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Sample records for rat forelimb reduces

  1. A Within-Animal Comparison of Skilled Forelimb Assessments in Rats

    PubMed Central

    Sloan, Andrew M.; Fink, Melyssa K.; Rodriguez, Amber J.; Lovitz, Adam M.; Khodaparast, Navid; Rennaker, Robert L.; Hays, Seth A.

    2015-01-01

    A variety of skilled reaching tasks have been developed to evaluate forelimb function in rodent models. The single pellet skilled reaching task and pasta matrix task have provided valuable insight into recovery of forelimb function in models of neurological injury and disease. Recently, several automated measures have been developed to reduce the cost and time burden of forelimb assessment in rodents. Here, we provide a within-subject comparison of three common forelimb assessments to allow direct evaluation of sensitivity and efficiency across tasks. Rats were trained to perform the single pellet skilled reaching task, the pasta matrix task, and the isometric pull task. Once proficient on all three tasks, rats received an ischemic lesion of motor cortex and striatum to impair use of the trained limb. On the second week post-lesion, all three tasks measured a significant deficit in forelimb function. Performance was well-correlated across tasks. By the sixth week post-lesion, only the isometric pull task measured a significant deficit in forelimb function, suggesting that this task is more sensitive to chronic impairments. The number of training days required to reach asymptotic performance was longer for the isometric pull task, but the total experimenter time required to collect and analyze data was substantially lower. These findings suggest that the isometric pull task represents an efficient, sensitive measure of forelimb function to facilitate preclinical evaluation in models of neurological injury and disease. PMID:26506434

  2. Characteristics of leading forelimb movements for obstacle avoidance during locomotion in rats.

    PubMed

    Aoki, Sho; Sato, Yamato; Yanagihara, Dai

    2012-10-01

    Walking smoothly and safely often involves stepping over an obstacle. The purpose of this study was to examine forelimb movements and toe trajectories in stepping over an obstacle during overground locomotion in rats. We performed a kinematic analysis of forelimb movements and measured electromyographic (EMG) activities in the biceps and triceps brachii of the forelimbs. We found that mean toe height just above the obstacle was lower in the leading forelimb than in the trailing forelimb. The toe positions of the leading forelimb at maximal elevation over the obstacle (peak toe position) were closer to the upper edge of the obstacle than those of the trailing forelimb. The linear distance between peak toe position and the upper edge of the obstacle was significantly less in the leading forelimb compared to the trailing forelimb. The peak toe position of the leading forelimb spatially corresponds to the transition point from flexion to extension of the elbow joint. This transition appeared to be controlled mainly by an offset of EMG activity of the elbow flexor, the biceps brachii muscle. In contrast, the trailing forelimb appeared to be controlled by the shoulder and wrist joints. These results suggest that the toe trajectory of the leading forelimb is more accurately regulated than that of the trailing forelimb. In addition, the activities of the elbow flexor may in part contribute to the toe trajectory of the leading forelimb. PMID:22902354

  3. Forelimb locomotor generators and quadrupedal locomotion in the neonatal rat.

    PubMed

    Ballion, B; Morin, D; Viala, D

    2001-11-01

    The spinal localization of the forelimb locomotor generators and their interactions with other spinal segments were investigated on in vitro brainstem-spinal cord preparations of new-born rats. Superfusion of the cervicothoracic cord (C1-T4) with high K+/low Mg2+ artificial cerebrospinal fluid (aCSF) evoked rhythmic motor root activity that was limited to low cervical (C7, C8) and high thoracic (T1) spinal levels. This activity consisted of synchronous, homolateral bursts and a typical alternating bilateral pattern. Rhythmic activity with similar locomotor-like characteristics could be induced with either serotonin (5-HT, 5 microm), N-methyl-d-aspartate (NMDA, 5 microm), kainate (10 microm) or a "cocktail" of 5-HT (5 microm) and NMDA (5 microm). During 5-HT/NMDA perfusion of the cervicothoracic cord, induced bursting was no longer restricted to C7-T1 levels, but also occurred at cervical C3-C5 levels and with C5-C8 homolateral alternation. Spinal transections between C6 and C7 cervical segments did not abolish rhythmic activity in C7-T1, but suppressed locomotor-like rhythmicity at C3-C5 levels. Reduced regions comprising the C7-C8 or C8-T1 segments maintained rhythmicity. Superfusion of the whole cord with 5-HT/NMDA induced ventral root bursting with similar frequencies at all recorded segments (cervical, thoracic and lumbar). After isolation, the T3-T10 cord was unable to sustain any rhythmic activity while cervical and lumbar segmental levels continued to burst, albeit at different frequencies. We also found that the faster caudal and the slower rostral locomotor generators interact to produce coordinated locomotor-like activity in all segments of the intact spinal cord. In conclusion, C7-T1 spinal levels display a strong motor rhythmogenic ability; with the lumbar generators, they contribute to coordinated rhythmic activity along the entire spinal cord of a quadrupedal locomoting mammal. PMID:11860467

  4. Tissue fluid shift, forelimb loading, and tail tension in tail-suspended rats

    NASA Technical Reports Server (NTRS)

    Hargens, A. R.; Steskal, J.; Johansson, C.; Tipton, C. M.

    1984-01-01

    The tail suspension model (head-down tilt) simulates hypogravity in terms of musculoskeletal loss in the rat. However, little is known of tissue fluid shifts and body weight distribution in this model. Tissue fluid pressures were measured by wick catheters in 12 Munich-Wistar rats before, during, and after 48 hrs of tail suspension (about 30 deg head-down tilt). Subcutaneous tissue fluid pressure in the neck increased from -2.2 + or - 0.4 (normal horizontal position) to +4.0 + or - 1.5 cm H2O during tail suspension, indicating a cephalic fluid shift and significant edema during head-down tilt. In a separate study, six rats were suspended at 30-70 deg, and forelimb load and tail tension were measured by a balance and force transducer, respectively. Approximately 50 percent of body weight (BW) was loaded on forelimbs at a head-down tilt angle of 30 deg and forelimb load declined linearly to 10 percent BW at 70 deg. Furthermore, tail tension increased from 50 percent BW at 30 deg to 85 percent BW at 70 deg. These results indicate that less than normal loads are applied to forelimbs of rats suspended at angles of less than 30 deg and that the tail bears an increasing proportion of the rat's body weight at head-down tilt angles of less than 30 deg.

  5. Functional, morphological and biomolecular assessment of posttraumatic neuro-muscular recovery in the rat forelimb model.

    PubMed

    Geuna, S; Tos, P; Raimondo, S; Lee, J M; Gambarotta, G; Nicolino, S; Fornaro, M; Papalia, I; Perroteau, I; Battiston, B

    2007-01-01

    Over the last five years, we have used the rat forelimb model for investigating neuromuscular recovery after microsurgical nerve reconstruction of median and ulnar nerves by end-to-side neurorrhaphy and muscle-vein-combined tubulization (using both straight and Y-shaped guides). The outcome of nerve repair at different postoperative times was assessed by functional, morphological and biomolecular analysis. Results showed that both end-to-side and tubulization repair of rat median and ulnar nerves led to successful axonal regeneration along the severed nerve trunk as well as to a partial recovery of the lost function as assessed by grasping test. Biomolecular analysis by means of reverse transcription polymerase chain reaction (RT-PCR) demonstrated early overexpression during nerve regeneration of the gliotrophic factor NRG1 and two of its receptors: erbB2 and erbB3. Finally, our experience also suggests that the rat forelimb experimental model is particularly appropriate for the study of microsurgical reconstruction of major mixed nerve trunks. Furthermore, since the forelimb model is less compromising for the animal, it should be preferred to the hindlimb model for many research purposes. PMID:17985570

  6. Functional and structural organization of the forelimb representation in cuneate nucleus in rat.

    PubMed

    Li, Cheng X; Yang, Qiuhong; Waters, Robert S

    2012-08-15

    We examined the physiological representation of the forelimb in the cuneate nucleus (CN) of forelimb-intact young adult rats (n=38) as the first part in a series of studies aimed at understanding the possible role that CN plays in delayed cortical reorganization that follows forelimb amputation. Metabolic labeling with cytochrome oxidase (CO) and electrophysiological mapping were used to examine the relationship between the structural and functional organization of CN. CN is a cylinder-shaped structure that lies bilaterally in the brainstem and extends nearly 4mm in the rostrocaudal direction. The forelimb is represented along the rostrocaudal extent. CN contains three zones; the rostral and caudal zones receive input largely from deep muscle and joint receptors and a middle zone, in the vicinity of the obex, receives input primarily from cutaneous receptors in the skin. The middle zone is somatotopically organized with the glabrous digits represented centrally, bordered on the medial side by ulnar wrist, ulnar forearm, and posterior upper arm representations; on the lateral side by radial wrist, radial forearm, and anterior upper arm representations; and on dorsal side by the dorsal digits and dorsal hand. The middle zone also contains well-defined CO-filled glomerular structures, called barrelettes, which are located within a homogenously stained field. The barrelettes are associated with the representation of the glabrous digits, with D5 represented most dorsal followed sequentially in a ventral-to-lateral direction by the representation of D4, D3, D2, and D1. The digit representations are topographically organized with the distal digit surface represented laterally with respect to the more medially lying proximal digit surface. The digit and palmar pads are also represented by barrelettes located on the medial side of CN. In contrast, the dorsal digit surfaces are represented dorsally and the dorsal hand is represented directly beneath the cuneate fasciculus, in a region devoid of barrelettes. The representations of the ulnar and radial wrist, forearm, and upper arm also lie within the homogeneously stained field in CN. The forelimb representation is bordered on the medial side by representation of trunk and hindlimb, and on the lateral side by representation of shoulder, ear, and head. While the present findings support and extend previous electrophysiological and anatomical studies of CN in the rat, they also provide a detailed physiological description of the functional organization of CN that is necessary for subsequent understanding of the functional reorganization of CN that may result following forelimb amputation. PMID:22800965

  7. Laminar-specific distribution of zinc: Evidence for presence of layer IV in forelimb motor cortex in the rat

    PubMed Central

    Alaverdashvili, Mariam; Hackett, Mark J.; Pickering, Ingrid J.; Paterson, Phyllis G.

    2015-01-01

    The rat is the most widely studied pre-clinical model system of various neurological and neurodegenerative disorders affecting hand function. Although brain injury to the forelimb region of the motor cortex in rats mostly induces behavioral abnormalities in motor control of hand movements, behavioral deficits in the sensory-motor domain are also observed. This questions the prevailing view that cortical layer IV, a recipient of sensory information from the thalamus, is absent in rat motor cortex. Because zinc-containing neurons are generally not found in pathways that run from the thalamus, an absence of zinc (Zn) in a cortical layer would be suggestive of sensory input from the thalamus. To test this hypothesis, we used synchrotron micro X-ray fluorescence imaging to measure Zn distribution across cortical layers. Zn maps revealed a heterogeneous layered Zn distribution in primary and secondary motor cortices of the forelimb region in the adult rat. Two wider bands with elevated Zn content were separated by a narrow band having reduced Zn content, and this was evident in two rat strains. The Zn distribution pattern was comparable to that in sensorimotor cortex, which is known to contain a well demarcated layer IV. Juxtaposition of Zn maps and the images of brain stained for Nissl bodies revealed a “Zn valley” in primary motor cortex, apparently starting at the ventral border of pyramidal layer III and ending at the close vicinity of layer V. This finding indicates the presence of a conspicuous cortical layer between layers III and V, i.e. layer IV, the presence of which previously has been disputed. The results have implications for the use of rat models to investigate human brain function and neuropathology, such as after stroke. The presence of layer IV in the forelimb region of the motor cortex suggests that therapeutic interventions used in rat models of motor cortex injury should target functional abnormalities in both motor and sensory domains. The finding is also critical for future investigation of the biochemical mechanisms through which therapeutic interventions can enhance neural plasticity, particularly through Zn dependent pathways. PMID:25192655

  8. Spinal interneurons and forelimb plasticity after incomplete cervical spinal cord injury in adult rats.

    PubMed

    Gonzalez-Rothi, Elisa Janine; Rombola, Angela M; Rousseau, Celeste A; Mercier, Lynne M; Fitzpatrick, Garrett M; Reier, Paul J; Fuller, David D; Lane, Michael A

    2015-06-15

    Cervical spinal cord injury (cSCI) disrupts bulbospinal projections to motoneurons controlling the upper limbs, resulting in significant functional impairments. Ongoing clinical and experimental research has revealed several lines of evidence for functional neuroplasticity and recovery of upper extremity function after SCI. The underlying neural substrates, however, have not been thoroughly characterized. The goals of the present study were to map the intraspinal motor circuitry associated with a defined upper extremity muscle, and evaluate chronic changes in the distribution of this circuit following incomplete cSCI. Injured animals received a high cervical (C2) lateral hemisection (Hx), which compromises supraspinal input to ipsilateral spinal motoneurons controlling the upper extremities (forelimb) in the adult rat. A battery of behavioral tests was used to characterize the time course and extent of forelimb motor recovery over a 16 week period post-injury. A retrograde transneuronal tracer - pseudorabies virus - was used to define the motor and pre-motor circuitry controlling the extensor carpi radialis longus (ECRL) muscle in spinal intact and injured animals. In the spinal intact rat, labeling was observed unilaterally within the ECRL motoneuron pool and within spinal interneurons bilaterally distributed within the dorsal horn and intermediate gray matter. No changes in labeling were observed 16 weeks post-injury, despite a moderate degree of recovery of forelimb motor function. These results suggest that recovery of the forelimb function assessed following C2Hx injury does not involve recruitment of new interneurons into the ipsilateral ECRL motor pathway. However, the functional significance of these existing interneurons to motor recovery requires further exploration. PMID:25625912

  9. Cortical PKC Inhibition Promotes Axonal Regeneration of the Corticospinal Tract and Forelimb Functional Recovery After Cervical Dorsal Spinal Hemisection in Adult Rats

    PubMed Central

    Wang, Xiaofei; Hu, Jianguo; She, Yun; Smith, George M.; Xu, Xiao-Ming

    2014-01-01

    Our previous study shows that conventional protein kinases C (cPKCs) are key signaling mediators that are activated by extracellular inhibitory molecules. Inhibition of cPKC by intrathecal infusion of a cPKC inhibitor, GÖ6976, into the site of dorsal hemisection (DH) induces regeneration of lesioned dorsal column sensory, but not corticospinal tract (CST), axons. Here, we investigated whether a direct cortical delivery of GÖ6976 into the soma of corticospinal neurons promotes regeneration of CST and the recovery of forelimb function in rats with cervical spinal cord injuries. We report that cortical delivery of GÖ6976 reduced injury-induced activation of conventional PKC? and PKC?1 in CST neurons, promoted regeneration of CST axons through and beyond a cervical DH at C4, formed new synapses on target neurons caudal to the injury, and enhanced forelimb functional recovery in adult rats. When combined with lenti-Chondroitinase ABC treatment, cortical administration of GÖ6976 promoted even greater CST axonal regeneration and recovery of forelimb function. Thus, this study has demonstrated a novel strategy that can promote anatomical regeneration of damaged CST axons and partial recovery of forelimb function. Importantly, such an effect is critically dependent on the efficient blockage of injury-induced PKC activation in the soma of layer V CST neurons. PMID:23810979

  10. A novel method for assessing proximal and distal forelimb function in the rat: the Irvine, Beatties and Bresnahan (IBB) forelimb scale.

    PubMed

    Irvine, Karen-Amanda; Ferguson, Adam R; Mitchell, Kathleen D; Beattie, Stephanie B; Beattie, Michael S; Bresnahan, Jacqueline C

    2010-01-01

    Several experimental models of cervical spinal cord injury (SCI) have been developed recently to assess the consequences of damage to this level of the spinal cord (Pearse et al., 2005, Gensel et al., 2006, Anderson et al., 2009), as the majority of human SCI occur here (Young, 2010; www.sci-info-pages.com). Behavioral deficits include loss of forelimb function due to damage to the white matter affecting both descending motor and ascending sensory systems, and to the gray matter containing the segmental circuitry for processing sensory input and motor output for the forelimb. Additionally, a key priority for human patients with cervical SCI is restoration of hand/arm function (Anderson, 2004). Thus, outcome measures that assess both proximal and distal forelimb function are needed. Although there are several behavioral assays that are sensitive to different aspects of forelimb recovery in experimental models of cervical SCI (Girgis et al., 2007, Gensel et al., 2006, Ballerman et al., 2001, Metz and Whishaw, 2000, Bertelli and Mira, 1993, Montoya et al., 1991, Whishaw and Pellis, 1990), few techniques provide detailed information on the recovery of fine motor control and digit movement. The current measurement technique, the Irvine, Beatties and Bresnahan forelimb scale (IBB), can detect recovery of both proximal and distal forelimb function including digit movements during a naturally occurring behavior that does not require extensive training or deprivation to enhance motivation. The IBB was generated by observing recovery after a unilateral C6 SCI, and involves video recording of animals eating two differently shaped cereals (spherical and doughnut) of a consistent size. These videos were then used to assess features of forelimb use, such as joint position, object support, digit movement and grasping technique. The IBB, like other forelimb behavioral tasks, shows a consistent pattern of recovery that is sensitive to injury severity. Furthermore, the IBB scale could be used to assess recovery following other types of injury that impact normal forelimb function. PMID:21206464

  11. Early life versus lifelong oral manganese exposure differently impairs skilled forelimb performance in adult rats

    PubMed Central

    Beaudin, Stephane A.; Nisam, Sean; Smith, Donald R.

    2013-01-01

    Recent studies of children suggest that exposure to elevated manganese (Mn) levels disrupt aspects of motor, cognitive and behavioral functions that are dependent on dopamine brain systems. Although basal ganglia motor functions are well-known targets of adult occupational Mn exposure, the extent of motor function deficits in adults as a result of early life Mn exposure is unknown. Here we used a rodent model early life versus lifelong oral Mn exposure and the Montoya staircase test to determine whether developmental Mn exposure produces long-lasting deficits in sensorimotor performance in adulthood. Long-Evans male neonate rats (n=11/treatment) were exposed daily to oral Mn at levels of 0, 25, or 50 mg Mn/kg/d from postnatal day (PND) 1-21 (early life only), or from PND 1 - throughout life. Staircase testing began at age PND 120 and lasted 1 month to objectively quantify measures of skilled forelimb use in reaching and pellet grasping/retrieval performance. Behavioral reactivity also was rated on each trial. Results revealed that (1) behavioral reactivity scores were significantly greater in the Mn-exposed groups, compared to controls, during the staircase acclimation/training stage, but not the latter testing stages, (2) early life Mn exposure alone caused long-lasting impairments in fine motor control of reaching skills at the higher, but not lower Mn dose, (3) lifelong Mn exposure from drinking water led to widespread impairment in reaching and grasping/retrieval performance in adult rats, with the lower Mn dose group showing the greatest impairment, and (4) lifelong Mn exposure produced similar (higher Mn group) or more severe (lower Mn group) impairments compared to their early life-only Mn exposed counterparts. Collectively, these results substantiate the emerging clinical evidence in children showing associations between environmental Mn exposure and deficits in fine sensorimotor function. They also show that the objective quantification of skilled motor performance using the staircase test can serve as a sensitive measure of early life insults from environmental agents. Supported by NIEHS R01ES018990. PMID:23623961

  12. Forelimb akinesia in the rat Parkinson model: differential effects of dopamine agonists and nigral transplants as assessed by a new stepping test.

    PubMed

    Olsson, M; Nikkhah, G; Bentlage, C; Björklund, A

    1995-05-01

    Methods for the assessment of akinesia in the unilateral rat Parkinson model have so far been lacking. The experiments reported here evaluate the usefulness of a new "stepping test" to monitor forelimb akinesia in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the mesencephalic dopamine (DA) system, and to assess the ability of DA-receptor agonists and fetal DA neuron transplants to reverse these deficits. The 6-OHDA lesion induced marked and long-lasting impairments in the initiation of stepping movements with the contralateral paw. Systemic injections of low doses (chosen to be subthreshold for induction of rotation) of the mixed D1 and D2 receptor agonist apomorphine, the D1-selective agonist SKF 38393, and to a lesser extent also the D2-selective agonist quinpirole were effective in reversing these deficits. Similar effects was seen after a subrotational dose of L-dopa, whereas amphetamine had no effect. Fetal nigral transplants, implanted as multiple deposits in the ipsilateral caudate-putamen and substantia nigra, restored initiation of stepping to a similar degree as the DA agonists. Nigral grafts placed in substantia nigra alone were also effective, although the improvement was less pronounced. Apomorphine, at a dose effective in the lesion-only animals, had no additive effect in the grafted rats, whereas amphetamine appeared to further improve stepping in the rats with intranigral transplants. Identical experiments were performed on skilled forelimb use in the so-called staircase test. Interestingly, neither the DA agonist drugs nor the nigral transplants had any effects on the lesion induced deficits in this more complex task. The results show that forelimb stepping is a highly useful test to monitor lesion-/and transplant-induced changes in forelimb akinesia, a behavioral parameter that may be analogous to limb akinesia and gait problems seen in patients with Parkinson's disease. PMID:7751951

  13. Lesion in the lateral cerebellum specifically produces overshooting of the toe trajectory in leading forelimb during obstacle avoidance in the rat.

    PubMed

    Aoki, Sho; Sato, Yamato; Yanagihara, Dai

    2013-10-01

    During locomotion, stepping over an obstacle under visual guidance is crucial to continuous safe walking. Studies of the role of the central nervous system in stepping movements have focused on cerebral cortical areas such as the primary motor cortex and posterior parietal cortex. There is speculation that the lateral cerebellum, which has strong anatomical connections with the cerebral cortex, also plays a key role in stepping movements over an obstacle, although this function of the lateral cerebellum has not yet been elucidated. Here we investigated the role of the lateral cerebellum during obstacle avoidance locomotion in rats with a lateral cerebellar lesion. A unilateral lesion in the lateral cerebellum did not affect limb movements during overground locomotion. Importantly, however, the lesioned animals showed overshooting of the toe trajectory specific to the leading forelimb ipsilateral to the lesion when stepping over an obstacle, and the peak toe position, in which the toe is maximally raised during stepping, shifted away from the upper edge of the obstacle. Recordings of EMG activity from elbow flexor and extensor muscles suggested that the overshooting toe trajectory in the ipsilateral leading forelimb possibly resulted from sustained elbow flexion and delayed elbow extension following prolonged activity of the biceps brachii. These results suggest that the lateral cerebellum specifically contributes to generating appropriate toe trajectories in the ipsilateral leading forelimb and to controlling related muscle activities in stepping over an obstacle, especially when accurate control of the distal extremity is achieved under visual guidance. PMID:23615542

  14. Rat Pups Reduce Ultrasonic Vocalization After Exposure

    E-print Network

    Barr, Gordon A.

    Rat Pups Reduce Ultrasonic Vocalization After Exposure to an Adult Male Rat Christoph P to the male emitted significantly fewer ultrasonic vocalizations than controls, but did not differ. Keywords: rat; ultrasonic vocalization; immobility; infanticide; anxiety-like behavior Animals have

  15. Cineradiographic (video X-ray) analysis of skilled reaching in a single pellet reaching task provides insight into relative contribution of body, head, oral, and forelimb movement in rats.

    PubMed

    Alaverdashvili, Mariam; Leblond, Hugues; Rossignol, Serge; Whishaw, Ian Q

    2008-10-10

    The forelimb movements (skilled reaching) used by rats to reach for a single food pellet to place into the mouth have been used to model many neurological conditions. They have been described as a sequence of oppositions of head-pellet, paw-pellet and pellet-mouth that can be described as movements of the distal portion of body segments in relation to their fixed proximal joints. Movement scoring is difficult, however, because the location and movement of body segments is estimated through the overlying fur and skin, which is pliable and partially obscures movement. Using moderately high-speed cineradiographic filming from lateral, dorsal, and frontal perspectives, the present study describes how forelimb and skeletal bones move during the skilled reaching act. The analysis indicates that: (i) head movements for orienting to food, enabled by the vertical orientation of the rostral spinal cord, are mainly independent of trunk movement, (ii) skilled reaching consists of a sequence of upper arm and extremity movements each involving a number of concurrent limb segment and joint movements and (iii) food pellets are retrieved from the paw using either the incisors and/or tongue. The findings are discussed in relation to the idea that X-ray cinematography is valuable tool for assisting descriptive analysis and can contribute to understanding general principles of the relations between whole body, head, oral, and upper extremity movement. PMID:18514337

  16. Assessing forelimb function after unilateral cervical spinal cord injury: novel forelimb tasks predict lesion severity and recovery.

    PubMed

    Khaing, Zin Z; Geissler, Sydney A; Jiang, Shan; Milman, Brian D; Aguilar, Sandra V; Schmidt, Christine E; Schallert, Timothy

    2012-02-10

    Cervical spinal cord injury (cSCI) can cause devastating neurological deficits, including impairment or loss of upper limb and hand function. Recently there has been increasing interest in cervical spinal cord injury models because the majority of spinal cord injuries are at cervical levels. Here we examined spontaneous functional recovery of adult rats with either laminectomy or lateral hemisection of the cervical spinal cord at C3-C4. Behavioral tests were carried out, including the forelimb locomotor scale (FLS), a postural instability test (PIT), a pasta-handling test that has been used to assess forepaw digit function and latency to eat, forelimb use during vertical-lateral wall exploration in a cylindrical enclosure, and vibrissae-elicited forelimb placing tests. In addition, a forelimb step-alternation test was developed to assess functional recovery at 12 weeks post-injury. All tests detected cSCI-induced deficits relative to laminectomy. Interestingly, the severity of deficits in the forelimb step-alternation test was associated with more extensive spinal damage, greater impairment, and less recovery in the FLS and other tests. For the pasta-handling test we found that rats with a milder cervical injury (alternators) were more likely to use both forepaws together compared to rats with a more severe injury (non-alternators). In addition, using the PIT, we detected enhanced function of the good limb, suggesting that neural plasticity on the unaffected side of the spinal cord may have occurred to compensate for deficits in the impaired forelimb. These outcome measures should be useful for investigating neural events associated with cSCI, and for developing novel treatment strategies. PMID:22022897

  17. Therapeutic intraspinal microstimulation improves forelimb function after cervical contusion injury

    PubMed Central

    Kasten, M.R.; Sunshine, M.D.; Secrist, E.S.; Horner, P.J.; Moritz, C.T.

    2013-01-01

    Objective Intraspinal microstimulation (ISMS) is a promising method for activating the spinal cord distal to an injury. The objectives of this study were to examine the ability of chronically implanted stimulating wires within the cervical spinal cord to (1) directly produce forelimb movements, and (2) assess whether ISMS stimulation improved subsequent volitional control of paretic extremities following injury. Approach We developed a technique for implanting intraspinal stimulating electrodes within the cervical spinal cord segments C6-T1 of Long-Evans rats. Beginning 4 weeks after a severe cervical contusion injury at C4–C5, animals in the treatment condition received therapeutic ISMS 7 hours/day, 5 days/week for the following 12 weeks. Main Results Over 12 weeks of therapeutic ISMS, stimulus-evoked forelimb movements were relatively stable. We also explored whether therapeutic ISMS promotes recovery of forelimb reaching movements. Animals receiving daily therapeutic ISMS performed significantly better than unstimulated animals during behavioral tests conducted without stimulation. Quantitative video analysis of forelimb movements showed that stimulated animals performed better in the movements reinforced by stimulation, including extending the elbow to advance the forelimb and opening the digits. While threshold current to elicit forelimb movement gradually increased over time, no differences were observed between chronically stimulated and unstimulated electrodes suggesting that no additional tissue damage was produced by the electrical stimulation. Significance The results indicate that therapeutic intraspinal stimulation delivered via chronic microwire implants within the cervical spinal cord confers benefits extending beyond the period of stimulation, suggesting future strategies for neural devices to promote sustained recovery after injury. PMID:23715242

  18. Therapeutic intraspinal microstimulation improves forelimb function after cervical contusion injury

    NASA Astrophysics Data System (ADS)

    Kasten, M. R.; Sunshine, M. D.; Secrist, E. S.; Horner, P. J.; Moritz, C. T.

    2013-08-01

    Objective. Intraspinal microstimulation (ISMS) is a promising method for activating the spinal cord distal to an injury. The objectives of this study were to examine the ability of chronically implanted stimulating wires within the cervical spinal cord to (1) directly produce forelimb movements, and (2) assess whether ISMS stimulation could improve subsequent volitional control of paretic extremities following injury. Approach. We developed a technique for implanting intraspinal stimulating electrodes within the cervical spinal cord segments C6-T1 of Long-Evans rats. Beginning 4 weeks after a severe cervical contusion injury at C4-C5, animals in the treatment condition received therapeutic ISMS 7 hours/day, 5 days/week for the following 12 weeks. Main results. Over 12 weeks of therapeutic ISMS, stimulus-evoked forelimb movements were relatively stable. We also explored whether therapeutic ISMS promoted recovery of forelimb reaching movements. Animals receiving daily therapeutic ISMS performed significantly better than unstimulated animals during behavioural tests conducted without stimulation. Quantitative video analysis of forelimb movements showed that stimulated animals performed better in the movements reinforced by stimulation, including extending the elbow to advance the forelimb and opening the digits. While threshold current to elicit forelimb movement gradually increased over time, no differences were observed between chronically stimulated and unstimulated electrodes suggesting that no additional tissue damage was produced by the electrical stimulation. Significance. The results indicate that therapeutic intraspinal stimulation delivered via chronic microwire implants within the cervical spinal cord confers benefits extending beyond the period of stimulation, suggesting future strategies for neural devices to promote sustained recovery after injury.

  19. Phylogeny and forelimb disparity in waterbirds.

    PubMed

    Wang, Xia; Clarke, Julia A

    2014-10-01

    Previous work has shown that the relative proportions of wing components (i.e., humerus, ulna, carpometacarpus) in birds are related to function and ecology, but these have rarely been investigated in a phylogenetic context. Waterbirds including "Pelecaniformes," Ciconiiformes, Procellariiformes, Sphenisciformes, and Gaviiformes form a highly supported clade and developed a great diversity of wing forms and foraging ecologies. In this study, forelimb disparity in the waterbird clade was assessed in a phylogenetic context. Phylogenetic signal was assessed via Pagel's lambda, Blomberg's K, and permutation tests. We find that different waterbird clades are clearly separated based on forelimb component proportions, which are significantly correlated with phylogeny but not with flight style. Most of the traditional contents of "Pelecaniformes" (e.g., pelicans, cormorants, and boobies) cluster with Ciconiiformes (herons and storks) and occupy a reduced morphospace. These taxa are closely related phylogenetically but exhibit a wide range of ecologies and flight styles. Procellariiformes (e.g., petrels, albatross, and shearwaters) occupy a wide range of morphospace, characterized primarily by variation in the relative length of carpometacarpus and ulna. Gaviiformes (loons) surprisingly occupy a wing morphospace closest to diving petrels and penguins. Whether this result may reflect wing proportions plesiomorphic for the waterbird clade or a functional signal is unclear. A Bayesian approach detecting significant rate shifts across phylogeny recovered two such shifts. At the base of the two sister clades Sphenisciformes + Procellariiformes, a shift to an increase evolutionary rate of change is inferred for the ulna and carpometacarpus. Thus, changes in wing shape begin prior to the loss of flight in the wing-propelled diving clade. Several shifts to slower rate of change are recovered within stem penguins. PMID:24989899

  20. The organization of the forelimb representation of the C57BL/6 mouse motor cortex as defined by intracortical microstimulation and cytoarchitecture.

    PubMed

    Tennant, Kelly A; Adkins, Deanna L; Donlan, Nicole A; Asay, Aaron L; Thomas, Nagheme; Kleim, Jeffrey A; Jones, Theresa A

    2011-04-01

    The organization of forelimb representation areas of the monkey, cat, and rat motor cortices has been studied in depth, but its characterization in the mouse lags far behind. We used intracortical microstimulation (ICMS) and cytoarchitectonics to characterize the general organization of the C57BL/6 mouse motor cortex, and the forelimb representation in more detail. We found that the forelimb region spans a large area of frontal cortex, bordered primarily by vibrissa, neck, shoulder, and hindlimb representations. It included a large caudal forelimb area, dominated by digit representation, and a small rostral forelimb area, containing elbow and wrist representations. When the entire motor cortex was mapped, the forelimb was found to be the largest movement representation, followed by head and hindlimb representations. The ICMS-defined motor cortex spanned cytoarchitecturally identified lateral agranular cortex (AGl) and also extended into medial agranular cortex. Forelimb and hindlimb representations extended into granular cortex in a region that also had cytoarchitectural characteristics of AGl, consistent with the primary motor-somatosensory overlap zone (OL) characterized in rats. Thus, the mouse motor cortex has homologies with the rat in having 2 forelimb representations and an OL but is distinct in the predominance of digit representations. PMID:20739477

  1. Does reorganization in the cuneate nucleus following neonatal forelimb amputation influence development of anomalous circuits within the somatosensory cortex?

    PubMed

    Lane, Richard D; Pluto, Charles P; Kenmuir, Cynthia L; Chiaia, Nicolas L; Mooney, Richard D

    2008-02-01

    Neonatal forelimb amputation in rats produces sprouting of sciatic nerve afferent fibers into the cuneate nucleus (CN) and results in 40% of individual CN neurons expressing both forelimb-stump and hindlimb receptive fields. The forelimb-stump region of primary somatosensory cortex (S-I) of these rats contains neurons in layer IV that express both stump and hindlimb receptive fields. However, the source of the aberrant input is the S-I hindlimb region conveyed to the S-I forelimb-stump region via intracortical projections. Although the reorganization in S-I reflects changes in cortical circuitry, it is possible that these in turn are dependent on the CN reorganization. The present study was designed to directly test whether the sprouting of sciatic afferents into the CN is required for expression of the hindlimb inputs in the S-I forelimb-stump field. To inhibit sprouting, neurotrophin-3 (NT-3) was applied to the cut nerves following amputation. At P60 or older, NT-3-treated rats showed minimal sciatic nerve fibers in the CN. Multiunit electrophysiological recordings in the CN of NT-3-treated, amputated rats revealed 6.3% of sites were both stump/hindlimb responsive, compared with 30.5% in saline-treated amputated animals. Evaluation of the S-I following GABA receptor blockade, revealed that the percentage of hindlimb responsive sites in the stump representation of the NT-3-treated rats (34.2%) was not significantly different from that in saline-treated rats (31.5%). These results indicate that brain stem reorganization in the form of sprouting of sciatic afferents into the CN is not necessary for development of anomalous hindlimb receptive fields within the S-I forelimb/stump region. PMID:18032566

  2. Ketogenic diet improves forelimb motor function after spinal cord injury in rodents.

    PubMed

    Streijger, Femke; Plunet, Ward T; Lee, Jae H T; Liu, Jie; Lam, Clarrie K; Park, Soeyun; Hilton, Brett J; Fransen, Bas L; Matheson, Keely A J; Assinck, Peggy; Kwon, Brian K; Tetzlaff, Wolfram

    2013-01-01

    High fat, low carbohydrate ketogenic diets (KD) are validated non-pharmacological treatments for some forms of drug-resistant epilepsy. Ketones reduce neuronal excitation and promote neuroprotection. Here, we investigated the efficacy of KD as a treatment for acute cervical spinal cord injury (SCI) in rats. Starting 4 hours following C5 hemi-contusion injury animals were fed either a standard carbohydrate based diet or a KD formulation with lipid to carbohydrate plus protein ratio of 3:1. The forelimb functional recovery was evaluated for 14 weeks, followed by quantitative histopathology. Post-injury 3:1 KD treatment resulted in increased usage and range of motion of the affected forepaw. Furthermore, KD improved pellet retrieval with recovery of wrist and digit movements. Importantly, after returning to a standard diet after 12 weeks of KD treatment, the improved forelimb function remained stable. Histologically, the spinal cords of KD treated animals displayed smaller lesion areas and more grey matter sparing. In addition, KD treatment increased the number of glucose transporter-1 positive blood vessels in the lesion penumbra and monocarboxylate transporter-1 (MCT1) expression. Pharmacological inhibition of MCTs with 4-CIN (?-cyano-4-hydroxycinnamate) prevented the KD-induced neuroprotection after SCI, In conclusion, post-injury KD effectively promotes functional recovery and is neuroprotective after cervical SCI. These beneficial effects require the function of monocarboxylate transporters responsible for ketone uptake and link the observed neuroprotection directly to the function of ketones, which are known to exert neuroprotection by multiple mechanisms. Our data suggest that current clinical nutritional guidelines, which include relatively high carbohydrate contents, should be revisited. PMID:24223849

  3. TRIMETHYLTIN REDUCES RECURRENT INHIBITION IN RATS

    EPA Science Inventory

    Rats with electrodes chronically implanted in the perforant path for electrical stimulation, and dentate gyrus for recording were treated with a single oral administration of either saline, 5 mg/kg trimethyltin (TMT) or 6 mg/kg TMT. Recurrent inhibition was assessed by paired pul...

  4. Reducing Fear of the Laboratory Rat: A Participant Modeling Approach.

    ERIC Educational Resources Information Center

    Barber, Nigel

    1994-01-01

    Reports on the use of participant modeling in a study of 56 college-level students to reduce fear of laboratory rats. Discovers that even mild exposure reduced fear significantly. Finds that women were more fearful initially but that their fear reduction was equal to that of men. (CFR)

  5. Precocial hindlimbs and altricial forelimbs: partitioning ontogenetic strategies in mallards (Anas platyrhynchos).

    PubMed

    Dial, Terry R; Carrier, David R

    2012-11-01

    Precocial development, in which juveniles are relatively mature at hatching or birth, is more common among vertebrates than altricial development, and is likely to be the basal condition. Altricial development characterizes many birds and mammals and is generally viewed as an alternate strategy, promoting fast growth rates, short developmental periods and relatively poor locomotor performance prior to attaining adult size. Many aquatic birds such as Anseriformes (ducks, geese and swans), Charadriformes (gulls and terns) and Gruiformes (rails) undergo distinctive developmental trajectories, in that hatchlings are able to run and swim the day they hatch, yet they do not begin to fly until fully grown. We hypothesized that there should be tradeoffs in apportioning bone and muscle mass to the hindlimb and forelimb that could account for these patterns in locomotor behavior within the mallard (Anas platyrhynchos). Growth of the musculoskeletal system in the forelimbs and hindlimbs was measured and compared with maximal aquatic and terrestrial sprint speeds and aerial descent rates throughout the 2-month-long mallard ontogenetic period. At 30 days post hatching, when body mass is 50% of adult values, hindlimb muscle mass averages 90% and forelimb muscle mass averages 10% of adult values; similarly, bone growth (length and width) in the hindlimbs and forelimbs averages 90 and 60% of adult values, respectively. The attainment of mallard locomotor performance parallels the morphological maturation of forelimb and hindlimb morphometrics - hindlimb performance initiates just after hatching at a relatively high level (~50% adult values) and gradually improves throughout the first month of development, while forelimb performance is relatively non-existent at hatching (~10% adult values), experiencing delayed and dramatic improvement in function, and maturing at the time of fledging. This divergence in ontogenetic strategy between locomotor modules could allow developing Anseriformes to inhabit aquatic, predator-reduced refuges without relying on flight for juvenile escape. Furthermore, by freeing the forelimbs from locomotor demand early in ontogeny, Anseriformes may bypass the potential canalization (i.e. retention) of juvenile form present within their precocial hindlimbs, to dramatically depart in forelimb form and function in the adult. PMID:22855613

  6. Reduced neurons in the ileum of proctocolectomized rat models.

    PubMed

    Zhao, Chun-Mei; Myrvold, Helge E; Chen, Duan

    2015-09-01

    Ileal pouch-anal anastomosis (IPAA) is the operation of choice following proctocolectomy for patients who suffer from ulcerative colitis and familial adenomatous polyposis. The aim of this study was to morphologically examine the neurons, endocrine cells and mast cells in the ileum of rats subjected to proctocolectomy followed by three different types of ileoanal anastomosis. Rats were subjected to either sham operation or proctocolectomy followed by ileoanal anastomosis end-to-end, side-to-end or IPAA (J-pouch). In comparison to sham-operated rats, the body weight was reduced in rats that underwent proctocolectomy with end-to-end or side-to-end, but not IPAA procedure. In all three models of ileoanal anastomosis, the ileum displayed crypt hyperplasia with a chronic inflammatory infiltrate located in the interstitium, hyperplasia of goblet cells, but reduced protein gene product 9.5 (PGP 9.5)-immunoreactive neurons in the mucosa as well as submucosa. Numbers of endocrine cells in the mucosa (chromogranin A immunostaining) and mast cells in the mucosa and submucosa (Astra blue staining) were unchanged after proctocolectomy. In conclusion, neurons, but neither endocrine cells nor mast cells, were reduced in the ileum of proctocolectomized rats followed by either of three different types of ileoanal anastomosis. PMID:25432768

  7. Estrogen reduces CCL4- induced liver fibrosis in rats

    PubMed Central

    Xu, Jun-Wang; Gong, Jun; Chang, Xin-Ming; Luo, Jin-Yan; Dong, Lei; Hao, Zhi-Ming; Jia, Ai; Xu, Gui-Ping

    2002-01-01

    AIM: Chronic liver diseases, such as fibrosis or cirrhosis, are more common in men than in women. This gender difference may be related to the effects of sex hormones on the liver. The aim of the present work was to investigate the effects of estrogen on CCL4-induced fibrosis of the liver in rats. METHODS: Liver fibrosis was induced in male, female and ovariectomized rats by CCL4 administration. All the groups were treated with estradiol (1 mg/kg) twice weekly. And tamoxifen was given to male fibrosis model. At the end of 8 wk, all the rats were killed to study serum indicators and the livers. RESULTS: Estradiol treatment reduced aspartate aminotransferase (AST), alanine aminotransferase (ALT), hyaluronic acid (HA) and type IV collagen (CIV) in sera, suppressed hepatic collagen content, decreased the areas of hepatic stellate cells (HSC) positive for ?-smooth muscle actin (?-SMA), and lowered the synthesis of hepatic type I collagen significantly in both sexes and ovariectomy fibrotic rats induced by CCL4 administration. Whereas, tamoxifen had the opposite effect. The fibrotic response of the female liver to CCL4 treatment was significantly weaker than that of male liver. CONCLUSION: Estradiol reduces CCL4-induced hepatic fibrosis in rats. The antifibrogenic role of estrogen in the liver may be one reason for the sex associated differences in the progression from hepatic fibrosis to cirrhosis. PMID:12378635

  8. Reduced exposure to microwave radiation by rats: frequency specific effects

    SciTech Connect

    D'Andrea, J.A.; DeWitt, J.R.; Portuguez, L.M.; Gandhi, O.P.

    1988-01-01

    Previous research has shown that SAR hotspots are induced within the laboratory rat and that the resulting thermal hotspots are not entirely dissipated by bloodflow. Two experiments were conducted to determine if hotspot formation in the body and tail of the rat, which is radiation frequency specific, would have behavioral consequences. In the first experiment rats were placed in a plexiglas cage one side of which, when occupied by the rat, commenced microwave radiation exposure; occupancy of the other side terminated exposure. Groups of rats were tested during a baseline period to determine the naturally preferred side of the cage. Subsequent exposure to 360-MHz, 700-MHz or 2450-MHz microwave radiation was made contingent on preferred-side occupancy. A significant reduction in occupancy of the preferred side of the cage, and hence, microwaves subsequently occurred. Reduced exposure to 360-MHz and 2450-MHz microwaves at 1, 2, 6 and 10 W/kg were significantly different from 700-MHz microwaves. In the second experiment semichronic exposures revealed the threshold for reduced exposure of 2450-MHz microwaves to be located between whole-body SAR's of 2.1 and 2.8 W/kg.

  9. Unsaturated Fatty Acids Supplementation Reduces Blood Lead Level in Rats

    PubMed Central

    Skoczy?ska, Anna; Wojakowska, Anna; Nowacki, Dorian; Bobak, ?ukasz; Turczyn, Barbara; Smyk, Beata; Szuba, Andrzej; Trziszka, Tadeusz

    2015-01-01

    Some dietary factors could inhibit lead toxicity. The aim of this study was to evaluate the effect of dietary compounds rich in unsaturated fatty acids (FA) on blood lead level, lipid metabolism, and vascular reactivity in rats. Serum metallothionein and organs' lead level were evaluated with the aim of assessing the possible mechanism of unsaturated FA impact on blood lead level. For three months, male Wistar rats that were receiving drinking water with (100?ppm?Pb) or without lead acetate were supplemented per os daily with virgin olive oil or linseed oil (0.2?mL/kg?b.w.) or egg derived lecithin fraction: “super lecithin” (50?g/kg?b.w.). Mesenteric artery was stimulated ex vivo by norepinephrine (NE) administered at six different doses. Lecithin supplementation slightly reduced pressor responses of artery to NE. Lead administered to rats attenuated the beneficial effect of unsaturated FA on lipid metabolism and vascular reactivity to adrenergic stimulation. On the other hand, the super lecithin and linseed oil that were characterized by low omega-6 to omega-3 ratio (about 1) reduced the blood lead concentration. This effect was observed in lead poisoned rats (p < 0.0001) and also in rats nonpoisoned with lead (p < 0.05). PMID:26075218

  10. Metformin reduces hepatic resistance and portal pressure in cirrhotic rats.

    PubMed

    Tripathi, Dinesh M; Erice, Eva; Lafoz, Erica; García-Calderó, Héctor; Sarin, Shiv K; Bosch, Jaime; Gracia-Sancho, Jordi; García-Pagán, Juan Carlos

    2015-09-01

    Increased hepatic vascular resistance is the primary factor in the development of portal hypertension. Metformin ameliorates vascular cells function in several vascular beds. Our study was aimed at evaluating the effects, and the underlying mechanisms, of metformin on hepatic and systemic hemodynamics in cirrhotic rats and its possible interaction with the effects of propranolol (Prop), the current standard treatment for portal hypertension. CCl4-cirrhotic rats received by gavage metformin 300 mg/kg or its vehicle once a day for 1 wk, before mean arterial pressure (MAP), portal pressure (PP), portal blood flow (PBF), hepatic vascular resistance, and putative molecular/cellular mechanisms were measured. In a subgroup of cirrhotic rats, the hemodynamic response to acute Prop (5 mg/kg iv) was assessed. Effects of metformin ± Prop on PP and MAP were validated in common bile duct ligated-cirrhotic rats. Metformin-treated CCl4-cirrhotic rats had lower PP and hepatic vascular resistance than vehicle-treated rats, without significant changes in MAP or PBF. Metformin caused a significant reduction in liver fibrosis (Sirius red), hepatic stellate cell activation (?-smooth muscle actin, platelet-derived growth factor receptor ? polypeptide, transforming growth factor-?R1, and Rho kinase), hepatic inflammation (CD68 and CD163), superoxide (dihydroethidium staining), and nitric oxide scavenging (protein nitrotyrosination). Prop, by decreasing PBF, further reduced PP. Similar findings were observed in common bile duct ligated-cirrhotic rats. Metformin administration reduces PP by decreasing the structural and functional components of the elevated hepatic resistance of cirrhosis. This effect is additive to that of Prop. The potential impact of this pharmacological combination, otherwise commonly used in patients with cirrhosis and diabetes, needs clinical evaluation. PMID:26138461

  11. Red maca (Lepidium meyenii) reduced prostate size in rats

    PubMed Central

    Gonzales, Gustavo F; Miranda, Sara; Nieto, Jessica; Fernández, Gilma; Yucra, Sandra; Rubio, Julio; Yi, Pedro; Gasco, Manuel

    2005-01-01

    Background Epidemiological studies have found that consumption of cruciferous vegetables is associated with a reduced risk of prostate cancer. This effect seems to be due to aromatic glucosinolate content. Glucosinolates are known for have both antiproliferative and proapoptotic actions. Maca is a cruciferous cultivated in the highlands of Peru. The absolute content of glucosinolates in Maca hypocotyls is relatively higher than that reported in other cruciferous crops. Therefore, Maca may have proapoptotic and anti-proliferative effects in the prostate. Methods Male rats treated with or without aqueous extracts of three ecotypes of Maca (Yellow, Black and Red) were analyzed to determine the effect on ventral prostate weight, epithelial height and duct luminal area. Effects on serum testosterone (T) and estradiol (E2) levels were also assessed. Besides, the effect of Red Maca on prostate was analyzed in rats treated with testosterone enanthate (TE). Results Red Maca but neither Yellow nor Black Maca reduced significantly ventral prostate size in rats. Serum T or E2 levels were not affected by any of the ecotypes of Maca assessed. Red Maca also prevented the prostate weight increase induced by TE treatment. Red Maca administered for 42 days reduced ventral prostatic epithelial height. TE increased ventral prostatic epithelial height and duct luminal area. These increases by TE were reduced after treatment with Red Maca for 42 days. Histology pictures in rats treated with Red Maca plus TE were similar to controls. Phytochemical screening showed that aqueous extract of Red Maca has alkaloids, steroids, tannins, saponins, and cardiotonic glycosides. The IR spectra of the three ecotypes of Maca in 3800-650 cm (-1) region had 7 peaks representing 7 functional chemical groups. Highest peak values were observed for Red Maca, intermediate values for Yellow Maca and low values for Black Maca. These functional groups correspond among others to benzyl glucosinolate. Conclusions Red Maca, a cruciferous plant from the highland of Peru, reduced ventral prostate size in normal and TE treated rats. PMID:15661081

  12. Dietary vitamin E reduces labile iron in rat tissues.

    PubMed

    Ibrahim, Wissam; Chow, Ching Kuang

    2005-01-01

    Previous studies have shown that dietary vitamin E reduced generation and/or levels of superoxide. As superoxide has potential to release iron from its transport and storage proteins, and labile or available form of iron is capable of catalyzing the formation of reactive hydroxyl radicals, the effect of dietary vitamin E on labile iron pool was studied in rats. One-month-old Sprague-Dawley male and female rats were fed a basal vitamin E-deficient diet supplemented with 0, 20, 200, or 2,000 IU vitamin E/kg diet for 90 days. The levels of labile iron were measured in the liver, kidney, spleen, heart and skeletal muscle. Additionally, the levels of lipid peroxidation products were measured. The results showed that, except for labile iron in the heart of male rats, dietary vitamin E dose dependently reduced the levels of labile iron and lipid peroxidation products in all tissues of male and female rats. The findings suggest that dietary vitamin E may protect against oxidative tissue damage by reducing the generation and/or level of superoxide, which in turn attenuates the release of iron from its protein complexes. PMID:16292753

  13. Melatonin reduces hepatic mitochondrial dysfunction in diabetic obese rats.

    PubMed

    Agil, Ahmad; El-Hammadi, Mazen; Jiménez-Aranda, Aroa; Tassi, Mohamed; Abdo, Walied; Fernández-Vázquez, Gumersindo; Reiter, Russel J

    2015-08-01

    Hepatic mitochondrial dysfunction is thought to play a role in the development of liver steatosis and insulin resistance, which are both common characteristics of obesity and type 2 diabetes mellitus (T2DM). It was hypothesized that the antioxidant properties of melatonin could potentially improve the impaired functions of hepatic mitochondria in diabetic obese animals. Male Zucker diabetic fatty (ZDF) rats and lean littermates (ZL) were given either melatonin (10 mg/kg BW/day) orally for 6 wk (M-ZDF and M-ZL) or vehicle as control groups (C-ZDF and C-ZL). Hepatic function was evaluated by measurement of serum alanine transaminase and aspartate transaminase levels, liver histopathology and electron microscopy, and hepatic mitochondrial functions. Several impaired functions of hepatic mitochondria were observed in C-ZDF in comparison with C-ZL rats. Melatonin treatment to ZDF rats decreases serum levels of ALT (P < 0.001), alleviates liver steatosis and vacuolation, and also mitigates diabetic-induced mitochondrial abnormalities, glycogen, and lipid accumulation. Melatonin improves mitochondrial dysfunction in M-ZDF rats by increasing activities of mitochondrial citrate synthase (P < 0.001) and complex IV of electron transfer chain (P < 0.05) and enhances state 3 respiration (P < 0.001), respiratory control index (RCR) (P < 0.01), and phosphorylation coefficient (ADP/O ratio) (P < 0.05). Also melatonin augments ATP production (P < 0.05) and diminishes uncoupling protein 2 levels (P < 0.001). These results demonstrate that chronic oral melatonin reduces liver steatosis and mitochondria dysfunction in ZDF rats. Therefore, it may be beneficial in the treatment of diabesity. PMID:25904243

  14. Noribogaine reduces nicotine self-administration in rats

    PubMed Central

    Chang, Qing; Hanania, Taleen; Mash, Deborah C

    2015-01-01

    Noribogaine, a polypharmacological drug with activities at opioid receptors, ionotropic nicotinic receptors, and serotonin reuptake transporters, has been investigated for treatment of substance abuse-related disorders. Smoking cessation has major benefits for both individuals and society, therefore the aim of this study was to evaluate the potential of noribogaine for use as a treatment for nicotine dependence. Adult male Sprague-Dawley rats were trained to self-administer nicotine intravenous. After initial food pellet training, followed by 26 sessions of nicotine self-administration training, the rats were administered noribogaine (12.5, 25 or 50 mg/kg orally), noribogaine vehicle, varenicline or saline using a within-subject design with a Latin square test schedule. Noribogaine dose-dependently decreased nicotine self-administration by up to 64% of saline-treated rats’ levels and was equi-effective to 1.7 mg/kg intraperitoneal varenicline. Noribogaine was less efficient at reducing food pellets self-administration than at nicotine self-administration, inhibiting the nondrug reinforcing effects of palatable pellets by 23% at the highest dose. These results suggest that noribogaine dose-dependently attenuates drug-taking behavior for nicotine, attenuates the reinforcing effects of nicotine and is comparable to varenicline power in that regard. The findings from the present study hold promise for a new therapy to aid smoking cessation. PMID:25995321

  15. Immunization of rats reduces nicotine distribution to brain.

    PubMed

    Hieda, Y; Keyler, D E; VanDeVoort, J T; Niedbala, R S; Raphael, D E; Ross, C A; Pentel, P R

    1999-04-01

    The effect of active immunization against nicotine on the initial distribution of nicotine to brain was studied in anesthetized rats. Animals received nicotine 0.03 mg/kg nicotine (equivalent to the nicotine dose absorbed by a human smoking two cigarettes) as a rapid injection in the jugular vein. In control animals, the arterial serum nicotine concentration initially exceeded the venous concentration 4.6-fold, similar to the initial arteriovenous difference produced by cigarette smoking in humans. Animals immunized with the nicotine analog CMUNic maintained this arteriovenous gradient, but with both arterial and venous nicotine concentrations several times higher than in controls. The arterial nicotine concentration was higher in immunized animals even at the first (7.5 s) sampling time. The brain nicotine concentration at 3 min was 36% lower in the immunized animals. The time course of nicotine distribution to brain was studied in a second group of animals. Brain nicotine concentration was reduced in rats immunized with CMUNic over the entire 6-min sampling period immediately following nicotine dosing (mean reduction 38%). A reduction was found at the earliest sampling time (30 s) and was maximal at 1 min (48%). Nicotine protein binding in serum was markedly increased in animals immunized with CMUNic compared to controls (91.2 versus 10.9%), and the unbound nicotine concentration in serum was lower (10.0 versus 13.4 ng/ml). The reduction in brain nicotine concentration correlated with antibody affinity for nicotine, and the percentage of nicotine bound in serum. These data demonstrate that nicotine-specific antibodies produced by active immunization rapidly bind nicotine in arterial blood, reduce the unbound nicotine concentration, and reduce the early distribution of nicotine to brain. Effects were observed using a clinically relevant nicotine dose and route of administration. These data suggest that the use of immunization to modify the behavioral effects of nicotine may be possible. PMID:10326777

  16. Forelimb kinematics during hopping and landing in toads.

    PubMed

    Cox, S M; Gillis, Gary B

    2015-10-01

    Coordinated landing in a variety of animals involves the re-positioning of limbs prior to impact to safely decelerate the body. However, limb kinematics strategies for landing vary considerably among species. For example, human legs are increasingly flexed before impact as drop height increases, while turkeys increasingly extend their legs before impact with increasing drop height. In anurans, landing typically involves the use of the forelimbs to decelerate the body after impact. Few detailed, quantitative descriptions of anuran forelimb kinematics during jumping exist and it is not known whether they prepare for larger landing forces by changing forelimb kinematics. In this study, we used high-speed video of 51 hops from five cane toads (Bufo marinus) to test the hypothesis that forelimb kinematics change predictably with distance. We measured excursions of the elbow (flexion/extension) and humerus (protraction/retraction and elevation/depression) throughout every hop. The results indicate that elbow and humeral excursions leading up to impact increase significantly with hop length, but do so without any change in the rate of movement. Instead, because the animal is in the air longer during longer hops, near-constant velocity movements lead to the larger excursions. These larger excursions in elbow extension result in animals hitting the ground with more extended forelimbs in longer hops, which in turn allows animals to decelerate over a greater distance. PMID:26254325

  17. Anatomical, architectural, and biochemical diversity of the murine forelimb muscles

    PubMed Central

    Mathewson, Margie A; Chapman, Mark A; Hentzen, Eric R; Fridén, Jan; Lieber, Richard L

    2012-01-01

    We characterized the architecture, fiber type, titin isoform distribution, and collagen content of 27 portions of 22 muscles in the murine forelimb. The mouse forelimb was different from the human arm in that it had the extensor digitorum lateralis muscle and no brachioradialis muscle. Architecturally, the mouse forelimb differed from humans with regard to load bearing, having a much larger contribution from extensors than flexors. In mice, the extensor : flexor PCSA ratio is 2.7, whereas in humans it is only 1.4. When the architectural difference index was calculated, similarities became especially apparent between flexors and extensors of the distal forelimb, as well as pronators. Discriminant analysis revealed that biochemical measures of collagen, titin, and myosin heavy chain were all strong between-species discriminators. In terms of composition, when compared with similar muscles in humans, mice had, on average, faster muscles with higher collagen content and larger titin isoforms. This report establishes the anatomical and biochemical properties of mouse forelimb muscles. Given the prevalence of this species in biological studies, these data will be invaluable for studying the biological basis of mouse muscle structure and function. PMID:22938020

  18. Intranasal IGF-1 Reduced Rat Pup Germinal Matrix Hemorrhage.

    PubMed

    Lekic, Tim; Flores, Jerry; Klebe, Damon; Doycheva, Desislava; Rolland, William B; Tang, Jiping; Zhang, John H

    2016-01-01

    Germinal matrix hemorrhage (GMH) is the most devastating neurological problem of premature infants. Current treatment strategies are ineffective and brain injury is unpreventable. Insulin-like growth factor 1 (IGF-1) is an endogenous protein shown to have multiple neuroprotective properties. We therefore hypothesized that IGF-1 would reduce brain injury after GMH. Neonatal rats (P7 age) received stereotactic collagenase into the right ganglionic eminence. The following groups were studied: (1) sham, (2) GMH?+?vehicle, (3) GMH?+?intranasal IGF-1. Three days later, the animals were evaluated using the righting-reflex (early neurobehavior), Evans blue dye leakage (blood-brain barrier (BBB) permeability), brain water content (edema), and hemoglobin assay (extent of bleeding). Three weeks later, juvenile rats were tested using a water maze (delayed neurobehavior), and then were sacrificed on day 28 for assessment of hydrocephalus (ventricular size). Intranasal IGF-1 treated animals had improved neurological function, and amelioration of BBB permeability, edema, and re-bleeding. IGF-1 may play a part in protective brain signaling following GMH, and our observed protective effect may offer new promise for treatment targeting this vulnerable patient population. PMID:26463950

  19. Exercise reduces angiotensin II responses in rat femoral veins.

    PubMed

    Chies, Agnaldo Bruno; Rossignoli, Patrícia de Souza; Baptista, Rafaela de Fátima Ferreira; de Lábio, Roger William; Payão, Spencer Luiz Marques

    2013-06-01

    The control of blood flow during exercise involves different mechanisms, one of which is the activation of the renin-angiotensin system, which contributes to exercise-induced blood flow redistribution. Moreover, although angiotensin II (Ang II) is considered a potent venoconstrictor agonist, little is known about its effects on the venous bed during exercise. Therefore, the present study aimed to assess the Ang II responses in the femoral vein taken from sedentary and trained rats at rest or subjected to a single bout of exercise immediately before organ bath experiments. Isolated preparations of femoral veins taken from resting-sedentary, exercised-sedentary, resting-trained and exercised-trained animals were studied in an organ bath. In parallel, the mRNA expression of prepro-endothelin-1 (ppET-1), as well as the ETA and ETB receptors, was quantified by real-time PCR in this tissue. The results show that, in the presence of L-NAME, Ang II responses in resting-sedentary animals were higher compared to the other groups. However, this difference disappeared after co-treatment with indomethacin, BQ-123 or BQ-788. Moreover, exercise reduced ppET-1 mRNA expression. These reductions in mRNA expression were more evident in resting-trained animals. In conclusion, either acute or repeated exercise adapts the rat femoral veins, thereby reducing the Ang II responses. This adaptation is masked by the action of locally produced nitric oxide and involves, at least partially, the ETB- mediated release of vasodilator prostanoids. Reductions in endothelin-1 production may also be involved in these exercise-induced modifications of Ang II responses in the femoral vein. PMID:23528515

  20. Internal and external feedback circuits for skilled forelimb movement

    PubMed Central

    Azim, Eiman; Fink, Andrew J.P.; Jessell, Thomas M.

    2015-01-01

    Skilled motor behavior emerges from interactions between efferent neural pathways that induce muscle contraction and feedback systems that report and refine movement. Two broad classes of feedback projections modify motor output, one from the periphery and a second that originates within the central nervous system. The mechanisms through which these pathways influence movement remain poorly understood, however. Here we discuss recent studies that delineate spinal circuitry that binds external and internal feedback pathways to forelimb motor behavior. A spinal presynaptic inhibitory circuit regulates the strength of external feedback, promoting limb stability during goal-directed reaching. A distinct excitatory propriospinal circuit conveys copies of motor commands to the cerebellum, establishing an internal feedback loop that rapidly modulates forelimb motor output. The behavioral consequences of manipulating these two circuits reveal distinct controls on motor performance, and provide an initial insight into feedback strategies that underlie skilled forelimb movement. PMID:25699987

  1. Exercise training reduces insulin resistance in postmyocardial infarction rats

    PubMed Central

    Wang, Youhua; Tian, Zhenjun; Zang, Weijin; Jiang, Hongke; Li, Youyou; Wang, Shengpeng; Chen, Shengfeng

    2015-01-01

    Myocardial infarction (MI) induces cardiac dysfunction and insulin resistance (IR). This study examines the effects of MI-related IR on vasorelaxation and its underlying mechanisms, with a specific focus on the role of exercise in reversing the impaired vasorelaxation. Adult male Sprague–Dawley rats were divided into three groups: Sham, MI, and MI+Exercise. MI+Exercise rats were subjected to 8 weeks of treadmill training. Cardiac contraction, myocardial and arterial structure, vasorelaxation, levels of inflammatory cytokines, expression of eNOS and TNF-?, and activation of PI3K/Akt/eNOS and p38 mitogen-activated protein kinase (p38 MAPK) were determined in aortas. MI significantly impaired endothelial structure and vasodilation (P < 0.05–0.01), as indicated by decreased arterial vasorelaxation to ACh and insulin. MI also attenuated the myocardial contractile response, decreased aortic PI3K/Akt/eNOS expression and phosphorylation by insulin, and increased IL-1?, IL-6, and TNF-? expression and p38 MAPK activity (P < 0.05–0.01). Exercise improved insulin sensitivity in aortas, facilitated myocardial contractile response and arterial vasorelaxation to ACh and insulin, and increased arterial PI3K/Akt/eNOS activity. Moreover, exercise markedly reversed increased p38 MAPK activity and normalized inflammatory cytokines in post-MI arteries. Inhibition of PI3K with LY-294002, and eNOS with L-NAME significantly blocked arterial vasorelaxation and PI3K/Akt/eNOS phosphorylation in response to insulin. In conclusion, these results demonstrate that endothelial dysfunction in response to insulin plays an important role in MI-related IR. The reversal of IR by exercise is most likely associated with normalizing inflammatory cytokines, increasing the activation of PI3K/Akt/eNOS, and reducing the activation of p38 MAPK. PMID:25907785

  2. Apc-driven colon carcinogenesis in Pirc rat is strongly reduced by polyethylene glycol.

    PubMed

    Femia, Angelo Pietro; Becherucci, Caterina; Crucitta, Stefania; Caderni, Giovanna

    2015-11-01

    Polyethylene glycol (PEG) is one of the most powerful agents in reducing chemically induced carcinogenesis in rat colon. However, contrasting results in Min mice dampened the enthusiasm on this potentially strong and virtually safe, cancer chemopreventing agent. Pirc (F344/NTac-Apc (am1137) ) rats carrying a germline heterozygous mutation in the Apc gene, spontaneously develop multiple tumours in the colon thus modelling both familial adenomatous polyposis (FAP) and sporadic colorectal cancer (CRC). Given this similarity, we thought that these rats could be appropriate to test the efficacy of PEG 8000 in reducing carcinogenesis. Pirc male rats aged one month were treated with 5% PEG in drinking water for 2 or 6 months. Precancerous lesions were dramatically reduced after 2 months of PEG treatment (Mucin depleted foci (MDF)/colon were 99 ± 17 and 12 ± 8 in Controls and PEG-treated rats, respectively; p < 0.001; mean ± SD). Similarly, colon tumors were significantly reduced after 6 months of treatment (tumors/rat were 8.1 ± 2.3 and 3.6 ± 2.2 in Controls and PEG-treated rats, respectively; p < 0.05; mean ± SD). Colon proliferation, a parameter correlated to cancer risk, was also significantly lower in PEG-treated rats than in Controls, while apoptosis was not significantly affected. In conclusion, PEG markedly reduces colon carcinogenesis in Pirc rats mutated in Apc; we thus suggest that PEG may be used as chemopreventive agent to reduce cancer risk in FAP and CRC patients. PMID:25912754

  3. Ergonomic task reduction prevents bone osteopenia in a rat model of upper extremity overuse

    PubMed Central

    BARBE, Mary F.; JAIN, Nisha X.; MASSICOTTE, Vicky S.; POPOFF, Steven N.; BARR-GILLESPIE, Ann E.

    2015-01-01

    We evaluated the effectiveness of ergonomic workload reduction of switching rats from a high repetition high force (HRHF) lever pulling task to a reduced force and reach rate task for preventing task-induced osteopenic changes in distal forelimb bones. Distal radius and ulna trabecular structure was examined in young adult rats performing one of three handle-pulling tasks for 12 wk: 1) HRHF, 2) low repetition low force (LRLF); or 3) HRHF for 4 wk and than LRLF thereafter (HRHF-to-LRLF). Results were compared to age-matched controls rats. Distal forelimb bones of 12-wk HRHF rats showed increased trabecular resorption and decreased volume, as control rats. HRHF-to-LRLF rats had similar trabecular bone quality as control rats; and decreased bone resorption (decreased trabecular bone volume and serum CTX1), increased bone formation (increased mineral apposition, bone formation rate, and serum osteocalcin), and decreased osteoclasts and inflammatory cytokines, than HRHF rats. Thus, an ergonomic intervention of HRHF-to-LRLF prevented loss of trabecular bone volume occurring with prolonged performance of a repetitive upper extremity task. These findings support the idea of reduced workload as an effective approach to management of work-related musculoskeletal disorders, and begin to define reach rate and load level boundaries for such interventions. PMID:25739896

  4. Dimensions of forelimb muscles in orangutans and chimpanzees

    PubMed Central

    Oishi, Motoharu; Ogihara, Naomichi; Endo, Hideki; Ichihara, Nobutsune; Asari, Masao

    2009-01-01

    Eight forelimbs of three orangutans and four chimpanzees were dissected and the muscle mass, fascicle length and physiological cross-sectional area (PCSA) of all forelimb muscles were systematically recorded to explore possible interspecies variation in muscle dimensions. Muscle mass and PCSA were divided by the total mass and total PCSA of the entire forelimb muscles for normalization. The results indicate that the mass and PCSA ratios of the monoarticular elbow flexors (M. brachialisand M. brachioradialis) are significantly larger in orangutans. In contrast, the mass ratios of the biarticular muscles in the upper arm (the short head of M. biceps brachiiand the long head of M. triceps brachii) are significantly larger in chimpanzees. For the rotator cuff muscles, the force-generating capacity of M. subscapularisis significantly larger in orangutans, whereas the opposite rotator cuff muscle, M. infraspinatus, is larger in chimpanzees. These differences in forelimb muscle dimensions of the two species may reflect functional specialization for their different positional and locomotor behaviors. PMID:19619166

  5. Developmental constraint on the evolution of marsupial forelimb morphology

    E-print Network

    Steppan, Scott

    of mammal limb variation, and rates of mammal limb evolution, conform to the predictions of this hypothesisDevelopmental constraint on the evolution of marsupial forelimb morphology W. James Cooper. Compared with the placental mammals, marsupials are born at an almost embryonic stage, but nearly all

  6. Antihyperlipidaemic, antihypertrophic, and reducing effects of zingerone on experimentally induced myocardial infarcted rats.

    PubMed

    Hemalatha, K L; Stanely Mainzen Prince, P

    2015-04-01

    The present study aims to evaluate the antihyperlipidaemic, antihypertrophic, and reducing effects of zingerone on isoproterenol-induced hyperlipidaemia and hypertrophy in rats. Rats were pretreated with zingerone (6 mg/kg body weight) daily for a period of 14 days and then induced myocardial infarction with isoproterenol (100 mg/kg body weight) on days 15 and 16. Isoproterenol increased serum creatine kinase and lactate dehydrogenase activities in the rats. Increased levels/concentrations of serum and heart cholesterol and triglycerides were observed in isoproterenol-induced myocardial infarcted rats. Isoproterenol also altered serum lipoproteins and the activity of liver 3-hydroxy-3-methyl glutaryl-coenzyme-A-reductase in the rats. The in vitro study revealed a very convincing reducing power of zingerone. Pretreatment with zingerone prevented hyperlipidaemia and cardiac hypertrophy, by virtue of its antihyperlipidaemic, antihypertrophic, and reducing properties in isoproterenol-induced myocardial infarcted rats. PMID:25558849

  7. Pyramidal tract neurons receptive to different forelimb joints act differently during locomotion

    PubMed Central

    Stout, Erik E.

    2012-01-01

    During locomotion, motor cortical neurons projecting to the pyramidal tract (PTNs) discharge in close relation to strides. How their discharges vary based on the part of the body they influence is not well understood. We addressed this question with regard to joints of the forelimb in the cat. During simple and ladder locomotion, we compared the activity of four groups of PTNs with somatosensory receptive fields involving different forelimb joints: 1) 45 PTNs receptive to movements of shoulder, 2) 30 PTNs receptive to movements of elbow, 3) 40 PTNs receptive to movements of wrist, and 4) 30 nonresponsive PTNs. In the motor cortex, a relationship exists between the location of the source of afferent input and the target for motor output. On the basis of this relationship, we inferred the forelimb joint that a PTN influences from its somatosensory receptive field. We found that different PTNs tended to discharge differently during locomotion. During simple locomotion shoulder-related PTNs were most active during late stance/early swing, and upon transition from simple to ladder locomotion they often increased activity and stride-related modulation while reducing discharge duration. Elbow-related PTNs were most active during late swing/early stance and typically did not change activity, modulation, or discharge duration on the ladder. Wrist-related PTNs were most active during swing and upon transition to the ladder often decreased activity and increased modulation while reducing discharge duration. These data suggest that during locomotion the motor cortex uses distinct mechanisms to control the shoulder, elbow, and wrist. PMID:22236716

  8. The timing and amount of vagus nerve stimulation during rehabilitative training affect post-stroke recovery of forelimb strength

    PubMed Central

    Hays, Seth A.; Khodaparast, Navid; Ruiz, Andrea; Sloan, Andrew M.; Hulsey, Daniel R.; Rennaker, Robert L.; Kilgard, Michael P.

    2014-01-01

    Loss of upper arm strength after stroke is a leading cause of disability. Strategies that can enhance the benefits of rehabilitative training could improve motor function after stroke. Recent studies in a rat model of ischemic stroke demonstrate that vagus nerve stimulation (VNS) paired with rehabilitative training substantially improves recovery of forelimb strength compared to extensive rehabilitative training without VNS. Here we report that the timing and amount of stimulation affect the degree of forelimb strength recovery. Similar amounts of delayed VNS delivered two hours after daily rehabilitative training sessions resulted in significantly less improvement compared to VNS that is paired with identical rehabilitative training. Significantly less recovery also occurred when several-fold more VNS was delivered during rehabilitative training. Both delayed and additional VNS confer moderately improved recovery compared to extensive rehabilitative training without VNS, but fail to enhance recovery to the same degree as VNS that is timed to occur with successful movements. These findings confirm that VNS paired with rehabilitative training holds promise for restoring forelimb strength post-stroke and indicate that both the timing and amount of VNS should be optimized to maximize therapeutic benefits. PMID:24818637

  9. Memory Retrieval before or after Extinction Reduces Recovery of Fear in Adolescent Rats

    ERIC Educational Resources Information Center

    Baker, Kathryn D.; McNally, Gavan P.; Richardson, Rick

    2013-01-01

    Adolescent rats exhibit impaired extinction retention compared to pre-adolescent and adult rats. A single nonreinforced exposure to the conditioned stimulus (CS; a retrieval trial) given shortly before extinction has been shown in some circumstances to reduce the recovery of fear after extinction in adult animals. This study investigated whether a…

  10. Systemic Propranolol Acts Centrally to Reduce Conditioned Fear in Rats Without Impairing Extinction

    E-print Network

    Quirk, Gregory J.

    Systemic Propranolol Acts Centrally to Reduce Conditioned Fear in Rats Without Impairing Extinction of conditioned fear. Less is known, however, about their role in fear expression and extinction. The -receptor in rats, we assessed the effects of systemic propranolol on the expression and extinction of two measures

  11. Sodium Salicylate Reduced Insulin Resistance in the Retina of a Type 2 Diabetic Rat Model

    PubMed Central

    Jiang, Youde; Thakran, Shalini; Bheemreddy, Rajini; Coppess, William; Walker, Robert J.; Steinle, Jena J.

    2015-01-01

    Sodium salicylate has been reported to reduce markers of diabetic retinopathy in a type 1 rat model. Because rates of type 2 diabetes are on the rise, we wanted to determine whether salicylate could improve insulin resistance in a type 2 rat model, as well as improve retinal function. We treated lean and obese BBZDR/Wor type 2 diabetic rats with salicylate in their chow for 2 months. Prior to salicylate treatment, rats underwent an electroretinogram to measure retinal function. After 2 months of treatment, rats underwent an additional electroretinogram prior to sacrifice. In addition to the animal model, we also treated retinal endothelial cells (REC) and rat Müller cells with salicylate and performed the same analyses as done for the rat retinal lysates. To investigate the role of salicylate in insulin signaling, we measured TNF? and caspase 3 levels by ELISA, as well as performed Western blotting for insulin receptor substrate 1, insulin receptor, SOCS3, and pro- and anti-apoptotic markers. Data demonstrated that salicylate significantly improved retinal function, as well as reduced TNF? and SOCS3-induced insulin resistance in all samples. Overall, results suggest that salicylate is effective in reducing insulin resistance in the retina of type 2 diabetic rat models. PMID:25874611

  12. Arginine and Conjugated Linoleic Acid Reduce Fat Mass in Rats 

    E-print Network

    Nall, Jennifer L.

    2010-10-12

    , it is able to diffuse into cells and act on its target molecules via cGMP-dependent pathways. NO regulates vascular tone, neurotransmission, immunity, and overall homeostasis. L-Arginine is the precursor for NO and is converted to NO by nitric oxide... of arginine (0 and 1.5%) and two levels of CLA (0 and 1.5%). The treatment groups were: ?Control rats (n = 6), fed 2.55% L-alanine (isonitrogenous control) plus 1.5% canola (lipid control). ?Arginine rats (n = 6), fed 1.25% L-arginine plus 1.5% canola...

  13. Pixantrone (BBR2778) reduces the severity of experimental autoimmune myasthenia gravis in Lewis rats.

    PubMed

    Ubiali, Federica; Nava, Sara; Nessi, Valeria; Longhi, Renato; Pezzoni, Gabriella; Capobianco, Raffaella; Mantegazza, Renato; Antozzi, Carlo; Baggi, Fulvio

    2008-02-15

    Pixantrone (BBR2778) (PIX) and mitoxantrone share the same mechanism of action because both drugs act as DNA intercalants and inhibitors of topoisomerase II. PIX is an interesting candidate immunosuppressant for the treatment of autoimmune diseases because of its reduced cardiotoxicity compared with mitoxantrone. The clinical response to conventional immunosuppressive treatments is poor in some patients affected by myasthenia gravis (MG), and new but well-tolerated drugs are needed for treatment-resistant MG. PIX was tested in vitro on rat T cell lines specific for the immunodominant peptide 97-116 derived from rat acetylcholine receptor (AChR), and showed strong antiproliferative activity in the nanomolar range. We demonstrate in this study that PIX administration reduced the severity of experimental autoimmune MG in Lewis rats. Biological and immunological analysis confirmed the effect of PIX, compared with vehicle-treated as well as mitoxantrone-treated experimental autoimmune MG rats. Anti-rat AChR Abs were significantly reduced in PIX-treated rats, and AChR content in muscles were found increased. Torpedo AChR-induced T cell proliferation tests were found reduced in both in vitro and ex vivo experiments. The effectiveness and the reduced cardiotoxicity make PIX a promising immunosuppressant agent suitable for clinical investigation in MG, although additional experiments are needed to confirm its safety profile in prolonged treatments. PMID:18250482

  14. Peripheral oxytocin administration reduces ethanol consumption in rats.

    PubMed

    MacFadyen, Kaley; Loveless, Rebecca; DeLucca, Brandon; Wardley, Krystal; Deogan, Sumeet; Thomas, Cameron; Peris, Joanna

    2016-01-01

    The neuropeptide oxytocin interacts with mesolimbic dopamine neurons to mediate reward associated with filial behaviors, but also other rewarding behaviors such as eating or taking drugs of abuse. Based on its efficacy to decrease intake of other abused substances, oxytocin administration is implicated as a possible treatment for excessive alcohol consumption. We tested this hypothesis by measuring ethanol intake in male Sprague-Dawley rats injected with oxytocin or saline using two different ethanol self-administration paradigms. First, a dose-response curve was constructed for oxytocin inhibition of fluid intake using a modified drinking-in-the-dark model with three bottles containing .05% saccharine, 10% ethanol in saccharine, and 15% ethanol in saccharine. Doses of oxytocin tested were 0.05, 0.1, 0.3, and 0.5mg/kg (I.P.). Next, rats received 0.3mg/kg oxytocin preceding operant sessions in which they were trained to lever-press for either plain gelatin or ethanol gelatin in order to compare oxytocin inhibition of ethanol intake versus caloric intake. For the three-bottle choice study, rats consumed significantly less ethanol when treated with the three higher doses of oxytocin on the injection day. In the operant study, 0.3mg/kg oxytocin significantly decreased ethanol gel consumption to a greater extent than plain gel consumption, both in terms of the amount of gel eaten and calories consumed. These data affirm oxytocin's efficacy for decreasing ethanol intake in rats, and confirm clinical studies suggesting oxytocin as a potential treatment for alcoholism. PMID:26519603

  15. Polyethylene glycol reduces inflammation and aberrant crypt foci in carcinogen-initiated rats.

    PubMed

    Karlsson, Pernilla C; Hughes, Roisin; Rafter, Joseph J; Bruce, W Robert

    2005-06-01

    Polyethylene glycol 8000 inhibits the formation of tumors and of aberrant crypt foci (ACF) in carcinogen-initiated rats. We asked: is the inhibition associated with a reduction of colonic inflammation and an increase in colonic cell permeability? Twenty-eight, male F 344 rats were divided into two groups, 10 control animals and 18 animals initiated with azoxymethane. Nine of the rats in the carcinogen-initiated group were given a diet with 5% PEG 8000 in an AIN-93 based, high fat diet. The other nine, and the control group received the diet without the addition of PEG. Nine weeks later, the rats receiving the diet containing PEG had a 43% reduction in ACF (P<0.001) compared with the carcinogen-initiated rats on the control diet, a result confirming earlier observations that PEG inhibits colon carcinogenesis. The animals receiving the diet containing PEG also had a 10-fold reduction in fecal granulocyte marker protein (GMP) (P<0.001) compared with both the carcinogen-treated and the control animals. PEG reduced inflammation below the levels of carcinogen-treated and of untreated animals. Fecal water from the rats receiving PEG did not reduce transepithelial resistance of, or manitol flux through, human Caco-cells grown as monolayers in vitro. PEG may reduce colon carcinogenesis through a mechanism involving colonic inflammation. PMID:15896454

  16. Functional anatomy of the cheetah (Acinonyx jubatus) forelimb.

    PubMed

    Hudson, Penny E; Corr, Sandra A; Payne-Davis, Rachel C; Clancy, Sinead N; Lane, Emily; Wilson, Alan M

    2011-04-01

    Despite the cheetah being the fastest living land mammal, we know remarkably little about how it attains such high top speeds (29 m s(-1)). Here we aim to describe and quantify the musculoskeletal anatomy of the cheetah forelimb and compare it to the racing greyhound, an animal of similar mass, but which can only attain a top speed of 17 m s(-1). Measurements were made of muscle mass, fascicle length and moment arms, enabling calculations of muscle volume, physiological cross-sectional area (PCSA), and estimates of joint torques and rotational velocities. Bone lengths, masses and mid-shaft cross-sectional areas were also measured. Several species differences were observed and have been discussed, such as the long fibred serratus ventralis muscle in the cheetah, which we theorise may translate the scapula along the rib cage (as has been observed in domestic cats), thereby increasing the cheetah's effective limb length. The cheetah's proximal limb contained many large PCSA muscles with long moment arms, suggesting that this limb is resisting large ground reaction force joint torques and therefore is not functioning as a simple strut. Its structure may also reflect a need for control and stabilisation during the high-speed manoeuvring in hunting. The large digital flexors and extensors observed in the cheetah forelimb may be used to dig the digits into the ground, aiding with traction when galloping and manoeuvring. PMID:21332715

  17. Comparative myology of the forelimb of squirrels (Sciuridae).

    PubMed

    Thorington, R W; Darrow, K; Betts, A D

    1997-11-01

    The musculature of the shoulder, arm, and forearm was studied in 19 genera of squirrels, representing the Pteromyinae (flying squirrels) and all 7 tribes of the Sciurinae (tree and ground squirrels). The objective was to locate derived anatomical features of functional or phylogenetic significance and to determine how much morphological variation underlies the diverse locomotor behavior of squirrels, which includes terrestrial and arboreal bounding, climbing, digging, and gliding. The fossil evidence suggests that arboreality is primitive for squirrels, and in fact tree squirrels appear to represent the primitive sciurid morphology. Ground squirrels are less uniform and exhibit a few derived features, including a clavobrachialis muscle not seen in other squirrels. Pygmy tree squirrels, which have evolved independently in three tribes, exhibit convergence of forelimb anatomy, including the loss or reduction of several muscles in the shoulder and forearm. The forelimb anatomy of flying squirrels is the most derived and differs from that of tree squirrels in details of shoulder, arm, and forearm musculature. Some of these muscular differences among squirrels have phylogenetic significance, being shared by closely related genera, but none has significance above the tribal level. Many of the differences suggest a variety of changes in function that are amenable to further study. PMID:9360319

  18. Computer Simulations Imply Forelimb-Dominated Underwater Flight in Plesiosaurs.

    PubMed

    Liu, Shiqiu; Smith, Adam S; Gu, Yuting; Tan, Jie; Liu, C Karen; Turk, Greg

    2015-12-01

    Plesiosaurians are an extinct group of highly derived Mesozoic marine reptiles with a global distribution that spans 135 million years from the Early Jurassic to the Late Cretaceous. During their long evolutionary history they maintained a unique body plan with two pairs of large wing-like flippers, but their locomotion has been a topic of debate for almost 200 years. Key areas of controversy have concerned the most efficient biologically possible limb stroke, e.g. whether it consisted of rowing, underwater flight, or modified underwater flight, and how the four limbs moved in relation to each other: did they move in or out of phase? Previous studies have investigated plesiosaur swimming using a variety of methods, including skeletal analysis, human swimmers, and robotics. We adopt a novel approach using a digital, three-dimensional, articulated, free-swimming plesiosaur in a simulated fluid. We generated a large number of simulations under various joint degrees of freedom to investigate how the locomotory repertoire changes under different parameters. Within the biologically possible range of limb motion, the simulated plesiosaur swims primarily with its forelimbs using an unmodified underwater flight stroke, essentially the same as turtles and penguins. In contrast, the hindlimbs provide relatively weak thrust in all simulations. We conclude that plesiosaurs were forelimb-dominated swimmers that used their hind limbs mainly for maneuverability and stability. PMID:26683221

  19. Computer Simulations Imply Forelimb-Dominated Underwater Flight in Plesiosaurs

    PubMed Central

    Liu, Shiqiu; Smith, Adam S.; Gu, Yuting; Tan, Jie; Liu, C. Karen; Turk, Greg

    2015-01-01

    Plesiosaurians are an extinct group of highly derived Mesozoic marine reptiles with a global distribution that spans 135 million years from the Early Jurassic to the Late Cretaceous. During their long evolutionary history they maintained a unique body plan with two pairs of large wing-like flippers, but their locomotion has been a topic of debate for almost 200 years. Key areas of controversy have concerned the most efficient biologically possible limb stroke, e.g. whether it consisted of rowing, underwater flight, or modified underwater flight, and how the four limbs moved in relation to each other: did they move in or out of phase? Previous studies have investigated plesiosaur swimming using a variety of methods, including skeletal analysis, human swimmers, and robotics. We adopt a novel approach using a digital, three-dimensional, articulated, free-swimming plesiosaur in a simulated fluid. We generated a large number of simulations under various joint degrees of freedom to investigate how the locomotory repertoire changes under different parameters. Within the biologically possible range of limb motion, the simulated plesiosaur swims primarily with its forelimbs using an unmodified underwater flight stroke, essentially the same as turtles and penguins. In contrast, the hindlimbs provide relatively weak thrust in all simulations. We conclude that plesiosaurs were forelimb-dominated swimmers that used their hind limbs mainly for maneuverability and stability. PMID:26683221

  20. A Three-Dimensional Analysis of Morphological Evolution and Locomotor Performance of the Carnivoran Forelimb

    PubMed Central

    Martín-Serra, Alberto; Figueirido, Borja; Palmqvist, Paul

    2014-01-01

    In this study, three-dimensional landmark-based methods of geometric morphometrics are used for estimating the influence of phylogeny, allometry and locomotor performance on forelimb shape in living and extinct carnivorans (Mammalia, Carnivora). The main objective is to investigate morphological convergences towards similar locomotor strategies in the shape of the major forelimb bones. Results indicate that both size and phylogeny have strong effects on the anatomy of all forelimb bones. In contrast, bone shape does not correlate in the living taxa with maximum running speed or daily movement distance, two proxies closely related to locomotor performance. A phylomorphospace approach showed that shape variation in forelimb bones mainly relates to changes in bone robustness. This indicates the presence of biomechanical constraints resulting from opposite demands for energetic efficiency in locomotion –which would require a slender forelimb– and resistance to stress –which would be satisfied by a robust forelimb–. Thus, we interpret that the need of maintaining a trade-off between both functional demands would limit shape variability in forelimb bones. Given that different situations can lead to one or another morphological solution, depending on the specific ecology of taxa, the evolution of forelimb morphology represents a remarkable “one-to-many mapping” case between anatomy and ecology. PMID:24454891

  1. Forelimbs of "Tyrannosaurus Rex": A Pathetic Vestigial Organ or an Integral Part of a Fearsome Predator?

    ERIC Educational Resources Information Center

    Lee, Scott A.; Thomas, Joshua D.

    2014-01-01

    In this paper, we examine a first-year torque and angular acceleration problem to address a possible use of the forelimbs of "Tyrannosaurus rex." A 1/40th-scale model (see Fig. 1) is brought to the classroom to introduce the students to the quandary: given that the forelimbs of "T. rex" were too short to reach its mouth, what…

  2. Effects of Cerebellar Nuclear Inactivation on the Learning of a Complex Forelimb Movement in Cats

    E-print Network

    Bracha, Vlastislav

    Effects of Cerebellar Nuclear Inactivation on the Learning of a Complex Forelimb Movement in Cats forelimb movement in cats. J. Neurophysiol. Lisberger et al. 1984; Robinson 1976), and the adaptation 79 al. 1983). Changes in the activity of cerebel-and dentate nuclei on the capacity of cats to acquire

  3. Brief maternal deprivation of rats reduces hepatic mixed function oxidase activities

    SciTech Connect

    Vesell, E.S. ); Heubel, F.; Netter, K.J. )

    1989-01-01

    Deprivation of pups from mother and sibs for 3 min daily from day 5 today 41 of life reduced activities of 4 hepatic mixed function oxidases (MFO) expressed per mg protein in male rats compared to unhandled control rats. These decreases, though generally small, 22.4% and under, reached statistical significance for the substrates aminopyrine, benzphetamine and ethoxycoumarin. This handling procedure did not consistently affect the inductive response to phenobarbital. Previously ignored as a source of variability in response to xenobiotics, handling appears from these results to merit further investigation as such a factor in uninduced rats. Differences among rats in handling could contribute to large day-to-day variations in their metabolism of xenobiotics.

  4. Berberine Reduces Neurotoxicity Related to Nonalcoholic Steatohepatitis in Rats.

    PubMed

    Ghareeb, Doaa A; Khalil, Sofia; Hafez, Hani S; Bajorath, Jürgen; Ahmed, Hany E A; Sarhan, Eman; Elwakeel, Eiman; El-Demellawy, Maha A

    2015-01-01

    Berberine is a plant alkaloid that has several pharmacological effects such as antioxidant, antilipidemic, and anti-inflammatory effects. Nonalcoholic steatohepatitis (NASH) triggers different aspects of disorders such as impaired endogenous lipid metabolism, hypercholesterolemia, oxidative stress, and neurotoxicity. In this study, we examined the mechanism by which NASH induces neurotoxicity and the protective effect of berberine against both NASH and its associated neurotoxicity. NASH induced rats showed significant impairments in lipid metabolism with increased serum triglycerides, cholesterol, and low-density lipoprotein (LDL). The NASH induced group also demonstrated a significant oxidative stress which is characterized by increased TBARs level and decreased antioxidant capacity such as GSH and SOD levels. Moreover, the NASH induction was associated with inflammation which was demonstrated by increased TNF? and nitric oxide levels. Hyperglycemia and hyperinsulinemia were observed in the NASH induced group. Also, our results showed a significant increase in the expression of the acetylcholine esterase (AChE) and amyloid beta precursor protein (A?PP). These changes were significantly correlated with decreased insulin degrading enzyme (IDE) and beta-amyloid40 (A? 40) and increased beta-amyloid42 (A? 42) in the hippocampal region. Daily administration of berberine (50?mg/kg) for three weeks ameliorated oxidative stress, inflammation, hyperlipidemia, hyperglycemia, hyperinsulinemia, and the observed neurotoxicity. PMID:26576191

  5. Berberine Reduces Neurotoxicity Related to Nonalcoholic Steatohepatitis in Rats

    PubMed Central

    Ghareeb, Doaa A.; Khalil, Sofia; Hafez, Hani S.; Bajorath, Jürgen; Ahmed, Hany E. A.; Sarhan, Eman; Elwakeel, Eiman; El-Demellawy, Maha A.

    2015-01-01

    Berberine is a plant alkaloid that has several pharmacological effects such as antioxidant, antilipidemic, and anti-inflammatory effects. Nonalcoholic steatohepatitis (NASH) triggers different aspects of disorders such as impaired endogenous lipid metabolism, hypercholesterolemia, oxidative stress, and neurotoxicity. In this study, we examined the mechanism by which NASH induces neurotoxicity and the protective effect of berberine against both NASH and its associated neurotoxicity. NASH induced rats showed significant impairments in lipid metabolism with increased serum triglycerides, cholesterol, and low-density lipoprotein (LDL). The NASH induced group also demonstrated a significant oxidative stress which is characterized by increased TBARs level and decreased antioxidant capacity such as GSH and SOD levels. Moreover, the NASH induction was associated with inflammation which was demonstrated by increased TNF? and nitric oxide levels. Hyperglycemia and hyperinsulinemia were observed in the NASH induced group. Also, our results showed a significant increase in the expression of the acetylcholine esterase (AChE) and amyloid beta precursor protein (A?PP). These changes were significantly correlated with decreased insulin degrading enzyme (IDE) and beta-amyloid40 (A?40) and increased beta-amyloid42 (A?42) in the hippocampal region. Daily administration of berberine (50?mg/kg) for three weeks ameliorated oxidative stress, inflammation, hyperlipidemia, hyperglycemia, hyperinsulinemia, and the observed neurotoxicity. PMID:26576191

  6. Further evidence that a new type of Japanese pickles reduce the blood pressure of spontaneously hypertensive rats.

    PubMed

    Oda, Kohei; Nagai, Takeshi; Ueno, Yoshie; Mori, Yoshiharu

    2015-01-01

    A new type of pickles (nukazuke) that contain GABA and angiotensin converting enzyme-inhibitory peptides and that reduce blood pressure of rats was studied further. Seven kinds of nukazuke forcefully administrated orally for one day reduced temporarily the blood pressure of spontaneously hypertensive rats. In addition, a fermented shougoin daikon administrated freely for 4 weeks did not increase the blood pressure of the rats, but suppressed it throughout the experiment. Taken together with previous data (Oda et al., Biosci. Biotechnol. Biochem., 2014) it was concluded that the nukazuke could reduce the blood pressure of spontaneously hypertensive rats. Thus, the newly developed functional pickles appear to be beneficial for pickles business. PMID:25346224

  7. 2-Arachidonoylglycerol into the lateral hypothalamus improves reduced sleep in adult rats subjected to maternal separation.

    PubMed

    Pérez-Morales, Marcel; Fajardo-Valdez, Alfonso; Méndez-Díaz, Mónica; Ruiz-Contreras, Alejandra E; Prospéro-García, Oscar

    2014-12-17

    We have previously reported that maternal separation (MS) for 3 h daily during the first two postnatal weeks increases wakefulness, whereas it reduces sleep in rats. Oleamide, an agonist of the cannabinoid receptor type 1, increases sleep in MS rats to such a level that we cannot differentiate their sleep patterns from those of their non-MS (NMS) siblings. However, 2-arachidonoylglycerol (2-AG), an endocannabinoid, infused into the lateral hypothalamus of NMS rats at the beginning of the dark phase of the cycle increases rapid eye movement sleep and the expression of c-Fos on the rapid eye movement sleep promoting melanin-concentrating hormone neurons. We recorded the sleep-wake cycle of adult rats subjected to MS for 3 h daily from postnatal days 2 to 16, as well as in their NMS siblings. Besides the electrodes for recording the sleep-wake cycle, a couple of cannulae aimed bilaterally to the lateral hypothalamus were implanted to infuse 2-AG. We found that administration of 2-AG into the lateral hypothalamus of MS rats at the beginning of the light phase of the cycle restores sleep, whereas sleep and wakefulness of NMS rats under 2-AG infusion do not show any significant change. PMID:25356522

  8. Forelimb myology of the pygmy hippopotamus (Choeropsis liberiensis).

    PubMed

    Fisher, Rebecca E; Scott, Kathleen M; Naples, Virginia L

    2007-06-01

    Based on morphological analyses, hippos have traditionally been classified as Suiformes, along with pigs and peccaries. However, molecular data indicate hippos and cetaceans are sister taxa (see review in Uhen, 2007, this issue). This study analyzes soft tissue characters of the pygmy hippo forelimb to elucidate the functional anatomy and evolutionary relationships of hippos within Artiodactyla. Two specimens from the National Zoological Park in Washington, D.C. were dissected, revealing several adaptations to an aquatic lifestyle. However, these adaptations differ functionally from most aquatic mammals as hippos walk along river or lake bottoms, rather than swim. Several findings highlight a robust mechanism for propelling the trunk forward through the water. For example, mm. pectoralis superficialis and profundus demonstrate broad sites of origin, while the long flexor tendons serve each of the digits, reflecting the fact that all toes are weight-bearing. Pygmy hippos also have eight mm. interossei and a well-developed m. lumbricalis IV. Retention of intrinsic adductors functions to prevent splaying of the toes, an advantageous arrangement in an animal walking on muddy substrates. Published descriptions indicate common hippos share all of these features. Hippo and ruminant forelimbs share several traits; however, hippos are unique among artiodactyls in retaining several primitive muscles (e.g., mm. palmaris longus and flexor digitorum brevis). These findings are consistent with the hypothesis that hippos diverged from other Artiodactyla early in the history of this group. Additional analyses of hindlimb and axial muscles may help determine whether this trajectory was closely allied to that of Cetacea. PMID:17516432

  9. Cardiac ?-Adrenoceptor Expression Is Reduced in Zucker Diabetic Fatty Rats as Type-2 Diabetes Progresses

    PubMed Central

    Haley, James M.; Thackeray, James T.; Thorn, Stephanie L.; DaSilva, Jean N.

    2015-01-01

    Objectives Reduced cardiac ?-adrenoceptor (?-AR) expression and cardiovascular dysfunction occur in models of hyperglycemia and hypoinsulinemia. Cardiac ?-AR expression in type-2 diabetes models of hyperglycemia and hyperinsulinemia, remain less clear. This study investigates cardiac ?-AR expression in type-2 diabetic Zucker diabetic fatty (ZDF) rats. Methods Ex vivo biodistribution experiments with [3H]CGP12177 were performed in Zucker lean (ZL) and ZDF rats at 10 and 16 weeks of age as diabetes develops. Blood glucose, body mass, and diet consumption were measured. Western blotting of ?-AR subtypes was completed in parallel. Echocardiography was performed at 10 and 16 weeks to assess systolic and diastolic function. Fasted plasma insulin, free fatty acids (FFA), leptin and fed-state insulin were also measured. Results At 10 weeks, myocardial [3H]CGP12177 was normal in hyperglycemic ZDF (17±4.1mM) compared to ZL, but reduced 16-25% at 16 weeks of age as diabetes and hyperglycemia (22±2.4mM) progressed. Reduced ?-AR expression not apparent at 10 weeks also developed by 16 weeks of age in ZDF brown adipose tissue. In the heart, Western blotting at 10 weeks indicated normal ?1-AR (98±9%), reduced ?2-AR (76±10%), and elevated ?3-AR (108±6). At 16 weeks, ?1-AR expression became reduced (69±16%), ?2-AR expression decreased further (68±14%), and ?3-AR remained elevated, similar to 10 weeks (112±9%). While HR was reduced at 10 and 16 weeks in ZDF rats, no significant changes were observed in diastolic or systolic function. Conclusions Cardiac ?-AR are reduced over 6 weeks of sustained hyperglycemia in type-2 diabetic ZDF rats. This indicates cardiac [3H]CGP12177 retention and ?1- and ?2-AR expression are inversely correlated with the progression of type-2 diabetes. PMID:25996498

  10. Deferoxamine reduces intracerebral hemorrhage-induced white matter damage in aged rats

    PubMed Central

    Ni, Wei; Okauchi, Masanobu; Hatakeyama, Tetsuhiro; Gu, Yuxiang; Keep, Richard F.; Xi, Guohua; Hua, Ya

    2015-01-01

    Iron contributes to c-Jun N-terminal kinases (JNK) activation in young rats and white matter injury in piglets after intracerebral hemorrhage (ICH). In the present study, we examined the effect of deferoxamine on ICH-induced white matter injury and JNK activation and in aged rats. Male Fischer 344 rats (18 months old) had either an intracaudate injection of 100 µl of autologous blood or a needle insertion (sham). The rats were treated with deferoxamine or vehicle with different regimen (dosage, duration and time window). White matter injury and activation of JNK were examined. We found that a dose of DFX should at more than 10 mg/kg for a therapeutic duration more than 2 days with a therapeutic time window of 12 hours to reduce ICH-induced white matter loss at 2 months. ICH-induced white matter injury was associated with JNK activation. The protein levels of phosphorylated-JNK (P-JNK) were upregulated at day-1 after ICH and then gradually decreased. P-JNK immunoreactivity was mostly located in white matter bundles. ICH-induced JNK activation was reduced by DFX treatment. This study demonstrated that DFX can reduce ICH-induced JNK activation and white matter damage. PMID:25749188

  11. Efficacy of AdiDetox™ in reducing the toxicity of fumonisin B1 in rats.

    PubMed

    Denli, Muzaffer; Blandon, Juan C; Salado, Silvia; Guynot, Maria E; Casas, Josefina; Pérez, Jose F

    2015-04-01

    The objective of this study is to evaluate the efficacy of a new mycotoxin inactivator (AdiDetox™) in reducing the toxic effects of fumonisin B1 (FB1) in the diet of rats. Sixty-four male Sprague-Dawley growing rats (125?g?±?1?g BW) were assigned to eight dietary treatments for seven days. The experiment had a 2?×?4 factorial arrangement with two levels of FB1 (0?mg and 15?mg of FB1/kg feed) and four levels of AdiDetox™ (0?g, 1?g, 2?g and 5?g /kg feed) in the diet. No significant differences were observed in the growth performance among treatments (P?>?0.05), though low levels of sphingosine (So) and sphinganine (Sa) were detected in the liver. However, So and Sa and the Sa/So ratio in kidneys were higher in rats receiving the FB1 diets (P?reduced the toxic effects of FB1, leading to a significant decrease in the Sa content and in the Sa/So ratio in kidneys. In conclusion, the results suggest that AdiDetox™ can effectively reduce toxicity of FB1 in growing rats. PMID:25660482

  12. Exendin-4 reduces tau hyperphosphorylation in type 2 diabetic rats via increasing brain insulin level.

    PubMed

    Yang, Yan; Ma, Delin; Xu, Weijie; Chen, Fuqiong; Du, Tingting; Yue, Wenzhu; Shao, Shiying; Yuan, Gang

    2016-01-01

    Type 2 diabetes (T2D) is a high risk factor for Alzheimer's disease (AD). Our previous study identified that hyperphosphorylation of tau protein, which is one of the pathophysiologic hallmarks of AD, also occurred in T2D rats' brain; while glucagon-like peptide-1 (GLP-1) mimetics, a type of drug used in T2D, could decrease the phosphorylation of tau, probably via augmenting insulin signaling pathway. The purpose of this study was to further explore the mechanisms that underlie the effect of exendin-4 (ex-4, a GLP-1 receptor agonist) in reducing tau phosphorylation. We found that peripheral ex-4 injection in T2D rats reduced hyperphosphorylation of tau protein in rat hippocampus, probably via increasing hippocampal insulin which activated insulin signaling. Furthermore, we found that ex-4 could neither activate insulin signaling, nor reduce tau phosphorylation in HT22 neuronal cells in the absence of insulin. These results suggested that insulin is required in reduction of tau hyperphosphorylation by ex-4 in brain rats with T2D. PMID:26640240

  13. Reduced amount of olfactory receptor neurons in the rat model of depression.

    PubMed

    Li, Qianlu; Yang, Deyu; Wang, Juan; Liu, Li; Feng, Guibo; Li, Juan; Liao, Juan; Wei, Youdong; Li, Zhiwei

    2015-08-31

    Reduced olfactory sensitivity has been reported in depressive disorder. However, the pathological mechanism is still unclear. The reduced olfactory bulb (OB) volume and reduced hippocampal neurogenesis has been unraveled in major depressive disorder (MDD). However, changes in olfactory epithelium (OE) have not been reported, which might contribute to olfactory deficits in MDD. In the context, we investigated the thickness of OE in a chronic unpredictable mild stress (CUMS) rat model of depression using hematoxylin and eosin (HE) staining. Simultaneously, the basal cells (labeled by nerve growth factor receptor (p75NGFR)), immature olfactory receptor neurons (ORNs) (marked by growth-associated protein 43 (GAP43)) and mature ORNs (labeled by olfactory marker protein (OMP)) in OE were detected by immunohistochemistry. The results showed that the thickness of OE, the number of basal cells, immature ORNs as well as mature ORNs decreased dramatically in the OE of CUMS rats. Those findings indicate that the reduced number of ORNs might induce OE atrophy in CUMS rats and the abnormalities of the OE may be partially responsible for the reduced olfactory sensitivity in MDD. PMID:26170245

  14. Amelioration of azoxymethane induced-carcinogenesis by reducing oxidative stress in rat colon by natural extracts

    PubMed Central

    2014-01-01

    Background Azoxymethane (AOM) is a potent carcinogenic agent commonly used to induce colon cancer in rats; the cytotoxicity of AOM is considered to mediate oxidative stress. This study investigated the chemopreventive effect of three natural extracts [pomegranate peel extract (PomPE), papaya peel extract (PapPE) and seaweed extract (SE)] against AOM-induced oxidative stress and carcinogenesis in rat colon. Methods Eighty Sprague–Dawley rats (aged 4 weeks) were randomly divided into 8 groups (10 rats/group). Control group was fed a basal diet; AOM-treated group was fed a basal diet and received AOM intraperitonial injections for two weeks at a dose of 15 mg/kg bodyweight, whereas the other six groups were received oral supplementation of PomPE, PapPE or SE, in the presence or absence of AOM injection. All animals were continuously fed ad-libitum until aged 16 weeks, then all rats were sacrificed and the colon tissues were examined microscopically for pathological changes and aberrant crypt foci (ACF) development, genotoxicity (induced micronuclei (MN) cells enumeration), and glutathione and lipid peroxidation. Results Our results showed that AOM-induced ACF development and pathological changes in the colonic mucosal tissues, increased bone marrow MN cells and oxidative stress (glutathione depletion, lipid peroxidation) in rat colonic cells. The concomitant treatment of AOM with PomPE, PapPE or SE significantly ameliorated the cytotoxic effects of AOM. Conclusions The results of this study provide in-vivo evidence that PomPE, PapPE and SE reduced the AOM-induced colon cancer in rats, through their potent anti-oxidant activities. PMID:24533833

  15. Green Tea Polyphenols Reduce Body Weight in Rats by Modulating Obesity-Related Genes

    PubMed Central

    Lu, Chuanwen; Zhu, Wenbin; Shen, Chwan-Li; Gao, Weimin

    2012-01-01

    Beneficial effects of green tea polyphenols (GTP) against obesity have been reported, however, the mechanism of this protection is not clear. Therefore, the objective of this study was to identify GTP-targeted genes in obesity using the high-fat-diet-induced obese rat model. A total of three groups (n?=?12/group) of Sprague Dawley (SD) female rats were tested, including the control group (rats fed with low-fat diet), the HF group (rats fed with high-fat diet), and the HF+GTP group (rats fed with high-fat diet and GTP in drinking water). The HF group increased body weight as compared to the control group. Supplementation of GTP in the drinking water in the HF+GTP group reduced body weight as compared to the HF group. RNA from liver samples was extracted for gene expression analysis. A total of eighty-four genes related to obesity were analyzed using PCR array. Compared to the rats in the control group, the rats in the HF group had the expression levels of 12 genes with significant changes, including 3 orexigenic genes (Agrp, Ghrl, and Nr3c1); 7 anorectic genes (Apoa4, Cntf, Ghr, IL-1?, Ins1, Lepr, and Sort); and 2 genes that relate to energy expenditure (Adcyap1r1 and Adrb1). Intriguingly, the HF+GTP group restored the expression levels of these genes in the high-fat-induced obese rats. The protein expression levels of IL-1? and IL-6 in the serum samples from the control, HF, and HF+GTP groups confirmed the results of gene expression. Furthermore, the protein expression levels of superoxide dismutase-1 (SOD1) and catechol-O-methyltransferase (COMT) also showed GTP-regulated protective changes in this obese rat model. Collectively, this study revealed the beneficial effects of GTP on body weight via regulating obesity-related genes, anti-inflammation, anti-oxidant capacity, and estrogen-related actions in high-fat-induced obese rats. PMID:22715380

  16. Intermittent hypoxia in rats reduces activation of Ca2+ sparks in mesenteric arteries.

    PubMed

    Jackson-Weaver, Olan; Osmond, Jessica M; Naik, Jay S; Gonzalez Bosc, Laura V; Walker, Benjimen R; Kanagy, Nancy L

    2015-12-01

    Ca(+) sparks are vascular smooth muscle cell (VSMC) Ca(2+)-release events that are mediated by ryanodine receptors (RyR) and promote vasodilation by activating large-conductance Ca(2+)-activated potassium channels and inhibiting myogenic tone. We have previously reported that exposing rats to intermittent hypoxia (IH) to simulate sleep apnea augments myogenic tone in mesenteric arteries through loss of hydrogen sulfide (H2S)-induced dilation. Because we also observed that H2S can increase Ca(2+) spark activity, we hypothesized that loss of H2S after IH exposure reduces Ca(2+) spark activity and that blocking Ca(2+) spark generation reduces H2S-induced dilation. Ca(2+) spark activity was lower in VSMC of arteries from IH compared with sham-exposed rats. Furthermore, depolarizing VSMC by increasing luminal pressure (from 20 to 100 mmHg) or by elevating extracellular [K(+)] increased spark activity in VSMC of arteries from sham rats but had no effect in arteries from IH rats. Inhibiting endogenous H2S production in sham arteries prevented these increases. NaHS or phosphodiesterase inhibition increased spark activity to the same extent in sham and IH arteries. Depolarization-induced increases in Ca(2+) spark activity were due to increased sparks per site, whereas H2S increases in spark activity were due to increased spark sites per cell. Finally, inhibiting Ca(2+) spark activity with ryanodine (10 ?M) enhanced myogenic tone in arteries from sham but not IH rats and blocked dilation to exogenous H2S in arteries from both sham and IH rats. Our results suggest that H2S regulates RyR activation and that H2S-induced dilation requires Ca(2+) spark activation. IH exposure decreases endogenous H2S-dependent Ca(2+) spark activation to cause membrane depolarization and enhance myogenic tone in mesenteric arteries. PMID:26408536

  17. Memantine reduces alcohol drinking but not relapse in alcohol-dependent rats.

    PubMed

    Alaux-Cantin, Stéphanie; Buttolo, Romain; Houchi, Hakim; Jeanblanc, Jérôme; Naassila, Mickaël

    2015-09-01

    Alcoholism is a chronic relapsing disorder with consequences on health and that requires more effective treatments. Among alternative therapies, the therapeutic potential of the non-competitive N-methyl-D-aspartate receptor antagonist memantine has been suggested. Despite promising results, its efficiency in the treatment of alcoholism remains controversial. Currently, there is no pre-clinical data regarding its effects on the motivation for ethanol in post-dependent (PD) animals exposed to intermittent ethanol vapor, a validated model of alcoholism. Thus, the objectives of this study were to evaluate the effects of acute injections of memantine (0, 12.5, 25 and 50?mg/kg) on operant ethanol self-administration in non-dependent (ND) and PD rats tested either during acute withdrawal or relapse after protracted abstinence. Our results showed that memantine (25?mg/kg) abolished ethanol self-administration in ND rats and reduced by half the one of PD rats during acute withdrawal. While this effect was observed only 6?hours after treatment in ND rats, it was long lasting in PD rats (at least 30?hours after injection). Furthermore, our results indicated that memantine did not modify the breaking point for ethanol. This suggests that memantine probably act by potentiating the pharmacological effect of ethanol but not by reducing motivation for ethanol. Finally, memantine was also ineffective in reducing relapse after protracted abstinence. Altogether, our pre-clinical results highlighted a potential therapeutic use of memantine that may be used as a replacement therapy drug but not as relapse-preventing drug. PMID:25138717

  18. Acute splenic irradiation reduces brain injury in the rat focal ischemic stroke model.

    PubMed

    Ostrowski, Robert P; Schulte, Reinhard W; Nie, Ying; Ling, Ted; Lee, Timothy; Manaenko, Anatol; Gridley, Daila S; Zhang, John H

    2012-12-01

    Removing the spleen prior to ischemic stroke abrogates immunologic response to brain injury and reduces cerebral infarction. However, the effectiveness of splenectomy for neuroprotection after stroke has not been established. Moreover, the risks of the surgical splenectomy in stroke patients create a major obstacle to removing the spleen's inflammatory response. We hypothesized that acute splenic irradiation will ablate splenic cells and thereby will diminish stroke progression. Male adult Sprague Dawley rats were subjected to 2-hour middle cerebral artery occlusion (MCAO), then CT scanned for spleen localization and irradiated to the lateral splenic region with 8Gy of Cobalt 60 at 3, 4, 6 or 8 hrs after start of cerebral ischemia. Untreated controls underwent the same procedures except that sham irradiation was applied. At 2 or 7 days after ischemia the rats were euthanized, and brains recovered for the assessment of brain injury and the extent of neuroinflammation. Irradiation at 3 hrs reduced spleen weight and lymphocyte blood levels after stroke. Splenic irradiation at 3 and 4 hrs after start of ischemia significantly reduced cerebral infarction volumes measured at 48 hrs and 7 days, respectively. The histological analysis on day 7 revealed reduced counts of microglia, infiltrating T cells, and apoptotic neurons in the rats irradiated at 4 hrs. The noninvasive single-dose procedure of splenic irradiation performed within a time interval of up to 4 hours offers neuroprotection against ischemic stroke possibly by abrogating deployment of splenic cells to the brain. PMID:23956805

  19. Combined Effects of Vincristine and Quercetin in Reducing Isoproterenol-Induced Cardiac Necrosis in Rats.

    PubMed

    Panda, Sunanda; Kar, Anand

    2015-10-01

    Combined effects of vincristine and quercetin in the regulation of isoproterenol (ISO)-induced cardiac necrosis have been evaluated in rats. ISO administration (100 mg/kg, s.c., for two consecutive days) increased the levels of serum creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), glutamate pyruvate transaminase (SGPT) and cardiac troponin (cTnT) as well as cardiac lipid peroxidation products (malondialdehyde and lipid hydroperoxides). However, it reduced the activities of superoxide dismutase (SOD), catalase and the glutathione peroxidase and the level of reduced glutathione. It also increased the heart rate and ST-segment elevation in ECG. Pretreatment of vincristine (25 ?g/kg) or quercetin (10 mg/kg) alone for 2 weeks ameliorated these cardiotoxic effects partially. However, treatment of both vincristine and quercetin for a similar period reduced the serum CK-MB, LDH, SGPT and cTnT levels near to normal levels in ISO-treated rats. Concomitantly, the test drugs improved the status of antioxidants and decreased the cardiac lipid peroxidation products. Combined treatment of both the drugs also restored the pathological electrocardiographic patterns and reduced the area of myocardial necrosis. Histopathology of heart in ISO-administered rats that received both vincristine and quercetin showed nearly normal myocardium with very little inflammatory infiltration. In conclusion, the present finding appears to be the first one, suggesting a better protection of cardiac tissues by combined treatment of vincristine and quercetin in isoproterenol-induced cardiac toxicity. PMID:25537132

  20. 5?-Reduced neurosteroids sex-dependently reverse central prenatal programming of neuroendocrine stress responses in rats.

    PubMed

    Brunton, Paula J; Donadio, Marcio V; Yao, Song T; Greenwood, Mike; Seckl, Jonathan R; Murphy, David; Russell, John A

    2015-01-14

    Maternal social stress during late pregnancy programs hypothalamo-pituitary-adrenal (HPA) axis hyper-responsiveness to stressors, such that adult prenatally stressed (PNS) offspring display exaggerated HPA axis responses to a physical stressor (systemic interleukin-1?; IL-1?) in adulthood, compared with controls. IL-1? acts via a noradrenergic relay from the nucleus tractus solitarii (NTS) to corticotropin releasing hormone neurons in the paraventricular nucleus (PVN). Neurosteroids can reduce HPA axis responses, so allopregnanolone and 3?-androstanediol (3?-diol; 5?-reduced metabolites of progesterone and testosterone, respectively) were given subacutely (over 24 h) to PNS rats to seek reversal of the "programmed" hyper-responsive HPA phenotype. Allopregnanolone attenuated ACTH responses to IL-1? (500 ng/kg, i.v.) in PNS females, but not in PNS males. However, 3?-diol normalized HPA axis responses to IL-1? in PNS males. Impaired testosterone and progesterone metabolism or increased secretion in PNS rats was indicated by greater plasma testosterone and progesterone concentrations in male and female PNS rats, respectively. Deficits in central neurosteroid production were indicated by reduced 5?-reductase mRNA levels in both male and female PNS offspring in the NTS, and in the PVN in males. In PNS females, adenovirus-mediated gene transfer was used to upregulate expression of 5?-reductase and 3?-hydroxysteroid dehydrogenase mRNAs in the NTS, and this normalized hyperactive HPA axis responses to IL-1?. Thus, downregulation of neurosteroid production in the brain may underlie HPA axis hyper-responsiveness in prenatally programmed offspring, and administration of 5?-reduced steroids acutely to PNS rats overrides programming of hyperactive HPA axis responses to immune challenge in a sex-dependent manner. PMID:25589761

  1. Forelimbs of Tyrannosaurus Rex: A pathetic vestigial organ or an integral part of a fearsome predator?

    NASA Astrophysics Data System (ADS)

    Lee, Scott A.; Thomas, Joshua D.

    2014-12-01

    In this paper, we examine a first-year torque and angular acceleration problem to address a possible use of the forelimbs of Tyrannosaurus rex. A 1/40th-scale model (see Fig. 1) is brought to the classroom to introduce the students to the quandary: given that the forelimbs of T. rex were too short to reach its mouth, what function did the forelimbs serve? This issue crosses several scientific disciplines including paleontology, ecology, and physics, making it a great starting point for thinking "outside the box." Noted paleontologist Kenneth Carpenter has suggested that the forelimbs of T. rex were an integral part of its predatory behavior. Given the large teeth of T. rex, it is assumed that they killed with their teeth. Lipkin and Carpenter1 have suggested that the forelimbs were used to hold a struggling victim (which had not been dispatched with the first bite) while the final, lethal bite was applied. If that is the case, then the forelimbs must be capable of large angular accelerations ? in order to grab the animal attempting to escape. The concepts of the typical first-year physics course are sufficient to test this hypothesis by solving ? =? /I . Naturally, students love solving any problem related to Tyrannosaurus rex!

  2. BMSCs reduce rat granulosa cell apoptosis induced by cisplatin and perimenopause

    PubMed Central

    2013-01-01

    Background The objective of this study was to evaluate the effect of bone marrow mesenchymal stem cells (BMSCs) on the apoptosis of granulosa cells (GCs) in rats. BMSCs and GCs were isolated from rats. GCs were separated into one of the following three groups: an untreated control group (control), a cisplatin (5 mg/L) treatment group (cisplatin), and group co-cultured with BMSCs and treated with cisplatin (BMSC). GC apoptosis was analyzed by annexin V staining and real-time PCR analysis for apoptosis-related genes. The effect of BMSCs was also determined in 9 to 10 month-old perimenopausal rats that were separated into the following groups: saline control, BMSC transplantation (1–2?×?106 cells), and estrogen treatment (0.158 mg/kg/d) groups. A young group consisting of 3 to 4 month-old rats that were treated with saline was also evaluated as a control. After 1 and 3 months, GC apoptosis was evaluated by TUNEL analysis. Results Cisplatin increased GC apoptosis from 0.59% to 13.04% in the control and cisplatin treatment groups, respectively, which was significantly reduced upon co-culture with BMSCs to 4.84%. Cisplatin treatment increased p21 and bax and decreased c-myc mRNA expression, which was reversed upon co-culture with BMSCs. As compared to young rats, increased apoptosis was observed in the perimenopausal rats (P?

  3. Low-Anxiety Rat Phenotypes Can Be Further Reduced through Genetic Intervention

    PubMed Central

    Granzotto, Natalli; Ramos, André

    2013-01-01

    Background A previous study using an intercross between the inbred rat strains Lewis (LEW) and Spontaneously Hypertensive Rats (SHR) identified a locus on chromosome 4, named Anxrr16, influencing an experimental index of anxiety and showing a transgressive effect, with alleles from the LEW strain (more anxious) decreasing rather than increasing anxiety. Objective To confirm the location and isolate the effect of a rat genome region named Anxrr16 through a planned genomic recombination strategy, where the target locus in SHR rats was replaced with LEW genetic material. Methods A new congenic strain, named SHR.LEW-Anxrr16 (SLA16), was developed from a cross between LEW (donor) and SHR (receptor) rats and then evaluated in several anxiety-related tests. The activity and attention levels of the new strain were also evaluated, since hyperactivity was observed during its construction and because SHR is a model of attention deficit hyperactivity disorder. Results Significant effects of Anxrr16 were found for open field central locomotion, as well as for other indices of anxiety from the light/dark box, triple test and T-maze. In all cases, the low-anxiety levels of SHR rats were further reduced by the insertion of LEW alleles. Differences in locomotor activity were found only in unfamiliar (hence stressful) environments and no genetic effects were observed in indices of attention. Conclusion The SLA16 strain can help in the identification of the molecular pathways involved in experimental anxiety and it demonstrates how apparently extreme phenotypes sometimes hide major opposite-acting genes. PMID:24386249

  4. Prenatal lipopolysaccharide exposure increases depression-like behaviors and reduces hippocampal neurogenesis in adult rats.

    PubMed

    Lin, Yu-Lung; Wang, Sabrina

    2014-02-01

    Major depression is one of the most prevalent mental disorders in the population. In addition to genetic influences, disturbances in fetal nervous system development might be a contributing factor. Maternal infection during pregnancy may affect fetal brain development and consequently lead to neurological and mental disorders. Previously, we used low-dose lipopolysaccharide (LPS) exposure on embryonic day 10.5 to mimic mild maternal infection in rats and found that dopaminergic and serotonergic neurons were reduced in the offspring. The offspring also showed more anxiety-like behavior and an enhanced stress response. In the present study we used forced swim test and chronic mild stress challenge to assess depression-like behaviors in the affected offspring and examined their adult hippocampal neurogenesis and brain-derived neurotrophic factor (BDNF) concentration. Our results showed that prenatally LPS-exposed rats (LPS rats) displayed more depression-like behaviors and had reduced adult neurogenesis and BDNF. The behavioral abnormalities and reduction in adult neurogenesis could be reversed by chronic fluoxetine (FLX) treatment. This study demonstrates that during the critical time of embryonic development LPS exposure can produce long-term behavioral changes and reduction in adult neurogenesis. The findings of enhanced depression-like behaviors, reduced adult neurogenesis, and their responsiveness to chronic antidepressant treatment suggest that prenatal LPS exposure could serve as an animal model of depression. PMID:24177209

  5. Ancestry of motor innervation to pectoral fin and forelimb

    PubMed Central

    Ma, Leung-Hang; Gilland, Edwin; Bass, Andrew H.; Baker, Robert

    2010-01-01

    Motor innervation to the tetrapod forelimb and fish pectoral fin is assumed to share a conserved spinal cord origin, despite major structural and functional innovations of the appendage during the vertebrate water-to-land transition. In this paper, we present anatomical and embryological evidence showing that pectoral motoneurons also originate in the hindbrain among ray-finned fish. New and previous data for lobe-finned fish, a group that includes tetrapods, and more basal cartilaginous fish showed pectoral innervation that was consistent with a hindbrain-spinal origin of motoneurons. Together, these findings support a hindbrain–spinal phenotype as the ancestral vertebrate condition that originated as a postural adaptation for pectoral control of head orientation. A phylogenetic analysis indicated that Hox gene modules were shared in fish and tetrapod pectoral systems. We propose that evolutionary shifts in Hox gene expression along the body axis provided a transcriptional mechanism allowing eventual decoupling of pectoral motoneurons from the hindbrain much like their target appendage gained independence from the head. PMID:20975699

  6. Secondhand Smoke Exposure Reduced the Compensatory Effects of IGF-I Growth Signaling in the Aging Rat Hearts

    PubMed Central

    Wu, Jia-Ping; Hsieh, Dennis Jine-Yuan; Kuo, Wei-Wen; Han, Chien-Kuo; Pai, Peiying; Yeh, Yu-Lan; Lin, Chien-Chung; Padma, V. Vijaya; Day, Cecilia Hsuan; Huang, Chih-Yang

    2015-01-01

    Background: Secondhand smoke (SHS) exposure is associated with increased risk of cardiovascular disease. Aging is a physiological process that involves progressive impairment of normal heart functions due to increased vulnerability to damage. This study examines secondhand smoke exposure in aging rats to determine the age-related death-survival balance. Methods: Rats were placed into a SHS exposure chamber and exposed to smog. Old age male Sprague-Dawley rats were exposed to 10 cigarettes for 30 min, day and night, continuing for one week. After 4 weeks the rats underwent morphological and functional studies. Left ventricular sections were stained with hematoxylin-eosin for histopathological examination. TUNEL detected apoptosis cells and protein expression related death and survival pathway were analyzed using western blot. Results: Death receptor-dependent apoptosis upregulation pathways and the mitochondria apoptosis proteins were apparent in young SHS exposure and old age rats. These biological markers were enhanced in aging SHS-exposed rats. The survival pathway was found to exhibit compensation only in young SHS-exposed rats, but not in the aging rats. Further decrease in the activity of this pathway was observed in aging SHS-exposed rats. TUNEL apoptotic positive cells were increased in young SHS-exposed rats, and in aging rats with or without SHS-exposure. Conclusions: Aging reduces IGF-I compensated signaling with accelerated cardiac apoptotic effects from second-hand smoke. PMID:26392808

  7. A Cervical Hemi-Contusion Spinal Cord Injury Model for the Investigation of Novel Therapeutics Targeting Proximal and Distal Forelimb Functional Recovery.

    PubMed

    Mondello, Sarah E; Sunshine, Michael D; Fischedick, Amanda E; Moritz, Chet T; Horner, Philip J

    2015-12-15

    Cervical spinal cord contusion is the most common human spinal cord injury, yet few rodent models replicate the pathophysiological and functional sequela of this injury. Here, we modified an electromechanical injury device and characterized the behavioral and histological changes occurring in response to a lateralized C4 contusion injury in rats. A key feature of the model includes a non-injurious touch phase where the spinal cord surface is dimpled with a consistent starting force. Animals were either left intact as a control, received a non-injury-producing touch on the surface of the cord ("sham"), or received a 0.6?mm or a 0.8?mm displacement injury. Rats were then tested on the forelimb asymmetry use test, CatWalk, and the Irvine, Beatties, and Bresnahan (IBB) cereal manipulation task to assess proximal and distal upper limb function for 12 weeks. Injuries of moderate (0.6?mm) and large (0.8?mm) displacement showed consistent differences in forelimb asymmetry, metrics of the CatWalk, and sub-scores of the IBB. Overall findings indicated long lasting proximal and distal upper limb deficits following 0.8?mm injury but transient proximal with prolonged distal limb deficits following 0.6?mm injury. Significant differences in loss of ipsilateral unmyelinated and myelinated white matter was detected between injury severities. Demyelination was primarily localized to the dorsolateral region of the hemicord and extended further rostral following 0.8?mm injury. These findings establish the C4 hemi-contusion injury as a consistent, graded model for testing novel treatments targeting forelimb functional recovery. PMID:25929319

  8. Palmitoylethanolamide treatment reduces retinal inflammation in streptozotocin-induced diabetic rats.

    PubMed

    Paterniti, Irene; Di Paola, Rosanna; Campolo, Michela; Siracusa, Rosalba; Cordaro, Marika; Bruschetta, Giuseppe; Tremolada, Gemma; Maestroni, Anna; Bandello, Francesco; Esposito, Emanuela; Zerbini, Gianpaolo; Cuzzocrea, Salvatore

    2015-12-15

    Although the pathogenesis of diabetic retinopathy (DR) is still insufficiently understood, new evidences indicate 'retinal inflammation' as an important player in the pathogenesis of the complication. Accordingly, common sets of upregulated inflammatory cytokines are found in serum, vitreous and aqueous samples obtained from subjects with DR, and these cytokines can have multiple interactions to impact the pathogenesis of the disease. Thus, based on previously published data, we investigated the effects of Palmitoylethanolamide (PEA), an endogenous lipid amide that belongs to the N-acyl-ethanolamines family, on DR in streptozotocin (STZ)-induced diabetic rats. PEA (10mg/kg) was administered orally daily starting 3 days after the iv administration of STZ. The rats were killed 15 and 60day later and eyes were enucleated to evaluate, through immunohistochemical analysis, the key inflammatory events involved in the breakdown of blood retinal barrier (BRB). Immunohistochemical analysis confirmed the presence of VEGF, ICAM-1, nitrotyrosine (a marker of peroxynitrite), and tight junctions in the retina of STZ-treated rats. Of interest, the extent of injury was significantly reduced after treatment with PEA. Altogether, this study provides the first evidence that PEA attenuates the degree of inflammation while preserving the blood-retinal barrier in rats with experimental DR. PMID:26607470

  9. Vardenafil reduces testicular damage following ischemia/reperfusion injury in rats.

    PubMed

    Erol, Bulent; Tokgoz, Husnu; Hanci, Volkan; Bektas, Sibel; Akduman, Bulent; Yencilek, Faruk; Mungan, Gorkem; Mungan, Aydin

    2009-07-01

    We investigated the effect of intraperitoneal vardenafil (1 mg/kg) administration during an ischemic period in a rat model of testicular torsion/detorsion (T/D). Twenty-one adult Wistar rats were equally randomized into a control group, a T/D group and a vardenafil group. The control group was designed to collect basal values for biochemical and histopathological parameters. The T/D group underwent testicular torsion for 1 hour. The vardenafil group received vardenafil (1 mg/kg) intraperitoneally at 30 minutes after torsion. All rats were sacrificed 4 hours after reperfusion to evaluate the tissue levels of malondialdehyde and total antioxidant status. Germ cell apoptosis was evaluated using the apoptosis protease activating factor 1 antibody in all groups. The expressions of endothelial nitric oxide synthase (NOS) and inducible NOS were also assessed in both testes of all rats. The malondialdehyde levels in the T/D group were significantly higher than in the control and vardenafil groups. There were also significant decreases in total antioxidant status in the T/D group compared with the control and vardenafil groups. Vardenafil treatment significantly reduced apoptosis protease activating factor 1, endothelial NOS and inducible NOS levels in the vardenafil group compared with the T/D group. Administration of 1 mg/kg vardenafil during testicular torsion decreased ischemia/reperfusion cellular damage. Our results indicate that the reduction in oxidative stress by vardenafil may play a major role in its cytoprotective effects. PMID:19605329

  10. A Novel Hemp Seed Meal Protein Hydrolysate Reduces Oxidative Stress Factors in Spontaneously Hypertensive Rats

    PubMed Central

    Girgih, Abraham T.; Alashi, Adeola M.; He, Rong; Malomo, Sunday A.; Raj, Pema; Netticadan, Thomas; Aluko, Rotimi E.

    2014-01-01

    This report shows the antioxidant effects of a hemp seed meal protein hydrolysate (HMH) in spontaneously hypertensive rats (SHR). Defatted hemp seed meal was hydrolyzed consecutively with pepsin and pancreatin to yield HMH, which was incorporated into rat feed as a source of antioxidant peptides. Young (8-week old) SHRs were divided into three groups (8 rats/group) and fed diets that contained 0.0%, 0.5% or 1.0% (w/w) HMH for eight weeks; half of the rats were sacrificed for blood collection. After a 4-week washout period, the remaining 20-week old SHRs were fed for an additional four weeks and sacrificed for blood collection. Plasma total antioxidant capacity (TAC) and superoxide dismutase (SOD), catalase (CAT) and total peroxides (TPx) levels were determined. Results showed that plasma TAC, CAT and SOD levels decreased in the older 20-week old SHRs when compared to the young SHRs. The presence of HMH in the diets led to significant (p < 0.05) increases in plasma SOD and CAT levels in both young and adult SHR groups; these increases were accompanied by decreases in TPx levels. The results suggest that HMH contained antioxidant peptides that reduced the rate of lipid peroxidation in SHRs with enhanced antioxidant enzyme levels and total antioxidant capacity. PMID:25493943

  11. A Magnesium Based Phosphate Binder Reduces Vascular Calcification without Affecting Bone in Chronic Renal Failure Rats

    PubMed Central

    Neven, Ellen; De Schutter, Tineke M.; Dams, Geert; Gundlach, Kristina; Steppan, Sonja; Büchel, Janine; Passlick-Deetjen, Jutta; D'Haese, Patrick C.; Behets, Geert J.

    2014-01-01

    The alternative phosphate binder calcium acetate/magnesium carbonate (CaMg) effectively reduces hyperphosphatemia, the most important inducer of vascular calcification, in chronic renal failure (CRF). In this study, the effect of low dose CaMg on vascular calcification and possible effects of CaMg on bone turnover, a persistent clinical controversy, were evaluated in chronic renal failure rats. Adenine-induced CRF rats were treated daily with 185 mg/kg CaMg or vehicle for 5 weeks. The aortic calcium content and area% calcification were measured to evaluate the effect of CaMg. To study the effect of CaMg on bone remodeling, rats underwent 5/6th nephrectomy combined with either a normal phosphorus diet or a high phosphorus diet to differentiate between possible bone effects resulting from either CaMg-induced phosphate deficiency or a direct effect of Mg. Vehicle or CaMg was administered at doses of 185 and 375 mg/kg/day for 8 weeks. Bone histomorphometry was performed. Aortic calcium content was significantly reduced by 185 mg/kg/day CaMg. CaMg ameliorated features of hyperparathyroid bone disease. In CRF rats on a normal phosphorus diet, the highest CaMg dose caused an increase in osteoid area due to phosphate depletion. The high phosphorus diet combined with the highest CaMg dose prevented the phosphate depletion and thus the rise in osteoid area. CaMg had no effect on osteoblast/osteoclast or dynamic bone parameters, and did not alter bone Mg levels. CaMg at doses that reduce vascular calcification did not show any harmful effect on bone turnover. PMID:25229549

  12. A magnesium based phosphate binder reduces vascular calcification without affecting bone in chronic renal failure rats.

    PubMed

    Neven, Ellen; De Schutter, Tineke M; Dams, Geert; Gundlach, Kristina; Steppan, Sonja; Büchel, Janine; Passlick-Deetjen, Jutta; D'Haese, Patrick C; Behets, Geert J

    2014-01-01

    The alternative phosphate binder calcium acetate/magnesium carbonate (CaMg) effectively reduces hyperphosphatemia, the most important inducer of vascular calcification, in chronic renal failure (CRF). In this study, the effect of low dose CaMg on vascular calcification and possible effects of CaMg on bone turnover, a persistent clinical controversy, were evaluated in chronic renal failure rats. Adenine-induced CRF rats were treated daily with 185 mg/kg CaMg or vehicle for 5 weeks. The aortic calcium content and area% calcification were measured to evaluate the effect of CaMg. To study the effect of CaMg on bone remodeling, rats underwent 5/6th nephrectomy combined with either a normal phosphorus diet or a high phosphorus diet to differentiate between possible bone effects resulting from either CaMg-induced phosphate deficiency or a direct effect of Mg. Vehicle or CaMg was administered at doses of 185 and 375 mg/kg/day for 8 weeks. Bone histomorphometry was performed. Aortic calcium content was significantly reduced by 185 mg/kg/day CaMg. CaMg ameliorated features of hyperparathyroid bone disease. In CRF rats on a normal phosphorus diet, the highest CaMg dose caused an increase in osteoid area due to phosphate depletion. The high phosphorus diet combined with the highest CaMg dose prevented the phosphate depletion and thus the rise in osteoid area. CaMg had no effect on osteoblast/osteoclast or dynamic bone parameters, and did not alter bone Mg levels. CaMg at doses that reduce vascular calcification did not show any harmful effect on bone turnover. PMID:25229549

  13. Losartan reduces oxidative damage to renal DNA and conserves plasma antioxidant capacity in diabetic rats.

    PubMed

    Lodovici, Maura; Bigagli, Elisabetta; Tarantini, Francesca; Di Serio, Claudia; Raimondi, Laura

    2015-11-01

    Increased reactive oxygen species (ROS) levels produced by hyperglycemia and angiotensin-II (AT-II) are considered among the pathogenic factors in the malignant transformation of diabetic renal cells. We aimed to investigate the potential role of AT-II in the increased cancer risk seen in diabetes; measuring oxidative damage to renal DNA and protective antioxidant defenses, including adiponectin (Adp) and plasma antioxidant capacity by the Ferric Reducing Ability of Plasma (FRAP) method. In the kidney of streptozotocin (STZ)-induced (55?mg/kg) diabetic rats either treated or not treated for 3 weeks with losartan, an AT-II type 1 receptor antagonist (20?mg/kg/day); we measured 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) levels, as an index of oxidative DNA damage, circulating Adp and FRAP. Diabetic rats showed significantly higher 8-oxodGuo levels in renal DNA (8.48?±?0.98?×?10(-6) dG, mean?±?SEM n?=?11) than normoglycemic ones (1.18?±?0.04?×?10(-6) dG, mean?±?SEM, n=7) and lower plasma Adp and FRAP levels in comparison to normoglycemics. The treatment of diabetic rats with losartan significantly (P?reduced 8-oxodGuo levels (5.4?±?0.58?×?10(-6) dG, mean?±?SEM n=9) in renal DNA and conserved FRAP values. Moreover, an inverse correlation was found between 8-oxodGuo in kidney DNA and circulating Adp levels in normoglycemic and diabetic rats. Losartan treatment preserves FRAP levels, reduces DNA oxidative injury and thus the carcinogenesis risk. Furthermore, our results indicate that Adp plasma levels are a further marker of oxidative injury to the kidney and confirm that it is an important part of the plasma antioxidant defense. PMID:25710927

  14. Estrogen Replacement Reduces Oxidative Stress in the Rostral Ventrolateral Medulla of Ovariectomized Rats

    PubMed Central

    Hao, Fan; Gu, Ying; Tan, Xing; Deng, Yu; Wu, Zhao-Tang; Xu, Ming-Juan; Wang, Wei-Zhong

    2016-01-01

    Cardiovascular disease prevalence rises rapidly after menopause, which is believed to be derived from the loss of estrogen. It is reported that sympathetic tone is increased in postmenopause. The high level of oxidative stress in the rostral ventrolateral medulla (RVLM) contributes to increased sympathetic outflow. The focus of this study was to determine if estrogen replacement reduces oxidative stress in the RVLM and sympathetic outflow in the ovariectomized (OVX) rats. The data of this study showed that OVX rat increased oxidative stress in the RVLM and sympathetic tone; estrogen replacement improved cardiovascular functions but also reduced the level of oxidative stress in the RVLM. These findings suggest that estrogen replacement decreases blood pressure and sympathoexcitation in the OVX rats, which may be associated with suppression in oxidative stress in the RVLM through downregulation of protein expression of NADPHase (NOX4) and upregulation of protein expression of SOD1. The data from this study is beneficial for our understanding of the mechanism of estrogen exerting cardiovascular protective effects on postmenopause. PMID:26640612

  15. Estrogen Replacement Reduces Oxidative Stress in the Rostral Ventrolateral Medulla of Ovariectomized Rats.

    PubMed

    Hao, Fan; Gu, Ying; Tan, Xing; Deng, Yu; Wu, Zhao-Tang; Xu, Ming-Juan; Wang, Wei-Zhong

    2016-01-01

    Cardiovascular disease prevalence rises rapidly after menopause, which is believed to be derived from the loss of estrogen. It is reported that sympathetic tone is increased in postmenopause. The high level of oxidative stress in the rostral ventrolateral medulla (RVLM) contributes to increased sympathetic outflow. The focus of this study was to determine if estrogen replacement reduces oxidative stress in the RVLM and sympathetic outflow in the ovariectomized (OVX) rats. The data of this study showed that OVX rat increased oxidative stress in the RVLM and sympathetic tone; estrogen replacement improved cardiovascular functions but also reduced the level of oxidative stress in the RVLM. These findings suggest that estrogen replacement decreases blood pressure and sympathoexcitation in the OVX rats, which may be associated with suppression in oxidative stress in the RVLM through downregulation of protein expression of NADPHase (NOX4) and upregulation of protein expression of SOD1. The data from this study is beneficial for our understanding of the mechanism of estrogen exerting cardiovascular protective effects on postmenopause. PMID:26640612

  16. Early deprivation under specific conditions leads to reduced interest in reward in adulthood in Wistar rats.

    PubMed

    Rüedi-Bettschen, Daniela; Pedersen, Else-Marie; Feldon, Joram; Pryce, Christopher R

    2005-01-30

    Early life adversity can lead to increased vulnerability to psychiatric disease including depression, with symptoms of depressed mood, impaired coping with negative events, anhedonia, reduced appetite, and elevated stress hormone activity. In rats, postnatal manipulation studies have focused on behavioural and endocrine anxiety effects, and have demonstrated that mild pup stimulation in the form of early handling (EH) is chronically anxiolytic relative to no stimulation in the form of non-handling (NH). Furthermore, apparently severe manipulations in the form of 3-4 h daily litter-dam separation (maternal separation) or pup-litter-dam separation (early deprivation, ED) are either without effect or even EH-like, relative to NH. In this Wistar rat study, we investigated the effects of ED under different circadian and thermal conditions on adulthood behavioural and endocrine responsiveness to environmental challenge, relative to NH. ED was performed on days 1-14, during either the Light or Dark phase and at either 21 degrees C (cold) or 32 degrees C (warm). Dark-cold ED adults exhibited reduced motivation to obtain sucrose in a progressive ratio schedule, tended to be less mobile in a forced swim test, but did not exhibit an escape deficit in a foot-shock pre-exposure/shuttle box test, or altered basal or stress endocrine activity. Light ED was completely without effect on adult phenotype. Even relative to stringent NH comparison, dark-cold ED leads to a long-term trait of mild gustatory anhedonia in Wistar rats. PMID:15582116

  17. Botulinum toxin in gastric submucosa reduces stimulated HCl production in rats

    PubMed Central

    Runfola, Matteo; Rossi, Simone; Panunzi, Simona; Spada, Pier Luigi; Gui, Daniele

    2003-01-01

    Background Botulinum toxin blocks acetylcholine release from nerve endings and acts as a long term, reversible inhibitor of muscle contraction as well as of salivary, sweat gland, adrenal and prostatic secretions. The aim of the present study is to investigate whether gastric submucosal injection of botulinum toxin type A reduces stimulated gastric production of HCl. Methods Sixty-four rats were randomized in two groups and laparotomized. One group was treated with botulinum toxin-A 10 U by multiple submucosal gastric injections, while the second group was injected with saline. Two weeks later, acid secretion was stimulated by pyloric ligation and acid output was measured. Body weight, food and water intake were also recorded daily. Results HCl production after pyloric ligation was found to be significantly lower in botulinum toxin-treated rats (657 ± 90.25 micromol HCl vs. 1247 ± 152. P = 0.0017). Botulinum toxin-treated rats also showed significantly lower food intake and weight gain. Conclusions Botulinum toxin type A reduces stimulated gastric acidity. This is likely due either to inhibition of the cholinergic stimulation of gastric parietal cells, or to an action on the myenteric nervous plexuses. Reduction of growth and food intake may reflect both impaired digestion and decreased gastric motility. PMID:12964945

  18. Candesartan reduces the hemorrhage associated with delayed tissue plasminogen activator treatment in rat embolic stroke.

    PubMed

    Ishrat, Tauheed; Pillai, Bindu; Ergul, Adviye; Hafez, Sherif; Fagan, Susan C

    2013-12-01

    We have previously reported that angiotensin receptor blockade reduces reperfusion hemorrhage in a suture occlusion model of stroke, despite increasing matrix metalloproteinase (MMP-9) activity. We hypothesized that candesartan will also decrease hemorrhage associated with delayed (6 h) tissue plasminogen activator (tPA) administration after embolic stroke, widening the therapeutic time window of tPA. Adult male Wistar rats were subjected to embolic middle cerebral artery occlusion (eMCAO) and treated with either candesartan (1 mg/kg) alone early at 3 h, delayed tPA (10 mg/kg) alone at 6 h, the combination of candesartan and tPA, or vehicle control. Rats were sacrificed at 24 and 48 h post-eMCAO and brains perfused for evaluation of neurological deficits, cerebral hemorrhage in terms of hemoglobin content, occurrence rate of hemorrhage, infarct size, tissue MMP activity and protein expression. The combination therapy of candesartan and tPA after eMCAO reduced the brain hemorrhage, and improved neurological outcome compared with rats treated with tPA alone. Further, candesartan in combination with tPA increased activity of MMP-9 but decreased MMP-3, nuclear factor kappa-B and tumor necrosis factor-? expression and enhanced activation of endothelial nitric oxide synthase. An activation of MMP-9 alone is insufficient to cause increased hemorrhage in embolic stroke. Combination therapy with acute candesartan plus tPA may be beneficial in ameliorating tPA-induced hemorrhage after embolic stroke. PMID:24194350

  19. Valproic Acid Pretreatment Reduces Brain Edema in a Rat Model of Surgical Brain Injury.

    PubMed

    Huang, Lei; Woo, Wendy; Sherchan, Prativa; Khatibi, Nikan H; Krafft, Paul; Rolland, William; Applegate, Richard L; Martin, Robert D; Zhang, John

    2016-01-01

    Surgically induced brain injury (SBI) results in brain edema and neurological decline. Valproic acid (VA) has been shown to be neuroprotective in several experimental brain diseases. In this study, we investigated the pretreatment effect of VA in a rat model of SBI. A total of 57 male Sprague-Dawley rats were use in four groups: sham, SBI?+?vehicle, SBI?+?low dose (100 mg/kg) VA, and SBI?+?high dose (300 mg/kg) VA. SBI was induced by partially resecting right frontal lobes. Shams underwent identical surgical procedures without brain resection. VA or vehicle was administered subcutaneously 30 min prior to SBI. At 24 and 72 h post SBI, neurobehavior and brain water content were assessed as well as matrix metalloproteinases (MMPs) activities. There was significantly higher brain water content within the right frontal lobe in SBI rats than in shams. Without neurobehavioral improvements, the low-dose but not high-dose VA significantly reduced brain edema at 24 h post SBI. The protection tends to persist to 72 h post SBI. At 24 h post SBI, low-dose VA did not significantly reduce the elevated MMP-9 activity associated with SBI. In conclusion, VA pretreatment attenuated brain edema at 24 h after SBI but lacked MMP inhibition. The single dose VA was not associated with neurobehavioral benefits. PMID:26463966

  20. Pyridoxine Administration Improves Behavioral and Anatomical Outcome after Unilateral Contusion Injury in the Rat

    PubMed Central

    Kuypers, Nicholas J.

    2010-01-01

    Abstract The purpose of this project was to evaluate the preclinical efficacy of pyridoxine, or vitamin B6. Rats received a 3.0?mm unilateral controlled cortical impact (CCI) injury of the sensorimotor cortex or sham surgery. Treatment with vitamin B6 (600 or 300?mg/kg IP) or vehicle was administered at 30?min and 24?h post-CCI. Somatosensory dysfunction was evaluated with the vibrissae–forelimb placing and bilateral tactile adhesive removal tests. Sensorimotor dysfunction was evaluated with the locomotor placing and the forelimb asymmetry tests. On the forelimb asymmetry test both treatment groups displayed no asymmetry bias on any of the testing days post-CCI and were statistically no different than the shams. Both vitamin B6 groups displayed a significant improvement in behavioral performance on the locomotor placing test compared to the vehicle-treated group. Administration of 600?mg/kg also significantly reduced tactile adhesive removal latencies on days 2, 4, 6, and 12 post-CCI. Both treatment groups were improved in their rate of recovery post-CCI on the vibrissae–forelimb placing test, but only the recovery seen in the 600-mg/kg group was significantly improved compared to vehicle. Finally, the 600-mg/kg dose resulted in significant cortical sparing compared to the vehicle-treated group. In general, the effects of vitamin B6 on recovery of function were dose-dependent, with the 600-mg/kg dose consistently showing greater recovery than the 300-mg/kg dose. More experimental analyses are warranted to evaluate the potential preclinical efficacy and mechanistic action of vitamin B6. PMID:20486803

  1. Spontaneously hypertensive rats display reduced microglial activation in response to ischemic stroke and lipopolysaccharide

    PubMed Central

    2012-01-01

    Background For successful translation to clinical stroke studies, the Stroke Therapy Academic Industry Round Table criteria have been proposed. Two important criteria are testing of therapeutic interventions in conscious animals and the presence of a co-morbidity factor. We chose to work with hypertensive rats since hypertension is an important modifiable risk factor for stroke and influences the clinical outcome. We aimed to compare the susceptibility to ischemia in hypertensive rats with those in normotensive controls in a rat model for induction of ischemic stroke in conscious animals. Methods The vasoconstrictor endothelin-1 was stereotactically applied in the vicinity of the middle cerebral artery of control Wistar Kyoto rats (WKYRs) and Spontaneously Hypertensive rats (SHRs) to induce a transient decrease in striatal blood flow, which was measured by the Laser Doppler technique. Infarct size was assessed histologically by Cresyl Violet staining. Sensory-motor functions were measured at several time points using the Neurological Deficit Score. Activation of microglia and astrocytes in the striatum and cortex was investigated by immunohistochemistry using antibodies against CD68/Iba-1 and glial fibrillary acidic protein. Results and conclusions The SHRs showed significantly larger infarct volumes and more pronounced sensory-motor deficits, compared to the WKYRs at 24?h after the insult. However, both differences disappeared between 24 and 72?h. In SHRs, microglia were less susceptible to activation by lipopolysaccharide and there was a reduced microglial activation after induction of ischemic stroke. These quantitative and qualitative differences may be relevant for studying the efficacy of new treatments for stroke in accordance to the Stroke Therapy Academic Industry Round Table criteria. PMID:22647642

  2. Canavanine activates imidazoline I-2 receptors to reduce hyperglycemia in type 1-like diabetic rats.

    PubMed

    Chang, Chin-Hong; Chao, Pin-Chun; Niu, Ho-Shan; Huang, Gin-Chi; Chen, Li-Jen; Cheng, Juei-Tang

    2015-10-01

    Canavanine is a guanidinium derivative that has the basic structure of a ligand for the imidazoline receptor (I-R). Furthermore, canavanine is found in an herb that has been shown to improve diabetic disorders. Thus, the present study was designed to investigate the anti-hyperglycemic action of canavanine in rats with streptozotocin (STZ)-induced type 1-like diabetes. Canavanine decreased hyperglycemia in the STZ-induced diabetic rats, and this action was blocked by the antagonist specific to imidazoline I-2 receptors (I-2R), BU224, in a dose-dependent manner. Additionally, canavanine increased the plasma ?-endorphin level, as measured using enzyme-linked immunosorbent assay (ELISA), and this increase was also blocked by BU224 in the same manner. Moreover, amiloride at a dose sufficient to block I-2AR attenuated the actions of canavanine, including the increased ?-endorphin level and the antihyperglycemic effect. Otherwise, canavanine increased the radioactive glucose uptake into skeletal muscles isolated from the diabetic rats. Furthermore, canavanine increased the phosphorylation of AMPK measured using Western blot analysis in these isolated skeletal muscles in a dose-dependent manner. Additionally, the insulin sensitivity of the diabetic rats was markedly increased by canavanine, and this action was also blocked by BU224. Overall, canavanine is capable of activating imidazoline I-2R; I-2AR is linked to an increase in the plasma level of ?-endorphin, and I-2BR is related to effects on the glucose uptake by skeletal muscle that reduces hyperglycemia in type 1-like diabetic rats. Therefore, canavanine can be developed as effective agent to treat the diabetic disorders in the future. PMID:26362499

  3. Exenatide reduces TNF-? expression and improves hippocampal neuron numbers and memory in streptozotocin treated rats.

    PubMed

    Solmaz, Volkan; Ç?nar, Bilge Piri; Yi?ittürk, Gürkan; Çavu?o?lu, Türker; Ta?k?ran, Dilek; Erba?, Oytun

    2015-10-15

    Recent studies suggest a possible link between type 2 diabetes and Alzheimer's disease (AD). Glucogan-like peptide 1 (GLP-1) facilitates insulin release from pancreas under hyperglycemic conditions. In addition to its metabolic effects, GLP-1 and its long-lasting analogs, including exenatide can stimulate neurogenesis and improve cognition in rodent AD model. The aim of the present study was to investigate the effects of exenatide on hippocampal cellularity, cognitive performance and inflammation response in a rat model of AD. Fourteen rats were used to create AD model using intracerebroventricular (ICV) streptozotocin (STZ) infusion while 7 rats were administered 0.9% NaCl only (sham-operated group). Following stereotaxic surgery, STZ received rats were randomly distributed into two groups, and treated with either saline or exenatide 20µgr/kg/day through intraperitoneally for two weeks. Then, cognitive performance (passive avoidance learning), brain tumor necrosis factor alpha (TNF-?) levels, choline acetyltransferase (ChAT) activity and hippocampal neuronal count were determined. While the brain TNF-? levels were significantly high in the saline-treated STZ group, exenatide treatment suppressed the increase in TNF-? levels. Saline-treated STZ group showed reduced ChAT activity compared to sham group. However, exenatide significantly preserved brain ChAT activity. The cognitive performance was also impaired in saline group while exenatide improved memory in rats. Moreover, exenatide treatment significantly prevented the decrease in hippocampal neurons. Overall, the results of the present study clearly indicated exenatide might have beneficial effects on impaired cognitive performance and hippocampal neuronal viability in AD by suppressing the inflammation response and increasing cholinergic activity. PMID:26386291

  4. Effectiveness of topical anesthetics on reducing tactile sensitivity in the paws of newborn rats.

    PubMed

    Strain, Misty M; Vineyard, Mary Ann; Roberto, Megan E; Brumley, Michele R

    2014-01-01

    The aim of this study was to evaluate the effectiveness of three local, topical anesthetics on touch response thresholds of the paws of 1-day-old rats. Touch response thresholds were measured using Semmes Weinstein monofilaments after treatment of the paws with EMLA (2.5% lidocaine and 2.5% prilocaine), alcaine (.5% proparacaine), triocaine (20% benzocaine, 6% lidocaine, and 4% tetracaine), or petroleum jelly (treatment control). Touch thresholds significantly increased after treatment with EMLA 18% of the time, and there was no evidence of a systemic effect. Touch thresholds were not significantly altered after treatment with alcaine, triocaine, or petroleum jelly. Therefore, EMLA appears to be a slightly effective topical anesthetic for reducing tactile sensitivity in newborn rats. PMID:23254968

  5. TNF? siRNA Reduces Brain TNF and EEG Delta Wave Activity in Rats

    PubMed Central

    Taishi, Ping; Churchill, Lynn; Wang, Mingxiang; Kay, Daniel; Davis, Christopher J.; Guan, Xin; De, Alok; Yasuda, Tadanobu; Liao, Fan; Krueger, James M.

    2007-01-01

    Tumor necrosis factor alpha (TNF?) is a pleiotropic cytokine with several CNS physiological and pathophysiological actions including sleep, memory, thermal and appetite regulation. Short interfering RNAs (siRNA) targeting TNF? were incubated with cortical cell cultures and microinjected into the primary somatosensory cortex (SSctx) of rats. The TNF? siRNA treatment specifically reduced TNF? mRNA by 45% in vitro without affecting interleukin-6 or gluR1-4 mRNA levels. In vivo the TNF? siRNA? reduced TNF? mRNA, interleukin-6 mRNA and gluR1 mRNA levels compared to treatment with a scrambled control siRNA. After in vivo microinjection, the density of TNF?-immunoreactive cells in layer V of the SSctx was also reduced. Electroencephalogram (EEG) delta wave power was decreased on days 2 and 3 on the side of the brain that received the TNF? siRNA microinjection relative to the side receiving the control siRNA. These findings support the hypothesis that TNF? siRNA attenuates TNF? mRNA and TNF? protein in the rat cortex and that those reductions reduce cortical EEG delta power. Results also are consistent with the notion that TNF? is involved in CNS physiology including sleep regulation. PMID:17531209

  6. Chronic metabolic acidosis reduces urinary oxalate excretion and promotes intestinal oxalate secretion in the rat.

    PubMed

    Whittamore, Jonathan M; Hatch, Marguerite

    2015-11-01

    Urinary oxalate excretion is reduced in rats during a chronic metabolic acidosis, but how this is achieved is not clear. In this report, we re-examine our prior work on the effects of a metabolic acidosis on urinary oxalate handling [Green et al., Am J Physiol Ren Physiol 289(3):F536-F543, 2005], offering a more detailed analysis and interpretation of the data, together with new, previously unpublished observations revealing a marked impact on intestinal oxalate transport. Sprague-Dawley rats were provided with 0.28 M ammonium chloride in their drinking water for either 4 or 14 days followed by 24 h urine collections, blood-gas and serum ion analysis, and measurements of (14)C-oxalate fluxes across isolated segments of the distal colon. Urinary oxalate excretion was significantly reduced by 75 % after just 4 days compared to control rats, and this was similarly sustained at 14 days. Oxalate:creatinine clearance ratios indicated enhanced net re-absorption of oxalate by the kidney during a metabolic acidosis, but this was not associated with any substantive changes to serum oxalate levels. In the distal colon, oxalate transport was dramatically altered from net absorption in controls (6.20 ± 0.63 pmol cm(-2) h(-1)), to net secretion in rats with a metabolic acidosis (-5.19 ± 1.18 and -2.07 ± 1.05 pmol cm(-2) h(-1) at 4 and 14 days, respectively). Although we cannot rule out modifications to bi-directional oxalate movements along the proximal tubule, these findings support a gut-kidney axis in the management of oxalate homeostasis, where this shift in renal handling during a metabolic acidosis is associated with compensatory adaptations by the intestine. PMID:26162424

  7. Reduced clearance of proteins labeled with diisopropylfluorophosphate in portacaval-shunted rats

    PubMed Central

    Dienel, Gerald A.; Cruz, Nancy F.

    2013-01-01

    Portacaval shunting is a model for hepatic encephalopathy that causes chronic hyperammonemia, disruption of metabolic, signaling, and neurotransmitter systems, and progressive morphological changes. Exposure of cultured cells to ammonia raises intralysosomal pH and inhibits proteolysis, and the present study tested the hypothesis that proteolytic capacity is diminished in portacaval-shunted rats. Proteins were labeled in vivo with tracer doses of diisopropylfluorophosphate (DFP) and clearance of label was assayed. This approach labeled proteins independent of protein synthesis, which is reported to be altered in shunted rats, and avoided complications arising from re-utilization of labeled amino acids that causes underestimation of degradation rate. Characterization of DFP labeling showed that protein labeling was fast, about 50% of the label was released during a 24h interval, labeling by DFP metabolites was negligible, inhibition of brain acetylcholinesterase was not detectable, and labeling by [3H]- and [14C]DFP was equivalent. To assay degradative capacity, proteins were first labeled with [3H]DFP, followed by labeling with [14C]DFP that was given 24 or 72h later. The 3H/14C ratio in each animal was used as a relative measure of removal of 3H-labeled proteins. 3H/14C ratios were generally significantly higher in portacaval-shunted rats than in controls, consistent with reduced proteolytic capacity. Assays of amino acid incorporation into brain protein generally replicated literature reports, supporting the conclusion that protein synthesis unlikely to be markedly inhibited and amino acid recycling influences calculated protein synthesis rates in shunted rats. Therapeutic strategies to reduce ammonia level would help normalize lysosomal functions and protein and lipid turnover. PMID:24154686

  8. Estradiol selectively reduces central neural activation induced by hypertonic NaCl infusion in ovariectomized rats

    PubMed Central

    Jones, Alexis B.; Bass, Eryn E.; Fan, Liming; Curtis, Kathleen S.

    2013-01-01

    We recently reported that the latency to begin drinking water during slow, intravenous infusion of a concentrated NaCl solution was shorter in estradiol-treated ovariectomized rats compared to oil vehicle-treated rats, despite comparably elevated plasma osmolality. To test the hypothesis that the decreased latency to begin drinking is attributable to enhanced detection of increased plasma osmolality by osmoreceptors located in the CNS, the present study used immunocytochemical methods to label fos, a marker of neural activation. Increased plasma osmolality did not activate the subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), or the nucleus of the solitary tract (NTS) in either oil vehicle-treated ratsor estradiol-treated rats. In contrast, hyperosmolality increased fos labeling in the area postrema (AP), the paraventricular nucleus of the hypothalamus (PVN) and the rostral ventrolateral medulla (RVLM) in both groups; however, the increase was blunted in estradiol-treated rats. These results suggest that estradiol has selective effects on the sensitivity of a population of osmo-/Na+-receptors located in the AP, which, in turn, alters activity in other central areas associated with responses to increased osmolality. In conjunction with previous reports that hyperosmolality increases blood pressure and that elevated blood pressure inhibits drinking, the current findings of reduced activation in AP, PVN, and RVLM–areas involved in sympathetic nerve activity–raise the possibility that estradiol blunts HS-induced blood pressure changes. Thus, estradiol may eliminate or reduce the initial inhibition of water intake that occurs during increased osmolality, and facilitate a more rapid behavioral response, as we observed in our recent study. PMID:22763321

  9. Inhibited osteoclastic bone resorption through alendronate treatment in rats reduces severe osteoarthritis progression.

    PubMed

    Siebelt, M; Waarsing, J H; Groen, H C; Müller, C; Koelewijn, S J; de Blois, E; Verhaar, J A N; de Jong, M; Weinans, H

    2014-09-01

    Osteoarthritis (OA) is a non-rheumatoid joint disease characterized by progressive degeneration of extra-cellular cartilage matrix (ECM), enhanced subchondral bone remodeling, osteophyte formation and synovial thickening. Alendronate (ALN) is a potent inhibitor of osteoclastic bone resorption and results in reduced bone remodeling. This study investigated the effects of pre-emptive use of ALN on OA related osteoclastic subchondral bone resorption in an in vivo rat model for severe OA. Using multi-modality imaging we measured effects of ALN treatment within cartilage and synovium. Severe osteoarthritis was induced in left rat knees using papain injections in combination with a moderate running protocol. Twenty rats were treated with subcutaneous ALN injections and compared to twenty untreated controls. Animals were longitudinally monitored for 12weeks with in vivo ?CT to measure subchondral bone changes and SPECT/CT to determine synovial macrophage activation using a folate-based radiotracer. Articular cartilage was analyzed at 6 and 12weeks with ex vivo contrast enhanced ?CT and histology to measure sulfated-glycosaminoglycan (sGAG) content and cartilage thickness. ALN treatment successfully inhibited subchondral bone remodeling. As a result we found less subchondral plate porosity and reduced osteophytosis. ALN treatment did not reduce subchondral sclerosis. However, after the OA induction phase, ALN treatment protected cartilage ECM from degradation and reduced synovial macrophage activation. Surprisingly, ALN treatment also improved sGAG content of tibia cartilage in healthy joints. Our data was consistent with the hypothesis that osteoclastic bone resorption might play an important role in OA and may be a driving force for progression of the disease. However, our study suggest that this effect might not solely be effects on osteoclastic activity, since ALN treatment also influenced macrophage functioning. Additionally, ALN treatment and physical activity exercised a positive effect in healthy control joints, which increased cartilage sGAG content. More research on this topic might lead to novel insights as to improve cartilage quality. PMID:24933343

  10. Comparative study of the forelimbs of the semifossorial prairie dog, Cynomys gunnisoni, and the scansorial fox squirrel, Sciurus niger.

    PubMed

    Stalheim-Smith, A

    1984-04-01

    A comparative study of the forelimbs of the semifossorial prairie dog, Cynomys gunnisoni , and the scansorial tree squirrel, Sciurus niger, was focused on the musculoskeletal design for digging in the former and climbing in the latter. Based on lever arm mechanics, it was expected that the forelimb of the prairie dog would show features appropriate to the production of relatively large forces and that of the fox squirrel to relatively great velocity. Force and lever arm measurements were made of select forelimb muscles at the shoulder, elbow, and wrist joints for a series of angles in both species. Contraction time and fatigue indexes were determined for the same forelimb muscles. Contrary to expectation, in the few cases in which significant (P less than .05) differences were found, the forces, lever arms, and torques (force times its lever arm) were greater in the smaller fox squirrel. The observed variation in the torques produced fits the demands on the forelimb during climbing and digging as estimated from films. Several forelimb muscles of the fox squirrel show significantly higher mean contraction times than do the homologous muscles of the prairie dog. There were no significant differences between the two species in the fatigability of the selected forelimb muscles, although the mean fatigue index was always higher (less fatigable muscle) in the prairie dog. Similarities in the forelimbs of these two sciurids suggest that only minor modifications may have been required of the ancestral forelimb in order for descendent forms to operate successfully as climbers and diggers . PMID:6726818

  11. Forelimb preferences in human beings and other species: multiple models for testing hypotheses on lateralization

    PubMed Central

    Versace, Elisabetta; Vallortigara, Giorgio

    2015-01-01

    Functional preferences in the use of right/left forelimbs are not exclusively present in humans but have been widely documented in a variety of vertebrate and invertebrate species. A matter of debate is whether non-human species exhibit a degree and consistency of functional forelimb asymmetries comparable to human handedness. The comparison is made difficult by the variability in hand use in humans and the few comparable studies conducted on other species. In spite of this, interesting continuities appear in functions such as feeding, object manipulation and communicative gestures. Studies on invertebrates show how widespread forelimb preferences are among animals, and the importance of experience for the development of forelimb asymmetries. Vertebrate species have been extensively investigated to clarify the origins of forelimb functional asymmetries: comparative evidence shows that selective pressures for different functions have likely driven the evolution of human handedness. Evidence of a complex genetic architecture of human handedness is in line with the idea of multiple evolutionary origins of this trait. PMID:25798121

  12. Tetrahydrocannabinolic acid reduces nausea-induced conditioned gaping in rats and vomiting in Suncus murinus

    PubMed Central

    Rock, E M; Kopstick, R L; Limebeer, C L; Parker, L A

    2013-01-01

    BACKGROUND AND PURPOSE We evaluated the anti-emetic and anti-nausea properties of the acid precursor of ?9-tetrahydrocannabinol (THC), tetrahydrocannabinolic acid (THCA), and determined its mechanism of action in these animal models. EXPERIMENTAL APPROACH We investigated the effect of THCA on lithium chloride- (LiCl) induced conditioned gaping (nausea-induced behaviour) to a flavour, and context (a model of anticipatory nausea) in rats, and on LiCl-induced vomiting in Suncus murinus. Furthermore, we investigated THCA's ability to induce hypothermia and suppress locomotion [rodent tasks to assess cannabinoid1 (CB1) receptor agonist-like activity], and measured plasma and brain THCA and THC levels. We also determined whether THCA's effect could be blocked by pretreatment with SR141716 (SR, a CB1 receptor antagonist). KEY RESULTS In rats, THCA (0.05 and/or 0.5 mg·kg?1) suppressed LiCl-induced conditioned gaping to a flavour and context; the latter effect blocked by the CB1 receptor antagonist, SR, but not by the 5-hydroxytryptamine-1A receptor antagonist, WAY100635. In S. murinus, THCA (0.05 and 0.5 mg·kg?1) reduced LiCl-induced vomiting, an effect that was reversed with SR. A comparatively low dose of THC (0.05 mg·kg?1) did not suppress conditioned gaping to a LiCl-paired flavour or context. THCA did not induce hypothermia or reduce locomotion, indicating non-CB1 agonist-like effects. THCA, but not THC was detected in plasma samples. CONCLUSIONS AND IMPLICATIONS THCA potently reduced conditioned gaping in rats and vomiting in S. murinus, effects that were blocked by SR. These data suggest that THCA may be a more potent alternative to THC in the treatment of nausea and vomiting. PMID:23889598

  13. 2-methoxycinnamaldehyde reduces IL-1beta-induced prostaglandin production in rat cerebral endothelial cells.

    PubMed

    Guo, Jian-You; Huo, Hai-Ru; Yang, Yuan-Xiao; Li, Cang-Hai; Liu, Hong-Bin; Zhao, Bao-Sheng; Li, Lan-Fang; Ma, Yue-Ying; Guo, Shu-Ying; Jiang, Ting-Liang

    2006-11-01

    Prostaglandin E2 (PGE2) works as a common final mediator of the febrile. Guizhi-Tang, one of the most famous traditional Chinese medical formula used to treat influenza, common cold and other pyretic conditions, was previously reported to reduce the production of PGE 2 in rats. 2-Methoxycinnamaldehyde is a principle compound isolated from Guizhi-Tang. The aim of the present study was to investigate the effects of 2-methoxycinnamaldehyde on PGE2 production of rat cerebral endothelial cells (CECs). 2-Methoxycinnamaldehyde dose-dependently inhibited interleukin (IL)-1beta-induced PGE2 production in CECs with IC50 values of 174 microM. IL-1beta stimulation increased the protein, activity and mRNA expression of cyclooxygenase (COX)-2 but not COX-1. 2-Methoxycinnamaldehyde reduced IL-1beta-induced protein and activity of COX-2, but did not influence the COX-2 mRNA expression. Our results show that prostaglandin production in CECs during stimulated conditions is sensitive to inhibition by 2-methoxycinnamaldehyde and suggest that 2-methoxycinnamaldehyde may reduce COX-2 protein level and activity but not COX-2 mRNA. PMID:17077517

  14. Evidence for reduced cancellous bone mass in the spontaneously hypertensive rat

    NASA Technical Reports Server (NTRS)

    Wang, T. M.; Hsu, J. F.; Jee, W. S.; Matthews, J. L.

    1993-01-01

    The histomorphometric changes in the proximal tibial metaphysis and epiphyseal growth plate and midtibial shaft of 26-week-old spontaneously hypertensive rats (SHR) compared with those of the corresponding normotensive Wistar-Kyoto (WKY) rats were studied. A decrease in body weight, growth plate thickness, and longitudinal growth rate of the proximal tibial epiphysis, trabecular bone volume, trabecular thickness and number, the number of osteoblasts and osteoprogenitor cells per millimeter square surface of the proximal tibial metaphysis, periosteal and endocortical apposition rate and bone formation rate of the tibial diaphysis were observed in the SHR. Additionally, systolic blood pressure, the number of osteoclasts per millimeter square surface and average number of nuclei per osteoclast of the proximal tibial metaphysis were significantly increased. Thus, osteoclastic activity is dominant over osteoblastic and chondroblastic activity in the SHR that results in a cancellous bone deficit in the skeleton. It will require additional work to ascertain the underlying cause for this condition as several factors in the SHR with a potential for causing this change are present, including elevated parathyroid hormone (PTH), depressed 1,25-(OH)2D3, low calcium absorption, reduced body weight (reduced loading) elevated blood pressure and possibly other direct cell differences in the mutant strain. At present elevated PTH and adaptation to underloading from reduced weight are postulated to be a likely cause, but additional studies are required to test this interpretation.

  15. Reduced Na-K-Cl cotransport in vascular smooth muscle cells from spontaneously hypertensive rats

    SciTech Connect

    O'Donnell, M.E.; Owen, N.E. )

    1988-08-01

    The authors have previously demonstrated the presence of a prominent, cyclic nucleotide-sensitive Na-K-Cl cotransport in vascular smooth muscle cells (VSMC). Others have observed that Na-K-Cl cotransport levels are reduced in erythrocytes of patients with essential hypertension and have proposed that a defect in this Na transport system may play a role in the pathogenesis of the disease. However, such a defect has not been demonstrated in the putative target tissue for essential hypertension, i.e., the VSMC. In the present study, they compared Na-K-Cl cotransport of VSMC from spontaneously hypertensive rats (SHR) with Na-K-Cl cotransport of VSMC from normotensive Wistar-Kyoto rats (WKY). They found that Na-K-Cl cotransport of SHR VSMC is significantly reduced relative to that of WKY VSMC. The apparent ion affinities for Na-K-Cl cotransport of SHR VSMC did not differ from those determined for WKY VSMC. Furthermore, cyclic nucleotide regulation of cotransport also appeared to be the same for the two types of VSMC. In contrast, maximal saturable binding of ({sup 3}H)bumetanide observed in SHR VSMC was markedly reduced compared with that of WKY VSMC, but the K{sub d} values were similar. The data suggest that the reduction in cotransport observed in SHR VSMC is the result of a decrease in the number of available cotransport sites.

  16. Swimming reduces the severity of physical and psychological dependence and voluntary morphine consumption in morphine dependent rats.

    PubMed

    Fadaei, Atefeh; Gorji, Hossein Miladi; Hosseini, Shahrokh Makvand

    2015-01-15

    Previous studies have indicated that voluntary exercise decreases the severity of the anxiogenic-like behaviors in both morphine-dependent and withdrawn rats. This study examined the effects of regular swimming exercise during the development of dependency and spontaneous morphine withdrawal on the anxiety-depression profile and voluntary morphine consumption in morphine dependent rats. The rats were chronically treated with bi-daily doses (10 mg/kg, at 12h intervals) of morphine over a period of 14 days. The exercising rats were allowed to swim (45 min/d, five days per a week, for 14 or 21 days) during the development of morphine dependence and withdrawal. Then, rats were tested for the severity of morphine dependence, the elevated plus-maze (EPM), sucrose preference test (SPT) and voluntary morphine consumption using a two-bottle choice paradigm in animal models of craving. The results showed that withdrawal signs were decreased in swimmer morphine dependent rats than sedentary rats (P<0.05). Also, the swimmer morphine-dependent and withdrawn rats exhibited an increase in EPM open arm time and entries (P<0.05), higher levels of sucrose preference (P<0.001) than sedentary rats. Voluntary consumption of oral morphine was less in the swimmer morphine-withdrawn rats than the sedentary groups during four periods of the intake of drug (P<0.01). We conclude that regular swimming exercise reduces the severity of morphine dependence and voluntary morphine consumption with reducing anxiety and depression in morphine-dependent and withdrawn rats. Thus, swimming exercise may be a potential method to ameliorate some of the deleterious behavioral consequences of morphine dependence. PMID:25498794

  17. The edible brown seaweed Ecklonia cava reduces hypersensitivity in postoperative and neuropathic pain models in rats.

    PubMed

    Kim, Jae Goo; Lim, Dong Wook; Cho, Suengmok; Han, Daeseok; Kim, Yun Tai

    2014-01-01

    The current study was designed to investigate whether edible brown seaweed Ecklonia cava extracts exhibits analgesic effects in plantar incision and spared nerve injury (SNI) rats. To evaluate pain-related behavior, we performed the mechanical withdrawal threshold (MWT) and thermal hypersensitivity tests measured by von Frey filaments and a hot/cold plate analgesia meter. Pain-related behavior was also determined through analysis of ultrasonic vocalization. The results of experiments showed MWT values of the group that was treated with E. cava extracts by 300 mg/kg significantly increased; on the contrary, number of ultrasonic distress vocalization of the treated group was reduced at 6 h and 24 h after plantar incision operation (62.8%, p < 0.05). Moreover, E. cava 300 mg/kg treated group increased the paw withdrawal latency in hot-and cold-plate tests in the plantar incision rats. After 15 days of continuous treatment with E. cava extracts at 300 mg/kg, the treated group showed significantly alleviated SNI-induced hypersensitivity response by MWT compared with the control group. In conclusion, these results suggest that E. cava extracts have potential analgesic effects in the case of postoperative pain and neuropathic pain in rats. PMID:24918539

  18. Targeted ablation of mesenteric projecting sympathetic neurons reduces the hemodynamic response to pain in conscious, spinal cord-transected rats

    PubMed Central

    Lujan, Heidi L.; Palani, Gurunanthan; Peduzzi, Jean D.

    2010-01-01

    Individuals with spinal cord injuries above thoracic level 6 (T6) experience episodic bouts of life-threatening hypertension as part of a condition termed autonomic dysreflexia. The paroxysmal hypertension can be caused by a painful stimulus below the level of the injury. Targeted ablation of mesenteric projecting sympathetic neurons may reduce the severity of autonomic dysreflexia by reducing sympathetic activity. Therefore, cholera toxin B subunit (CTB) conjugated to saporin (SAP; a ribosomal inactivating protein that binds to and inactivates ribosomes) was injected into the celiac ganglion to test the hypothesis that targeted ablation of mesenteric projecting sympathetic neurons reduces the pressor response to pain in conscious, spinal cord-transected rats. Nine Sprague-Dawley male rats underwent a spinal cord transection between thoracic vertebrae 4 and 5. Following recovery (5 wk), all rats were instrumented with a radio telemetry device for recording arterial pressure and bilateral catheters in the gluteus maximus muscles for the infusion of hypertonic saline (hNa+Cl?). Subsequently, the hemodynamic responses to intramuscular injection of hNa+Cl? (100 ?l and 250 ?l, in random order) were determined. Following the experiments in the no celiac ganglia injected condition (NGI), rats received injections of CTB-SAP (n = 5) or CTB (n = 3) into the celiac ganglia. CTB-SAP rats, compared with NGI and CTB rats, had reduced pressor responses to hNa+Cl?. Furthermore, the number of stained neurons in the celiac ganglia and spinal cord (segments T6–T12), was reduced in CTB-SAP rats. Thus, CTB-SAP retrogradely transported from the celiac ganglia is effective at ablating mesenteric projecting sympathetic neurons and reducing the pressor response to pain in spinal cord-transected rats. PMID:20219868

  19. Oral N-acetylcysteine reduces bleomycin-induced lung damage and mucin Muc5ac expression in rats.

    PubMed

    Mata, M; Ruíz, A; Cerdá, M; Martinez-Losa, M; Cortijo, J; Santangelo, F; Serrano-Mollar, A; Llombart-Bosch, A; Morcillo, E J

    2003-12-01

    Oxidative stress is involved in the pathogenesis of pulmonary fibrosis, therefore antioxidants may be of therapeutic value. Clinical work indicates that N-acetylcysteine (NAC) may be beneficial in this disease. The activity of this antioxidant was examined on bleomycin-induced lung damage, mucus secretory cells hyperplasia and mucin Muc5ac gene expression in rats. NAC (3 mmol x kg(-1) x day(-1)) or saline was given orally to Sprague-Dawley rats for 1 week prior to a single intratracheal instillation of bleomycin (2.5 U x kg(-1)) and for 14 days postinstillation. NAC decreased collagen deposition in bleomycin-exposed rats (hydroxyproline content was 4,257+/-323 and 3,200+/-192 microg x lung(-1) in vehicle- and NAC-treated rats, respectively) and lessened the fibrotic area assessed by morphometric analysis. The bleomycin-induced increases in lung tumour necrosis factor-alpha and myeloperoxidase activity were reduced by NAC treatment. The numbers of mucus secretory cells in airway epithelium, and the Muc5ac messenger ribonucleic acid and protein expression, were markedly augmented in rats exposed to bleomycin. These changes were significantly reduced in NAC-treated rats. These results indicate that bleomycin increases the number of airway secretory cells and their mucin production, and that oral N-acetylcysteine improved pulmonary lesions and reduced the mucus hypersecretion in the bleomycin rat model. PMID:14680076

  20. The CCKB antagonist CI988 reduces food intake in fasted rats via a dopamine mediated pathway.

    PubMed

    Frommelt, Lisa; Lembke, Vanessa; Hofmann, Tobias; Goebel-Stengel, Miriam; Mönnikes, Hubert; Wiedenmann, Bertram; Klapp, Burghard F; Stengel, Andreas; Kobelt, Peter

    2013-01-01

    Studies have shown a reduction of food intake following peripheral and brain injection of CCK. However, it remains to be established whether endogenous central CCK is involved in the regulation of food intake. We investigated the role of central CCK in the regulation of food intake by pharmacological manipulation of the CCK(B) (CCK(2)) receptor system. Intracerebroventricularly (ICV) cannulated male Sprague Dawley rats were fasted for 24h and received an ICV injection of the CCK(B) receptor antagonist CI988 at a dose of 10 nmol or 49 nmol or vehicle. Another group received two consecutive ICV injections consisting of the corticotropin-releasing factor (CRF) receptor-1 (CRF(1)) antagonist, CP376395 (3 nmol) or the CRF(2) receptor antagonist, K41498 (2 nmol) alone, or followed by CI988 (49 nmol). Lastly, another group of rats received an intraperitoneal (IP) injection of the dopamine antagonist, flupentixol (~197 and ~493nmol/kg) alone, or followed by CI988 (49 nmol, ICV). Cumulative food intake was assessed for 11h. Vehicle injected rats showed a robust feeding response. CI988 at 49 nmol reduced food intake by 30% starting at 2h post injection. CP376395 and K41498 had no effect on food intake. Flupentixol injected IP at a dose of 197 and 493 nmol/kg alone did not modulate food intake whereas the higher dose blocked the CI988-induced reduction of feeding. During the dark phase, CI988 had no effect on food intake in unfasted rats. In summary, CCK(B) signaling is involved in the regulation of food intake after a fast likely by downstream dopamine signaling. PMID:23200724

  1. D-Serine and D-Cycloserine Reduce Compulsive Alcohol Intake in Rats.

    PubMed

    Seif, Taban; Simms, Jeffrey A; Lei, Kelly; Wegner, Scott; Bonci, Antonello; Messing, Robert O; Hopf, F Woodward

    2015-09-01

    There is considerable interest in NMDAR modulators to enhance memory and treat neuropsychiatric disorders such as addiction, depression, and schizophrenia. D-serine and D-cycloserine, the NMDAR activators at the glycine site, are of particular interest because they have been used in humans without serious adverse effects. Interestingly, D-serine also inhibits some NMDARs active at hyperpolarized potentials (HA-NMDARs), and we previously found that HA-NMDARs within the nucleus accumbens core (NAcore) are critical for promoting compulsion-like alcohol drinking, where rats consume alcohol despite pairing with an aversive stimulus such as quinine, a paradigm considered to model compulsive aspects of human alcohol use disorders (AUDs). Here, we examined the impact of D-serine and D-cycloserine on this aversion-resistant alcohol intake (that persists despite adulteration with quinine) and consumption of quinine-free alcohol. Systemic D-serine reduced aversion-resistant alcohol drinking, without altering consumption of quinine-free alcohol or saccharin with or without quinine. Importantly, D-serine within the NAcore but not the dorsolateral striatum also selectively reduced aversion-resistant alcohol drinking. In addition, D-serine inhibited EPSCs evoked at -70?mV in vitro by optogenetic stimulation of mPFC-NAcore terminals in alcohol-drinking rats, similar to reported effects of the NMDAR blocker AP5. Further, D-serine preexposure occluded AP5 inhibition of mPFC-evoked EPSCs, suggesting that D-serine reduced EPSCs by inhibiting HA-NMDARs. Systemic D-cycloserine also selectively reduced intake of quinine-adulterated alcohol, and D-cycloserine inhibited NAcore HA-NMDARs in vitro. Our results indicate that HA-NMDAR modulators can reduce aversion-resistant alcohol drinking, and support testing of D-serine and D-cycloserine as immediately accessible, FDA-approved drugs to treat AUDs. PMID:25801502

  2. A Peptide to Reduce Pulmonary Edema in a Rat Model of Lung Transplantation

    PubMed Central

    Finsterwalder, Richard; Friedl, Heinz P.; Rauscher, Sabine; Gröger, Marion; Kocher, Alfred; Wagner, Christine; Wagner, Stephan N.; Fischer, Gottfried; Schultz, Marcus J.; Wiedemann, Dominik; Petzelbauer, Peter

    2015-01-01

    Background Despite significant advances in organ preservation, surgical techniques and perioperative care, primary graft dysfunction is a serious medical problem in transplantation medicine in general and a specific problem in patients undergoing lung transplantation. As a result, patients develop lung edema, causing reduced tissue oxygenation capacity, reduced lung compliance and increased requirements for mechanical ventilatory support. Yet, there is no effective strategy available to protect the grafted organ from stress reactions induced by ischemia/reperfusion and by the surgical procedure itself. Methods We assessed the effect of a cingulin-derived peptide, XIB13 or a random peptide in an established rat model of allogeneic lung transplantation. Donor lungs and recipients received therapeutic peptide at the time of transplantation and outcome was analyzed 100min and 28 days post grafting. Results XIB13 improved blood oxygenation and reduced vascular leak 100min post grafting. Even after 28 days, lung edema was significantly reduced by XIB13 and lungs had reduced fibrotic or necrotic zones. Moreover, the induction of an allogeneic T cell response was delayed indicating a reduced antigen exchange between the donor and the host. Conclusions In summary, we provide a new tool to strengthen endothelial barrier function thereby improving outcomes in lung transplantation. PMID:26536466

  3. Motor cortex electrical stimulation promotes axon outgrowth to brain stem and spinal targets that control the forelimb impaired by unilateral corticospinal injury

    PubMed Central

    Carmel, Jason B.; Kimura, Hiroki; Berrol, Lauren J.; Martin, John H.

    2012-01-01

    We previously showed that electrical stimulation of motor cortex (M1) after unilateral pyramidotomy in the rat increased corticospinal tract (CST) axon length, strengthened spinal connections, and restored forelimb function. Here, we tested: 1) if M1 stimulation only increases spinal axon length or if it also promotes connections to brain stem forelimb control centers, especially magnocellular red nucleus; and 2) if stimulation-induced increase in axon length depends on whether pyramidotomy denervated the structure. After unilateral pyramidotomy, we electrically stimulated the forelimb area of intact M1, to activate the intact CST and other corticofugal pathways, for 10 days. We anterogradely labeled stimulated M1 and measured axon length using stereology. Stimulation increased axon length in both the spinal cord and magnocellular red nucleus, even though the spinal cord is denervated by pyramidotomy and the red nucleus is not. Stimulation also promoted outgrowth in the cuneate and parvocellular red nuclei. In the spinal cord, electrical stimulation caused increased axon length ipsilateral, but not contralateral, to stimulation. Thus, stimulation promoted outgrowth preferentially to the sparsely corticospinal-innervated and impaired side. Outgrowth resulted in greater axon density in the ipsilateral dorsal horn and intermediate zone, resembling the contralateral termination pattern. Importantly, as in spinal cord, increase in axon length in brain stem also was preferentially directed towards areas less densely innervated by the stimulated system. Thus, M1 electrical stimulation promotes increases in corticofugal axon length to multiple M1 targets. We propose the axon length change was driven by competition into an adaptive pattern resembling lost connections. PMID:23360401

  4. Soyo-san reduces depressive-like behavior and proinflammatory cytokines in ovariectomized female rats

    PubMed Central

    2014-01-01

    Background Soyo-san is a traditional oriental medicinal formula, a mixture of 9 crude drugs, and it has been clinically used for treating mild depressive disorders. The role of pro- and anti-inflammatory cytokines in psychiatric disorders has been the focus of great research attention in recent years. In the present study, we detected the antidepressant effect of soyo-san in the ovariectomized and repeated stressed female rats. Methods This study was designed to evaluate the antidepressant-like effect of soyo-san on the forced swimming test (FST). The rats were randomly divided into the following groups: the nonoperated and nonstressed group (non-op), the nonoperated and stressed group (non-op?+?ST), the ovariectomized and stress group (OVX) and sham operated and stressed group (sham), the ovariectomized and stressed group (OVX?+?ST), the ovariectomized, stressed and soyo-san 100 mg/kg treated group (SOY100) and the ovariectomized, stressed and soyo-san 400 mg/kg treated group (SOY400). The rats were exposed to immobilization stress (IMO) for 14day (2 h/14day), and soyo-san (100 mg/kg and 400 mg/kg) was administrated during the same time. In the same animals, the levels of corticosterone and interleukin-1-beta (IL-1?) were examined in the serum. Also, the change of IL-1? expression in brain regions was examined after behavior test. Results In the FST, the lower dose (100 mg/kg) of extract was effective in reducing immobility, along with an increase in swimming time. The serum levels of corticosterone and IL-1? in the SOY groups were significantly lower than those in the control group. In the brain, the expression of IL-1? positive neurons in the control group were significantly increased in the paraventricular nucleus (PVN) and hippocampus compared to the non-op. However, soyo-san groups significantly reduced the IL-1?-ir neurons in the PVN and hippocampal regions compared to the control. Conclusion The present results demonstrated that soyo-san effectively reduced behavioral and patho-physiological depression-like responses. Trial registration: Our results suggest that soyo-san may be useful for immune regulator in repeated stress-induced ovariectomized female rats. PMID:24444307

  5. Saffron Reduced Toxic Effects of its Constituent, Safranal, in Acute and Subacute Toxicities in Rats

    PubMed Central

    Ziaee, Toktam; Razavi, Bibi Marjan; Hosseinzadeh, Hossein

    2014-01-01

    Background: Saffron and its constituents are widely used around the world as a spice and medicinal plant. Different constituents in medicinal herbs are thought to have the potential to induce useful and/or adverse effects. So, efforts have been made to find the best and most valuable tools to reduce their adverse effects. Objectives: According to Iranian traditional medicine (ITM), it is believed that administration of whole herbs exhibits more activity and fewer side effects than isolated constituents. Since toxicological studies have indicated that safranal is more toxic than other active components in saffron stigma, thus this study was undertaken to evaluate the effect of co-administration of saffron extract and safranal in acute and sub-acute toxicities in rats. Materials and Methods: In acute toxicity, rats received safranal (1.2 mL/kg, IP) plus saffron aqueous extract (25-100 mg/kg, IP). One and four days after the treatment, percentage of mortality was assessed. In subacute toxicity, rats were randomly divided into six groups. Group 1) safranal (0.2 mL/kg, IP), Groups 2, 3 and 4) safranal plus saffron aqueous extract (5, 10 and 20 mg/kg, IP) Groups 5 and 6) Paraffin and normal saline, as solvents of safranal and saffron aqueous extract, respectively. Treatments were continued for 21 days. For sub-acute toxicity, the percentages of lethality as well as some biochemical parameters were evaluated. Results: Our results showed that four days co-treatment of safranal and saffron significantly reduced mortality, so that the effect was more obvious in lower doses. Sub-acute toxicity studies showed that saffron could increase survival in rats so that no mortality was observed at dose of 10 mg/kg. Our data also indicated that the levels of triglyceride, BUN and ALT significantly increased after sub-acute interaperitoneal (IP) administration of safranal (0.2 mL/kg/day) and co-treatment of saffron aqueous extract (5 and 10 mg/kg) plus safranal significantly improved all toxic effects of safranal on biochemical parameters. Conclusions: The co-administration of saffron aqueous extract and safranal reduced toxic effects of safranal in acute and sub-acute toxicities. PMID:24644432

  6. Melatonin treatment reduces astrogliosis and apoptosis in rats with traumatic brain injury

    PubMed Central

    Babaee, Abdolreza; Eftekhar-Vaghefi, Seyed Hassan; Asadi-shekaari, Majid; Shahrokhi, Nader; Soltani, Samereh Dehghani; Malekpour-Afshar, Reza; Basiri, Mohsen

    2015-01-01

    Objective(s): Melatonin is known as an anti-inflammatory agent, and it has been proven to exert neuroprotection through inhibition of cell death (apoptosis) in several models of brain injury. Secondary injury following the primary traumatic brain injury (TBI) results in glial cells activation, especially astrocytes. In fact, astrocyte activation causes the production of pro-inflammatory cytokines that may lead to secondary injury. Since most TBI research studies have focused on injured neurons and paid little attention to glial cells, the aim of current study was to investigate the effects of melatonin against astrocytes activation (astrogliosis), as well as inhibition of apoptosis in brain tissue of male rats after TBI. Materials and Methods: The animals were randomly allocated into five groups: sham group, TBI+ vehicle group (1% ethanol in saline) and TBI+ melatonin groups (5 mg/kg, 10 mg/kg and 20 mg/kg). All rats were intubated and then exposed to diffuse TBI, except for the sham group. Immunohistochemical methods were conducted using glial fibrillary acidic protein (GFAP) marker and TUNEL assay to evaluate astrocyte reactivity and cell death, respectively. Results: The results showed that based on the number of GFAP positive astrocytes in brain cortex, astrogliosis was reduced significantly (P<0.05) in melatonin- treated groups (no dose dependent) compared to the vehicle group. Furthermore, based on TUNEL results, melatonin treatment considerably reduced the number of apoptotic cells (P<0.05). Conclusion: In total, the present findings suggest that melatonin treatment following TBI diminishes astrocyte reactivity and neuronal cells apoptosis in brain cortex in the rat model. PMID:26523219

  7. Alcohol Binge Drinking during Adolescence or Dependence during Adulthood Reduces Prefrontal Myelin in Male Rats

    PubMed Central

    Vargas, Wanette M.; Bengston, Lynn; Gilpin, Nicholas W.; Whitcomb, Brian W.

    2014-01-01

    Teen binge drinking is associated with low frontal white matter integrity and increased risk of alcoholism in adulthood. This neuropathology may result from alcohol exposure or reflect a pre-existing condition in people prone to addiction. Here we used rodent models with documented clinical relevance to adolescent binge drinking and alcoholism in humans to test whether alcohol damages myelinated axons of the prefrontal cortex. In Experiment 1, outbred male Wistar rats self-administered sweetened alcohol or sweetened water intermittently for 2 weeks during early adolescence. In adulthood, drinking behavior was tested under nondependent conditions or after dependence induced by 1 month of alcohol vapor intoxication/withdrawal cycles, and prefrontal myelin was examined 1 month into abstinence. Adolescent binge drinking or adult dependence induction reduced the size of the anterior branches of the corpus callosum, i.e., forceps minor (CCFM), and this neuropathology correlated with higher relapse-like drinking in adulthood. Degraded myelin basic protein in the gray matter medial to the CCFM of binge rats indicated myelin was damaged on axons in the mPFC. In follow-up studies we found that binge drinking reduced myelin density in the mPFC in adolescent rats (Experiment 2) and heavier drinking predicted worse performance on the T-maze working memory task in adulthood (Experiment 3). These findings establish a causal role of voluntary alcohol on myelin and give insight into specific prefrontal axons that are both sensitive to alcohol and could contribute to the behavioral and cognitive impairments associated with early onset drinking and alcoholism. PMID:25355229

  8. Aqueous Extract of Ipomoea batatas Reduces Food Intake in Male Wistar Rats: A Pilot Study

    PubMed Central

    Olubobokun, TH; Aluko, EO; Iyare, EE; Anyaehie, USB; Olatunbosun, ED; Aizenabor, GI

    2014-01-01

    Background: Food intake is regulated by the complex interaction of psychological and physiological events associated with ingestion. Food that increases short-term satiety decreases the amount of energy ingested subsequently and thus could potentially help in weight management in the long run. Potato, a common starchy tuber in our environment is believed to contain substances that can help maintain and increases short-term satiety. Aim: This study was conducted to determine the effect of the aqueous extract of sweet potato (Ipomoea batatas [IB]) on food intake in male Wistar rats. Materials and Methods: The sweet potato tubers were chopped into small pieces and homogenized in distilled water for 30 s. Homogenate was filtered through muslin cloth and then centrifuged at 120 rpm for 20 min. For use, the residue was evaporated to dryness. The dried extract was reconstituted in freshly prepared normal saline for administration to test animals. The 20 acclimatized male Wistar rats weighing 170-180 g were used for this study. The animals were randomly assigned into four groups of five rats each. Group 1 served as the control and was fed with 0.3 ml of normal saline while Groups 2-4 were fed with IB extract. Results: The results showed that in the extract-treated groups, the food intake was significantly reduced at P < 0.01 in a dose dependent manner when compared with the control group. Conclusion: Consumption of IB caused a reduction in food intake probably by reducing appetite and increasing satiety. PMID:25221722

  9. Alcohol binge drinking during adolescence or dependence during adulthood reduces prefrontal myelin in male rats.

    PubMed

    Vargas, Wanette M; Bengston, Lynn; Gilpin, Nicholas W; Whitcomb, Brian W; Richardson, Heather N

    2014-10-29

    Teen binge drinking is associated with low frontal white matter integrity and increased risk of alcoholism in adulthood. This neuropathology may result from alcohol exposure or reflect a pre-existing condition in people prone to addiction. Here we used rodent models with documented clinical relevance to adolescent binge drinking and alcoholism in humans to test whether alcohol damages myelinated axons of the prefrontal cortex. In Experiment 1, outbred male Wistar rats self-administered sweetened alcohol or sweetened water intermittently for 2 weeks during early adolescence. In adulthood, drinking behavior was tested under nondependent conditions or after dependence induced by 1 month of alcohol vapor intoxication/withdrawal cycles, and prefrontal myelin was examined 1 month into abstinence. Adolescent binge drinking or adult dependence induction reduced the size of the anterior branches of the corpus callosum, i.e., forceps minor (CCFM), and this neuropathology correlated with higher relapse-like drinking in adulthood. Degraded myelin basic protein in the gray matter medial to the CCFM of binge rats indicated myelin was damaged on axons in the mPFC. In follow-up studies we found that binge drinking reduced myelin density in the mPFC in adolescent rats (Experiment 2) and heavier drinking predicted worse performance on the T-maze working memory task in adulthood (Experiment 3). These findings establish a causal role of voluntary alcohol on myelin and give insight into specific prefrontal axons that are both sensitive to alcohol and could contribute to the behavioral and cognitive impairments associated with early onset drinking and alcoholism. PMID:25355229

  10. Reduced mechanical efficiency in left?ventricular trabeculae of the spontaneously hypertensive rat

    PubMed Central

    Han, June?Chiew; Tran, Kenneth; Johnston, Callum M.; Nielsen, Poul M. F.; Barrett, Carolyn J.; Taberner, Andrew J.; Loiselle, Denis S.

    2014-01-01

    Abstract Long?term systemic arterial hypertension, and its associated compensatory response of left?ventricular hypertrophy, is fatal. This disease leads to cardiac failure and culminates in death. The spontaneously hypertensive rat (SHR) is an excellent animal model for studying this pathology, suffering from ventricular failure beginning at about 18 months of age. In this study, we isolated left?ventricular trabeculae from SHR?F hearts and contrasted their mechanoenergetic performance with those from nonfailing SHR (SHR?NF) and normotensive Wistar rats. Our results show that, whereas the performance of the SHR?F differed little from that of the SHR?NF, both SHR groups performed less stress?length work than that of Wistar trabeculae. Their lower work output arose from reduced ability to produce sufficient force and shortening. Neither their heat production nor their enthalpy output (the sum of work and heat), particularly the energy cost of Ca2+ cycling, differed from that of the Wistar controls. Consequently, mechanical efficiency (the ratio of work to change of enthalpy) of both SHR groups was lower than that of the Wistar trabeculae. Our data suggest that in hypertension?induced left?ventricular hypertrophy, the mechanical performance of the tissue is compromised such that myocardial efficiency is reduced. PMID:25413328

  11. Red yeast rice repairs kidney damage and reduces inflammatory transcription factors in rat models of hyperlipidemia

    PubMed Central

    DING, MEI; SI, DAOYUAN; ZHANG, WENQI; FENG, ZHAOHUI; HE, MIN; YANG, PING

    2014-01-01

    Xuezhikang (XZK), an extract of red yeast rice, has been widely used for the management of hyperlipidemia and coronary heart disease (CHD); however, the effects of XZK treatment on kidney injury have not yet been fully identified. The aim of the current study was to evaluate the effects of XZK on the kidneys and investigate the related mechanisms in a rat model of hyperlipidemia. Thus, the effect on inflammatory transcription factors and kidney damage was investigated with in vitro and in vivo experiments on hyperlipidemic rats following XZK treatment. The results revealed that the plasma levels of total cholesterol (TC), triglycerides (TG) and low-density lipoprotein-cholesterol (LDL-C) were significantly decreased, while the levels of high-density lipoprotein-cholesterol (HDL-C) were significantly upregulated in the XZK treatment group, as compared with those in the hyperlipidemia group (P<0.05). In addition, the results demonstrated that XZK was able to repair the kidney damage caused by hyperlipidemia. Furthermore, the expression levels of the inflammatory transcription factors, tumor necrosis factor-? and interleukin-6, were shown to be reduced in the XZK group when compared with the hyperlipidemia group. In summary, XZK reduces kidney injury, downregulates the levels of TG, TC and LDL-C, as well as the expression levels of inflammatory transcription factors, and upregulates HDL-C. These results further the understanding of the molecular pathogenic mechanisms underlying hyperlipidemia and aid the development of XZK as an effective therapeutic agent for hyperlipidemia. PMID:25371725

  12. Reduced kynurenine aminotransferase-I activity in SHR rats may be due to lack of KAT-Ib activity.

    PubMed

    Kapoor, V; Thuruthyil, S J; Human, B

    1998-05-11

    Kynurenine aminotransferase I (KAT-I), which also shows glutamine transaminase K (GTK) activity, catalyses the conversion of kynurenine to kynurenic acid, an endogenous glutamate antagonist. Both the GTK and KAT enzyme activities were found to be significantly reduced in kidney, brain and medulla oblongata homogenates of spontaneously hypertensive (SHR) compared to Wistar-Kyoto (WKY) rats. Enzyme activity stains on native gel separations of partially purified kidney homogenates was associated with two major bands of GTK (KAT-I)-activity in WKY and Wistar rats, KAT-Ia and KAT-Ib. SHR rats however showed only KAT-Ia activity. These findings suggest that the absence of KAT-Ib activity may result in a reduced ability to synthesise kynurenic acid in SHR rats, this may help to explain the enhanced sensitivity to glutamate seen in this strain. PMID:9631442

  13. Clopidogrel reduces the inflammatory response of lung in a rat model of decompression sickness.

    PubMed

    Bao, Xiao-Chen; Chen, Hong; Fang, Yi-Qun; Yuan, Heng-Rong; You, Pu; Ma, Jun; Wang, Fang-Fang

    2015-06-01

    Inflammation and platelet activation are critical phenomena in the setting of decompression sickness. Clopidogrel (Clo) inhibits platelet activation and may also reduce inflammation. The goal of this study was to investigate if Clo had a protective role in decompression sickness (DCS) through anti-inflammation way. Male Sprague-Dawley rats (n=111) were assigned to three groups: control+vehicle group, DCS+vehicle, DCS+Clo group. The experimental group received 50 mg/kg of Clo or vehicle for 3 days, then compressed to 1,600 kPa (150 msw) in 28 s, maintained at 150 msw for 242 s and decompressed to surface at 3m/s. In a control experiment, rats were also treated with vehicle for 3 days and maintained at atmospheric pressure for an equivalent period of time. Clinical assessment took place over a period of 30 min after surfacing. At the end, blood samples were collected for blood cells counts and cytokine detection. The pathology and the wet/dry ratio of lung tissues, immunohistochemical detection of lung tissue CD41 expression, the numbers of P-selectin positive platelets and platelet-leukocyte conjugates in blood were tested. We found that Clo significantly reduced the DCS mortality risk (mortality rate: 11/45 with Clo vs. 28/46 in the untreated group, P<0.01). Clo reduced the lung injury, the wet/dry ratio of lung, the accumulation of platelet and leukocyte in lung, the fall in platelet count, the WBC count, the numbers of activated platelets and platelet-leukocyte complexes in peripheral blood. It was concluded that Clo can play a protective role in decompression sickness through reducing post-decompression platelet activation and inflammatory process. PMID:25784626

  14. Eribis peptide 94 reduces infarct size in rat hearts via activation of centrally located ? opioid receptors.

    PubMed

    Gross, Garrett J; Hsu, Anna; Nithipatikom, Kasem; Bobrova, Irina; Bissessar, Erik

    2012-02-01

    Eribis peptide 94 (EP 94) is a novel enkephalin derivative that binds with high potency to ? and ? opioid receptors with less affinity for the ? opioid receptor. This compound has recently been shown to produce an acute reduction in myocardial infarct size in the anesthetized pig and rat partially via an endothelial nitric oxide synthase and KATP channel-dependent mechanism. EP 94 also was found to produce a chronic reduction in infarct size 24 hours postdrug administration via the upregulation of inducible nitric oxide synthase in rats. Despite these findings, no data have emerged in which the opioid receptor subtype responsible for cardioprotection has been identified and the site of action, heart, other peripheral organs, or the central nervous system, has not been addressed. In the current study, EP 94, was administered in 2 divided doses (0.5 ?g/kg, intravenously) at 5 and 10 minutes into the ischemic period, and the opioid antagonists were administered 10 minutes before the onset of the 30-minute ischemic period. The selective antagonists used were the ? receptor antagonist CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2), the ? receptor antagonists naltrindole and BNTX (7-benzylidenenaltrexone), and the ? receptor antagonist nor-BNI (norbinaltorphimine). Surprisingly, only CTOP completely blocked the cardioprotective effect of EP 94, whereas naltrindole, BNTX, and nor-BNI had modest but nonsignificant effects. Because there is controversial evidence suggesting that ? receptors may be absent in the adult rat myocardium, it was hypothesized that the protective effect of EP 94 may be mediated by an action outside the heart, perhaps in the central nervous system. To test this hypothesis, rats were pretreated with the nonselective opioid antagonist, naloxone hydrochloride, which penetrates the blood-brain barrier or naloxone methiodide, the quaternary salt of naloxone hydrochloride, which does not penetrate the blood-brain barrier before EP 94 administration. In support of a central nervous system site of action for EP 94, naloxone hydrochloride completely blocked its cardioprotective effect, whereas naloxone methiodide had no effect. These results suggest that EP 94 reduces infarct size (expressed as a percent of the area at risk) in the rat primarily via activation of central ? opioid receptors. PMID:22130105

  15. Pyruvate administered to newborn rats with insulin-induced hypoglycemic brain injury reduces neuronal death and cognitive impairment.

    PubMed

    Zhou, Dong; Qian, Jing; Chang, Hong; Xi, Bo; Sun, Ruo-peng

    2012-01-01

    Based on previous studies, we had made a try to administer sodium pyruvate to newborn Wistar rats suffering repetitive and profound hypoglycemia, which can induce brain injury. Fluoro-Jade B was used to marked degenerative neurons 1 day after the third hypoglycemic insult, and Morris water navigation task was performed to assess cognitive function when the rats were 6 weeks old. We found that administration of sodium pyruvate to those rats whose hypoglycemia was terminated by dextrose can reduce neurodegeneration induced by hypoglycemia and improve the cognitive function. Supplementing sodium pyruvate with glucose to terminate severe neonatal hypoglycemia is an effective intervention. PMID:21603897

  16. Indomethacin administered early in the postnatal period results in reduced glomerular number in the adult rat.

    PubMed

    Kent, A L; Koina, M E; Gubhaju, L; Cullen-McEwen, L A; Bertram, J F; Lynnhtun, J; Shadbolt, B; Falk, M C; Dahlstrom, J E

    2014-11-15

    Indomethacin and ibuprofen are administered to close a patent ductus arteriosus (PDA) during active glomerulogenesis. Light and electron microscopic glomerular changes with no change in glomerular number were seen following indomethacin and ibuprofen treatment during glomerulogenesis at 14 days after birth in a neonatal rat model. This present study aimed to determine whether longstanding renal structural changes are present at 30 days and 6 mo (equivalent to human adulthood). Rat pups were administered indomethacin or ibuprofen antenatally on days 18-20 (0.5 mg·kg(-1)·dose(-1) indomethacin; 10 mg·kg(-1)·dose(-1) ibuprofen) or postnatally intraperitoneally from day 1 to 3 or day 1 to 5 (0.2 mg·kg(-1)·dose(-1) indomethacin; 10 mg·kg(-1)·dose(-1) ibuprofen). Control groups received no treatment or normal saline intraperitoneally. Pups were killed at 30 days of age and 6 mo of age. Tissue blocks from right kidneys were prepared for light and electron microscopic examination, while total glomerular number was determined in left kidneys using unbiased stereology. Eight pups were included in each group from 14 maternal rats. At 30 days and 6 mo, there were persistent electron microscopy abnormalities of the glomerular basement membrane in those receiving postnatal indomethacin and ibuprofen. There were no significant light microscopy findings at 30 days or 6 mo. At 6 mo, there were significantly fewer glomeruli in those receiving postnatal indomethacin but not ibuprofen (P = 0.003). In conclusion, indomethacin administered during glomerulogenesis appears to reduce the number of glomeruli in adulthood. Alternative options for closing a PDA should be considered including ibuprofen as well as emerging therapies such as paracetamol. PMID:25186294

  17. Detection of lameness and determination of the affected forelimb in lame horses by use of continuous wavelet transformation and neural network

    E-print Network

    Skubic, Marjorie

    1 Detection of lameness and determination of the affected forelimb in lame horses by use in horses. Animals--12 adult horses with mild lameness in the forelimbs. Procedure--Position of the head recordings without lameness, 8 recordings of horses with mild lameness of the right forelimb, and 8

  18. Reduced brown adipose tissue thermogenesis during environmental interactions in transgenic rats with ataxin-3-mediated ablation of hypothalamic orexin neurons.

    PubMed

    Mohammed, Mazher; Ootsuka, Youichirou; Yanagisawa, Masashi; Blessing, William

    2014-10-15

    Thermogenesis in brown adipose tissue (BAT) contributes to substantial increases in body temperature evoked by threatening or emotional stimuli. BAT thermogenesis also contributes to increases in body temperature that occur during active phases of the basic rest-activity cycle (BRAC), as part of normal daily life. Hypothalamic orexin-synthesizing neurons influence many physiological and behavioral variables, including BAT and body temperature. In conscious unrestrained animals maintained for 3 days in a quiet environment (24-26°C) with ad libitum food and water, we compared temperatures in transgenic rats with ablation of orexin neurons induced by expression of ataxin-3 (Orx_Ab) with wild-type (WT) rats. Both baseline BAT temperature and baseline body temperature, measured at the onset of BRAC episodes, were similar in Orx_Ab and WT rats. The time interval between BRAC episodes was also similar in the two groups. However, the initial slopes and amplitudes of BRAC-related increases in BAT and body temperature were reduced in Orx_Ab rats. Similarly, the initial slopes and amplitudes of the increases in BAT temperatures induced by sudden exposure to an intruder rat (freely moving or confined to a small cage) or by sudden exposure to live cockroaches were reduced in resident Orx_Ab rats. Constriction of the tail artery induced by salient alerting stimuli was also reduced in Orx_Ab rats. Our results suggest that orexin-synthesizing neurons contribute to the intensity with which rats interact with the external environment, both when the interaction is "spontaneous" and when the interaction is provoked by threatening or salient environmental events. PMID:25324552

  19. Fenofibrate--a lipid-lowering drug--reduces voluntary alcohol drinking in rats.

    PubMed

    Karahanian, Eduardo; Quintanilla, Maria Elena; Fernandez, Katia; Israel, Yedy

    2014-11-01

    The administration of disulfiram raises blood acetaldehyde levels when ethanol is ingested, leading to an aversion to alcohol. This study was aimed at assessing the effect of fenofibrate on voluntary ethanol ingestion in rats. Fenofibrate reduces blood triglyceride levels by increasing fatty acid oxidation by liver peroxisomes, along with an increase in the activity of catalase, which can oxidize ethanol to acetaldehyde. UChB drinker rats were allowed to consume alcohol 10% v/v freely for 60 days, until consumption stabilized at around 7 g ethanol/kg/24 h. About 1-1.2 g ethanol/kg of this intake is consumed in the first 2 h of darkness of the circadian cycle. Fenofibrate subsequently administered (50 mg/kg/day by mouth [p.o.]) for 14 days led to a 60-70% (p < 0.001) reduction of 24-h ethanol consumption. When ethanol intake was determined within the first 2 h of darkness, the reduction was 85-90% (p < 0.001). We determined whether animals chronically allowed access to ethanol and subsequently treated with fenofibrate, would a) increase liver catalase activity, and b) increase blood acetaldehyde levels after a 24-h ethanol deprivation and the subsequent administration of 1 g ethanol/kg. The oral administration of 1 g ethanol/kg produced a rapid increase in blood (arterial) acetaldehyde in fenofibrate-treated animals versus controls also administered 1 g/kg ethanol (70 ?M vs. 7 ?M; p < 0.001). Liver catalase activity following fenofibrate treatment was increased 3-fold (p < 0.01). Other hepatic enzymes responsible for the metabolism of ethanol (alcohol dehydrogenase and aldehyde dehydrogenase) remained unchanged. No liver damage was induced, as measured by serum glutamic-pyruvic transaminase (GPT) activity. The effect of fenofibrate in reducing alcohol intake was fully reversible. Overall, in rats allowed chronic ethanol intake, by mouth (p.o.), fenofibrate administration increased liver catalase activity and reduced voluntary ethanol intake. The administration of 1 g ethanol/kg (p.o.) to these animals increased blood acetaldehyde levels in fenofibrate-treated animals, suggesting the possible basis for the reduction in ethanol intake. PMID:25241056

  20. Prenatal ethanol exposure reduces the effects of excitatory amino acids in the rat hippocampus

    SciTech Connect

    Noble, E.P.; Ritchie, T. )

    1989-01-01

    Chronic alcohol ingestion during pregnancy can lead to the Fetal Alcohol Syndrome (FAS), a disorder marked by learning disabilities. A rat model of FAS was used by introducing pregnant Sprague-Dawley rats to a liquid diet containing 35% ethanol-derived calories (E), while a second group was pair-fed an isocaloric liquid diet without ethanol (P). A third group of pregnant dams received ad libitum lab chow (C). At parturition, pups from the E and P groups were cross fostered by C mothers and all groups received lab chow. During adulthood, male offspring were sacrificed and hippocampal and prefrontal cortical slices were prelabeled with (3H)inositol. Phosphoinositide (PI) hydrolysis was determined by measuring the accumulation of (3H)inositol phosphates in the presence of LiCl in response to activation of various excitatory amino acid (EAA) receptors. In hippocampal slices, ibotenate- and quisqualate-induced PI hydrolysis was reduced in E compared to P and C animals. Moreover, the inhibitory effect of N-methyl-D-aspartate (NMDA) on carbachol-induced PI hydrolysis, evident in P and C animals, was completely abolished in the hippocampus of E animals. In contrast, in the prefrontal cerebral cortex, this inhibitory effect of NMDA prevailed even in the E animals. The evidence suggests that prenatal ethanol exposure alters the activity of EAA receptors in the hippocampal generation of 2nd messengers.

  1. Strontium ranelate reduces cartilage degeneration and subchondral bone remodeling in rat osteoarthritis model

    PubMed Central

    Yu, De-gang; Ding, Hui-feng; Mao, Yuan-qing; Liu, Ming; Yu, Bo; Zhao, Xin; Wang, Xiao-qing; Li, Yang; Liu, Guang-wang; Nie, Shao-bo; Liu, Shen; Zhu, Zhen-an

    2013-01-01

    Aim: To investigate whether strontium ranelate (SR), a new antiosteoporotic agent, could attenuate cartilage degeneration and subchondral bone remodeling in osteoarthritis (OA). Methods: Medial meniscal tear (MMT) operation was performed in adult SD rats to induce OA. SR (625 or 1800 mg·kg?1·d?1) was administered via gavage for 3 or 6 weeks. After the animals were sacrificed, articular cartilage degeneration was evaluated using toluidine blue O staining, SOX9 immunohistochemistry and TUNEL assay. The changes in microarchitecture indices and tissue mineral density (TMD), chemical composition (mineral-to-collagen ratio), and intrinsic mechanical properties of the subchondral bones were measured using micro-CT scanning, confocal Raman microspectroscopy and nanoindentation testing, respectively. Results: The high-dose SR significantly attenuated cartilage matrix and chondrocyte loss at 6 weeks, and decreased chondrocyte apoptosis, improved the expression of SOX9, a critical transcription factor responsible for the expression of anabolic genes type II collagen and aggrecan, at both 3 and 6 weeks. Meanwhile, the high-dose SR also significantly attenuated the subchondral bone remodeling at both 3 and 6 weeks, as shown by the improved microarchitecture indices, TMD, mineral-to-collagen ratio and intrinsic mechanical properties. In contrast, the low-dose SR did not significantly change all the detection indices of cartilage and bone at both 3 and 6 weeks. Conclusion: The high-dose SR treatment can reduce articular cartilage degeneration and subchondral bone remodeling in the rat MMT model of OA. PMID:23334238

  2. A novel chemically modified curcumin reduces severity of experimental periodontal disease in rats: initial observations.

    PubMed

    Elburki, Muna S; Rossa, Carlos; Guimaraes, Morgana R; Goodenough, Mark; Lee, Hsi-Ming; Curylofo, Fabiana A; Zhang, Yu; Johnson, Francis; Golub, Lorne M

    2014-01-01

    Tetracycline-based matrix metalloproteinase- (MMP-) inhibitors are currently approved for two inflammatory diseases, periodontitis and rosacea. The current study addresses the therapeutic potential of a novel pleiotropic MMP-inhibitor not based on an antibiotic. To induce experimental periodontitis, endotoxin (LPS) was repeatedly injected into the gingiva of rats on one side of the maxilla; the contralateral (control) side received saline injections. Two groups of rats were treated by daily oral intubation with a chemically modified curcumin, CMC 2.24, for two weeks; the control groups received vehicle alone. After sacrifice, gingiva, blood, and maxilla were collected, the jaws were defleshed, and periodontal (alveolar) bone loss was quantified morphometrically and by ?-CT scan. The gingivae were pooled per experimental group, extracted, and analyzed for MMPs (gelatin zymography; western blot) and for cytokines (e.g., IL-1?; ELISA); serum and plasma samples were analyzed for cytokines and MMP-8. The LPS-induced pathologically excessive bone loss was reduced to normal levels based on either morphometric (P = 0.003) or ?-CT (P = 0.008) analysis. A similar response was seen for MMPs and cytokines in the gingiva and blood. This initial study, on a novel triketonic zinc-binding CMC, indicates potential efficacy on inflammatory mediators and alveolar bone loss in experimental periodontitis and warrants future therapeutic and pharmacokinetic investigations. PMID:25104884

  3. Photoacoustic detection of functional responses in the motor cortex of awake behaving monkey during forelimb movement

    E-print Network

    Jo, Janggun; Zhang, Hongyu; Cheney, Paul D.; Yang, Xinmai

    2012-10-22

    Photoacoustic (PA) imaging was applied to detect the neuronal activity in the motor cortex of an awake, behaving monkey during forelimb movement. An adult macaque monkey was trained to perform a reach-to-grasp task while PA images were acquired...

  4. Muscular reconstruction and functional morphology of the forelimb of early Miocene sloths (Xenarthra, Folivora) of Patagonia.

    PubMed

    Toledo, Néstor; Bargo, M Susana; Vizcaíno, Sergio F

    2013-02-01

    Early Miocene sloths are represented by a diversity of forms ranging from 38 to 95 kg, being registered mainly from Santacrucian Age deposits in southern-most shores of Patagonia, Argentina. Their postcranial skeleton differs markedly in shape from those of their closest living relatives (arboreal forms of less than 10 kg), Bradypus and Choloepus. In order to gain insight on functional properties of the Santacrucian sloths forelimb, musculature was reconstructed and a comparative, qualitative morphofunctional analysis was performed, allowing proposing hypotheses about biological role of the limb in substrate preferences, and locomotor strategies. The anatomy of the forelimb of Santacrucian sloths resembles more closely extant anteaters such as Tamandua and Myrmecophaga, due to the robustness of the elements, development of features related to attachment of ligaments and muscles, and conservative, pentadactylous, and strong-clawed manus. The reconstructed forelimb musculature was very well developed and resembles that of extant Pilosa (especially anteaters), although retaining the basic muscular configuration of generalized mammals. This musculature allowed application of powerful forces, especially in adduction of the forelimb, flexion and extension of the antebrachium, and manual prehension. These functional properties are congruent with both climbing and digging activities, and provide support for proposed Santacrucian sloths as good climbing mammals, possibly arboreal or semiarboreal, being also capable diggers. Their climbing strategies were limited, thus these forms relied mainly on great muscular strength and curved claws of the manus to move cautiously on branches. PMID:23193102

  5. Population Coding of Forelimb Joint Kinematics by Peripheral Afferents in Monkeys

    E-print Network

    Kawato, Mitsuo

    Population Coding of Forelimb Joint Kinematics by Peripheral Afferents in Monkeys Tatsuya Umeda1 Sciences (NINS), Okazaki, Japan, 2 Department of Neurophysiology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan, 3 PRESTO, Japan Science and Technology Agency

  6. Comparative Myology of the Forelimb of Squirrels (Sciuridae) RICHARD W. THORINGTON, JR.,* KAROLYN DARROW,

    E-print Network

    Miller, Scott

    , representing the Pteromyinae (flying squirrels) and all 7 tribes of the Sciurinae (tree and ground squirrels in the shoulder and forearm. The forelimb anatomy of flying squirrels is the most derived and differs from in 19 genera and 25 species, including 6 genera of flying squirrels and representatives of all 7

  7. Reduced impact of emotion on choice behavior in presymptomatic BACHD rats, a transgenic rodent model for Huntington Disease.

    PubMed

    Adjeroud, Najia; Yagüe, Sara; Yu-Taeger, Libo; Bozon, Bruno; Leblanc-Veyrac, Pascale; Riess, Olaf; Allain, Philippe; Nguyen, Huu Phuc; Doyère, Valérie; El Massioui, Nicole

    2015-11-01

    Executive dysfunction and psychiatric symptoms are hallmarks of Huntington disease (HD), a neurodegenerative disorder genetically characterized by expanded CAG repeats in the HTT gene. Using the BACHD rat model of HD (97 CAG-CAA repeats), the present research seeks to characterize the progressive emergence of decision-making impairments in a rat version of the Iowa Gambling Task (RGT) and the impact of emotional modulation, whether positive or negative, on choice behavior. The choice efficiency shown both by WT rats (independent of their age) and the youngest BACHD rats (2 and 8months old) evidenced that they are able to integrate outcomes of past decisions to determine expected reward values for each option. However, 18months old BACHD rats made fewer choices during the RGT session and were less efficient in choosing advantageous options than younger animals. Presenting either chocolate pellets or electrical footshocks half-way through a second RGT session reduced exploratory activity (inefficient nose-poking) and choices with a weaker effect on BACHD animals than on WT. Choice efficiency was left intact in transgenic rats. Our results bring new knowledge on executive impairments and impact of emotional state on decision-making at different stages of the disease, increasing the face-validity of the BACHD rat model. PMID:26463506

  8. Efficacy of hand-broadcast application of baits containing 0.005% diphacinone in reducing rat populations in Hawaiian forests

    USGS Publications Warehouse

    Foote, David; Lindsey, Gerald D.; Perry, Charlotte F.; Spurr, Eric

    2013-01-01

    Introduced black rats (Rattus rattus), Polynesian rats (R. exulans/i>), and Norway rats (R. norvegicus) impact insular bird, plant, and invertebrate populations worldwide. We investigated the efficacy of hand-broadcast application of Ramik® Green containing 0.005% diphacinone for rodent control in paired 4-ha treatment and non-treatment plots in both wet and mesic forest in Hawai?i. Radio telemetry of black rats, the predominant species, indicated 100% mortality in both treatment plots within about one week of bait application. Live trapping and non-toxic census bait block monitoring two to four weeks after each of 12 repeat bait applications in the wet forest, and three repeat bait applications in the mesic forest, indicated rat abundance was reduced on average by 84–88%. However, reinvasion could have occurred within this time. Rat populations in the treatment plots usually recovered to pre-poison levels within two to five months. House mice (Mus musculus), Indian mongooses (Herpestes auropunctatus), and feral cats (Felis catus) also ate bait or other animals that had eaten bait. This study demonstrates the efficacy of ground-based broadcast toxicant baits for the control of rats in Hawaiian montane wet forests.

  9. Reversal of islet GIP receptor down-regulation and resistance to GIP by reducing hyperglycemia in the Zucker rat

    SciTech Connect

    Piteau, Shalea; Olver, Amy; Kim, Su-Jin; Winter, Kyle; Pospisilik, John Andrew; Lynn, Francis; Manhart, Susanne; Demuth, Hans-Ulrich; Speck, Madeleine; Pederson, Raymond A.; McIntosh, Christopher H.S.

    2007-11-03

    In type 2 diabetes (T2DM) {beta}-cell responsiveness to glucose-dependent insulinotropic polypeptide (GIP) is reduced. In a model of T2DM, the VDF Zucker rat, GIP receptor mRNA and protein levels were shown to be down-regulated. Possible restoration of responsiveness to GIP in Zucker rats by reducing hyperglycemia has been examined. ZDF rats with extreme hyperglycemia demonstrated greater islet GIP receptor mRNA down-regulation (94.3 {+-} 3.8%) than ZF rats (48.8 {+-} 22.8%). GIP receptor mRNA levels in ZDF rats returned to 83.0 {+-} 17.9% of lean following normalization of hyperglycemia by phlorizin treatment and pancreas perfusions demonstrated markedly improved GIP responsiveness. Treatment of VDF rats with a DP IV inhibitor (P32/98) resulted in improved glucose tolerance and restored sensitivity to GIP in isolated pancreata. These findings support the proposal that GIP receptor down-regulation in rodent T2DM is secondary to chronic hyperglycemia and that normalization of glycemia can restore GIP sensitivity.

  10. Reduced sleep, stress responsivity, and female sex contribute to persistent inflammation-induced mechanical hypersensitivity in rats.

    PubMed

    Page, Gayle G; Opp, Mark R; Kozachik, Sharon L

    2014-08-01

    Studies in humans suggest that female sex, reduced sleep opportunities and biological stress responsivity increase risk for developing persistent pain conditions. To investigate the relative contribution of these three factors to persistent pain, we employed the Sciatic Inflammatory Neuritis (SIN) model of repeated left sciatic perineurial exposures to zymosan, an inflammatory stimulus, to determine their impact upon the development of persistent mechanical hypersensitivity. Following an initial moderate insult, a very low zymosan dose was infused daily for eight days to model a sub-threshold inflammatory perturbation to which only susceptible animals would manifest or maintain mechanical hypersensitivity. Using Sprague Dawley rats, maintaining wakefulness throughout the first one-half of the 12-h light phase resulted in a bilateral reduction in paw withdrawal thresholds (PWTs); zymosan infusion reduced ipsilateral PWTs in all animals and contralateral PWTs only in females. This sex difference was validated in Fischer 344, Lewis and Sprague Dawley rats, suggesting that females are the more susceptible phenotype for both local and centrally driven responses to repeated low-level inflammatory perturbations. Hypothalamic-pituitary-adrenal (HPA) axis hyporesponsive Lewis rats exhibited the most robust development of mechanical hypersensitivity and HPA axis hyperresponsive Fischer 344 rats matched the Lewis rats' mechanical hypersensitivity throughout the latter four days of the protocol. If HPA axis phenotype does indeed influence these findings, the more balanced responsivity of Sprague Dawley rats would seem to promote resilience in this paradigm. Taken together, these findings are consistent with what is known regarding persistent pain development in humans. PMID:24594386

  11. Calcium montmorillonite clay reduces urinary biomarkers of fumonisin B? exposure in rats and humans.

    PubMed

    Robinson, A; Johnson, N M; Strey, A; Taylor, J F; Marroquin-Cardona, A; Mitchell, N J; Afriyie-Gyawu, E; Ankrah, N A; Williams, J H; Wang, J S; Jolly, P E; Nachman, R J; Phillips, T D

    2012-01-01

    Fumonisin B? (FB?) is often a co-contaminant with aflatoxin (AF) in grains and may enhance AF's carcinogenicity by acting as a cancer promoter. Calcium montmorillonite (i.e. NovaSil, NS) is a possible dietary intervention to help decrease chronic aflatoxin exposure where populations are at risk. Previous studies show that an oral dose of NS clay was able to reduce AF exposure in a Ghanaian population. In vitro analyses from our laboratory indicated that FB? (like aflatoxin) could also be sorbed onto the surfaces of NS. Hence, our objectives were to evaluate the efficacy of NS clay to reduce urinary FB? in a rodent model and then in a human population highly exposed to AF. In the rodent model, male Fisher rats were randomly assigned to either FB? control, FB??+?2% NS or absolute control group. FB? alone or with clay was given as a single dose by gavage. For the human trial, participants received NS (1.5 or 3?g?day?¹) or placebo (1.5?g?day?¹) for 3 months. Urines from weeks 8 and 10 were collected from the study participants for analysis. In rats, NS significantly reduced urinary FB? biomarker by 20% in 24?h and 50% after 48?h compared to controls. In the humans, 56% of the urine samples analysed (n?=?186) had detectable levels of FB?. Median urinary FB? levels were significantly (p?90% in the high dose NS group (3?g?day?¹) compared to the placebo. This work indicates that our study participants in Ghana were exposed to FB? (in addition to AFs) from the diet. Moreover, earlier studies have shown conclusively that NS reduces the bioavailability of AF and the findings from this study suggest that NS clay also reduces the bioavailability FB?. This is important since AF is a proven dietary risk factor for hepatocellular carcinoma (HCC) in humans and FB? is suspected to be a dietary risk factor for HCC and oesophageal cancer in humans. PMID:22324939

  12. Diet induced obesity in rats reduces NHE3 and Na(+) /K(+) -ATPase expression in the kidney.

    PubMed

    Briffa, J F; Grinfeld, E; Jenkin, K A; Mathai, M L; Poronnik, P; McAinch, A J; Hryciw, D H

    2015-10-01

    The consumption of a high fat diet (HFD) is associated with proteinuria and altered sodium handling and excretion, which can lead to kidney disease. In the proximal tubule, the Na(+) /H(+) Exchanger 3 (NHE3) is responsible for normal protein reabsorption and the reabsorption of approximately 70% of the renal sodium load. It is the Na(+) /K(+) -ATPase that provides the driving force for the reabsorption of sodium and its exit across the basolateral membrane. This study investigates the effects that consumption of a HFD for 12 weeks has on NHE3 and Na(+) /K(+) -ATPase expression in the kidney. Western blot analysis identified a significant reduction in NHE3 and its modulator, phosphorylated protein kinase B, in renal lysate from obese rats. In the obese rats, a reduction in NHE3 expression in the proximal tubule may impact on the acidification of endosomes which are responsible for albumin uptake, suggesting a key role for the exchanger in protein endocytosis in obesity. Western blot analysis identified a reduction in Na(+) /K(+) -ATPase which could also potentially impact on albumin uptake and sodium reabsorption. This study demonstrates that consumption of a HFD for 12 weeks reduces renal NHE3 and Na(+) /K(+) -ATPase expression, an effect that may contribute to the albuminuria associated with obesity. Furthermore the reduction in these transporters is not likely to contribute to the reduced sodium excretion in obesity. These data highlight a potential link between NHE3 and Na(+) /K(+) -ATPase in the pathophysiological changes in renal protein handling observed in obesity. PMID:26173747

  13. Bexarotene Reduces Blood-Brain Barrier Permeability in Cerebral Ischemia-Reperfusion Injured Rats

    PubMed Central

    Xu, Lu; Cao, Fang; Xu, Feng; He, Baicheng; Dong, Zhi

    2015-01-01

    Background Matrix metalloproteinase-9 (MMP-9) over-expression disrupts the blood-brain barrier (BBB) in the ischemic brain. The retinoid X receptor agonist bexarotene suppresses MMP-9 expression in endothelial cells and displays neuroprotective effects. Therefore, we hypothesized that bexarotene may have a beneficial effect on I/R-induced BBB dysfunction. Methods A total of 180 rats were randomized into three groups (n = 60 each): (i) a sham-operation group, (ii) a cerebral ischemia-reperfusion (I/R) group, and (iii) an I/R+bexarotene group. Brain water content was measured by the dry wet weight method. BBB permeability was analyzed by Evans Blue staining and the magnetic resonance imaging contrast agent Omniscan. MMP-9 mRNA expression, protein expression, and activity were assessed by reverse transcription polymerase chain reaction, Western blotting, and gelatin zymography, respectively. Apolipoprotein E (apoE), claudin-5, and occludin expression were analyzed by Western blotting. Results After 24 h, 48 h, and 72 h post-I/R, several effects were observed with bexarotene administration: (i) brain water content and BBB permeability were significantly reduced; (ii) MMP-9 mRNA and protein expression as well as activity were significantly decreased; (iii) claudin-5 and occludin expression were significantly increased; and (iv) apoE expression was significantly increased. Conclusions Bexarotene decreases BBB permeability in rats with cerebral I/R injury. This effect may be due in part to bexarotene’s upregulation of apoE expression, which has been previously shown to reduce BBB permeability through suppressing MMP-9-mediated degradation of the tight junction proteins claudin-5 and occludin. This work offers insight to aid future development of therapeutic agents for cerebral I/R injury in human patients. PMID:25844636

  14. Chewing reduces sympathetic nervous response to stress and prevents poststress arrhythmias in rats.

    PubMed

    Koizumi, So; Minamisawa, Susumu; Sasaguri, Kenichi; Onozuka, Minoru; Sato, Sadao; Ono, Yumie

    2011-10-01

    Reducing stress is important in preventing sudden death in patients with cardiovascular disease, as stressful events may cause autonomic imbalance and trigger fatal arrhythmias. Since chewing has been shown to inhibit stress-induced neuronal responses in the hypothalamus, we hypothesized that chewing could ameliorate stress-induced autonomic imbalance and prevent arrhythmias. To test this hypothesis, we analyzed changes in radiotelemetered electrocardiograms in rats that were allowed to chew a wooden stick during a 1-h period of immobilization stress. Chewing significantly reduced the occurrence of ventricular premature beats (VPBs) and complex ventricular ectopy after immobilization and prevented stress-induced prolongation of the QT interval of VPBs throughout the 10-h experimental period. It also prevented prolongation of the QRS complex and fluctuations in the QT interval in normal sinus rhythm beats preceding VPBs during both immobilization and in the poststress period. Fast Fourier transform-based spectral analysis of heart-rate variability further showed that chewing significantly inhibited the stress-induced increase in the power ratio of low-to-high frequency activity (LF/HF: a marker of sympathetic activity) during immobilization and in addition was associated with blunting of the stress-induced increase in plasma noradrenaline observed at the termination of immobilization. Similar suppressive effects on the occurrence of VPBs and the LF/HF were observed in rats that were administered the ?-adrenergic blocker propranolol before immobilization. These results indicate that chewing can ameliorate sympathetic hyperactivity during stress and prevent poststress arrhythmias and suggest that chewing may provide a nonpharmacological and cost-effective treatment option for patients with a high risk of stress-induced fatal arrhythmia. PMID:21821783

  15. Dehydration-Induced Anorexia Reduces Astrocyte Density in the Rat Corpus Callosum

    PubMed Central

    Reyes-Haro, Daniel; Labrada-Moncada, Francisco Emmanuel; Miledi, Ricardo; Martínez-Torres, Ataúlfo

    2015-01-01

    Anorexia nervosa is an eating disorder associated with severe weight loss as a consequence of voluntary food intake avoidance. Animal models such as dehydration-induced anorexia (DIA) mimic core features of the disorder, including voluntary reduction in food intake, which compromises the supply of energy to the brain. Glial cells, the major population of nerve cells in the central nervous system, play a crucial role in supplying energy to the neurons. The corpus callosum (CC) is the largest white matter tract in mammals, and more than 99% of the cell somata correspond to glial cells in rodents. Whether glial cell density is altered in anorexia is unknown. Thus, the aim of this study was to estimate glial cell density in the three main regions of the CC (genu, body, and splenium) in a murine model of DIA. The astrocyte density was significantly reduced (~34%) for the DIA group in the body of the CC, whereas in the genu and the splenium no significant changes were observed. DIA and forced food restriction (FFR) also reduced the ratio of astrocytes to glial cells by 57.5% and 22%, respectively, in the body of CC. Thus, we conclude that DIA reduces astrocyte density only in the body of the rat CC. PMID:26090235

  16. Chandelier cartridges in the prefrontal cortex are reduced in isolation reared rats.

    PubMed

    Bloomfield, Claire; French, Sarah J; Jones, Declan N C; Reavill, Charlie; Southam, Eric; Cilia, Jackie; Totterdell, Susan

    2008-08-01

    Chandelier neurons are a subset of parvalbumin containing cortical interneurons characterised by their preferential targeting of the axon initial segments of pyramidal neurons. They have been the focus of recent interest after evidence that the arrays of boutons are reduced in the prefrontal cortex of schizophrenic patients, post mortem. Since one chandelier neuron may innervate the axon initial segments of several hundred pyramidal neurons, it is hypothesized that their special connectivity might facilitate synchronisation of cortical outputs and play a key role in working memory. Disruption in their function is therefore thought to play a potentially important role in cortically associated symptoms of schizophrenia. Using the isolation rearing animal model of schizophrenia, we examined immunolabelling for GABA-transporter 1, a marker of chandelier cartridges. We show that the numbers of arrays of chandelier axons are reduced by 36% in the ventral prelimbic cortex of isolation-reared rats, compared with their socially-housed litter mates. This mimics findings in the PFC of schizophrenic patients where GAT-1-positive cartridges are reduced by 40% and is the first study to demonstrate changes in chandelier cartridges in an animal model of schizophrenia. PMID:18512213

  17. Potent NK1 antagonism by SR-140333 reduces rat colonic secretory response to immunocyte activation.

    PubMed

    Moriarty, D; Selve, N; Baird, A W; Goldhill, J

    2001-04-01

    The potent neurokinin receptor 1 (NK1) antagonist SR-140333 has previously been shown to reduce castor oil-induced secretion in animal models. The importance of tachykinins in neuroimmune control of secretion and the effect of SR-140333 on key points in this pathway were elucidated in the present study to determine the type of intestinal dysfunction best targeted by this antagonist. Rat colonic secretion and substance P (SP) release were determined in vitro with the use of Ussing chamber and enzyme immunoassay techniques. NK1 receptors played a secretory role as receptor agonists stimulated secretion and SR-140333 antagonized the response to SP response (pK(b) = 9.2). Sensory fiber stimulation released SP and evoked a large secretion that was reduced by 69% in the presence of SR-140333 (10 nM). Likewise, mastocytes also released SP. The subsequent secretory response was reduced by 43% in the presence of SR-140333 (50 nM). SP was also released from granulocytes; however, this did not cause secretion. Functional NK3 receptors were present in the colon as senktide stimulated secretion, an effect that was increased during stress. We conclude that NK3 receptors may play a role in stress-related disorders, whereas NK1 receptors are more important in mast cell/afferent-mediated secretion. PMID:11245602

  18. From fish to modern humans – comparative anatomy, homologies and evolution of the pectoral and forelimb musculature

    PubMed Central

    Diogo, R; Abdala, V; Aziz, M A; Lonergan, N; Wood, B A

    2009-01-01

    In a recent study Diogo & Abdala [(2007) JMorphol268, 504–517] reported the results of the first part of a research project on the comparative anatomy, homologies and evolution of the pectoral muscles of osteichthyans (bony fish and tetrapods). That report mainly focused on actinopterygian fish but also compared these fish with certain non-mammalian sarcopterygians. This study, which reports the second part of the research project, focuses mainly on sarcopterygians and particularly on how the pectoral and forelimb muscles have evolved during the transitions from sarcopterygian fish and non-mammalian tetrapods to monotreme and therian mammals and humans. The data obtained by our own dissections of all the pectoral and forelimb muscles of representative members of groups as diverse as sarcopterygian fish, amphibians, reptiles, monotremes and therian mammals such as rodents, tree-shrews, colugos and primates, including humans, are compared with the information available in the literature. Our observations and comparisons clearly stress that, with regard to the number of pectoral and forelimb muscles, the most striking transition within sarcopterygian evolutionary history was that leading to the origin of tetrapods. Whereas extant sarcopterygian fish have an abductor and adductor of the fin and a largely undifferentiated hypaxial and epaxial musculature, extant salamanders such as Ambystoma have more than 40 pectoral and forelimb muscles. There is no clear increase in the number of pectoral and forelimb muscles within the evolutionary transition that led to the origin of mammals and surely not to that leading to the origin of primates and humans. PMID:19438764

  19. Consistent features in the forelimb representation of primary motor cortex in rhesus macaques.

    PubMed

    Park, M C; Belhaj-Saïf, A; Gordon, M; Cheney, P D

    2001-04-15

    The purpose of this study was to systematically map the forelimb area of primary motor cortex (M1) in rhesus macaques in an effort to investigate further the organization of motor output to distal and proximal muscles. We used stimulus-triggered averaging (StTAing) of electromyographic activity to map the cortical representation of 24 simultaneously recorded forelimb muscles. StTAs were obtained by applying 15 microA stimuli to M1 sites while the monkey performed a reach and prehension task. Motor output to body regions other than the forelimb (e.g., face, trunk, and hindlimb) was identified using repetitive intracortical microstimulation to evoke movements. Detailed, muscle-based maps of M1 revealed a central core of distal (wrist, digit, and intrinsic hand) muscle representation surrounded by a "horseshoe"-shaped zone of proximal (shoulder and elbow) muscle representation. The core distal and proximal zones were separated by a relatively large region representing combinations of both distal and proximal muscles. On the basis of its size and characteristics, we argue that this zone is not simply the result of stimulus-current spread, but rather a distinct zone within the forelimb representation containing cells that specify functional synergies of distal and proximal muscles. Electrode tracks extending medially from the medial arm of the proximal muscle representation evoked trunk and hindlimb responses. No distal or proximal muscle poststimulus effects were found in this region. These results argue against the existence of a second, major noncontiguous distal or proximal forelimb representation located medially within the macaque M1 representation. PMID:11306630

  20. Yacon diet (Smallanthus sonchifolius, Asteraceae) improves hepatic insulin resistance via reducing Trb3 expression in Zucker fa/fa rats

    PubMed Central

    Satoh, H; Audrey Nguyen, M T; Kudoh, A; Watanabe, T

    2013-01-01

    Objective: Yacon is a perennial plant forming a clump of >20 big, edible underground tubers. Yacon, which originates from South America, has become increasingly popular in the Japanese diet for tubers have a lower caloric value and a high fiber content. Recent studies have suggested that yacon feeding ameliorates diabetes as indicated by reduced blood glucose. Methods: We fed male Zucker fa/fa rats for 5 weeks with isocaloric normal chow diet containing from 6.5% control aroid or 6.5% yacon. Insulin sensitivity was evaluated by euglycemic-hyperinsulinemic clamp study. Results: Body weight was comparable between yacon- and aroid-fed rats. In the basal state, yacon feeding had an effect to lower fasting glucose levels from 184.1±4.1 to 167.8±2.7?mg?dl?1 (P<0.01), as well as basal hepatic glucose output (HGO) from 9.9±0.4 to 7.4 ± 0.2?mg?kg?1 per min (P<0.01). During the clamp studies, the glucose infusion rate required to maintain euglycemia was increased by 12.3% in yacon-fed rat. The insulin suppression of HGO was also increased in yacon-fed rats compared with control rats (85.3±2.4% vs 77.0±3.0% P<0.05), whereas the glucose disposal rate was not different between the two groups. Consistent with the clamp data, the insulin-stimulated phosphorylation of Akt was significantly enhanced in liver but not in skeletal muscle. Furthermore, tribbles 3 (Trb3) expression, which is a negative regulator of Akt activity, was markedly reduced in the liver of yacon-fed rats compared with control rats. Conclusion: These results indicate that the effect of yacon feeding to reduce blood glucose is likely due to its beneficial effects on hepatic insulin sensitivity in the insulin resistant state. PMID:23712282

  1. Complete forelimb myology of the basal theropod dinosaur Tawa hallae based on a novel robust muscle reconstruction method.

    PubMed

    Burch, Sara H

    2014-09-01

    The forelimbs of nonavian theropod dinosaurs have been the subject of considerable study and speculation due to their varied morphology and role in the evolution of flight. Although many studies on the functional morphology of a limb require an understanding of its musculature, comparatively little is known about the forelimb myology of theropods and other bipedal dinosaurs. Previous phylogenetically based myological reconstructions have been limited to the shoulder, restricting their utility in analyses of whole-limb function. The antebrachial and manual musculature in particular have remained largely unstudied due to uncertain muscular homologies in archosaurs. Through analysis of the musculature of extant taxa in a robust statistical framework, this study presents new hypotheses of homology for the distal limb musculature of archosaurs and provides the first complete reconstruction of dinosaurian forelimb musculature, including the antebrachial and intrinsic manual muscles. Data on the forelimb myology of a broad sample of extant birds, crocodylians, lizards, and turtles were analyzed using maximum likelihood ancestral state reconstruction and examined together with the osteology of the early theropod Tawa hallae from the Late Triassic of New Mexico to formulate a complete plesiomorphic myology for the theropod forelimb. Comparisons with previous reconstructions show that the shoulder musculature of basal theropods is more similar to that of basal ornithischians and sauropodomorphs than to that of dromaeosaurids. Greater development of the supracoracoideus and deltoideus musculature in theropods over other bipedal dinosaurs correlates with stronger movements of the forelimb at the shoulder and an emphasis on apprehension of relatively large prey. This emphasis is further supported by the morphology of the antebrachium and the intrinsic manual musculature, which exhibit a high degree of excursion and a robust morphology well-suited for powerful digital flexion. The forelimb myology of Tawa established here helps infer the ancestral conformation of the forelimb musculature and the osteological correlates of major muscle groups in early theropods. These data are critical for investigations addressing questions relating to the evolution of specialized forelimb function across Theropoda. PMID:25040486

  2. [Exogenous hydrogen sulfide reduces vascular aging in D-galactose-induced subacute aging rats].

    PubMed

    Qiao, Wei-Li; Yang, Wen-Xue; Liu, Lei; Shi, Yue; Cui, Jie; Liu, Hong; Yan, Chang-Dong

    2014-06-25

    The present study was aimed to observe the protective effect of exogenous hydrogen sulfide (H?S) on vascular structural and functional changes of aorta in D-galactose-induced subacute aging rats. Adult male SD rats were randomly divided to five groups: the vehicle group, the D-galactose (D-gal) group, and the three NaHS groups treated with low (1 ?mol·kg?¹·d?¹), middle (10 ?mol·kg?¹·d?¹) or high (100 ?mol·kg?¹·d?¹) dose of NaHS respectively. The D-gal group rats were given subcutaneously injection of 125 mg/kg D-gal per day for eight weeks to induce subacute aging model. In the NaHS group, D-gal was administered as above but with NaHS intraperitoneally injected at a dosage of 1, 10, 100 ?mol·kg?¹·d?¹ respectively. Equivalent volumes of saline were administered per day for eight weeks in vehicle group. Morphological changes of aorta were observed by HE and Masson staining. The level of H?S in serum, the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA), as well as anti-superoxide anions in vascular tissue were determined by spectrophotometry. Angiotensin II (AngII) levels in plasma were measured using competitive enzyme immunoassay. The expression of angiotensin II type 1 receptor (AT1R) in aorta was determined by Western blot. The results showed that the aging aortic morphologic changes in model rats were ameliorated in NaHS groups. Decreased vascular endothelial exfoliative cells and vascular smooth muscle cell (SMC) proliferation were shown in NaHS groups by HE staining. Masson staining analysis showed reduced relative contents of collagen fibers (P < 0.05) and SMC (P < 0.05) in NaHS groups. Compared to vehicle group, serum concentration of H?S in D-gal group was decreased, while it was increased in NaHS groups after treatment with NaHS (P < 0.05). In the D-gal group, the concentration of AngII in plasma was significantly increased compared with that in vehicle group, while it was decreased in NaHS groups (P < 0.05). Moreover, levels of vascular tissue anti-superoxide anion and the activity of SOD were obviously higher, MDA was significantly lower in all NaHS treated groups than those in the D-gal group respectively (P < 0.05). Western blot analysis showed that the expression of AT1R was increased in D-gal group compared with that in vehicle group, while it was decreased after treatment with NaHS compared with that in D-gal group (P < 0.05). These results suggest that exogenous H?S can ameliorate the age-related changes of aortic morphology, decrease the concentration of AngII in plasma, down-regulate the expression of AT1R in vascular tissue, and mitigate the level of oxidative stress. These changes delay the vascular aging in aging rats ultimately. PMID:24964843

  3. The mineralocorticoid receptor antagonist eplerenone reduces renal interstitial fibrosis after long-term cyclosporine treatment in rat: antagonizing cyclosporine nephrotoxicity

    PubMed Central

    2013-01-01

    Background Chronic cyclosporine-(CsA)-mediated loss of kidney function is a major clinical problem in organ transplantation. We hypothesized that the mineralocorticoid receptor antagonist eplerenone (EPL) prevents chronic CsA-induced renal interstitial volume increase, tubule loss, and functional impairment in a rat model. Methods Sprague–Dawley rats received CsA alone (15 mg/kg/d p.o.), CsA and EPL (approximately 100 mg/kg/day p.o.) or vehicle (control) for 12 weeks. At 11 weeks, chronic indwelling arterial and venous catheters were implanted for continuous measurements of arterial blood pressure (BP) and GFR (inulin clearance) in conscious, freely moving animals. Plasma was sampled for analysis and kidney tissue was fixed for quantitative stereological analyses. Results Compared to controls, CsA-treatment reduced relative tubular volume (0.73±0.03 vs. 0.85±0.01, p<0.05) and increased relative interstitial volume (0.080±0.004 vs. 0.045±0.003, p<0.05); EPL attenuated these changes (0.82±0.02, p<0.05, and 0.060±0.006, p<0.05, respectively). CsA-treated rats had more sclerotic glomeruli and a higher degree of vascular depositions in arterioles; both were significantly reduced in CsA+EPL-treated animals. CsA increased BP and reduced body weight gain and GFR. In CsA+EPL rats, weight gain, GFR and BP at rest (daytime) were normalized; however, BP during activity (night) remained elevated. Plasma sodium and potassium concentrations, kidney-to-body weight ratios and CsA whole blood concentration were similar in CsA and CsA+EPL rats. Conclusions It is concluded that in the chronic cyclosporine rat nephropathy model, EPL reduces renal tissue injury, hypofiltration, hypertension, and growth impairment. MR antagonists should be tested for their renoprotective potential in patients treated with calcineurin inhibitors. PMID:23425330

  4. The incentive amplifying effects of nicotine are reduced by selective and non-selective dopamine antagonists in rats

    PubMed Central

    Palmatier, Matthew I.; Kellicut, Marissa R.; Sheppard, A. Brianna; Brown, Russell W.; Robinson, Donita L.

    2015-01-01

    Nicotine is a psychomotor stimulant with ‘reinforcement enhancing’ effects – the actions of nicotine in the brain increase responding for non-nicotine rewards. We hypothesized that this latter effect of nicotine depends on increased incentive properties of anticipatory cues; consistent with this hypothesis, multiple laboratories have reported that nicotine increases sign tracking, i.e. approach to a conditioned stimulus (CS), in Pavlovian conditioned-approach tasks. Incentive motivation and sign tracking are mediated by mesolimbic dopamine (DA) transmission and nicotine facilitates mesolimbic DA release. Therefore, we hypothesized that the incentive-promoting effects of nicotine would be impaired by DA antagonists. To test this hypothesis, separate groups of rats were injected with nicotine (0.4 mg/kg base) or saline prior to Pavlovian conditioning sessions in which a CS (30 s illumination of a light or presentation of a lever) was immediately followed by a sweet reward delivered in an adjacent location. Both saline and nicotine pretreated rats exhibited similar levels of conditioned approach to the reward location (goal tracking), but nicotine pretreatment significantly increased approach to the CS (sign tracking), regardless of type (lever or light). The DAD1 antagonist SCH-23390 and the DAD2/3 antagonist eticlopride reduced conditioned approach in all rats, but specifically reduced goal tracking in the saline pretreated rats and sign tracking in the nicotine pretreated rats. The non-selective DA antagonist flupenthixol reduced sign-tracking in nicotine rats at all doses tested; however, only the highest dose of flupenthixol reduced goal tracking in both nicotine and saline groups. The reductions in conditioned approach behavior, especially those by SCH-23390, were dissociated from simple motor suppressant effects of the antagonists. These experiments are the first to investigate the effects of dopaminergic drugs on the facilitation of sign-tracking engendered by nicotine and they implicate dopaminergic systems both in conditioned approach as well as the incentive-promoting effects of nicotine. PMID:25230311

  5. Neonatal low-protein diet reduces the masticatory efficiency in rats.

    PubMed

    Ferraz-Pereira, Kelli N; da Silva Aragão, Raquel; Verdier, Dorly; Toscano, Ana E; Lacerda, Diego C; Manhães-de-Castro, Raul; Kolta, Arlette

    2015-11-01

    Little is known about the effects of undernutrition on the specific muscles and neuronal circuits involved in mastication. The aim of this study was to document the effects of neonatal low-protein diet on masticatory efficiency. Newborn rats whose mothers were fed 17 % (nourished (N), n 60) or 8 % (undernourished (U), n 56) protein were compared. Their weight was monitored and their masticatory jaw movements were video-recorded. Whole-cell patch-clamp recordings were performed in brainstem slice preparations to investigate the intrinsic membrane properties and N-methyl-d-aspartate-induced bursting characteristics of the rhythmogenic neurons (N, n 43; U, n 39) within the trigeminal main sensory nucleus (NVsnpr). Morphometric analysis (N, n 4; U, n 5) were conducted on masseteric muscles serial cross-sections. Our results showed that undernourished animals had lower numbers of masticatory sequences (P=0·049) and cycles (P=0·045) and slower chewing frequencies (P=0·004) (N, n 32; U, n 28). Undernutrition reduced body weight but had little effect on many basic NVsnpr neuronal electrophysiological parameters. It did, however, affect sag potentials (P<0·001) and rebound firing (P=0·005) that influence firing pattern. Undernutrition delayed the appearance of bursting and reduced the propensity to burst (P=0·002), as well as the bursting frequency (P=0·032). Undernourished animals showed increased and reduced proportions of fibre type IIA (P<0·0001) and IIB (P<0·0001), respectively. In addition, their fibre areas (IIA, P<0·001; IIB, P<0·001) and perimeters (IIA, P<0·001; IIB, P<0·001) were smaller. The changes observed at the behavioural, neuronal and muscular levels suggest that undernutrition reduces chewing efficiency by slowing, weakening and delaying maturation of the masticatory muscles and the associated neuronal circuitry. PMID:26337745

  6. Amitifadine, a triple monoamine re-uptake inhibitor, reduces nicotine self-administration in female rats.

    PubMed

    Levin, Edward D; Wells, Corinne; Johnson, Joshua E; Rezvani, Amir H; Bymaster, Frank P; Rose, Jed E

    2015-10-01

    A wider diversity of drug treatments to aid smoking cessation is needed to help tailor the most efficacious treatment for different types of smokers. This study was conducted to determine whether amitifadine, which inhibits re-uptake of dopamine, norepinephrine and serotonin, would decrease nicotine self-administration at doses that do not cause adverse side effects. Adult female Sprague-Dawley rats were trained to self-administer nicotine intravenous (IV) and were given acute doses of amitifadine in a repeated measures counterbalanced design. Effects of amitifadine on locomotor activity and food motivated responding were also evaluated. Chronic amitifadine effects were also examined. The 30mg/kg amitifadine dose significantly reduced nicotine self-administration. The 5 and 10mg/kg doses reduced nicotine self-administration during the first 15min of the session when the greatest amount of nicotine was self-administered. The 30mg/kg amitifadine dose, but not the lower doses caused a significant reduction in locomotor activity averaged over the one-hour session and reduced food motivated responding. The 10mg/kg dose caused hypoactivity at the beginning of the session, but 5mg/kg did not cause any hypoactivity. The effects of chronic amitifadine treatment (10mg/kg) over the course of 15 sessions was also determined. Amitifadine caused a significant reduction in nicotine self-administration, which was not seen to diminish over two consecutive weeks of treatment and a week after enforced abstinence. Amitifadine significantly reduced nicotine self-administration. This prompts further research to determine if amitifadine might be an effective treatment for smoking cessation. PMID:26101069

  7. Dietary docosahexaenoic acid supplementation reduces SERCA Ca2+ transport efficiency in rat skeletal muscle.

    PubMed

    Fajardo, Val Andrew; Bombardier, Eric; Irvine, Thomas; Metherel, Adam H; Stark, Ken D; Duhamel, Todd; Rush, James W E; Green, Howard J; Tupling, A Russell

    2015-04-01

    Docosahexaenoic acid (DHA) can reduce the efficiency and increase the energy consumption of Na(+)/K(+)-ATPase pump and mitochondrial electron transport chain by promoting Na(+) and H(+) membrane permeability, respectively. In skeletal muscle, the sarco(endo) plasmic reticulum Ca(2+)-ATPase (SERCA) pumps are major contributors to resting metabolic rate. Whether DHA can affect SERCA efficiency remains unknown. Here, we examined the hypothesis that dietary supplementation with DHA would reduce Ca(2+) transport efficiency of the SERCA pumps in skeletal muscle. Total lipids were extracted from enriched sarcoplasmic reticulum (SR) membranes that were isolated from red vastus lateralis skeletal muscles of rats that were either fed a standard chow diet supplemented with soybean oil or supplemented with DHA for 8 weeks. The fatty acid composition of total SR membrane lipids and the major phospholipid species were determined using electrospray ionization mass spectrometry (ESI-MS). After 8 weeks of DHA supplementation, total SR DHA content was significantly elevated (control, 4.1 ± 1.0% vs. DHA, 9.9 ± 1.7%; weight percent of total fatty acids) while total arachidonic acid was reduced (control, 13.5 ± 0.4% vs. DHA-fed, 9.4 ± 0.2). Similar changes in these fatty acids were observed in phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol, altogether indicating successful incorporation of DHA into the SR membranes post-diet. As hypothesized, DHA supplementation reduced SERCA Ca(2+) transport efficiency (control, 0.018 ± 0.0002 vs. DHA-fed, 0.014 ± 0.0009) possibly through enhanced SR Ca(2+) permeability (ionophore ratio: control, 2.8 ± 0.2 vs. DHA-fed, 2.2 ± 0.3). Collectively, our results suggest that DHA may promote skeletal muscle-based metabolism and thermogenesis through its influence on SERCA. PMID:25772907

  8. Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats

    PubMed Central

    2012-01-01

    Correction to Rao J S, Kim H W, Kellom M, Greenstein D, Chen M, Kraft A D, Harry G J, Rapoport S I, Basselin M. Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats. Journal of Neuroinflammation 8:101.

  9. PHTHALATE ESTER-INDUCED GUBERNACULAR LESIONS ARE ASSOCIATED WITH REDUCED INSL-3 GENE EXPRESSION IN THE FETAL RAT TESTIS

    EPA Science Inventory

    Phthalate ester-induced gubernacular ligament lesions are associated with reduced Insl3 gene expression in the fetal rat testis during sexual differentiation.
    VS Wilson, C Lambright, J Furr, J Ostby, C Wood, G Held, LE Gray Jr.
    U.S. EPA, ORD, NHEERL, Reproductive Toxicology...

  10. Aerosolised surfactant generated by a novel noninvasive apparatus reduced acute lung injury in rats

    PubMed Central

    Sun, Yu; Yang, Rui; Zhong, Ji-gen; Fang, Feng; Jiang, Jin-jin; Liu, Ming-yao; Lu, Jian

    2009-01-01

    Introduction Exogenous surfactant has been explored as a potential therapy for acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In the present study, a nebuliser driven by oxygen lines found in the hospital was developed to deliver aerosolised porcine pulmonary surfactant (PPS). We hypothesised that aerosolised surfactant inhaled through spontaneous breathing may effectively reduce severe lung injury. Methods Rats were intravenously injected with oleic acid (OA) to induce ALI and 30 minutes later they were divided into five groups: model (injury only), PPS aerosol (PPS-aer), saline aerosol (saline-aer), PPS instillation (PPS-inst), and saline instillation (Saline-Inst). Blood gases, lung histology, and protein and TNF-? concentrations in the bronchoalveolar lavage fluid (BALF) were examined. Results The PPS aerosol particles were less than 2.0 ?m in size as determined by a laser aerosol particle counter. Treatment of animals with a PPS aerosol significantly increased the phospholipid content in the BALF, improved lung function, reduced pulmonary oedema, decreased total protein and TNF-? concentrations in BALF, ameliorated lung injury and improved animal survival. These therapeutic effects are similar to those seen in the PPS-inst group. Conclusions This new method of PPS aerosolisation combines the therapeutic effects of a surfactant with partial oxygen inhalation under spontaneous breathing. It is an effective, simple and safe method of administering an exogenous surfactant. PMID:19257907

  11. The addition of whole soy flour to cafeteria diet reduces metabolic risk markers in wistar rats

    PubMed Central

    2013-01-01

    Background Soybean is termed a functional food because it contains bioactive compounds. However, its effects are not well known under unbalanced diet conditions. This work is aimed at evaluating the effect of adding whole soy flour to a cafeteria diet on intestinal histomorphometry, metabolic risk and toxicity markers in rats. Methods In this study, 30 male adult Wistar rats were used, distributed among three groups (n?=?10): AIN-93 M diet, cafeteria diet (CAF) and cafeteria diet with soy flour (CAFS), for 56 days. The following parameters were measured: food intake; weight gain; serum concentrations of triglycerides, total cholesterol, HDL-c, glycated hemoglobin (HbA1c), aspartate (AST) and alanine (ALT) aminotransferases and Thiobarbituric Acid Reactive Substances (TBARS); humidity and lipid fecal content; weight and fat of the liver. The villous height, the crypt depth and the thickness of the duodenal and ileal circular and longitudinal muscle layers of the animals were also measured. Results There was a significant reduction in the food intake in the CAF group. The CAFS showed lower serum concentrations of triglycerides and serum TBARS and a lower percentage of hepatic fat, with a corresponding increase in thickness of the intestinal muscle layers. In the CAF group, an increase in the HbA1c, ALT, lipid excretion, liver TBARS and crypt depth, was observed associated with lower HDL-c and villous height. The addition of soy did not promote any change in these parameters. Conclusions The inclusion of whole soy flour in a high-fat diet may be helpful in reducing some markers of metabolic risk; however, more studies are required to clarify its effects on unbalanced diets. PMID:24119309

  12. Activity-based anorexia is associated with reduced hippocampal cell proliferation in adolescent female rats.

    PubMed

    Barbarich-Marsteller, Nicole C; Fornal, Casimir A; Takase, Luiz F; Bocarsly, Miriam E; Arner, Candice; Walsh, B Timothy; Hoebel, Bartley G; Jacobs, Barry L

    2013-01-01

    Activity-based anorexia (ABA) is an animal model of anorexia nervosa that mimics core features of the clinical psychiatric disorder, including severe food restriction, weight loss, and hyperactivity. The ABA model is currently being used to study starvation-induced changes in the brain. Here, we examined hippocampal cell proliferation in animals with ABA (or the appropriate control conditions). Adolescent female Sprague-Dawley rats were assigned to 4 groups: control (24h/day food access), food-restricted (1h/day food access), exercise (24h/day food and wheel access), and ABA (1h/day food access, 24h/day wheel access). After 3 days of ABA, 5-bromo-2'-deoxyuridine (BrdU; 200mg/kg, i.p.) was injected and the rats were perfused 2h later. Brains were removed and subsequently processed for BrdU and Ki67 immunohistochemistry. The acute induction of ABA reduced cell proliferation in the dentate gyrus. This effect was significant in the hilus region of the dentate gyrus, but not in the subgranular zone, where adult neurogenesis occurs. Marked decreases in cell proliferation were also observed in the surrounding dorsal hippocampus and in the corpus callosum. These results indicate a primary effect on gliogenesis rather than neurogenesis following 3 days of ABA. For each brain region studied (except SGZ), there was a strong positive correlation between the level of cell proliferation and body weight/food intake. Future studies should examine whether these changes are maintained following long-term weight restoration and whether alterations in neurogenesis occur following longer exposures to ABA. PMID:22981561

  13. Relaxation of rat aorta by farrerol correlates with potency to reduce intracellular calcium of VSMCs.

    PubMed

    Qin, Xiaojiang; Hou, Xiaomin; Zhang, Mingsheng; Liang, Taigang; Zhi, Jianmin; Han, Lingge; Li, Qingshan

    2014-01-01

    Farrerol, isolated from Rhododendron dauricum L., has been proven to be an important multifunctional physiologically active component, but its vasoactive mechanism is not clear. The present study was performed to observe the vasoactive effects of farrerol on rat aorta and to investigate the possible underlying mechanisms. Isolated aortic rings of rat were mounted in an organ bath system and the myogenic effects stimulated by farrerol were studied. Intracellular Ca2+ ([Ca2+]in) was measured by molecular probe fluo-4-AM and the activities of L-type voltage-gated Ca2+ channels (LVGC) were studied with whole-cell patch clamp in cultured vascular smooth muscle cells (VSMCs). The results showed that farrerol significantly induced dose-dependent relaxation on aortic rings, while this vasorelaxation was not affected by NG-nitro-l-arginine methylester ester or endothelium denudation. In endothelium-denuded aortas, farrerol also reduced Ca2+-induced contraction on the basis of the stable contraction induced by KCl or phenylephrine (PE) in Ca2+-free solution. Moreover, after incubation with verapamil, farrerol can induce relaxation in endothelium-denuded aortas precontracted by PE, and this effect can be enhanced by ruthenium red, but not by heparin. With laser scanning confocal microscopy method, the farrerol-induced decline of [Ca2+]in in cultured VSMCs was observed. Furthermore, we found that farrerol could suppress Ca2+ influx via LVGC by patch clamp technology. These findings suggested that farrerol can regulate the vascular tension and could be developed as a practicable vasorelaxation drug. PMID:24747597

  14. Reduced Renshaw Recurrent Inhibition after Neonatal Sciatic Nerve Crush in Rats

    PubMed Central

    Shu, Liang; Su, Jingjing; Jing, Lingyan; Huang, Ying; Di, Yu; Peng, Lichao; Liu, Jianren

    2014-01-01

    Renshaw recurrent inhibition (RI) plays an important gated role in spinal motion circuit. Peripheral nerve injury is a common disease in clinic. Our current research was designed to investigate the change of the recurrent inhibitory function in the spinal cord after the peripheral nerve crush injury in neonatal rat. Sciatic nerve crush was performed on 5-day-old rat puppies and the recurrent inhibition between lateral gastrocnemius-soleus (LG-S) and medial gastrocnemius (MG) motor pools was assessed by conditioning monosynaptic reflexes (MSR) elicited from the sectioned dorsal roots and recorded either from the LG-S and MG nerves by antidromic stimulation of the synergist muscle nerve. Our results demonstrated that the MSR recorded from both LG-S or MG nerves had larger amplitude and longer latency after neonatal sciatic nerve crush. The RI in both LG-S and MG motoneuron pools was significantly reduced to virtual loss (15–20% of the normal RI size) even after a long recovery period upto 30 weeks after nerve crush. Further, the degree of the RI reduction after tibial nerve crush was much less than that after sciatic nerve crush indicatig that the neuron-muscle disconnection time is vital to the recovery of the spinal neuronal circuit function during reinnervation. In addition, sciatic nerve crush injury did not cause any spinal motor neuron loss but severally damaged peripheral muscle structure and function. In conclusion, our results suggest that peripheral nerve injury during neonatal early development period would cause a more sever spinal cord inhibitory circuit damage, particularly to the Renshaw recurrent inhibition pathway, which might be the target of neuroregeneration therapy. PMID:24778886

  15. Phenobarbital reduces blood glucose and gluconeogenesis through down-regulation of phosphoenolpyruvate carboxykinase (GTP) gene expression in rats.

    PubMed

    Oda, Hiroaki; Okuda, Yuji; Yoshida, Yukiko; Kimura, Noriko; Kakinuma, Atsushi

    2015-10-23

    The regulatory mechanism of phosphoenolpyruvate carboykinase (GTP) (EC 4.1.1.32) (PEPCK) gene expression and gluconeogenesis by phenobarbital (PB), which is known to induce drug-metabolizing enzymes, was investigated. Higher level of PEPCK mRNA was observed in spherical rat primary hepatocytes on EHS-gel than monolayer hepatocytes on TIC (type I collagen). We found that PB directly suppressed PEPCK gene expression in spherical hepatocytes on EHS-gel, but not in those on TIC. PB strongly suppressed cAMP-dependent induction of PEPCK gene expression. Tyrosine aminotransferase (TAT), another gluconeogenic enzyme, was induced by cAMP, but not suppressed by PB. Chronic administration of PB reduced hepatic PEPCK mRNA in streptozotocin-induced diabetic and nondiabetic rats, and PB reduced blood glucose level in diabetic rats. Increased TAT mRNA in diabetic rats was not suppressed by PB. These results indicated that PB-dependent reduction is specific to PEPCK. From pyrvate challenge test, PB suppressed the increased gluconeogenesis in diabetic rats. PEPCK gene promoter activity was suppressed by PB in HepG2 cells. In conclusion, we found that spherical hepatocytes cultured on EHS-gel are capable to respond to PB to suppress PEPCK gene expression. Moreover, our results indicate that hypoglycemic action of PB result from transcriptional repression of PEPCK gene and subsequent suppression of gluconeogenesis. PMID:26348778

  16. Forelimb preferences in quadrupedal marsupials and their implications for laterality evolution in mammals

    PubMed Central

    2013-01-01

    Background Acquisition of upright posture in evolution has been argued to facilitate manual laterality in primates. Owing to the high variety of postural habits marsupials can serve as a suitable model to test whether the species-typical body posture shapes forelimb preferences in non-primates or this phenomenon emerged only in the course of primate evolution. In the present study we aimed to explore manual laterality in marsupial quadrupeds and compare them with the results in the previously studied bipedal species. Forelimb preferences were assessed in captive grey short-tailed opossum (Monodelphis domestica) and sugar glider (Petaurus breviceps) in four different types of unimanual behaviour per species, which was not artificially evoked. We examined the possible effects of sex, age and task, because these factors have been reported to affect motor laterality in placental mammals. Results In both species the direction of forelimb preferences was strongly sex-related. Male grey short-tailed opossums showed right-forelimb preference in most of the observed unimanual behaviours, while male sugar gliders displayed only a slight, not significant rightward tendency. In contrast, females in both species exhibited consistent group-level preference of the left forelimb. We failed to reveal significant differences in manual preferences between tasks of potentially differing complexity: reaching a stable food item and catching live insects, as well as between the body support and food manipulation. No influence of subjects’ age on limb preferences was found. Conclusions The direction of sex-related differences in the manual preferences found in quadrupedal marsupials seems to be not typical for placental mammals. We suggest that the alternative way of interhemispheric connection in absence of corpus callosum may result in a fundamentally distinct mechanism of sex effect on limb preferences in marsupials compared to placentals. Our data confirm the idea that non-primate mammals differ from primates in sensitivity to task complexity. Comparison of marsupial species studied to date indicate that the vertical body orientation and the bipedalism favor the expression of individual– and population–level forelimb preferences in marsupials much like it does in primates. Our findings give the first evidence for the effect of species-typical posture on the manual laterality in non-primate mammals. PMID:23497116

  17. Sodium salicylate reduces inhibitory postsynaptic currents in neurons of rat auditory cortex.

    PubMed

    Wang, Hai-Tao; Luo, Bin; Zhou, Ke-Qing; Xu, Tian-Le; Chen, Lin

    2006-05-01

    Sodium salicylate (SS) is a medicine for anti-inflammation and for chronic pain relief with a side effect of tinnitus. To understand the cellular mechanisms of tinnitus induced by SS in the central auditory system, we examined effects of SS on evoked and miniature inhibitory postsynaptic currents (eIPSCs and mIPSCs) recorded from layer II/III pyramidal neurons of rat auditory cortex in a brain slice preparation with whole-cell patch-clamp techniques. Both eIPSCs and mIPSCs recorded from the auditory cortex could be completely blocked by bicuculline, a selective GABA(A) receptor antagonist. SS did not change the input resistance of neurons but was found to reversibly depress eIPSCs in a concentration-dependent manner. SS reduced eIPSCs to 82.3% of the control level at 0.5 mM (n=7) and to 60.9% at 1.4 mM (n=12). In addition, SS at 1.4 mM significantly reduced the amplitude of mIPSCs from 24.12+/-1.44 pA to 19.92+/-1.31 pA and reduced the frequency of mIPSCs from 1.34+/-0.23 Hz to 0.89+/-0.13 Hz (n=6). Our results demonstrate that SS attenuates inhibitory postsynaptic currents in the auditory cortex, suggesting that the alteration of inhibitory neural circuits may be one of the cellular mechanisms for tinnitus induced by SS in the central auditory region. PMID:16632286

  18. Exercise training enhances rat pancreatic islets anaplerotic enzymes content despite reduced insulin secretion.

    PubMed

    Zoppi, Claudio C; Calegari, Vivian C; Silveira, Leonardo R; Carneiro, Everardo M; Boschero, Antonio C

    2011-09-01

    Endurance exercise has been shown to reduce pancreatic islets glucose-stimulated insulin secretion (GSIS). Anaplerotic/cataplerotic pathways are directly related to GSIS signaling. However, the effect of endurance training upon pancreatic islets anaplerotic enzymes is still unknown. In this sense, we tested the hypothesis that endurance exercise decreases GSIS by reducing anaplerotic/cataplerotic enzymes content. Male Wistar rats were randomly assigned to one of the four experimental groups as follows: control sedentary group (CTL), trained 1 day per week (TRE1×), trained 3 days per week (TRE3×) and trained 5 days per week (TRE5x) and submitted to an 8 weeks endurance-training protocol. After the training protocol, pancreatic islets were isolated and incubated with basal (2.8 mM) and stimulating (16.7 mM) glucose concentrations for GSIS measurement by radioimmunoassay. In addition, pyruvate carboxylase (PYC), pyruvate dehydrogenase (PDH), pyruvate dehydrogenase kinase 4 (PDK4), ATP-citrate lyase (ACL) and glutamate dehydrogenase (GDH) content were quantified by western blotting. Our data showed that 8 weeks of chronic endurance exercise reduced GSIS by 50% in a dose-response manner according to weekly exercise frequency. PYC showed significant twofold increase in TRE3×. PYC enhancement was even higher in TRE5× (p < 0.0001). PDH and PDK4 reached significant 25 and 50% enhancement, respectively compared with CTL. ACL and GDH also reported significant 50 and 75% increase, respectively. The absence of exercise-induced correlations among GSIS and anaplerotic/cataplerotic enzymes suggests that exercise may control insulin release by activating other signaling pathways. The observed anaplerotic and cataplerotic enzymes enhancement might be related to ?-cell surviving rather than insulin secretion. PMID:21287194

  19. Evidence that Memantine Reduces Chronic Tinnitus Caused by Acoustic Trauma in Rats

    PubMed Central

    Zheng, Yiwen; McNamara, Emily; Stiles, Lucy; Darlington, Cynthia L.; Smith, Paul F.

    2012-01-01

    Subjective tinnitus is a chronic neurological disorder in which phantom sounds are perceived. Increasing evidence suggests that tinnitus is caused by neuronal hyperactivity in auditory brain regions, either due to a decrease in synaptic inhibition or an increase in synaptic excitation. One drug investigated for the treatment of tinnitus has been the uncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, memantine, although the evidence relating to it has been unconvincing to date. We re-investigated the effects of memantine on the behavioral manifestations of tinnitus induced by acoustic trauma (a 16-kHz, 110-dB pure tone presented unilaterally for 1?h) in rats. We used a conditioned lick suppression model in which lick suppression was associated with the perception of high frequency sound resembling tinnitus and a suppression ratio (SR) was calculated by comparing the number of licks in the 15-s period preceding the stimulus presentation (A) and the 15-s period during the stimulus presentation (B), i.e., SR?=?B/(A?+?B). Acoustic trauma resulted in a significant increase in the auditory brainstem-evoked response (ABR) threshold in the affected ear (P???0.0001) and a decrease in the SR compared to sham controls in response to 32?kHz tones in five out of eight acoustic trauma-exposed animals. A 5-mg/kg dose of memantine significantly reduced the proportion of these animals which exhibited tinnitus-like behavior (2/5 compared to 5/5; P???0.006), suggesting that the drug reduced tinnitus. These results suggest that memantine may reduce tinnitus caused by acoustic trauma. PMID:23015804

  20. Reduced-calorie avocado paste attenuates metabolic factors associated with a hypercholesterolemic-high fructose diet in rats.

    PubMed

    Pahua-Ramos, María Elena; Garduño-Siciliano, Leticia; Dorantes-Alvarez, Lidia; Chamorro-Cevallos, German; Herrera-Martínez, Julieta; Osorio-Esquivel, Obed; Ortiz-Moreno, Alicia

    2014-03-01

    The objective of this study was to evaluate the effect of reduced-calorie avocado paste on lipid serum profile, insulin sensitivity, and hepatic steatosis in rats fed a hypercholesterolemic-high fructose diet. Thirty five male Wistar rats were randomly separated in five groups: Control group (ground commercial diet); hypercholesterolemic diet plus 60% fructose solution (HHF group); hypercholesterolemic diet plus 60% fructose solution supplemented with avocado pulp (HHF+A group); hypercholesterolemic diet plus 60% fructose solution supplemented with reduced-calorie avocado paste (HHF+P group); and hypercholesterolemic diet plus 60% fructose solution supplemented with a reduced-calorie avocado paste plus fiber (HHF+FP group). The A, P, and FP were supplemented at 2 g/kg/d. The study was carried out for seven weeks. Rats belonging to the HHF group exhibited significantly (P???0.05) higher total cholesterol, triglycerides, and insulin levels in serum as well as lower insulin sensitivity than the control group. Supplementation with reduced-calorie avocado paste showed a significant (P???0.05) decrease in total cholesterol (43.1%), low-density lipoprotein (45.4%), and triglycerides (32.8%) in plasma as well as elevated insulin sensitivity compared to the HHF group. Additionally, the liver enzymes alanine aminotransferase and aspartate aminotransferase decreased significantly in the HHF-P group (39.8 and 35.1%, respectively). These results are likely due to biocompounds present in the reduced-calorie avocado paste, such as polyphenols, carotenoids, chlorophylls, and dietary fibre, which are capable of reducing oxidative stress. Therefore, reduced-calorie avocado paste attenuates the effects of a hypercholesterolemic-high fructose diet in rats. PMID:24249159

  1. Careful climbing in the Miocene: the forelimbs of Ardipithecus ramidus and humans are primitive.

    PubMed

    Lovejoy, C Owen; Simpson, Scott W; White, Tim D; Asfaw, Berhane; Suwa, Gen

    2009-10-01

    The Ardipithecus ramidus hand and wrist exhibit none of the derived mechanisms that restrict motion in extant great apes and are reminiscent of those of Miocene apes, such as Proconsul. The capitate head is more palmar than in all other known hominoids, permitting extreme midcarpal dorsiflexion. Ar. ramidus and all later hominids lack the carpometacarpal articular and ligamentous specializations of extant apes. Manual proportions are unlike those of any extant ape. Metacarpals 2 through 5 are relatively short, lacking any morphological traits associable with knuckle-walking. Humeral and ulnar characters are primitive and like those of later hominids. The Ar. ramidus forelimb complex implies palmigrady during bridging and careful climbing and exhibits none of the adaptations to vertical climbing, forelimb suspension, and knuckle-walking that are seen in extant African apes. PMID:19810196

  2. Inhibition of NO biosynthesis, but not elevated blood pressure, reduces angiogenesis in rat models of secondary hypertension.

    PubMed

    Kiefer, Fabrice N; Misteli, Heidi; Kalak, Nabil; Tschudin, Karin; Fingerle, Jürgen; Van der Kooij, Maaike; Stumm, Michael; Sumanovski, Lazar T; Sieber, Cornel C; Battegay, Edouard J

    2002-01-01

    Arterial hypertension (AH) is characterized by reduced nitric oxide (NO) biosynthesis, vasoconstriction, and reduced microvascular density. In this study we asked whether AH also reduces the number of microvessels by impairing angiogenesis. AH was induced in Dahl salt-sensitive rats (DSS) with a salt diet and in Wistar-Kyoto rats by inhibiting NO formation with Nomega-nitro-L-arginine (NNA). Three weeks after induction of AH, two wound chambers containing collagen I (Vitrogen) were sutured into the mesenteric cavity of each animal. After additional 14 days, wound chamber neovascularization and the extent of vascularized connective tissue ingrowth were quantified. In NNA-induced AH, the number of newly formed vessels and the ingrowth of vascularized connective tissue into the wound chamber decreased as compared to controls. However, the number of newly formed vessels and the ingrowth of vascularized connective tissue did not change with increasing blood pressure in salt-fed DSS rats as compared to those fed a normal diet. Inhibition of NO biosynthesis, but not necessarily elevating blood pressure, reduces angiogenesis. Microvascular rarefaction in AH may be partially due to reduced angiogenesis because of impaired NO biosynthesis. PMID:12035872

  3. Noopept reduces the postischemic functional and metabolic disorders in the brain of rats with different sensitivity to hypoxia.

    PubMed

    Zarubina, I V; Shabanov, P D

    2009-03-01

    Chronic cerebral ischemia was induced by ligation of both common carotid arteries in Wistar rats, divided by sensitivity to hypoxia into highly sensitive and low-sensitive. Noopept (peptide preparation), injected (0.5 mg/kg) during 7 days after occlusion of the carotid arteries, reduced the neurological disorders in rats with high and low sensitivity to hypoxia and improved their survival during the postischemic period. Noopept normalized behavior disordered by cerebral ischemia (according to the open field and elevated plus maze tests), prevented accumulation of LPO products and inhibition of antioxidant systems in the brain of rats with high and low sensitivity to hypoxia. Hence, noopept exhibited a neuroprotective effect in cerebral ischemia. PMID:19529857

  4. Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats

    NASA Technical Reports Server (NTRS)

    Turner, R. T.; Evans, G. L.; Cavolina, J. M.; Halloran, B.; Morey-Holton, E.

    1998-01-01

    Gonadal insufficiency and reduced mechanical usage are two important risk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory rat are well known, but the influence of mechanical usage in this response has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the proximal tibial metaphysis were determined in hindlimb-unloaded, ovariectomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered to weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps programed to deliver 20 microg human PTH (approximately 80 microg/kg x day) during a daily 1-h infusion for 7 days. Compared with sham-operated rats, OVX increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radial bone growth, decreased osteoblast number, increased osteoclast number, and resulted in a further decrease in cancellous bone volume compared with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weight-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cancellous bone volume in OVX weight-bearing rats and greatly reduced cancellous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in trabecular thickness, but the hormone was ineffective in preventing either the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flurochrome label, osteoblast number, and bone formation in the proximal tibial metaphysis regardless of the level of mechanical usage. These findings demonstrate that programed administration of PTH is effective in increasing osteoblast number and bone formation and has beneficial effects on bone volume in the absence of weight-bearing and gonadal hormones. We conclude that the actions of PTH on cancellous bone are independent of the level of mechanical usage.

  5. Cervical intraspinal microstimulation evokes robust forelimb movements before and after injury

    NASA Astrophysics Data System (ADS)

    Sunshine, Michael D.; Cho, Frances S.; Lockwood, Danielle R.; Fechko, Amber S.; Kasten, Michael R.; Moritz, Chet T.

    2013-06-01

    Objective. Intraspinal microstimulation (ISMS) is a promising method for reanimating paralyzed limbs following neurological injury. ISMS within the cervical and lumbar spinal cord is capable of evoking a variety of highly-functional movements prior to injury, but the ability of ISMS to evoke forelimb movements after cervical spinal cord injury is unknown. Here we examine the forelimb movements and muscles activated by cervical ISMS both before and after contusion injury. Approach. We documented the forelimb muscles activated and movements evoked via systematic stimulation of the rodent cervical spinal cord both before injury and three, six and nine weeks following a moderate C4/C5 lateralized contusion injury. Animals were anesthetized with isoflurane to permit construction of somatotopic maps of evoked movements and quantify evoked muscle synergies between cervical segments C3 and T1. Main results. When ISMS was delivered to the cervical spinal cord, a variety of responses were observed at 68% of locations tested, with a spatial distribution that generally corresponded to the location of motor neuron pools. Stimulus currents required to achieve movement and the number of sites where movements could be evoked were unchanged by spinal cord injury. A transient shift toward extension-dominated movements and restricted muscle synergies were observed at three and six weeks following injury, respectively. By nine weeks after injury, however, ISMS-evoked patterns were similar to spinally-intact animals. Significance. The results demonstrate the potential for cervical ISMS to reanimate hand and arm function following spinal cord injury. Robust forelimb movements can be evoked both before and during the chronic stages of recovery from a clinically relevant and sustained cervical contusion injury.

  6. DNA double strand break repair in brain: reduced NHEJ activity in aging rat neurons.

    PubMed

    Vyjayanti, V N; Rao, Kalluri Subba

    2006-01-23

    Linearised pUC 19 DNA with cohesive, blunt and non-matching ends, generated by prior treatment with different restriction enzymes was presented as substrate to measure the NHEJ activity to repair DNA double strand breaks in extracts prepared from isolated neurons from neonatal, young adult and old rat cerebral cortex. Highest end joining activity was noticed with the substrates having cohesive 3' overhang (PstI) or 5' overhang (EcoRI) ends and this activity is significantly reduced with age. However, blunt and non-matching ends were very poorly repaired at all ages. Further, the end joining activity in neurons is not faithful and sequence changes occur during the repair process. Also, the end joining activity in old neuronal extracts, but not in young extracts, was found to decline very rapidly with time of cold storage. These findings, the first of their kind, thus demonstrate that neuronal cells have the capacity to repair DNA double strand breaks through error prone NHEJ mode and that the cohesive end joining activity decreases with age of the animal. PMID:16226837

  7. Ascorbic Acid Reduces the Adverse Effects of Delayed Administration of Tissue Plasminogen Activator in a Rat Stroke Model.

    PubMed

    Allahtavakoli, Mohammad; Amin, Fatemeh; Esmaeeli-Nadimi, Ali; Shamsizadeh, Ali; Kazemi-Arababadi, Mohammad; Kennedy, Derek

    2015-11-01

    Delayed treatment of stroke with recombinant tissue plasminogen activator (r-tPA) induces overexpression of matrix metalloproteinase 9 (MMP-9) which leads to breakdown of the blood-brain barrier (BBB) and causes more injuries to the brain parenchyma. In this study, the effect of ascorbic acid (AA), an antioxidant agent, on the delayed administration of r-tPA in a rat model of permanent middle cerebral artery occlusion (MCAO) was investigated. Forty male rats were randomly divided into four groups: untreated control rats (ischaemic animals), AA-treated (500 mg/kg; 5 hr after stroke) rats, r-tPA-treated (5 hr after stroke 1 mg/kg) rats and rats treated with the combination of AA and r-tPA. Middle cerebral artery occlusion was induced by occluding the right middle cerebral artery (MCA). Infarct size, BBB, brain oedema and the levels of MMP-9 were measured at the end of study. Neurological deficits were evaluated at 24 and 48 hr after stroke. Compared to the control or r-tPA-treated animals, AA alone (p < 0.001) or in combination with r-tPA (p < 0.05) significantly decreased infarct volume. Ascorbic acid alone or r-tPA + AA significantly reduced BBB permeability (p < 0.05), levels of MMP-9 (p < 0.05 versus control; p < 0.01 versus r-tPA) and brain oedema (p < 0.001) when compared to either the control or the r-tPA-treated animals. Latency to the removal of sticky labels from the forepaw was also significantly decreased after the administration of AA + r-tPA (p < 0.05) at 24 or 48 hr after stroke. Based on our data, acute treatment with AA may be considered as a useful candidate to reduce the side effects of delayed application of r-tPA in stroke therapy. PMID:25899606

  8. Pharmacological kynurenine 3-monooxygenase enzyme inhibition significantly reduces neuropathic pain in a rat model.

    PubMed

    Rojewska, Ewelina; Piotrowska, Anna; Makuch, Wioletta; Przewlocka, Barbara; Mika, Joanna

    2016-03-01

    Recent studies have highlighted the involvement of the kynurenine pathway in the pathology of neurodegenerative diseases, but the role of this system in neuropathic pain requires further extensive research. Therefore, the aim of our study was to examine the role of kynurenine 3-monooxygenase (Kmo), an enzyme that is important in this pathway, in a rat model of neuropathy after chronic constriction injury (CCI) to the sciatic nerve. For the first time, we demonstrated that the injury-induced increase in the Kmo mRNA levels in the spinal cord and the dorsal root ganglia (DRG) was reduced by chronic administration of the microglial inhibitor minocycline and that this effect paralleled a decrease in the intensity of neuropathy. Further, minocycline administration alleviated the lipopolysaccharide (LPS)-induced upregulation of Kmo mRNA expression in microglial cell cultures. Moreover, we demonstrated that not only indirect inhibition of Kmo using minocycline but also direct inhibition using Kmo inhibitors (Ro61-6048 and JM6) decreased neuropathic pain intensity on the third and the seventh days after CCI. Chronic Ro61-6048 administration diminished the protein levels of IBA-1, IL-6, IL-1beta and NOS2 in the spinal cord and/or the DRG. Both Kmo inhibitors potentiated the analgesic properties of morphine. In summary, our data suggest that in neuropathic pain model, inhibiting Kmo function significantly reduces pain symptoms and enhances the effectiveness of morphine. The results of our studies show that the kynurenine pathway is an important mediator of neuropathic pain pathology and indicate that Kmo represents a novel pharmacological target for the treatment of neuropathy. PMID:26524415

  9. Curcumin reduces the toxic effects of iron loading in rat liver epithelial cells

    PubMed Central

    Messner, Donald J.; Sivam, Gowsala; Kowdley, Kris V.

    2008-01-01

    Background/aims Iron overload can cause liver toxicity and increase the risk of liver failure or hepatocellular carcinoma in humans. Curcumin (diferuloylmethane), a component of the food spice turmeric, has antioxidant, iron binding, and hepatoprotective properties. The aim of this study was to quantify its effects on iron overload and resulting downstream toxic effects in cultured T51B rat liver epithelial cells. Methods T51B cells were loaded with ferric ammonium citrate (FAC) with or without the iron delivery agent 8-hydroxyquinoline. Cytotoxicity was measured by MTT assay. Iron uptake and iron bioavailability were documented by chemical assay, quench of calcein fluorescence, and ferritin induction. Reactive oxygen species (ROS) were measured by fluorescence assay using 2?,7?-dichlorodihydrofluorescein diacetate. Oxidative stress signaling to jnk, c-jun, and p38 was measured by western blot with phospho-specific antibodies. Results Curcumin bound iron, but did not block iron uptake or bioavailability in T51B cells given FAC. However, it reduced cytotoxicity, blocked generation of ROS, and eliminated signaling to cellular stress pathways caused by iron. Inhibition was observed over a wide range of FAC concentrations (50 – 500 ?M), with an apparent IC50 in all cases between 5 and 10 ?M curcumin. In contrast, desferoxamine blocked both iron uptake and toxic effects of iron at concentrations that depended on the FAC concentration. Effects of curcumin also differed from those of ?-tocopherol, which did not bind iron and was less effective at blocking iron-stimulated ROS generation. Conclusions Curcumin reduced iron-dependent oxidative stress and iron toxicity in T51B cells without blocking iron uptake. PMID:18492020

  10. Elbow joint adductor moment arm as an indicator of forelimb posture in extinct quadrupedal tetrapods

    PubMed Central

    Fujiwara, Shin-ichi; Hutchinson, John R.

    2012-01-01

    Forelimb posture has been a controversial aspect of reconstructing locomotor behaviour in extinct quadrupedal tetrapods. This is partly owing to the qualitative and subjective nature of typical methods, which focus on bony articulations that are often ambiguous and unvalidated postural indicators. Here we outline a new, quantitatively based forelimb posture index that is applicable to a majority of extant tetrapods. By determining the degree of elbow joint adduction/abduction mobility in several tetrapods, the carpal flexor muscles were determined to also play a role as elbow adductors. Such adduction may play a major role during the stance phase in sprawling postures. This role is different from those of upright/sagittal and sloth-like creeping postures, which, respectively, depend more on elbow extensors and flexors. Our measurements of elbow muscle moment arms in 318 extant tetrapod skeletons (Lissamphibia, Synapsida and Reptilia: 33 major clades and 263 genera) revealed that sprawling, sagittal and creeping tetrapods, respectively, emphasize elbow adductor, extensor and flexor muscles. Furthermore, scansorial and non-scansorial taxa, respectively, emphasize flexors and extensors. Thus, forelimb postures of extinct tetrapods can be qualitatively classified based on our quantitative index. Using this method, we find that Triceratops (Ceratopsidae), Anhanguera (Pterosauria) and desmostylian mammals are categorized as upright/sagittally locomoting taxa. PMID:22357261

  11. Budesonide ameliorates lung function of the cigarette smoke-exposed rats through reducing matrix metalloproteinase-1 content

    PubMed Central

    Sun, Jiawei; Zhang, Ping; Zhang, Bin; Li, Kang; Li, Zhu; Li, Junhong; Zhang, Yongjian; Sun, Wuzhuang

    2015-01-01

    Objectives: This study was conducted to investigate an effect of inhaled budesonide on cigarette smoke-exposed lungs with a possible mechanism involved in the event. Methods: Rats were exposed to air (control) and cigarette smoke (smoking) in presence and absence of budesonide. Inflammatory cell count in bronchoalveolar lavage fluid (BALF), lung function testing, mean liner intercept (MLI) in lung tissue, mean alveolar number (MAN) and a ratio of bronchial wall thickness and external diameter (BWT/D) were determined in the grouped rats, respectively. Contents of matrix metalloproteinase (MMP)-1, MMP-2 and tissue inhibitor of metalloproteinase (TIMP)-2 productions in BALF were examined as well. Results: There were significant changes in the above assessments in the smoking rats as compared to those in the control rats (all P < 0.01 and 0.05). Budesonide inhalation significantly decreased the numbers of the BALF cells and partly reversed lung function decline in the challenged rats (P < 0.01 and 0.05). However, this corticosteroid did not influence pathological changes in fine structures of the tobacco smoke-exposed lungs. Treatment with budesonide resulted in an obvious decrease in the MMP-1 but not MMP-2 and TIMP-2 productions (P < 0.05). Conclusion: Inhaled budesonide mitigates the ongoing inflammatory process in the smoked lungs and ameliorates declining lung function through reducing MMP-1 content. PMID:26191209

  12. Short-term administration of conjugated linoleic acid reduces liver triglyceride concentration and phosphatidate phosphohydrolase activity in OLETF rats.

    PubMed

    Rahman, Shaikh Mizanoor; Huda, M Nazmul; Uddin, M Nasir; Akhteruzzaman, Sharif

    2002-09-30

    The present study explored the short-term effects of dietary conjugated-linoleic acid (CLA) on liver lipid metabolism in starved/refed Otsuka Long Evans Tokushima Fatty (OLETF) rats. Male OLETF rats (12 weeks old) were starved for 24 hours, then refed for 48 hours with either a CLA diet [7.5% CLA and 7.5% Safflower oil (SAF)] or a SAF control diet (15% SAF). The results demonstrated a 30% reduction of hepatic triglyceride (TG) concentration in the CLA group when compared to the control group. Liver cholesterol concentration was also 26% lower in the CLA fed rats. The activity of mitochondrial carnitine palmitoyltransferase, the rate-limiting enzyme of fatty acid oxidation, was moderately elevated by 1.2-fold in the livers of the CLA group when compared to the control. In contrast, phosphatidate phosphohydrolase, the rate-limiting enzyme for TG synthesis, was found to be 20% lower in the livers of the CLA-fed rats. Therefore, dietary CLA evidently lowers liver lipid concentrations through a reduced TG synthesis and enhanced fatty acid oxidation in starved/refed OLETF rats. PMID:12359092

  13. FT011, a Novel Cardiorenal Protective Drug, Reduces Inflammation, Gliosis and Vascular Injury in Rats with Diabetic Retinopathy

    PubMed Central

    Deliyanti, Devy; Zhang, Yuan; Khong, Fay; Berka, David R.; Stapleton, David I.; Kelly, Darren J.; Wilkinson-Berka, Jennifer L.

    2015-01-01

    Diabetic retinopathy features inflammation as well as injury to glial cells and the microvasculature, which are influenced by hypertension and overactivity of the renin-angiotensin system. FT011 is an anti-inflammatory and anti-fibrotic agent that has been reported to attenuate organ damage in diabetic rats with cardiomyopathy and nephropathy. However, the potential therapeutic utility of FT011 for diabetic retinopathy has not been evaluated. We hypothesized that FT011 would attenuate retinopathy in diabetic Ren-2 rats, which exhibit hypertension due to an overactive extra-renal renin-angiotensin system. Diabetic rats were studied for 8 and 32 weeks and received intravitreal injections of FT011 (50 ?M) or vehicle (0.9% NaCl). Comparisons were to age-matched controls. In the 8-week study, retinal inflammation was examined by quantitating vascular leukocyte adherence, microglial/macrophage density and the expression of inflammatory mediators. Macroglial Müller cells, which exhibit a pro-inflammatory and pro-angiogenic phenotype in diabetes, were evaluated in the 8-week study as well as in culture following exposure to hyperglycaemia and FT011 (10, 30, 100 ?M) for 72 hours. In the 32-week study, severe retinal vasculopathy was examined by quantitating acellular capillaries and extracellular matrix proteins. In diabetic rats, FT011 reduced retinal leukostasis, microglial density and mRNA levels of intercellular adhesion molecule-1 (ICAM-1). In Müller cells, FT011 reduced diabetes-induced gliosis and vascular endothelial growth factor (VEGF) immunolabeling and the hyperglycaemic-induced increase in ICAM-1, monocyte chemoattractant protein-1, CCL20, cytokine-induced neutrophil chemoattractant-1, VEGF and IL-6. Late intervention with FT011 reduced acellular capillaries and the elevated mRNA levels of collagen IV and fibronectin in diabetic rats. In conclusion, the protective effects of FT011 in cardiorenal disease extend to key elements of diabetic retinopathy and highlight its potential as a treatment approach. PMID:26222724

  14. Ursodeoxycholic acid pretreatment reduces oral bioavailability of the multiple drug resistance-associated protein 2 substrate baicalin in rats.

    PubMed

    Wu, Tao; Li, Xi-Ping; Xu, Yan-Jiao; Du, Guang; Liu, Dong

    2013-11-01

    Baicalin is a major bioactive component of Scutellaria baicalensis and a substrate of multiple drug resistance-associated protein 2. Expression of multiple drug resistance-associated protein 2 is regulated by NF-E2-related factor 2. The aim of this study was to explore whether ursodeoxycholic acid, an NF-E2-related factor 2 activator, could influence the oral bioavailability of baicalin. A single dose of baicalin (200?mg/kg) was given orally to rats pretreated with ursodeoxycholic acid (75?mg/kg and 150?mg/kg, per day, intragastrically) or normal saline (per day, intragastrically) for six consecutive days. The plasma concentration of baicalin was measured with the HPLC method. The result indicated that the oral bioavailability of baicalin was significantly and dose-dependently reduced in rats pretreated with ursodeoxycholic acid. Compared with control rats, the mean area under concentration-time curve of baicalin was reduced from 13.25?±?0.24?mg/L h to 7.62?±?0.15?mg/L h and 4.97?±?0.21?mg/L h, and the C(max) value was decreased from 1.31?±?0.03?mg/L to 0.62?±?0.05?mg/L and 0.36?±?0.04?mg/L in rats pretreated with ursodeoxycholic acid at doses of 75?mg/kg and 150?mg/kg, respectively, for six consecutive days. Hence, ursodeoxycholic acid treatment reduced the oral bioavailability of baicalin in rats, probably due to the enhanced efflux of baicalin from the intestine and liver by multiple drug resistance-associated protein 2. PMID:24135887

  15. Reduced connectivity and inter-hemispheric symmetry of the sensory system in a rat model of vulnerability to developing depression.

    PubMed

    Ben-Shimol, E; Gass, N; Vollmayr, B; Sartorius, A; Goelman, G

    2015-12-01

    Defining the markers corresponding to a high risk of developing depression in humans would have major clinical significance; however, few studies have been conducted since they are not only complex but also require homogeneous groups. This study compared congenital learned helpless (cLH) rats, selectively bred for high stress sensitivity and learned helplessness (LH) behavior, to congenital non-learned helpless (cNLH) rats that were bred for resistance to uncontrollable stress. Naïve cLH rats show some depression-like behavior but full LH behavior need additional stress, making this model ideal for studying vulnerability to depression. Resting-state functional connectivity obtained from seed correlation analysis was calculated for multiple regions that were selected by anatomy AND by a data-driven approach, independently. Significance was determined by t-statistic AND by permutation analysis, independently. A significant reduction in functional connectivity was observed by both analyses in the cLH rats in the sensory, motor, cingulate, infralimbic, accumbens and the raphe nucleus. These reductions corresponded primarily to reduced inter-hemispheric connectivity. The main reduction however was in the sensory system. It is argued that reduced connectivity and inter-hemispheric connectivity of the sensory system reflects an internal convergence state which may precede other depressive symptomatology and therefore could be used as markers for vulnerability to the development of depression. PMID:26431623

  16. Prolactin anterior pituitary expression and circulating levels are reduced in obese and diabetic rats: role of TGF-? and TNF-?.

    PubMed

    Lemini, María; Ruiz-Herrera, Xarubet; Ledesma-Colunga, María G; Díaz-Lezama, Nundehui; De Los Ríos, Ericka A; López-Barrera, Fernando; Méndez, Isabel; Martínez de la Escalera, Gonzalo; Macotela, Yazmín; Clapp, Carmen

    2015-05-01

    The levels of the hormone prolactin (PRL) are reduced in the circulation of patients with Type 2 diabetes and in obese children, and lower systemic PRL levels correlate with an increased prevalence of diabetes and a higher risk of metabolic syndrome. The secretion of anterior pituitary (AP) PRL in metabolic diseases may be influenced by the interplay between transforming growth factor ? (TGF-?) and tumor necrosis factor ? (TNF-?), which inhibit and can stimulate AP PRL synthesis, respectively, and are known contributors to insulin resistance and metabolic complications. Here, we show that TGF-? and TNF-? antagonize the effect of each other on the expression and release of PRL by the GH4C1 lactotrope cell line. The levels of AP mRNA and circulating PRL decrease in high-fat diet-induced obese rats in parallel with increased and reduced AP levels of TGF-? and TNF-? mRNA, respectively. Likewise, AP expression and circulating levels of PRL are reduced in streptozotocin-induced diabetic rats and are associated with higher AP expression and protein levels of TGF-? and TNF-?. The opposing effects of the two cytokines on cultured AP cells, together with their altered expression in the AP of obese and diabetic rats suggest they are linked to the reduced PRL production and secretion characteristics of metabolic diseases. PMID:25715833

  17. Exercise induces angiogenesis but does not alter movement representations within rat motor cortex.

    PubMed

    Kleim, Jeffrey A; Cooper, Natalie R; VandenBerg, Penny M

    2002-04-26

    The effects of exercise on the topography of movement representations and blood vessel density within the rat forelimb motor cortex was examined. Adult male rats were allocated to either a Voluntary eXercise (VX) or Inactive Condition (IC). VX animals were housed for 30 days with unlimited access to running wheels while IC animals were housed in standard laboratory cages. VX animals exhibited a progressive increase in the distance traveled per day and ran an average of 58.3 km across the 30-day training period. Microelectrode stimulation was used to derive high resolution maps of the forelimb representations within the motor cortex of animals from both conditions. No significant differences in the area of either distal (wrist/digit) or proximal (elbow/shoulder) movement representations were found between VX and IC animals. However, VX animals did have a significantly greater density of blood vessels within layer V of the forelimb motor cortex. These results demonstrate that increases in forelimb motor activity sufficient to induce cortical angiogenesis does not alter the topography of forelimb movement representations within forelimb motor cortex. PMID:11937064

  18. Renal proximal tubules from old Fischer 344 rats grow into epithelial cells in cultures and exhibit increased oxidative stress and reduced D1 receptor function.

    PubMed

    Asghar, Mohammad; Chillar, Annirudha; Lokhandwala, Mustafa F

    2008-11-01

    Earlier we reported defects in D1 receptor function in renal proximal tubules (RPTs) of aged Fischer 344 (F344) and obese Zucker rats. However, the defects in the receptor function in RPTs of obese Zucker rats do not pass onto primary cultures of RPTs from these animals. Here, we determined whether the defects in D1 receptor function in RPTs of aged F344 rats pass onto the primary cultures. RPTs from aged (24-mo) and adult (6-mo) F344 rats were grown into primary cultures. The microscopic studies showed that cells in cultures from adult and old rats were healthy as determined by the shape and size of the cells and nuclei. D1 receptor agonist SKF-38393 produced inhibition of (86)Rb (rubidium) uptake, index of Na-K-ATPase activity, in cells from adult rats, but this was reduced in old rats. Also, SKF-38393 increased the [(35)S]GTPgammaS binding, index of receptor activation, in the membranes of cells from adult rats but to a lesser extent from old rats. Furthermore, there was a downward trend in the levels of D1 receptor numbers and in the receptor proteins in old rats. Interestingly, gp(91phox) subunit of NADPH oxidase and cellular protein carbonyl levels (oxidative stress marker) were higher in cultures from old rats. These results show that RPTs from adult and old F344 rats grow into epithelial cells in cultures. Furthermore, cells in cultures from old rats are at a higher level of oxidative stress, which may be contributing to the reduced D1 receptor function in the cells from old compared with adult rats. PMID:18799649

  19. Concurrent repletion of iron and zinc reduces intestinal oxidative damage in iron- and zinc-deficient rats

    PubMed Central

    Bodiga, Sreedhar; Krishnapillai, Madhavan Nair

    2007-01-01

    AIM: To understand the interactions between iron and zinc during absorption in iron- and zinc-deficient rats, and their consequences on intestinal oxidant-antioxidant balance. METHODS: Twenty-four weanling Wistar-Kyoto rats fed an iron- and zinc-deficient diet (< 6.5 mg Fe and 4.0 mg Zn/kg diet) for 4 wk were randomly divided into three groups (n = 8, each) and orally gavaged with 4 mg iron, 3.3 mg zinc, or 4 mg iron + 3.3 mg zinc for 2 wk. At the last day of repletion, 3 h before the animals were sacrificed, they received either 37 mBq of 55Fe or 65Zn, to study their localization in the intestine, using microautoradiography. Hemoglobin, iron and zinc content in plasma and liver were measured as indicators of iron and zinc status. Duodenal sections were used for immunochemical staining of ferritin and metallothionein. Duodenal homogenates (mitochondrial and cytosolic fractions), were used to assess aconitase activity, oxidative stress, functional integrity and the response of antioxidant enzymes. RESULTS: Concurrent repletion of iron- and zinc-deficient rats showed reduced localization of these minerals compared to rats that were teated with iron or zinc alone; these data provide evidence for antagonistic interactions. This resulted in reduced formation of lipid and protein oxidation products and better functional integrity of the intestinal mucosa. Further, combined repletion lowered iron-associated aconitase activity and ferritin expression, but significantly elevated metallothionein and glutathione levels in the intestinal mucosa. The mechanism of interactions during combined supplementation and its subsequent effects appeared to be due to through modulation of cytosolic aconitase, which in turn influenced the labile iron pool and metallothionein levels, and hence reduced intestinal oxidative damage. CONCLUSION: Concurrent administration of iron and zinc corrects iron and zinc deficiency, and also reduces the intestinal oxidative damage associated with iron supplementation. PMID:17963296

  20. Biliary and duodenal drainage for reducing the radiotoxic risk of antineoplastic 131I-hypericin in rat models.

    PubMed

    Li, Yue; Jiang, Cuihua; Jiang, Xiao; Sun, Ziping; Cona, Marlein Miranda; Liu, Wei; Zhang, Jian; Ni, Yicheng

    2015-12-01

    Necrosis targeting radiopharmaceutical (131)I-hypericin ((131)I-Hyp) has been studied for the therapy of solid malignancies. However, serious side effects may be caused by its unwanted radioactivity after being metabolized by the liver and excreted via bile in the digestive tract. Thus the aim of this study was to investigate two kinds of bile draining for reducing them. Thirty-eight normal rats were intravenously injected with (131)I-Hyp, 24 of which were subjected to the common bile duct (CBD) drainage for gamma counting of collected bile and tissues during 1-6, 7-12, 13-18, and 19-24?h (n?=?6 each group), 12 of which were divided into two groups (n?=?6 each group) for comparison of the drainage efficiency between CBD catheterization and duodenum intubation by collecting their bile at the first 4?h. Afterwards the 12 rats together with the last two rats which were not drained were scanned via single-photon emission computerized tomography/computed tomography (SPECT/CT) to check the differences. The images showed that almost no intestinal radioactivity can be found in those 12 drained rats while discernible radioactivity in the two undrained rats. The results also indicated that the most of the radioactivity was excreted from the bile within the first 12?h, accounting to 92% within 24?h. The radioactive metabolites in the small and large intestines peaked at 12?h and 18?h, respectively. No differences were found in those two ways of drainages. Thus bile drainage is highly recommended for the patients who were treated by (131)I-Hyp if human being and rats have a similar excretion pattern. This strategy can be clinically achieved by using a nasobiliary or nasoduodenal drainage catheter. PMID:25956680

  1. Reduced glomerular size selectivity in late streptozotocin-induced diabetes in rats: application of a distributed two-pore model

    PubMed Central

    Lubbad, Loay; Öberg, Carl M; Dhanasekaran, Subramanian; Nemmar, Abderrahim; Hammad, Fayez; Pathan, Javed Y; Rippe, Bengt; Bakoush, Omran

    2015-01-01

    Microalbuminuria is an early manifestation of diabetic nephropathy. Potential contributors to this condition are reduced glomerular filtration barrier (GFB) size- and charge selectivity, and impaired tubular reabsorption of filtered proteins. However, it was recently reported that no significant alterations in charge selectivity of the GFB occur in early experimental diabetic nephropathy. We here aimed at investigating the functional changes in the GFB in long-term type-1 diabetes in rats, applying a novel distributed two-pore model. We examined glomerular permeability in 15 male Wistar rats with at least 3 months of streptozotocin (STZ)-induced diabetes (blood glucose ?20 mmol/L) and in age-matched control rats. The changes in glomerular permeability were assessed by determining the glomerular sieving coefficients (?) for FITC-Ficoll (molecular radius 20–90 Å) using size exclusion HPLC. The values of ? for FITC-Ficoll of radius >50 Å were significantly increased in STZ-diabetic rats compared to age-matched controls (? for 50–69 Å = 0.001 vs. 0.0002, and ? for 70–90 Å = 0.0007 vs. 0.00006, P < 0.001), while ? for FITC-Ficoll <50 Å tended to be lower in diabetic rats than in controls (? for 36–49 Å = 0.013 vs. 0.016, ns). According to the distributed two-pore model, there was primarily an increase in macromolecular transport through large pores in the glomerular filter of diabetic rats associated with a loss of small-pore area. Deterioration in the glomerular size selectivity due to an increase in the number and size-spread of large pores, with no changes in the permeability of the small-pore system, represent the major functional changes observed after 3 months of induced experimental diabetes. PMID:26009635

  2. Milk-soluble formula increases food intake and reduces Il6 expression in elderly rat hypothalami.

    PubMed

    Ould Hamouda, Hassina; Delplanque, Bernadette; Benomar, Yacir; Crépin, Delphine; Riffault, Laure; LeRuyet, Pascale; Bonhomme, Cécile; Taouis, Mohammed

    2015-07-01

    Malnutrition in the elderly is accompanied by several metabolic dysfunctions, especially alterations in energy homeostasis regulation and a loss of insulin responsiveness. Nutritional recommendations aim to enrich food with high protein and energy supplements, and protein composition and lipid quality have been widely studied. Despite the numerous studies that have examined attempts to overcome malnutrition in the elderly through such nutritional supplementation, it is still necessary to study the effects of a combination of protein, lipids, and vitamin D (VitD). This can be done in animal models of elderly malnutrition. In the present study, we investigated the effects of several diet formulae on insulin responsiveness, inflammation, and the hypothalamic expression of key genes that are involved in energy homeostasis control. To mimic elderly malnutrition in humans, elderly Wistar rats were food restricted (R, -50%) for 12 weeks and then refed for 4 weeks with one of four different isocaloric diets: a control diet; a diet where milk soluble protein (MSP) replaced casein; a blend of milk fat, rapeseed, and DHA (MRD); or a full formula (FF) diet that combined MSP and a blend of MRD (FF). All of the refeeding diets contained VitD. We concluded that: (i) food restriction led to the upregulation of insulin receptor in liver and adipose tissue accompanied by increased Tnf? in the hypothalamus; (ii) in all of the refed groups, refeeding led to similar body weight gain during the refeeding period; and (iii) refeeding with MSP and MRD diets induced higher food intake on the fourth week of refeeding, and this increase was associated with reduced hypothalamic interleukin 6 expression. PMID:25994005

  3. Polychlorinated biphenyls and methylmercury act synergistically to reduce rat brain dopamine content in vitro.

    PubMed Central

    Bemis, J C; Seegal, R F

    1999-01-01

    Consumption of contaminated Great Lakes fish by pregnant women is associated with decreased birth weight and deficits in cognitive function in their infants and children. These fish contain many known and suspected anthropogenic neurotoxicants, making it difficult to determine which contaminant(s) are responsible for the observed deficits. We have undertaken a series of experiments to determine the relevant toxicants by comparing the neurotoxic effects of two of these contaminants--polychlorinated biphenyls (PCBs) and methylmercury (MeHg)--both of which are recognized neurotoxicants. Striatal punches obtained from adult rat brain were exposed to PCBs only, MeHg only, or the two in combination, and tissue and media concentrations of dopamine (DA) and its metabolites were determined by high performance liquid chromatography. Exposure to PCBs only reduced tissue DA and elevated media DA in a dose-dependent fashion. Exposure to MeHg only did not significantly affect either measure. However, when striatal punches were simultaneously exposed to PCBs and MeHg, there were significantly greater decreases in tissue DA concentrations and elevations in media DA than those caused by PCBs only, in the absence of changes in media lactate dehydrogenase concentrations. Elevations in both tissue and media 3, 4-dihydroxyphenylacetic acid concentrations were also observed. We suggest that the significant interactions between these two toxicants may be due to a common site of action (i.e., toxicant-induced increases in intracellular calcium and changes in second messenger systems) that influences DA function. The synergism between these contaminants suggests that future revisions of fish-consumption guidelines should consider contaminant interactions. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:10544155

  4. Cinnamaldehyde reduces IL-1beta-induced cyclooxygenase-2 activity in rat cerebral microvascular endothelial cells.

    PubMed

    Guo, Jian-You; Huo, Hai-Ru; Zhao, Bao-Sheng; Liu, Hong-Bin; Li, Lan-Fang; Ma, Yue-Ying; Guo, Shu-Ying; Jiang, Ting-Liang

    2006-05-10

    Cinnamaldehyde is a principle compound isolated from Guizhi-Tang, which is a famous traditional Chinese medical formula used to treat influenza, common cold and other pyretic conditions. The aim of the present study was to investigate the effects of cinnamaldehyde on expression and activity of cyclooxygenase (COX) and prostaglandin E(2) (PGE(2)) in rat cerebral microvascular endothelial cells (RCMEC). RCMEC were cultured, and identified by immunohistochemistry for von Willebrand factor in cytoplasm of the cells. Then cells were incubated in M199 medium containing interleukin (IL)-1beta in the presence or absence of cinnamaldehyde. After incubation, the medium was collected and the amount of PGE(2) was measured by enzyme-linked immunosorbent assay (ELISA). The cells were harvested, mRNA expression and activity of COX were analyzed by real-time reverse transcription-polymerase chain reaction (RT-PCR) with SYBR Green dye and ELISA respectively. Positive immunostaining for von Willebrand factor was present diffusely in the cytoplasm of >95% RCMEC. IL-1beta increased the mRNA expression and activity of COX-2, and production of PGE(2) in a dose- and time-dependent manner in RCMEC, while mRNA and activity of COX-1 were not significantly altered. Cinnamaldehyde significantly decreased IL-1beta-induced COX-2 activity and PGE(2) production in a dose-dependent manner, while it showed no inhibitory effect on IL-1beta-induced COX-2 mRNA expression in cultured RCMEC. In conclusion, cinnamaldehyde reduces IL-1beta-induced COX-2 activity, but not IL-1beta-induced COX-2 mRNA expression, and consequently inhibits production of PGE(2) in cultured RCMEC. PMID:16624280

  5. Hepatic AQP9 expression in male rats is reduced in response to PPAR? agonist treatment.

    PubMed

    Lebeck, Janne; Cheema, Muhammad Umar; Skowronski, Mariusz T; Nielsen, Søren; Praetorius, Jeppe

    2015-02-01

    The peroxisome proliferator receptor ? (PPAR?) is a key regulator of the hepatic response to fasting with effects on both lipid and carbohydrate metabolism. A role in hepatic glycerol metabolism has also been found; however, the results are somewhat contradictive. Aquaporin 9 (AQP9) is a pore-forming transmembrane protein that facilitates hepatic uptake of glycerol. Its expression is inversely regulated by insulin in male rodents, with increased expression during fasting. Previous results indicate that PPAR? plays a crucial role in the induction of AQP9 mRNA during fasting. In the present study, we use PPAR? agonists to explore the effect of PPAR? activation on hepatic AQP9 expression and on the abundance of enzymes involved in glycerol metabolism using both in vivo and in vitro systems. In male rats with free access to food, treatment with the PPAR? agonist WY 14643 (3 mg·kg(-1)·day(-1)) caused a 50% reduction in hepatic AQP9 abundance with the effect being restricted to AQP9 expressed in periportal hepatocytes. The pharmacological activation of PPAR? had no effect on the abundance of GlyK, whereas it caused an increased expression of hepatic GPD1, GPAT1, and L-FABP protein. In WIF-B9 and HepG2 hepatocytes, both WY 14643 and another PPAR? agonist GW 7647 reduced the abundance of AQP9 protein. In conclusion, pharmacological PPAR? activation results in a marked reduction in the abundance of AQP9 in periportal hepatocytes. Together with the effect on the enzymatic apparatus for glycerol metabolism, our results suggest that PPAR? activation in the fed state directs glycerol into glycerolipid synthesis rather than into de novo synthesis of glucose. PMID:25477377

  6. Melatonin reduces excitotoxic blood-brain barrier breakdown in neonatal rats.

    PubMed

    Moretti, R; Zanin, A; Pansiot, J; Spiri, D; Manganozzi, L; Kratzer, I; Favero, G; Vasiljevic, A; Rinaldi, V E; Pic, I; Massano, D; D'Agostino, I; Baburamani, A; La Rocca, M A; Rodella, L F; Rezzani, R; Ek, J; Strazielle, N; Ghersi-Egea, J-F; Gressens, P; Titomanlio, L

    2015-12-17

    The blood-brain barrier (BBB) is a complex structure that protects the central nervous system from peripheral insults. Understanding the molecular basis of BBB function and dysfunction holds significant potential for future strategies to prevent and treat neurological damage. The aim of our study was (1) to investigate BBB alterations following excitotoxicity and (2) to test the protective properties of melatonin. Ibotenate, a glutamate analog, was injected intracerebrally in postnatal day 5 (P5) rat pups to mimic excitotoxic injury. Animals were than randomly divided into two groups, one receiving intraperitoneal (i.p.) melatonin injections (5mg/kg), and the other phosphate buffer saline (PBS) injections. Pups were sacrificed 2, 4 and 18h after ibotenate injection. We determined lesion size at 5days by histology, the location and organization of tight junction (TJ) proteins by immunohistochemical studies, and BBB leakage by dextran extravasation. Expression levels of BBB genes (TJs, efflux transporters and detoxification enzymes) were determined in the cortex and choroid plexus by quantitative PCR. Dextran extravasation was seen 2h after the insult, suggesting a rapid BBB breakdown that was resolved by 4h. Extravasation was significantly reduced in melatonin-treated pups. Gene expression and immunohistochemical assays showed dynamic BBB modifications during the first 4h, partially prevented by melatonin. Lesion-size measurements confirmed white matter neuroprotection by melatonin. Our study is the first to evaluate BBB structure and function at a very early time point following excitotoxicity in neonates. Melatonin neuroprotects by preventing TJ modifications and BBB disruption at this early phase, before its previously demonstrated anti-inflammatory, antioxidant and axonal regrowth-promoting effects. PMID:26542996

  7. Physical Exercise Reduces Circulating Lipopolysaccharide and TLR4 Activation and Improves Insulin Signaling in Tissues of DIO Rats

    PubMed Central

    Oliveira, Alexandre G.; Carvalho, Bruno M.; Tobar, Natália; Ropelle, Eduardo R.; Pauli, José R.; Bagarolli, Renata A.; Guadagnini, Dioze; Carvalheira, José B.C.; Saad, Mario J.A.

    2011-01-01

    OBJECTIVE Insulin resistance in diet-induced obesity (DIO) is associated with a chronic systemic low-grade inflammation, and Toll–like receptor 4 (TLR4) plays an important role in the link among insulin resistance, inflammation, and obesity. The current study aimed to analyze the effect of exercise on TLR4 expression and activation in obese rats and its consequences on insulin sensitivity and signaling. RESEARCH DESIGN AND METHODS The effect of chronic and acute exercise was investigated on insulin sensitivity, insulin signaling, TLR4 activation, c-Jun NH2-terminal kinase (JNK) and I?B kinase (IKK?) activity, and lipopolysaccharide (LPS) serum levels in tissues of DIO rats. RESULTS The results showed that chronic exercise reduced TLR4 mRNA and protein expression in liver, muscle, and adipose tissue. However, both acute and chronic exercise blunted TLR4 signaling in these tissues, including a reduction in JNK and IKK? phosphorylation and IRS-1 serine 307 phosphorylation, and, in parallel, improved insulin-induced IR, IRS-1 tyrosine phosphorylation, and Akt serine phosphorylation, and reduced LPS serum levels. CONCLUSIONS Our results show that physical exercise in DIO rats, both acute and chronic, induces an important suppression in the TLR4 signaling pathway in the liver, muscle, and adipose tissue, reduces LPS serum levels, and improves insulin signaling and sensitivity. These data provide considerable progress in our understanding of the molecular events that link physical exercise to an improvement in inflammation and insulin resistance. PMID:21282367

  8. Microencapsulated Bifidobacterium longum subsp. infantis ATCC 15697 Favorably Modulates Gut Microbiota and Reduces Circulating Endotoxins in F344 Rats

    PubMed Central

    Saha, Shyamali; Prakash, Satya

    2014-01-01

    The gut microbiota is a bacterial bioreactor whose composition is an asset for human health. However, circulating gut microbiota derived endotoxins cause metabolic endotoxemia, promoting metabolic and liver diseases. This study investigates the potential of orally delivered microencapsulated Bifidobacterium infantis ATCC 15697 to modulate the gut microbiota and reduce endotoxemia in F344 rats. The rats were gavaged daily with saline or microencapsulated B. infantis ATCC 15697. Following 38 days of supplementation, the treated rats showed a significant (P < 0.05) increase in fecal Bifidobacteria (4.34 ± 0.46 versus 2.45 ± 0.25% of total) and B. infantis (0.28 ± 0.21 versus 0.52 ± 0.12 % of total) and a significant (P < 0.05) decrease in fecal Enterobacteriaceae (0.80 ± 0.45 versus 2.83 ± 0.63% of total) compared to the saline control. In addition, supplementation with the probiotic formulation reduced fecal (10.52 ± 0.18 versus 11.29 ± 0.16?EU/mg; P = 0.01) and serum (0.33 ± 0.015 versus 0.30 ± 0.015?EU/mL; P = 0.25) endotoxins. Thus, microencapsulated B. infantis ATCC 15697 modulates the gut microbiota and reduces colonic and serum endotoxins. Future preclinical studies should investigate the potential of the novel probiotic formulation in metabolic and liver diseases. PMID:24967382

  9. Involvement of aberrant DNA methylation on reduced expression of lysophosphatidic acid receptor-1 gene in rat tumor cell lines

    SciTech Connect

    Tsujiuchi, Toshifumi . E-mail: ttujiuch@life.kindai.ac.jp; Shimizu, Kyoko; Onishi, Mariko; Sugata, Eriko; Fujii, Hiromasa; Mori, Toshio; Honoki, Kanya; Fukushima, Nobuyuki

    2006-10-27

    Lysophosphatidic acid (LPA) is a bioactive phospholipid that stimulates cell proliferation, migration, and protects cells from apoptosis. It interacts with specific G protein-coupled transmembrane receptors. Recently, it has been reported that alterations of LPA receptor expression might be important in the malignant transformation of tumor cells. Therefore, to assess an involvement of DNA methylation in reduced expression of the LPA receptor-1 (lpa1) gene, we investigated the expression of the lpa1 gene and its DNA methylation patterns in rat tumor cell lines. Both rat brain-derived neuroblastoma B103 and liver-derived hepatoma RH7777 cells used in this study indicated no expression of lpa1. For the analysis of methylation status, bisulfite sequencing was performed with B103 and RH7777 cells, comparing with other lpa1 expressed cells and normal tissues of brain and liver. The lpa1 expressed cells and tissues were all unmethylated in this region of lpa1. In contrast, both B103 and RH7777 cells were highly methylated, correlating with reduced expression of the lpa1. Treatment with 5-aza 2'-deoxycytidine induced expression of lpa1 gene in B103 and RH7777 cells after 24 h. In RH7777 cells treated with 5-aza 2'-deoxycytidine, stress fiber formation was also observed in response to LPA in RH7777 cells, but not in untreated RH7777 cells. These results suggest that aberrant DNA methylation of the lpa1 gene may be involved in its reduced expression in rat tumor cells.

  10. ?-Glucans (Saccharomyces cereviseae) Reduce Glucose Levels and Attenuate Alveolar Bone Loss in Diabetic Rats with Periodontal Disease

    PubMed Central

    2015-01-01

    The objective of this study was to assess the effects of oral ingestion of ?-glucans isolated from Saccharomyces cereviseae on the metabolic profile, expression of gingival inflammatory markers and amount of alveolar bone loss in diabetic rats with periodontal disease. Diabetes mellitus was induced in 48 Wistar rats by intraperitoneal injection of streptozotocin (80 mg/kg). After confirming the diabetes diagnosis, the animals were treated with ?-glucans (by gavage) for 28 days. On the 14th day of this period, periodontal disease was induced using a ligature protocol. ?-glucans reduced the amount of alveolar bone loss in animals with periodontal disease in both the diabetic and non-diabetic groups (p < 0.05). ?-glucans reduced blood glucose, cholesterol and triacylglycerol levels in diabetic animals, both with and without periodontal disease (p < 0.05). Furthermore, treatment with ?-glucans reduced the expression of cyclooxygenase-2 and receptor activator of nuclear factor kappa-B ligand and increased osteoprotegerin expression in animals with diabetes and periodontal disease (p < 0.05). It was concluded that treatment with ?-glucans has beneficial metabolic and periodontal effects in diabetic rats with periodontal disease. PMID:26291983

  11. Direct gene delivery of human tissue kallikrein reduces blood pressure in spontaneously hypertensive rats.

    PubMed Central

    Wang, C; Chao, L; Chao, J

    1995-01-01

    Hypertension is a multigene and multifactorial disorder affecting approximately 25% of the population. To demonstrate potential therapeutic effects of human tissue kallikrein in hypertension, spontaneously hypertensive rats were subjected to somatic gene therapy. Two human tissue kallikrein DNA constructs, one under the promoter control of the metallothionein metal response element and the other under the control of the Rous sarcoma virus 3'-LTR, were generated. We delivered naked DNA constructs into spontaneously hypertensive rats via intravenous injection. The expression of human tissue kallikrein in rats was identified in the heart, lung, and kidney by reverse transcription polymerase chain reaction followed by Southern blot analysis and an ELISA specific for human tissue kallikrein. A single injection of both human kallikrein plasmid DNA constructs caused a sustained reduction of blood pressure which began 1 wk after injection and continued for 6 wk. A maximal effect of blood pressure reduction of 46 mmHg in rats was observed 2-3 wk after injection with kallikrein DNA as compared to rats with vector DNA (n = 6, P < 0.05). The hypotensive effect caused by somatic gene delivery of human tissue kallikrein in hypertensive rats is reversed by subcutaneous injection of aprotinin, a potent tissue kallikrein inhibitor. No antibodies to either human tissue kallikrein or kallikrein DNA were detected in rat sera after injection of the human kallikrein gene. These results show that direct gene delivery of human tissue kallikrein causes a sustained reduction in systolic blood pressure in genetically hypertensive rats and indicate that the feasibility of kallikrein gene therapy for treating human hypertension should be studied. Images PMID:7535795

  12. All-Trans Retinoic Acid Reduces Joint Adhesion Formation: An Experimental Study in Rats

    PubMed Central

    Wang, Yuguang; Zhang, Chao; Cheng, Huan; Douglas, Patricia; Wang, Zhiqiang; Lu, Yun

    2015-01-01

    Background Intra-articular adhesion is a common complication in post-surgical knees. The formation of post-surgical joint adhesion could lead to serious conditions. All-trans retinoic acid (ATRA) is a physiological metabolite of vitamin A that has a wide range of biological activities. The aim of the study was to verify the effects of (ATRA) in preventing adhesions in the post-operative rat knee. Material/Methods Eighty healthy adult male Wistar rats underwent femoral condyle-exposing surgery. After surgery, cotton pads soaked with the vehicle or various concentrations of ATRA (0.1%, 0.05%, 0.025%) were applied to the surgery site for 5 min. The post-surgical knee joints were fixed with micro-Kirschner wires in a flexed position for 4 weeks. The rats were killed 4 weeks after surgery. The effect of ATRA on the prevention of intra-articular adhesion was evaluated using histological analyses, hydroxyproline content, visual score, and inflammatory factor activity evaluation. Results No obvious postoperative complications or signs of infection in the rats were observed. None of the rats died before the scheduled time. The rats in the 0.1% ATRA group showed better outcomes, as suggested by the visual scores, hydroxyproline contents, and inflammatory factors expressional levels, than the other 2 groups. The local application of 0.1% ATRA was able to suppress adhesions, collagen expression, and inflammatory activity in the post-surgical rat knees. Conclusions In the rat knee surgery model, the application of intra-articular ATRA was able to decrease intra-articular scar adhesion formation, collagen expression, and inflammatory activities. ATRA was found to work in a dose-dependent manner, with 0.1% being possible optimal concentration. PMID:26044570

  13. Inhibition of lipoxygenase pathway reduces blood pressure in renovascular hypertensive rats.

    PubMed

    Nozawa, K; Tuck, M L; Golub, M; Eggena, P; Nadler, J L; Stern, N

    1990-12-01

    To assess the potential role of the lipoxygenase (LO) pathway in the vasculature in an angiotensin II (ANG II)-dependent model of hypertension, we investigated the effect of LO pathway inhibition on blood pressure in the two-kidney, one-clip (2K,1C) Goldblatt hypertensive rat. The development of renovascular hypertension in 2K,1C rats was attenuated by oral administration of phenidone (Phe, 60 mg.kg-1.day-1), a nonselective LO inhibitor, throughout the 3 wk of observation after renal artery constriction. In contrast, the same treatment protocol had no effect on the evolution of hypertension in the deoxycorticosterone acetate-salt rat, which is considered to be an ANG II-independent form of hypertension. The hypotensive effect of Phe was not associated with changes in plasma renin or aldosterone concentration (PRC and PAC, respectively). In vitro synthesis of 12-hydroxyeicosatetraenoic acid (12-HETE) by aortic segments was increased in 2K,1C hypertensive rats compared with sham-operated rats. In addition, the synthesis of 12-HETE was suppressed by the in vitro addition of Phe (10(-4) M) to aortic-segment incubates obtained from 2K,1C rats and sham-operated rats. Acute administration of Phe (30 or 60 mg/kg) in 2K,1C hypertensive rats produced a rapid and sustained decrease in mean blood pressure (MBP). This decrease in MBP was accompanied by a brisk rise in PRC and PAC. In contrast, bolus administration of indomethacin, a selective cyclooxygenase inhibitor, did not affect MBP, PRC, or PAC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2124426

  14. How forelimb and hindlimb function changes with incline and perch diameter in the green anole, Anolis carolinensis.

    PubMed

    Foster, Kathleen L; Higham, Timothy E

    2012-07-01

    The range of inclines and perch diameters in arboreal habitats poses a number of functional challenges for locomotion. To effectively overcome these challenges, arboreal lizards execute complex locomotor behaviors involving both the forelimbs and the hindlimbs. However, few studies have examined the role of forelimbs in lizard locomotion. To characterize how the forelimbs and hindlimbs differentially respond to changes in substrate diameter and incline, we obtained three-dimensional high-speed video of green anoles (Anolis carolinensis) running on flat (9 cm wide) and narrow (1.3 cm) perches inclined at 0, 45 and 90 deg. Changes in perch diameter had a greater effect on kinematics than changes in incline, and proximal limb variables were primarily responsible for these kinematic changes. In addition, a number of joint angles exhibited greater excursions on the 45 deg incline compared with the other inclines. Anolis carolinensis adopted strategies to maintain stability similar to those of other arboreal vertebrates, increasing limb flexion, stride frequency and duty factor. However, the humerus and femur exhibited several opposite kinematic trends with changes in perch diameter. Further, the humerus exhibited a greater range of motion than the femur. A combination of anatomy and behavior resulted in differential kinematics between the forelimb and the hindlimb, and also a potential shift in the propulsive mechanism with changes in external demand. This suggests that a better understanding of single limb function comes from an assessment of both forelimbs and hindlimbs. Characterizing forelimb and hindlimb movements may reveal interesting functional differences between Anolis ecomorphs. Investigations into the physiological mechanisms underlying the functional differences between the forelimb and the hindlimb are needed to fully understand how arboreal animals move in complex habitats. PMID:22675190

  15. Blimp1 regulates development of the posterior forelimb, caudal pharyngeal arches, heart and sensory vibrissae in mice.

    PubMed

    Robertson, Elizabeth J; Charatsi, Iphigenie; Joyner, Clive J; Koonce, Chad H; Morgan, Marc; Islam, Ayesha; Paterson, Carol; Lejsek, Emily; Arnold, Sebastian J; Kallies, Axel; Nutt, Stephen L; Bikoff, Elizabeth K

    2007-12-01

    The zinc-finger transcriptional repressor Blimp1 (Prdm1) controls gene expression patterns during differentiation of B lymphocytes and regulates epigenetic changes required for specification of primordial germ cells. Blimp1 is dynamically expressed at diverse tissue sites in the developing mouse embryo, but its functional role remains unknown because Blimp1 mutant embryos arrest at E10.5 due to placental insufficiency. To explore Blimp1 activities at later stages in the embryo proper, here we used a conditional inactivation strategy. A Blimp1-Cre transgenic strain was also exploited to generate a fate map of Blimp1-expressing cells. Blimp1 plays essential roles in multipotent progenitor cell populations in the posterior forelimb, caudal pharyngeal arches, secondary heart field and sensory vibrissae and maintains key signalling centres at these diverse tissues sites. Interestingly, embryos carrying a hypomorphic Blimp1gfp reporter allele survive to late gestation and exhibit similar, but less severe developmental abnormalities, whereas transheterozygous Blimp1(gfp/-) embryos with further reduced expression levels, display exacerbated defects. Collectively, the present experiments demonstrate that Blimp1 requirements in diverse cell types are exquisitely dose dependent. PMID:18039967

  16. Adrenalectomy reduces neuropeptide Y–induced insulin release and NPY receptor expression in the rat ventromedial hypothalamus

    PubMed Central

    Wisialowski, Todd; Parker, Rachel; Preston, Elaine; Sainsbury, Amanda; Kraegen, Edward; Herzog, Herbert; Cooney, Gregory

    2000-01-01

    Chronic central administration of neuropeptide Y (NPY) causes hyperphagia, hyperinsulinemia, and obesity, a response that is prevented by prior adrenalectomy (ADX) in rats. The basis of NPY’s effect and how the acute responses to this peptide are affected by ADX remain unknown. This study investigates the role of glucocorticoids in acute NPY-stimulated food intake, acute NPY-induced insulin release, and hypothalamic NPY-receptor mRNA expression levels. NPY-induced food intake was similar in ADX and control rats after acute intracerebroventricular injection of NPY. Injection of NPY caused a significant increase in plasma insulin in control rats, but this effect was completely absent in ADX rats in which basal plasma insulin levels were also lower than controls. In addition, ADX significantly reduced the number of neurons expressing NPY receptor Y1 and Y5 mRNAs in the ventromedial hypothalamus (VMH), without affecting Y1- or Y5-mRNA expression in the paraventricular hypothalamus or the arcuate nucleus. These data indicate that glucocorticoids are necessary for acute NPY-mediated insulin release and suggest that the mechanisms involve glucocorticoid regulation of Y1 and Y5 receptors specifically within the VMH nucleus. PMID:10792000

  17. Roux-en-Y gastric bypass surgery reduces bone mineral density and induces metabolic acidosis in rats.

    PubMed

    Abegg, Kathrin; Gehring, Nicole; Wagner, Carsten A; Liesegang, Annette; Schiesser, Marc; Bueter, Marco; Lutz, Thomas A

    2013-11-01

    Roux-en-Y gastric bypass (RYGB) surgery leads to bone loss in humans, which may be caused by vitamin D and calcium malabsorption and subsequent secondary hyperparathyroidism. However, because these conditions occur frequently in obese people, it is unclear whether they are the primary causes of bone loss after RYGB. To determine the contribution of calcium and vitamin D malabsorption to bone loss in a rat RYGB model, adult male Wistar rats were randomized for RYGB surgery, sham-operation-ad libitum fed, or sham-operation-body weight-matched. Bone mineral density, calcium and phosphorus balance, acid-base status, and markers of bone turnover were assessed at different time points for 14 wk after surgery. Bone mineral density decreased for several weeks after RYGB. Intestinal calcium absorption was reduced early after surgery, but plasma calcium and parathyroid hormone levels were normal. 25-hydroxyvitamin D levels decreased, while levels of active 1,25-dihydroxyvitamin D increased after surgery. RYGB rats displayed metabolic acidosis due to increased plasma lactate levels and increased urinary calcium loss throughout the study. These results suggest that initial calcium malabsorption may play a key role in bone loss early after RYGB in rats, but other factors, including chronic metabolic acidosis, contribute to insufficient bone restoration after normalization of intestinal calcium absorption. Secondary hyperparathyroidism is not involved in postoperative bone loss. Upregulated vitamin D activation may compensate for any vitamin D malabsorption. PMID:24026074

  18. DL-propargylglycine reduces blood pressure and renal injury but increases kidney weight in angiotensin-II infused rats.

    PubMed

    Oosterhuis, Nynke R; Frenay, Anne-Roos S; Wesseling, Sebastiaan; Snijder, Pauline M; Slaats, Gisela G; Yazdani, Saleh; Fernandez, Bernadette O; Feelisch, Martin; Giles, Rachel H; Verhaar, Marianne C; Joles, Jaap A; van Goor, Harry

    2015-09-15

    Hydrogen sulfide (H2S), carbon monoxide (CO) and nitric oxide (NO) share signaling and vasorelaxant properties and are involved in proliferation and apoptosis. Inhibiting NO production or availability induces hypertension and proteinuria, which is prevented by concomitant blockade of the H2S producing enzyme cystathionine ?-lyase (CSE) by d,l-propargylglycine (PAG). We hypothesized that blocking H2S production ameliorates Angiotensin II (AngII)-induced hypertension and renal injury in a rodent model. Effects of concomitant administration of PAG or saline were therefore studied in healthy (CON) and AngII hypertensive rats. In CON rats, PAG did not affect systolic blood pressure (SBP), but slightly increased proteinuria. In AngII rats PAG reduced SBP, proteinuria and plasma creatinine (180 ± 12 vs. 211 ± 19 mmHg; 66 ± 35 vs. 346 ± 92 mg/24 h; 24 ± 6 vs. 47 ± 15 ?mol/L, respectively; p < 0.01). Unexpectedly, kidney to body weight ratio was increased in all groups by PAG (p < 0.05). Renal injury induced by AngII was reduced by PAG (p < 0.001). HO-1 gene expression was increased by PAG alone (p < 0.05). PAG increased inner cortical tubular cell proliferation after 1 week and decreased outer cortical tubular nucleus number/field after 4 weeks. In vitro proximal tubular cell size increased after exposure to PAG. In summary, blocking H2S production with PAG reduced SBP and renal injury in AngII infused rats. Independent of the cardiovascular and renal effects, PAG increased HO-1 gene expression and kidney weight. PAG alone increased tubular cell size and proliferation in-vivo and in-vitro. Our results are indicative of a complex interplay of gasotransmitter signaling/action of mutually compensatory nature in the kidney. PMID:26192363

  19. Acquisition of a High-precision Skilled Forelimb Reaching Task in Rats.

    PubMed

    Zemmar, Ajmal; Kast, Brigitte; Lussi, Karin; Luft, Andreas R; Schwab, Martin E

    2015-01-01

    Movements are the main measurable output of central nervous system function. Developing behavioral paradigms that allow detailed analysis of motor learning and execution is of critical importance in order to understand the principles and processes that underlie motor function. Here we present a paradigm to study movement acquisition within a daily session of training (within-session) representing the fast learning component and primary acquisition as well as skilled motor learning over several training sessions (between-session) representing the slow learning component and consolidation of the learned task. This behavioral paradigm increases the degree of difficulty and complexity of the motor skill task due to two features: First, the animal realigns its body prior to each pellet retrieval forcing renewed orientation and preventing movement execution from the same angle. Second, pellets are grasped from a vertical post that matches the diameter of the pellet and is placed in front of the cage. This requires a precise grasp for successful pellet retrieval and thus prevents simple pulling of the pellet towards the animal. In combination with novel genetics, imaging and electrophysiological technologies, this behavioral method will aid to understand the morphological, anatomical and molecular underpinnings of motor learning and memory. PMID:26131653

  20. Despite increased plasma concentration, inflammation reduces potency of calcium channel antagonists due to lower binding to the rat heart

    PubMed Central

    Sattari, Saeed; Dryden, William F; Eliot, Lise A; Jamali, Fakhreddin

    2003-01-01

    Rheumatoid arthritis reduces verapamil oral clearance thereby increases plasma concentration of the drug. This coincides with reduced drug effects through an unknown mechanism. The effect of interferon-induced acute inflammation on the pharmacokinetics and electrocardiogram of verapamil (20 mg kg?1, p.o.) and nifedipine (0.1 mg kg?1, i.v.) was studied in Sprague–Dawley rats. The effect of both acute and chronic inflammation on radioligand binding to cardiac L-type calcium channels was also investigated. Acute inflammation resulted in increased plasma concentration of verapamil but had no effect on that of nifedipine. Verapamil binding to plasma proteins was unaffected. As has been reported for humans, the increased verapamil concentration coincided with a reduction in the degree to which PR interval is prolonged by the drug. The effect of nifedipine on PR interval was also reduced by inflammation. Maximum binding of 3H-nitrendipine to cardiac cell membrane was significantly reduced from 63.2±2.5 fmol mg?1 protein in controls to 46.4±2.0 in acute inflammation and from 66.8±2.2 fmol mg?1 protein in controls to 42.2±2.0 in chronic inflammation. Incubation of the normal cardiac cell membranes with 100 and 1000 pg ml?1 of rat tissue necrosis factor-? did not influence the binding indices to the calcium channels. Our data suggest that the reduced calcium channel responsiveness is because of altered binding to channels. PMID:12839868

  1. Trans-canal laser irradiation reduces tinnitus perception of salicylate treated rat.

    PubMed

    Park, Young Min; Na, Woo Sung; Park, Il Yong; Suh, Myung-Whan; Rhee, Chung-Ku; Chung, Phil-Sang; Jung, Jae Yun

    2013-06-01

    The aim of this study was to find out the effect of low-level laser therapy (LLLT) on salicylate-induced tinnitus in the rat model. Fourteen Sprague-Dawley rats (8 weeks; 240-280 gm) were divided into 2 groups (study group, control group). Rats of both groups were treated with 400 mg/kg/day of sodium salicylate for 8 consecutive days. Tinnitus was monitored using GPIAS (Gap Prepulse Inhibition of Acoustic Startle) 2 h after first salicylate treatment, and every 24 h during 9 days of treatment. Rats in laser group were irradiated to each ear with wavelength of 830 nm diode laser (165 mW/cm(2)) for 30 min daily for 8 days. During salicylate treatment, rats of study group irradiated with low level laser showed significantly higher GPIAS values throughout the experiment. Therapeutic effect of LLLT is demonstrated in animal tinnitus model by means of GPIAS. Further experimental studies are needed to find possible mechanisms and better methods to improve LLLT efficacy. PMID:23583341

  2. 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. PMID:25994128

  3. The forelimb of Tyrannosaurus rex: a pathetic vestigial organ or an integral part of a fearsome predator?

    NASA Astrophysics Data System (ADS)

    Lee, Scott A.; Thomas, Joshua

    2014-03-01

    The function of the forelimb of Tyrannosaurus rex remains a controversial topic since it was too short to transfer food directly to the mouth. Since Tyrannosaurus rex was bipedal, the forelimb was not involved in locomotion. Suggestions for its possible use include providing an initial push for a laying animal to stand or to hold position during mating. We report numerical calculations performed to determine the moment of inertia of the forearm and the torques generated by the muscles of the arm, based on three-dimensional representations of the forelimb. Our results imply that the forelimb was capable of very high angular accelerations, on the order of 130 radians/s2. This corresponds to a tangential acceleration of the manus on the order of 90 m/s2 or about 9g, indicating that the manus could be moved extremely quickly to control a struggling prey animal immediately before the death blow was delivered by the teeth of Tyrannosaurus rex. Rather than a pathetic vestigial organ, these calculations suggest that the forelimbs were an integral part of the predation tactics of Tyrannosaurus rex.

  4. Plasma redox status is impaired in the portacaval shunted rat – the risk of the reduced antioxidant ability

    PubMed Central

    Aller, Maria-Angeles; García-Fernández, Maria-Inmaculada; Sánchez-Patán, Fernando; Santín, Luis; Rioja, José; Anchuelo, Raquel; Arias, Jaime; Arias, Jorge-Luis

    2008-01-01

    Background Portacaval shunting in rats produces a reduction of hepatic oxidant scavenging ability. Since this imbalance in hepatic oxidant/antioxidant homeostasis could coexist with systemic changes of oxidant stress/antioxidant status, plasma oxidants and antioxidant redox status in plasma of portacaval shunted-rats were determined. Results Male Wistar male: Control (n = 11) and with portacaval shunt (PCS; n = 11) were used. Plasma levels of the oxidant serum advanced oxidation protein products (AOPP), lipid hydroperoxides (LOOH), the antioxidant total thiol (GSH) and total antioxidant status (TAX) were measured. Albumin, ammonia, Aspartate-aminotransferase (AST), Alanine-aminotransferase (ALT), thiostatin and alpha-1-acid glycoprotein (?1-AGP) were also assayed 4 weeks after the operation. AOPPs were significantly higher (50.51 ± 17.87 vs. 36.25 ± 7.21 ?M; p = 0.02) and TAX was significantly lower (0.65 ± 0.03 vs. 0.73 ± 0.06 mM; p = 0.007) in PCS compared to control rats. Also, there was hypoalbuminemia (2.54 ± 0.08 vs. 2.89 ± 0.18 g/dl; p = 0.0001) and hyperammonemia (274.00 ± 92.25 vs. 104.00 ± 48.05 ?M; p = 0.0001) and an increase of thiostatin (0.23 ± 0.04 vs. 0.09 ± 0.01 mg/ml; p = 0.001) in rats with a portacaval shunt. The serum concentration of ammonia is correlated with albumin levels (r = 0.624; p = 0.04) and TAX correlates with liver weight (r = 0.729; p = 0.017) and albumin levels (r = 0.79; p = 0.007) Conclusion These findings suggest that in rats with a portacaval shunt a systemic reduction of oxidant scavenging ability, correlated with hyperammonemia, is principally produced. It could be hypothesized, therefore, that the reduced antioxidant defences would mediate a systemic inflammation. PMID:18251997

  5. Photoacoustic detection of functional responses in the motor cortex of awake behaving monkey during forelimb movement

    NASA Astrophysics Data System (ADS)

    Jo, Janggun; Zhang, Hongyu; Cheney, Paul D.; Yang, Xinmai

    2012-11-01

    Photoacoustic (PA) imaging was applied to detect the neuronal activity in the motor cortex of an awake, behaving monkey during forelimb movement. An adult macaque monkey was trained to perform a reach-to-grasp task while PA images were acquired through a 30-mm diameter implanted cranial chamber. Increased PA signal amplitude results from an increase in regional blood volume and is interpreted as increased neuronal activity. Additionally, depth-resolved PA signals enabled the study of functional responses in deep cortical areas. The results demonstrate the feasibility of utilizing PA imaging for studies of functional activation of cerebral cortex in awake monkeys performing behavioral tasks.

  6. Forelimb muscle architecture and myosin isoform composition in the groundhog (Marmota monax).

    PubMed

    Rupert, Joseph E; Rose, Jacob A; Organ, Jason M; Butcher, Michael T

    2015-01-15

    Scratch-digging mammals are commonly described as having large, powerful forelimb muscles for applying high force to excavate earth, yet studies quantifying the architectural properties of the musculature are largely unavailable. To further test hypotheses about traits that represent specializations for scratch-digging, we quantified muscle architectural properties and myosin expression in the forelimb of the groundhog (Marmota monax), a digger that constructs semi-complex burrows. Architectural properties measured were muscle moment arm, muscle mass (MM), belly length (ML), fascicle length (l(F)), pennation angle and physiological cross-sectional area (PCSA), and these metrics were used to estimate maximum isometric force, joint torque and power. Myosin heavy chain (MHC) isoform composition was determined in selected forelimb muscles by SDS-PAGE and densitometry analysis. Groundhogs have large limb retractors and elbow extensors that are capable of applying moderately high torque at the shoulder and elbow joints, respectively. Most of these muscles (e.g. latissimus dorsi and pectoralis superficialis) have high l(F)/ML ratios, indicating substantial shortening ability and moderate power. The unipennate triceps brachii long head has the largest PCSA and is capable of the highest joint torque at both the shoulder and elbow joints. The carpal and digital flexors show greater pennation and shorter fascicle lengths than the limb retractors and elbow extensors, resulting in higher PCSA/MM ratios and force production capacity. Moreover, the digital flexors have the capacity for both appreciable fascicle shortening and force production, indicating high muscle work potential. Overall, the forelimb musculature of the groundhog is capable of relatively low sustained force and power, and these properties are consistent with the findings of a predominant expression of the MHC-2A isoform. Aside from the apparent modifications to the digital flexors, the collective muscle properties observed are consistent with its behavioral classification as a less-specialized burrower and these may be more representative of traits common to numerous rodents with burrowing habits or mammals with some fossorial ability. PMID:25452499

  7. 17?-estradiol ameliorates light-induced retinal damage in Sprague-Dawley rats by reducing oxidative stress.

    PubMed

    Wang, Shaolan; Wang, Baoying; Feng, Yan; Mo, Mingshu; Du, Fangying; Li, Hongbo; Yu, Xiaorui

    2015-01-01

    Oxidative stress is considered as a major cause of light-induced retinal neurodegeneration. The protective role of 17?-estradiol (?E2) in neurodegenerative disorders is well known, but its underlying mechanism remains unclear. Here, we utilized a light-induced retinal damage model to explore the mechanism by which ?E2 exerts its neuroprotective effect. Adult male and female ovariectomized (OVX) rats were exposed to 8,000 lx white light for 12 h to induce retinal light damage. Electroretinogram (ERG) assays and hematoxylin and eosin (H&E) staining revealed that exposure to light for 12 h resulted in functional damage to the rat retina, histological changes, and retinal neuron loss. However, intravitreal injection (IVI) of ?E2 significantly rescued this impaired retinal function in both female and male rats. Based on the level of malondialdehyde (MDA) production (a biomarker of oxidative stress), an increase in retinal oxidative stress followed light exposure, and ?E2 administration reduced this light-induced oxidative stress. Quantitative reverse-transcriptase (qRT)-PCR indicated that the messenger RNA (mRNA) levels of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (Gpx) were downregulated in female OVX rats but were upregulated in male rats after light exposure, suggesting a gender difference in the regulation of these antioxidant enzyme genes in response to light. However, ?E2 administration restored or enhanced the SOD and Gpx expression levels following light exposure. Although the catalase (CAT) expression level was insensitive to light stimulation, ?E2 also increased the CAT gene expression level in both female OVX and male rats. Further examination indicated that the antioxidant proteins thioredoxin (Trx) and nuclear factor erythroid 2-related factor 2 (Nrf2) are also involved in ?E2-mediated antioxidation and that the cytoprotective protein heme oxygenase-1 (HO-1) plays a key role in the endogenous defense mechanism against light exposure in a ?E2-independent manner. Taken together, we provide evidence that ?E2 protects against light-induced retinal damage via its antioxidative effect, and its underlying mechanism involves the regulation of the gene expression levels of antioxidant enzymes (SOD, CAT, and Gpx) and proteins (Trx and Nrf2). Our study provides conceptual evidence in support of estrogen replacement therapy for postmenopausal women to reduce the risk of age-related macular degeneration. PMID:25038876

  8. Diuresis and reduced urinary osmolality in rats produced by small-molecule UT-A-selective urea transport inhibitors

    PubMed Central

    Esteva-Font, Cristina; Cil, Onur; Phuan, Puay-Wah; Su, Tao; Lee, Sujin; Anderson, Marc O.; Verkman, A. S.

    2014-01-01

    Urea transport (UT) proteins of the UT-A class are expressed in epithelial cells in kidney tubules, where they are required for the formation of a concentrated urine by countercurrent multiplication. Here, using a recently developed high-throughput assay to identify UT-A inhibitors, a screen of 50,000 synthetic small molecules identified UT-A inhibitors of aryl-thiazole, ?-sultambenzosulfonamide, aminocarbonitrile butene, and 4-isoxazolamide chemical classes. Structure-activity analysis identified compounds that inhibited UT-A selectively by a noncompetitive mechanism with IC50 down to ?1 ?M. Molecular modeling identified putative inhibitor binding sites on rat UT-A. To test compound efficacy in rats, formulations and administration procedures were established to give therapeutic inhibitor concentrations in blood and urine. We found that intravenous administration of an indole thiazole or a ?-sultambenzosulfonamide at 20 mg/kg increased urine output by 3–5-fold and reduced urine osmolality by ?2-fold compared to vehicle control rats, even under conditions of maximum antidiuresis produced by 1-deamino-8-d-arginine vasopressin (DDAVP). The diuresis was reversible and showed urea > salt excretion. The results provide proof of concept for the diuretic action of UT-A-selective inhibitors. UT-A inhibitors are first in their class salt-sparing diuretics with potential clinical indications in volume-overload edemas and high-vasopressin-associated hyponatremias.—Esteva-Font, C., Cil, O., Phuan, P.-W., Su, T., Lee, S., Anderson, M. O., Verkman, A. S. Diuresis and reduced urinary osmolality in rats produced by small-molecule UT-A-selective urea transport inhibitors. PMID:24843071

  9. Blooming reduces the antioxidant capacity of dark chocolate in rats without lowering its capacity to improve lipid profiles.

    PubMed

    Shadwell, Naomi; Villalobos, Fatima; Kern, Mark; Hong, Mee Young

    2013-05-01

    Dark chocolate contains high levels of antioxidants which are linked to a reduced risk of cardiovascular disease. Chocolate blooming occurs after exposure to high temperatures. Although bloomed chocolate is safe for human consumption, it is not known whether or not the biological function of bloomed chocolate is affected. We hypothesized that bloomed chocolate would reduce the antioxidant potential and lipid-lowering properties of chocolate through altered expression of related genes. Thirty Sprague-Dawley rats were divided into 3 groups and fed either the control (CON), regular dark chocolate (RDC), or bloomed dark chocolate (BDC) diet. After 3 weeks, serum lipid levels and antioxidant capacity were measured. Hepatic expression of key genes was determined by real time polymerase chain reaction (PCR). Sensory characteristics of bloomed versus regular chocolate were assessed in 28 semi-trained panelists. Rats fed RDC exhibited greater serum antioxidant capacities compared to the CON (P < .05). Antioxidant levels of BDC were not different from RDC or CON. Both RDC and BDC lowered TG compared to CON (P < .05). The rats fed RDC had higher high-density lipoprotein levels compared to the CON (P < .05). In rats given RDC, fatty acid synthase gene expression was down-regulated and low-density lipoprotein receptor transcription was up-regulated (P < .05). Sensory panelists preferred the appearance and surface smoothness of the regular chocolate compared to bloomed chocolate (P < .001). Although blooming blunted the robust antioxidant response produced by regular dark chocolate, these results suggest that bloomed dark chocolate yields similarly beneficial effects on most blood lipid parameters or biomarkers. However, regular dark chocolate may be more beneficial for the improvement of antioxidant status and modulation of gene expression involved in lipid metabolism and promoted greater sensory ratings. PMID:23684443

  10. The chemopreventive potential of Curcuma purpurascens rhizome in reducing azoxymethane-induced aberrant crypt foci in rats

    PubMed Central

    Rouhollahi, Elham; Moghadamtousi, Soheil Zorofchian; Al-Henhena, Nawal; Kunasegaran, Thubasni; Hasanpourghadi, Mohadeseh; Looi, Chung Yeng; Abd Malek, Sri Nurestri; Awang, Khalijah; Abdulla, Mahmood Ameen; Mohamed, Zahurin

    2015-01-01

    Curcuma purpurascens BI. rhizome, a member of the Zingiberaceae family, is a popular spice in Indonesia that is traditionally used in assorted remedies. Dichloromethane extract of C. purpurascens BI. rhizome (DECPR) has previously been shown to have an apoptosis-inducing effect on colon cancer cells. In the present study, we examined the potential of DECPR to prevent colon cancer development in rats treated with azoxymethane (AOM) (15 mg/kg) by determining the percentage inhibition in incidence of aberrant crypt foci (ACF). Starting from the day immediately after AOM treatment, three groups of rats were orally administered once a day for 2 months either 10% Tween 20 (5 mL/kg, cancer control), DECPR (250 mg/kg, low dose), or DECPR (500 mg/kg, high dose). Meanwhile, the control group was intraperitoneally injected with 5-fluorouracil (35 mg/kg) for 5 consecutive days. After euthanizing the rats, the number of ACF was enumerated in colon tissues. Bax, Bcl-2, and proliferating cell nuclear antigen (PCNA) protein expressions were examined using immunohistochemical and Western blot analyses. Antioxidant enzymatic activity was measured in colon tissue homogenates and associated with malondialdehyde level. The percentage inhibition of ACF was 56.04% and 68.68% in the low- and high-dose DECPR-treated groups, respectively. The ACF inhibition in the treatment control group was 74.17%. Results revealed that DECPR exposure at both doses significantly decreased AOM-induced ACF formation, which was accompanied by reduced expression of PCNA. Upregulation of Bax and downregulation of Bcl-2 suggested the involvement of apoptosis in the chemopreventive effect of DECPR. In addition, the oxidative stress resulting from AOM treatment was significantly attenuated after administration of DECPR, which was shown by the elevated antioxidant enzymatic activity and reduced malondialdehyde level. Taken together, the present data clearly indicate that DECPR significantly inhibits ACF formation in AOM-treated rats and may offer protection against colon cancer development. PMID:26251570

  11. Reduced serine racemase expression in aging rat cerebellum is associated with oxidative DNA stress and hypermethylation in the promoter.

    PubMed

    Zhang, He; Kuang, Xiu-Li; Chang, Yuhua; Lu, Jinfang; Jiang, Haiyan; Wu, Shengzhou

    2015-12-10

    Regulation of serine racemase (SR) occurs at transcriptional and translational levels; post-translational modification, cytosolic distribution as well as allosteric effect regulate SR activity. In this study, we report a new route of SR regulation, i.e. oxidative stress and hypermethylation of the srr (gene of SR) promoter correlate with its reduced transcription in aging rat cerebella. We first showed that the mRNA and protein level of srr were decreased in the homogenates of rat cerebellum at age 12 months compared with the counterparts from age 20 days. The reduction of SR protein level in aging cerebella was evidenced by decreased immunostaining observed in the cell body of granule cells or Purkinje cells. Staining for 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker for oxidative stress to DNA, was much stronger in granule cell or Purkinje cell nuclei from rat cerebella at 12 months compared with staining at 20 days. We further detected srr promoter hypermethylation at 12 months compared with that at 20 days by use of bisulfite sequencing PCR, coinciding with elevated protein levels of DNA methyltransferase 1 (DNMT1) in homogenates of aging cerebella. In vitro, we demonstrated that chronic treatment with the oxidant, menadione (VK3), reduced srr mRNA levels, which was reversed by the DNA demethylating agent 5-Aza-dC-2'-deoxycytidine (5-Aza-dC) in primary cerebellar granule cell cultures. Together, the in vivo and ex vivo results suggest that oxidative DNA stress and srr promoter hypermethylation are associated with reduced srr gene transcription and corresponding reduced protein expression in aging cerebella. PMID:26505919

  12. Astaxanthin reduces type 2 diabetic?associated cognitive decline in rats via activation of PI3K/Akt and attenuation of oxidative stress.

    PubMed

    Li, Xiaobin; Qi, Zhonghua; Zhao, Longshan; Yu, Zhan

    2016-01-01

    Astaxanthin (AST) is an oxygenated derivative of carotenoid, which possesses a strong antioxidant activity. AST can effectively remove active oxygen from the body, and is thus considered to have an important role in disease prevention and treatment. The present study aimed to determine the effects of AST on type 2 diabetic?associated cognitive decline (DACD) in rats. Rats were intraperitoneally injected with streptozotocin (STZ), in order to establish a model of diabetes mellitus (DM). A total of 40 rats were randomly divided into five groups: The control group, the DM group, the AST (50 mg/kg) group, the AST (100 mg/kg) group, and the AST+LY294002 group (AST, 50 mg/kg and LY, 0.25 µg/100 g). Following a 14?day treatment with AST, the body weight, blood glucose levels and cognitive function were determined. In addition, the protein expression levels of phosphatidylinositol 3?kinase (PI3K)/Akt, glutathione peroxidase and superoxide dismutase activity, glutathione and malondialdehyde content, and inducible nitric oxide synthase (iNOS), caspase?3 and caspase?9 activity were detected in the rats with DM. AST clearly augmented body weight and reduced blood glucose levels in rats with DM. Furthermore, treatment with AST significantly improved the cognitive function of rats with DM. Treatment with AST activated the PI3K/Akt pathway, and suppressed oxidative stress in the DM rats. In the cerebral cortex and hippocampus of the rats with DM, the activities of iNOS, caspase?3 and caspase?9 were markedly reduced. Furthermore, treatment with the Akt inhibitor LY294002 reduced the effectiveness of AST on DACD in rats. In conclusion, AST may reduce type 2 DACD in rats via activation of PI3K/Akt and attenuation of oxidative stress. PMID:26648531

  13. IPRODIONE DELAYS MALE RAT PUBERTAL DEVELOPMENT, REDUCING SERUM TESTOSTERONE AND EX VIVO TESTOSTERONE PRODUCTION

    EPA Science Inventory

    Iprodione (IPRO) is a dichlorophenyl dicarboximide fungicide similar to the androgen receptor (AR) antagonist vinclozolin. The current studies were designed to determine if IPRO would delay male rat pubertal development like vinclozolin and to identify the mechanism(s) of action...

  14. Immuno-Modulator Metallo-Peptide Reduces Inflammatory State in Obese Zucker Fa/Fa Rats

    PubMed Central

    Gómez-Solís, Antonieta; Reyes-Esparza, Jorge; García-Vázquez, Francisco; Álvarez-Ayala, Elizabeth; Rodríguez-Fragoso, Lourdes

    2014-01-01

    Metabolic syndrome is a prothrombotic and proinflammatory chronic state. In obesity, the adipose tissue secretes various adipokines that take part in a variety of physiological and pathophysiological processes, including immunity and inflammation. Previous studies using a liver damage model treated with the immune-modulator metallo-peptide (IMMP) showed lessening in the degree of inflammation. Therefore, this study was set up to evaluate the anti-inflammatory effect of IMMP in obese Zucker fa/fa rats. We used Zucker-Lepr fa/fa and Zucker-Lean in this protocol. The groups received IMMP 50 ng/kg by i.p., three times per week for 8 weeks. Blood samples were collected by cardiac puncture and the serum was preserved at -80°C until analysis; the liver was excised and preserved in formaldehyde 4%. Analyses were performed to determine cytokine, insulin, glucose, triglyceride and cholesterol levels in serum, and histological analysis was also performed. IMMP treatment of obese rats resulted in decreased levels of proinflammatory cytokines (leptin, lL-6, IL-1betha, INF-gamma) and a chemokine (MCP-1), and increased levels of anti-inflammatory adipokine (adiponectin). In addition, treatment decreased the damage and hepatic steatosis generated in the tissue of obese rats. The IMMP exerted an anti-inflammatory effect in obese rats and therefore may be an effective and safe therapeutic alternative in the treatment of metabolic syndrome. PMID:25324698

  15. Early handling reduces vulnerability of rats to activity-based anorexia.

    PubMed

    Carrera, O; Gutiérrez, E; Boakes, R A

    2006-11-01

    Resistance to restricted feeding with and without wheel access was tested in rats handled (H) for 20 days since birth. Weight loss produced by 1.5-hr restricted food access was less in H than in non-handled (NH) males when tested aged 41 days. At this age combining food restriction with access to a running wheel (a procedure commonly known as activity-based anorexia, ABA) produced very rapid weight loss and no effect of handling was detected. When 75-day females were tested in the same way, under the ABA procedure H rats took longer than NH controls to reach the removal criterion. Simply restricting food access in these females produced variable weight loss, without detection of any handling effect. No differences in food intake or running were detected between H and NH rats in either males or females. In conclusion, handling seems to have a direct effect on rats' later response to either food deprivation alone or to an ABA procedure. PMID:17016834

  16. Chronic exercise training versus acute endurance exercise in reducing neurotoxicity in rats exposed to lead acetate?

    PubMed Central

    Shahandeh, Mohammad; Roshan, Valiollah Dabidi; Hosseinzadeh, Somayeh; Mahjoub, Soleiman; Sarkisian, Vaginak

    2013-01-01

    After intraperitoneal injection of 20 mg/kg lead acetate, rats received 8 weeks of treadmill exercise (15–22 m/min, 25–64 minutes) and/or treadmill exercise at 1.6 km/h until exhaustion. The markers related to neurotoxicity were measured by enzyme-linked immunosorbent assay method. 8 weeks of treadmill exercise significantly increased brain-derived neurotrophic factor level in the hippocampus (P = 0.04) and plasma level of total antioxidant capacity of rats exposed to lead acetate (P < 0.001), and significantly decreased plasma level of malondialdehyde (P < 0.001). Acute exercise only decreased the hippocampal malondialdehyde level (P = 0.09) and increased brain-derived neurotrophic factor level in the hippocampus (P = 0.66). Acute exercise also enhanced the total antioxidant capacity in rats exposed to lead acetate, insignificantly (P = 0.99). These findings suggest that chronic treadmill exercise can significantly decrease neurotoxicity and alleviate oxidative stress in rats exposed to lead acetate. However, acute endurance exercise was not associated with these beneficial effects. PMID:25206718

  17. Cerium Dioxide Nanoparticle Exposure Improves Microvascular Dysfunction and Reduces Oxidative Stress in Spontaneously Hypertensive Rats

    PubMed Central

    Minarchick, Valerie C.; Stapleton, Phoebe A.; Sabolsky, Edward M.; Nurkiewicz, Timothy R.

    2015-01-01

    The elevated production of reactive oxygen species (ROS) in the vascular wall is associated with cardiovascular diseases such as hypertension. This increase in oxidative stress contributes to various mechanisms of vascular dysfunction, such as decreased nitric oxide bioavailability. Therefore, anti-oxidants are being researched to decrease the high levels of ROS, which could improve the microvascular dysfunction associated with various cardiovascular diseases. From a therapeutic perspective, cerium dioxide nanoparticles (CeO2 NP) hold great anti-oxidant potential, but their in vivo activity is unclear. Due to this potential anti-oxidant action, we hypothesize that injected CeO2 NP would decrease microvascular dysfunction and oxidative stress associated with hypertension. In order to simulate a therapeutic application, spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats were intravenously injected with either saline or CeO2 NP (100 ?g suspended in saline). Twenty-four hours post-exposure mesenteric arteriolar reactivity was assessed via intravital microscopy. Endothelium-dependent and –independent function was assessed via acetylcholine and sodium nitroprusside. Microvascular oxidative stress was analyzed using fluorescent staining in isolated mesenteric arterioles. Finally, systemic inflammation was examined using a multiplex analysis and venular leukocyte flux was counted. Endothelium-dependent dilation was significantly decreased in the SH rats (29.68 ± 3.28%, maximal response) and this microvascular dysfunction was significantly improved following CeO2 NP exposure (43.76 ± 4.33%, maximal response). There was also an increase in oxidative stress in the SH rats, which was abolished following CeO2 NP treatment. These results provided evidence that CeO2 NP act as an anti-oxidant in vivo. There were also changes in the inflammatory profile in the WKY and SH rats. In WKY rats, IL-10 and TNF-? were increased following CeO2 NP treatment. Finally, leukocyte flux was increased in the SH rats (34 ± 4 vs. 17 ± 3 cells/min in the normotensive controls), but this activation was decreased following exposure (15 ± 2 vs. 34 ± 4 cells/min). These results indicated that CeO2 NP may alter the inflammatory response in both SH and WKY rats. Taken together, these results provide evidence that CeO2 NP act as an anti-oxidant in vivo and may improve microvascular reactivity in a model of hypertension. PMID:26635625

  18. Ethanol reduces evoked dopamine release and slows clearance in the rat medial prefrontal cortex

    PubMed Central

    Shnitko, Tatiana A.; Kennerly, Laura C.; Spear, Linda P.; Robinson, Donita L.

    2014-01-01

    Background Ethanol intoxication affects cognitive performance, contributing to attentional deficits and poor decision making, which may occur via actions in the medial prefrontal cortex (mPFC). mPFC function is modulated by the catecholamines dopamine and norepinephrine. In this study, we examine the acute effects of ethanol on electrically-evoked dopamine release and clearance in the mPFC of anaesthetized rats naïve to alcohol or chronically exposed to alcohol during adolescence. Methods Dopamine release and clearance was evoked by electrical stimulation of the VTA and measured in the mPFC of anaesthetized rats with fast-scan cyclic voltammetry. In Experiments 1 and 2, effects of a high dose of ethanol (4g/kg, i.p.) on dopamine neurotransmission in the mPFC of ethanol-naïve rats and rats given ethanol exposure during adolescence were investigated. Effects of cumulative dosing of ethanol (0.5–4g/kg) on the dopamine release and clearance were investigated in Experiment 3. Experiment 4 studied effects of ethanol locally applied to the ventral tegmental area (VTA) on the dopamine neurotransmission in the mPFC of ethanol-naïve rats. Results A high dose of ethanol decreased evoked dopamine release within 10 min of administration in ethanol-naïve rats. When tested via cumulative dosing from 0.5–4g/kg, both 2 and 4g/kg ethanol inhibited evoked dopamine release in the mPFC of ethanol-naïve rats, while 4g/kg ethanol also slowed dopamine clearance. A similar effect on electrically-evoked dopamine release in the mPFC was observed after infusion of ethanol into the VTA. Interestingly, intermittent ethanol exposure during adolescence had no effect on observed changes in mPFC dopamine release and clearance induced by acute ethanol administration. Conclusions Taken together, these data describe ethanol-induced reductions in the dynamics of VTA-evoked mPFC dopamine release and clearance, with the VTA contributing to the attenuation of evoked mPFC dopamine release induced by ethanol. PMID:25581652

  19. Apomorphine and 7-OH DPAT reduce ethanol intake of P and HAD rats.

    PubMed

    Russell, R N; McBride, W J; Lumeng, L; Li, T K; Murphy, J M

    1996-01-01

    Adult male rats of the alcohol-preferring (P) line (N = 10) and high alcohol drinking (HAD) line (N = 12) were used to study the effects of IP administration of 0.125-0.50 mg/kg 7-OH DPAT (a putative D agonist) and 0.25-1.0 mg/kg apomorphine (a dopamine agonist with 50-fold higher affinities for the D1 and D2 receptors than for the D3 receptor) on the concurrent intakes of 10% (v/v) ethanol and 0.0125% (g/v) saccharin during a daily 4-h scheduled access period. Control intakes by the P rats for the 4-h period were 17.9 +/- 0.5 and 7.2 +/- 0.4 ml for the ethanol and saccharin solutions, respectively. For the HAD line, ethanol consumption was 18.7 +/- 0.2 ml and saccharin intake was 8.7 +/- 1.6 ml for the 4-h period. In terms of grams ethanol/kg body wt, the 4-h intakes were 2.2 +/- 0.2 for the P line and 3.0 +/- 0.3 for the HAD rats. Both P and HAD rats consumed approximately 40% of their total ethanol intake in the first 15 min of access while consuming only about 15% of their total saccharin intake during this 15-min period. The putative D3 agonist 7-OH DPAT produced a decrease in ethanol intake in the first h to 45-55% of control levels for the P rat (p < 0.01) and to 25-70% of control values in the HAD line (p < 0.001). Apomorphine caused a dose-dependent decrease in ethanol intake in the first hour to 15-70% of control values in the P rat (p < 0.001) and to 25-60% of control levels in the HAD line (p < 0.001). Saccharin and 4-h food intakes for both lines were not altered by either 7-OH DPAT or apomorphine. Overall, these results suggest that D2 and D3 dopamine receptors may play a role in mediating alcohol drinking behavior of the selectively bred HAD and P lines of rats. PMID:8888949

  20. Salt Appetite Is Reduced by a Single Experience of Drinking Hypertonic Saline in the Adult Rat

    PubMed Central

    Greenwood, Michael P.; Greenwood, Mingkwan; Paton, Julian F. R.; Murphy, David

    2014-01-01

    Salt appetite, the primordial instinct to favorably ingest salty substances, represents a vital evolutionary important drive to successfully maintain body fluid and electrolyte homeostasis. This innate instinct was shown here in Sprague-Dawley rats by increased ingestion of isotonic saline (IS) over water in fluid intake tests. However, this appetitive stimulus was fundamentally transformed into a powerfully aversive one by increasing the salt content of drinking fluid from IS to hypertonic saline (2% w/v NaCl, HS) in intake tests. Rats ingested HS similar to IS when given no choice in one-bottle tests and previous studies have indicated that this may modify salt appetite. We thus investigated if a single 24 h experience of ingesting IS or HS, dehydration (DH) or 4% high salt food (HSD) altered salt preference. Here we show that 24 h of ingesting IS and HS solutions, but not DH or HSD, robustly transformed salt appetite in rats when tested 7 days and 35 days later. Using two-bottle tests rats previously exposed to IS preferred neither IS or water, whereas rats exposed to HS showed aversion to IS. Responses to sweet solutions (1% sucrose) were not different in two-bottle tests with water, suggesting that salt was the primary aversive taste pathway recruited in this model. Inducing thirst by subcutaneous administration of angiotensin II did not overcome this salt aversion. We hypothesised that this behavior results from altered gene expression in brain structures important in thirst and salt appetite. Thus we also report here lasting changes in mRNAs for markers of neuronal activity, peptide hormones and neuronal plasticity in supraoptic and paraventricular nuclei of the hypothalamus following rehydration after both DH and HS. These results indicate that a single experience of drinking HS is a memorable one, with long-term changes in gene expression accompanying this aversion to salty solutions. PMID:25111786

  1. Tempol Treatment Reduces Anxiety-Like Behaviors Induced by Multiple Anxiogenic Drugs in Rats

    PubMed Central

    Patki, Gaurav; Salvi, Ankita; Liu, Hesong; Atrooz, Fatin; Alkadhi, Isam; Kelly, Matthew; Salim, Samina

    2015-01-01

    We have published that pharmacological induction of oxidative stress (OS) causes anxiety-like behavior in rats. Using animal models, we also have established that psychological stress induces OS and leads to anxiety-like behaviors. All evidence points towards the causal role of OS in anxiety-like behaviors. To fully ascertain the role of OS in anxiety-like behaviors, it is reasonable to test whether the pro-anxiety effects of anxiogenic drugs caffeine or N-methyl-beta-carboline-3-carboxamide (FG-7142) can be mitigated using agents that minimize OS. In this study, osmotic pumps were either filled with antioxidant tempol or saline. The pumps were attached to the catheter leading to the brain cannula and inserted into the subcutaneous pocket in the back pocket of the rat. Continuous i.c.v. infusion of saline or tempol in the lateral ventricle of the brain (4.3mmol/day) was maintained for 1 week. Rats were intraperitoneally injected either with saline or an anxiogenic drug one at a time. Two hours later all groups were subjected to behavioral assessments. Anxiety-like behavior tests (open-field, light-dark and elevated plus maze) suggested that tempol prevented anxiogenic drug-induced anxiety-like behavior in rats. Furthermore, anxiogenic drug-induced increase in stress examined via plasma corticosterone and increased oxidative stress levels assessed via plasma 8-isoprostane were prevented with tempol treatment. Protein carbonylation assay also suggested preventive effect of tempol in the prefrontal cortex brain region of rats. Antioxidant protein expression and pro-inflammatory cytokine levels indicate compromised antioxidant defense as well as an imbalance of inflammatory response. PMID:25793256

  2. Rats undernourished in utero have altered Ca2+ signaling and reduced fertility in adulthood

    PubMed Central

    Muzi-Filho, Humberto; Souza, Alessandro M; Bezerra, Camila G P; Boldrini, Leonardo C; Takiya, Christina M; Oliveira, Felipe L; Nesi, Renata T; Valença, Samuel S; Silva, Ananssa M S; Zapata-Sudo, Gisele; Sudo, Roberto T; Einicker-Lamas, Marcelo; Vieyra, Adalberto; Lara, Lucienne S; Cunha, Valeria M N

    2015-01-01

    Epidemiological and animal studies have shown that placental undernutrition impairs reproduction in adult offspring, but the underlying molecular mechanisms within the male genital tract remain unknown. Due to its special physiological characteristics in transport and the modulation of the environment to which its luminal content is exposed, we hypothesized that the vas deferens would be a highly sensitive target. The goals were to investigate whether intrauterine malnutrition affects molecular mechanisms related to Ca2+- and oxidative stress-modulated processes and causes structural alterations in the adult rat vas deferens that could attenuate fecundity and fertility. Male adult rats malnourished in utero had increased vas deferens weight associated with thickening of the muscular coat, a decrease in the total and haploid germ cells, a marked increase in the immature cells, and a decline in the numbers of pregnant females and total offspring per male rat. The ex vivo response of vas deferens from malnourished rats demonstrated an accentuated decrease in the contractile response to phenylephrine. The vas deferens had a marked decrease in Ca2+ transport due to the uncoupling of Ca2+-stimulated ATP hydrolysis and ATP-driven Ca2+ flux, and the downregulation of both sarco-endoplasmic reticulum Ca2+-ATPase 2 and the coupling factor 12-kDa FK506-binding protein. An increase in protein carbonylation (a marker of oxidative damage) and an imbalance between protein kinases C and A were observed as a legacy of undernutrition in early life. These results provide the structural and molecular basis to explain at least in part how maternal undernutrition affects fecundity and fertility in adult male rats. PMID:26508737

  3. Melatonin prevents oxidative damage induced by maternal ethanol administration and reduces homocysteine in the cerebellum of rat pups.

    PubMed

    Bagheri, Farzaneh; Goudarzi, Iran; Lashkarbolouki, Taghi; Elahdadi Salmani, Mahmoud

    2015-01-01

    Chronic alcoholism leads to elevated plasma and brain homocysteine (Hcy) levels, as demonstrated by animal experiments. This study was designed to evaluate the alterations in offspring rat cerebellum following increase of plasma Hcy level induced by maternal exposure to ethanol and to investigate the possible protective role of melatonin administration upon cerebellar ethanol-induced neurotoxicity. The adult female rats were divided randomly into 4 groups, including one control and three experimental groups, after vaginal plagues. Group I received normal saline, group II received ethanol (4 g/kg), group III received ethanol+melatonin (10mg/kg) and group IV received melatonin on day 6 of gestation until weaning. 21 days after birth, plasma Hcy level, level of lipid peroxidation, the activities of several antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and levels of bcl-2 and bax mRNA expression in cerebellum were determined. Our results demonstrated that ethanol could induce lipid peroxidation, and decrease antioxidants activities and increase plasma total Hcy level. We also observed that ethanol impaired performance on the rotarod and locomotor activities of rats. However, treatment with melatonin significantly attenuated motoric impairment, the lipid peroxidation process and restored the levels of antioxidant activities and significantly reduced plasma total Hcy levels. Moreover, melatonin reduced bax/bcl-2 ratio in the presence of ethanol. We conclude that these results provide evidence that ethanol neurotoxicity in part is related to increase of plasma Hcy levels and melatonin with reducing of plasma Hcy level has neuroprotective effects against ethanol toxicity in cerebellum. PMID:25797213

  4. Nutritional Recovery with a Soybean Diet after Weaning Reduces Lipogenesis but Induces Inflammation in the Liver in Adult Rats Exposed to Protein Restriction during Intrauterine Life and Lactation

    PubMed Central

    Reis, Sílvia Regina de Lima; Feres, Naoel Hassan; Ignacio-Souza, Leticia Martins; Veloso, Roberto Vilela; Arantes, Vanessa Cristina; Kawashita, Nair Honda; Colodel, Edson Moleta; Botosso, Bárbara Laet; Reis, Marise Auxiliadora de Barros; Latorraca, Márcia Queiroz

    2015-01-01

    We evaluated the effects of postweaning nutritional recovery with a soybean flour diet on de novo hepatic lipogenesis and inflammation in adult rats exposed to protein restriction during intrauterine life and lactation. Rats from mothers fed with protein (casein) in a percentage of 17% (control, C) or 6% (low, L) during pregnancy and lactation were fed with diet that contained 17% casein (CC and LC groups, resp.) or soybean (CS and LS groups, resp.) after weaning until 90 days of age. LS and CS rats had low body weight, normal basal serum triglyceride levels, increased ALT concentrations, and high HOMA-IR indices compared with LC and CC rats. The soybean diet reduced PPAR? as well as malic enzyme and citrate lyase contents and activities. The lipogenesis rate and liver fat content were lower in LS and CS rats relative to LC and CC rats. TNF? mRNA and protein levels were higher in LS and CS rats than in LC and CC rats. NF-?B mRNA levels were lower in the LC and LS groups compared with the CC and LC groups. Thus, the soybean diet prevented hepatic steatosis at least in part through reduced lipogenesis but resulted in TNF?-mediated inflammation. PMID:25892856

  5. A Phospholipid-Protein Complex from Krill with Antioxidative and Immunomodulating Properties Reduced Plasma Triacylglycerol and Hepatic Lipogenesis in Rats

    PubMed Central

    Ramsvik, Marie S.; Bjørndal, Bodil; Bruheim, Inge; Bohov, Pavol; Berge, Rolf K.

    2015-01-01

    Dietary intake of marine omega-3 polyunsaturated fatty acids (n-3 PUFAs) can change the plasma profile from atherogenic to cardioprotective. In addition, there is growing evidence that proteins of marine origin may have health benefits. We investigated a phospholipid-protein complex (PPC) from krill that is hypothesized to influence lipid metabolism, inflammation, and redox status. Male Wistar rats were fed a control diet (2% soy oil, 8% lard, 20% casein), or diets where corresponding amounts of casein and lard were replaced with PPC at 3%, 6%, or 11% (wt %), for four weeks. Dietary supplementation with PPC resulted in significantly lower levels of plasma triacylglycerols in the 11% PPC-fed group, probably due to reduced hepatic lipogenesis. Plasma cholesterol levels were also reduced at the highest dose of PPC. In addition, the plasma and liver content of n-3 PUFAs increased while n-6 PUFAs decreased. This was associated with increased total antioxidant capacity in plasma and increased liver gene expression of mitochondrial superoxide dismutase (Sod2). Finally, a reduced plasma level of the inflammatory mediator interleukin-2 (IL-2) was detected in the PPC-fed animals. The present data show that PPC has lipid-lowering effects in rats, and may modulate risk factors related to cardiovascular disease progression. PMID:26193284

  6. Neurovascular protection by telmisartan via reducing neuroinflammation in stroke-resistant spontaneously hypertensive rat brain after ischemic stroke.

    PubMed

    Kono, Syoichiro; Kurata, Tomoko; Sato, Kota; Omote, Yoshio; Hishikawa, Nozomi; Yamashita, Toru; Deguchi, Kentaro; Abe, Koji

    2015-03-01

    Telmisartan is a highly lipid-soluble angiotensin receptor blocker (ARB), which improves insulin sensitivity and reduces triglyceride levels and, thus, is called metabo-sartan. We examined the effects of telmisartan on neurovascular unit (N-acetylglucosamine oligomer [NAGO], collagen IV, and glial fibrillary acidic protein [GFAP]) and neuroinflammation (matrix metalloproteinase-9 [MMP-9] and inflammasome) in brain of stroke-resistant spontaneously hypertensive rat (SHR-SR). At 12 weeks of age, SHR-SR received transient middle cerebral artery occlusion (tMCAO) for 90 minutes and were divided into the following 3 groups, that is, vehicle group, low-dose telmisartan group (.3 mg/kg/d), and high-dose telmisartan group (3 mg/kg/d, postoral). Immunohistologic analysis at ages 6, 12, and 18 months showed progressive decreases of NAGO-positive endothelium and collagen IV-positive basement membrane and progressive increases of MMP-9-positive neurons, GFAP-positive astrocytes, and NLRP3-positive inflammasome in the cerebral cortex of vehicle group. Low-dose telmisartan reduced such changes without lowering blood pressure (BP), and high-dose telmisartan further improved such changes with lowering BP. The present findings suggest that a persistent hypertension caused a long-lasting inflammation after tMCAO in SHR-SR, which accelerated neurovascular disruption and emergent inflammasome, and that telmisartan greatly reduced such inflammation and protected the neurovascular unit via its pleiotropic effects in living hypertensive rat brain after ischemic stroke. PMID:25534368

  7. Functional anatomy of the gibbon forelimb: adaptations to a brachiating lifestyle

    PubMed Central

    Michilsens, Fana; Vereecke, Evie E; D'Août, Kristiaan; Aerts, Peter

    2009-01-01

    It has been shown that gibbons are able to brachiate with very low mechanical costs. The conversion of muscle activity into smooth, purposeful movement of the limb depends on the morphometry of muscles and their mechanical action on the skeleton. Despite the gibbon's reputation for excellence in brachiation, little information is available regarding either its gross musculoskeletal anatomy or its more detailed muscle–tendon architecture. We provide quantitative anatomical data on the muscle–tendon architecture (muscle mass, physiological cross-sectional area, fascicle length and tendon length) of the forelimb of four gibbon species, collected by detailed dissections of unfixed cadavers. Data are compared between different gibbon species and with similar published data of non-brachiating primates such as macaques, chimpanzees and humans. No quantitative differences are found between the studied gibbon species. Both their forelimb anatomy and muscle dimensions are comparable when normalized to the same body mass. Gibbons have shoulder flexors, extensors, rotator muscles and elbow flexors with a high power or work-generating capacity and their wrist flexors have a high force-generating capacity. Compared with other primates, the elbow flexors of gibbons are particularly powerful, suggesting that these muscles are particularly important for a brachiating lifestyle. Based on this anatomical study, the shoulder flexors, extensors, rotator muscles, elbow flexors and wrist flexors are expected to contribute the most to brachiation. PMID:19519640

  8. Three-dimensional skeletal kinematics of the shoulder girdle and forelimb in walking Alligator

    PubMed Central

    Baier, David B; Gatesy, Stephen M

    2013-01-01

    Crocodylians occupy a key phylogenetic position for investigations of archosaur locomotor evolution. Compared to the well-studied hindlimb, relatively little is known about the skeletal movements and mechanics of the forelimb. In this study, we employed manual markerless XROMM (X-ray Reconstruction Of Moving Morphology) to measure detailed 3-D kinematics of the shoulder girdle and forelimb bones of American alligators (Alligator mississippiensis) walking on a treadmill. Digital models of the interclavicle, scapulocoracoid, humerus, radius and ulna were created using a 3-D laser scanner. Models were articulated and aligned to simultaneously recorded frames of fluoroscopic and standard light video to reconstruct and measure joint motion. Joint coordinate systems were established for the coracosternal, glenohumeral and elbow joints. Our analysis revealed that the limb joints only account for about half of fore/aft limb excursion; the remaining excursion results from shoulder girdle movements and lateral bending of the vertebral column. Considerable motion of each scapulocoracoid relative to the vertebral column is consistent with coracosternal mobility. The hemisellar design of the glenohumeral joint permits some additional translation, or sliding in the fore-aft plane, but this movement does not have much of an effect on the distal excursion of the bone. PMID:24102540

  9. Comparison of the muscle mechanics of the forelimb of three climbers.

    PubMed

    Stalheim-Smith, A

    1989-10-01

    The climbing behavior, muscle mechanics, and functional properties of selected forelimb muscles were examined to ascertain how three distantly related mammals may be adapted for climbing. To determine if features of the fox squirrel (Stalheim-Smith: J. Morphol. 180:55-68, '84) are general or unique features for a climber, two distantly related climbers, the raccoon (Procyon lotor) and the opossum (Didelphis virginiana), were studied. Muscle mechanics varied: the elbow flexors of the fox squirrel produced significantly more torque per unit mass than did the corresponding muscles of the opossum except at 80 degrees, but not more than the corresponding muscles of the raccoon. On the other hand, there were no statistically significant differences in torque per unit mass among the elbow extensors of the three climbers. Both elbow flexors and elbow extensor had faster contraction times and were more fatigable in the fox squirrel than in the opossum or in the raccoon. The data suggest that the musculoskeletal characteristics of the forelimbs of climbers vary according to behavioral, and possibly phylogenetic, differences. PMID:2810372

  10. Three-dimensional Torques and Power of Horse Forelimb Joints at Trot

    E-print Network

    Clayton, H M; Mullineaux, D R

    2011-01-01

    Reasons for Performing Study: Equine gait analysis has focused on 2D analysis in the sagittal plane, while descriptions of 3D kinetics and ground reaction force could provide more information on the Equine gait analysis. Hypothesis or Objectives: The aim of this study was to characterize the 3D torques and powers of the forelimb joints at trotting. Methods: Eight sound horses were used in the study. A full 3D torque and power for elbow, carpus, fetlock, pastern and coffin joints of right forelimb in horses at trot were obtained by calculating the inverse kinetics of simplified link segmental model. Results: Over two third of energy (70%) generated by all joints come from stance phase, and most of energy generated was by elbow joint both in stance (77%) and sway (88%) phases. Energy absorbed by all joints during stance (40%) and sway (60%) phases respectively is not a big difference. During stance phase, all most two third of energy (65%) absorbed was by fetlock joint, while over two third of energy (74%) abso...

  11. Planar Covariation of Hindlimb and Forelimb Elevation Angles during Terrestrial and Aquatic Locomotion of Dogs

    PubMed Central

    Catavitello, Giovanna; Ivanenko, Yuri P.; Lacquaniti, Francesco

    2015-01-01

    The rich repertoire of locomotor behaviors in quadrupedal animals requires flexible inter-limb and inter-segmental coordination. Here we studied the kinematic coordination of different gaits (walk, trot, gallop, and swim) of six dogs (Canis lupus familiaris) and, in particular, the planar covariation of limb segment elevation angles. The results showed significant variations in the relative duration of rearward limb movement, amplitude of angular motion, and inter-limb coordination, with gait patterns ranging from a lateral sequence of footfalls during walking to a diagonal sequence in swimming. Despite these differences, the planar law of inter-segmental coordination was maintained across different gaits in both forelimbs and hindlimbs. Notably, phase relationships and orientation of the covariation plane were highly limb specific, consistent with the functional differences in their neural control. Factor analysis of published muscle activity data also demonstrated differences in the characteristic timing of basic activation patterns of the forelimbs and hindlimbs. Overall, the results demonstrate that the planar covariation of inter-segmental coordination has emerged for both fore- and hindlimbs and all gaits, although in a limb-specific manner. PMID:26218076

  12. Diuresis and reduced urinary osmolality in rats produced by small-molecule UT-A-selective urea transport inhibitors.

    PubMed

    Esteva-Font, Cristina; Cil, Onur; Phuan, Puay-Wah; Su, Tao; Lee, Sujin; Anderson, Marc O; Verkman, A S

    2014-09-01

    Urea transport (UT) proteins of the UT-A class are expressed in epithelial cells in kidney tubules, where they are required for the formation of a concentrated urine by countercurrent multiplication. Here, using a recently developed high-throughput assay to identify UT-A inhibitors, a screen of 50,000 synthetic small molecules identified UT-A inhibitors of aryl-thiazole, ?-sultambenzosulfonamide, aminocarbonitrile butene, and 4-isoxazolamide chemical classes. Structure-activity analysis identified compounds that inhibited UT-A selectively by a noncompetitive mechanism with IC50 down to ?1 ?M. Molecular modeling identified putative inhibitor binding sites on rat UT-A. To test compound efficacy in rats, formulations and administration procedures were established to give therapeutic inhibitor concentrations in blood and urine. We found that intravenous administration of an indole thiazole or a ?-sultambenzosulfonamide at 20 mg/kg increased urine output by 3-5-fold and reduced urine osmolality by ?2-fold compared to vehicle control rats, even under conditions of maximum antidiuresis produced by 1-deamino-8-D-arginine vasopressin (DDAVP). The diuresis was reversible and showed urea > salt excretion. The results provide proof of concept for the diuretic action of UT-A-selective inhibitors. UT-A inhibitors are first in their class salt-sparing diuretics with potential clinical indications in volume-overload edemas and high-vasopressin-associated hyponatremias. PMID:24843071

  13. Peanut protein reduces body protein mass and alters skeletal muscle contractile properties and lipid metabolism in rats.

    PubMed

    Jacques, Hélène; Leblanc, Nadine; Papineau, Roxanne; Richard, Denis; Côté, Claude H

    2010-05-01

    It is well known that diets high in nuts or peanuts favourably affect plasma lipid concentrations. However, few studies have examined the effects of nut and peanut protein (PP) on body composition and skeletal muscle properties. The present study was aimed at evaluating the effect of dietary PP compared with two animal proteins, casein (C) and cod protein (CP) on body composition, skeletal muscle contractile properties and lipid metabolism in rats. Thirty-two male rats were assigned to one of the following four diets containing either C, CP, PP or C+peanut protein (CPP, 50:50) mixture. After 28 d of ad libitum feeding and after 12-h fast, blood, liver and muscle were collected for measurements of plasma and hepatic cholesterol and TAG, plasma glucose and insulin and contractile properties. Rats fed with the low-quality protein, PP, had lower body weight gain, body protein mass, soleus mass and liver weight than those fed with the high-quality dietary proteins, C and CP. PP also caused a deficit in contractile properties in soleus. Likewise, PP increased plasma cholesterol and body fat mass compared with CP. However, these elevations were accompanied with increased hepatic TAG concentrations and lowered intestinal fat excretion. These results show that PP intake alters body composition by reducing skeletal muscle mass and liver weight as well as muscle contractility and lipid metabolism. Adding a complete protein such as C might partially counteract these adverse effects. PMID:20028600

  14. Stress-dose hydrocortisone reduces critical illness-related corticosteroid insufficiency associated with severe traumatic brain injury in rats

    PubMed Central

    2013-01-01

    Introduction The spectrum of critical illness-related corticosteroid insufficiency (CIRCI) in severe traumatic brain injury (TBI) is not fully defined and no effective treatments for TBI-induced CIRCI are available to date. Despite growing interest in the use of stress-dose hydrocortisone as a potential therapy for CIRCI, there remains a paucity of data regarding its benefits following severe TBI. This study was designed to investigate the effects of stress-dose hydrocortisone on CIRCI development and neurological outcomes in a rat model of severe traumatic brain injury. Methods Rats were subjected to lateral fluid percussion injury of 3.2-3.5 atmosphere. These rats were then treated with either a stress-dose hydrocortisone (HC, 3 mg/kg/d for 5 days, 1.5 mg/kg on day 6, and 0.75 mg on day 7), a low-dose methylprednisolone (MP, 1 mg/kg/d for 5 days, 0.5 mg/kg on day 6, and 0.25 mg on day 7) or control saline solution intraperitoneally daily for 7 days after injury. Results We investigated the effects of stress-dose HC on the mortality, CIRCI occurrence, and neurological deficits using an electrical stimulation test to assess corticosteroid response and modified neurological severity score (mNSS). We also studied pathological changes in the hypothalamus, especially in the paraventricular nuclei (PVN), after stress-dose HC or a low dose of MP was administered, including apoptosis detected by a TUNEL assay, blood–brain barrier (BBB) permeability assessed by brain water content and Evans Blue extravasation into the cerebral parenchyma, and BBB integrity evaluated by CD31 and claudin-5 expression. We made the following observations. First, 70% injured rats developed CIRCI, with a peak incidence on post-injury day 7. The TBI-associated CIRCI was closely correlated with an increased mortality and delayed neurological recovery. Second, post-injury administration of stress-dose HC, but not MP or saline increased corticosteroid response, prevented CIRCI, reduced mortality, and improved neurological function during the first 14 days post injury dosing. Thirdly, these beneficial effects were closely related to improved vascular function by the preservation of tight junctions in surviving endothelial cells, and reduced neural apoptosis in the PVN of hypothalamus. Conclusions Our findings indicate that post-injury administration of stress-dose HC, but not MP reduces CIRCI and improves neurological recovery. These improvements are associated with reducing the damage to the tight junction of vascular endothelial cells and blocking neuronal apoptosis in the PVN of the hypothalamus. PMID:24131855

  15. Clomiphene citrate reduces procarbazine-induced sterility in a rat model.

    PubMed

    Weissenberg, R; Lahav, M; Raanani, P; Singer, R; Regev, A; Sagiv, M; Giler, S; Theodor, E

    1995-01-01

    Chemotherapy with the cytotoxic drug procarbazine (PCB) causes permanent infertility in most male patients. Since many patients treated with this cytotoxic drug are of reproductive age, it is important to develop a method to protect spermatogenesis and fertility. It has been hypothesised that 'spermatogenic arrest' by pharmacological intervention may render the testes less susceptible to the effects of chemotherapy. The present study investigated whether recovery of fertility in a male rat model could be achieved by suppression of spermatogenesis with high doses of clomiphene citrate (CC) prior to PCB administration. It was demonstrated that young male rats treated with a combination of CC and PCB partially recovered spermatogenesis and achieved almost normal fertility. In contrast, animals treated with PCB alone exhibited abnormal spermatogenesis and remained infertile. PMID:7819047

  16. Lipid Nanocapsules Loaded with Rhenium-188 Reduce Tumor Progression in a Rat Hepatocellular Carcinoma Model

    PubMed Central

    Vanpouille-Box, Claire; Lacoeuille, Franck; Roux, Jérôme; Aubé, Christophe; Garcion, Emmanuel; Lepareur, Nicolas; Oberti, Frédéric; Bouchet, Francis; Noiret, Nicolas; Garin, Etienne; Benoît, Jean-Pierre; Couturier, Olivier; Hindré, François

    2011-01-01

    Background Due to their nanometric scale (50 nm) along with their biomimetic properties, lipid nanocapsules loaded with Rhenium-188 (LNC188Re-SSS) constitute a promising radiopharmaceutical carrier for hepatocellular carcinoma treatment as its size may improve tumor penetration in comparison with microspheres devices. This study was conducted to confirm the feasibility and to assess the efficacy of internal radiation with LNC188Re-SSS in a chemically induced hepatocellular carcinoma rat model. Methodology/Principal Findings Animals were treated with an injection of LNC188Re-SSS (80 MBq or 120 MBq). The treated animals (80 MBq, n?=?12; 120 MBq, n?=?11) were compared with sham (n?=?12), blank LNC (n?=?7) and 188Re-perrhenate (n?=?4) animals. The evaluation criteria included rat survival, tumor volume assessment, and vascular endothelial growth factor quantification. Following treatment with LNC188Re-SSS (80 MBq) therapeutic efficiency was demonstrated by an increase in the median survival from 54 to 107% compared with control groups with up to 7 long-term survivors in the LNC188Re-SSS group. Decreased vascular endothelial growth factor expression in the treated rats could indicate alterations in the angiogenesis process. Conclusions/Significance Overall, these results demonstrate that internal radiation with LNC188Re-SSS is a promising new strategy for hepatocellular carcinoma treatment. PMID:21408224

  17. Camphor Tree Seed Kernel Oil Reduces Body Fat Deposition and Improves Blood Lipids in Rats.

    PubMed

    Fu, Jing; Wang, Baogui; Gong, Deming; Zeng, Cheng; Jiang, Yihao; Zeng, Zheling

    2015-08-01

    The total and positional fatty acid composition in camphor tree (Cinnamomum camphora) seed kernel oil (CKO) were analyzed, and for the first time, the effect of CKO on body fat deposition and blood lipids in rats was studied. The major fatty acids in CKO were determined to be decanoic acid (C10:0, 51.49%) and dodecanoic acid (C12:0, 40.08%), and uniformly distributed at Sn-1, 3, and Sn-2 positions in triglyceride (TG). Rats were randomly divided into control, CKO, lard, and soybean oil groups. At the end of the experiment, levels of blood lipids and the fats of abdomen in the rats were measured. The main organ were weighted and used for the histological examination. The results showed that body weight and fat deposition in CKO group were significantly lower than the lard and soybean groups. Moderate consumption of CKO was found to improve the levels of blood TG and low density lipoprotein cholesterol. PMID:26130050

  18. Low G preconditioning reduces liver injury induced by high +Gz exposure in rats

    PubMed Central

    Shi, Bin; Feng, Zhi-Qiang; Li, Wen-Bing; Zhang, Hong-Yi

    2015-01-01

    AIM: To investigate the effect of repeated lower +Gz exposure on liver injury induced by high +Gz exposure in rats. METHODS: Sixty male Wister rats were randomly divided into a blank control group, a low G preconditioning group (LG) (exposed to +4 Gz/5 min per day for 3 d before +10 Gz/5 min exposure), and a +10 Gz/5 min group (10G) (n = 20 in each group). Blood specimens and liver tissue were harvested at 0 h and 6 h after +10 Gz/5 min exposure. Liver function was analyzed by measuring serum alanine transaminase (ALT) and aspartate aminotransferase (AST) levels, and liver injury was further assessed by histopathological observation. Malondialdehyde (MDA), superoxide dismutase (SOD) and Na+-K+-ATPase were determined in hepatic tissue. RESULTS: The group LG had lower ALT, AST, and MDA values at 0 h after exposure than those in group 10G. SOD values and Na+-K+-ATPase activity in the LG group were higher than in group 10G 0 h post-exposure. Hepatocyte injury was significantly less in group LG than in group 10G on histopathological evaluation. CONCLUSION: It is suggested that repeated low +Gz exposure shows a protective effect on liver injury induced by high +Gz exposure in rats. PMID:26074692

  19. Fish oil-supplemented parenteral nutrition could alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis.

    PubMed

    Li, Xiaolong; Zhang, Xianxiang; Yang, Enqin; Zhang, Nanyang; Cao, Shougen; Zhou, Yanbing

    2015-09-01

    The objectives were to confirm that intravenous fish oil (FO) emulsions could alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis and to explore the mechanisms of these effects. Thirty-six adult male Sprague-Dawley rats were divided into 4 groups randomly. Two days after central venous catheterization, rats were subjected to cecal ligation and puncture to produce abdominal sepsis. Rats were assigned to receive normal saline or total parenteral nutrition (TPN) containing standard soybean oil emulsions or FO-supplemented TPN at the onset of sepsis for 5 days. A sham operation and control treatment were performed in control group rats. Acute lung injury scores, peripheral blood lymphocyte subsets, plasma cytokines, and Foxp3 expression in the spleen were determined. Compared with the normal saline and TPN without FO, FO-supplemented TPN beneficially altered the distributions of the T-lymphocyte subsets and downregulated the acute lung injury scores, plasma cytokines, and expression of Foxp3 due to sepsis. Fish oil-supplemented TPN can decrease acute lung injury scores, alleviate histopathology, reduce the bacterial load in the peritoneal lavage fluid, modulate the lymphocyte subpopulation in the peripheral blood, downregulate Foxp3 expression in the spleen, and reduce plasma cytokines, which means that FO-supplemented TPN can alleviate acute lung injury, modulate immunity, and reduce inflammation in rats with abdominal sepsis. PMID:26231659

  20. Reduced vascular responses to soluble guanylyl cyclase but increased sensitivity to sildenafil in female rats with type 2 diabetes.

    PubMed

    Goulopoulou, Styliani; Hannan, Johanna L; Matsumoto, Takayuki; Ogbi, Safia; Ergul, Adviye; Webb, R Clinton

    2015-07-15

    Impaired nitric oxide (NO), soluble guanylyl cyclase (sGC), and cyclic guanosine monophosphate (cGMP) signaling (NO-sGC-cGMP) has been implicated in the pathogenesis of diabetic vascular dysfunction. Efforts to directly target this signaling have led to the development of sGC agonists that activate the heme group of sGC (stimulators) or preferentially activate sGC when the heme is oxidized (activators). In this study, we hypothesized that resistance arteries from female rats with spontaneous type 2 diabetes (Goto-Kakizaki rats, GK) would have reduced vasodilatory responses to heme-dependent sGC activation and increased responses to heme-independent sGC activation compared with control rats (Wistar). Endothelium-dependent and -independent relaxation was assessed in isolated segments from mesenteric resistance arteries (MA) mounted in a wire myograph. GK MA had reduced responses to acetylcholine (pEC50: 7.96 ± 0.06 vs. 7.66 ± 0.05, P < 0.05) and sodium nitroprusside (pEC50: 8.34 ± 0.05 vs. 7.77 ± 0.04, P < 0.05). There were no group differences in 8-bromoguanosine cGMP-induced relaxation and protein kinase G1 expression (P > 0.05). GK MA had attenuated responses to BAY 41-2272 (heme-dependent sGC stimulator; pEC50: 7.56 ± 0.05 vs. 6.93 ± 0.06, P < 0.05) and BAY 58-2667 (heme-independent sGC activator; pEC50: 10.82 ± 0.07 vs. 10.27 ± 0.08, P < 0.05) and increased sensitivity to sildenafil [phosphodiesterase 5 (PDE5) inhibitor; pEC50: 7.89 ± 0.14 vs. 8.25 ± 0.13, P < 0.05]. Isolated resistance arteries from female rats of reproductive age that spontaneously develop type 2 diabetes have increased sensitivity to PDE5 inhibition and reduced responsiveness to sGC activators and stimulators. PMID:25957216

  1. Neither Milk Production, Milk Transfer Nor Pup Growth Hormone Account for Reduced Body Weights of Rat Pups Reared In Hypergravity

    NASA Technical Reports Server (NTRS)

    Bear, L. A.; Chowdhury, J. H.; Grindeland, R. E.; Wade, C. E.; Ronca, A. E.; Dalton, Bonnie (Technical Monitor)

    2002-01-01

    Studies spanning the gravity continuum from 0 to 2-g are revealing new insights into how mammalian reproduction and development may proceed in the microgravity of space. Rat pups reared from either conception or midgestation in hypergravity (hg) weigh 6-15% less than 1-g controls. In the present study we analyzed maternal and pup factors that may account for reduced body weight of hg reared pups. Beginning on Gestational day (G)11 of the rats' 22 day pregnancy, rat dams and their litters were continuously exposed to either 1.5-g, 1.75-g or 2.0-g. Prolaction (Prl) and oxytocin (OT) were measured in hg-exposed dams during either pregnancy (G20) or lactation (Postnatal day [P] 10). Gravity related differences in Prl were not observed whereas OT was depressed during lactation in hg dams relative to controls (p less than 0.05). Milk transfer measured during a discrete suckling episode was actually increased in hg-reared litters and comparable numbers of milk-letdowns were observed in the two conditions. Recent reports using dwarfing phenotypes in mouse mutants have provided evidence for postnatal dependence on growth hormone (GH) and insulin-like growth factors (IGFs). Plasma GH measured in P10 pups using enzyme immunoassay (EIA) was significantly elevated in hg pups relative to 1-g controls (mean +/- sd., ng/ml: 2.0-g, 10.6 [3.0], 1.5-g 8.9 [4.0], 1.0-g, 7.95 [3.1]). Together, these findings suggest that neither milk production, milk transfer nor pup GH play significant roles in reduced body weights of hg-reared pups. Studies underway are focused on insulin-like growth factors.

  2. Ultramicronized palmitoylethanolamide reduces viscerovisceral hyperalgesia in a rat model of endometriosis plus ureteral calculosis: role of mast cells.

    PubMed

    Iuvone, Teresa; Affaitati, Giannapia; De Filippis, Daniele; Lopopolo, Mariangela; Grassia, Gianluca; Lapenna, Domenico; Negro, Luana; Costantini, Raffaele; Vaia, Massimo; Cipollone, Francesco; Ialenti, Armando; Giamberardino, Maria Adele

    2016-01-01

    The effects of ultramicronized palmitoylethanolamide were evaluated on pain behaviours and markers of mast cell (MC) activity in a rat model of endometriosis plus ureteral calculosis (ENDO+STONE)-induced viscerovisceral hyperalgesia (VVH). Female Sprague-Dawley rats that underwent surgical induction of endometriosis were randomly assigned to receive active (ultramicronized palmitoylethanolamide 10 mg·kg·d, orally) or placebo treatment for 25 days. At day 21, they underwent ureteral stone formation and were video-recorded till day 25 to evaluate ureteral and uterine pain behaviours. At autopsy (day 25), ureteral condition and number and diameter of endometrial cysts were evaluated. The following were then measured: number and percentage of degranulating MCs, number of vessels, chymase, nerve growth factor (NGF), vascular endothelial growth factor (VEGF), and Flk-1 (VEGF receptor) in cysts, and NGF in dorsal root ganglia (DRG). Ultramicronized palmitoylethanolamide-treated vs placebo-treated rats showed significantly lower number, duration and complexity of ureteral crises, shorter duration of uterine pain, and smaller cyst diameter (0.0001 < P < 0.004); a significantly higher percentage of expelled stones (P < 0.0001); significantly lower MC number (P < 0.01), vessel number (P < 0.01), chymase (P < 0.05), NGF (P < 0.05), VEGF (P < 0.01), and Flk-1 (P < 0.01) expression in cysts and NGF expression in DRG (P < 0.01). In all animals, the global duration of ureteral crises correlated linearly and directly with cyst diameter, MC number and chymase in cysts, and NGF in cysts and DRG (0.02 < P < 0.0002). Ultramicronized palmitoylethanolamide significantly reduces VVH from ENDO+STONE, probably by modulating MC expression/activity in cysts, thus reducing central sensitization due to noxious signals from endometriotic lesions. The results suggest potential utility of the compound for VVH in clinics. PMID:25974242

  3. Calcium and ?-tocopherol suppress cured-meat promotion of chemically induced colon carcinogenesis in rats and reduce associated biomarkers in human volunteers123

    PubMed Central

    Martin, Océane CB; Santarelli, Raphaelle L; Taché, Sylviane; Naud, Nathalie; Guéraud, Françoise; Audebert, Marc; Dupuy, Jacques; Meunier, Nathalie; Attaix, Didier; Vendeuvre, Jean-Luc; Mirvish, Sidney S; Kuhnle, Gunter CG; Cano, Noel; Corpet, Denis E

    2013-01-01

    Background: Processed meat intake has been associated with increased colorectal cancer risk. We have shown that cured meat promotes carcinogen-induced preneoplastic lesions and increases specific biomarkers in the colon of rats. Objectives: We investigated whether cured meat modulates biomarkers of cancer risk in human volunteers and whether specific agents can suppress cured meat–induced preneoplastic lesions in rats and associated biomarkers in rats and humans. Design: Six additives (calcium carbonate, inulin, rutin, carnosol, ?-tocopherol, and trisodium pyrophosphate) were added to cured meat given to groups of rats for 14 d, and fecal biomarkers were measured. On the basis of these results, calcium and tocopherol were kept for the following additional experiments: cured meat, with or without calcium or tocopherol, was given to dimethylhydrazine-initiated rats (47% meat diet for 100 d) and to human volunteers in a crossover study (180 g/d for 4 d). Rat colons were scored for mucin-depleted foci, putative precancer lesions. Biomarkers of nitrosation, lipoperoxidation, and cytotoxicity were measured in the urine and feces of rats and volunteers. Results: Cured meat increased nitroso compounds and lipoperoxidation in human stools (both P < 0.05). Calcium normalized both biomarkers in rats and human feces, whereas tocopherol only decreased nitro compounds in rats and lipoperoxidation in feces of volunteers (all P < 0.05). Last, calcium and tocopherol reduced the number of mucin-depleted foci per colon in rats compared with nonsupplemented cured meat (P = 0.01). Conclusion: Data suggest that the addition of calcium carbonate to the diet or ?-tocopherol to cured meat may reduce colorectal cancer risk associated with cured-meat intake. This trial was registered at clinicaltrials.gov as NCT00994526. PMID:24025632

  4. Arctigenin reduces blood pressure by modulation of nitric oxide synthase and NADPH oxidase expression in spontaneously hypertensive rats.

    PubMed

    Liu, Ying; Wang, Guoyuan; Yang, Mingguang; Chen, Haining; Zhao, Yan; Yang, Shucai; Sun, Changhao

    2015-12-25

    Arctigenin is a bioactive constituent from dried seeds of Arctium lappa L., which was traditionally used as medicine. Arctigenin exhibits various bioactivities, but its effects on blood pressure regulation are still not widely studied. In this study, we investigated antihypertensive effects of arctigenin by long-term treatment in spontaneously hypertensive rats (SHRs). Arctigenin (50 mg/kg) or vehicle was administered to SHRs or Wistar rats as negative control by oral gavage once a day for total 8 weeks. Nifedipine (3 mg/kg) was used as a positive drug control. After treatment, hemodynamic and physical parameters, vascular reactivity in aorta, the concentration of plasma arctigenin and serum thromboxane B2, NO release and vascular p-eNOS, p-Akt, caveolin-1 protein expression, and vascular superoxide anion generation and p47phox protein expression were detected and analyzed. The results showed that arctigenin significantly reduced systolic blood pressure and ameliorated endothelial dysfunction of SHRs. Arctigenin reduced the levels of thromboxane B2 in plasma and superoxide anion in thoracic aorta of SHRs. Furthermore, arctigenin increased the NO production by enhancing the phosphorylation of Akt and eNOS (Ser 1177), and inhibiting the expression of NADPH oxidase in thoracic aorta of SHRs. Our data suggested that antihypertensive mechanisms of arctigenin were associated with enhanced eNOS phosphorylation and decreased NADPH oxidase-mediated superoxide anion generation. PMID:26585490

  5. Botulinum neurotoxin A subtype 2 reduces pathological behaviors more effectively than subtype 1 in a rat Parkinson's disease model.

    PubMed

    Itakura, Masanori; Kohda, Tomoko; Kubo, Takeya; Semi, Yuko; Azuma, Yasu-Taka; Nakajima, Hidemitsu; Kozaki, Shunji; Takeuchi, Tadayoshi

    2014-05-01

    Recent reports indicate that interruption of acetylcholine release by intrastriatal injection of botulinum neurotoxin type A (BoNT/A) in a rat Parkinson's disease model reduces pathogenic behavior without adverse side effects such as memory dysfunction. Current knowledge suggests that BoNT/A subtype 1 (BoNT/A1) and BoNT/A subtype 2 (BoNT/A2) exert different effects. In the present study, we compared the effects of BoNT/A1 and BoNT/A2 on rotation behavior and in vivo cleavage of presynaptic protein SNAP-25 in a rat unilateral 6-hydroxydopamine-induced Parkinson's disease model. BoNT/A2 more effectively reduced pathogenic behavior by efficiently cleaving SNAP-25 in the striatum compared with that of BoNT/A1. Our results suggest that BoNT/A2 has greater clinical therapeutic value for treating subjects with Parkinson's disease compared to that of BoNT/A1. PMID:24713302

  6. Reducing effect of a combination of Phaseolus vulgaris and Cynara scolymus extracts on food intake and glycemia in rats.

    PubMed

    Loi, Barbara; Fantini, Noemi; Colombo, Giancarlo; Gessa, Gian Luigi; Riva, Antonella; Bombardelli, Ezio; Morazzoni, Paolo; Carai, Mauro A M

    2013-02-01

    Extracts from Phaseolus vulgaris and Cynara scolymus may reduce food intake and/or postprandial glycemia. This study investigated the effect of standardized extracts of P. vulgaris and C. scolymus and their combination on food intake and glycemia in rats. P. vulgaris and C. scolymus extracts, and their 1:2 combination, were administered acutely to rats (a) given access to regular food and water, (b) given access to regular food, water, and a chocolate-flavored beverage, or (c) infused with a starch bolus. P. vulgaris extract and the combination produced comparable reductions in intake of regular food and chocolate-flavored beverage; conversely, C. scolymus extract was ineffective on both parameters. P. vulgaris and C. scolymus extracts additively contributed to the reducing effect of the combination on glycemic rise. These results suggest that a mixture of P. vulgaris and C. scolymus extracts is preferable over each single extract, as it combines the anorectic effect of the P. vulgaris extract with the hypoglycemic effect of both extracts. These data support the recent clinical use of the combination of P. vulgaris and C. scolymus extracts in the control of appetite, food intake, and postprandial glycemia and represent a successful example of translational research in the nutraceutical field. PMID:22565861

  7. Chondroitinase ABC promotes compensatory sprouting of the intact corticospinal tract and recovery of forelimb function following unilateral pyramidotomy in adult mice.

    PubMed

    Starkey, Michelle L; Bartus, Katalin; Barritt, Andrew W; Bradbury, Elizabeth J

    2012-12-01

    Chondroitin sulphate proteoglycans (CSPGs) are extracellular matrix molecules whose inhibitory activity is attenuated by the enzyme chondroitinase ABC (ChABC). Here we assess whether CSPG degradation can promote compensatory sprouting of the intact corticospinal tract (CST) following unilateral injury and restore function to the denervated forelimb. Adult C57BL/6 mice underwent unilateral pyramidotomy and treatment with either ChABC or a vehicle control. Significant impairments in forepaw symmetry were observed following pyramidotomy, with injured mice preferentially using their intact paw during spontaneous vertical exploration of a cylinder. No recovery on this task was observed in vehicle-treated mice. However, ChABC-treated mice showed a marked recovery of function, with forelimb symmetry fully restored by 5 weeks post-injury. Functional recovery was associated with robust sprouting of the uninjured CST, with numerous axons observed crossing the midline in the brainstem and spinal cord and terminating in denervated grey matter. CST fibres in the denervated side of the spinal cord following ChABC treatment were closely associated with the synaptic marker vGlut1. Immunohistochemical assessment of chondroitin-4-sulphate revealed that CSPGs were heavily digested around lamina X, alongside midline crossing axons and in grey matter regions where sprouting axons and reduced peri-neuronal net staining was observed. Thus, we demonstrate that CSPG degradation promotes midline crossing and reinnervation of denervated target regions by intact CST axons and leads to restored function in the denervated forepaw. Enhancing compensatory sprouting using ChABC provides a route to restore function that could be applied to disorders such as spinal cord injury and stroke. PMID:23061434

  8. Brain Rewarding Stimulation Reduces Extracellular Glutamate Through Glial Modulation in Medial Prefrontal Cortex of Rats.

    PubMed

    Murakami, Gen; Nakamura, Masato; Takita, Masatoshi; Ishida, Yasushi; Ueki, Takatoshi; Nakahara, Daiichiro

    2015-11-01

    Growing evidence implicates a critical involvement of prefrontal glial modulation of extracellular glutamate (GLU) in aversive behaviors. However, nothing is known about whether prefrontal glial cells modulate GLU levels in rewarding behaviors. To address this question, we measured GLU efflux in the medial prefrontal cortex (PFC) of rats associated with rewarding behaviors. We used intracranial self-stimulation (ICSS) of the medial forebrain bundle (MFB) as the rewarding behavior. GLU was indirectly measured using microdialysis combined with on-line fluorometric detection of NADH resulting from the reaction of GLU and NAD(+) catalyzed by GLU dehydrogenase with a time resolution of 1?min. ICSS caused a minute-by-minute change of extracellular GLU in the medial PFC, with a slight decrease during the stimulation, followed by an increase afterward. This bidirectional change was tetrodotoxin insensitive and abolished by the gliotoxin fluorocitrate. To confirm and extend the previous studies of aversion-induced increase of extracellular GLU in the medial PFC, we also measured prefrontal GLU efflux associated with an aversive stimulation, immobilization stress. The temporal change in extracellular GLU caused by this stress was markedly different from that observed during ICSS. A rapid increase in GLU was detected during the aversive stimulation, followed by a large increase afterward. This bimodal change was tetrodotoxin insensitive, similar to that detected for ICSS. These findings indicate a bidirectional regulation of extracellular GLU by prefrontal glial cells associated with rat ICSS behavior, and reveal that glial modulation of GLU neurochemistry in the medial PFC contributes to rewarding as well as aversive behaviors in rats. PMID:25924203

  9. Crocin reduced acrylamide-induced neurotoxicity in Wistar rat through inhibition of oxidative stress

    PubMed Central

    Mehri, Soghra; Abnous, Khalil; Khooei, Alireza; Mousavi, Seyed Hadi; Shariaty, Vahideh Motamed; Hosseinzadeh, Hossein

    2015-01-01

    Objective(s): Acrylamide (ACR) has many applications in different industries. ACR damages the central and the peripheral nervous system in human and animals. Importance of ACR-induced neurotoxicity encouraged researchers to find both different mechanisms involved in ACR neurotoxicity and potent neuroprotective agents. Therefore, this study was designed to investigate the protective effect of crocin, an active constituent of Crocus sativus L. (saffron) on ACR-induced neurotoxicity in Wistar rats. Materials and Methods: Animals were treated with ACR (50 mg/kg, IP) 11 days for induction neurotoxicity. Crocin (12.5, 25 and 50 mg/kg, IP) were used during treatment with ACR. At the end of treatment, gait score examination was performed. Then, rats were sacrificed and the severity of damage in brain tissue was determined using pathological tests. The level of malondialdehyde (MDA) and glutathione (GSH) content were evaluated in cerebral cortex and cerebellum to determine the role of oxidative stress in this model. Results: Exposure to ACR induced severe gait abnormalities and pathological changes, but administration of crocin markedly improved behavioral index and histopathological damages. The elevation of lipid peroxidation parallel with reduction of GSH level was observed in cerebral cortex and cerebellum following exposure to ACR. Treatment with crocin markedly decreased MDA level, while elevated GSH content in nervous system as compared to ACR-treated animals. Conclusion: The administration of crocin markedly improved behavioral and histopathological damages in Wistar rats exposed to ACR. Reduction of oxidative stress can be considered as an important mechanism of neuroprotective effects of crocin against ACR-induced toxicity. PMID:26523222

  10. EXPOSURE TO DIETHYL HEXYL PHTHALATE (DEHP) DELAYS PUBERTY AND REDUCES ANDROGEN-DEPENDENT TISSUE WEIGHTS IN LONG EVANS HOODED AND SPRAGUE DAWLEY MALE RATS

    EPA Science Inventory

    DEHP is a plasticizer that alters sexual differentiation in the male rat by reducing fetal Leydig cell testosterone synthesis and insl3 mRNA levels. When exposure includes the pubertal stage of life, DEHP and other phthalates delay puberty and reduce androgen-dependent tissue wei...

  11. Dietary supplementation with the microalga Galdieria sulphuraria (Rhodophyta) reduces prolonged exercise-induced oxidative stress in rat tissues.

    PubMed

    Carfagna, Simona; Napolitano, Gaetana; Barone, Daniela; Pinto, Gabriele; Pollio, Antonino; Venditti, Paola

    2015-01-01

    We studied the effects of ten-day 1% Galdieria sulphuraria dietary supplementation on oxidative damage and metabolic changes elicited by acute exercise (6-hour swimming) determining oxygen consumption, lipid hydroperoxides, protein bound carbonyls in rat tissue (liver, heart, and muscle) homogenates and mitochondria, tissue glutathione peroxidase and glutathione reductase activities, glutathione content, and rates of H2O2 mitochondrial release. Exercise increased oxidative damage in tissues and mitochondria and decreased tissue content of reduced glutathione. Moreover, it increased State 4 and decreased State 3 respiration in tissues and mitochondria. G. sulphuraria supplementation reduced the above exercise-induced variations. Conversely, alga supplementation was not able to modify the exercise-induced increase in mitochondrial release rate of hydrogen peroxide and in liver and heart antioxidant enzyme activities. The alga capacity to reduce lipid oxidative damage without reducing mitochondrial H2O2 release can be due to its high content of C-phycocyanin and glutathione, which are able to scavenge peroxyl radicals and contribute to phospholipid hydroperoxide metabolism, respectively. In conclusion, G. sulphuraria ability to reduce exercise-linked oxidative damage and mitochondrial dysfunction makes it potentially useful even in other conditions leading to oxidative stress, including hyperthyroidism, chronic inflammation, and ischemia/reperfusion. PMID:25874021

  12. Dietary Supplementation with the Microalga Galdieria sulphuraria (Rhodophyta) Reduces Prolonged Exercise-Induced Oxidative Stress in Rat Tissues

    PubMed Central

    Carfagna, Simona; Napolitano, Gaetana; Barone, Daniela; Pinto, Gabriele; Venditti, Paola

    2015-01-01

    We studied the effects of ten-day 1% Galdieria sulphuraria dietary supplementation on oxidative damage and metabolic changes elicited by acute exercise (6-hour swimming) determining oxygen consumption, lipid hydroperoxides, protein bound carbonyls in rat tissue (liver, heart, and muscle) homogenates and mitochondria, tissue glutathione peroxidase and glutathione reductase activities, glutathione content, and rates of H2O2 mitochondrial release. Exercise increased oxidative damage in tissues and mitochondria and decreased tissue content of reduced glutathione. Moreover, it increased State 4 and decreased State 3 respiration in tissues and mitochondria. G. sulphuraria supplementation reduced the above exercise-induced variations. Conversely, alga supplementation was not able to modify the exercise-induced increase in mitochondrial release rate of hydrogen peroxide and in liver and heart antioxidant enzyme activities. The alga capacity to reduce lipid oxidative damage without reducing mitochondrial H2O2 release can be due to its high content of C-phycocyanin and glutathione, which are able to scavenge peroxyl radicals and contribute to phospholipid hydroperoxide metabolism, respectively. In conclusion, G. sulphuraria ability to reduce exercise-linked oxidative damage and mitochondrial dysfunction makes it potentially useful even in other conditions leading to oxidative stress, including hyperthyroidism, chronic inflammation, and ischemia/reperfusion. PMID:25874021

  13. Maternal nutrient restriction reduces carotid artery constriction without increasing nitric oxide synthesis in the late gestation rat fetus.

    PubMed

    Campbell, Morag E; Williams, Sarah J; Veerareddy, Sukrutha; Davidge, Sandra T

    2005-11-01

    Chronic reduction in substrate delivery to the fetus may induce redistribution of fetal cardiac output to maintain nutrient delivery to vital organs, including the brain. Reduced vasoconstriction, in conjunction with increased local synthesis of nitric oxide may contribute to "brain sparing." The authors hypothesized that maternal undernutrition would reduce vasoconstrictor responses in fetal carotid arteries due to increased nitric oxide. Timed pregnant Sprague-Dawley rats were randomized on day 0 of pregnancy to control (C) or nutrient restricted (NR) diet. Dams were killed on day 20 of pregnancy. Fetal carotid artery responses were assessed using a pressurized myograph system. Fetal body weight was reduced by NR diet. In NR fetuses, liver, lung, kidney, and heart weights were lower, whereas proportional brain weight was greater. Carotid artery constriction to endothelin-1 was similar in both groups; however, phenylephrine-induced constriction was decreased in NR arteries. Arteries from control fetuses constricted in response to increasing concentrations of L-NAME, whereas arteries from NR did not. There was also no effect of L-NAME on constriction to phenylephrine in arteries from NR fetuses. Our study indicates that the reduced carotid artery vasoconstriction to phenylephrine in NR fetuses, which is consistent with the maintenance of fetal brain blood flow, was not mediated by enhanced nitric oxide. Reduced phenylephrine but not endothelin-1-induced constriction suggests specific effects on adrenergic carotid artery function, which may implicate this pathway in the vascular adaptation to fetal undernutrition. PMID:16183825

  14. Moxibustion Reduces Ovarian Granulosa Cell Apoptosis Associated with Perimenopause in a Natural Aging Rat Model

    PubMed Central

    Shi, Xiao-Lan; Zhao, Chen; Yang, Shuai; Hu, Xiao-Ying; Liu, Shi-Min

    2015-01-01

    In recent years, concerns about the adverse effects of hormone replacement therapy have increased interest in alternative therapies for the management of the symptoms of perimenopause. Here, we investigated the effects of moxibustion, a traditional Chinese practice that is involved in heated Artemisia vulgaris (mugwort) stimulation, on hormonal imbalance and ovarian granulosa cell (GC) apoptosis in a rat model of perimenopause. Our results showed that mild warm moxibustion (MWM) modulated the circulating levels of estradiol and follicle-stimulating hormone and their receptors and inhibited apoptosis in the ovaries of perimenopausal rats, similar to the effect of estrogen. Further investigation revealed that the effects of MWM on ovary tissues and cultured GCs were mediated by the modulation of the activity of Forkhead box protein O1 and involved the JAK2/STAT3 pathway. Our results provide information on the factors and pathways modulated by MWM and shed light on the mechanism underlying the beneficial effect of moxibustion on the symptoms of perimenopause. PMID:26550020

  15. Hypocretin receptor 2 antagonism dose-dependently reduces escalated heroin self-administration in rats.

    PubMed

    Schmeichel, Brooke E; Barbier, Estelle; Misra, Kaushik K; Contet, Candice; Schlosburg, Joel E; Grigoriadis, Dimitri; Williams, John P; Karlsson, Camilla; Pitcairn, Caleb; Heilig, Markus; Koob, George F; Vendruscolo, Leandro F

    2015-04-01

    The hypocretin/orexin (HCRT) system has been associated with both positive and negative drug reinforcement, implicating HCRT receptor 1 (HCRT-R1) signaling in drug-related behaviors for all major drug classes, including opioids. However, to date there are limited studies investigating the role of HCRT receptor 2 (HCRT-R2) signaling in compulsive-like drug seeking. Escalation of drug intake with extended access has been suggested to model the transition from controlled drug use to compulsive-like drug seeking/taking. The current study examined the effects of a HCRT-R2 antagonist, NBI-80713, on heroin self-administration in rats allowed short- (1 h; ShA) or long- (12 h; LgA) access to intravenous heroin self-administration. Results indicate that systemically administered NBI-80713 dose-dependently decreased heroin self-administration in LgA, but not in ShA, animals. Quantitative PCR analyses showed an increase in Hcrtr2 mRNA levels in the central amygdala, a stress-related brain region, of LgA rats. These observations suggest a functional role for HCRT-R2 signaling in compulsive-like heroin self-administration associated with extended access and indicate HCRT-R2 antagonism as a potential pharmacological target for the treatment of heroin dependence. PMID:25367502

  16. Voluntary Exercise Can Ameliorate Insulin Resistance by Reducing iNOS-Mediated S-Nitrosylation of Akt in the Liver in Obese Rats

    PubMed Central

    Nakamoto, Hideko; Kaneki, Masao; Goto, Sataro; Shimokado, Kentaro; Kobayashi, Hiroyuki; Naito, Hisashi

    2015-01-01

    Voluntary exercise can ameliorate insulin resistance. The underlying mechanism, however, remains to be elucidated. We previously demonstrated that inducible nitric oxide synthase (iNOS) in the liver plays an important role in hepatic insulin resistance in the setting of obesity. In this study, we tried to verify our hypothesis that voluntary exercise improves insulin resistance by reducing the expression of iNOS and subsequent S-nitrosylation of key molecules of glucose metabolism in the liver. Twenty-one Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus, and 18 non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats were randomly assigned to a sedentary group or exercise group subjected to voluntary wheel running for 20 weeks. The voluntary exercise significantly reduced the fasting blood glucose and HOMA-IR in the OLETF rats. In addition, the exercise decreased the amount of iNOS mRNA in the liver in the OLETF rats. Moreover, exercise reduced the levels of S-nitrosylated Akt in the liver, which were increased in the OLETF rats, to those observed in the LETO rats. These findings support our hypothesis that voluntary exercise improves insulin resistance, at least partly, by suppressing the iNOS expression and subsequent S-nitrosylation of Akt, a key molecule of the signal transduction pathways in glucose metabolism in the liver. PMID:26172834

  17. Exercise-Induced Neuroprotection in the Spastic Han Wistar Rat: The Possible Role of Brain-Derived Neurotrophic Factor

    PubMed Central

    Van Kummer, Brooke H.; Cohen, Randy W.

    2015-01-01

    Moderate aerobic exercise has been shown to enhance motor skills and protect the nervous system from neurodegenerative diseases, like ataxia. Our lab uses the spastic Han Wistar rat as a model of ataxia. Mutant rats develop forelimb tremor and hind limb rigidity and have a decreased lifespan. Our lab has shown that exercise reduced Purkinje cell degeneration and delayed motor dysfunction, significantly increasing lifespan. Our study investigated how moderate exercise may mediate neuroprotection by analyzing brain-derived neurotrophic factor (BDNF) and its receptor TrkB. To link BDNF to exercise-induced neuroprotection, mutant and normal rats were infused with the TrkB antagonist K252a or vehicle into the third ventricle. During infusion, rats were subjected to moderate exercise regimens on a treadmill. Exercised mutants receiving K252a exhibited a 21.4% loss in Purkinje cells compared to their controls. Cerebellar TrkB expression was evaluated using non-drug-treated mutants subjected to various treadmill running regimens. Running animals expressed three times more TrkB than sedentary animals. BDNF was quantified via Sandwich ELISA, and cerebellar expression was found to be 26.6% greater in mutant rats on 7-day treadmill exercise regimen compared to 30 days of treadmill exercise. These results suggest that BDNF is involved in mediating exercise-induced neuroprotection. PMID:25710032

  18. Behavioral Differences between Neonatal and Adult 6-Hydroxydopamine-Treated Rats to Dopamine Agonists: Relevance to Neurological Symptoms in Clinical Syndromes with Reduced Brain Dopamine1

    PubMed Central

    BREESE, GEORGE R.; BAUMEISTER, ALAN A.; McCOWN, THOMAS J.; EMERICK, SUSAN G.; FRYE, GERALD D.; CROTTY, KAREN; MUELLER, ROBERT A.

    2011-01-01

    Administration of L-dopa or apomorphine to neonatal and adult 6-hydroxydopamine (6-OHDA)-treated rats resulted in different behavioral responses depending on the age at which dopaminergic fibers were destroyed. When neonatal 6-OHDA-treated rats were tested as adults, they exhibited marked stereotypies, self-biting and self-mutilation behavior (SMB) when given these dopamine agonists. Self-biting as well as the incidence of SMB in neonatal 6-OHDA-treated rats showed dose-related changes between 10 and 100 mg/kg of L-dopa. This SMB and self-biting after L-dopa was observed as early as 22 to 24 days of age. Adult 6-OHDA-treated rats did not exhibit SMB or self-biting to L-dopa (100 mg/kg) or apomorphine (10 mg/kg), but did display paw treading and head nodding—behaviors not observed in neonatal 6-OHDA-treated rats. In addition, the locomotor response to apomorphine (1 mg/kg) was significantly greater in adult 6-OHDA-treated rats than in neonatal 6-OHDA-treated rats. Brain dopamine was reduced markedly in striatum, nucleus accumbens and olfactory tubercles in both 6-OHDA treatment groups with the reduction being slightly greater in rats treated with 6-OHDA neonatally. Serotonin content was elevated in striatum of rats treated neonatally with 6-OHDA, but not in adult 6-OHDA-treated rats. SMB and behaviors observed after L-dopa in rats treated neonatally with 6-OHDA were not apparent after L-dopa in rats with brain serotonin or norepinephrine reduced. Rats with brain dopaminergic fibers destroyed neonatally exhibited self-biting and SMB after L-dopa, suggesting that neonatal reduction of this amine is responsible for the SMB and self-biting in neonatal 6-OHDA-treated rats. 5-Hydroxytryptophan administration to neonatal 6-OHDA-treated rats did not induce SMB, indicating that release of serotonin by L-dopa is not responsible for this behavior. Because inhibition of dopamine-?-hydroxylase did not alter the SMB response to L-dopa observed in neonatal 6-OHDA-treated rats, norepinephrine synthesized from L-dopa does not appear to contribute to the response. High closes of a decarboxylase inhibitor sufficient to inhibit conversion of dopa to dopamine in brain did not reduce the incidence of SMB. Administration of haloperidol (1 mg/kg) reduced the incidence of SMB, but did not antagonize the self-biting or the taffy pulling exhibited by L-dopa. In contrast, cisflupentixol completely blocked the SMB and self-biting induced by L-dopa. The latter findings suggest that these behaviors in neonatal 6-OHDA-treated rats are more associated with D-1 than D-2 receptor function. The age-dependent effects of dopamine agonists observed in these studies provide an explanation for the different symptomatology observed in Lesch-Nyhan patients and Parkinson’s disease—neurological disorders with reduced brain dopamine. PMID:6149306

  19. Induction of postaxial forelimb ectrodactyly with anticonvulsant agents in A/J mice.

    PubMed

    Collins, M D; Fradkin, R; Scott, W J

    1990-01-01

    Exposure of A/J mice on day 9.5 of gestation to the derivatives of three acidic anticonvulsant agents, namely dimethadione, sodium valproate, and sodium diphenylhydantoin, each induced postaxial forelimb ectrodactyly predominantly of the right side. This specific malformation has previously been associated with the administration of acetazolamide to rodents; however, several agents can induce this same defect including other carbonic anhydrase inhibitors, carbon dioxide, cadmium, ethanol, ammonium chloride, and 13-cis retinoic acid. The relative potency of the three agents indicates no direct relationship to the pKa of the acid. Other than ectrodactyly, each of the anticonvulsant agents induced a compound-specific spectrum of malformations despite the uniform administration time. This finding suggests that these agents are capable of acting via different mechanisms or by the differential spatial and temporal dynamics of a common mechanism. PMID:2106175

  20. Reorganization of Motor Cortex after Controlled Cortical Impact in Rats and Implications for Functional Recovery

    PubMed Central

    Nishibe, Mariko; Barbay, Scott; Guggenmos, David

    2010-01-01

    Abstract We report the results of controlled cortical impact (CCI) centered on the caudal forelimb area (CFA) of rat motor cortex to determine the feasibility of examining cortical plasticity in a spared cortical motor area (rostral forelimb area, RFA). We compared the effects of three CCI parameter sets (groups CCI-1, CCI-2, and CCI-3) that differed in impactor surface shape, size, and location, on behavioral recovery and RFA structural and functional integrity. Forelimb deficits in the limb contralateral to the injury were evident in all three CCI groups assessed by skilled reach and footfault tasks that persisted throughout the 35-day post-CCI assessment period. Nissl-stained coronal sections revealed that the RFA was structurally intact. Intracortical microstimulation experiments conducted at 7 weeks post-CCI demonstrated that RFA was functionally viable. However, the size of the forelimb representation decreased significantly in CCI-1 compared to the control group. Subdivided into component movement categories, there was a significant group effect for proximal forelimb movements. The RFA area reduction and reorganization are discussed in relation to possible diaschisis, and to compensatory functional behavior, respectively. Also, an inverse correlation between the anterior extent of the lesion and the size of the RFA was identified and is discussed in relation to corticocortical connectivity. The results suggest that CCI can be applied to rat CFA while sparing RFA. This CCI model can contribute to our understanding of neural plasticity in premotor cortex as a substrate for functional motor recovery. PMID:20873958

  1. Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo

    PubMed Central

    Wu, Liying; Huang, Xin; Wu, Kuiwu; Xu, Lun; Li, Dahu; Liu, Shuhong; Zhao, Yongqi; Fan, Ming; Zhu, Lingling

    2015-01-01

    Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG) of the hippocampus and the sub-ventricular zone (SVZ) of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCs)in vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45?50 Torr) and DG (approximately 10 Torr) were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr). Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1? and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain. PMID:26466323

  2. A low-carbohydrate/high-fat diet reduces blood pressure in spontaneously hypertensive rats without deleterious changes in insulin resistance.

    PubMed

    Bosse, John D; Lin, Han Yi; Sloan, Crystal; Zhang, Quan-Jiang; Abel, E Dale; Pereira, Troy J; Dolinsky, Vernon W; Symons, J David; Jalili, Thunder

    2013-06-15

    Previous studies reported that diets high in simple carbohydrates could increase blood pressure in rodents. We hypothesized that the converse, a low-carbohydrate/high-fat diet, might reduce blood pressure. Six-week-old spontaneously hypertensive rats (SHR; n = 54) and Wistar-Kyoto rats (WKY; n = 53, normotensive control) were fed either a control diet (C; 10% fat, 70% carbohydrate, 20% protein) or a low-carbohydrate/high-fat diet (HF; 20% carbohydrate, 60% fat, 20% protein). After 10 wk, SHR-HF had lower (P < 0.05) mean arterial pressure than SHR-C (148 ± 3 vs. 159 ± 3 mmHg) but a similar degree of cardiac hypertrophy (33.4 ± 0.4 vs. 33.1 ± 0.4 heart weight/tibia length, mg/mm). Mesenteric arteries and the entire aorta were used to assess vascular function and endothelial nitric oxide synthase (eNOS) signaling, respectively. Endothelium-dependent (acetylcholine) relaxation of mesenteric arteries was improved (P < 0.05) in SHR-HF vs. SHR-C, whereas contraction (potassium chloride, phenylephrine) was reduced (P < 0.05). Phosphorylation of eNOSSer1177 increased (P < 0.05) in arteries from SHR-HF vs. SHR-C. Plasma glucose, insulin, and homoeostatic model of insulin assessment were lower (P < 0.05) in SHR-HF vs. SHR-C, whereas peripheral insulin sensitivity (insulin tolerance test) was similar. After a 10-h fast, insulin stimulation (2 U/kg ip) increased (P < 0.05) phosphorylation of AktSer473 and S6 in heart and gastrocnemius similarly in SHR-C vs. SHR-HF. In conclusion, a low-carbohydrate/high-fat diet reduced blood pressure and improved arterial function in SHR without producing signs of insulin resistance or altering insulin-mediated signaling in the heart, skeletal muscle, or vasculature. PMID:23604708

  3. Infrared heat treatment reduces food intake and modifies expressions of TRPV3-POMC in the dorsal medulla of obesity prone rats

    PubMed Central

    HU, JAY; CHOO, HYUNWOO JUNE; MA, SHENG-XING

    2013-01-01

    Purpose Infrared heat, a transient receptor potential vanilloid type-3 (TRPV3) sensitive stimulus, may have potential physiological effects beneficial to treating metabolic syndrome. Materials and methods Obesity prone (OP) and obesity resistant (OR) rats were fed for seven days on a high-fat diet. Heat treated OP rats were exposed twice daily to infrared light for 20 min each, separated by 80 min of rest. Food intake, blood pressure, blood glucose, and body weight measurements were taken daily and compared between treated OP rats, untreated OP rats, and OR controls. The animals were perfused with 4% paraformaldehyde, and immunohistochemistry was performed on the coronal brainstem sections with polyclonal antibodies against TRPV3 and pro-opiomelanocortin (POMC). The positive-staining cells in the medulla nuclei were quantified using a microscope with reticule grid. Results Food intake, body weight, and mean arterial blood pressure (MAP) were higher in OP rats, a diet-induced metabolic syndrome model, accompanied by a reduced expression of POMC, an anorectic agent, in the hypoglossal nucleus (HN) and medial nucleus tractus solitarius (mNTS). Food intake in heat-treated OP rats was significantly decreased. POMC positive neuron count was increased in the HN and mNTS of OP rats following treatment. TRPV3 positive staining neurons were increased in the HN and mNTS of OP control rats and decreased following the heat treatments. Conclusion Lowered POMC and heightened TRPV3 expressions in the HN and mNTS are involved in development of hyperphagia and obesity in OP rats. Exposure to infrared heat modifies TRPV3 and POMC expression in the brainstem, reducing food intake. PMID:21967110

  4. Inhibition of Brain Mitogen-Activated Protein Kinase Signaling Reduces Central Endoplasmic Reticulum Stress and Inflammation and Sympathetic Nerve Activity in Heart Failure Rats.

    PubMed

    Wei, Shun-Guang; Yu, Yang; Weiss, Robert M; Felder, Robert B

    2016-01-01

    Mitogen-activated protein kinase (MAPK) signaling and endoplasmic reticulum (ER) stress in the brain have been implicated in the pathophysiology of hypertension. This study determined whether ER stress occurs in subfornical organ and hypothalamic paraventricular nucleus in heart failure (HF) and how MAPK signaling interacts with ER stress and other inflammatory mediators. HF rats had significantly higher levels of the ER stress biomarkers (glucose-regulated protein 78, activating transcription factor 6, activating transcription factor 4, X-box binding protein 1, P58(IPK), and C/EBP homologous protein) in subfornical organ and paraventricular nucleus, which were attenuated by a 4-week intracerebroventricular infusion of inhibitors selective for p44/42 MAPK (PD98059), p38 MAPK (SB203580), or c-Jun N-terminal kinase (SP600125). HF rats also had higher mRNA levels of tumor necrosis factor-?, interleukin-1?, cyclooxygenase-2, and nuclear factor-?B p65, and a lower mRNA level of I?B-?, in subfornical organ and paraventricular nucleus, compared with SHAM rats, and these indicators of increased inflammation were attenuated in the HF rats treated with the MAPK inhibitors. Plasma norepinephrine level was higher in HF rats than in SHAM rats but was reduced in the HF rats treated with PD98059 and SB203580. A 4-week intracerebroventricular infusion of PD98059 also improved some hemodynamic and anatomic indicators of left ventricular function in HF rats. These data demonstrate that ER stress increases in the subfornical organ and paraventricular nucleus of rats with ischemia-induced HF and that inhibition of brain MAPK signaling reduces brain ER stress and inflammation and decreases sympathetic excitation in HF. An interaction between MAPK signaling and ER stress in cardiovascular regions of the brain may contribute to the development of HF. PMID:26573710

  5. Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat

    PubMed Central

    Onal, Ozkan; Yetisir, Fahri; Sarer, A. Ebru Salman; Zeybek, N. Dilara; Onal, C. Oztug; Yurekli, Banu; Celik, H. Tugrul; Sirma, Ayse; K?l?c, Mehmet

    2015-01-01

    Objectives. Intestinal ischemia-reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine. Material and Method. Twenty eight Wistar rats were randomized into four groups with seven rats in each group. Control group was administered serum physiologic (SF) intraperitoneally (ip) for five days. Ozone group was administered 1 mg/kg ozone ip for five days. Ischemia Reperfusion (IR) group underwent superior mesenteric artery occlusion for one hour and then reperfusion for two hours. Ozone + IR group was administered 1?mg/kg ozone ip for five days and at sixth day IR model was applied. Rats were anesthetized with ketamine?xyzlazine and their intracardiac blood was drawn completely and they were sacrificed. Intestinal tissue samples were examined under light microscope. Levels of superoxide dismutase (SOD), catalase (CAT), glutathioneperoxidase (GSH-Px), malondyaldehide (MDA), and protein carbonyl (PCO) were analyzed in tissue samples. Total oxidant status (TOS), and total antioxidant capacity (TAC) were analyzed in blood samples. Data were evaluated statistically by Kruskal Wallis test. Results. In the ozone administered group, degree of intestinal injury was not different from the control group. IR caused an increase in intestinal injury score. The intestinal epithelium maintained its integrity and decrease in intestinal injury score was detected in Ozone + IR group. SOD, GSH-Px, and CAT values were high in ozone group and low in IR. TOS parameter was highest in the IR group and the TAC parameter was highest in the ozone group and lowest in the IR group. Conclusion. In the present study, IR model caused an increase in intestinal injury.In the present study, ozone administration had an effect improving IR associated tissue injury. In the present study, ozone therapy prevented intestine from ischemia reperfusion injury. It is thought that the therapeutic effect of ozone is associated with increase in antioxidant enzymes and protection of cells from oxidation and inflammation. PMID:26161005

  6. Dexmedetomidine Inhibits TLR4/NF-?B Activation and Reduces Acute Kidney Injury after Orthotopic Autologous Liver Transplantation in Rats

    PubMed Central

    Yao, Hui; Chi, Xinjin; Jin, Yi; Wang, Yiheng; Huang, Pinjie; Wu, Shan; Xia, Zhengyuan; Cai, Jun

    2015-01-01

    Patients who undergo orthotopic liver transplantation often sustain acute kidney injury(AKI). The toll-like receptor 4(TLR4)/Nuclear factor-?B(NF-?B) pathway plays a role in AKI. Dexmedetomidine(Dex) has been shown to attenuate AKI. The current study aimed to determine whether liver transplantation-induced AKI is associated with inflammatory response, and to assess the effects of dexmedetomidine pretreatment on kidneys in rats following orthotopic autologous liver transplantation(OALT). Seventy-seven adult male rats were randomized into 11 groups. Kidney tissue histopathology and levels of blood urea nitrogen(BUN) and serum creatinine(SCr) were evaluated. Levels of TLR4, NF-?B, tumor necrosis factor-?, and interleukin-1? levels were measured in kidney tissues. OALT resulted in significant kidney functional impairment and tissue injury. Pre-treatment with dexmedetomidine decreased BUN and SCr levels and reduced kidney pathological injury, TLR4 expression, translocation of NF-?B, and cytokine production. The effects of dexmedetomidine were reversed by pre-treatment with atipamezole and BRL44408, but not ARC239. These results were confirmed by using ?2A-adrenergic receptor siRNA which reversed the protective effect of dexmedetomidine on attenuating NRK-52E cells injury induced by hypoxia reoxygenation. In conclusion, Dexmedetomidine-pretreatment attenuates OALT-induced AKI in rats which may be contributable to its inhibition of TLR4/MyD88/NF-?B pathway activation. The renoprotective effects are related to ?2A-adrenergic receptor subtypes. PMID:26585410

  7. Dexmedetomidine Inhibits TLR4/NF-?B Activation and Reduces Acute Kidney Injury after Orthotopic Autologous Liver Transplantation in Rats.

    PubMed

    Yao, Hui; Chi, Xinjin; Jin, Yi; Wang, Yiheng; Huang, Pinjie; Wu, Shan; Xia, Zhengyuan; Cai, Jun

    2015-01-01

    Patients who undergo orthotopic liver transplantation often sustain acute kidney injury(AKI). The toll-like receptor 4(TLR4)/Nuclear factor-?B(NF-?B) pathway plays a role in AKI. Dexmedetomidine(Dex) has been shown to attenuate AKI. The current study aimed to determine whether liver transplantation-induced AKI is associated with inflammatory response, and to assess the effects of dexmedetomidine pretreatment on kidneys in rats following orthotopic autologous liver transplantation(OALT). Seventy-seven adult male rats were randomized into 11 groups. Kidney tissue histopathology and levels of blood urea nitrogen(BUN) and serum creatinine(SCr) were evaluated. Levels of TLR4, NF-?B, tumor necrosis factor-?, and interleukin-1? levels were measured in kidney tissues. OALT resulted in significant kidney functional impairment and tissue injury. Pre-treatment with dexmedetomidine decreased BUN and SCr levels and reduced kidney pathological injury, TLR4 expression, translocation of NF-?B, and cytokine production. The effects of dexmedetomidine were reversed by pre-treatment with atipamezole and BRL44408, but not ARC239. These results were confirmed by using ?2A-adrenergic receptor siRNA which reversed the protective effect of dexmedetomidine on attenuating NRK-52E cells injury induced by hypoxia reoxygenation. In conclusion, Dexmedetomidine-pretreatment attenuates OALT-induced AKI in rats which may be contributable to its inhibition of TLR4/MyD88/NF-?B pathway activation. The renoprotective effects are related to ?2A-adrenergic receptor subtypes. PMID:26585410

  8. Leucine or carbohydrate supplementation reduces AMPK and eEF2 phosphorylation and extends postprandial muscle protein synthesis in rats

    PubMed Central

    Wilson, Gabriel J.; Layman, Donald K.; Moulton, Christopher J.; Norton, Layne E.; Anthony, Tracy G.; Proud, Christopher G.; Rupassara, S. Indu; Garlick, Peter J.

    2015-01-01

    Muscle protein synthesis (MPS) increases after consumption of a protein-containing meal but returns to baseline values within 3 h despite continued elevations of plasma amino acids and mammalian target of rapamycin (mTORC1) signaling. This study evaluated the potential for supplemental leucine (Leu), carbohydrates (CHO), or both to prolong elevated MPS after a meal. Male Sprague-Dawley rats (~270 g) trained to consume three meals daily were food deprived for 12 h, and then blood and gastrocnemius muscle were collected 0, 90, or 180 min after a standard 4-g test meal (20% whey protein). At 135 min postmeal, rats were orally administered 2.63 g of CHO, 270 mg of Leu, both, or water (sham control). Following test meal consumption, MPS peaked at 90 min and then returned to basal (time 0) rates at 180 min, although ribosomal protein S6 kinase and eIF4E-binding protein-1 phosphorylation remained elevated. In contrast, rats administered Leu and/or CHO supplements at 135 min postmeal maintained peak MPS through 180 min. MPS was inversely associated with the phosphorylation states of translation elongation factor 2, the “cellular energy sensor” adenosine monophosphate-activated protein kinase-? (AMPK?) and its substrate acetyl-CoA carboxylase, and increases in the ratio of AMP/ATP. We conclude that the incongruity between MPS and mTORC1 at 180 min reflects a block in translation elongation due to reduced cellular energy. Administering Leu or CHO supplements ~2 h after a meal maintains cellular energy status and extends the postprandial duration of MPS. PMID:21917636

  9. Reducing hemorrhagic complication by dabigatran via neurovascular protection after recanalization with tissue plasminogen activator in ischemic stroke of rat.

    PubMed

    Kono, Syoichiro; Deguchi, Kentaro; Omote, Yoshio; Yunoki, Taijun; Yamashita, Toru; Kurata, Tomoko; Ikeda, Yoshio; Abe, Koji

    2014-01-01

    This study assesses the risks and benefits of tissue plasminogen activator (tPA) treatment under oral anticoagulation with dabigatran compared with warfarin or vehicle control in transient middle cerebral artery occlusion (tMCAO). After pretreatment with warfarin (0.2 mg/kg/day), dabigatran (20 mg/kg/day), or vehicle (0.5% carboxymethyl cellulose sodium salt) for 7 days, tMCAO was induced for 120 min, followed by reperfusion and tPA (10 mg/kg/10 ml). Clinical parameters, including cerebral infarction volume, hemorrhagic volume, and blood coagulation, were examined. At 24 hr after reperfusion, markers for the neurovascular unit at the peri-ischemic lesion were immunohistochemically examined in brain sections, and MMP-9 activity was measured by zymography. Paraparesis and intracerebral hemorrhage volume were significantly improved in the dabigatran-pretreated group compared with the warfarin-pretreated group. A marked dissociation between astrocyte foot processes and the basal lamina or pericyte was observed in the warfarin-pretreated group, which was greatly improved in the dabigatran-pretreated group. Furthermore, a remarkable activation of MMP-9 in the ipsilateral warfarin-pretreated rat brain was greatly reduced in dabigatran-pretreated rats. The present study reveals that the mechanism of intracerebral hemorrhage with warfarin-pretreatment plus tPA in ischemic stroke rats is the dissociation of the neurovascular unit, including the pericyte. Neurovascular protection by dabigatran, which was first shown in this study, could partially explain the reduction in hemorrhagic complication by dabigatran reported from clinical study. PMID:24265137

  10. Microgram amounts of abscisic acid in fruit extracts improve glucose tolerance and reduce insulinemia in rats and in humans.

    PubMed

    Magnone, Mirko; Ameri, Pietro; Salis, Annalisa; Andraghetti, Gabriella; Emionite, Laura; Murialdo, Giovanni; De Flora, Antonio; Zocchi, Elena

    2015-12-01

    2-Cis,4-trans-abscisic acid (ABA) is a plant hormone that is present also in animals. Several lines of evidence suggest that ABA contributes to the regulation of glycemia in mammals: nanomolar ABA stimulates insulin release from ?-pancreatic cells and glucose transporter-4-mediated glucose uptake by myoblasts and adipocytes in vitro; plasma ABA increases in normal human subjects, but not in diabetic patients, after a glucose load for an oral glucose tolerance test (OGTT). The presence of ABA in fruits prompted an exploration of the bioavailability of dietary ABA and the effect of ABA-rich fruit extracts on glucose tolerance. Rats underwent an OGTT, with or without 1 µg/kg ABA, either synthetic or present in a fruit extract. Human volunteers underwent an OGTT or a standard breakfast and lunch, with or without a fruit extract, yielding an ABA dose of 0.85 or 0.5 µg/kg, respectively. Plasma glucose, insulin, and ABA were measured at different time points. Oral ABA at 0.5-1 µg/kg significantly lowered glycemia and insulinemia in rats and in humans. Thus, the glycemia-lowering effect of low-dose ABA in vivo does not depend on an increased insulin release. Low-dose ABA intake may be proposed as an aid to improving glucose tolerance in patients with diabetes who are deficient in or resistant to insulin.-Magnone, M., Ameri, P., Salis, A., Andraghetti, G., Emionite, L., Murialdo, G., De Flora, A., Zocchi, E. Microgram amounts of abscisic acid in fruit extracts improve glucose tolerance and reduce insulinemia in rats and in humans. PMID:26243865

  11. Thiol-oxidation reduces the release of amylase induced by ?-adrenergic receptor activation in rat parotid acinar cells.

    PubMed

    Guo, Ming-Yu; Satoh, Keitaro; Qi, Bing; Narita, Takanori; Katsumata-Kato, Osamu; Matsuki-Fukushima, Miwako; Fujita-Yoshigaki, Junko; Sugiya, Hiroshi

    2010-10-01

    In parotid acinar cells, the activation of ?-adrenergic receptors induces the accumulation of intracellular cAMP, and consequently provokes the exocytotic release of amylase, a digestive enzyme. The cellular redox status plays a pivotal role in regulating various cellular functions. Cellular redox imbalance caused by the oxidation of cellular antioxidants, as a result of oxidative stress, induces significant biological damage. In this study, we examined the effects of diamide, a thiol-oxidizing reagent, on amylase release by rat parotid acinar cells. In cells treated with diamide, the formation of cAMP and the release of amylase induced by the ?-agonist isoproterenol (IPR) were partially reduced. The inhibitory effect of diamide on the IPR-induced release of amylase could be abrogated by reduced glutathione or dithiothreitol. Diamide had no effect on the amylase release induced by forskolin, an adenylate cyclase activator, or by mastoparan, a heterotrimeric GTPbinding protein activator. In cells treated with diamide, the binding affinity for [(3)H]DHA, but not the number of binding sites, was reduced. These results suggest that ?-adrenergic receptor function is reduced by thiol-oxidation, which inhibits amylase secretion by parotid acinar cells. PMID:21079359

  12. High-protein diet selectively reduces fat mass and improves glucose tolerance in Western-type diet-induced obese rats.

    PubMed

    Stengel, Andreas; Goebel-Stengel, Miriam; Wang, Lixin; Hu, Eugenia; Karasawa, Hiroshi; Pisegna, Joseph R; Taché, Yvette

    2013-09-15

    Obesity is an increasing health problem. Because drug treatments are limited, diets remain popular. High-protein diets (HPD) reduce body weight (BW), although the mechanisms are unclear. We investigated physiological mechanisms altered by switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD. Male rats were fed standard (SD) or WTD (45% calories from fat). After developing DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body composition, glucose tolerance, insulin sensitivity, and intestinal hormone plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25% greater BW gain after 9 wk compared with SD (P < 0.05). Diet-induced obese rats switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9 (-9%) and decreased BW during the 2-wk period compared with SD/SD (P < 0.05). During these 2 wk, WTD/HPD rats lost 72% more fat mass than WTD/SD (P < 0.05), whereas lean mass was unaltered. WTD/HPD rats had lower blood glucose than WTD/SD at 30 min postglucose gavage (P < 0.05). The increase of pancreatic polypeptide and peptide YY during the 2-h dark-phase feeding was higher in WTD/HPD compared with WTD/SD (P < 0.05). These data indicate that HPD reduces BW in WTD rats, which may be related to decreased FI and the selective reduction of fat mass accompanied by improved glucose tolerance, suggesting relevant benefits of HPD in the treatment of obesity. PMID:23883680

  13. Hydroxypropyl methylcellulose, a viscous soluble fiber, reduces insulin resistance and decreases fatty liver in Zucker Diabetic Fatty rats

    PubMed Central

    2012-01-01

    Background Diets producing a high glycemic response result in exaggerated insulin secretion which induces hepatic lipogenesis, contributing to development of insulin resistance and fatty liver. Viscous dietary fibers blunt the postprandial rise in blood glucose, however their effect on type 2 diabetes and obesity are not entirely known. This study examined the effect of chronic consumption of the viscous, non-fermentable dietary fiber, hydroxypropyl methylcellulose (HPMC), on glucose control, insulin resistance and liver lipids in an obese diabetic rat model. Methods Three groups of Zucker Diabetic Fatty (ZDF) rats were fed diets containing either 5% non-viscous cellulose (control), low viscosity HPMC (LV-HPMC) or high viscosity HPMC (HV- HPMC) for six weeks. Zucker lean littermates consuming cellulose served as a negative control. Markers of glucose control, including oral glucose tolerance test, glycated hemoglobin and urinary glucose, were measured as well as adiposity and the accumulation of liver lipids. Results The HPMC diets increased the viscosity of the small intestinal contents and reduced the postprandial rise in blood glucose. The food efficiency ratio was greater with HPMC feeding compared to the obese control and urinary excretion of glucose and ketone bodies was reduced. The two HPMC groups had lower glycated hemoglobin and kidney weights and a reduced area under the curve during a glucose tolerance test, indicating improved glucose control. Epididymal fat pad weight as percent of body weight was reduced in the HV-HPMC group compared to the obese control group. The HV-HPMC group also had lower concentrations of liver lipid and cholesterol and reduced liver weight. However, HV-HPMC feeding did not affect hepatic gene expression of SREBP-1c or FAS. Muscle concentration of acylcarnitines, a lipid intermediate in fatty acid ?-oxidation, was not different between the HPMC groups and obese control, suggesting no change in muscle fatty acid oxidation by HPMC. Conclusions Consumption of the viscous non-fermentable fiber HPMC decreased diabetic wasting, improved glucose control and reduced insulin resistance and fatty liver in a model of obesity with diabetes. PMID:23146593

  14. Intrathecal catheterization alone reduces autotomy after sciatic cryoneurolysis in the rat.

    PubMed

    Serpell, M G; DeLeo, J A; Coombs, D W; Colburn, R W; Twitchell, B B; Willenbring, S; Fromm, C

    1993-01-01

    There is substantial evidence that sciatic cryoneurolysis (SCN, freeze lesion of the sciatic nerve) is a neuropathic pain model in the rat. During characterization of this model, SCN was performed 4 days after either a sham operation or the insertion of an indwelling intrathecal catheter preparatory to selective spinal drug administration. Body weight and autotomy scores were recorded for the next 22 days until sacrifice. The catheter group experienced significant weight loss (7.5%) by 4 days but rapidly regained to parity with the sham group. Autotomy scores and the frequency of severe autotomy (score > 3) were less at day 22 in the catheter group as compared with the sham-control group (p < 0.005, p < 0.03, respectively). Intrathecal catheterization itself effects the degree of behavioral response to neurogenic pain and thus, should be controlled for in studies using nociceptive animal models. PMID:8255149

  15. Role of glucocorticoids in the response of rat leg muscles to reduced activity

    NASA Technical Reports Server (NTRS)

    Jaspers, Stephen R.; Tischler, Marc E.

    1986-01-01

    Adrenalectomy did not prevent atrophy of rat soleus muscle during 6 days of tail cast suspension. Cortisol treatment enhanced the atrophy and caused atrophy of the weight-bearing soleus and both extensor digitorum longus (EDL) muscles. Unloading led to increased sarcoplasmic protein concentration in the soleus but cortisol administration increased the myhofibrillar (+stromal) protein concentration in both muscles. Suspension of hindlimbs of adrenalectomized animals led to faster protein degradation, slower sarcoplasmic protein degradation, and faster myofibrillar protein synthesis in the isolated soleus, whereas with cortisol-treated animals, the difference in synthesis of myofibrillar proteins was enhanced and that of sarcoplasmic proteins was abolished. Both soleus and EDL of suspended, cortisol-treated animals showed faster protein degradation. It is unlikely that any elevation in circulating glucocorticoids was solely responsible for atrophy of the soleus in this model, but catabolic amounts of glucocorticoids could alter the response of muscle to unloading.

  16. Exogenous normal lymph reduces liver injury induced by lipopolysaccharides in rats

    PubMed Central

    Zhao, Z.G.; Zhang, L.L.; Niu, C.Y.; Zhang, J.

    2014-01-01

    The liver is one of the target organs damaged by septic shock, wherein the spread of endotoxins begins. This study aimed to investigate the effects of exogenous normal lymph (ENL) on lipopolysaccharide (LPS)-induced liver injury in rats. Male Wistar rats were randomly divided into sham, LPS, and LPS+ENL groups. LPS (15 mg/kg) was administered intravenously via the left jugular vein to the LPS and LPS+ENL groups. At 15 min after the LPS injection, saline or ENL without cell components (5 mL/kg) was administered to the LPS and LPS+ENL groups, respectively, at a rate of 0.5 mL/min. Hepatocellular injury indices and hepatic histomorphology, as well as levels of P-selectin, intercellular adhesion molecule 1 (ICAM-1), myeloperoxidase (MPO), and Na+-K+-ATPase, were assessed in hepatic tissues. Liver tissue damage occurred after LPS injection. All levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in plasma as well as the wet/dry weight ratio of hepatic tissue in plasma increased. Similarly, P-selectin, ICAM-1, and MPO levels in hepatic tissues were elevated, whereas Na+-K+-ATPase activity in hepatocytes decreased. ENL treatment lessened hepatic tissue damage and decreased levels of AST, ALT, ICAM-1, and MPO. Meanwhile, the treatment increased the activity of Na+-K+-ATPase. These results indicated that ENL could alleviate LPS-induced liver injury, thereby suggesting an alternative therapeutic strategy for the treatment of liver injury accompanied by severe infection or sepsis. PMID:24519128

  17. Dibutyryl cAMP reduces nonparenchymal cell damage during cold preservation of rat livers.

    PubMed

    Van Ness, K; Podkameni, D; Schwartz, M; Boros, P; Miller, C

    1995-06-01

    Sinusoidal lining cells are the main target for cold preservation injury and are further damaged with reperfusion. Different agents known to increase intracellular cAMP levels have been shown beneficial. This study was designed to assess the possible protective effect of a cAMP analogue on nonparenchymal cells of rat livers, during cold storage and during reperfusion. Parameters reflecting the status of the liver microvasculature were analyzed. The initial effluent collected after preservation reflects release during the cold storage period; therefore we measured interleukin-1 (IL-1) and endothelin-1 (ET-1) levels in these samples in order to detect and quantitate the degree of activation and/or disruption of Kupffer and sinusoidal endothelial lining cells. Rat livers were harvested after in situ flush with Ringer's lactate with or without 2 mM dibutyryl cAMP, excised, and stored in the same solution at 4 degrees C. After 6 hr, livers were perfused with Krebs-Henseleit buffer for 90 min. Physiological parameters were monitored throughout the perfusion. Perfusate samples were collected every 30 min for RIA measurements of IL-1 and ET-1. Treatment resulted in a significant decrease in release of ET-1 and IL-1 during storage. Likewise, livers treated with cAMP had a significantly improved bile output and decreased portal vein resistance during reperfusion. The beneficial effect granted by the analogue during cold storage and reperfusion was evident on parenchymal and nonparenchymal cells. Levels of ET-1 and IL-1 in the caval effluent confirm and quantitate preservation damage. PMID:7791353

  18. Ethyl pyruvate reduces hepatic mitochondrial swelling and dysfunction in a rat model of sepsis

    PubMed Central

    Jiang, Zhiyi; Li, Xiaoyue; Lin, Zongqin; Chen, Juan; Guan, Xiangdong; Chen, Minying

    2015-01-01

    Sepsis causes mitochondrial oxidative injury and swelling. Ethyl pyruvate (EP) is a cytoprotective agent, while aquaporin-8 (AQP8) is a mitochondrial water channel that can induce mitochondrial swelling. We assessed whether EP protects mitochondria during sepsis, and whether AQP8 contributes to the underlying mechanisms. A cecal ligation and puncture (CLP) sepsis model was established in Sprague-Dawley rats, randomized to 3 groups: sham (n=20), CLP (n=59) and CLP+EP (n=51). All rats received postoperative intraperitoneal fluid resuscitation (30 ml/kg); the CLP+EP group also received intraperitoneal EP (100 mg/kg). Survival was assessed at 24 hours. Hepatic mitochondrial ultrastructure was characterized by electron microscopy. The membrane potential of isolated hepatic mitochondria was determined using JC-1 and flow cytometry. Mitochondrial AQP8 expression and cytochrome C (Cyt C) release were measured by Western blotting (values normalized to ß-actin). Survival in the sham, CLP and CLP+EP groups was 100%, 21% and 41%, respectively. Mitochondrial cross-sectional area was smaller in the CLP+EP group than in the CLP group (0.231±0.110 vs. 0.641±0.460 µm2; P<0.001), with a tendency for a lower form factor (a measure of contour irregularity) in the CLP+EP group. Mitochondrial depolarization by CLP was inhibited by EP. Mitochondrial Cyt C release was higher in the CLP group than in the sham (1.211±0.24 vs. 0.48±0.03) or CLP+EP (0.35±0.39) groups. AQP8 expression was similar between groups, with a trend for lower expression in the CLP+EP group compared with the CLP group. EP improves sepsis outcome by targeting the mitochondrion, possibly through modulation of AQP8 expression. PMID:26339342

  19. Nicotiflorin reduces cerebral ischemic damage and upregulates endothelial nitric oxide synthase in primarily cultured rat cerebral blood vessel endothelial cells.

    PubMed

    Li, Runping; Guo, Meili; Zhang, Ge; Xu, Xiongfei; Li, Quan

    2006-08-11

    Nicotiflorin is a flavonoid glycoside extracted from a traditional Chinese medicine Flos Carthami. In the current study, we investigated the neuroprotective effect of nicotiflorin on a transient focal cerebral ischemia-reperfusion model in rats. Nicotiflorin (2.5-10 mg/kg) administered after onset of ischemia markedly reduced brain infarct volume by 24.5-63.2% and neurological deficits. Also the effect of nicotiflorin on endothelial nitric oxide synthase (eNOS) activity, mRNA and protein expression after hypoxia-reoxygenation (H-R) treatment was investigated in an in vitro model mimic cerebrum ischemia-reperfusion in vivo. After total 4 h hypoxia and 12 h reoxygenation, eNOS activity, mRNA and protein levels in the primarily cultured rat cerebral blood vessel endothelial cells treated with nicotiflorin (25-100 microg/ml) 2 h after onset of hypoxia were significantly higher than eNOS activity, mRNA and protein levels in the pure H-R cells and also higher than eNOS activity, mRNA and protein levels in cells cultured under normoxic conditions. The results demonstrated that nicotiflorin had a protective effect against cerebral ischemic damage. The results also gave an important elucidation for the mechanism underlying the protective effect at the cellular level. PMID:16806761

  20. Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain.

    PubMed

    Yoshino, Fumihiko; Yoshida, Ayaka; Umigai, Naofumi; Kubo, Koya; Lee, Masaichi-Chang-Il

    2011-11-01

    Crocetin is a natural carotenoid compound of gardenia fruits and saffron, which has various effects in biological systems. In this study, we investigated the antioxidant effects of crocetin on reactive oxygen species such as hydroxyl radical using in vitro X-band electron spin resonance and spin trapping. Crocetin significantly inhibited hydroxyl radical generation compared with the control. Moreover, we performed electron spin resonance computed tomography ex vivo with the L-band electron spin resonance imaging system and determined the electron spin resonance signal decay rate in the isolated brain of stroke-prone spontaneously hypertensive rats, a high-oxidative stress model. Crocetin significantly reduced oxidative stress in the isolated brain by acting as a scavenger of reactive oxygen species, especially hydroxyl radical, as demonstrated by in vitro and ex vivo electron spin resonance analysis. The distribution of crocetin was also determined in the plasma and the brain of stroke-prone spontaneously hypertensive rats using high-performance liquid chromatography. After oral administration, crocetin was detected at high levels in the plasma and the brain. Our results suggest that crocetin may participate in the prevention of reactive oxygen species-induced disease due to a reduction of oxidative stress induced by reactive oxygen species in the brain. PMID:22128217

  1. Crocetin reduces the oxidative stress induced reactive oxygen species in the stroke-prone spontaneously hypertensive rats (SHRSPs) brain

    PubMed Central

    Yoshino, Fumihiko; Yoshida, Ayaka; Umigai, Naofumi; Kubo, Koya; Lee, Masaichi-Chang-il

    2011-01-01

    Crocetin is a natural carotenoid compound of gardenia fruits and saffron, which has various effects in biological systems. In this study, we investigated the antioxidant effects of crocetin on reactive oxygen species such as hydroxyl radical using in vitro X-band electron spin resonance and spin trapping. Crocetin significantly inhibited hydroxyl radical generation compared with the control. Moreover, we performed electron spin resonance computed tomography ex vivo with the L-band electron spin resonance imaging system and determined the electron spin resonance signal decay rate in the isolated brain of stroke-prone spontaneously hypertensive rats, a high-oxidative stress model. Crocetin significantly reduced oxidative stress in the isolated brain by acting as a scavenger of reactive oxygen species, especially hydroxyl radical, as demonstrated by in vitro and ex vivo electron spin resonance analysis. The distribution of crocetin was also determined in the plasma and the brain of stroke-prone spontaneously hypertensive rats using high-performance liquid chromatography. After oral administration, crocetin was detected at high levels in the plasma and the brain. Our results suggest that crocetin may participate in the prevention of reactive oxygen species-induced disease due to a reduction of oxidative stress induced by reactive oxygen species in the brain. PMID:22128217

  2. Systemic transplantation of mesenchymal stem cells can reduce cognitive and motor deficits in rats with unilateral lesions of the neostriatum.

    PubMed

    Edalatmanesh, Mohammad-Amin; Matin, Maryam M; Neshati, Zeinab; Bahrami, Ahmad-Reza; Kheirabadi, Masoumeh

    2010-03-01

    Huntington's disease (HD) is an inherited neurodegenerative disorder that usually occurs in the third or fourth decades of life. Stem cell therapy is one of the approaches for HD treatment. Since mesenchymal stem cells (MSCs) have the ability to migrate into the lesioned site, we transplanted rat bone marrow-derived MSCs intravenously, following unilateral intrastriatal lesion made by quinolinic acid (QA) in Wistar rats. QA administration caused widespread neuropathological deficits similar to those found in HD, including impairments in motor and cognitive functions. Animals receiving MSCs exhibited significant improvement in motor and cognitive performance compared with sham group animals that did not receive cells. Animals were tested by apomorphine-induced rotations, beam walk, cylinder and hang wire tests at different times after cell transplantation. Results indicate that systemic transplantation of MSCs can significantly reduce the behavioral abnormalities of these animals. This method of systemic injection has a great advantage over invasive surgical techniques for transplantation of cells at the lesioned site. PMID:19570323

  3. Influence of oxidizing or reducing agents on gastrointestinal absorption of U, Pu, Am, Cm and Pm by rats.

    PubMed

    Sullivan, M F; Ruemmler, P S; Ryan, J L; Buschbom, R L

    1986-02-01

    Absorption of 233U, 238Pu, 241Am, and 244Cm from the gastrointestinal (GI) tract was measured in rats, fed ad libitum or fasted, that were gavaged with solutions containing ferric iron, ferrous iron, iron powder, quinhydrone or ascorbic acid. Absorption and retention of all of these actinides was increased substantially by fasting and by the addition of mild oxidizing agents, ferric iron and quinhydrone. In contrast, absorption and retention were decreased to below the fasted level by all the reducing agents except ascorbic acid, which caused diarrhea and an increase in absorption. Absorption of the lanthanide element 147Pm from the intestine of fasted rats was also increased by ferric iron. Some of these actinide elements are polyvalent and are, in some cases, known to be absorbed from the GI tract more readily in their higher oxidation states. This suggested an oxidation-reduction mechanism for the effect of fasting and the action of the chemical agents used. However, the improbability that either 241Am(III) 244Cm(III) or 147Pm is converted to a different oxidation state under these conditions makes that mechanism unlikely. Other explanations are suggested. PMID:3005196

  4. Rapeseed oil fortified with micronutrients reduces atherosclerosis risk factors in rats fed a high-fat diet

    PubMed Central

    2011-01-01

    Background Micronutrients polyphenols, tocopherols and phytosterols in rapeseed exert potential benefit to cardiovascular system, but most of these micronutrients are removed by the refining process. The aim of this study was to determine the effect of rapeseed oil fortified with these micronutrients on the atherosclerosis risk factors in rats fed a high-fat diet. Methods The rodent diet contained 20% fat whose source was refined rapeseed oil (RRO) or fortified refined rapeseed oil with low, middle and high quantities of these micronutrients (L-, M- and H-FRRO). Forty male SD rats were divided into four groups. One group received RRO diet and other groups received L-, M- and H-FRRO diet for 10 weeks. Results Micronutrients supplementation significantly increased plasma antioxidant defense capacities, as evaluated by the significant elevation in the activities of GPx, CAT and SOD as well as the level of GSH, and the significant decline in lipid peroxidation. These micronutrients also reduced the plasma contents of TG, TC and LDL-C and increased the ratio of HDL-C/LDL-C. In addition, in parallel with the enhancement of these micronutrients, plasma levels of IL-6 and CRP declined remarkably. Conclusion Rapeseed oil fortified with micronutrients polyphenols, tocopherols and phytosterols may contribute to prevent atherogenesis by ameliorating plasma oxidative stress, lipid profile and inflammation. PMID:21663699

  5. Oxidative stress and reduced responsiveness of challenged circulating leukocytes following pulmonary instillation of metal-rich particulate matter in rats

    PubMed Central

    2014-01-01

    Welding fume is an exposure that consists of a mixture of metal-rich particulate matter with gases (ozone, carbon monoxide) and/or vapors (VOCs). Data suggests that welders are immune compromised. Given the inability of pulmonary leukocytes to properly respond to a secondary infection in animal models, the question arose whether the dysfunction persisted systemically. Our aim was to evaluate the circulating leukocyte population in terms of cellular activation, presence of oxidative stress, and functionality after a secondary challenge, following welding fume exposure. Rats were intratracheally instilled (ITI) with PBS or 2 mg of welding fume collected from a stainless steel weld. Rats were sacrificed 4 and 24 h post-exposure and whole blood was collected. Whole blood was used for cellular differential counts, RNA isolation with subsequent microarray and Ingenuity Pathway Analysis, and secondary stimulation with LPS utilizing TruCulture technology. In addition, mononuclear cells were isolated 24 h post-exposure to measure oxidative stress by flow cytometry and confocal microscopy. Welding fume exposure had rapid effects on the circulating leukocyte population as identified by relative mRNA expression changes. Instillation of welding fume reduced inflammatory protein production of circulating leukocytes when challenged with the secondary stimulus LPS. The effects were not related to transcription, but were observed in conjunction with oxidative stress. These findings support previous studies of an inadequate pulmonary immune response following a metal-rich exposure and extend those findings showing leukocyte dysfunction occurs systemically. PMID:25123171

  6. Protection against nitric oxide-induced apoptosis in rat mesangial cells demands mitogen-activated protein kinases and reduced glutathione.

    PubMed

    Sandau, K B; Callsen, D; Brüne, B

    1999-10-01

    Inflammatory diseases such as proliferative glomerulonephritis are associated with the production of nitric oxide (NO), which can initiate apoptotic/necrotic cell death. We studied the role of the p42/44 mitogen-activated protein kinases (MAPKs) and c-Jun N-terminal kinases1/2 (JNK1/2) in NO-evoked cytotoxicity in rat mesangial cells (MC). The NO donor S-nitrosoglutathione time- and concentration-dependently promoted apoptotic cell death as detected by JNK1/2 and caspase-3 activation as well as DNA fragmentation. By using Ro 318220, a JNK1/2 activator, we established a correlation between apoptosis and JNK1/2 activation. Apoptosis is antagonized by the addition of fetal calf serum or the simultaneous generation of NO and superoxide (O(2)(-)), another biological inflammatory mediator. Fetal calf serum-induced protection required p42/44 MAPK activation as inhibition of the p42/44 MAPK pathway by the MAPK kinase-1 inhibitor PD 98059 attenuated MC protection. In contrast, cytoprotection by NO/O(2)(-) cogeneration demanded reduced glutathione but was p42/44 MAPK unrelated. Depletion of glutathione reversed NO/O(2)(-)-evoked survival to cell destruction and reinstalled JNK1/2 activity. In conclusion, different signal transduction pathways facilitate protection against NO-induced JNK1/2 activation and apoptosis in rat MC. PMID:10496957

  7. Dietary saturated fatty acids reduce hepatic lipid accumulation but induce fibrotic change in alcohol-fed rats

    PubMed Central

    Chen, Ya-Ling; Peng, Hsiang-Chi; Wang, Xiang-Dong

    2015-01-01

    Background In this study, we evaluated the influence of an ethanol-containing diet with high saturated fatty acids (SFAs) on alcoholic liver disease (ALD) in rats. Methods Male Wistar rats weighing about 160 g were divided into four groups: an ethanol (E) group fed an ethanol-containing liquid diet with 36% total calories as fat (corn oil, olive oil and safflower oil); a control (C) group pair-fed an isoenergetic diet without ethanol; an ethanol with saturated fat (EHS) group fed an ethanol-containing diet which contained 40% total calories as fat (90% lard); and a control with saturated fat (CHS) group fed an isoenergetic diet without ethanol, which contained 40% total calories as fat. Results After 8 weeks of treatment, the liver weight and plasma aspartate aminotransferase (AST) activities in E and EHS groups were significantly higher than those of C group. Significantly higher scores of inflammation, necrosis, and fatty changes were found in E group, whereas significantly higher scores of necrosis, bile duct hyperplasia, and fibrosis were found in EHS group. Although significantly lower plasma adiponectin concentrations were observed in both E and EHS groups, compared to C group, plasma adiponectin in EHS group was significantly higher than that in E group. There was no change in hepatic peroxisome proliferator activated receptor (PPAR)-? expression between E and C groups, and rats in EHS group showed a significantly elevated level compared to the other groups. A lower hepatic sirtuins (SIRT)-1 level was found in E group, but it did not reach statistical significance. Moreover, the highest plasma TGF-?1 level was found in EHS group. Compared to C group, the hepatic reduced glutathione/oxidized glutathione ratio and thiobarbituric acid (TBA)-reactive substance level were significantly increased in E and EHS groups; however, there was no significant difference between E and EHS groups. Significantly increased hepatic CYP2E1 expression was observed in both E and EHS groups, while at the same time, hepatic CYP2E1 in EHS group was the highest among all groups. The hepatic tumor necrosis factor (TNF)-?, interleukin (IL)-1?, IL-6, and IL-10 concentrations in the E group were significantly higher than those in C group, whereas the hepatic IL-6 and IL-10 concentrations in ES group were significantly lower than those of E group. Conclusions These results suggested that dietary saturated fats may inhibit hepatic fat accumulation and induce hepatic fibrosis in rats under chronic alcohol intake. PMID:26151057

  8. Conjugated linoleic acid combined with physical activity reduces body fat accumulation but does not modify lean body mass in male and female Wistar rats.

    PubMed

    Salgado, Jocelem Mastrodi; Ferreira, Tânia Rachel Baroni; Donado-Pestana, Carlos M; de Almeida, Omer Cavalcanti; das Neves, Aline Mouro Ribeiro; Mansi, Débora Niero; Dias, Carlos Tadeu Dos Santos

    2012-04-01

    Several biological and clinical studies have suggested that conjugated linoleic acid (CLA) prevents body fat accumulation and increases lean body mass. CLA is available as a concentrated dietary supplement and is purported to provide the aforementioned benefits for people who perform physical activity. This study was conducted to evaluate the effect of a CLA-supplemented diet combined with physical activity on the body composition of Wistar rats. Two groups of Wistar rats of both sexes, between 45 and 60 days old, were fed a diet containing 5.5% soybean oil (control group) or a CLA-supplemented diet (0.5% CLA and 5.0% soybean oil) (test group). Half the rats in both groups were assigned to exercise by running on a treadmill. The biochemical and anatomical body compositions were analyzed. In both groups, CLA had no effect on the dietary consumption or the weight of the liver, heart, and lungs. However, it did influence the overall weight gain of exercised male rats and the chemical and anatomical body composition in exercised and sedentary rats of both sexes. The results confirm that a CLA-supplemented diet with and without physical activity reduced body fat accumulation in rats of both sexes. However, there is no evidence of an increase in the lean body mass of the exercised rats. PMID:22191570

  9. Behavioral differences between neonatal and adult 6-hydroxydopamine-treated rats to dopamine agonists: relevance to neurological symptoms in clinical syndromes with reduced brain dopamine.

    PubMed

    Breese, G R; Baumeister, A A; McCown, T J; Emerick, S G; Frye, G D; Crotty, K; Mueller, R A

    1984-11-01

    Administration of L-dopa or apomorphine to neonatal and adult 6-hydroxydopamine (6-OHDA)-treated rats resulted in different behavioral responses depending on the age at which dopaminergic fibers were destroyed. When neonatal 6-OHDA-treated rats were tested as adults, they exhibited marked stereotypies, self-biting and self-mutilation behavior (SMB) when given these dopamine agonists. Self-biting as well as the incidence of SMB in neonatal 6-OHDA-treated rats showed dose-related changes between 10 and 100 mg/kg of L-dopa. This SMB and self-biting after L-dopa was observed as early as 22 to 24 days of age. Adult 6-OHDA-treated rats did not exhibit SMB or self-biting to L-dopa (100 mg/kg) or apomorphine (10 mg/kg), but did display paw treading and head nodding--behaviors not observed in neonatal 6-OHDA-treated rats. In addition, the locomotor response to apomorphine (1 mg/kg) was significantly greater in adult 6-OHDA-treated rats than in neonatal 6-OHDA-treated rats. Brain dopamine was reduced markedly in striatum, nucleus accumbens and olfactory tubercles in both 6-OHDA treatment groups with the reduction being slightly greater in rats treated with 6-OHDA neonatally. Serotonin content was elevated in striatum of rats treated neonatally with 6-OHDA, but not in adult 6-OHDA-treated rats. SMB and behaviors observed after L-dopa in rats treated neonatally with 6-OHDA were not apparent after L-dopa in rats with brain serotonin or norepinephrine reduced. Rats with brain dopaminergic fibers destroyed neonatally exhibited self-biting and SMB after L-dopa, suggesting that neonatal reduction of this amine is responsible for the SMB and self-biting in neonatal 6-OHDA-treated rats. 5-Hydroxytryptophan administration to neonatal 6-OHDA-treated rats did not induce SMB, indicating that release of serotonin by L-dopa is not responsible for this behavior. Because inhibition of dopamine-beta-hydroxylase did not alter the SMB response to L-dopa observed in neonatal 6-OHDA-treated rats, norepinephrine synthesized from L-dopa does not appear to contribute to the response. High doses of a decarboxylase inhibitor sufficient to inhibit conversion of dopa to dopamine in brain did not reduce the incidence of SMB. Administration of haloperidol (1 mg/kg) reduced the incidence of SMB, but did not antagonize the self-biting or the taffy pulling exhibited by L-dopa. In contrast, cisflupentixol completely blocked the SMB and self-biting induced by L-dopa.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:6149306

  10. Whole-body exposure to 2.45 GHz electromagnetic fields does not alter 12-arm radial-maze with reduced access to spatial cues in rats.

    PubMed

    Cosquer, Brigitte; Kuster, Niels; Cassel, Jean-Christophe

    2005-06-20

    Lai et al. [Lai H, Horita A, Guy AW. Microwave irradiation affects radial-arm maze performance in the rat. Bioelectromagnetics 1994;15(2):95-104] reported that exposure of rats to pulsed 2.45 GHz microwaves altered maze performance. Their maze was bordered by 20 cm high opaque walls. Using a maze test based on unrestrained access to spatial cues (no walls), we could not replicate this result [Cassel JC, Cosquer B, Galani R, Kuster N. Whole-body exposure to 2.45 GHz electromagnetic fields does not alter radial-maze performance in rats. Behav Brain Res 2004;155:37-43]. Here, we attempted another replication using a maze apparatus bordered by 30 cm high opaque walls. Performance of exposed rats was normal. These results show that microwave exposure as used herein does not alter spatial working memory, when access to spatial cues is reduced. PMID:15922061

  11. Topical combinations aimed at treating microvascular dysfunction reduce allodynia in rat models of CRPS-I and neuropathic pain

    PubMed Central

    Ragavendran, J. Vaigunda; Laferrière, André; Xiao, Wen Hua; Bennett, Gary J.; Padi, Satyanarayana S.V.; Zhang, Ji; Coderre, Terence J.

    2015-01-01

    Growing evidence indicates that various chronic pain syndromes exhibit tissue abnormalities caused by microvasculature dysfunction in the blood vessels of skin, muscle or nerve. We tested whether topical combinations aimed at improving microvascular function would relieve allodynia in animal models of complex regional pain syndrome type I (CRPS-I) and neuropathic pain. We hypothesized that topical administration of either ?2-adrenergic (?2A) receptor agonists or nitric oxide (NO) donors combined with either phosphodiesterase (PDE) or phosphatidic acid (PA) inhibitors would effectively reduce allodynia in these animal models of chronic pain. Single topical agents produced significant dose-dependent anti-allodynic effects in rats with chronic post-ischemia pain, and the anti-allodynic dose-response curves of PDE and PA inhibitors were shifted 2.5–10 fold leftward when combined with non-analgesic doses of ?2A receptor agonists or NO donors. Topical combinations also produced significant anti-allodynic effects in rats with sciatic nerve injury, painful diabetic neuropathy and chemotherapy-induced painful neuropathy. These effects were shown to be produced by a local action, lasted up to 6 h after acute treatment, and did not produce tolerance over 15 days of chronic daily dosing. The present results support the hypothesis that allodynia in animal models of CRPS-I and neuropathic pain is effectively relieved by topical combinations of ?2A or NO donors with PDE or PA inhibitors. This suggests that topical treatments aimed at improving microvascular function may reduce allodynia in patients with CRPS-I and neuropathic pain. Perspective This article presents the synergistic anti-allodynic effects of combinations of ?2A or NO donors with PDE or PA inhibitors in animal models of CRPS-I and neuropathic pain. The data suggest effective clinical treatment of chronic neuropathic pain may be achieved by therapies that alleviate microvascular dysfunction in affected areas. PMID:23273834

  12. Ketone bodies attenuate excitotoxic cell injury in the rat hippocampal slice under conditions of reduced glucose availability.

    PubMed

    Youssef, Farid F

    2015-03-01

    Calorie restriction and the ketogenic diet have been successfully used in models of neuroprotection. However, there are limitations in clinical application of these diets and attention has turned to understanding their mechanism of action. Ketone bodies are produced in both diets and maybe involved in their ability to attenuate neuronal injury. This study seeks to assess the effects of ketone bodies on neuronal transmission and their efficacy in reducing the impact of known excitotoxins. We made use of extracellular recordings from rat hippocampal slices and demonstrate that ketone bodies had no effect on neuronal transmission or induction of long-term potentiation (LTP). Perfusion of slices with N-methyl-d-aspartate (NMDA, 15 ?M) produced neuronal depression suggestive of cell injury (antidromic recording also demonstrated similar depression), such that recovery of population spike potentials after 60 minutes was 27% in normal (10 mM) glucose but only 7% during reduced (2·5 mM) glucose availability. Experiments in ketone bodies demonstrated improved recovery (31%) but only under conditions of low glucose. Similarly, there was enhanced recovery of slices treated with kainic acid (KA, 30 ?M) in reduced glucose media (13-27%), but no difference in normal glucose. These findings suggest that ketone bodies do not alter neuronal function but can alter the response to excitotoxins when energy supplies are impaired, probably by acting as an alternative energy substrate. PMID:25082548

  13. DEHP reduces thyroid hormones via interacting with hormone synthesis-related proteins, deiodinases, transthyretin, receptors, and hepatic enzymes in rats.

    PubMed

    Liu, Changjiang; Zhao, Letian; Wei, Li; Li, Lianbing

    2015-08-01

    Di-(2-ethylhexyl) phthalate (DEHP) is used extensively in many personal care and consumer products, resulting in widespread nonoccupational human exposure through multiple routes and media. Limited studies suggest that exposure to DEHP may be associated with altered thyroid function, but detailed mechanisms are unclear. In order to elucidate potential mechanisms by which DEHP disturbs thyroid hormone homeostasis, Sprague-Dawley (SD) rats were dosed with DEHP by gavage at 0, 250, 500, and 750 mg/kg/day for 30 days and sacrificed within 24 h after the last dose. Gene expressions of thyroid hormone receptors, deiodinases, transthyretin, and hepatic enzymes were measured by RT-PCR; protein levels of transthyretin were also analyzed by Western blot. Results showed that DEHP caused histological changes in the thyroid and follicular epithelial cell hypertrophy and hyperplasia were observed. DEHP significantly reduced thyroid hormones (T3, T4) and thyrotropin releasing hormone (TRH) levels, whereas thyroid stimulating hormone (TSH) was not affected. After exposure to DEHP, biosynthesis of thyroid hormones was suppressed, and sodium iodide symporter (NIS) and thyroid peroxidase (TPO) levels were significantly reduced. Additionally, levels of deiodinases and transthyretin were also affected. TSH receptor (TSHr) level was downregulated, while TRH receptor (TRHr) level was upregulated. Metabolism of thyroid hormones was accelerated due to elevated gene expression of hepatic enzymes (UDPGTs and CYP2B1) by DEHP. Taken together, observed findings indicate that DEHP could reduce thyroid hormones through influencing biosynthesis, biotransformation, biotransport, receptor levels, and metabolism of thyroid hormones. PMID:25913319

  14. Output Properties of the Cortical Hindlimb Motor Area in Spinal Cord-Injured Rats.

    PubMed

    Frost, Shawn B; Dunham, Caleb L; Barbay, Scott; Krizsan-Agbas, Dora; Winter, Michelle K; Guggenmos, David J; Nudo, Randolph J

    2015-11-01

    The purpose of this study was to examine neuronal activity levels in the hindlimb area of motor cortex following spinal cord injury (SCI) in rats and compare the results with measurements in normal rats. Fifteen male Fischer-344 rats received a 200 Kdyn contusion injury in the thoracic cord at level T9-T10. After a minimum of 4 weeks following SCI, intracortical microstimulation (ICMS) and single-unit recording techniques were used in both the forelimb and hindlimb motor areas (FLA, HLA) under ketamine anesthesia. Although movements could be evoked using ICMS in the forelimb area with relatively low current levels, no movements or electromyographical responses could be evoked from ICMS in the HLA in any of the injured rats. During the same procedure, electrophysiological recordings were obtained with a single-shank, 16-channel Michigan probe (Neuronexus) to monitor activity. Neural spikes were discriminated using principle component analysis. Neural activity (action potentials) was collected and digitized for a duration of 5?min. Despite the inability to evoke movement from stimulation of cortex, robust single-unit activity could be recorded reliably from hindlimb motor cortex in SCI rats. Activity in the motor cortex of SCI rats was significantly higher compared with uninjured rats, and increased in hindlimb and forelimb motor cortex by similar amounts. These results demonstrate that in a rat model of thoracic SCI, an increase in single-unit cortical activity can be reliably recorded for several weeks post-injury. PMID:26406381

  15. Endothelin B receptor agonist, IRL-1620, reduces neurological damage following permanent middle cerebral artery occlusion in rats.

    PubMed

    Leonard, Mary G; Briyal, Seema; Gulati, Anil

    2011-10-28

    Endothelin and its receptors have long been considered therapeutic targets in the treatment of ischemic stroke. Recent studies indicate that ET(B) receptors may provide both vasodilatation and neuroprotection. The purpose of this study was to determine the effect of selectively activating the ET(B) receptors following permanent middle cerebral artery occlusion in rats. IRL-1620 [Suc-[Glu9,Ala11,15]-Endothelin-1(8-12)], a highly selective ET(B) agonist, was used alone and in conjunction with BQ788, an ET(B) antagonist, to determine the role of ET(B) receptors in cerebral ischemia. Rats were assessed for neurological deficit and motor function, and their brains were evaluated to determine infarct area, oxidative stress parameters, and ET receptor protein levels. Animals treated with IRL-1620 showed significant improvement in all neurological and motor function tests when compared with both vehicle-treated and BQ788-treated middle cerebral artery occluded groups. In addition, there was a significant decrease in infarct volume 24h after occlusion in animals treated with IRL-1620 (24.47±4.37mm(3)) versus the vehicle-treated group (153.23±32.18mm(3)). Blockade of ET(B) receptors by BQ788 followed by either vehicle or IRL-1620 treatment resulted in infarct volumes similar to those of rats treated with vehicle alone (163.51±25.41 and 139.21±15.20mm(3), respectively). Lipid peroxidation, as measured by malondialdehyde, increased and antioxidants (superoxide dismutase and reduced glutathione) decreased following infarct. Treatment with IRL-1620 reversed these effects, indicating that ET(B) receptor activation reduces oxidative stress injury following ischemic stroke. Animals pretreated with BQ788 showed similar oxidative stress damage as those in the vehicle-treated group. No significant difference was observed in ET(B) receptor levels in any of the groups. The present study demonstrates that ET(B) receptor activation may be a novel neuroprotective therapy in the treatment of focal ischemic stroke. PMID:21959172

  16. Lipolysis, lipogenesis, and adiposity are reduced while fatty acid oxidation is increased in visceral and subcutaneous adipocytes of endurance-trained rats

    PubMed Central

    Pistor, Kathryn E; Sepa-Kishi, Diane M; Hung, Steven; Ceddia, Rolando B

    2014-01-01

    This study examined the alterations in triglyceride (TG) breakdown and storage in subcutaneous inguinal (SC Ing) and epididymal (Epid) fat depots following chronic endurance training. Male Wistar rats were either kept sedentary (Sed) or subjected to endurance training (Ex) at 70–85% peak VO2 for 6 weeks. At weeks 0, 3, and 6 blood was collected at rest and immediately after a bout of submaximal exercise of similar relative intensity to assess whole-body lipolysis. At week 6, adipocytes were isolated from Epid and SC Ing fat pads for the determination of lipolysis under basal or isoproterenol- and forskolin-stimulated conditions, basal and insulin-stimulated glucose incorporation into lipids, and fatty acid oxidation (FAO). Body weight, fat pad mass, and insulin were reduced by endurance training. Also, circulating non-esterified fatty acids (NEFAs) were 33% lower in Ex than Sed rats when exercising at the same relative intensity. This coincided with reduced isoproterenol-stimulated lipolysis in the Epid (27%) and SC Ing (25%) adipocytes in Ex rats. Similarly, forskolin-stimulated lipolysis was reduced in Epid (51%) and SC Ing (49%) adipocytes from Ex rats. Insulin-stimulated glucose incorporation into lipids in adipocytes from both fat depots from Ex rats was also lower (?43%) than Sed controls. Conversely, FAO was increased in Epid (1.71-fold) and SC Ing (1.82-fold) adipocytes of Ex rats. In conclusion, chronic endurance exercise reduced lipolysis and lipogenesis while increasing FAO in Epid and SC Ing adipocytes. These are compatible with an energy-sparing adaptive response to reduced adiposity under chronic endurance training conditions. PMID:26167399

  17. Presynaptic inhibition preferentially reduces the NMDA receptor-mediated component of transmission in rat midbrain dopamine neurons

    PubMed Central

    Wu, Yan-Na; Shen, Ke-Zhong; Johnson, Steven W

    1999-01-01

    We used patch pipettes to record whole-cell currents from single dopamine neurons in slices of rat midbrain. Pharmacological methods were used to isolate EPSCs evoked by focal electrical stimulation.Baclofen was significantly more potent for inhibiting NMDA receptor-mediated EPSCs (IC50=0.24??M) compared with inhibition of EPSCs mediated by AMPA receptors (IC50=1.72??M). The increased potency of baclofen for inhibiting the NMDA component persisted in superfusate that contained zero Mg2+ and when postsynaptic K+ conductances were reduced by Cs+ and QX-314. Effects of baclofen on EPSCs were blocked by the GABAB receptor antagonist CGP-35348.Adenosine was 20 fold more potent for reducing the NMDA component of transmission (IC50=31??M) compared with inhibition of AMPA receptor-mediated EPSCs (IC50=654??M). Effects of adenosine on EPSCs were blocked by the A1 receptor antagonist DPCPX.Both baclofen and adenosine significantly increased the ratio of EPSCs in paired-pulse studies, suggesting presynaptic sites of action. Although adenosine (1?mM) did not reduce currents evoked by exogenous NMDA (10??M), baclofen (1??M) reduced NMDA currents by 29%. Neither baclofen nor adenosine altered currents evoked by exogenous AMPA (1??M).We conclude that adenosine acts at presynaptic A1 receptors to cause a preferential reduction in the NMDA component of synaptic transmission. In contrast, baclofen preferentially reduces NMDA EPSCs by acting at both pre- and postsynaptic GABAB receptors. By regulating NMDA receptor function, A1 and GABAB receptors may play important roles in regulating the excitability of dopamine neurons. PMID:10455292

  18. Local Loperamide Injection Reduces Mechanosensitivity of Rat Cutaneous, Nociceptive C-Fibers

    PubMed Central

    Ringkamp, Matthias; Tal, Michael; Hartke, Timothy V.; Wooten, Matthew; McKelvy, Alvin; Turnquist, Brian P.; Guan, Yun; Meyer, Richard A.; Raja, Srinivasa N.

    2012-01-01

    Loperamide reverses signs of mechanical hypersensitivity in an animal model of neuropathic pain suggesting that peripheral opioid receptors may be suitable targets for the treatment of neuropathic pain. Since little is known about loperamide effects on the responsiveness of primary afferent nerve fibers, in vivo electrophysiological recordings from unmyelinated afferents innervating the glabrous skin of the hind paw were performed in rats with an L5 spinal nerve lesion or sham surgery. Mechanical threshold and responsiveness to suprathreshold stimulation were tested before and after loperamide (1.25, 2.5 and 5 µg in 10 µl) or vehicle injection into the cutaneous receptive field. Loperamide dose-dependently decreased mechanosensitivity in unmyelinated afferents of nerve-injured and sham animals, and this effect was not blocked by naloxone pretreatment. We then investigated loperamide effects on nerve conduction by recording compound action potentials in vitro during incubation of the sciatic nerve with increasing loperamide concentrations. Loperamide dose-dependently decreased compound action potentials of myelinated and unmyelinated fibers (ED50?=?8 and 4 µg/10 µl, respectively). This blockade was not prevented by pre-incubation with naloxone. These results suggest that loperamide reversal of behavioral signs of neuropathic pain may be mediated, at least in part, by mechanisms independent of opioid receptors, most probably by local anesthetic actions. PMID:22848720

  19. Histone deacetylase inhibition reduces hypothyroidism-induced neurodevelopmental defects in rats.

    PubMed

    Kumar, Praveen; Mohan, Vishwa; Sinha, Rohit Anthony; Chagtoo, Megha; Godbole, Madan M

    2015-11-01

    Thyroid hormone (TH) through its receptor (TR?/?) influences spatio-temporal regulation of its target gene repertoire during brain development. Though hypothyroidism in WT rodent models of perinatal hypothyroidism severely impairs neurodevelopment, its effect on TR?/? knockout mice is less severe. An explanation to this paradox is attributed to a possible repressive action of unliganded TRs during development. Since unliganded TRs suppress gene expression through the recruitment of histone deacetylase (HDACs) via co-repressor complexes, we tested whether pharmacological inhibition of HDACs may prevent the effects of hypothyroidism on brain development. Using valproate, an HDAC inhibitor, we show that HDAC inhibition significantly blocks the deleterious effects of hypothyroidism on rat cerebellum, evident by recovery of TH target genes like Bdnf, Pcp2 and Mbp as well as improved dendritic structure of cerebellar Purkinje neurons. Together with this, HDAC inhibition also rescues hypothyroidism-induced motor and cognitive defects. This study therefore provides an insight into the role of HDACs in TH insufficiency during neurodevelopment and their inhibition as a possible therapeutics for treatment. PMID:26427529

  20. Simvastatin reduces fetal testosterone production and permanently alters reproductive tract development in the male rat

    EPA Science Inventory

    Androgen signaling by fetal Leydig cells is critical in the proper development of the male reproductive tract. As cholesterol is a precursor for hormone biosynthesis,inhibition of the cholesterol pathway during sex differentiation may reduce testosterone {T). We hypothesized tha...

  1. Calcium montmorillonite clay reduces urinary biomarkers of fumonisin B1 exposure in rats and humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Fumonisin B1 (FB1) is often a co-contaminant with aflatoxin (AF) in grains and may enhance AF’s carcinogenicity by acting as a cancer promoter. An oral dose of calcium montmorillonite clay (i.e. NovaSil, NS) was able to reduce aflatoxin exposure in a Ghanaian population at risk. In vitro...

  2. Evidence for TRPA1 involvement in central neural mechanisms in a rat model of dry eye.

    PubMed

    Katagiri, A; Thompson, R; Rahman, M; Okamoto, K; Bereiter, D A

    2015-04-01

    Dry eye (DE) disease is commonly associated with ocular surface inflammation, an unstable tear film and symptoms of irritation. However, little is known about the role of central neural mechanisms in DE. This study used a model for persistent aqueous tear deficiency, exorbital gland removal, to assess the effects of mustard oil (MO), a transient receptor potential ankyrin (TRPA1) agonist, on eyeblink and eyewipe behavior and Fos-like immunoreactivity (Fos-LI) in the trigeminal brainstem of male rats. Spontaneous tear secretion was reduced by about 50% and spontaneous eyeblinks were increased more than 100% in DE rats compared to sham rats. MO (0.02-0.2%) caused dose-related increases in eyeblink and forelimb eyewipe behavior in DE and sham rats. Exorbital gland removal alone was sufficient to increase Fos-LI at the ventrolateral pole of trigeminal interpolaris/caudalis (Vi/Vc) transition region, but not at more caudal regions of the trigeminal brainstem. Under barbiturate anesthesia ocular surface application of MO (2-20%) produced Fos-LI in the Vi/Vc transition, in the mid-portions of Vc and in the trigeminal caudalis/upper cervical spinal cord (Vc/C1) region that was significantly greater in DE rats than in sham controls. MO caused an increase in Fos-LI ipsilaterally in superficial laminae at the mid-Vc and Vc/C1 regions in a dose-dependent manner. Smaller, but significant, increases in Fos-LI also were seen in the contralateral Vc/C1 region in DE rats. TRPA1 protein levels in trigeminal ganglia from DE rats ipsilateral and contralateral to gland removal were similar. Persistent tear reduction enhanced the behavioral and trigeminal brainstem neural responses to ocular surface stimulation by MO. These results suggested that TRPA1 mechanisms play a significant role in the sensitization of ocular-responsive trigeminal brainstem neurons in this model for tear deficient DE. PMID:25639234

  3. Extracellular magnesium and calcium reduce myotonia in ClC-1 inhibited rat muscle.

    PubMed

    Skov, Martin; Riisager, Anders; Fraser, James A; Nielsen, Ole B; Pedersen, Thomas H

    2013-06-01

    Loss-of-function mutations in the ClC-1 Cl(-) channel trigger skeletal muscle hyperexcitability in myotonia congenita. For reasons that remain unclear, the severity of the myotonic symptoms can vary markedly even among patients with identical ClC-1 mutations, and may become exacerbated during pregnancy and with diuretic treatment. Since both these conditions are associated with hypomagnesemia and hypocalcemia, we explored whether extracellular Mg(2+) and Ca(2+) ([Mg(2+)]o and [Ca(2+)]o) can affect myotonia. Experimental myotonia was induced in isolated rat muscles by ClC-1 inhibition and effects of [Mg(2+)]o or [Ca(2+)]o on myotonic contractions were determined. Both cations dampened myotonia within their physiological concentration ranges. Thus, myotonic contractile activity was 6-fold larger at 0.3 than at 1.2 mM [Mg(2+)]o and 82-fold larger at 0.3 than at 1.27 mM [Ca(2+)]o. In intracellular recordings of action potentials, the threshold for action potential excitation was raised by 4-6 mV when [Mg(2+)]o was elevated from 0.6 to 3 mM, compatible with an increase in the depolarization of the membrane potential necessary to activate the Na(+) channels. Supporting this notion, mathematical simulations showed that myotonia went from appearing with normal Cl(-) channel function to disappearing in the absence of Cl(-) channel function when Na(+) channel activation was depolarized by 6 mV. In conclusion, variation in serum Mg(2+) and Ca(2+) may contribute to phenotypic variation in myotonia congenita patients. PMID:23623567

  4. Offspring-exposure reduces depressive-like behaviour in the parturient female rat.

    PubMed

    Pawluski, Jodi L; Lieblich, Stephanie E; Galea, Liisa A M

    2009-01-30

    In women, breastfeeding generally results in reductions in anxiety and increased positive mood. However, approximately 10-15% of women experience depressed mood and increased anxiety during the first year postpartum. Recent research has demonstrated that offspring-exposure is important for the reduction in behaviours related to depression and anxiety in the mother. It remains to be determined whether these effects are due to factors related to pregnancy and/or pup-exposure, are associated with the degree of maternal behaviour by the mother towards offspring, or persist after weaning. To address these questions the present study used four groups of female rats; primiparous, nulliparous, primip-no-pups (primiparous females with pups permanently removed), and sensitized females. Depressive- and anxiety-like behaviours were assessed 1 week after weaning/pup-exposure (4 weeks after birth for primip-no-pups animals) using the forced swim test for measures of depressive-like behaviour, and the open field test and elevated plus maze for measure of anxiety-like behaviour. Results demonstrate that primiparous females without pup-exposure have increased depressive-like, but not anxiety-like, behaviour compared to primiparous and sensitized females. In addition, kyphotic nursing by primiparous mothers was negatively related to behavioural measures of depression and anxiety. From this work it is clear that pup-exposure is important for reductions in depressive-like behaviour in parturient females. Further research is needed to determine the extent of these changes and the neural and hormonal correlates of these events. PMID:18760310

  5. Quipazine reduces food intake in the rat by activation of 5-HT2-receptors.

    PubMed Central

    Hewson, G.; Leighton, G. E.; Hill, R. G.; Hughes, J.

    1988-01-01

    1. To determine which subtype(s) of 5-hydroxytryptamine (5-HT) receptor are involved in the anorectic action of quipazine, the ability of selective antagonists at 5-HT2- and 5-HT3-receptors, and an antagonist at 5-HT1-like receptors, to block this response were investigated in non-deprived rats, trained to eat a palatable diet. 2. Quipazine (0.5-8 mg kg-1, i.p.) produced a dose-related reduction in the intake of palatable diet. 3. The anorectic effect of 4 mg kg-1 quipazine was antagonized by the nonselective 5-HT-receptor antagonist methysergide (5 mg kg-1, i.p.) and by the selective 5-HT2-receptor antagonists ketanserin (1 mg kg-1 and 2.5 mg kg-1, i.p.) and ritanserin (0.5 mg kg-1 and 1 mg kg-1, i.p.). The selective 5-HT3-receptor antagonist GR38032F (1 mg kg-1, i.p.) and (-)-pindolol (4 mg kg-1, i.p.), which blocks some of the effects mediated at 5-HT1-like receptors, did not block the reduction in food intake produced by this dose of quipazine. 4. None of the 5-HT-receptor antagonists had any effect on food intake when they were administered alone, suggesting that endogenous 5-HT is not involved in the tonic control of food intake under the conditions of these experiments. 5. It is concluded that the anorectic action of quipazine is mediated, at least in part, by activation of 5-HT2-receptors. PMID:2906561

  6. Lycopene supplementation reduces TNF-? via RAGE in the kidney of obese rats

    PubMed Central

    Pierine, D T; Navarro, M E L; Minatel, I O; Luvizotto, R A M; Nascimento, A F; Ferreira, A L A; Yeum, K-J; Corrêa, C R

    2014-01-01

    Background: The kidney is a target organ for injuries caused by advanced glycation end products (AGEs) in obesity. The receptor of AGEs (RAGE) is proinflammatory and appears to have a role in the pathogenesis of renal disease due to obesity. Objective: The aim was to verify the effect of obesity on renal damage and the effect of lycopene on these complications Design and Methods: Male Wistar rats were randomly assigned to receive a control diet (C, n=7) or a high-fat diet plus sucrose (HD+S, n=14) for 6 weeks. After this period, the HD+S animals were randomized into two groups: HD+S (n=7) and HD+S supplemented with lycopene (HD+S+L, n=7). The animals received maize oil (C and HD+S) or lycopene (HD+S+L) for a 6-week period. Results: The HD+S and HD+S+L animals demonstrated insulin resistance (OGTT glucose after 150?min; C: 117.6±3.9

  7. Effects of leptin replacement alone and with exendin-4 on food intake and weight regain in weight-reduced diet-induced obese rats

    PubMed Central

    Haver, Alvin; Chelikani, Prasanth K.; Apenteng, Bettye; Perriotte-Olson, Curtis; Anders, Krista; Steenson, Sharalyn; Blevins, James E.

    2012-01-01

    Weight loss in obese humans produces a relative leptin deficiency, which is postulated to activate potent orexigenic and energy conservation mechanisms to restrict weight loss and promote weight regain. Here we determined whether leptin replacement alone or with GLP-1 receptor agonist exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced diet-induced obese (DIO) rats. Forty percent restriction in daily intake of a high-fat diet in DIO rats for 4 wk reduced body weight by 12%, body fat by 29%, and plasma leptin by 67% and normalized leptin sensitivity. When food restriction ended, body weight, body fat, and plasma leptin increased rapidly. Daily administration of leptin [3-h intraperitoneal (ip) infusions (4 nmol·kg?1·h?1)] at onset and end of dark period for 3 wk did not attenuate hyperphagia and weight regain, nor did it affect mean daily meal sizes or meal numbers. Exendin-4 (50 pmol·kg?1·h?1) infusions during the same intervals prevented postrestriction hyperphagia and weight regain by normalizing meal size. Coadministration of leptin and exendin-4 did not reduce body weight more than exendin-4 alone. Instead, leptin began to attenuate the inhibitory effects of exendin-4 on food intake, meal size, and weight regain by the end of the second week of administration. Plasma leptin in rats receiving leptin was sevenfold greater than in rats receiving vehicle and 17-fold greater than in rats receiving exendin-4. Together, these results do not support the hypothesis that leptin replacement alone or with exendin-4 attenuates weight regain or promotes greater weight loss in weight-reduced DIO rats. PMID:22510712

  8. Reduced aerobic capacity causes leaky ryanodine receptors that trigger arrhythmia in a rat strain artificially selected and bred for low aerobic running capacity

    PubMed Central

    Høydal, MA; Stølen, TO; Johnsen, AB; Alvez, M; Catalucci, D; Condorelli, G; Koch, LG; Britton, SL; Smith, GL; Wisløff, U

    2014-01-01

    Aim Rats selectively bred for inborn Low Capacity of Running (LCR) display a series of poor health indices where as rats selected for High Capacity of Running (HCR) display a healthy profile. We hypothesized that selection of low aerobic capacity over generations leads to a phenotype with increased diastolic Ca2+ leak that trigger arrhythmia. Methods We used rats selected for HCR (N=10) or LCR (N=10) to determine the effect of inborn aerobic capacity on Ca2+ leak and susceptibility of ventricular arrhythmia. We studied isolated FURA2/AM loaded cardiomyocytes to detect Ca2+-handling and function on an inverted epi-fluorescence microscope. To determine arrhythmogenicity we did a final experiment with electrical burst pacing in Langendorff perfused hearts. Results Ca2+-handling was impaired by reduced Ca2+ amplitude, prolonged time to 50% Ca2+ decay, and reduced sarcoplasmic reticulum (SR) Ca2+-content. Impaired Ca2+ removal was influenced by reduced SR Ca2+ ATP-ase 2a (SERCA2a) function and increased sodium/Ca2+-exchanger (NCX) in LCR rats. Diastolic Ca2 leak was 87% higher in LCR rats. The leak was reduced by CaMKII inhibition. Expression levels of phosphorylated theorine-286 CaMKII levels and increased RyR2 phosphorylation at the Serine-2814 site mechanistically support our findings of increased leak in LCR. LCR rats had significantly higher incidence of ventricular fibrillation. Conclusion Selection of inborn low aerobic capacity over generations leads to a phenotype with increased risk of ventricular fibrillation. Increased phosphorylation of CaMKII at serine-2814 at the cardiac ryanodine receptor appears as an important mechanism of impaired Ca2+ handling and diastolic Ca2+ leak that results in increased susceptibility to ventricular fibrillation. PMID:24444142

  9. SnCl(2) reduces voltage-activated calcium channel currents of dorsal root ganglion neurons of rats.

    PubMed

    Tomaszewski, Anke; Büsselberg, Dietrich

    2008-11-01

    Stannous dichloride (SnCl(2)) occurs in the environment where it has been especially enriched in aquatic ecosystems. Furthermore, it is used in food manufacturing (e.g. for stabilizing soft drinks or as an anti-corrosive substance) and in nuclear medicine where it is employed as a reducing agent for technecium-99m (99mTc) and therefore is applied intravenously to human beings. SnCl(2) is known to have toxic effects on the nervous system which can be related to alterations of intracellular calcium homeostasis ([Ca(2+)](i)). In this study the whole cell patch clamp technique is used on dorsal root ganglion neurons of 3-week-old "Wistar" rats to evaluate the effects of SnCl(2) on voltage-activated calcium channel currents (I(Ca(V))). I(Ca(V)) were reduced concentration-dependently by SnCl(2) (1-50microM). 1microM SnCl(2) reduced I(Ca(V)) by 8.1+/-4.5% (peak current) and 19.2+/-8.9% (sustained current), whereas 50microM inhibited I(Ca(V)) by 50.6+/-4.3% (peak current) and 55.6+/-11.3% (sustained current). Sustained currents were slightly but not significantly more reduced than peak currents. The effect appeared not to be reversible. The threshold concentration was below 1microM. The current-voltage relation did not shift which is an indication that different calcium channel subtypes were equally affected. There was a slight but not significant shift of the activation/inactivation curves towards the depolarizing direction. We conclude that voltage-gated calcium channels are affected by Sn(2+) similarly to other divalent metal cations (e.g. Pb(2+) or Zn(2+)). The reduction of I(Ca(V)) could be related to the neurotoxic effects of SnCl(2). PMID:18644406

  10. Arginase inhibition improves coronary microvascular function and reduces infarct size following ischemia-reperfusion in a rat model

    PubMed Central

    Grönros, Julia; Kiss, Attila; Palmér, Malin; Jung, Christian; Berkowitz, Dan; Pernow, John

    2013-01-01

    Aim Ischemia-reperfusion injury is associated with reduced bioavailability of nitric oxide and microvascular dysfunction. One emerging mechanism behind reduced nitric oxide bioavailability is upregulation of arginase which metabolizes the nitric oxide synthase substrate L-arginine. This study investigated the effects of arginase inhibition on coronary flow velocity and infarct size during reperfusion. Methods Anaesthetized rats, subjected to 30 min coronary artery ligation and reperfusion up to 8 days, were treated with vehicle or the arginase inhibitor N?-hydroxy-nor-L-arginine (nor-NOHA; 100 mg/kg) intravenously 15 min before ischemia. Coronary flow velocity was determined repeatedly during reperfusion. Results Arginase activity in the ischemic-reperfused myocardium was increased already at 20 min of reperfusion and maintained at 8 days. Infarct size was reduced by arginase inhibition at 2 h (39 ± 3% of the area at risk vs. 51 ± 2% in the vehicle group, P<0.01) and at 8 days of reperfusion (13 ± 2% of the left ventricle vs. 22 ± 2%, P<0.05). Basal coronary flow velocity was higher during reperfusion in the group given nor-NOHA and it correlated inversely to infarct size (P<0.01, r=?0.60). Hyperemic coronary flow velocity was also increased in the nor-NOHA treated group compared to vehicle at 24 h and at day 8 (P<0.05). Conclusion It is concluded that arginase activity is increased already during early reperfusion. Arginase inhibition increases coronary flow velocity and reduces infarct size that is sustained 8 days after reperfusion. Inhibition of arginase may thus be a promising therapeutic target to prevent the development of microvascular dysfunction and myocardial injury following ischemia-reperfusion. PMID:23497275

  11. Endogenous antioxidant defense induction by melon superoxide dismutase reduces cardiac hypertrophy in spontaneously hypertensive rats.

    PubMed

    Carillon, Julie; Rugale, Caroline; Rouanet, Jean-Max; Cristol, Jean-Paul; Lacan, Dominique; Jover, Bernard

    2014-08-01

    We assessed the influence of SODB, a melon superoxide dismutase (SOD), on left ventricular (LV) hypertrophy in SHR. SODB (4 or 40U SOD) was given orally for 4 or 28 days to SHR. For each treatment period, LV weight index (LVWI) and cardiomyocytes size were measured. SOD, glutathione peroxidase (GPx) and catalase expressions, and LV production and presence of superoxide anion were determined. Pro-inflammatory markers were also measured. SODB reduced LVWI and cardiomyocytes size after 4 or 28 days. Cardiac SOD and GPx increased by 30-40% with SODB. The presence but not production of superoxide anion was significantly reduced by SODB. No effect of SODB was detected on inflammatory status in any group. The beneficial effect of SODB on cardiac hypertrophy seems to be related to the stimulation of endogenous antioxidant defense, suggesting that SODB may be of interest as a dietary supplementation during conventional antihypertensive therapy. PMID:24601674

  12. Inhibition of xanthine oxidase reduces wasting and improves outcome in a rat model of cancer cachexia.

    PubMed

    Springer, Jochen; Tschirner, Anika; Hartman, Kai; Palus, Sandra; Wirth, Eva K; Ruis, Silvia Busquets; Möller, Nadine; von Haehling, Stephan; Argiles, Josep M; Köhrle, Josef; Adams, Volker; Anker, Stefan D; Doehner, Wolfram

    2012-11-01

    Cachexia is a common co-morbidity in cancer occurring in up to 80% of patients depending on the type of cancer. Uric acid (UA), the end-product of the purine metabolism, is elevated in cachexia due to tissue wasting and upregulated xanthine oxidase (XO) activity. High serum UA levels indicate increased XO-dependent production of oxygen free radicals (reactive oxygen species; ROS) and correlate with metabolic illness and poor survival. We hypothesized that XO-inhibition might reduce inflammatory signals accounting for tissue wasting and improve survival in experimental cancer cachexia. Animals were inoculated intraperitoneally with AH-130 hepatoma cells and treated with two XO-inhibitors: allopurinol [Allo, low (LD) and high dose (HD) 4 and 40 mg/kg/d] and its more effective active metabolite oxypurinol (Oxy, 4 and 40 mg/kg/d) or placebo for 15 days. Weight loss and tissue wasting of both fat and lean tissue (assessed by NMR-scanning) was reduced by both LD and HD Allo and LD-Oxy, but not by HD-Oxy. A robust induction of XO-activity for generation of reactive oxygen species was seen in the placebo group (assessed by electron paramagnetic spectroscopy), which was reduced by XO-inhibition. Increased ROS induced cytokine signaling, proteolytic activity and tissue degradation were all attenuated by XO inhibition. Survival was significantly and dose dependently improved. Food intake and spontaneous locomotor activity were higher, indicating a higher quality of life. Inhibition of XO can reduce tissue wasting and improve survival in cancer cachexia and clearly clinical studies are needed. PMID:22336965

  13. Effect of maternal separation on mitochondrial function and role of exercise in a rat model of Parkinson's disease.

    PubMed

    Hendricks, Sharief; Ojuka, Edward; Kellaway, Lauriston A; Mabandla, Musa V; Russell, Vivienne A

    2012-09-01

    Early life stress, such as maternal separation, causes adaptive changes in neural mechanisms that have adverse effects on the neuroplasticity of the brain in adulthood. As a consequence, children who are exposed to stress during development may be predisposed to neurodegenerative disorders in adulthood. A possible mechanism for increased vulnerability to neurodegeneration may be dysfunctional mitochondria. Protection from neurotoxins, such as 6-hydroxydopamine (6-OHDA), has been observed following voluntary exercise. The mechanism of this neuroprotection is not understood and mitochondria may play a role. The purpose of this study was to determine the effects of maternal separation and exercise on mitochondrial function in a rat model of Parkinson's disease. Maternally separated (pups separated from the dam for 3 h per day from postnatal day (P) 2-14) and non-separated rats were placed in individual cages with or without attached running wheels for 1 week prior to unilateral infusion of 6-OHDA (5 ?g/4 ?l, 0.5 ?l/min) into the left medial forebrain bundle at P60. After 2 h recovery, rats were returned to their cages and wheel revolutions recorded for a further 2 weeks. On P72, the rats' motor function was assessed using the forelimb akinesia test. On P74, rats were sacrificed for measurement of mitochondrial function. Exercise increased the respiratory control index (RCI) in the non-lesioned hemisphere of 6-OHDA-lesioned rats. This effect was evident in the striatum of non-separated rats and the prefrontal cortex of maternally separated rats. These results suggest that early life stress may reduce the adaptive response to exercise in the striatum, a major target of dopamine neurons, but not the prefrontal cortex in this model of Parkinson's disease. PMID:22527997

  14. The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: Synergism with the benzodiazepine diazepam

    SciTech Connect

    Schultz, M.K.; Wright, L.K.M.; Stone, M.F.; Schwartz, J.E.; Kelley, N.R.; Moffett, M.C.; Lee, R.B.; Lumley, L.A.

    2012-03-15

    Therapy of seizure activity following exposure to the nerve agent soman (GD) includes treatment with the anticonvulsant diazepam (DZP), an allosteric modulator of ?-aminobutyric acid A (GABA{sub A}) receptors. However, seizure activity itself causes the endocytosis of GABA{sub A} receptors and diminishes the inhibitory effects of GABA, thereby reducing the efficacy of DZP. Treatment with an N-methyl-D-aspartic acid (NMDA) receptor antagonist prevents this reduction in GABAergic inhibition. We examined the efficacy of the NMDA receptor antagonist caramiphen edisylate (CED; 20 mg/kg, im) and DZP (10 mg/kg, sc), administered both separately and in combination, at 10, 20 or 30 min following seizure onset for attenuation of the deleterious effects associated with GD exposure (1.2 LD{sub 50}; 132 ?g/kg, sc) in rats. Outcomes evaluated were seizure duration, neuropathology, acetylcholinesterase (AChE) activity, body weight, and temperature. We also examined the use of the reversible AChE inhibitor physostigmine (PHY; 0.2 mg/kg, im) as a therapy for GD exposure. We found that the combination of CED and DZP yielded a synergistic effect, shortening seizure durations and reducing neuropathology compared to DZP alone, when treatment was delayed 20–30 min after seizure onset. PHY reduced the number of animals that developed seizures, protected a fraction of AChE from GD inhibition, and attenuated post-exposure body weight and temperature loss independent of CED and/or DZP treatment. We conclude that: 1) CED and DZP treatment offers considerable protection against the effects of GD and 2) PHY is a potential therapeutic option following GD exposure, albeit with a limited window of opportunity. -- Highlights: ? Soman (GD) produced seizure activity resulting in neuropathology in rats. ? Tx: caramiphen (CED) and/or diazepam (DZP) @ 10, 20 or 30 min after seizure onset. ? CED/DZP showed superior anticonvulsant and neuroprotective capacity. ? Physostigmine (PHY) was examined as an adjunct post-exposure therapy. ? PHY attenuated GD-induced seizure development, but not seizure duration.

  15. PHTHALATE ESTER-INDUCED GUBERNACULAR LIGAMENT LESIONS ARE ASSOCIATED WITH REDUCED INSL3 GENE EXPRESSION IN THE FETAL RAT TESTIS DURING SEXUAL DIFFERENTIATION

    EPA Science Inventory

    Phthalate ester-induced gubernacular ligament lesions are associated with reduced Insl3 gene expression in the fetal rat testis during sexual differentiation.
    Vickie S Wilson, Christy Lambright, Johnathan Furr, Joseph Ostby, Carmen Wood, Gary Held, L.Earl Gray Jr.
    U.S. EPA,...

  16. CHRONIC EXPOSURE TO DI(2-ETHYLHEXYL) PHTHALATE (DEHP) DELAYS PUBERTY AND REDUCES ANDROGEN-DEPENDENT TISSUE WEIGHTS IN THE MALE RAT

    EPA Science Inventory

    DEHP, dibutyl (DBP)-, and benzyl butyl (BBP)- phthalate are plasticizers that cause adverse developmental reproductive effects in laboratory animals. They alter sexual differentiation in the rat by reducing fetal Leydig cell testosterone synthesis and insl3 mRNA levels, which in ...

  17. Targeted gene transfer of hepatocyte growth factor to alveolar type II epithelial cells reduces lung fibrosis in rats.

    PubMed

    Gazdhar, Amiq; Temuri, Almas; Knudsen, Lars; Gugger, Mathias; Schmid, Ralph A; Ochs, Matthias; Geiser, Thomas

    2013-01-01

    Inefficient alveolar wound repair contributes to the development of pulmonary fibrosis. Hepatocyte growth factor (HGF) is a potent growth factor for alveolar type II epithelial cells (AECII) and may improve repair and reduce fibrosis. We studied whether targeted gene transfer of HGF specifically to AECII improves lung fibrosis in bleomycin-induced lung fibrosis. A plasmid encoding human HGF expressed from the human surfactant protein C promoter (pSpC-hHGF) was designed, and extracorporeal electroporation-mediated gene transfer of HGF specifically to AECII was performed 7 days after bleomycin-induced lung injury in the rat. Animals were killed 7 days after hHGF gene transfer. Electroporation-mediated HGF gene transfer resulted in HGF expression specifically in AECII at biologically relevant levels. HGF gene transfer reduced pulmonary fibrosis as assessed by histology, hydroxyproline determination, and design-based stereology compared with controls. Our results indicate that the antifibrotic effect of HGF is due in part to a reduction of transforming growth factor-?(1), modulation of the epithelial-mesenchymal transition, and reduction of extravascular fibrin deposition. We conclude that targeted HGF gene transfer specifically to AECII decreases bleomycin-induced lung fibrosis and may therefore represent a novel cell-specific gene transfer technology to treat pulmonary fibrosis. PMID:23134111

  18. Antenatal Hypoxia Induces Programming of Reduced Arterial Blood Pressure Response in Female Rat Offspring: Role of Ovarian Function

    PubMed Central

    Xiao, DaLiao; Huang, Xiaohui; Xue, Qin; Zhang, Lubo

    2014-01-01

    In utero exposure to adverse environmental factors increases the risk of cardiovascular disease in adulthood. The present study tested the hypothesis that antenatal hypoxia causes a gender-dependent programming of altered arterial blood pressure response (BP) in adult offspring. Time-dated pregnant rats were divided into normoxic and hypoxic (10.5% O2 from days 15 to 21 of gestation) groups. The experiments were conducted in adult offspring. Antenatal hypoxia caused intrauterine growth restriction, and resulted in a gender-dependent increase Angiotensin II (Ang II)-induced BP response in male offspring, but significant decrease in BP response in female offspring. The baroreflex sensitivity was not significantly altered. Consistent with the reduced blood pressure response, antenatal hypoxia significantly decreased Ang II-induced arterial vasoconstriction in female offspring. Ovariectomy had no significant effect in control animals, but significantly increased Ang II-induced maximal BP response in prenatally hypoxic animals and eliminated the difference of BP response between the two groups. Estrogen replacement in ovariectomized animals significantly decreased the BP response to angiotensin II I only in control, but not in hypoxic animals. The result suggests complex programming mechanisms of antenatal hypoxia in regulation of ovary function. Hypoxia-mediated ovary dysfunction results in the phenotype of reduced vascular contractility and BP response in female adult offspring. PMID:24905716

  19. Altered neuronal intrinsic properties and reduced synaptic transmission of the rat's medial geniculate body in salicylate-induced tinnitus.

    PubMed

    Su, Yan-Yan; Luo, Bin; Jin, Yan; Wu, Shu-Hui; Lobarinas, Edward; Salvi, Richard J; Chen, Lin

    2012-01-01

    Sodium salicylate (NaSal), an aspirin metabolite, can cause tinnitus in animals and human subjects. To explore neural mechanisms underlying salicylate-induced tinnitus, we examined effects of NaSal on neural activities of the medial geniculate body (MGB), an auditory thalamic nucleus that provides the primary and immediate inputs to the auditory cortex, by using the whole-cell patch-clamp recording technique in MGB slices. Rats treated with NaSal (350 mg/kg) showed tinnitus-like behavior as revealed by the gap prepulse inhibition of acoustic startle (GPIAS) paradigm. NaSal (1.4 mM) decreased the membrane input resistance, hyperpolarized the resting membrane potential, suppressed current-evoked firing, changed the action potential, and depressed rebound depolarization in MGB neurons. NaSal also reduced the excitatory and inhibitory postsynaptic response in the MGB evoked by stimulating the brachium of the inferior colliculus. Our results demonstrate that NaSal alters neuronal intrinsic properties and reduces the synaptic transmission of the MGB, which may cause abnormal thalamic outputs to the auditory cortex and contribute to NaSal-induced tinnitus. PMID:23071681

  20. Reduced myelinated fiber size correlates with loss of axonal neurofilaments in peripheral nerve of chronically streptozotocin diabetic rats.

    PubMed Central

    Yagihashi, S.; Kamijo, M.; Watanabe, K.

    1990-01-01

    Peripheral sensory nerve abnormalities were investigated in long-term streptozotocin diabetic rats using quantitative analysis. To determine whether the characteristic structural changes occur with a proximodistal gradient, three levels of the sensory peripheral nervous system were investigated: the postganglionic segment of the dorsal root, the midportion of the sciatic nerve, and the distal sural nerve. Reduction of myelinated fiber size due to reduced axonal caliber was the most characteristic change at both proximal and distal levels of the peripheral nerve. The relationship between axonal size and myelin spiral length indicated a more severe axonal atrophy in the distal portion. The axonal atrophy was related to a proportional loss of axonal neurofilaments at proximal levels, whereas in the distal sural nerve the loss of neurofilaments exceeded that which would be expected for axonal size. The universal reduction of axonal size in diabetic nerve may be accounted for by impaired supply of neurofilaments or reduced neurofilament synthesis. Such cytoskeletal defects may, in turn, lead to distal axonal degeneration or contribute to the susceptibility of diabetic nerve to various external noxi, including ischemia and hypoglycemia. PMID:2141449

  1. Inhibition of mTOR Pathway by Rapamycin Reduces Brain Damage in Rats Subjected to Transient Forebrain Ischemia

    PubMed Central

    Yang, Xiao; Hei, Changhun; Liu, Ping; Song, Yaozu; Thomas, Taylor; Tshimanga, Sylvie; Wang, Feng; Niu, Jianguo; Sun, Tao; Li, P. Andy

    2015-01-01

    The aims of this study are to clarify the role of mTOR in mediating cerebral ischemic brain damage and the effects of rapamycin on ischemic outcomes. Ten minutes of forebrain ischemia was induced in rats, and their brains were sampled after 3 h, 16 h, and 7 days reperfusion for histology, immunohistochemistry and biochemical analysis. Our data demonstrated that cerebral ischemia resulted in both apoptotic and necrotic neuronal death; cerebral ischemia and reperfusion led to significant increases of mRNA and protein levels of p-mTOR and its downstream p-P70S6K and p-S6; elevation of LC3-II, and release of cytochrome c into the cytoplasm in both the cortex and hippocampus. Inhibition of mTOR by rapamycin markedly reduced ischemia-induced damage; suppressed p-Akt, p-mTOR, p-P70S6K and p-S6 protein levels; decreased LC3-II and Beclin-1; and prevented cytochrome c release in the two structures. All together, these data provide evidence that cerebral ischemia activates mTOR and autophagy pathways. Inhibition of mTOR deactivates the mTOR pathway, suppresses autophagy, prevents cytochrome c release and reduces ischemic brain damage. PMID:26681922

  2. Running Reduces Uncontrollable Stress-Evoked Serotonin and Potentiates Stress-Evoked Dopamine Concentrations in the Rat Dorsal Striatum

    PubMed Central

    Clark, Peter J.; Amat, Jose; McConnell, Sara O.; Ghasem, Parsa R.; Greenwood, Benjamin N.; Maier, Steven F.; Fleshner, Monika

    2015-01-01

    Accumulating evidence from both the human and animal literature indicates that exercise reduces the negative consequences of stress. The neurobiological etiology for this stress protection, however, is not completely understood. Our lab reported that voluntary wheel running protects rats from expressing depression-like instrumental learning deficits on the shuttle box escape task after exposure to unpredictable and inescapable tail shocks (uncontrollable stress). Impaired escape behavior is a result of stress-sensitized serotonin (5-HT) neuron activity in the dorsal raphe (DRN) and subsequent excessive release of 5-HT into the dorsal striatum following exposure to a comparatively mild stressor. However, the possible mechanisms by which exercise prevents stress-induced escape deficits are not well characterized. The purpose of this experiment was to test the hypothesis that exercise blunts the stress-evoked release of 5-HT in the dorsal striatum. Changes to dopamine (DA) levels were also examined, since striatal DA signaling is critical for instrumental learning and can be influenced by changes to 5-HT activity. Adult male F344 rats, housed with or without running wheels for 6 weeks, were either exposed to tail shock or remained undisturbed in laboratory cages. Twenty-four hours later, microdialysis was performed in the medial (DMS) and lateral (DLS) dorsal striatum to collect extracellular 5-HT and DA before, during, and following 2 mild foot shocks. We report wheel running prevents foot shock-induced elevation of extracellular 5-HT and potentiates DA concentrations in both the DMS and DLS approximately 24 h following exposure to uncontrollable stress. These data may provide a possible mechanism by which exercise prevents depression-like instrumental learning deficits following exposure to acute stress. PMID:26555633

  3. Modulation of hemodynamic and vascular filtration changes in diabetic rats by dietary myo-inositol

    SciTech Connect

    Pugliese, G.; Tilton, R.G.; Speedy, A.; Santarelli, E.; Eades, D.M.; Province, M.A.; Kilo, C.; Sherman, W.R.; Williamson, J.R. )

    1990-03-01

    To assess the potential of myo-inositol-supplemented diets to prevent diabetes-induced vascular functional changes, we examined the effects of diets supplemented with 0.5, 1, or 2% myo-inositol on blood flow and vascular filtration function in nondiabetic control rats and rats with streptozocin-induced diabetes (STZ-D). After 1 mo of diabetes and dietary myo-inositol supplementation, (1) 131I-labeled bovine serum albumin (BSA) permeation of vessels was assessed in multiple tissues, (2) glomerular filtration rate (GFR) was estimated as renal plasma clearance of 57Co-labeled EDTA, (3) regional blood flows were measured with 15-microns 85Sr-labeled microspheres, and (4) endogenous albumin and IgG urinary excretion rates were quantified by radial immunodiffusion assay. In STZ-D rats, 131I-BSA tissue clearance increased significantly (2- to 4-fold) in the anterior uvea, choroid-sclera, retina, sciatic nerve, aorta, new granulation tissue, diaphragm, and kidney but was unchanged in skin, forelimb muscle, and heart. myo-Inositol-supplemented diets reduced diabetes-induced increases in 131I-BSA clearance (in a dose-dependent manner) in all tissues; however, only in new granulation tissue and diaphragm did the 2% myo-inositol diet completely normalize vascular albumin permeation. Diabetes-induced increases in GFR and in urinary albumin and IgG excretion were also substantially reduced or normalized by dietary myo-inositol supplements. Increased blood flow in anterior uvea, choroid-sclera, kidney, new granulation tissue, and skeletal muscle in STZ-D rats also was substantially reduced or normalized by the 2% myo-inositol diet. myo-Inositol had minimal if any effects on the above parameters in control rats.

  4. Development of a universal measure of quadrupedal forelimb-hindlimb coordination using digital motion capture and computerised analysis

    E-print Network

    Hamilton, Lindsay; Franklin, Robin J. M.; Jeffery, Nick D.

    2007-09-18

    AcceResearch article Development of a universal measure of quadrupedal forelimb-hindlimb coordination using digital motion capture and computerised analysis Lindsay Hamilton, Robin JM Franklin and Nick D Jeffery* Address: Brain Repair Centre... , progress towards appli- cation in human patients has been sufficiently rapid that a series of guidance articles has recently been published to ensure results of clinical trials are readily interpretable [8- 10]. However, there remains a recognised need...

  5. Low dose nicotine self-administration is reduced in adult male rats naïve to high doses of nicotine: Implications for nicotine product standards

    PubMed Central

    Smith, Tracy T.; Schassburger, Rachel L.; Buffalari, Deanne M.

    2014-01-01

    Product standards that greatly reduce the content of nicotine within cigarettes may result in improved public health. The present study used an animal model to investigate whether individuals who start smoking following implementation of regulation may be affected differently from current smokers who form the basis of most clinical studies. One group of adult male rats (n=14/group) acquired nicotine self-administration at a high nicotine dose (60 ?g/kg/infusion) before experiencing a reduction to one of three low doses of nicotine (3.75, 7.5, or 15 ?g/kg/infusion) or vehicle. Their self-administration behavior at the low doses was compared to a group of adult male rats given the opportunity to acquire nicotine self-administration at one of the same low doses or vehicle (n=7-14/group). Second, the self-administration behavior of the acquisition group of rats was compared to their own self-administration behavior following experience self-administering a high dose of nicotine. A cocktail of non-nicotine cigarette smoke constituents was included in the vehicle for all rats across all phases of the study. Rats with a history of self-administering a high dose of nicotine had a higher rate of self-administration across the low doses than rats with no history. Additionally, the number of earned infusions increased after rats experienced self-administration of a higher dose of nicotine. These data show that low-dose nicotine self-administration is higher following a dose reduction than during acquisition. If a nicotine reduction policy were implemented, this policy may be especially effective at reducing acquisition of smoking. PMID:24999867

  6. Breviscapine reduces acute lung injury induced by left heart ischemic reperfusion in rats by inhibiting the expression of ICAM-1 and IL-18.

    PubMed

    Wang, Yuxia; Ji, Mingli; Chen, Liping; Wu, Xinjun; Wang, Lei

    2013-11-01

    It has been demonstrated that breviscapine is able to treat coronary disease and reduce the inflammatory response; however, there are no relevant reports concerning its effects on the expression of inflammatory factors in acute lung injury induced by left heart ischemic reperfusion and the underlying mechanisms. In this study, we created a left heart ischemia-reperfusion model in rats to investigate the effects of breviscapine on the expression of interleukin 18 (IL-18) and intercellular adhesion molecule-1 (ICAM-1), as well as to determine the possible mechanisms involved in the protective effects of breviscapine on respiratory function. The left heart ischemia-reperfusion model was created by ligating the anterior descending branch of the coronary artery for 30 mins followed by reperfusion. Rats in the treatment group (TG) were treated with breviscapine (10 mg/kg) and the rats in the control group (CG) received normal saline. Ten rats in the two groups were sacrificed at three points: 30 min after ligating (T1), 30 min after reperfusion (T2) and 60 min after reperfusion (T3). A respiration curve was produced and the arterial partial pressure of oxygen (PaO2) was measured for all rats. Additionally, the expression levels of IL-18 and ICAM-1 were determined and the correlation between IL-18 and ICAM-1 expression in lung tissue was analyzed. The level of IL-18 in peripheral blood and bronchialalveolar lavage fluid (BALF) was also measured. The respiration amplitude was lower and the duration time was shorter in the TG rats than in the CG rats at T1, T2 and T3. The expression levels of IL-18 and ICAM-1 in the TG group were clearly reduced. The level of IL-18 in the peripheral blood and BALF was downregulated following the administration of breviscapine. These results demonstrate that breviscapine inhibits the expression of IL-18 and ICAM-1, thereby protecting the lungs from inflammatory cascade responses. PMID:24223666

  7. Dietary L-arginine supplementation reduces fat mass in diet-induced obese rats 

    E-print Network

    Jobgen, Wenjuan Shi

    2009-06-02

    of NO produced by iNOS can oxidize biomolecules (including proteins, fatty acids, and DNA), thereby damaging cell membranes, inhibiting vital biochemical reactions (e.g., the mitochondrial Krebs cycle and respiratory chain), and even causing cell death (Fang... activity in adipose tissue to reduce its uptake of TAG and thus fat storage (Fried et al. 1993a). Acetyl-CoA, a common intermediate of glucose, fatty acid and amino acid oxidation, either enters the Krebs cycle for complete oxidation or is utilized...

  8. Positive allosteric modulators of AMPA receptors reduce proton-induced receptor desensitization in rat hippocampal neurons.

    PubMed

    Lei, S; Orser, B A; Thatcher, G R; Reynolds, J N; MacDonald, J F

    2001-05-01

    Whole-cell or outside-out patch recordings were used to investigate the effects of protons and positive modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors on the desensitization of glutamate-evoked AMPA receptor currents in isolated hippocampal CA1 neurons. Protons inhibited glutamate-evoked currents (IC(50) of 6.2 pH units) but also enhanced the apparent rate and extent of AMPA receptor desensitization. The proton-induced enhancement of desensitization could not be attributed to a reduction in the rate of recovery from desensitization or to a change in the kinetics of deactivation. Non-stationary variance analysis indicated that protons reduced maximum open probability without changing the conductance of AMPA channels. The positive modulators of AMPA receptor desensitization, cyclothiazide and GT-21-005 (an organic nitrate), reduced the proton sensitivity of AMPA receptor desensitization, which suggests that they interact with protons to diminish desensitization. In contrast, the effects of wheat germ agglutinin and aniracetam on AMPA receptor desensitization were independent of pH. These results demonstrate that a reduction in the proton sensitivity of receptor desensitization contributes to the mechanism of action of some positive modulators of AMPA receptors. PMID:11353019

  9. Reduced ethanol consumption by alcohol-preferring (P) rats following pharmacological silencing and deep brain stimulation of the nucleus accumbens shell

    PubMed Central

    Wilden, Jessica A.; Qing, Kurt Y.; Hauser, Sheketha R.; McBride, William J.; Irazoqui, Pedro P.; Rodd, Zachary A.

    2015-01-01

    Object There is increasing interest in deep brain stimulation (DBS) for the treatment of addiction. Initial testing must be conducted in animals, and the alcohol-preferring (P) rat meets the criteria for an animal model of alcoholism. This study is composed of 2 experiments designed to examine the effects of 1) pharmacological inactivation and 2) DBS of the nucleus accumbens shell (AcbSh) on the consumption of alcohol by P rats. Methods In the first experiment, the effects of reversible inactivation of the AcbSh were investigated by administering intracranial injections of ?–aminobutyric acid (GABA) agonists. Bilateral microinjections of drug were administered to the AcbSh in P rats (8–10 rats/group), after which the animals were placed in operant chambers containing 2 levers—one used to administer water and the other to administer 15% EtOH—to examine the acquisition and maintenance of oral EtOH self-administration. In the second experiment, a DBS electrode was placed in each P rat’s left AcbSh. The animals then received 100 or 200 ?A (3–4 rats/group) of DBS to examine the effect on daily consumption of oral EtOH in a free-access paradigm. Results In the first experiment, pharmacological silencing of the AcbSh with GABA agonists did not decrease the acquisition of EtOH drinking behavior but did reduce EtOH consumption by 55% in chronically drinking rats. Similarly, in the second experiment, 200 ?A of DBS consistently reduced EtOH intake by 47% in chronically drinking rats. The amount of EtOH consumption returned to baseline levels following termination of therapy in both experiments. Conclusions Pharmacological silencing and DBS of the AcbSh reduced EtOH intake after chronic EtOH use had been established in rodents. The AcbSh is a neuroanatomical substrate for the reinforcing effects of alcohol and may be a target for surgical intervention in cases of alcoholism. PMID:24460492

  10. Tezosentan, a Novel Endothelin Receptor Antagonist, Markedly Reduces Rat Hepatic Ischemia and Reperfusion Injury in Three Different Models

    PubMed Central

    Farmer, Douglas G.; Kaldas, Fady; Anselmo, Dean; Katori, Masamichi; Shen, Xiu-Da; Lassman, Charles; Kaldas, Marian; Clozel, Martine; Busuttil, Ronald W.; Kupiec-Weglinski, Jerzy

    2010-01-01

    This study investigated the effects of dual endothelin (ET) receptor blockade in rat models of liver ischemia and reperfusion injury (IRI). Three models of IRI were used: (1) in vivo total hepatic warm ischemia with portal shunting for 60 minutes with control (saline) and treatment groups (15 mg/kg tezosentan intravenously prior to reperfusion), (2) ex vivo hepatic perfusion after 24 hours of cold storage in University of Wisconsin solution with control and treatment groups (10 mg/kg tezosentan in the perfusate), and (3) syngeneic liver transplantation (LT) after 24 hours of cold storage in University of Wisconsin solution with control and treatment groups (10 mg/kg tezosentan intravenously prior to reperfusion). Tezosentan treatment significantly improved serum transaminase and histology after IRI in all 3 models. This correlated with reduced vascular resistance, improved bile production, and an improved oxygen extraction ratio. Treatment led to a reduction in neutrophil infiltration and interleukin-1 beta and macrophage inflammatory protein 2 production. A reduction in endothelial cell injury as measured by purine nucleoside phosphorylase was seen. Survival after LT was significantly increased with tezosentan treatment (90% versus 50%). In conclusion, this is the first investigation to examine dual receptor ET blockade in 3 models of hepatic IRI and the first to use the parenterally administered agent tezosentan. The results demonstrate that in both warm and cold IRI tezosentan administration improves sinusoidal hemodynamics and is associated with improved tissue oxygenation and reduced endothelial cell damage. In addition, reduced tissue inflammation, injury, and leukocyte chemotactic signaling were seen. These results provide compelling data for the further investigation of the use of tezosentan in hepatic IRI. PMID:19025917

  11. A history of alternative reinforcement reduces stimulus generalization of ethanol-seeking in a rat recovery model

    PubMed Central

    Ginsburg, Brett C.; Lamb, R. J.

    2012-01-01

    BACKGROUND Longer periods of recovery reduce the likelihood of relapse, which may be due to a reduced ability of various stimuli to occasion alcohol or drug seeking. However, this hypothesis remains largely uninvestigated. METHODS Here we assessed the ability of intermediate stimuli to occasion responding for ethanol in rats trained to discriminate an 8kHz tone signaling a food fixed-ratio (FR) of 5 and an ethanol FR5, from a 16kHz tone signaling a food FR150 and ethanol FR5. In the presence of the 8kHz tone responding for food predominates, and in the presence of the 16 kHz tone, responding for ethanol predominates. RESULTS In the context of alternation between these conditions, varying the tone from 8 to 16kHz produces a graded increase in ethanol (versus food) responding, consistent with a stimulus generalization function. A recent history of responding under food-predominant choice conditions, either during the test session or in the four sessions that precede it shifts the generalization function downwards. Extending this history to nine sessions shifts the curve further downwards. The stimulus generalization function was similar in a separate group, trained with different relative ratios for food and ethanol, but with similar behavioral allocation under each discriminative stimulus. Finally, withholding access to food and ethanol for 4 or 16 sessions did not affect the stimulus generalization gradient. CONCLUSION These results suggest that longer histories of reinforced alternative behavior might reduce the likelihood of relapse by decreasing the control exerted over alcohol- or drug-seeking by stimuli similar to those that previously occasioned alcohol- or drug-seeking. PMID:23122598

  12. Reduced Hippocampal Brain-Derived Neurotrophic Factor (BDNF) in Neonatal Rats after Prenatal Exposure to Propylthiouracil (PTU)

    PubMed Central

    Chakraborty, Goutam; Magagna-Poveda, Alejandra; Parratt, Carolyn; Umans, Jason G.; MacLusky, Neil J.

    2012-01-01

    Thyroid hormone is critical for central nervous system development. Fetal hypothyroidism leads to reduced cognitive performance in offspring as well as other effects on neural development in both humans and experimental animals. The nature of these impairments suggests that thyroid hormone may exert its effects via dysregulation of the neurotrophin brain-derived neurotrophic factor (BDNF), which is critical to normal development of the central nervous system and has been implicated in neurodevelopmental disorders. The only evidence of BDNF dysregulation in early development, however, comes from experimental models in which severe prenatal hypothyroidism occurred. By contrast, milder prenatal hypothyroidism has been shown to alter BDNF levels and BDNF-dependent functions only much later in life. We hypothesized that mild experimental prenatal hypothyroidism might lead to dysregulation of BDNF in the early postnatal period. BDNF levels were measured by ELISA at 3 or 7 d after birth in different regions of the brains of rats exposed to propylthiouracil (PTU) in the drinking water. The dose of PTU that was used induced mild maternal thyroid hormone insufficiency. Pups, but not the parents, exhibited alterations in tissue BDNF levels. Hippocampal BDNF levels were reduced at both d 3 and 7, but no significant reductions were observed in either the cerebellum or brain stem. Unexpectedly, more males than females were born to PTU-treated dams, suggesting an effect of PTU on sex determination. These results support the hypothesis that reduced hippocampal BDNF levels during early development may contribute to the adverse neurodevelopmental effects of mild thyroid hormone insufficiency during pregnancy. PMID:22253429

  13. Inhibition of immunoproteasome reduces infarction volume and attenuates inflammatory reaction in a rat model of ischemic stroke

    PubMed Central

    Chen, X; Zhang, X; Wang, Y; Lei, H; Su, H; Zeng, J; Pei, Z; Huang, R

    2015-01-01

    The detailed knowledge about the contribution of immunoproteasome to the neuroinflammation in ischemic stroke is still not available. The immunoreactivity of low molecular mass peptide 2 (LMP2) and low molecular mass peptide 7 (LMP7) was evident in the ipsilateral ischemic cerebral cortex and striatum following transient middle cerebral artery occlusion (MCAO). Both LMP2 and LMP7 increased as early as 4?h after the MCAO, further increased at 24?h, peaked at 72?h and decreased 7 days later. LMP2 and LMP7 were mainly present in astrocytes and microglia/macrophage cells, respectively. LMP2 knockdown by shRNA (short hairpin RNA) markedly reduced the levels of LMP2 and LMP7 protein and caused 75.5 and 78.6% decrease in the caspase-like (C-L) and chymotrypsin-like (CT-L) activities, respectively. Compared with cont-shRNA group (39.7%, infarction volumes/total ipsilateral hemisphere), the infarction volumes were reduced to 22.5% in LMP2-shRNA group. Additionally, LMP2 knockdown significantly reduced activated astrocytes and microglia, the expression nuclear factor kappa B (NF-?B) p65, tumor necrosis factor-? (TNF-?) and interleukin-1? (IL-1?) and caused less accumulation of ischemia-induced protein ubiquitination compared with MG132. These findings demonstrate that inhibition of LMP2 significantly attenuates inflammatory reaction and offers neuroprotection against focal cerebral ischemia in rats, suggesting that selective immunoproteasome inhibitors may be a promising strategy for stroke treatment. PMID:25633295

  14. Reduced utilization of selenium by naked mole rats due to a specific defect in GPx1 expression.

    PubMed

    Kasaikina, Marina V; Lobanov, Alexei V; Malinouski, Mikalai Y; Lee, Byung Cheon; Seravalli, Javier; Fomenko, Dmitri E; Turanov, Anton A; Finney, Lydia; Vogt, Stefan; Park, Thomas J; Miller, Richard A; Hatfield, Dolph L; Gladyshev, Vadim N

    2011-05-13

    Naked mole rat (MR) Heterocephalus glaber is a rodent model of delayed aging because of its unusually long life span (>28 years). It is also not known to develop cancer. In the current work, tissue imaging by x-ray fluorescence microscopy and direct analyses of trace elements revealed low levels of selenium in the MR liver and kidney, whereas MR and mouse brains had similar selenium levels. This effect was not explained by uniform selenium deficiency because methionine sulfoxide reductase activities were similar in mice and MR. However, glutathione peroxidase activity was an order of magnitude lower in MR liver and kidney than in mouse tissues. In addition, metabolic labeling of MR cells with (75)Se revealed a loss of the abundant glutathione peroxidase 1 (GPx1) band, whereas other selenoproteins were preserved. To characterize the MR selenoproteome, we sequenced its liver transcriptome. Gene reconstruction revealed standard selenoprotein sequences except for GPx1, which had an early stop codon, and SelP, which had low selenocysteine content. When expressed in HEK 293 cells, MR GPx1 was present in low levels, and its expression could be rescued neither by removing the early stop codon nor by replacing its SECIS element. In addition, GPx1 mRNA was present in lower levels in MR liver than in mouse liver. To determine if GPx1 deficiency could account for the reduced selenium content, we analyzed GPx1 knock-out mice and found reduced selenium levels in their livers and kidneys. Thus, MR is characterized by the reduced utilization of selenium due to a specific defect in GPx1 expression. PMID:21372135

  15. Reduced Utilization of Selenium by Naked Mole Rats Due to a Specific Defect in GPx1 Expression*

    PubMed Central

    Kasaikina, Marina V.; Lobanov, Alexei V.; Malinouski, Mikalai Y.; Lee, Byung Cheon; Seravalli, Javier; Fomenko, Dmitri E.; Turanov, Anton A.; Finney, Lydia; Vogt, Stefan; Park, Thomas J.; Miller, Richard A.; Hatfield, Dolph L.; Gladyshev, Vadim N.

    2011-01-01

    Naked mole rat (MR) Heterocephalus glaber is a rodent model of delayed aging because of its unusually long life span (>28 years). It is also not known to develop cancer. In the current work, tissue imaging by x-ray fluorescence microscopy and direct analyses of trace elements revealed low levels of selenium in the MR liver and kidney, whereas MR and mouse brains had similar selenium levels. This effect was not explained by uniform selenium deficiency because methionine sulfoxide reductase activities were similar in mice and MR. However, glutathione peroxidase activity was an order of magnitude lower in MR liver and kidney than in mouse tissues. In addition, metabolic labeling of MR cells with 75Se revealed a loss of the abundant glutathione peroxidase 1 (GPx1) band, whereas other selenoproteins were preserved. To characterize the MR selenoproteome, we sequenced its liver transcriptome. Gene reconstruction revealed standard selenoprotein sequences except for GPx1, which had an early stop codon, and SelP, which had low selenocysteine content. When expressed in HEK 293 cells, MR GPx1 was present in low levels, and its expression could be rescued neither by removing the early stop codon nor by replacing its SECIS element. In addition, GPx1 mRNA was present in lower levels in MR liver than in mouse liver. To determine if GPx1 deficiency could account for the reduced selenium content, we analyzed GPx1 knock-out mice and found reduced selenium levels in their livers and kidneys. Thus, MR is characterized by the reduced utilization of selenium due to a specific defect in GPx1 expression. PMID:21372135

  16. The anticholinergic and antiglutamatergic drug caramiphen reduces seizure duration in soman-exposed rats: synergism with the benzodiazepine diazepam.

    PubMed

    Schultz, M K; Wright, L K M; Stone, M F; Schwartz, J E; Kelley, N R; Moffett, M C; Lee, R B; Lumley, L A

    2012-03-15

    Therapy of seizure activity following exposure to the nerve agent soman (GD) includes treatment with the anticonvulsant diazepam (DZP), an allosteric modulator of ?-aminobutyric acid A (GABA(A)) receptors. However, seizure activity itself causes the endocytosis of GABA(A) receptors and diminishes the inhibitory effects of GABA, thereby reducing the efficacy of DZP. Treatment with an N-methyl-d-aspartic acid (NMDA) receptor antagonist prevents this reduction in GABAergic inhibition. We examined the efficacy of the NMDA receptor antagonist caramiphen edisylate (CED; 20mg/kg, im) and DZP (10mg/kg, sc), administered both separately and in combination, at 10, 20 or 30min following seizure onset for attenuation of the deleterious effects associated with GD exposure (1.2 LD(50); 132?g/kg, sc) in rats. Outcomes evaluated were seizure duration, neuropathology, acetylcholinesterase (AChE) activity, body weight, and temperature. We also examined the use of the reversible AChE inhibitor physostigmine (PHY; 0.2mg/kg, im) as a therapy for GD exposure. We found that the combination of CED and DZP yielded a synergistic effect, shortening seizure durations and reducing neuropathology compared to DZP alone, when treatment was delayed 20-30min after seizure onset. PHY reduced the number of animals that developed seizures, protected a fraction of AChE from GD inhibition, and attenuated post-exposure body weight and temperature loss independent of CED and/or DZP treatment. We conclude that: 1) CED and DZP treatment offers considerable protection against the effects of GD and 2) PHY is a potential therapeutic option following GD exposure, albeit with a limited window of opportunity. PMID:22310180

  17. Functional adaptations in the forelimb muscles of non-human great apes

    PubMed Central

    Myatt, Julia P; Crompton, Robin H; Payne-Davis, Rachel C; Vereecke, Evie E; Isler, Karin; Savage, Russell; D'Août, Kristiaan; Günther, Michael M; Thorpe, Susannah K S

    2012-01-01

    The maximum capability of a muscle can be estimated from simple measurements of muscle architecture such as muscle belly mass, fascicle length and physiological cross-sectional area. While the hindlimb anatomy of the non-human apes has been studied in some detail, a comparative study of the forelimb architecture across a number of species has never been undertaken. Here we present data from chimpanzees, bonobos, gorillas and an orangutan to ascertain if, and where, there are functional differences relating to their different locomotor repertoires and habitat usage. We employed a combination of analyses including allometric scaling and ancovas to explore the data, as the sample size was relatively small and heterogeneous (specimens of different sizes, ages and sex). Overall, subject to possible unidentified, confounding factors such as age effects, it appears that the non-human great apes in this sample (the largest assembled to date) do not vary greatly across different muscle architecture parameters, even though they perform different locomotor behaviours at different frequencies. Therefore, it currently appears that the time spent performing a particular behaviour does not necessarily impose a dominating selective influence on the soft-tissue portion of the musculoskeletal system; rather, the overall consistency of muscle architectural properties both between and within the Asian and African apes strengthens the case for the hypothesis of a possible ancient shared evolutionary origin for orthogrady under compressive and/or suspensory loading in the great apes. PMID:22034995

  18. Apparent density patterns in subchondral bone of the sloth and anteater forelimb.

    PubMed

    Patel, Biren A; Carlson, Kristian J

    2008-10-23

    Vertebrate morphologists often are interested in inferring limb-loading patterns in animals characterized by different locomotor repertoires. Because bone apparent density (i.e. mass per unit volume of bone inclusive of porosities) is a determinant of compressive strength, and thus indicative of compressive loading, recent comparative studies in primates have proposed a structure-function relationship between apparent density of subchondral bone and locomotor behaviours that vary in compressive loading. If such patterns are found in other mammals, then these relationships would be strengthened further. Here, we examine the distal radius of suspensory sloths that generally load their forelimbs (FLs) in tension and of quadrupedal anteaters that generally load their FLs in compression. Computed tomography osteoabsorptiometry was used to visualize the patterns in subchondral apparent density. Suspensory sloths exhibit relatively smaller areas of high apparent density than quadrupedal anteaters. This locomotor-based pattern is analogous to the pattern observed in suspensory and quadrupedal primates. Similarity between xenarthran and primate trends suggests broad-scale applicability for analysing subchondral bone apparent density and supports the idea that bone functionally alters its material properties in response to locomotor behaviours. PMID:18628113

  19. The effects of graded forelimb afferent volleys on acetylcholine release from cat sensorimotor cortex.

    PubMed Central

    Mullin, W J; Phillis, J W

    1975-01-01

    1. The acetylcholine (ACh)-releasing system in the cerebral cortex of pentobarbital anaesthetized cats was investigated by examining the effect of graded afferent volleys in forelimb nerves on ACh release from the sensorimotor cortices contralateral and ipsilateral to the site of stimulation. 2. Cortical ACh release was determined by bio-assay of neostigmine-containing perfusates which had been in contact with the cortical surfaces for 5-10 min periods. 3. Afferent volleys, generated by stimuli that were effective in activating as many fibres of a fibre group as possible without stimulating fibres in the group with the next highest threshold for activation, were monitored from dorsal roots C7 or C8 before entering the spinal cord. 4. Stimulation of the deep (DR) and superficial (SR) radial nerves and the radial (R) nerve proximal to the junction of the DR and SR were effective in enhancing ACh release only when either group III or groups III and IV fibres were included in the afferent volley. 5. The rates of ACh release from the primary receiving area of the sensorimotor cortex contralateral to the site of stimulation did not differ from those from the same area of the ipsilateral sensorimotor cortex. 6. The pertinence of this data to the various hypotheses concerning the nature of the ACh-releasing pathways to the cerebral cortex is discussed. PMID:1133777

  20. Modeling the Backbone Dynamics of Reduced and Oxidized Solvated Rat Microsomal Cytochrome b5

    PubMed Central

    Giachetti, Andrea; Penna, Giovanni La; Perico, Angelo; Banci, Lucia

    2004-01-01

    In this article, a description of the statistics and dynamics of cytochrome b5 in both reduced and oxidized forms is given. Results of molecular dynamics computer simulations in the explicit solvent have been combined with mode-coupling diffusion models including and neglecting the molecule-solvent correlations. R1 and R1? nuclear magnetic relaxation parameters of 15N in the protein backbone have been calculated and compared with experiments. Slight changes in charge density in the heme upon oxidation produces a cascade of changes in charge distributions from heme propionates up to charged residues ?1.5 nm from Fe. These changes in charge distributions modify the molecular surface and the water shell surrounding the protein. The statistical changes upon oxidation can be included in diffusive models that physically explain the upper and lower limits of R1? relaxation parameters at high off-resonance fields. PMID:15240483

  1. Palmitoylethanolamide Treatment Reduces Blood Pressure in Spontaneously Hypertensive Rats: Involvement of Cytochrome P450-Derived Eicosanoids and Renin Angiotensin System

    PubMed Central

    Mattace Raso, Giuseppina; Pirozzi, Claudio; d'Emmanuele di Villa Bianca, Roberta; Simeoli, Raffaele; Santoro, Anna; Lama, Adriano; Di Guida, Francesca; Russo, Roberto; De Caro, Carmen; Sorrentino, Raffaella; Calignano, Antonio; Meli, Rosaria

    2015-01-01

    Palmitoylethanolamide (PEA), a peroxisome proliferator-activated receptor-? agonist, has been demonstrated to reduce blood pressure and kidney damage secondary to hypertension in spontaneously hypertensive rat (SHR). Currently, no information is available concerning the putative effect of PEA on modulating vascular tone. Here, we investigate the mechanisms underpinning PEA blood pressure lowering effect, exploring the contribution of epoxyeicosatrienoic acids, CYP-dependent arachidonic acid metabolites, as endothelium-derived hyperpolarizing factors (EDHF), and renin angiotensin system (RAS) modulation. To achieve this aim SHR and Wistar-Kyoto rats were treated with PEA (30 mg/kg/day) for five weeks. Functional evaluations on mesenteric bed were performed to analyze EDHF-mediated vasodilation. Moreover, mesenteric bed and carotid were harvested to measure CYP2C23 and CYP2J2, the key isoenzymes in the formation of epoxyeicosatrienoic acids, and the soluble epoxide hydrolase, which is responsible for their degradation in the corresponding diols. Effect of PEA on RAS modulation was investigated by analyzing angiotensin converting enzyme and angiotensin receptor 1 expression. Here, we showed that EDHF-mediated dilation in response to acetylcholine was increased in mesenteric beds of PEA-treated SHR. Western blot analysis revealed that the increase in CYP2C23 and CYP2J2 observed in SHR was significantly attenuated in mesenteric beds of PEA-treated SHR, but unchanged in the carotids. Interestingly, in both vascular tissues, PEA significantly decreased the soluble epoxide hydrolase protein level, accompanied by a reduced serum concentration of its metabolite 14-15 dihydroxyeicosatrienoic acid, implying a reduction in epoxyeicosatrienoic acid hydrolisis. Moreover, PEA treatment down-regulated angiotensin receptor 1 and angiotensin converting enzyme expression, indicating a reduction in angiotensin II-mediated effects. Consistently, a damping of the activation of angiotensin receptor 1 underlying pathways in mesenteric beds was shown in basal conditions in PEA-treated SHR. In conclusion, our data demonstrate the involvement of epoxyeicosatrienoic acids and renin angiotensin system in the blood pressure lowering effect of PEA. PMID:25951330

  2. Aging reduces the GABA-dependent /sup 36/Cl/sup -/ flux in rat brain membrane vesicles

    SciTech Connect

    Concas, A.; Pepitoni, S.; Atsoggiu, T.; Toffano, G.; Biggio, G.

    1988-01-01

    The function of the chloride channel associated to GABA/sub A/ receptor complex was analyzed in the brain of aged rats by measuring the chloride flux across the neuronal membrane and its modulation by drugs acting at the level of the GABA receptor complex and /sup 35/S-TBPS binding. The basal /sup 36/Cl/sup -/ uptake by brain membrane vesicles of aged rats was higher than that observed in those of adult rats. The higher /sup 36/Cl/sup -/ uptake found in cortical membrane vesicles of senescent rats was not sensitive to the action of bicuculline indicating that it was not the consequence of a tonic GABAergic modulation. Moreover, the stimulation of /sup 36/Cl/sup -/ uptake induced by GABA was markedly lower in membrane vesicles of aged rats than that observed in those of adult rats. Accordingly, the stimulation of /sup 36/Cl/sup -/ efflux elicited by GABA and pentobarbital was higher in membrane vesicles of adult rats with respect to that of old rats. Finally a significant decrease of /sup 35/S-TBPS binding was observed in membrane preparation from the cerebral cortex, cerebellum and hippocampus of aged-rats.

  3. Simulated microgravity alters multipotential differentiation of rat mesenchymal stem cells in association with reduced telomerase activity

    NASA Astrophysics Data System (ADS)

    Sun, Lianwen; Gan, Bo; Fan, Yubo; Xie, Tian; Hu, Qinghua; Zhuang, Fengyuan

    Microgravity is one of the most important characteristics in space flight. Exposure to microgravity results in extensive physiological changes in humans. Bone loss is one of the changes with serious consequences; however, the mechanism retains unclear. As the origin of osteoprogenitors, mesenchymal stem cells (MSCs) may play an important role in it. After cultured under simulated microgravity (in a rotary cell culture system, RCCS), MSCs were stained using oil red O to identify adipocytes. The mRNA level of bone morphogenetic protein (BMP)-2 and peroxisome proliferators-activated receptor (PPAR) ?2 was determined by RT-PCR. Otherwise, MSCs were induced to osteogenic differentiation after microgravity culture, and then the activity of alkaline phosphatase (ALP) was determined by PNPP and the content of osteocalcin (OC) by ELISA. Furthermore, the telomerase activity in MSCs was measured by TRAP. The results showed that simulated microgravity inhibited osteoblastic differentiation and induced adipogenic differentiation accompanied by the change of gene expression of BMP-2 and PPAR?2 in MSCs. Meanwhile, the telomerase activity decreased significantly in MSCs under simulated microgravity. The reduced bone formation in space flight may partly be due to the altered potential differentiation of MSCs associated with telomerase activity which plays a key role in regulating the lifespan of cell proliferation and differentiation. Therefore, telomerase activation/replacement may act as a potential countermeasure for microgravity-induced bone loss.

  4. Sensorimotor restriction affects complex movement topography and reachable space in the rat motor cortex

    PubMed Central

    Budri, Mirco; Lodi, Enrico; Franchi, Gianfranco

    2014-01-01

    Long-duration intracortical microstimulation (ICMS) studies with 500 ms of current pulses suggest that the forelimb area of the motor cortex is organized into several spatially distinct functional zones that organize movements into complex sequences. Here we studied how sensorimotor restriction modifies the extent of functional zones, complex movements, and reachable space representation in the rat forelimb M1. Sensorimotor restriction was achieved by means of whole-forelimb casting of 30 days duration. Long-duration ICMS was carried out 12 h and 14 days after cast removal. Evoked movements were measured using a high-resolution 3D optical system. Long-term cast caused: (i) a reduction in the number of sites where complex forelimb movement could be evoked; (ii) a shrinkage of functional zones but no change in their center of gravity; (iii) a reduction in movement with proximal/distal coactivation; (iv) a reduction in maximal velocity, trajectory and vector length of movement, but no changes in latency or duration; (v) a large restriction of reachable space. Fourteen days of forelimb freedom after casting caused: (i) a recovery of the number of sites where complex forelimb movement could be evoked; (ii) a recovery of functional zone extent and movement with proximal/distal coactivation; (iii) an increase in movement kinematics, but only partial restoration of control rat values; (iv) a slight increase in reachability parameters, but these remained far below baseline values. We pose the hypothesis that specific aspects of complex movement may be stored within parallel motor cortex re-entrant systems. PMID:25565987

  5. Inducible Lentivirus-Mediated siRNA against TLR4 Reduces Nociception in a Rat Model of Bone Cancer Pain

    PubMed Central

    Pan, Ruirui; Di, Huiting; Zhang, Jinming; Huang, Zhangxiang; Sun, Yuming; Yu, Weifeng; Wu, Feixiang

    2015-01-01

    Although bone cancer pain is still not fully understood by scientists and clinicians alike, studies suggest that toll like receptor 4 (TLR4) plays an important role in the initiation and/or maintenance of pathological pain state in bone cancer pain. A promising treatment for bone cancer pain is the downregulation of TLR4 by RNA interference; however, naked siRNA (small interference RNA) is not effective in long-term treatments. In order to concoct a viable prolonged treatment for bone cancer pain, an inducible lentivirus LvOn-siTLR4 (tetracycline inducible lentivirus carrying siRNA targeting TLR4) was prepared and the antinociception effects were observed in bone cancer pain rats induced by Walker 256 cells injection in left leg. Results showed that LvOn-siTLR4 intrathecal injection with doxycycline (Dox) oral administration effectively reduced the nociception induced by Walker 256 cells while inhibiting the mRNA and protein expression of TLR4. Proinflammatory cytokines as TNF-? and IL-1? in spinal cord were also decreased. These findings suggest that TLR4 could be a target for bone cancer pain treatment and tetracycline inducible lentivirus LvOn-siTLR4 represents a new potential option for long-term treatment of bone cancer pain. PMID:26556957

  6. Glutamate reduces glucose utilization while concomitantly enhancing AQP9 and MCT2 expression in cultured rat hippocampal neurons

    PubMed Central

    Tescarollo, Fabio; Covolan, Luciene; Pellerin, Luc

    2014-01-01

    The excitatory neurotransmitter glutamate has been reported to have a major impact on brain energy metabolism. Using primary cultures of rat hippocampal neurons, we observed that glutamate reduces glucose utilization in this cell type, suggesting alteration in mitochondrial oxidative metabolism. The aquaglyceroporin AQP9 and the monocarboxylate transporter MCT2, two transporters for oxidative energy substrates, appear to be present in mitochondria of these neurons. Moreover, they not only co-localize but they interact with each other as they were found to co-immunoprecipitate from hippocampal neuron homogenates. Exposure of cultured hippocampal neurons to glutamate 100 ?M for 1 h led to enhanced expression of both AQP9 and MCT2 at the protein level without any significant change at the mRNA level. In parallel, a similar increase in the protein expression of LDHA was evidenced without an effect on the mRNA level. These data suggest that glutamate exerts an influence on neuronal energy metabolism likely through a regulation of the expression of some key mitochondrial proteins. PMID:25161606

  7. Hypertonic Saline (NaCl 7.5 %) Reduces LPS-Induced Acute Lung Injury in Rats.

    PubMed

    Petroni, Ricardo Costa; Biselli, Paolo Jose Cesare; de Lima, Thais Martins; Theobaldo, Mariana Cardillo; Caldini, Elia Tamaso; Pimentel, Rosângela Nascimento; Barbeiro, Hermes Vieira; Kubo, Suely Ariga; Velasco, Irineu Tadeu; Soriano, Francisco Garcia

    2015-12-01

    Acute respiratory distress syndrome (ARDS) is the most severe lung inflammatory manifestation and has no effective therapy nowadays. Sepsis is one of the main illnesses among ARDS causes. The use of fluid resuscitation is an important treatment for sepsis, but positive fluid balance may induce pulmonary injury. As an alternative, fluid resuscitation with hypertonic saline ((HS) NaCl 7.5 %) has been described as a promising therapeutical agent in sepsis-induced ARDS by the diminished amount of fluid necessary. Thus, we evaluated the effect of hypertonic saline in the treatment of LPS-induced ARDS. We found that hypertonic saline (NaCl 7.5 %) treatment in rat model of LPS-induced ARDS avoided pulmonary function worsening and inhibited type I collagen deposition. In addition, hypertonic saline prevented pulmonary injury by decreasing metalloproteinase 9 (MMP-9) activity in tissue. Focal adhesion kinase (FAK) activation was reduced in HS group as well as neutrophil infiltration, NOS2 expression and NO content. Our study shows that fluid resuscitation with hypertonic saline decreases the progression of LPS-induced ARDS due to inhibition of pulmonary remodeling that is observed when regular saline is used. PMID:25962375

  8. DFL23448, A Novel Transient Receptor Potential Melastin 8-Selective Ion Channel Antagonist, Modifies Bladder Function and Reduces Bladder Overactivity in Awake Rats.

    PubMed

    Mistretta, Francesco A; Russo, Andrea; Castiglione, Fabio; Bettiga, Arianna; Colciago, Giorgia; Montorsi, Francesco; Brandolini, Laura; Aramini, Andrea; Bianchini, Gianluca; Allegretti, Marcello; Bovolenta, Silvia; Russo, Roberto; Benigni, Fabio; Hedlund, Petter

    2016-01-01

    The transient receptor potential melastin 8 ion channel (TRPM8) is implicated in bladder sensing but limited information on TRPM8 antagonists in bladder overactivity is available. This study characterizes a new TRPM8-selective antagonist (DFL23448 [5-(2-ethyl-2H-tetrazol-5-yl)-2-(3-fluorophenyl)-1,3-thiazol-4-ol]) and evaluates it in cold-induced behavioral tests and tests on bladder function and experimental bladder overactivity in vivo in rats. DFL23448 displayed IC50 values of 10 and 21 nM in hTRPM8 human embryonic kidney 293 cells activated by Cooling Agent 10 or cold, but it had limited activity (IC50 > 10 ?M) at transient receptor potential vanilloids TRPV1, TRPA1, or TRPV4 or at various G protein-coupled receptors. In rats, DFL23448 administered intravenously or orally had a half-life of 37 minutes or 4.9 hours, respectively. DLF23448 (10 mg/kg i.v.) reduced icilin-induced "wet dog-like" shakes in rats. Intravesical DFL23448 (10 mg/l), but not vehicle, increased micturition intervals, micturition volume, and bladder capacity. During bladder overactivity by intravesical prostaglandin E2 (PGE2), vehicle controls exhibited reductions in micturition intervals, micturition volumes, and bladder capacity by 37%-39%, whereas the same parameters only decreased by 12%-15% (P < 0.05-0.01 versus vehicle) in DFL23448-treated rats. In vehicle-treated rats, but not in DFL23448-treated rats, intravesical PGE2 increased bladder pressures. Intravenous DFL23448 at 10 mg/kg, but not 1 mg/kg DFL23448 or vehicle, increased micturition intervals, micturition volumes, and bladder capacity. During bladder overactivity by intravesical PGE2, micturition intervals, micturition volumes, and bladder capacity decreased in vehicle- and 1 mg/kg DFL23448-treated rats, but not in 10 mg/kg DFL23448-treated rats. Bladder pressures increased less in rats treated with DFL23448 10 mg/kg than in vehicle- or 1 mg/kg DFL23448-treated rats. DFL23448 (10 mg/kg i.v.), but not vehicle, prevented cold stress-induced bladder overactivity. Our results support a role for bladder TRPM8-mediated signals in experimental bladder overactivity. PMID:26546575

  9. Effects of reduced pulmonary flow and hypoxia on metabolism of serotonin by rat lungs perfused in situ.

    PubMed

    Watkins, C A; Rannels, D E

    1987-12-01

    To investigate the extent to which reduced pulmonary flow may affect non-ventilatory functions of the lung, pulmonary artery pressures were altered systematically in an in vitro perfused lung preparation. Metabolic integrity of the tissue was assessed at two levels: disposition of exogenous serotonin (5-hydroxytryptamine; 5-HT) was monitored as a specific indicator of endothelial cell metabolism; and whole-tissue rates of protein synthesis and levels of ATP were evaluated as indices of general metabolic activity and energy availability. Rat lungs were perfused with recirculating cell-free buffer (37 degrees C) for 1 or 3 h at high (36) or low (3 ml.min-1.g-1) pulmonary flow; initial rates of 5-HT metabolism were measured over a subsequent 2-min interval of single-pass perfusion. Metabolism of 5-HT was inhibited and protein synthesis decreased 35% at low pulmonary flow. These changes did not appear to result directly from hypoxia, nor from the associated fall in tissue ATP. The effects of low flow were not reversed at high PO2, nor was 5-HT metabolism inhibited by restricted oxygen availability at high flow rates. After as long as 3 h exposure to a combination of low flow, ventilation (V = 0), and temperature (27 degrees C) and to the volatile anesthetic, halothane, inhibitory effects on both amine and protein metabolism were rapidly reversible. Reductions in the rate of 5-HT metabolism at reduced flow involved a decrease in the maximal velocity (Vmax: 8.0 to 2.2 nmol.min-1.g-1), without change in the apparent Km (2.6-3.2 microM) of the pathway for amine metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3688535

  10. INADEQUATE COPPER INTAKE REDUCES SERUM INSULIN-LIKE GROWTH FACTOR-1 (IGF-1) CONCENTRATION AND BONE STRENGTH IN GROWING RATS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine whether the interaction between graded intakes of zinc (Zn) and copper (Cu) affected serum IGF-1 concentration and bone quality in growing rats. In a 3x3 factorial design, weanling male rats (n = 84) were randomly assigned to 12 groups and were fed one of 9 modi...

  11. Ketamine exerts antidepressant effects and reduces IL-1? and IL-6 levels in rat prefrontal cortex and hippocampus

    PubMed Central

    YANG, CHUN; HONG, TAO; SHEN, JIANG; DING, JIE; DAI, XIONG-WEI; ZHOU, ZHI-QIANG; YANG, JIAN-JUN

    2013-01-01

    Ketamine has fast-acting and robust antidepressant effects in animal models and depressed patients. It has been hypothesized that its underlying mechanism of action is associated with the inflammatory response in the central nervous system. Therefore, the present study was designed to investigate the antidepressant effects of ketamine and the expression of interleukin (IL)-1? and IL-6 in the prefrontal cortex and hippocampus of a rat model. Twenty Wistar rats were randomly divided into 2 groups (each group, n=10); the saline group and the ketamine group. On the 1st day, rats undertook a forced swimming test (FST) for 15 min (pre-test session). On the 2nd day, saline or ketamine was administered intraperitoneally 30 min before the test session. Following this, rats performed another FST for 5 min (test session) and the immobility time was recorded. The rats were then sacrificed, and the prefrontal cortex and hippocampus were harvested for determination of IL-1? and IL-6 levels. Compared with the saline group, ketamine administration significantly decreased the immobility time of rats during the FST (P<0.05). In addition, the ketamine group demonstrated a statistically significant decrease in the expression of IL-1? and IL-6 in rat prefrontal cortex and hippocampus compared with the saline group (P<0.05). Ketamine-induced antidepressant effects are associated with decreased levels of IL-1? and IL-6 in rat prefrontal cortex and hippocampus. PMID:23596475

  12. INADEQUATE COPPER (CU) INTAKE REDUCES SERUM INSULIN-LIKE GROWTH FACTOR-1 (IGF-1) AND BONE STRENGTH IN GROWING RATS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine whether the interaction between graded intakes of zinc (Zn) and copper (Cu) affected serum IGF-1 concentration and bone quality in growing rats. In a 3x3 factorial design, weanling male rats (n = 84) were randomly assigned to 12 groups and were fed one of 9 modi...

  13. Periadventitial atRA citrate-based polyester membranes reduce neointimal hyperplasia and restenosis after carotid injury in rats.

    PubMed

    Gregory, Elaine K; Webb, Antonio R; Vercammen, Janet M; Flynn, Megan E; Ameer, Guillermo A; Kibbe, Melina R

    2014-11-15

    Oral all-trans retinoic acid (atRA) has been shown to reduce the formation of neointimal hyperplasia; however, the dose required was 30 times the chemotherapeutic dose, which already has reported side effects. As neointimal formation is a localized process, new approaches to localized delivery are required. This study assessed whether atRA within a citrate-based polyester, poly(1,8 octanediolcitrate) (POC), perivascular membrane would prevent neointimal hyperplasia following arterial injury. atRA-POC membranes were prepared and characterized for atRA release via high-performance liquid chromatography with mass spectrometry detection. Rat adventitial fibroblasts (AF) and vascular smooth muscle cells (VSMC) were exposed to various concentrations of atRA; proliferation, apoptosis, and necrosis were assessed in vitro. The rat carotid artery balloon injury model was used to evaluate the impact of the atRA-POC membranes on neointimal formation, cell proliferation, apoptosis, macrophage infiltration, and vascular cell adhesion molecule 1 (VCAM-1) expression in vivo. atRA-POC membranes released 12 ?g of atRA over 2 wk, with 92% of the release occurring in the first week. At 24 h, atRA (200 ?mol/l) inhibited [(3)H]-thymidine incorporation into AF and VSMC by 78% and 72%, respectively (*P = 0.001), with negligible apoptosis or necrosis. Histomorphometry analysis showed that atRA-POC membranes inhibited neointimal formation after balloon injury, with a 56%, 57%, and 50% decrease in the intimal area, intima-to-media area ratio, and percent stenosis, respectively (P = 0.001). atRA-POC membranes had no appreciable effect on apoptosis or proliferation at 2 wk. Regarding biocompatibility, we found a 76% decrease in macrophage infiltration in the intima layer (P < 0.003) in animals treated with atRA-POC membranes, with a coinciding 53% reduction in VCAM-1 staining (P < 0.001). In conclusion, perivascular delivery of atRA inhibited neointimal formation and restenosis. These data suggest that atRA-POC membranes may be suitable as localized therapy to inhibit neointimal hyperplasia following open cardiovascular procedures. PMID:25239800

  14. Periadventitial atRA citrate-based polyester membranes reduce neointimal hyperplasia and restenosis after carotid injury in rats

    PubMed Central

    Gregory, Elaine K.; Webb, Antonio R.; Vercammen, Janet M.; Flynn, Megan E.; Ameer, Guillermo A.

    2014-01-01

    Oral all-trans retinoic acid (atRA) has been shown to reduce the formation of neointimal hyperplasia; however, the dose required was 30 times the chemotherapeutic dose, which already has reported side effects. As neointimal formation is a localized process, new approaches to localized delivery are required. This study assessed whether atRA within a citrate-based polyester, poly(1,8 octanediolcitrate) (POC), perivascular membrane would prevent neointimal hyperplasia following arterial injury. atRA-POC membranes were prepared and characterized for atRA release via high-performance liquid chromatography with mass spectrometry detection. Rat adventitial fibroblasts (AF) and vascular smooth muscle cells (VSMC) were exposed to various concentrations of atRA; proliferation, apoptosis, and necrosis were assessed in vitro. The rat carotid artery balloon injury model was used to evaluate the impact of the atRA-POC membranes on neointimal formation, cell proliferation, apoptosis, macrophage infiltration, and vascular cell adhesion molecule 1 (VCAM-1) expression in vivo. atRA-POC membranes released 12 ?g of atRA over 2 wk, with 92% of the release occurring in the first week. At 24 h, atRA (200 ?mol/l) inhibited [3H]-thymidine incorporation into AF and VSMC by 78% and 72%, respectively (*P = 0.001), with negligible apoptosis or necrosis. Histomorphometry analysis showed that atRA-POC membranes inhibited neointimal formation after balloon injury, with a 56%, 57%, and 50% decrease in the intimal area, intima-to-media area ratio, and percent stenosis, respectively (P = 0.001). atRA-POC membranes had no appreciable effect on apoptosis or proliferation at 2 wk. Regarding biocompatibility, we found a 76% decrease in macrophage infiltration in the intima layer (P < 0.003) in animals treated with atRA-POC membranes, with a coinciding 53% reduction in VCAM-1 staining (P < 0.001). In conclusion, perivascular delivery of atRA inhibited neointimal formation and restenosis. These data suggest that atRA-POC membranes may be suitable as localized therapy to inhibit neointimal hyperplasia following open cardiovascular procedures. PMID:25239800

  15. Dieckol isolated from Ecklonia cava protects against high-glucose induced damage to rat insulinoma cells by reducing oxidative stress and apoptosis.

    PubMed

    Lee, Seung-Hong; Park, Mi-Hwa; Kang, Sung-Myung; Ko, Seok-Chun; Kang, Min-Cheol; Cho, Seungmok; Park, Pyo-Jam; Jeon, Byong-Tae; Kim, Se-Kwon; Han, Ji-Sook; Jeon, You-Jin

    2012-01-01

    Pancreatic ? cells are very sensitive to oxidative stress and this might play an important role in ? cell death with diabetes. The protective effect of dieckol, one of the phlorotannin polyphenol compounds purified from Ecklonia cava (E. cava), against high glucose-induced oxidative stress was investigated by using rat insulinoma cells. A high-glucose (30 mM) treatment induced the death of rat insulinoma cells, but dieckol, at a concentration 17.5 or 70 µM, significantly inhibited the high-glucose induced glucotoxicity. Treatment with dieckol also dose-dependently reduced thiobarbituric acid reactive substances (TBARS), the generation of intracellular reactive oxygen species (ROS), and the nitric oxide level increased by a high glucose concentration. In addition, the dieckol treatment increased the activities of antioxidative enzymes including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) in high glucose-pretreated rat insulinoma cells. Dieckol protected rat insulinoma cells damage under high glucose conditions. These effects were mediated by suppressing apoptosis and were associated with increased anti-apoptotic Bcl-2 expression, and reduced pro-apoptotic cleaved caspase-3 expression. These findings indicate that dieckol might be useful as a potential pharmaceutical agent to protect against the glucotoxicity caused by hyperglycemia-induced oxidative stress associated with diabetes. PMID:22878185

  16. Dietary conjugated linoleic acids alter serum IGF-I and IGF binding protein concentrations and reduce bone formation in rats fed (n-6) or (n-3) fatty acids.

    PubMed

    Li, Y; Seifert, M F; Ney, D M; Grahn, M; Grant, A L; Allen, K G; Watkins, B A

    1999-07-01

    A study was designed to examine the effects of dietary conjugated linoleic acid (CLA) on serum concentrations of insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBP) and the relationship of these factors to bone metabolism. Weanling male rats were fed AIN-93G diet containing 70 g/kg of added fat for 42 days. Treatments included 0 g/kg or 10 g/kg of CLA and soybean oil (SBO) or menhaden oil + safflower oil (MSO) following a 2 x 2 factorial design. Serum IGFBP was influenced by dietary polyunsaturated fatty acid (PUFA) type ((n-6) and (n-3)) and CLA (p = 0.01 for 38-43 kDa bands corresponding to IGFBP-3). CLA increased IGFBP level in rats fed SBO (p = 0.05) but reduced it in those fed MSO (p = 0.01). Rats fed MSO had the highest serum IGFBP-3 level. Both (n-3) fatty acids and CLA lowered ex vivo prostaglandin E2 production in bone organ culture. In tibia, rats given CLA had reduced mineral apposition rate (3.69 vs. 2.79 microm/day) and bone formation rate (BFR) (0.96 vs. 0.65 microm3/microm2/day); however, the BFR tended to be higher with MSO. Dietary lipid treatments did not affect serum intact osteocalcin or bone mineral content. These results showed that dietary PUFA type and CLA modulate local factors that regulate bone metabolism. PMID:10404015

  17. Formaldehyde inhalation reduces respiratory mechanics in a rat model with allergic lung inflammation by altering the nitric oxide/cyclooxygenase-derived products relationship.

    PubMed

    Lino-dos-Santos-Franco, Adriana; Gimenes-Júnior, João Antonio; Ligeiro-de-Oliveira, Ana Paula; Breithaupt-Faloppa, Ana Cristina; Acceturi, Beatriz Golegã; Vitoretti, Luana Beatriz; Machado, Isabel Daufenback; Oliveira-Filho, Ricardo Martins; Farsky, Sandra Helena Poliselli; Moriya, Henrique Takachi; Tavares-de-Lima, Wothan

    2013-09-01

    Bronchial hyperresponsiveness is a hallmark of asthma and many factors modulate bronchoconstriction episodes. A potential correlation of formaldehyde (FA) inhalation and asthma has been observed; however, the exact role of FA remains controversial. We investigated the effects of FA inhalation on Ovalbumin (OVA) sensitisation using a parameter of respiratory mechanics. The involvement of nitric oxide (NO) and cyclooxygenase-derived products were also evaluated. The rats were submitted, or not, to FA inhalation (1%, 90 min/day, 3 days) and were OVA-sensitised and challenged 14 days later. Our data showed that previous FA exposure in allergic rats reduced bronchial responsiveness, respiratory resistance (Rrs) and elastance (Ers) to methacholine. FA exposure in allergic rats also increased the iNOS gene expression and reduced COX-1. L-NAME treatment exacerbated the bronchial hyporesponsiveness and did not modify the Ers and Rrs, while Indomethacin partially reversed all of the parameters studied. The L-NAME and Indomethacin treatments reduced leukotriene B? levels while they increased thromboxane B? and prostaglandin E?. In conclusion, FA exposure prior to OVA sensitisation reduces the respiratory mechanics and the interaction of NO and PGE? may be representing a compensatory mechanism in order to protect the lung from bronchoconstriction effects. PMID:23871789

  18. Reduced activity of SKCa and Na-K ATPase underlies the accelerated impairment of EDH-type relaxations in mesenteric arteries of aging spontaneously hypertensive rats

    PubMed Central

    Kong, Billy W C; Man, Ricky Y K; Gao, Yuansheng; Vanhoutte, Paul M; Leung, Susan W S

    2015-01-01

    Aging is accompanied by endothelial dysfunction due to reduced bioavailability of nitric oxide (NO) and/or reduced endothelium-dependent hyperpolarizations (EDH). This study examines the hypothesis that hypertension aggravates the impairment of EDH-type relaxation due to aging. EDH-type relaxations were studied in superior mesenteric arteries isolated from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats of 12, 36, 60, and 72 weeks of age. EDH-type relaxations in WKY were reduced with aging, and this was associated with an impairment of the function of small-conductance calcium-activated potassium channels (SKCa) and sodium-potassium ATPase (Na-K ATPase). EDH-type relaxation in SHR was smaller than that in WKY arteries, and further reduction occurred with aging. Pharmacological experiments suggested a reduced involvement of SKCa and Na-K ATPase and activation of adenosine monophosphate-activated protein kinase and silent information regulator T1 (sirtuin-1; SIRT1) in mesenteric arteries of 12-week-old SHR. These pharmacological findings suggest that in superior mesenteric arteries of the rat, the reduction in EDH-type relaxation occurs with aging and that such a reduction is exacerbated in hypertension. The latter exacerbation appears to involve proteins associated with the process of cellular senescence and is related to impaired function of SKCa and Na-K ATPase, a phenomenon that is also observed in mesenteric arteries of older normotensive rats. PMID:26171229

  19. Soluble polysaccharide and biomass of red microalga Porphyridium sp. alter intestinal morphology and reduce serum cholesterol in rats.

    PubMed

    Dvir, I; Chayoth, R; Sod-Moriah, U; Shany, S; Nyska, A; Stark, A H; Madar, Z; Arad, S M

    2000-10-01

    The present study investigated the effects of the red microalga Porphyridium sp. on gastrointestinal physiology and lipid metabolism in male Sprague-Dawley rats. Diets containing dietary fibre from pelleted red microalgal cells (biomass) or their sulfated polysaccharide, pectin or cellulose (control) were fed to rats for a period of 30 d. All three fibre-supplemented diets increased the length of both the small intestine and colon, with a significantly greater effect in rats fed the algal polysaccharide. The polysaccharide also increased mucosa and muscularis cross-sectional area of the jejunum, and caused hypertrophy in the muscularis layer. The algal biomass significantly lowered gastrointestinal transit time by 44% in comparison with the control rats. Serum and mucosal cholecystokinin levels were lower in rats on the pectin and polysaccharide diets, while cholecystokinin levels in rats fed algal biomass were not different from those in the control animals. In comparison with the control diet, all the experimental diets significantly lowered serum cholesterol levels (22-29%). Feeding of non-fermentable algal polysaccharide or biomass significantly increased faecal weight and bile acid excretion compared with pectin-fed or control rats. The algal polysaccharide and biomass were thus shown to be potent hypocholesterolaemic agents active at low concentrations in the diet. Both metabolic and morphological changes were observed following consumption of algae, suggesting several possible mechanisms by which the alga affects lipid metabolism. The results presented in the present study encourage the use of red microalga as a functional food. PMID:11103217

  20. Reduced Motivation in the BACHD Rat Model of Huntington Disease Is Dependent on the Choice of Food Deprivation Strategy

    PubMed Central

    Riess, Olaf; Nguyen, Huu Phuc

    2014-01-01

    Huntington disease (HD) is an inherited neurodegenerative disease characterized by motor, cognitive, psychiatric and metabolic symptoms. Animal models of HD show phenotypes that can be divided into similar categories, with the metabolic phenotype of certain models being characterized by obesity. Although interesting in terms of modeling metabolic symptoms of HD, the obesity phenotype can be problematic as it might confound the results of certain behavioral tests. This concerns the assessment of cognitive function in particular, as tests for such phenotypes are often based on food depriving the animals and having them perform tasks for food rewards. The BACHD rat is a recently established animal model of HD, and in order to ensure that behavioral characterization of these rats is done in a reliable way, a basic understanding of their physiology is needed. Here, we show that BACHD rats are obese and suffer from discrete developmental deficits. When assessing the motivation to lever push for a food reward, BACHD rats were found to be less motivated than wild type rats, although this phenotype was dependent on the food deprivation strategy. Specifically, the phenotype was present when rats of both genotypes were deprived to 85% of their respective free-feeding body weight, but not when deprivation levels were adjusted in order to match the rats' apparent hunger levels. The study emphasizes the importance of considering metabolic abnormalities as a confounding factor when performing behavioral characterization of HD animal models. PMID:25144554

  1. Chronic high fat feeding increases anxiety-like behaviour and reduces transcript abundance of glucocorticoid signalling genes in the hippocampus of female rats.

    PubMed

    Sivanathan, Shathveekan; Thavartnam, Kabriya; Arif, Shahneen; Elegino, Trisha; McGowan, Patrick O

    2015-06-01

    The consumption of diets high in saturated fats and obesity have been associated with impaired physical and mental health. Previous studies indicate that chronic high fat diet consumption leads to systemic inflammation in humans and non-human animal models. Studies in non-human animals suggest that altered physiological responses to stress are also a consequence of high fat diet consumption. Glucocorticoid signalling mechanisms may link immune and stress-related pathways in the brain, and were shown to be significantly altered in the brains of female rat offspring of mothers exposed to chronic high fat diet during pregnancy and lactation. For adult females, the consequence of chronic high fat diet consumption on these signalling pathways and their relationship to stress-related behaviour is not known. In this study, we examined the effects of chronic consumption of a high fat diet compared to a low fat control diet among adult female Long Evans rats. We found significant differences in weight gain, caloric intake, anxiety-related behaviours, and glucocorticoid-related gene expression over a 10-week exposure period. As expected, rats in the high fat diet group gained the most weight and consumed the greatest number of calories. Rats in the high fat diet group showed significantly greater levels of anxiety-related behaviour in the Light Dark and Open Field tasks compared to rats in the low fat diet group. Rats consuming high fat diet also exhibited reduced transcript abundance in the hippocampus of stress-related mineralocorticoid receptor and glucocorticoid receptor genes, as well as nuclear factor kappa beta gene expression, implicated in inflammatory processes. Together, these data indicate that chronic high fat diet consumption may increase anxiety-like behaviour at least in part via alterations in glucocorticoid signalling mechanisms in limbic brain regions. PMID:25721737

  2. Selenium and L-carnitine reduce oxidative stress in the heart of rat induced by 2.45-GHz radiation from wireless devices.

    PubMed

    Türker, Yasin; Naz?ro?lu, Mustafa; Gümral, Nurhan; Celik, Omer; Sayg?n, Mustafa; Cömlekçi, Selçuk; Flores-Arce, Manuel

    2011-12-01

    The aim of this study was to investigate the possible protective role of selenium and L-carnitine on oxidative stress induced by 2.45-GHz radiation in heart of rat. For this purpose, 30 male Wistar Albino rats were equally divided into five groups namely controls, sham controls, radiation-exposed rats, radiation-exposed rats treated with intraperitoneal injections of sodium selenite at a dose of 1.5 mg/kg/day, and radiation-exposed rats treated with intraperitoneal injections of L-carnitine at a dose of 1.5 mg/kg/day. Except for the controls and sham controls, the animals were exposed to 2.45-GHz radiation during 60 min/day for 28 days. The lipid peroxidation (LP) levels were higher in the radiation-exposed groups than in the control and sham control groups. The lipid peroxidation level in the irradiated animals treated with selenium and L-carnitine was lower than in those that were only exposed to 2.45-GHz radiation. The concentrations of vitamins A, C, and E were lower in the irradiated-only group relative to control and sham control groups, but their concentrations were increased in the groups treated with selenium- and L-carnitine. The activity of glutathione peroxidase was higher in the selenium-treated group than in the animals that were irradiated but received no treatment. The erythrocyte-reduced glutathione and ?-carotene concentrations did not change in any of the groups. In conclusion, 2.45-GHz electromagnetic radiation caused oxidative stress in the heart of rats. There is an apparent protective effect of selenium and L-carnitine by inhibition of free radical formation and support of the antioxidant redox system. PMID:21360060

  3. Radiation cataractogenesis induced by neutron or gamma irradiation in the rat lens is reduced by vitamin E

    SciTech Connect

    Ross, W.M.; Creighton, M.O.; Trevithick, J.R. )

    1990-09-01

    Although cataract of the eye lens is a known late effect of ionizing radiation exposure, most of the experimental work to date has concentrated on single, acute high doses or multiple, fractionated, chronic exposures. Many papers have dealt with biochemical alterations in metabolism and cellular components, with microscopic and electron microscopic lesions to the epithelial and cortical layers, and with clinical cataract formation. However, the minimum cataractogenic dose for rats has for many years been considered to be about 2 Gy for a single, acute dose of low LET radiation. Our purpose in designing this pilot study was three fold: firstly, to determine whether any physical damage could be detected after low, acute exposure to neutron radiation (10 and 100 cGy); secondly, to compare the relative effectiveness of fast (14 MeV) neutrons with gamma-rays; and thirdly, to investigate the possibility that vitamin E could protect the lenses from radiation damage. The results revealed that morphological damage was already discernible within minutes after exposure to neutrons or gamma-rays, that it became greater after 24 hours, that neutrons were more damaging than gamma-rays, and that vitamin E could effectively reduce the cataractogenic damage induced by ionizing radiation. Control, non-irradiated lenses with or without vitamin E, either in vivo or in vitro, showed no damage. Also, it appeared that in vitro irradiation was more damaging to lenses than in vivo irradiation, so this culture technique may prove to be a sensitive tool for assessing early damage caused by ionizing radiation.

  4. A single dose of PPAR? agonist pioglitazone reduces cortical oxidative damage and microglial reaction following lateral fluid percussion brain injury in rats.

    PubMed

    Pilipovi?, Kristina; Župan, Željko; Dolenec, Petra; Mrši?-Pel?i?, Jasenka; Župan, Gordana

    2015-06-01

    Neuroprotective actions of the peroxisome proliferator-activated receptor-? (PPAR?) agonists have been observed in various animal models of the brain injuries. In this study we examined the effects of a single dose of pioglitazone on oxidative and inflammatory parameters as well as on neurodegeneration and the edema formation in the rat parietal cortex following traumatic brain injury (TBI) induced by the lateral fluid percussion injury (LFPI) method. Pioglitazone was administered in a dose of 1mg/kg at 10min after the brain trauma. The animals of the control group were sham-operated and injected by vehicle. The rats were decapitated 24h after LFPI and their parietal cortices were analyzed by biochemical and histological methods. Cortical edema was evaluated in rats sacrificed 48h following TBI. Brain trauma caused statistically significant oxidative damage of lipids and proteins, an increase of glutathione peroxidase (GSH-Px) activity, the cyclooxygenase-2 (COX-2) overexpression, reactive astrocytosis, the microglia activation, neurodegeneration, and edema, but it did not influence the superoxide dismutase activity and the expressions of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha in the rat parietal cortex. Pioglitazone significantly decreased the cortical lipid and protein oxidative damage, increased the GSH-Px activity and reduced microglial reaction. Although a certain degree of the TBI-induced COX-2 overexpression, neurodegeneration and edema decrease was detected in pioglitazone treated rats, it was not significant. In the injured animals, cortical reactive astrocytosis was unchanged by the tested PPAR? agonist. These findings demonstrate that pioglitazone, administered only in a single dose, early following LFPI, reduced cortical oxidative damage, increased antioxidant defense and had limited anti-inflammatory effect, suggesting the need for further studies of this drug in the treatment of TBI. PMID:25579788

  5. Alagebrium inhibits neointimal hyperplasia and restores distributions of wall shear stress by reducing downstream vascular resistance in obese and diabetic rats.

    PubMed

    Wang, Hongfeng; Weihrauch, Dorothee; Kersten, Judy R; Toth, Jeffrey M; Passerini, Anthony G; Rajamani, Anita; Schrepfer, Sonja; LaDisa, John F

    2015-10-01

    Mechanisms of restenosis in type 2 diabetes mellitus (T2DM) are incompletely elucidated, but advanced glycation end-product (AGE)-induced vascular remodeling likely contributes. We tested the hypothesis that AGE-related collagen cross-linking (ARCC) leads to increased downstream vascular resistance and altered in-stent hemodynamics, thereby promoting neointimal hyperplasia (NH) in T2DM. We proposed that decreasing ARCC with ALT-711 (Alagebrium) would mitigate this response. Abdominal aortic stents were implanted in Zucker lean (ZL), obese (ZO), and diabetic (ZD) rats. Blood flow, vessel diameter, and wall shear stress (WSS) were calculated after 21 days, and NH was quantified. Arterial segments (aorta, carotid, iliac, femoral, and arterioles) were harvested to detect ARCC and protein expression, including transforming growth factor-? (TGF-?) and receptor for AGEs (RAGE). Downstream resistance was elevated (60%), whereas flow and WSS were significantly decreased (44% and 56%) in ZD vs. ZL rats. NH was increased in ZO but not ZD rats. ALT-711 reduced ARCC and resistance (46%) in ZD rats while decreasing NH and producing similar in-stent WSS across groups. No consistent differences in RAGE or TGF-? expression were observed in arterial segments. ALT-711 modified lectin-type oxidized LDL receptor 1 but not RAGE expression by cells on decellularized matrices. In conclusion, ALT-711 decreased ARCC, increased in-stent flow rate, and reduced NH in ZO and ZD rats through RAGE-independent pathways. The study supports an important role for AGE-induced remodeling within and downstream of stent implantation to promote enhanced NH in T2DM. PMID:26254329

  6. Resting Orientations of Dinosaur Scapulae and Forelimbs: A Numerical Analysis, with Implications for Reconstructions and Museum Mounts

    PubMed Central

    Senter, Phil; Robins, James H.

    2015-01-01

    The inclination of the scapular blade and the resting pose of the forelimb in dinosaurs differ among reconstructions and among skeletal mounts. For most dinosaurian taxa, no attempt has previously been made to quantify the correct resting positions of these elements. Here, we used data from skeletons preserved in articulation to quantify the resting orientations of the scapula and forelimb in dinosaurs. Specimens were included in the study only if they were preserved lying on their sides; for each specimen the angle between forelimb bones at a given joint was included in the analysis only if the joint was preserved in articulation. Using correlation analyses of the angles between the long axis of the sacrum, the first dorsal centrum, and the scapular blade in theropods and Eoraptor, we found that vertebral hyperextension does not influence scapular orientation in saurischians. Among examined taxa, the long axis of the scapular blade was found to be most horizontal in bipedal saurischians, most vertical in basal ornithopods, and intermediate in hadrosauroids. We found that in bipedal dinosaurs other than theropods with semilunate carpals, the resting orientation of the elbow is close to a right angle and the resting orientation of the wrist is such that the hand exhibits only slight ulnar deviation from the antebrachium. In theropods with semilunate carpals the elbow and wrist are more flexed at rest, with the elbow at a strongly acute angle and with the wrist approximately at a right angle. The results of our study have important implications for correct orientations of bones in reconstructions and skeletal mounts. Here, we provide recommendations on bone orientations based on our results. PMID:26675035

  7. Di(n)butyl phthalate reduces testicular weight, testosterone and associated gene expression in fetal Harlan Sprague Dawley rats.

    EPA Science Inventory

    Certain phthalate esters (PE) cause reproductive malformations in male rats when exposure occurs during sexual differentiation in utero. Reductions in fetal testosterone levels are causally linked to the induction of these malformations. While reproductive development studies on ...

  8. A mixed polyunsaturated fatty acid diet normalizes hippocampal neurogenesis and reduces anxiety in serotonin transporter knockout rats.

    PubMed

    Schipper, Pieter; Kiliaan, Amanda J; Homberg, Judith R

    2011-08-01

    The aim of this study was to investigate the effects of a mixed dietary intervention on behavioral symptoms in serotonin transporter knockout (5-HTT?/?) rats modeling the human 5-HTT length polymorphic region short-allele. Twenty female 5-HTT?/? and 19 wild-type (5-HTT?/?) rats were fed for 3 months on a mixed polyunsaturated fatty acid (PUFA) diet comprising n-3 PUFAs, B vitamins and phospholipids, or an isocaloric control diet, and a subgroup was subsequently tested in an array of anxiety-related behavioral tests. All brains were harvested and immunostained for doublecortin, a neurogenesis marker. In addition, hippocampal volume was measured. 5-HTT?/? rats on the control diet displayed increased anxiety-related behavioral responses, and impaired fear extinction. These effects were completely offset by the mixed PUFA diet, whereas this diet had no behavioral effect in 5-HTT?/? rats. In parallel, dentate gyrus doublecortin immunoreactivity was increased in 5-HTT?/? rats fed on the control diet, which was reversed by the mixed PUFA diet. Hippocampal volume was unaffected by the mixed PUFA diet in 5-HTT?/? subjects, whereas it increased in 5-HTT?/? rats. We conclude that a mixed n-3 PUFA diet ameliorates anxiety-related symptoms in a genotype-dependent manner, potentially by normalizing neurogenesis. We suggest that such a mixed diet may serve as an attractive adjuvant to treat anxiety in 5-HTT length polymorphic region short-allele carriers. PMID:21606840

  9. Interleukin-1 Receptor Antagonist Reduces Neonatal Lipopolysaccharide-Induced Long-Lasting Neurobehavioral Deficits and Dopaminergic Neuronal Injury in Adult Rats

    PubMed Central

    Pang, Yi; Tien, Lu-Tai; Zhu, Hobart; Shen, Juying; Wright, Camilla F.; Jones, Tembra K.; Mamoon, Samir A.; Bhatt, Abhay J.; Cai, Zhengwei; Fan, Lir-Wan

    2015-01-01

    Our previous study showed that a single lipopolysaccharide (LPS) treatment to neonatal rats could induce a long-lasting neuroinflammatory response and dopaminergic system injury late in life. This is evidenced by a sustained activation of microglia and elevated interleukin-1? (IL-1?) levels, as well as reduced tyrosine hydroxylase (TH) expression in the substantia nigra (SN) of P70 rat brain. The object of the current study was to test whether co-administration of IL-1 receptor antagonist (IL-1ra) protects against LPS-induced neurological dysfunction later in life. LPS (1 mg/kg) with or without IL-1ra (0.1 mg/kg), or sterile saline was injected intracerebrally into postnatal day 5 (P5) Sprague-Dawley male rat pups. Motor behavioral tests were carried out from P7 to P70 with subsequent examination of brain injury. Our results showed that neonatal administration of IL-1ra significantly attenuated LPS-induced motor behavioral deficits, loss of TH immunoreactive neurons, as well as microglia activation in the SN of P70 rats. These data suggest that IL-1? may play a pivotal role in mediating a chronic neuroinflammation status by a single LPS exposure in early postnatal life, and blockading IL-1? might be a novel approach to protect the dopaminergic system against perinatal infection/inflammation exposure. PMID:25898410

  10. Tissue oxygen is reduced in white matter of spontaneously hypertensive-stroke prone rats: a longitudinal study with electron paramagnetic resonance.

    PubMed

    Weaver, John; Jalal, Fakhreya Y; Yang, Yi; Thompson, Jeffrey; Rosenberg, Gary A; Liu, Ke J

    2014-05-01

    Small vessel disease is associated with white-matter (WM) magnetic resonance imaging (MRI) hyperintensities (WMHs) in patients with vascular cognitive impairment (VCI) and subsequent damage to the WM. Although WM is vulnerable to hypoxic-ischemic injury and O? is critical in brain physiology, tissue O? level in the WM has not been measured and explored in vivo. We hypothesized that spontaneously hypertensive stroke-prone rat (SHR/SP) fed a Japanese permissive diet (JPD) and subjected to unilateral carotid artery occlusion (UCAO), a model to study VCI, would lead to reduced tissue oxygen (pO?) in the deep WM. We tested this hypothesis by monitoring WM tissue pO? using in vivo electron paramagnetic resonance (EPR) oximetry in SHR/SP rats over weeks before and after JPD/UCAO. The SHR/SP rats experienced an increase in WM pO? from 9 to 12 weeks with a maximal 32% increase at week 12, followed by a dramatic decrease in WM pO? to near hypoxic conditions during weeks 13 to 16 after JPD/UCAO. The decreased WM pO? was accompanied with WM damage and hemorrhages surrounding microvessels. Our findings suggest that changes in WM pO? may contribute to WM damage in SHR/SP rat model, and that EPR oximetry can monitor brain pO? in the WM of small animals. PMID:24549186

  11. A Phospholipid-Protein Complex from Antarctic Krill Reduced Plasma Homocysteine Levels and Increased Plasma Trimethylamine-N-Oxide (TMAO) and Carnitine Levels in Male Wistar Rats

    PubMed Central

    Bjørndal, Bodil; Ramsvik, Marie S.; Lindquist, Carine; Nordrehaug, Jan E.; Bruheim, Inge; Svardal, Asbjørn; Nygård, Ottar; Berge, Rolf K.

    2015-01-01

    Seafood is assumed to be beneficial for cardiovascular health, mainly based on plasma lipid lowering and anti-inflammatory effects of n-3 polyunsaturated fatty acids. However, other plasma risk factors linked to cardiovascular disease are less studied. This study aimed to penetrate the effect of a phospholipid-protein complex (PPC) from Antarctic krill on one-carbon metabolism and production of trimethylamine-N-oxide (TMAO) in rats. Male Wistar rats were fed isoenergetic control, 6%, or 11% PPC diets for four weeks. Rats fed PPC had reduced total homocysteine plasma level and increased levels of choline, dimethylglycine and cysteine, whereas the plasma level of methionine was unchanged compared to control. PPC feeding increased the plasma level of TMAO, carnitine, its precursors trimethyllysine and ?-butyrobetaine. There was a close correlation between plasma TMAO and carnitine, trimethyllysine, and ?-butyrobetaine, but not between TMAO and choline. The present data suggest that PPC has a homocysteine lowering effect and is associated with altered plasma concentrations of metabolites related to one-carbon metabolism and B-vitamin status in rats. Moreover, the present study reveals a non-obligatory role of gut microbiota in the increased plasma TMAO level as it can be explained by the PPC’s content of TMAO. The increased level of carnitine and carnitine precursors is interpreted to reflect increased carnitine biosynthesis. PMID:26371012

  12. Reduced silent information regulator 1 signaling exacerbates myocardial ischemia-reperfusion injury in type 2 diabetic rats and the protective effect of melatonin.

    PubMed

    Yu, Liming; Liang, Hongliang; Dong, Xiaochao; Zhao, Guolong; Jin, Zhenxiao; Zhai, Mengen; Yang, Yang; Chen, Wensheng; Liu, Jincheng; Yi, Wei; Yang, Jian; Yi, Dinghua; Duan, Weixun; Yu, Shiqiang

    2015-10-01

    Diabetes mellitus (DM) increases myocardial oxidative stress and endoplasmic reticulum (ER) stress. Melatonin confers cardioprotective effect by suppressing oxidative damage. However, the effect and mechanism of melatonin on myocardial ischemia-reperfusion (MI/R) injury in type 2 diabetic state are still unknown. In this study, we developed high-fat diet-fed streptozotocin (HFD-STZ) rat, a well-known type 2 diabetic model, to evaluate the effect of melatonin on MI/R injury with a focus on silent information regulator 1 (SIRT1) signaling, oxidative stress, and PERK/eIF2?/ATF4-mediated ER stress. HFD-STZ treated rats were exposed to melatonin treatment in the presence or the absence of sirtinol (a SIRT1 inhibitor) and subjected to MI/R surgery. Compared with nondiabetic animals, type 2 diabetic rats exhibited significantly decreased myocardial SIRT1 signaling, increased apoptosis, enhanced oxidative stress, and ER stress. Additionally, further reduced SIRT1 signaling, aggravated oxidative damage, and ER stress were found in diabetic animals subjected to MI/R surgery. Melatonin markedly reduced MI/R injury by improving cardiac functional recovery and decreasing myocardial apoptosis in type 2 diabetic animals. Melatonin treatment up-regulated SIRT1 expression, reduced oxidative damage, and suppressed PERK/eIF2?/ATF4 signaling. However, these effects were all attenuated by SIRT1 inhibition. Melatonin also protected high glucose/high fat cultured H9C2 cardiomyocytes against simulated ischemia-reperfusion injury-induced ER stress by activating SIRT1 signaling while SIRT1 siRNA blunted this action. Taken together, our study demonstrates that reduced cardiac SIRT1 signaling in type 2 diabetic state aggravates MI/R injury. Melatonin ameliorates reperfusion-induced oxidative stress and ER stress via activation of SIRT1 signaling, thus reducing MI/R damage and improving cardiac function. PMID:26327197

  13. Vitamin B complex attenuated heat hyperalgesia following infraorbital nerve constriction in rats and reduced capsaicin in vivo and in vitro effects.

    PubMed

    Kopruszinski, Caroline M; Reis, Renata C; Bressan, Elisangela; Reeh, Peter W; Chichorro, Juliana G

    2015-09-01

    Vitamins of the B complex attenuate some neuropathic pain sensory aspects in various animal models and in patients, but the mechanisms underlying their effects remain to be elucidated. Herein it was investigated if the treatment with a vitamin B complex (VBC) reduces heat hyperalgesia in rats submitted to infraorbital nerve constriction and the possibility that TRPV1 receptors represent a target for B vitamins. In the present study, the VBC refers to a combination of vitamins B1, B6 and B12 at low- (18, 18 and 1.8mg/kg, respectively) or high- (180, 180 and 18mg/kg, respectively) doses. Acute treatment of rats with either the low- or the high-doses combination reduced heat hyperalgesia after nerve injury, but the high-doses combination resulted in a long-lasting effect. Repeated treatment with the low-dose combination reduced heat hyperalgesia on day four after nerve injury and showed a synergist effect with a single injection of carbamazepine (3 or 10mg/kg), which per se failed to modify the heat threshold. In naïve rats, acute treatment with the high-dose of VBC or B1 and B12 vitamins independently reduced heat hyperalgesia evoked by capsaicin (3µg into the upper lip). Moreover, the VBC, as well as, each one of the B vitamins independently reduced the capsaicin-induced calcium responses in HEK 293 cells transiently transfected with the human TRPV1 channels. Altogether, these results indicate that B vitamins can be useful to control heat hyperalgesia associated with trigeminal neuropathic pain and that modulation of TRPV1 receptors may contribute to their anti-hyperalgesic effects. PMID:26048309

  14. Modulation by Cytochrome P450-4A ?-Hydroxylase Enzymes of Adrenergic Vasoconstriction and Response to Reduced PO2 in Mesenteric Resistance Arteries of Dahl Salt-Sensitive Rats

    PubMed Central

    Raffai, Gábor; Wang, Jingli; Roman, Richard J.; Anjaiah, Siddam; Weinberg, Brian; Falck, John R.; Lombard, Julian H.

    2010-01-01

    Objective This study evaluated the contribution of the 20-HETE/cytochrome P450-4A ?-hydroxylase (CYP4A) system to the early development of salt-induced vascular changes in Dahl salt-sensitive (SS) rats. Methods CYP4A expression and 20-HETE production were evaluated and responses to norepinephrine, endothelin, and reduced PO2 were determined by video microscopy in isolated mesenteric resistance arteries from SS rats fed high salt (HS; 4% NaCl) diet for 3 days vs. low salt (LS; 0.4% NaCl) controls. Results CYP4A enzyme inhibition with dibromododecenyl methylsulfimide (DDMS) selectively reduced norepinephrine sensitivity and restored impaired vasodilation in response to reduced PO2 in SS rats fed HS diet. In the presence of DDMS, vasodilatation to reduced PO2 was eliminated by indomethacin and unaffected by L-NAME in rats fed LS diet, and eliminated by L-NAME and unaffected by indomethacin in rats fed HS diet. The 20-HETE agonist WIT003 restored norepinephrine sensitivity in DDMS-treated arteries of HS fed rats. HS diet increased vascular 20-HETE production and CYP4A protein levels by ~24% and ~31% respectively, although these differences were not significant. Conclusions These findings support the hypothesis that the 20-HETE/CYP4A system modulates vessel responses to norepinephrine and vascular relaxation to reduced PO2 in mesenteric resistance arteries of SS rats fed HS diet. PMID:21040118

  15. The supplementation of Korean mistletoe water extracts reduces hot flushes, dyslipidemia, hepatic steatosis, and muscle loss in ovariectomized rats.

    PubMed

    Kim, Min Jung; Park, Jong-Heum; Kwon, Dae Young; Yang, Hye Jeong; Kim, Da Sol; Kang, Suna; Shin, Bae Keun; Moon, Na Rang; Song, Beom-Seok; Kim, Jae-Hun; Park, Sunmin

    2015-04-01

    Since Korean mistletoe (Viscum album) has been used for alleviating metabolic diseases, it may also prevent the impairment of energy, glucose, lipid, and bone metabolisms in an estrogen-deficient animal model. We determined that long-term consumption of Korean mistletoe water extract (KME) can alleviate menopausal symptoms such as hot flush, increased abdominal fat mass, dyslipidemia, hyperglycemia, and decreased bone mineral density in ovariectomized (OVX) rats fed a high-fat diet, and explored the mechanisms of the effects. OVX rats were divided into four groups and fed high-fat diets supplemented with either 0.6% dextrin (control), 0.2% lyophilized KME + 0.4% dextrin (KME-L), or 0.6% lyophilized KME (KME-H). Sham rats were fed with the high-fat diets with 0.6% dextrin as a normal-control without estrogen deficiency. After eight weeks, OVX rats exhibited impaired energy, glucose and lipid metabolism, and decreased uterine and bone masses. KME-L did not alleviate energy dysfunction. However, KME-H lowered serum levels of total-, LDL-cholesterol, and triglycerides and elevated serum HDL-cholesterol levels in OVX rats with dyslipidemia, to similar levels as normal-control rats. Furthermore, KME-H improved HOMA-IR, an indicator of insulin resistance, in OVX rats. Surprisingly, KME-H fed rats had greater lean mass in the abdomen and leg without differences in fat mass but neither dosage of KME altered bone mineral density in the lumbar spine and femur. The increased lean mass was related to greater phosphorylation of mTOR and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) in the quadriceps muscles. Hepatic triglyceride contents were lowered with KME-H in OVX rats by increasing carnitine palmitoyltransferase-1 (CPT-1) expression and decreasing fatty acid synthase (FAS) and sterol regulatory element-binding protein-1c (SREBP-1c) expression. In conclusion, KME may be useful for preventing some menopausal symptoms such as hot flushes, dyslipidemia, hepatic steatosis, and loss of muscle mass in post-menopausal women. PMID:25258426

  16. Is salamander limb regeneration really perfect? Anatomical and morphogenetic analysis of forelimb muscle regeneration in GFP-transgenic axolotls as a basis for regenerative, developmental, and evolutionary studies.

    PubMed

    Diogo, R; Nacu, E; Tanaka, E M

    2014-06-01

    The axolotl Ambystoma mexicanum is one of the most commonly used model organisms in developmental and regenerative studies because it can reconstitute what is believed to be a completely normal anatomical and functional forelimb/hindlimb after amputation. However, to date it has not been confirmed whether each regenerated forelimb muscle is really a "perfect" copy of the original muscle. This study describes the regeneration of the arm, forearm, hand, and some pectoral muscles (e.g., coracoradialis) in transgenic axolotls that express green fluorescent protein (GFP) in muscle fibers. The observations found that: (1) there were muscle anomalies in 43% of the regenerated forelimbs; (2) however, on average in each regenerated forelimb there are anomalies in only 2.5% of the total number of muscles examined, and there were no significant differences observed in the specific insertion and origin of the other muscles analyzed; (3) one of the most notable and common anomalies (seen in 35% of the regenerated forelimbs) was the presence of a fleshy coracoradialis at the level of the arm; this is a particularly outstanding configuration because in axolotls and in urodeles in general this muscle only has a thin tendon at the level of the arm, and the additional fleshy belly in the regenerated arms is strikingly similar to the fleshy biceps brachii of amniotes, suggesting a remarkable parallel between a regeneration defect and a major phenotypic change that occurred during tetrapod limb evolution; (4) during forelimb muscle regeneration there was a clear proximo-distal and radio-ulnar morphogenetic gradient, as seen in normal development, but also a ventro-dorsal gradient in the order of regeneration, which was not previously described in the literature. These results have broader implications for regenerative, evolutionary, developmental and morphogenetic studies. PMID:24692358

  17. Neural Precursor Cell Transplantation Enhances Functional Recovery and Reduces Astrogliosis in Bilateral Compressive/Contusive Cervical Spinal Cord Injury

    PubMed Central

    Wilcox, Jared T.; Satkunendrarajah, Kajana; Zuccato, Jeffrey A.; Nassiri, Farshad

    2014-01-01

    Spinal cord injury has a significant societal and personal impact. Although the majority of injuries involve the cervical spinal cord, few studies of cell transplantation have used clinically relevant models of cervical spinal cord injury, limiting translation into clinical trials. Given this knowledge gap, we sought to examine the effects of neural stem/precursor cell (NPC) transplants in a rodent model of bilateral cervical contusion-compression spinal cord injury. Bilateral C6-level clip contusion-compression injuries were performed in rats, which were then blindly randomized at 2 weeks after injury into groups receiving adult brain-derived NPCs, vehicle, or sham operation. Long-term survival of NPCs was evident at 10 weeks after transplant. Cell grafts were localized rostrocaudally surrounding the lesion, throughout white and gray matter. Graft-derived cells were found within regions of gliotic scar and motor tracts and deposited myelin around endogenous axons. The majority of NPCs developed an oligodendroglial phenotype with greater neuronal profiles in rostral grafts. Following NPC transplantation, white matter was significantly increased compared with control. Astrogliosis and glial scar deposition, measured by GFAP-positive and chondroitin sulfate proteoglycan-positive volume, was significantly reduced. Forelimb grip strength, fine motor control during locomotion, and axonal conduction (by in vivo electrophysiology) was greater in cell-treated animals compared with vehicle controls. Transplantation of NPCs in the bilaterally injured cervical spinal cord results in significantly improved spinal cord tissue and forelimb function, warranting further study in preclinical cervical models to improve this treatment paradigm for clinical translation. PMID:25107585

  18. Early-life exposure to noise reduces mPFC astrocyte numbers and T-maze alternation/discrimination task performance in adult male rats.

    PubMed

    Ruvalcaba-Delgadillo, Yaveth; Luquín, Sonia; Ramos-Zúñiga, Rodrigo; Feria-Velasco, Alfredo; González-Castañeda, Rocío Elizabeth; Pérez-Vega, Maria Isabel; Jáuregui-Huerta, Fernando; García-Estrada, Joaquín

    2015-01-01

    In this experiment, we evaluated the long-term effects of noise by assessing both astrocyte changes in medial prefrontal cortex (mPFC) and mPFC-related alternation/discrimination tasks. Twenty-one-day-old male rats were exposed during a period of 15 days to a standardized rats' audiogram-fitted adaptation of a human noisy environment. We measured serum corticosterone (CORT) levels at the end of the exposure and periodically registered body weight gain. In order to evaluate the long-term effects of this exposure, we assessed the rats' performance on the T-maze apparatus 3 months later. Astrocyte numbers and proliferative changes in mPFC were also evaluated at this stage. We found that environmental noise (EN) exposure significantly increased serum CORT levels and negatively affected the body weight gain curve. Accordingly, enduring effects of noise were demonstrated on mPFC. The ability to solve alternation/discrimination tasks was reduced, as well as the number of astroglial cells. We also found reduced cytogenesis among the mPFC areas evaluated. Our results support the idea that early exposure to environmental stressors may have long-lasting consequences affecting complex cognitive processes. These results also suggest that glial changes may become an important element behind the cognitive and morphological alterations accompanying the PFC changes seen in some stress-related pathologies. PMID:26168952

  19. Emu Oil Reduces Small Intestinal Inflammation in the Absence of Clinical Improvement in a Rat Model of Indomethacin-Induced Enteropathy

    PubMed Central

    Abimosleh, Suzanne M.; Tran, Cuong D.; Howarth, Gordon S.

    2013-01-01

    Nonsteroidal-anti-inflammatory-drug (NSAID) enteropathy is characterized by small intestinal damage and ulceration. Emu Oil (EO) has previously been reported to reduce intestinal inflammation. Aim. We investigated EO for its potential to attenuate NSAID-enteropathy in rats. Methods. Male Sprague Dawley rats (n = 10/group) were gavaged with Water, Olive Oil (OO), or EO (0.5?mL; days 0–12) and with 0.5?mL Water or the NSAID, Indomethacin (8?mg/kg; days 5–12) daily. Disease activity index (DAI), 13C-sucrose breath test (SBT), organ weights, intestinal damage severity (IDS), and myeloperoxidase (MPO) activity were assessed. P < 0.05 was considered significant. Results. In Indomethacin-treated rats, DAI was elevated (days 10–12) and SBT values (56%) and thymus weight (55%) were decreased, relative to normal controls. Indomethacin increased duodenum (68%), colon (24%), SI (48%), caecum (48%), liver (51%) and spleen (88%) weights, IDS scores, and MPO levels (jejunum: 195%, ileum: 104%) compared to normal controls. Jejunal MPO levels were decreased (64%) by both EO and OO, although only EO decreased ileal MPO (50%), compared to Indomethacin controls. Conclusions. EO reduced acute intestinal inflammation, whereas other parameters of Indomethacin-induced intestinal injury were not affected significantly. Increased EO dose and/or frequency of administration could potentially improve clinical efficacy. PMID:23573127

  20. Reducing effect of a combination of Phaseolus vulgaris and Cynara scolymus extracts on operant self-administration of a chocolate-flavoured beverage in rats.

    PubMed

    Zaru, Alessandro; Maccioni, Paola; Riva, Antonella; Morazzoni, Paolo; Bombardelli, Ezio; Gessa, Gian Luigi; Carai, Mauro A M; Colombo, Giancarlo

    2013-06-01

    Treatment with a rational combination of standardized extracts of Phaseolus vulgaris and Cynara scolymus reduced food intake and glycemia in rats. The present study was designed to assess the effect of this extract combination and of each single extract in an experimental model of food craving, made up of rats displaying exaggerated seeking and taking behaviors for a chocolate-flavoured beverage. After training to lever-respond for the chocolate-flavoured beverage, rats were treated with vehicle, Phaseolus vulgaris extract alone (200 mg/kg), Cynara scolymus extract alone (400 mg/kg), or combination of Phaseolus vulgaris (200 mg/kg) and Cynara scolymus (400 mg/kg) extracts. The Phaseolus vulgaris extract and the extract combination exerted similar and substantial decrements in the number of lever-responses and amount of self-administered chocolate-flavoured beverage; conversely, the Cynara scolymus extract was totally ineffective. These results suggest that (i) the capacity of the extract combination to reduce the self-administration of the chocolate-flavoured beverage entirely relied on the Phaseolus vulgaris extract, (ii) Phaseolus vulgaris extract may interfere with the mechanisms regulating food-related addictive-like behaviors, and (iii) combinations of Phaseolus vulgaris and Cynara scolymus extracts may possess a broad spectrum of activities, from treatment of metabolic syndrome to overweight, obesity, and possibly food-related addictive disorders. PMID:22899449

  1. Autoradiographic localization of a non-reducible somatostatin analog (/sup 125/I-CGP 23996) binding sites in the rat brain: comparison with membrane binding

    SciTech Connect

    Epelbaum, J.; Dussaillant, M.; Enjalbert, A.; Kordon, C.; Rostene, W.

    1985-07-01

    The regional distribution of somatostatin binding sites in the rat brain was determined by quantitative autoradiography, using /sup 125/I-CGP 23996, a non-reducible somatostatin analog. In preliminary experiments, kinetic properties of /sup 125/I-CGP 23996 binding to rat brain membranes and slide mounted frozen brain sections were compared and found similar. In addition, distribution of /sup 125/I-CGP 23996 and /sup 125/I-N-Tyr-SRIF14 binding sites on membrane prepared from 10 different rat brain structures were closely correlated (r = 0.91, 2 p less than 0.01), indicating that the non-reducible analog recognizes the same binding site as the Tyr-extended native peptide. Highest levels of /sup 125/I-CGP 23996 binding sites were found in anterior temporal, frontal and cingular cortex as well as hippocampus. Moderate levels were found in the remaining part of the limbic system including amygdala, olfactory tubercles and bed nucleus of the stria terminalis. In the brain stem, nuclei involved in the auditory system such as the ventral cochlear nucleus and the superior olive nucleus, contained high levels of /sup 125/I-CGP 23996 binding sites. The distribution of /sup 125/I-CGP 23996 binding sites roughly correlated with that of the endogenous peptide in most structures, except in the mediobasal hypothalamus.

  2. Forelimb muscle function in pig-nosed turtles, Carettochelys insculpta: testing neuromotor conservation between rowing and flapping in swimming turtles

    PubMed Central

    Rivera, Angela R. V.; Blob, Richard W.

    2013-01-01

    Changes in muscle activation patterns can lead to new locomotor modes; however, neuromotor conservation—the evolution of new forms of locomotion through changes in structure without concurrent changes to underlying motor patterns—has been documented across diverse styles of locomotion. Animals that swim using appendages do so via rowing (anteroposterior oscilations) or flapping (dorsoventral oscilations). Yet few studies have compared motor patterns between these swimming modes. In swimming turtles, propulsion is generated exclusively by limbs. Kinematically, turtles swim using multiple styles of rowing (freshwater species), flapping (sea turtles) and a unique hybrid style with superficial similarity to flapping by sea turtles and characterized by increased dorsoventral motions of synchronously oscillated forelimbs that have been modified into flippers (Carettochelys insculpta). We compared forelimb motor patterns in four species of turtle (two rowers, Apalone ferox and Trachemys scripta; one flapper, Caretta caretta; and Carettochelys) and found that, despite kinematic differences, motor patterns were generally similar among species with a few notable exceptions: specifically, presence of variable bursts for pectoralis and triceps in Trachemys (though timing of the non-variable pectoralis burst was similar), and the timing of deltoideus activity in Carettochelys and Caretta compared with other taxa. The similarities in motor patterns we find for several muscles provide partial support for neuromotor conservation among turtles using diverse locomotor styles, but the differences implicate deltoideus as a prime contributor to flapping limb motions. PMID:23966596

  3. Extract of Rhizoma Polygonum cuspidatum reduces early renal podocyte injury in streptozotocin-induced diabetic rats and its active compound emodin inhibits methylglyoxal-mediated glycation of proteins

    PubMed Central

    SOHN, EUNJIN; KIM, JUNGHYUN; KIM, CHAN SIK; JO, KYUHYUNG; KIM, JIN SOOK

    2015-01-01

    Podocyte injury contributes to renal damage and, eventually, to the occurrence of proteinuria in diabetic nephropathy. The aim of the present study was to investigate the effect of an ethanol extract from Rhizoma Polygonum cuspidatum (P. cuspidatum) on proteinuria and podocyte injury, and elucidate the underlying mechanism for streptozotocin (STZ)-induced diabetic nephropathy. The protective effects of P. cuspidatum extract (PCE) on renal podocytes in STZ-induced diabetic rats were also investigated. PCE (100 or 350 mg/kg/day) was administered to STZ-induced diabetic rats for 16 weeks, and blood glucose levels, body weight and proteinuria were measured. A double labeling technique with the terminal deoxynucleotidyl transferase dUTP nick end labeling assay was performed and synaptopodin expression was observed. In addition, cleaved caspase-3, methylglyoxal (MGO) and 8-hydroxydeoxyguanosine (8-OHdG) expression levels were measured. STZ-induced diabetic rats developed hyperglycemia and proteinuria. Increased apoptosis of the podocytes and increased cleaved caspase-3, MGO and 8-OHdG expression levels, as well as decreased synaptopodin expression were detected in the glomeruli of STZ-induced diabetic rats. However, treatment with PCE for 16 weeks restored protein levels to normal, and reduced podocyte loss and apoptosis. Levels of caspase-3 and MGO expression, as well as oxidative stress were ameliorated by PCE treatment. In addition, emodin, a biologically active ingredient of PCE, exerted an MGO scavenging effect and inhibited MGO-derived advanced glycation end-product formation. These findings indicate that PCE may be administered to prevent proteinuria and podocyte loss in STZ-induced diabetic rats partly by inhibiting podocyte apoptosis and cleaved caspase-3 expression, and by restoring the balance of oxidative stress and MGO expression. PMID:26299942

  4. Extract of Rhizoma Polygonum cuspidatum reduces early renal podocyte injury in streptozotocin?induced diabetic rats and its active compound emodin inhibits methylglyoxal?mediated glycation of proteins.

    PubMed

    Sohn, Eunjin; Kim, Junghyun; Kim, Chan Sik; Jo, Kyuhyung; Kim, Jin Sook

    2015-10-01

    Podocyte injury contributes to renal damage and, eventually, to the occurrence of proteinuria in diabetic nephropathy. The aim of the present study was to investigate the effect of an ethanol extract from Rhizoma Polygonum cuspidatum (P. cuspidatum) on proteinuria and podocyte injury, and elucidate the underlying mechanism for streptozotocin (STZ)?induced diabetic nephropathy. The protective effects of P. cuspidatum extract (PCE) on renal podocytes in STZ?induced diabetic rats were also investigated. PCE (100 or 350 mg/kg/day) was administered to STZ?induced diabetic rats for 16 weeks, and blood glucose levels, body weight and proteinuria were measured. A double labeling technique with the terminal deoxynucleotidyl transferase dUTP nick end labeling assay was performed and synaptopodin expression was observed. In addition, cleaved caspase?3, methylglyoxal (MGO) and 8?hydroxydeoxyguanosine (8?OHdG) expression levels were measured. STZ?induced diabetic rats developed hyperglycemia and proteinuria. Increased apoptosis of the podocytes and increased cleaved caspase?3, MGO and 8?OHdG expression levels, as well as decreased synaptopodin expression were detected in the glomeruli of STZ?induced diabetic rats. However, treatment with PCE for 16 weeks restored protein levels to normal, and reduced podocyte loss and apoptosis. Levels of caspase?3 and MGO expression, as well as oxidative stress were ameliorated by PCE treatment. In addition, emodin, a biologically active ingredient of PCE, exerted an MGO scavenging effect and inhibited MGO?derived advanced glycation end?product formation. These findings indicate that PCE may be administered to prevent proteinuria and podocyte loss in STZ?induced diabetic rats partly by inhibiting podocyte apoptosis and cleaved caspase?3 expression, and by restoring the balance of oxidative stress and MGO expression. PMID:26299942

  5. Multi-walled carbon nanotubes increase anxiety levels in rats and reduce exploratory activity in the open field test.

    PubMed

    Sayapina, N V; Batalova, T A; Chaika, V V; Kuznetsov, V L; Sergievich, A A; Kolosov, V P; Perel'man, Yu M; Golokhvast, K S

    2015-09-01

    The results of the first study on the effects of multi-walled carbon nanotubes (MWNTs) on the exploratory activity and the emotional state in laboratory rats assessed by the open field test are reported. During three or ten days, rats received 8-10 nm MWNTs added to their food at a dose of 500 mg/kg. It was demonstrated that, in the group of rats which were fed with MWNTs, the integrated anxiety level index began to increase as early as the third day of the experiment; on the tenth day, it appeared to be twice increased. It was also demonstrated that MWNTs decreased the integrated exploratory activity index nearly twofold on the third day and nearly fourfold on the tenth day. PMID:26530062

  6. Increased neuroinflammatory and arachidonic acid cascade markers, and reduced synaptic proteins, in brain of HIV-1 transgenic rats

    PubMed Central

    2011-01-01

    Background Cognitive impairment has been reported in human immune deficiency virus-1- (HIV-1-) infected patients as well as in HIV-1 transgenic (Tg) rats. This impairment has been linked to neuroinflammation, disturbed brain arachidonic acid (AA) metabolism, and synapto-dendritic injury. We recently reported upregulated brain AA metabolism in 7- to 9-month-old HIV-1 Tg rats. We hypothesized that these HIV-1 Tg rats also would show upregulated brain inflammatory and AA cascade markers and a deficit of synaptic proteins. Methods We measured protein and mRNA levels of markers of neuroinflammation and the AA cascade, as well as pro-apoptotic factors and synaptic proteins, in brains from 7- to 9-month-old HIV-1 Tg and control rats. Results Compared with control brain, HIV-1 Tg rat brain showed immunoreactivity to glycoprotein 120 and tat HIV-1 viral proteins, and significantly higher protein and mRNA levels of (1) the inflammatory cytokines interleukin-1? and tumor necrosis factor ?, (2) the activated microglial/macrophage marker CD11b, (3) AA cascade enzymes: AA-selective Ca2+-dependent cytosolic phospholipase A2 (cPLA2)-IVA, secretory sPLA2-IIA, cyclooxygenase (COX)-2, membrane prostaglandin E2 synthase, 5-lipoxygenase (LOX) and 15-LOX, cytochrome p450 epoxygenase, and (4) transcription factor NF-?Bp50 DNA binding activity. HIV-1 Tg rat brain also exhibited signs of cell injury, including significantly decreased levels of brain-derived neurotrophic factor (BDNF) and drebrin, a marker of post-synaptic excitatory dendritic spines. Expression of Ca2+-independent iPLA2-VIA and COX-1 was unchanged. Conclusions HIV-1 Tg rats show elevated brain markers of neuroinflammation and AA metabolism, with a deficit in several synaptic proteins. These changes are associated with viral proteins and may contribute to cognitive impairment. The HIV-1 Tg rat may be a useful model for understanding progression and treatment of cognitive impairment in HIV-1 patients. PMID:21846384

  7. Preconditioning cortical lesions reduce the incidence of peri-infarct depolarizations during focal ischemia in the Spontaneously Hypertensive Rat: interaction with prior anesthesia and the impact of hyperglycemia.

    PubMed

    Zhao, Liang; Nowak, Thaddeus S

    2015-07-01

    The relationship between peri-infarct depolarizations (PIDs) and infarction was investigated in a model of preconditioning by cortical freeze lesions (cryogenic lesions, CL) in the Spontaneously Hypertensive Rat. Small (< 5 mm(3)) lesions produced 24 hours before permanent focal ischemia were protective, without impacting baseline cerebral blood flow (CBF) and metabolism. Prior CL reduced infarct volume, associated with improved penumbral CBF as previously showed for ischemic preconditioning. The brief initial procedure avoided sham effects on infarct volume after subsequent occlusion under brief anesthesia. However, under prolonged isoflurane anesthesia for perfusion monitoring both sham and CL rats showed reduced PID incidence relative to naive animals. This anesthesia effect could be eliminated by using ?-chloralose during perfusion imaging. As an additional methodological concern, blood glucose was frequently elevated at the time of the second surgery, reflecting buprenorphine-induced pica and other undefined mechanisms. Even modest hyperglycemia (>10 mmol/L) reduced PID incidence. In normoglycemic animals CL preconditioning reduced PID number by 50%, demonstrating associated effects on PID incidence, penumbral perfusion, and infarct progression. Hyperglycemia suppressed PIDs without affecting the relationship between CBF and infarction. This suggests that the primary effect of preconditioning is to improve penumbral perfusion, which in turn impacts PID incidence and infarct size. PMID:25757750

  8. The role of nitric oxide synthase in reduced vasocontractile responsiveness induced by prolonged ?1-adrenergic receptor stimulation in rat thoracic aorta

    PubMed Central

    Gürdal, Hakan; Can, Alp; U?ur, Mehmet

    2005-01-01

    Prolonged exposure (6–12?h) of rat aorta to alpha1-adrenergic receptor (?1AR) agonist phenylephrine (Phe) leads to a decrease in ?1AR-mediated vasoconstriction. This reduced responsiveness to ?1AR stimulation was strongly dependent on the intactness of the endothelium. We examined the effect of Phe on nitric oxide synthase (NOS) activity by measuring the conversion of [3H]L-arginine to [3H]L-citrulline in rat aorta or in endothelial cells isolated from rat aorta. Phe stimulation increased NOS activity in control aortas. This response was antagonized by prazosin. However, Phe increased neither the activity of NOS nor intracellular Ca2+ in the isolated endothelial cells from the control aortas, whereas acetylcholine (Ach) was able to stimulate both responses in these cells. This result suggests that Phe stimulates ?1AR on vascular smooth muscle cells and has an indirect influence on endothelial cells to increase NOS activity. In Phe-exposed aortic rings, basal NOS activity was found to have increased compared to vehicle-exposed control rings. Stimulation with Phe or Ach caused a small increase over basal NOS activity in these preparations. Prolonged exposure to Phe also caused an enhancement of Ach-mediated vasorelaxation in rat aorta. Immunoblot and reverse transcription–polymerase chain reaction experiments showed that prolonged exposure of rat aorta to Phe resulted in an increased expression of eNOS, but not iNOS. This increase was antagonized by nonselective antagonist prazosin. Immunohistochemical staining experiments also showed that expression of eNOS increased in endothelial cells after Phe exposure of the aortas. These results, all together, showed that prolonged exposure of rat aorta to ?1AR agonist Phe enhanced the expression of eNOS and basal NOS activity, which probably causes a decreased vasocontractile response to Phe or to other agonists such as 5HT (5-hydroxytryptamine) in rat aorta. This phenomenon can be considered more as a functional antagonism of vasocontractile response to agonists mediated by endothelium than a specific desensitization of ?1AR-mediated signalling in vascular smooth muscle cells. PMID:15753950

  9. Erythropoietin delivered via intra-arterial infusion reduces endoplasmic reticulum stress in brain microvessels of rats following cerebral ischemia and reperfusion.

    PubMed

    Zhao, Haiping; Wang, Rongliang; Wu, Xiaoning; Liang, Jia; Qi, Zhifeng; Liu, Xiangrong; Min, Lianqiu; Ji, Xunming; Luo, Yumin

    2015-03-01

    Local infusion of low dose erythropoietin (EPO) alleviates cerebral ischemia and reperfusion (I/R) injury in rats; however, the underlying molecular mechanisms are still unclear. The present study investigated the effect of low dose EPO treatment on I/R-induced endoplasmic reticulum (ER) stress in brain tissue and isolated microvessels in rodents. Sprague-Dawley rats were subjected to 2 h ischemia/24 h reperfusion by middle cerebral artery (MCA) occlusion, then administered fluorescein isothiocyanate-labeled EPO via MCA infusion (MCAI) or subcutaneous injection (SI) to compare the efficiency of two modes of delivery. Neurobehavioral deficits and infarct volume, and the expression of ER stress-associated proteins and apoptosis in brain tissue or isolated microvessels, as well as the transcriptional activity of 16 factors involved in ER stress and the unfolded protein response in brain tissue was asscessed. A higher EPO level in cerebrospinal fluid and brain tissue was observed in rats treated with EPO by MCAI (800 IU/kg) than by SI (5000 IU/kg). Moreover, neurobehavioral deficits and infarct volume were reduced in rats treated with EPO by MCAI and salubrinal. EPO suppressed the expression of ER stress signals glucose-regulated protein 78, activating transcription factor (ATF) 6?, and CCAAT enhancer-binding protein homologous protein (CHOP), as well as that of the pro-apoptotic protein caspase-3 in brain microvessels, and decreased the number of CHOP-positive, apoptotic neurons. EPO treatment also reduced the transcriptional activities of CHOP, forkhead box protein O1, and ATF4. These results provide evidence that low dose EPO treatment via MCAI provides neuroprotection following acute ischemic stroke by inhibiting the ER stress response. PMID:25626440

  10. Calcium montmorillonite clay reduces AFB1 and FB1 biomarkers in rats exposed to single and co-exposures of aflatoxin and fumonisin

    PubMed Central

    Mitchell, Nicole J.; Xue, Kathy S.; Lin, Shuhan; Marroquin-Cardona, Alicia; Brown, Kristal A.; Elmore, Sarah E.; Tang, Lili; Romoser, Amelia; Gelderblom, Wentzel C. A.; Wang, Jia-Sheng; Phillips, Timothy D.

    2014-01-01

    Aflatoxins (AFs) and fumonisins (FBs) can co-contaminate foodstuffs and have been associated with hepatocellular and esophageal carcinomas in humans at high risk for exposure. One strategy to reduce exposure (and toxicity) from contaminated foodstuffs is the dietary inclusion of a montmorillonite clay (UPSN) that binds AFs and FBs in the GI tract. In this study, the binding capacity of UPSN was evaluated for AFB1, FB1 and a combination thereof in Fischer-344 rats. Rats were pre-treated with different dietary levels of UPSN (0.25 or 2%) for 1 week. Rats were gavaged with a single dose of either 0.125 mg AFB1 or 25 mg FB1/kg b.w. and a combination thereof in the presence and absence of an aqueous solution of UPSN. The kinetics of mycotoxin excretion were monitored by analyzing serum AFB1-albumin, urinary AF (AFM1), and FB1 biomarkers over a period of 72 hr. UPSN decreased AFM1 excretion by 88-97%, indicating highly effective binding. FB1 excretion was reduced, to a lesser extent, ranging between 45 to 85%. When in combination, both AFB1 and FB1 binding occurred, but capacity was decreased by almost half. In the absence of UPSN, the combined AFB1 and FB1 treatment decreased the urinary biomarkers by 67 and 45% respectively, but increased levels of AFB1-albumin, presumably by modulating its cytochrome metabolism. UPSN significantly reduced bioavailability of both AFB1 and FB1 when in combination; suggesting that it can be utilized to reduce levels below their respective thresholds for affecting adverse biological effects. PMID:24193864

  11. Calcium montmorillonite clay reduces AFB1 and FB1 biomarkers in rats exposed to single and co-exposures of aflatoxin and fumonisin.

    PubMed

    Mitchell, Nicole J; Xue, Kathy S; Lin, Shuhan; Marroquin-Cardona, Alicia; Brown, Kristal A; Elmore, Sarah E; Tang, Lili; Romoser, Amelia; Gelderblom, Wentzel C A; Wang, Jia-Sheng; Phillips, Timothy D

    2014-07-01

    Aflatoxins (AFs) and fumonisins (FBs) can co-contaminate foodstuffs and have been associated with hepatocellular and esophageal carcinomas in humans at high risk for exposure. One strategy to reduce exposure (and toxicity) from contaminated foodstuffs is the dietary inclusion of a montmorillonite clay (UPSN) that binds AFs and FBs in the gastrointestinal tract. In this study, the binding capacity of UPSN was evaluated for AFB1, FB1 and a combination thereof in Fischer 344 rats. Rats were pre-treated with different dietary levels of UPSN (0.25% or 2%) for 1 week. Rats were gavaged with a single dose of either 0.125 mg AFB1 or 25 mg FB1 per kg body weight and a combination thereof in the presence and absence of an aqueous solution of UPSN. The kinetics of mycotoxin excretion were monitored by analyzing serum AFB1 -albumin, urinary AF (AFM1) and FB1 biomarkers over a period of 72 h. UPSN decreased AFM1 excretion by 88-97%, indicating highly effective binding. FB1 excretion was reduced, to a lesser extent, ranging from 45% to 85%. When in combination, both AFB1 and FB1 binding occurred, but capacity was decreased by almost half. In the absence of UPSN, the combined AFB1 and FB1 treatment decreased the urinary biomarkers by 67% and 45% respectively, but increased levels of AFB1 -albumin, presumably by modulating its cytochrome metabolism. UPSN significantly reduced bioavailability of both AFB1 and FB1 when in combination; suggesting that it can be utilized to reduce levels below their respective thresholds for affecting adverse biological effects. PMID:24193864

  12. The herbicide linuron reduces testosterone production from the fetal rat testis both in utero and in vitro

    EPA Science Inventory

    In utero exposure to linuron, an urea-based herbicide, results in a pattern of malformations of androgen-dependent tissues in adult male rat offspring resembling that produced by some phthalate esters which are known to decrease fetal testosterone production. This study investiga...

  13. Embelia ribes extract reduces high fat diet and low dose streptozotocin-induced diabetic nephrotoxicity in rats

    PubMed Central

    Chaudhari, Hemantkumar Somabhai; Bhandari, Uma; Khanna, Geetika

    2013-01-01

    Nephropathy associated with type 2 diabetes is the single most common cause of end-stage renal disease. The aim of the present study was to evaluate the preventive effect of ethanolic extract of Embelia ribes fruit (EER) against high fat diet (HFD) and low dose streptozotocin (STZ)-induced diabetic nephrotoxicity in Wistar rats. HFD-fed and low dose STZ (35 mg/kg, i.p)-induced diabetic rats were treated with EER (100 and 200 mg/kg/day) for 21 days while continuing on HFD. Preventive effects of EER were demonstrated by significant reduction (p< 0.01) in body weight gain, fasting blood glucose, blood pressure, serum lactate dehydrogenase (LDH), creatinine, alkaline phosphatase (ALP), total cholesterol and triglyceride levels, while elevation in serum albumin and total protein levels. Insulin sensitizing effects were seen during oral glucose tolerance testing. Further, EER treatment significantly (p< 0.01) decreased the kidney thiobarbituric acid-reactive substance (TBARS) levels, while increasing the superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) levels in diabetic rats. Histological studies of kidney also supported the experimental findings. Taken together, our data suggest that EER attenuates renal injury in type 2 diabetic rats, possibly by improvement in glucose and lipid metabolism, enhancement of insulin sensitivity, blood pressure lowering, and inhibition of lipid peroxidation process.

  14. TREATMENT OF CONTAMINATED SOIL WITH PHOSPHORUS AND MANGANESE OXIDE REDUCES LEAD ADSORPTION BY SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    A study was conducted to determine the extent of adsorption of Pb into young rats that were fed Pb contaminated soil treated with two different sources of P and P plus Mn oxide. Attempts were also made to compare an in vitro, physiologically based extraction procedure test (PBET)...

  15. Safflower yellow reduces lipid peroxidation, neuropathology, tau phosphorylation and ameliorates amyloid ?-induced impairment of learning and memory in rats.

    PubMed

    Ma, Qin; Ruan, Ying-Ying; Xu, Hui; Shi, Xiao-Meng; Wang, Zhi-Xiang; Hu, Yan-Li

    2015-12-01

    Insoluble plaques of amyloid ? proteins (A?) and neurofibrillary tangles of hyperphosphorylated tau are key markers for Alzheimer's disease (AD). Safflower yellow (SY) is one of traditional Chinese medicine extracted from safflower, which is suggested to have therapeutic potential for neurodegenerative disorders. However, whether SY can ameliorate impairment of learning and memory in AD model, and its causal mechanism are still unclear. Here, we applied different doses of SY intragastrically to Wistar rats injected with amyloid ? (1-42) for 1 month. By the Morris water maze test, we found that treatment of SY significantly attenuated amyloid ? (1-42)-induced impairment of memory in rats. Mechanistically, SY treatment increased the level of superoxidedismutase (SOD) and Glutathione peroxidase (GSH-Px), and decreased the level of malondialdehyde (MDA) and acetylcholinesterase (T-CHE) in brain tissues of AD rats. Pathological analysis also showed that SY treatment inhibited the morphological alteration of neurons and tau hyperphosphorylation induced by amyloid ? (1-42)-injection in the cortex and hippocampus. Moreover, SY treatment inhibited CDK-5 and GSK-3 signaling pathways, which are upregulated in AD rats. Our data indicate that safflower yellow can serve as a therapeutic candidate for Alzheimer's disease. PMID:26653563

  16. Nicotine and elevated body temperature reduce the complexity of the genioglossus and diaphragm EMG signals in rats during early maturation

    NASA Astrophysics Data System (ADS)

    Akkurt, David; Akay, Yasemin M.; Akay, Metin

    2009-10-01

    In this paper, we examined the effect of nicotine exposure and increased body temperature on the complexity (dynamics) of the genioglossus muscle (EMGg) and the diaphragm muscle (EMGdia) to explore the effects of nicotine and hyperthermia. Nonlinear dynamical analysis of the EMGdia and EMGg signals was performed using the approximate entropy method on 15 (7 saline- and 8 nicotine-treated) juvenile rats (P25-P35) and 19 (11 saline- and 8 nicotine-treated) young adult rats (P36-P44). The mean complexity values were calculated over the ten consecutive breaths using the approximate entropy method during mild elevated body temperature (38 °C) and severe elevated body temperature (39-40 °C) in two groups. In the first (nicotine) group, rats were treated with single injections of nicotine enough to produce brain levels of nicotine similar to those achieved in human smokers (2.5 (mg kg-1)/day) until the recording day. In the second (control) group, rats were treated with injections of saline, beginning at postnatal 5 days until the recording day. Our results show that warming the rat by 2-3 °C and nicotine exposure significantly decreased the complexity of the EMGdia and EMGg for the juvenile age group. This reduction in the complexity of the EMGdia and EMGg for the nicotine group was much greater than the normal during elevated body temperatures. We speculate that the generalized depressive effects of nicotine exposure and elevated body temperature on the respiratory neural firing rate and the behavior of the central respiratory network could be responsible for the drastic decrease in the complexity of the EMGdia and EMGg signals, the outputs of the respiratory neural network during early maturation.

  17. High-Fat Diet Reduces the Formation of Butyrate, but Increases Succinate, Inflammation, Liver Fat and Cholesterol in Rats, while Dietary Fibre Counteracts These Effects

    PubMed Central

    Jakobsdottir, Greta; Xu, Jie; Molin, Göran; Ahrné, Siv; Nyman, Margareta

    2013-01-01

    Introduction Obesity is linked to type 2 diabetes and risk factors associated to the metabolic syndrome. Consumption of dietary fibres has been shown to have positive metabolic health effects, such as by increasing satiety, lowering blood glucose and cholesterol levels. These effects may be associated with short-chain fatty acids (SCFAs), particularly propionic and butyric acids, formed by microbial degradation of dietary fibres in colon, and by their capacity to reduce low-grade inflammation. Objective To investigate whether dietary fibres, giving rise to different SCFAs, would affect metabolic risk markers in low-fat and high-fat diets using a model with conventional rats for 2, 4 and 6 weeks. Material and Methods Conventional rats were administered low-fat or high-fat diets, for 2, 4 or 6 weeks, supplemented with fermentable dietary fibres, giving rise to different SCFA patterns (pectin – acetic acid; guar gum – propionic acid; or a mixture – butyric acid). At the end of each experimental period, liver fat, cholesterol and triglycerides, serum and caecal SCFAs, plasma cholesterol, and inflammatory cytokines were analysed. The caecal microbiota was analysed after 6 weeks. Results and Discussion Fermentable dietary fibre decreased weight gain, liver fat, cholesterol and triglyceride content, and changed the formation of SCFAs. The high-fat diet primarily reduced formation of SCFAs but, after a longer experimental period, the formation of propionic and acetic acids recovered. The concentration of succinic acid in the rats increased in high-fat diets with time, indicating harmful effect of high-fat consumption. The dietary fibre partly counteracted these harmful effects and reduced inflammation. Furthermore, the number of Bacteroides was higher with guar gum, while noticeably that of Akkermansia was highest with the fibre-free diet. PMID:24236183

  18. SGLT2 selective inhibitor ipragliflozin reduces body fat mass by increasing fatty acid oxidation in high-fat diet-induced obese rats.

    PubMed

    Yokono, Masanori; Takasu, Toshiyuki; Hayashizaki, Yuka; Mitsuoka, Keisuke; Kihara, Rumi; Muramatsu, Yuko; Miyoshi, Sousuke; Tahara, Atsuo; Kurosaki, Eiji; Li, Qun; Tomiyama, Hiroshi; Sasamata, Masao; Shibasaki, Masayuki; Uchiyama, Yasuo

    2014-03-15

    Ipragliflozin is a novel and selective sodium-glucose cotransporter 2 (SGLT2) inhibitor that induces sustained increases in urinary glucose excretion by inhibiting renal glucose reabsorption and thereby exerting a subsequent antihyperglycemic effect. Here, we examined the effect of ipragliflozin on body weight in high-fat diet-induced (HFD) obese rats. Treatment of ipragliflozin (10mg/kg once daily) reduced body weight despite a slight increase in food intake. Dual-energy X-ray absorptiometry and computed tomography demonstrated that the reduction in body weight was accompanied by reduced visceral and subcutaneous fat masses but not lean mass or bone mineral content. Analysis of plasma and urinary parameters suggested the possibility that ipragliflozin enhanced lipolysis and fatty acid oxidation, and indirect calorimetry showed that ipragliflozin decreased the heat production rate from glucose but increased the rate from fat and lowered the respiratory exchange ratio. In conclusion, these data demonstrate that ipragliflozin-induced urinary glucose excretion specifically reduces fat mass with steady calorie loss by promoting the use of fatty acids instead of glucose as an energy source in HFD rats. By improving hyperglycemia and promoting weight reduction, ipragliflozin may prove useful in treating type 2 diabetes in obese individuals. PMID:24486393

  19. The Ethanol Extract of the Inner Bark of Caesalpinia pyramidalis (Tul.) Reduces Urinary Bladder Damage during Cyclophosphamide-Induced Cystitis in Rats

    PubMed Central

    Moraes, Janaína P.; Pereira, Denyson S.; Matos, Alexandre S.; Santana, Danielle G.; Santos, Cliomar A.; Estevam, Charles S.; Fakhouri, Ricardo; de Lucca Junior, Waldecy; Camargo, Enilton A.

    2013-01-01

    Hemorrhagic cystitis (HC) is a common side effect of cyclophosphamide therapy, which deserves new therapeutic strategies, such as those based on natural products. The ethanol extract of the inner bark of Caesalpinia pyramidalis (Tul.) (EECp) possesses anti-inflammatory, antinociceptive, and antioxidant activities as previously showed by our group. We have investigated the effect of EECp on the cyclophosphamide-induced HC. Cystitis was induced in male Wistar rats by the injection of cyclophosphamide. These animals were pretreated with EECp (100–400?mg/kg), vehicle, or mesna. Myeloperoxidase activity and malondialdehyde formation were measured in urinary bladder and other tissues. Bladder edema and histopathological alterations and serum nitric oxide metabolites concentration NOx? were also evaluated. Treatment with EECp (100–400?mg/kg) or mesna impaired the increase of myeloperoxidase activity in urinary bladder and the serum NOx? induced by cyclophosphamide but did not reduce edema in this tissue, as did mesna. Total histological score was reduced by EECp (100?mg/kg). Lung myeloperoxidase activity, which was increased by cyclophosphamide, was decreased significantly by EECp (400?mg/kg). EECp also diminished the malondialdehyde formation in bladder, lung, and spleen, although these parameters were not affected by cyclophosphamide. These results indicate that EECp reduced urinary bladder damage during cyclophosphamide-induced HC in rats. PMID:24348180

  20. Supplemental fermented plant product (‘Manda Koso’) reduces succinate and deoxycholate, as well as elevates IgA and mucin levels, in rats fed a high-fat diet

    PubMed Central

    YANG, YONGSHOU; SITANGGANG, NOVITA VIVI; OKAZAKI, YUKAKO; TOMOTAKE, HIROYUKI; ARITA, KENTARO; ASHIDA, TAKAYUKI; KATO, NORIHISA

    2015-01-01

    ‘Manda Koso’ is a commercial fermented plant product (FPP) made from 53 types of fruits and vegetables that have been fermented for >3 years and 3 months. We hypothesized that FPP intake improves the luminal environment of rats fed a high-fat diet. Thus, the present study examined the effects of consumption of 5% FPP diet for 3 weeks on colonic luminal parameters in rats fed a 30% beef tallow diet. Food intake and body weight gain were unaffected. Consumption of the FPP diet did not influence the proportions of Bifidobacterium, Lactobacillus, Bacteroides, Prevotella or Clostridium in cecal contents. However, the FPP diet caused a significant reduction (?88%) in the level of cecal succinate, a putative inflammatory signal (P<0.01), but did not affect the levels of n-butyrate, propionate, acetate and lactate. The fecal levels of deoxycholate and hyodeoxycholate, which are toxic bile acids, were also significantly reduced by the FPP diet (P<0.05). The FPP diet significantly increased fecal immunoglobulin A and mucins responsible for intestinal immune and barrier functions (P<0.05). The results suggest that the consumption of FPP is beneficial for the colonic luminal environment in rats fed a high-fat diet. PMID:26623016

  1. Phaleria macrocarpa Boerl. (Thymelaeaceae) leaves increase SR-BI expression and reduce cholesterol levels in rats fed a high cholesterol diet.

    PubMed

    Andriani, Yosie; Tengku-Muhammad, Tengku Sifzizul; Mohamad, Habsah; Saidin, Jasnizat; Syamsumir, Desy Fitrya; Chew, Guat-Siew; Abdul Wahid, Mohd Effendy

    2015-01-01

    In vitro and in vivo studies of the activity of Phaleria macrocarpa Boerl (Thymelaeaceae) leaves against the therapeutic target for hypercholesterolemia were done using the HDL receptor (SR-BI) and hypercholesterolemia-induced Sprague Dawley rats. The in vitro study showed that the active fraction (CF6) obtained from the ethyl acetate extract (EMD) and its component 2',6',4-trihydroxy-4'-methoxybenzophenone increased the SR-BI expression by 95% and 60%, respectively. The in vivo study has proven the effect of EMD at 0.5 g/kgbw dosage in reducing the total cholesterol level by 224.9% and increasing the HDL cholesterol level by 157% compared to the cholesterol group. In the toxicity study, serum glutamate oxalate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) activity were observed to be at normal levels. The liver histology also proved no toxicity and abnormalities in any of the treatment groups, so it can be categorized as non-toxic to the rat liver. The findings taken together show that P. macrocarpa leaves are safe and suitable as an alternative control and prevention treatment for hypercholesterolemia in Sprague Dawley rats. PMID:25759957

  2. Ellagic acid reduces L-type Ca2+ current and contractility through modulation of NO-GC-cGMP pathways in rat ventricular myocytes.

    PubMed

    Olgar, Yusuf; Ozturk, Nihal; Usta, Co?kun; Puddu, Paolo E; Ozdemir, Semir

    2014-12-01

    There is evidence that phenolic structure may have biological functions. Ellagic acid (EA), a phenolic compound, has been suggested to have cardioprotective effects. EA effects were investigated on cardiac Ca currents and contractility in rat ventricular myocytes to elucidate the underlying mechanisms. Freshly isolated ventricular myocytes from rat hearts were used. EA dose-dependently reduced Ca currents (ICaL) with EC50 = 23 nM, whereas it did not affect the inactivation and reactivation parameters. Inhibition of adenylate cyclase by SQ-22536 (10 ?M) and probucol (5 ?M) had no effect on EA modulation of ICaL. Nitric oxide synthase block by L-NAME (500 ?M) and of guanylate cyclase by ODQ (1 ?M) abolished EA inhibitory effects on ICaL. Moreover, EA blunted ventricular myocytes' fractional shortening in a concentration-dependent manner. In conclusion, EA affects ionic and mechanical properties of rat ventricular myocytes starting at nanomolar concentrations. EA suppresses ICaL and exerts negative inotropic effects through activation of NOS-GC-cGMP pathways. Thus, EA may be useful in pathophysiological conditions such as hypertension and ischemic heart diseases. PMID:25165997

  3. Effects of competitive red blood cell binding and reduced hematocrit on the blood and plasma levels of (/sup 14/C)Indapamide in the rat

    SciTech Connect

    Lettieri, J.T.; Portelli, S.T.

    1983-02-01

    The effects of chlorthalidone and acetazolamide on the red blood cell binding of indapamide were investigated. Both drugs caused a substantial decrease in the amount of indapamide bound to the erythrocytes in vitro. This effect was demonstrated by a change in the indapamide blood/plasma ratio from approximately 6 in control samples, to a value of 1 when either of the displacing agents was added. Coadministration of acetazolamide with /sup 14/C-labeled indapamide to rats, resulted in a 5-fold drop in the blood levels of total radioactivity, relative to rats dosed with (/sup 14/C)indapamide alone. Concomitantly, there was a 2-fold increase in the plasma levels of total radioactivity after acetazolamide coadministration. In rats whose hematocrits had been reduced by extensive bleeding, there were only minor alterations in the blood/plasma partitioning of (/sup 14/C)indapamide. Thus, chlorthalidone and acetazolamide were able to displace indapamide from erythrocytes in vitro and in vivo, possibly by competition at a carbonic anhydrase binding site. The pharmacokinetics of drugs which are extensively bound to erythrocytes may be significantly altered by the presence of other agents capable of competitive binding.

  4. A 3D analysis of fore- and hindlimb motion during locomotion: comparison of overground and ladder walking in rats.

    PubMed

    Garnier, Cyril; Falempin, Maurice; Canu, Marie-Hélène

    2008-01-10

    The locomotor pattern, generated by the central pattern generator, is under the dependence of descending and peripheral pathways. The afferent feedback from peripheral receptors allows the animal to correct for disturbances that occur during walking, while supraspinal structures are important for locomotion in demanding situations such as ladder walking. Such walking, by regards to the control needed for accuracy of movements, is now widely used for description of consequences of nervous system dysfunction on motor performance. It is important to have a good knowledge of the changes in kinematic parameters according to walking conditions, since it might reflect different neural mechanisms. The aim of this work was to perform a 3D kinematic analysis of both hind- and forelimb during overground and ladder walking, to study qualitative and quantitative locomotor characteristics in different modes of locomotion. The analysis was performed on 5 rats. Movements of the right hind- and forelimb were evaluated using a 3D optical analyser, and EMG of the soleus and tibialis anterior muscles was synchronously recorded. Results indicate that kinematic and electromyographic characteristics of locomotion are dependent on the type of support. Changes were more obvious for hindlimb than for forelimb. Velocity, stride length and tibialis anterior burst duration were lower on ladder than on runway. In addition, during ladder walking, a protraction was noticed, rats bring their feet more rostral at the end of the swing phase. All these changes constitute an adaptive strategy to allow a better tactile activity with forelimbs and to avoid foot misplacement. PMID:17764759

  5. Absorption and Bioavailability of Nano-Size Reduced Calcium Citrate Fortified Milk Powder in Ovariectomized and Ovariectomized-Osteoporosis Rats.

    PubMed

    Erfanian, Arezoo; Mirhosseini, Hamed; Rasti, Babak; Hair-Bejo, Mohd; Bin Mustafa, Shuhaimi; Abd Manap, Mohd Yazid

    2015-06-24

    The aim of this study was to evaluate the effects of fortification and nano-size reduction on calcium absorption and bioavailability of milk powder formula in sham, ovariectomized, and ovariectomized-osteoporosis rats as a menopause and menopause-osteoporosis model. Skim milk powder and skim milk powder fortified with calcium citrate and the suitable doses of inulin, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamins D3, K1, and B6 were formulated based on the North American and Western European recommended dietary allowances. Optimization on cycle and pressure of high-pressure homogenizer was done to produce nano-fortified milk powder. In vivo study demonstrated that fortification and calcium citrate nano-fortified milk powder increased absorption and bioavailability of calcium, as well as bone stiffness and bone strength in sham, ovariectomized, and ovariectomized-osteoporosis rats. This study successfully developed an effective fortified milk powder for food application. PMID:26022498

  6. The effects of cocaine on different redox forms of cysteine and homocysteine, and on labile, reduced sulfur in the rat plasma following active versus passive drug injections.

    PubMed

    Kowalczyk-Pachel, Danuta; Chwatko, Gra?yna; Iciek, Ma?gorzata; Czy?yk, Joanna; Filip, Ma?gorzata; W?odek, Lidia; Lorenc-Koci, El?bieta

    2013-10-01

    The aim of the present studies was to evaluate cocaine-induced changes in the concentrations of different redox forms of cysteine (Cys) and homocysteine (Hcy), and products of anaerobic Cys metabolism, i.e., labile, reduced sulfur (LS) in the rat plasma. The above-mentioned parameters were determined after i.p. acute and subchronic cocaine treatment as well as following i.v. cocaine self-administration using the yoked procedure. Additionally, Cys, Hcy, and LS levels were measured during the 10-day extinction training in rats that underwent i.v. cocaine administration. Acute i.p. cocaine treatment increased the total and protein-bound Hcy contents, decreased LS, and did not change the concentrations of Cys fractions in the rat plasma. In turn, subchronic i.p. cocaine administration significantly increased free Hcy and lowered the total and protein-bound Cys concentrations while LS level was unchanged. Cocaine self-administration enhanced the total and protein-bound Hcy levels, decreased LS content, and did not affect the Cys fractions. On the other hand, yoked cocaine infusions did not alter the concentration of Hcy fractions while decreased the total and protein-bound Cys and LS content. This extinction training resulted in the lack of changes in the examined parameters in rats with a history of cocaine self-administration while in the yoked cocaine group an increase in the plasma free Cys fraction and LS was seen. Our results demonstrate for the first time that cocaine does evoke significant changes in homeostasis of thiol amino acids Cys and Hcy, and in some products of anaerobic Cys metabolism, which are dependent on the way of cocaine administration. PMID:23677450

  7. Reduced c-Fos expression in medullary catecholaminergic neurons in rats 20 h after exposure to chronic intermittent hypoxia

    PubMed Central

    Herr, Kate Benincasa; Stettner, Georg M.

    2013-01-01

    Persons affected by obstructive sleep apnea (OSA) have increased arterial blood pressure and elevated activity in upper airway muscles. Many cardiorespiratory features of OSA have been reproduced in rodents subjected to chronic-intermittent hypoxia (CIH). We previously reported that, following exposure to CIH, rats have increased noradrenergic terminal density in brain stem sensory and motor nuclei and upregulated expression of the excitatory ?1-adrenergic receptors in the hypoglossal motor nucleus. This suggested that CIH may enhance central catecholaminergic transmission. We now quantified c-Fos expression in different groups of pontomedullary catecholaminergic neurons as an indirect way of assessing their baseline activity in rats subjected to CIH or sham treatment (7 AM-5 PM daily for 35 days). One day after the last CIH exposure, the rats were gently kept awake for 2.5 h and then were anesthetized and perfused, and their pontomedullary brain sections were subjected to dopamine ?-hydroxylase (DBH) and c-Fos immunohistochemistry. DBH-positive cells were counted in the A1/C1, A2/C2, A5, subcoeruleus (sub-C) and A7 groups of catecholaminergic neurons, and the percentages of those expressing c-Fos were determined. We found that fewer DBH cells expressed c-Fos in CIH- than in sham-treated rats in the medulla (significant in the A1 group). In the pons (rostral A5, sub-C, and A7), c-Fos expression did not differ between the CIH- and sham-treated animals. We suggest that, when measured 20 h after the last CIH exposure, catecholaminergic transmission is enhanced through terminal sprouting and receptor upregulation rather than through increased baseline activity in pontomedullary catecholaminergic neurons. PMID:23364524

  8. [Methods for intravenous injection and blood collection in the guinea pig via veins of the forelimb without anesthesia (author's transl)].

    PubMed

    Takahashi, K W; Sakuma, S; Ueda, H; Ebino, K Y; Saito, T R; Imamichi, T

    1980-07-01

    Methods for intravenous injection and blood collection by way of the forelimb in guinea pigs without anesthesia were investigated, with the results as follows: 1) Both the accessory cephalic and cephalic veins were found available for injection as well as for drawing blood samples. Venipuncture was accomplished with greater ease by using the accessory cephalic vein. 2) The following procedure has proven practical. (i) Clip the hair over the site. (ii) Restrain the animal to immobilize the foreleg in slight extension by grasping it at the elbow joint with the thumb and fore