor CPG networks consisting of reciprocally coupled, but differently composed, flexor and extensor CPG networks. There was a clear difference between phase tuning in rostral and caudal MNs, suggesting a distinct operation of CPG networks in different lumbar segments. The highly asymmetric features were preserved throughout all ranges of locomotor frequencies investigated and with different combinations of locomotor-inducing drugs. The asymmetric nature of CPG operation and phase tuning of the conductance profiles provide important clues to the organization of the rodent locomotor CPG and are compatible with a multilayered and distributed structure of the network. PMID:18829847

Drosophila Clock Is Required in Brain Pacemaker Neurons to Prevent Premature Locomotor Aging Independently of Its Circadian Function

PubMed Central

Issa, Abdul-Raouf; Seugnet, Laurent; Klarsfeld, André

2017-01-01

Circadian clocks control many self-sustained rhythms in physiology and behavior with approximately 24-hour periodicity. In many organisms, oxidative stress and aging negatively impact the circadian system and sleep. Conversely, loss of the clock decreases resistance to oxidative stress, and may reduce lifespan and speed up brain aging and neurodegeneration. Here we examined the effects of clock disruptions on locomotor aging and longevity in Drosophila. We found that lifespan was similarly reduced in three arrhythmic mutants (ClkAR, cyc0 and tim0) and in wild-type flies under constant light, which stops the clock. In contrast, ClkAR mutants showed significantly faster age-related locomotor deficits (as monitored by startle-induced climbing) than cyc0 and tim0, or than control flies under constant light. Reactive oxygen species accumulated more with age in ClkAR mutant brains, but this did not appear to contribute to the accelerated locomotor decline of the mutant. Clk, but not Cyc, inactivation by RNA interference in the pigment-dispersing factor (PDF)-expressing central pacemaker neurons led to similar loss of climbing performance as ClkAR. Conversely, restoring Clk function in these cells was sufficient to rescue the ClkAR locomotor phenotype, independently of behavioral rhythmicity. Accelerated locomotor decline of the ClkAR mutant required expression of the PDF receptor and correlated to an apparent loss of dopaminergic neurons in the posterior protocerebral lateral 1 (PPL1) clusters. This neuronal loss was rescued when the ClkAR mutation was placed in an apoptosis-deficient background. Impairing dopamine synthesis in a single pair of PPL1 neurons that innervate the mushroom bodies accelerated locomotor decline in otherwise wild-type flies. Our results therefore reveal a novel circadian-independent requirement for Clk in brain circadian neurons to maintain a subset of dopaminergic cells and avoid premature locomotor aging in Drosophila. PMID:28072817

Behavioral Characterization of the Effects of Cannabis Smoke and Anandamide in Rats

PubMed Central

Bruijnzeel, Adriaan W.; Qi, Xiaoli; Guzhva, Lidia V.; Wall, Shannon; Deng, Jie V.; Gold, Mark S.; Febo, Marcelo; Setlow, Barry

2016-01-01

Cannabis is the most widely used illicit drug in the world. Delta-9-tetrahydrocannabinol (Δ9-THC) is the main psychoactive component of cannabis and its effects have been well-studied. However, cannabis contains many other cannabinoids that affect brain function. Therefore, these studies investigated the effect of cannabis smoke exposure on locomotor activity, rearing, anxiety-like behavior, and the development of dependence in rats. It was also investigated if cannabis smoke exposure leads to tolerance to the locomotor-suppressant effects of the endogenous cannabinoid anandamide. Cannabis smoke was generated by burning 5.7% Δ9-THC cannabis cigarettes in a smoking machine. The effect of cannabis smoke on the behavior of rats in a small and large open field and an elevated plus maze was evaluated. Cannabis smoke exposure induced a brief increase in locomotor activity followed by a prolonged decrease in locomotor activity and rearing in the 30-min small open field test. The cannabinoid receptor type 1 (CB1) receptor antagonist rimonabant increased locomotor activity and prevented the smoke-induced decrease in rearing. Smoke exposure also increased locomotor activity in the 5-min large open field test and the elevated plus maze test. The smoke exposed rats spent more time in the center zone of the large open field, which is indicative of a decrease in anxiety-like behavior. A high dose of anandamide decreased locomotor activity and rearing in the small open field and this was not prevented by rimonabant or pre-exposure to cannabis smoke. Serum Δ9-THC levels were 225 ng/ml after smoke exposure, which is similar to levels in humans after smoking cannabis. Exposure to cannabis smoke led to dependence as indicated by more rimonabant-precipitated somatic withdrawal signs in the cannabis smoke exposed rats than in the air-control rats. In conclusion, chronic cannabis smoke exposure in rats leads to clinically relevant Δ9-THC levels, dependence, and has a biphasic effect on locomotor activity. PMID:27065006

Behavioral Characterization of the Effects of Cannabis Smoke and Anandamide in Rats.

PubMed

Bruijnzeel, Adriaan W; Qi, Xiaoli; Guzhva, Lidia V; Wall, Shannon; Deng, Jie V; Gold, Mark S; Febo, Marcelo; Setlow, Barry

2016-01-01

Cannabis is the most widely used illicit drug in the world. Delta-9-tetrahydrocannabinol (Δ9-THC) is the main psychoactive component of cannabis and its effects have been well-studied. However, cannabis contains many other cannabinoids that affect brain function. Therefore, these studies investigated the effect of cannabis smoke exposure on locomotor activity, rearing, anxiety-like behavior, and the development of dependence in rats. It was also investigated if cannabis smoke exposure leads to tolerance to the locomotor-suppressant effects of the endogenous cannabinoid anandamide. Cannabis smoke was generated by burning 5.7% Δ9-THC cannabis cigarettes in a smoking machine. The effect of cannabis smoke on the behavior of rats in a small and large open field and an elevated plus maze was evaluated. Cannabis smoke exposure induced a brief increase in locomotor activity followed by a prolonged decrease in locomotor activity and rearing in the 30-min small open field test. The cannabinoid receptor type 1 (CB1) receptor antagonist rimonabant increased locomotor activity and prevented the smoke-induced decrease in rearing. Smoke exposure also increased locomotor activity in the 5-min large open field test and the elevated plus maze test. The smoke exposed rats spent more time in the center zone of the large open field, which is indicative of a decrease in anxiety-like behavior. A high dose of anandamide decreased locomotor activity and rearing in the small open field and this was not prevented by rimonabant or pre-exposure to cannabis smoke. Serum Δ9-THC levels were 225 ng/ml after smoke exposure, which is similar to levels in humans after smoking cannabis. Exposure to cannabis smoke led to dependence as indicated by more rimonabant-precipitated somatic withdrawal signs in the cannabis smoke exposed rats than in the air-control rats. In conclusion, chronic cannabis smoke exposure in rats leads to clinically relevant Δ9-THC levels, dependence, and has a biphasic effect on locomotor activity.

Neurologic music therapy in upper-limb rehabilitation in children with severe bilateral cerebral palsy: a randomized controlled trial.

PubMed

Marrades-Caballero, Eugenio; Santonja-Medina, Clara S; Sanz-Mengibar, Jose M; Santonja-Medina, Fernando

2018-02-26

After receiving neurologic music therapy, functional improvements in children with severe bilateral cerebral palsy have not been found in the literature. Musical training with instruments allows interrelationships between movement, emotions and cognition for task-based learning, in order to improve motor control. To understand whether neurologic music therapy has an impact on the functionality of children with severe cerebral palsy. A randomized controlled assessor-blind trial was carried out. Children were recruited and treated in their own community center. Eighteen children with severe bilateral cerebral palsy between 4 and 16 years old were studied. The intervention group (n=18) received music therapy for 16 weeks, in addition to its usual physiotherapy input. Two music therapists implemented a neurologic music therapy program of therapeutic instrumental music performance. The control group (n=9) received its usual therapeutic input, similar to the intervention group, but not neurologic music therapy. Overall and specific "Chailey levels of Ability" were quantified, as well as the Locomotor Stages. Significant improvements in the overall and specific "arm and hand position" as well as "activities" from the Chailey Levels of Ability and the Locomotor Stages were observed (p<.05) in the group which received the music therapy (corregir si se acepta en la editing proofs). All these improvements persisted after 4 months. The control group showed no improvements after a four-month follow-up. Optimized intervention of neurologic music therapy can improve the functionality of children with severe bilateral cerebral palsy. Music therapy is a useful tool in rehabilitation and its positive effects remain four months after completing the treatment.

Search and Neutralize Factors (Cspgs) that Induce Decline in Transmission to Motoneurons from Spared Fibers after Chronic Spinal Cord Injury

DTIC Science & Technology

2014-04-01

conducted experiments using intraspinal injections of AAV10-NG2Ab combined with AAV10 vector expressing neurotrophin 3 (AAV10-NT3-gfp) in adult rat...mediated delivery of NG2-Ab and neurotrophin NT3 expressing units significantly improved locomotor function following SCI. These behavioral improvements...mediated delivery of NG2-Ab combined with neurotrophin NT3 in rats that received either hemisection or contusion SCI. We found that rats that

Metabolomic Changes in Rat Model of Cauda Equina Injury.

PubMed

Liu, Yang; Yang, Rui; Kong, Qingjie; Wang, Yuan; Zhang, Bin; Sun, Jingchuan; Yang, Yong; Zheng, Bing; Yuan, Hongbin; Shi, Jiangang

2017-06-01

To show the differences of metabolomic changes in a rat model of cauda equina injury (CEI) and find potent metabolic biomarkers of CEI. A total of 28 Sprague-Dawley rats were used in this study. After the rats were given anesthesia and fixed in a prone position, a piece of silicone block was placed into the epidural space below the lamina. Behavior tests including the Basso, Beattie, and Bresnahan open field locomotor scale and an inclined plane test were conducted 1 day and 2 days after surgery. The cauda equina tissue was collected 12 hours, 1 day, and 2 days after surgery. Ultraperformance liquid chromatography coupled with quadruple time-of-flight mass spectrometry was used for a quantitative analysis of cauda equine metabolic changes in rats from different groups. The differences between the metabolic profiles of the rats in 4 groups were analyzed using partial least squares discriminant analysis. In behavior tests and histologic analyses given 2 days after surgery, the animals showed remarkable organ dysfunction and pathologic damage. Metabolic profiles showed remarkable differences between the control and model groups. Thirty-four potential CEI metabolite biomarkers were identified between the control group and different time-point model groups. These potential biomarkers appeared in 15 metabolic pathways. Our results may improve the cause of CEI and provide a basis for clinical diagnosis and locating biomarkers in the early stages of the pathologic process of CEI. Copyright © 2017 Elsevier Inc. All rights reserved.

Cell cycle inhibition limits development and maintenance of neuropathic pain following spinal cord injury

PubMed Central

Wu, Junfang; Zhao, Zaorui; Zhu, Xiya; Renn, Cynthia L.; Dorsey, Susan G.; Faden, Alan I.

2016-01-01

Chronic pain after spinal cord injury (SCI) may present as hyperalgesia, allodynia, and/or spontaneous pain and is often resistant to conventional pain medications. Identifying more effective interventions to manage SCI-Pain requires improved understanding of the pathophysiological mechanisms involved. Cell cycle activation (CCA) has been implicated as a key pathophysiological event following SCI. We have shown that early central or systemic administration of a cell cycle inhibitor reduces CCA, prevents glial changes, and limits SCI-induced hyperesthesia. Here we compared the effects of early versus late treatment with the pan-cyclin dependent kinase inhibitor flavopiridol on allodynia as well as spontaneous pain. Adult C57BL/6 male mice subjected to moderate SCI were treated with intraperitoneal injections of flavopiridol (1 mg/kg), daily for 7 days beginning either 3 h or 5 weeks after injury. Mechanical/thermal allodynia was evaluated, as well as spontaneous pain using the mouse grimace scale (MGS). We show that sensitivity to mechanical and thermal stimulation, and locomotor dysfunction were significantly reduced by early flavopiridol treatment compared to vehicle treated controls. SCI caused robust and extended increases of MGS up to 3 weeks after trauma. Early administration of flavopiridol significantly shortened duration of MGS changes. Late flavopiridol intervention significantly limited hyperesthesia at 7 days after treatment, associated with reduced glial changes, but without effect on locomotion. Thus, our data suggest that cell cycle modulation may provide an effective therapeutic strategy to reduce hyperesthesia after SCI, with a prolonged therapeutic window. PMID:26797506

Selective preservation of cholinergic MeCP2 rescues specific Rett-syndrome-like phenotypes in MeCP2stop mice.

PubMed

Zhou, Huanhuan; Wu, Wei; Zhang, Ying; He, Haiyang; Yuan, Zhefeng; Zhu, Zhiwei; Zhao, Zhengyan

2017-03-30

RTT is a neurodevelopmental disorder characterized by growth regression, motor dysfunction, stereotypic hand movements, and autism features. Typical Rett syndrome (RTT) is predominantly caused by mutations in X-linked MeCP2 gene which encodes methyl-CpG-binding protein 2 (MeCP2). The brain-abundant MeCP2 protein mainly functions as a transcriptional regulator for neurodevelopment-associated genes. Specific functions of MeCP2 in certain neuron types remain to be known. Although cholinergic system is an important modulating system in brain, how MeCP2 in cholinergic neurons contribute to RTT has not been clearly understood. Here we use a mouse model with selectively activated endogenous MeCP2 in cholinergic neurons in otherwise MeCP2 stop mice to determine the cholinergic MeCP2 effects on rescuing the RTT-like phenotypes. We found cholinergic MeCP2 preservation could reverse some aspects of the RTT-like phenotypes in mice including hypolocomotion and increased anxiety level, and delay the onset of underweight, instead of improving the hypersocial abnormality and the poor general conditions such as short lifespan, low brain weight, and increasing severity score. Our findings suggest that selective activation of cholinergic MeCP2 is sufficient to reverse the locomotor impairment and increased anxiety-like behaviors at least in early symptomatic stage, supporting future development of RTT therapies associated with cholinergic system. Copyright © 2017 Elsevier B.V. All rights reserved.

Transplantation of Human Skin-Derived Mesenchymal Stromal Cells Improves Locomotor Recovery After Spinal Cord Injury in Rats.

PubMed

Melo, Fernanda Rosene; Bressan, Raul Bardini; Forner, Stefânia; Martini, Alessandra Cadete; Rode, Michele; Delben, Priscilla Barros; Rae, Giles Alexander; Figueiredo, Claudia Pinto; Trentin, Andrea Gonçalves

2017-07-01

Spinal cord injury (SCI) is a devastating neurologic disorder with significant impacts on quality of life, life expectancy, and economic burden. Although there are no fully restorative treatments yet available, several animal and small-scale clinical studies have highlighted the therapeutic potential of cellular interventions for SCI. Mesenchymal stem cells (MSCs)-which are conventionally isolated from the bone marrow-recently emerged as promising candidates for treating SCI and have been shown to provide trophic support, ameliorate inflammatory responses, and reduce cell death following the mechanical trauma. Here we evaluated the human skin as an alternative source of adult MSCs suitable for autologous cell transplantation strategies for SCI. We showed that human skin-derived MSCs (hSD-MSCs) express a range of neural markers under standard culture conditions and are able to survive and respond to neurogenic stimulation in vitro. In addition, using histological analysis and behavioral assessment, we demonstrated as a proof-of-principle that hSD-MSC transplantation reduces the severity of tissue loss and facilitates locomotor recovery in a rat model of SCI. Altogether, the study provides further characterization of skin-derived MSC cultures and indicates that the human skin may represent an attractive source for cell-based therapies for SCI and other neurological disorders. Further investigation is needed to elucidate the mechanisms by which hSD-MSCs elicit tissue repair and/or locomotor recovery.

Feasibility of Synergy-Based Exoskeleton Robot Control in Hemiplegia.

PubMed

Hassan, Modar; Kadone, Hideki; Ueno, Tomoyuki; Hada, Yasushi; Sankai, Yoshiyuki; Suzuki, Kenji

2018-06-01

Here, we present a study on exoskeleton robot control based on inter-limb locomotor synergies using a robot control method developed to target hemiparesis. The robot control is based on inter-limb locomotor synergies and kinesiological information from the non-paretic leg and a walking aid cane to generate motion patterns for the assisted leg. The developed synergy-based system was tested against an autonomous robot control system in five patients with hemiparesis and varying locomotor abilities. Three of the participants were able to walk using the robot. Results from these participants showed an improved spatial symmetry ratio and more consistent step length with the synergy-based method compared with that for the autonomous method, while the increase in the range of motion for the assisted joints was larger with the autonomous system. The kinematic synergy distribution of the participants walking without the robot suggests a relationship between each participant's synergy distribution and his/her ability to control the robot: participants with two independent synergies accounting for approximately 80% of the data variability were able to walk with the robot. This observation was not consistently apparent with conventional clinical measures such as the Brunnstrom stages. This paper contributes to the field of robot-assisted locomotion therapy by introducing the concept of inter-limb synergies, demonstrating performance differences between synergy-based and autonomous robot control, and investigating the range of disability in which the system is usable.

The anatomy and physiology of the locomotor system.

PubMed

Farley, Alistair; McLafferty, Ella; Hendry, Charles

Mobilisation is one of the activities of living. The term locomotor system refers to those body tissues and organs responsible for movement. Nurses and healthcare workers should be familiar with the body structures that enable mobilisation to assist those in their care with this activity. This article outlines the structure and function of the locomotor system, including the skeleton, joints, muscles and muscle attachments. Two common bone disorders, osteoporosis and osteoarthritis, are also considered.

[Watsu: a modern method in physiotherapy, body regeneration, and sports].

PubMed

Weber-Nowakowska, Katarzyna; Gebska, Magdalena; Zyzniewska-Banaszak, Ewelina

2013-01-01

Progress in existing methods of physiotherapy and body regeneration and introduction of new methods has made it possible to precisely select the techniques according to patient needs. The modern therapist is capable of improving the physical and mental condition of the patient. Watsu helps the therapist eliminate symptoms from the locomotor system and reach the psychic sphere at the same time.

[Physical activity diminishes aging-related decline of physical and cognitive performance].

PubMed

Apor, Péter; Babai, László

2014-05-25

Aging-related decline of muscle force, walking speed, locomotor coordination, aerobic capacity and endurance exert prognostic impact on life expectancy. Proper use of training may diminish the aging process and it may improve the quality of life of elderly persons. This paper provides a brief summary on the impact of training on aging-related decline of physical and cognitive functions.

Smart Soup, a Traditional Chinese Medicine Formula, Ameliorates Amyloid Pathology and Related Cognitive Deficits

PubMed Central

Li, Xiaohang; Cui, Jin; Ding, Jianqing; Wang, Ying; Zeng, Xianglu; Ling, Yun; Shen, Xiaoheng; Chen, Shengdi; Huang, Chenggang; Pei, Gang

2014-01-01

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that causes substantial public health care burdens. Intensive efforts have been made to find effective and safe disease-modifying treatment and symptomatic intervention alternatives against AD. Smart Soup (SS), a Chinese medicine formula composed of Rhizoma Acori Tatarinowii (AT), Poria cum Radix Pini (PRP) and Radix Polygalae (RP), is a typical prescription against memory deficits. Here, we assessed the efficacy of SS against AD. Oral administration of SS ameliorated the cognitive impairment of AD transgenic mice, with reduced Aβ levels, retarded Aβ amyloidosis and reduced Aβ-induced gliosis and neuronal loss in the brains of AD mice. Consistently, SS treatment reduced amyloid-related locomotor dysfunctions and premature death of AD transgenic Drosophila. Mechanistic studies showed that RP reduced Aβ generation, whereas AT and PRP exerted neuroprotective effects against Aβ. Taken together, our study indicates that SS could be effective against AD, providing a practical therapeutic strategy against the disease. PMID:25386946

Foot Structure in Boys with Down Syndrome.

PubMed

Puszczałowska-Lizis, Ewa; Nowak, Krzysztof; Omorczyk, Jarosław; Ambroży, Tadeusz; Bujas, Przemysław; Nosiadek, Leszek

2017-01-01

Down syndrome (DS) is associated with numerous developmental abnormalities, some of which cause dysfunctions of the posture and the locomotor system. The analysis of selected features of the foot structure in boys with DS versus their peers without developmental disorders is done. The podoscopic examination was performed on 30 boys with DS aged 14-15 years. A control group consisted of 30 age- and gender-matched peers without DS. The feet of boys with DS are flatter compared to their healthy peers. The hallux valgus angle is not the most important feature differentiating the shape of the foot in the boys with DS and their healthy peers. In terms of the V toe setting, healthy boys had poorer results. Specialized therapeutic treatment in individuals with DS should involve exercises to increase the muscle strength around the foot joints, enhancing the stabilization in the joints and proprioception. Introducing orthotics and proper footwear is also important. It is also necessary to monitor the state of the foot in order to modify undertaken therapies.

Antidepressant-like effects of a cocoa polyphenolic extract in Wistar-Unilever rats.

PubMed

Messaoudi, Michaël; Bisson, Jean-François; Nejdi, Amine; Rozan, Pascale; Javelot, Hervé

2008-12-01

Depression is a major public health problem affecting about 12% of the world population. Drugs exist but they have many side effects. In the last few years, natural substances (e.g. flavonoids) have been tested to cure such disorders. Cocoa polyphenolic extract is a complex compound prepared from non-roasted cocoa beans containing high levels of flavonoids. The antidepressant-like effect of cocoa polyphenolic extract was evaluated using the forced swimming test in rats. Cocoa polyphenolic extract significantly reduced the duration of immobility at both doses of 24 mg/kg/14 days and 48 mg/kg/14 days, although no change of motor dysfunction was observed with the two doses tested in the open field. The results of the forced swimming test after a subchronic treatment and after an additional locomotor activity test confirm the assumption that the antidepressant-like effect of cocoa polyphenolic extract in the forced swimming test model is specific. Further, it can be speculated that this effect might be related to its content of active polyphenols.

Influence of Brain Stem on Axial and Hindlimb Spinal Locomotor Rhythm Generating Circuits of the Neonatal Mouse.

PubMed

Jean-Xavier, Céline; Perreault, Marie-Claude

2018-01-01

The trunk plays a pivotal role in limbed locomotion. Yet, little is known about how the brain stem controls trunk activity during walking. In this study, we assessed the spatiotemporal activity patterns of axial and hindlimb motoneurons (MNs) during drug-induced fictive locomotor-like activity (LLA) in an isolated brain stem-spinal cord preparation of the neonatal mouse. We also evaluated the extent to which these activity patterns are affected by removal of brain stem. Recordings were made in the segments T7, L2, and L5 using calcium imaging from individual axial MNs in the medial motor column (MMC) and hindlimb MNs in lateral motor column (LMC). The MN activities were analyzed during both the rhythmic and the tonic components of LLA, the tonic component being used as a readout of generalized increase in excitability in spinal locomotor networks. The most salient effect of brain stem removal was an increase in locomotor rhythm frequency and a concomitant reduction in burst durations in both MMC and LMC MNs. The lack of effect on the tonic component of LLA indicated specificity of action during the rhythmic component. Cooling-induced silencing of the brain stem reproduced the increase in rhythm frequency and accompanying decrease in burst durations in L2 MMC and LMC, suggesting a dependency on brain stem neuron activity. The work supports the idea that the brain stem locomotor circuits are operational already at birth and further suggests an important role in modulating trunk activity. The brain stem may influence the axial and hindlimb spinal locomotor rhythm generating circuits by extending their range of operation. This may represent a critical step of locomotor development when learning how to walk in different conditions and environments is a major endeavor.

Influence of Brain Stem on Axial and Hindlimb Spinal Locomotor Rhythm Generating Circuits of the Neonatal Mouse

PubMed Central

Jean-Xavier, Céline; Perreault, Marie-Claude

2018-01-01

The trunk plays a pivotal role in limbed locomotion. Yet, little is known about how the brain stem controls trunk activity during walking. In this study, we assessed the spatiotemporal activity patterns of axial and hindlimb motoneurons (MNs) during drug-induced fictive locomotor-like activity (LLA) in an isolated brain stem-spinal cord preparation of the neonatal mouse. We also evaluated the extent to which these activity patterns are affected by removal of brain stem. Recordings were made in the segments T7, L2, and L5 using calcium imaging from individual axial MNs in the medial motor column (MMC) and hindlimb MNs in lateral motor column (LMC). The MN activities were analyzed during both the rhythmic and the tonic components of LLA, the tonic component being used as a readout of generalized increase in excitability in spinal locomotor networks. The most salient effect of brain stem removal was an increase in locomotor rhythm frequency and a concomitant reduction in burst durations in both MMC and LMC MNs. The lack of effect on the tonic component of LLA indicated specificity of action during the rhythmic component. Cooling-induced silencing of the brain stem reproduced the increase in rhythm frequency and accompanying decrease in burst durations in L2 MMC and LMC, suggesting a dependency on brain stem neuron activity. The work supports the idea that the brain stem locomotor circuits are operational already at birth and further suggests an important role in modulating trunk activity. The brain stem may influence the axial and hindlimb spinal locomotor rhythm generating circuits by extending their range of operation. This may represent a critical step of locomotor development when learning how to walk in different conditions and environments is a major endeavor. PMID:29479302

Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats

PubMed Central

Eagle, Andrew L.; Singh, Robby; Kohler, Robert J.; Friedman, Amy L.; Liebowitz, Chelsea P.; Galloway, Matthew P.; Enman, Nicole M.; Jutkiewicz, Emily M.; Perrine, Shane A.

2017-01-01

Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague–Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0,10 or 20mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, asexpected. However, compared to control ratson Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement. PMID:25712697

Locomotor Muscle Fatigue Does Not Alter Oxygen Uptake Kinetics during High-Intensity Exercise.

PubMed

Hopker, James G; Caporaso, Giuseppe; Azzalin, Andrea; Carpenter, Roger; Marcora, Samuele M

2016-01-01

The [Formula: see text] slow component ([Formula: see text]) that develops during high-intensity aerobic exercise is thought to be strongly associated with locomotor muscle fatigue. We sought to experimentally test this hypothesis by pre-fatiguing the locomotor muscles used during subsequent high-intensity cycling exercise. Over two separate visits, eight healthy male participants were asked to either perform a non-metabolically stressful 100 intermittent drop-jumps protocol (pre-fatigue condition) or rest for 33 min (control condition) according to a random and counterbalanced order. Locomotor muscle fatigue was quantified with 6-s maximal sprints at a fixed pedaling cadence of 90 rev·min -1 . Oxygen kinetics and other responses (heart rate, capillary blood lactate concentration and rating of perceived exertion, RPE) were measured during two subsequent bouts of 6 min cycling exercise at 50% of the delta between the lactate threshold and [Formula: see text] determined during a preliminary incremental exercise test. All tests were performed on the same cycle ergometer. Despite significant locomotor muscle fatigue ( P = 0.03), the [Formula: see text] was not significantly different between the pre-fatigue (464 ± 301 mL·min -1 ) and the control (556 ± 223 mL·min -1 ) condition ( P = 0.50). Blood lactate response was not significantly different between conditions ( P = 0.48) but RPE was significantly higher following the pre-fatiguing exercise protocol compared with the control condition ( P < 0.01) suggesting higher muscle recruitment. These results demonstrate experimentally that locomotor muscle fatigue does not significantly alter the [Formula: see text] kinetic response to high intensity aerobic exercise, and challenge the hypothesis that the [Formula: see text] is strongly associated with locomotor muscle fatigue.

Statistical Analysis of Zebrafish Locomotor Response.

PubMed

Liu, Yiwen; Carmer, Robert; Zhang, Gaonan; Venkatraman, Prahatha; Brown, Skye Ashton; Pang, Chi-Pui; Zhang, Mingzhi; Ma, Ping; Leung, Yuk Fai

2015-01-01

Zebrafish larvae display rich locomotor behaviour upon external stimulation. The movement can be simultaneously tracked from many larvae arranged in multi-well plates. The resulting time-series locomotor data have been used to reveal new insights into neurobiology and pharmacology. However, the data are of large scale, and the corresponding locomotor behavior is affected by multiple factors. These issues pose a statistical challenge for comparing larval activities. To address this gap, this study has analyzed a visually-driven locomotor behaviour named the visual motor response (VMR) by the Hotelling's T-squared test. This test is congruent with comparing locomotor profiles from a time period. Different wild-type (WT) strains were compared using the test, which shows that they responded differently to light change at different developmental stages. The performance of this test was evaluated by a power analysis, which shows that the test was sensitive for detecting differences between experimental groups with sample numbers that were commonly used in various studies. In addition, this study investigated the effects of various factors that might affect the VMR by multivariate analysis of variance (MANOVA). The results indicate that the larval activity was generally affected by stage, light stimulus, their interaction, and location in the plate. Nonetheless, different factors affected larval activity differently over time, as indicated by a dynamical analysis of the activity at each second. Intriguingly, this analysis also shows that biological and technical repeats had negligible effect on larval activity. This finding is consistent with that from the Hotelling's T-squared test, and suggests that experimental repeats can be combined to enhance statistical power. Together, these investigations have established a statistical framework for analyzing VMR data, a framework that should be generally applicable to other locomotor data with similar structure.

Locomotor Training and Factors Associated with Blood Glucose Regulation After Spinal Cord Injury.

PubMed

Chilibeck, Philip D; Guertin, Pierre A

2017-01-01

Individuals with spinal cord injury (SCI) have increased rates of glucose intolerance, insulin insensitivity, and type II diabetes caused mainly by the deconditioning of paralyzed muscle. The purpose of this systematic review was to determine the effectiveness of locomotor training in individuals with SCI on blood glucose control. We searched studies on locomotor training for individuals with SCI with outcomes of glucose, insulin, or outcomes that could change glucose handling (i.e. increases in muscle mass, shifts in muscle fiber type composition, changes in transport proteins, or enzymes involved in glucose metabolism) in PubMed and EMBASE. Eleven studies (10 with incomplete SCI; 1 with complete SCI) were included in our review. Locomotor training included body weight supported treadmill training (BWSTT) with manual or robotic assistance, with and without functional electrical stimulation (FES), or involved FES-assisted over ground training. Six months of locomotor training in individuals with SCI resulted in significant decreases in glucose (15%) and insulin (33%) areas under the curve during oral glucose tolerance tests. Two to twelve months of locomotor training reversed some of the muscle atrophy - with muscle being the site of most glucose consumption, this is important for glucose control. Training also increased capacity for glucose storage, enzymes involved in glucose phosphorylation (hexokinase) and oxidation (citrate synthase), and glucose transport proteins (GLUT-4). Fiber type composition shifted to a slower fiber type, which favors glucose handling. There were no effects on fat mass. Locomotor training in individuals with SCI (generally an incomplete injury) increases capacity to handle glucose and results in muscular changes that should reduce the risk of type II diabetes. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Manipulation of dopamine metabolism contributes to attenuating innate high locomotor activity in ICR mice.

PubMed

Yamaguchi, Takeshi; Nagasawa, Mao; Ikeda, Hiromi; Kodaira, Momoko; Minaminaka, Kimie; Chowdhury, Vishwajit S; Yasuo, Shinobu; Furuse, Mitsuhiro

2017-06-15

Attention-deficit hyperactivity disorder (ADHD) is defined as attention deficiency, restlessness and distraction. The main characteristics of ADHD are hyperactivity, impulsiveness and carelessness. There is a possibility that these abnormal behaviors, in particular hyperactivity, are derived from abnormal dopamine (DA) neurotransmission. To elucidate the mechanism of high locomotor activity, the relationship between innate activity levels and brain monoamines and amino acids was investigated in this study. Differences in locomotor activity between ICR, C57BL/6J and CBA/N mice were determined using the open field test. Among the three strains, ICR mice showed the greatest amount of locomotor activity. The level of striatal and cerebellar DA was lower in ICR mice than in C57BL/6J mice, while the level of L-tyrosine (L-Tyr), a DA precursor, was higher in ICR mice. These results suggest that the metabolic conversion of L-Tyr to DA is lower in ICR mice than it is in C57BL/6J mice. Next, the effects of intraperitoneal injection of (6R)-5, 6, 7, 8-tetrahydro-l-biopterin dihydrochloride (BH 4 ) (a co-enzyme for tyrosine hydroxylase) and L-3,4-dihydroxyphenylalanine (L-DOPA) on DA metabolism and behavior in ICR mice were investigated. The DA level in the brain was increased by BH 4 administration, but the increased DA did not influence behavior. However, L-DOPA administration drastically lowered locomotor activity and increased DA concentration in several parts of the brain. The reduced locomotor activity may have been a consequence of the overproduction of DA. In conclusion, the high level of locomotor activity in ICR mice may be explained by a strain-specific DA metabolism. Copyright © 2017 Elsevier B.V. All rights reserved.

Locomotor Activity and Body Temperature Patterns over a Temperature Gradient in the Highveld Mole-Rat (Cryptomys hottentotus pretoriae).

PubMed

Haupt, Meghan; Bennett, Nigel C; Oosthuizen, Maria K

2017-01-01

African mole-rats are strictly subterranean mammals that live in extensive burrow systems. High humidity levels in the burrows prevent mole-rats from thermoregulating using evaporative cooling. However, the relatively stable environment of the burrows promotes moderate temperatures and small daily temperature fluctuations. Mole-rats therefore display a relatively wide range of thermoregulation abilities. Some species cannot maintain their body temperatures at a constant level, whereas others employ behavioural thermoregulation. Here we test the effect of ambient temperature on locomotor activity and body temperature, and the relationship between the two parameters, in the highveld mole-rat. We exposed mole-rats to a 12L:12D and a DD light cycle at ambient temperatures of 30°C, 25°C and 20°C while locomotor activity and body temperature were measured simultaneously. In addition, we investigated the endogenous rhythms of locomotor activity and body temperature at different ambient temperatures. Mole-rats displayed nocturnal activity at all three ambient temperatures and were most active at 20°C, but least active at 30°C. Body temperature was highest at 30°C and lowest at 20°C, and the daily cycle was highly correlated with locomotor activity. We show that the mole-rats have endogenous rhythms for both locomotor activity and body temperature. However, the endogenous body temperature rhythm appears to be less robust compared to the locomotor activity rhythm. Female mole-rats appear to be more sensitive to temperature changes than males, increased heterothermy is evident at lower ambient temperatures, whilst males show smaller variation in their body temperatures with changing ambient temperatures. Mole-rats may rely more heavily on behavioural thermoregulation as it is more energy efficient in an already challenging environment.

Nitric oxide-mediated modulation of the murine locomotor network

PubMed Central

Foster, Joshua D.; Dunford, Catherine; Sillar, Keith T.

2013-01-01

Spinal motor control networks are regulated by neuromodulatory systems to allow adaptability of movements. The present study aimed to elucidate the role of nitric oxide (NO) in the modulation of mammalian spinal locomotor networks. This was investigated with isolated spinal cord preparations from neonatal mice in which rhythmic locomotor-related activity was induced pharmacologically. Bath application of the NO donor diethylamine NONOate (DEA/NO) decreased the frequency and modulated the amplitude of locomotor-related activity recorded from ventral roots. Removal of endogenous NO with coapplication of a NO scavenger (PTIO) and a nitric oxide synthase (NOS) blocker [nitro-l-arginine methyl ester (l-NAME)] increased the frequency and decreased the amplitude of locomotor-related activity. This demonstrates that endogenously derived NO can modulate both the timing and intensity of locomotor-related activity. The effects of DEA/NO were mimicked by the cGMP analog 8-bromo-cGMP. In addition, the soluble guanylyl cyclase (sGC) inhibitor ODQ blocked the effects of DEA/NO on burst amplitude and frequency, although the frequency effect was only blocked at low concentrations of DEA/NO. This suggests that NO-mediated modulation involves cGMP-dependent pathways. Sources of NO were studied within the lumbar spinal cord during postnatal development (postnatal days 1–12) with NADPH-diaphorase staining. NOS-positive cells in the ventral horn exhibited a rostrocaudal gradient, with more cells in rostral segments. The number of NOS-positive cells was also found to increase during postnatal development. In summary, we have shown that NO, derived from sources within the mammalian spinal cord, modulates the output of spinal motor networks and is therefore likely to contribute to the fine-tuning of locomotor behavior. PMID:24259545

[Thermal tolerance, diel variation of body temperature, and thermal dependence of locomotor performance of hatchling soft-shelled turtles, Trionyx sinensis].

PubMed

Sun, Pingyue; Xu, Xiaoyin; Chen, Huili; Ji, Xiang

2002-09-01

The thermal tolerance, body temperature, and influence of temperature on locomotor performance of hatchling soft-shelled turtles (Trionyx sinensis) were studied under dry and wet conditions, and the selected body temperature of hatchlings was 28.0 and 30.3 degrees C, respectively. Under wet condition, the critical thermal maximum and minimum averaged 40.9 and 7.8 degrees C, respectively. In the environments without thermal gradients, the diel variation of body temperature was highly consistent with the variation of both air and water temperatures, and the body temperature was more directly affected by water temperature than by air temperature, which implied that the physiological thermoregulation of hatchling T. sinensis was very weak. In the environments with thermal gradients, hatchling turtles could maintain relatively high and constant body temperatures, primarily through behavioral thermoregulation. The locomotor performance of hatchling turtles was highly dependent on their body temperature. Within a certain range, the locomotor performance increased with increasing body temperature. In our study, the optimal body temperature for locomotor performance was 31.5 degrees C, under which, the maximum continuous running distance, running distance per minute, and number of stops per minute averaged 1.87 m, 4.92 m.min-1, and 6.2 times.min-1, respectively. The correspondent values at 33.0 degrees C averaged 1.30 m, 4.28 m.min-1, and 7.7 times.min-1, respectively, which indicated that the locomotor performance of hatchling turtles was impaired at 33.0 degrees C. Therefore, extremely high body temperatures might have an adverse effect on locomotor performance of hatchling turtles.

Statistical Analysis of Zebrafish Locomotor Response

PubMed Central

Zhang, Gaonan; Venkatraman, Prahatha; Brown, Skye Ashton; Pang, Chi-Pui; Zhang, Mingzhi; Ma, Ping; Leung, Yuk Fai

2015-01-01

Zebrafish larvae display rich locomotor behaviour upon external stimulation. The movement can be simultaneously tracked from many larvae arranged in multi-well plates. The resulting time-series locomotor data have been used to reveal new insights into neurobiology and pharmacology. However, the data are of large scale, and the corresponding locomotor behavior is affected by multiple factors. These issues pose a statistical challenge for comparing larval activities. To address this gap, this study has analyzed a visually-driven locomotor behaviour named the visual motor response (VMR) by the Hotelling’s T-squared test. This test is congruent with comparing locomotor profiles from a time period. Different wild-type (WT) strains were compared using the test, which shows that they responded differently to light change at different developmental stages. The performance of this test was evaluated by a power analysis, which shows that the test was sensitive for detecting differences between experimental groups with sample numbers that were commonly used in various studies. In addition, this study investigated the effects of various factors that might affect the VMR by multivariate analysis of variance (MANOVA). The results indicate that the larval activity was generally affected by stage, light stimulus, their interaction, and location in the plate. Nonetheless, different factors affected larval activity differently over time, as indicated by a dynamical analysis of the activity at each second. Intriguingly, this analysis also shows that biological and technical repeats had negligible effect on larval activity. This finding is consistent with that from the Hotelling’s T-squared test, and suggests that experimental repeats can be combined to enhance statistical power. Together, these investigations have established a statistical framework for analyzing VMR data, a framework that should be generally applicable to other locomotor data with similar structure. PMID:26437184

Single prolonged stress effects on sensitization to cocaine and cocaine self-administration in rats.

PubMed

Eagle, Andrew L; Singh, Robby; Kohler, Robert J; Friedman, Amy L; Liebowitz, Chelsea P; Galloway, Matthew P; Enman, Nicole M; Jutkiewicz, Emily M; Perrine, Shane A

2015-05-01

Posttraumatic stress disorder (PTSD) is often comorbid with substance use disorders (SUD). Single prolonged stress (SPS) is a well-validated rat model of PTSD that provides a framework to investigate drug-induced behaviors as a preclinical model of the comorbidity. We hypothesized that cocaine sensitization and self-administration would be increased following exposure to SPS. Male Sprague-Dawley rats were exposed to SPS or control treatment. After SPS, cocaine (0, 10 or 20 mg/kg, i.p.) was administered for 5 consecutive days and locomotor activity was measured. Another cohort was assessed for cocaine self-administration (0.1 or 0.32 mg/kg/i.v.) after SPS. Rats were tested for acquisition, extinction and cue-induced reinstatement behaviors. Control animals showed a dose-dependent increase in cocaine-induced locomotor activity after acute cocaine whereas SPS rats did not. Using a sub-threshold sensitization paradigm, control rats did not exhibit enhanced locomotor activity at Day 5 and therefore did not develop behavioral sensitization, as expected. However, compared to control rats on Day 5 the locomotor response to 20mg/kg repeated cocaine was greatly enhanced in SPS-treated rats, which exhibited enhanced cocaine locomotor sensitization. The effect of SPS on locomotor activity was unique in that SPS did not modify cocaine self-administration behaviors under a simple schedule of reinforcement. These data show that SPS differentially affects cocaine-mediated behaviors causing no effect to cocaine self-administration, under a simple schedule of reinforcement, but significantly augmenting cocaine locomotor sensitization. These results suggest that SPS shares common neurocircuitry with stimulant-induced plasticity, but dissociable from that underlying psychostimulant-induced reinforcement. Copyright © 2015. Published by Elsevier B.V.

Locomotor Muscle Fatigue Does Not Alter Oxygen Uptake Kinetics during High-Intensity Exercise

PubMed Central

Hopker, James G.; Caporaso, Giuseppe; Azzalin, Andrea; Carpenter, Roger; Marcora, Samuele M.

2016-01-01

The V˙O2 slow component (V˙O2sc) that develops during high-intensity aerobic exercise is thought to be strongly associated with locomotor muscle fatigue. We sought to experimentally test this hypothesis by pre-fatiguing the locomotor muscles used during subsequent high-intensity cycling exercise. Over two separate visits, eight healthy male participants were asked to either perform a non-metabolically stressful 100 intermittent drop-jumps protocol (pre-fatigue condition) or rest for 33 min (control condition) according to a random and counterbalanced order. Locomotor muscle fatigue was quantified with 6-s maximal sprints at a fixed pedaling cadence of 90 rev·min−1. Oxygen kinetics and other responses (heart rate, capillary blood lactate concentration and rating of perceived exertion, RPE) were measured during two subsequent bouts of 6 min cycling exercise at 50% of the delta between the lactate threshold and V˙O2max determined during a preliminary incremental exercise test. All tests were performed on the same cycle ergometer. Despite significant locomotor muscle fatigue (P = 0.03), the V˙O2sc was not significantly different between the pre-fatigue (464 ± 301 mL·min−1) and the control (556 ± 223 mL·min−1) condition (P = 0.50). Blood lactate response was not significantly different between conditions (P = 0.48) but RPE was significantly higher following the pre-fatiguing exercise protocol compared with the control condition (P < 0.01) suggesting higher muscle recruitment. These results demonstrate experimentally that locomotor muscle fatigue does not significantly alter the V˙O2 kinetic response to high intensity aerobic exercise, and challenge the hypothesis that the V˙O2sc is strongly associated with locomotor muscle fatigue. PMID:27790156

Differential effects of 5-HT2C receptor activation by WAY 161503 on nicotine-induced place conditioning and locomotor activity in rats.

PubMed

Hayes, Dave J; Mosher, Tera M; Greenshaw, Andrew J

2009-02-11

Numerous studies indicate a role for both the serotonin 2C receptor (5-HT(2C)) and the nicotinic acetylcholine receptor in locomotion, reinforcement and motivated behaviours. Nicotine, a potent nicotinic acetylcholine receptor agonist, interacts with the dopaminergic and serotonergic systems and is known to positively affect reward-related behaviours. The current study examined the effects of 5-HT(2C) receptor activation on nicotine-induced (0.6 mg/kg) place conditioning and spontaneous locomotion. Using Sprague-Dawley rats, the effects of the selective 5-HT(2C) receptor agonist WAY 161503 (0-1.0 mg/kg) and the selective 5-HT(2C) receptor antagonist SB 242084 (1.0 mg/kg) alone, in combination, and on nicotine-induced (0.6 mg/kg) spontaneous locomotor activity were assessed. The effects of WAY 161503 (1.0, 3.0 mg/kg) were also investigated in nicotine-induced place conditioning using a two-compartment biased design; amphetamine (1.0 mg/kg) served as a positive control. As differential effects were observed between place conditioning and locomotor activity, the subjects used in the place conditioning experiments were also tested for effects on locomotor activity. WAY 161503 decreased baseline and nicotine-induced locomotor activity at the highest dose tested (1.0mg/kg) and these effects were attenuated by SB 242084. Amphetamine and nicotine both induced robust place preferences and WAY 161503 did not have any effects in the context of place conditioning. In contrast, WAY 161503 (1.0 mg/kg) blocked nicotine-induced locomotor activity. These results suggest that 5-HT(2C) receptors may play an inhibitory role in nicotine-induced locomotor activity, but do not appear to influence place conditioning under the current conditions.

Locomotor Activity and Body Temperature Patterns over a Temperature Gradient in the Highveld Mole-Rat (Cryptomys hottentotus pretoriae)

PubMed Central

Haupt, Meghan; Bennett, Nigel C.

2017-01-01

African mole-rats are strictly subterranean mammals that live in extensive burrow systems. High humidity levels in the burrows prevent mole-rats from thermoregulating using evaporative cooling. However, the relatively stable environment of the burrows promotes moderate temperatures and small daily temperature fluctuations. Mole-rats therefore display a relatively wide range of thermoregulation abilities. Some species cannot maintain their body temperatures at a constant level, whereas others employ behavioural thermoregulation. Here we test the effect of ambient temperature on locomotor activity and body temperature, and the relationship between the two parameters, in the highveld mole-rat. We exposed mole-rats to a 12L:12D and a DD light cycle at ambient temperatures of 30°C, 25°C and 20°C while locomotor activity and body temperature were measured simultaneously. In addition, we investigated the endogenous rhythms of locomotor activity and body temperature at different ambient temperatures. Mole-rats displayed nocturnal activity at all three ambient temperatures and were most active at 20°C, but least active at 30°C. Body temperature was highest at 30°C and lowest at 20°C, and the daily cycle was highly correlated with locomotor activity. We show that the mole-rats have endogenous rhythms for both locomotor activity and body temperature. However, the endogenous body temperature rhythm appears to be less robust compared to the locomotor activity rhythm. Female mole-rats appear to be more sensitive to temperature changes than males, increased heterothermy is evident at lower ambient temperatures, whilst males show smaller variation in their body temperatures with changing ambient temperatures. Mole-rats may rely more heavily on behavioural thermoregulation as it is more energy efficient in an already challenging environment. PMID:28072840

Cocaine counteracts LPS-induced hypolocomotion and triggers locomotor sensitization expression.

PubMed

Tortorelli, Lucas Silva; Engelke, Douglas Senna; Lunardi, Paula; Mello E Souza, Tadeu; Santos-Junior, Jair Guilherme; Gonçalves, Carlos-Alberto

2015-01-01

Neuroimmune signalling underlies addiction and comorbid depression. Clinical observations indicate that infections and chronic lesions are more frequent in drug users and elevated inflammatory states are evident in cocaine dependents. Therefore, lipopolysaccharide (LPS) and inflammatory cytokines represent an important tool for the investigation of sickness, depressive illness and addiction behaviour. A major component of addiction is the progressive and persistent increase in locomotor activity after repeated drug administration and even prolonged periods of abstinence. The aim of this study was to investigate the response of locomotor sensitization when a non-sensitizing dose of cocaine is paired with a systemic inflammatory stimulus. LPS and cocaine were administered intraperitonealy in young-adult male C57bl/6 mice during a 5-day acquisition phase. After a 48-h withdrawal period all groups were challenged with cocaine to evaluate locomotor expression. During the acquisition phase, the LPS-treated groups displayed characteristic hypolocomotion related to sickness behaviour. The low dose of cocaine did not increase the distance travelled, characterizing a non-sensitization dose. Groups that received both LPS and cocaine did not display hypolocomotion, indicating that cocaine might counteract hypolocomotion sickness behaviour. Moreover, during challenge, only these animals expressed locomotor sensitization. Our results indicate that LPS could facilitate the expression of locomotor sensitization in mice and that the immune system may modulate cocaine-induced sensitization. Copyright © 2015 Elsevier B.V. All rights reserved.

Using a Split-belt Treadmill to Evaluate Generalization of Human Locomotor Adaptation.

PubMed

Vasudevan, Erin V L; Hamzey, Rami J; Kirk, Eileen M

2017-08-23

Understanding the mechanisms underlying locomotor learning helps researchers and clinicians optimize gait retraining as part of motor rehabilitation. However, studying human locomotor learning can be challenging. During infancy and childhood, the neuromuscular system is quite immature, and it is unlikely that locomotor learning during early stages of development is governed by the same mechanisms as in adulthood. By the time humans reach maturity, they are so proficient at walking that it is difficult to come up with a sufficiently novel task to study de novo locomotor learning. The split-belt treadmill, which has two belts that can drive each leg at a different speed, enables the study of both short- (i.e., immediate) and long-term (i.e., over minutes-days; a form of motor learning) gait modifications in response to a novel change in the walking environment. Individuals can easily be screened for previous exposure to the split-belt treadmill, thus ensuring that all experimental participants have no (or equivalent) prior experience. This paper describes a typical split-belt treadmill adaptation protocol that incorporates testing methods to quantify locomotor learning and generalization of this learning to other walking contexts. A discussion of important considerations for designing split-belt treadmill experiments follows, including factors like treadmill belt speeds, rest breaks, and distractors. Additionally, potential but understudied confounding variables (e.g., arm movements, prior experience) are considered in the discussion.

Locomotor-respiratory coupling during axillary crutch ambulation.

PubMed

Hurst, C A; Kirby, R L; MacLeod, D A

2001-11-01

To test the hypotheses that locomotor-respiratory coupling occurs in humans using axillary crutches in a swing-through ambulation pattern and that expiration occurs during crutch-stance phase during locomotor-respiratory coupling. Eighteen able-bodied persons were trained in one-footed swing-through gait with axillary crutches. Then, as subjects walked at "somewhat hard" speeds (Borg) on a motorized treadmill for 5 min, we recorded signals from a crutch pressure switch and a mouthpiece-mounted thermocouple. Coupling was defined as being present when the onset of inspiration varied by < or = 5% with respect to the onset of the crutch gait cycle for a minimum of 10 consecutive gait cycles and when there was no drift on a raster plot of the respiratory phases relative to the onset of the gait cycle. Ten (56%) of the 18 subjects exhibited locomotor-respiratory coupling on 1-4 occasions each, with episodes lasting 11.3-148 sec. In 17 (89%) of the 19 episodes of 1:1 locomotor-respiratory coupling, expiration occurred during the crutch-stance phase of the gait cycle and inspiration occurred during crutch swing. Transient 1:1 locomotor-respiratory coupling occurs in many able-bodied subjects ambulating with axillary crutches and a swing-through gait. Expiration is most often associated with the crutch-stance phase of the gait cycle. This study may have implications for training axillary crutch users.

Altered locomotor and stereotyped responses to acute methamphetamine in adolescent, maternally separated rats

PubMed Central

Pritchard, Laurel M.; Hensleigh, Emily; Lynch, Sarah

2012-01-01

Rationale Neonatal maternal separation (MS) has been used to model the effects of early life stress in rodents. MS alters behavioral responses to a variety of abused drugs, but few studies have examined its effects on methamphetamine sensitivity. Objectives We sought to determine the effects of MS on locomotor and stereotyped responses to low-to-moderate doses of methamphetamine in male and female adolescent rats. Methods Male and female rat pups were subjected to three hours per day of MS on postnatal days (PN) 2–14, or a brief handling control procedure during the same period. During adolescence (approximately PN 40), all rats were tested for locomotor activity and stereotyped behavior in response to acute methamphetamine administration (0, 1.0 or 3.0 mg/kg, s.c.). Results MS rats of both sexes exhibited increased locomotor activity in a novel environment, relative to handled controls. MS increased the locomotor response to METH, and this effect occurred at different doses for male (3.0 mg/kg) and female (1.0 mg/kg) rats. MS also increased stereotyped behavior in response to METH (1.0 mg/kg) in both sexes. Conclusions MS enhances the locomotor response to METH in a dose- and sex-dependent manner. These results suggest that individuals with a history of early life stress may be particularly vulnerable to the psychostimulant effects of METH, even at relatively low doses. PMID:22414962

Human spinal locomotor control is based on flexibly organized burst generators.

PubMed

Danner, Simon M; Hofstoetter, Ursula S; Freundl, Brigitta; Binder, Heinrich; Mayr, Winfried; Rattay, Frank; Minassian, Karen

2015-03-01

Constant drive provided to the human lumbar spinal cord by epidural electrical stimulation can cause local neural circuits to generate rhythmic motor outputs to lower limb muscles in people paralysed by spinal cord injury. Epidural spinal cord stimulation thus allows the study of spinal rhythm and pattern generating circuits without their configuration by volitional motor tasks or task-specific peripheral feedback. To reveal spinal locomotor control principles, we studied the repertoire of rhythmic patterns that can be generated by the functionally isolated human lumbar spinal cord, detected as electromyographic activity from the legs, and investigated basic temporal components shared across these patterns. Ten subjects with chronic, motor-complete spinal cord injury were studied. Surface electromyographic responses to lumbar spinal cord stimulation were collected from quadriceps, hamstrings, tibialis anterior, and triceps surae in the supine position. From these data, 10-s segments of rhythmic activity present in the four muscle groups of one limb were extracted. Such samples were found in seven subjects. Physiologically adequate cycle durations and relative extension- and flexion-phase durations similar to those needed for locomotion were generated. The multi-muscle activation patterns exhibited a variety of coactivation, mixed-synergy and locomotor-like configurations. Statistical decomposition of the electromyographic data across subjects, muscles and samples of rhythmic patterns identified three common temporal components, i.e. basic or shared activation patterns. Two of these basic patterns controlled muscles to contract either synchronously or alternatingly during extension- and flexion-like phases. The third basic pattern contributed to the observed muscle activities independently from these extensor- and flexor-related basic patterns. Each bifunctional muscle group was able to express both extensor- and flexor-patterns, with variable ratios across the samples of rhythmic patterns. The basic activation patterns can be interpreted as central drives implemented by spinal burst generators that impose specific spatiotemporally organized activation on the lumbosacral motor neuron pools. Our data thus imply that the human lumbar spinal cord circuits can form burst-generating elements that flexibly combine to obtain a wide range of locomotor outputs from a constant, repetitive input. It may be possible to use this flexibility to incorporate specific adaptations to gait and stance to improve locomotor control, even after severe central nervous system damage. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Human spinal locomotor control is based on flexibly organized burst generators

PubMed Central

Danner, Simon M.; Hofstoetter, Ursula S.; Freundl, Brigitta; Binder, Heinrich; Mayr, Winfried; Rattay, Frank

2015-01-01

Constant drive provided to the human lumbar spinal cord by epidural electrical stimulation can cause local neural circuits to generate rhythmic motor outputs to lower limb muscles in people paralysed by spinal cord injury. Epidural spinal cord stimulation thus allows the study of spinal rhythm and pattern generating circuits without their configuration by volitional motor tasks or task-specific peripheral feedback. To reveal spinal locomotor control principles, we studied the repertoire of rhythmic patterns that can be generated by the functionally isolated human lumbar spinal cord, detected as electromyographic activity from the legs, and investigated basic temporal components shared across these patterns. Ten subjects with chronic, motor-complete spinal cord injury were studied. Surface electromyographic responses to lumbar spinal cord stimulation were collected from quadriceps, hamstrings, tibialis anterior, and triceps surae in the supine position. From these data, 10-s segments of rhythmic activity present in the four muscle groups of one limb were extracted. Such samples were found in seven subjects. Physiologically adequate cycle durations and relative extension- and flexion-phase durations similar to those needed for locomotion were generated. The multi-muscle activation patterns exhibited a variety of coactivation, mixed-synergy and locomotor-like configurations. Statistical decomposition of the electromyographic data across subjects, muscles and samples of rhythmic patterns identified three common temporal components, i.e. basic or shared activation patterns. Two of these basic patterns controlled muscles to contract either synchronously or alternatingly during extension- and flexion-like phases. The third basic pattern contributed to the observed muscle activities independently from these extensor- and flexor-related basic patterns. Each bifunctional muscle group was able to express both extensor- and flexor-patterns, with variable ratios across the samples of rhythmic patterns. The basic activation patterns can be interpreted as central drives implemented by spinal burst generators that impose specific spatiotemporally organized activation on the lumbosacral motor neuron pools. Our data thus imply that the human lumbar spinal cord circuits can form burst-generating elements that flexibly combine to obtain a wide range of locomotor outputs from a constant, repetitive input. It may be possible to use this flexibility to incorporate specific adaptations to gait and stance to improve locomotor control, even after severe central nervous system damage. PMID:25582580

Association between stride time fractality and gait adaptability during unperturbed and asymmetric walking.

PubMed

Ducharme, Scott W; Liddy, Joshua J; Haddad, Jeffrey M; Busa, Michael A; Claxton, Laura J; van Emmerik, Richard E A

2018-04-01

Human locomotion is an inherently complex activity that requires the coordination and control of neurophysiological and biomechanical degrees of freedom across various spatiotemporal scales. Locomotor patterns must constantly be altered in the face of changing environmental or task demands, such as heterogeneous terrains or obstacles. Variability in stride times occurring at short time scales (e.g., 5-10 strides) is statistically correlated to larger fluctuations occurring over longer time scales (e.g., 50-100 strides). This relationship, known as fractal dynamics, is thought to represent the adaptive capacity of the locomotor system. However, this has not been tested empirically. Thus, the purpose of this study was to determine if stride time fractality during steady state walking associated with the ability of individuals to adapt their gait patterns when locomotor speed and symmetry are altered. Fifteen healthy adults walked on a split-belt treadmill at preferred speed, half of preferred speed, and with one leg at preferred speed and the other at half speed (2:1 ratio asymmetric walking). The asymmetric belt speed condition induced gait asymmetries that required adaptation of locomotor patterns. The slow speed manipulation was chosen in order to determine the impact of gait speed on stride time fractal dynamics. Detrended fluctuation analysis was used to quantify the correlation structure, i.e., fractality, of stride times. Cross-correlation analysis was used to measure the deviation from intended anti-phasing between legs as a measure of gait adaptation. Results revealed no association between unperturbed walking fractal dynamics and gait adaptability performance. However, there was a quadratic relationship between perturbed, asymmetric walking fractal dynamics and adaptive performance during split-belt walking, whereby individuals who exhibited fractal scaling exponents that deviated from 1/f performed the poorest. Compared to steady state preferred walking speed, fractal dynamics increased closer to 1/f when participants were exposed to asymmetric walking. These findings suggest there may not be a relationship between unperturbed preferred or slow speed walking fractal dynamics and gait adaptability. However, the emergent relationship between asymmetric walking fractal dynamics and limb phase adaptation may represent a functional reorganization of the locomotor system (i.e., improved interactivity between degrees of freedom within the system) to be better suited to attenuate externally generated perturbations at various spatiotemporal scales. Copyright © 2018 Elsevier B.V. All rights reserved.

Treatment of GABA from Fermented Rice Germ Ameliorates Caffeine-Induced Sleep Disturbance in Mice

PubMed Central

Mabunga, Darine Froy N.; Gonzales, Edson Luck T.; Kim, Hee Jin; Choung, Se Young

2015-01-01

γ-Aminobutyric acid (GABA), a major inhibitory neurotransmitter in the mammalian central nervous system, is involved in sleep physiology. Caffeine is widely used psychoactive substance known to induce wakefulness and insomnia to its consumers. This study was performed to examine whether GABA extracts from fermented rice germ ameliorates caffeine-induced sleep disturbance in mice, without affecting spontaneous locomotor activity and motor coordination. Indeed, caffeine (10 mg/kg, i.p.) delayed sleep onset and reduced sleep duration of mice. Conversely, rice germ ferment extracts-GABA treatment (10, 30, or 100 mg/kg, p.o.), especially at 100 mg/kg, normalized the sleep disturbance induced by caffeine. In locomotor tests, rice germ ferment extracts-GABA slightly but not significantly reduced the caffeine-induced increase in locomotor activity without affecting motor coordination. Additionally, rice germ ferment extracts-GABA per se did not affect the spontaneous locomotor activity and motor coordination of mice. In conclusion, rice germ ferment extracts-GABA supplementation can counter the sleep disturbance induced by caffeine, without affecting the general locomotor activities of mice. PMID:25995826

Effects of scallop shell extract on scopolamine-induced memory impairment and MK801-induced locomotor activity.

PubMed

Hasegawa, Yasushi; Inoue, Tatsuro; Kawaminami, Satoshi; Fujita, Miho

2016-07-01

To evaluate the neuroprotective effects of the organic components of scallop shells (scallop shell extract) on memory impairment and locomotor activity induced by scopolamine or 5-methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine (MK801). Effect of the scallop shell extract on memory impairment and locomotor activity was investigated using the Y-maze test, the Morris water maze test, and the open field test. Scallop shell extract significantly reduced scopolamine-induced short-term memory impairment and partially reduced scopolamine-induced spatial memory impairment in the Morris water maze test. Scallop shell extract suppressed scopolamine-induced elevation of acetylcholine esterase activity in the cerebral cortex. Treatment with scallop shell extract reversed the increase in locomotor activity induced by scopolamine. Scallop shell extract also suppressed the increase in locomotor activity induced by MK801. Our results provide initial evidence that scallop shell extract reduces scopolamine-induced memory impairment and suppresses MK-801-induced hyperlocomotion. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Effects of zacopride and BMY25801 (batanopride) on radiation-induced emesis and locomotor behavior in the ferret

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, G.L.; Landauer, M.R.

1990-01-01

The antiemetic and locomotor effects of two substituted benzamides, zacopride and batanopride (BMY25801), were compared in ferrets after bilateral Co irradiation at 2, 4, or 6 Gy. Both zacopride and BMY25801 were effective against emesis and related signs. Zacopride, tested at several doses (0.003, 0.03 and 0.3 mg/kg), appeared to be more potent because it abolished emesis at 100-fold lower doses than did BMY25801 (3mg/kg). The ED value for the antiemetic effect of zacopride was 0.026 mg/kg (confidence levels = 0.0095, 0.072 mg/kg). However, analysis of emetic parameters recorded from vomiting animals (e.g., latency to first emesis) demonstrated that BMY25801more » provided greater antiemetic protection in this population than zacopride without and apparent side effects. Locomotor activity was significantly depressed by both radiation (all doses) and zacopride alone (0.03 mg/kg and 0.3 mg/kg). BMY25801 alone did not affect locomotor activity, and protected against the radiation-induced locomotor decrement.« less

Administration of raloxifene reduces sensorimotor and working memory deficits following traumatic brain injury.

PubMed

Kokiko, Olga N; Murashov, Alexander K; Hoane, Michael R

2006-06-30

Hormonal differences between males and females have surfaced as a crucial component in the search for effective treatments after experimental models of traumatic brain injury (TBI). Recent findings have shown that selective estrogen receptor modulators (SERMs) may have therapeutic benefit. The present study examined the effects of raloxifene, a SERM, on functional recovery after bilateral cortical contusion injury (bCCI) or sham procedure. Male rats received injections of raloxifene (3.0mg/kg, i.p.) or vehicle (1.0 ml/kg, i.p.) 15 min, 24, 48, 72, and 96 h after bCCI or sham procedure. Rats were tested on both sensorimotor (bilateral tactile removal and locomotor placing tests) and cognitive tests (reference and working memory in the Morris water maze). Raloxifene-treated animals showed a significant reduction in the initial magnitude of the deficit and facilitated the rate of recovery for the bilateral tactile removal test, compared to vehicle-treated animals. The raloxifene-treated animals also showed a significant improvement in the acquisition of working memory compared to vehicle-treated animals. However, raloxifene did not significantly improve the acquisition of reference memory or locomotor placing ability. Raloxifene treatment also did not result in a significant reduction in the size of the lesion cavity. Thus, the task-dependent improvements seen following raloxifene treatment do not appear to be the result of cortical neuroprotection. However, these results suggest that raloxifene improves functional outcome following bCCI and may present an interesting avenue for future research.

Behavioral toxicity of selected radioprotectors

NASA Astrophysics Data System (ADS)

Landauer, M. R.; Davis, H. D.; Kumar, K. S.; Weiss, J. F.

1992-10-01

Effective radioprotection with minimal behavioral disruption is essential for the selection of protective agents to be used in manned spaceflight. This overview summarizes the studies on the behavioral toxicity of selected radioprotectors classified as phosphorothioates (WR-2721, WR-3689), bioactive lipids (16, 16 dimethylprostaglandin E2(DiPGE2), platelet activating factor (PAF), leukotriene C4), and immunomodulators (glucan, synthetic trehalose dicorynomycolate, and interleukin-1). Behavioral toxicity was examined in laboratory mice using a locomotor activity test. For all compounds tested, there was a dose-dependent decrease in locomotor behavior that paralleled the dose-dependent increase in radioprotection. While combinations of radioprotective compounds (DiPGE2 plus WR-2721) increased radioprotection, they also decreased locomotor activity. The central nervous system stimulant, caffeine, was able to mitigate the locomotor decrement produced by WR-3689 or PAF.

Cardiovascular risk reduction by reversing endothelial dysfunction:ARBs, ACE inhibitors, or both? Expectations from The ONTARGET Trial Programme

PubMed Central

Ruilope, Luis Miguel; Redón, Josep; Schmieder, Roland

2007-01-01

Endothelial dysfunction is the initial pathophysiological step in a progression of vascular damage that leads to overt cardiovascular and chronic kidney disease. Angiotensin II, the primary agent of the renin–angiotensin system (RAS), has a central role in endothelial dysfunction. Therefore, RAS blockade with an angiotensin receptor blocker (ARB) and/or angiotensin-converting enzyme (ACE) inhibitor provides a rational approach to reverse endothelial dysfunction, reduce microalbuminuria, and, thus, improves cardiovascular and renal prognosis. ARBs and ACE inhibitors act at different points in the RAS pathway and recent evidence suggests that there are differences regarding their effects on endothelial dysfunction. In addition to blood pressure lowering, studies have shown that ARBs reduce target-organ damage, including improvements in endothelial dysfunction, arterial stiffness, the progression of renal dysfunction in patients with type 2 diabetes, proteinuria, and left ventricular hypertrophy. The ONgoing Telmisartan Alone in combination with Ramipril Global Endpoint Trial (ONTARGET) Programme is expected to provide the ultimate evidence of whether improved endothelial function translates into reduced cardiovascular and renal events in high-risk patients, and to assess possible differential outcomes with telmisartan, the ACE inhibitor ramipril, or a combination of both (dual RAS blockade). Completion of ONTARGET is expected in 2008. PMID:17583170

Effects of brief mindful acceptance induction on implicit dysfunctional attitudes and concordance between implicit and explicit dysfunctional attitudes.

PubMed

Keng, Shian-Ling; Seah, Stanley T H; Tong, Eddie M W; Smoski, Moria

2016-08-01

Mindfulness-based interventions have been shown to be effective in alleviating depressive symptoms. While much work has examined the effects of mindfulness training on subjective symptoms and experiences, and less is known regarding whether mindfulness training may alter relatively uncontrollable cognitive processes associated with depressed mood, particularly implicit dysfunctional attitudes. The present study examined the effects of a brief mindful acceptance induction on implicit dysfunctional attitudes and degree of concordance between implicit and explicit dysfunctional attitudes in the context of sad mood. A total of 79 adult participants with elevated depressive symptoms underwent an autobiographical mood induction procedure before being randomly assigned to mindful acceptance or thought wandering inductions. Results showed that the effect of mindful acceptance on implicit dysfunctional attitude was significantly moderated by trait mindfulness. Participants high on trait mindfulness demonstrated significant improvements in implicit dysfunctional attitudes following the mindful acceptance induction. Those low on trait mindfulness demonstrated significantly worse implicit dysfunctional attitudes following the induction. Significantly greater levels of concordance between implicit and explicit dysfunctional attitudes were observed in the mindful acceptance condition versus the thought wandering condition. The findings highlight changes in implicit dysfunctional attitudes and improvements in self-concordance as two potential mechanisms underlying the effects of mindfulness-based interventions. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of Training Programs to Optimize Planetary Ambulation

NASA Technical Reports Server (NTRS)

Bloomberg, J. J.; Mulavara, A. P.; Peters, B. T.; Cohen, H. S.; Miller, C. A.; Brady, R.; Warren, L. E.; Rutley, T. M.; Kozlovskaya, I. B.

2007-01-01

Astronauts experience disturbances in functional mobility following their return to Earth due to adaptive responses that occur during exposure to the microgravity conditions of space flight. Despite significant time spent performing in-flight exercise routines, these training programs have not been able to mitigate postflight alterations in postural and locomotor function. Therefore, the goal of our two inter-related projects (NSBRI-ground based and ISS flight study, "Mobility") is to develop and test gait training programs that will serve to optimize functional mobility during the adaptation period immediately following space flight, thereby improving the safety and efficiency of planetary ambulation. The gait training program entails manipulating the sensory conditions of treadmill exercise to systematically challenge the balance and gait control system. This enhances the overall adaptability of locomotor function enabling rapid reorganization of gait control to respond to ambulation in different gravitational environments. To develop the training program, we are conducting a series of ground-based studies evaluating the training efficacy associated with variation in visual flow, body loading, and support surface stability during treadmill walking. We will also determine the optimal method to present training stimuli within and across training sessions to maximize both the efficacy and efficiency of the training procedure. Results indicate that variations in both visual flow and body unloading during treadmill walking leads to modification in locomotor control and can be used as effective training modalities. Additionally, the composition and timing of sensory challenges experienced during each training session has significant impact on the ability to rapidly reorganize locomotor function when exposed to a novel sensory environment. We have developed the capability of producing support surface variation during gait training by mounting a treadmill on a six-degree-of-freedom motion device. This hardware development will allow us to evaluate the efficacy of this type of training in conjunction with variation in visual flow and body unloading.

Decoding bipedal locomotion from the rat sensorimotor cortex

NASA Astrophysics Data System (ADS)

Rigosa, J.; Panarese, A.; Dominici, N.; Friedli, L.; van den Brand, R.; Carpaneto, J.; DiGiovanna, J.; Courtine, G.; Micera, S.

2015-10-01

Objective. Decoding forelimb movements from the firing activity of cortical neurons has been interfaced with robotic and prosthetic systems to replace lost upper limb functions in humans. Despite the potential of this approach to improve locomotion and facilitate gait rehabilitation, decoding lower limb movement from the motor cortex has received comparatively little attention. Here, we performed experiments to identify the type and amount of information that can be decoded from neuronal ensemble activity in the hindlimb area of the rat motor cortex during bipedal locomotor tasks. Approach. Rats were trained to stand, step on a treadmill, walk overground and climb staircases in a bipedal posture. To impose this gait, the rats were secured in a robotic interface that provided support against the direction of gravity and in the mediolateral direction, but behaved transparently in the forward direction. After completion of training, rats were chronically implanted with a micro-wire array spanning the left hindlimb motor cortex to record single and multi-unit activity, and bipolar electrodes into 10 muscles of the right hindlimb to monitor electromyographic signals. Whole-body kinematics, muscle activity, and neural signals were simultaneously recorded during execution of the trained tasks over multiple days of testing. Hindlimb kinematics, muscle activity, gait phases, and locomotor tasks were decoded using offline classification algorithms. Main results. We found that the stance and swing phases of gait and the locomotor tasks were detected with accuracies as robust as 90% in all rats. Decoded hindlimb kinematics and muscle activity exhibited a larger variability across rats and tasks. Significance. Our study shows that the rodent motor cortex contains useful information for lower limb neuroprosthetic development. However, brain-machine interfaces estimating gait phases or locomotor behaviors, instead of continuous variables such as limb joint positions or speeds, are likely to provide more robust control strategies for the design of such neuroprostheses.

The Terregator Mobile Robot

DTIC Science & Technology

1991-05-01

Configuration 17 4.3 Locomotor 19 4.3.1 Base Frame 20 4.3.2 Motors and Drive Train 21 4.3.3 Roll Frame 25 4.3.4 Rack Mount Enclosure 26 4.4 On-Board...tipover, or pitfalls to lesser locomotors . The Terregator can subtcnd moves of millimeter resolution at speeds of zero to several miles per hour. The...guidance systems to achieve a prototypical "intelligent inachine". A mobile base, or locomotor , which will transport the remaining components of an

Locomotor behavior of fish hatched from embryos exposed to flight conditions

NASA Technical Reports Server (NTRS)

Kleerekoper, H.

1978-01-01

Embryos of Fundulus heteroclitus in various stages of development were exposed to space flight conditions aboard Apollo spacecraft and Cosmos satellites. The objective of the study was to ascertain whether fish hatched from these embryos displayed locomotor behavior different from that of control fish of the same age. An electronic monitoring technique was used to record behavior. Results indicate no change in locomotor behavior in fish on Apollo Spacecraft, but inexplicable significant changes were noted in fish aboard Cosmos Satellites.

A Comparison of Robotic, Body Weight Supported Locomotor Training and Aquatic Therapy in Chronic Motor Incomplete Spinal Cord Injury Subjects

DTIC Science & Technology

2015-06-01

Award Number: W81XWH-10-1-0981 TITLE: "A Comparison of Robotic , Body Weight-Supported Locomotor Training and Aquatic Therapy in Chronic Motor...ABSTRACT U c. THIS PAGE U 19b. TELEPHONE NUMBER (include area code) email: pgorman@umm.edu "A Comparison of Robotic , Body Weight-Supported...months, three times a week aquatic therapy with similar intensity robotically assisted, body weight supported locomotor training (RABWSLT) upon

Selection towards different adaptive optima drove the early diversification of locomotor phenotypes in the radiation of Neotropical geophagine cichlids.

PubMed

Astudillo-Clavijo, Viviana; Arbour, Jessica H; López-Fernández, Hernán

2015-05-01

Simpson envisaged a conceptual model of adaptive radiation in which lineages diversify into "adaptive zones" within a macroevolutionary adaptive landscape. However, only a handful of studies have empirically investigated this adaptive landscape and its consequences for our interpretation of the underlying mechanisms of phenotypic evolution. In fish radiations the evolution of locomotor phenotypes may represent an important dimension of ecomorphological diversification given the implications of locomotion for feeding and habitat use. Neotropical geophagine cichlids represent a newly identified adaptive radiation and provide a useful system for studying patterns of locomotor diversification and the implications of selective constraints on phenotypic divergence in general. We use multivariate ordination, models of phenotypic evolution and posterior predictive approaches to investigate the macroevolutionary adaptive landscape and test for evidence of early divergence of locomotor phenotypes in Geophagini. The evolution of locomotor phenotypes was characterized by selection towards at least two distinct adaptive peaks and the early divergence of modern morphological disparity. One adaptive peak included the benthic and epibenthic invertivores and was characterized by fishes with deep, laterally compressed bodies that optimize precise, slow-swimming manoeuvres. The second adaptive peak resulted from a shift in adaptive optima in the species-rich ram-feeding/rheophilic Crenicichla-Teleocichla clade and was characterized by species with streamlined bodies that optimize fast starts and rapid manoeuvres. Evolutionary models and posterior predictive approaches favoured an early shift to a new adaptive peak over decreasing rates of evolution as the underlying process driving the early divergence of locomotor phenotypes. The influence of multiple adaptive peaks on the divergence of locomotor phenotypes in Geophagini is compatible with the expectations of an ecologically driven adaptive radiation. This study confirms that the diversification of locomotor phenotypes represents an important dimension of phenotypic evolution in the geophagine adaptive radiation. It also suggests that the commonly observed early burst of phenotypic evolution during adaptive radiations may be better explained by the concentration of shifts to new adaptive peaks deep in the phylogeny rather than overall decreasing rates of evolution.

Naringin Improves Diet-Induced Cardiovascular Dysfunction and Obesity in High Carbohydrate, High Fat Diet-Fed Rats

PubMed Central

Alam, Md. Ashraful; Kauter, Kathleen; Brown, Lindsay

2013-01-01

Obesity, insulin resistance, hypertension and fatty liver, together termed metabolic syndrome, are key risk factors for cardiovascular disease. Chronic feeding of a diet high in saturated fats and simple sugars, such as fructose and glucose, induces these changes in rats. Naturally occurring compounds could be a cost-effective intervention to reverse these changes. Flavonoids are ubiquitous secondary plant metabolites; naringin gives the bitter taste to grapefruit. This study has evaluated the effect of naringin on diet-induced obesity and cardiovascular dysfunction in high carbohydrate, high fat-fed rats. These rats developed increased body weight, glucose intolerance, increased plasma lipid concentrations, hypertension, left ventricular hypertrophy and fibrosis, liver inflammation and steatosis with compromised mitochondrial respiratory chain activity. Dietary supplementation with naringin (approximately 100 mg/kg/day) improved glucose intolerance and liver mitochondrial dysfunction, lowered plasma lipid concentrations and improved the structure and function of the heart and liver without decreasing total body weight. Naringin normalised systolic blood pressure and improved vascular dysfunction and ventricular diastolic dysfunction in high carbohydrate, high fat-fed rats. These beneficial effects of naringin may be mediated by reduced inflammatory cell infiltration, reduced oxidative stress, lowered plasma lipid concentrations and improved liver mitochondrial function in rats. PMID:23446977

Electrolytic lesions of the nucleus accumbens enhance locomotor sensitization to nicotine in rats.

PubMed

Kelsey, John E; Willmore, Ellen J

2006-06-01

Electrolytic lesions of the medial core of the nucleus accumbens (NAc) in male Long-Evans rats increased spontaneous locomotion, enhanced the locomotor stimulating effect of acute 5.0 mg/kg cocaine, enhanced the development and subsequent expression of locomotor sensitization produced by repeated injections of 0.4 mg/kg nicotine but not 7.5 mg/kg cocaine, and enhanced the expression of conditioned locomotion. Given that 6-hydroxydopamine lesions of the NAc typically have effects on locomotor-related processes that are opposite of those produced by electrolytic and excitotoxic lesions, these data are consistent with a hypothesis that the NAc output, especially from the core, inhibits a variety of such processes and that the DA input to the NAc enhances these processes by inhibiting this inhibitory output. Copyright 2006 APA, all rights reserved.

A visual study of chemotaxis of human lymphocytes using a collagen-gel assay.

PubMed

Wilkinson, P C

1985-01-21

Time-lapse cinematography was used to study the chemotactic responsiveness of human blood lymphocytes as defined by morphological orientation and directional locomotion in gradients. At present, evidence for lymphocyte chemotaxis is indirect since neither of these essential features can be demonstrated with Boyden filter assays. Few lymphocytes direct from blood were motile, but culture in vitro for 1-3 days increased the proportion of locomotor forms to 30-40%. These cells were placed on 3-D collagen gels, and a chemotactic source was presented nearby on a small filter placed on the surface of, or within, the gel. The minority of lymphocytes that were capable of locomotion showed chemotactic responses to filters soaked in lipopolysaccharide if fresh human serum (20%), but not heat-inactivated serum, was present. Lymphocytes responded by protrusion of a lamella in the direction of the gradient source: 76% of locomotor lymphocytes showed their first orientation into the 180 degrees sector facing the source. They then moved directionally towards the source. The response to purified C5 peptides was equivocal. The locomotor lymphocytes showed a chemotactic response to supernatant fluids derived from cultures of the adherent mononuclear cell fraction from human blood (greater than 80% monocytes), judged by the same criteria. No particular lymphocyte type constituted the locomotor population. After exposure to LPS-activated serum, both T and B lymphocytes showed locomotor forms. There were slightly more T4+ cells among the locomotor population than among the population as a whole.

Evaluating diagnosis-based risk-adjustment methods in a population with spinal cord dysfunction.

PubMed

Warner, Grace; Hoenig, Helen; Montez, Maria; Wang, Fei; Rosen, Amy

2004-02-01

To examine performance of models in predicting health care utilization for individuals with spinal cord dysfunction. Regression models compared 2 diagnosis-based risk-adjustment methods, the adjusted clinical groups (ACGs) and diagnostic cost groups (DCGs). To improve prediction, we added to our model: (1) spinal cord dysfunction-specific diagnostic information, (2) limitations in self-care function, and (3) both 1 and 2. Models were replicated in 3 populations. Samples from 3 populations: (1) 40% of veterans using Veterans Health Administration services in fiscal year 1997 (FY97) (N=1,046,803), (2) veteran sample with spinal cord dysfunction identified by codes from the International Statistical Classification of Diseases, 9th Revision, Clinical Modifications (N=7666), and (3) veteran sample identified in Veterans Affairs Spinal Cord Dysfunction Registry (N=5888). Not applicable. Inpatient, outpatient, and total days of care in FY97. The DCG models (R(2) range,.22-.38) performed better than ACG models (R(2) range,.04-.34) for all outcomes. Spinal cord dysfunction-specific diagnostic information improved prediction more in the ACG model than in the DCG model (R(2) range for ACG,.14-.34; R(2) range for DCG,.24-.38). Information on self-care function slightly improved performance (R(2) range increased from 0 to.04). The DCG risk-adjustment models predicted health care utilization better than ACG models. ACG model prediction was improved by adding information.

Female Sexual Dysfunction Among Muslim Women: Increasing Awareness to Improve Overall Evaluation and Treatment.

PubMed

Rahman, Sameena

2018-04-17

Muslim women are an increasingly underserved population in the United States and worldwide. Diagnosis and treatment of female sexual dysfunction bring unique challenges because of the conservative nature of those practicing the religion. Several cultural and religious codes of conduct affect sexual behavior and the dysfunction that can ensue. To assess and describe the types of sexual dysfunction that have been found in Muslim women internationally and encourage a better understanding of their issues to enhance health care delivery. A comprehensive review of the literature through Ovid and PubMed was performed in search of articles reviewing female sexual dysfunction, Muslim women, and Islam. A brief explanation and review of the interpretations of sexuality within Islam are discussed. The link is made between conservative sexual relations and interpretations and the types of sexual dysfunction experienced. Female sexual dysfunction is explored in relation to how female chastity is extolled and how cultural procedures continue despite the ethical and health concerns related to them. Most Muslim women experience sexual dysfunction similar to other women, including arousal, desire, and orgasmic disorders related to organic and psychologic factors. Sexual pain disorders might be more prevalent in this population, particularly concerning unconsummated marriage. There are special concerns related to maintaining virginity and preserving the hymen until marriage. Female genital cutting, practiced by some Muslim countries, has potential sexual consequences. Understanding Islamic views on sexuality and how they can affect sexual dysfunction in Muslim women is critical in opening lines of communication with patients and approaching female sexual dysfunction impartially. Although some issues that arise might introduce ethical dilemmas for the provider, having the cultural competence to address these issues will facilitate improved health care delivery. Rahman S. Female Sexual Dysfunction Among Muslim Women: Increasing Awareness to Improve Overall Evaluation and Treatment. Sex Med Rev 2018;X:XX-XX. Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Short- and long-term outcomes of 1000 adult lung transplant recipients at a single center.

PubMed

Kreisel, Daniel; Krupnick, Alexander S; Puri, Varun; Guthrie, Tracey J; Trulock, Elbert P; Meyers, Bryan F; Patterson, G Alexander

2011-01-01

Lung transplantation has become accepted therapy for end-stage pulmonary disease. The objective of this study was to review a single-institution experience of adult lung transplants. We reviewed 1000 adult lung transplants that were performed at Washington University between July 1988 and January 2009. Transplants were performed for emphysema (52%), cystic fibrosis (18.2%), pulmonary fibrosis (16.1%), and pulmonary vascular disease (7.2%). Overall recipient age was 48 ± 13 years with an increase from 43 ± 12 years (July 1988-November 1993) to 50 ± 14 years (June 2005-January 2009). Overall incidence of primary graft dysfunction was 22.1%. Hospital mortality was higher for patients who had primary graft dysfunction (primary graft dysfunction, 13.6%; no primary graft dysfunction, 4%; P < .001). Freedom from bronchiolitis obliterans syndrome was 84% at 1 year, 38.2% at 5 years, and 12.2% at 10 years. Survival at 1, 5, 10, and 15 years was 84%, 56.4%, 32.2%, and 17.8%, respectively. Five-year survival improved from 49.6% (July 1988-November 1993) to 62.1% (October 2001-June 2005). Primary graft dysfunction was associated with lower survival at 1, 5, and 10 years (primary graft dysfunction: 72.8%, 43.9%, and 18.7%, respectively; no primary graft dysfunction: 87.1%, 59.8%, and 35.7%, respectively, P < .001) and lower rates of freedom from bronchiolitis obliterans syndrome (primary graft dysfunction: 78%, 27.5%, and 8.5%, respectively; no primary graft dysfunction: 85.4%, 40.7%, and 13.1%, respectively, P = .007). Five-year survival has improved over the study period, but long-term outcomes are limited by bronchiolitis obliterans syndrome. Primary graft dysfunction is associated with higher rates of bronchiolitis obliterans syndrome and impaired short- and long-term survival. A better understanding of primary graft dysfunction and bronchiolitis obliterans syndrome is critical to improve outcomes. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Monitoring Elite Soccer Players' External Loads Using Real-Time Data.

PubMed

Barrett, Steve

2017-11-01

To assess the validity of measuring locomotor activities and PlayerLoad using real-time (RT) data collection during soccer training. Twenty-nine English soccer players participated. Each player wore the same MEMS device (Micromechanical Electrical Systems; S5, Optimeye; CatapultSports, Melbourne, Australia) during 21 training sessions (N = 331 data sets) in the 2015-16 and 2016-17 seasons. An RT receiver (TRX; Catapultsports, Melbourne, Australia) was used to collect the locomotor activities and PlayerLoad data in RT and compared with the postevent downloaded (PED) data. PlayerLoad and locomotor activities (total distance covered; total high-speed running distance covered, >5.5#x00A0;m/s; total sprinting distance covered, >7 m/s; maximum velocity) were analyzed. Correlations were near perfect for all variables analyzed (r = .98-1.00), with a varied level of noise between RT and PED also (0.3-9.7% coefficient of variation). Locomotor activities and PlayerLoad can use both RT and PED concurrently to quantify a player's physical output during a training session. Caution should be taken with higher-velocity-based locomotor activities during RT compared to PED.

[Studies upon behaviour of snails in anthropogenically changed water environment. 1. Locomotor activity of Lymnaea stagnalis (L.), with regard to subpopulations infected with developmental stages of digeneans].

PubMed

Pokora, Zbigniew

2002-01-01

The aim of the paper was to analyse the locomotor activity of snails, Lymnaea stagnalis, with regard to physico-chemical properties of water in an inhabited reservoir and parasitic infection. The material was collected in selected anthropogenic water environments situated in the Upper Silesian Industrial Region (sinkhole ponds, sand- and clay-excavations). The locomotor activity of each snail was analysed in laboratory conditions by designation of number of penetrated segments, marked in tanks filled with water originating from a given reservoir, during 15', with intervals of 1'. It was observed the significant relationship between locomotor activity of examined snails and the water carbonaceous hardness (r = -0,812, at range of the independent variable 173.0-863.5 mg CaCO3/dm3). Correlation coefficients with other physico-chemical parameters of water were close to zero. Locomotion of snails infected with developmental stages of digenetic trematodes was significantly lower comparing to non-infected individuals. Locomotor activity of these former ones was dependend more on degree of the digestive gland damage by the parasite than on the infection agent.

The development of a non-invasive behavioral model of thermal heat stress in laboratory mice (Mus musculus).

PubMed

Mufford, J T; Paetkau, M J; Flood, N J; Regev-Shoshani, G; Miller, C C; Church, J S

2016-08-01

Many behavioral and physiological studies of laboratory mice employ invasive methods such as radio telemetry to measure key aspects of behavior and physiology. Radio telemetry requires surgical implants, which may impact mouse health and behavior, and thus reduce the reliability of the data collected. We developed a method to measure key aspects of thermoregulatory behavior without compromising animal welfare. We examined the thermoregulatory response to heat stress in a custom-built arena that permitted the use of simultaneous and continuous infrared thermography (IRT) and video capture. This allowed us to measure changes in surface body temperature and determine total distance traveled using EthoVision XT animal tracking software. Locomotor activity and surface body temperature differed between heat-stressed mice and mice kept within their thermal comfort zone. The former had an increase in surface body temperature and a decline in locomotor activity, whereas the latter had a stable surface body temperature and showed greater activity levels. Surface body temperature and locomotor activity are conventionally quantified by measurements taken at regular intervals, which limit the use and accuracy of the data. We obtained data of high resolution (i.e., recorded continuously) and accuracy that allowed for the examination of key physiological measurements such as energy expenditure and peripheral vasomotor tone. This novel experimental method for studying thermoregulatory behavior in mice using non-invasive tools has advantages over radio-telemetry and represents an improvement in laboratory animal welfare. Copyright © 2015 Elsevier B.V. All rights reserved.

Do constraints associated with the locomotor habitat drive the evolution of forelimb shape? A case study in musteloid carnivorans

PubMed Central

Fabre, Anne-Claire; Cornette, Raphael; Goswami, Anjali; Peigné, Stéphane

2015-01-01

Convergence in morphology can result from evolutionary adaptations in species living in environments with similar selective pressures. Here, we investigate whether the shape of the forelimb long bones has converged in environments imposing similar functional constraints, using musteloid carnivores as a model. The limbs of quadrupeds are subjected to many factors that may influence their shape. They need to support body mass without collapsing or breaking, yet at the same time resist the stresses and strains induced by locomotion. This likely imposes strong constraints on their morphology. Our geometric morphometric analyses show that locomotion, body mass and phylogeny all influence the shape of the forelimb. Furthermore, we find a remarkable convergence between: (i) aquatic and semi-fossorial species, both displaying a robust forelimb, with a shape that improves stability and load transfer in response to the physical resistance imposed by the locomotor environment; and (ii) aquatic and arboreal/semi-arboreal species, with both groups displaying a broad capitulum. This augments the degree of pronation/supination, an important feature for climbing as well as grasping and manipulation ability, behaviors common to aquatic and arboreal species. In summary, our results highlight how musteloids with different locomotor ecologies show differences in the anatomy of their forelimb bones. Yet, functional demands for limb movement through dense media also result in convergence in forelimb long-bone shape between diverse groups, for example, otters and badgers. PMID:25994128

Effects of Robot-assisted Gait Training Combined with Functional Electrical Stimulation on Recovery of Locomotor Mobility in Chronic Stroke Patients: A Randomized Controlled Trial.

PubMed

Bae, Young-Hyeon; Ko, Young Jun; Chang, Won Hyuk; Lee, Ju Hyeok; Lee, Kyeong Bong; Park, Yoo Jung; Ha, Hyun Geun; Kim, Yun-Hee

2014-12-01

[Purpose] The purpose of the present study was to investigate the effects of robot-assisted gait training combined with functional electrical stimulation on locomotor recovery in patients with chronic stroke. [Subjects] The 20 subjects were randomly assigned into either an experimental group (n = 10) that received a combination of robot-assisted gait training and functional electrical stimulation on the ankle dorsiflexor of the affected side or a control group (n = 10) that received robot-assisted gait training only. [Methods] Both groups received the respective therapies for 30 min/day, 3 days/week for 5 weeks. The outcome was measured using the Modified Motor Assessment Scale (MMAS), Timed Up-and-Go Test (TUG), Berg Balance Scale (BBS), and gait parameters through gait analysis (Vicon 370 motion analysis system, Oxford Metrics Ltd., Oxford, UK). All the variables were measured before and after training. [Results] Step length and maximal knee extension were significantly greater than those before training in the experimental group only. Maximal Knee flexion showed a significant difference between the experimental and control groups. The MMAS, BBS, and TUG scores improved significantly after training compared with before training in both groups. [Conclusion] We suggest that the combination of robot-assisted gait training and functional electrical stimulation encourages patients to actively participate in training because it facilitates locomotor recovery without the risk of adverse effects.

Do constraints associated with the locomotor habitat drive the evolution of forelimb shape? A case study in musteloid carnivorans.

PubMed

Fabre, Anne-Claire; Cornette, Raphael; Goswami, Anjali; Peigné, Stéphane

2015-06-01

Convergence in morphology can result from evolutionary adaptations in species living in environments with similar selective pressures. Here, we investigate whether the shape of the forelimb long bones has converged in environments imposing similar functional constraints, using musteloid carnivores as a model. The limbs of quadrupeds are subjected to many factors that may influence their shape. They need to support body mass without collapsing or breaking, yet at the same time resist the stresses and strains induced by locomotion. This likely imposes strong constraints on their morphology. Our geometric morphometric analyses show that locomotion, body mass and phylogeny all influence the shape of the forelimb. Furthermore, we find a remarkable convergence between: (i) aquatic and semi-fossorial species, both displaying a robust forelimb, with a shape that improves stability and load transfer in response to the physical resistance imposed by the locomotor environment; and (ii) aquatic and arboreal/semi-arboreal species, with both groups displaying a broad capitulum. This augments the degree of pronation/supination, an important feature for climbing as well as grasping and manipulation ability, behaviors common to aquatic and arboreal species. In summary, our results highlight how musteloids with different locomotor ecologies show differences in the anatomy of their forelimb bones. Yet, functional demands for limb movement through dense media also result in convergence in forelimb long-bone shape between diverse groups, for example, otters and badgers. © 2015 Anatomical Society.

Reversal of mitochondrial dysfunction by coenzyme Q10 supplement improves endothelial function in patients with ischaemic left ventricular systolic dysfunction: a randomized controlled trial.

PubMed

Dai, Yuk-Ling; Luk, Ting-Hin; Yiu, Kai-Hang; Wang, Mei; Yip, Pandora M C; Lee, Stephen W L; Li, Sheung-Wai; Tam, Sidney; Fong, Bonnie; Lau, Chu-Pak; Siu, Chung-Wah; Tse, Hung-Fat

2011-06-01

Coronary artery disease (CAD) is associated with endothelial dysfunction and mitochondrial dysfunction (MD). The aim of this study was to investigate whether co-enzyme Q10 (CoQ) supplementation, which is an obligatory coenzyme in the mitochondrial respiratory transport chain, can reverse MD and improve endothelial function in patients with ischaemic left ventricular systolic dysfunction (LVSD). We performed a randomized, double-blind, placebo-controlled trial to determine the effects of CoQ supplement (300 mg/day, n=28) vs. placebo (controls, n=28) for 8 weeks on brachial flow-mediated dilation (FMD) in patients with ischaemic LVSD(left ventricular ejection fraction <45%). Mitochondrial function was determined by plasma lactate/pyruvate ratio (LP ratio). After 8 weeks, CoQ-treated patients had significant increases in plasma CoQ concentration (treatment effect 2.20 μg/mL, P<0.001) and FMD (treatment effect 1.51%, P=0.03); and decrease in LP ratio (treatment effect -2.46, P=0.03) compared with controls. However, CoQ treatment did not alter nitroglycerin-mediated dilation, blood pressure, blood levels of fasting glucose, haemoglobin A1c, lipid profile, high-sensitivity C-reactive protein and oxidative stress as determined by serum superoxide dismutase and 8-isoprostane (all P>0.05). Furthermore, the reduction in LP ratio significantly correlated with improvement in FMD (r=-0.29, P=0.047). In patients with ischaemic LVSD, 8 weeks supplement of CoQ improved mitochondrial function and FMD; and the improvement of FMD correlated with the change in mitochondrial function, suggesting that CoQ improved endothelial function via reversal of mitochondrial dysfunction in patients with ischaemic LVSD. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Spaceflight Sensorimotor Analogs: Simulating Acute and Adaptive Effects

NASA Technical Reports Server (NTRS)

Taylor, Laura C.; Harm, Deborah L.; Kozlovskaya, Inessa; Reschke, Millard F.; Wood, Scott J.

2009-01-01

Adaptive changes in sensorimotor function during spaceflight are reflected by spatial disorientation, motion sickness, gaze destabilization and decrements in balance, locomotion and eye-hand coordination that occur during and following transitions between different gravitational states. The purpose of this study was to conduct a meta-synthesis of data from spaceflight analogs to evaluate their effectiveness in simulating adaptive changes in sensorimotor function. METHODS. The analogs under review were categorized as either acute analogs used to simulate performance decrements accompanied with transient changes, or adaptive analogs used to drive sensorimotor learning to altered sensory feedback. The effectiveness of each analog was evaluated in terms of mechanisms of action, magnitude and time course of observed deficits compared to spaceflight data, and the effects of amplitude and exposure duration. RESULTS. Parabolic flight has been used extensively to examine effects of acute variation in gravitational loads, ranging from hypergravity to microgravity. More recently, galvanic vestibular stimulation has been used to elicit acute postural, locomotor and gaze dysfunction by disrupting vestibular afferents. Patient populations, e.g., with bilateral vestibular loss or cerebellar dysfunction, have been proposed to model acute sensorimotor dysfunction. Early research sponsored by NASA involved living onboard rotating rooms, which appeared to approximate the time course of adaptation and post-exposure recovery observed in astronauts following spaceflight. Exposure to different bed-rest paradigms (6 deg head down, dry immersion) result in similar motor deficits to that observed following spaceflight. Shorter adaptive analogs have incorporated virtual reality environments, visual distortion paradigms, exposure to conflicting tilt-translation cues, and exposure to 3Gx centrifugation. As with spaceflight, there is considerable variability in responses to most of the analogs reviewed. DISCUSSION. A true ground-based flight analog for sensorimotor function is not feasible. A combination of flight analogs; however, can be used to selectively mimic different aspects of the spaceflight-induced sensorimotor performance decrements.

Locomotor activity of rats with SCI is improved by dexmedetomidine by targeting the expression of inflammatory factors.

PubMed

Wang, Wei-Guo; Wang, Lin; Jiao, Zhen-Hua; Xue, Bin; Xu, Zhan-Wang

2018-04-26

Dexmedetomidine, a well‑known selective α‑2 adrenoceptor agonist, inhibits the apoptosis of neurons and protects other organs from oxidative damage. In the present study, the effect of dexmedetomidine on spinal cord injury (SCI) in a rat model was investigated. The SCI rat model was prepared using the weight‑drop method, and the effect of dexmedetomidine on locomotor activity was analyzed using the Basso, Beattie and Bresnahan (BBB) rating scale. Western blot analysis was used to observe changes in the expression of apoptosis‑related proteins, including B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑associated X protein (Bax). The results revealed that treatment of the SCI rats with dexmedetomidine at a dose of 50 mg/kg significantly prevented the formation of edema in the tissues of the spinal cord. Dexmedetomidine also inhibited the SCI‑induced accumulation of neutrophils in the spinal cord. The BBB scores were significantly increased (P<0.05) in the rats with SCI treated with dexmedetomidine after 10 days. The results of grid walking test revealed a marked decrease in the number of missteps following 10 days of dexmedetomidine treatment. The expression levels of tumor necrosis factor (TNF)‑α and interleukin (IL)‑1β were significantly reduced (P<0.05) in the spinal cord tissues of the dexmedetomidine group, compared with those in the control group of rats. Dexmedetomidine treatment following SCI exerted an inhibitory effect on the SCI‑induced increase in the expression of Bax. The expression of Bcl‑2 was increased in the dexmedetomidine treated rats, compared with that in the control group. Taken together, dexmedetomidine improved the locomotor activity of the rats through the inhibition of edema, reduction in the expression levels of TNF‑α and IL‑1β, and inhibition of the induction of apoptosis. Therefore, dexmedetomidine may be of therapeutic importance for patients with SCI.

Training Enhances Both Locomotor and Cognitive Adaptability to a Novel Sensory Environment

NASA Technical Reports Server (NTRS)

Bloomberg, J. J.; Peters, B. T.; Mulavara, A. P.; Brady, R. A.; Batson, C. D.; Ploutz-Snyder, R. J.; Cohen, H. S.

2010-01-01

During adaptation to novel gravitational environments, sensorimotor disturbances have the potential to disrupt the ability of astronauts to perform required mission tasks. The goal of this project is to develop a sensorimotor adaptability (SA) training program to facilitate rapid adaptation. We have developed a unique training system comprised of a treadmill placed on a motion-base facing a virtual visual scene that provides an unstable walking surface combined with incongruent visual flow designed to enhance sensorimotor adaptability. The goal of our present study was to determine if SA training improved both the locomotor and cognitive responses to a novel sensory environment and to quantify the extent to which training would be retained. Methods: Twenty subjects (10 training, 10 control) completed three, 30-minute training sessions during which they walked on the treadmill while receiving discordant support surface and visual input. Control subjects walked on the treadmill but did not receive any support surface or visual alterations. To determine the efficacy of training all subjects performed the Transfer Test upon completion of training. For this test, subjects were exposed to novel visual flow and support surface movement, not previously experienced during training. The Transfer Test was performed 20 minutes, 1 week, 1, 3 and 6 months after the final training session. Stride frequency, auditory reaction time, and heart rate data were collected as measures of postural stability, cognitive effort and anxiety, respectively. Results: Using mixed effects regression methods we determined that subjects who received SA training showed less alterations in stride frequency, auditory reaction time and heart rate compared to controls. Conclusion: Subjects who received SA training improved performance across a number of modalities including enhanced locomotor function, increased multi-tasking capability and reduced anxiety during adaptation to novel discordant sensory information. Trained subjects maintained their level of performance over six months.

[The formation of the self-maintenance skills in the pre-school children presenting with locomotor and coordination disorders].

PubMed

Poletaeva-Dubrovina, N A; Burkova, A M

2016-01-01

The Ministry of Health of the Russian Federation acknowledges the sharp rise in the prevalence of congenital malformation in this country during the past 30 years. In 2010-2011, this pathology was estimated to occur in 3% of the children. It includes a variety of locomotor and coordination disorders of which the most widespread are infantile cerebral paralysis, ataxia, consequences of perinatal lesions of the central nervous system, etc. This article contains a detailed description of these locomotor and coordination disorders. The objective of the present work was to elaborate and evaluate the program for the formation of the self-maintenance skills in the pre-school children presenting with locomotor and coordination disorders under conditions of family guidance and education. The study was carried out from September 2013 till May 2014 based at MUP DOD "Semeiny klub Nadezhda" ("The Hope Family Club", Municipal unitary facility for children's additional education) and supported by B.N. El'tsin Ural Federal University. It included 10 children suffering from locomotor and coordination disorders of different severity and members of their families. The following methods were used: the self-service skills scorecard , monitoring formation of the motor skills, and Wilcoxon's T-test. The use of the program based on the cooperation with the children's families allowed to achieve positive dynamics in the patients' conditions. Moreover, 30% of them acquired the full scope of the self-maintenance skills. The most pronounced changes in the motor abilities were apparent in the movements of the upper and lower extremitis, walking, and motion in space. The proposed program for the formation of the self-maintenance skills in the pre-school children presenting with locomotor and coordination disorders proved to be highly efficacious. The study has demonstrated the importance of the parents' involvement in the process of formation of the self-maintenance skills and motor abilities. It is concluded that the formation of the self-maintenance skills and locomotor abilities are two interdependent processes.

Virus-mediated shRNA knockdown of prodynorphin in the rat nucleus accumbens attenuates depression-like behavior and cocaine locomotor sensitization.

PubMed

Cohen, Ami; Whitfield, Timothy W; Kreifeldt, Max; Koebel, Pascale; Kieffer, Brigitte L; Contet, Candice; George, Olivier; Koob, George F

2014-01-01

Dynorphins, endogenous opioid peptides that arise from the precursor protein prodynorphin (Pdyn), are hypothesized to be involved in the regulation of mood states and the neuroplasticity associated with addiction. The current study tested the hypothesis that dynorphin in the nucleus accumbens (NAcc) mediates such effects. More specifically, we examined whether knockdown of Pdyn within the NAcc in rats would alter the expression of depressive-like and anxiety-like behavior, as well as cocaine locomotor sensitization. Wistar rats were injected with adeno-associated viral (AAV) vectors encoding either a Pdyn-specific short hairpin RNA (AAV-shPdyn) or a scrambled shRNA (AAV-shScr) as control. Four weeks later, rats were tested for anxiety-like behavior in the elevated plus maze test and depressive-like behavior in the forced swim test (FST). Finally, rats received one daily injection of saline or cocaine (20 mg/kg, i.p.), followed by assessment of locomotion for 4 consecutive days. Following 3 days of abstinence, the rats completed 2 additional daily cocaine/saline locomotor trials. Pdyn knockdown in the NAcc led to a significant reduction in depressive-like behavior in the FST, but had no effect on anxiety-like behavior in the elevated plus maze. Pdyn knockdown did not alter baseline locomotor behavior, the locomotor response to acute cocaine, or the initial sensitization of the locomotor response to cocaine over the first 4 cocaine treatment days. However, following 3 days abstinence the locomotor response to the cocaine challenge returned to their original levels in the AAV-shPdyn rats while remaining heightened in the AAV-shScr rats. These results suggest that dynorphin in a very specific area of the nucleus accumbens contributes to depressive-like states and may be involved in neuroadaptations in the NAcc that contribute to the development of cocaine addiction as a persistent and lasting condition.

Initiation of calorie restriction in middle-aged male rats attenuates aging-related motoric decline and bradykinesia without increased striatal dopamine

PubMed Central

Salvatore, Michael F.; Terrebonne, Jennifer; Fields, Victoria; Nodurft, Danielle; Runfalo, Cori; Latimer, Brian; Ingram, Donald K.

2015-01-01

Aging-related bradykinesia affects ~15% of those reaching age 65 and 50% of those reaching their 80s. Given this high risk and lack of pharmacological therapeutics, non-invasive lifestyle strategies should be identified to diminish its risk and identify the neurobiological targets to reduce aging-related bradykinesia. Early-life, long-term calorie restriction (CR) attenuates aging-related bradykinesia in rodents. Here, we addressed whether CR initiation at middle age could attenuate aging-related bradykinesia and motoric decline measured as rotarod performance. A 30% CR regimen was implemented for 6 months duration in 12-month old male Brown-Norway Fischer 344 F1 hybrid rats after establishing individual baseline locomotor activities. Locomotor capacity was assessed every 6 weeks thereafter. The ad libitum (AL) group exhibited predictably decreased locomotor activity, except movement speed, out to 18 months of age. In contrast, in the CR group, movement number and horizontal activity did not decrease during the 6-month trial and aging-related decline in rotarod performance was attenuated. The response to CR was influenced by baseline locomotor activity. The lower the locomotor activity level at baseline, the greater the response to CR. Rats in the lower 50th percentile surpassed their baseline level of activity, whereas rats in the top 50th percentile decreased at 6 weeks and then returned to baseline by 12 weeks of CR. We hypothesized that nigrostriatal dopamine tissue content would be greater in the CR group and observed a modest increase only in substantia nigra with no group differences in striatum, nucleus accumbens, or ventral tegmental area. These results indicate initiation of CR at middle age may reduce aging-related bradykinesia and, furthermore, subjects with below average locomotor activity may increase baseline activity. Sustaining nigral DA neurotransmission may be one component of preserving locomotor capabilities during aging. PMID:26610387

Differential Effects of Sex Pheromone Compounds on Adult Female Sea Lamprey (Petromyzon marinus) Locomotor Patterns.

PubMed

Walaszczyk, Erin J; Goheen, Benjamin B; Steibel, Juan Pedro; Li, Weiming

2016-06-01

Synchronization of male and female locomotor activity plays a critical role in ensuring reproductive success, especially in semelparous species. The goal of this study was to elucidate the effects of individual chemical signals, or pheromones, on the locomotor activity in the sea lamprey (Petromyzon marinus). In their native habitat, adult preovulated females (POF) and ovulated females (OF) are exposed to sex pheromone compounds that are released from spermiated males and attract females to nests during their migration and spawning periods. In this study, locomotor activity of individual POF and OF was measured hourly in controlled laboratory conditions using an automated video-tracking system. Differences in the activity between a baseline day (no treatment exposure) and a treatment day (sex pheromone compound or control exposure) were examined for daytime and nighttime periods. Results showed that different pheromone compound treatments affected both POF and OF sea lamprey (p < 0.05) but in different ways. Spermiated male washings (SMW) and one of its main components, 7α,12α,24-trihydroxy-5α-cholan-3-one 24 sulfate (3kPZS), decreased activity of POF during the nighttime. SMW also reduced activity in POF during the daytime. In contrast, SMW increased activity of OF during the daytime, and an additional compound found in SMW, petromyzonol sulfate (PZS), decreased the activity during the nighttime. In addition, we examined factors that allowed us to infer the overall locomotor patterns. SMW increased the maximum hourly activity during the daytime, decreased the maximum hourly activity during the nighttime, and reduced the percentage of nocturnal activity in OF. Our findings suggest that adult females have evolved to respond to different male compounds in regards to their locomotor activity before and after final maturation. This is a rare example of how species-wide chemosensory stimuli can affect not only the amounts of activity but also the overall locomotor pattern in a vertebrate species. © 2016 The Author(s).

Mechanisms of motor recovery after subtotal spinal cord injury: insights from the study of mice carrying a mutation (WldS) that delays cellular responses to injury.

PubMed

Zhang, Z; Guth, L; Steward, O

1998-01-01

Partial lesions of the mammalian spinal cord result in an immediate motor impairment that recovers gradually over time; however, the cellular mechanisms responsible for the transient nature of this paralysis have not been defined. A unique opportunity to identify those injury-induced cellular responses that mediate the recovery of function has arisen from the discovery of a unique mutant strain of mice in which the onset of Wallerian degeneration is dramatically delayed. In this strain of mice (designated WldS for Wallerian degeneration, slow), many of the cellular responses to spinal cord injury are also delayed. We have used this experimental animal model to evaluate possible causal relationships between these delayed cellular responses and the onset of functional recovery. For this purpose, we have compared the time course of locomotor recovery in C57BL/6 (control) mice and in WldS (mutant) mice by hemisecting the spinal cord at T8 and evaluating locomotor function at daily postoperative intervals. The time course of locomotor recovery (as determined by the Tarlov open-field walking procedure) was substantially delayed in mice carrying the WldS mutation: C57BL/6 control mice began to stand and walk within 6 days (mean Tarlov score of 4), whereas mutant mice did not exhibit comparable locomotor function until 16 days postoperatively. (a) The rapid return of locomotor function in the C57BL/6 mice suggests that the recovery resulted from processes of functional plasticity rather than from regeneration or collateral sprouting of nerve fibers. (b) The marked delay in the return of locomotor function in WldS mice indicates that the processes of neuroplasticity are induced by degenerative changes in the damaged neurons. (c) These strains of mice can be effectively used in future studies to elucidate the specific biochemical and physiological alterations responsible for inducing functional plasticity and restoring locomotor function after spinal cord injury.

Recruitment of faster motor units is associated with greater rates of fascicle strain and rapid changes in muscle force during locomotion

PubMed Central

Lee, Sabrina S. M.; de Boef Miara, Maria; Arnold, Allison S.; Biewener, Andrew A.; Wakeling, James M.

2013-01-01

SUMMARY Animals modulate the power output needed for different locomotor tasks by changing muscle forces and fascicle strain rates. To generate the necessary forces, appropriate motor units must be recruited. Faster motor units have faster activation–deactivation rates than slower motor units, and they contract at higher strain rates; therefore, recruitment of faster motor units may be advantageous for tasks that involve rapid movements or high rates of work. This study identified motor unit recruitment patterns in the gastrocnemii muscles of goats and examined whether faster motor units are recruited when locomotor speed is increased. The study also examined whether locomotor tasks that elicit faster (or slower) motor units are associated with increased (or decreased) in vivo tendon forces, force rise and relaxation rates, fascicle strains and/or strain rates. Electromyography (EMG), sonomicrometry and muscle-tendon force data were collected from the lateral and medial gastrocnemius muscles of goats during level walking, trotting and galloping and during inclined walking and trotting. EMG signals were analyzed using wavelet and principal component analyses to quantify changes in the EMG frequency spectra across the different locomotor conditions. Fascicle strain and strain rate were calculated from the sonomicrometric data, and force rise and relaxation rates were determined from the tendon force data. The results of this study showed that faster motor units were recruited as goats increased their locomotor speeds from level walking to galloping. Slow inclined walking elicited EMG intensities similar to those of fast level galloping but different EMG frequency spectra, indicating that recruitment of the different motor unit types depended, in part, on characteristics of the task. For the locomotor tasks and muscles analyzed here, recruitment patterns were generally associated with in vivo fascicle strain rates, EMG intensity and tendon force. Together, these data provide new evidence that changes in motor unit recruitment have an underlying mechanical basis, at least for certain locomotor tasks. PMID:22972893

The within-match patterns of locomotor efficiency during professional soccer match play: Implications for injury risk?

PubMed

Barrett, Steve; Midgley, Adrian; Reeves, Matt; Joel, Tom; Franklin, Ed; Heyworth, Rob; Garrett, Andrew; Lovell, Ric

2016-10-01

The principle aim of the current study was to examine within-match patterns of locomotor efficiency in professional soccer, determined as the ratio between tri-axial accelerometer data (PlayerLoad™) and locomotor activities. Between match variability and determinants of PlayerLoad™ during match play were also assessed. A single cohort, observational study. Tri-axial accelerometer data (PlayerLoad™) was recorded during 86 competitive soccer matches in 63 English championship players (574 match observations). Accelerometer data accumulated (PlayerLoad Vector Magnitude [PLVM]) from the individual-component planes of PlayerLoad™ (anterior-posterior PlayerLoad™ [PLAP], medial-lateral PlayerLoad™ [PLML] and vertical PlayerLoad™ [PLV]), together with locomotor activity (Total Distance Covered [TDC]) were determined in 15-min segments. Locomotor efficiency was calculated using the ratio of PLVM and TDC (PlayerLoad™ per metre). The proportion of variance explaining the within-match trends in PLVM, PLAP, APML, APv, and TDC was determined owing to matches, individual players, and positional role. PLVM, PLAP, APML, APv and TDC reduced after the initial 15-min match period (p=0.001; η(2)=0.22-0.43, large effects). PL:TDC increased in the last 15min of each half (p=0.001; η(2)=0.25, large effect). The variance in PLVM during soccer match-play was explained by individual players (63.9%; p=0.001) and between-match variation (21.6%; p=0.001), but not positional role (14.1%; p=0.364). Locomotor efficiency is lower during the latter stages of each half of competitive soccer match-play, a trend synonymous with observations of increased injury incidence and fatigue in these periods. Locomotor efficiency may be a valuable metric to identify fatigue and heightened injury risk during soccer training and match-play. Copyright © 2015 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Recruitment of faster motor units is associated with greater rates of fascicle strain and rapid changes in muscle force during locomotion.

PubMed

Lee, Sabrina S M; de Boef Miara, Maria; Arnold, Allison S; Biewener, Andrew A; Wakeling, James M

2013-01-15

Animals modulate the power output needed for different locomotor tasks by changing muscle forces and fascicle strain rates. To generate the necessary forces, appropriate motor units must be recruited. Faster motor units have faster activation-deactivation rates than slower motor units, and they contract at higher strain rates; therefore, recruitment of faster motor units may be advantageous for tasks that involve rapid movements or high rates of work. This study identified motor unit recruitment patterns in the gastrocnemii muscles of goats and examined whether faster motor units are recruited when locomotor speed is increased. The study also examined whether locomotor tasks that elicit faster (or slower) motor units are associated with increased (or decreased) in vivo tendon forces, force rise and relaxation rates, fascicle strains and/or strain rates. Electromyography (EMG), sonomicrometry and muscle-tendon force data were collected from the lateral and medial gastrocnemius muscles of goats during level walking, trotting and galloping and during inclined walking and trotting. EMG signals were analyzed using wavelet and principal component analyses to quantify changes in the EMG frequency spectra across the different locomotor conditions. Fascicle strain and strain rate were calculated from the sonomicrometric data, and force rise and relaxation rates were determined from the tendon force data. The results of this study showed that faster motor units were recruited as goats increased their locomotor speeds from level walking to galloping. Slow inclined walking elicited EMG intensities similar to those of fast level galloping but different EMG frequency spectra, indicating that recruitment of the different motor unit types depended, in part, on characteristics of the task. For the locomotor tasks and muscles analyzed here, recruitment patterns were generally associated with in vivo fascicle strain rates, EMG intensity and tendon force. Together, these data provide new evidence that changes in motor unit recruitment have an underlying mechanical basis, at least for certain locomotor tasks.

Design and development of anthropometric device for the standardization of sizes of knee-ankle-foot orthoses.

PubMed

Dwivedi, M; Shetty, K D; Nath, L Narendra

2009-01-01

An anthropometric device (AD) was designed and developed to collect data on foot and knee of locomotor disabled people. The aim was to standardize the sizes of knee-ankle-foot orthoses (KAFOs) in a standard modular form so that they can be mass produced to cater for fitting to a large number of locomotor disabled people. The anthropometric data collected on large numbers of locomotor disabled people were processed, with the help of a computer programme, to arrive at standard sizes for three modules, i.e. a foot plate (seven sizes), knee pieces (six sizes) and a lateral upright in a universal size. These modules were produced by plastic injection moulding and compression moulding processes using glass-reinforced polypropylene. KAFOs were assembled and fitted to locomotor disabled people. Feedback obtained was encouraging and this vindicated the concept, design and utility of the AD.

Evidence That GABA Mediates Dopaminergic and Serotonergic Pathways Associated with Locomotor Activity in Juvenile Chinook Salmon (Oncorhynchus tshawytscha)

USGS Publications Warehouse

Clements, S.; Schreck, C.B.

2004-01-01

The authors examined the control of locomotor activity in juvenile salmon (Oncorhynchus tshawytscha) by manipulating 3 neurotransmitter systems-gamma-amino-n-butyric acid (GABA), dopamine, and serotonin-as well as the neuropeptide corticotropin releasing hormone (CRH). Intracerebroventricular (ICV) injections of CRH and the GABAAagonist muscimol stimulated locomotor activity. The effect of muscimol was attenuated by administration of a dopamine receptor antagonist, haloperidol. Conversely, the administration of a dopamine uptake inhibitor (4???,4??? -difluoro-3-alpha-[diphenylmethoxy] tropane hydrochloride [DUI]) potentiated the effect of muscimol. They found no evidence that CRH-induced hyperactivity is mediated by dopaminergic systems following concurrent injections of haloperidol or DUI with CRH. Administration of muscimol either had no effect or attenuated the locomotor response to concurrent injections of CRH and fluoxetine, whereas the GABAA antagonist bicuculline methiodide potentiated the effect of CRH and fluoxetine.

Locomotion in response to shifting climate zones: not so fast.

PubMed

Feder, Martin E; Garland, Theodore; Marden, James H; Zera, Anthony J

2010-01-01

Although a species' locomotor capacity is suggestive of its ability to escape global climate change, such a suggestion is not necessarily straightforward. Species vary substantially in locomotor capacity, both ontogenetically and within/among populations, and much of this variation has a genetic basis. Accordingly, locomotor capacity can and does evolve rapidly, as selection experiments demonstrate. Importantly, even though this evolution of locomotor capacity may be rapid enough to escape changing climate, genetic correlations among traits (often due to pleiotropy) are such that successful or rapid dispersers are often limited in colonization or reproductive ability, which may be viewed as a trade-off. The nuanced assessment of this variation and evolution is reviewed for well-studied models: salmon, flying versus flightless insects, rodents undergoing experimental evolution, and metapopulations of butterflies. This work reveals how integration of physiology with population biology and functional genomics can be especially informative.

[Sacroiliac joint dysfunction with groin pain after an operation for lumbar spinal disorder. A case report].

PubMed

Shimoda, Yusuke; Morimoto, Daijiro; Isu, Toyohiko; Motegi, Hiroaki; Imai, Tetsuaki; Matsumoto, Ryouji; Isobe, Masanori; Kim, Kyongsong; Sugawara, Atsushi

2010-11-01

A 75-year-old male presented with groin pain after an operation to treat lumbar spondylolisthesis (L5). Groin tenderness was localized to the medial border of the anterior superior iliac spine (ASIS). Radiographical and physical examination raised the suspicion of sacroiliac joint (SIJ) dysfunction. Injection of a painkiller into the SIJ relieved symptoms, including groin tenderness. Symptoms improved gradually, and finally disappeared after five SIJ injections. Groin pain has been reported as a referred symptom of SIJ dysfunction in 9.3-23% of patients. Prior to the patient undergoing surgery to treat lumbar spondylolisthesis, SIJ dysfunction had not been noted on physical examination. Long periods spent in the abnormal posture due to lumbar spondylolisthesis induced SIJ stress. After the operation, an improvement in daily activity actually increased stress on the SIJ, resulting in SIJ dysfunction. Certain pathologies, including SIJ dysfunction, should be considered as residual symptoms after operations for lumbar spinal diseases.

The effects and mechanisms of mitochondrial nutrient alpha-lipoic acid on improving age-associated mitochondrial and cognitive dysfunction: an overview.

PubMed

Liu, Jiankang

2008-01-01

We have identified a group of nutrients that can directly or indirectly protect mitochondria from oxidative damage and improve mitochondrial function and named them "mitochondrial nutrients". The direct protection includes preventing the generation of oxidants, scavenging free radicals or inhibiting oxidant reactivity, and elevating cofactors of defective mitochondrial enzymes with increased Michaelis-Menten constant to stimulate enzyme activity, and also protect enzymes from further oxidation, and the indirect protection includes repairing oxidative damage by enhancing antioxidant defense systems either through activation of phase 2 enzymes or through increase in mitochondrial biogenesis. In this review, we take alpha-lipoic acid (LA) as an example of mitochondrial nutrients by summarizing the protective effects and possible mechanisms of LA and its derivatives on age-associated cognitive and mitochondrial dysfunction of the brain. LA and its derivatives improve the age-associated decline of memory, improve mitochondrial structure and function, inhibit the age-associated increase of oxidative damage, elevate the levels of antioxidants, and restore the activity of key enzymes. In addition, co-administration of LA with other mitochondrial nutrients, such as acetyl-L: -carnitine and coenzyme Q10, appears more effective in improving cognitive dysfunction and reducing oxidative mitochondrial dysfunction. Therefore, administrating mitochondrial nutrients, such as LA and its derivatives in combination with other mitochondrial nutrients to aged people and patients suffering from neurodegenerative diseases, may be an effective strategy for improving mitochondrial and cognitive dysfunction.

Effects of training and weight support on muscle activation in Parkinson's disease.

PubMed

Rose, Martin H; Løkkegaard, Annemette; Sonne-Holm, Stig; Jensen, Bente R

2013-12-01

The aim of this study was to investigate the effect of high-intensity locomotor training on knee extensor and flexor muscle activation and adaptability to increased body-weight (BW) support during walking in patients with Parkinson's disease (PD). Thirteen male patients with idiopathic PD and eight healthy participants were included. The PD patients completed an 8-week training program on a lower-body, positive-pressure treadmill. Knee extensor and flexor muscles activation during steady treadmill walking (3 km/h) were measured before, at the mid-point, and after training. Increasing BW support decreased knee extensor muscle activation (normalization) and increased knee flexor muscle activation (abnormal) in PD patients when compared to healthy participants. Training improved flexor peak muscle activation adaptability to increased (BW) support during walking in PD patients. During walking without BW support shorter knee extensor muscle off-activation time and increased relative peak muscle activation was observed in PD patients and did not improve with 8 weeks of training. In conclusion, patients with PD walked with excessive activation of the knee extensor and flexor muscles when compared to healthy participants. Specialized locomotor training may facilitate adaptive processes related to motor control of walking in PD patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

Reactions of the rat musculoskeletal system to compressive spinal cord injury (SCI) and whole body vibration (WBV) therapy

PubMed Central

Schwarz, A.; Pick, C.; Harrach, R.; Stein, G.; Bendella, H.; Ozsoy, O.; Ozsoy, U.; Schoenau, E.; Jaminet, P.; Sarikcioglu, L.; Dunlop, S.; Angelov, D.N.

2015-01-01

Traumatic spinal cord injury (SCI) causes a loss of locomotor function with associated compromise of the musculo-skeletal system. Whole body vibration (WBV) is a potential therapy following SCI, but little is known about its effects on the musculo-skeletal system. Here, we examined locomotor recovery and the musculo-skeletal system after thoracic (T7-9) compression SCI in adult rats. Daily WBV was started at 1, 7, 14 and 28 days after injury (WBV1-WBV28 respectively) and continued over a 12-week post-injury period. Intact rats, rats with SCI but no WBV (sham-treated) and a group that received passive flexion and extension (PFE) of their hind limbs served as controls. Compared to sham-treated rats, neither WBV nor PFE improved motor function. Only WBV14 and PFE improved body support. In line with earlier studies we failed to detect signs of soleus muscle atrophy (weight, cross sectional diameter, total amount of fibers, mean fiber diameter) or bone loss in the femur (length, weight, bone mineral density). One possible explanation is that, despite of injury extent, the preservation of some axons in the white matter, in combination with quadripedal locomotion, may provide sufficient trophic and neuronal support for the musculoskeletal system. PMID:26032204

Quercetin Improves Neurobehavioral Performance Through Restoration of Brain Antioxidant Status and Acetylcholinesterase Activity in Manganese-Treated Rats.

PubMed

Adedara, Isaac A; Ego, Valerie C; Subair, Temitayo I; Oyediran, Oluwasetemi; Farombi, Ebenezer O

2017-04-01

The present study investigated the neuroprotective mechanism of quercetin by assessing the biochemical and behavioral characteristics in rats sub-chronically treated with manganese alone at 15 mg/kg body weight or orally co-treated with quercetin at 10 and 20 mg/kg body weight for 45 consecutive days. Locomotor behavior was monitored using video-tracking software during a 10-min trial in a novel environment whereas the brain regions namely the hypothalamus, cerebrum and cerebellum of the rats were processed for biochemical analyses. Results indicated that co-treatment with quercetin significantly (p < 0.05) prevented manganese-induced locomotor and motor deficits specifically the decrease in total distance travelled, total body rotation, maximum speed, absolute turn angle as well as the increase in time of immobility and grooming. The improvement in the neurobehavioral performance of manganese-treated rats following quercetin co-treatment was confirmed by track and occupancy plot analyses. Moreover, quercetin assuaged manganese-induced decrease in antioxidant enzymes activities and the increase in acetylcholinesterase activity, hydrogen peroxide generation and lipid peroxidation levels in the hypothalamus, cerebrum and cerebellum of the rats. Taken together, quercetin mechanisms of ameliorating manganese-induced neurotoxicity is associated with restoration of acetylcholinesterase activity, augmentation of redox status and inhibition of lipid peroxidation in brain of rats.

NECTARINE PROMOTES LONGEVITY IN DROSOPHILA MELANOGASTER

PubMed Central

Boyd, Olga; Weng, Peter; Sun, Xiaoping; Alberico, Thomas; Laslo, Mara; Obenland, David M.; Kern, Bradley; Zou, Sige

2011-01-01

Fruits containing high antioxidant capacities and other bioactivities are ideal for promoting longevity and healthspan. However, few fruits are known to improve the survival and healthspan in animals, let alone the underlying mechanisms. Here we investigate the effect of nectarine, a globally consumed fruit, on lifespan and healthspan in Drosophila melanogaster. Wild-type flies were fed the standard, dietary restriction (DR) or high fat diets supplemented with 0–4% nectarine extract. We measured lifespan, food intake, locomotor activity, fecundity, gene expression changes, and oxidative damage indicated by the level of 4-Hydroxynonenal-protein adduct in these flies. We also measured lifespan, locomotor activity and oxidative damage of sod1 mutant flies on the standard diet supplemented with 0–4% nectarine. Supplementation of 4% nectarine extended lifespan, increased fecundity and decreased expression of some metabolic genes, including a key gluconeogenesis gene PEPCK, and oxidative stress response genes, including peroxiredoxins, in female wild-type flies fed the standard, DR or high fat diet. Nectarine reduced oxidative damage in wild-type females fed the high fat diet. Moreover, nectarine improved the survival and reduced oxidative damage in female sod1 mutant flies. Together, these findings suggest that nectarine promotes longevity and healthspan partly through modulating glucose metabolism and reducing oxidative damage. PMID:21406223

Reactions of the rat musculoskeletal system to compressive spinal cord injury (SCI) and whole body vibration (WBV) therapy.

PubMed

Schwarz, A; Pick, C; Harrach, R; Stein, G; Bendella, H; Ozsoy, O; Ozsoy, U; Schoenau, E; Jaminet, P; Sarikcioglu, L; Dunlop, S; Angelov, D N

2015-06-01

Traumatic spinal cord injury (SCI) causes a loss of locomotor function with associated compromise of the musculo-skeletal system. Whole body vibration (WBV) is a potential therapy following SCI, but little is known about its effects on the musculo-skeletal system. Here, we examined locomotor recovery and the musculo-skeletal system after thoracic (T7-9) compression SCI in adult rats. Daily WBV was started at 1, 7, 14 and 28 days after injury (WBV1-WBV28 respectively) and continued over a 12-week post-injury period. Intact rats, rats with SCI but no WBV (sham-treated) and a group that received passive flexion and extension (PFE) of their hind limbs served as controls. Compared to sham-treated rats, neither WBV nor PFE improved motor function. Only WBV14 and PFE improved body support. In line with earlier studies we failed to detect signs of soleus muscle atrophy (weight, cross sectional diameter, total amount of fibers, mean fiber diameter) or bone loss in the femur (length, weight, bone mineral density). One possible explanation is that, despite of injury extent, the preservation of some axons in the white matter, in combination with quadripedal locomotion, may provide sufficient trophic and neuronal support for the musculoskeletal system.

The Anti-Inflammatory Compound Curcumin Enhances Locomotor and Sensory Recovery after Spinal Cord Injury in Rats by Immunomodulation

PubMed Central

Machova Urdzikova, Lucia; Karova, Kristyna; Ruzicka, Jiri; Kloudova, Anna; Shannon, Craig; Dubisova, Jana; Murali, Raj; Kubinova, Sarka; Sykova, Eva; Jhanwar-Uniyal, Meena; Jendelova, Pavla

2015-01-01

Well known for its anti-oxidative and anti-inflammation properties, curcumin is a polyphenol found in the rhizome of Curcuma longa. In this study, we evaluated the effects of curcumin on behavioral recovery, glial scar formation, tissue preservation, axonal sprouting, and inflammation after spinal cord injury (SCI) in male Wistar rats. The rats were randomized into two groups following a balloon compression injury at the level of T9–T10 of the spinal cord, namely vehicle- or curcumin-treated. Curcumin was applied locally on the surface of the injured spinal cord immediately following injury and then given intraperitoneally daily; the control rats were treated with vehicle in the same manner. Curcumin treatment improved behavioral recovery within the first week following SCI as evidenced by improved Basso, Beattie, and Bresnahan (BBB) test and plantar scores, representing locomotor and sensory performance, respectively. Furthermore, curcumin treatment decreased glial scar formation by decreasing the levels of MIP1α, IL-2, and RANTES production and by decreasing NF-κB activity. These results, therefore, demonstrate that curcumin has a profound anti-inflammatory therapeutic potential in the treatment of spinal cord injury, especially when given immediately after the injury. PMID:26729105

Acute and chronic hypoxia: implications for cerebral function and exercise tolerance

PubMed Central

Goodall, Stuart; Twomey, Rosie; Amann, Markus

2015-01-01

Purpose To outline how hypoxia profoundly affects neuronal functionality and thus compromise exercise-performance. Methods Investigations using electroencephalography (EEG) and transcranial magnetic stimulation (TMS) detecting neuronal changes at rest and those studying fatiguing effects on whole-body exercise performance in acute (AH) and chronic hypoxia (CH) were evaluated. Results At rest during very early hypoxia (<1-h), slowing of cerebral neuronal activity is evident despite no change in corticospinal excitability. As time in hypoxia progresses (3-h), increased corticospinal excitability becomes evident; however, changes in neuronal activity are unknown. Prolonged exposure (3–5 d) causes a respiratory alkalosis which modulates Na+ channels, potentially explaining reduced neuronal excitability. Locomotor exercise in AH exacerbates the development of peripheral-fatigue; as the severity of hypoxia increases, mechanisms of peripheral-fatigue become less dominant and CNS hypoxia becomes the predominant factor. The greatest central-fatigue in AH occurs when SaO2 is ≤75%, a level that coincides with increasing impairments in neuronal activity. CH does not improve the level of peripheral-fatigue observed in AH; however, it attenuates the development of central-fatigue paralleling increases in cerebral O2 availability and corticospinal excitability. Conclusions The attenuated development of central-fatigue in CH might explain, the improvements in locomotor exercise-performance commonly observed after acclimatisation to high altitude. PMID:25593787

Home tank water versus novel water differentially affect alcohol-induced locomotor activity and anxiety related behaviours in zebrafish.

PubMed

Tran, Steven; Facciol, Amanda; Gerlai, Robert

2016-05-01

The zebrafish may be uniquely well suited for studying alcohol's mechanisms of action in vivo, since alcohol can be administered via immersion in a non-invasive manner. Despite the robust behavioural effects of alcohol administration in mammals, studies reporting the locomotor stimulant and anxiolytic effects of alcohol in zebrafish have been inconsistent. In the current study, we examined whether differences in the type of water used for alcohol exposure and behavioural testing contribute to these inconsistencies. To answer this question, we exposed zebrafish to either home water from their housing tanks or novel water from an isolated reservoir (i.e. water lacking zebrafish chemosensory and olfactory cues) with 0% or 1% v/v alcohol for 30 min, a 2 × 2 between subject experimental designs. Behavioural responses were quantified throughout the 30-minute exposure session via a video tracking system. Although control zebrafish exposed to home water and novel water were virtually indistinguishable in their behavioural responses, alcohol's effect on locomotor activity and anxiety-like behavioural responses were dependent on the type of water used for testing. Alcohol exposure in home tank water produced a mild anxiolytic and locomotor stimulant effect, whereas alcohol exposure in novel water produced an anxiogenic effect without altering locomotor activity. These results represent a dissociation between alcohol's effects on locomotor and anxiety related responses, and also illustrate how environmental factors, in this case familiarity with the water, may interact with such effects. In light of these findings, we urge researchers to explicitly state the type of water used. Copyright © 2016 Elsevier Inc. All rights reserved.

Novelty response and 50 kHz ultrasonic vocalizations: Differential prediction of locomotor and affective response to amphetamine in Sprague-Dawley rats.

PubMed

Garcia, Erik J; Cain, Mary E

2016-02-01

Novelty and sensation seeking (NSS) predisposes humans and rats to experiment with psychostimulants. In animal models, different tests of NSS predict different phases of drug dependence. Ultrasonic vocalizations (USVs) are evoked by psychomotor stimulants and measure the affective/motivation response to stimuli, yet the role NSS has on USVs in response to amphetamine is not determined. The aim of the present study was to determine if individual differences in NSS and USVs can predict locomotor and USV response to amphetamine (0.0, 0.3, and 1.0 mg/kg) after acute and chronic exposure. Thirty male rats were tested for their response to novelty (IEN), choice to engage in novelty (NPP), and heterospecific play (H-USV). Rats were administered non-contingent amphetamine or saline for seven exposures, and USVs and locomotor activity were measured. After a 14-day rest, rats were administered a challenge dose of amphetamine. Regression analyses indicated that amphetamine dose-dependently increased locomotor activity and the NPP test negatively predicted treatment-induced locomotor activity. The H-USV test predicted treatment-induced frequency-modulated (FM) USVs, but the strength of prediction depended on IEN response. Results provide evidence that locomotor activity and FM USVs induced by amphetamine represent different behavioral responses. The prediction of amphetamine-induced FM USVs by the H-USV screen was changed by the novelty response, indicating that the affective value of amphetamine-measured by FM USVs-depends on novelty response. This provides evidence that higher novelty responders may develop a tolerance faster and may escalate intake faster.

The effects of long-term dopaminergic treatment on locomotor behavior in rats.

PubMed

Oliveira de Almeida, Welinton Alessandro; Maculano Esteves, Andrea; Leite de Almeida-Júnior, Canuto; Lee, Kil Sun; Kannebley Frank, Miriam; Oliveira Mariano, Melise; Frussa-Filho, Roberto; Tufik, Sergio; Tulio de Mello, Marco

2014-12-01

Long-term treatments with dopaminergic agents are associated with adverse effects, including augmentation. Augmentation consists of an exacerbation of restless legs syndrome (a sleep-related movement disorder) symptoms during treatment compared to those experienced during the period before therapy was initiated. The objective of this study was to examine locomotor activity in rats after long-term dopaminergic treatment and its relationship with expression of the D2 receptor, in addition to demonstrating possible evidence of augmentation. The rats were divided into control (CTRL) and drug (Pramipexole-PPX) groups that received daily saline vehicle and PPX treatments, respectively, for 71 days. The locomotor behavior of the animals was evaluated weekly in the Open Field test for 71 days. The expression of the dopamine D2 receptor was evaluated by Western Blot analysis. The animals that received the PPX demonstrated a significant reduction in locomotor activity from day 1 to day 57 and a significant increase in immobility time from day 1 to day 64 relative to baseline values, but these values had returned to baseline levels at 71 days. No changes in the expression of the D2 receptor were demonstrated after treatment with a dopaminergic agonist. This study suggests changes in locomotor activity in rats after long-term PPX treatment that include an immediate reduction of locomotion and an increase in immobilization, and after 64 days, these values returned to baseline levels without evidence of augmentation. In addition, it was not possible to demonstrate a relationship between locomotor activity and the expression of D2 receptors under these conditions.

The Effect of Inspiratory Muscle Training on Respiratory and Limb Locomotor Muscle Deoxygenation During Exercise with Resistive Inspiratory Loading.

PubMed

Turner, L A; Tecklenburg-Lund, S L; Chapman, R; Shei, R-J; Wilhite, D P; Mickleborough, T

2016-07-01

We investigated how inspiratory muscle training impacted respiratory and locomotor muscle deoxygenation during submaximal exercise with resistive inspiratory loading. 16 male cyclists completed 6 weeks of either true (n=8) or sham (n=8) inspiratory muscle training. Pre- and post-training, subjects completed 3, 6-min experimental trials performed at ~80%  ˙VO2peak with interventions of either moderate inspiratory loading, heavy inspiratory loading, or maximal exercise imposed in the final 3 min. Locomotor and respiratory muscle oxy-, deoxy-, and total-haemoglobin and myoglobin concentration was continuously monitored using near-infrared spectroscopy. Locomotor muscle deoxygenation changes from 80%  ˙VO2peak to heavy inspiratory loading were significantly reduced pre- to post-training from 4.3±5.6 µM to 2.7±4.7 µM. Respiratory muscle deoxygenation was also significantly reduced during the heavy inspiratory loading trial (4.6±3.5 µM to 1.9±1.5 µM) post-training. There was no significant difference in oxy-, deoxy-, or total-haemoglobin and myoglobin during any of the other loading trials, from pre- to post-training, in either group. After inspiratory muscle training, highly-trained cyclists exhibited decreased locomotor and respiratory muscle deoxygenation during exercise with heavy inspiratory loading. These data suggest that inspiratory muscle training reduces oxygen extraction by the active respiratory and limb muscles, which may reflect changes in respiratory and locomotor muscle oxygen delivery. © Georg Thieme Verlag KG Stuttgart · New York.

The effects of long-term dopaminergic treatment on locomotor behavior in rats

PubMed Central

Oliveira de Almeida, Welinton Alessandro; Maculano Esteves, Andrea; Leite de Almeida-Júnior, Canuto; Lee, Kil Sun; Kannebley Frank, Miriam; Oliveira Mariano, Melise; Frussa-Filho, Roberto; Tufik, Sergio; Tulio de Mello, Marco

2014-01-01

Long-term treatments with dopaminergic agents are associated with adverse effects, including augmentation. Augmentation consists of an exacerbation of restless legs syndrome (a sleep-related movement disorder) symptoms during treatment compared to those experienced during the period before therapy was initiated. The objective of this study was to examine locomotor activity in rats after long-term dopaminergic treatment and its relationship with expression of the D2 receptor, in addition to demonstrating possible evidence of augmentation. The rats were divided into control (CTRL) and drug (Pramipexole—PPX) groups that received daily saline vehicle and PPX treatments, respectively, for 71 days. The locomotor behavior of the animals was evaluated weekly in the Open Field test for 71 days. The expression of the dopamine D2 receptor was evaluated by Western Blot analysis. The animals that received the PPX demonstrated a significant reduction in locomotor activity from day 1 to day 57 and a significant increase in immobility time from day 1 to day 64 relative to baseline values, but these values had returned to baseline levels at 71 days. No changes in the expression of the D2 receptor were demonstrated after treatment with a dopaminergic agonist. This study suggests changes in locomotor activity in rats after long-term PPX treatment that include an immediate reduction of locomotion and an increase in immobilization, and after 64 days, these values returned to baseline levels without evidence of augmentation. In addition, it was not possible to demonstrate a relationship between locomotor activity and the expression of D2 receptors under these conditions. PMID:26483930

Gross Motor Development in Children Aged 3-5 Years, United States 2012.

PubMed

Kit, Brian K; Akinbami, Lara J; Isfahani, Neda Sarafrazi; Ulrich, Dale A

2017-07-01

Objective Gross motor development in early childhood is important in fostering greater interaction with the environment. The purpose of this study is to describe gross motor skills among US children aged 3-5 years using the Test of Gross Motor Development (TGMD-2). Methods We used 2012 NHANES National Youth Fitness Survey (NNYFS) data, which included TGMD-2 scores obtained according to an established protocol. Outcome measures included locomotor and object control raw and age-standardized scores. Means and standard errors were calculated for demographic and weight status with SUDAAN using sample weights to calculate nationally representative estimates, and survey design variables to account for the complex sampling methods. Results The sample included 339 children aged 3-5 years. As expected, locomotor and object control raw scores increased with age. Overall mean standardized scores for locomotor and object control were similar to the mean value previously determined using a normative sample. Girls had a higher mean locomotor, but not mean object control, standardized score than boys (p < 0.05). However, the mean locomotor standardized scores for both boys and girls fell into the range categorized as "average." There were no other differences by age, race/Hispanic origin, weight status, or income in either of the subtest standardized scores (p > 0.05). Conclusions In a nationally representative sample of US children aged 3-5 years, TGMD-2 mean locomotor and object control standardized scores were similar to the established mean. These results suggest that standardized gross motor development among young children generally did not differ by demographic or weight status.

Down-regulation of Decapping Protein 2 mediates chronic nicotine exposure-induced locomotor hyperactivity in Drosophila.

PubMed

Ren, Jing; Sun, Jinghan; Zhang, Yunpeng; Liu, Tong; Ren, Qingzhong; Li, Yan; Guo, Aike

2012-01-01

Long-term tobacco use causes nicotine dependence via the regulation of a wide range of genes and is accompanied by various health problems. Studies in mammalian systems have revealed some key factors involved in the effects of nicotine, including nicotinic acetylcholine receptors (nAChRs), dopamine and other neurotransmitters. Nevertheless, the signaling pathways that link nicotine-induced molecular and behavioral modifications remain elusive. Utilizing a chronic nicotine administration paradigm, we found that adult male fruit flies exhibited locomotor hyperactivity after three consecutive days of nicotine exposure, while nicotine-naive flies did not. Strikingly, this chronic nicotine-induced locomotor hyperactivity (cNILH) was abolished in Decapping Protein 2 or 1 (Dcp2 or Dcp1) -deficient flies, while only Dcp2-deficient flies exhibited higher basal levels of locomotor activity than controls. These results indicate that Dcp2 plays a critical role in the response to chronic nicotine exposure. Moreover, the messenger RNA (mRNA) level of Dcp2 in the fly head was suppressed by chronic nicotine treatment, and up-regulation of Dcp2 expression in the nervous system blocked cNILH. These results indicate that down-regulation of Dcp2 mediates chronic nicotine-exposure-induced locomotor hyperactivity in Drosophila. The decapping proteins play a major role in mRNA degradation; however, their function in the nervous system has rarely been investigated. Our findings reveal a significant role for the mRNA decapping pathway in developing locomotor hyperactivity in response to chronic nicotine exposure and identify Dcp2 as a potential candidate for future research on nicotine dependence.

Bupropion hydrochloride produces conditioned hyperactivity in rats.

PubMed

Wilkinson, Jamie L; Bevins, Rick A

2007-04-23

Bupropion is marketed as an antidepressant, Wellbutrin and smoking cessation aid, Zyban. Although the therapeutic neurological mechanisms of bupropion have not been fully elucidated, bupropion shares some behavioral similarities with classic psychomotor stimulants. The present study sought to further investigate these psychomotor stimulant effects of bupropion by assessing whether repeated administration of bupropion in a distinct environment produced conditioned hyperactivity. Paired rats received 10 daily i.p. injections of bupropion (2.5-30 mg/kg) before placement in locomotor chambers for 30 min. Bupropion (10-30 mg/kg) produced acute locomotor hyperactivity compared to Unpaired controls. After repeated administration, there was no progressive increase or decrease in bupropion-induced activity. In a subsequent drug-free session conditioned hyperactivity was observed at 5-30 mg/kg doses. In a follow-up experiment, we examined whether responsiveness to novelty predicted the subsequent unconditioned and conditioned locomotor effect of bupropion. Reactivity to inescapable novelty, novel environment approach, and novel-object interaction were measured before locomotor conditioning with 30 mg/kg bupropion. We replicated the previous experiment, but scores on the novelty screens did not predict locomotor response to bupropion. This study extends the literature by demonstrating that environmental cues repeatedly paired with the stimulant effects of bupropion come to evoke elevated activity in the absence of drug (i.e., conditioned hyperactivity). This finding is consistent with the literature suggesting that bupropion shares many behavioral similarities with other psychomotor stimulants which also produce conditioned hyperactivity. However, a predictive relation between reactivity to forced novelty and the subsequent locomotor effect of bupropion may not be one of these similarities.

Down-Regulation of Decapping Protein 2 Mediates Chronic Nicotine Exposure-Induced Locomotor Hyperactivity in Drosophila

PubMed Central

Ren, Jing; Sun, Jinghan; Zhang, Yunpeng; Liu, Tong; Ren, Qingzhong; Li, Yan; Guo, Aike

2012-01-01

Long-term tobacco use causes nicotine dependence via the regulation of a wide range of genes and is accompanied by various health problems. Studies in mammalian systems have revealed some key factors involved in the effects of nicotine, including nicotinic acetylcholine receptors (nAChRs), dopamine and other neurotransmitters. Nevertheless, the signaling pathways that link nicotine-induced molecular and behavioral modifications remain elusive. Utilizing a chronic nicotine administration paradigm, we found that adult male fruit flies exhibited locomotor hyperactivity after three consecutive days of nicotine exposure, while nicotine-naive flies did not. Strikingly, this chronic nicotine-induced locomotor hyperactivity (cNILH) was abolished in Decapping Protein 2 or 1 (Dcp2 or Dcp1) -deficient flies, while only Dcp2-deficient flies exhibited higher basal levels of locomotor activity than controls. These results indicate that Dcp2 plays a critical role in the response to chronic nicotine exposure. Moreover, the messenger RNA (mRNA) level of Dcp2 in the fly head was suppressed by chronic nicotine treatment, and up-regulation of Dcp2 expression in the nervous system blocked cNILH. These results indicate that down-regulation of Dcp2 mediates chronic nicotine-exposure-induced locomotor hyperactivity in Drosophila. The decapping proteins play a major role in mRNA degradation; however, their function in the nervous system has rarely been investigated. Our findings reveal a significant role for the mRNA decapping pathway in developing locomotor hyperactivity in response to chronic nicotine exposure and identify Dcp2 as a potential candidate for future research on nicotine dependence. PMID:23300696

Motor unit recruitment patterns 1: responses to changes in locomotor velocity and incline.

PubMed

Hodson-Tole, Emma F; Wakeling, James M

2008-06-01

Mammalian skeletal muscles are composed of a mixture of motor unit types, which contribute a range of mechanical and physiological properties to the muscle. For a muscle to effectively contribute to smooth, co-ordinated movement it must activate an appropriate number and combination of motor units to generate the required force over a suitable time period. Much evidence exists indicating that motor units are activated in an orderly fashion, from the slowest through to the fastest. A growing body of evidence, however, indicates that such a recruitment strategy does not always hold true. Here we investigate how motor unit recruitment patterns were influenced by changes in locomotor velocity and incline. Kinematics data and myoelectric signals were collected from three rat ankle extensor muscles during running on a treadmill at nine velocity and incline combinations. Wavelet and principal component analysis were used to simultaneously decompose the signals into time and frequency space. The relative frequency components of the signals were quantified during 20 time windows of a stride from each locomotor condition. Differences in signal frequency components existed between muscles and locomotor conditions. Faster locomotor velocities led to a relative increase in high frequency components, whereas greater inclines led to a relative increase in the low frequency components. These data were interpreted as representing changes in motor unit recruitment patterns in response to changes in the locomotor demand. Motor units were not always recruited in an orderly manner, indicating that recruitment is a multi-factorial phenomenon that is not yet fully understood.

Effects of running with backpack loads during simulated gravitational transitions: Improvements in postural control

NASA Astrophysics Data System (ADS)

Brewer, Jeffrey David

The National Aeronautics and Space Administration is planning for long-duration manned missions to the Moon and Mars. For feasible long-duration space travel, improvements in exercise countermeasures are necessary to maintain cardiovascular fitness, bone mass throughout the body and the ability to perform coordinated movements in a constant gravitational environment that is six orders of magnitude higher than the "near weightlessness" condition experienced during transit to and/or orbit of the Moon, Mars, and Earth. In such gravitational transitions feedback and feedforward postural control strategies must be recalibrated to ensure optimal locomotion performance. In order to investigate methods of improving postural control adaptation during these gravitational transitions, a treadmill based precision stepping task was developed to reveal changes in neuromuscular control of locomotion following both simulated partial gravity exposure and post-simulation exercise countermeasures designed to speed lower extremity impedance adjustment mechanisms. The exercise countermeasures included a short period of running with or without backpack loads immediately after partial gravity running. A novel suspension type partial gravity simulator incorporating spring balancers and a motor-driven treadmill was developed to facilitate body weight off loading and various gait patterns in both simulated partial and full gravitational environments. Studies have provided evidence that suggests: the environmental simulator constructed for this thesis effort does induce locomotor adaptations following partial gravity running; the precision stepping task may be a helpful test for illuminating these adaptations; and musculoskeletal loading in the form of running with or without backpack loads may improve the locomotor adaptation process.

Outcome of therapy in the conservative management of temporomandibular pain dysfunction disorder.

PubMed

Suvinen, T I; Hanes, K R; Reade, P C

1997-10-01

The present study considered predictors of the outcome of treatment for temporomandibular pain dysfunction disorder (TMPD). Thirty-seven patients were assessed with objective and self-report measures of physiological and psychosocial aspects of this disorder at initial assessment and at 6-month follow-up subsequent to conservative physical therapy. Patients were subdivided into slow and rapid responders to conservative physical therapy based on self-reported level of improvement. Measures employed included the Temporomandibular Pain Dysfunction Disorder Questionnaire and the Temporomandibular Pain Dysfunction Disorder Clinical Form. Eighty-one per cent of patients showed a 50% or greater improvement in pain severity at follow-up, with minimal differential changes across the two groups found in the physiological symptoms, while the rapid responding group showed greater improvement in terms of psychosocial factors. These findings indicated that psychosocial factors, particularly coping strategies and illness behaviour, cannot be ignored in the management of TMPD.

The delta-opioid receptor agonist SNC80 [(+)-4-[alpha(R)-alpha-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-(3-methoxybenzyl)-N,N-diethylbenzamide] synergistically enhances the locomotor-activating effects of some psychomotor stimulants, but not direct dopamine agonists, in rats.

PubMed

Jutkiewicz, Emily M; Baladi, Michelle G; Folk, John E; Rice, Kenner C; Woods, James H

2008-02-01

The nonpeptidic delta-opioid agonist SNC80 [(+)-4-[alpha(R)-alpha-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-(3-methoxybenzyl)-N,N-diethylbenzamide] produces many stimulant-like behavioral effects in rodents and monkeys, such as locomotor stimulation, generalization to cocaine in discrimination procedures, and antiparkinsonian effects. Tolerance to the locomotor-stimulating effects of SNC80 develops after a single administration of SNC80 in rats; it is not known whether cross-tolerance develops to the effects of other stimulant compounds. In the initial studies to determine whether SNC80 produced cross-tolerance to other stimulant compounds, it was discovered that amphetamine-stimulated locomotor activity was greatly enhanced in SNC80-pretreated rats. This study evaluated acute cross-tolerance between delta-opioid agonists and other locomotor-stimulating drugs. Locomotor activity was measured in male Sprague-Dawley rats implanted with radiotransmitters, and activity levels were recorded in the home cage environment. Three-hour SNC80 pretreatment produced tolerance to further delta-opioid receptor stimulation but also augmented greatly amphetamine-stimulated locomotor activity in a dose-dependent manner. Pretreatments with other delta-opioid agonists, (+)BW373U86 [(+)-4-[alpha(R)-alpha-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-3-hydroxybenzyl]-N,N-diethylbenzamide] and oxymorphindole (17-methyl-6,7-dehydro-4,5-epoxy-3,14-dihydroxy-6,7,2',3'-indolomorphinan), also modified amphetamine-induced activity levels. SNC80 pretreatment enhanced the stimulatory effects of the dopamine/norepinephrine transporter ligands cocaine and nomifensine (1,2,3,4-tetrahydro-2-methyl-4-phenyl-8-isoquinolinanmine maleate salt), but not the direct dopamine receptor agonists SKF81297 [R-(+)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide] and quinpirole [trans-(-)-(4alphaR)-4,4a, 5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo[3,4-g] quinoline monohydrochloride]. In conclusion, SNC80 enhanced the locomotor-stimulating effects of monoamine transporter ligands suggesting that delta-opioid receptor activation might alter the functional activity of monoamine transporters or presynaptic monoamine terminals.

Effectiveness of exercise intervention on improving fundamental movement skills and motor coordination in overweight/obese children and adolescents: A systematic review.

PubMed

Han, Ahreum; Fu, Allan; Cobley, Stephen; Sanders, Ross H

2018-01-01

Childhood obesity is negatively associated with fundamental movement skill and motor coordination, which in turn constrains physical activity participation and adherence thereby forming a 'vicious cycle'. However, developing motor skill and coordination in childhood could help to break the vicious cycle to reduce childhood obesity. The objective of this systematic review was to determine the effectiveness of exercise and physical activity interventions on improving fundamental movement skill and motor coordination in overweight/obese children and adolescents. A systematic review with quality assessment. A comprehensive systematic search was conducted from MEDLINE, SPORTDiscus, CINAHL, Scopus, Web of Science, EMBASE without date restriction for randomized control trials, interventions or longitudinal studies of movement skill/motor skill/motor coordination in overweight/obese participants between 0-18 years of age. A total of 3944 publications were screened, and 17 published studies were included. Altogether 38 tests for locomotor, object-control, balance and complex task tests were examined in selected studies, with 33 reporting increases after interventions, while only five tests indicated no change. The evidence strongly suggests that exercise/physical activity interventions were effective in improving locomotor skill, object-control skill and complex tasks in overweight/obese peers. However, the results for balance were equivocal. Results from existing studies suggest overweight/obese peers have lower levels of fundamental movement skill than their healthy weight peers. However, exercise/physical activity interventions are effective in improving their skills. To maximize skill improvement, we recommend focused fundamental movement skill and motor coordination activities for skill development. These progressions in interventions may help break the vicious cycle of childhood obesity. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Xenon improves neurological outcome and reduces secondary injury following trauma in an in vivo model of traumatic brain injury

PubMed Central

Luh, Clara; Gruss, Marco; Radyushkin, Konstantin; Hirnet, Tobias; Werner, Christian; Engelhard, Kristin; Franks, Nicholas P; Thal, Serge C; Dickinson, Robert

2015-01-01

Objectives To determine the neuroprotective efficacy of the inert gas xenon following traumatic brain injury, and to determine whether application of xenon has a clinically relevant therapeutic time window. Design Controlled animal study. Setting University research laboratory. Subjects Male C57BL/6N mice (n=196) Interventions 75% xenon, 50% xenon or 30% xenon, with 25% oxygen (balance nitrogen) treatment following mechanical brain lesion by controlled cortical impact. Measurements & Main Results Outcome following trauma was measured using: 1) functional neurological outcome score, 2) histological measurement of contusion volume, 3) analysis of locomotor function and gait. Our study shows that xenon-treatment improves outcome following traumatic brain injury. Neurological outcome scores were significantly (p<0.05) better in xenon-treated groups in the early phase (24 hours) and up to 4 days after injury. Contusion volume was significantly (p<0.05) reduced in the xenon-treated groups. Xenon treatment significantly (p<0.05) reduced contusion volume when xenon was given 15 minutes after injury or when treatment was delayed 1 hour or 3 hours after injury. Neurological outcome was significantly (p<0.05) improved when xenon treatment was given 15 minutes or 1 hour after injury. Improvements in locomotor function (p<0.05) were observed in the xenon-treated group, 1 month after trauma. Conclusions These results show for the first time that xenon improves neurological outcome and reduces contusion volume following traumatic brain injury in mice. In this model, xenon application has a therapeutic time window of up to at least 3 hours. These findings support the idea that xenon may be of benefit as a neuroprotective treatment in brain trauma patients. PMID:25188549

Xenon improves neurologic outcome and reduces secondary injury following trauma in an in vivo model of traumatic brain injury.

PubMed

Campos-Pires, Rita; Armstrong, Scott P; Sebastiani, Anne; Luh, Clara; Gruss, Marco; Radyushkin, Konstantin; Hirnet, Tobias; Werner, Christian; Engelhard, Kristin; Franks, Nicholas P; Thal, Serge C; Dickinson, Robert

2015-01-01

To determine the neuroprotective efficacy of the inert gas xenon following traumatic brain injury and to determine whether application of xenon has a clinically relevant therapeutic time window. Controlled animal study. University research laboratory. Male C57BL/6N mice (n = 196). Seventy-five percent xenon, 50% xenon, or 30% xenon, with 25% oxygen (balance nitrogen) treatment following mechanical brain lesion by controlled cortical impact. Outcome following trauma was measured using 1) functional neurologic outcome score, 2) histological measurement of contusion volume, and 3) analysis of locomotor function and gait. Our study shows that xenon treatment improves outcome following traumatic brain injury. Neurologic outcome scores were significantly (p < 0.05) better in xenon-treated groups in the early phase (24 hr) and up to 4 days after injury. Contusion volume was significantly (p < 0.05) reduced in the xenon-treated groups. Xenon treatment significantly (p < 0.05) reduced contusion volume when xenon was given 15 minutes after injury or when treatment was delayed 1 or 3 hours after injury. Neurologic outcome was significantly (p < 0.05) improved when xenon treatment was given 15 minutes or 1 hour after injury. Improvements in locomotor function (p < 0.05) were observed in the xenon-treated group, 1 month after trauma. These results show for the first time that xenon improves neurologic outcome and reduces contusion volume following traumatic brain injury in mice. In this model, xenon application has a therapeutic time window of up to at least 3 hours. These findings support the idea that xenon may be of benefit as a neuroprotective treatment in patients with brain trauma.

Automatic 3D segmentation of spinal cord MRI using propagated deformable models

NASA Astrophysics Data System (ADS)

De Leener, B.; Cohen-Adad, J.; Kadoury, S.

2014-03-01

Spinal cord diseases or injuries can cause dysfunction of the sensory and locomotor systems. Segmentation of the spinal cord provides measures of atrophy and allows group analysis of multi-parametric MRI via inter-subject registration to a template. All these measures were shown to improve diagnostic and surgical intervention. We developed a framework to automatically segment the spinal cord on T2-weighted MR images, based on the propagation of a deformable model. The algorithm is divided into three parts: first, an initialization step detects the spinal cord position and orientation by using the elliptical Hough transform on multiple adjacent axial slices to produce an initial tubular mesh. Second, a low-resolution deformable model is iteratively propagated along the spinal cord. To deal with highly variable contrast levels between the spinal cord and the cerebrospinal fluid, the deformation is coupled with a contrast adaptation at each iteration. Third, a refinement process and a global deformation are applied on the low-resolution mesh to provide an accurate segmentation of the spinal cord. Our method was evaluated against a semi-automatic edge-based snake method implemented in ITK-SNAP (with heavy manual adjustment) by computing the 3D Dice coefficient, mean and maximum distance errors. Accuracy and robustness were assessed from 8 healthy subjects. Each subject had two volumes: one at the cervical and one at the thoracolumbar region. Results show a precision of 0.30 +/- 0.05 mm (mean absolute distance error) in the cervical region and 0.27 +/- 0.06 mm in the thoracolumbar region. The 3D Dice coefficient was of 0.93 for both regions.

Rapamycin suppresses brain aging in senescence-accelerated OXYS rats.

PubMed

Kolosova, Nataliya G; Vitovtov, Anton O; Muraleva, Natalia A; Akulov, Andrey E; Stefanova, Natalia A; Blagosklonny, Mikhail V

2013-06-01

Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span inC elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wister rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

Rapamycin suppresses brain aging in senescence-accelerated OXYS rats

PubMed Central

Kolosova, Nataliya G.; Vitovtov, Anton O.; Muraleva, Natalia A; Akulov, Andrey E.; Stefanova, Natalia A.; Blagosklonny, Mikhail V.

2013-01-01

Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span in C elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wistar rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging. PMID:23817674

SSRI-induced sexual dysfunction: fluoxetine, paroxetine, sertraline, and fluvoxamine in a prospective, multicenter, and descriptive clinical study of 344 patients.

PubMed

Montejo-González, A L; Llorca, G; Izquierdo, J A; Ledesma, A; Bousoño, M; Calcedo, A; Carrasco, J L; Ciudad, J; Daniel, E; De la Gandara, J; Derecho, J; Franco, M; Gomez, M J; Macias, J A; Martin, T; Perez, V; Sanchez, J M; Sanchez, S; Vicens, E

1997-01-01

The authors analyzed the incidence of sexual dysfunction (SD) with different selective serotonin reuptake inhibitors (SSRIs; fluoxetine, fluvoxamine, paroxetine, and sertraline) and hence the qualitative and quantitative changes in SD throughout time in a prospective and multicenter study. Outpatients (192 women and 152 men; age = 39.6 +/- 11.4 years) under treatment with SSRIs were interviewed with an SD questionnaire designed for this purpose by the authors and that included questions about the following: decreased libido, delayed orgasm or anorgasmia, delayed ejaculation, inability to ejaculate, impotence, and general sexual satisfaction. Patients with the following criteria were included: normal sexual function before SSRI intake, exclusive treatment with SSRIs or treatment associated with benzodiazepines, previous heterosexual or self-erotic current sexual practices. Excluded were patients with previous sexual dysfunction, association of SSRIs with neuroleptics, recent hormone intake, and significant medical illnesses. There was a significant increase in the incidence of SD when physicians asked the patients direct questions (58%) versus when SD was spontaneously reported (14%). There were some significant differences among different SSRIs: paroxetine provoked more delay of orgasm or ejaculation and more impotence than fluvoxamine, fluoxetine and sertraline (chi 2, p < .05). Only 24.5% of the patients had a good tolerance of their sexual dysfunction. Twelve male patients who suffered from premature ejaculation before the treatment preferred to maintain delayed ejaculation, and their sexual satisfaction, and that of their partners, clearly improved. Sexual dysfunction was positively correlated with dose. Patients experienced substantial improvement in sexual function when the dose was diminished or the drug was withdrawn. Men showed more incidence of sexual dysfunction than women, but women's sexual dysfunction was more intense than men's. In only 5.8% of patients, the dysfunction disappeared completely within 6 months, but 81.4% showed no improvement at all by the end of this period. Twelve of 15 patients experienced total improvement when the treatment was changed to moclobemide (450-600 mg/day), and 3 of 5 patients improved when treatment was changed to amineptine (200 mg/day).

Oral treatment with Cu(II)(atsm) increases mutant SOD1 in vivo but protects motor neurons and improves the phenotype of a transgenic mouse model of amyotrophic lateral sclerosis.

PubMed

Roberts, Blaine R; Lim, Nastasia K H; McAllum, Erin J; Donnelly, Paul S; Hare, Dominic J; Doble, Philip A; Turner, Bradley J; Price, Katherine A; Lim, Sin Chun; Paterson, Brett M; Hickey, James L; Rhoads, Timothy W; Williams, Jared R; Kanninen, Katja M; Hung, Lin W; Liddell, Jeffrey R; Grubman, Alexandra; Monty, Jean-Francois; Llanos, Roxana M; Kramer, David R; Mercer, Julian F B; Bush, Ashley I; Masters, Colin L; Duce, James A; Li, Qiao-Xin; Beckman, Joseph S; Barnham, Kevin J; White, Anthony R; Crouch, Peter J

2014-06-04

Mutations in the metallo-protein Cu/Zn-superoxide dismutase (SOD1) cause amyotrophic lateral sclerosis (ALS) in humans and an expression level-dependent phenotype in transgenic rodents. We show that oral treatment with the therapeutic agent diacetyl-bis(4-methylthiosemicarbazonato)copper(II) [Cu(II)(atsm)] increased the concentration of mutant SOD1 (SOD1G37R) in ALS model mice, but paradoxically improved locomotor function and survival of the mice. To determine why the mice with increased levels of mutant SOD1 had an improved phenotype, we analyzed tissues by mass spectrometry. These analyses revealed most SOD1 in the spinal cord tissue of the SOD1G37R mice was Cu deficient. Treating with Cu(II)(atsm) decreased the pool of Cu-deficient SOD1 and increased the pool of fully metallated (holo) SOD1. Tracking isotopically enriched (65)Cu(II)(atsm) confirmed the increase in holo-SOD1 involved transfer of Cu from Cu(II)(atsm) to SOD1, suggesting the improved locomotor function and survival of the Cu(II)(atsm)-treated SOD1G37R mice involved, at least in part, the ability of the compound to improve the Cu content of the mutant SOD1. This was supported by improved survival of SOD1G37R mice that expressed the human gene for the Cu uptake protein CTR1. Improving the metal content of mutant SOD1 in vivo with Cu(II)(atsm) did not decrease levels of misfolded SOD1. These outcomes indicate the metal content of SOD1 may be a greater determinant of the toxicity of the protein in mutant SOD1-associated forms of ALS than the mutations themselves. Improving the metal content of SOD1 therefore represents a valid therapeutic strategy for treating ALS caused by SOD1. Copyright © 2014 the authors 0270-6474/14/348021-11$15.00/0.

Neuronal control of locomotor handedness in Drosophila.

PubMed

Buchanan, Sean M; Kain, Jamey S; de Bivort, Benjamin L

2015-05-26

Genetically identical individuals display variability in their physiology, morphology, and behaviors, even when reared in essentially identical environments, but there is little mechanistic understanding of the basis of such variation. Here, we investigated whether Drosophila melanogaster displays individual-to-individual variation in locomotor behaviors. We developed a new high-throughout platform capable of measuring the exploratory behavior of hundreds of individual flies simultaneously. With this approach, we find that, during exploratory walking, individual flies exhibit significant bias in their left vs. right locomotor choices, with some flies being strongly left biased or right biased. This idiosyncrasy was present in all genotypes examined, including wild-derived populations and inbred isogenic laboratory strains. The biases of individual flies persist for their lifetime and are nonheritable: i.e., mating two left-biased individuals does not yield left-biased progeny. This locomotor handedness is uncorrelated with other asymmetries, such as the handedness of gut twisting, leg-length asymmetry, and wing-folding preference. Using transgenics and mutants, we find that the magnitude of locomotor handedness is under the control of columnar neurons within the central complex, a brain region implicated in motor planning and execution. When these neurons are silenced, exploratory laterality increases, with more extreme leftiness and rightiness. This observation intriguingly implies that the brain may be able to dynamically regulate behavioral individuality.

Effect of clozapine on locomotor activity and anxiety-related behavior in the neonatal mice administered MK-801.

PubMed

Pınar, Neslihan; Akillioglu, Kubra; Sefil, Fatih; Alp, Harun; Sagir, Mustafa; Acet, Ahmet

2015-08-11

Atypical antipsychotics have been used to treat fear and anxiety disturbance that are highly common in schizophrenic patients. It is suggested that disruptions of N-methyl-d-aspartate (NMDA)-mediated transmission of glutamate may underlie the pathophysiology of schizophrenia. The present study was conducted to analyze the effectiveness of clozapine on the anxiety-related behavior and locomotor function of the adult brain, which had previously undergone NMDA receptor blockade during a developmental period. In order to block the NMDA receptor, male mice were administered 0.25 mg/kg of MK-801 on days 7 to 10 postnatal. In adulthood, they were administered intraperitoneally 0.5 mg/kg of clozapine and tested with open-field and elevated plus maze test, to assess their emotional behavior and locomotor activity. In the group receiving MK-801 in the early developmental period the elevated plus maze test revealed a reduction in the anxiety-related behavior (p<0.05), while the open-field test indicated a decrease in locomotor activity (p<0.01). Despite these reductions, clozapine could not reverse the NMDA receptor blockade. Also, as an atypical antipsychotic agent, clozapine could not reverse impairment in the locomotor activity and anxiety-related behavior, induced by administration of the MK-801 in neonatal period.

Effects of early adolescent methamphetamine exposure on anxiety-like behavior and corticosterone levels in mice.

PubMed

Rud, Micaela A; Do, Thao N; Siegel, Jessica A

2016-10-28

Methamphetamine (MA) is an addictive psychomotor stimulant that affects the central nervous system and alters behavior. The effects of MA are modulated by age, and while much research has examined the effects of MA use in adults, relatively little research has examined the effects in adolescents. As the brain is developing during adolescence, it is important that we understand the effects of MA exposure in adolescence. This research examined the effects of acute MA exposure on locomotor and anxiety-like behavior in the open field test and plasma corticosterone levels in adolescent male C57BL/6J mice. Baseline locomotor and anxiety-like behaviors were assessed in the open field test. Immediately following baseline measurements, mice were exposed to saline or 4mg/kg MA and locomotor and anxiety-like behavior were measured. Serum was collected immediately after testing and plasma corticosterone levels measured. There were no group differences in baseline behavioral measurements. MA-exposed adolescent mice showed increased locomotor activity and anxiety-like behavior in the open field compared with saline controls. There was no effect of MA on plasma corticosterone levels. These data suggest that acute MA exposure during adolescence increases locomotor activity and anxiety-like behavior, but does not alter plasma corticosterone levels. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Locomotor Sub-functions for Control of Assistive Wearable Robots.

PubMed

Sharbafi, Maziar A; Seyfarth, Andre; Zhao, Guoping

2017-01-01

A primary goal of comparative biomechanics is to understand the fundamental physics of locomotion within an evolutionary context. Such an understanding of legged locomotion results in a transition from copying nature to borrowing strategies for interacting with the physical world regarding design and control of bio-inspired legged robots or robotic assistive devices. Inspired from nature, legged locomotion can be composed of three locomotor sub-functions, which are intrinsically interrelated: Stance : redirecting the center of mass by exerting forces on the ground. Swing : cycling the legs between ground contacts. Balance : maintaining body posture. With these three sub-functions, one can understand, design and control legged locomotory systems with formulating them in simpler separated tasks. Coordination between locomotor sub-functions in a harmonized manner appears then as an additional problem when considering legged locomotion. However, biological locomotion shows that appropriate design and control of each sub-function simplifies coordination. It means that only limited exchange of sensory information between the different locomotor sub-function controllers is required enabling the envisioned modular architecture of the locomotion control system. In this paper, we present different studies on implementing different locomotor sub-function controllers on models, robots, and an exoskeleton in addition to demonstrating their abilities in explaining humans' control strategies.

7α-Hydroxypregnenolone regulating locomotor behavior identified in the brain and pineal gland across vertebrates.

PubMed

Tsutsui, Kazuyoshi; Haraguchi, Shogo; Vaudry, Hubert

2017-09-14

The brain synthesizes steroids de novo from cholesterol, which are called neurosteroids. Based on extensive studies on neurosteroids over the past thirty years, it is now accepted that neurosteroidogenesis in the brain is a conserved property across vertebrates. However, the formation of bioactive neurosteroids in the brain is still incompletely elucidated in vertebrates. In fact, we recently identified 7α-hydroxypregnenolone (7α-OH PREG) as a novel bioactive neurosteroid stimulating locomotor behavior in the brain of several vertebrates. The follow-up studies have demonstrated that the stimulatory action of brain 7α-OH PREG on locomotor behavior is mediated by the dopaminergic system across vertebrates. More recently, we have further demonstrated that the pineal gland, an endocrine organ located close to the brain, is a major site of the formation of bioactive neurosteroids. In addition to the brain, the pineal gland actively produces 7α-OH PREG de novo from cholesterol as a major pineal neurosteroid that acts on the brain to control locomotor rhythms. This review summarizes the identification, biosynthesis and mode of action of brain and pineal 7α-OH PREG, a new bioactive neurosteroid regulating locomotor behavior, across vertebrates. Copyright © 2017 Elsevier Inc. All rights reserved.

Locomotor Sub-functions for Control of Assistive Wearable Robots

PubMed Central

Sharbafi, Maziar A.; Seyfarth, Andre; Zhao, Guoping

2017-01-01

A primary goal of comparative biomechanics is to understand the fundamental physics of locomotion within an evolutionary context. Such an understanding of legged locomotion results in a transition from copying nature to borrowing strategies for interacting with the physical world regarding design and control of bio-inspired legged robots or robotic assistive devices. Inspired from nature, legged locomotion can be composed of three locomotor sub-functions, which are intrinsically interrelated: Stance: redirecting the center of mass by exerting forces on the ground. Swing: cycling the legs between ground contacts. Balance: maintaining body posture. With these three sub-functions, one can understand, design and control legged locomotory systems with formulating them in simpler separated tasks. Coordination between locomotor sub-functions in a harmonized manner appears then as an additional problem when considering legged locomotion. However, biological locomotion shows that appropriate design and control of each sub-function simplifies coordination. It means that only limited exchange of sensory information between the different locomotor sub-function controllers is required enabling the envisioned modular architecture of the locomotion control system. In this paper, we present different studies on implementing different locomotor sub-function controllers on models, robots, and an exoskeleton in addition to demonstrating their abilities in explaining humans' control strategies. PMID:28928650

Effect of clozapine on locomotor activity and anxiety-related behavior in the neonatal mice administered MK-801

PubMed Central

Pinar, Neslihan; Akillioglu, Kubra; Sefil, Fatih; Alp, Harun; Sagir, Mustafa; Acet, Ahmet

2015-01-01

Atypical antipsychotics have been used to treat fear and anxiety disturbance that are highly common in schizophrenic patients. It is suggested that disruptions of N-methyl-d-aspartate (NMDA)-mediated transmission of glutamate may underlie the pathophysiology of schizophrenia. The present study was conducted to analyze the effectiveness of clozapine on the anxiety-related behavior and locomotor function of the adult brain, which had previously undergone NMDA receptor blockade during a developmental period. In order to block the NMDA receptor, male mice were administered 0.25 mg/kg of MK-801 on days 7 to 10 postnatal. In adulthood, they were administered intraperitoneally 0.5 mg/kg of clozapine and tested with open-field and elevated plus maze test, to assess their emotional behavior and locomotor activity. In the group receiving MK-801 in the early developmental period the elevated plus maze test revealed a reduction in the anxiety-related behavior (p<0.05), while the open-field test indicated a decrease in locomotor activity (p<0.01). Despite these reductions, clozapine could not reverse the NMDA receptor blockade. Also, as an atypical antipsychotic agent, clozapine could not reverse impairment in the locomotor activity and anxiety-related behavior, induced by administration of the MK-801 in neonatal period. PMID:26295298

Tail autotomy and subsequent regeneration alter the mechanics of locomotion in lizards.

PubMed

Jagnandan, Kevin; Russell, Anthony P; Higham, Timothy E

2014-11-01

Animals can undergo significant weight change for a variety of reasons. Autotomy, the voluntary shedding of an appendage in response to a predator stimulus, provides an effective model for measuring the effects of rapid weight change on locomotor behavior and the responses to more gradual weight gain, particularly in lizards capable of both autotomizing and regenerating their tail. Although the general effects of autotomy on locomotor performance are commonly explored, we investigated changes in locomotor mechanics associated with tail loss and long-term regeneration for the first time by measuring morphology, 3D kinematics and ground reaction forces (GRFs) in the leopard gecko Eublepharis macularius. Tail autotomy resulted in a 13% anterior shift in the center of mass (CoM), which only partially recovered after full regeneration of the tail. Although no changes in body or forelimb kinematics were evident, decreases in hindlimb joint angles signify a more sprawled posture following autotomy. Changes in hindlimb GRFs resulted in an increase in weight-specific propulsive force, without a corresponding change in locomotor speed. Hindlimb kinematics and GRFs following autotomy recovered to pre-autotomy values as the tail regenerated. These results suggest an active locomotor response to tail loss that demonstrates the causal relationships between variations in morphology, kinematics and force. © 2014. Published by The Company of Biologists Ltd.

The role of the laterodorsal tegmental nucleus in methamphetamine conditioned place preference and locomotor activity.

PubMed

Dobbs, Lauren K; Cunningham, Christopher L

2014-05-15

Methamphetamine (METH) indirectly stimulates the laterodorsal tegmental nucleus (LDT) acetylcholine (ACh) neurons to increase ACh within the ventral tegmental area (VTA). LDT ACh inhibition attenuates METH and saline locomotor activity. The aim of these experiments was to determine whether LDT ACh contributes to METH conditioned place preference (CPP). C57BL/6J mice received a bilateral electrolytic or sham lesion of the LDT. After recovery, mice received alternating pairings of METH (0.5 mg/kg) and saline with distinct tactile floor cues over 8 days. During preference tests, mice were given access to both floor types and time spent on each was recorded. Mice were tested again after exposure to both extinction and reconditioning trials. Brains were then processed for choline acetyltransferase immunohistochemistry to label LDT ACh neurons. Lesioned mice had significantly fewer LDT ACh neurons and showed increased saline and METH locomotor activity during the first conditioning trial compared to sham mice. Locomotor activity (saline and METH) was negatively correlated with the number of LDT ACh neurons. Lesioned and sham mice showed similar METH CPP following conditioning, extinction and reconditioning trials. LDT ACh neurons are not necessary for METH reward as indexed by CPP, but may be important for basal and METH-induced locomotor activity. Copyright © 2014 Elsevier B.V. All rights reserved.

Green tea consumption affects cognitive dysfunction in the elderly: a pilot study.

PubMed

Ide, Kazuki; Yamada, Hiroshi; Takuma, Norikata; Park, Mijong; Wakamiya, Noriko; Nakase, Junpei; Ukawa, Yuuichi; Sagesaka, Yuko M

2014-09-29

Green tea is known to have various health benefits for humans. However, the effect of green tea consumption on cognitive dysfunction remains to be clinically verified. We conducted a clinical study to investigate the effects of green tea consumption on cognitive dysfunction. Twelve elderly nursing home residents with cognitive dysfunction (Mini-Mental State Examination Japanese version (MMSE-J) score: <28) participated in the study (2 men, 10 women; mean age, 88 years). The participants consumed green tea powder 2 g/day for 3 months. After three months of green tea consumption, the participants' MMSE-J scores were significantly improved (before, 15.3 ± 7.7; after, 17.0 ± 8.2; p = 0.03). This result suggests that green tea consumption may be effective in improving cognitive function or reducing the progression of cognitive dysfunction; however, long-term large-scale controlled studies are needed to further clarify the effect.