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Sample records for altered brain activity

  1. Alterations of brain activity in fibromyalgia patients.

    PubMed

    Sawaddiruk, Passakorn; Paiboonworachat, Sahattaya; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2017-04-01

    Fibromyalgia is a chronic pain syndrome, characterized by widespread musculoskeletal pain with diffuse tenderness at multiple tender points. Despite intense investigations, the pathophysiology of fibromyalgia remains elusive. Evidence shows that it could be due to changes in either the peripheral or central nervous system (CNS). For the CNS changes, alterations in the high brain area of fibromyalgia patients have been investigated but the definite mechanisms are still unclear. Magnetic Resonance Imaging (MRI) and Functional Magnetic Resonance (fMRI) have been used to gather evidence regarding the changes of brain morphologies and activities in fibromyalgia patients. Nevertheless, due to few studies, limited knowledge for alterations in brain activities in fibromyalgia is currently available. In this review, the changes in brain activity in various brain areas obtained from reports in fibromyalgia patients are comprehensively summarized. Changes of the grey matter in multiple regions such as the superior temporal gyrus, posterior thalamus, amygdala, basal ganglia, cerebellum, cingulate cortex, SII, caudate and putamen from the MRI as well as the increase of brain activities in the cerebellum, prefrontal cortex, anterior cingulate cortex, thalamus, somatosensory cortex, insula in fMRI studies are presented and discussed. Moreover, evidence from pharmacological interventions offering benefits for fibromyalgia patients by reducing brain activity is presented. Because of limited knowledge regarding the roles of brain activity alterations in fibromyalgia, this summarized review will encourage more future studies to elucidate the underlying mechanisms involved in the brains of these patients.

  2. Altered Resting-State Brain Activity in Obstructive Sleep Apnea

    PubMed Central

    Zhang, Quan; Wang, Dawei; Qin, Wen; Li, Qiong; Chen, Baoyuan; Zhang, Yunting; Yu, Chunshui

    2013-01-01

    Study Objectives: Structural and functional brain changes may contribute to neural dysfunction in patients with obstructive sleep apnea (OSA). However, the effect of OSA on resting-state brain activity has not been established. The objective of this study was to investigate alterations in resting-state functional connectivity (rsFC) of the common brain networks in patients with OSA and their relationships with changes in gray matter volume (GMV) in the corresponding brain regions. Designs: Resting-state functional and structural MRI data were acquired from patients with OSA and healthy controls. Seven brain networks were identified by independent component analysis. The rsFC in each network was compared between groups and the GMV of brain regions with significant differences in rsFC was also compared. Setting: University hospital. Patients and Participants: Twenty-four male patients with untreated OSA and 21 matched healthy controls. Interventions: N/A. Measurements and Results: OSA specifically affected the cognitive and sensorimotor-related brain networks but not the visual and auditory networks. The medial prefrontal cortex and left dorsolateral prefrontal cortex (DLPFC) showed decreased rsFC and GMV in patients with OSA, suggesting structural and functional deficits. The right DLPFC and left precentral gyrus showed decreased rsFC and unchanged GMV, suggesting a functional deficit. The right posterior cingulate cortex demonstrated increased rsFC and unchanged GMV, suggesting functional compensation. In patients with OSA, the rsFC of the right DLPFC was negatively correlated with the apnea-hypopnea index. Conclusions: OSA specifically affects resting-state functional connectivity in cognitive and sensorimotor-related brain networks, which may be related to the impaired cognitive and motor functions in these patients. Citation: Zhang Q; Wang D; Qin W; Li Q; Chen B; Zhang Y; Yu C. Altered resting-state brain activity in obstructive sleep apnea. SLEEP 2013

  3. Altered brain activity for phonological manipulation in dyslexic Japanese children.

    PubMed

    Kita, Yosuke; Yamamoto, Hisako; Oba, Kentaro; Terasawa, Yuri; Moriguchi, Yoshiya; Uchiyama, Hitoshi; Seki, Ayumi; Koeda, Tatsuya; Inagaki, Masumi

    2013-12-01

    Because of unique linguistic characteristics, the prevalence rate of developmental dyslexia is relatively low in the Japanese language. Paradoxically, Japanese children have serious difficulty analysing phonological processes when they have dyslexia. Neurobiological deficits in Japanese dyslexia remain unclear and need to be identified, and may lead to better understanding of the commonality and diversity in the disorder among different linguistic systems. The present study investigated brain activity that underlies deficits in phonological awareness in Japanese dyslexic children using functional magnetic resonance imaging. We developed and conducted a phonological manipulation task to extract phonological processing skills and to minimize the influence of auditory working memory on healthy adults, typically developing children, and dyslexic children. Current experiments revealed that several brain regions participated in manipulating the phonological information including left inferior and middle frontal gyrus, left superior temporal gyrus, and bilateral basal ganglia. Moreover, dyslexic children showed altered activity in two brain regions. They showed hyperactivity in the basal ganglia compared with the two other groups, which reflects inefficient phonological processing. Hypoactivity in the left superior temporal gyrus was also found, suggesting difficulty in composing and processing phonological information. The altered brain activity shares similarity with those of dyslexic children in countries speaking alphabetical languages, but disparity also occurs between these two populations. These are initial findings concerning the neurobiological impairments in dyslexic Japanese children.

  4. Altered Spontaneous Brain Activity in Betel Quid Dependence

    PubMed Central

    Liu, Tao; Li, Jian-jun; Zhao, Zhong-yan; Yang, Guo-shuai; Pan, Meng-jie; Li, Chang-qing; Pan, Su-yue; Chen, Feng

    2016-01-01

    Abstract It has been suggested by the first voxel-based morphometry investigation that betel quid dependence (BQD) individuals are presented with brain structural changes in previous reports, and there may be a neurobiological basis for BQD individuals related to an increased risk of executive dysfunction and disinhibition, subjected to the reward system, cognitive system, and emotion system. However, the effects of BQD on neural activity remain largely unknown. Individuals with impaired cognitive control of behavior often reveal altered spontaneous cerebral activity in resting-state functional magnetic resonance imaging and those changes are usually earlier than structural alteration. Here, we examined BQD individuals (n = 33) and age-, sex-, and education-matched healthy control participants (n = 32) in an resting-state functional magnetic resonance imaging study to observe brain function alterations associated with the severity of BQD. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were both evaluated to stand for spontaneous cerebral activity. Gray matter volumes of these participants were also calculated for covariate. In comparison with healthy controls, BQD individuals demonstrated dramatically decreased ALFF and ReHo values in the prefrontal gurus along with left fusiform, and increased ALFF and ReHo values in the primary motor cortex area, temporal lobe as well as some regions of occipital lobe. The betel quid dependence scores (BQDS) were negatively related to decreased activity in the right anterior cingulate. The abnormal spontaneous cerebral activity revealed by ALFF and ReHo calculation excluding the structural differences in patients with BQD may help us probe into the neurological pathophysiology underlying BQD-related executive dysfunction and disinhibition. Diminished spontaneous brain activity in the right anterior cingulate cortex may, therefore, represent a biomarker of BQD individuals. PMID

  5. Alteration of spontaneous brain activity in COPD patients

    PubMed Central

    Zhang, Jiaxing; Chen, Ji; Yu, Qian; Fan, Cunxiu; Zhang, Ran; Lin, Jianzhong; Yang, Tianhe; Fan, Ming

    2016-01-01

    Background and objective Airflow limitation in chronic obstructive pulmonary disease (COPD) results in a decrease in oxygen transport to the brain. The aim of the present study was to explore the alteration of spontaneous brain activity induced by hypoxia in patients with COPD. Patients and methods Twenty-five stable patients with COPD and 25 matching healthy volunteers were investigated. Amplitude of low-frequency fluctuation (ALFF) of blood oxygenation level-dependent signal at resting state in the brain was analyzed using functional magnetic resonance imaging. Results Whole-brain analysis using functional magnetic resonance imaging revealed significant decreases in ALFF in the bilateral posterior cingulate gyri and right lingual gyrus and an increase in ALFF in the left postcentral gyrus of patients with COPD. After controlling for SaO2, patients with COPD only showed an increase in ALFF in the left postcentral gyrus. Region of interest analysis showed a decrease in ALFF in the left precentral gyrus and an increase in ALFF in the left caudate nucleus of patients with COPD. In all subjects, ALFF in the bilateral posterior cingulate gyri and right lingual gyrus showed positive correlations with visual reproduction. Conclusion We demonstrated abnormal spontaneous brain activity of patients with COPD, which may have a pathophysiologic meaning. PMID:27555761

  6. Alterations in brain activation during cholinergic enhancement with rivastigmine in Alzheimer's disease

    PubMed Central

    Rombouts, S; Barkhof, F; van Meel, C S; Scheltens, P

    2002-01-01

    Background: Rivastigmine enhances cholinergic activity and has been shown in clinical trials to decrease the rate of deterioration in Alzheimer's disease. It remains unclear where in the brain it exerts its effect. Functional magnetic resonance imaging (fMRI) can be used to measure changes in brain function and relate these to cognition. Objectives: To use fMRI to study brain activation with rivastigmine treatment. Methods: The effect on brain activation of a single dose of rivastigmine was tested in seven patients with mild Alzheimer's disease using fMRI during face encoding, and in five patients during a parametric working memory task. Results: During face encoding, rivastigmine increased bilateral activation in the fusiform gyrus. Brain activation was also enhanced in the prefrontal cortex in a simple working memory task. When working memory load was further increased, not only was increased activation seen, but in certain areas there was also decreased activation. Conclusions: These findings link the previously observed increase in cognitive performance in Alzheimer's disease after treatment with a cholinesterase inhibitor to altered brain activation. Although the results cannot be generalised to the Alzheimer's disease population at large, they provide evidence that in mild Alzheimer's disease, rivastigmine enhances brain activation in the fusiform and frontal cortices. This is compatible with the concept of cholinergic circuitry. PMID:12438467

  7. Altered intrinsic brain activity in patients with paroxysmal kinesigenic dyskinesia by PRRT2 mutation: altered brain activity by PRRT2 mutation.

    PubMed

    Luo, ChunYan; Chen, Yongping; Song, Wei; Chen, Qin; Gong, QiYong; Shang, Hui-Fang

    2013-11-01

    The proline-rich transmembrane protein 2 (PRRT2) gene has been recently identified as a causative gene of paroxysmal kinesigenic dyskinesia (PKD), with an insertion mutation c.649_650insC (p.P217fsX7) reported as the most common mutation. However, the pathogenic mechanism of the mutation of PRRT2 remains largely unknown. Resting-state functional magnetic resonance imaging is a promising approach to assess cerebral function and reveals underlying functional changes. Resting-state functional magnetic resonance imaging was performed in 4 Chinese PKD patients with p.P217fsX7 mutation, 6 Chinese PKD patients without the mutation, and 10 healthy control subjects. Voxel-based analysis was used to characterize alterations in the amplitude of low-frequency fluctuation (ALFF). When compared with the healthy control subjects, both groups of PKD patients showed alterations in spontaneous brain activities within cortical-basal ganglia circuitry. Besides, the group of patients with p.P217fsX7 mutation also exhibited increased ALFF in the right postcenral gyrus and right rolandic operculum area, while the alteration of ALFF in group of patients without the mutation additionally involved the middle orbitofrontal cortex. Direct comparative analysis between these two patient groups revealed significantly increased ALFF in the right postcentral gyrus in the group with p.P217fsX7 mutation. Increased spontaneous brain activity in the cortical-basal ganglia circuitry, especially in the motor preparation areas, is a common pathophysiology in PKD. Differences in the spatial patterns of increased ALFF between patients with and those without the mutation might reflect the distinct pathological mechanism resulting from PRRT2 mutation.

  8. Deep brain stimulation during early adolescence prevents microglial alterations in a model of maternal immune activation.

    PubMed

    Hadar, Ravit; Dong, Le; Del-Valle-Anton, Lucia; Guneykaya, Dilansu; Voget, Mareike; Edemann-Callesen, Henriette; Schweibold, Regina; Djodari-Irani, Anais; Goetz, Thomas; Ewing, Samuel; Kettenmann, Helmut; Wolf, Susanne A; Winter, Christine

    2016-12-07

    In recent years schizophrenia has been recognized as a neurodevelopmental disorder likely involving a perinatal insult progressively affecting brain development. The poly I:C maternal immune activation (MIA) rodent model is considered as a neurodevelopmental model of schizophrenia. Using this model we and others demonstrated the association between neuroinflammation in the form of altered microglia and a schizophrenia-like endophenotype. Therapeutic intervention using the anti-inflammatory drug minocycline affected altered microglia activation and was successful in the adult offspring. However, less is known about the effect of preventive therapeutic strategies on microglia properties. Previously we found that deep brain stimulation of the medial prefrontal cortex applied pre-symptomatically to adolescence MIA rats prevented the manifestation of behavioral and structural deficits in adult rats. We here studied the effects of deep brain stimulation during adolescence on microglia properties in adulthood. We found that in the hippocampus and nucleus accumbens, but not in the medial prefrontal cortex, microglial density and soma size were increased in MIA rats. Pro-inflammatory cytokine mRNA was unchanged in all brain areas before and after implantation and stimulation. Stimulation of either the medial prefrontal cortex or the nucleus accumbens normalized microglia density and soma size in main projection areas including the hippocampus and in the area around the electrode implantation. We conclude that in parallel to an alleviation of the symptoms in the rat MIA model, deep brain stimulation has the potential to prevent the neuroinflammatory component in this disease.

  9. Acetylcholinesterase activity and antioxidant capacity of zebrafish brain is altered by heavy metal exposure.

    PubMed

    Richetti, S K; Rosemberg, D B; Ventura-Lima, J; Monserrat, J M; Bogo, M R; Bonan, C D

    2011-01-01

    Pollution is a world problem with immeasurable consequences. Heavy metal compounds are frequently found as components of anthropogenic pollution. Here we evaluated the effects of the treatment with cadmium acetate, lead acetate, mercury chloride, and zinc chloride in acetylcholinesterase activity and gene expression pattern, as well as the effects of these treatments in antioxidant competence in the brain of an aquatic and well-established organism for toxicological analysis, zebrafish (Danio rerio, Cyprinidae). Mercury chloride and lead acetate promoted a significant decrease in acetylcholinesterase activity whereas they did not alter the gene expression pattern. In addition, the antioxidant competence was decreased after exposure to mercury chloride. The data presented here allowed us to hypothesize a signal transmission impairment, through alterations in cholinergic transmission, and also in the antioxidant competence of zebrafish brain tissue as some of the several effects elicited by these pollutants.

  10. The hyperactive syndrome: metanalysis of genetic alterations, pharmacological treatments and brain lesions which increase locomotor activity.

    PubMed

    Viggiano, Davide

    2008-12-01

    The large number of transgenic mice realized thus far with different purposes allows addressing new questions, such as which animals, over the entire set of transgenic animals, show a specific behavioural abnormality. In the present study, we have used a metanalytical approach to organize a database of genetic modifications, brain lesions and pharmacological interventions that increase locomotor activity in animal models. To further understand the resulting data set, we have organized a second database of the alterations (genetic, pharmacological or brain lesions) that reduce locomotor activity. Using this approach, we estimated that 1.56% of the genes in the genome yield to hyperactivity and 0.75% of genes produce hypoactivity when altered. These genes have been classified into genes for neurotransmitter systems, hormonal, metabolic systems, ion channels, structural proteins, transcription factors, second messengers and growth factors. Finally, two additional classes included animals with neurodegeneration and inner ear abnormalities. The analysis of the database revealed several unexpected findings. First, the genes that, when mutated, induce hyperactive behaviour do not pertain to a single neurotransmitter system. In fact, alterations in most neurotransmitter systems can give rise to a hyperactive phenotype. In contrast, fewer changes can decrease locomotor activity. Specifically, genetic and pharmacological alterations that enhance the dopamine, orexin, histamine, cannabinoids systems or that antagonize the cholinergic system induce an increase in locomotor activity. Similarly, imbalances in the two main neurotransmitters of the nervous system, GABA and glutamate usually result in hyperactive behaviour. It is remarkable that no genetic alterations pertaining to the GABA system have been reported to reduce locomotor behaviour. Other neurotransmitters, such as norepinephrine and serotonin, have a more complex influence. For instance, a decrease in norepinephrine

  11. Proteolytic activity is altered in brain tissue of rats upon chronic exposure to ozone

    SciTech Connect

    Benuck, M.; Banay-Schwartz, M.; Lajtha, A. )

    1993-01-01

    Tissue from pons medulla of rats exposed in vivo to various levels of ozone was assayed for calpain and cathepsin D activity. Chronic exposure to ozone increased calpain activity, which was 35% to 46% higher in the homogenates of animals exposed to 1.0 ppm ozone than in those of animals exposed to 0.5 ppm ozone or of controls. An increase in activity of 26% was also observed in the soluble supernatant. The increase in activity did not seem to be caused by ozone effects on calpastatin. Addition of 32 mM carnitine to the incubation mixture increased total activity 3-4 fold, making the differences in activity proportionately smaller. Cathepsin D activity was little altered. Changes in calpain activity and in the generation of free oxygen radicals have been implicated in the aging process, long-term exposure to ozone may magnify changes. Ozone exposure may cause changes in brain protein metabolism. 15 refs., 2 tabs.

  12. Alterations of Regional Spontaneous Brain Activity and Gray Matter Volume in the Blind

    PubMed Central

    Jiang, Aili; Tian, Jing; Li, Rui; Liu, Yong; Jiang, Tianzi; Qin, Wen; Yu, Chunshui

    2015-01-01

    Visual deprivation can induce alterations of regional spontaneous brain activity (RSBA). However, the effects of onset age of blindness on the RSBA and the association between the alterations of RSBA and brain structure are still unclear in the blind. In this study, we performed resting-state functional and structural magnetic resonance imaging on 50 sighted controls and 91 blind subjects (20 congenitally blind, 27 early blind, and 44 late blind individuals). Compared with the sighted control, we identified increased RSBA in the blind in primary and high-level visual areas and decreased RSBA in brain regions which are ascribed to sensorimotor and salience networks. In contrast, blind subjects exhibited significantly decreased gray matter volume (GMV) in the visual areas, while they exhibited significantly increased GMV in the sensorimotor areas. Moreover, the onset age of blindness was negatively correlated with the GMV of visual areas in blind subjects, whereas it exerted complex influences on the RSBA. Finally, significant negative correlations were shown between RSBA and GMV values. Our results demonstrated system-dependent, inverse alterations in RSBA and GMV after visual deprivation. Furthermore, the onset age of blindness has different effects on the reorganizations in RSBA and GMV. PMID:26568891

  13. Brain Injury Alters Ectonucleotidase Activities and Adenine Nucleotide Levels in Rat Serum

    PubMed Central

    Laketa, Danijela; Savić, Jasmina; Bjelobaba, Ivana; Lavrnja, Irena; Vasić, Vesna; Stojiljković, Mirjana; Nedeljković, Nadežda

    2015-01-01

    Summary Background Cortical stab injury (CSI) induces changes in the activity, expression and cellular distribution of specific ectonucleotidases at the injury site. Also, several experimentally induced neuropathologies are associated with changes in soluble ectonucleotidase activities in the plasma and serum, whilst various insults to the brain alter purine compounds levels in cerebrospinal fluid, but also in serum, indicating that insults to the brain may induce alterations in nucleotides release and rate of their hydrolysis in the vascular system. Since adenine nucleotides and adenosine regulate diverse cellular functions in the vascular system, including vascular tone, platelet aggregation and inflammatory responses of lymphocytes and macrophages, alterations of ectonucleotidase activities in the vascular system may be relevant for the clinical outcome of the primary insult. Methods We explored ectonucleotidase activities using specific enzyme assays and determined adenine nucleotides concentrations by the UPLC method in the rat serum after cortical stab injury. Results At 4-h post-injury, ATP and AMP hydrolysis increased by about 60% and 40%, respectively, while phosphodiesterase activity remained unchanged. Also, at 4-h post-injury a marked decrease in ATP concentration and more than 2-fold increase in AMP concentration were recorded. Conclusions CSI induces rapid up-regulation of nucleotide catabolizing soluble ectonucleotidases in rat serum, which leads to the observed shift in serum nucleotide levels. The results obtained imply that ectonucleotidases and adenine nucleotides participate in the communication between the brain and the vascular system in physiological and pathological conditions and thereby may be involved in the development of various human neuropathologies.

  14. Brain-encysting trematodes and altered monoamine activity in naturally infected killifish Fundulus parvipinnis.

    PubMed

    Shaw, J C; Øverli, Ø

    2012-12-01

    This paper presents novel evidence to address mechanisms by which trematode parasites effect behavioural changes in naturally infected fish hosts. California killifish Fundulus parvipinnis infected with the brain-encysting trematode Euhaplorchis californiensis display conspicuous swimming behaviours that render them 30 times more likely to be eaten by birds, the parasite's final host. Prevalence of E. californiensis reaches nearly 100% in most F. parvipinnis populations, with parasite biomass constituting almost 2% of F. parvipinnis biomass in some locations. Despite having thousands of cysts on their brains, infected fish grow and mature at rates comparable to those of uninfected populations. The lack of general pathology combined with the specificity of the altered behaviours suggests that the behavioural changes are due to parasite manipulation. The monoamine neurotransmitters serotonin and dopamine, which control locomotion and social behaviour in fishes and other vertebrates, were examined to explore the underlying mechanisms of this behaviour modification. Whereas previous studies were similarly conducted with experimentally infected fish, in this study, brain dopaminergic and serotonergic activity were analysed in naturally infected fish to assess how E. californiensis may alter F. parvipinnis monoamines in a naturally occurring system. A parasite density-associated decrease in serotonergic activity occurred in the hippocampus of naturally infected fish, as well as a decrease in dopaminergic activity in the raphe nuclei, suggesting that E. californiensis inhibits serotonin and dopamine signaling in naturally infected F. parvipinnis. The neurochemical profile of infected fish is consistent with the hypothesis that E. californiensis affects brain monoaminergic systems in order to induce impulse-driven, active, and aggressive behaviour in its hosts.

  15. Administration of memantine and imipramine alters mitochondrial respiratory chain and creatine kinase activities in rat brain.

    PubMed

    Réus, Gislaine Z; Stringari, Roberto B; Rezin, Gislaine T; Fraga, Daiane B; Daufenbach, Juliana F; Scaini, Giselli; Benedet, Joana; Rochi, Natália; Streck, Emílio L; Quevedo, João

    2012-04-01

    Several studies have appointed for a role of glutamatergic system and/or mitochondrial function in major depression. In the present study, we evaluated the creatine kinase and mitochondrial respiratory chain activities after acute and chronic treatments with memantine (N-methyl-D: -aspartate receptor antagonist) and imipramine (tricyclic antidepressant) in rats. To this aim, rats were acutely or chronically treated for 14 days once a day with saline, memantine (5, 10 and 20 mg/kg) and imipramine (10, 20 and 30 mg/kg). After acute or chronic treatments, we evaluated mitochondrial respiratory chain complexes (I, II, II-III and IV) and creatine kinase activities in prefrontal cortex, hippocampus and striatum. Our results showed that both acute and chronic treatments with memantine or imipramine altered respiratory chain complexes and creatine kinase activities in rat brain; however, these alterations were different with relation to protocols (acute or chronic), complex, dose and brain area. Finally, these findings further support the hypothesis that the effects of imipramine and memantine could be involve mitochondrial function modulation.

  16. Alterations in Daytime and Nighttime Activity in Piglets after Focal and Diffuse Brain Injury.

    PubMed

    Olson, Emily; Badder, Carlie; Sullivan, Sarah; Smith, Colin; Propert, Kathleen; Margulies, Susan S

    2016-04-15

    We have developed and implemented a noninvasive, objective neurofunctional assessment for evaluating the sustained effects of traumatic brain injury (TBI) in piglets with both diffuse and focal injury types. Derived from commercial actigraphy methods in humans, this assessment continuously monitors the day/night activity of piglets using close-fitting jackets equipped with tri-axial accelerometers to monitor movements of the thorax. Acceleration metrics were correlated (N = 7 naïve piglets) with video images to define values associated with a range of activities, from recumbancy (rest) to running. Both focal (N = 8) and diffuse brain injury (N = 9) produced alterations in activity that were significant 4 days post-TBI. Compared to shams (N = 6) who acclimated to the animal facility 4 days after an anesthesia experience by blurring the distinction between day and night activity, post-TBI time-matched animals had larger fractions of inactive periods during the daytime than nighttime, and larger fractions of active time in the night were spent in high activity (e.g., constant walking, intermittent running) than during the day. These persistent disturbances in rest and activity are similar to those observed in human adults and children post-TBI, establishing actigraphy as a translational metric, used in both humans and large animals, for assessment of injury severity, progressions, and intervention.

  17. Exercise-induced Alteration in Brain Activity during Motor Performance under Cognitive Stress

    DTIC Science & Technology

    2014-07-02

    stress . It is possible that the correlated activity between EEG and EMG is used for “fine-tuning” brain activity during the performance of fine motor...brain and muscle during simple fine motor performance under stress after high-intensity physical exertion. Healthy young adults were assigned to...leg resistance exercise. Oscillations in EEG and corticomuscular coherence in beta band both tended to decrease 1. REPORT DATE (DD-MM-YYYY) 4. TITLE

  18. From Nose to Brain: Un-Sensed Electrical Currents Applied in the Nose Alter Activity in Deep Brain Structures

    PubMed Central

    Weiss, Tali; Shushan, Sagit; Ravia, Aharon; Hahamy, Avital; Secundo, Lavi; Weissbrod, Aharon; Ben-Yakov, Aya; Holtzman, Yael; Cohen-Atsmoni, Smadar; Roth, Yehudah; Sobel, Noam

    2016-01-01

    Rules linking patterns of olfactory receptor neuron activation in the nose to activity patterns in the brain and ensuing odor perception remain poorly understood. Artificially stimulating olfactory neurons with electrical currents and measuring ensuing perception may uncover these rules. We therefore inserted an electrode into the nose of 50 human volunteers and applied various currents for about an hour in each case. This induced assorted non-olfactory sensations but never once the perception of odor. To validate contact with the olfactory path, we used functional magnetic resonance imaging to measure resting-state brain activity in 18 subjects before and after un-sensed stimulation. We observed stimulation-induced neural decorrelation specifically in primary olfactory cortex, implying contact with the olfactory path. These results suggest that indiscriminate olfactory activation does not equate with odor perception. Moreover, this effort serendipitously uncovered a novel path for minimally invasive brain stimulation through the nose. PMID:27591145

  19. From Nose to Brain: Un-Sensed Electrical Currents Applied in the Nose Alter Activity in Deep Brain Structures.

    PubMed

    Weiss, Tali; Shushan, Sagit; Ravia, Aharon; Hahamy, Avital; Secundo, Lavi; Weissbrod, Aharon; Ben-Yakov, Aya; Holtzman, Yael; Cohen-Atsmoni, Smadar; Roth, Yehudah; Sobel, Noam

    2016-09-02

    Rules linking patterns of olfactory receptor neuron activation in the nose to activity patterns in the brain and ensuing odor perception remain poorly understood. Artificially stimulating olfactory neurons with electrical currents and measuring ensuing perception may uncover these rules. We therefore inserted an electrode into the nose of 50 human volunteers and applied various currents for about an hour in each case. This induced assorted non-olfactory sensations but never once the perception of odor. To validate contact with the olfactory path, we used functional magnetic resonance imaging to measure resting-state brain activity in 18 subjects before and after un-sensed stimulation. We observed stimulation-induced neural decorrelation specifically in primary olfactory cortex, implying contact with the olfactory path. These results suggest that indiscriminate olfactory activation does not equate with odor perception. Moreover, this effort serendipitously uncovered a novel path for minimally invasive brain stimulation through the nose.

  20. Altered regional homogeneity of spontaneous brain activity in idiopathic trigeminal neuralgia

    PubMed Central

    Wang, Yanping; Zhang, Xiaoling; Guan, Qiaobing; Wan, Lihong; Yi, Yahui; Liu, Chun-Feng

    2015-01-01

    The pathophysiology of idiopathic trigeminal neuralgia (ITN) has conventionally been thought to be induced by neurovascular compression theory. Recent structural brain imaging evidence has suggested an additional central component for ITN pathophysiology. However, far less attention has been given to investigations of the basis of abnormal resting-state brain activity in these patients. The objective of this study was to investigate local brain activity in patients with ITN and its correlation with clinical variables of pain. Resting-state functional magnetic resonance imaging data from 17 patients with ITN and 19 age- and sex-matched healthy controls were analyzed using regional homogeneity (ReHo) analysis, which is a data-driven approach used to measure the regional synchronization of spontaneous brain activity. Patients with ITN had decreased ReHo in the left amygdala, right parahippocampal gyrus, and left cerebellum and increased ReHo in the right inferior temporal gyrus, right thalamus, right inferior parietal lobule, and left postcentral gyrus (corrected). Furthermore, the increase in ReHo in the left precentral gyrus was positively correlated with visual analog scale (r=0.54; P=0.002). Our study found abnormal functional homogeneity of intrinsic brain activity in several regions in ITN, suggesting the maladaptivity of the process of daily pain attacks and a central role for the pathophysiology of ITN. PMID:26508861

  1. Altered Spontaneous Brain Activity in Betel Quid Dependence: A Resting-state Functional Magnetic Resonance Imaging Study.

    PubMed

    Liu, Tao; Li, Jian-Jun; Zhao, Zhong-Yan; Yang, Guo-Shuai; Pan, Meng-Jie; Li, Chang-Qing; Pan, Su-Yue; Chen, Feng

    2016-02-01

    It has been suggested by the first voxel-based morphometry investigation that betel quid dependence (BQD) individuals are presented with brain structural changes in previous reports, and there may be a neurobiological basis for BQD individuals related to an increased risk of executive dysfunction and disinhibition, subjected to the reward system, cognitive system, and emotion system. However, the effects of BQD on neural activity remain largely unknown. Individuals with impaired cognitive control of behavior often reveal altered spontaneous cerebral activity in resting-state functional magnetic resonance imaging and those changes are usually earlier than structural alteration.Here, we examined BQD individuals (n = 33) and age-, sex-, and education-matched healthy control participants (n = 32) in an resting-state functional magnetic resonance imaging study to observe brain function alterations associated with the severity of BQD. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were both evaluated to stand for spontaneous cerebral activity. Gray matter volumes of these participants were also calculated for covariate.In comparison with healthy controls, BQD individuals demonstrated dramatically decreased ALFF and ReHo values in the prefrontal gurus along with left fusiform, and increased ALFF and ReHo values in the primary motor cortex area, temporal lobe as well as some regions of occipital lobe. The betel quid dependence scores (BQDS) were negatively related to decreased activity in the right anterior cingulate.The abnormal spontaneous cerebral activity revealed by ALFF and ReHo calculation excluding the structural differences in patients with BQD may help us probe into the neurological pathophysiology underlying BQD-related executive dysfunction and disinhibition. Diminished spontaneous brain activity in the right anterior cingulate cortex may, therefore, represent a biomarker of BQD individuals.

  2. Traumatic alterations in GABA signaling disrupt hippocampal network activity in the developing brain

    PubMed Central

    Dzhala, Volodymyr; Valeeva, Guzel; Glykys, Joseph; Khazipov, Rustem; Staley, Kevin

    2012-01-01

    Severe head trauma causes widespread neuronal shear injuries and acute seizures. Shearing of neural processes might contribute to seizures by disrupting the transmembrane ion gradients that subserve normal synaptic signaling. To test this possibility, we investigated changes in intracellular chloride concentration ([Cl−]i) associated with the widespread neural shear injury induced during preparation of acute brain slices. In hippocampal slices and intact hippocampal preparations from immature CLM-1 mice, increases in [Cl−]i correlated with disruption of neural processes and biomarkers of cell injury. Traumatized neurons with higher [Cl−]i demonstrated excitatory GABA signaling, remained synaptically active, and facilitated network activity as assayed by the frequency of extracellular action potentials and spontaneous network-driven oscillations. These data support a more inhibitory role for GABA in the unperturbed immature brain, demonstrate the utility of the acute brain slice preparation for the study of the consequences of trauma, and provide potential mechanisms for both GABA-mediated excitatory network events in the slice preparation and early post-traumatic seizures. PMID:22442068

  3. The unrested resting brain: sleep deprivation alters activity within the default-mode network.

    PubMed

    Gujar, Ninad; Yoo, Seung-Schik; Hu, Peter; Walker, Matthew P

    2010-08-01

    The sleep-deprived brain has principally been characterized by examining dysfunction during cognitive task performance. However, far less attention has been afforded the possibility that sleep deprivation may be as, if not more, accurately characterized on the basis of abnormal resting-state brain activity. Here we report that one night of sleep deprivation significantly disrupts the canonical signature of task-related deactivation, resulting in a double dissociation within anterior as well as posterior midline regions of the default network. Indeed, deactivation within these regions alone discriminated sleep-deprived from sleep-control subjects with a 93% degree of sensitivity and 92% specificity. In addition, the relative balance of deactivation within these default nodes significantly correlated with the amount of prior sleep in the control group (and not extended time awake in the deprivation group). Therefore, the stability and the balance of task-related deactivation in key default-mode regions may be dependent on prior sleep, such that a lack thereof disrupts this signature pattern of brain activity, findings that may offer explanatory insights into conditions associated with sleep loss at both a clinical as well as societal level.

  4. Maternal immune activation alters glutamic acid decarboxylase-67 expression in the brains of adult rat offspring

    PubMed Central

    Cassella, Sarah N.; Hemmerle, Ann M.; Lundgren, Kerstin H.; Kyser, Tara L.; Ahlbrand, Rebecca; Bronson, Stefanie L.; Richtand, Neil M.; Seroogy, Kim B.

    2016-01-01

    Activation of the maternal innate immune system, termed “maternal immune activation” (MIA), represents a common environmental risk factor for schizophrenia. Whereas evidence suggests dysregulation of GABA systems may underlie the pathophysiology of schizophrenia, a role for MIA in alteration of GABAergic systems is less clear. Here, pregnant rats received either the viral mimetic polyriboinosinic-polyribocytidilic acid or vehicle injection on gestational day 14. Glutamic acid decarboxylase-67 (GAD67) mRNA expression was examined in male offspring at postnatal day (P)14, P30 and P60. At P60, GAD67 mRNA was elevated in hippocampus and thalamus and decreased in prefrontal cortex of MIA offspring. MIA-induced alterations in GAD expression could contribute to the pathophysiology of schizophrenia. PMID:26830319

  5. It still hurts: altered endogenous opioid activity in the brain during social rejection and acceptance in major depressive disorder.

    PubMed

    Hsu, D T; Sanford, B J; Meyers, K K; Love, T M; Hazlett, K E; Walker, S J; Mickey, B J; Koeppe, R A; Langenecker, S A; Zubieta, J-K

    2015-02-01

    The μ-opioid receptor (MOR) system, well known for dampening physical pain, is also hypothesized to dampen 'social pain.' We used positron emission tomography scanning with the selective MOR radioligand [(11)C]carfentanil to test the hypothesis that MOR system activation (reflecting endogenous opioid release) in response to social rejection and acceptance is altered in medication-free patients diagnosed with current major depressive disorder (MDD, n=17) compared with healthy controls (HCs, n=18). During rejection, MDD patients showed reduced endogenous opioid release in brain regions regulating stress, mood and motivation, and slower emotional recovery compared with HCs. During acceptance, only HCs showed increased social motivation, which was positively correlated with endogenous opioid release in the nucleus accumbens, a reward structure. Altered endogenous opioid activity in MDD may hinder emotional recovery from negative social interactions and decrease pleasure derived from positive interactions. Both effects may reinforce depression, trigger relapse and contribute to poor treatment outcomes.

  6. Alterations in Brain Activation During Cognitive Empathy Are Related to Social Functioning in Schizophrenia

    PubMed Central

    Smith, Matthew J.; Schroeder, Matthew P.; Abram, Samantha V.; Goldman, Morris B.; Parrish, Todd B.; Wang, Xue; Derntl, Birgit; Habel, Ute; Decety, Jean; Reilly, James L.; Csernansky, John G.; Breiter, Hans C.

    2015-01-01

    Impaired cognitive empathy (ie, understanding the emotional experiences of others) is associated with poor social functioning in schizophrenia. However, it is unclear whether the neural activity underlying cognitive empathy relates to social functioning. This study examined the neural activation supporting cognitive empathy performance and whether empathy-related activation during correctly performed trials was associated with self-reported cognitive empathy and measures of social functioning. Thirty schizophrenia outpatients and 24 controls completed a cognitive empathy paradigm during functional magnetic resonance imaging. Neural activity corresponding to correct judgments about the expected emotional expression in a social interaction was compared in schizophrenia subjects relative to control subjects. Participants also completed a self-report measure of empathy and 2 social functioning measures (social competence and social attainment). Schizophrenia subjects demonstrated significantly lower accuracy in task performance and were characterized by hypoactivation in empathy-related frontal, temporal, and parietal regions as well as hyperactivation in occipital regions compared with control subjects during accurate cognitive empathy trials. A cluster with peak activation in the supplementary motor area (SMA) extending to the anterior midcingulate cortex (aMCC) correlated with social competence and social attainment in schizophrenia subjects but not controls. These results suggest that neural correlates of cognitive empathy may be promising targets for interventions aiming to improve social functioning and that brain activation in the SMA/aMCC region could be used as a biomarker for monitoring treatment response. PMID:24583906

  7. Alterations in brain activation during cognitive empathy are related to social functioning in schizophrenia.

    PubMed

    Smith, Matthew J; Schroeder, Matthew P; Abram, Samantha V; Goldman, Morris B; Parrish, Todd B; Wang, Xue; Derntl, Birgit; Habel, Ute; Decety, Jean; Reilly, James L; Csernansky, John G; Breiter, Hans C

    2015-01-01

    Impaired cognitive empathy (ie, understanding the emotional experiences of others) is associated with poor social functioning in schizophrenia. However, it is unclear whether the neural activity underlying cognitive empathy relates to social functioning. This study examined the neural activation supporting cognitive empathy performance and whether empathy-related activation during correctly performed trials was associated with self-reported cognitive empathy and measures of social functioning. Thirty schizophrenia outpatients and 24 controls completed a cognitive empathy paradigm during functional magnetic resonance imaging. Neural activity corresponding to correct judgments about the expected emotional expression in a social interaction was compared in schizophrenia subjects relative to control subjects. Participants also completed a self-report measure of empathy and 2 social functioning measures (social competence and social attainment). Schizophrenia subjects demonstrated significantly lower accuracy in task performance and were characterized by hypoactivation in empathy-related frontal, temporal, and parietal regions as well as hyperactivation in occipital regions compared with control subjects during accurate cognitive empathy trials. A cluster with peak activation in the supplementary motor area (SMA) extending to the anterior midcingulate cortex (aMCC) correlated with social competence and social attainment in schizophrenia subjects but not controls. These results suggest that neural correlates of cognitive empathy may be promising targets for interventions aiming to improve social functioning and that brain activation in the SMA/aMCC region could be used as a biomarker for monitoring treatment response.

  8. Early and later life stress alter brain activity and sleep in rats.

    PubMed

    Mrdalj, Jelena; Pallesen, Ståle; Milde, Anne Marita; Jellestad, Finn Konow; Murison, Robert; Ursin, Reidun; Bjorvatn, Bjørn; Grønli, Janne

    2013-01-01

    Exposure to early life stress may profoundly influence the developing brain in lasting ways. Neuropsychiatric disorders associated with early life adversity may involve neural changes reflected in EEG power as a measure of brain activity and disturbed sleep. The main aim of the present study was for the first time to characterize possible changes in adult EEG power after postnatal maternal separation in rats. Furthermore, in the same animals, we investigated how EEG power and sleep architecture were affected after exposure to a chronic mild stress protocol. During postnatal day 2-14 male rats were exposed to either long maternal separation (180 min) or brief maternal separation (10 min). Long maternally separated offspring showed a sleep-wake nonspecific reduction in adult EEG power at the frontal EEG derivation compared to the brief maternally separated group. The quality of slow wave sleep differed as the long maternally separated group showed lower delta power in the frontal-frontal EEG and a slower reduction of the sleep pressure. Exposure to chronic mild stress led to a lower EEG power in both groups. Chronic exposure to mild stressors affected sleep differently in the two groups of maternal separation. Long maternally separated offspring showed more total sleep time, more episodes of rapid eye movement sleep and higher percentage of non-rapid eye movement episodes ending in rapid eye movement sleep compared to brief maternal separation. Chronic stress affected similarly other sleep parameters and flattened the sleep homeostasis curves in all offspring. The results confirm that early environmental conditions modulate the brain functioning in a long-lasting way.

  9. Altered Resting-State Brain Activity and Connectivity in Depressed Parkinson's Disease.

    PubMed

    Hu, Xiao; Song, Xiaopeng; Li, Erfeng; Liu, Jiajia; Yuan, Yonggui; Liu, Weiguo; Liu, Yijun

    2015-01-01

    Depressive symptoms are common in Parkinson's disease (PD), but the neurophysiological mechanisms of depression in PD are poorly understood. The current study attempted to examine disrupted spontaneous local brain activities and functional connectivities that underlie the depression in PD. We recruited a total of 20 depressed PD patients (DPD), 40 non-depressed PD patients (NDPD) and 43 matched healthy controls (HC). All the subjects underwent neuropsychological tests and resting-state fMRI scanning. The between-group differences in the amplitude of low frequency fluctuations (ALFF) of BOLD signals were examined using post-hoc tests after the analysis of covariance. Compared with the NDPD and HC, the DPD group showed significantly increased ALFF in the left median cingulated cortex (MCC). The functional connectivity (FC) between left MCC and all the other voxels in the brain were then calculated. Compared with the HC and NDPD group, the DPD patients showed stronger FC between the left MCC and some of the major nodes of the default mode network (DMN), including the post cingulated cortex/precuneus, medial prefrontal cortex, inferior frontal gyrus, and cerebellum. Correlation analysis revealed that both the ALFF values in the left MCC and the FC between the left MCC and the nodes of DMN were significantly correlated with the Hamilton Depression Rating Scale score. Moreover, higher local activities in the left MCC were associated with increased functional connections between the MCC and the nodes of DMN in PD. These abnormal activities and connectivities of the limbic-cortical circuit may indicate impaired high-order cortical control or uncontrol of negative mood in DPD, which suggested a possible neural mechanism of the depression in PD.

  10. Does changing from a first generation antipsychotic (perphenazin) to a second generation antipsychotic (risperidone) alter brain activation and motor activity? A case report

    PubMed Central

    2013-01-01

    Background In patients with schizophrenia, altered brain activation and motor activity levels are central features, reflecting cognitive impairments and negative symptoms, respectively. Newer studies using nonlinear methods have addressed the severe disturbances in neurocognitive functioning that is regarded as one of the core features of schizophrenia. Our aim was to compare brain activation and motor activity in a patient during pharmacological treatment that was switched from a first- to a second-generation antipsychotic drug. We hypothesised that this change of medication would increase level of responding in both measures. Case presentation We present the case of a 53-year-old male with onset of severe mental illness in adolescence, ICD-10 diagnosed as schizophrenia of paranoid type, chronic form. We compared brain activation and motor activity in this patient during pharmacological treatment with a first-generation (perphenazin), and later switched to a second-generation (risperidone) antipsychotic drug. We used functional magnetic resonance imaging (fMRI) to measure brain activation and wrist worn actigraphy to measure motor activity. Conclusion Our study showed that brain activation decreased in areas critical for cognitive functioning in this patient, when changing from a first to a second generation antipsychotic drug. However the mean motor activity level was unchanged, although risperidone reduced variability, particularly short-term variability from minute to minute. Compared to the results from previous studies, the present findings indicate that changing to a second-generation antipsychotic alters variability measures towards that seen in a control group, but with reduced brain activation, which was an unexpected finding. PMID:23648137

  11. Neurophysiological activity underlying altered brain metabolism in epileptic encephalopathies with CSWS.

    PubMed

    De Tiège, Xavier; Trotta, Nicola; Op de Beeck, Marc; Bourguignon, Mathieu; Marty, Brice; Wens, Vincent; Nonclercq, Antoine; Goldman, Serge; Van Bogaert, Patrick

    2013-08-01

    We investigated the neurophysiological correlate of altered regional cerebral glucose metabolism observed in children with epileptic encephalopathy with continuous spike-waves during sleep (CSWS) by using a multimodal approach combining time-sensitive magnetic source imaging (MSI) and positron emission tomography with [(18)F]-fluorodeoxyglucose (FDG-PET). Six patients (4 boys and 2 girls, age range: 4-8 years, 3 patients with Landau-Kleffner syndrome (LKS), 3 patients with atypical rolandic epilepsy (ARE)) were investigated by FDG-PET and MSI at the acute phase of CSWS. In all patients, the onset(s) of spike-waves discharges were associated with significant focal hypermetabolism. The propagation of epileptic discharges to other brain areas was associated with focal hypermetabolism (five patients), hypometabolism (one patient) or the absence of any significant metabolic change (one patient). Interestingly, most of the hypometabolic areas were not involved in the epileptic network per se. This study shows that focal hypermetabolism observed at the acute phase of CSWS are related to the onset or propagation sites of spike-wave discharges. Spike-wave discharges propagation can be associated to other types of metabolic changes, suggesting the occurrence of various neurophysiological mechanisms at the cellular level. Most of the hypometabolic areas are not involved in the epileptic network as such and are probably related to a mechanism of remote inhibition. These findings highlight the critical value of combining FDG-PET with time-sensitive functional neuroimaging approaches such as MSI to assess CSWS epileptic network when surgery is considered as a therapeutic approach.

  12. Prenatal drug exposure to illicit drugs alters working memory-related brain activity and underlying network properties in adolescence.

    PubMed

    Schweitzer, Julie B; Riggins, Tracy; Liang, Xia; Gallen, Courtney; Kurup, Pradeep K; Ross, Thomas J; Black, Maureen M; Nair, Prasanna; Salmeron, Betty Jo

    2015-01-01

    The persistence of effects of prenatal drug exposure (PDE) on brain functioning during adolescence is poorly understood. We explored neural activation to a visuospatial working memory (VSWM) versus a control task using functional magnetic resonance imaging (fMRI) in adolescents with PDE and a community comparison group (CC) of non-exposed adolescents. We applied graph theory metrics to resting state data using a network of nodes derived from the VSWM task activation map to further explore connectivity underlying WM functioning. Participants (ages 12-15 years) included 47 adolescents (27 PDE and 20 CC). All analyses controlled for potentially confounding differences in birth characteristics and postnatal environment. Significant group by task differences in brain activation emerged in the left middle frontal gyrus (BA 6) with the CC group, but not the PDE group, activating this region during VSWM. The PDE group deactivated the culmen, whereas the CC group activated it during the VSWM task. The CC group demonstrated a significant relation between reaction time and culmen activation, not present in the PDE group. The network analysis underlying VSWM performance showed that PDE group had lower global efficiency than the CC group and a trend level reduction in local efficiency. The network node corresponding to the BA 6 group by task interaction showed reduced nodal efficiency and fewer direct connections to other nodes in the network. These results suggest that adolescence reveals altered neural functioning related to response planning that may reflect less efficient network functioning in youth with PDE.

  13. Altered Expression of Brain Proteinase-Activated Receptor-2, Trypsin-2 and Serpin Proteinase Inhibitors in Parkinson's Disease.

    PubMed

    Hurley, Michael J; Durrenberger, Pascal F; Gentleman, Steve M; Walls, Andrew F; Dexter, David T

    2015-09-01

    Neuroinflammation is thought to contribute to cell death in neurodegenerative disorders, but the factors involved in the inflammatory process are not completely understood. Proteinase-activated receptor-2 (PAR2) expression in brain is increased in Alzheimer's disease and multiple sclerosis, but the status of PAR2 in Parkinson's disease is unknown. This study examined expression of PAR2 and endogenous proteinase activators (trypsin-2, mast cell tryptase) and proteinase inhibitors (serpin-A5, serpin-A13) in areas vulnerable and resistant to neurodegeneration in Parkinson's disease at different Braak α-synuclein stages of the disease in post-mortem brain. In normal aged brain, expression of PAR-2, trypsin-2, and serpin-A5 and serpin-A13 was found in neurons and microglia, and alterations in the amount of immunoreactivity for these proteins were found in some brain regions. Namely, there was a decrease in neurons positive for serpin-A5 in the dorsal motor nucleus, and serpin-A13 expression was reduced in the locus coeruleus and primary motor cortex, while expression of PAR2, trypsin-2 and both serpins was reduced in neurons within the substantia nigra. There was an increased number of microglia that expressed serpin-A5 in the dorsal motor nucleus of vagus and elevated numbers of microglia that expressed serpin-A13 in the substantia nigra of late Parkinson's disease cases. The number of microglia that expressed trypsin-2 increased in primary motor cortex of incidental Lewy body disease cases. Analysis of Parkinson's disease cases alone indicated that serpin-A5 and serpin-A13, and trypsin-2 expression in midbrain and cerebral cortex was different in cases with a high incidence of L-DOPA-induced dyskinesia and psychosis compared to those with low levels of these treatment-induced side effects. This study showed that there was altered expression in brain of PAR2 and some proteins that can control its function in Parkinson's disease. Given the role of PAR2 in

  14. Zebrafish locomotor capacity and brain acetylcholinesterase activity is altered by Aphanizomenon flos-aquae DC-1 aphantoxins.

    PubMed

    Zhang, De Lu; Hu, Chun Xiang; Li, Dun Hai; Liu, Yong Ding

    2013-08-15

    Aphanizomenon flos-aquae (A. flos-aquae) is a source of neurotoxins known as aphantoxins or paralytic shellfish poisons (PSPs) that present a major threat to the environment and to human health. Generally, altered neurological function is reflected in behavior. Although the molecular mechanism of action of PSPs is well known, its neurobehavioral effects on adult zebrafish and its relationship with altered neurological functions are poorly understood. Aphantoxins purified from a natural isolate of A. flos-aquae DC-1 were analyzed by HPLC. The major analogs found in the toxins were the gonyautoxins 1 and 5 (GTX1 and GTX5; 34.04% and 21.28%, respectively) and the neosaxitoxin (neoSTX, 12.77%). Zebrafish (Danio rerio) were intraperitoneally injected with 5.3 and 7.61 μg STXeq/kg (low and high dose, respectively) of A. flos-aquae DC-1 aphantoxins. The swimming activity was investigated by observation combined with video at 6 timepoints from 1 to 24 h post-exposure. Both aphantoxin doses were associated with delayed touch responses, reduced head-tail locomotory abilities, inflexible turning of head, and a tailward-shifted center of gravity. The normal S-pattern (or undulating) locomotor trajectory was replaced by a mechanical motor pattern of swinging the head after wagging the tail. Finally, these fish principally distributed at the top and/or bottom water of the aquarium, and showed a clear polarized distribution pattern at 12 h post-exposure. Further analysis of neurological function demonstrated that both aphantoxin doses inhibited brain acetylcholinesterase activity. All these changes were dose- and time-dependent. These results demonstrate that aphantoxins can alter locomotor capacity, touch responses and distribution patterns by damaging the cholinergic system of zebrafish, and suggest that zebrafish locomotor behavior and acetylcholinesterase can be used as indicators for investigating aphantoxins and blooms in nature.

  15. Prenatal ethanol exposure alters ethanol-induced Fos immunoreactivity and dopaminergic activity in the mesocorticolimbic pathway of the adolescent brain.

    PubMed

    Fabio, M C; Vivas, L M; Pautassi, R M

    2015-08-20

    Prenatal ethanol exposure (PEE) promotes alcohol intake during adolescence, as shown in clinical and pre-clinical animal models. The mechanisms underlying this effect of prenatal ethanol exposure on postnatal ethanol intake remain, however, mostly unknown. Few studies assessed the effects of moderate doses of prenatal ethanol on spontaneous and ethanol-induced brain activity on adolescence. This study measured, in adolescent (female) Wistar rats prenatally exposed to ethanol (0.0 or 2.0g/kg/day, gestational days 17-20) or non-manipulated (NM group) throughout pregnancy, baseline and ethanol-induced cathecolaminergic activity (i.e., colocalization of c-Fos and tyrosine hydroxylase) in ventral tegmental area (VTA), and baseline and ethanol-induced Fos immunoreactivity (ir) in nucleus accumbens shell and core (AcbSh and AcbC, respectively) and prelimbic (PrL) and infralimbic (IL) prefrontal cortex. The rats were challenged with ethanol (dose: 0.0, 1.25, 2.5 or 3.25g/kg, i.p.) at postnatal day 37. Rats exposed to vehicle prenatally (VE group) exhibited reduced baseline dopaminergic tone in VTA; an effect that was inhibited by prenatal ethanol exposure (PEE group). Dopaminergic activity in VTA after the postnatal ethanol challenge was greater in PEE than in VE or NM animals. Ethanol-induced Fos-ir at AcbSh was found after 1.25g/kg and 2.5g/kg ethanol, in VE and PEE rats, respectively. PEE did not alter ethanol-induced Fos-ir at IL but reduced ethanol-induced Fos-ir at PrL. These results suggest that prenatal ethanol exposure heightens dopaminergic activity in the VTA and alters the response of the mesocorticolimbic pathway to postnatal ethanol exposure. These effects may underlie the enhanced vulnerability to develop alcohol-use disorders of adolescents with a history of in utero ethanol exposure.

  16. It still hurts: altered opioid activity in the brain during social rejection and acceptance in major depressive disorder

    PubMed Central

    Hsu, David T; Sanford, Benjamin J; Meyers, Kortni K; Love, Tiffany M; Hazlett, Kathleen E; Walker, Sara J; Mickey, Brian J; Koeppe, Robert A; Langenecker, Scott A; Zubieta, Jon-Kar

    2015-01-01

    The μ-opioid receptor (MOR) system, well known for dampening physical pain, is also hypothesized to dampen “social pain.” We used positron emission tomography scanning with the selective MOR radioligand [11C]carfentanil to test the hypothesis that MOR system activation in response to social rejection and acceptance is altered in medication-free patients diagnosed with current major depressive disorder (MDD, n = 17) compared to healthy controls (HCs, n = 18). During rejection, MDD patients showed reduced MOR activation (e.g., reduced endogenous opioid release) in brain regions regulating stress, mood, and motivation, and slower emotional recovery compared to HCs. During acceptance, only HCs showed increased social motivation, which was positively correlated with MOR activation in the nucleus accumbens, a reward structure. Abnormal MOR function in MDD may hinder emotional recovery from negative social interactions and decrease pleasure derived from positive interactions. Both effects may reinforce depression, trigger relapse, and contribute to poor treatment outcomes. PMID:25600108

  17. Functional MRI signal fluctuations highlight altered resting brain activity in Huntington's disease.

    PubMed

    Sarappa, Chiara; Salvatore, Elena; Filla, Alessandro; Cocozza, Sirio; Russo, Cinzia Valeria; Saccà, Francesco; Brunetti, Arturo; De Michele, Giuseppe; Quarantelli, Mario

    2016-10-12

    The fractional Amplitude of Low Frequency Fluctuations (fALFF) and the degree of local synchronization (Regional Homogeneity - ReHo) of resting-state BOLD signal have been suggested to map spontaneous neuronal activity and local functional connectivity, respectively. We compared voxelwise, independent of atrophy, the fALFF and ReHo patterns of 11 presymptomatic (ps-HD) and 28 symptomatic (sHD) Huntington's disease mutation carriers, with those of 40 normal volunteers, and tested their possible correlations with the motor and cognitive subscores of the Unified Huntington's Disease Rating Scale. In sHD patients, fALFF was mainly reduced bilaterally in parietal lobes (right precuneus being already affected in psHD), and in superior frontal gyri, and increased bilaterally in cerebellar lobules VI, VIII and IX, as well as in the right inferior temporal gyrus. In sHD, and to a lesser extent in psHD, ReHo was bilaterally reduced in putamina, cerebellar lobules III to VI, and superior medial frontal gyri, and increased in both psHD and sHD in fronto-basal cortices, and in the right temporal lobe. fALFF correlated inversely with cognitive scores in lobule IX of the cerebellum (mainly with total Stroop score, p < 0.0001), and in the medial portions of both thalami. These results are consistent with a reduced neuronal activity in the cortical components of the executive networks, known to be affected in Huntington's Disease, and with reduced local functional integration in subcortical and cerebellar components of the sensori-motor network. Cerebellar clusters of significant correlation of fALFF with executive function scores may be related to compensatory mechanisms.

  18. Age-related learning and memory deficits in rats: role of altered brain neurotransmitters, acetylcholinesterase activity and changes in antioxidant defense system.

    PubMed

    Haider, Saida; Saleem, Sadia; Perveen, Tahira; Tabassum, Saiqa; Batool, Zehra; Sadir, Sadia; Liaquat, Laraib; Madiha, Syeda

    2014-06-01

    Oxidative stress from generation of increased reactive oxygen species or free radicals of oxygen has been reported to play an important role in the aging. To investigate the relationship between the oxidative stress and memory decline during aging, we have determined the level of lipid peroxidation, activities of antioxidant enzymes, and activity of acetylcholine esterase (AChE) in brain and plasma as well as biogenic amine levels in brain from Albino-Wistar rats at age of 4 and 24 months. The results showed that the level of lipid peroxidation in the brain and plasma was significantly higher in older than that in the young rats. The activities of antioxidant enzymes displayed an age-dependent decline in both brain and plasma. Glutathione peroxidase and catalase activities were found to be significantly decreased in brain and plasma of aged rats. Superoxide dismutase (SOD) was also significantly decreased in plasma of aged rats; however, a decreased tendency (non-significant) of SOD in brain was also observed. AChE activity in brain and plasma was significantly decreased in aged rats. Learning and memory of rats in the present study was assessed by Morris Water Maze (MWM) and Elevated plus Maze (EPM) test. Short-term memory and long-term memory was impaired significantly in older rats, which was evident by a significant increase in the latency time in MWM and increase in transfer latency in EPM. Moreover, a marked decrease in biogenic amines (NA, DA, and 5-HT) was also found in the brain of aged rats. In conclusion, our data suggest that increased oxidative stress, decline of antioxidant enzyme activities, altered AChE activity, and decreased biogenic amines level in the brain of aged rats may potentially be involved in diminished memory function.

  19. A novel fMRI paradigm suggests that pedaling-related brain activation is altered after stroke.

    PubMed

    Promjunyakul, Nutta-On; Schmit, Brian D; Schindler-Ivens, Sheila M

    2015-01-01

    The purpose of this study was to examine the feasibility of using functional magnetic resonance imaging (fMRI) to measure pedaling-related brain activation in individuals with stroke and age-matched controls. We also sought to identify stroke-related changes in brain activation associated with pedaling. Fourteen stroke and 12 control subjects were asked to pedal a custom, MRI-compatible device during fMRI. Subjects also performed lower limb tapping to localize brain regions involved in lower limb movement. All stroke and control subjects were able to pedal while positioned for fMRI. Two control subjects were withdrawn due to claustrophobia, and one control data set was excluded from analysis due to an incidental finding. In the stroke group, one subject was unable to enter the gantry due to excess adiposity, and one stroke data set was excluded from analysis due to excessive head motion. Consequently, 81% of subjects (12/14 stroke, 9/12 control) completed all procedures and provided valid pedaling-related fMRI data. In these subjects, head motion was ≤3 mm. In both groups, brain activation localized to the medial aspect of M1, S1, and Brodmann's area 6 (BA6) and to the cerebellum (vermis, lobules IV, V, VIII). The location of brain activation was consistent with leg areas. Pedaling-related brain activation was apparent on both sides of the brain, with values for laterality index (LI) of -0.06 (0.20) in the stroke cortex, 0.05 (±0.06) in the control cortex, 0.29 (0.33) in the stroke cerebellum, and 0.04 (0.15) in the control cerebellum. In the stroke group, activation in the cerebellum - but not cortex - was significantly lateralized toward the damaged side of the brain (p = 0.01). The volume of pedaling-related brain activation was smaller in stroke as compared to control subjects. Differences reached statistical significance when all active regions were examined together [p = 0.03; 27,694 (9,608) μL stroke; 37,819 (9,169) μL control]. When individual regions

  20. A novel fMRI paradigm suggests that pedaling-related brain activation is altered after stroke

    PubMed Central

    Promjunyakul, Nutta-on; Schmit, Brian D.; Schindler-Ivens, Sheila M.

    2015-01-01

    The purpose of this study was to examine the feasibility of using functional magnetic resonance imaging (fMRI) to measure pedaling-related brain activation in individuals with stroke and age-matched controls. We also sought to identify stroke-related changes in brain activation associated with pedaling. Fourteen stroke and 12 control subjects were asked to pedal a custom, MRI-compatible device during fMRI. Subjects also performed lower limb tapping to localize brain regions involved in lower limb movement. All stroke and control subjects were able to pedal while positioned for fMRI. Two control subjects were withdrawn due to claustrophobia, and one control data set was excluded from analysis due to an incidental finding. In the stroke group, one subject was unable to enter the gantry due to excess adiposity, and one stroke data set was excluded from analysis due to excessive head motion. Consequently, 81% of subjects (12/14 stroke, 9/12 control) completed all procedures and provided valid pedaling-related fMRI data. In these subjects, head motion was ≤3 mm. In both groups, brain activation localized to the medial aspect of M1, S1, and Brodmann’s area 6 (BA6) and to the cerebellum (vermis, lobules IV, V, VIII). The location of brain activation was consistent with leg areas. Pedaling-related brain activation was apparent on both sides of the brain, with values for laterality index (LI) of –0.06 (0.20) in the stroke cortex, 0.05 (±0.06) in the control cortex, 0.29 (0.33) in the stroke cerebellum, and 0.04 (0.15) in the control cerebellum. In the stroke group, activation in the cerebellum – but not cortex – was significantly lateralized toward the damaged side of the brain (p = 0.01). The volume of pedaling-related brain activation was smaller in stroke as compared to control subjects. Differences reached statistical significance when all active regions were examined together [p = 0.03; 27,694 (9,608) μL stroke; 37,819 (9,169) μL control]. When individual

  1. Altered intrinsic regional brain spontaneous activity in patients with comitant strabismus: a resting-state functional MRI study

    PubMed Central

    Huang, Xin; Li, Sheng-Hong; Zhou, Fu-Qing; Zhang, Ying; Zhong, Yu-Lin; Cai, Feng-Qin; Shao, Yi; Zeng, Xian-Jun

    2016-01-01

    Objective To investigate the underlying regional homogeneity (ReHo) of brain-activity abnormalities in patients with comitant strabismus (CS) and their relationship with behavioral performance. Methods Twenty patients with CS (ten men and ten women) and 20 (ten men and ten women) age-, sex-, and education-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging scans. The ReHo method was used to assess local features of spontaneous brain activities. Patients with CS were distinguished from HCs by receiver operating characteristic curve. Correlation analysis was performed to explore the relationship between the observed mean ReHo values of the different brain areas and behavioral performance. Results Compared to HCs, the patients with CS showed significantly increased ReHo values in the right inferior temporal cortex/fusiform gyrus/cerebellum anterior lobe, right lingual gyrus, and bilateral cingulate gyrus. We did not find any relationship between the observed mean ReHo values of the different brain areas and behavioral performance. Conclusion CS causes dysfunction in many brain regions, which may explain the fusion compensation in CS. PMID:27350747

  2. Altered brain arginine metabolism in schizophrenia

    PubMed Central

    Liu, P; Jing, Y; Collie, N D; Dean, B; Bilkey, D K; Zhang, H

    2016-01-01

    Previous research implicates altered metabolism of l-arginine, a versatile amino acid with a number of bioactive metabolites, in the pathogenesis of schizophrenia. The present study, for we believe the first time, systematically compared the metabolic profile of l-arginine in the frontal cortex (Brodmann's area 8) obtained post-mortem from schizophrenic individuals and age- and gender-matched non-psychiatric controls (n=20 per group). The enzyme assays revealed no change in total nitric oxide synthase (NOS) activity, but significantly increased arginase activity in the schizophrenia group. Western blot showed reduced endothelial NOS protein expression and increased arginase II protein level in the disease group. High-performance liquid chromatography and liquid chromatography/mass spectrometric assays confirmed significantly reduced levels of γ-aminobutyric acid (GABA), but increased agmatine concentration and glutamate/GABA ratio in the schizophrenia cases. Regression analysis indicated positive correlations between arginase activity and the age of disease onset and between l-ornithine level and the duration of illness. Moreover, cluster analyses revealed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which were altered in the schizophrenia group. The present study provides further evidence of altered brain arginine metabolism in schizophrenia, which enhances our understanding of the pathogenesis of schizophrenia and may lead to the future development of novel preventions and/or therapeutics for the disease. PMID:27529679

  3. Hypersexuality or altered sexual preference following brain injury.

    PubMed

    Miller, B L; Cummings, J L; McIntyre, H; Ebers, G; Grode, M

    1986-08-01

    Eight patients are described in whom either hypersexuality (four cases) or change in sexual preference (four cases) occurred following brain injury. In this series disinhibition of sexual activity and hypersexuality followed medial basal-frontal or diencephalic injury. This contrasted with the patients demonstrating altered sexual preference whose injuries involved limbic system structures. In some patients altered sexual behaviour may be the presenting or dominant feature of brain injury.

  4. Hypersexuality or altered sexual preference following brain injury.

    PubMed Central

    Miller, B L; Cummings, J L; McIntyre, H; Ebers, G; Grode, M

    1986-01-01

    Eight patients are described in whom either hypersexuality (four cases) or change in sexual preference (four cases) occurred following brain injury. In this series disinhibition of sexual activity and hypersexuality followed medial basal-frontal or diencephalic injury. This contrasted with the patients demonstrating altered sexual preference whose injuries involved limbic system structures. In some patients altered sexual behaviour may be the presenting or dominant feature of brain injury. Images PMID:3746322

  5. Variants in the DYX2 locus are associated with altered brain activation in reading-related brain regions in subjects with reading disability.

    PubMed

    Cope, Natalie; Eicher, John D; Meng, Haiying; Gibson, Christopher J; Hager, Karl; Lacadie, Cheryl; Fulbright, Robert K; Constable, R Todd; Page, Grier P; Gruen, Jeffrey R

    2012-10-15

    Reading disability (RD) is a complex genetic disorder with unknown etiology. Genes on chromosome 6p22, including DCDC2, KIAA0319, and TTRAP, have been identified as RD associated genes. Imaging studies have shown both functional and structural differences between brains of individuals with and without RD. There are limited association studies performed between RD genes, specifically genes on 6p22, and regional brain activation during reading tasks. Using fourteen variants in DCDC2, KIAA0319, and TTRAP and exhaustive reading measures, we first tested for association with reading performance in 82 parent-offspring families (326 individuals). Next, we determined the association of these variants with activation of sixteen brain regions of interest during four functional magnetic resonance imaging-reading tasks. We nominally replicated associations between reading performance and variants of DCDC2 and KIAA0319. Furthermore, we observed a number of associations with brain activation patterns during imaging-reading tasks with all three genes. The strongest association occurred between activation of the left anterior inferior parietal lobe and complex tandem repeat BV677278 in DCDC2 (uncorrected p=0.00003, q=0.0442). Our results show that activation patterns across regions of interest in the brain are influenced by variants in the DYX2 locus. The combination of genetic and functional imaging data show a link between genes and brain functioning during reading tasks in subjects with RD. This study highlights the many advantages of imaging data as an endophenotype for discerning genetic risk factors for RD and other communication disorders and underscores the importance of integrating neurocognitive, imaging, and genetic data in future investigations.

  6. Variants in the DYX2 locus are associated with altered brain activation in reading-related brain regions in subjects with reading disability

    PubMed Central

    Cope, Natalie; Eicher, John D.; Meng, Haiying; Gibson, Christopher J.; Hager, Karl; Lacadie, Cheryl; Fulbright, Robert K.; Constable, R. Todd; Page, Grier P.; Gruen, Jeffrey R.

    2012-01-01

    Reading disability (RD) is a complex genetic disorder with unknown etiology. Genes on chromosome 6p22, including DCDC2, KIAA0319, and TTRAP, have been identified as RD associated genes. Imaging studies have shown both functional and structural differences between brains of individuals with and without RD. There are limited association studies performed between RD genes, specifically genes on 6p22, and regional brain activation during reading tasks. Using fourteen variants in DCDC2, KIAA0319, and TTRAP and exhaustive reading measures, we first tested for association with reading performance in 82 parent-offspring families (326 individuals). Next, we determined the association of these variants with activation of sixteen brain regions of interest during four functional magnetic resonance imaging-reading tasks. We nominally replicated associations between reading performance and variants of DCDC2 and KIAA0319. Furthermore, we observed a number of associations with brain activation patterns during imaging-reading tasks with all three genes. The strongest association occurred between activation of the left anterior inferior parietal lobe and complex tandem repeat BV677278 in DCDC2 (uncorrected p=0.00003, q=0.0442). Our results show that activation patterns across regions of interest in the brain are influenced by variants in the DYX2 locus. The combination of genetic and functional imaging data show a link between genes and brain functioning during reading tasks in subjects with RD. This study highlights the many advantages of imaging data as an endophenotype for discerning genetic risk factors for RD and other communication disorders and underscores the importance of integrating neurocognitive, imaging, and genetic data in future investigations. PMID:22750057

  7. Administration of DHA Reduces Endoplasmic Reticulum Stress-Associated Inflammation and Alters Microglial or Macrophage Activation in Traumatic Brain Injury

    PubMed Central

    Harvey, Lloyd D.; Yin, Yan; Attarwala, Insiya Y.; Begum, Gulnaz; Deng, Julia; Yan, Hong Q.; Dixon, C. Edward

    2015-01-01

    We investigated the effects of the administration of docosahexaenoic acid (DHA) post-traumatic brain injury (TBI) on reducing neuroinflammation. TBI was induced by cortical contusion injury in Sprague Dawley rats. Either DHA (16 mg/kg in dimethyl sulfoxide) or vehicle dimethyl sulfoxide (1 ml/kg) was administered intraperitonially at 5 min after TBI, followed by a daily dose for 3 to 21 days. TBI triggered activation of microglia or macrophages, detected by an increase of Iba1 positively stained microglia or macrophages in peri-lesion cortical tissues at 3, 7, and 21 days post-TBI. The inflammatory response was further characterized by expression of the proinflammatory marker CD16/32 and the anti-inflammatory marker CD206 in Iba1+ microglia or macrophages. DHA-treated brains showed significantly fewer CD16/32+ microglia or macrophages, but an increased CD206+ phagocytic microglial or macrophage population. Additionally, DHA treatment revealed a shift in microglial or macrophage morphology from the activated, amoeboid-like state into the more permissive, surveillant state. Furthermore, activated Iba1+ microglial or macrophages were associated with neurons expressing the endoplasmic reticulum (ER) stress marker CHOP at 3 days post-TBI, and the administration of DHA post-TBI concurrently reduced ER stress and the associated activation of Iba1+ microglial or macrophages. There was a decrease in nuclear translocation of activated nuclear factor kappa-light-chain-enhancer of activated B cells protein at 3 days in DHA-treated tissue and reduced neuronal degeneration in DHA-treated brains at 3, 7, and 21 days after TBI. In summary, our study demonstrated that TBI mediated inflammatory responses are associated with increased neuronal ER stress and subsequent activation of microglia or macrophages. DHA administration reduced neuronal ER stress and subsequent association with microglial or macrophage polarization after TBI, demonstrating its therapeutic potential to

  8. Altered baseline brain activity with 72 h of simulated microgravity--initial evidence from resting-state fMRI.

    PubMed

    Liao, Yang; Zhang, Jinsong; Huang, Zhiping; Xi, Yibin; Zhang, Qianru; Zhu, Tianli; Liu, Xufeng

    2012-01-01

    To provide the basis and reference to further insights into the neural activity of the human brain in a microgravity environment, we discuss the amplitude changes of low-frequency brain activity fluctuations using a simulated microgravity model. Twelve male participants between 24 and 31 years old received resting-state fMRI scans in both a normal condition and after 72 hours in a -6° head down tilt (HDT). A paired sample t-test was used to test the amplitude differences of low-frequency brain activity fluctuations between these two conditions. With 72 hours in a -6° HDT, the participants showed a decreased amplitude of low-frequency fluctuations in the left thalamus compared with the normal condition (a combined threshold of P<0.005 and a minimum cluster size of 351 mm(3) (13 voxels), which corresponded with the corrected threshold of P<0.05 determined by AlphaSim). Our findings indicate that a gravity change-induced redistribution of body fluid may disrupt the function of the left thalamus in the resting state, which may contribute to reduced motor control abilities and multiple executive functions in astronauts in a microgravity environment.

  9. Effects of CPAP-therapy on brain electrical activity in obstructive sleep apneic patients: a combined EEG study using LORETA and Omega complexity : reversible alterations of brain activity in OSAS.

    PubMed

    Toth, Marton; Faludi, Bela; Kondakor, Istvan

    2012-10-01

    Effects of initiation of continuous positive airway pressure (CPAP) therapy on EEG background activity were investigated in patients with obstructive sleep apnea syndrome (OSAS, N = 25) to test possible reversibility of alterations of brain electrical activity caused by chronic hypoxia. Normal control group (N = 14) was also examined. Two EEG examinations were done in each groups: at night and in the next morning. Global and regional (left vs. right, anterior vs. posterior) measures of spatial complexity (Omega complexity) were used to characterize the degree of spatial synchrony of EEG. Low resolution electromagnetic tomography (LORETA) was used to localize generators of EEG activity in separate frequency bands. Before CPAP-treatment, a significantly lower Omega complexity was found globally and over the right hemisphere. Due to CPAP-treatment, these significant differences vanished. Significantly decreased Omega complexity was found in the anterior region after treatment. LORETA showed a decreased activity in all of the beta bands after therapy in the right hippocampus, premotor and temporo-parietal cortex, and bilaterally in the precuneus, paracentral and posterior cingulate cortex. No significant changes were seen in control group. Comparing controls and patients before sleep, an increased alpha2 band activity was seen bilaterally in the precuneus, paracentral and posterior cingulate cortex, while in the morning an increased beta3 band activity in the left precentral and bilateral premotor cortex and a decreased delta band activity in the right temporo-parietal cortex and insula were observed. These findings indicate that effect of sleep on EEG background activity is different in OSAS patients and normal controls. In OSAS patients, significant changes lead to a more normal EEG after a night under CPAP-treatment. Compensatory alterations of brain electrical activity in regions associated with influencing sympathetic outflow, visuospatial abilities, long

  10. Altered behavior and neural activity in conspecific cagemates co-housed with mouse models of brain disorders.

    PubMed

    Yang, Hyunwoo; Jung, Seungmoon; Seo, Jinsoo; Khalid, Arshi; Yoo, Jung-Seok; Park, Jihyun; Kim, Soyun; Moon, Jangsup; Lee, Soon-Tae; Jung, Keun-Hwa; Chu, Kon; Lee, Sang Kun; Jeon, Daejong

    2016-09-01

    The psychosocial environment is one of the major contributors of social stress. Family members or caregivers who consistently communicate with individuals with brain disorders are considered at risk for physical and mental health deterioration, possibly leading to mental disorders. However, the underlying neural mechanisms of this phenomenon remain poorly understood. To address this, we developed a social stress paradigm in which a mouse model of epilepsy or depression was housed long-term (>4weeks) with normal conspecifics. We characterized the behavioral phenotypes and electrophysiologically investigated the neural activity of conspecific cagemate mice. The cagemates exhibited deficits in behavioral tasks assessing anxiety, locomotion, learning/memory, and depression-like behavior. Furthermore, they showed severe social impairment in social behavioral tasks involving social interaction or aggression. Strikingly, behavioral dysfunction remained in the cagemates 4weeks following co-housing cessation with the mouse models. In an electrophysiological study, the cagemates showed an increased number of spikes in medial prefrontal cortex (mPFC) neurons. Our results demonstrate that conspecifics co-housed with mouse models of brain disorders develop chronic behavioral dysfunctions, and suggest a possible association between abnormal mPFC neural activity and their behavioral pathogenesis. These findings contribute to the understanding of the psychosocial and psychiatric symptoms frequently present in families or caregivers of patients with brain disorders.

  11. Blocking systemic nitric oxide production alters neuronal activation in brain structures involved in cardiovascular regulation during polymicrobial sepsis.

    PubMed

    Bruhn, Fernando Henrique Pascoti; Corrêa, Pollyanna Barbosa Farias; Oliveira-Pelegrin, Gabriela Ravanelli; Rocha, Maria José Alves

    2009-04-10

    In a previous study, we concluded that overproduction of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) in the late phase of sepsis prevents hypothalamic activation, blunts vasopressin secretion and contributes to hypotension, irreversible shock and death. The aim of this follow-up study was to evaluate if the same neuronal activation pattern happens in brain structures related to cardiovascular functions. Male Wistar rats received intraperitoneal injections of aminoguanidine, an iNOS inhibitor, or saline 30 min before cecal ligation and puncture (CLP) or sham surgeries. The animals were perfused 6 or 24h after the surgeries and the brains were removed and processed for Fos immunocytochemistry. We observed an increase (P<0.001) in c-fos expression 6h after CLP in the area postrema (AP), nucleus of the tractus solitarius (NTS), ventral lateral medulla (VLM), locus coeruleus (LC) and parabrachial nucleus (PB). At 24h after CLP, however, c-fos expression was strongly decreased in all these nuclei (P<0.05), except for the VLM. Aminoguanidine reduced c-fos expression in the AP and NTS at 6h after CLP, but showed an opposite effect at 24h, with an increase in the AP, NTS, and also in the VLM. No such effect was observed in the LC and PB at 6 or 24h. In all control animals, c-fos expression was minimal or absent. We conclude that in the early phase of sepsis iNOS-derived NO may be partially responsible for the activation of brain structures related to cardiovascular regulation. During the late phase, however, this activation is reduced or abolished.

  12. Altered brain activation during response inhibition and error processing in subjects with Internet gaming disorder: a functional magnetic imaging study.

    PubMed

    Ko, Chih-Hung; Hsieh, Tsyh-Jyi; Chen, Chiao-Yun; Yen, Cheng-Fang; Chen, Cheng-Sheng; Yen, Ju-Yu; Wang, Peng-Wei; Liu, Gin-Chung

    2014-12-01

    The aim of the present study was to evaluate the impulsivity and brain correlates of response inhibition and error processing among subjects with Internet gaming disorder (IGD). We evaluated the response inhibition and error processing by functional magnetic resonance imaging (fMRI) in subjects with IGD and controls. Twenty-six men with IGD for at least 2 years and 23 controls with no history of IGD were recruited as the IGD and control groups, respectively. All subjects performed the event-related designed Go/No-go task under fMRI and completed questionnaires related to Internet addiction and impulsivity. The IGD group exhibited a higher score for impulsivity than the control group. The IGD group also exhibited higher brain activation when processing response inhibition over the left orbital frontal lobe and bilateral caudate nucleus than controls. Both the IGD and control groups exhibited activation of the insula and anterior cingulate cortex during error processing. The activation over the right insula was lower in the subjects with IGD than the control group. Our results support the fact that the fronto-striatal network involved in response inhibition, and the salience network, anchored by the anterior cingulate and insula, contributes to error processing. Further, adults with IGD have impaired insular function in error processing and greater activation of the fronto-striatal network in order to maintain their response inhibition performance.

  13. Exercise Improves Executive Function and Achievement and Alters Brain Activation in Overweight Children: A Randomized Controlled Trial

    PubMed Central

    Davis, Catherine L.; Tomporowski, Phillip D.; McDowell, Jennifer E.; Austin, Benjamin P.; Miller, Patricia H.; Yanasak, Nathan E.; Allison, Jerry D.; Naglieri, Jack A.

    2010-01-01

    Objective This experiment tested the hypothesis that exercise would improve executive function. Design Sedentary, overweight 7- to 11-year-old children (N = 171, 56% female, 61% Black, M ± SD age 9.3 ± 1.0 yrs, body mass index (BMI) 26 ± 4.6 kg/m2, BMI z-score 2.1 ± 0.4) were randomized to 13 ± 1.6 weeks of an exercise program (20 or 40 minutes/day), or a control condition. Main outcome measures Blinded, standardized psychological evaluations (Cognitive Assessment System and Woodcock-Johnson Tests of Achievement III) assessed cognition and academic achievement. Functional magnetic resonance imaging measured brain activity during executive function tasks. Results Intent to treat analysis revealed dose response benefits of exercise on executive function and mathematics achievement. Preliminary evidence of increased bilateral prefrontal cortex activity and reduced bilateral posterior parietal cortex activity due to exercise was also observed. Conclusion Consistent with results obtained in older adults, a specific improvement on executive function and brain activation changes due to exercise were observed. The cognitive and achievement results add evidence of dose response, and extend experimental evidence into childhood. This study provides information on an educational outcome. Besides its importance for maintaining weight and reducing health risks during a childhood obesity epidemic, physical activity may prove to be a simple, important method of enhancing aspects of children’s mental functioning that are central to cognitive development. This information may persuade educators to implement vigorous physical activity. PMID:21299297

  14. Grainyhead-like 3 (Grhl3) deficiency in brain leads to altered locomotor activity and decreased anxiety-like behaviours in aged mice.

    PubMed

    Dworkin, Sebastian; Auden, Alana; Partridge, Darren D; Daglas, Maria; Medcalf, Robert L; Mantamadiotis, Theo; Georgy, Smitha R; Darido, Charbel; Jane, Stephen M; Ting, Stephen B

    2016-12-01

    The highly conserved Grainyhead-like (Grhl) family of transcription factors, comprising three members in vertebrates (Grhl1-3), play critical regulatory roles during embryonic development, cellular proliferation and apoptosis. Although loss of Grhl function leads to multiple neural abnormalities in numerous animal models, a comprehensive analysis of Grhl expression and function in the mammalian brain has not been reported. Here we show that only Grhl3 expression is detectable in the embryonic mouse brain; particularly within the habenula, an organ known to modulate repressive behaviours. Using both Grhl3-knockout mice (Grhl3(-/-) ), and brain-specific conditional deletion of Grhl3 in adult mice (Nestin-Cre/Grhl3(flox/flox) ), we performed histological expression analyses and behavioural tests to assess long-term effects of Grhl3 loss on motor co-ordination, spatial memory, anxiety and stress. We found that complete deletion of Grhl3 did not lead to noticeable structural or cell-intrinsic defects in the embryonic brain, however aged Grhl3 conditional knockout (cKO) mice showed enlarged lateral ventricles and displayed marked changes in motor function and behaviours suggestive of decreased fear and anxiety. We conclude that loss of Grhl3 in the brain leads to significant alterations in locomotor activity and decreased self-inhibition, and as such, these mice may serve as a novel model of human conditions of impulsive behaviour or hyperactivity. This article is protected by copyright. All rights reserved.

  15. Altered intrinsic regional spontaneous brain activity in patients with optic neuritis: a resting-state functional magnetic resonance imaging study

    PubMed Central

    Shao, Yi; Cai, Feng-Qin; Zhong, Yu-Lin; Huang, Xin; Zhang, Ying; Hu, Pei-Hong; Pei, Chong-Gang; Zhou, Fu-Qing; Zeng, Xian-Jun

    2015-01-01

    Objective To investigate the underlying regional homogeneity (ReHo) in brain-activity deficit in patients with optic neuritis (ON) and its relationship with behavioral performance. Materials and methods In total, twelve patients with ON (four males and eight females) and twelve (four males and eight females) age-, sex-, and education-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. The ReHo method was used to assess the local features of spontaneous brain activity. Correlation analysis was used to explore the relationship between the observed mean ReHo values of the different brain areas and the visual evoked potential (VEP) in patients with ON. Results Compared with the healthy controls, patients with ON showed lower ReHo in the left cerebellum, posterior lobe, left middle temporal gyrus, right insula, right superior temporal gyrus, left middle frontal gyrus, bilateral anterior cingulate cortex, left superior frontal gyrus, right superior frontal gyrus, and right precentral gyrus, and higher ReHo in the cluster of the left fusiform gyrus and right inferior parietal lobule. Meanwhile, we found that the VEP amplitude of the right eye in patients with ON showed a positive correlation with the ReHo signal value of the left cerebellum posterior lobe (r=0.701, P=0.011), the right superior frontal gyrus (r=0.731, P=0.007), and the left fusiform gyrus (r=0.644, P=0.024). We also found that the VEP latency of the right eye in ON showed a positive correlation with the ReHo signal value of the right insula (r=0.595, P=0.041). Conclusion ON may involve dysfunction in the default-mode network, which may reflect the underlying pathologic mechanism. PMID:26715848

  16. How does transcranial DC stimulation of the primary motor cortex alter regional neuronal activity in the human brain?

    PubMed

    Lang, Nicolas; Siebner, Hartwig R; Ward, Nick S; Lee, Lucy; Nitsche, Michael A; Paulus, Walter; Rothwell, John C; Lemon, Roger N; Frackowiak, Richard S

    2005-07-01

    Transcranial direct current stimulation (tDCS) of the primary motor hand area (M1) can produce lasting polarity-specific effects on corticospinal excitability and motor learning in humans. In 16 healthy volunteers, O positron emission tomography (PET) of regional cerebral blood flow (rCBF) at rest and during finger movements was used to map lasting changes in regional synaptic activity following 10 min of tDCS (+/-1 mA). Bipolar tDCS was given through electrodes placed over the left M1 and right frontopolar cortex. Eight subjects received anodal or cathodal tDCS of the left M1, respectively. When compared to sham tDCS, anodal and cathodal tDCS induced widespread increases and decreases in rCBF in cortical and subcortical areas. These changes in rCBF were of the same magnitude as task-related rCBF changes during finger movements and remained stable throughout the 50-min period of PET scanning. Relative increases in rCBF after real tDCS compared to sham tDCS were found in the left M1, right frontal pole, right primary sensorimotor cortex and posterior brain regions irrespective of polarity. With the exception of some posterior and ventral areas, anodal tDCS increased rCBF in many cortical and subcortical regions compared to cathodal tDCS. Only the left dorsal premotor cortex demonstrated an increase in movement related activity after cathodal tDCS, however, modest compared with the relatively strong movement-independent effects of tDCS. Otherwise, movement related activity was unaffected by tDCS. Our results indicate that tDCS is an effective means of provoking sustained and widespread changes in regional neuronal activity. The extensive spatial and temporal effects of tDCS need to be taken into account when tDCS is used to modify brain function.

  17. Activation changes in zebra finch (Taeniopygia guttata) brain areas evoked by alterations of the earth magnetic field.

    PubMed

    Keary, Nina; Bischof, Hans-Joachim

    2012-01-01

    Many animals are able to perceive the earth magnetic field and to use it for orientation and navigation within the environment. The mechanisms underlying the perception and processing of magnetic field information within the brain have been thoroughly studied, especially in birds, but are still obscure. Three hypotheses are currently discussed, dealing with ferromagnetic particles in the beak of birds, with the same sort of particles within the lagena organs, or describing magnetically influenced radical-pair processes within retinal photopigments. Each hypothesis is related to a well-known sensory organ and claims parallel processing of magnetic field information with somatosensory, vestibular and visual input, respectively. Changes in activation within nuclei of the respective sensory systems have been shown previously. Most of these previous experiments employed intensity enhanced magnetic stimuli or lesions. We here exposed unrestrained zebra finches to either a stationary or a rotating magnetic field of the local intensity and inclination. C-Fos was used as an activity marker to examine whether the two treatments led to differences in fourteen brain areas including nuclei of the somatosensory, vestibular and visual system. An ANOVA revealed an overall effect of treatment, indicating that the magnetic field change was perceived by the birds. While the differences were too small to be significant in most areas, a significant enhancement of activation by the rotating stimulus was found in a hippocampal subdivision. Part of the hyperpallium showed a strong, nearly significant, increase. Our results are compatible with previous studies demonstrating an involvement of at least three different sensory systems in earth magnetic field perception and suggest that these systems, probably less elaborated, may also be found in nonmigrating birds.

  18. Alteration in glutathione content and associated enzyme activities in the synaptic terminals but not in the non-synaptic mitochondria from the frontal cortex of Parkinson's disease brains.

    PubMed

    Harish, G; Mahadevan, Anita; Srinivas Bharath, M M; Shankar, S K

    2013-01-01

    Altered redox dynamics contribute to physiological aging and Parkinson's disease (PD). This is reflected in the substantia nigra (SN) of PD patients as lowered antioxidant levels and elevated oxidative damage. Contrary to this observation, we previously reported that non-SN regions such as caudate nucleus and frontal cortex (FC) exhibited elevated antioxidants and lowered mitochondrial and oxidative damage indicating constitutive protective mechanisms in PD brains. To investigate whether the sub-cellular distribution of antioxidants could contribute to these protective effects, we examined the distribution of antioxidant/oxidant markers in the neuropil fractions [synaptosomes, non-synaptic mitochondria and cytosol] of FC from PD (n = 9) and controls (n = 8). In the control FC, all the antioxidant activities [Superoxide dismutase (SOD), glutathione (GSH), GSH peroxidase (GPx), GSH-S-transferase (GST)] except glutathione reductase (GR) were the highest in cytosol, but several fold lower in mitochondria and much lower in synaptosomes. However, FC synaptosomes from PD brains had significantly higher levels of GSH (p = 0.01) and related enzymes [GPx (p = 0.02), GR (p = 0.06), GST (p = 0.0001)] compared to controls. Conversely, mitochondria from the FC of PD cases displayed elevated SOD activity (p = 0.02) while the GSH and related enzymes were relatively unaltered. These changes in the neuropil fractions were associated with unchanged or lowered oxidative damage. Further, the mitochondrial content in the synaptosomes of both PD and control brains was ≥five-fold lower compared to the non-synaptic mitochondrial fraction. Altered distribution of oxidant/antioxidant markers in the neuropil fractions of the human brain during aging and PD has implications for (1) degenerative and protective mechanisms (2) distinct antioxidant mechanisms in synaptic terminals compared to other compartments.

  19. Altered baseline brain activity in children with bipolar disorder during mania state: a resting-state study

    PubMed Central

    Lu, Dali; Jiao, Qing; Zhong, Yuan; Gao, Weijia; Xiao, Qian; Liu, Xiaoqun; Lin, Xiaoling; Cheng, Wentao; Luo, Lanzhu; Xu, Chuanjian; Lu, Guangming; Su, Linyan

    2014-01-01

    Background Previous functional magnetic resonance imaging (fMRI) studies have shown abnormal functional connectivity in regions involved in emotion processing and regulation in pediatric bipolar disorder (PBD). Recent studies indicate, however, that task-dependent neural changes only represent a small fraction of the brain’s total activity. How the brain allocates the majority of its resources at resting state is still unknown. We used the amplitude of low-frequency fluctuation (ALFF) method of fMRI to explore the spontaneous neuronal activity in resting state in PBD patients. Methods Eighteen PBD patients during the mania phase and 18 sex-, age- and education-matched healthy subjects were enrolled in this study and all patients underwent fMRI scanning. The ALFF method was used to compare the resting-state spontaneous neuronal activity between groups. Correlation analysis was performed between the ALFF values and Young Mania Rating Scale scores. Results Compared with healthy controls, PBD patients presented increased ALFF in bilateral caudate and left pallidum as well as decreased ALFF in left precuneus, left superior parietal lobule, and bilateral inferior occipital gyrus. Additionally, ALFF values in left pallidum were positively correlated with Young Mania Rating Scale score in PBD. Conclusion The abnormal resting-state neuronal activities of the basal ganglia, parietal cortex, and occipital cortex may play an important role in the pathophysiology in PBD patients. PMID:24570585

  20. Diet-induced obesity progressively alters cognition, anxiety-like behavior and lipopolysaccharide-induced depressive-like behavior: focus on brain indoleamine 2,3-dioxygenase activation.

    PubMed

    André, Caroline; Dinel, Anne-Laure; Ferreira, Guillaume; Layé, Sophie; Castanon, Nathalie

    2014-10-01

    Obesity is associated with a high prevalence of mood symptoms and cognitive dysfunctions that emerges as significant risk factors for important health complications such as cardiovascular diseases and type 2 diabetes. It is therefore important to identify the dynamic of development and the pathophysiological mechanisms underlying these neuropsychiatric symptoms. Obesity is also associated with peripheral low-grade inflammation and increased susceptibility to immune-mediated diseases. Excessive production of proinflammatory cytokines and the resulting activation of the brain tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) have been shown to promote neurobehavioral complications, particularly depression. In that context, questions arise about the impact of diet-induced obesity on the onset of neuropsychiatric alterations and the increased susceptibility to immune-mediated diseases displayed by obese patients, particularly through brain IDO activation. To answer these questions, we used C57Bl/6 mice exposed to standard diet or western diet (WD; consisting of palatable energy-dense food) since weaning and for 20 weeks. We then measured inflammatory and behavioral responses to a systemic immune challenge with lipopolysaccharide (LPS) in experimental conditions known to alter cognitive and emotional behaviors independently of any motor impairment. We first showed that in absence of LPS, 9 weeks of WD is sufficient to impair spatial recognition memory (in the Y-maze). On the other hand, 18 weeks of WD increased anxiety-like behavior (in the elevated plus-maze), but did not affect depressive-like behavior (in the tail-suspension and forced-swim tests). However, 20 weeks of WD altered LPS-induced depressive-like behavior compared to LPS-treated lean mice and exacerbated hippocampal and hypothalamic proinflammatory cytokine expression and brain IDO activation. Taken together, these results show that WD exposure alters cognition and anxiety in unstimulated

  1. Altered neuronal mitochondrial coenzyme A synthesis in neurodegeneration with brain iron accumulation caused by abnormal processing, stability, and catalytic activity of mutant pantothenate kinase 2.

    PubMed

    Kotzbauer, Paul T; Truax, Adam C; Trojanowski, John Q; Lee, Virginia M-Y

    2005-01-19

    Mutations in the pantothenate kinase 2 (PANK2) gene have been identified in patients with neurodegeneration with brain iron accumulation (NBIA; formerly Hallervorden-Spatz disease). However, the mechanisms by which these mutations cause neurodegeneration are unclear, especially given the existence of multiple pantothenate kinase genes in humans and multiple PanK2 transcripts with potentially different subcellular localizations. We demonstrate that PanK2 protein is localized to mitochondria of neurons in human brain, distinguishing it from other pantothenate kinases that do not possess mitochondrial-targeting sequences. PanK2 protein translated from the most 5' start site is sequentially cleaved at two sites by the mitochondrial processing peptidase, generating a long-lived 48 kDa mature protein identical to that found in human brain extracts. The mature protein catalyzes the initial step in coenzyme A (CoA) synthesis but displays feedback inhibition in response to species of acyl CoA rather than CoA itself. Some, but not all disease-associated point mutations result in significantly reduced catalytic activity. The most common mutation, G521R, results in marked instability of the intermediate PanK2 isoform and reduced production of the mature isoform. These results suggest that NBIA is caused by altered neuronal mitochondrial lipid metabolism caused by mutations disrupting PanK2 protein levels and catalytic activity.

  2. Copper deficiency in neonatal mice alters brain catecholamine levels

    SciTech Connect

    Bailey, W.R.; Prohaska, J.R. )

    1991-03-15

    Copper (Cu) deficiency was investigated in Swiss albino mice to develop a model that alters brain catecholamine metabolism without serious growth impairment. Cu deficiency was induced by feeding a diet low in Cu to dams beginning either 7 days (d) prior, 4d prior, 4d after, or on the day of parturition. All 4-week-old male Cu-deficient ({minus}Cu) offspring were anemic and exhibited biochemical characteristics of Cu deficiency when compared to their respective +Cu control mice. However, the best model, which resulted in altered catecholamine metabolism characterized by elevation of dopamine (DA) and depression in norepinephrine (NE) in brain, heart, and spleen, was when treatment began 4d prior to birth. Body and brain weight were not altered. However, levels of Cu in brain and liver of {minus}Cu mice were markedly reduced to 21% and 31% of those measured in +Cu controls, respectively. Furthermore, brain NE and DA concentrations of {minus}Cu mice were 72% and 132% of those quantified in +Cu offspring, respectively. A plausible explanation is that dietary Cu deficiency results in lower activity of brain dopamine-{beta}-monooxygenase, the Cu dependent enzyme that catalyzes conversion of DA to NE. It is not yet known if these changes in Ne and DA pool size altered the quantity or characteristics of the neuronal catecholamine receptors, and more importantly, whether or not the observed changes are reversible by nutritional intervention.

  3. Altered likelihood of brain activation in attention and working memory networks in patients with multiple sclerosis: An ALE meta-analysis☆

    PubMed Central

    Kollndorfer, K.; Krajnik, J.; Woitek, R.; Freiherr, J.; Prayer, D.; Schöpf, V.

    2013-01-01

    Multiple sclerosis (MS) is a chronic neurological disease, frequently affecting attention and working memory functions. Functional imaging studies investigating those functions in MS patients are hard to compare, as they include heterogeneous patient groups and use different paradigms for cognitive testing. The aim of this study was to investigate alterations in neuronal activation between MS patients and healthy controls performing attention and working memory tasks. Two meta-analyses of previously published fMRI studies investigating attention and working memory were conducted for MS patients and healthy controls, respectively. Resulting maps were contrasted to compare brain activation in patients and healthy controls. Significantly increased brain activation in the inferior parietal lobule and the dorsolateral prefrontal cortex was detected for healthy controls. In contrast, higher neuronal activation in MS patients was obtained in the left ventrolateral prefrontal cortex and the right premotor area. With this meta-analytic approach previous results of investigations examining cognitive function using fMRI are summarized and compared. Therefore a more general view on cognitive dysfunction in this heterogeneous disease is enabled. PMID:24056084

  4. Administration of Harmine and Imipramine Alters Creatine Kinase and Mitochondrial Respiratory Chain Activities in the Rat Brain

    PubMed Central

    Réus, Gislaine Z.; Stringari, Roberto B.; Gonçalves, Cinara L.; Scaini, Giselli; Carvalho-Silva, Milena; Jeremias, Gabriela C.; Jeremias, Isabela C.; Ferreira, Gabriela K.; Streck, Emílio L.; Hallak, Jaime E.; Zuardi, Antônio W.; Crippa, José A.; Quevedo, João

    2012-01-01

    The present study evaluated mitochondrial respiratory chain and creatine kinase activities after administration of harmine (5, 10, and 15 mg/kg) and imipramine (10, 20, and 30 mg/kg) in rat brain. After acute treatment occurred an increase of creatine kinase in the prefrontal with imipramine (20 and 30 mg/kg) and harmine in all doses, in the striatum with imipramine (20 and 30 mg/kg) and harmine (5 and 10 mg/kg); harmine (15 mg/kg) decreased creatine kinase. In the chronic treatment occurred an increase of creatine kinase with imipramine (20 mg/kg), harmine (5 mg/kg) in the prefrontal with imipramine (20 and 30 mg/kg) and harmine (5 and 10 mg/kg) in the striatum. In the acute treatment, the complex I increased in the prefrontal with harmine (15 mg/kg) and in the striatum with harmine (10 mg/kg); the complex II decreased with imipramine (20 and 30 mg/kg) in the striatum; the complex IV increased with imipramine (30 mg/kg) in the striatum. In the chronic treatment, the complex I increased with harmine (5 mg/kg) in the prefrontal; the complex II increased with imipramine (20 mg/kg) in the prefrontal; the complex IV increased with harmine (5 mg/kg) in the striatum. Finally, these findings further support the hypothesis that harmine and imipramine could be involved in mitochondrial function. PMID:21969912

  5. Whole-transcriptome brain expression and exon-usage profiling in major depression and suicide: evidence for altered glial, endothelial and ATPase activity

    PubMed Central

    Pantazatos, Spiro P.; Huang, Yung-yu; Rosoklija, Gorazd B.; Dwork, Andrew J.; Arango, Victoria; Mann, J. John

    2016-01-01

    Brain gene expression profiling studies of suicide and depression using oligonucleotide microarrays have often failed to distinguish these two phenotypes. Moreover, next generation sequencing (NGS) approaches are more accurate in quantifying gene expression and can detect alternative splicing. Using RNA-seq, we examined whole-exome gene and exon expression in non-psychiatric controls (CON, N=29), DSM-IV major depressive disorder suicides (MDD-S, N=21) and MDD non-suicides (MDD, N=9) in dorsal lateral prefrontal cortex (Brodmann Area 9) of sudden-death medication-free individuals postmortem. Using small RNA-seq, we also examined miRNA expression (9 samples per group). DeSeq2 identified thirty-five genes differentially expressed between groups and surviving adjustment for false discovery rate (adjusted p<0.1). In depression, altered genes include humanin like-8 (MTRNRL8), interleukin-8 (IL8), and serpin peptidase inhibitor, clade H (SERPINH1) and chemokine ligand 4 (CCL4), while exploratory gene ontology (GO) analyses revealed lower expression of immune-related pathways such as chemokine receptor activity, chemotaxis and cytokine biosynthesis, and angiogenesis and vascular development in (adjusted p<0.1). Hypothesis-driven GO analysis suggests lower expression of genes involved in oligodendrocyte differentiation, regulation of glutamatergic neurotransmission, and oxytocin receptor expression in both suicide and depression, and provisional evidence for altered DNA-dependent ATPase expression in suicide only. DEXSEq analysis identified differential exon usage in ATPase, class II, type 9B (adjusted p<0.1) in depression. Differences in miRNA expression or structural gene variants were not detected. Results lend further support for models in which deficits in microglial, endothelial (blood-brain barrier), ATPase activity and astrocytic cell functions contribute to MDD and suicide, and identify putative pathways and mechanisms for further study in these disorders. PMID

  6. Heavy Metals and Epigenetic Alterations in Brain Tumors

    PubMed Central

    Caffo, Maria; Caruso, Gerardo; Fata, Giuseppe La; Barresi, Valeria; Visalli, Maria; Venza, Mario; Venza, Isabella

    2014-01-01

    Heavy metals and their derivatives can cause various diseases. Numerous studies have evaluated the possible link between exposure to heavy metals and various cancers. Recent data show a correlation between heavy metals and aberration of genetic and epigenetic patterns. From a literature search we noticed few experimental and epidemiological studies that evaluate a possible correlation between heavy metals and brain tumors. Gliomas arise due to genetic and epigenetic alterations of glial cells. Changes in gene expression result in the alteration of the cellular division process. Epigenetic alterations in brain tumors include the hypermethylation of CpG group, hypomethylation of specific genes, aberrant activation of genes, and changes in the position of various histones. Heavy metals are capable of generating reactive oxygen assumes that key functions in various pathological mechanisms. Alteration of homeostasis of metals could cause the overproduction of reactive oxygen species and induce DNA damage, lipid peroxidation, and alteration of proteins. In this study we summarize the possible correlation between heavy metals, epigenetic alterations and brain tumors. We report, moreover, the review of relevant literature. PMID:25646073

  7. Traumatic Alterations in Consciousness: Traumatic Brain Injury

    PubMed Central

    Blyth, Brian J.; Bazarian, Jeffrey J.

    2010-01-01

    Mild traumatic brain injury (mTBI) refers to the clinical condition of transient alteration of consciousness as a result of traumatic injury to the brain. The priority of emergency care is to identify and facilitate the treatment of rare but potentially life threatening intra-cranial injuries associated with mTBI through the judicious application of appropriate imaging studies and neurosurgical consultation. Although post-mTBI symptoms quickly and completely resolve in the vast majority of cases, a significant number of patients will complain of lasting problems that may cause significant disability. Simple and early interventions such as patient education and appropriate referral can reduce the likelihood of chronic symptoms. Although definitive evidence is lacking, mTBI is likely to be related to significant long-term sequelae such as Alzheimer's disease and other neurodegenerative processes. PMID:20709244

  8. REPEATED ANABOLIC/ANDROGENIC STEROID EXPOSURE DURING ADOLESCENCE ALTERS PHOSPHATE-ACTIVATED GLUTAMINASE AND GLUTAMATE RECEPTOR 1 SUBUNIT IMMUNOREACTIVITY IN HAMSTER BRAIN: CORRELATION WITH OFFENSIVE AGGRESSION

    PubMed Central

    Fischer, Shannon G.; Ricci, Lesley A.; Melloni, Richard H.

    2007-01-01

    Male Syrian hamsters (Mesocricetus auratus) treated with moderately high doses (5.0mg/kg/day) of anabolic/androgenic steroids (AAS) during adolescence (P27–P56) display highly escalated offensive aggression. The current study examined whether adolescent AAS-exposure influenced the immunohistochemical localization of phosphate-activated glutaminase (PAG), the rate-limiting enzyme in the synthesis of glutamate, a fast-acting neurotransmitter implicated in the modulation of aggression in various species and models of aggression, as well as glutamate receptor 1 subunit (GluR1). Hamsters were administered AAS during adolescence, scored for offensive aggression using the resident-intruder paradigm, and then examined for changes in PAG and GluR1 immunoreactivity in areas of the brain implicated in aggression control. When compared with sesame oil-treated control animals, aggressive AAS-treated hamsters displayed a significant increase in the number of PAG- and area density of GluR1- containing neurons in several notable aggression regions, although the differential pattern of expression did not appear to overlap across brain regions. Together, these results suggest that altered glutamate synthesis and GluR1 receptor expression in specific aggression areas may be involved in adolescent AAS-induced offensive aggression. PMID:17418431

  9. Altered brain activation and functional connectivity in working memory related networks in patients with type 2 diabetes: An ICA-based analysis.

    PubMed

    Zhang, Yang; Lu, Shan; Liu, Chunlei; Zhang, Huimei; Zhou, Xuanhe; Ni, Changlin; Qin, Wen; Zhang, Quan

    2016-03-29

    Type 2 diabetes mellitus (T2DM) can cause multidimensional cognitive deficits, among which working memory (WM) is usually involved at an early stage. However, the neural substrates underlying impaired WM in T2DM patients are still unclear. To clarify this issue, we utilized functional magnetic resonance imaging (fMRI) and independent component analysis to evaluate T2DM patients for alterations in brain activation and functional connectivity (FC) in WM networks and to determine their associations with cognitive and clinical variables. Twenty complication-free T2DM patients and 19 matched healthy controls (HCs) were enrolled, and fMRI data were acquired during a block-designed 1-back WM task. The WM metrics of the T2DM patients showed no differences compared with those of the HCs, except for a slightly lower accuracy rate in the T2DM patients. Compared with the HCs, the T2DM patients demonstrated increased activation within their WM fronto-parietal networks, and activation strength was significantly correlated with WM performance. The T2DM patients also showed decreased FC within and between their WM networks. Our results indicate that the functional integration of WM sub-networks was disrupted in the complication-free T2DM patients and that strengthened regional activity in fronto-parietal networks may compensate for the WM impairment caused by T2DM.

  10. Altered brain activation and functional connectivity in working memory related networks in patients with type 2 diabetes: An ICA-based analysis

    PubMed Central

    Zhang, Yang; Lu, Shan; Liu, Chunlei; Zhang, Huimei; Zhou, Xuanhe; Ni, Changlin; Qin, Wen; Zhang, Quan

    2016-01-01

    Type 2 diabetes mellitus (T2DM) can cause multidimensional cognitive deficits, among which working memory (WM) is usually involved at an early stage. However, the neural substrates underlying impaired WM in T2DM patients are still unclear. To clarify this issue, we utilized functional magnetic resonance imaging (fMRI) and independent component analysis to evaluate T2DM patients for alterations in brain activation and functional connectivity (FC) in WM networks and to determine their associations with cognitive and clinical variables. Twenty complication-free T2DM patients and 19 matched healthy controls (HCs) were enrolled, and fMRI data were acquired during a block-designed 1-back WM task. The WM metrics of the T2DM patients showed no differences compared with those of the HCs, except for a slightly lower accuracy rate in the T2DM patients. Compared with the HCs, the T2DM patients demonstrated increased activation within their WM fronto-parietal networks, and activation strength was significantly correlated with WM performance. The T2DM patients also showed decreased FC within and between their WM networks. Our results indicate that the functional integration of WM sub-networks was disrupted in the complication-free T2DM patients and that strengthened regional activity in fronto-parietal networks may compensate for the WM impairment caused by T2DM. PMID:27021340

  11. Profile of altered brain iron acquisition in restless legs syndrome.

    PubMed

    Connor, James R; Ponnuru, Padmavathi; Wang, Xin-Sheng; Patton, Stephanie M; Allen, Richard P; Earley, Christopher J

    2011-04-01

    of restless legs syndrome brains. This study reveals that there are alterations in the iron management protein profile in restless legs syndrome compared with controls at the site of blood-brain interface suggesting fundamental differences in brain iron acquisition in individuals with restless legs syndrome. Furthermore, the decrease in transferrin receptor expression in the microvasculature in the presence of relative brain iron deficiency reported in restless legs syndrome brains may underlie the problems associated with brain iron acquisition in restless legs syndrome. The consistent finding of loss of iron regulatory protein activity in restless legs syndrome brain tissue further implicates this protein as a factor in the underlying cause of the iron deficiency in the restless legs syndrome brain. The data herein provide evidence for regulation of iron uptake and storage within brain microvessels that challenge the existing paradigm that the blood-brain barrier is merely a transport system.

  12. Altered Brain Glucose Consumption in Cogan's Syndrome

    PubMed Central

    Ruffini, Livia; Ghirardini, Stella; Scarlattei, Maura; Baldari, Giorgio; Cidda, Carla; Gandolfi, Stefano A.; Orsoni, Jelka G.

    2016-01-01

    Purpose. Prospective, controlled cohort study to investigate possible alterations in brain glucose metabolism (CMRglc) in patients with Cogan's syndrome (CS). Patients and Methods. Functional mapping of the CMRglc was obtained by quantitative molecular imaging positron emission tomography, combined with computed tomography (FDG-PET/CT). The patients were divided into three clinical groups: typical CS; atypical CS (ACS); autoimmune inner ear disease (AIED). The unmatched control group (CG) consisted of subjects requiring FDG-PET/CT for an extracranial pathology. Statistical mapping searched areas of significant glucose hypometabolism in all the affected patients (DG) and in each clinical subgroup. The results were compared with those of the CG. Results. 44 patients were enrolled (DG) and assigned to the three study groups: 8 patients to the CS group; 21 patients to the ACS group; and 15 to the AIED group. Sixteen subjects formed the CG group. Areas of significant brain glucose hypometabolism were identified in all the study groups, with the largest number and extension in the DG and CS. Conclusions. This study revealed areas of significantly altered CMRglc in patients with CS (any subform) without neurologic complains and normal conventional neuroimaging. Our results suggest that FDG-PET/CT may represent a very useful tool for the global assessment of patients with Cogan's syndrome. PMID:28050276

  13. Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease.

    PubMed

    Zhang, Liang; Trushin, Sergey; Christensen, Trace A; Bachmeier, Benjamin V; Gateno, Benjamin; Schroeder, Andreas; Yao, Jia; Itoh, Kie; Sesaki, Hiromi; Poon, Wayne W; Gylys, Karen H; Patterson, Emily R; Parisi, Joseph E; Diaz Brinton, Roberta; Salisbury, Jeffrey L; Trushina, Eugenia

    2016-01-05

    Altered brain metabolism is associated with progression of Alzheimer's Disease (AD). Mitochondria respond to bioenergetic changes by continuous fission and fusion. To account for three dimensional architecture of the brain tissue and organelles, we applied 3-dimensional electron microscopy (3D EM) reconstruction to visualize mitochondrial structure in the brain tissue from patients and mouse models of AD. We identified a previously unknown mitochondrial fission arrest phenotype that results in elongated interconnected organelles, "mitochondria-on-a-string" (MOAS). Our data suggest that MOAS formation may occur at the final stages of fission process and was not associated with altered translocation of activated dynamin related protein 1 (Drp1) to mitochondria but with reduced GTPase activity. Since MOAS formation was also observed in the brain tissue of wild-type mice in response to hypoxia or during chronological aging, fission arrest may represent fundamental compensatory adaptation to bioenergetic stress providing protection against mitophagy that may preserve residual mitochondrial function. The discovery of novel mitochondrial phenotype that occurs in the brain tissue in response to energetic stress accurately detected only using 3D EM reconstruction argues for a major role of mitochondrial dynamics in regulating neuronal survival.

  14. Unpredictable Chronic Stress Alters Adenosine Metabolism in Zebrafish Brain.

    PubMed

    Zimmermann, F F; Altenhofen, S; Kist, L W; Leite, C E; Bogo, M R; Cognato, G P; Bonan, C D

    2016-05-01

    Stress is considered a risk factor for several human disorders. Despite the broad knowledge of stress responses in mammals, data on the relationship between unpredictable chronic stress (UCS) and its effects on purinergic signaling are limited. ATP hydrolysis by ectonucleotidases is an important source of adenosine, and adenosine deaminase (ADA) contributes to the control of the nucleoside concentrations. Considering that some stress models could affect signaling systems, the objective of this study was to investigate whether UCS alters ectonucleotidase and ADA pathway in zebrafish brain. Additionally, we analyzed ATP metabolism as well as ada1, ada2.1, ada2.2, adaL, and adaasi gene expression in zebrafish brain. Our results have demonstrated that UCS did not alter ectonucleotidase and soluble ADA activities. However, ecto-ADA activity was significantly decreased (26.8%) in brain membranes of animals exposed to UCS when compared to the control group. Quantitative reverse transcription PCR (RT-PCR) analysis did not show significant changes on ADA gene expression after the UCS exposure. The brain ATP metabolism showed a marked increase in adenosine levels (ADO) in animals exposed to UCS. These data suggest an increase on extracellular adenosine levels in zebrafish brain. Since this nucleoside has neuromodulatory and anxiolytic effects, changes in adenosine levels could play a role in counteracting the stress, which could be related to a compensatory mechanism in order to restore the homeostasis.

  15. Benevolent sexism alters executive brain responses.

    PubMed

    Dardenne, Benoit; Dumont, Muriel; Sarlet, Marie; Phillips, Christophe; Balteau, Evelyne; Degueldre, Christian; Luxen, André; Salmon, Eric; Maquet, Pierre; Collette, Fabienne

    2013-07-10

    Benevolence is widespread in our societies. It is defined as considering a subordinate group nicely but condescendingly, that is, with charity. Deleterious consequences for the target have been reported in the literature. In this experiment, we used functional MRI (fMRI) to identify whether being the target of (sexist) benevolence induces changes in brain activity associated with a working memory task. Participants were confronted by benevolent, hostile, or neutral comments before and while performing a reading span test in an fMRI environment. fMRI data showed that brain regions associated previously with intrusive thought suppression (bilateral, dorsolateral, prefrontal, and anterior cingulate cortex) reacted specifically to benevolent sexism compared with hostile sexism and neutral conditions during the performance of the task. These findings indicate that, despite being subjectively positive, benevolence modifies task-related brain networks by recruiting supplementary areas likely to impede optimal cognitive performance.

  16. Resting State Brain Entropy Alterations in Relapsing Remitting Multiple Sclerosis

    PubMed Central

    Zhou, Fuqing; Zhuang, Ying; Gong, Honghan; Zhan, Jie; Grossman, Murray; Wang, Ze

    2016-01-01

    Brain entropy (BEN) mapping provides a novel approach to characterize brain temporal dynamics, a key feature of human brain. Using resting state functional magnetic resonance imaging (rsfMRI), reliable and spatially distributed BEN patterns have been identified in normal brain, suggesting a potential use in clinical populations since temporal brain dynamics and entropy may be altered in disease conditions. The purpose of this study was to characterize BEN in multiple sclerosis (MS), a neurodegenerative disease that affects millions of people. Since currently there is no cure for MS, developing treatment or medication that can slow down its progression represents a high research priority, for which validating a brain marker sensitive to disease and the related functional impairments is essential. Because MS can start long time before any measurable symptoms and structural deficits, assessing the dynamic brain activity and correspondingly BEN may provide a critical way to study MS and its progression. Because BEN is new to MS, we aimed to assess BEN alterations in the relapsing-remitting MS (RRMS) patients using a patient versus control design, to examine the correlation of BEN to clinical measurements, and to check the correlation of BEN to structural brain measures which have been more often used in MS studies. As compared to controls, RRMS patients showed increased BEN in motor areas, executive control area, spatial coordinating area, and memory system. Increased BEN was related to greater disease severity as measured by the expanded disability status scale (EDSS) and greater tissue damage as indicated by the mean diffusivity. Patients also showed decreased BEN in other places, which was associated with less disability or fatigue, indicating a disease-related BEN re-distribution. Our results suggest BEN as a novel and useful tool for characterizing RRMS. PMID:26727514

  17. Violent Video Games Alter Brain Function in Young Men

    MedlinePlus

    ... News from the RSNA Annual Meeting Violent Video Games Alter Brain Function in Young Men At A ... MRI, researchers have found that playing violent video games for one week causes changes in brain function. ...

  18. Genetic variants of FOXP2 and KIAA0319/TTRAP/THEM2 locus are associated with altered brain activation in distinct language-related regions.

    PubMed

    Pinel, Philippe; Fauchereau, Fabien; Moreno, Antonio; Barbot, Alexis; Lathrop, Mark; Zelenika, Diana; Le Bihan, Denis; Poline, Jean-Baptiste; Bourgeron, Thomas; Dehaene, Stanislas

    2012-01-18

    Recent advances have been made in the genetics of two human communication skills: speaking and reading. Mutations of the FOXP2 gene cause a severe form of language impairment and orofacial dyspraxia, while single-nucleotide polymorphisms (SNPs) located within a KIAA0319/TTRAP/THEM2 gene cluster and affecting the KIAA0319 gene expression are associated with reading disability. Neuroimaging studies of clinical populations point to partially distinct cerebral bases for language and reading impairments. However, alteration of FOXP2 and KIAA0319/TTRAP/THEM2 polymorphisms on typically developed language networks has never been explored. Here, we genotyped and scanned 94 healthy subjects using fMRI during a reading task. We studied the correlation of genetic polymorphisms with interindividual variability in brain activation and functional asymmetry in frontal and temporal cortices. In FOXP2, SNPs rs6980093 and rs7799109 were associated with variations of activation in the left frontal cortex. In the KIAA0319/TTRAP/THEM2 locus, rs17243157 was associated with asymmetry in functional activation of the superior temporal sulcus (STS). Interestingly, healthy subjects bearing the KIAA0319/TTRAP/THEM2 variants previously identified as enhancing the risk of dyslexia showed a reduced left-hemispheric asymmetry of the STS. Our results confirm that both FOXP2 and KIAA0319/TTRAP/THEM2 genes play an important role in human language development, but probably through different cerebral pathways. The observed cortical effects mirror previous fMRI results in developmental language and reading disorders, and suggest that a continuum may exist between these pathologies and normal interindividual variability.

  19. Complement Activation Alters Platelet Function

    DTIC Science & Technology

    2013-10-01

    mice and mice transfused with Syk inhibitor-treated platelets . Platelet lodging was remarkably decreased in lungs of mice transfused with Syk...AD_________________ Award Number: W81XWH-12-1-0523 TITLE: Complement Activation Alters Platelet ...30September2012–29September2013 4. TITLE AND SUBTITLE Complement Activation Alters Platelet Function 5a. CONTRACT NUMBER W81XWH-12-1-0523 5b. GRANT NUMBER

  20. Methamphetamine Alters Brain Structures, Impairs Mental Flexibility

    MedlinePlus

    ... Adolescent Brain Comorbidity College-Age & Young Adults Criminal Justice Drugged Driving Drug Testing Drugs and the Brain ... Brain College-Age and Young Adults Comorbidity Criminal Justice Drug Testing Drugged Driving Evidence-Based Practices Genetics ...

  1. Brain mitochondrial ATP-insensitive large conductance Ca⁺²-activated K⁺ channel properties are altered in a rat model of amyloid-β neurotoxicity.

    PubMed

    Jafari, A; Noursadeghi, E; Khodagholi, F; Saghiri, R; Sauve, R; Aliaghaei, A; Eliassi, A

    2015-07-01

    Mitochondrial dysfunction is a hallmark of amyloid-beta (Aβ)-induced neuronal toxicity in Alzheimer's disease (AD). However, the underlying mechanism of how Aβ affects mitochondrial function remains uncertain. Because mitochondrial potassium channels have been involved in several mitochondrial functions including cytoprotection, apoptosis and calcium homeostasis, a study was undertaken to investigate whether the gating behavior of the mitochondrial ATP- and ChTx-insensitive-IbTx-sensitive Ca(2+)-activated potassium channel (mitoBKCa) is altered in a rat model of Aβ neurotoxicity. Aβ1-42 (4 μg/μl) was intracerebroventricularly injected in male Wistar rats (220-250 g). Brain Aβ accumulation was confirmed two weeks later on the basis of an immunohistochemistry staining assay, and physiological impacts measured in passive avoidance task cognitive performance experiments. Brain mitochondrial inner membranes were then extracted and membrane vesicles prepared for channel incorporation into bilayer lipid. Purity of the cell fraction was confirmed by Western blot using specific markers of mitochondria, plasma membrane, endoplasmic reticulum, and Golgi. Our results first provide evidence for differences in mitoBKCa ion permeation properties with channels coming from Aβ vesicle preparations characterized by an inward rectifying I-V curve, in contrast to control mitoBKCa channels which showed a linear I-V relationship under the same ionic conditions (200 mM cis/50mM trans). More importantly the open probability of channels from Aβ vesicles appeared 1.5 to 2.5 smaller compared to controls, the most significant decrease being observed at depolarizing potentials (30 mV to 50 mV). Because BKCa-β4 subunit has been documented to shift the BKCa channel voltage dependence curve, a Western blot analysis was undertaken where expression of mitoBKCa α and β4 subunits was estimated using anti-α and β4 subunit antibodies. Our results indicated a significant increase in mito

  2. Altered baseline brain activity in experts measured by amplitude of low frequency fluctuations (ALFF): a resting state fMRI study using expertise model of acupuncturists.

    PubMed

    Dong, Minghao; Li, Jun; Shi, Xinfa; Gao, Shudan; Fu, Shijun; Liu, Zongquan; Liang, Fanrong; Gong, Qiyong; Shi, Guangming; Tian, Jie

    2015-01-01

    It is well established that expertise modulates evoked brain activity in response to specific stimuli. Recently, researchers have begun to investigate how expertise influences the resting brain. Among these studies, most focused on the connectivity features within/across regions, i.e., connectivity patterns/strength. However, little concern has been given to a more fundamental issue whether or not expertise modulates baseline brain activity. We investigated this question using amplitude of low-frequency (<0.08 Hz) fluctuation (ALFF) as the metric of brain activity and a novel expertise model, i.e., acupuncturists, due to their robust proficiency in tactile perception and emotion regulation. After the psychophysical and behavioral expertise screening procedure, 23 acupuncturists and 23 matched non-acupuncturists (NA) were enrolled. Our results explicated higher ALFF for acupuncturists in the left ventral medial prefrontal cortex (VMPFC) and the contralateral hand representation of the primary somatosensory area (SI) (corrected for multiple comparisons). Additionally, ALFF of VMPFC was negatively correlated with the outcomes of the emotion regulation task (corrected for multiple comparisons). We suggest that our study may reveal a novel connection between the neuroplasticity mechanism and resting state activity, which would upgrade our understanding of the central mechanism of learning. Furthermore, by showing that expertise can affect the baseline brain activity as indicated by ALFF, our findings may have profound implication for functional neuroimaging studies especially those involving expert models, in that difference in baseline brain activity may either smear the spatial pattern of activations for task data or introduce biased results into connectivity-based analysis for resting data.

  3. Altered Brain Microstate Dynamics in Adolescents with Narcolepsy

    PubMed Central

    Drissi, Natasha M.; Szakács, Attila; Witt, Suzanne T.; Wretman, Anna; Ulander, Martin; Ståhlbrandt, Henriettae; Darin, Niklas; Hallböök, Tove; Landtblom, Anne-Marie; Engström, Maria

    2016-01-01

    Narcolepsy is a chronic sleep disorder caused by a loss of hypocretin-1 producing neurons in the hypothalamus. Previous neuroimaging studies have investigated brain function in narcolepsy during rest using positron emission tomography (PET) and single photon emission computed tomography (SPECT). In addition to hypothalamic and thalamic dysfunction they showed aberrant prefrontal perfusion and glucose metabolism in narcolepsy. Given these findings in brain structure and metabolism in narcolepsy, we anticipated that changes in functional magnetic resonance imaging (fMRI) resting state network (RSN) dynamics might also be apparent in patients with narcolepsy. The objective of this study was to investigate and describe brain microstate activity in adolescents with narcolepsy and correlate these to RSNs using simultaneous fMRI and electroencephalography (EEG). Sixteen adolescents (ages 13–20) with a confirmed diagnosis of narcolepsy were recruited and compared to age-matched healthy controls. Simultaneous EEG and fMRI data were collected during 10 min of wakeful rest. EEG data were analyzed for microstates, which are discrete epochs of stable global brain states obtained from topographical EEG analysis. Functional MRI data were analyzed for RSNs. Data showed that narcolepsy patients were less likely than controls to spend time in a microstate which we found to be related to the default mode network and may suggest a disruption of this network that is disease specific. We concluded that adolescents with narcolepsy have altered resting state brain dynamics. PMID:27536225

  4. Alteration in synaptic junction proteins following traumatic brain injury.

    PubMed

    Merlo, Lucia; Cimino, Francesco; Angileri, Filippo Flavio; La Torre, Domenico; Conti, Alfredo; Cardali, Salvatore Massimiliano; Saija, Antonella; Germanò, Antonino

    2014-08-15

    Extensive research and scientific efforts have been focused on the elucidation of the pathobiology of cellular and axonal damage following traumatic brain injury (TBI). Conversely, few studies have specifically addressed the issue of synaptic dysfunction. Synaptic junction proteins may be involved in post-TBI alterations, leading to synaptic loss or disrupted plasticity. A Synapse Protein Database on synapse ontology identified 109 domains implicated in synaptic activities and over 5000 proteins, but few of these demonstrated to play a role in the synaptic dysfunction after TBI. These proteins are involved in neuroplasticity and neuromodulation and, most importantly, may be used as novel neuronal markers of TBI for specific intervention.

  5. Altered spontaneous brain activity pattern in patients with high myopia using amplitude of low-frequency fluctuation: a resting-state fMRI study

    PubMed Central

    Huang, Xin; Zhou, Fu-Qing; Hu, Yu-Xiang; Xu, Xiao-Xuan; Zhou, Xiong; Zhong, Yu-Lin; Wang, Jun; Wu, Xiao-Rong

    2016-01-01

    Objective Many previous reports have demonstrated significant neural anatomy changes in the brain of high myopic (HM) patients, whereas the spontaneous brain activity changes in the HM patients at rest are not well studied. Our objective was to use amplitude of low-frequency fluctuation (ALFF) method to investigate the changes in spontaneous brain activity in HM patients and their relationships with clinical features. Methods A total of 38 patients with HM (17 males and 21 females) and 38 healthy controls (HCs) (17 males and 21 females) closely matched in age, sex, and education underwent resting-state functional magnetic resonance imaging scans. The ALFF method was used to assess local features of spontaneous brain activity. The relationship between the mean ALFF signal values in many brain regions and the clinical features in HM patients was calculated by correlation analysis. Results Compared with HCs, the HM patients had significantly lower ALFF in the right inferior and middle temporal gyrus, left middle temporal gyrus, left inferior frontal gyrus/putamen, right inferior frontal gyrus/putamen/insula, right middle frontal gyrus, and right inferior parietal lobule and higher ALFF values in the bilateral midcingulate cortex, left postcentral gyrus, and left precuneus/inferior parietal lobule. However, no relationship was found between the mean ALFF signal values of the different areas and the clinical manifestations in HM. Conclusion The HM patients were affected with brain dysfunction in many regions, which may indicate the presence of neurobiological changes involving deficits in language understanding and attentional control in HM patients. PMID:27881920

  6. Identification of altered brain metabolites associated with TNAP activity in a mouse model of hypophosphatasia using untargeted NMR-based metabolomics analysis

    PubMed Central

    Cruz, Thomas; Gleizes, Marie; Balayssac, Stéphane; Mornet, Etienne; Marsal, Grégory; Millán, José Luis; Martino, Myriam Malet; Nowak, Lionel G; Gilard, Véronique; Fonta, Caroline

    2017-01-01

    Tissue Nonspecific Alkaline Phosphatase (TNAP) is a key player of bone mineralization and TNAP gene (ALPL) mutations in human are responsible for hypophosphatasia (HPP), a rare heritable disease affecting the mineralization of bones and teeth. Moreover, TNAP is also expressed by brain cells and the severe forms of HPP are associated with neurological disorders, including epilepsy and brain morphological anomalies. However TNAP’s role in the nervous system remains poorly understood. In order to investigate its neuronal functions, we aimed to identify without any a priori the metabolites regulated by TNAP in the nervous tissue. For this purpose we used 1H- and 31P NMR to analyze the brain metabolome of Alpl (Akp2) mice null for TNAP function, a well-described model of infantile HPP. Among 39 metabolites identified in brain extracts of one week-old animals, 8 displayed significantly different concentration in Akp2−/− compared to Akp2+/+ and Akp2+/− mice: cystathionine, adenosine, GABA, methionine, histidine, 3-methylhistidine, N-acetylaspartate (NAA) and N-acetyl-aspartyl-glutamate (NAAG), with cystathionine and adenosine levels displaying the strongest alteration. These metabolites identify several biochemical processes that directly or indirectly involve TNAP function, in particular through the regulation of ecto-nucleotide levels and of pyridoxal phosphate-dependent enzymes. Some of these metabolites are involved in neurotransmission (GABA, adenosine), in myelin synthesis (NAA, NAAG), and in the methionine cycle and transsulfuration pathway (cystathionine, methionine). Their disturbances may contribute to the neurodevelopmental and neurological phenotype of HPP. PMID:28072448

  7. Violent Video Games Alter Brain Function in Young Men

    MedlinePlus

    ... RSS feed News from the RSNA Annual Meeting Violent Video Games Alter Brain Function in Young Men ... Using functional MRI, researchers have found that playing violent video games for one week causes changes in ...

  8. Methylglyoxal can mediate behavioral and neurochemical alterations in rat brain.

    PubMed

    Hansen, Fernanda; Pandolfo, Pablo; Galland, Fabiana; Torres, Felipe Vasconcelos; Dutra, Márcio Ferreira; Batassini, Cristiane; Guerra, Maria Cristina; Leite, Marina Concli; Gonçalves, Carlos-Alberto

    2016-10-01

    Diabetes is associated with loss of cognitive function and increased risk for Alzheimer's disease (AD). Advanced glycation end products (AGEs) are elevated in diabetes and AD and have been suggested to act as mediators of the cognitive decline observed in these pathologies. Methylglyoxal (MG) is an extremely reactive carbonyl compound that propagates glycation reactions and is, therefore, able to generate AGEs. Herein, we evaluated persistent behavioral and biochemical parameters to explore the hypothesis that elevated exogenous MG concentrations, induced by intracerebroventricular (ICV) infusion, lead to cognitive decline in Wistar rats. A high and sustained administration of MG (3μmol/μL; subdivided into 6days) was found to decrease the recognition index of rats, as evaluated by the object-recognition test. However, MG was unable to impair learning-memory processes, as shown by the habituation in the open field (OF) and Y-maze tasks. Moreover, a single high dose of MG induced persistent alterations in anxiety-related behavior, diminishing the anxiety-like parameters evaluated in the OF test. Importantly, MG did not alter locomotion behavior in the different tasks performed. Our biochemical findings support the hypothesis that MG induces persistent alterations in the hippocampus, but not in the cortex, related to glyoxalase 1 activity, AGEs content and glutamate uptake. Glial fibrillary acidic protein and S100B content, as well as S100B secretion (astroglial-related parameters of brain injury), were not altered by ICV MG administration. Taken together, our data suggest that MG interferes directly in brain function and that the time and the levels of exogenous MG determine the different features that can be seen in diabetic patients.

  9. Mitochondrial bioenergetic alterations after focal traumatic brain injury in the immature brain.

    PubMed

    Kilbaugh, Todd J; Karlsson, Michael; Byro, Melissa; Bebee, Ashley; Ralston, Jill; Sullivan, Sarah; Duhaime, Ann-Christine; Hansson, Magnus J; Elmér, Eskil; Margulies, Susan S

    2015-09-01

    Traumatic brain injury (TBI) is one of the leading causes of death in children worldwide. Emerging evidence suggests that alterations in mitochondrial function are critical components of secondary injury cascade initiated by TBI that propogates neurodegeneration and limits neuroregeneration. Unfortunately, there is very little known about the cerebral mitochondrial bioenergetic response from the immature brain triggered by traumatic biomechanical forces. Therefore, the objective of this study was to perform a detailed evaluation of mitochondrial bioenergetics using high-resolution respirometry in a high-fidelity large animal model of focal controlled cortical impact injury (CCI) 24h post-injury. This novel approach is directed at analyzing dysfunction in electron transport, ADP phosphorylation and leak respiration to provide insight into potential mechanisms and possible interventions for mitochondrial dysfunction in the immature brain in focal TBI by delineating targets within the electron transport system (ETS). Development and application of these methodologies have several advantages, and adds to the interpretation of previously reported techniques, by having the added benefit that any toxins or neurometabolites present in the ex-vivo samples are not removed during the mitochondrial isolation process, and simulates the in situ tricarboxylic acid (TCA) cycle by maximizing key substrates for convergent flow of electrons through both complexes I and II. To investigate alterations in mitochondrial function after CCI, ipsilateral tissue near the focal impact site and tissue from the corresponding contralateral side were examined. Respiration per mg of tissue was also related to citrate synthase activity (CS) and calculated flux control ratios (FCR), as an attempt to control for variability in mitochondrial content. Our biochemical analysis of complex interdependent pathways of electron flow through the electron transport system, by most measures, reveals a bilateral

  10. Modulation in Activation and Expression of PTEN, Akt1, and PDK1: Further Evidence Demonstrating Altered Phosphoinositide 3-kinase Signaling in Postmortem Brain of Suicide Subjects

    PubMed Central

    Dwivedi, Yogesh; Rizavi, Hooriyah S.; Zhang, Hui; Roberts, Rosalinda C.; Conley, Robert R.; Pandey, Ghanshyam N.

    2010-01-01

    Background Phosphoinositide 3-kinase (PI 3-K) signaling plays a crucial role in neuronal growth and plasticity. Recently, we demonstrated that suicide brain is associated with decreased activation and expression of selective catalytic and regulatory subunits of PI 3-K. The present investigation examined the regulation and functional significance of compromised PI 3-K in suicide brain at the level of upstream phosphatase and tensin homolog on chromosome ten (PTEN) and downstream substrates 3-phosphoinositide-dependent kinase 1 (PDK1) and Akt. Method mRNA expression of Akt1, Akt3, PTEN, and PDK1 by competitive RT-PCR; protein expression of Akt1, Akt3, PTEN, PDK1, phosphorylated-Akt1 (Ser473), phosphorylated-Akt1(Thr308), phosphorylated-PDK1, and phosphorylated-PTEN by Western blot; and catalytic activities of Akt1, Akt3, and PDK1 by enzymatic assays were determined in prefrontal cortex (PFC) and hippocampus obtained from suicide subjects and nonpsychiatric controls. Results No significant changes in the expression of Akt1 or Akt3 were observed; however, catalytic activity of Akt1, but not of Akt3, was decreased in PFC and hippocampus of suicide subjects, which was associated with decreased phosphorylation of Akt1 at Ser473 and Thr308. The catalytic activity of PDK1 and the level of phosphorylated-PDK1 were also decreased in both brain areas without any change in expression levels of PDK1. On the other hand, mRNA and protein expression of PTEN was increased, whereas the level of phosphorylated-PTEN was decreased. Conclusion Our study demonstrates abnormalities in PI 3-K signaling at several levels in brain of suicide subjects and suggests the possible involvement of aberrant PI 3-K/Akt signaling in the pathogenic mechanisms of suicide. PMID:20163786

  11. Altered Cognitive Control Activations after Moderate-to-Severe Traumatic Brain Injury and Their Relationship to Injury Severity and Everyday-Life Function.

    PubMed

    Olsen, Alexander; Brunner, Jan Ferenc; Indredavik Evensen, Kari Anne; Finnanger, Torun Gangaune; Vik, Anne; Skandsen, Toril; Landrø, Nils Inge; Håberg, Asta Kristine

    2015-08-01

    This study investigated how the neuronal underpinnings of both adaptive and stable cognitive control processes are affected by traumatic brain injury (TBI). Functional magnetic resonance imaging (fMRI) was undertaken in 62 survivors of moderate-to-severe TBI (>1 year after injury) and 68 healthy controls during performance of a continuous performance test adapted for use in a mixed block- and event-related design. Survivors of TBI demonstrated increased reliance on adaptive task control processes within an a priori core region for cognitive control in the medial frontal cortex. TBI survivors also had increased activations related to time-on-task effects during stable task-set maintenance in right inferior parietal and prefrontal cortices. Increased brain activations in TBI survivors had a dose-dependent linear positive relationship to injury severity and were negatively correlated with self-reported cognitive control problems in everyday-life situations. Results were adjusted for age, education, and fMRI task performance. In conclusion, evidence was provided that the neural underpinnings of adaptive and stable control processes are differently affected by TBI. Moreover, it was demonstrated that increased brain activations typically observed in survivors of TBI might represent injury-specific compensatory adaptations also utilized in everyday-life situations.

  12. Altered Cognitive Control Activations after Moderate-to-Severe Traumatic Brain Injury and Their Relationship to Injury Severity and Everyday-Life Function

    PubMed Central

    Olsen, Alexander; Brunner, Jan Ferenc; Indredavik Evensen, Kari Anne; Finnanger, Torun Gangaune; Vik, Anne; Skandsen, Toril; Landrø, Nils Inge; Håberg, Asta Kristine

    2015-01-01

    This study investigated how the neuronal underpinnings of both adaptive and stable cognitive control processes are affected by traumatic brain injury (TBI). Functional magnetic resonance imaging (fMRI) was undertaken in 62 survivors of moderate-to-severe TBI (>1 year after injury) and 68 healthy controls during performance of a continuous performance test adapted for use in a mixed block- and event-related design. Survivors of TBI demonstrated increased reliance on adaptive task control processes within an a priori core region for cognitive control in the medial frontal cortex. TBI survivors also had increased activations related to time-on-task effects during stable task-set maintenance in right inferior parietal and prefrontal cortices. Increased brain activations in TBI survivors had a dose-dependent linear positive relationship to injury severity and were negatively correlated with self-reported cognitive control problems in everyday-life situations. Results were adjusted for age, education, and fMRI task performance. In conclusion, evidence was provided that the neural underpinnings of adaptive and stable control processes are differently affected by TBI. Moreover, it was demonstrated that increased brain activations typically observed in survivors of TBI might represent injury-specific compensatory adaptations also utilized in everyday-life situations. PMID:24557637

  13. Intensive reasoning training alters patterns of brain connectivity at rest.

    PubMed

    Mackey, Allyson P; Miller Singley, Alison T; Bunge, Silvia A

    2013-03-13

    Patterns of correlated activity among brain regions reflect functionally relevant networks that are widely assumed to be stable over time. We hypothesized that if these correlations reflect the prior history of coactivation of brain regions, then a marked shift in cognition could alter the strength of coupling between these regions. We sought to test whether intensive reasoning training in humans would result in tighter coupling among regions in the lateral frontoparietal network, as measured with resting-state fMRI (rs-fMRI). Rather than designing an artificial training program, we studied individuals who were preparing for a standardized test that places heavy demands on relational reasoning, the Law School Admissions Test (LSAT). LSAT questions require test takers to group or sequence items according to a set of complex rules. We recruited young adults who were enrolled in an LSAT course that offers 70 h of reasoning instruction (n = 25), and age- and IQ-matched controls intending to take the LSAT in the future (n = 24). rs-fMRI data were collected for all subjects during two scanning sessions separated by 90 d. An analysis of pairwise correlations between brain regions implicated in reasoning showed that fronto-parietal connections were strengthened, along with parietal-striatal connections. These findings provide strong evidence for neural plasticity at the level of large-scale networks supporting high-level cognition.

  14. Altered whole-brain connectivity in albinism.

    PubMed

    Welton, Thomas; Ather, Sarim; Proudlock, Frank A; Gottlob, Irene; Dineen, Robert A

    2017-02-01

    Albinism is a group of congenital disorders of the melanin synthesis pathway. Multiple ocular, white matter and cortical abnormalities occur in albinism, including a greater decussation of nerve fibres at the optic chiasm, foveal hypoplasia and nystagmus. Despite this, visual perception is largely preserved. It was proposed that this may be attributable to reorganisation among cerebral networks, including an increased interhemispheric connectivity of the primary visual areas. A graph-theoretic model was applied to explore brain connectivity networks derived from resting-state functional and diffusion-tensor magnetic resonance imaging data in 23 people with albinism and 20 controls. They tested for group differences in connectivity between primary visual areas and in summary network organisation descriptors. Main findings were supplemented with analyses of control regions, brain volumes and white matter microstructure. Significant functional interhemispheric hyperconnectivity of the primary visual areas in the albinism group were found (P = 0.012). Tests of interhemispheric connectivity based on the diffusion-tensor data showed no significant group difference (P = 0.713). Second, it was found that a range of functional whole-brain network metrics were abnormal in people with albinism, including the clustering coefficient (P = 0.005), although this may have been driven partly by overall differences in connectivity, rather than reorganisation. Based on the results, it was suggested that changes occur in albinism at the whole-brain level, and not just within the visual processing pathways. It was proposed that their findings may reflect compensatory adaptations to increased chiasmic decussation, foveal hypoplasia and nystagmus. Hum Brain Mapp 38:740-752, 2017. © 2016 Wiley Periodicals, Inc.

  15. Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain

    PubMed Central

    Zhang, Xiaowei; Bearer, Elaine L.; Boulat, Benoit; Hall, F. Scott; Uhl, George R.; Jacobs, Russell E.

    2010-01-01

    The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn2+ into the prefrontal cortex indicated that DAT KO mice have a truncated Mn2+ distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn2+ transport into more posterior midbrain nuclei and contralateral mesolimbic structures at

  16. Killing two birds with one stone: the potential role of aripiprazole for patients with comorbid major depressive disorder and nicotine dependence via altering brain activity in the anterior cingulate cortex.

    PubMed

    Chu, Che-Sheng; Tzeng, Nian-Sheng; Chang, Hsin-An; Chang, Chuan-Chia; Chen, Tien-Yu

    2014-09-01

    The high comorbidity between major depressive disorder (MDD) and nicotine dependence (ND) is well recognized. Patients with comorbid MDD and ND often have increased suicidal risk and poor outcomes. A dysfunctional dopaminergic brain reward system might be a neurobiological link between MDD and ND. Aripiprazole has been considered as a dopamine stabilizer and was the first atypical antipsychotic agent approved by the US Food and Drug Administration as an adjunctive to the treatment of unipolar MDD. Bupropion is well known as a dual norepinephrine and dopamine reuptake inhibitor, and has been shown to be effective in smoking cessation. One reason bupropion is useful in treating ND is that it enhances the level of dopamine in the brain. Aripiprazole might act as a dopamine agonist similar to the way that bupropion does because of its partial dopamine D2 agonist and 30% intrinsic dopaminergic activity. Several recent studies have applied the unique pharmacodynamic characteristics of aripiprazole to treat patients with ND. Based on neuroimaging findings, aripiprazole can reduce substance cravings by altering brain activity, particularly in the brain regions of the anterior cingulate cortex. Therefore, we hypothesize that adjunctive aripiprazole with antidepressant may be an effective treatment for patients with MDD and ND comorbidity. A new drug invention that combines an antidepressant with an adequate dose of aripiprazole thus should be considered. The neurobiological basis for this combination to treat patients with MDD and ND comorbidity deserves further study.

  17. [Characteristics of the super-slow electrical activity of the brain when exposed to the action of neurotropic substances altering short-term memory].

    PubMed

    Borodkin, Iu S; Vereshchak, N I; Lapina, I A

    1976-01-01

    Superslow electrical activity was studied after the action of neurotropic drugs on curarized rabbits with gold electrodes implanted in the deep brain structures. Intramuscular administration of 1/5 mg/kg dose of ethimizol, of 5 mg/kg of ethipyrol, or of 1/5 mg/kg of metamizyl led to a reciprocity of the oscillation amplitudes between the field CA-3 of the dorsal hippocampus and the medial nuclear groups of the reticular formation. Ethimizol and ethipyrol, though producing a similar final effect, act differently on the duration and phases of slow oscillations. Micropolarization of the dorsal hippocampus field CA-3 with a 2.5 microampere current lengthened the action of the neurotropic drugs, up to six hours in the case of ethimyzol. A mathematical vector analysis has shown that the angle of the wave amplitude vector in space depends both on the characteristics of the neurotropic drug and the excitability level of field CA-3 of the dorsl hippo-campus. A slow electrical potential reflecting the capacity of the electric field of a brain structure is likely to be one the major components controlling the conformation position of the receptor proteins.

  18. A functional MRI study of altered spontaneous brain activity pattern in patients with congenital comitant strabismus using amplitude of low-frequency fluctuation

    PubMed Central

    Tan, Gang; Huang, Xin; Zhang, Ying; Wu, An-Hua; Zhong, Yu-Lin; Wu, Kai; Zhou, Fu-Qing; Shao, Yi

    2016-01-01

    Objective The aim of this study was to use amplitude of low-frequency fluctuation (ALFF) to investigate local features of spontaneous brain activity in patients with congenital comitant strabismus and clarify their relationship with emotional and psychosocial problems. Methods A total of 20 patients with congenital comitant strabismus (ten males and ten females), and 20 healthy controls (ten males and ten females) closely matched in age, sex, and education underwent resting-state functional magnetic resonance imaging scans. The ALFF method was used to assess local features of spontaneous brain activity. Congenital comitant strabismus patients were distinguished from healthy controls by receiver operating characteristic curve. Correlation analysis was performed to explore the relationships between the observed mean ALFF signal values of the different areas and the Chinese version of the Hospital Anxiety and Depression Scale. Results Compared with healthy controls, patients with congenital comitant strabismus had significantly lower ALFF in the bilateral medialfrontal gyrus and higher values in the bilateral cerebellum posterior lobe and left angular gyrus. In the congenital comitant strabismus group, the Hospital Anxiety and Depression Scale-depression score showed a negative correlation with the ALFF signal values of the bilateral medial frontal gyrus (r=−0.550, P=0.012) and a negative correlation was noted between the mean ALFF signal values of the left angular gyrus and strabismus duration (r=−0.515, P=0.020). Conclusion Congenital comitant strabismus mainly involves dysfunction in the bilateral medial frontal gyrus, bilateral cerebellum posterior lobe, and left angular gyrus, which may reflect the underlying pathologic mechanism of congenital strabismus. PMID:27284244

  19. Altered intrinsic regional brain activity in male patients with severe obstructive sleep apnea: a resting-state functional magnetic resonance imaging study

    PubMed Central

    Peng, De-Chang; Dai, Xi-Jian; Gong, Hong-Han; Li, Hai-Jun; Nie, Xiao; Zhang, Wei

    2014-01-01

    Background Previous studies have demonstrated that obstructive sleep apnea (OSA) is associated with abnormal brain structural deficits. However, little is known about the changes in local synchronization of spontaneous activity in patients with OSA. The primary aim of the present study was to investigate spontaneous brain activity in patients with OSA compared with good sleepers (GSs) using regional homogeneity (ReHo) analysis based on resting-state functional magnetic resonance imaging (MRI). Methods Twenty-five untreated male patients with severe OSA and 25 male GSs matched for age and years of education were included in this study. The ReHo method was calculated to assess the strength of local signal synchrony and was compared between the two groups. The observed mean ReHo values were entered into Statistical Package for the Social Sciences software to assess their correlation with behavioral performance. Results Compared with GSs, patients with OSA showed significantly lower ReHo in the right medial frontal gyrus (BA11), right superior frontal gyrus (BA10), right cluster of the precuneus and angular gyrus (BA39), and left superior parietal lobule (BA7), and higher ReHo in the right posterior lobe of the cerebellum, right cingulate gyrus (BA23), and bilateral cluster covering the lentiform nucleus, putamen, and insula (BA13). The lower mean ReHo value in the right cluster of the precuneus and angular gyrus had a significant negative correlation with sleep time (r=−0.430, P=0.032), and higher ReHo in the right posterior lobe of the cerebellum showed a significant positive correlation with stage 3 sleep (r=0.458, P=0.021) and in the right cingulate gyrus showed a significant positive correlation with percent rapid eye movement sleep (r=0.405, P=0.045). Conclusion Patients with OSA showed significant regional spontaneous activity deficits in default mode network areas. The ReHo method is a useful noninvasive imaging tool for detection of early changes in cerebral

  20. Mice lacking brain/kidney phosphate-activated glutaminase (GLS1) have impaired glutamatergic synaptic transmission, altered breathing, disorganized goal-directed behavior and die shortly after birth

    PubMed Central

    Masson, Justine; Darmon, Michèle; Conjard, Agnès; Chuhma, Nao; Ropert, Nicole; Thoby-Brisson, Muriel; Foutz, Arthur S.; Parrot, Sandrine; Miller, Gretchen M.; Jorisch, Renée; Polan, Jonathan; Hamon, Michel; Hen, René; Rayport, Stephen

    2009-01-01

    Neurotransmitter glutamate has been thought to derive mainly from glutamine via the action of glutaminase type 1 (GLS1). To address the importance of this pathway in glutamatergic transmission, we knocked out GLS1 in mice. The insertion of a STOP cassette by homologous recombination produced a null allele that blocked transcription, encoded no immunoreactive protein and abolished GLS1 enzymatic activity. Null mutants were slightly smaller, were deficient in goal-directed behavior, hypoventilated and died in the first post-natal day. No gross or microscopic defects were detected in peripheral organs or in the central nervous system. In cultured neurons from the null mutants, miniature EPSC amplitude and duration were normal; however, the amplitude of evoked EPSCs decayed more rapidly with sustained 10 Hz stimulation, consistent with an observed reduction in depolarization-evoked glutamate release. Because of this activity-dependent impairment in glutamatergic transmission, we surmised that respiratory networks, which require temporal summation of synaptic input, would be particularly affected. We found that the amplitude of inspirations was decreased in vivo, chemosensitivity to CO2 was severely altered, and the frequency of pacemaker activity recorded in the respiratory generator in the Pre-Bötzinger complex, a glutamatergic brainstem network that can be isolated in vitro, was increased. Our results show that while alternate pathways to GLS1 glutamate synthesis support baseline glutamatergic transmission, the GLS1 pathway is essential for maintaining the function of active synapses, and so the mutation is associated with impaired respiratory function, abnormal goal-directed behavior and neonatal demise. PMID:16641247

  1. Alteration of Political Belief by Non-invasive Brain Stimulation.

    PubMed

    Chawke, Caroline; Kanai, Ryota

    2015-01-01

    People generally have imperfect introspective access to the mechanisms underlying their political beliefs, yet can confidently communicate the reasoning that goes into their decision making process. An innate desire for certainty and security in ones beliefs may play an important and somewhat automatic role in motivating the maintenance or rejection of partisan support. The aim of the current study was to clarify the role of the DLPFC in the alteration of political beliefs. Recent neuroimaging studies have focused on the association between the DLPFC (a region involved in the regulation of cognitive conflict and error feedback processing) and reduced affiliation with opposing political candidates. As such, this study used a method of non-invasive brain simulation (tRNS) to enhance activity of the bilateral DLPFC during the incorporation of political campaign information. These findings indicate a crucial role for this region in political belief formation. However, enhanced activation of DLPFC does not necessarily result in the specific rejection of political beliefs. In contrast to the hypothesis the results appear to indicate a significant increase in conservative values regardless of participant's initial political orientation and the political campaign advertisement they were exposed to.

  2. Alteration of Political Belief by Non-invasive Brain Stimulation

    PubMed Central

    Chawke, Caroline; Kanai, Ryota

    2016-01-01

    People generally have imperfect introspective access to the mechanisms underlying their political beliefs, yet can confidently communicate the reasoning that goes into their decision making process. An innate desire for certainty and security in ones beliefs may play an important and somewhat automatic role in motivating the maintenance or rejection of partisan support. The aim of the current study was to clarify the role of the DLPFC in the alteration of political beliefs. Recent neuroimaging studies have focused on the association between the DLPFC (a region involved in the regulation of cognitive conflict and error feedback processing) and reduced affiliation with opposing political candidates. As such, this study used a method of non-invasive brain simulation (tRNS) to enhance activity of the bilateral DLPFC during the incorporation of political campaign information. These findings indicate a crucial role for this region in political belief formation. However, enhanced activation of DLPFC does not necessarily result in the specific rejection of political beliefs. In contrast to the hypothesis the results appear to indicate a significant increase in conservative values regardless of participant's initial political orientation and the political campaign advertisement they were exposed to. PMID:26834603

  3. Structural brain alterations can be detected early in HIV infection

    PubMed Central

    Ochs, Renee; Wu, Ying; Sammet, Christina L.; Shoukry, Alfred; Epstein, Leon G.

    2012-01-01

    Objective: Brain changes occurring early in HIV infection are not well characterized. The Chicago Early HIV Infection Study aimed to evaluate the presence and extent of structural brain alterations using quantitative MRI. Methods: Forty-three HIV and 21 control subjects were enrolled. Mean length of infection was estimated as less than 1 year based on assay results. High-resolution neuroanatomical images were acquired. Automated image analysis was used to derive measurements for total brain, ventricular volume, and for tissue classes (total and cortical gray matter, white matter, and CSF). A separate image analysis algorithm was used to calculate measurements for individual brain regions. Cognitive function was assessed by neuropsychological evaluation. Results: Reductions were quantified in total (p = 0.0547) and cortical (p = 0.0109) gray matter in the HIV group. Analysis of individual brain regions with a separate image analysis algorithm revealed consistent findings of reductions in cerebral cortex (p = 0.042) and expansion of third ventricle (p = 0.046). The early HIV group also demonstrated weaker performance on several neuropsychological tests, with the most pronounced difference in psychomotor speed (p = 0.001). Conclusions: This cross-sectional brain volumetric study indicates structural alterations early in HIV infection. The findings challenge the prevailing assumption that the brain is spared in this period. Revisiting the question of the brain's vulnerability to processes unfolding in the initial virus-host interaction and the early natural history may yield new insights into neurologic injury in HIV infection and inform neuroprotection strategies. PMID:23197750

  4. Altered resting brain function and structure in professional badminton players.

    PubMed

    Di, Xin; Zhu, Senhua; Jin, Hua; Wang, Pin; Ye, Zhuoer; Zhou, Ke; Zhuo, Yan; Rao, Hengyi

    2012-01-01

    Neuroimaging studies of professional athletic or musical training have demonstrated considerable practice-dependent plasticity in various brain structures, which may reflect distinct training demands. In the present study, structural and functional brain alterations were examined in professional badminton players and compared with healthy controls using magnetic resonance imaging (MRI) and resting-state functional MRI. Gray matter concentration (GMC) was assessed using voxel-based morphometry (VBM), and resting-brain functions were measured by amplitude of low-frequency fluctuation (ALFF) and seed-based functional connectivity. Results showed that the athlete group had greater GMC and ALFF in the right and medial cerebellar regions, respectively. The athlete group also demonstrated smaller ALFF in the left superior parietal lobule and altered functional connectivity between the left superior parietal and frontal regions. These findings indicate that badminton expertise is associated with not only plastic structural changes in terms of enlarged gray matter density in the cerebellum, but also functional alterations in fronto-parietal connectivity. Such structural and functional alterations may reflect specific experiences of badminton training and practice, including high-capacity visuo-spatial processing and hand-eye coordination in addition to refined motor skills.

  5. Altered Resting State Brain Networks in Parkinson’s Disease

    PubMed Central

    Göttlich, Martin; Münte, Thomas F.; Heldmann, Marcus; Kasten, Meike; Hagenah, Johann; Krämer, Ulrike M.

    2013-01-01

    Parkinson’s disease (PD) is a neurodegenerative disorder affecting dopaminergic neurons in the substantia nigra leading to dysfunctional cortico-striato-thalamic-cortical loops. In addition to the characteristic motor symptoms, PD patients often show cognitive impairments, affective changes and other non-motor symptoms, suggesting system-wide effects on brain function. Here, we used functional magnetic resonance imaging and graph-theory based analysis methods to investigate altered whole-brain intrinsic functional connectivity in PD patients (n = 37) compared to healthy controls (n = 20). Global network properties indicated less efficient processing in PD. Analysis of brain network modules pointed to increased connectivity within the sensorimotor network, but decreased interaction of the visual network with other brain modules. We found lower connectivity mainly between the cuneus and the ventral caudate, medial orbitofrontal cortex and the temporal lobe. To identify regions of altered connectivity, we mapped the degree of intrinsic functional connectivity both on ROI- and on voxel-level across the brain. Compared to healthy controls, PD patients showed lower connectedness in the medial and middle orbitofrontal cortex. The degree of connectivity was also decreased in the occipital lobe (cuneus and calcarine), but increased in the superior parietal cortex, posterior cingulate gyrus, supramarginal gyrus and supplementary motor area. Our results on global network and module properties indicated that PD manifests as a disconnection syndrome. This was most apparent in the visual network module. The higher connectedness within the sensorimotor module in PD patients may be related to compensation mechanism in order to overcome the functional deficit of the striato-cortical motor loops or to loss of mutual inhibition between brain networks. Abnormal connectivity in the visual network may be related to adaptation and compensation processes as a consequence of

  6. Altered resting-state whole-brain functional networks of neonates with intrauterine growth restriction.

    PubMed

    Batalle, Dafnis; Muñoz-Moreno, Emma; Tornador, Cristian; Bargallo, Nuria; Deco, Gustavo; Eixarch, Elisenda; Gratacos, Eduard

    2016-04-01

    The feasibility to use functional MRI (fMRI) during natural sleep to assess low-frequency basal brain activity fluctuations in human neonates has been demonstrated, although its potential to characterise pathologies of prenatal origin has not yet been exploited. In the present study, we used intrauterine growth restriction (IUGR) as a model of altered neurodevelopment due to prenatal condition to show the suitability of brain networks to characterise functional brain organisation at neonatal age. Particularly, we analysed resting-state fMRI signal of 20 neonates with IUGR and 13 controls, obtaining whole-brain functional networks based on correlations of blood oxygen level-dependent (BOLD) signal in 90 grey matter regions of an anatomical atlas (AAL). Characterisation of the networks obtained with graph theoretical features showed increased network infrastructure and raw efficiencies but reduced efficiency after normalisation, demonstrating hyper-connected but sub-optimally organised IUGR functional brain networks. Significant association of network features with neurobehavioral scores was also found. Further assessment of spatiotemporal dynamics displayed alterations into features associated to frontal, cingulate and lingual cortices. These findings show the capacity of functional brain networks to characterise brain reorganisation from an early age, and their potential to develop biomarkers of altered neurodevelopment.

  7. Seizures and antiepileptic drugs: does exposure alter normal brain development?

    PubMed

    Marsh, Eric D; Brooks-Kayal, Amy R; Porter, Brenda E

    2006-12-01

    Seizures and antiepileptic drugs (AEDs) affect brain development and have long-term neurological consequences. The specific molecular and cellular changes, the precise timing of their influence during brain development, and the full extent of the long-term consequences of seizures and AEDs exposure have not been established. This review critically assesses both the basic and clinical science literature on the effects of seizures and AEDs on the developing brain and finds that evidence exists to support the hypothesis that both seizures and antiepileptic drugs influence a variety of biological process, at specific times during development, which alter long-term cognition and epilepsy susceptibility. More research, both clinical and experimental, is needed before changes in current clinical practice, based on the scientific data, can be recommended.

  8. Brain anatomy alterations associated with Social Networking Site (SNS) addiction.

    PubMed

    He, Qinghua; Turel, Ofir; Bechara, Antoine

    2017-03-23

    This study relies on knowledge regarding the neuroplasticity of dual-system components that govern addiction and excessive behavior and suggests that alterations in the grey matter volumes, i.e., brain morphology, of specific regions of interest are associated with technology-related addictions. Using voxel based morphometry (VBM) applied to structural Magnetic Resonance Imaging (MRI) scans of twenty social network site (SNS) users with varying degrees of SNS addiction, we show that SNS addiction is associated with a presumably more efficient impulsive brain system, manifested through reduced grey matter volumes in the amygdala bilaterally (but not with structural differences in the Nucleus Accumbens). In this regard, SNS addiction is similar in terms of brain anatomy alterations to other (substance, gambling etc.) addictions. We also show that in contrast to other addictions in which the anterior-/ mid- cingulate cortex is impaired and fails to support the needed inhibition, which manifests through reduced grey matter volumes, this region is presumed to be healthy in our sample and its grey matter volume is positively correlated with one's level of SNS addiction. These findings portray an anatomical morphology model of SNS addiction and point to brain morphology similarities and differences between technology addictions and substance and gambling addictions.

  9. Brain anatomy alterations associated with Social Networking Site (SNS) addiction

    PubMed Central

    He, Qinghua; Turel, Ofir; Bechara, Antoine

    2017-01-01

    This study relies on knowledge regarding the neuroplasticity of dual-system components that govern addiction and excessive behavior and suggests that alterations in the grey matter volumes, i.e., brain morphology, of specific regions of interest are associated with technology-related addictions. Using voxel based morphometry (VBM) applied to structural Magnetic Resonance Imaging (MRI) scans of twenty social network site (SNS) users with varying degrees of SNS addiction, we show that SNS addiction is associated with a presumably more efficient impulsive brain system, manifested through reduced grey matter volumes in the amygdala bilaterally (but not with structural differences in the Nucleus Accumbens). In this regard, SNS addiction is similar in terms of brain anatomy alterations to other (substance, gambling etc.) addictions. We also show that in contrast to other addictions in which the anterior-/ mid- cingulate cortex is impaired and fails to support the needed inhibition, which manifests through reduced grey matter volumes, this region is presumed to be healthy in our sample and its grey matter volume is positively correlated with one’s level of SNS addiction. These findings portray an anatomical morphology model of SNS addiction and point to brain morphology similarities and differences between technology addictions and substance and gambling addictions. PMID:28332625

  10. Brain Activities and Educational Technology

    ERIC Educational Resources Information Center

    Riza, Emel

    2002-01-01

    There are close relationships between brain activities and educational technology. Brain is very important and so complicated part in our bodies. From long time scientists pay attention to that part and did many experiments, but they just reached little information like a drop in the sea. However from time to time they gave us some light to…

  11. [Physical activity and brain function].

    PubMed

    Kempermann, G

    2012-06-01

    Physical activity has direct and indirect effects on brain function in health and disease. Findings demonstrating that physical activity improves cognitive and non-cognitive functions and is preventive for several neuropsychiatric disorders have attracted particular interest. This short review focuses on sports and physical exercise in normal brain function and summarizes which mechanisms might underlie the observed effects, which methodological problems exist, which relationships exist to concepts of plasticity and neural reserves and what evolutionary relevance the initially surprising finding that physical exercise is good for the brain has.

  12. Repeated anabolic/androgenic steroid exposure during adolescence alters phosphate-activated glutaminase and glutamate receptor 1 (GluR1) subunit immunoreactivity in Hamster brain: correlation with offensive aggression.

    PubMed

    Fischer, Shannon G; Ricci, Lesley A; Melloni, Richard H

    2007-06-04

    Male Syrian hamsters (Mesocricetus auratus) treated with moderately high doses (5.0mg/kg/day) of anabolic/androgenic steroids (AAS) during adolescence (P27-P56) display highly escalated offensive aggression. The current study examined whether adolescent AAS-exposure influenced the immunohistochemical localization of phosphate-activated glutaminase (PAG), the rate-limiting enzyme in the synthesis of glutamate, a fast-acting neurotransmitter implicated in the modulation of aggression in various species and models of aggression, as well as glutamate receptor 1 subunit (GluR1). Hamsters were administered AAS during adolescence, scored for offensive aggression using the resident-intruder paradigm, and then examined for changes in PAG and GluR1 immunoreactivity in areas of the brain implicated in aggression control. When compared with sesame oil-treated control animals, aggressive AAS-treated hamsters displayed a significant increase in the number of PAG- and area density of GluR1-containing neurons in several notable aggression regions, although the differential pattern of expression did not appear to overlap across brain regions. Together, these results suggest that altered glutamate synthesis and GluR1 receptor expression in specific aggression areas may be involved in adolescent AAS-induced offensive aggression.

  13. Brain Gym. Simple Activities for Whole Brain Learning.

    ERIC Educational Resources Information Center

    Dennison, Paul E.; Dennison, Gail E.

    This booklet contains simple movements and activities that are used with students in Educational Kinesiology to enhance their experience of whole brain learning. Whole brain learning through movement repatterning and Brain Gym activities enable students to access those parts of the brain previously unavailable to them. These movements of body and…

  14. Altered lipid metabolism in brain injury and disorders.

    PubMed

    Adibhatla, Rao Muralikrishna; Hatcher, J F

    2008-01-01

    Deregulated lipid metabolism may be of particular importance for CNS injuries and disorders, as this organ has the highest lipid concentration next to adipose tissue. Atherosclerosis (a risk factor for ischemic stroke) results from accumulation of LDL-derived lipids in the arterial wall. Pro-inflammatory cytokines (TNF-alpha and IL-1), secretory phospholipase A2 IIA and lipoprotein-PLA2 are implicated in vascular inflammation. These inflammatory responses promote atherosclerotic plaques, formation and release of the blood clot that can induce ischemic stroke. TNF-alpha and IL-1 alter lipid metabolism and stimulate production of eicosanoids, ceramide, and reactive oxygen species that potentiate CNS injuries and certain neurological disorders. Cholesterol is an important regulator of lipid organization and the precursor for neurosteroid biosynthesis. Low levels of neurosteroids were related to poor outcome in many brain pathologies. Apolipoprotein E is the principal cholesterol carrier protein in the brain, and the gene encoding the variant Apolipoprotein E4 is a significant risk factor for Alzheimer's disease. Parkinson's disease is to some degree caused by lipid peroxidation due to phospholipases activation. Niemann-Pick diseases A and B are due to acidic sphingomyelinase deficiency, resulting in sphingomyelin accumulation, while Niemann-Pick disease C is due to mutations in either the NPC1 or NPC2 genes, resulting in defective cholesterol transport and cholesterol accumulation. Multiple sclerosis is an autoimmune inflammatory demyelinating condition of the CNS. Inhibiting phospholipase A2 attenuated the onset and progression of experimental autoimmune encephalomyelitis. The endocannabinoid system is hypoactive in Huntington's disease. Ethyl-eicosapetaenoate showed promise in clinical trials. Amyotrophic lateral sclerosis causes loss of motorneurons. Cyclooxygenase-2 inhibition reduced spinal neurodegeneration in amyotrophic lateral sclerosis transgenic mice

  15. Brain structural alterations associated with young women with subthreshold depression

    PubMed Central

    Li, Haijiang; Wei, Dongtao; Sun, Jiangzhou; Chen, Qunlin; Zhang, Qinglin; Qiu, Jiang

    2015-01-01

    Neuroanatomical abnormalities in patients with major depression disorder (MDD) have been attracted great research attention. However, the structural alterations associated with subthreshold depression (StD) remain unclear and, therefore, require further investigation. In this study, 42 young women with StD, and 30 matched non-depressed controls (NCs) were identified based on two-time Beck Depression Inventory scores. Whole-brain voxel-based morphometry (VBM) and region of interest method were used to investigate altered gray matter volume (GMV) and white matter volume (WMV) among a non-clinical sample of young women with StD. VBM results indicated that young women with StD showed significantly decreased GMV in the right inferior parietal lobule than NCs; increased GMV in the amygdala, posterior cingulate cortex, and precuneus; and increased WMV in the posterior cingulate cortex and precuneus. Together, structural alterations in specific brain regions, which are known to be involved in the fronto-limbic circuits implicated in depression may precede the occurrence of depressive episodes and influence the development of MDD. PMID:25982857

  16. Brain structural alterations associated with young women with subthreshold depression.

    PubMed

    Li, Haijiang; Wei, Dongtao; Sun, Jiangzhou; Chen, Qunlin; Zhang, Qinglin; Qiu, Jiang

    2015-05-18

    Neuroanatomical abnormalities in patients with major depression disorder (MDD) have been attracted great research attention. However, the structural alterations associated with subthreshold depression (StD) remain unclear and, therefore, require further investigation. In this study, 42 young women with StD, and 30 matched non-depressed controls (NCs) were identified based on two-time Beck Depression Inventory scores. Whole-brain voxel-based morphometry (VBM) and region of interest method were used to investigate altered gray matter volume (GMV) and white matter volume (WMV) among a non-clinical sample of young women with StD. VBM results indicated that young women with StD showed significantly decreased GMV in the right inferior parietal lobule than NCs; increased GMV in the amygdala, posterior cingulate cortex, and precuneus; and increased WMV in the posterior cingulate cortex and precuneus. Together, structural alterations in specific brain regions, which are known to be involved in the fronto-limbic circuits implicated in depression may precede the occurrence of depressive episodes and influence the development of MDD.

  17. Repeated swim stress alters brain benzodiazepine receptors measured in vivo

    SciTech Connect

    Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

    1989-06-01

    The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of (/sup 3/H)Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in (14C)iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress (an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures), although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results.

  18. Altered Brain Functional Activity in Infants with Congenital Bilateral Severe Sensorineural Hearing Loss: A Resting-State Functional MRI Study under Sedation

    PubMed Central

    Che, Jing; Li, Qiang; Chai, Chao; Zheng, Meizhu; Shen, Wen

    2017-01-01

    Early hearing deprivation could affect the development of auditory, language, and vision ability. Insufficient or no stimulation of the auditory cortex during the sensitive periods of plasticity could affect the function of hearing, language, and vision development. Twenty-three infants with congenital severe sensorineural hearing loss (CSSHL) and 17 age and sex matched normal hearing subjects were recruited. The amplitude of low frequency fluctuations (ALFF) and regional homogeneity (ReHo) of the auditory, language, and vision related brain areas were compared between deaf infants and normal subjects. Compared with normal hearing subjects, decreased ALFF and ReHo were observed in auditory and language-related cortex. Increased ALFF and ReHo were observed in vision related cortex, which suggest that hearing and language function were impaired and vision function was enhanced due to the loss of hearing. ALFF of left Brodmann area 45 (BA45) was negatively correlated with deaf duration in infants with CSSHL. ALFF of right BA39 was positively correlated with deaf duration in infants with CSSHL. In conclusion, ALFF and ReHo can reflect the abnormal brain function in language, auditory, and visual information processing in infants with CSSHL. This demonstrates that the development of auditory, language, and vision processing function has been affected by congenital severe sensorineural hearing loss before 4 years of age. PMID:28255465

  19. Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states.

    PubMed

    Lecrux, C; Hamel, E

    2016-10-05

    Brain imaging techniques that use vascular signals to map changes in neuronal activity, such as blood oxygenation level-dependent functional magnetic resonance imaging, rely on the spatial and temporal coupling between changes in neurophysiology and haemodynamics, known as 'neurovascular coupling (NVC)'. Accordingly, NVC responses, mapped by changes in brain haemodynamics, have been validated for different stimuli under physiological conditions. In the cerebral cortex, the networks of excitatory pyramidal cells and inhibitory interneurons generating the changes in neural activity and the key mediators that signal to the vascular unit have been identified for some incoming afferent pathways. The neural circuits recruited by whisker glutamatergic-, basal forebrain cholinergic- or locus coeruleus noradrenergic pathway stimulation were found to be highly specific and discriminative, particularly when comparing the two modulatory systems to the sensory response. However, it is largely unknown whether or not NVC is still reliable when brain states are altered or in disease conditions. This lack of knowledge is surprising since brain imaging is broadly used in humans and, ultimately, in conditions that deviate from baseline brain function. Using the whisker-to-barrel pathway as a model of NVC, we can interrogate the reliability of NVC under enhanced cholinergic or noradrenergic modulation of cortical circuits that alters brain states.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.

  20. Fueling and imaging brain activation

    PubMed Central

    Dienel, Gerald A

    2012-01-01

    Metabolic signals are used for imaging and spectroscopic studies of brain function and disease and to elucidate the cellular basis of neuroenergetics. The major fuel for activated neurons and the models for neuron–astrocyte interactions have been controversial because discordant results are obtained in different experimental systems, some of which do not correspond to adult brain. In rats, the infrastructure to support the high energetic demands of adult brain is acquired during postnatal development and matures after weaning. The brain's capacity to supply and metabolize glucose and oxygen exceeds demand over a wide range of rates, and the hyperaemic response to functional activation is rapid. Oxidative metabolism provides most ATP, but glycolysis is frequently preferentially up-regulated during activation. Underestimation of glucose utilization rates with labelled glucose arises from increased lactate production, lactate diffusion via transporters and astrocytic gap junctions, and lactate release to blood and perivascular drainage. Increased pentose shunt pathway flux also causes label loss from C1 of glucose. Glucose analogues are used to assay cellular activities, but interpretation of results is uncertain due to insufficient characterization of transport and phosphorylation kinetics. Brain activation in subjects with low blood-lactate levels causes a brain-to-blood lactate gradient, with rapid lactate release. In contrast, lactate flooding of brain during physical activity or infusion provides an opportunistic, supplemental fuel. Available evidence indicates that lactate shuttling coupled to its local oxidation during activation is a small fraction of glucose oxidation. Developmental, experimental, and physiological context is critical for interpretation of metabolic studies in terms of theoretical models. PMID:22612861

  1. Anatomical brain atlas for NIRS measurements of brain activation

    NASA Astrophysics Data System (ADS)

    Caffini, Matteo; Zucchelli, Lucia; Contini, Davide; Cubeddu, Rinaldo; Spinelli, Lorenzo; Boas, David; Torricelli, Alessandro

    2011-07-01

    Anatomical brain atlases have been introduced in the analysis NIRS data of brain activation and good spatial activation localization has been proved. We applied this method to visualize NIRS data from different protocols.

  2. Altered brain network modules induce helplessness in major depressive disorder

    PubMed Central

    Peng, Daihui; Shi, Feng; Shen, Ting; Peng, Ziwen; Zhang, Chen; Liu, Xiaohua; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Shen, Dinggang

    2017-01-01

    Objective The abnormal brain functional connectivity (FC) has been assumed to be a pathophysiological aspect of major depressive disorder (MDD). However, it is poorly understood, regarding the underlying patterns of global FC network and their relationships with the clinical characteristics of MDD. Methods Resting-state functional magnetic resonance imaging data were acquired from 16 first episode, medication-naïve MDD patients and 16 healthy control subjects. The global FC network was constructed using 90 brain regions. The global topological patterns, e.g., small-worldness and modularity, and their relationships with depressive characteristics were investigated. Furthermore, the participant coefficient and module degree of MDD patients were measured to reflect the regional roles in module network, and the impairment of FC was examined by network based statistic. Results Small-world property was not altered in MDD. However, MDD patients exhibited 5 atypically reorganized modules compared to the controls. A positive relationship was also found among MDD patients between the intra-module I and helplessness factor evaluated via the Hamilton Depression Scale. Specifically, eight regions exhibited the abnormal participant coefficient or module degree, e.g., left superior orbital frontal cortex and right amygdala. The decreased FC was identified among the sub-network of 24 brain regions, e.g., frontal cortex, supplementary motor area, amygdala, thalamus, and hippocampus. Limitation The limited size of MDD samples precluded meaningful study of distinct clinical characteristics in relation to aberrant FC. Conclusions The results revealed altered patterns of brain module network at the global level in MDD patients, which might contribute to the feelings of helplessness. PMID:25033474

  3. Altered spontaneous brain activity pattern in patients with late monocular blindness in middle-age using amplitude of low-frequency fluctuation: a resting-state functional MRI study

    PubMed Central

    Li, Qing; Huang, Xin; Ye, Lei; Wei, Rong; Zhang, Ying; Zhong, Yu-Lin; Jiang, Nan; Shao, Yi

    2016-01-01

    Objective Previous reports have demonstrated significant brain activity changes in bilateral blindness, whereas brain activity changes in late monocular blindness (MB) at rest are not well studied. Our study aimed to investigate spontaneous brain activity in patients with late middle-aged MB using the amplitude of low-frequency fluctuation (ALFF) method and their relationship with clinical features. Methods A total of 32 patients with MB (25 males and 7 females) and 32 healthy control (HC) subjects (25 males and 7 females), similar in age, sex, and education, were recruited for the study. All subjects were performed with resting-state functional magnetic resonance imaging scanning. The ALFF method was applied to evaluate spontaneous brain activity. The relationships between the ALFF signal values in different brain regions and clinical features in MB patients were investigated using correlation analysis. Results Compared with HCs, the MB patients had marked lower ALFF values in the left cerebellum anterior lobe, right parahippocampal gyrus, right cuneus, left precentral gyrus, and left paracentral lobule, but higher ALFF values in the right middle frontal gyrus, left middle frontal gyrus, and left supramarginal gyrus. However, there was no linear correlation between the mean ALFF signal values in brain regions and clinical manifestations in MB patients. Conclusion There were abnormal spontaneous activities in many brain regions including vision and vision-related regions, which might indicate the neuropathologic mechanisms of vision loss in the MB patients. Meanwhile, these brain activity changes might be used as a useful clinical indicator for MB. PMID:27980398

  4. Mild Cognitive Impairment Is Not “Mild” at All in Altered Activation of Episodic Memory Brain Networks: Evidence from ALE Meta-Analysis

    PubMed Central

    Wang, Pengyun; Li, Juan; Li, Hui-Jie; Huo, Lijuan; Li, Rui

    2016-01-01

    The present study conducted a quantitative meta-analysis aiming at assessing consensus across the functional neuroimaging studies of episodic memory in individuals with amnestic mild cognitive impairment (aMCI) and elucidating consistent activation patterns. An activation likelihood estimation (ALE) was conducted on the functional neuroimaging studies of episodic encoding and retrieval in aMCI individuals published up to March 31, 2015. Analyses covered 24 studies, which yielded 770 distinct foci. Compared to healthy controls, aMCI individuals showed statistically significant consistent activation differences in a widespread episodic memory network, not only in the bilateral medial temporal lobe and prefrontal cortex, but also in the angular gyrus, precunes, posterior cingulate cortex, and even certain more basic structures. The present ALE meta-analysis revealed that the abnormal patterns of widespread episodic memory network indicated that individuals with aMCI may not be completely “mild” in nature. PMID:27872591

  5. Smoking, alcoholism and genetic polymorphisms alter CYP2B6 levels in human brain.

    PubMed

    Miksys, Sharon; Lerman, Caryn; Shields, Peter G; Mash, Deborah C; Tyndale, Rachel F

    2003-07-01

    CYP2B6 metabolizes drugs such as nicotine and bupropion, and many toxins and carcinogens. Nicotine induces CYP2B1 in rat brain and in humans polymorphic variation in CYP2B6 affects smoking cessation rates. The aim of this study was to compare CYP2B6 expression in brains of human smokers and non-smokers and alcoholics and non-alcoholics (n=26). CYP2B6 expression was brain region-specific, and was observed in both neurons and astrocytes. CYP2B6 levels were higher in brains of smokers and alcoholics, particularly in cerebellar Purkinje cells and hippocampal pyramidal neurons, cells known to be damaged in alcoholics. Significantly more (p<0.05) CYP2B6 protein was seen in four brain regions of smoking alcoholics compared to non-smoking non-alcoholics: hippocampus (5.8-fold), caudate nucleus (3.3-fold), putamen (3.0-fold) and cerebellar hemisphere (1.6-fold). The genetic variant C1459T (R487C) has been associated with reduced hepatic enzyme levels, stability and activity. Preliminary genotyping of this small sample (n=24) suggested that individuals with the CC genotype had higher brain CYP2B6 than those with the CT or TT genotype. Higher brain CYP2B6 activity in smokers and alcoholics may cause altered sensitivity to centrally acting drugs, increased susceptibility to neurotoxins and carcinogenic xenobiotics and contribute to central tolerance to nicotine.

  6. Sodium tungstate induced neurological alterations in rat brain regions and their response to antioxidants.

    PubMed

    Sachdeva, Sherry; Pant, Satish C; Kushwaha, Pramod; Bhargava, Rakesh; Flora, Swaran J S

    2015-08-01

    Tungsten, recognized recently as an environmental contaminant, is being used in arms and ammunitions as substitute to depleted uranium. We studied the effects of sodium tungstate on oxidative stress, few selected neurological variables like acetylcholinesterase, biogenic amines in rat brain regions (cerebral cortex, hippocampus and cerebellum) and their prevention following co-administration of N-acetylcysteine (NAC), naringenin and quercetin. Animals were sub-chronically exposed to sodium tungstate (100 ppm in drinking water) and orally co-supplemented with different antioxidants (0.30 mM) for three months. Sodium tungstate significantly decreased the activity of acetylcholinesterase, dopamine, nor-epinephrine and 5-hydroxytryptamine levels while it increased monoamine oxidase activity in different brain regions. Tungstate exposure produced a significant increase in biochemical variables indicative of oxidative stress while, neurological alterations were more pronounced in the cerebral cortex compared to other regions. Co-administration of NAC and flavonoids with sodium tungstate significantly restored glutathione, prevented changes in the brain biogenic amines, reactive oxygen species (ROS) and TBARS levels in the different brain regions. The protection was more prominent in the animals co-administered with NAC. We can thus conclude that sodium tungstate induced brain oxidative stress and the alterations in some neurological variables can effectively be reduced by co-supplementation of NAC.

  7. Activated oxygen alters cerebral microvascular responses in newborn pigs

    SciTech Connect

    Leffler, C.W.; Busiia, D.W.; Armstead, W.M.; Mirro, R.; Thelin, O. )

    1990-02-26

    In piglets, cerebral ischemia/reperfusion blocks prostanoid dependent cerebral vasodilation to hypercapnia (CO{sub 2}) and hypotension but not prostanoid independent dilation to isoproterenol (Isu) or constriction to norepinephrine (NE). Ischemia/reperfusion increases activated-O{sub 2} production by piglet brains. Using cranial windows in piglets, the authors investigated the hypothesis that activated oxygen can block prostanoid dependent cerebral vasodilator responses to CO{sub 2} and hypotension without altering responses to Isu and NE. Exposure to an activated oxygen generating system of xanthine oxidase, hypoxanthine, and Fe that made about 3 times the activated-O{sub 2} on the brain surface as ischemia/reperfusion caused reversible pial arteriolar dilation. After exposure, pial arteriolar dilation was reduced to CO{sub 2} and hypotension but not to Isu. NE constrictor responses were also unaltered. H{sub 2}O{sub 2} or H{sub 2}O{sub 2} + Fe caused constriction followed by reversible dilation. After exposure, pial arteriolar dilation in response to CO{sub 2} and hypotension was not altered. However, addition of xanthine oxidase and hypoxanthine with H{sub 2}O{sub 2} and Fe totally eliminated pial arteriolar dilator responses to CO{sub 2} and hypotension but did not decrease dilation caused by Isu or constriction caused by NE. The authors conclude that activated oxygen could produce the altered prostanoid dependent pial arteriolar responses observed following ischemia in piglets.

  8. Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons.

    PubMed

    Chen, Zhe-Yu; Patel, Paresh D; Sant, Gayatree; Meng, Chui-Xiang; Teng, Kenneth K; Hempstead, Barbara L; Lee, Francis S

    2004-05-05

    Brain-derived neurotrophic factor (BDNF) plays a critical role in nervous system and cardiovascular development and function. Recently, a common single nucleotide polymorphism in the bdnf gene, resulting in a valine to methionine substitution in the prodomain (BDNF(Met)), has been shown to lead to memory impairment and susceptibility to neuropsychiatric disorders in humans heterozygous for the variant BDNF. When expressed by itself in hippocampal neurons, less BDNF(Met) is secreted in an activity-dependent manner. The nature of the cellular defect when both BDNF(Met) and wild-type BDNF (BDNF(Val)) are present in the same cell is not known. Given that this is the predominant expression profile in humans, we examined the effect of coexpressed BDNF(Met) on BDNF(Val) intracellular trafficking and processing. Our data indicate that abnormal trafficking of BDNF(Met) occurred only in neuronal and neurosecretory cells and that BDNF(Met) could alter the intracellular distribution and activity-dependent secretion of BDNF(Val). We determined that, when coexpressed in the same cell, approximately 70% of the variant BDNF forms BDNF(Val).BDNF(Met) heterodimers, which are inefficiently sorted into secretory granules resulting in a quantitative decreased secretion. Finally, we determined the form of BDNF secreted in an activity-dependent manner and observed no differences in the forms of BDNF(Met) or the BDNF(Val).BDNF(Met) heterodimer compared with BDNF(Val). Together, these findings indicate that components of the regulated secretory machinery interacts specifically with a signal in the BDNF prodomain and that perturbations in BDNF trafficking may lead to selective impairment in CNS function.

  9. Immune activation in lactating dams alters sucklings' brain cytokines and produces non-overlapping behavioral deficits in adult female and male offspring: A novel neurodevelopmental model of sex-specific psychopathology.

    PubMed

    Arad, Michal; Piontkewitz, Yael; Albelda, Noa; Shaashua, Lee; Weiner, Ina

    2017-02-08

    Early immune activation (IA) in rodents, prenatal through the mother or early postnatal directly to the neonate, is widely used to produce behavioral endophenotypes relevant to schizophrenia and depression. Given that maternal immune response plays a crucial role in the deleterious effects of prenatal IA, and lactation is a critical vehicle of immunological support to the neonate, we predicted that immune activation of the lactating dam will produce long-term abnormalities in the sucklings. Nursing dams were injected on postnatal day 4 with the viral mimic poly-I:C (4mg/kg) or saline. Cytokine assessment was performed in dams' plasma and milk 2h, and in the sucklings' hippocampus, 6h and 24h following poly-I:C injection. Male and female sucklings were assessed in adulthood for: a) performance on behavioral tasks measuring constructs considered relevant to schizophrenia (selective attention and executive control) and depression (despair and anhedonia); b) response to relevant pharmacological treatments; c) brain structural changes. Maternal poly-I:C injection caused cytokine alterations in the dams' plasma and milk, as well as in the sucklings' hippocampus. Lactational poly-I:C exposure led to sex-dimorphic (non-overlapping) behavioral abnormalities in the adult offspring, with male but not female offspring exhibiting attentional and executive function abnormalities (manifested in persistent latent inhibition and slow reversal) and hypodopaminergia, and female but not male offspring exhibiting despair and anhedonia (manifested in increased immobility in the forced swim test and reduced saccharine preference) and hyperdopaminergia, mimicking the known sex-bias in schizophrenia and depression. The behavioral double-dissociation predicted distinct pharmacological profiles, recapitulating the pharmacology of negative/cognitive symptoms and depression. In-vivo imaging revealed hippocampal and striatal volume reductions in both sexes, as found in both disorders. This is

  10. Benefits of agomelatine in behavioral, neurochemical and blood brain barrier alterations in prenatal valproic acid induced autism spectrum disorder.

    PubMed

    Kumar, Hariom; Sharma, B M; Sharma, Bhupesh

    2015-12-01

    Valproic acid administration during gestational period causes behavior and biochemical deficits similar to those observed in humans with autism spectrum disorder. Although worldwide prevalence of autism spectrum disorder has been increased continuously, therapeutic agents to ameliorate the social impairment are very limited. The present study has been structured to investigate the therapeutic potential of melatonin receptor agonist, agomelatine in prenatal valproic acid (Pre-VPA) induced autism spectrum disorder in animals. Pre-VPA has produced reduction in social interaction (three chamber social behavior apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complex I, II, IV). Furthermore, Pre-VPA has increased locomotor activity (actophotometer), anxiety, brain oxidative stress (thiobarbituric acid reactive species, glutathione, and catalase), nitrosative stress (nitrite/nitrate), inflammation (brain and ileum myeloperoxidase activity), calcium levels and blood brain barrier leakage in animals. Treatment with agomelatine has significantly attenuated Pre-VPA induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, agomelatine also attenuated Pre-VPA induced increase in locomotion, anxiety, brain oxidative stress, nitrosative stress, inflammation, calcium levels and blood brain barrier leakage. It is concluded that, Pre-VPA has induced autism spectrum disorder, which was attenuated by agomelatine. Agomelatine has shown ameliorative effect on behavioral, neurochemical and blood brain barrier alteration in Pre-VPA exposed animals. Thus melatonin receptor agonists may provide beneficial therapeutic strategy for managing autism spectrum disorder.

  11. Experimental traumatic brain injury alters ethanol consumption and sensitivity.

    PubMed

    Lowing, Jennifer L; Susick, Laura L; Caruso, James P; Provenzano, Anthony M; Raghupathi, Ramesh; Conti, Alana C

    2014-10-15

    Altered alcohol consumption patterns after traumatic brain injury (TBI) can lead to significant impairments in TBI recovery. Few preclinical models have been used to examine alcohol use across distinct phases of the post-injury period, leaving mechanistic questions unanswered. To address this, the aim of this study was to describe the histological and behavioral outcomes of a noncontusive closed-head TBI in the mouse, after which sensitivity to and consumption of alcohol were quantified, in addition to dopaminergic signaling markers. We hypothesized that TBI would alter alcohol consumption patterns and related signal transduction pathways that were congruent to clinical observations. After midline impact to the skull, latency to right after injury, motor deficits, traumatic axonal injury, and reactive astrogliosis were evaluated in C57BL/6J mice. Amyloid precursor protein (APP) accumulation was observed in white matter tracts at 6, 24, and 72 h post-TBI. Increased intensity of glial fibrillary acidic protein (GFAP) immunoreactivity was observed by 24 h, primarily under the impact site and in the nucleus accumbens, a striatal subregion, as early as 72 h, persisting to 7 days, after TBI. At 14 days post-TBI, when mice were tested for ethanol sensitivity after acute high-dose ethanol (4 g/kg, intraperitoneally), brain-injured mice exhibited increased sedation time compared with uninjured mice, which was accompanied by deficits in striatal dopamine- and cAMP-regulated neuronal phosphoprotein, 32 kDa (DARPP-32) phosphorylation. At 17 days post-TBI, ethanol intake was assessed using the Drinking-in-the-Dark paradigm. Intake across 7 days of consumption was significantly reduced in TBI mice compared with sham controls, paralleling the reduction in alcohol consumption observed clinically in the initial post-injury period. These data demonstrate that TBI increases sensitivity to ethanol-induced sedation and affects downstream signaling mediators of striatal

  12. Ontogenetic noradrenergic lesion alters histaminergic activity in adult rats.

    PubMed

    Nowak, Przemyslaw; Jochem, Jerzy; Zwirska-Korczala, Krystyna; Josko, Jadwiga; Noras, Lukasz; Kostrzewa, Richard M; Brus, Ryszard

    2008-04-01

    To determine whether noradrenergic nerves might have a modulatory role on the sensitivity or reactivity of histaminergic receptor systems in brain, behavioral effects of the respective histamine H1, H2 and H3 antagonists S(+)chlorpheniramine, cimetidine and thioperimide in control adult rats were compared to the effects in adult rats that had been lesioned as neonates with the noradrenergic neurotoxin DSP-4. On the 1st and 3rd days after birth rat pups were treated with either saline or DSP-4 (50 mg/kg sc), then returned to their home cages with the dam. At 8 weeks when rats were tested, S(+)chlorpheniramine (10 mg/kg ip) was found to increase locomotor activity in intact and DSP-4 lesioned rats, while cimetidine (5 mg/kg, ip) and thioperimide (5 mg/kg, ip) increased activity several-fold solely in the DSP-4 group. Exploratory activity, nociceptive activity, and irritability were little altered by the histamine antagonists, although oral activity was increased by thioperimide in intact and lesioned rats, and by cimetidine or S(+)chlorpheniramine in DSP-4 rats. High performance liquid chromatography with electrochemical detection was used to determine that DSP-4 produced a 90% reduction in frontal cortex, hippocampus and hypothalamus, with a 90% elevation of NE in cerebellum--reflecting reactive sprouting of noradrenergic fibers consequent to lesion of noradrenergic tracts projecting to proximal brain regions. These findings indicate that perinatal noradrenergic fiber lesioning in rat brain is associated with an altered behavioral spectrum by histamine H1, H2 and H3 receptor antagonists, thereby implicating histaminergic systems as modulators of noradrenergic systems in brain.

  13. Mitochondrial bioenergetic alterations after focal traumatic brain injury in the immature brain☆

    PubMed Central

    Kilbaugh, Todd; Karlsson, Michael; Byro, Melissa; Bebee, Ashley; Ralston, Jill; Sullivan, Sarah; Duhaime, Ann-Christine; Hansson, Magnus J.; Elmer, Eskil; Margulies, Susan S.

    2015-01-01

    Traumatic brain injury (TBI) is one of the leading causes of death in children worldwide. Emerging evidence suggests that alterations in mitochondrial function are critical components of secondary injury cascade initiated by TBI that propogates neurodegeneration and limits neuroregeneration. Unfortunately, there is very little known about the cerebral mitochondrial bioenergetic response from the immature brain triggered by traumatic biomechanical forces. Therefore, the objective of this study was to perform a detailed evaluation of mitochondrial bioenergetics using high-resolution respirometry in a high-fidelity large animal model of focal controlled cortical impact injury (CCI) 24 h post-injury. This novel approach is directed at analyzing dysfunction in electron transport, ADP phosphorylation and leak respiration to provide insight into potential mechanisms and possible interventions for mitochondrial dysfunction in the immature brain in focal TBI by delineating targets within the electron transport system (ETS). Development and application of these methodologies have several advantages, and adds to the interpretation of previously reported techniques, by having the added benefit that any toxins or neurometabolites present in the ex-vivo samples are not removed during the mitochondrial is olation process, and simulates the in situ tricarboxylic acid (TCA) cycle by maximizing key substrates for convergent flow of electrons through both complexes I and II. To investigate alterations in mitochondrial function after CCI, ipsilateral tissue near the focal impact site and tissue from the corresponding contralateral side were examined. Respiration per mg of tissue was also related to citrate synthase activity (CS) and calculated flux control ratios (FCR), as an attempt to control for variability in mitochondrial content. Our biochemical analysis of complex interdependent pathways of electron flow through the electron transport system, by most measures, reveals a

  14. Human traumatic brain injury alters plasma microRNA levels.

    PubMed

    Redell, John B; Moore, Anthony N; Ward, Norman H; Hergenroeder, Georgene W; Dash, Pramod K

    2010-12-01

    Circulating microRNAs (miRNAs) present in the serum/plasma are characteristically altered in many pathological conditions, and have been employed as diagnostic markers for specific diseases. We examined if plasma miRNA levels are altered in patients with traumatic brain injury (TBI) relative to matched healthy volunteers, and explored their potential for use as diagnostic TBI biomarkers. The plasma miRNA profiles from severe TBI patients (Glasgow Coma Scale [GCS] score ≤8) and age-, gender-, and race-matched healthy volunteers were compared by microarray analysis. Of the 108 miRNAs identified in healthy volunteer plasma, 52 were altered after severe TBI, including 33 with decreased and 19 with increased relative abundance. An additional 8 miRNAs were detected only in the TBI plasma. We used quantitative RT-PCR to determine if plasma miRNAs could identify TBI patients within the first 24 h post-injury. Receiver operating characteristic curve analysis indicated that miR-16, miR-92a, and miR-765 were good markers of severe TBI (0.89, 0.82, and 0.86 AUC values, respectively). Multiple logistic regression analysis revealed that combining these miRNAs markedly increased diagnostic accuracy (100% specificity and 100% sensitivity), compared to either healthy volunteers or orthopedic injury patients. In mild TBI patients (GCS score > 12), miR-765 levels were unchanged, while the plasma levels of miR-92a and miR-16 were significantly increased within the first 24 h of injury compared to healthy volunteers, and had AUC values of 0.78 and 0.82, respectively. Our results demonstrate that circulating miRNA levels are altered after TBI, providing a rich new source of potential molecular biomarkers. Plasma-derived miRNA biomarkers, used in combination with established clinical practices such as imaging, neurocognitive, and motor examinations, have the potential to improve TBI patient classification and possibly management.

  15. Transcriptional profiling reveals that C5a alters microRNA in brain endothelial cells.

    PubMed

    Eadon, Michael T; Jacob, Alexander; Cunningham, Patrick N; Quigg, Richard J; Garcia, Joe G N; Alexander, Jessy J

    2014-11-01

    Blood-brain barrier (BBB) disturbance is a crucial occurrence in many neurological diseases, including systemic lupus erythematosus (SLE). Our previous studies showed that experimental lupus serum altered the integrity of the mouse brain endothelial layer, an important constituent of the BBB. Complement activation occurs in lupus with increased circulating complement components. Using a genomics approach, we identified the microRNA (miRNA) altered in mouse brain endothelial cells (bEnd3) by lupus serum and the complement protein, C5a. Of the 318 miRNA evaluated, 23 miRNAs were altered by lupus serum and 32 were altered by C5a alone compared with controls. Seven miRNAs (P < 0 · 05) were differentially expressed by both treatments: mmu-miR-133a*, mmu-miR-193*, mmu-miR-26b, mmu-miR-28*, mmu-miR-320a, mmu-miR-423-3p and mmu-miR-509-5p. The microarray results were validated by quantitative RT-PCR. In line with the in vitro results, expression of miR-26b and miR-28* were also significantly up-regulated in lupus mouse brain which was reduced by C5a receptor inhibition. Target prediction analysis revealed miR gene targets encoding components involved in inflammation, matrix arrangement, and apoptosis, pathways known to play important roles in central nervous system lupus. Our findings suggest that the miRNAs reported in this study may represent novel therapeutic targets in central nervous system lupus and other similar neuroinflammatory settings.

  16. Transcriptional profiling reveals that C5a alters microRNA in brain endothelial cells

    PubMed Central

    Eadon, Michael T; Jacob, Alexander; Cunningham, Patrick N; Quigg, Richard J; Garcia, Joe G N; Alexander, Jessy J

    2014-01-01

    Blood–brain barrier (BBB) disturbance is a crucial occurrence in many neurological diseases, including systemic lupus erythematosus (SLE). Our previous studies showed that experimental lupus serum altered the integrity of the mouse brain endothelial layer, an important constituent of the BBB. Complement activation occurs in lupus with increased circulating complement components. Using a genomics approach, we identified the microRNA (miRNA) altered in mouse brain endothelial cells (bEnd3) by lupus serum and the complement protein, C5a. Of the 318 miRNA evaluated, 23 miRNAs were altered by lupus serum and 32 were altered by C5a alone compared with controls. Seven miRNAs (P < 0·05) were differentially expressed by both treatments: mmu-miR-133a*, mmu-miR-193*, mmu-miR-26b, mmu-miR-28*, mmu-miR-320a, mmu-miR-423-3p and mmu-miR-509-5p. The microarray results were validated by quantitative RT-PCR. In line with the in vitro results, expression of miR-26b and miR-28* were also significantly up-regulated in lupus mouse brain which was reduced by C5a receptor inhibition. Target prediction analysis revealed miR gene targets encoding components involved in inflammation, matrix arrangement, and apoptosis, pathways known to play important roles in central nervous system lupus. Our findings suggest that the miRNAs reported in this study may represent novel therapeutic targets in central nervous system lupus and other similar neuroinflammatory settings. PMID:24801999

  17. Somatic retrotransposition alters the genetic landscape of the human brain

    PubMed Central

    Baillie, J. Kenneth; Barnett, Mark W.; Upton, Kyle R.; Gerhardt, Daniel J.; Richmond, Todd A.; De Sapio, Fioravante; Brennan, Paul; Rizzu, Patrizia; Smith, Sarah; Fell, Mark; Talbot, Richard T.; Gustincich, Stefano; Freeman, Thomas C.; Mattick, John S.; Hume, David A.; Heutink, Peter; Carninci, Piero; Jeddeloh, Jeffrey A.; Faulkner, Geoffrey J.

    2011-01-01

    Retrotransposons are mobile genetic elements that employ a germ line “copy-and-paste” mechanism to spread throughout metazoan genomes1. At least 50% of the human genome is derived from retrotransposons, with three active families (L1, Alu and SVA) associated with insertional mutagenesis and disease2-3. Epigenetic and post-transcriptional suppression block retrotransposition in somatic cells4-5, excluding early embryo development and some malignancies6-7. Recent reports of L1 expression8-9 and copy number variation10-11 (CNV) in the human brain suggest L1 mobilization may also occur during later development. However, the corresponding integration sites have not been mapped. Here we apply a high-throughput method to identify numerous L1, Alu and SVA germ line mutations, as well as 7,743 putative somatic L1 insertions in the hippocampus and caudate nucleus of three individuals. Surprisingly, we also found 13,692 and 1,350 somatic Alu and SVA insertions, respectively. Our results demonstrate that retrotransposons mobilize to protein-coding genes differentially expressed and active in the brain. Thus, somatic genome mosaicism driven by retrotransposition may reshape the genetic circuitry that underpins normal and abnormal neurobiological processes. PMID:22037309

  18. Alterations of blood brain barrier function in hyperammonemia: an overview.

    PubMed

    Skowrońska, Marta; Albrecht, Jan

    2012-02-01

    Ammonia is a neurotoxin involved in the pathogenesis of neurological conditions associated with hyperammonemia, including hepatic encephalopathy, a condition associated with acute--(ALF) or chronic liver failure. This article reviews evidence that apart from directly affecting the metabolism and function of the central nervous system cells, ammonia influences the passage of different molecules across the blood brain barrier (BBB). A brief description is provided of the tight junctions, which couple adjacent cerebral capillary endothelial cells to each other to form the barrier. Ammonia modulates the transcellular passage of low-to medium-size molecules, by affecting their carriers located at the BBB. Ammonia induces interrelated aberrations of the transport of the large neutral amino acids and aromatic amino acids (AAA), whose influx is augmented by exchange with glutamine produced in the course of ammonia detoxification, and maybe also modulated by the extracellularly acting gamma-glutamyl moiety transferring enzyme, gamma-glutamyl-transpeptidase. Impaired AAA transport affects neurotransmission by altering intracerebral synthesis of catecholamines (serotonin and dopamine), and producing "false neurotransmitters" (octopamine and phenylethylamine). Ammonia also modulates BBB transport of the cationic amino acids: the nitric oxide precursor, arginine, and ornithine, which is an ammonia trap, and affects the transport of energy metabolites glucose and creatine. Moreover, ammonia acting either directly or in synergy with liver injury-derived inflammatory cytokines also evokes subtle increases of the transcellular passage of molecules of different size (BBB "leakage"), which appears to be responsible for the vasogenic component of cerebral edema associated with ALF.

  19. Ketogenic diet alters dopaminergic activity in the mouse cortex.

    PubMed

    Church, William H; Adams, Ryan E; Wyss, Livia S

    2014-06-13

    The present study was conducted to determine if the ketogenic diet altered basal levels of monoamine neurotransmitters in mice. The catecholamines dopamine (DA) and norephinephrine (NE) and the indolamine serotonin (5HT) were quantified postmortem in six different brain regions of adult mice fed a ketogenic diet for 3 weeks. The dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the serotonin metabolite 5-hydroxyindole acetic acid (5HIAA) were also measured. Tissue punches were collected bilaterally from the motor cortex, somatosensory cortex, nucleus accumbens, anterior caudate-putamen, posterior caudate-putamen and the midbrain. Dopaminergic activity, as measured by the dopamine metabolites to dopamine content ratio - ([DOPAC]+[HVA])/[DA] - was significantly increased in the motor and somatosensory cortex regions of mice fed the ketogenic diet when compared to those same areas in brains of mice fed a normal diet. These results indicate that the ketogenic diet alters the activity of the meso-cortical dopaminergic system, which may contribute to the diet's therapeutic effect in reducing epileptic seizure activity.

  20. Altered pattern of brain dopamine synthesis in male adolescents with attention deficit hyperactivity disorder

    PubMed Central

    Forssberg, Hans; Fernell, Elisabeth; Waters, Susanna; Waters, Nicholas; Tedroff, Joakim

    2006-01-01

    Background Limited data from positron emission tomography (PET) studies of subjects with attention-deficit/hyperactivity disorder (ADHD) indicate alterations in brain dopamine neurotransmission. However, these studies have used conventional univariate approaches that are less sensitive to detect complex interactions that may exist between different brain dopamine pathways and individual symptoms of ADHD. We aimed to investigate these potential interactions in adolescents with ADHD. Methods We used a 3D PET scan to measure utilization of native L-[11C]-DOPA to map dopamine presynaptic function in various cortical, striatal and midbrain regions in a group of 8 male adolescents with ADHD and 6 age matched controls. To evaluate the interactions between the studied brain regions, multivariate statistical methods were used. Results Abnormal dopaminergic function was found in multiple brain regions of patients with ADHD. A main finding was lower L-[11C]-DOPA utilization in adolescent with ADHD as compared to control subjects, especially in subcortical regions. This pattern of dopaminergic activity was correlated specifically with symptoms of inattention. Conclusion Dopamine signalling in the brain plays an important modulatory role in a variety of motor and cognitive functions. We have identified region-specific functional abnormalities in dopaminergic function, which may help better account for the symptoms of ADHD. PMID:17144907

  1. Altered Brain Reactivity to Game Cues After Gaming Experience.

    PubMed

    Ahn, Hyeon Min; Chung, Hwan Jun; Kim, Sang Hee

    2015-08-01

    Individuals who play Internet games excessively show elevated brain reactivity to game-related cues. This study attempted to test whether this elevated cue reactivity observed in game players is a result of repeated exposure to Internet games. Healthy young adults without a history of excessively playing Internet games were recruited, and they were instructed to play an online Internet game for 2 hours/day for five consecutive weekdays. Two control groups were used: the drama group, which viewed a fantasy TV drama, and the no-exposure group, which received no systematic exposure. All participants performed a cue reactivity task with game, drama, and neutral cues in the brain scanner, both before and after the exposure sessions. The game group showed an increased reactivity to game cues in the right ventrolateral prefrontal cortex (VLPFC). The degree of VLPFC activation increase was positively correlated with the self-reported increase in desire for the game. The drama group showed an increased cue reactivity in response to the presentation of drama cues in the caudate, posterior cingulate, and precuneus. The results indicate that exposure to either Internet games or TV dramas elevates the reactivity to visual cues associated with the particular exposure. The exact elevation patterns, however, appear to differ depending on the type of media experienced. How changes in each of the regions contribute to the progression to pathological craving warrants a future longitudinal study.

  2. Insulin resistance in brain alters dopamine turnover and causes behavioral disorders

    PubMed Central

    Kleinridders, Andre; Cai, Weikang; Cappellucci, Laura; Ghazarian, Armen; Collins, William R.; Vienberg, Sara G.; Pothos, Emmanuel N.; Kahn, C. Ronald

    2015-01-01

    Diabetes and insulin resistance are associated with altered brain imaging, depression, and increased rates of age-related cognitive impairment. Here we demonstrate that mice with a brain-specific knockout of the insulin receptor (NIRKO mice) exhibit brain mitochondrial dysfunction with reduced mitochondrial oxidative activity, increased levels of reactive oxygen species, and increased levels of lipid and protein oxidation in the striatum and nucleus accumbens. NIRKO mice also exhibit increased levels of monoamine oxidase A and B (MAO A and B) leading to increased dopamine turnover in these areas. Studies in cultured neurons and glia cells indicate that these changes in MAO A and B are a direct consequence of loss of insulin signaling. As a result, NIRKO mice develop age-related anxiety and depressive-like behaviors that can be reversed by treatment with MAO inhibitors, as well as the tricyclic antidepressant imipramine, which inhibits MAO activity and reduces oxidative stress. Thus, insulin resistance in brain induces mitochondrial and dopaminergic dysfunction leading to anxiety and depressive-like behaviors, demonstrating a potential molecular link between central insulin resistance and behavioral disorders. PMID:25733901

  3. Alteration of Blood–Brain Barrier Integrity by Retroviral Infection

    PubMed Central

    Afonso, Philippe V.; Ozden, Simona; Cumont, Marie-Christine; Seilhean, Danielle; Cartier, Luis; Rezaie, Payam; Mason, Sarah; Lambert, Sophie; Huerre, Michel; Gessain, Antoine; Couraud, Pierre-Olivier; Pique, Claudine

    2008-01-01

    The blood–brain barrier (BBB), which forms the interface between the blood and the cerebral parenchyma, has been shown to be disrupted during retroviral-associated neuromyelopathies. Human T Lymphotropic Virus (HTLV-1) Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a slowly progressive neurodegenerative disease associated with BBB breakdown. The BBB is composed of three cell types: endothelial cells, pericytes and astrocytes. Although astrocytes have been shown to be infected by HTLV-1, until now, little was known about the susceptibility of BBB endothelial cells to HTLV-1 infection and the impact of such an infection on BBB function. We first demonstrated that human cerebral endothelial cells express the receptors for HTLV-1 (GLUT-1, Neuropilin-1 and heparan sulfate proteoglycans), both in vitro, in a human cerebral endothelial cell line, and ex vivo, on spinal cord autopsy sections from HAM/TSP and non-infected control cases. In situ hybridization revealed HTLV-1 transcripts associated with the vasculature in HAM/TSP. We were able to confirm that the endothelial cells could be productively infected in vitro by HTLV-1 and that blocking of either HSPGs, Neuropilin 1 or Glut1 inhibits this process. The expression of the tight-junction proteins within the HTLV-1 infected endothelial cells was altered. These cells were no longer able to form a functional barrier, since BBB permeability and lymphocyte passage through the monolayer of endothelial cells were increased. This work constitutes the first report of susceptibility of human cerebral endothelial cells to HTLV-1 infection, with implications for HTLV-1 passage through the BBB and subsequent deregulation of the central nervous system homeostasis. We propose that the susceptibility of cerebral endothelial cells to retroviral infection and subsequent BBB dysfunction is an important aspect of HAM/TSP pathogenesis and should be considered in the design of future therapeutics strategies. PMID:19008946

  4. Focused ultrasound modulates region-specific brain activity

    PubMed Central

    Yoo, Seung-Schik; Bystritsky, Alexander; Lee, Jong-Hwan; Zhang, Yongzhi; Fischer, Krisztina; Min, Byoung-Kyong; McDannold, Nathan J.; Pascual-Leone, Alvaro; Jolesz, Ferenc A.

    2012-01-01

    We demonstrated the in vivo feasibility of using focused ultrasound (FUS) to transiently modulate (through either stimulation or suppression) the function of regional brain tissue in rabbits. FUS was delivered in a train of pulses at low acoustic energy, far below the cavitation threshold, to the animal's somatomotor and visual areas, as guided by anatomical and functional information from magnetic resonance imaging (MRI). The temporary alterations in the brain function affected by the sonication were characterized by both electrophysiological recordings and functional brain mapping achieved through the use of functional MRI (fMRI). The modulatory effects were bimodal, whereby the brain activity could either be stimulated or selectively suppressed. Histological analysis of the excised brain tissue after the sonication demonstrated that the FUS did not elicit any tissue damages. Unlike transcranial magnetic stimulation, FUS can be applied to deep structures in the brain with greater spatial precision. Transient modulation of brain function using image-guided and anatomically-targeted FUS would enable the investigation of functional connectivity between brain regions and will eventually lead to a better understanding of localized brain functions. It is anticipated that the use of this technology will have an impact on brain research and may offer novel therapeutic interventions in various neurological conditions and psychiatric disorders. PMID:21354315

  5. Effect of Hemin on Brain Alterations and Neuroglobin Expression in Water Immersion Restraint Stressed Rats

    PubMed Central

    Ragy, Merhan; Ali, Fatma; Ramzy, Maggie M.

    2016-01-01

    In the brain, the heme oxygenase (HO) system has been reported to be very active and its modulation seems to play a crucial role in the pathophysiology of neurodegenerative disorders. Hemin as HO-1 inducer has been shown to attenuate neuronal injury so the goal of this study was to assess the effect of hemin therapy on the acute stress and how it would modulate neurological outcome. Thirty male albino rats were divided into three groups: control group and stressed group with six-hour water immersion restraint stress (WIRS) and stressed group, treated with hemin, in which each rat received a single intraperitoneal injection of hemin at a dose level of 50 mg/kg body weight at 12 hours before exposure to WIRS. Stress hormones, oxidative stress markers, malondialdehyde (MDA), and total antioxidant capacity (TAC) were measured and expressions of neuroglobin and S100B mRNA in brain tissue were assayed. Our results revealed that hemin significantly affects brain alterations induced by acute stress and this may be through increased expression of neuroglobin and through antioxidant effect. Hemin decreased blood-brain barrier damage as it significantly decreased the expression of S100B. These results suggest that hemin may be an effective therapy for being neuroprotective against acute stress. PMID:27073715

  6. Alteration and Reorganization of Functional Networks: A New Perspective in Brain Injury Study

    PubMed Central

    Castellanos, Nazareth P.; Bajo, Ricardo; Cuesta, Pablo; Villacorta-Atienza, José Antonio; Paúl, Nuria; Garcia-Prieto, Juan; del-Pozo, Francisco; Maestú, Fernando

    2011-01-01

    Plasticity is the mechanism underlying the brain’s potential capability to compensate injury. Recently several studies have shown how functional connections among the brain areas are severely altered by brain injury and plasticity leading to a reorganization of the networks. This new approach studies the impact of brain injury by means of alteration of functional interactions. The concept of functional connectivity refers to the statistical interdependencies between physiological time series simultaneously recorded in various areas of the brain and it could be an essential tool for brain functional studies, being its deviation from healthy reference an indicator for damage. In this article, we review studies investigating functional connectivity changes after brain injury and subsequent recovery, providing an accessible introduction to common mathematical methods to infer functional connectivity, exploring their capabilities, future perspectives, and clinical uses in brain injury studies. PMID:21960965

  7. Simulation of Local Blood Flow in Human Brain under Altered Gravity

    NASA Technical Reports Server (NTRS)

    Kim, Chang Sung; Kiris, Cetin; Kwak, Dochan

    2003-01-01

    In addition to the altered gravitational forces, specific shapes and connections of arteries in the brain vary in the human population (Cebral et al., 2000; Ferrandez et al., 2002). Considering the geometric variations, pulsatile unsteadiness, and moving walls, computational approach in analyzing altered blood circulation will offer an economical alternative to experiments. This paper presents a computational approach for modeling the local blood flow through the human brain under altered gravity. This computational approach has been verified through steady and unsteady experimental measurements and then applied to the unsteady blood flows through a carotid bifurcation model and an idealized Circle of Willis (COW) configuration under altered gravity conditions.

  8. Intrahippocampal Infusion of Crotamine Isolated from Crotalus durissus terrificus Alters Plasma and Brain Biochemical Parameters †

    PubMed Central

    Gonçalves, Rithiele; Vargas, Liane S.; Lara, Marcus V. S.; Güllich, Angélica; Mandredini, Vanusa; Ponce-Soto, Luis; Marangoni, Sergio; Dal Belo, Cháriston A.; Mello-Carpes, Pâmela B.

    2014-01-01

    Crotamine is one of the main constituents of the venom of the South American rattlesnake Crotalus durissus terrificus. Here we sought to investigate the inflammatory and toxicological effects induced by the intrahippocampal administration of crotamine isolated from Crotalus whole venom. Adult rats received an intrahippocampal infusion of crotamine or vehicle and were euthanized 24 h or 21 days after infusion. Plasma and brain tissue were collected for biochemical analysis. Complete blood count, creatinine, urea, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), creatine-kinase (CK), creatine kinase-muscle B (CK-MB) and oxidative parameters (assessed by DNA damage and micronucleus frequency in leukocytes, lipid peroxidation and protein carbonyls in plasma and brain) were quantified. Unpaired and paired t-tests were used for comparisons between saline and crotamine groups, and within groups (24 h vs. 21 days), respectively. After 24 h crotamine infusion promoted an increase of urea, GOT, GPT, CK, and platelets values (p ≤ 0.01), while red blood cells, hematocrit and leukocytes values decreased (p ≤ 0.01). Additionally, 21 days after infusion crotamine group showed increased creatinine, leukocytes, TBARS (plasma and brain), carbonyl (plasma and brain) and micronucleus compared to the saline-group (p ≤ 0.01). Our findings show that crotamine infusion alter hematological parameters and cardiac markers, as well as oxidative parameters, not only in the brain, but also in the blood, indicating a systemic pro-inflammatory and toxicological activity. A further scientific attempt in terms of preserving the beneficial activity over toxicity is required. PMID:25380458

  9. Sleep Deprivation Reveals Altered Brain Perfusion Patterns in Somnambulism

    PubMed Central

    Dang-Vu, Thien Thanh; Zadra, Antonio; Labelle, Marc-Antoine; Petit, Dominique; Soucy, Jean-Paul; Montplaisir, Jacques

    2015-01-01

    Background Despite its high prevalence, relatively little is known about the pathophysiology of somnambulism. Increasing evidence indicates that somnambulism is associated with functional abnormalities during wakefulness and that sleep deprivation constitutes an important drive that facilitates sleepwalking in predisposed patients. Here, we studied the neural mechanisms associated with somnambulism using Single Photon Emission Computed Tomography (SPECT) with 99mTc-Ethylene Cysteinate Dimer (ECD), during wakefulness and after sleep deprivation. Methods Ten adult sleepwalkers and twelve controls with normal sleep were scanned using 99mTc-ECD SPECT in morning wakefulness after a full night of sleep. Eight of the sleepwalkers and nine of the controls were also scanned during wakefulness after a night of total sleep deprivation. Between-group comparisons of regional cerebral blood flow (rCBF) were performed to characterize brain activity patterns during wakefulness in sleepwalkers. Results During wakefulness following a night of total sleep deprivation, rCBF was decreased bilaterally in the inferior temporal gyrus in sleepwalkers compared to controls. Conclusions Functional neural abnormalities can be observed during wakefulness in somnambulism, particularly after sleep deprivation and in the inferior temporal cortex. Sleep deprivation thus not only facilitates the occurrence of sleepwalking episodes, but also uncovers patterns of neural dysfunction that characterize sleepwalkers during wakefulness. PMID:26241047

  10. Developmental Hypothyroidism Alters Brain-Derived Neurotrophic Factor (BDNF) Expression in Adulthood.

    EPA Science Inventory

    Severe developmental thyroid hormone (TH) insufficiency results in alterations in brain structure/function and lasting behavioral impairments. Environmental toxicants reduce circulating levels of TH, but the disruption is modest and the doseresponse relationships of TH and neuro...

  11. Altered resting brain connectivity in persistent cancer related fatigue.

    PubMed

    Hampson, Johnson P; Zick, Suzanna M; Khabir, Tohfa; Wright, Benjamin D; Harris, Richard E

    2015-01-01

    There is an estimated 3 million women in the US living as breast cancer survivors and persistent cancer related fatigue (PCRF) disrupts the lives of an estimated 30% of these women. PCRF is associated with decreased quality of life, decreased sleep quality, impaired cognition and depression. The mechanisms of cancer related fatigue are not well understood; however, preliminary findings indicate dysfunctional activity in the brain as a potential factor. Here we investigate the relationship between PCRF on intrinsic resting state connectivity in this population. Twenty-three age matched breast cancer survivors (15 fatigued and 8 non-fatigued) who completed all cancer-related treatments at least 12 weeks prior to the study, were recruited to undergo functional connectivity magnetic resonance imaging (fcMRI). Intrinsic resting state networks were examined with both seed based and independent component analysis methods. Comparisons of brain connectivity patterns between groups as well as correlations with self-reported fatigue symptoms were performed. Fatigued patients displayed greater left inferior parietal lobule to superior frontal gyrus connectivity as compared to non-fatigued patients (P < 0.05 FDR corrected). This enhanced connectivity was associated with increased physical fatigue (P = 0.04, r = 0.52) and poor sleep quality (P = 0.04, r = 0.52) in the fatigued group. In contrast greater connectivity in the non-fatigued group was found between the right precuneus to the periaqueductal gray as well as the left IPL to subgenual cortex (P < 0.05 FDR corrected). Mental fatigue scores were associated with greater default mode network (DMN) connectivity to the superior frontal gyrus (P = 0.05 FDR corrected) among fatigued subjects (r = 0.82) and less connectivity in the non-fatigued group (r = -0.88). These findings indicate that there is enhanced intrinsic DMN connectivity to the frontal gyrus in breast cancer survivors with persistent fatigue. As

  12. Altered resting brain connectivity in persistent cancer related fatigue

    PubMed Central

    Hampson, Johnson P.; Zick, Suzanna M.; Khabir, Tohfa; Wright, Benjamin D.; Harris, Richard E.

    2015-01-01

    There is an estimated 3 million women in the US living as breast cancer survivors and persistent cancer related fatigue (PCRF) disrupts the lives of an estimated 30% of these women. PCRF is associated with decreased quality of life, decreased sleep quality, impaired cognition and depression. The mechanisms of cancer related fatigue are not well understood; however, preliminary findings indicate dysfunctional activity in the brain as a potential factor. Here we investigate the relationship between PCRF on intrinsic resting state connectivity in this population. Twenty-three age matched breast cancer survivors (15 fatigued and 8 non-fatigued) who completed all cancer-related treatments at least 12 weeks prior to the study, were recruited to undergo functional connectivity magnetic resonance imaging (fcMRI). Intrinsic resting state networks were examined with both seed based and independent component analysis methods. Comparisons of brain connectivity patterns between groups as well as correlations with self-reported fatigue symptoms were performed. Fatigued patients displayed greater left inferior parietal lobule to superior frontal gyrus connectivity as compared to non-fatigued patients (P < 0.05 FDR corrected). This enhanced connectivity was associated with increased physical fatigue (P = 0.04, r = 0.52) and poor sleep quality (P = 0.04, r = 0.52) in the fatigued group. In contrast greater connectivity in the non-fatigued group was found between the right precuneus to the periaqueductal gray as well as the left IPL to subgenual cortex (P < 0.05 FDR corrected). Mental fatigue scores were associated with greater default mode network (DMN) connectivity to the superior frontal gyrus (P = 0.05 FDR corrected) among fatigued subjects (r = 0.82) and less connectivity in the non-fatigued group (r = −0.88). These findings indicate that there is enhanced intrinsic DMN connectivity to the frontal gyrus in breast cancer survivors with persistent fatigue. As

  13. The slowed brain: cortical oscillatory activity in hepatic encephalopathy.

    PubMed

    Butz, Markus; May, Elisabeth S; Häussinger, Dieter; Schnitzler, Alfons

    2013-08-15

    Oscillatory activity of the human brain has received growing interest as a key mechanism of large-scale integration across different brain regions. Besides a crucial role of oscillatory activity in the emergence of other neurological and psychiatric diseases, recent evidence indicates a key role in the pathophysiology of hepatic encephalopathy (HE). This review summarizes the current knowledge on pathological alterations of oscillatory brain activity in association with liver dysfunction and HE in the context of spontaneous brain activity, motor symptoms, sensory processing, and attention. The existing literature demonstrates a prominent slowing of the frequency of oscillatory activity as shown for spontaneous brain activity at rest, with respect to deficits of motor behavior and motor symptoms, and in the context of visual attention processes. The observed slowing extends across different subsystems of the brain and has been confirmed across different frequency bands, providing evidence for ubiquitous changes of oscillatory activity in HE. For example, the frequency of cortico-muscular coherence in HE patients appears at the frequency of the mini-asterixis (⩽12Hz), while cirrhotics without overt signs of HE show coherence similar to healthy subjects, i.e. at 13-30Hz. Interestingly, the so-called critical flicker frequency (CFF) as a measure of the processing of an oscillating visual stimulus has emerged as a useful tool to quantify HE disease severity, correlating with behavioral and neurophysiological alterations. Moreover, the CFF reliably distinguishes patients with manifest HE from cirrhotics without any signs of HE and healthy controls using a cut-off frequency of 39Hz. In conclusion, oscillatory activity is globally slowed in HE in close association with HE symptoms and disease severity. Although the underlying causal mechanisms are not yet understood, these results indicate that pathological changes of oscillatory activity play an important role in the

  14. Sustained deep-tissue pain alters functional brain connectivity.

    PubMed

    Kim, Jieun; Loggia, Marco L; Edwards, Robert R; Wasan, Ajay D; Gollub, Randy L; Napadow, Vitaly

    2013-08-01

    Recent functional brain connectivity studies have contributed to our understanding of the neurocircuitry supporting pain perception. However, evoked-pain connectivity studies have employed cutaneous and/or brief stimuli, which induce sensations that differ appreciably from the clinical pain experience. Sustained myofascial pain evoked by pressure cuff affords an excellent opportunity to evaluate functional connectivity change to more clinically relevant sustained deep-tissue pain. Connectivity in specific networks known to be modulated by evoked pain (sensorimotor, salience, dorsal attention, frontoparietal control, and default mode networks: SMN, SLN, DAN, FCN, and DMN) was evaluated with functional-connectivity magnetic resonance imaging, both at rest and during a sustained (6-minute) pain state in healthy adults. We found that pain was stable, with no significant changes of subjects' pain ratings over the stimulation period. Sustained pain reduced connectivity between the SMN and the contralateral leg primary sensorimotor (S1/M1) representation. Such SMN-S1/M1 connectivity decreases were also accompanied by and correlated with increased SLN-S1/M1 connectivity, suggesting recruitment of activated S1/M1 from SMN to SLN. Sustained pain also increased DAN connectivity to pain processing regions such as mid-cingulate cortex, posterior insula, and putamen. Moreover, greater connectivity during pain between contralateral S1/M1 and posterior insula, thalamus, putamen, and amygdala was associated with lower cuff pressures needed to reach the targeted pain sensation. These results demonstrate that sustained pain disrupts resting S1/M1 connectivity by shifting it to a network known to process stimulus salience. Furthermore, increased connectivity between S1/M1 and both sensory and affective processing areas may be an important contribution to interindividual differences in pain sensitivity.

  15. Prenatal tactile stimulation attenuates drug-induced behavioral sensitization, modifies behavior, and alters brain architecture.

    PubMed

    Muhammad, Arif; Kolb, Bryan

    2011-07-11

    Based on the findings of postnatal tactile stimulation (TS), a favorable experience in rats, the present study examined the influence of prenatal TS on juvenile behavior, adult amphetamine (AMPH) sensitization, and structural alteration in the prefrontal cortex (PFC) and the striatum. Female rats received TS through a baby hair brush throughout pregnancy, and the pups born were tested for open field locomotion, elevated plus maze (EPM), novel object recognition (NOR), and play fighting behaviors. Development and persistence of drug-induced behavioral sensitization in adults were tested by repeated AMPH administration and a challenge, respectively. Structural plasticity in the brain was assessed from the prefrontal cortical thickness and striatum size from serial coronal sections. The results indicate that TS females showed enhanced exploration in the open field. TS decreased the frequency of playful attacks whereas the response to face or evade an attack was not affected. Anxiety-like behavior and cognitive performance were not influenced by TS. AMPH administration resulted in gradual increase in locomotor activity (i.e., behavioral sensitization) that persisted at least for 2 weeks. However, both male and female TS rats exhibited attenuated AMPH sensitization compared to sex-matched controls. Furthermore, the drug-associated alteration in the prefrontal cortical thickness and striatum size observed in controls were prevented by TS experience. In summary, TS during prenatal development modified juvenile behavior, attenuated drug-induced behavioral sensitization in adulthood, and reorganized brain regions implicated in drug addiction.

  16. Perinatal Risk Factors Altering Regional Brain Structure in the Preterm Infant

    ERIC Educational Resources Information Center

    Thompson, Deanne K.; Warfield, Simon K.; Carlin, John B.; Pavlovic, Masa; Wang, Hong X.; Bear, Merilyn; Kean, Michael J.; Doyle, Lex W.; Egan, Gary F.; Inder, Terrie E.

    2007-01-01

    Neuroanatomical structure appears to be altered in preterm infants, but there has been little insight into the major perinatal risk factors associated with regional cerebral structural alterations. MR images were taken to quantitatively compare regional brain tissue volumes between term and preterm infants and to investigate associations between…

  17. The restless brain: how intrinsic activity organizes brain function.

    PubMed

    Raichle, Marcus E

    2015-05-19

    Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive at all levels of neuroscience, it ignores the alternative possibility that brain functions are mainly intrinsic and ongoing, involving information processing for interpreting, responding to and predicting environmental demands. I suggest that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain's energy resources, its limited access to sensory information and a dynamic, intrinsic functional organization. The nature of this intrinsic activity, which exhibits a surprising level of organization with dimensions of both space and time, is revealed in the ongoing activity of the brain and its metabolism. As we look to the future, understanding the nature of this intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux. The reward for doing so will be a much better understanding of human behaviour in health and disease.

  18. The restless brain: how intrinsic activity organizes brain function

    PubMed Central

    Raichle, Marcus E.

    2015-01-01

    Traditionally studies of brain function have focused on task-evoked responses. By their very nature such experiments tacitly encourage a reflexive view of brain function. While such an approach has been remarkably productive at all levels of neuroscience, it ignores the alternative possibility that brain functions are mainly intrinsic and ongoing, involving information processing for interpreting, responding to and predicting environmental demands. I suggest that the latter view best captures the essence of brain function, a position that accords well with the allocation of the brain's energy resources, its limited access to sensory information and a dynamic, intrinsic functional organization. The nature of this intrinsic activity, which exhibits a surprising level of organization with dimensions of both space and time, is revealed in the ongoing activity of the brain and its metabolism. As we look to the future, understanding the nature of this intrinsic activity will require integrating knowledge from cognitive and systems neuroscience with cellular and molecular neuroscience where ion channels, receptors, components of signal transduction and metabolic pathways are all in a constant state of flux. The reward for doing so will be a much better understanding of human behaviour in health and disease. PMID:25823869

  19. gamma-Aminobutyric acid agonists and antagonists alter chloride flux across brain membranes.

    PubMed

    Allan, A M; Harris, R A

    1986-05-01

    gamma-Aminobutyric acid (GABA), the major inhibitory neurotransmitter in the mammalian brain, increases membrane chloride conductance. Previously, we reported that GABA increases 36Cl- uptake by membrane vesicles (microsacs) prepared from mouse brain. Employing this technique, we found that the GABAA agonists, muscimol, isoguvacine, 4,5,6,7-tetrahydroisoxazolo(5,4-C)pyridine-3-ol, and 3-amino-1-propane sulfonate, all produced a concentration-dependent increase in 36Cl- influx, but baclofen, a GABAB agonist, failed to alter 36Cl- flux. Inhibition of GABA-dependent 36Cl- influx was produced by the convulsant drugs, bicuculline, picrotoxin, and pentylenetetrazole. Ion specificity was demonstrated by a failure of GABA agonists to stimulate influx of 45Ca2+, 86Rb+, 22Na+, or 35SO4(2). GABA-stimulated uptake of 36Cl- was largest in cortex and cerebellum and smaller in hippocampus and striatum. There was little difference in sensitivity to GABA among the areas. Analysis of subcellular fractions prepared from mouse brain demonstrated that the GABA-dependent 36Cl- influx was enriched in the synaptosomal fraction. The nonspecific (GABA-independent) uptake of 36Cl- was enriched in the myelin fraction. These experiments provide evidence for a functional coupling among GABA receptors and the chloride ionophore and suggest that the GABA-activated chloride channel is a site of action for several convulsant compounds.

  20. Sleep variability in adolescence is associated with altered brain development.

    PubMed

    Telzer, Eva H; Goldenberg, Diane; Fuligni, Andrew J; Lieberman, Matthew D; Gálvan, Adriana

    2015-08-01

    Despite the known importance of sleep for brain development, and the sharp increase in poor sleep during adolescence, we know relatively little about how sleep impacts the developing brain. We present the first longitudinal study to examine how sleep during adolescence is associated with white matter integrity. We find that greater variability in sleep duration one year prior to a DTI scan is associated with lower white matter integrity above and beyond the effects of sleep duration, and variability in bedtime, whereas sleep variability a few months prior to the scan is not associated with white matter integrity. Thus, variability in sleep duration during adolescence may have long-term impairments on the developing brain. White matter integrity should be increasing during adolescence, and so sleep variability is directly at odds with normative developmental trends.

  1. Altered effective connectivity of default model brain network underlying amnestic MCI

    NASA Astrophysics Data System (ADS)

    Yan, Hao; Wang, Yonghui; Tian, Jie

    2012-02-01

    Mild cognitive impairment (MCI) is the transitional, heterogeneous continuum from healthy elderly to Alzheimer's disease (AD). Previous studies have shown that brain functional activity in the default mode network (DMN) is impaired in MCI patients. However, the altered effective connectivity of the DMN in MCI patients remains largely unknown. The present study combined an independent component analysis (ICA) approach with Granger causality analysis (mGCA) to investigate the effective connectivity within the DMN in 12 amnestic MCI patients and 12 age-matched healthy elderly. Compared to the healthy control, the MCI exhibited decreased functional activity in the posterior DMN regions, as well as a trend towards activity increases in anterior DMN regions. Results from mGCA further supported this conclusion that the causal influence projecting to the precuneus/PCC became much weaker in MCI, while stronger interregional interactions emerged within the frontal-parietal cortices. These findings suggested that abnormal effective connectivity within the DMN may elucidate the dysfunctional and compensatory processes in MCI brain networks.

  2. Acute restraint differently alters defensive responses and fos immunoreactivity in the rat brain.

    PubMed

    de Andrade, J S; Abrão, R O; Céspedes, I C; Garcia, M C; Nascimento, J O G; Spadari-Bratfisch, R C; Melo, L L; da Silva, R C B; Viana, M B

    2012-06-15

    Results from a previous study show that rats exposed to acute restraint display anxiogenic-like behavior, evidenced by facilitation of avoidance responses in the elevated T-maze (ETM) model of anxiety. In contrast, escape responses were unaltered by stress exposure. Since ETM avoidance and escape tasks seem to activate distinct sets of brain structures, it is possible that the differences observed with acute restraint are due to particularities in the neurobiological mechanisms which modulate these responses. In the present study, analysis of fos protein immunoreactivity (fos-ir) was used to map areas activated by exposure of male Wistar rats to restraint stress (30 min) previously (30 min) to the ETM. Corticosterone levels were also measured in stressed and non-stressed animals. Confirming previous observations restraint facilitated avoidance performance, an anxiogenic result, while leaving escape unaltered. Performance of the avoidance task increased fos-ir in the frontal cortex, intermediate lateral septum, basolateral amygdala, basomedial amygdala, lateral amygdala, anterior hypothalamus and dorsal raphe nucleus. In contrast, performance of escape increased fos-ir in the ventromedial hypothalamus, dorsolateral periaqueductal gray and locus ceruleus. Both behavioral tasks also increased fos-ir in the dorsomedial hypothalamus. Restraint significantly raised corticosterone levels. Additionally after restraint, fos-ir was predominantly seen in the basolateral amygdala and dorsal raphe of animals submitted to the avoidance task. This data confirms that different sets of brain structures are activated by ETM avoidance and escape tasks and suggests that acute restraint differently alters ETM behavior and the pattern of fos activation in the brain.

  3. Methamphetamine exposure during brain development alters the brain acetylcholine system in adolescent mice.

    PubMed

    Siegel, Jessica A; Park, Byung S; Raber, Jacob

    2011-10-01

    Children exposed to methamphetamine during brain development as a result of maternal drug use have long-term hippocampus-dependent cognitive impairments, but the mechanisms underlying these impairments are not understood. The acetylcholine system plays an important role in cognitive function and potential methamphetamine-induced acetylcholine alterations may be related to methamphetamine-induced cognitive impairments. In this study, we investigated the potential long-term effects of methamphetamine exposure during hippocampal development on the acetylcholine system in adolescence mice on postnatal day 30 and in adult mice on postnatal day 90. Methamphetamine exposure increased the density of acetylcholine neurons in regions of the basal forebrain and the area occupied by acetylcholine axons in the hippocampus in adolescent female mice. In contrast, methamphetamine exposure did not affect the density of GABA cells or total neurons in the basal forebrain. Methamphetamine exposure also increased the number of muscarinic acetylcholine receptors in the hippocampus of adolescent male and female mice. Our results demonstrate for the first time that methamphetamine exposure during hippocampal development affects the acetylcholine system in adolescent mice and that these changes are more profound in females than males.

  4. Alterations of amino Acid level in depressed rat brain.

    PubMed

    Yang, Pei; Li, Xuechun; Ni, Jian; Tian, Jingchen; Jing, Fu; Qu, Changhai; Lin, Longfei; Zhang, Hui

    2014-10-01

    Amino-acid neurotransmitter system dysfunction plays a major role in the pathophysiology of depression. Several studies have demonstrated the potential of amino acids as a source of neuro-specific biomarkers could be used in future diagnosis of depression. Only partial amino acids such as glycine and asparagine were determined from certain parts of rats' brain included hippocampi and cerebral cortex in previous studies. However, according to systematic biology, amino acids in different area of brain are interacted and interrelated. Hence, the determination of 34 amino acids through entire rats' brain was conducted in this study in order to demonstrate more possibilities for biomarkers of depression by discovering other potential amino acids in more areas of rats' brain. As a result, 4 amino acids (L-aspartic acid, L-glutamine, taurine and γ-amino-n-butyric acid) among 34 were typically identified as potentially primary biomarkers of depression by data statistics. Meanwhile, an antidepressant called Fluoxetine was employed to verify other potential amino acids which were not identified by data statistics. Eventually, we found L-α-amino-adipic acid could also become a new potentially secondary biomarker of depression after drug validation. In conclusion, we suggested that L-aspartic acid, L-glutamine, taurine, γ-amino-n-butyric acid and L-α-amino-adipic acid might become potential biomarkers for future diagnosis of depression and development of antidepressant.

  5. Altered processing of sweet taste in the brain of diet soda drinkers.

    PubMed

    Green, Erin; Murphy, Claire

    2012-11-05

    Artificially sweetened beverage consumption has been linked to obesity, and it has been hypothesized that considerable exposure to nonnutritive sweeteners may be associated with impaired energy regulation. The reward system plays an integral role in modulating energy intake, but little is known about whether habitual use of artificial sweetener (i.e., diet soda consumption) may be related to altered reward processing of sweet taste in the brain. To investigate this, we examined fMRI response after a 12-hour fast to sucrose (a nutritive sweetener) and saccharin (a nonnutritive sweetener) during hedonic evaluation in young adult diet soda drinkers and non-diet soda drinkers. Diet soda drinkers demonstrated greater activation to sweet taste in the dopaminergic midbrain (including ventral tegmental area) and right amygdala. Saccharin elicited a greater response in the right orbitofrontal cortex (Brodmann Area 47) relative to sucrose in non-diet soda drinkers. There was no difference in fMRI response to the nutritive or nonnutritive sweetener for diet soda drinkers. Within the diet soda drinkers, fMRI activation of the right caudate head in response to saccharin was negatively associated with the amount of diet sodas consumed per week; individuals who consumed a greater number of diet sodas had reduced caudate head activation. These findings suggest that there are alterations in reward processing of sweet taste in individuals who regularly consume diet soda, and this is associated with the degree of consumption. These findings may provide some insight into the link between diet soda consumption and obesity.

  6. Brain network alterations and vulnerability to simulated neurodegeneration in breast cancer.

    PubMed

    Kesler, Shelli R; Watson, Christa L; Blayney, Douglas W

    2015-08-01

    Breast cancer and its treatments are associated with mild cognitive impairment and brain changes that could indicate an altered or accelerated brain aging process. We applied diffusion tensor imaging and graph theory to measure white matter organization and connectivity in 34 breast cancer survivors compared with 36 matched healthy female controls. We also investigated how brain networks (connectomes) in each group responded to simulated neurodegeneration based on network attack analysis. Compared with controls, the breast cancer group demonstrated significantly lower fractional anisotropy, altered small-world connectome properties, lower brain network tolerance to systematic region (node), and connection (edge) attacks and significant cognitive impairment. Lower tolerance to network attack was associated with cognitive impairment in the breast cancer group. These findings provide further evidence of diffuse white matter pathology after breast cancer and extend the literature in this area with unique data demonstrating increased vulnerability of the post-breast cancer brain network to future neurodegenerative processes.

  7. C5a alters blood-brain barrier integrity in experimental lupus.

    PubMed

    Jacob, Alexander; Hack, Bradley; Chiang, Eddie; Garcia, Joe G N; Quigg, Richard J; Alexander, Jessy J

    2010-06-01

    The blood-brain barrier (BBB) is a crucial anatomic location in the brain. Its dysfunction complicates many neurodegenerative diseases, from acute conditions, such as sepsis, to chronic diseases, such as systemic lupus erythematosus (SLE). Several studies suggest an altered BBB in lupus, but the underlying mechanism remains unknown. In the current study, we observed a definite loss of BBB integrity in MRL/MpJ-Tnfrsf6(lpr) (MRL/lpr) lupus mice by IgG infiltration into brain parenchyma. In line with this result, we examined the role of complement activation, a key event in this setting, in maintenance of BBB integrity. Complement activation generates C5a, a molecule with multiple functions. Because the expression of the C5a receptor (C5aR) is significantly increased in brain endothelial cells treated with lupus serum, the study focused on the role of C5a signaling through its G-protein-coupled receptor C5aR in brain endothelial cells, in a lupus setting. Reactive oxygen species production increased significantly in endothelial cells, in both primary cells and the bEnd3 cell line treated with lupus serum from MRL/lpr mice, compared with those treated with control serum from MRL(+/+) mice. In addition, increased permeability monitored by changes in transendothelial electrical resistance, cytoskeletal remodeling caused by actin fiber rearrangement, and increased iNOS mRNA expression were observed in bEnd3 cells. These disruptive effects were alleviated by pretreating cells with a C5a receptor antagonist (C5aRant) or a C5a antibody. Furthermore, the structural integrity of the vasculature in MRL/lpr brain was maintained by C5aR inhibition. These results demonstrate the regulation of BBB integrity by the complement system in a neuroinflammatory setting. For the first time, a novel role of C5a in the maintenance of BBB integrity is identified and the potential of C5a/C5aR blockade highlighted as a promising therapeutic strategy in SLE and other neurodegenerative diseases.

  8. Alterations of telomere length in human brain tumors.

    PubMed

    Kheirollahi, Majid; Mehrazin, Masoud; Kamalian, Naser; Mehdipour, Parvin

    2011-09-01

    Telomeres at the ends of human chromosomes consist of tandem hexametric (TTAGGG)n repeats, which protect them from degradation. At each cycle of cell division, most normal somatic cells lose approximately 50-100 bp of the terminal telomeric repeat DNA. Precise prediction of growth and estimation of the malignant potential of brain tumors require additional markers. DNA extraction was performed from the 51 frozen tissues, and a non-radioactive chemiluminescent assay was used for Southern blotting. One sample t-test shows highly significant difference in telomere length in meningioma and astrocytoma with normal range. According to our results, higher grades of meningioma and astrocytoma tumors show more heterogeneity in telomere length, and also it seems shortening process of telomeres is an early event in brain tumors.

  9. Activities That Build the Young Child's Brain.

    ERIC Educational Resources Information Center

    Gellens, Suzanne R.

    This book presents 350 classroom-tested activities for use with children to create an environment that will stimulate young children's brains. Designed to be used by families, classroom teachers, family childcare providers, or others caring for young children, the book includes information on current brain research and describes interest areas in…

  10. HIV alters neuronal mitochondrial fission/fusion in the brain during HIV-associated neurocognitive disorders.

    PubMed

    Fields, Jerel Adam; Serger, Elisabeth; Campos, Sofia; Divakaruni, Ajit S; Kim, Changyoun; Smith, Kendall; Trejo, Margarita; Adame, Anthony; Spencer, Brian; Rockenstein, Edward; Murphy, Anne N; Ellis, Ronald J; Letendre, Scott; Grant, Igor; Masliah, Eliezer

    2016-02-01

    HIV-associated neurocognitive disorders (HAND) still occur in approximately 50% of HIV patients, and therapies to combat HAND progression are urgently needed. HIV proteins are released from infected cells and cause neuronal damage, possibly through mitochondrial abnormalities. Altered mitochondrial fission and fusion is implicated in several neurodegenerative disorders. Here, we hypothesized that mitochondrial fission/fusion may be dysregulated in neurons during HAND. We have identified decreased mitochondrial fission protein (dynamin 1-like; DNM1L) in frontal cortex tissues of HAND donors, along with enlarged and elongated mitochondria localized to the soma of damaged neurons. Similar pathology was observed in the brains of GFAP-gp120 tg mice. In vitro, recombinant gp120 decreased total and active DNM1L levels, reduced the level of Mitotracker staining, and increased extracellular acidification rate (ECAR) in primary neurons. DNM1L knockdown enhanced the effects of gp120 as measured by reduced Mitotracker signal in the treated cells. Interestingly, overexpression of DNM1L increased the level of Mitotracker staining in primary rat neurons and reduced neuroinflammation and neurodegeneration in the GFAP-gp120-tg mice. These data suggest that mitochondrial biogenesis dynamics are shifted towards mitochondrial fusion in brains of HAND patients and this may be due to gp120-induced reduction in DNM1L activity. Promoting mitochondrial fission during HIV infection of the CNS may restore mitochondrial biogenesis and prevent neurodegeneration.

  11. HIV alters neuronal mitochondrial fission/fusion in the brain during HIV-Associated Neurocognitive Disorders

    PubMed Central

    Fields, Jerel Adam; Serger, Elisabeth; Campos, Sofia; Divakaruni, Ajit S.; Kim, Changyoun; Smith, Kendall; Trejo, Margarita; Adame, Anthony; Spencer, Brian; Rockenstein, Edward; Murphy, Anne N.; Ellis, Ronald J.; Letendre, Scott; Grant, Igor; Masliah, Eliezer

    2015-01-01

    HIV-associated neurocognitive disorders (HAND) still occur in approximately 50% of HIV patients, and therapies to combat HAND progression are urgently needed. HIV proteins are released from infected cells and cause neuronal damage, possibly through mitochondrial abnormalities. Altered mitochondrial fission and fusion is implicated in several neurodegenerative disorders. Here, we hypothesized that mitochondrial fission/fusion may be dysregulated in neurons during HAND. We have identified decreased mitochondrial fission protein (dynamin 1-like; DNM1L) in frontal cortex tissues of HAND donors, along with enlarged and elongated mitochondria localized to the soma of damaged neurons. Similar pathology was observed in the brains of GFAP-gp120 tg mice. In vitro, recombinant gp120 decreased total and active DNM1L levels, reduced the level of Mitotracker staining, and increased extracellular acidification rate (ECAR) in primary neurons. DNM1L knockdown enhanced the effects of gp120 as measured by reduced Mitotracker signal in the treated cells. Interestingly, overexpression of DNM1L increased the level of Mitotracker staining in primary rat neurons and reduced neuroinflammation and neurodegeneration in the GFAP-gp120-tg mice. These data suggest that mitochondrial biogenesis dynamics are shifted towards mitochondrial fusion in brains of HAND patients and this may be due to gp120-induced reduction in DNM1L activity. Promoting mitochondrial fission during HIV infection of the CNS may restore mitochondrial biogenesis and prevent neurodegeneration. PMID:26611103

  12. Understanding the brain by controlling neural activity

    PubMed Central

    Krug, Kristine; Salzman, C. Daniel; Waddell, Scott

    2015-01-01

    Causal methods to interrogate brain function have been employed since the advent of modern neuroscience in the nineteenth century. Initially, randomly placed electrodes and stimulation of parts of the living brain were used to localize specific functions to these areas. Recent technical developments have rejuvenated this approach by providing more precise tools to dissect the neural circuits underlying behaviour, perception and cognition. Carefully controlled behavioural experiments have been combined with electrical devices, targeted genetically encoded tools and neurochemical approaches to manipulate information processing in the brain. The ability to control brain activity in these ways not only deepens our understanding of brain function but also provides new avenues for clinical intervention, particularly in conditions where brain processing has gone awry. PMID:26240417

  13. Metabolic alterations in developing brain after injury – knowns and unknowns

    PubMed Central

    McKenna, Mary C.; Scafidi, Susanna; Robertson, Courtney L.

    2016-01-01

    Brain development is a highly orchestrated complex process. The developing brain utilizes many substrates including glucose, ketone bodies, lactate, fatty acids and amino acids for energy, cell division and the biosynthesis of nucleotides, proteins and lipids. Metabolism is crucial to provide energy for all cellular processes required for brain development and function including ATP formation, synaptogenesis, synthesis, release and uptake of neurotransmitters, maintaining ionic gradients and redox status, and myelination. The rapidly growing population of infants and children with neurodevelopmental and cognitive impairments and life-long disability resulting from developmental brain injury is a significant public health concern. Brain injury in infants and children can have devastating effects because the injury is superimposed on the high metabolic demands of the developing brain. Acute injury in the pediatric brain can derail, halt or lead to dysregulation of the complex and highly regulated normal developmental processes. This paper provides a brief review of metabolism in developing brain and alterations found clinically and in animal models of developmental brain injury. The metabolic changes observed in three major categories of injury that can result in life-long cognitive and neurological disabilities, including neonatal hypoxia-ischemia, pediatric traumatic brain injury, and brain injury secondary to prematurity are reviewed. PMID:26148530

  14. Abdominal Pain, the Adolescent and Altered Brain Structure and Function

    PubMed Central

    Becerra, Lino; Heinz, Nicole; Ludwick, Allison; Rasooly, Tali; Wu, Rina; Johnson, Adriana; Schechter, Neil L.; Borsook, David; Nurko, Samuel

    2016-01-01

    Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder of unknown etiology. Although relatively common in children, how this condition affects brain structure and function in a pediatric population remains unclear. Here, we investigate brain changes in adolescents with IBS and healthy controls. Imaging was performed with a Siemens 3 Tesla Trio Tim MRI scanner equipped with a 32-channel head coil. A high-resolution T1-weighted anatomical scan was acquired followed by a T2-weighted functional scan. We used a surface-based morphometric approach along with a seed-based resting-state functional connectivity (RS-FC) analysis to determine if groups differed in cortical thickness and whether areas showing structural differences also showed abnormal RS-FC patterns. Patients completed the Abdominal Pain Index and the GI Module of the Pediatric Quality of Life Inventory to assess abdominal pain severity and impact of GI symptoms on health-related quality of life (HRQOL). Disease duration and pain intensity were also assessed. Pediatric IBS patients, relative to controls, showed cortical thickening in the posterior cingulate (PCC), whereas cortical thinning in posterior parietal and prefrontal areas were found, including the dorsolateral prefrontal cortex (DLPFC). In patients, abdominal pain severity was related to cortical thickening in the intra-abdominal area of the primary somatosensory cortex (SI), whereas HRQOL was associated with insular cortical thinning. Disease severity measures correlated with cortical thickness in bilateral DLPFC and orbitofrontal cortex. Patients also showed reduced anti-correlations between PCC and DLPFC compared to controls, a finding that may reflect aberrant connectivity between default mode and cognitive control networks. We are the first to demonstrate concomitant structural and functional brain changes associated with abdominal pain severity, HRQOL related to GI-specific symptoms, and disease-specific measures in

  15. Brain monoamine metabolism is altered in rats following spontaneous, long-distance running.

    PubMed

    Elam, M; Svensson, T H; Thorén, P

    1987-06-01

    Brain monoamine metabolism in rats was studied during spontaneous, long-term running in a microprocessor-controlled wheel cage. Immediately after heavy spontaneous exercise, DOPA accumulation was decreased in dopamine-rich brain regions such as the limbic forebrain and corpus striatum, indicating a decreased rate of synthesis of dopamine in brain. In contrast, DOPA accumulation was increased in the noradrenaline-predominated region of the brain stem, indicating an increased synthesis of noradrenaline in this region. Alterations in brain monoamine metabolism were normalized in exercising animals analysed 24 h after the last running period. Changes in brain monoamine metabolism may be involved in the mechanisms underlying the clinically observed psychological effects of physical exercise.

  16. Staying Socially Active Nourishes the Aging Brain

    MedlinePlus

    ... fullstory_163679.html Staying Socially Active Nourishes the Aging Brain Researchers suggest making friends of all ages ... and Human Services. More Health News on: Healthy Aging Recent Health News Related MedlinePlus Health Topics Healthy ...

  17. [The child's brain: normal (unaltered) development and development altered by perinatal injury].

    PubMed

    Marín-Padilla, Miguel

    2013-09-06

    In this study we analyse some of the morphological and functional aspects of normal and altered development (the latter due to perinatal injury) in the child's brain. Both normal and altered development are developmental processes that progressively interconnect the different regions. The neuropathological development of subpial and periventricular haemorrhages, as well as that of white matter infarct, are analysed in detail. Any kind of brain damage causes a local lesion with possible remote repercussions. All the components (neurons, fibres, blood capillaries and neuroglias) of the affected region undergo alterations. Those that are destroyed are eliminated by the inflammatory process and those that survive are transformed. The pyramidal neurons with amputated apical dendrites are transformed and become stellate cells, the axonal terminals and those of the radial glial cells are regenerated and the region involved is reinnervated and revascularised with an altered morphology and function (altered local corticogenesis). The specific microvascular system of the grey matter protects its neurons from infarction of the white matter. Although it survives, the grey matter is left disconnected from the afferent and efferent fibres, amputated by the infarct with alterations affecting its morphology and possibly its functioning (altered local corticogenesis). Any local lesion can modify the morphological and functional development of remote regions that are functionally interconnected with it (altered remote corticogenesis). We suggest that any local brain injury can alter the morphology and functioning of the regions that are morphologically and functionally interconnected with it and thus end up affecting the child's neurological and psychological development. These changes can cross different regions of the brain (epileptic auras) and, if they eventually reach the motor region, will give rise to the motor storm that characterises epilepsy.

  18. Enzymatic activities in brains of diabetic rats treated with vanadyl sulphate and sodium tungstate.

    PubMed

    Lemberg, A; Fernández, M A; Ouviña, G; Rodríguez, R R; Peredo, H A; Susemihl, C; Villarreal, I; Filinger, E J

    2007-12-01

    The hypothesis of the present study was that diabetes mellitus might affect brain metabolism. Streptozotocin (STZ)-induced diabetic rats, treated with vanadyl sulphate (V) and sodium tungstate (T) were employed to observe the aspartate aminotransferase (AST), alanine aminotransferase (ALT) and creatine kinase (CK) activities in brain homogenates. Significant increases in AST, ALT and CK activities were found in diabetic brain homogenates against controls, suggesting increments of transamination in brain and/or increases in cell membrane permeability to these enzymes. The increase in brain CK possibly expresses alterations in energy production. The decrease in CK activity caused by V and T treatment in diabetic rats suggests that both agents tend to normalize energy consumption. It is also possible that V and T-induced hypoglycemic effects cause metabolic alterations in brain.

  19. Nutritional n-3 PUFAs deficiency during perinatal periods alters brain innate immune system and neuronal plasticity-associated genes.

    PubMed

    Madore, Charlotte; Nadjar, Agnès; Delpech, Jean-Christophe; Sere, A; Aubert, A; Portal, Céline; Joffre, Corinne; Layé, Sophie

    2014-10-01

    Low dietary intake of the n-3 polyunsaturated fatty acids (PUFAs) is a causative factor of neurodevelopmental disorders. However the mechanisms linking n-3 PUFAs low dietary intake and neurodevelopmental disorders are poorly understood. Microglia, known mainly for their immune function in the injured or infected brain, have recently been demonstrated to play a pivotal role in regulating maturation of neuronal circuits during normal brain development. Disruption of this role during the perinatal period therefore could significantly contribute to psychopathologies with a neurodevelopmental neurodevelopmental component. N-3 PUFAs, essential lipids and key structural components of neuronal membrane phospholipids, are highly incorporated in cell membranes during the gestation and lactation phase. We previously showed that in a context of perinatal n-3 PUFAs deficiency, accretion of these latter is decreased and this is correlated to an alteration of endotoxin-induced inflammatory response. We thus postulated that dietary n-3 PUFAs imbalance alters the activity of microglia in the developing brain, leading to abnormal formation of neuronal networks. We first confirmed that mice fed with a n-3 PUFAs deficient diet displayed decreased n-3 PUFAs levels in the brain at post-natal days (PND)0 and PND21. We then demonstrated that n-3 PUFAs deficiency altered microglia phenotype and motility in the post-natal developing brain. This was paralleled by an increase in pro-inflammatory cytokines expression at PND21 and to modification of neuronal plasticity-related genes expression. Overall, our findings show for the first time that a dietary n-3 PUFAs deficiency from the first day of gestation leads to the development of a pro-inflammatory condition in the central nervous system that may contribute to neurodevelopmental alterations.

  20. Brain extraction using geodesic active contours

    NASA Astrophysics Data System (ADS)

    Huang, Albert; Abugharbieh, Rafeef; Tam, Roger; Traboulsee, Anthony

    2006-03-01

    Extracting the brain cortex from magnetic resonance imaging (MRI) head scans is an essential preprocessing step of which the accuracy greatly affects subsequent image analysis. The currently popular Brain Extraction Tool (BET) produces a brain mask which may be too smooth for practical use. This paper presents a novel brain extraction tool based on three-dimensional geodesic active contours, connected component analysis and mathematical morphology. Based on user-specified intensity and contrast levels, the proposed algorithm allows an active contour to evolve naturally and extract the brain cortex. Experiments on synthetic MRI data and scanned coronal and axial MRI image volumes indicate successful extraction of tight perimeters surrounding the brain cortex. Quantitative evaluations on both synthetic phantoms and manually labeled data resulted in better accuracy than BET in terms of true and false voxel assignment. Based on these results, we illustrate that our brain extraction tool is a robust and accurate approach for the challenging task of automatically extracting the brain cortex in MRI data.

  1. Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export

    PubMed Central

    Legati, Andrea; Giovannini, Donatella; Nicolas, Gaël; López-Sánchez, Uriel; Quintáns, Beatriz; Oliveira, João; Sears, Renee L.; Marisa Ramos, Eliana; Spiteri, Elizabeth; Sobrido, María-Jesús; Carracedo, Ángel; Castro-Fernández, Cristina; Cubizolle, Stéphanie; Fogel, Brent L.; Goizet, Cyril; Jen, Joanna C.; Kirdlarp, Suppachok; Lang, Anthony E.; Miedzybrodzka, Zosia; Mitarnun, Witoon; Paucar, Martin; Paulson, Henry; Pariente, Jérémie; Richard, Anne-Claire; Salins, Naomi S.; Simpson, Sheila A.; Striano, Pasquale; Svenningsson, Per; Tison, François; Unni, Vivek K.; Vanakker, Olivier; Wessels, Marja W.; Wetchaphanphesat, Suppachok; Yang, Michele; Boller, Francois; Campion, Dominique; Hannequin, Didier; Sitbon, Marc; Geschwind, Daniel H.; Battini, Jean-Luc; Coppola, Giovanni

    2015-01-01

    Primary familial brain calcification (PFBC) is a neurological disease characterized by calcium phosphate deposits in the basal ganglia and other brain regions, thus far associated with SLC20A2, PDGFB, or PDGFRB mutations. We identified in multiple PFBC families mutations in XPR1, a gene encoding a retroviral receptor with phosphate export function. These mutations alter phosphate export, providing a direct evidence of an impact of XPR1 and phosphate homeostasis in PFBC. PMID:25938945

  2. Altered subcellular localization of ornithine decarboxylase in Alzheimer's disease brain

    SciTech Connect

    Nilsson, Tatjana . E-mail: Tatjana.Nilsson@ki.se; Bogdanovic, Nenad; Volkman, Inga; Winblad, Bengt; Folkesson, Ronnie; Benedikz, Eirikur

    2006-06-02

    The amyloid precursor protein can through ligand-mimicking induce expression of ornithine decarboxylase (ODC), the initial and rate-limiting enzyme in polyamine biosynthesis. We report here the regional distribution and cellular localization of ODC immunoreactivity in Alzheimer's disease (AD) brains. In frontal cortex and hippocampus of control cases, the most pronounced ODC immunoreactivity was found in the nucleus. In possible and definite AD the immunoreactivity had shifted to the cytoplasm. In cerebellum of control cases, ODC staining was found in a small portion of Purkinje cells, mostly in the nucleus. In AD, both possible and definite, the number of stained Purkinje cells increased significantly and immunoreactivity was shifted to the cytoplasm, even though it was still prominent in the nucleus. In conclusion, our study reveals an early shift of the ODC immunoreactivity in AD from the nuclear compartment towards the cytoplasm.

  3. Alterations of natural killer cells in traumatic brain injury.

    PubMed

    Kong, Xiao-Dong; Bai, Sheng; Chen, Xin; Wei, Hui-Jie; Jin, Wei-Na; Li, Min-Shu; Yan, Yaping; Shi, Fu-Dong

    2014-12-01

    To investigate the relationship between natural killer (NK) cells and traumatic brain injury (TBI), we tracked an established phenotype of circulating NK cells at several time points in patients with different grades of TBI. In serial peripheral blood samples, NK cells were prospectively measured by flow cytometry of CD3(-) CD56(+) lymphocytes. Compared to healthy controls, TBI patients had reductions in both the percentage and the absolute number of NK cells. Furthermore, the magnitude of NK cell reduction correlated with the degree of TBI severity at several time points. That is, NK cell population size was independently associated with lower Glasgow Coma Scale scores. In addition, at some time points, a positive correlation was found between the NK cell counts and Glasgow Outcome Scale scores. Our results indicate that TBI induces a reduction in the number of NK cells, and the magnitude of the reduction appears to parallel the severity of TBI.

  4. Central Thalamic Deep-Brain Stimulation Alters Striatal-Thalamic Connectivity in Cognitive Neural Behavior

    PubMed Central

    Lin, Hui-Ching; Pan, Han-Chi; Lin, Sheng-Huang; Lo, Yu-Chun; Shen, Elise Ting-Hsin; Liao, Lun-De; Liao, Pei-Han; Chien, Yi-Wei; Liao, Kuei-Da; Jaw, Fu-Shan; Chu, Kai-Wen; Lai, Hsin-Yi; Chen, You-Yin

    2016-01-01

    Central thalamic deep brain stimulation (CT-DBS) has been proposed as an experimental therapeutic approach to produce consistent sustained regulation of forebrain arousal for several neurological diseases. We investigated local field potentials (LFPs) induced by CT-DBS from the thalamic central lateral nuclei (CL) and the striatum as potential biomarkers for the enhancement of lever-pressing skill learning. LFPs were simultaneously recorded from multiple sites in the CL, ventral striatum (Vstr), and dorsal striatum (Dstr). LFP oscillation power and functional connectivity were assessed and compared between the CT-DBS and sham control groups. The theta and alpha LFP oscillations were significantly increased in the CL and striatum in the CT-DBS group. Furthermore, interhemispheric coherences between bilateral CL and striatum were increased in the theta band. Additionally, enhancement of c-Fos activity, dopamine D2 receptor (Drd2), and α4-nicotinic acetylcholine receptor (α4-nAChR) occurred after CT-DBS treatment in the striatum and hippocampus. CT-DBS strengthened thalamic-striatal functional connectivity, which demonstrates that the inter-regional connectivity enhancement might contribute to synaptic plasticity in the striatum. Altered dopaminergic and cholinergic receptors resulted in modulation of striatal synaptic plasticity's ability to regulate downstream signaling cascades for higher brain functions of lever-pressing skill learning. PMID:26793069

  5. Central Thalamic Deep-Brain Stimulation Alters Striatal-Thalamic Connectivity in Cognitive Neural Behavior.

    PubMed

    Lin, Hui-Ching; Pan, Han-Chi; Lin, Sheng-Huang; Lo, Yu-Chun; Shen, Elise Ting-Hsin; Liao, Lun-De; Liao, Pei-Han; Chien, Yi-Wei; Liao, Kuei-Da; Jaw, Fu-Shan; Chu, Kai-Wen; Lai, Hsin-Yi; Chen, You-Yin

    2015-01-01

    Central thalamic deep brain stimulation (CT-DBS) has been proposed as an experimental therapeutic approach to produce consistent sustained regulation of forebrain arousal for several neurological diseases. We investigated local field potentials (LFPs) induced by CT-DBS from the thalamic central lateral nuclei (CL) and the striatum as potential biomarkers for the enhancement of lever-pressing skill learning. LFPs were simultaneously recorded from multiple sites in the CL, ventral striatum (Vstr), and dorsal striatum (Dstr). LFP oscillation power and functional connectivity were assessed and compared between the CT-DBS and sham control groups. The theta and alpha LFP oscillations were significantly increased in the CL and striatum in the CT-DBS group. Furthermore, interhemispheric coherences between bilateral CL and striatum were increased in the theta band. Additionally, enhancement of c-Fos activity, dopamine D2 receptor (Drd2), and α4-nicotinic acetylcholine receptor (α4-nAChR) occurred after CT-DBS treatment in the striatum and hippocampus. CT-DBS strengthened thalamic-striatal functional connectivity, which demonstrates that the inter-regional connectivity enhancement might contribute to synaptic plasticity in the striatum. Altered dopaminergic and cholinergic receptors resulted in modulation of striatal synaptic plasticity's ability to regulate downstream signaling cascades for higher brain functions of lever-pressing skill learning.

  6. EEG Oscillatory States: Universality, Uniqueness and Specificity across Healthy-Normal, Altered and Pathological Brain Conditions

    PubMed Central

    Fingelkurts, Alexander A.; Fingelkurts, Andrew A.

    2014-01-01

    For the first time the dynamic repertoires and oscillatory types of local EEG states in 13 diverse conditions (examined over 9 studies) that covered healthy-normal, altered and pathological brain states were quantified within the same methodological and conceptual framework. EEG oscillatory states were assessed by the probability-classification analysis of short-term EEG spectral patterns. The results demonstrated that brain activity consists of a limited repertoire of local EEG states in any of the examined conditions. The size of the state repertoires was associated with changes in cognition and vigilance or neuropsychopathologic conditions. Additionally universal, optional and unique EEG states across 13 diverse conditions were observed. It was demonstrated also that EEG oscillations which constituted EEG states were characteristic for different groups of conditions in accordance to oscillations’ functional significance. The results suggested that (a) there is a limit in the number of local states available to the cortex and many ways in which these local states can rearrange themselves and still produce the same global state and (b) EEG individuality is determined by varying proportions of universal, optional and unique oscillatory states. The results enriched our understanding about dynamic microstructure of EEG-signal. PMID:24505292

  7. Altered small-world brain networks in schizophrenia patients during working memory performance.

    PubMed

    He, Hao; Sui, Jing; Yu, Qingbao; Turner, Jessica A; Ho, Beng-Choon; Sponheim, Scott R; Manoach, Dara S; Clark, Vincent P; Calhoun, Vince D

    2012-01-01

    Impairment of working memory (WM) performance in schizophrenia patients (SZ) is well-established. Compared to healthy controls (HC), SZ patients show aberrant blood oxygen level dependent (BOLD) activations and disrupted functional connectivity during WM performance. In this study, we examined the small-world network metrics computed from functional magnetic resonance imaging (fMRI) data collected as 35 HC and 35 SZ performed a Sternberg Item Recognition Paradigm (SIRP) at three WM load levels. Functional connectivity networks were built by calculating the partial correlation on preprocessed time courses of BOLD signal between task-related brain regions of interest (ROIs) defined by group independent component analysis (ICA). The networks were then thresholded within the small-world regime, resulting in undirected binarized small-world networks at different working memory loads. Our results showed: 1) at the medium WM load level, the networks in SZ showed a lower clustering coefficient and less local efficiency compared with HC; 2) in SZ, most network measures altered significantly as the WM load level increased from low to medium and from medium to high, while the network metrics were relatively stable in HC at different WM loads; and 3) the altered structure at medium WM load in SZ was related to their performance during the task, with longer reaction time related to lower clustering coefficient and lower local efficiency. These findings suggest brain connectivity in patients with SZ was more diffuse and less strongly linked locally in functional network at intermediate level of WM when compared to HC. SZ show distinctly inefficient and variable network structures in response to WM load increase, comparing to stable highly clustered network topologies in HC.

  8. The Influence of Neuronal Activity on Breast Tumor Metastasis to the Brain

    DTIC Science & Technology

    2009-09-01

    drugs to alter brain activity: caffeine, methylphenidate and modafinil . While the smallest effect may be expected from caffeine which is not as potent...caffeine, we have initiated experiments to test the effects of modafinil on breast tumor metastasis to the brain in our model. Unfortunately, we have had

  9. Potentiation of neurotoxicity of Lathyrus sativus by manganese: alterations in blood-brain barrier permeability.

    PubMed

    Mishra, Geeta; Shukla, Rakesh; Hasan, Mahdi; Khanna, Subhash K; Das, Mukul

    2009-05-01

    Environmental factors have been speculated to play an important role in potentiating the neurotoxicity of Lathyrus sativus (LS). Hence, blood-brain barrier permeability and neurotoxicity studies were carried out in manganese- and LS-exposed animals. Dietary feeding of LS (80%) plus Mn (0.4 mg/100 g diet) for 90 days to guinea pigs showed significant (p < 0.05) decrease in brain nucleotidase and ATPase activities when compared to control or LS alone treated groups. Combined treatment of LS and Mn showed a significant (p < 0.05) decrease in neuronal aryl hydrocarbon hydroxylase (36-40%), ethoxyresorufin-O-deethylase (40-45%), glutathione-S-transferase (27-31%), and quinone reductase (24-25%) activities when compared to control and LS alone treated animals. Lipid peroxidation, a marker for membrane damage, was found to be relatively more enhanced (58-141%) along with significant (p < 0.05) depletion of GSH levels in LS+Mn-treated animals when compared to control, Mn alone, and LS alone treated groups. The neuronal catalase activity of lathyrus plus Mn-treated animals showed a pronounced decrease (37-49%) when compared to control, Mn, and lathyrus alone treated groups. On the contrary, glutathione peroxidase in brain of Mn and lathyrus alone treated animals indicated a respective increase (p < 0.05) of 18% and 20%, while the combined effect of lathyrus plus Mn exhibited an increase of almost 50% when compared to control guinea pigs. Single parenteral administration of Mn (15 mg/kg b.wt) to guinea pigs followed by single oral intubation of beta-N-oxalyl-L-alpha, beta-diamino propionic acid (ODAP, 75 mg/guinea pig) resulted in a significant increase (143%) in neuronal ODAP content. ODAP (50 mg/kg,iv) treatment to mice pretreated with MnCl2 (10 mg/kg b.wt for 3 days or 40 mg/kg b.wt for 1 day), caused an enhancement in blood-brain barrier (BBB) permeability (129-196%), while ODAP and Mn alone showed relatively less enhancement (66-87%). The lumbar region of LS+Mn showed a

  10. Subtle alterations in brain anatomy may change an individual's personality in chronic pain.

    PubMed

    Gustin, Sylvia M; McKay, Jamie G; Petersen, Esben T; Peck, Chris C; Murray, Greg M; Henderson, Luke A

    2014-01-01

    It is well established that gross prefrontal cortex damage can affect an individual's personality. It is also possible that subtle prefrontal cortex changes associated with conditions such as chronic pain, and not detectable until recent advances in human brain imaging, may also result in subtle changes in an individual's personality. In an animal model of chronic neuropathic pain, subtle prefrontal cortex changes including altered basal dendritic length, resulted in altered decision making ability. Using multiple magnetic resonance imaging techniques, we found in humans, although gray matter volume and on-going activity were unaltered, chronic neuropathic pain was associated with reduced free and bound proton movement, indicators of subtle anatomical changes, in the medial prefrontal cortex, anterior cingulate cortex and mediodorsal thalamus. Furthermore, proton spectroscopy revealed an increase in neural integrity in the medial prefrontal cortex in neuropathic pain patients, the degree of which was significantly correlated to the personality temperament of novelty seeking. These data reveal that even subtle changes in prefrontal cortex anatomy may result in a significant change in an individual's personality.

  11. Subtle Alterations in Brain Anatomy May Change an Individual’s Personality in Chronic Pain

    PubMed Central

    Gustin, Sylvia M.; McKay, Jamie G.; Petersen, Esben T.; Peck, Chris C.; Murray, Greg M.; Henderson, Luke A.

    2014-01-01

    It is well established that gross prefrontal cortex damage can affect an individual’s personality. It is also possible that subtle prefrontal cortex changes associated with conditions such as chronic pain, and not detectable until recent advances in human brain imaging, may also result in subtle changes in an individual’s personality. In an animal model of chronic neuropathic pain, subtle prefrontal cortex changes including altered basal dendritic length, resulted in altered decision making ability. Using multiple magnetic resonance imaging techniques, we found in humans, although gray matter volume and on-going activity were unaltered, chronic neuropathic pain was associated with reduced free and bound proton movement, indicators of subtle anatomical changes, in the medial prefrontal cortex, anterior cingulate cortex and mediodorsal thalamus. Furthermore, proton spectroscopy revealed an increase in neural integrity in the medial prefrontal cortex in neuropathic pain patients, the degree of which was significantly correlated to the personality temperament of novelty seeking. These data reveal that even subtle changes in prefrontal cortex anatomy may result in a significant change in an individual’s personality. PMID:25291361

  12. Persistent behavioral impairments and alterations of brain dopamine system after early postnatal administration of thimerosal in rats.

    PubMed

    Olczak, Mieszko; Duszczyk, Michalina; Mierzejewski, Pawel; Meyza, Ksenia; Majewska, Maria Dorota

    2011-09-30

    The neurotoxic organomercurial thimerosal (THIM), used for decades as vaccine preservative, is a suspected factor in the pathogenesis of some neurodevelopmental disorders. Previously we showed that neonatal administration of THIM at doses equivalent to those used in infant vaccines or higher, causes lasting alterations in the brain opioid system in rats. Here we investigated neonatal treatment with THIM (at doses 12, 240, 1440 and 3000 μg Hg/kg) on behaviors, which are characteristically altered in autism, such as locomotor activity, anxiety, social interactions, spatial learning, and on the brain dopaminergic system in Wistar rats of both sexes. Adult male and female rats, which were exposed to the entire range of THIM doses during the early postnatal life, manifested impairments of locomotor activity and increased anxiety/neophobia in the open field test. In animals of both sexes treated with the highest THIM dose, the frequency of prosocial interactions was reduced, while the frequency of asocial/antisocial interactions was increased in males, but decreased in females. Neonatal THIM treatment did not significantly affect spatial learning and memory. THIM-exposed rats also manifested reduced haloperidol-induced catalepsy, accompanied by a marked decline in the density of striatal D₂ receptors, measured by immunohistochemical staining, suggesting alterations to the brain dopaminergic system. Males were more sensitive than females to some neurodisruptive/neurotoxic actions of THIM. These data document that early postnatal THIM administration causes lasting neurobehavioral impairments and neurochemical alterations in the brain, dependent on dose and sex. If similar changes occur in THIM/mercurial-exposed children, they could contribute do neurodevelopmental disorders.

  13. Similarities in lindane induced alteration in cytochrome P450s and associated signaling events in peripheral blood lymphocytes and brain.

    PubMed

    Khan, Anwar Jamal; Sharma, Amit; Dinesh, K; Parmar, Devendra

    2013-10-01

    Studies were initiated to investigate the similarities in alterations in cytochrome P450s (CYPs) and associated signaling events in brain and peripheral blood lymphocytes (PBL) induced by lindane, an organochlorine pesticide. Adult male albino wistar rats were treated orally with different doses (2.5- or 5.0- or 10- or 15 mg/kg/body weight) of lindane daily for 4 days. In another experiment, the treatment of low dose (2.5mg/kg) of lindane was continued for 15- and 21 days. A dose- and time-dependent increase was observed in the activity of CYP dependent enzymes in brain microsomes and PBL isolated from the treated rats. However, the magnitude of induction was several folds less in PBL. As observed in brain, RT-PCR and Western immunoblotting demonstrated that increase in CYP enzymes in PBL is due to the increase in the mRNA expression of specific CYP isoenzymes. Similarities were also observed in activation of ERK and JNK MAP kinases and c-jun in PBL or brain isolated from rats treated with lindane. Similarities in the induction of CYPs and activation of MAP kinases in PBL and brain suggest that CYP expression profiles in PBL could be used for monitoring the exposure and toxicity of environmental chemicals.

  14. Neuronal and glial alterations due to focal cortical hypoxia induced by direct cobalt chloride (CoCl2) brain injection.

    PubMed

    Caltana, Laura; Merelli, Amalia; Lazarowski, Alberto; Brusco, Alicia

    2009-05-01

    Ischemic brain injury is a dynamic process that involves oxidative stress, inflammation, and cell death, as well as activation of endogenous adaptive and regenerative mechanisms depending on activation of transcription factors such as hypoxia inducible factor 1-alpha (HIF-1alpha). Because CoCl2 activates HIF-1alpha, we described a new focal-hypoxia model by direct intracerebral CoCl2 injection. Adult male Wistar rats were intracerebrally injected with CoCl2 (2 microl-50 mM), in frontoparietal cortex of right hemisphere, and saline (2 microl) in the contralateral hemisphere. In slides of fixed brains at 1, 6, 9, 24 h or 5 day after treatment, TTC, histochemistry (toluidine blue, Hoescht-33342, TUNEL), immunostaining (HIF-1alpha, GFAP), Lycopersicon esculentum lectin staining, and electron microscopy (EM) were performed. Immediately after 1 h post CoCl2 injection, HIF-1alpha stabilization and neuronal nuclear shrinkage and cromathin condensation were observed by immunostaining and EM, respectively. Neuronal apoptotic nuclear morphology and GFAP immunoreactivity and lectin maximal reactivity were detected during 6-9 h. Ultrastructural alterations of morphology included edematous perinuclear cytoplasm, organelles and endoplasmic reticulum (RE) enlargement, mitochondrial swelling with increased matrix density, and deposits of electron-dense material. Neurons showed particular nuclear indentations. Astrocytes and oligodendrocytes presented alterations in both nuclei and RE with dilated lumen and altered mitochondrias, and all these ultrastructural changes became detectable at day 5. CoCl2 cortical injection mimics focal brain ischemia, inducing neuronal death and glial activation. This model brings the opportunity to develop focal ischemia in selected brain areas to study their functional consequences and potential pharmacological therapies for in vivo models of stroke.

  15. Whole-brain activity mapping onto a zebrafish brain atlas.

    PubMed

    Randlett, Owen; Wee, Caroline L; Naumann, Eva A; Nnaemeka, Onyeka; Schoppik, David; Fitzgerald, James E; Portugues, Ruben; Lacoste, Alix M B; Riegler, Clemens; Engert, Florian; Schier, Alexander F

    2015-11-01

    In order to localize the neural circuits involved in generating behaviors, it is necessary to assign activity onto anatomical maps of the nervous system. Using brain registration across hundreds of larval zebrafish, we have built an expandable open-source atlas containing molecular labels and definitions of anatomical regions, the Z-Brain. Using this platform and immunohistochemical detection of phosphorylated extracellular signal–regulated kinase (ERK) as a readout of neural activity, we have developed a system to create and contextualize whole-brain maps of stimulus- and behavior-dependent neural activity. This mitogen-activated protein kinase (MAP)-mapping assay is technically simple, and data analysis is completely automated. Because MAP-mapping is performed on freely swimming fish, it is applicable to studies of nearly any stimulus or behavior. Here we demonstrate our high-throughput approach using pharmacological, visual and noxious stimuli, as well as hunting and feeding. The resultant maps outline hundreds of areas associated with behaviors.

  16. Protein-energy malnutrition during pregnancy alters caffeine's effect on brain tissue of neonate rats.

    PubMed

    Mori, M; Wilber, J F; Nakamoto, T

    1984-12-17

    We studied whether protein-energy malnutrition changed brain susceptibility to a small dose of caffeine in newborn rats. Since we had demonstrated previously that caffeine intake during lactation increased the brain neuropeptide on newborns, we investigated further the effects of the prenatal administration of caffeine on TRH and cyclo (His-Pro). From day 13 of gestation to delivery day, pregnant rats in one group were fed either a 20% or a 6% protein diet ad libitum, and those in the other group were pair-fed with each protein diet supplemented with caffeine at an effective dose of 2 mg/100 g body weight. Upon delivery, brain weight, brain protein, RNA, DNA and the neuropeptides thyrotropin-releasing hormone (TRH) and cyclo (His-Pro) were measured in the newborn rats. A 6% protein without caffeine diet caused reductions in brain weights and brain protein, RNA and DNA contents, but did not alter brain TRH and cyclo (His-Pro) concentrations in the newborn animals. In the offspring from dams fed a 6% protein diet, caffeine administration significantly elevated brain weights and brain contents of protein, RNA and DNA. In contrast, these values were similar between noncaffeine and caffeine-supplemented animals in a 20% protein diet group. Brain TRH and cyclo (His-Pro) concentrations were not changed by caffeine administration. These data suggest that caffeine augments protein synthesis in the newborn rat brain when malnourished, but that the same dose of caffeine did not affect protein synthesis in brains of newborn rats from normally nourished dams. Therefore, the present findings indicate that the nutritional status of mothers during pregnancy has important implication in the impact of caffeine on their offspring's brains.

  17. How air pollution alters brain development: the role of neuroinflammation

    PubMed Central

    Brockmeyer, Sam

    2016-01-01

    Abstract The present review synthesizes lines of emerging evidence showing how several samples of children populations living in large cities around the world suffer to some degree neural, behavioral and cognitive changes associated with air pollution exposure. The breakdown of natural barriers warding against the entry of toxic particles, including the nasal, gut and lung epithelial barriers, as well as widespread breakdown of the blood-brain barrier facilitatethe passage of airborne pollutants into the body of young urban residents. Extensive neuroinflammation contributes to cell loss within the central nervous system, and likely is a crucial mechanism by which cognitive deficits may arise. Although subtle, neurocognitive effects of air pollution are substantial, apparent across all populations, and potentially clinically relevant as early evidence of evolving neurodegenerative changes. The diffuse nature of the neuroinflammation risk suggests an integrated neuroscientific approach incorporating current clinical, cognitive, neurophysiological, radiological and epidemiologic research. Neuropediatric air pollution research requires extensive multidisciplinary collaborations to accomplish the goal of protecting exposed children through multidimensional interventions having both broad impact and reach. While intervening by improving environmental quality at a global scale is imperative, we also need to devise efficient strategies on how the neurocognitive effects on local pediatric populations should be monitored. PMID:28123818

  18. Repeated forced swimming impairs prepulse inhibition and alters brain-derived neurotrophic factor and astroglial parameters in rats.

    PubMed

    Borsoi, Milene; Antonio, Camila Boque; Müller, Liz Girardi; Viana, Alice Fialho; Hertzfeldt, Vivian; Lunardi, Paula Santana; Zanotto, Caroline; Nardin, Patrícia; Ravazzolo, Ana Paula; Rates, Stela Maris Kuze; Gonçalves, Carlos-Alberto

    2015-01-01

    Glutamate perturbations and altered neurotrophin levels have been strongly associated with the neurobiology of neuropsychiatric disorders. Environmental stress is a risk factor for mood disorders, disrupting glutamatergic activity in astrocytes in addition to cognitive behaviours. Despite the negative impact of stress-induced neuropsychiatric disorders on public health, the molecular mechanisms underlying the response of the brain to stress has yet to be fully elucidated. Exposure to repeated swimming has proven useful for evaluating the loss of cognitive function after pharmacological and behavioural interventions, but its effect on glutamate function has yet to be fully explored. In the present study, rats previously exposed to repeated forced swimming were evaluated using the novel object recognition test, object location test and prepulse inhibition (PPI) test. In addition, quantification of brain-derived neurotrophic factor (BDNF) mRNA expression and protein levels, glutamate uptake, glutathione, S100B, GluN1 subunit of N-methyl-D-aspartate receptor and calmodulin were evaluated in the frontal cortex and hippocampus after various swimming time points. We found that swimming stress selectively impaired PPI but did not affect memory recognition. Swimming stress altered the frontal cortical and hippocampal BDNF expression and the activity of hippocampal astrocytes by reducing hippocampal glutamate uptake and enhancing glutathione content in a time-dependent manner. In conclusion, these data support the assumption that astrocytes may regulate the activity of brain structures related to cognition in a manner that alters complex behaviours. Moreover, they provide new insight regarding the dynamics immediately after an aversive experience, such as after behavioural despair induction, and suggest that forced swimming can be employed to study altered glutamatergic activity and PPI disruption in rodents.

  19. In Situ Biospectroscopic Investigation of Rapid Ischemic and Postmortem Induced Biochemical Alterations in the Rat Brain

    PubMed Central

    2015-01-01

    Rapid advances in imaging technologies have pushed novel spectroscopic modalities such as Fourier transform infrared spectroscopy (FTIR) and X-ray absorption spectroscopy (XAS) at the sulfur K-edge to the forefront of direct in situ investigation of brain biochemistry. However, few studies have examined the extent to which sample preparation artifacts confound results. Previous investigations using traditional analyses, such as tissue dissection, homogenization, and biochemical assay, conducted extensive research to identify biochemical alterations that occur ex vivo during sample preparation. In particular, altered metabolism and oxidative stress may be caused by animal death. These processes were a concern for studies using biochemical assays, and protocols were developed to minimize their occurrence. In this investigation, a similar approach was taken to identify the biochemical alterations that are detectable by two in situ spectroscopic methods (FTIR, XAS) that occur as a consequence of ischemic conditions created during humane animal killing. FTIR and XAS are well suited to study markers of altered metabolism such as lactate and creatine (FTIR) and markers of oxidative stress such as aggregated proteins (FTIR) and altered thiol redox (XAS). The results are in accordance with previous investigations using biochemical assays and demonstrate that the time between animal death and tissue dissection results in ischemic conditions that alter brain metabolism and initiate oxidative stress. Therefore, future in situ biospectroscopic investigations utilizing FTIR and XAS must take into consideration that brain tissue dissected from a healthy animal does not truly reflect the in vivo condition, but rather reflects a state of mild ischemia. If studies require the levels of metabolites (lactate, creatine) and markers of oxidative stress (thiol redox) to be preserved as close as possible to the in vivo condition, then rapid freezing of brain tissue via decapitation into

  20. Altered prion protein glycosylation in the aging mouse brain.

    PubMed

    Goh, Angeline Xi-Hua; Li, Chaoyang; Sy, Man-Sun; Wong, Boon-Seng

    2007-02-01

    The normal cellular prion protein (PrP(C)) is a glycoprotein with two highly conserved potential N-linked glycosylation sites. All prion diseases, whether inherited, infectious or sporadic, are believed to share the same pathogenic mechanism that is based on the conversion of the normal cellular prion protein (PrP(C)) to the pathogenic scrapie prion protein (PrP(Sc)). However, the clinical and histopathological presentations of prion diseases are heterogeneous, depending not only on the strains of PrP(Sc) but also on the mechanism of diseases, such as age-related sporadic vs. infectious prion diseases. Accumulated evidence suggests that N-linked glycans on PrP(C) are important in disease phenotype. A better understanding of the nature of the N-linked glycans on PrP(C) during the normal aging process may provide new insights into the roles that N-linked glycans play in the pathogenesis of prion diseases. By using a panel of 19 lectins in an antibody-lectin enzyme-linked immunosorbent assay (ELISA), we found that the lectin binding profiles of PrP(C) alter significantly during aging. There is an increasing prevalence of complex oligosaccharides on the aging PrP(C), which are features of PrP(Sc). Taken together, this study suggests a link between the glycosylation patterns on PrP(C) during aging and PrP(Sc).

  1. CCR2 Antagonism Alters Brain Macrophage Polarization and Ameliorates Cognitive Dysfunction Induced by Traumatic Brain Injury

    PubMed Central

    Jopson, Timothy D.; Liu, Sharon; Riparip, Lara-Kirstie; Guandique, Cristian K.; Gupta, Nalin; Ferguson, Adam R.

    2015-01-01

    Traumatic brain injury (TBI) is a major risk factor for the development of multiple neurodegenerative diseases. With respect to the increasing prevalence of TBI, new therapeutic strategies are urgently needed that will prevent secondary damage to primarily unaffected tissue. Consistently, neuroinflammation has been implicated as a key mediator of secondary damage following the initial mechanical insult. Following injury, there is uncertainty regarding the role that accumulating CCR2+ macrophages play in the injury-induced neuroinflammatory sequelae and cognitive dysfunction. Using CX3CR1GFP/+CCR2RFP/+ reporter mice, we show that TBI initiated a temporally restricted accumulation of peripherally derived CCR2+ macrophages, which were concentrated in the hippocampal formation, a region necessary for learning and memory. Multivariate analysis delineated CCR2+ macrophages' neuroinflammatory response while identifying a novel therapeutic treatment window. As a proof of concept, targeting CCR2+ macrophages with CCX872, a novel Phase I CCR2 selective antagonist, significantly reduced TBI-induced inflammatory macrophage accumulation. Concomitantly, there was a significant reduction in multiple proinflammatory and neurotoxic mediators with this treatment paradigm. Importantly, CCR2 antagonism resulted in a sparing of TBI-induced hippocampal-dependent cognitive dysfunction and reduced proinflammatory activation profile 1 month after injury. Thus, therapeutically targeting the CCR2+ subset of monocytes/macrophages may provide a new avenue of clinical intervention following TBI. PMID:25589768

  2. Physical exercise improves brain cortex and cerebellum mitochondrial bioenergetics and alters apoptotic, dynamic and auto(mito)phagy markers.

    PubMed

    Marques-Aleixo, I; Santos-Alves, E; Balça, M M; Rizo-Roca, D; Moreira, P I; Oliveira, P J; Magalhães, J; Ascensão, A

    2015-08-20

    We here investigate the effects of two exercise modalities (endurance treadmill training-TM and voluntary free-wheel activity-FW) on the brain cortex and cerebellum mitochondrial bioenergetics, permeability transition pore (mPTP), oxidative stress, as well as on proteins involved in mitochondrial biogenesis, apoptosis, and quality control. Eighteen male rats were assigned to sedentary-SED, TM and FW groups. Behavioral alterations and ex vivo brain mitochondrial function endpoints were assessed. Proteins involved in oxidative phosphorylation (OXPHOS, including the adenine nucleotide translocator), oxidative stress markers and regulatory proteins (SIRT3, p66shc, UCP2, carbonyls, MDA, -SH, aconitase, Mn-SOD), as well as proteins involved in mitochondrial biogenesis (PGC1α, TFAM) were evaluated. Apoptotic signaling was measured through quantifying caspase 3, 8 and 9-like activities, Bax, Bcl2, CypD, and cofilin expression. Mitochondrial dynamics (Mfn1/2, OPA1 and DRP1) and auto(mito)phagy (LC3II, Beclin1, Pink1, Parkin, p62)-related proteins were also measured by Western blotting. Only the TM exercise group showed increased spontaneous alternation and exploratory activity. Both exercise regimens improved mitochondrial respiratory activity, increased OXPHOS complexes I, III and V subunits in both brain subareas and decreased oxidative stress markers. Increased resistance to mPTP and decreased apoptotic signaling were observed in the brain cortex from TM and in the cerebellum from TM and FW groups. Also, exercise increased the expression of proteins involved in mitochondrial biogenesis, autophagy and fusion, simultaneous with decreased expression of mitochondrial fission-related protein DRP1. In conclusion, physical exercise improves brain cortex and cerebellum mitochondrial function, decreasing oxidative stress and apoptotic related markers. It is also possible that favorable alterations in mitochondrial biogenesis, dynamics and autophagy signaling induced by exercise

  3. Altered regulation of brain-derived neurotrophic factor protein in hippocampus following slice preparation.

    PubMed

    Danzer, S C; Pan, E; Nef, S; Parada, L F; McNamara, J O

    2004-01-01

    Brain-derived neurotrophic factor (BDNF) and its cognate receptor tyrosine kinase B (TrkB) play important roles in regulating survival, structure, and function of CNS neurons. One method of studying the functions of these molecules has utilized in vitro hippocampal slice preparations. An important caveat to using slices, however, is that slice preparation itself might alter the expression of BDNF, thereby confounding experimental results. To address this concern, BDNF immunoreactivity was examined in rodent slices using two different methods of slice preparation. Rapid and anatomically selective regulation of BDNF content followed slice preparation using both methodologies; however, different patterns of altered BDNF immunoreactivity were observed. First, in cultured slices, BDNF content decreased in the dentate molecular layer and increased in the CA3 pyramidal cell layer and the mossy fiber pathway of the hippocampus after 30 min. Furthermore, an initially "punctate" pattern of BDNF labeling observed in the mossy fiber pathway of control sections changed to homogenous labeling of the pathway in vitro. In contrast to these findings, slices prepared as for acute slice physiology exhibited no change in BDNF content in the molecular layer and mossy fiber pathway 30 min after slicing, but exhibited significant increases in the dentate granule and CA3 pyramidal cell layers. These findings demonstrate that BDNF protein content is altered following slice preparation, that different methods of slice preparation produce different patterns of BDNF regulation, and raise the possibility that BDNF release and TrkB activation may also be regulated. These consequences of hippocampal slice preparation may confound analyses of exogenous or endogenous BDNF on hippocampal neuronal structure or function.

  4. GH and Pituitary Hormone Alterations After Traumatic Brain Injury.

    PubMed

    Karaca, Züleyha; Tanrıverdi, Fatih; Ünlühızarcı, Kürşad; Kelestimur, Fahrettin

    2016-01-01

    Traumatic brain injury (TBI) is a crucially important public health problem around the world, which gives rise to increased mortality and is the leading cause of physical and psychological disability in young adults, in particular. Pituitary dysfunction due to TBI was first described 95 years ago. However, until recently, only a few papers have been published in the literature and for this reason, TBI-induced hypopituitarism has been neglected for a long time. Recent studies have revealed that TBI is one of the leading causes of hypopituitarism. TBI which causes hypopituitarism may be characterized by a single head injury such as from a traffic accident or by chronic repetitive head trauma as seen in combative sports including boxing, kickboxing, and football. Vascular damage, hypoxic insult, direct trauma, genetic predisposition, autoimmunity, and neuroinflammatory changes may have a role in the development of hypopituitarism after TBI. Because of the exceptional structure of the hypothalamo-pituitary vasculature and the special anatomic location of anterior pituitary cells, GH is the most commonly lost hormone after TBI, and the frequency of isolated GHD is considerably high. TBI-induced pituitary dysfunction remains undiagnosed and therefore untreated in most patients because of the nonspecific and subtle clinical manifestations of hypopituitarism. Treatment of TBI-induced hypopituitarism depends on the deficient anterior pituitary hormones. GH replacement therapy has some beneficial effects on metabolic parameters and neurocognitive dysfunction. Patients with TBI without neuroendocrine changes and those with TBI-induced hypopituitarism share the same clinical manifestations, such as attention deficits, impulsion impairment, depression, sleep abnormalities, and cognitive disorders. For this reason, TBI-induced hypopituitarism may be neglected in TBI victims and it would be expected that underlying hypopituitarism would aggravate the clinical picture of TBI

  5. Altered processing of sweet taste in the brain of diet soda drinkers

    PubMed Central

    Green, Erin; Murphy, Claire

    2012-01-01

    Artificially sweetened beverage consumption has been linked to obesity, and it has been hypothesized that considerable exposure to nonnutritive sweeteners may be associated with impaired energy regulation. The reward system plays an integral role in modulating energy intake, but little is known about whether habitual use of artificial sweetener (i.e., diet soda consumption) may be related to altered reward processing of sweet taste in the brain. To investigate this, we examined fMRI response after a 12-hour fast to sucrose (a nutritive sweetener) and saccharin (a nonnutritive sweetener) during hedonic evaluation in young adult diet soda drinkers and non-diet soda drinkers. Diet soda drinkers demonstrated greater activation to sweet taste in the dopaminergic midbrain (including ventral tegmental area) and right amygdala. Saccharin elicited a greater response in the right orbitofrontal cortex (Brodmann Area 47) relative to sucrose in non-diet soda drinkers. There was no difference in fMRI response to the nutritive or nonnutritive sweetener for diet soda drinkers. Within the diet soda drinkers, fMRI activation of the right caudate head in response to saccharin was negatively associated with the amount of diet sodas consumed per week; individuals who consumed a greater number of diet sodas had reduced caudate head activation. These findings suggest that there are alterations in reward processing of sweet taste in individuals who regularly consume diet soda, and this is associated with the degree of consumption. These findings may provide some insight into the link between diet soda consumption and obesity. PMID:22583859

  6. Food restriction during pregnancy alters brain's antioxidant network in dams and their offspring.

    PubMed

    Stone, Vinícius; August, Pauline M; Stocher, Daniela P; Klein, Caroline P; Couto, Pablo R G; Silva, Yasmini D; Sagini, João P; Salomon, Tiago B; Benfato, Mara S; Matté, Cristiane

    2016-01-01

    Dietary restriction increases life span and protects distinct organisms against a series of diseases, among which, those related to oxidative stress, like neurodegenerative diseases. Interferences in the maternal environment are known to reprogram the offspring metabolism response, impacting in the risk of chronic diseases development in adulthood. We aimed to assess the effects of 40% food restriction on reactive species levels, enzymatic and non-enzymatic antioxidant defenses, and oxidative damage parameters in the cerebellum and total cerebral cortex of pregnant rats and their offspring. Dams and pups showed oxidative modulation caused by food restriction in both structures. Dichlorofluorescein oxidation, reflecting reactive species levels, was reduced in the cerebellum of dams and offspring, while the cerebral cortex was not affected. Decreased mitochondrial superoxide levels were found in the cerebellum and cerebral cortex of pups, while nitric oxide was increased in the cortex. We also measured the activities of important antioxidant enzymes responsible by reactive oxygen species elimination. Superoxide dismutase activity was increased in the cerebellum of dams and in both structures of pups, while it was decreased in dams' cerebral cortex. Both brain structures were affected concerning to catalase, glutathione peroxidase, and glutaredoxin activities, which were reduced in pups and dams. Non-enzymatic defenses were decreased in pups, while dams showed an adaptive pattern in the cerebellum and no alteration in the cerebral cortex. Even though the results suggest increased oxidative status, lipids and proteins were not oxidatively affected. Our data suggest that intrauterine food restriction may disrupt oxidative status, impairing the antioxidant network.

  7. Nanotools for Neuroscience and Brain Activity Mapping

    PubMed Central

    Alivisatos, A. Paul; Andrews, Anne M.; Boyden, Edward S.; Chun, Miyoung; Church, George M.; Deisseroth, Karl; Donoghue, John P.; Fraser, Scott E.; Lippincott-Schwartz, Jennifer; Looger, Loren L.; Masmanidis, Sotiris; McEuen, Paul L.; Nurmikko, Arto V.; Park, Hongkun; Peterka, Darcy S.; Reid, Clay; Roukes, Michael L.; Scherer, Axel; Schnitzer, Mark; Sejnowski, Terrence J.; Shepard, Kenneth L.; Tsao, Doris; Turrigiano, Gina; Weiss, Paul S.; Xu, Chris; Yuste, Rafael; Zhuang, Xiaowei

    2013-01-01

    Neuroscience is at a crossroads. Great effort is being invested into deciphering specific neural interactions and circuits. At the same time, there exist few general theories or principles that explain brain function. We attribute this disparity, in part, to limitations in current methodologies. Traditional neurophysiological approaches record the activities of one neuron or a few neurons at a time. Neurochemical approaches focus on single neurotransmitters. Yet, there is an increasing realization that neural circuits operate at emergent levels, where the interactions between hundreds or thousands of neurons, utilizing multiple chemical transmitters, generate functional states. Brains function at the nanoscale, so tools to study brains must ultimately operate at this scale, as well. Nanoscience and nanotechnology are poised to provide a rich toolkit of novel methods to explore brain function by enabling simultaneous measurement and manipulation of activity of thousands or even millions of neurons. We and others refer to this goal as the Brain Activity Mapping Project. In this Nano Focus, we discuss how recent developments in nanoscale analysis tools and in the design and synthesis of nanomaterials have generated optical, electrical, and chemical methods that can readily be adapted for use in neuroscience. These approaches represent exciting areas of technical development and research. Moreover, unique opportunities exist for nanoscientists, nanotechnologists, and other physical scientists and engineers to contribute to tackling the challenging problems involved in understanding the fundamentals of brain function. PMID:23514423

  8. Early life stress affects limited regional brain activity in depression.

    PubMed

    Du, Lian; Wang, Jingjie; Meng, Ben; Yong, Na; Yang, Xiangying; Huang, Qingling; Zhang, Yan; Yang, Lingling; Qu, Yuan; Chen, Zhu; Li, Yongmei; Lv, Fajin; Hu, Hua

    2016-05-03

    Early life stress (ELS) can alter brain function and increases the risk of major depressive disorder (MDD) in later life. This study investigated whether ELS contributes to differences in regional brain activity between MDD patients and healthy controls (HC), as measured by amplitude of low-frequency fluctuation (ALFF)/fractional (f)ALFF. Eighteen first-episode, treatment-naïve MDD patients and HC were assessed with the Childhood Trauma Questionnaire and resting-state functional magnetic resonance imaging. We compared ALFF/fALFF between MDD patients and HC, with or without controlling for ELS, and determined whether ELS level was correlated with regional brain activity in each group. After regressing out ELS, we found that ALFF increased in bilateral amygdala and left orbital/cerebellum, while fALFF decreased in left inferior temporal and right middle frontal gyri in MDD patients relative to controls. ELS positively correlated with regional activity in the left cerebellum in MDD and in the right post-central/inferior temporal/superior frontal cingulate, inferior frontal gyrus and bilateral cerebellum in HC. Our findings indicate that there is only very limited region showing correlation between ELS and brain activity in MDD, while diverse areas in HC, suggesting ELS has few impacts on MDD patients.

  9. Early life stress affects limited regional brain activity in depression

    PubMed Central

    Du, Lian; Wang, Jingjie; Meng, Ben; Yong, Na; Yang, Xiangying; Huang, Qingling; Zhang, Yan; Yang, Lingling; Qu, Yuan; Chen, Zhu; Li, Yongmei; Lv, Fajin; Hu, Hua

    2016-01-01

    Early life stress (ELS) can alter brain function and increases the risk of major depressive disorder (MDD) in later life. This study investigated whether ELS contributes to differences in regional brain activity between MDD patients and healthy controls (HC), as measured by amplitude of low-frequency fluctuation (ALFF)/fractional (f)ALFF. Eighteen first-episode, treatment-naïve MDD patients and HC were assessed with the Childhood Trauma Questionnaire and resting-state functional magnetic resonance imaging. We compared ALFF/fALFF between MDD patients and HC, with or without controlling for ELS, and determined whether ELS level was correlated with regional brain activity in each group. After regressing out ELS, we found that ALFF increased in bilateral amygdala and left orbital/cerebellum, while fALFF decreased in left inferior temporal and right middle frontal gyri in MDD patients relative to controls. ELS positively correlated with regional activity in the left cerebellum in MDD and in the right post-central/inferior temporal/superior frontal cingulate, inferior frontal gyrus and bilateral cerebellum in HC. Our findings indicate that there is only very limited region showing correlation between ELS and brain activity in MDD, while diverse areas in HC, suggesting ELS has few impacts on MDD patients. PMID:27138376

  10. Silver and titanium dioxide nanoparticles alter oxidative/inflammatory response and renin-angiotensin system in brain.

    PubMed

    Krawczyńska, Agata; Dziendzikowska, Katarzyna; Gromadzka-Ostrowska, Joanna; Lankoff, Anna; Herman, Andrzej Przemysław; Oczkowski, Michał; Królikowski, Tomasz; Wilczak, Jacek; Wojewódzka, Maria; Kruszewski, Marcin

    2015-11-01

    The study was designed to examine the effects of silver AgNPs, 20 nm) and titanium dioxide (Aeroxide(®) P25 TiO2NPs, 21 nm) nanoparticles on brain oxidative stress parameters, its antioxidant potential and brain renin-angiotensin system (RAS) in vivo. The analysis was performed 28 days after single dose injection of TiO2NPs and AgNPs (10 or 5 mg/kg body weight, respectively). The AgNPs, but not TiO2NPs, administration resulted in decreased lipid and cholesterol peroxidation. Antioxidant enzymes gene expression and/or activity were changed differently for TiO2NPs and AgNPs group. The TiO2NPs decreased aromatase gene expression, and glutathione peroxidase and reductase activities. In AgNPs group the sodium dismutase 1 and glutathione reductase mRNA levels were decreased as opposed to their activities. Both NPs altered the expression of brain RAS genes (angiotensinogen, renin, angiotensin I converting enzyme 1 and 2), but only TiO2NPs caused similar changes on protein level. The expression of amyloid beta precursor protein gene was not altered by any kind of injected NPs. The TiO2NPs were more potent modulator of gene expression in the brain than AgNPs, despite the two times lower dosage. These results suggest that AgNPs and TiO2NPs exposure may modulate the brain function, but with different strength.

  11. Altered Neuroinflammation and Behavior after Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease.

    PubMed

    Kokiko-Cochran, Olga; Ransohoff, Lena; Veenstra, Mike; Lee, Sungho; Saber, Maha; Sikora, Matt; Teknipp, Ryan; Xu, Guixiang; Bemiller, Shane; Wilson, Gina; Crish, Samuel; Bhaskar, Kiran; Lee, Yu-Shang; Ransohoff, Richard M; Lamb, Bruce T

    2016-04-01

    Traumatic brain injury (TBI) has acute and chronic sequelae, including an increased risk for the development of Alzheimer's disease (AD). TBI-associated neuroinflammation is characterized by activation of brain-resident microglia and infiltration of monocytes; however, recent studies have implicated beta-amyloid as a major manipulator of the inflammatory response. To examine neuroinflammation after TBI and development of AD-like features, these studies examined the effects of TBI in the presence and absence of beta-amyloid. The R1.40 mouse model of cerebral amyloidosis was used, with a focus on time points well before robust AD pathologies. Unexpectedly, in R1.40 mice, the acute neuroinflammatory response to TBI was strikingly muted, with reduced numbers of CNS myeloid cells acquiring a macrophage phenotype and decreased expression of inflammatory cytokines. At chronic time points, macrophage activation substantially declined in non-Tg TBI mice; however, it was relatively unchanged in R1.40 TBI mice. The persistent inflammatory response coincided with significant tissue loss between 3 and 120 days post-injury in R1.40 TBI mice, which was not observed in non-Tg TBI mice. Surprisingly, inflammatory cytokine expression was enhanced in R1.40 mice compared with non-Tg mice, regardless of injury group. Although R1.40 TBI mice demonstrated task-specific deficits in cognition, overall functional recovery was similar to non-Tg TBI mice. These findings suggest that accumulating beta-amyloid leads to an altered post-injury macrophage response at acute and chronic time points. Together, these studies emphasize the role of post-injury neuroinflammation in regulating long-term sequelae after TBI and also support recent studies implicating beta-amyloid as an immunomodulator.

  12. Altered brain-gut axis in autism: comorbidity or causative mechanisms?

    PubMed

    Mayer, Emeran A; Padua, David; Tillisch, Kirsten

    2014-10-01

    The concept that alterated communications between the gut microbiome and the brain may play an important role in human brain disorders has recently received considerable attention. This is the result of provocative preclinical and some clinical evidence supporting early hypotheses about such communication in health and disease. Gastrointestinal symptoms are a common comorbidity in patients with autism spectrum disorders (ASD), even though the underlying mechanisms are largely unknown. In addition, alteration in the composition and metabolic products of the gut microbiome has long been implicated as a possible causative mechanism contributing to ASD pathophysiology, and this hypothesis has been supported by several recently published evidence from rodent models of autism induced by prenatal insults to the mother. Recent evidence in one such model involving maternal infection, that is characterized by alterations in behavior, gut physiology, microbial composition, and related metabolite profile, suggests a possible benefit of probiotic treatment on several of the observed abnormal behaviors.

  13. Lipid alterations in lipid rafts from Alzheimer's disease human brain cortex.

    PubMed

    Martín, Virginia; Fabelo, Noemí; Santpere, Gabriel; Puig, Berta; Marín, Raquel; Ferrer, Isidre; Díaz, Mario

    2010-01-01

    Lipid rafts are membrane microdomains intimately associated with cell signaling. These biochemical microstructures are characterized by their high contents of sphingolipids, cholesterol and saturated fatty acids and a reduced content of polyunsaturated fatty acids (PUFA). Here, we have purified lipid rafts of human frontal brain cortex from normal and Alzheimer's disease (AD) and characterized their biochemical lipid composition. The results revealed that lipid rafts from AD brains exhibit aberrant lipid profiles compared to healthy brains. In particular, lipid rafts from AD brains displayed abnormally low levels of n-3 long chain polyunsaturated fatty acids (LCPUFA, mainly 22:6n-3, docosahexaenoic acid) and monoenes (mainly 18:1n-9, oleic acid), as well as reduced unsaturation and peroxidability indexes. Also, multiple relationships between phospholipids and fatty acids were altered in AD lipid rafts. Importantly, no changes were observed in the mole percentage of lipid classes and fatty acids in rafts from normal brains throughout the lifespan (24-85 years). These indications point to the existence of homeostatic mechanisms preserving lipid raft status in normal frontal cortex. The disruption of such mechanisms in AD brains leads to a considerable increase in lipid raft order and viscosity, which may explain the alterations in lipid raft signaling observed in AD.

  14. Altered brain structural networks in attention deficit/hyperactivity disorder children revealed by cortical thickness.

    PubMed

    Liu, Tian; Chen, Yanni; Li, Chenxi; Li, Youjun; Wang, Jue

    2017-01-18

    This study investigated the cortical thickness and topological features of human brain anatomical networks related to attention deficit/hyperactivity disorder. Data were collected from 40 attention deficit/hyperactivity disorder children and 40 normal control children. Interregional correlation matrices were established by calculating the correlations of cortical thickness between all pairs of cortical regions (68 regions) of the whole brain. Further thresholds were applied to create binary matrices to construct a series of undirected and unweighted graphs, and global, local, and nodal efficiencies were computed as a function of the network cost. These experimental results revealed abnormal cortical thickness and correlations in attention deficit/hyperactivity disorder, and showed that the brain structural networks of attention deficit/hyperactivity disorder subjects had inefficient small-world topological features. Furthermore, their topological properties were altered abnormally. In particular, decreased global efficiency combined with increased local efficiency in attention deficit/hyperactivity disorder children led to a disorder-related shift of the network topological structure toward regular networks. In addition, nodal efficiency, cortical thickness, and correlation analyses revealed that several brain regions were altered in attention deficit/hyperactivity disorder patients. These findings are in accordance with a hypothesis of dysfunctional integration and segregation of the brain in patients with attention deficit/hyperactivity disorder and provide further evidence of brain dysfunction in attention deficit/hyperactivity disorder patients by observing cortical thickness on magnetic resonance imaging.

  15. Agrin in Alzheimer's Disease: Altered Solubility and Abnormal Distribution within Microvasculature and Brain Parenchyma

    NASA Astrophysics Data System (ADS)

    Donahue, John E.; Berzin, Tyler M.; Rafii, Michael S.; Glass, David J.; Yancopoulos, George D.; Fallon, Justin R.; Stopa, Edward G.

    1999-05-01

    Agrin is a heparan sulfate proteoglycan that is widely expressed in neurons and microvascular basal lamina in the rodent and avian central nervous system. Agrin induces the differentiation of nerve-muscle synapses, but its function in either normal or diseased brains is not known. Alzheimer's disease (AD) is characterized by loss of synapses, changes in microvascular architecture, and formation of neurofibrillary tangles and senile plaques. Here we have asked whether AD causes changes in the distribution and biochemical properties of agrin. Immunostaining of normal, aged human central nervous system revealed that agrin is expressed in neurons in multiple brain areas. Robust agrin immunoreactivity was observed uniformly in the microvascular basal lamina. In AD brains, agrin is highly concentrated in both diffuse and neuritic plaques as well as neurofibrillary tangles; neuronal expression of agrin also was observed. Furthermore, patients with AD had microvascular alterations characterized by thinning and fragmentation of the basal lamina. Detergent extraction and Western blotting showed that virtually all the agrin in normal brain is soluble in 1% SDS. In contrast, a large fraction of the agrin in AD brains is insoluble under these conditions, suggesting that it is tightly associated with β -amyloid. Together, these data indicate that the agrin abnormalities observed in AD are closely linked to β -amyloid deposition. These observations suggest that altered agrin expression in the microvasculature and the brain parenchyma contribute to the pathogenesis of AD.

  16. Task-Driven Activity Reduces the Cortical Activity Space of the Brain: Experiment and Whole-Brain Modeling.

    PubMed

    Ponce-Alvarez, Adrián; He, Biyu J; Hagmann, Patric; Deco, Gustavo

    2015-08-01

    How a stimulus or a task alters the spontaneous dynamics of the brain remains a fundamental open question in neuroscience. One of the most robust hallmarks of task/stimulus-driven brain dynamics is the decrease of variability with respect to the spontaneous level, an effect seen across multiple experimental conditions and in brain signals observed at different spatiotemporal scales. Recently, it was observed that the trial-to-trial variability and temporal variance of functional magnetic resonance imaging (fMRI) signals decrease in the task-driven activity. Here we examined the dynamics of a large-scale model of the human cortex to provide a mechanistic understanding of these observations. The model allows computing the statistics of synaptic activity in the spontaneous condition and in putative tasks determined by external inputs to a given subset of brain regions. We demonstrated that external inputs decrease the variance, increase the covariances, and decrease the autocovariance of synaptic activity as a consequence of single node and large-scale network dynamics. Altogether, these changes in network statistics imply a reduction of entropy, meaning that the spontaneous synaptic activity outlines a larger multidimensional activity space than does the task-driven activity. We tested this model's prediction on fMRI signals from healthy humans acquired during rest and task conditions and found a significant decrease of entropy in the stimulus-driven activity. Altogether, our study proposes a mechanism for increasing the information capacity of brain networks by enlarging the volume of possible activity configurations at rest and reliably settling into a confined stimulus-driven state to allow better transmission of stimulus-related information.

  17. Altered alpha brain oscillations during multistable perception in schizophrenia.

    PubMed

    Basar-Eroglu, Canan; Mathes, Birgit; Khalaidovski, Ksenia; Brand, Andreas; Schmiedt-Fehr, Christina

    2016-05-01

    Schizophrenia is a complex mental disorder with impairments in integrating sensory and cognitive functions, leading to severe problems in coherent perception. This impairment might be accelerated during multistable perception. Multistable perception is a phenomenon, where a visual pattern gives rise to at least two different perceptual representations. We addressed this issue by assessing event-related alpha oscillations during continuous viewing of an ambiguous and unambiguous control stimulus. Perceptual reversals were indicated by a manual response, allowing differentiation between phases of reversion and non-reversion (that is perceptual stability) in both tasks. During the ambiguous task, patients and controls showed a comparable number of perceptual reversals. Alpha amplitudes in patients were larger in non-reversion phases, accompanied by a stronger decrease of alpha activity preceding the perceptual reversal. This group difference was pronounced for lower alpha activity and not apparent during the unambiguous task. This indicates that ambiguous perception taps into the specific deficits that patients experience in maintaining coherent perception. Given that top-down influences in generating a meaningful percept seems to be low in patients, they appear more dependent on sensory information. Similar, bottom-up mechanisms might be more important in triggering perceptual reversals in patients than in controls.

  18. Thinking Patterns, Brain Activity and Strategy Choice

    NASA Astrophysics Data System (ADS)

    Nishimura, Kazuo; Okada, Akira; Inagawa, Michiyo; Tobinaga, Yoshikazu

    2012-03-01

    In this study we analyzed the relationship between thinking patterns, behavior and associated brain activity. Subjects completed a self-report assessing whether they could voluntarily stop thinking or not, and were then divided into two groups: those with the ability to stop thinking and those without. We measured subjects' brain activity using magnetoencephalography while giving them a series of tasks intended to encourage or discourage spontaneous thinking. Our findings revealed differences between the two groups in terms of which portions of the brain were active during the two types of task. A second questionnaire confirmed a relationship between the ability to stop thinking and strategy choices in a dilemma game. We found that subjects without the ability to stop thinking had a tendency to choose cooperative behavior.

  19. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group

    PubMed Central

    Schmaal, L; Veltman, D J; van Erp, T G M; Sämann, P G; Frodl, T; Jahanshad, N; Loehrer, E; Tiemeier, H; Hofman, A; Niessen, W J; Vernooij, M W; Ikram, M A; Wittfeld, K; Grabe, H J; Block, A; Hegenscheid, K; Völzke, H; Hoehn, D; Czisch, M; Lagopoulos, J; Hatton, S N; Hickie, I B; Goya-Maldonado, R; Krämer, B; Gruber, O; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Wright, M J; Hall, G B; MacQueen, G M; Frey, E M; Carballedo, A; van Velzen, L S; van Tol, M J; van der Wee, N J; Veer, I M; Walter, H; Schnell, K; Schramm, E; Normann, C; Schoepf, D; Konrad, C; Zurowski, B; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Sussmann, J E; Godlewska, B R; Cowen, P J; Fischer, F H; Rose, M; Penninx, B W J H; Thompson, P M; Hibar, D P

    2016-01-01

    The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=−0.14, % difference=−1.24). This effect was driven by patients with recurrent MDD (Cohen's d=−0.17, % difference=−1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=−0.20, % difference=−1.85) and a trend toward smaller amygdala (Cohen's d=−0.11, % difference=−1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status. PMID:26122586

  20. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

    PubMed

    Schmaal, L; Veltman, D J; van Erp, T G M; Sämann, P G; Frodl, T; Jahanshad, N; Loehrer, E; Tiemeier, H; Hofman, A; Niessen, W J; Vernooij, M W; Ikram, M A; Wittfeld, K; Grabe, H J; Block, A; Hegenscheid, K; Völzke, H; Hoehn, D; Czisch, M; Lagopoulos, J; Hatton, S N; Hickie, I B; Goya-Maldonado, R; Krämer, B; Gruber, O; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Wright, M J; Hall, G B; MacQueen, G M; Frey, E M; Carballedo, A; van Velzen, L S; van Tol, M J; van der Wee, N J; Veer, I M; Walter, H; Schnell, K; Schramm, E; Normann, C; Schoepf, D; Konrad, C; Zurowski, B; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Sussmann, J E; Godlewska, B R; Cowen, P J; Fischer, F H; Rose, M; Penninx, B W J H; Thompson, P M; Hibar, D P

    2016-06-01

    The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

  1. Metabolomics Reveals Metabolic Alterations by Intrauterine Growth Restriction in the Fetal Rabbit Brain

    PubMed Central

    van Vliet, Erwin; Eixarch, Elisenda; Illa, Miriam; Arbat-Plana, Ariadna; González-Tendero, Anna; Hogberg, Helena T.; Zhao, Liang; Hartung, Thomas; Gratacos, Eduard

    2013-01-01

    Background Intrauterine Growth Restriction (IUGR) due to placental insufficiency occurs in 5–10% of pregnancies and is a major risk factor for abnormal neurodevelopment. The perinatal diagnosis of IUGR related abnormal neurodevelopment represents a major challenge in fetal medicine. The development of clinical biomarkers is considered a promising approach, but requires the identification of biochemical/molecular alterations by IUGR in the fetal brain. This targeted metabolomics study in a rabbit IUGR model aimed to obtain mechanistic insight into the effects of IUGR on the fetal brain and identify metabolite candidates for biomarker development. Methodology/Principal Findings At gestation day 25, IUGR was induced in two New Zealand rabbits by 40–50% uteroplacental vessel ligation in one horn and the contralateral horn was used as control. At day 30, fetuses were delivered by Cesarian section, weighed and brains collected for metabolomics analysis. Results showed that IUGR fetuses had a significantly lower birth and brain weight compared to controls. Metabolomics analysis using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and database matching identified 78 metabolites. Comparison of metabolite intensities using a t-test demonstrated that 18 metabolites were significantly different between control and IUGR brain tissue, including neurotransmitters/peptides, amino acids, fatty acids, energy metabolism intermediates and oxidative stress metabolites. Principle component and hierarchical cluster analysis showed cluster formations that clearly separated control from IUGR brain tissue samples, revealing the potential to develop predictive biomarkers. Moreover birth weight and metabolite intensity correlations indicated that the extent of alterations was dependent on the severity of IUGR. Conclusions IUGR leads to metabolic alterations in the fetal rabbit brain, involving neuronal viability, energy metabolism, amino acid levels, fatty

  2. Structural Brain Alterations in Children an Average of 5 Years after Surgery and Chemotherapy for Brain Tumors

    PubMed Central

    Nelson, Mary Baron; Macey, Paul M.; Harper, Ronald M.; Jacob, Eufemia; Patel, Sunita K.; Finlay, Jonathan L.; Nelson, Marvin D.; Compton, Peggy

    2014-01-01

    Background Young children with brain tumors are often treated with high-dose chemotherapy after surgery to avoid brain tissue injury associated with irradiation. The effects of systemic chemotherapy on healthy brain tissue in this population, however, are unclear. Our objective was to compare gray and white matter integrity using MRI procedures in children with brain tumors (n=7, mean age 8.3 years), treated with surgery and high-dose chemotherapy followed by autologous hematopoietic cell rescue (AuHCR) an average of 5.4 years earlier, to age- and gender-matched healthy controls (n=9, mean age 9.3 years). Methods Diffusion tensor imaging data were collected to evaluate tissue integrity throughout the brain, as measured by mean diffusivity (MD), a marker of glial, neuronal, and axonal status, and fractional anisotropy (FA), an index of axonal health. Individual MD and FA maps were calculated, normalized, smoothed, and compared between groups using analysis of covariance, with age and sex as covariates. Results Higher mean diffusivity values, indicative of injury, emerged in patients compared with controls (p<0.05, corrected for multiple comparisons), and were especially apparent in the central thalamus, external capsule, putamen, globus pallidus and pons. Reduced FA values in some regions did not reach significance after correction for multiple comparisons. Conclusions Children treated with surgery and high-dose chemotherapy with AuHCR for brain tumors an average of 5.4 years earlier show alterations in white and gray matter in multiple brain areas distant from the tumor site, raising the possibility for long-term consequences of the tumor or treatment. PMID:24830985

  3. Brain death induces the alteration of liver protein expression profiles in rabbits.

    PubMed

    Du, Bing; Li, Ling; Zhong, Zhibiao; Fan, Xiaoli; Qiao, Bingbing; He, Chongxiang; Fu, Zhen; Wang, Yanfeng; Ye, Qifa

    2014-08-01

    At present, there is no accurate method for evaluating the quality of liver transplant from a brain-dead donor. Proteomics are used to investigate the mechanisms involved in brain death‑induced liver injury and to identify sensitive biomarkers. In the present study, age‑ and gender‑matched rabbits were randomly divided into the brain death and sham groups. The sham served as the control. A brain‑death model was established using an intracranial progressive pressurized method. The differentially expressed proteins extracted from the liver tissues of rabbits that were brain‑dead for 6 h in the two groups were determined by two‑dimensional gel electrophoresis and matrix‑assisted laser desorption ionization time of flight mass spectrometry. Although there was no obvious functional and morphological difference in 2, 4 and 6 h after brain death, results of the proteomics analysis revealed 973±34 and 987±38 protein spots in the control and brain death groups, respectively. Ten proteins exhibited a ≥2‑fold alteration. The downregulated proteins were: aldehyde dehydrogenase, runt‑related transcription factor 1 (RUNX1), inorganic pyrophosphatase, glutamate‑cysteine ligase regulatory subunit and microsomal cytochrome B5. By contrast, the expression of dihydropyrimidinase-related protein 4, peroxiredoxin‑6, 3‑phosphoinositide‑dependent protein kinase‑1, 3-mercaptopyruvate and alcohol dehydrogenase were clearly upregulated. Immunohistochemistry and western blot analysis results revealed that the expression of RUNX1 was gradually increased in a time‑dependent manner in 2, 4, and 6 h after brain death. In conclusion, alteration of the liver protein expression profile induced by brain death indicated the occurrence of complex pathological changes even if no functional or morphological difference was identified. Thus, RUNX1 may be a sensitive predict factor for evaluating the quality of brain death donated liver.

  4. Growth-Related Neural Reorganization and the Autism Phenotype: A Test of the Hypothesis that Altered Brain Growth Leads to Altered Connectivity

    ERIC Educational Resources Information Center

    Lewis, John D.; Elman, Jeffrey L.

    2008-01-01

    Theoretical considerations, and findings from computational modeling, comparative neuroanatomy and developmental neuroscience, motivate the hypothesis that a deviant brain growth trajectory will lead to deviant patterns of change in cortico-cortical connectivity. Differences in brain size during development will alter the relative cost and…

  5. Brain Microstructural Abnormalities Are Related to Physiological Alterations in End-Stage Renal Disease

    PubMed Central

    Tian, Junzhang; Dong, Jianwei; He, Jinlong; Zhan, Wenfeng; Xu, Lijuan; Xu, Yikai; Jiang, Guihua

    2016-01-01

    Purpose To study whole-brain microstructural alterations in patients with end-stage renal disease (ESRD) and examine the relationship between brain microstructure and physiological indictors in the disease. Materials and Methods Diffusion tensor imaging data were collected from 35 patients with ESRD (28 men, 18–61 years) and 40 age- and gender-matched healthy controls (HCs, 32 men, 22–58 years). A voxel-wise analysis was then used to identify microstructural alterations over the whole brain in the ESRD patients compared with the HCs. Multiple biochemical measures of renal metabolin, vascular risk factors, general cognitive ability and dialysis duration were correlated with microstructural integrity for the patients. Results Compared to the HCs, the ESRD patients exhibited disrupted microstructural integrity in not only white matter (WM) but also gray matter (GM) regions, as characterized by decreased fractional anisotropy (FA) and increased mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). Further correlation analyses revealed that the in MD, AD and RD values showed significantly positive correlations with the blood urea nitrogen in the left superior temporal gyrus and significantly negative correlations with the calcium levels in the left superior frontal gyrus (orbital part) in the patients. Conclusion Our findings suggest that ESRD is associated with widespread diffusion abnormalities in both WM and GM regions in the brain, and microstructural integrity of several GM regions are related to biochemical alterations in the disease. PMID:27227649

  6. Fetal alcohol exposure alters neurosteroid levels in the developing rat brain.

    PubMed

    Caldeira, Jerri C; Wu, Yan; Mameli, Manuel; Purdy, Robert H; Li, Pui-Kai; Akwa, Yvette; Savage, Daniel D; Engen, John R; Valenzuela, C Fernando

    2004-09-01

    Neurosteroids are modulators of neuronal function that may play important roles in brain maturation. We determined whether chronic prenatal ethanol exposure altered neurosteroid levels in the developing brain. Rat dams were exposed to: (i) a 5% ethanol-containing liquid diet that produces peak maternal blood alcohol levels near the legal intoxication limit (approximately 0.08 g/dL); (ii) an isocaloric liquid diet containing maltose-dextrin instead of ethanol with pair-feeding; (iii) rat chow ad libitum. Neurosteroid levels were assessed in offspring brains using radioimmunoassay or gas chromatography-mass spectrometry techniques. A prenatal ethanol exposure-induced increase in pregnenolone sulfate levels, but not dehydroepiandrosterone sulfate levels, was evident at the earliest time point studied (embryonic day 14). This effect lasted until post-natal day 5. Levels of other neurosteroids were assessed at embryonic day 20; pregnenolone levels, but not allopregnanolone levels, were elevated. Pregnenolone sulfate levels were not altered in the maternal brain. Neither pregnenolone nor pregnenolone sulfate levels were significantly altered in the fetal liver, placenta and maternal blood, indicating that the effect of ethanol is not secondary to accumulation of peripherally-produced steroids. Fetal ethanol exposure has been shown to decrease both cellular and behavioral responsiveness to neurosteroids, and our findings provide a plausible explanation for this effect.

  7. ALTERATION IN MICROSOMAL PROTEIN SYNTHESIS DURING EARLY DEVELOPMENT OF MOUSE BRAIN*

    PubMed Central

    Johnson, Terry C.; Belytschko, Gail

    1969-01-01

    The loss of protein synthesis during early mouse-brain development was shown to be the result, at least in part, of the inability of microsomes obtained from more mature neural tissue to participate in rapid polypeptide synthesis. The loss of brain microsomal activity was observed shortly after birth and continued until the animals were approximately ten days old. Despite the difference in synthetic activity, sucrose gradient profiles of microsomes and polyribosomes from young and more mature brain tissue were quite similar. The loss in protein synthesis was shown to be independent of available mRNA and not attributable to aminoacyl-RNA synthetases and tRNA binding activity. PMID:5257009

  8. Sex-based differences in brain alterations across chronic pain conditions.

    PubMed

    Gupta, Arpana; Mayer, Emeran A; Fling, Connor; Labus, Jennifer S; Naliboff, Bruce D; Hong, Jui-Yang; Kilpatrick, Lisa A

    2017-01-02

    Common brain mechanisms are thought to play a significant role across a multitude of chronic pain syndromes. In addition, there is strong evidence for the existence of sex differences in the prevalence of chronic pain and in the neurobiology of pain. Thus, it is important to consider sex when developing general principals of pain neurobiology. The goal of the current Mini-Review is to evaluate what is known about sex-specific brain alterations across multiple chronic pain populations. A total of 15 sex difference and 143 single-sex articles were identified from among 412 chronic pain neuroimaging articles. Results from sex difference studies indicate more prominent primary sensorimotor structural and functional alterations in female chronic pain patients compared with male chronic pain patients: differences in the nature and degree of insula alterations, with greater insula reactivity in male patients; differences in the degree of anterior cingulate structural alterations; and differences in emotional-arousal reactivity. Qualitative comparisons of male-specific and female-specific studies appear to be consistent with the results from sex difference studies. Given these differences, mixed-sex studies of chronic pain risk creating biased data or missing important information and single-sex studies have limited generalizability. The advent of large-scale neuroimaging databases will likely aid in building a more comprehensive understanding of sex differences and commonalities in brain mechanisms underlying chronic pain. © 2016 Wiley Periodicals, Inc.

  9. Maternal vitamin D deficiency alters fetal brain development in the BALB/c mouse.

    PubMed

    Hawes, Jazmin E; Tesic, Dijana; Whitehouse, Andrew J; Zosky, Graeme R; Smith, Jeremy T; Wyrwoll, Caitlin S

    2015-06-01

    Prenatal exposure to vitamin D is thought to be critical for optimal fetal neurodevelopment, yet vitamin D deficiency is apparent in a growing proportion of pregnant women. The aim of this study was to determine whether a mouse model of vitamin D-deficiency alters fetal neurodevelopment. Female BALB/c mice were placed on either a vitamin D control (2,195 IU/kg) or deficient (0 IU/kg) diet for 5 weeks prior to and during pregnancy. Fetal brains were collected at embryonic day (E) 14.5 or E17.5 for morphological and gene expression analysis. Vitamin D deficiency during pregnancy reduced fetal crown-rump length and head size. Moreover, lateral ventricle volume was reduced in vitamin D-deficient foetuses. Expression of neurotrophin genes brain-derived neurotrophic factor (Bdnf) and transforming growth factor-β1 (Tgf-β1) was altered, with Bdnf reduced at E14.5 and increased at E17.5 following vitamin D deficiency. Brain expression of forkhead box protein P2 (Foxp2), a gene known to be important in human speech and language, was also altered. Importantly, Foxp2 immunoreactive cells in the developing cortex were reduced in vitamin D-deficient female foetuses. At E17.5, brain tyrosine hydroxylase (TH) gene expression was reduced in females, as was TH protein localization (to identify dopamine neurons) in the substantia nigra of vitamin D-deficient female foetuses. Overall, we show that prenatal vitamin D-deficiency leads to alterations in fetal mouse brain morphology and genes related to neuronal survival, speech and language development, and dopamine synthesis. Vitamin D appears to play an important role in mouse neurodevelopment.

  10. Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors

    PubMed Central

    Fordahl, Steve; Cooney, Paula; Qiu, Yunping; Xie, Guoxiang; Jia, Wei; Erikson, Keith M.

    2011-01-01

    Overexposure to waterborne manganese (Mn) is linked with cognitive impairment in children and neurochemical abnormalities in other experimental models. In order to characterize the threshold between Mn-exposure and altered neurochemistry, it is important to identify biomarkers that positively correspond with brain Mn-accumulation. The objective of this study was to identify Mn-induced alterations in plasma, liver, and brain metabolites using liquid/gas chromatography-time of flight-mass spectrometry metabolomic analyses; and to monitor corresponding Mn-induced behavior changes. Weanling Sprague-Dawley rats had access to deionized drinking water either Mn-free or containing 1g Mn/L for six weeks. Behaviors were monitored during the sixth week for a continuous 24h period while in a home cage environment using video surveillance. Mn-exposure significantly increased liver, plasma, and brain Mn concentrations compared to control, specifically targeting the globus pallidus (GP). Mn significantly altered 98 metabolites in the brain, liver, and plasma; notably shifting cholesterol and fatty acid metabolism in the brain (increased oleic and palmitic acid; 12.57 and 15.48 fold change (FC), respectively), and liver (increased oleic acid, 14.51 FC; decreased hydroxybutyric acid, −14.29 FC). Additionally, Mn-altered plasma metabolites homogentisic acid, chenodeoxycholic acid, and aspartic acid correlated significantly with GP and striatal Mn. Total distance traveled was significantly increased and positively correlated with Mn-exposure, while nocturnal stereotypic and exploratory behaviors were reduced with Mn-exposure and performed largely during the light cycle compared to unexposed rats. These data provide putative biomarkers for Mn-neurotoxicity and suggest that Mn disrupts the circadian cycle in rats. PMID:22056924

  11. Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors.

    PubMed

    Fordahl, Steve; Cooney, Paula; Qiu, Yunping; Xie, Guoxiang; Jia, Wei; Erikson, Keith M

    2012-01-01

    Overexposure to waterborne manganese (Mn) is linked with cognitive impairment in children and neurochemical abnormalities in other experimental models. In order to characterize the threshold between Mn-exposure and altered neurochemistry, it is important to identify biomarkers that positively correspond with brain Mn-accumulation. The objective of this study was to identify Mn-induced alterations in plasma, liver, and brain metabolites using liquid/gas chromatography-time of flight-mass spectrometry metabolomic analyses; and to monitor corresponding Mn-induced behavior changes. Weanling Sprague-Dawley rats had access to deionized drinking water either Mn-free or containing 1g Mn/L for 6 weeks. Behaviors were monitored during the sixth week for a continuous 24h period while in a home cage environment using video surveillance. Mn-exposure significantly increased liver, plasma, and brain Mn concentrations compared to control, specifically targeting the globus pallidus (GP). Mn significantly altered 98 metabolites in the brain, liver, and plasma; notably shifting cholesterol and fatty acid metabolism in the brain (increased oleic and palmitic acid; 12.57 and 15.48 fold change (FC), respectively), and liver (increased oleic acid, 14.51 FC; decreased hydroxybutyric acid, -14.29 FC). Additionally, Mn-altered plasma metabolites homogentisic acid, chenodeoxycholic acid, and aspartic acid correlated significantly with GP and striatal Mn. Total distance traveled was significantly increased and positively correlated with Mn-exposure, while nocturnal stereotypic and exploratory behaviors were reduced with Mn-exposure and performed largely during the light cycle compared to unexposed rats. These data provide putative biomarkers for Mn-neurotoxicity and suggest that Mn disrupts the circadian cycle in rats.

  12. Structural brain alterations in patients with lumbar disc herniation: a preliminary study.

    PubMed

    Luchtmann, Michael; Steinecke, Yvonne; Baecke, Sebastian; Lützkendorf, Ralf; Bernarding, Johannes; Kohl, Jana; Jöllenbeck, Boris; Tempelmann, Claus; Ragert, Patrick; Firsching, Raimund

    2014-01-01

    Chronic pain is one of the most common health complaints in industrial nations. For example, chronic low back pain (cLBP) disables millions of people across the world and generates a tremendous economic burden. While previous studies provided evidence of widespread functional as well as structural brain alterations in chronic pain, little is known about cortical changes in patients suffering from lumbar disc herniation. We investigated morphometric alterations of the gray and white matter of the brain in patients suffering from LDH. The volumes of the gray and white matter of 12 LDH patients were determined in a prospective study and compared to the volumes of healthy controls to distinguish local differences. High-resolution MRI brain images of all participants were performed using a 3 Tesla MRI scanner. Voxel-based morphometry was used to investigate local differences in gray and white matter volume between patients suffering from LDH and healthy controls. LDH patients showed significantly reduced gray matter volume in the right anterolateral prefrontal cortex, the right temporal lobe, the left premotor cortex, the right caudate nucleus, and the right cerebellum as compared to healthy controls. Increased gray matter volume, however, was found in the right dorsal anterior cingulate cortex, the left precuneal cortex, the left fusiform gyrus, and the right brainstem. Additionally, small subcortical decreases of the white matter were found adjacent to the left prefrontal cortex, the right premotor cortex and in the anterior limb of the left internal capsule. We conclude that the lumbar disk herniation can lead to specific local alterations of the gray and white matter in the human brain. The investigation of LDH-induced brain alterations could provide further insight into the underlying nature of the chronification processes and could possibly identify prognostic factors that may improve the conservative as well as the operative treatment of the LDH.

  13. Radiation-Induced Alterations in Mouse Brain Development Characterized by Magnetic Resonance Imaging

    SciTech Connect

    Gazdzinski, Lisa M.; Cormier, Kyle; Lu, Fred G.; Lerch, Jason P.; Wong, C. Shun; Nieman, Brian J.

    2012-12-01

    Purpose: The purpose of this study was to identify regions of altered development in the mouse brain after cranial irradiation using longitudinal magnetic resonance imaging (MRI). Methods and Materials: Female C57Bl/6 mice received a whole-brain radiation dose of 7 Gy at an infant-equivalent age of 2.5 weeks. MRI was performed before irradiation and at 3 time points following irradiation. Deformation-based morphometry was used to quantify volume and growth rate changes following irradiation. Results: Widespread developmental deficits were observed in both white and gray matter regions following irradiation. Most of the affected brain regions suffered an initial volume deficit followed by growth at a normal rate, remaining smaller in irradiated brains compared with controls at all time points examined. The one exception was the olfactory bulb, which in addition to an early volume deficit, grew at a slower rate thereafter, resulting in a progressive volume deficit relative to controls. Immunohistochemical assessment revealed demyelination in white matter and loss of neural progenitor cells in the subgranular zone of the dentate gyrus and subventricular zone. Conclusions: MRI can detect regional differences in neuroanatomy and brain growth after whole-brain irradiation in the developing mouse. Developmental deficits in neuroanatomy persist, or even progress, and may serve as useful markers of late effects in mouse models. The high-throughput evaluation of brain development enabled by these methods may allow testing of strategies to mitigate late effects after pediatric cranial irradiation.

  14. Estrogen alters the diurnal rhythm of alpha 1-adrenergic receptor densities in selected brain regions

    SciTech Connect

    Weiland, N.G.; Wise, P.M.

    1987-11-01

    Norepinephrine regulates the proestrous and estradiol-induced LH surge by binding to alpha 1-adrenergic receptors. The density of alpha 1-receptors may be regulated by estradiol, photoperiod, and noradrenergic neuronal activity. We wished to determine whether alpha 1-receptors exhibit a diurnal rhythm in ovariectomized and/or estradiol-treated female rats, whether estradiol regulates alpha 1-receptors in those areas of brain involved with LH secretion and/or sexual behavior, and whether the concentrations of alpha-receptors vary inversely relative to previously reported norepinephrine turnover patterns. Young female rats, maintained on a 14:10 light-dark cycle were ovariectomized. One week later, half of them were outfitted sc with Silastic capsules containing estradiol. Groups of animals were decapitated 2 days later at 0300, 1000, 1300, 1500, 1800, and 2300 h. Brains were removed, frozen, and sectioned at 20 micron. Sections were incubated with (/sup 3/H)prazosin in Tris-HCl buffer, washed, dried, and exposed to LKB Ultrofilm. The densities of alpha 1-receptors were quantitated using a computerized image analysis system. In ovariectomized rats, the density of alpha 1-receptors exhibited a diurnal rhythm in the suprachiasmatic nucleus (SCN), medial preoptic nucleus (MPN), and pineal gland. In SCN and MPN, receptor concentrations were lowest during the middle of the day and rose to peak levels at 1800 h. In the pineal gland, the density of alpha 1-receptors was lowest at middark phase, rose to peak levels before lights on, and remained elevated during the day. Estradiol suppressed the density of alpha 1 binding sites in the SCN, MPN, median eminence, ventromedial nucleus, and the pineal gland but had no effect on the lateral septum. Estrogen treatment altered the rhythm of receptor densities in MPN, median eminence, and the pineal gland.

  15. [Glial activation and brain aging].

    PubMed

    Sugaya, K

    2001-10-01

    While basal forebrain cholinergic neurons degenerate in aging and Alzheimer's disease, the cholinergic groups of the upper brainstem are preserved. Since the brainstem reticular-like cholinergic neurons differ from the rostral cholinergic phenotype by their high expression of nitric oxide synthase (NOS) mRNA, we hypothesized that they contain biochemical mechanisms to protect themselves against self-induced damage by nitric oxide (NO). Our initial question was a source of the NO during the aging process. We found a significant correlation between cognitive function and markers for glial activation and oxidative stress using aged rats. This result indicates that oxidative stress accompanied by glial activation may be occurred in the cognitively impaired animals. We also found mitochondrial DNA (mDNA) was significantly damaged in these animals, while accumulation of oxidative damage was not evident in other molecules. Therefore, oxidative damage to the mDNA by glial activation may occur in the cells having poor protection against oxidative stress during aging. Then the dysfunction of mitochondria, induced by the mDNA damage, may induce cell death as well as produce another oxidative stress to cause neuronal damage. The damaged neurons induce further glial activation and such self-accelerated immune-like response results in progressive neurodegeneration.

  16. Active ultramicrobacterial alteration of iron in granite

    NASA Astrophysics Data System (ADS)

    Brown, D. Ann; Sherriff, Barbara L.

    1997-07-01

    Microorganisms are able to exist in extreme environments, where they often form biofilms. We are investigating an iron metabolizing biofilm consortium derived from groundwater draining the Canadian Shield. This was first discovered in the Underground Research Laboratory of Atomic Energy of Canada Ltd., where its influence on the management of nuclear fuel waste was examined. Incubations have shown that the microbial consortium contains different morphological forms. Ultramicrobacteria, 0.3 micrometers diameter cocci, are dominant on magnetite surfaces, which they are able to transform rapidly to hematite. Larger rods, 1.0 micrometers long, aggregate on silicon minerals containing little iron. Carbon is limited in these natural groundwaters so that iron is utilized as an alternative energy source. The cell surface of the organisms and the extracellular polymers of the biofilm are both negatively-charged allowing metal cations to be quickly bound by physicochemical sorption, thus providing nucleation sites for mineralization within the boundaries. The biofilm consortium is able to mediate a wide range of iron reactions. Aerobically a ferric gel is precipitated throughout the biofilm slime, which alters first to ferrihydrite and later to hematite. When anaerobic fermentation produces a reducing environment the iron is converted to the ferrous state which may then be precipitated as ferrous hydroxide, vivianite or siderite. Since iron is widespread in the natural environment, these reactions could have important geochemical implications.

  17. Chronic maternal morphine alters calbindin D-28k expression pattern in postnatal mouse brain.

    PubMed

    Mithbaokar, Pratibha; Fiorito, Filomena; Della Morte, Rossella; Maharajan, Veeramani; Costagliola, Anna

    2016-01-01

    The distribution pattern of calbindin (CB)-D28k-expressing neurons results to be altered in several brain regions of chronic morphine exposed adult mice. In this study, the influence of chronic maternal exposure to morphine on the distribution pattern of CB-D28k-expressing neurons in the brain of mouse offspring was investigated. Females of CD-1 mice were daily administered with saline or morphine for 7 days before mating, during the whole gestation period, and until 21 day post-partum. Their offspring were sacrificed on postnatal day 18, and the brains were examined by histology using cresyl violet and by immunohistochemistry using a rabbit polyclonal anti-CB-D28k antibody. Histology revealed no significant differences in the distribution pattern and the number of neurons between the offspring forebrain of the control group of mice and the two groups of mice treated with different doses of morphine. However, immunohistochemical analysis revealed that the number of CB-D28k-immunoreactive neurons remarkably decreased in the cingulate cortex, in the layers II-IV of the parietal cortex and in all regions of the hippocampus, while it increased in the layers V-VI of the parietal cortex and in the subicular region of the offspring brain of morphine treated mice. Overall, our findings demonstrate that maternal exposure to morphine alters the pattern of CB-D28k-expressing neuron pattern in specific regions of murine developing brain, in a layer- and dose-dependent way, thus suggesting that these alterations might represent a mechanism by which morphine modifies the functional aspects of developing brain.

  18. Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure.

    PubMed

    Cauley, Edmund; Wang, Xin; Dyavanapalli, Jhansi; Sun, Ke; Garrott, Kara; Kuzmiak-Glancy, Sarah; Kay, Matthew W; Mendelowitz, David

    2015-10-01

    Hypertension, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affect nearly 23 million people worldwide. A distinctive hallmark of these cardiovascular diseases is autonomic imbalance, with increased sympathetic activity and decreased parasympathetic vagal tone. Recent device-based approaches, such as implantable vagal stimulators that stimulate a multitude of visceral sensory and motor fibers in the vagus nerve, are being evaluated as new therapeutic approaches for these and other diseases. However, little is known about how parasympathetic activity to the heart is altered with these diseases, and this lack of knowledge is an obstacle in the goal of devising selective interventions that can target and selectively restore parasympathetic activity to the heart. To identify the changes that occur within the brain stem to diminish the parasympathetic cardiac activity, left ventricular hypertrophy was elicited in rats by aortic pressure overload using a transaortic constriction approach. Cardiac vagal neurons (CVNs) in the brain stem that generate parasympathetic activity to the heart were identified with a retrograde tracer and studied using patch-clamp electrophysiological recordings in vitro. Animals with left cardiac hypertrophy had diminished excitation of CVNs, which was mediated both by an augmented frequency of spontaneous inhibitory GABAergic neurotransmission (with no alteration of inhibitory glycinergic activity) as well as a diminished amplitude and frequency of excitatory neurotransmission to CVNs. Opportunities to alter these network pathways and neurotransmitter receptors provide future targets of intervention in the goal to restore parasympathetic activity and autonomic balance to the heart in cardiac hypertrophy and other cardiovascular diseases.

  19. Brain Activity on Navigation in Virtual Environments.

    ERIC Educational Resources Information Center

    Mikropoulos, Tassos A.

    2001-01-01

    Assessed the cognitive processing that takes place in virtual environments by measuring electrical brain activity using Fast Fourier Transform analysis. University students performed the same task in a real and a virtual environment, and eye movement measurements showed that all subjects were more attentive when navigating in the virtual world.…

  20. Transcriptomic alterations in the brain of painted turtles (Chrysemys picta) developmentally exposed to bisphenol A or ethinyl estradiol.

    PubMed

    Manshack, Lindsey K; Conard, Caroline M; Bryan, Sara J; Deem, Sharon L; Holliday, Dawn K; Bivens, Nathan J; Givan, Scott A; Rosenfeld, Cheryl S

    2017-04-01

    Developmental exposure of turtles and other reptiles to endocrine-disrupting chemicals (EDCs), including bisphenol A (BPA) and ethinyl estradiol (EE), can stimulate partial to full gonadal sex-reversal in males. We have also recently shown that in ovo exposure to either EDC can induce similar sex-dependent behavioral changes typified by improved spatial learning and memory or possibly feminized brain responses. Observed behavioral changes are presumed to be due to BPA- and EE-induced brain transcriptomic alterations during development. To test this hypothesis, we treated painted turtles (Chrysemys picta) at developmental stage 17, incubated at 26°C (male-inducing temperature), with 1) BPA (1 ng/µl), 2) EE (4 ng/µl), or 3) vehicle ethanol (control group). Ten months after hatching and completion of the behavioral tests, juvenile turtles were euthanized, brains were collected and frozen in liquid nitrogen, and RNA was isolated for RNA-Seq analysis. Turtles exposed to BPA clustered separately from EE-exposed and control individuals. More transcripts and gene pathways were altered in BPA vs. EE individuals. The one transcript upregulated in both BPA- and EE-exposed individuals was the mitochondrial-associated gene, ND5, which is involved in oxidative phosphorylation. Early exposure of turtles to BPA increases transcripts linked with ribosomal and mitochondrial functions, especially bioenergetics, which has been previously linked with improved cognitive performance. In summary, even though both BPA and EE resulted in similar behavioral alterations, they diverge in the pattern of neural transcript alterations with early BPA significantly upregulating several genes involved in oxidative phosphorylation, mitochondrial activity, and ribosomal function, which could enhance cognitive performance.

  1. Electromagnetic imaging of dynamic brain activity

    SciTech Connect

    Mosher, J.; Leahy, R. . Dept. of Electrical Engineering); Lewis, P.; Lewine, J.; George, J. ); Singh, M. . Dept. of Radiology)

    1991-01-01

    Neural activity in the brain produces weak dynamic electromagnetic fields that can be measured by an array of sensors. Using a spatio-temporal modeling framework, we have developed a new approach to localization of multiple neural sources. This approach is based on the MUSIC algorithm originally developed for estimating the direction of arrival of signals impinging on a sensor array. We present applications of this technique to magnetic field measurements of a phantom and of a human evoked somatosensory response. The results of the somatosensory localization are mapped onto the brain anatomy obtained from magnetic resonance images.

  2. Electromagnetic imaging of dynamic brain activity

    SciTech Connect

    Mosher, J.; Leahy, R.; Lewis, P.; Lewine, J.; George, J.; Singh, M.

    1991-12-31

    Neural activity in the brain produces weak dynamic electromagnetic fields that can be measured by an array of sensors. Using a spatio-temporal modeling framework, we have developed a new approach to localization of multiple neural sources. This approach is based on the MUSIC algorithm originally developed for estimating the direction of arrival of signals impinging on a sensor array. We present applications of this technique to magnetic field measurements of a phantom and of a human evoked somatosensory response. The results of the somatosensory localization are mapped onto the brain anatomy obtained from magnetic resonance images.

  3. High-fat diet transition reduces brain DHA levels associated with altered brain plasticity and behaviour.

    PubMed

    Sharma, Sandeep; Zhuang, Yumei; Gomez-Pinilla, Fernando

    2012-01-01

    To assess how the shift from a healthy diet rich in omega-3 fatty acids to a diet rich in saturated fatty acid affects the substrates for brain plasticity and function, we used pregnant rats fed with omega-3 supplemented diet from their 2nd day of gestation period as well as their male pups for 12 weeks. Afterwards, the animals were randomly assigned to either a group fed on the same diet or a group fed on a high-fat diet (HFD) rich in saturated fats for 3 weeks. We found that the HFD increased vulnerability for anxiety-like behavior, and that these modifications harmonized with changes in the anxiety-related NPY1 receptor and the reduced levels of BDNF, and its signalling receptor pTrkB, as well as the CREB protein. Brain DHA contents were significantly associated with the levels of anxiety-like behavior in these rats.

  4. Altered brain ion gradients following compensation for elevated CO2 are linked to behavioural alterations in a coral reef fish

    PubMed Central

    Heuer, R. M.; Welch, M. J.; Rummer, J. L.; Munday, P. L.; Grosell, M.

    2016-01-01

    Neurosensory and behavioural disruptions are some of the most consistently reported responses upon exposure to ocean acidification-relevant CO2 levels, especially in coral reef fishes. The underlying cause of these disruptions is thought to be altered current across the GABAA receptor in neuronal cells due to changes in ion gradients (HCO3− and/or Cl−) that occur in the body following compensation for elevated ambient CO2. Despite these widely-documented behavioural disruptions, the present study is the first to pair a behavioural assay with measurements of relevant intracellular and extracellular acid-base parameters in a coral reef fish exposed to elevated CO2. Spiny damselfish (Acanthochromis polyacanthus) exposed to 1900 μatm CO2 for 4 days exhibited significantly increased intracellular and extracellular HCO3− concentrations and elevated brain pHi compared to control fish, providing evidence of CO2 compensation. As expected, high CO2 exposed damselfish spent significantly more time in a chemical alarm cue (CAC) than control fish, supporting a potential link between behavioural disruption and CO2 compensation. Using HCO3− measurements from the damselfish, the reversal potential for GABAA (EGABA) was calculated, illustrating that biophysical properties of the brain during CO2 compensation could change GABAA receptor function and account for the behavioural disturbances noted during exposure to elevated CO2. PMID:27620837

  5. Altered brain ion gradients following compensation for elevated CO2 are linked to behavioural alterations in a coral reef fish.

    PubMed

    Heuer, R M; Welch, M J; Rummer, J L; Munday, P L; Grosell, M

    2016-09-13

    Neurosensory and behavioural disruptions are some of the most consistently reported responses upon exposure to ocean acidification-relevant CO2 levels, especially in coral reef fishes. The underlying cause of these disruptions is thought to be altered current across the GABAA receptor in neuronal cells due to changes in ion gradients (HCO3(-) and/or Cl(-)) that occur in the body following compensation for elevated ambient CO2. Despite these widely-documented behavioural disruptions, the present study is the first to pair a behavioural assay with measurements of relevant intracellular and extracellular acid-base parameters in a coral reef fish exposed to elevated CO2. Spiny damselfish (Acanthochromis polyacanthus) exposed to 1900 μatm CO2 for 4 days exhibited significantly increased intracellular and extracellular HCO3(-) concentrations and elevated brain pHi compared to control fish, providing evidence of CO2 compensation. As expected, high CO2 exposed damselfish spent significantly more time in a chemical alarm cue (CAC) than control fish, supporting a potential link between behavioural disruption and CO2 compensation. Using HCO3(-) measurements from the damselfish, the reversal potential for GABAA (EGABA) was calculated, illustrating that biophysical properties of the brain during CO2 compensation could change GABAA receptor function and account for the behavioural disturbances noted during exposure to elevated CO2.

  6. Structural and functional alterations in mitochondrial membrane in picrotoxin-induced epileptic rat brain.

    PubMed

    Acharya, Munjal M; Katyare, Surendra S

    2005-03-01

    Mitochondrial function is a key determinant of both excitability and viability of neurons. Present studies were carried out to decipher cerebral mitochondrial oxidative energy metabolism and membrane function in the chronic condition of generalized seizures induced by picrotoxin (PTX) in rats. PTX-induced convulsions resulted in decreased respiration rates (14-41%) with glutamate, pyruvate + malate, and succinate as substrate. The ADP phosphorylation rates were drastically reduced by 44-65%. An opposite trend was observed with ascorbate + N,N,N',N'-tetramethyl-p-phenylenediamine [corrected] (TMPD) as substrate. In general, uncoupling of the mitochondrial electron transport was observed after PTX treatment. Malate dehydrogenase (MDH) and succinate dehydrogenase (SDH) activities were decreased by 20-80%; also, there was significant reduction in cytochrome b content after PTX treatment, while the F(o)F(1) ATPase (complex V) activity increased in basal and 2,4-dinitrophenol (DNP)-stimulated condition, indicating increased membrane fragility. The substrate kinetics analysis had shown that K(m) and V(max) of the higher affinity kinetic component of ATPase increased significantly by 1.2- to 1.4-fold in epileptic condition. Temperature kinetic analysis revealed 1.2-fold increase in energies of activation with decreased transition temperature. The total phospholipid (TPL) and cholesterol (CHL) contents decreased significantly with lowering of diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidylserine (PS), while lysophospholipid (lyso), sphingomyelin (SPM), and phosphatidylcholine components were found to be elevated. Brain mitochondrial membrane was somewhat more fluidized in epileptic animals. Possible consequences of mitochondrial respiratory chain (MRC) dysfunction are discussed. In conclusion, impairment of MRC function along with structural alterations suggests novel pathophysiological mechanisms important for

  7. Consistently altered expression of gene sets in postmortem brains of individuals with major psychiatric disorders

    PubMed Central

    Darby, M M; Yolken, R H; Sabunciyan, S

    2016-01-01

    The measurement of gene expression in postmortem brain is an important tool for understanding the pathogenesis of serious psychiatric disorders. We hypothesized that major molecular deficits associated with psychiatric disease would affect the entire brain, and such deficits may be shared across disorders. We performed RNA sequencing and quantified gene expression in the hippocampus of 100 brains in the Stanley Array Collection followed by replication in the orbitofrontal cortex of 57 brains in the Stanley Neuropathology Consortium. We then identified genes and canonical pathway gene sets with significantly altered expression in schizophrenia and bipolar disorder in the hippocampus and in schizophrenia, bipolar disorder and major depression in the orbitofrontal cortex. Although expression of individual genes varied, gene sets were significantly enriched in both of the brain regions, and many of these were consistent across diagnostic groups. Further examination of core gene sets with consistently increased or decreased expression in both of the brain regions and across target disorders revealed that ribosomal genes are overexpressed while genes involved in neuronal processes, GABAergic signaling, endocytosis and antigen processing have predominantly decreased expression in affected individuals compared to controls without a psychiatric disorder. Our results highlight pathways of central importance to psychiatric health and emphasize messenger RNA processing and protein synthesis as potential therapeutic targets for all three of the disorders. PMID:27622934

  8. Ionizing Radiation Alters the Properties of Sodium Channels in Rat Brain Synaptosomes

    DTIC Science & Technology

    1986-01-01

    International So, iet% for Ncurochemistry SIonizing Radiation Alters the Properties of Sodium to Channels in Rat Brain Synaptosomes Michael J. Mullin, Walter...its binding site in the channel, Ionizing radiation reduced radiation on the voltage-sensitive sodium channels in rat the veratridine-stimulated...in the order of membrane lipids. Key greatest. Batrachotoxin-stimulated 22Na’ uptake was Words: Ionizing radiation- Sodium channels-Mem- less sensitive

  9. Traffic pollution exposure is associated with altered brain connectivity in school children.

    PubMed

    Pujol, Jesus; Martínez-Vilavella, Gerard; Macià, Dídac; Fenoll, Raquel; Alvarez-Pedrerol, Mar; Rivas, Ioar; Forns, Joan; Blanco-Hinojo, Laura; Capellades, Jaume; Querol, Xavier; Deus, Joan; Sunyer, Jordi

    2016-04-01

    Children are more vulnerable to the effects of environmental elements due to their active developmental processes. Exposure to urban air pollution has been associated with poorer cognitive performance, which is thought to be a result of direct interference with brain maturation. We aimed to assess the extent of such potential effects of urban pollution on child brain maturation using general indicators of vehicle exhaust measured in the school environment and a comprehensive imaging evaluation. A group of 263 children, aged 8 to 12 years, underwent MRI to quantify regional brain volumes, tissue composition, myelination, cortical thickness, neural tract architecture, membrane metabolites, functional connectivity in major neural networks and activation/deactivation dynamics during a sensory task. A combined measurement of elemental carbon and NO2 was used as a putative marker of vehicle exhaust. Air pollution exposure was associated with brain changes of a functional nature, with no evident effect on brain anatomy, structure or membrane metabolites. Specifically, a higher content of pollutants was associated with lower functional integration and segregation in key brain networks relevant to both inner mental processes (the default mode network) and stimulus-driven mental operations. Age and performance (motor response speed) both showed the opposite effect to that of pollution, thus indicating that higher exposure is associated with slower brain maturation. In conclusion, urban air pollution appears to adversely affect brain maturation in a critical age with changes specifically concerning the functional domain.

  10. Alterations in the sense of time, space, and body in the mindfulness-trained brain: a neurophenomenologically-guided MEG study.

    PubMed

    Berkovich-Ohana, Aviva; Dor-Ziderman, Yair; Glicksohn, Joseph; Goldstein, Abraham

    2013-01-01

    Meditation practice can lead to what have been referred to as "altered states of consciousness."One of the phenomenological characteristics of these states is a joint alteration in the sense of time, space, and body. Here, we set out to study the unique experiences of alteration in the sense of time and space by collaborating with a select group of 12 long-term mindfulness meditation (MM) practitioners in a neurophenomenological setup, utilizing first-person data to guide the neural analyses. We hypothesized that the underlying neural activity accompanying alterations in the sense of time and space would be related to alterations in bodily processing. The participants were asked to volitionally bring about distinct states of "Timelessness" (outside time) and "Spacelessness" (outside space) while their brain activity was recorded by MEG. In order to rule out the involvement of attention, memory, or imagination, we used control states of "Then" (past) and "There" (another place). MEG sensors evidencing alterations in power values were identified, and the brain regions underlying these changes were estimated via spatial filtering (beamforming). Particularly, we searched for similar neural activity hypothesized to underlie both the state of "Timelessness" and "Spacelessness." The results were mostly confined to the theta band, and showed that: (1) the "Then"/"There" overlap yielded activity in regions related to autobiographic memory and imagery (right posterior parietal lobule (PPL), right precentral/middle frontal gyrus (MFG), bilateral precuneus); (2) "Timelessness"/"Spacelessness" conditions overlapped in a different network, related to alterations in the sense of the body (posterior cingulate, right temporoparietal junction (TPJ), cerebellum); and (3) phenomenologically-guided neural analyses enabled us to dissociate different levels of alterations in the sense of the body. This study illustrates the utility of employing experienced contemplative practitioners

  11. Unlike lithium, anticonvulsants and antidepressants do not alter rat brain myo-inositol.

    PubMed

    McGrath, Brent M; Greenshaw, Andrew J; McKay, Ryan; Slupsky, Carolyn M; Silverstone, Peter H

    2007-10-08

    Lithium is the first-line in bipolar disorder treatment. Lithium's clinical efficacy might be due to its inhibition of myo-inositol turnover in the phosphatidylinositol second messenger system. This study aimed to determine whether this action can extend to antidepressants and anticonvulsants also used to treat bipolar symptoms. Male rats were treated for 2 weeks with an intraperitoneal injection of phenelzine, fluoxetine, desipramine, carbamazepine, lamotrigine, sodium valproate or vehicle. Brains were dissected and myo-inositol concentrations were analyzed using high-field nuclear magnetic resonance spectroscopy at 18.8 T and quantified using Chenomx Profiler software. Brain regions assessed included the prefrontal, temporal and occipital cortical areas as well as the hippocampus. The main finding is that contrary to lithium, the anticonvulsants and antidepressants do not alter brain myo-inositol concentration. This suggests that these agents might work via a mechanism that is not centered on changes in myo-inositol concentration.

  12. Carbonated soft drinks induce oxidative stress and alter the expression of certain genes in the brains of Wistar rats.

    PubMed

    El-Terras, Adel; Soliman, Mohamed Mohamed; Alkhedaide, Adel; Attia, Hossam Fouad; Alharthy, Abdullah; Banaja, Abdel Elah

    2016-04-01

    In Saudi Arabia, the consumption of carbonated soft drinks is common and often occurs with each meal. Carbonated soft drink consumption has been shown to exhibit effects on the liver, kidney and bone. However, the effects of these soft drinks on brain activity have not been widely examined, particularly at the gene level. Therefore, the current study was conducted with the aim of evaluating the effects of chronic carbonated soft drink consumption on oxidative stress, brain gene biomarkers associated with aggression and brain histology. In total, 40 male Wistar rats were divided into four groups: Group 1 served as a control and was provided access to food and water ad libitum; and groups 2‑4 were given free access to food and carbonated soft drinks only (Cola for group 2, Pepsi for group 3 and 7‑UP for group 4). Animals were maintained on these diets for 3 consecutive months. Upon completion of the experimental period, animals were sacrificed and serological and histopathological analyses were performed on blood and tissues samples. Reverse transcription‑polymerase chain reaction was used to analyze alterations in gene expression levels. Results revealed that carbonated soft drinks increased the serum levels of malondialdehyde (MDA). Carbonated soft drinks were also observed to downregulate the expression of antioxidants glutathione reductase (GR), catalase and glutathione peroxidase (GPx) in the brain when compared with that in the control rats. Rats administered carbonated soft drinks also exhibited decreased monoamine oxidase A (MAO‑A) and acetylcholine esterase (AChE) serum and mRNA levels in the brain. In addition, soft drink consumption upregulated mRNA expression of dopamine D2 receptor (DD2R), while 5-hydroxytryptamine transporter (5‑HTT) expression was decreased. However, following histological examination, all rats had a normal brain structure. The results of this study demonstrated that that carbonated soft drinks induced oxidative stress and

  13. Childhood maltreatment is associated with altered frontolimbic neurobiological activity during wakefulness in adulthood

    PubMed Central

    Insana, Salvatore P.; Banihashemi, Layla; Herringa, Ryan J.; Kolko, David J.; Germain, Anne

    2015-01-01

    Childhood maltreatment can disturb brain development, and subsequently lead to adverse socioemotional and mental health problems across the lifespan. The long-term association between childhood maltreatment and resting-wake brain activity during adulthood is unknown and was examined in the current study. Forty one medically stable and medication-free military veterans (M=29.31±6.01 years, 78% male) completed a battery of clinical assessments and had [18F]-fluorodeoxyglucose positron emission tomography neuroimaging scans during quiet wakefulness. After statistically adjusting for later-life trauma and mental health problems, childhood maltreatment was negatively associated with brain activity within a-priori defined regions that included the left orbital frontal cortex and left hippocampus. Childhood maltreatment was significantly associated with increased and decreased brain activity within six additional whole-brain clusters that included frontal, parietal-temporal, cerebellar, limbic, and midbrain regions. Childhood maltreatment is associated with altered neural activity in adulthood within regions that are involved in executive functioning and cognitive control, socioemotional processes, autonomic functions, and sleep/wake regulation. This study provides support for taking a lifespan developmental approach to understanding the effects of early-life maltreatment on later-life neurobiology, socioemotional functioning, and mental health. PMID:26198818

  14. How networks communicate: propagation patterns in spontaneous brain activity.

    PubMed

    Mitra, Anish; Raichle, Marcus E

    2016-10-05

    Initially regarded as 'noise', spontaneous (intrinsic) activity accounts for a large portion of the brain's metabolic cost. Moreover, it is now widely known that infra-slow (less than 0.1 Hz) spontaneous activity, measured using resting state functional magnetic resonance imaging of the blood oxygen level-dependent (BOLD) signal, is correlated within functionally defined resting state networks (RSNs). However, despite these advances, the temporal organization of spontaneous BOLD fluctuations has remained elusive. By studying temporal lags in the resting state BOLD signal, we have recently shown that spontaneous BOLD fluctuations consist of remarkably reproducible patterns of whole brain propagation. Embedded in these propagation patterns are unidirectional 'motifs' which, in turn, give rise to RSNs. Additionally, propagation patterns are markedly altered as a function of state, whether physiological or pathological. Understanding such propagation patterns will likely yield deeper insights into the role of spontaneous activity in brain function in health and disease.This article is part of the themed issue 'Interpreting blood oxygen level-dependent: a dialogue between cognitive and cellular neuroscience'.

  15. Prolonged Mitosis of Neural Progenitors Alters Cell Fate in the Developing Brain.

    PubMed

    Pilaz, Louis-Jan; McMahon, John J; Miller, Emily E; Lennox, Ashley L; Suzuki, Aussie; Salmon, Edward; Silver, Debra L

    2016-01-06

    Embryonic neocortical development depends on balanced production of progenitors and neurons. Genetic mutations disrupting progenitor mitosis frequently impair neurogenesis; however, the link between altered mitosis and cell fate remains poorly understood. Here we demonstrate that prolonged mitosis of radial glial progenitors directly alters neuronal fate specification and progeny viability. Live imaging of progenitors from a neurogenesis mutant, Magoh(+/-), reveals that mitotic delay significantly correlates with preferential production of neurons instead of progenitors, as well as apoptotic progeny. Independently, two pharmacological approaches reveal a causal relationship between mitotic delay and progeny fate. As mitotic duration increases, progenitors produce substantially more apoptotic progeny or neurons. We show that apoptosis, but not differentiation, is p53 dependent, demonstrating that these are distinct outcomes of mitotic delay. Together our findings reveal that prolonged mitosis is sufficient to alter fates of radial glia progeny and define a new paradigm to understand how mitosis perturbations underlie brain size disorders such as microcephaly.

  16. Irradiation Alters MMP-2/TIMP-2 System and Collagen Type IV Degradation in Brain

    SciTech Connect

    Lee, Won Hee; Warrington, Junie P.; Sonntag, William E.; Lee, Yong Woo

    2012-04-01

    Purpose: Blood-brain barrier (BBB) disruption is one of the major consequences of radiation-induced normal tissue injury in the central nervous system. We examined the effects of whole-brain irradiation on matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) and extracellular matrix (ECM) degradation in the brain. Methods and Materials: Animals received either whole-brain irradiation (a single dose of 10 Gy {gamma}-rays or a fractionated dose of 40 Gy {gamma}-rays, total) or sham-irradiation and were maintained for 4, 8, and 24 h following irradiation. mRNA expression levels of MMPs and TIMPs in the brain were analyzed by real-time reverse transcriptase-polymerase chain reaction (PCR). The functional activity of MMPs was measured by in situ zymography, and degradation of ECM was visualized by collagen type IV immunofluorescent staining. Results: A significant increase in mRNA expression levels of MMP-2, MMP-9, and TIMP-1 was observed in irradiated brains compared to that in sham-irradiated controls. In situ zymography revealed a strong gelatinolytic activity in the brain 24 h postirradiation, and the enhanced gelatinolytic activity mediated by irradiation was significantly attenuated in the presence of anti-MMP-2 antibody. A significant reduction in collagen type IV immunoreactivity was also detected in the brain at 24 h after irradiation. In contrast, the levels of collagen type IV were not significantly changed at 4 and 8 h after irradiation compared with the sham-irradiated controls. Conclusions: The present study demonstrates for the first time that radiation induces an imbalance between MMP-2 and TIMP-2 levels and suggests that degradation of collagen type IV, a major ECM component of BBB basement membrane, may have a role in the pathogenesis of brain injury.

  17. The association between regular cannabis exposure and alterations of human brain morphology: an updated review of the literature.

    PubMed

    Lorenzetti, Valentina; Solowij, Nadia; Fornito, Alex; Lubman, Dan Ian; Yucel, Murat

    2014-01-01

    Cannabis is the most widely used illicit drug worldwide, though it is unclear whether its regular use is associated with persistent alterations in brain morphology. This review examines evidence from human structural neuroimaging investigations of regular cannabis users and focuses on achieving three main objectives. These include examining whether the literature to date provides evidence that alteration of brain morphology in regular cannabis users: i) is apparent, compared to non-cannabis using controls; ii) is associated with patterns of cannabis use; and with iii) measures of psychopathology and neurocognitive performance. The published findings indicate that regular cannabis use is associated with alterations in medial temporal, frontal and cerebellar brain regions. Greater brain morphological alterations were evident among samples that used at higher doses for longer periods. However, the evidence for an association between brain morphology and cannabis use parameters was mixed. Further, there is poor evidence for an association between measures of brain morphology and of psychopathology symptoms/neurocognitive performance. Overall, numerous methodological issues characterize the literature to date. These include investigation of small sample sizes, heterogeneity across studies in sample characteristics (e.g., sex, comorbidity) and in employed imaging techniques, as well as the examination of only a limited number of brain regions. These factors make it difficult to draw firm conclusions from the existing findings. Nevertheless, this review supports the notion that regular cannabis use is associated with alterations of brain morphology, and highlights the need to consider particular methodological issues when planning future cannabis research.

  18. ALTERATIONS IN BRAIN CREATINE CONCENTRATIONS UNDER LONG-TERM SOCIAL ISOLATION (EXPERIMENTAL STUDY).

    PubMed

    Koshoridze, N; Kuchukashvili, Z; Menabde, K; Lekiashvili, Sh; Koshoridze, M

    2016-02-01

    Stress represents one of the main problems of modern humanity. This study was done for understanding more clearly alterations in creatine content of the brain under psycho-emotional stress induced by long-term social isolation. It was shown that under 30 days social isolation creatine amount in the brain was arisen, while decreasing concentrations of synthesizing enzymes (AGAT, GAMT) and creatine transporter protein (CrT). Another important point was that such changes were accompanied by down-regulation of creatine kinase (CK), therefore the enzyme's concentration was lowered. In addition, it was observed that content of phosphocreatine (PCr) and ATP were also reduced, thus indicating down-regulation of energy metabolism of brain that is really a crucial point for its normal functioning. To sum up the results it can be underlined that long-term social isolation has negative influence on energy metabolism of brain; and as a result reduce ATP content, while increase of free creatine concentration, supposedly maintaining maximal balance for ATP amount, but here must be also noted that up-regulated oxidative pathways might have impact on blood brain barrier, resulting on its permeability.

  19. Adolescent binge ethanol treatment alters adult brain regional volumes, cortical extracellular matrix protein and behavioral flexibility.

    PubMed

    Coleman, Leon Garland; Liu, Wen; Oguz, Ipek; Styner, Martin; Crews, Fulton T

    2014-01-01

    Adolescents binge drink more than any other age group, increasing risk of disrupting the development of the frontal cortex. We hypothesized that adolescent binge drinking would lead to persistent alterations in adulthood. In this study, we modeled adolescent weekend underage binge-drinking, using adolescent mice (post-natal days [P] 28-37). The adolescent intermittent binge ethanol (AIE) treatment includes 6 binge intragastric doses of ethanol in an intermittent pattern across adolescence. Assessments were conducted in adulthood following extended abstinence to determine if there were persistent changes in adults. Reversal learning, open field and other behavioral assessments as well as brain structure using magnetic imaging and immunohistochemistry were determined. We found that AIE did not impact adult Barnes Maze learning. However, AIE did cause reversal learning deficits in adults. AIE also caused structural changes in the adult brain. AIE was associated with adulthood volume enlargements in specific brain regions without changes in total brain volume. Enlarged regions included the orbitofrontal cortex (OFC, 4%), cerebellum (4.5%), thalamus (2%), internal capsule (10%) and genu of the corpus callosum (7%). The enlarged OFC volume in adults after AIE is consistent with previous imaging studies in human adolescents. AIE treatment was associated with significant increases in the expression of several extracellular matrix (ECM) proteins in the adult OFC including WFA (55%), Brevican (32%), Neurocan (105%), Tenacin-C (25%), and HABP (5%). These findings are consistent with AIE causing persistent changes in brain structure that could contribute to a lack of behavioral flexibility.

  20. Adolescent binge ethanol treatment alters adult brain regional volumes, cortical extracellular matrix protein and behavioral flexibility

    PubMed Central

    Coleman, Leon Garland; Liu, Wen; Oguz, Ipek; Styner, Martin; Crews, Fulton T.

    2014-01-01

    Adolescents binge drink more than any other age group, increasing risk of disrupting the development of the frontal cortex. We hypothesized that adolescent binge drinking would lead to persistent alterations in adulthood. In this study, we modeled adolescent weekend underage binge-drinking, using adolescent mice (post-natal days [P] 28–37). The adolescent intermittent binge ethanol (AIE) treatment includes 6 binge intragastric doses of ethanol in an intermittent pattern across adolescence. Assessments were conducted in adulthood following extended abstinence to determine if there were persistent changes in adults. Reversal learning, open field and other behavioral assessments as well as brain structure using magnetic imaging and immunohistochemistry were determined. We found AIE did not impact adult Barnes Maze learning. However, AIE did cause reversal learning deficits in adults. AIE also caused structural changes in the adult brain. AIE was associated with adulthood volume enlargements in specific brain regions without changes in total brain volume. Enlarged regions included the orbitofrontal cortex (OFC, 4%), cerebellum (4.5%), thalamus (2%), internal capsule (10%) and genu of the corpus callosum (7%). The enlarged OFC volume in adults after AIE is consistent with previous imaging studies in human adolescents. AIE treatment was associated with significant increases in the expression of several extracellular matrix (ECM) proteins in the adult OFC including WFA (55%), Brevican (32%), Neurocan (105%), Tenacin-C (25%), and HABP (5%). These findings are consistent with AIE causing persistent changes in brain structure that could contribute to a lack of behavioral flexibility. PMID:24275185

  1. Sexual differentiation of the brain: a model for drug-induced alterations of the reproductive system

    SciTech Connect

    Gorski, R.A.

    1986-12-01

    The process of the sexual differentiation of the brain represents a valuable model system for the study of the chemical modification of the mammalian brain. Although there are numerous functional and structural sex differences in the adult brain, these are imposed on an essentially feminine or bipotential brain by testicular hormones during a critical phase of perinatal development in the rat. It is suggested that a relatively marked structural sex difference in the rat brain, the sexually dimorphic nucleus of the preoptic area (SDN-POA), is a morphological signature of the permanent or organizational action of estradiol derived from the aromatization of testicular testosterone. The SDN-POA of the male rat is severalfold larger in volume and is composed of more neurons than that of the female. The observation that the mitotic formation of the neurons of the SDN-POA is specifically prolonged has enabled us to identify the time course and pathway of neuronal migration into the nucleus. Study of the development of the SDN-POA suggests that estradiol in the male increases the number of neurons which survive a phase of neuronal death by exerting a neurite growth promoting action and/or a direct neuronotrophic action. Finally, although it is clear that gonadal hormones have dramatic permanent effects on the brain during perinatal development, even after puberty and in adulthood gonadal steroids can alter neuronal structure and, perhaps as a corollary to this, have permanent effects on reproductive function. Although the brain may be most sensitive to gonadal hormones or exogenous chemical factors during perinatal development, such as sensitivity does not appear limited to this period.

  2. C5a alters blood-brain barrier integrity in a human in vitro model of systemic lupus erythematosus.

    PubMed

    Mahajan, Supriya D; Parikh, Neil U; Woodruff, Trent M; Jarvis, James N; Lopez, Molly; Hennon, Teresa; Cunningham, Patrick; Quigg, Richard J; Schwartz, Stanley A; Alexander, Jessy J

    2015-09-01

    The blood-brain barrier (BBB) plays a crucial role in brain homeostasis, thereby maintaining the brain environment precise for optimal neuronal function. Its dysfunction is an intriguing complication of systemic lupus erythematosus (SLE). SLE is a systemic autoimmune disorder where neurological complications occur in 5-50% of cases and is associated with impaired BBB integrity. Complement activation occurs in SLE and is an important part of the clinical profile. Our earlier studies demonstrated that C5a generated by complement activation caused the loss of brain endothelial layer integrity in rodents. The goal of the current study was to determine the translational potential of these studies to a human system. To assess this, we used a two dimensional in vitro BBB model constructed using primary human brain microvascular endothelial cells and astroglial cells, which closely emulates the in vivo BBB allowing the assessment of BBB integrity. Increased permeability monitored by changes in transendothelial electrical resistance and cytoskeletal remodelling caused by actin fiber rearrangement were observed when the cells were exposed to lupus serum and C5a, similar to the observations in mice. In addition, our data show that C5a/C5aR1 signalling alters nuclear factor-κB translocation into nucleus and regulates the expression of the tight junction proteins, claudin-5 and zonula occludens 1 in this setting. Our results demonstrate for the first time that C5a regulates BBB integrity in a neuroinflammatory setting where it affects both endothelial and astroglial cells. In addition, we also demonstrate that our previous findings in a mouse model, were emulated in human cells in vitro, bringing the studies one step closer to understanding the translational potential of C5a/C5aR1 blockade as a promising therapeutic strategy in SLE and other neurodegenerative diseases.

  3. Alterations of resting state functional network connectivity in the brain of nicotine and alcohol users.

    PubMed

    Vergara, Victor M; Liu, Jingyu; Claus, Eric D; Hutchison, Kent; Calhoun, Vince

    2016-11-15

    Alcohol and nicotine intake result in neurological alterations at the circuit level. Resting state functional connectivity has shown great potential in identifying these alterations. However, current studies focus on specific seeds and leave out many brain regions where effects might exist. The present study uses a data driven technique for brain segmentation covering the whole brain. Functional magnetic-resonance-imaging (fMRI) data were collected from 188 subjects:51 non-substance consumption controls (CTR), 36 smoking-and-drinking subjects (SAD), 28 drinkers (DRN), and 73 smokers (SMK). Data were processed using group independent component analysis to derive resting state networks (RSN). The resting state functional network connectivity (rsFNC) was then calculated through correlation between time courses. One-way ANOVA tests were used to detect rsFNC differences among the four groups. A total of 50 ANOVA tests were significant after multi-comparison correction. Results delineate a general pattern of hypo-connectivity in the substance consumers. Precuneus, postcentral gyrus, insula and visual cortex were the main brain areas with rsFNC reduction suggesting reduced interoceptive awareness in drinkers. In addition, connectivity reduction between postcentral and one RSN covering right fusiform and lingual gyri showed significant association with severity of hazardous drinking. In smokers, connectivity changes agreed with the idea of a shift towards endogenous information processing, represented by the DMN. Hypo-connectivity between thalamus and putamen was observed in smokers. In contrast, the angular gyrus showed hyper-connectivity with the precuneus linked to smoking and significantly correlated with nicotine dependence severity. In spite of the presence of common effects, our results suggest that particular effects of alcohol and nicotine can be separated and identified. Results also suggest that concurrent use of both substances affects brain connectivity in a

  4. Using Brain Electrical Activity Mapping to Diagnose Learning Disabilities.

    ERIC Educational Resources Information Center

    Torello, Michael, W.; Duffy, Frank H.

    1985-01-01

    Cognitive neuroscience assumes that measurement of brain electrical activity should relate to cognition. Brain Electrical Activity Mapping (BEAM), a non-invasive technique, is used to record changes in activity from one brain area to another and is 80 to 90 percent successful in classifying subjects as dyslexic or normal. (MT)

  5. Brain Activation During Singing: "Clef de Sol Activation" Is the "Concert" of the Human Brain.

    PubMed

    Mavridis, Ioannis N; Pyrgelis, Efstratios-Stylianos

    2016-03-01

    Humans are the most complex singers in nature, and the human voice is thought by many to be the most beautiful musical instrument. Aside from spoken language, singing represents a second mode of acoustic communication in humans. The purpose of this review article is to explore the functional anatomy of the "singing" brain. Methodologically, the existing literature regarding activation of the human brain during singing was carefully reviewed, with emphasis on the anatomic localization of such activation. Relevant human studies are mainly neuroimaging studies, namely functional magnetic resonance imaging and positron emission tomography studies. Singing necessitates activation of several cortical, subcortical, cerebellar, and brainstem areas, served and coordinated by multiple neural networks. Functionally vital cortical areas of the frontal, parietal, and temporal lobes bilaterally participate in the brain's activation process during singing, confirming the latter's role in human communication. Perisylvian cortical activity of the right hemisphere seems to be the most crucial component of this activation. This also explains why aphasic patients due to left hemispheric lesions are able to sing but not speak the same words. The term clef de sol activation is proposed for this crucial perisylvian cortical activation due to the clef de sol shape of the topographical distribution of these cortical areas around the sylvian fissure. Further research is needed to explore the connectivity and sequence of how the human brain activates to sing.

  6. Elderly patients have an altered gut-brain axis regardless of the presence of cirrhosis

    PubMed Central

    Bajaj, Jasmohan S.; Ahluwalia, Vishwadeep; Steinberg, Joel L.; Hobgood, Sarah; Boling, Peter A.; Godschalk, Michael; Habib, Saima; White, Melanie B.; Fagan, Andrew; Gavis, Edith A.; Ganapathy, Dinesh; Hylemon, Phillip B.; Stewart, Karen E.; Keradman, Raffi; Liu, Eric J.; Wang, Jessica; Gillevet, Patrick M.; Sikaroodi, Masoumeh; Moeller, F. Gerard; Wade, James B.

    2016-01-01

    Cognitive difficulties manifested by the growing elderly population with cirrhosis could be amnestic (memory-related) or non-amnestic (memory-unrelated). The underlying neuro-biological and gut-brain changes are unclear in this population. We aimed to define gut-brain axis alterations in elderly cirrhotics compared to non-cirrhotic individuals based on presence of cirrhosis and on neuropsychological performance. Age-matched outpatients with/without cirrhosis underwent cognitive testing (amnestic/non-amnestic domains), quality of life (HRQOL), multi-modal MRI (fMRI go/no-go task, volumetry and MR spectroscopy), blood (inflammatory cytokines) and stool collection (for microbiota). Groups were studied based on cirrhosis/not and also based on neuropsychological performance (amnestic-type, amnestic/non-amnestic-type and unimpaired). Cirrhotics were impaired on non-amnestic and selected amnestic tests, HRQOL and systemic inflammation compared to non-cirrhotics. Cirrhotics demonstrated significant changes on MR spectroscopy but not on fMRI or volumetry. Correlation networks showed that Lactobacillales members were positively while Enterobacteriaceae and Porphyromonadaceae were negatively linked with cognition. Using the neuropsychological classification amnestic/non-amnestic-type individuals were majority cirrhosis and had worse HRQOL, higher inflammation and decreased autochthonous taxa relative abundance compared to the rest. This classification also predicted fMRI, MR spectroscopy and volumetry changes between groups. We conclude that gut-brain axis alterations may be associated with the type of neurobehavioral decline or inflamm-aging in elderly cirrhotic subjects. PMID:27922089

  7. When “altering brain function” becomes “mind control”

    PubMed Central

    Koivuniemi, Andrew; Otto, Kevin

    2014-01-01

    Functional neurosurgery has seen a resurgence of interest in surgical treatments for psychiatric illness. Deep brain stimulation (DBS) technology is the preferred tool in the current wave of clinical experiments because it allows clinicians to directly alter the functions of targeted brain regions, in a reversible manner, with the intent of correcting diseases of the mind, such as depression, addiction, anorexia nervosa, dementia, and obsessive compulsive disorder. These promising treatments raise a critical philosophical and humanitarian question. “Under what conditions does ‘altering brain function’ qualify as ‘mind control’?” In order to answer this question one needs a definition of mind control. To this end, we reviewed the relevant philosophical, ethical, and neurosurgical literature in order to create a set of criteria for what constitutes mind control in the context of DBS. We also outline clinical implications of these criteria. Finally, we demonstrate the relevance of the proposed criteria by focusing especially on serendipitous treatments involving DBS, i.e., cases in which an unintended therapeutic benefit occurred. These cases highlight the importance of gaining the consent of the subject for the new therapy in order to avoid committing an act of mind control. PMID:25352789

  8. The brain functional connectome is robustly altered by lack of sleep.

    PubMed

    Kaufmann, Tobias; Elvsåshagen, Torbjørn; Alnæs, Dag; Zak, Nathalia; Pedersen, Per Ø; Norbom, Linn B; Quraishi, Sophia H; Tagliazucchi, Enzo; Laufs, Helmut; Bjørnerud, Atle; Malt, Ulrik F; Andreassen, Ole A; Roussos, Evangelos; Duff, Eugene P; Smith, Stephen M; Groote, Inge R; Westlye, Lars T

    2016-02-15

    Sleep is a universal phenomenon necessary for maintaining homeostasis and function across a range of organs. Lack of sleep has severe health-related consequences affecting whole-body functioning, yet no other organ is as severely affected as the brain. The neurophysiological mechanisms underlying these deficits are poorly understood. Here, we characterize the dynamic changes in brain connectivity profiles inflicted by sleep deprivation and how they deviate from regular daily variability. To this end, we obtained functional magnetic resonance imaging data from 60 young, adult male participants, scanned in the morning and evening of the same day and again the following morning. 41 participants underwent total sleep deprivation before the third scan, whereas the remainder had another night of regular sleep. Sleep deprivation strongly altered the connectivity of several resting-state networks, including dorsal attention, default mode, and hippocampal networks. Multivariate classification based on connectivity profiles predicted deprivation state with high accuracy, corroborating the robustness of the findings on an individual level. Finally, correlation analysis suggested that morning-to-evening connectivity changes were reverted by sleep (control group)-a pattern which did not occur after deprivation. We conclude that both, a day of waking and a night of sleep deprivation dynamically alter the brain functional connectome.

  9. Fear of negative evaluation is associated with altered brain function in nonclinical subjects.

    PubMed

    Kajimura, Shogo; Kochiyama, Takanori; Nakai, Ryusuke; Abe, Nobuhito; Nomura, Michio

    2015-12-30

    Social anxiety disorder (SAD), which involves excessive anxiety and fear of negative evaluation, is accompanied by abnormalities in brain function. While social anxiety appears to be represented on a spectrum ranging from nonclinical behavior to clinical manifestation, neural alteration in nonclinical populations remains unclear. This study examined the relationship between psychological measures of social anxiety, mainly using the Fear of Negative Evaluation Scale (FNES), and brain function (functional connectivity, degree centrality, and regional betweenness centrality). Results showed that FNES scores and functional connectivity of the parahippocampal gyrus and orbitofrontal cortex and the betweenness centrality of the right parietal cortex were negatively correlated. These regions are altered in SAD patients, and each is associated with social cognition and emotional processing. The results supported the perspective that social anxiety occurs on a spectrum and indicated that the FNES is a useful means of detecting neural alterations that may relate to the social anxiety spectrum. In addition, the findings indicated that graph analysis was useful in investigating the neural underpinnings of SAD in addition to other psychiatric symptoms.

  10. Alteration of Electro-Cortical Activity in Microgravity

    NASA Astrophysics Data System (ADS)

    Schneider, Stefan; Brummer, Vera; Carnahan, Heather; Askew, Christopher D.; Guardiera, Simon; Struder, Heiko K.

    2008-06-01

    There is growing interest in the effects of weightlessness on central nervous system (CNS) activity. Due to technical and logistical limitations it presently seems impossible to apply imaging techniques as fMRI or PET in weightless environments e.g. on ISS or during parabolic flights. Within this study we evaluated changes in brain cortical activity using low resolution brain electromagnetic tomography (LORETA) during parabolic flights. Results showed a distinct inhibition of right frontal area activity >12Hz during phases of microgravity compared to normal gravity. We conclude that the inhibition of high frequency frontal activity during microgravity may serve as a marker of emotional anxiety and/or indisposition associated with weightlessness. This puts a new light on the debate as to whether cognitive and sensorimotor impairments are attributable to primary physiological effects or secondary psychological effects of a weightless environment.

  11. Material and physical model for evaluation of deep brain activity contribution to EEG recordings

    NASA Astrophysics Data System (ADS)

    Ye, Yan; Li, Xiaoping; Wu, Tiecheng; Li, Zhe; Xie, Wenwen

    2015-12-01

    Deep brain activity is conventionally recorded with surgical implantation of electrodes. During the neurosurgery, brain tissue damage and the consequent side effects to patients are inevitably incurred. In order to eliminate undesired risks, we propose that deep brain activity should be measured using the noninvasive scalp electroencephalography (EEG) technique. However, the deeper the neuronal activity is located, the noisier the corresponding scalp EEG signals are. Thus, the present study aims to evaluate whether deep brain activity could be observed from EEG recordings. In the experiment, a three-layer cylindrical head model was constructed to mimic a human head. A single dipole source (sine wave, 10 Hz, altering amplitudes) was embedded inside the model to simulate neuronal activity. When the dipole source was activated, surface potential was measured via electrodes attached on the top surface of the model and raw data were recorded for signal analysis. Results show that the dipole source activity positioned at 66 mm depth in the model, equivalent to the depth of deep brain structures, is clearly observed from surface potential recordings. Therefore, it is highly possible that deep brain activity could be observed from EEG recordings and deep brain activity could be measured using the noninvasive scalp EEG technique.

  12. Altered brain connectivity in patients with schizophrenia is consistent across cognitive contexts

    PubMed Central

    Orban, Pierre; Desseilles, Martin; Mendrek, Adrianna; Bourque, Josiane; Bellec, Pierre; Stip, Emmanuel

    2017-01-01

    Background Schizophrenia has been defined as a dysconnection syndrome characterized by aberrant functional brain connectivity. Using task-based fMRI, we assessed to what extent the nature of the cognitive context may further modulate abnormal functional brain connectivity. Methods We analyzed data matched for motion in patients with schizophrenia and healthy controls who performed 3 different tasks. Tasks 1 and 2 both involved emotional processing and only slighlty differed (incidental encoding v. memory recognition), whereas task 3 was a much different mental rotation task. We conducted a connectome-wide general linear model analysis aimed at identifying context-dependent and independent functional brain connectivity alterations in patients with schizophrenia. Results After matching for motion, we included 30 patients with schizophrenia and 30 healthy controls in our study. Abnormal connectivity in patients with schizophrenia followed similar patterns regardless of the degree of similarity between cognitive tasks. Decreased connectivity was most notable in the medial prefrontal cortex, the anterior and posterior cingulate, the temporal lobe, the lobule IX of the cerebellum and the premotor cortex. Limitations A more circumscribed yet significant context-dependent effect might be detected with larger sample sizes or cognitive domains other than emotional and visuomotor processing. Conclusion The context-independence of functional brain dysconnectivity in patients with schizophrenia provides a good justification for pooling data from multiple experiments in order to identify connectivity biomarkers of this mental illness. PMID:27091719

  13. Problematic internet use is associated with structural alterations in the brain reward system in females.

    PubMed

    Altbäcker, Anna; Plózer, Enikő; Darnai, Gergely; Perlaki, Gábor; Horváth, Réka; Orsi, Gergely; Nagy, Szilvia Anett; Bogner, Péter; Schwarcz, Attila; Kovács, Norbert; Komoly, Sámuel; Clemens, Zsófia; Janszky, József

    2016-12-01

    Neuroimaging findings suggest that excessive Internet use shows functional and structural brain changes similar to substance addiction. Even though it is still under debate whether there are gender differences in case of problematic use, previous studies by-passed this question by focusing on males only or by using gender matched approach without controlling for potential gender effects. We designed our study to find out whether there are structural correlates in the brain reward system of problematic Internet use in habitual Internet user females. T1-weighted Magnetic Resonance (MR) images were collected in 82 healthy habitual Internet user females. Structural brain measures were investigated using both automated MR volumetry and voxel based morphometry (VBM). Self-reported measures of problematic Internet use and hours spent online were also assessed. According to MR volumetry, problematic Internet use was associated with increased grey matter volume of bilateral putamen and right nucleus accumbens while decreased grey matter volume of orbitofrontal cortex (OFC). Similarly, VBM analysis revealed a significant negative association between the absolute amount of grey matter OFC and problematic Internet use. Our findings suggest structural brain alterations in the reward system usually related to addictions are present in problematic Internet use.

  14. Altered microstructure within social-cognitive brain networks during childhood in Williams syndrome.

    PubMed

    Haas, Brian W; Barnea-Goraly, Naama; Sheau, Kristen E; Yamagata, Bun; Ullas, Shruti; Reiss, Allan L

    2014-10-01

    Williams syndrome (WS) is a neurodevelopmental condition caused by a hemizygous deletion of ∼26-28 genes on chromosome 7q11.23. WS is associated with a distinctive pattern of social cognition. Accordingly, neuroimaging studies show that WS is associated with structural alterations of key brain regions involved in social cognition during adulthood. However, very little is currently known regarding the neuroanatomical structure of social cognitive brain networks during childhood in WS. This study used diffusion tensor imaging to investigate the structural integrity of a specific set of white matter pathways (inferior fronto-occipital fasciculus [IFOF] and uncinate fasciculus [UF]) and associated brain regions [fusiform gyrus (FG), amygdala, hippocampus, medial orbitofrontal gyrus (MOG)] known to be involved in social cognition in children with WS and a typically developing (TD) control group. Children with WS exhibited higher fractional anisotropy (FA) and axial diffusivity values and lower radial diffusivity and apparent diffusion coefficient (ADC) values within the IFOF and UF, higher FA values within the FG, amygdala, and hippocampus and lower ADC values within the FG and MOG compared to controls. These findings provide evidence that the WS genetic deletion affects the development of key white matter pathways and brain regions important for social cognition.

  15. Cell Type Specific Analysis of Human Brain Transcriptome Data to Predict Alterations in Cellular Composition.

    PubMed

    Xu, Xiaoxiao; Nehorai, Arye; Dougherty, Joseph

    2013-07-01

    The central nervous system (CNS) is composed of hundreds of distinct cell types, each expressing different subsets of genes from the genome. High throughput gene expression analysis of the CNS from patients and controls is a common method to screen for potentially pathological molecular mechanisms of psychiatric disease. One mechanism by which gene expression might be seen to vary across samples would be alterations in the cellular composition of the tissue. While the expressions of gene 'markers' for each cell type can provide certain information of cellularity, for many rare cell types markers are not well characterized. Moreover, if only small sets of markers are known, any substantial variation of a marker's expression pattern due to experiment conditions would result in poor sensitivity and specificity. Here, our proposed method combines prior information from mice cell-specific transcriptome profiling experiments with co-expression network analysis, to select large sets of potential cell type-specific gene markers in a systematic and unbiased manner. The method is efficient and robust, and identifies sufficient markers for further cellularity analysis. We then employ the markers to analytically detect changing cellular composition in human brain. Application of our method to temporal human brain microarray data successfully detects changes in cellularity over time that roughly correspond to known epochs of human brain development. Furthermore, application of our method to human brain samples with the neurodevelopmental disorder of autism supports the interpretation that the changes in astrocytes and neurons might contribute to the disorder.

  16. Scale-free brain activity: past, present and future

    PubMed Central

    He, Biyu J.

    2014-01-01

    Brain activity observed at many spatiotemporal scales exhibits a 1/f-like power spectrum, including neuronal membrane potentials, neural field potentials, noninvasive electroencephalography, magnetoencephalography and functional magnetic resonance imaging signals. A 1/f-like power spectrum is indicative of arrhythmic brain activity that does not contain a predominant temporal scale (hence, “scale-free”). This characteristic of scale-free brain activity distinguishes it from brain oscillations. While scale-free brain activity and brain oscillations coexist, our understanding of the former remains very limited. Recent research has shed light on the spatiotemporal organization, functional significance and potential generative mechanisms of scale-free brain activity, as well as its developmental and clinical relevance. A deeper understanding of this prevalent brain signal should provide new insights and analytical tools for cognitive neuroscience. PMID:24788139

  17. Alterations in Brain Structure and Functional Connectivity in Alcohol Dependent Patients and Possible Association with Impulsivity

    PubMed Central

    Dong, Yue; Ma, Mengying; Ma, Yi; Dong, Yuru; Niu, Yajuan; Jiang, Yin; Wang, Hong; Wang, Zhiyan; Wu, Liuzhen; Sun, Hongqiang; Cui, Cailian

    2016-01-01

    Background Previous studies have documented that heightened impulsivity likely contributes to the development and maintenance of alcohol use disorders. However, there is still a lack of studies that comprehensively detected the brain changes associated with abnormal impulsivity in alcohol addicts. This study was designed to investigate the alterations in brain structure and functional connectivity associated with abnormal impulsivity in alcohol dependent patients. Methods Brain structural and functional magnetic resonance imaging data as well as impulsive behavior data were collected from 20 alcohol dependent patients and 20 age- and sex-matched healthy controls respectively. Voxel-based morphometry was used to investigate the differences of grey matter volume, and tract-based spatial statistics was used to detect abnormal white matter regions between alcohol dependent patients and healthy controls. The alterations in resting-state functional connectivity in alcohol dependent patients were examined using selected brain areas with gray matter deficits as seed regions. Results Compared with healthy controls, alcohol dependent patients had significantly reduced gray matter volume in the mesocorticolimbic system including the dorsal posterior cingulate cortex, the dorsal anterior cingulate cortex, the medial prefrontal cortex, the orbitofrontal cortex and the putamen, decreased fractional anisotropy in the regions connecting the damaged grey matter areas driven by higher radial diffusivity value in the same areas and decreased resting-state functional connectivity within the reward network. Moreover, the gray matter volume of the left medial prefrontal cortex exhibited negative correlations with various impulse indices. Conclusions These findings suggest that chronic alcohol dependence could cause a complex neural changes linked to abnormal impulsivity. PMID:27575491

  18. Multifunctional Roles of Enolase in Alzheimer Disease Brain: Beyond Altered Glucose Metabolism

    PubMed Central

    Butterfield, D. Allan; Bader Lange, Miranda L.

    2015-01-01

    Enolase enzymes are abundantly expressed, cytosolic carbon-oxygen lyases known for their role in glucose metabolism. Recently, enolase has been shown to possess a variety of different regulatory functions, beyond glycolysis and gluconeogenesis, associated with hypoxia, ischemia, and Alzheimer disease (AD). AD is an age-associated neurodegenerative disorder characterized pathologically by elevated oxidative stress and subsequent damage to proteins, lipids, and nucleic acids, appearance of neurofibrillary tangles and senile plaques, and loss of synapse and neuronal cells. It is unclear if development of a hypometabolic environment is a consequence of or contributes to AD pathology, since there is not only a significant decline in brain glucose levels in AD, but also there is an increase in proteomics identified oxidatively modified glycolytic enzymes that are rendered inactive, including enolase. Previously, our laboratory identified α-enolase as one the most frequently up-regulated and oxidatively modified proteins in amnestic mild cognitive impairment (MCI), early-onset AD (EOAD), and AD. However, the glycolytic conversion of 2-phosphoglycerate to phosphoenolpyruvate catalyzed by enolase does not directly produce ATP or NADH; therefore it is surprising that, among all glycolytic enzymes, α-enolase was one of only two glycolytic enzymes consistently up-regulated from MCI to AD. These findings suggest enolase is involved with more than glucose metabolism in AD brain, but may possess other functions, normally necessary to preserve brain function. This review examines potential altered function(s) of brain enolase in MCI, EOAD, and AD, alterations that may contribute to the biochemical, pathological, clinical characteristics, and progression of this dementing disorder. PMID:19780894

  19. Brain Connectivity Alterations Are Associated with the Development of Dementia in Parkinson's Disease.

    PubMed

    Bertrand, Josie-Anne; McIntosh, Anthony R; Postuma, Ronald B; Kovacevic, Natasha; Latreille, Véronique; Panisset, Michel; Chouinard, Sylvain; Gagnon, Jean-François

    2016-04-01

    Dementia affects a high proportion of Parkinson's disease (PD) patients and poses a burden on caregivers and healthcare services. Electroencephalography (EEG) is a common nonevasive and nonexpensive technique that can easily be used in clinical settings to identify brain functional abnormalities. Only few studies had identified EEG abnormalities that can predict PD patients at higher risk for dementia. Brain connectivity EEG measures, such as multiscale entropy (MSE) and phase-locking value (PLV) analyses, may be more informative and sensitive to brain alterations leading to dementia than previously used methods. This study followed 62 dementia-free PD patients for a mean of 3.4 years to identify cerebral alterations that are associated with dementia. Baseline resting state EEG of patients who developed dementia (N = 18) was compared to those of patients who remained dementia-free (N = 44) and of 37 healthy subjects. MSE and PLV analyses were performed. Partial least squares statistical analysis revealed group differences associated with the development of dementia. Patients who developed dementia showed higher signal complexity and lower PLVs in low frequencies (mainly in delta frequency) than patients who remained dementia-free and controls. Conversely, both patient groups showed lower signal variability and higher PLVs in high frequencies (mainly in gamma frequency) compared to controls, with the strongest effect in patients who developed dementia. These findings suggest that specific disruptions of brain communication can be measured before PD patients develop dementia, providing a new potential marker to identify patients at highest risk of developing dementia and who are the best candidates for neuroprotective trials.

  20. Early postnatal diazepam exposure alters sex differences in the rat brain.

    PubMed

    Segovia, S; Pérez-Laso, C; Rodríguez-Zafra, M; Calés, J M; Del Abril, A; De Blas, M R; Collado, P; Valencia, A; Guillamón, A

    1991-06-01

    The volume and neuron number of the sexually dimorphic accessory olfactory bulb and locus coeruleus are altered by early postnatal exposure (from the day of birth to postnatal day 16) to diazepam. After diazepam treatment, both volume and neuron number were decreased in the male accessory olfactory bulb and in the female locus coeruleus. These results indicate that early postnatal diazepam administration can bear gender-dependent teratogenic effects upon sexually dimorphic nuclei and suggest that endogenous benzodiazepines may be involved in the sexual differentiation of the brain.

  1. Active interoceptive inference and the emotional brain

    PubMed Central

    Friston, Karl J.

    2016-01-01

    We review a recent shift in conceptions of interoception and its relationship to hierarchical inference in the brain. The notion of interoceptive inference means that bodily states are regulated by autonomic reflexes that are enslaved by descending predictions from deep generative models of our internal and external milieu. This re-conceptualization illuminates several issues in cognitive and clinical neuroscience with implications for experiences of selfhood and emotion. We first contextualize interoception in terms of active (Bayesian) inference in the brain, highlighting its enactivist (embodied) aspects. We then consider the key role of uncertainty or precision and how this might translate into neuromodulation. We next examine the implications for understanding the functional anatomy of the emotional brain, surveying recent observations on agranular cortex. Finally, we turn to theoretical issues, namely, the role of interoception in shaping a sense of embodied self and feelings. We will draw links between physiological homoeostasis and allostasis, early cybernetic ideas of predictive control and hierarchical generative models in predictive processing. The explanatory scope of interoceptive inference ranges from explanations for autism and depression, through to consciousness. We offer a brief survey of these exciting developments. This article is part of the themed issue ‘Interoception beyond homeostasis: affect, cognition and mental health’. PMID:28080966

  2. Brain alterations in low-frequency fluctuations across multiple bands in obsessive compulsive disorder.

    PubMed

    Giménez, Mònica; Guinea-Izquierdo, Andrés; Villalta-Gil, Victoria; Martínez-Zalacaín, Ignacio; Segalàs, Cinto; Subirà, Marta; Real, Eva; Pujol, Jesús; Harrison, Ben J; Haro, Josep Maria; Sato, Joao R; Hoexter, Marcelo Q; Cardoner, Narcís; Alonso, Pino; Menchón, José Manuel; Soriano-Mas, Carles

    2016-10-22

    The extent of functional abnormalities in frontal-subcortical circuits in obsessive-compulsive disorder (OCD) is still unclear. Although neuroimaging studies, in general, and resting-state functional Magnetic Resonance Imaging (rs-fMRI), in particular, have provided relevant information regarding such alterations, rs-fMRI studies have been typically limited to the analysis of between-region functional connectivity alterations at low-frequency signal fluctuations (i.e., <0.08 Hz). Conversely, the local attributes of Blood Oxygen Level Dependent (BOLD) signal across different frequency bands have been seldom studied, although they may provide valuable information. Here, we evaluated local alterations in low-frequency fluctuations across different oscillation bands in OCD. Sixty-five OCD patients and 50 healthy controls underwent an rs-fMRI assessment. Alterations in the fractional amplitude of low-frequency fluctuations (fALFF) were evaluated, voxel-wise, across four different bands (from 0.01 Hz to 0.25 Hz). OCD patients showed decreased fALFF values in medial orbitofrontal regions and increased fALFF values in the dorsal-medial prefrontal cortex (DMPFC) at frequency bands <0.08 Hz. This pattern was reversed at higher frequencies, where increased fALFF values also appeared in medial temporal lobe structures and medial thalamus. Clinical variables (i.e., symptom-specific severities) were associated with fALFF values across the different frequency bands. Our findings provide novel evidence about the nature and regional distribution of functional alterations in OCD, which should contribute to refine neurobiological models of the disorder. We suggest that the evaluation of the local attributes of BOLD signal across different frequency bands may be a sensitive approach to further characterize brain functional alterations in psychiatric disorders.

  3. Release of neuronal HMGB1 by ethanol through decreased HDAC activity activates brain neuroimmune signaling.

    PubMed

    Zou, Jian Y; Crews, Fulton T

    2014-01-01

    Neuroimmune gene induction is involved in many brain pathologies including addiction. Although increased expression of proinflammatory cytokines has been found in ethanol-treated mouse brain and rat brain slice cultures as well as in post-mortem human alcoholic brain, the mechanisms remain elusive. High-mobility group box 1 (HMGB1) protein is a nuclear protein that has endogenous cytokine-like activity. We previously found increased HMGB1 in post-mortem alcoholic human brain as well as in ethanol treated mice and rat brain slice cultures. The present study investigated the mechanisms for ethanol-induced release of HMGB1 and neuroimmune activation in a model of rat hippocampal-entorhinal cortex (HEC) brain slice cultures. Ethanol exposure triggered dose-dependent HMGB1 release, predominantly from neuronal cells. Inhibitors of histone deacetylases (HDACs) promoted nucleocytoplasmic mobilization of HDAC1/4 and HMGB1 resulting in increased total HMGB1 and acetylated HMGB1 release. Similarly, ethanol treatment was found to induce the translocation of HDAC1/4 and HMGB1 proteins from nuclear to cytosolic fractions. Furthermore, ethanol treatment reduced HDAC1/4 mRNA and increased acetylated HMGB1 release into the media. These results suggest decreased HDAC activity may be critical in regulating acetylated HMGB1 release from neurons in response to ethanol. Ethanol and HMGB1 treatment increased mRNA expression of proinflammatory cytokines TNFα and IL-1β as well as toll-like receptor 4 (TLR4). Targeting HMGB1 or microglial TLR4 by using siRNAs to HMGB1 and TLR4, HMGB1 neutralizing antibody, HMGB1 inhibitor glycyrrhizin and TLR4 antagonist as well as inhibitor of microglial activation all blocked ethanol-induced expression of proinflammatory cytokines TNFα and IL-1β. These results support the hypothesis that ethanol alters HDACs that regulate HMGB1 release and that danger signal HMGB1 as endogenous ligand for TLR4 mediates ethanol-induced brain neuroimmune signaling

  4. Mild Traumatic Brain Injury with Social Defeat Stress Alters Anxiety, Contextual Fear Extinction, and Limbic Monoamines in Adult Rats

    PubMed Central

    Davies, Daniel R.; Olson, Dawne; Meyer, Danielle L.; Scholl, Jamie L.; Watt, Michael J.; Manzerra, Pasquale; Renner, Kenneth J.; Forster, Gina L.

    2016-01-01

    Mild traumatic brain injury (mTBI) produces symptoms similar to those typifying posttraumatic stress disorder (PTSD) in humans. We sought to determine whether a rodent model of stress concurrent with mTBI produces characteristics of PTSD such as impaired contextual fear extinction, while also examining concurrent alterations to limbic monoamine activity in brain regions relevant to fear and anxiety states. Male rats were exposed to social stress or control conditions immediately prior to mTBI induction, and 6 days later were tested either for anxiety-like behavior using the elevated plus maze (EPM), or for contextual fear conditioning and extinction. Brains were collected 24 h after EPM testing, and tissue from various limbic regions analyzed for content of monoamines, their precursors and metabolites using HPLC with electrochemical detection. Either social defeat or mTBI alone decreased time spent in open arms of the EPM, indicating greater anxiety-like behavior. However, this effect was enhanced by the combination of treatments. Further, rats exposed to both social defeat and mTBI exhibited greater freezing within extinction sessions compared to all other groups, suggesting impaired contextual fear extinction. Social defeat combined with mTBI also had greater effects on limbic monoamines than either insult alone, particularly with respect to serotonergic effects associated with anxiety and fear learning. The results suggest social stress concurrent with mTBI produces provides a relevant animal model for studying the prevention and treatment of post-concussive psychobiological outcomes. PMID:27147992

  5. Hepatic alterations are accompanied by changes to bile acid transporter-expressing neurons in the hypothalamus after traumatic brain injury

    PubMed Central

    Nizamutdinov, Damir; DeMorrow, Sharon; McMillin, Matthew; Kain, Jessica; Mukherjee, Sanjib; Zeitouni, Suzanne; Frampton, Gabriel; Bricker, Paul Clint S.; Hurst, Jacob; Shapiro, Lee A.

    2017-01-01

    Annually, there are over 2 million incidents of traumatic brain injury (TBI) and treatment options are non-existent. While many TBI studies have focused on the brain, peripheral contributions involving the digestive and immune systems are emerging as factors involved in the various symptomology associated with TBI. We hypothesized that TBI would alter hepatic function, including bile acid system machinery in the liver and brain. The results show activation of the hepatic acute phase response by 2 hours after TBI, hepatic inflammation by 6 hours after TBI and a decrease in hepatic transcription factors, Gli 1, Gli 2, Gli 3 at 2 and 24 hrs after TBI. Bile acid receptors and transporters were decreased as early as 2 hrs after TBI until at least 24 hrs after TBI. Quantification of bile acid transporter, ASBT-expressing neurons in the hypothalamus, revealed a significant decrease following TBI. These results are the first to show such changes following a TBI, and are compatible with previous studies of the bile acid system in stroke models. The data support the emerging idea of a systemic influence to neurological disorders and point to the need for future studies to better define specific mechanisms of action. PMID:28106051

  6. Low-pressure hydrocephalic state and viscoelastic alterations in the brain.

    PubMed

    Pang, D; Altschuler, E

    1994-10-01

    Most shunt-dependent hydrocephalic patients present with predictable symptoms of headache and mental status changes when their cerebrospinal fluid shunts malfunction. Their intracranial pressure (ICP) is usually high, and they usually respond to routine shunt revision. This report describes 12 shunted patients who were admitted with the full-blown hydrocephalic syndrome but with low to low-normal ICP. All 12 patients had been maintained previously on medium-pressure shunts. Their symptoms included headache, lethargy, obtundation, and cranial neuropathies. At peak symptoms, their ventricular sizes were large (ventricular/biparietal ratio of 0.35 to 0.45) in six and massive (ventricular/biparietal ratio > 0.45) in six and their ICPs ranged from 2.2 to 6.6 mm Hg, with a mean of 4.4 +/- 1.3 mm Hg (+/- standard deviation), i.e., below or well within the pressure range of their shunts. The pressure volume index of three patients at peak symptoms ranged from 39.2 to 48.5 ml, with a mean of 43.9 +/- 4.6 ml, which represents a 190% increase from the predicted normal value. Seven patients failed to improve with multiple shunt revisions, including the use of low-pressure valves. In 11 patients, symptoms and ventriculomegaly were not reversed except with prolonged external ventricular drainage at subzero pressures (mean external ventricular drainage nadir pressure of -5.7 +/- 3.6 mm Hg, for a mean period of 22.2 days). During external ventricular drainage treatment, symptoms correlated only with ventricular size and not with ICP. All 11 were subsequently treated successfully with a new medium- or low-pressure shunt. One patient was treated successfully with prolonged shunt pumping. We postulate that: 1) the development of this low-pressure hydrocephalic state is related to alteration of the viscoelastic modulus of the brain, secondary to expulsion of extracellular water from the brain parenchyma, and to structural changes in brain tissues due to prolonged overstretching; 2

  7. Anxiety and error-related brain activity.

    PubMed

    Hajcak, Greg; McDonald, Nicole; Simons, Robert F

    2003-10-01

    Error-related negativity (ERN/Ne) is a component of the event-related brain potential (ERP) associated with monitoring action and detecting errors. It is a sharp negative deflection that generally occurs from 50 to 150 ms following response execution and has been associated with anterior cingulate cortex (ACC) activity. An enhanced ERN has been observed in patients with obsessive-compulsive disorder (OCD)--reflecting abnormal ACC activity hypothesized as part of the pathophysiology of OCD. We recently reported that the ERN is also enhanced in a group of college students with OC characteristics. The present study extended these findings by measuring the ERN in college undergraduates who scored high on either the Penn State Worry Questionnaire (PSWQ) or a combined version of the Snake (SNAQ) and Spider (SPQ) Questionnaires. Results indicate that, like OC subjects, subjects who score high on a measure of general anxiety and worry have enhanced error-related brain activity relative to both phobic and non-anxious control subjects. The enhanced ERN was found to generalize beyond OCD within the anxiety spectrum disorders but also shows some specificity within these disorders.

  8. Altered spontaneous activity in antisocial personality disorder revealed by regional homogeneity.

    PubMed

    Tang, Yan; Liu, Wangyong; Chen, Jingang; Liao, Jian; Hu, Dewen; Wang, Wei

    2013-08-07

    There is increasing evidence that antisocial personality disorder (ASPD) stems from brain abnormalities. However, there are only a few studies investigating brain structure in ASPD. The aim of this study was to find regional coherence abnormalities in resting-state functional MRI of ASPD. Thirty-two ASPD individuals and 34 controls underwent a resting-state functional MRI scan. The regional homogeneity (ReHo) approach was used to examine whether ASPD was related to alterations in resting-state neural activity. Support vector machine discriminant analysis was used to evaluate the sensitivity/specificity characteristics of the ReHo index in discriminating between the ASPD individuals and controls. The results showed that, compared with controls, ASPD individuals show lower ReHo in the right cerebellum posterior lobe (Crus1) and the right middle frontal gyrus, as well as higher ReHo in the right middle occipital gyrus (BA 19), left inferior temporal gyrus (BA 37), and right inferior occipital gyrus (cuneus, BA 18). All alternation regions reported a predictive accuracy above 70%. To our knowledge, this study was the first to study the change in regional activity coherence in the resting brain of ASPD individuals. These results not only elucidated the pathological mechanism of ASPD from a resting-state functional viewpoint but also showed that these alterations in ReHo may serve as potential markers for the detection of ASPD.

  9. The Physiochemistry of Capped Nanosilver Predicts Its Biological Activity in Rat Brain Endothelial Cells (REBEC4)

    EPA Science Inventory

    The “capping” or coating of nanosilver (nanoAg) extends its potency by limiting its oxidation and aggregation and stabilizing its size and shape. The ability of such coated nanoAg to alter the permeability and activate oxidative stress pathways in rat brain endothelia...

  10. The Influence of Neuronal Activity on Breast Tumor Metastasis to the Brain

    DTIC Science & Technology

    2008-09-01

    different drugs to alter brain activity: caffeine, methylphenidate and modafinil . While the smallest effect may be expected from caffeine which is not...another of the drugs (methylphenidate). Experiments with modafinil are planned to start next month. In the last year of the grant we plan on

  11. Response-restriction analysis: II. Alteration of activity preferences.

    PubMed Central

    Hanley, Gregory P; Iwata, Brian A; Roscoe, Eileen M; Thompson, Rachel H; Lindberg, Jana S

    2003-01-01

    We used response-restriction (RR) assessments to identify the preferences of 7 individuals with mental retardation for a variety of vocational and leisure activities. We subsequently increased their engagement in nonpreferred activities using several procedures: response restriction per se versus a Premack-type contingency (Study 1), supplemental reinforcement for engagement in target activities (Study 2), and noncontingent pairing of reinforcers with nonpreferred activities (Study 3). Results indicated that preferences are not immutable and can be altered through a variety of relatively benign interventions and that the results of RR assessments may be helpful in determining which types of procedures may be most effective on an individual basis. PMID:12723867

  12. Trpc2-deficient lactating mice exhibit altered brain and behavioral responses to bedding stimuli.

    PubMed

    Hasen, Nina S; Gammie, Stephen C

    2011-03-01

    The trpc2 gene encodes an ion channel involved in pheromonal detection and is found in the vomeronasal organ. In tprc2(-/-) knockout (KO) mice, maternal aggression (offspring protection) is impaired and brain Fos expression in females in response to a male are reduced. Here we examine in lactating wild-type (WT) and KO mice behavioral and brain responses to different olfactory/pheromonal cues. Consistent with previous studies, KO dams exhibited decreased maternal aggression and nest building, but we also identified deficits in nighttime nursing and increases in pup weight. When exposed to the bedding tests, WT dams typically ignored clean bedding, but buried male-soiled bedding from unfamiliar males. In contrast, KO dams buried both clean and soiled bedding. Differences in brain Fos expression were found between WT and KO mice in response to either no bedding, clean bedding, or soiled bedding. In the accessory olfactory bulb, a site of pheromonal signal processing, KO mice showed suppressed Fos activation in the anterior mitral layer relative to WT mice in response to clean and soiled bedding. However, in the medial and basolateral amygdala, KO mice showed a robust Fos response to bedding, suggesting that regions of the amygdala canonically associated with pheromonal sensing can be active in the brains of KO mice, despite compromised signaling from the vomeronasal organ. Together, these results provide further insights into the complex ways by which pheromonal signaling regulates the brain and behavior of the maternal female.

  13. Brain hyperthermia alters local cerebral glucose utilization: a comparison of hyperthermic agents.

    PubMed

    Mickley, G A; Cobb, B L; Farrell, S T

    1997-01-01

    Microwaves have been proposed to alter neural functioning through both thermal and non-thermal mechanisms. We attempted to determine if local cerebral glucose utilization (LCGU) depends on the type of hyperthermic agent employed. We exposed the heads of rats to two different hyperthermic agents (5.6 GHz microwave exposure or exposure to hot/moist air) to create a 2 degree C rise in midbrain temperature. Other rats were sham exposed and remained normothermic. The 2-Deoxy-D-glucose (2DG) autoradiographic method was then used to determine LCGU during a 45-min period of stable hyperthermia. Hyperthermia (created by either hyperthermic agent) caused a general rise in brain glucose utilization. Hot-air exposed rats showed significantly higher LCGUs than microwaved rats in portions of the motor cortex, hypothalamus, lateral lemniscus and the substantia nigra (reticulata). Microwave exposure did not produce significantly higher levels of LCGU (compared to hot-air exposed hyperthermic controls) in any of the 47 brain areas sampled. A time analysis of lateral hypothalamic (LH) temperature during these different heating procedures revealed that microwave exposure produced a more-rapid rise in temperature than did not/moist air. Thus, we wondered if the nuclei-specific differences in LCGU could be explained by localized differences in rate of brain heating during the two hyperthermic treatments. In a second study we carefully matched both the rate of lateral hypothalamic temperature rise and the peak temperatures achieved by our two hyperthermic methods and again measured LH LCGUs. We found that this precise matching eliminated the difference in hypothalamic LCGU previously observed following microwave or hot-air exposure. These data suggest that hyperthermia causes a general rise in brain metabolism and that (as long as steady state and rate of local brain temperature increase are well matched) microwave and hot-air induced hyperthermia produce similar changes in LCGU.

  14. Brain-derived neurotrophic factor in human subjects with function-altering melanocortin-4 receptor variants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In rodents, hypothalamic brain-derived neurotrophic factor (BDNF) expression appears to be regulated by melanocortin-4 receptor (MC4R) activity. The impact of MC4R genetic variation on circulating BDNF in humans is unknown. The objective of this study is to compare BDNF concentrations of subjects wi...

  15. Alterations in Brain Inflammation, Synaptic Proteins, and Adult Hippocampal Neurogenesis during Epileptogenesis in Mice Lacking Synapsin2

    PubMed Central

    Chugh, Deepti; Ali, Idrish; Bakochi, Anahita; Bahonjic, Elma; Etholm, Lars; Ekdahl, Christine T.

    2015-01-01

    Synapsins are pre-synaptic vesicle-associated proteins linked to the pathogenesis of epilepsy through genetic association studies in humans. Deletion of synapsins causes an excitatory/inhibitory imbalance, exemplified by the epileptic phenotype of synapsin knockout mice. These mice develop handling-induced tonic-clonic seizures starting at the age of about 3 months. Hence, they provide an opportunity to study epileptogenic alterations in a temporally controlled manner. Here, we evaluated brain inflammation, synaptic protein expression, and adult hippocampal neurogenesis in the epileptogenic (1 and 2 months of age) and tonic-clonic (3.5-4 months) phase of synapsin 2 knockout mice using immunohistochemical and biochemical assays. In the epileptogenic phase, region-specific microglial activation was evident, accompanied by an increase in the chemokine receptor CX3CR1, interleukin-6, and tumor necrosis factor-α, and a decrease in chemokine keratinocyte chemoattractant/ growth-related oncogene. Both post-synaptic density-95 and gephyrin, scaffolding proteins at excitatory and inhibitory synapses, respectively, showed a significant up-regulation primarily in the cortex. Furthermore, we observed an increase in the inhibitory adhesion molecules neuroligin-2 and neurofascin and potassium chloride co-transporter KCC2. Decreased expression of γ-aminobutyric acid receptor-δ subunit and cholecystokinin was also evident. Surprisingly, hippocampal neurogenesis was reduced in the epileptogenic phase. Taken together, we report molecular alterations in brain inflammation and excitatory/inhibitory balance that could serve as potential targets for therapeutics and diagnostic biomarkers. In addition, the regional differences in brain inflammation and synaptic protein expression indicate an epileptogenic zone from where the generalized seizures in synapsin 2 knockout mice may be initiated or spread. PMID:26177381

  16. Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain

    PubMed Central

    Olesen, R H; Hyde, T M; Kleinman, J E; Smidt, K; Rungby, J; Larsen, A

    2016-01-01

    The incidence of Alzheimer's disease (AD) is increasing. Major risk factors for AD are advancing age and diabetes. Lately, obesity has been associated with an increased risk of dementia. Obese and diabetic individuals are prone to decreased circulating levels of zinc, reducing the amount of zinc available for crucial intracellular processes. In the brain, zinc co-localizes with glutamate in synaptic vesicles, and modulates NMDA receptor activity. Intracellular zinc is involved in apoptosis and fluctuations in cytoplasmic Zn2+ affect modulation of intracellular signaling. The ZNT and ZIP proteins participate in intracellular zinc homeostasis. Altered expression of zinc-regulatory proteins has been described in AD patients. Using microarray data from human frontal cortex (BrainCloud), this study investigates expression of the SCLA30A (ZNT) and SCLA39A (ZIP) families of genes in a Caucasian and African-American sample of 145 neurologically and psychiatrically normal individuals. Expression of ZNT3 and ZNT4 were significantly reduced with increasing age, whereas expression of ZIP1, ZIP9 and ZIP13 were significantly increased. Increasing body mass index (BMI) correlated with a significant reduction in ZNT1 expression similar to what is seen in the early stages of AD. Increasing BMI also correlated with reduced expression of ZNT6. In conclusion, we found that the expression of genes that regulate intracellular zinc homeostasis in the human frontal cortex is altered with increasing age and affected by increasing BMI. With the increasing rates of obesity throughout the world, these findings warrant continuous scrutiny of the long-term consequences of obesity on brain function and the development of neurodegenerative diseases. PMID:27300264

  17. Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain.

    PubMed

    Olesen, R H; Hyde, T M; Kleinman, J E; Smidt, K; Rungby, J; Larsen, A

    2016-06-14

    The incidence of Alzheimer's disease (AD) is increasing. Major risk factors for AD are advancing age and diabetes. Lately, obesity has been associated with an increased risk of dementia. Obese and diabetic individuals are prone to decreased circulating levels of zinc, reducing the amount of zinc available for crucial intracellular processes. In the brain, zinc co-localizes with glutamate in synaptic vesicles, and modulates NMDA receptor activity. Intracellular zinc is involved in apoptosis and fluctuations in cytoplasmic Zn(2+) affect modulation of intracellular signaling. The ZNT and ZIP proteins participate in intracellular zinc homeostasis. Altered expression of zinc-regulatory proteins has been described in AD patients. Using microarray data from human frontal cortex (BrainCloud), this study investigates expression of the SCLA30A (ZNT) and SCLA39A (ZIP) families of genes in a Caucasian and African-American sample of 145 neurologically and psychiatrically normal individuals. Expression of ZNT3 and ZNT4 were significantly reduced with increasing age, whereas expression of ZIP1, ZIP9 and ZIP13 were significantly increased. Increasing body mass index (BMI) correlated with a significant reduction in ZNT1 expression similar to what is seen in the early stages of AD. Increasing BMI also correlated with reduced expression of ZNT6. In conclusion, we found that the expression of genes that regulate intracellular zinc homeostasis in the human frontal cortex is altered with increasing age and affected by increasing BMI. With the increasing rates of obesity throughout the world, these findings warrant continuous scrutiny of the long-term consequences of obesity on brain function and the development of neurodegenerative diseases.

  18. Dopamine release in the nucleus accumbens is altered following traumatic brain injury.

    PubMed

    Chen, Yuan-Hao; Huang, Eagle Yi-Kung; Kuo, Tung-Tai; Hoffer, Barry J; Miller, Jonathan; Chou, Yu-Ching; Chiang, Yung-Hsiao

    2017-04-21

    Mild-to-severe traumatic brain injury (TBI) is frequently associated with prolonged dysfunction of reward circuitry, including motivation and salience, which suggests alterations of dopamine (DA) processing within the core and shell of the nucleus accumbens (NAC). Using fast-scan cyclic voltammetry in a rodent model of traumatic brain injury, we found that stimulus-evoked DA release is distinct in the core and shell of the NAC, with the shell being less responsive to tonic stimulation and more sensitive to the number of pulses when phasic stimulation is applied. Exposure to TBI was associated with major changes in both release and reuptake of DA in both the core and shell of NAC, with greater changes seen in the core. These alterations evolved over time, becoming most severe 1-2weeks after injury with subsequent recovery, and the extent and progression of these abnormalities was correlated with severity of injury. Taken together, these data support behavior and anatomical studies suggesting the NAC core and striatum may subserve parallel functions, whereas the shell is distinct. These data offer a unique window on how different neurological systems respond to TBI and may help explain affective and cognitive changes that are seen.

  19. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways

    PubMed Central

    Rogers, G B; Keating, D J; Young, R L; Wong, M-L; Licinio, J; Wesselingh, S

    2016-01-01

    The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut–brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies. PMID:27090305

  20. Localized Brain Volume and White Matter Integrity Alterations in Adolescent Anorexia Nervosa

    PubMed Central

    Frank, Guido K.W.; Shott, Megan E.; Hagman, Jennifer O.; Yang, Tony T.

    2014-01-01

    Objective The neurobiological underpinnings of anorexia nervosa (AN) are poorly understood. In this study we tested whether brain gray matter (GM) and white matter (WM) in adolescents with AN would show alterations comparable to adults. Method We used magnetic resonance imaging to study GM and WM volume, and diffusion tensor imaging to assess fractional anisotropy for WM integrity in 19 adolescents with AN and 22 controls. Results Individuals with AN showed greater left orbitofrontal, right insular, and bilateral temporal cortex GM, as well as temporal lobe WM volumes compared to controls. WM integrity in adolescents with AN was lower (lower fractional anisotropy) in fornix, posterior frontal, and parietal areas, but higher in anterior frontal, orbitofrontal, and temporal lobes. In individuals with AN, orbitofrontal GM volume correlated negatively with sweet taste pleasantness. An additional comparison of this study cohort with adult individuals with AN and healthy controls supported greater orbitofrontal cortex and insula volumes in AN across age groups. Conclusions This study indicates larger orbitofrontal and insular GM volumes, as well as lower fornix WM integrity in adolescents with AN, similar to adults. The pattern of larger anteroventral GM and WM volume as well as WM integrity, but lower WM integrity in posterior frontal and parietal regions may indicate that developmental factors such as GM pruning and WM growth could contribute to brain alterations in AN. The negative correlation between taste pleasantness and orbitofrontal cortex volume in individuals with AN could contribute to food avoidance in this disorder. PMID:24074473

  1. Brain Mechanical Property Measurement Using MRE with Intrinsic Activation

    PubMed Central

    Pattison, Adam J.; McGarry, Matthew D.; Perreard, Irina M.; Swienckowski, Jessica G.; Eskey, Clifford J.; Lollis, S. Scott; Paulsen, Keith D.

    2013-01-01

    Problem Addressed Many pathologies alter the mechanical properties of tissue. Magnetic resonance elastography (MRE) has been developed to noninvasively characterize these quantities in vivo. Typically, small vibrations are induced in the tissue of interest with an external mechanical actuator. The resulting displacements are measured with phase contrast sequences and are then used to estimate the underlying mechanical property distribution. Several MRE studies have quantified brain tissue properties. However, the cranium and meninges, especially the dura, are very effective at damping externally applied vibrations from penetrating deeply into the brain. Here, we report a method, termed ‘intrinsic activation’, that eliminates the requirement for external vibrations by measuring the motion generated by natural blood vessel pulsation. Methodology A retrospectively gated phase contrast MR angiography sequence was used to record the tissue velocity at eight phases of the cardiac cycle. The velocities were numerically integrated via the Fourier transform to produce the harmonic displacements at each position within the brain. The displacements were then reconstructed into images of the shear modulus based on both linear elastic and poroelastic models. Results, Significance and Potential Impact The mechanical properties produced fall within the range of brain tissue estimates reported in the literature and, equally important, the technique yielded highly reproducible results. The mean shear modulus was 8.1 kPa for linear elastic reconstructions and 2.4 kPa for poroelastic reconstructions where fluid pressure carries a portion of the stress. Gross structures of the brain were visualized, particularly in the poroelastic reconstructions. Intra-subject variability was significantly less than the inter-subject variability in a study of 6 asymptomatic individuals. Further, larger changes in mechanical properties were observed in individuals when examined over time than when

  2. Human activities change marine ecosystems by altering predation risk.

    PubMed

    Madin, Elizabeth M P; Dill, Lawrence M; Ridlon, April D; Heithaus, Michael R; Warner, Robert R

    2016-01-01

    In ocean ecosystems, many of the changes in predation risk - both increases and decreases - are human-induced. These changes are occurring at scales ranging from global to local and across variable temporal scales. Indirect, risk-based effects of human activity are known to be important in structuring some terrestrial ecosystems, but these impacts have largely been neglected in oceans. Here, we synthesize existing literature and data to explore multiple lines of evidence that collectively suggest diverse human activities are changing marine ecosystems, including carbon storage capacity, in myriad ways by altering predation risk. We provide novel, compelling evidence that at least one key human activity, overfishing, can lead to distinct, cascading risk effects in natural ecosystems whose magnitude exceeds that of presumed lethal effects and may account for previously unexplained findings. We further discuss the conservation implications of human-caused indirect risk effects. Finally, we provide a predictive framework for when human alterations of risk in oceans should lead to cascading effects and outline a prospectus for future research. Given the speed and extent with which human activities are altering marine risk landscapes, it is crucial that conservation and management policy considers the indirect effects of these activities in order to increase the likelihood of success and avoid unfortunate surprises.

  3. Order/disorder in brain electrical activity

    NASA Astrophysics Data System (ADS)

    Rosso, O. A.; Figliola, Y. A.

    2004-04-01

    The processing of information by the brain is reflected in dynamical changes of the electrical activity in time, frequency, and space. Therefore, the concomitant studies require methods capable of describing the quantitative variation of the signal in both time and frequency. Here we present a quantitative EEG (qEEG) analysis, based on the Orthogonal Discrete Wavelet Transform (ODWT), of generalized epileptic tonic-clonic EEG signals. Two quantifiers: the Relative Wavelet Energy (RWE) and the Normalized Total Wavelet Entropy (NTWS) have been used. The RWE gives information about the relative energy associated with the different frequency bands present in the EEG and their corresponding degree of importance. The NTWS is a measure of the order/disorder degree in the EEG signal. These two quantifiers were computing in EEG signals as provided by scalp electrodes of epileptic patients. We showed that the epileptic recruitment rhythm observed for generalized epileptic tonic-clonic seizures is accurately described by the RWE quantifier. In addition, a significant decrease in the NTWS was observed in the recruitment epoch, indicating a more rhythmic and ordered behavior in the brain electrical activity.

  4. Exploring Patterns of Alteration in Alzheimer's Disease Brain Networks: A Combined Structural and Functional Connectomics Analysis

    PubMed Central

    Palesi, Fulvia; Castellazzi, Gloria; Casiraghi, Letizia; Sinforiani, Elena; Vitali, Paolo; Gandini Wheeler-Kingshott, Claudia A. M.; D'Angelo, Egidio

    2016-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a severe derangement of cognitive functions, primarily memory, in elderly subjects. As far as the functional impairment is concerned, growing evidence supports the “disconnection syndrome” hypothesis. Recent investigations using fMRI have revealed a generalized alteration of resting state networks (RSNs) in patients affected by AD and mild cognitive impairment (MCI). However, it was unclear whether the changes in functional connectivity were accompanied by corresponding structural network changes. In this work, we have developed a novel structural/functional connectomic approach: resting state fMRI was used to identify the functional cortical network nodes and diffusion MRI to reconstruct the fiber tracts to give a weight to internodal subcortical connections. Then, local and global efficiency were determined for different networks, exploring specific alterations of integration and segregation patterns in AD and MCI patients compared to healthy controls (HC). In the default mode network (DMN), that was the most affected, axonal loss, and reduced axonal integrity appeared to compromise both local and global efficiency along posterior-anterior connections. In the basal ganglia network (BGN), disruption of white matter integrity implied that main alterations occurred in local microstructure. In the anterior insular network (AIN), neuronal loss probably subtended a compromised communication with the insular cortex. Cognitive performance, evaluated by neuropsychological examinations, revealed a dependency on integration and segregation of brain networks. These findings are indicative of the fact that cognitive deficits in AD could be associated not only with cortical alterations (revealed by fMRI) but also with subcortical alterations (revealed by diffusion MRI) that extend beyond the areas primarily damaged by neurodegeneration, toward the support of an emerging concept of AD as a

  5. Brain-derived neurotrophic factor signaling is altered in the forebrain of Engrailed-2 knockout mice.

    PubMed

    Zunino, G; Messina, A; Sgadò, P; Baj, G; Casarosa, S; Bozzi, Y

    2016-06-02

    Engrailed-2 (En2), a homeodomain transcription factor involved in regionalization and patterning of the midbrain and hindbrain regions has been associated to autism spectrum disorders (ASDs). En2 knockout (En2(-/-)) mice show ASD-like features accompanied by a significant loss of GABAergic subpopulations in the hippocampus and neocortex. Brain-derived neurotrophic factor (BDNF) is a crucial factor for the postnatal development of forebrain GABAergic neurons, and altered GABA signaling has been hypothesized to underlie the symptoms of ASD. Here we sought to determine whether interneuron loss in the En2(-/-) forebrain might be related to altered expression of BDNF and its signaling receptors. We first evaluated the expression of different BDNF mRNA isoforms in the neocortex and hippocampus of wild-type (WT) and En2(-/-) mice. Quantitative RT-PCR showed a marked down-regulation of several splicing variants of BDNF mRNA in the neocortex but not hippocampus of adult En2(-/-) mice, as compared to WT controls. Accordingly, levels of mature BDNF protein were lower in the neocortex but not hippocampus of En2(-/-) mice, as compared to WT. Increased levels of phosphorylated TrkB and decreased levels of p75 receptor were also detected in the neocortex of mutant mice. Accordingly, the expression of low density lipoprotein receptor (LDLR) and RhoA, two genes regulated via p75 was significantly altered in forebrain areas of mutant mice. These data indicate that BDNF signaling alterations might be involved in the anatomical changes observed in the En2(-/-) forebrain and suggest a pathogenic role of altered BDNF signaling in this mouse model of ASD.

  6. Postnatal disruption of the disintegrin/metalloproteinase ADAM10 in brain causes epileptic seizures, learning deficits, altered spine morphology, and defective synaptic functions.

    PubMed

    Prox, Johannes; Bernreuther, Christian; Altmeppen, Hermann; Grendel, Jasper; Glatzel, Markus; D'Hooge, Rudi; Stroobants, Stijn; Ahmed, Tariq; Balschun, Detlef; Willem, Michael; Lammich, Sven; Isbrandt, Dirk; Schweizer, Michaela; Horré, Katrien; De Strooper, Bart; Saftig, Paul

    2013-08-07

    The metalloproteinase ADAM10 is of importance for Notch-dependent cortical brain development. The protease is tightly linked with α-secretase activity toward the amyloid precursor protein (APP) substrate. Increasing ADAM10 activity is suggested as a therapy to prevent the production of the neurotoxic amyloid β (Aβ) peptide in Alzheimer's disease. To investigate the function of ADAM10 in postnatal brain, we generated Adam10 conditional knock-out (A10cKO) mice using a CaMKIIα-Cre deleter strain. The lack of ADAM10 protein expression was evident in the brain cortex leading to a reduced generation of sAPPα and increased levels of sAPPβ and endogenous Aβ peptides. The A10cKO mice are characterized by weight loss and increased mortality after weaning associated with seizures. Behavioral comparison of adult mice revealed that the loss of ADAM10 in the A10cKO mice resulted in decreased neuromotor abilities and reduced learning performance, which were associated with altered in vivo network activities in the hippocampal CA1 region and impaired synaptic function. Histological and ultrastructural analysis of ADAM10-depleted brain revealed astrogliosis, microglia activation, and impaired number and altered morphology of postsynaptic spine structures. A defect in spine morphology was further supported by a reduction of the expression of NMDA receptors subunit 2A and 2B. The reduced shedding of essential postsynaptic cell adhesion proteins such as N-Cadherin, Nectin-1, and APP may explain the postsynaptic defects and the impaired learning, altered network activity, and synaptic plasticity of the A10cKO mice. Our study reveals that ADAM10 is instrumental for synaptic and neuronal network function in the adult murine brain.

  7. Brain Activity with Reading Sentences and Emoticons

    NASA Astrophysics Data System (ADS)

    Yuasa, Masahide; Saito, Keiichi; Mukawa, Naoki

    In this paper, we describe a person's brain activity when he/she sees an emoticon at the end of a sentence. An emoticon consists of some characters that resemble the human face and expresses a sender's emotion. With the help of a computer network, we use e-mail, messenger, avatars and so on, in order to convey what we wish to, to a receiver. Moreover, we send an emotional expression by using an emoticon at the end of a sentence. In this research, we investigate the effect of an emoticon as nonverbal information, using an fMRI study. The experimental results show that the right and left inferior frontal gyrus were activated and we detect a sentence with an emoticon as the verbal and nonverval information.

  8. Altered long non-coding RNA transcriptomic profiles in brain microvascular endothelium after cerebral ischemia.

    PubMed

    Zhang, J; Yuan, L; Zhang, X; Hamblin, M H; Zhu, T; Meng, F; Li, Y; Chen, Y E; Yin, K J

    2016-03-01

    The brain endothelium is an important therapeutic target for the inhibition of cerebrovascular dysfunction in ischemic stroke. Previously, we documented the important regulatory roles of microRNAs in the cerebral vasculature, in particular the cerebral vascular endothelium. However, the functional significance and molecular mechanisms of other classes of non-coding RNAs in the regulation of cerebrovascular endothelial pathophysiology after stroke are completely unknown. Using RNA sequencing (RNA-seq) technology, we profiled long non-coding RNA (lncRNA) expressional signatures in primary brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation (OGD), an in vitro mimic of ischemic stroke conditions. After 16h of OGD exposure, the expression levels for 362 of the 10,677 lncRNAs analyzed changed significantly, including a total of 147 lncRNAs increased and 70 lncRNAs decreased by more than 2-fold. Among them, the most highly upregulated lncRNAs include Snhg12, Malat1, and lnc-OGD 1006, whereas the most highly downregulated lncRNAs include 281008D09Rik, Peg13, and lnc-OGD 3916. Alteration of the most highly upregulated/downregulated ODG-responsive lncRNAs was further confirmed in cultured BMECs after OGD as well as isolated cerebral microvessels in mice following transient middle cerebral artery occlusion (MCAO) and 24h reperfusion by the quantitative real-time PCR approach. Moreover, promoter analysis of altered ODG-responsive endothelial lncRNA genes by bioinformatics showed substantial transcription factor binding sites on lncRNAs, implying potential transcriptional regulation of those lncRNAs. These findings are the first to identify OGD-responsive brain endothelial lncRNAs, which suggest potential pathological roles for these lncRNAs in mediating endothelial responses to ischemic stimuli. Endothelial-selective lncRNAs may function as a class of novel master regulators in cerebrovascular endothelial pathologies after ischemic stroke.

  9. Protein-energy malnutrition alters thermoregulatory homeostasis and the response to brain ischemia.

    PubMed

    Smith, Shari E; Prosser-Loose, Erin J; Colbourne, Frederick; Paterson, Phyllis G

    2011-02-01

    Co-existing protein-energy malnutrition (PEM), characterized by deficits in both protein and energy status, impairs functional outcome following global ischemia and has been associated with increased reactive gliosis. Since temperature is a key determinant of brain damage following an ischemic insult, the objective was to investigate whether alterations in post-ischemic temperature regulation contribute to PEM-induced reactive gliosis following ischemia. Male Sprague-Dawley rats (190-280 g) were assigned to either control diet (18% protein) or PEM induced by feeding a low protein diet (2% protein) for 7 days prior to either global ischemia or sham surgery. There was a rapid disruption in thermoregulatory function in rats fed the low protein diet as assessed by continuous recording of core temperature with bio-electrical sensor transmitters. Both daily temperature fluctuation and mean temperature increased within the first 24 hours, and these remained significantly elevated throughout the 7 day pre-ischemic period (p < 0.027). In the immediate post-surgical period, PEM decreased body temperature to a greater extent than that in well-nourished controls (p = 0.003). The increase in daily temperature fluctuation caused by PEM persisted throughout the 7 day post-surgical period (p < 0.001), and this interacted with the effects of global ischemia on days 8 (p = 0.018) and 11 (p = 0.021). The astrocytic and microglial responses induced at 7 days after global ischemia were not influenced by PEM, but this preliminary analysis needs to be confirmed with a more reliable global ischemia model. In conclusion, exposure to a low protein diet rapidly impairs the ability to maintain thermoregulatory homeostasis, and the resultant PEM also diminishes the ability to thermoregulate in response to a challenge. Since temperature regulation is a key determinant of brain injury following ischemia, these findings suggest that the pathophysiology of brain injury could be altered in stroke

  10. Alterations of p11 in brain tissue and peripheral blood leukocytes in Parkinson’s disease

    PubMed Central

    Green, Holly; Zhang, Xiaoqun; Tiklova, Katarina; Volakakis, Nikolaos; Brodin, Lovisa; Berg, Louise; Perlmann, Thomas; Svenningsson, Per

    2017-01-01

    Individuals with Parkinson’s disease (PD) often suffer from comorbid depression. P11 (S100A10), a member of the S100 family of proteins, is expressed widely throughout the body and is involved in major depressive disorder and antidepressant response. Central p11 levels are reduced in postmortem tissue from depressed individuals; however, p11 has not yet been investigated in PD patients with depression or those without depression. We investigated p11 levels in postmortem PD brains and assessed whether peripheral p11 levels correlate with disease severity. Substantia nigra, putamen, and cortical p11 protein levels were assessed in postmortem brain samples from PD patients and matched controls. In a different set of postmortem brains, p11 mRNA expression was measured in dopaminergic cells from the substantia nigra. Both p11 protein and mRNA levels were decreased in PD patients. Peripheral p11 protein levels were investigated in distinct leukocyte populations from PD patients with depression and those without depression. Monocyte, natural killer (NK) cell, and cytotoxic T-cell p11 levels were positively associated with the severity of PD, and NK cell p11 levels were positively associated with depression scores. Given that inflammation plays a role in both PD and depression, it is intriguing that peripheral p11 levels are altered in immune cells in both conditions. Our data provide insight into the pathological alterations occurring centrally and peripherally in PD. Moreover, if replicated in other cohorts, p11 could be an easily accessible biomarker for monitoring the severity of PD, especially in the context of comorbid depression. PMID:28137881

  11. Altered Brain Function, Structure, and Developmental Trajectory in Children Born Late Preterm

    PubMed Central

    Brumbaugh, Jane E.; Conrad, Amy L.; Lee, Jessica K.; DeVolder, Ian J.; Zimmerman, M. Bridget; Magnotta, Vincent A.; Axelson, Eric D.; Nopoulos, Peggy C.

    2016-01-01

    Background Late preterm birth (34-36 weeks’ gestation) is a common occurrence with potential for altered brain development. Methods This observational cohort study compared children at age 6-13 years based on the presence or absence of the historical risk factor of late preterm birth. Children completed a battery of cognitive assessments and underwent magnetic resonance imaging of the brain. Results Late preterm children (n=52) demonstrated slower processing speed (p=0.035) and scored more poorly in visual-spatial perception (p=0.032) and memory (p=0.007) than full term children (n=74). Parents of late preterm children reported more behavioral difficulty (p=0.004). There were no group differences in cognitive ability or academic achievement. Imaging revealed similar intracranial volumes but less total tissue and more cerebrospinal fluid (p=0.004) for late preterm children compared to full term children. The tissue difference was driven by differences in the cerebrum (p=0.028) and distributed across cortical (p=0.051) and subcortical tissue (p=0.047). Late preterm children had a relatively smaller thalamus (p=0.012) than full term children. Only full term children demonstrated significant decreases in cortical tissue volume (p<0.001) and thickness (p<0.001) with age. Conclusion Late preterm birth may affect cognition, behavior, and brain structure well beyond infancy. PMID:27064239

  12. Structural Alterations of the Social Brain: A Comparison between Schizophrenia and Autism

    PubMed Central

    Radeloff, Daniel; Ciaramidaro, Angela; Siniatchkin, Michael; Hainz, Daniela; Schlitt, Sabine; Weber, Bernhard; Poustka, Fritz; Bölte, Sven; Walter, Henrik; Freitag, Christine Margarete

    2014-01-01

    Autism spectrum disorder and schizophrenia share a substantial number of etiologic and phenotypic characteristics. Still, no direct comparison of both disorders has been performed to identify differences and commonalities in brain structure. In this voxel based morphometry study, 34 patients with autism spectrum disorder, 21 patients with schizophrenia and 26 typically developed control subjects were included to identify global and regional brain volume alterations. No global gray matter or white matter differences were found between groups. In regional data, patients with autism spectrum disorder compared to typically developed control subjects showed smaller gray matter volume in the amygdala, insula, and anterior medial prefrontal cortex. Compared to patients with schizophrenia, patients with autism spectrum disorder displayed smaller gray matter volume in the left insula. Disorder specific positive correlations were found between mentalizing ability and left amygdala volume in autism spectrum disorder, and hallucinatory behavior and insula volume in schizophrenia. Results suggest the involvement of social brain areas in both disorders. Further studies are needed to replicate these findings and to quantify the amount of distinct and overlapping neural correlates in autism spectrum disorder and schizophrenia. PMID:25188200

  13. Exercise Challenge in Gulf War Illness Reveals Two Subgroups with Altered Brain Structure and Function

    PubMed Central

    Rayhan, Rakib U.; Stevens, Benson W.; Raksit, Megna P.; Ripple, Joshua A.; Timbol, Christian R.; Adewuyi, Oluwatoyin; VanMeter, John W.; Baraniuk, James N.

    2013-01-01

    Nearly 30% of the approximately 700,000 military personnel who served in Operation Desert Storm (1990–1991) have developed Gulf War Illness, a condition that presents with symptoms such as cognitive impairment, autonomic dysfunction, debilitating fatigue and chronic widespread pain that implicate the central nervous system. A hallmark complaint of subjects with Gulf War Illness is post-exertional malaise; defined as an exacerbation of symptoms following physical and/or mental effort. To study the causal relationship between exercise, the brain, and changes in symptoms, 28 Gulf War veterans and 10 controls completed an fMRI scan before and after two exercise stress tests to investigate serial changes in pain, autonomic function, and working memory. Exercise induced two clinical Gulf War Illness subgroups. One subgroup presented with orthostatic tachycardia (n = 10). This phenotype correlated with brainstem atrophy, baseline working memory compensation in the cerebellar vermis, and subsequent loss of compensation after exercise. The other subgroup developed exercise induced hyperalgesia (n = 18) that was associated with cortical atrophy and baseline working memory compensation in the basal ganglia. Alterations in cognition, brain structure, and symptoms were absent in controls. Our novel findings may provide an understanding of the relationship between the brain and post-exertional malaise in Gulf War Illness. PMID:23798990

  14. Mutant IDH1 Disrupts the Mouse Subventricular Zone and Alters Brain Tumor Progression.

    PubMed

    Pirozzi, Christopher J; Carpenter, Austin B; Waitkus, Matthew S; Wang, Catherine Y; Zhu, Huishan; Hansen, Landon J; Chen, Lee H; Greer, Paula K; Feng, Jie; Wang, Yu; Bock, Cheryl B; Fan, Ping; Spasojevic, Ivan; McLendon, Roger E; Bigner, Darell D; He, Yiping; Yan, Hai

    2017-02-01

    IDH1 mutations occur in the majority of low-grade gliomas and lead to the production of the oncometabolite, D-2-hydroxyglutarate (D-2HG). To understand the effects of tumor-associated mutant IDH1 (IDH1-R132H) on both the neural stem cell (NSC) population and brain tumorigenesis, genetically faithful cell lines and mouse model systems were generated. Here, it is reported that mouse NSCs expressing Idh1-R132H displayed reduced proliferation due to p53-mediated cell cycle arrest as well as a decreased ability to undergo neuronal differentiation. In vivo, Idh1-R132H expression reduced proliferation of cells within the germinal zone of the subventricular zone (SVZ). The NSCs within this area were dispersed and disorganized in mutant animals, suggesting that Idh1-R132H perturbed the NSCs and the microenvironment from which gliomas arise. Additionally, tumor-bearing animals expressing mutant Idh1 displayed a prolonged survival and also overexpressed Olig2, features consistent with IDH1-mutated human gliomas. These data indicate that mutant Idh1 disrupts the NSC microenvironment and the candidate cell of origin for glioma; thus, altering the progression of tumorigenesis. Additionally, this study provides a mutant Idh1 brain tumor model that genetically recapitulates human disease, laying the foundation for future investigations on mutant IDH1-mediated brain tumorigenesis and targeted therapy.

  15. Exercise challenge in Gulf War Illness reveals two subgroups with altered brain structure and function.

    PubMed

    Rayhan, Rakib U; Stevens, Benson W; Raksit, Megna P; Ripple, Joshua A; Timbol, Christian R; Adewuyi, Oluwatoyin; VanMeter, John W; Baraniuk, James N

    2013-01-01

    Nearly 30% of the approximately 700,000 military personnel who served in Operation Desert Storm (1990-1991) have developed Gulf War Illness, a condition that presents with symptoms such as cognitive impairment, autonomic dysfunction, debilitating fatigue and chronic widespread pain that implicate the central nervous system. A hallmark complaint of subjects with Gulf War Illness is post-exertional malaise; defined as an exacerbation of symptoms following physical and/or mental effort. To study the causal relationship between exercise, the brain, and changes in symptoms, 28 Gulf War veterans and 10 controls completed an fMRI scan before and after two exercise stress tests to investigate serial changes in pain, autonomic function, and working memory. Exercise induced two clinical Gulf War Illness subgroups. One subgroup presented with orthostatic tachycardia (n = 10). This phenotype correlated with brainstem atrophy, baseline working memory compensation in the cerebellar vermis, and subsequent loss of compensation after exercise. The other subgroup developed exercise induced hyperalgesia (n = 18) that was associated with cortical atrophy and baseline working memory compensation in the basal ganglia. Alterations in cognition, brain structure, and symptoms were absent in controls. Our novel findings may provide an understanding of the relationship between the brain and post-exertional malaise in Gulf War Illness.

  16. A new stress model, a scream sound, alters learning and monoamine levels in rat brain.

    PubMed

    Hu, Lili; Yang, Juan; Song, Tusheng; Hou, Ni; Liu, Yong; Zhao, Xiaoge; Zhang, Dianzeng; Wang, Lumin; Wang, Tao; Huang, Chen

    2014-01-17

    Most existing animal models for stress involve the simultaneous application of physical and psychological stress factors. In the current study, we described and used a novel psychological stress model (scream sound stress). To study the validity of it, we carried out acute and chronic scream sound stress. First, adult Sprague-Dawley (SD) rats were randomly divided into white noise, stress and background groups. The white noise group and stress group were treated with white noise and scream sound for 4h in the morning respectively. Compared with white noise and background groups, exposure to acute scream sound increased corticosterone (CORT) level and decreased latency in Morris water maze (MWM) test. The levels of noradrenaline (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were altered in the striatum, hypothalamus and hippocampus of stress rats. Second, adult SD rats were randomly divided into background and stress groups, which were treated with scream sound for three weeks. Exposure to chronic scream sound suppressed body weight gain, increased corticosterone (CORT) level, influenced the morphology of adrenal gland, improved spleen and thymus indices, and decreased latency in MWM test. NE, DA, DOPAC, HVA and 5-HIAA levels were also altered in the brain of stress rats. Our results suggested that scream sound, as a novel stressor, facilitated learning ability, as well as altered monoamine levels in the rat brain. Moreover, scream sound is easy to apply and can be applied in more animals at the same time.

  17. A Meta-Analysis of Changes in Brain Activity in Clinical Depression

    PubMed Central

    Palmer, Susan M.; Crewther, Sheila G.; Carey, Leeanne M.

    2015-01-01

    Insights into neurobiological mechanisms of depression are increasingly being sought via brain imaging studies. Our aim was to quantitatively summarize overlap and divergence in regions of altered brain activation associated with depression under emotionally valenced compared to cognitively demanding task conditions, and with reference to intrinsic functional connectivity. We hypothesized differences reflective of task demands. A co-ordinate-based meta-analysis technique, activation likelihood estimation, was used to analyze relevant imaging literature. These studies compared brain activity in depressed adults relative to healthy controls during three conditions: (i) emotionally valenced (cognitively easy) tasks (n = 29); (ii) cognitively demanding tasks (n = 15); and (iii) resting conditions (n = 21). The meta-analyses identified five, eight, and seven significant clusters of altered brain activity under emotion, cognition, and resting conditions, respectively, in depressed individuals compared to healthy controls. Regions of overlap and divergence between pairs of the three separate meta-analyses were quantified. There were no significant regions of overlap between emotion and cognition meta-analyses, but several divergent clusters were found. Cognitively demanding conditions were associated with greater activation of right medial frontal and insula regions while bilateral amygdala was more significantly altered during emotion (cognitively undemanding) conditions; consistent with task demands. Overlap was present in left amygdala and right subcallosal cingulate between emotion and resting meta-analyses, with no significant divergence. Our meta-analyses highlight alteration of common brain regions, during cognitively undemanding emotional tasks and resting conditions but divergence of regions between emotional and cognitively demanding tasks. Regions altered reflect current biological and system-level models of depression and highlight the relationship

  18. CHRONIC FETAL HYPOXIA PRODUCES SELECTIVE BRAIN INJURY ASSOCIATED WITH ALTERED NITRIC OXIDE SYNTHASES

    PubMed Central

    DONG, Yafeng; YU, Zhiyong; SUN, Yan; ZHOU, Hui; STITES, Josh; NEWELL, Katherine; WEINER, Carl P.

    2011-01-01

    OBJECTIVE The impact of chronic hypoxia on the nitric oxide synthase isoenzymes (NOSs) in specific brain structures is unknown. STUDY DESIGN Time-mated pregnant guinea pigs were exposed to 10.5% O2 for 14d (HPX) or room air (NMX); L-NIL (an iNOS inhibitor, 1mg/kg/day) was administered to HPX animals for 14d (L-NIL+HPX). Fetal brains were harvested at term. Multi-labeled immunofluorescence was used to generate a brain injury map. Laser capture microdissection and quantitative PCR were applied and cell injury markers, apoptosis activation, neuron loss, total NO, and the levels of individual NOSs quantified. RESULTS Chronic hypoxia causes selective fetal brain injury rather than globally. Injury is associated with differentially affected NO synthases in both neurons and glial cells, with iNOS up regulated at all injury sites. L-NIL attenuated the injury despite continued hypoxia. CONCLUSIONS These studies demonstrate chronic hypoxia selectively injures the fetal brain in part by the differential regulation of NOSs in an anatomic and cell specific manner. PMID:21272843

  19. Altered regional connectivity reflecting effects of different anaesthesia protocols in the mouse brain.

    PubMed

    Wu, Tong; Grandjean, Joanes; Bosshard, Simone C; Rudin, Markus; Reutens, David; Jiang, Tianzi

    2017-04-01

    Studies in mice using resting-state functional magnetic resonance imaging (rs-fMRI) have provided opportunities to investigate the effects of pharmacological manipulations on brain function and map the phenotypes of mouse models of human brain disorders. Mouse rs-fMRI is typically performed under anaesthesia, which induces both regional suppression of brain activity and disruption of large-scale neural networks. Previous comparative studies using rodents investigating various drug effects on long-distance functional connectivity (FC) have reported agent-specific FC patterns, however, effects of regional suppression are sparsely explored. Here we examined changes in regional connectivity under six different anaesthesia conditions using mouse rs-fMRI with the goal of refining the framework of understanding the brain activation under anaesthesia at a local level. Regional homogeneity (ReHo) was used to map local synchronization in the brain, followed by analysis of several brain areas based on ReHo maps. The results revealed high local coherence in most brain areas. The primary somatosensory cortex and caudate-putamen showed agent-specific properties. Lower local coherence in the cingulate cortex was observed under medetomidine, particularly when compared to the combination of medetomidine and isoflurane. The thalamus was associated with retained local coherence across anaesthetic levels and multiple nuclei. These results show that anaesthesia induced by the investigated anaesthetics through different molecular targets promote agent-specific regional connectivity. In addition, ReHo is a data-driven method with minimum user interaction, easy to use and fast to compute. Given that examination of the brain at a local level is widely applied in human rs-fMRI studies, our results show its sensitivity to extract information on varied neuronal activity under six different regimens relevant to mouse functional imaging. These results, therefore, will inform future rs

  20. Alterations of motor performance and brain cortex mitochondrial function during ethanol hangover.

    PubMed

    Bustamante, Juanita; Karadayian, Analia G; Lores-Arnaiz, Silvia; Cutrera, Rodolfo A

    2012-08-01

    Ethanol has been known to affect various behavioral parameters in experimental animals, even several hours after ethanol (EtOH) is absent from blood circulation, in the period known as hangover. The aim of this study was to assess the effects of acute ethanol hangover on motor performance in association with the brain cortex energetic metabolism. Evaluation of motor performance and brain cortex mitochondrial function during alcohol hangover was performed in mice 6 hours after a high ethanol dose (hangover onset). Animals were injected i.p. either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover group). Ethanol hangover group showed a bad motor performance compared with control animals (p < .05). Oxygen uptake in brain cortex mitochondria from hangover animals showed a 34% decrease in the respiratory control rate as compared with the control group. Mitochondrial complex activities were decreased being the complex I-III the less affected by the hangover condition; complex II-III was markedly decreased by ethanol hangover showing 50% less activity than controls. Complex IV was 42% decreased as compared with control animals. Hydrogen peroxide production was 51% increased in brain cortex mitochondria from the hangover group, as compared with the control animals. Quantification of the mitochondrial transmembrane potential indicated that ethanol injected animals presented 17% less ability to maintain the polarized condition as compared with controls. These results indicate that a clear decrease in proton motive force occurs in brain cortex mitochondria during hangover conditions. We can conclude that a decreased motor performance observed in the hangover group of animals could be associated with brain cortex mitochondrial dysfunction and the resulting impairment of its energetic metabolism.

  1. Motivation alters response bias and neural activation patterns in a perceptual decision-making task.

    PubMed

    Reckless, G E; Bolstad, I; Nakstad, P H; Andreassen, O A; Jensen, J

    2013-05-15

    Motivation has been demonstrated to affect individuals' response strategies in economic decision-making, however, little is known about how motivation influences perceptual decision-making behavior or its related neural activity. Given the important role motivation plays in shaping our behavior, a better understanding of this relationship is needed. A block-design, continuous performance, perceptual decision-making task where participants were asked to detect a picture of an animal among distractors was used during functional magnetic resonance imaging (fMRI). The effect of positive and negative motivation on sustained activity within regions of the brain thought to underlie decision-making was examined by altering the monetary contingency associated with the task. In addition, signal detection theory was used to investigate the effect of motivation on detection sensitivity, response bias and response time. While both positive and negative motivation resulted in increased sustained activation in the ventral striatum, fusiform gyrus, left dorsolateral prefrontal cortex (DLPFC) and ventromedial prefrontal cortex, only negative motivation resulted in the adoption of a more liberal, closer to optimal response bias. This shift toward a liberal response bias correlated with increased activation in the left DLPFC, but did not result in improved task performance. The present findings suggest that motivation alters aspects of the way perceptual decisions are made. Further, this altered response behavior is reflected in a change in left DLPFC activation, a region involved in the computation of perceptual decisions.

  2. Bilingualism alters brain functional connectivity between "control" regions and "language" regions: Evidence from bimodal bilinguals.

    PubMed

    Li, Le; Abutalebi, Jubin; Zou, Lijuan; Yan, Xin; Liu, Lanfang; Feng, Xiaoxia; Wang, Ruiming; Guo, Taomei; Ding, Guosheng

    2015-05-01

    Previous neuroimaging studies have revealed that bilingualism induces both structural and functional neuroplasticity in the dorsal anterior cingulate cortex (dACC) and the left caudate nucleus (LCN), both of which are associated with cognitive control. Since these "control" regions should work together with other language regions during language processing, we hypothesized that bilingualism may also alter the functional interaction between the dACC/LCN and language regions. Here we tested this hypothesis by exploring the functional connectivity (FC) in bimodal bilinguals and monolinguals using functional MRI when they either performed a picture naming task with spoken language or were in resting state. We found that for bimodal bilinguals who use spoken and sign languages, the FC of the dACC with regions involved in spoken language (e.g. the left superior temporal gyrus) was stronger in performing the task, but weaker in the resting state as compared to monolinguals. For the LCN, its intrinsic FC with sign language regions including the left inferior temporo-occipital part and right inferior and superior parietal lobules was increased in the bilinguals. These results demonstrate that bilingual experience may alter the brain functional interaction between "control" regions and "language" regions. For different control regions, the FC alters in different ways. The findings also deepen our understanding of the functional roles of the dACC and LCN in language processing.

  3. Diffuse axonal injury in brain trauma: insights from alterations in neurofilaments

    PubMed Central

    Siedler, Declan G.; Chuah, Meng Inn; Kirkcaldie, Matthew T. K.; Vickers, James C.; King, Anna E.

    2014-01-01

    Traumatic brain injury (TBI) from penetrating or closed forces to the cranium can result in a range of forms of neural damage, which culminate in mortality or impart mild to significant neurological disability. In this regard, diffuse axonal injury (DAI) is a major neuronal pathophenotype of TBI and is associated with a complex set of cytoskeletal changes. The neurofilament triplet proteins are key structural cytoskeletal elements, which may also be important contributors to the tensile strength of axons. This has significant implications with respect to how axons may respond to TBI. It is not known, however, whether neurofilament compaction and the cytoskeletal changes that evolve following axonal injury represent a component of a protective mechanism following damage, or whether they serve to augment degeneration and progression to secondary axotomy. Here we review the structure and role of neurofilament proteins in normal neuronal function. We also discuss the processes that characterize DAI and the resultant alterations in neurofilaments, highlighting potential clues to a possible protective or degenerative influence of specific neurofilament alterations within injured neurons. The potential utility of neurofilament assays as biomarkers for axonal injury is also discussed. Insights into the complex alterations in neurofilaments will contribute to future efforts in developing therapeutic strategies to prevent, ameliorate or reverse neuronal degeneration in the central nervous system (CNS) following traumatic injury. PMID:25565963

  4. Parasitic castration by the digenian trematode Allopodocotyle sp. alters gene expression in the brain of the host mollusc Haliotis asinina.

    PubMed

    Rice, Tamika; McGraw, Elizabeth; O'Brien, Elizabeth K; Reverter, Antonio; Jackson, Daniel J; Degnan, Bernard M

    2006-06-26

    Infection of molluscs by digenean trematode parasites typically results in the repression of reproduction -- the so-called parasitic castration. This is known to occur by altering the expression of a range of host neuropeptide genes. Here we analyse the expression levels of 10 members of POU, Pax, Sox and Hox transcription factor gene families, along with genes encoding FMRFamide, prohormone convertase and beta-tubulin, in the brain ganglia of actively reproducing (summer), non-reproducing (winter) and infected Haliotis asinina (a vetigastropod mollusc). A number of the regulatory genes are differentially expressed in parasitised H. asinina, but in only a few cases do expression patterns in infected animals match those occurring in animals where reproduction is normally repressed.

  5. Melanoma tumors alter proinflammatory cytokine production and monoamine brain function, and induce depressive-like behavior in male mice.

    PubMed

    Lebeña, Andrea; Vegas, Oscar; Gómez-Lázaro, Eneritz; Arregi, Amaia; Garmendia, Larraitz; Beitia, Garikoitz; Azpiroz, Arantza

    2014-10-01

    Depression is a commonly observed disorder among cancer patients; however, the mechanisms underlying the relationship between these disorders are not well known. We used an animal model to study the effects of tumor development on depressive-like behavior manifestation, proinflammatory cytokine expression, and central monoaminergic activity. Male OF1 mice were inoculated with B16F10 melanoma tumor cells and subjected to a 21-day behavioral evaluation comprising the novel palatable food (NPF) test and tail suspension test (TST). The mRNA expression levels of proinflammatory cytokines, interleukin (IL)-1β and IL-6, and tumor necrosis factor-alpha (TNF-α), were measured in the hypothalamus and hippocampus and the levels of IL-6 and TNF-α were measured in the blood plasma. We similarly determined the monoamine turnover in various brain areas. The tumors resulted in increasing the immobility in TST and the expression level of IL-6 in the hippocampus. These increases corresponded with a decrease in dopaminergic activity in the striatum and a decrease in serotonin turnover in the prefrontal cortex. Similarly, a high level of tumor development produced increases in the brain expression levels of IL-6 and TNF-α and plasma levels of IL-6. Our findings suggest that these alterations in inflammatory cytokines and monoaminergic system function might be responsible for the manifestation of depressive-like behaviors in tumor-bearing mice.

  6. Specific and Evolving Resting-State Network Alterations in Post-Concussion Syndrome Following Mild Traumatic Brain Injury

    PubMed Central

    Messé, Arnaud; Caplain, Sophie; Pélégrini-Issac, Mélanie; Blancho, Sophie; Lévy, Richard; Aghakhani, Nozar; Montreuil, Michèle; Benali, Habib; Lehéricy, Stéphane

    2013-01-01

    Post-concussion syndrome has been related to axonal damage in patients with mild traumatic brain injury, but little is known about the consequences of injury on brain networks. In the present study, our aim was to characterize changes in functional brain networks following mild traumatic brain injury in patients with post-concussion syndrome using resting-state functional magnetic resonance imaging data. We investigated 17 injured patients with persistent post-concussion syndrome (under the DSM-IV criteria) at 6 months post-injury compared with 38 mild traumatic brain injury patients with no post-concussion syndrome and 34 healthy controls. All patients underwent magnetic resonance imaging examinations at the subacute (1–3 weeks) and late (6 months) phases after injury. Group-wise differences in functional brain networks were analyzed using graph theory measures. Patterns of long-range functional networks alterations were found in all mild traumatic brain injury patients. Mild traumatic brain injury patients with post-concussion syndrome had greater alterations than patients without post-concussion syndrome. In patients with post-concussion syndrome, changes specifically affected temporal and thalamic regions predominantly at the subacute stage and frontal regions at the late phase. Our results suggest that the post-concussion syndrome is associated with specific abnormalities in functional brain network that may contribute to explain deficits typically observed in PCS patients. PMID:23755237

  7. ALTERED EXPRESSION OF NEUROPLASTICITY-RELATED GENES IN THE BRAIN OF DEPRESSED SUICIDES

    PubMed Central

    FUCHSOVA, B.; ALVAREZ JULIÁ, A.; RIZAVI, H. S.; FRASCH, A. C.; PANDEY, G. N.

    2015-01-01

    Background Expression of the neuronal membrane glycoprotein M6a (GPM6A), the proteolipid protein (PLP/DM20) family member, is downregulated in the hippocampus of chronically stressed animals. Its neuroplastic function involves a role in neurite formation, filopodium outgrowth and synaptogenesis through an unknown mechanism. Disruptions in neuroplasticity mechanisms have been shown to play a significant part in the etiology of depression. Thus, the current investigation examined whether GPM6A expression is also altered in human depressed brain. Methods Expression levels and coexpression patterns of GPM6A, GPM6B, and PLP1 (two other members of PLP/DM20 family) as well as of the neuroplasticity-related genes identified to associate with GPM6A were determined using quantitative polymerase chain reaction (qPCR) in postmortem samples from the hippocampus (n =18) and the prefrontal cortex (PFC) (n= 25) of depressed suicide victims and compared with control subjects (hippocampus n= 18; PFC n =25). Neuroplasticity-related proteins that form complexes with GPM6A were identified by coimmunoprecipitation technique followed by mass spectrometry. Results Results indicated transcriptional downregulation of GPM6A and GPM6B in the hippocampus of depressed suicides. The expression level of calcium/calmodulin-dependent protein kinase II alpha (CAMK2A) and coronin1A (CORO1A) was also significantly decreased. Subsequent analysis of coexpression patterns demonstrated coordinated gene expression in the hippocampus and in the PFC indicating that the function of these genes might be coregulated in the human brain. However, in the brain of depressed suicides this coordinated response was disrupted. Conclusions Disruption of coordinated gene expression as well as abnormalities in GPM6A and GPM6B expression and expression of the components of GPM6A complexes were detected in the brain of depressed suicides. PMID:25934039

  8. Alzheimer's disease and type 2 diabetes-related alterations in brain mitochondria, autophagy and synaptic markers.

    PubMed

    Carvalho, Cristina; Santos, Maria S; Oliveira, Catarina R; Moreira, Paula I

    2015-08-01

    We aimed to investigate mitochondrial function, biogenesis and autophagy in the brain of type 2 diabetes (T2D) and Alzheimer's disease (AD) mice. Isolated brain mitochondria and homogenates from cerebral cortex and hippocampus of wild-type (WT), triple transgenic AD (3xTg-AD) and T2D mice were used to evaluate mitochondrial functional parameters and protein levels of mitochondrial biogenesis, autophagy and synaptic integrity markers, respectively. A significant decrease in mitochondrial respiration, membrane potential and energy levels was observed in T2D and 3xTg-AD mice. Also, a significant decrease in the levels of autophagy-related protein 7 (ATG7) and glycosylated lysosomal membrane protein 1 (LAMP1) was observed in cerebral cortex and hippocampus of T2D and 3xTg-AD mice. Moreover, both brain regions of 3xTg-AD mice present lower levels of nuclear respiratory factor (NRF) 1 while the levels of NRF2 are lower in both brain regions of T2D and 3xTg-AD mice. A decrease in mitochondrial encoded, nicotinamide adenine dinucleotide dehydrogenase subunit 1 (ND1) was also observed in T2D and 3xTg-AD mice although only statistically significant in T2D cortex. Furthermore, a decrease in the levels of postsynaptic density protein 95 (PSD95) in the cerebral cortex of 3xTg-AD mice and in hippocampus of T2D and 3xTg-AD mice and a decrease in the levels of synaptosomal-associated protein 25 (SNAP 25) in the hippocampus of T2D and 3xTg-AD mice were observed suggesting synaptic integrity loss. These results support the idea that alterations in mitochondrial function, biogenesis and autophagy cause synaptic damage in AD and T2D.

  9. Plumbagin alters telomere dynamics, induces DNA damage and cell death in human brain tumour cells.

    PubMed

    Khaw, Aik Kia; Sameni, Safoura; Venkatesan, Shriram; Kalthur, Guruprasad; Hande, M Prakash

    2015-11-01

    Natural plant products may possess much potential in palliative therapy and supportive strategies of current cancer treatments with lesser cytotoxicity to normal cells compared to conventional chemotherapy. In the current study, anti-cancer properties of plumbagin, a plant-derived naphthoquinone, on brain cancer cells were determined. Plumbagin treatment resulted in the induction of DNA damage, cell cycle arrest and apoptosis, followed by suppression of the colony forming ability of the brain tumour cells. These effects were substantiated by upregulation of PTEN, TNFRSF1A and downregulation of E2F1 genes, along with a drop in MDM2, cyclin B1, survivin and BCL2 protein expression. Plumbagin induced elevated levels of caspase-3/7 activity as well. For the first time, we show here that plumbagin inhibits telomerase in brain tumour cells and results in telomere shortening following chronic long-term treatment. This observation implies considerable cytotoxicity of plumbagin towards cancer cells with higher telomerase activity. Collectively, our findings suggest plumbagin as a potential chemotherapeutic phytochemical in brain tumour treatment modalities.

  10. Causal interaction following the alteration of target region activation during motor imagery training using real-time fMRI

    PubMed Central

    Zhao, Xiaojie; Zhang, Hang; Song, Sutao; Ye, Qing; Guo, Jia; Yao, Li

    2013-01-01

    Motor imagery training is an effective approach for motor skill learning and motor function rehabilitation. As a novel method of motor imagery training, real-time fMRI (rtfMRI) enables individuals to acquire self-control of localized brain activation, achieving desired changes in behavior. The regulation of target region activation by rtfMRI often alters the activation of related brain regions. However, the interaction between the target region and these related regions is unclear. The Granger causality model (GCM) is a data-driven method that can explore the causal interaction between brain regions. In this study, we employed rtfMRI to train subjects to regulate the activation of the ipsilateral dorsal premotor area (dPMA) during motor imagery training, and we calculated the causal interaction of the dPMA with other motor-related regions based on the GCM. The results demonstrated that as the activity of the dPMA changed during rtfMRI training, the interaction of the target region with other related regions became significantly altered, and behavioral performance was improved after training. The altered interaction primarily exhibited as an increased unidirectional interaction from the dPMA to the other regions. These findings support the dominant role of the dPMA in motor skill learning via rtfMRI training and may indicate how activation of the target region interacts with the activation of other related regions. PMID:24379775

  11. Regionally selective alterations in local cerebral glucose utilization evoked by charybdotoxin, a blocker of central voltage-activated K+-channels.

    PubMed

    Cochran, S M; Harvey, A L; Pratt, J A

    2001-11-01

    The quantitative [14C]-2-deoxyglucose autoradiographic technique was employed to investigate the effect of charybdotoxin, a blocker of certain voltage-activated K+ channels, on functional activity, as reflected by changes in local rates of cerebral glucose utilization in rat brain. Intracerebroventricular administration of charybdotoxin, at doses below those producing seizure activity, produced a heterogeneous effect on glucose utilization throughout the brain. Out of the 75 brain regions investigated, 24 displayed alterations in glucose utilization. The majority of these changes were observed with the intermediate dose of charybdotoxin administered (12.5 pmol), with the lower (6.25 pmol) and higher (25 pmol) doses of charybdotoxin producing a much more restricted pattern of change in glucose utilization. In brain regions which displayed alterations in glucose at all doses of charybdotoxin administered, no dose dependency in terms of the magnitude of change was observed. The 21 brain regions which displayed altered functional activity after administration of 12.5 pmol charybdotoxin were predominantly limited to the hippocampus, limbic and motor structures. In particular, glucose utilization was altered within three pathways implicated within learning and memory processes, the septohippocampal pathway, Schaffer collaterals within the hippocampus and the Papez circuit. The nigrostriatal pathway also displayed altered local cerebral glucose utilization. These data indicate that charybdotoxin produces alterations in functional activity within selected pathways in the brain. Furthermore the results raise the possibility that manipulation of particular subtypes of Kv1 channels in the hippocampus and related structures may be a means of altering cognitive processes without causing global changes in neural activity throughout the brain.

  12. Dorsal raphe nucleus of brain in the rats flown in space inflight and postflight alteration of structure

    NASA Astrophysics Data System (ADS)

    Krasnov, I.

    structures in DRN of "postflight" rats were not differ significantly fo rm analogous parameters of "inflight" rats. The results of study point out the decrease in mircrogravity in functional activity of DRN - main serotoniner gic center of brain and in combination with the data (Krasnov et. A.; 1998; Krasnov, Dyachkova, 2000) about inflight alteration in locus coeruleus - main noradrenergic center allow to propose the mechanism of decline of growth hormone secretion in mammals during space flight.

  13. Altered brain functional connectivity in relation to perception of scrutiny in social anxiety disorder.

    PubMed

    Giménez, Mónica; Pujol, Jesús; Ortiz, Hector; Soriano-Mas, Carles; López-Solà, Marina; Farré, Magí; Deus, Joan; Merlo-Pich, Emilio; Martín-Santos, Rocio

    2012-06-30

    Although the fear of being scrutinized by others in a social context is a key symptom in social anxiety disorder (SAD), the neural processes underlying the perception of scrutiny have not previously been studied by functional magnetic resonance imaging (fMRI). We used fMRI to map brain activation during a perception-of-scrutiny task in 20 SAD patients and 20 controls. A multi-dimensional analytic approach was used. Scrutiny perception was mediated by activation of the medial frontal cortex, insula-operculum region and cerebellum, and the additional recruitment of visual areas and the thalamus in patients. Between-group comparison demonstrated significantly enhanced brain activation in patients in the primary visual cortex and cerebellum. Functional connectivity mapping demonstrated an abnormal connectivity between regions underlying general arousal and attention. SAD patients showed significantly greater task-induced functional connectivity in the thalamo-cortical and the fronto-striatal circuits. A statistically significant increase in task-induced functional connectivity between the anterior cingulate cortex and scrutiny-perception-related regions was observed in the SAD patients, suggesting the existence of enhanced behavior-inhibitory control. The presented data indicate that scrutiny perception in SAD enhances brain activity in arousal-attention systems, suggesting that fMRI may be a useful tool to explore such a behavioral dimension.

  14. Brain reward system's alterations in response to food and monetary stimuli in overweight and obese individuals.

    PubMed

    Verdejo-Román, Juan; Vilar-López, Raquel; Navas, Juan F; Soriano-Mas, Carles; Verdejo-García, Antonio

    2017-02-01

    The brain's reward system is crucial to understand obesity in modern society, as increased neural responsivity to reward can fuel the unhealthy food choices that are driving the growing obesity epidemic. Brain's reward system responsivity to food and monetary rewards in individuals with excessive weight (overweight and obese) versus normal weight controls, along with the relationship between this responsivity and body mass index (BMI) were tested. The sample comprised 21 adults with obesity (BMI > 30), 21 with overweight (BMI between 25 and 30), and 39 with normal weight (BMI < 25). Participants underwent a functional magnetic resonance imaging (fMRI) session while performing two tasks that involve the processing of food (Willing to Pay) and monetary rewards (Monetary Incentive Delay). Neural activations within the brain reward system were compared across the three groups. Curve fit analyses were conducted to establish the association between BMI and brain reward system's response. Individuals with obesity had greater food-evoked responsivity in the dorsal and ventral striatum compared with overweight and normal weight groups. There was an inverted U-shape association between BMI and monetary-evoked responsivity in the ventral striatum, medial frontal cortex, and amygdala; that is, individuals with BMIs between 27 and 32 had greater responsivity to monetary stimuli. Obesity is associated with greater food-evoked responsivity in the ventral and dorsal striatum, and overweight is associated with greater monetary-evoked responsivity in the ventral striatum, the amygdala, and the medial frontal cortex. Findings suggest differential reactivity of the brain's reward system to food versus monetary rewards in obesity and overweight. Hum Brain Mapp 38:666-677, 2017. © 2016 Wiley Periodicals, Inc.

  15. [Alterations in recruitment and activation of Rab proteins during mycobacterial infection].

    PubMed

    Castaño, Diana; Rojas, Mauricio

    2010-01-01

    At the phagosome level, Mycobacterium spp. alters activation and recruitment of several "Ras gene from rat brain" proteins, commonly known as Rab. Mycobacterial phagosomes have a greater and sustained expression of Rab5, Rab11, Rab14 and Rab22a, and lowered or no expression of Rab7, Rab9 and Rab6. This correlates with increased fusion of the phagosomes with early and recycling endosomes acquiring some features of early phagosomes, allowing the bacteria to gain access to nutrients and preventing the activation of anti-mycobacterial mechanisms. The expression of constitutively active mutants of Rab from the early stage endosomes prevents the maturation of phagosomes containing latex beads or heat-inactivated mycobacteria. Silencing of these mutants by interference RNA or dominant negative forms induces the maturation of mycobacterial phagosomes. The mechanisms have not been established by which mycobacteria alter the expression of these GTPases and thereby shift the phagolysosomal maturation. The problem can be explained by alterations in the recruitment of proteins that interact with Rab, such as phosphoinositide 3-kinases and early endosomal antigen 1. Identifying the mechanisms used by Mycobacterium spp. to disrupt the cycle of Rab activation will be essential to understand the pathophysiology of mycobacterial infections and usefully to potential drug targets.

  16. On a Quantum Model of Brain Activities

    NASA Astrophysics Data System (ADS)

    Fichtner, K.-H.; Fichtner, L.; Freudenberg, W.; Ohya, M.

    2010-01-01

    One of the main activities of the brain is the recognition of signals. A first attempt to explain the process of recognition in terms of quantum statistics was given in [6]. Subsequently, details of the mathematical model were presented in a (still incomplete) series of papers (cf. [7, 2, 5, 10]). In the present note we want to give a general view of the principal ideas of this approach. We will introduce the basic spaces and justify the choice of spaces and operations. Further, we bring the model face to face with basic postulates any statistical model of the recognition process should fulfill. These postulates are in accordance with the opinion widely accepted in psychology and neurology.

  17. Neuropathology and neurobehavioral alterations in a rat model of traumatic brain injury to occupants of vehicles targeted by underbody blasts.

    PubMed

    Tchantchou, Flaubert; Fourney, William L; Leiste, Ulrich H; Vaughan, Joshua; Rangghran, Parisa; Puche, Adam; Fiskum, Gary

    2017-03-01

    Many victims of blast-induced traumatic brain injury are occupants of military vehicles targeted by land mines. Recently improved vehicle designs protect these individuals against blast overpressure, leaving acceleration as the main force potentially responsible for brain injury. We recently developed a unique rat model of under-vehicle blast-induced hyperacceleration where exposure to acceleration as low as 50G force results in histopathological evidence of diffuse axonal injury and astrocyte activation, with no evidence of neuronal cell death. This study investigated the effects of much higher blast-induced accelerations (1200 to 2800G) on neuronal cell death, neuro-inflammation, behavioral deficits and mortality. Adult male rats were subjected to this range of accelerations, in the absence of exposure to blast overpressure, and evaluated over 28days for working memory (Y maze) and anxiety (elevated plus maze). In addition, brains obtained from rats at one and seven days post-injury were used for neuropathology and neurochemical assays. Sixty seven percent of rats died soon after being subjected to blasts resulting in 2800G acceleration. All rats exposed to 2400G acceleration survived and exhibited transient deficits in working memory and long-term anxiety like behaviors, while those exposed to 1200 acceleration G force only demonstrated increased anxiety. Behavioral deficits were associated with acute microglia/macrophage activation, increased hippocampal neuronal death, and reduced levels of tight junction- and synapse- associated proteins. Taken together, these results suggest that exposure of rats to high underbody blast-induced G forces results in neurologic injury accompanied by neuronal apoptosis, neuroinflammation and evidence for neurosynaptic alterations.

  18. Nylon wool purification alters the activation of T cells.

    PubMed

    Wohler, Jillian E; Barnum, Scott R

    2009-02-01

    Purification of lymphocytes, particularly T cells, is commonly performed using nylon wool. This enrichment method selectively retains B cells and some myeloid cells allowing a significantly more pure T cell population to flow through a nylon wool column. T cells purified in this fashion are assumed to be unaltered and functionally naïve, however some studies have suggested aberrant in vitro T cell responses after nylon wool treatment. We found that nylon wool purification significantly altered T cell proliferation, expression of activation markers and production of cytokines. Our results suggest that nylon wool treatment modifies T cell activation responses and that caution should be used when choosing this purification method.

  19. Physical activity and brain plasticity in late adulthood.

    PubMed

    Erickson, Kirk I; Gildengers, Ariel G; Butters, Meryl A

    2013-03-01

    The human brain shrinks with advancing age, but recent research suggests that it is also capable of remarkable plasticity, even in late life. In this review we summarize the research linking greater amounts of physical activity to less cortical atrophy, better brain function, and enhanced cognitive function, and argue that physical activity takes advantage of the brain's natural capacity for plasticity. Further, although the effects of physical activity on the brain are relatively widespread, there is also some specificity, such that prefrontal and hippocampal areas appear to be more influenced than other areas of the brain. The specificity of these effects, we argue, provides a biological basis for understanding the capacity for physical activity to influence neurocognitive and neuropsychiatric disorders such as depression. We conclude that physical activity is a promising intervention that can influence the endogenous pharmacology of the brain to enhance cognitive and emotional function in late adulthood.

  20. Aging process alters hippocampal and cortical secretase activities of Wistar rats.

    PubMed

    Bertoldi, Karine; Cechinel, Laura Reck; Schallenberger, Bruna; Meireles, Louisiana; Basso, Carla; Lovatel, Gisele Agustini; Bernardi, Lisiane; Lamers, Marcelo Lazzaron; Siqueira, Ionara Rodrigues

    2017-01-15

    A growing body of evidence has demonstrated amyloid plaques in aged brain; however, little attention has been given to amyloid precursor protein (APP) processing machinery during the healthy aging process. The amyloidogenic and non-amyloidogenic pathways, represented respectively by β- and α-secretases (BACE and TACE), are responsible for APP cleavage. Our working hypothesis is that the normal aging process could imbalance amyloidogenic and non-amyloidogenic pathways specifically BACE and TACE activities. Besides, although it has been showed that exercise can modulate secretase activities in Alzheimer Disease models the relationship between exercise effects and APP processing during healthy aging process is rarely studied. Our aim was to investigate the aging process and the exercise effects on cortical and hippocampal BACE and TACE activities and aversive memory performance. Young adult and aged Wistar rats were subjected to an exercise protocol (20min/day for 2 weeks) and to inhibitory avoidance task. Biochemical parameters were evaluated 1h and 18h after the last exercise session in order to verify transitory and delayed exercise effects. Aged rats exhibited impaired aversive memory and diminished cortical TACE activity. Moreover, an imbalance between TACE and BACE activities in favor of BACE activity was observed in aged brain. Moderate treadmill exercise was unable to alter secretase activities in any brain areas or time points evaluated. Our results suggest that aging-related aversive memory decline is partly linked to decreased cortical TACE activity. Additionally, an imbalance between secretase activities can be related to the higher vulnerability to neurodegenerative diseases induced by aging.

  1. Effect of hypoxia and pharmacological treatment on some enzyme activities in dog brain areas.

    PubMed

    Arrigoni, E; Benzi, G; Curti, D; Dagani, F; Gallico, S; Gorini, A; Mandelli, V; Marzatico, F; Moretti, A; Villa, R F

    1984-05-01

    The effects of nicergoline on changes in enzymatic activities induced by hypoxia and post-hypoxic recovery were studied in various brain areas of young-adult and mature Beagle dogs. In different fractions (homogenate in toto, purified mitochondria, crude synaptosomes, SM1 and SM2 synaptic mitochondria) the maximal rate (Vmax) was investigated of the more representative enzymatic activities of: a) glycolysis, b) Krebs' cycle, c) electron transfer chain, d) amino acid and acetylcholine metabolism, e) lysosomal function. The physiopathological conditions caused alterations in different enzymatic activities depending on the area and subfraction investigated. Nicergoline tended to antagonize some of these alterations. Its action was mainly on non-synaptic mitochondria by a "braking" effect on some key enzyme activities of mitochondrial metabolism (i.e. citrate synthase, cytochrome oxidase and glutamate dehydrogenase) which suggests a sparing action in the brain.

  2. NLRP3 INFLAMMASOME ACTIVATION CONTRIBUTES TO LONG-TERM BEHAVIORAL ALTERATIONS IN MICE INJECTED WITH LIPOPOLYSACCHARIDE

    PubMed Central

    ZHU, WEI; CAO, FENG-SHENG; FENG, JUN; CHEN, HUA-WENG; WAN, JIE-RU; LU, QING; WANG, JIAN

    2017-01-01

    Lipopolysaccharide (LPS) might affect the central nervous system by causing neuroinflammation, which subsequently leads to brain damage and dysfunction. In this study, we evaluated the role of nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation in long-term behavioral alterations of 8-week-old male C57BL/6 mice injected intraperitoneally with LPS (5 mg/kg). At different time points after injection, we assessed locomotor function with a 24-point neurologic deficit scoring system and the rotarod test; assessed recognition memory with the novel object recognition test; and assessed emotional abnormality (anhedonia and behavioral despair) with the tail suspension test, forced swim test, and sucrose preference test. We also assessed protein expression of NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1 p10 in hippocampus by Western blotting; measured levels of interleukin (IL)-1β, IL-18, tumor necrosis factor α (TNFα), and IL-10 in hippocampus; measured TNFα and IL-1β in serum by ELISA; and evaluated microglial activity in hippocampus by Iba1 immunofluorescence. We found that LPS-injected mice displayed long-term depression-like behaviors and recognition memory deficit; elevated expression of NLRP3, ASC, and caspase-1 p10; increased levels of IL-1β, IL-18, and TNFα; decreased levels of IL-10; and increased microglial activation. These effects were blocked by the NLRP3 inflammasome inhibitor Ac-Tyr-Val-Ala-Asp-chloromethylketone. The results demonstrate proof of concept that NLRP3 inflammasome activation contributes to long-term behavioral alterations in LPS-exposed mice, probably through enhanced inflammation, and that NLRP3 inflammasome inhibition might alleviate peripheral and brain inflammation and thereby ameliorate long-term behavioral alterations in LPS-exposed mice. PMID:27923741

  3. Altered whole-brain white matter networks in preclinical Alzheimer's disease.

    PubMed

    Fischer, Florian Udo; Wolf, Dominik; Scheurich, Armin; Fellgiebel, Andreas

    2015-01-01

    Surrogates of whole-brain white matter (WM) networks reconstructed using diffusion tensor imaging (DTI) are novel markers of structural brain connectivity. Global connectivity of networks has been found impaired in clinical Alzheimer's disease (AD) compared to cognitively healthy aging. We hypothesized that network alterations are detectable already in preclinical AD and investigated major global WM network properties. Other structural markers of neurodegeneration typically affected in prodromal AD but seeming largely unimpaired in preclinical AD were also examined. 12 cognitively healthy elderly with preclinical AD as classified by florbetapir-PET (mean age 73.4 ± 4.9) and 31 age-matched controls without cerebral amyloidosis (mean age 73.1 ± 6.7) from the ADNI were included. WM networks were reconstructed from DTI using tractography and graph theory. Indices of network capacity and the established imaging markers of neurodegeneration hippocampal volume, and cerebral glucose utilization as measured by fludeoxyglucose-PET were compared between the two groups. Additionally, we measured surrogates of global WM integrity (fractional anisotropy, mean diffusivity, volume). We found an increase of shortest path length and a decrease of global efficiency in preclinical AD. These results remained largely unchanged when controlling for WM integrity. In contrast, neither markers of neurodegeneration nor WM integrity were altered in preclinical AD subjects. Our results suggest an impairment of WM networks in preclinical AD that is detectable while other structural imaging markers do not yet indicate incipient neurodegeneration. Moreover, these findings are specific to WM networks and cannot be explained by other surrogates of global WM integrity.

  4. Prenatal alcohol exposure alters methyl metabolism and programs serotonin transporter and glucocorticoid receptor expression in brain.

    PubMed

    Ngai, Ying Fai; Sulistyoningrum, Dian C; O'Neill, Ryan; Innis, Sheila M; Weinberg, Joanne; Devlin, Angela M

    2015-09-01

    Prenatal alcohol exposure (PAE) programs the fetal hypothalamic-pituitary-adrenal (HPA) axis, resulting in HPA dysregulation and hyperresponsiveness to stressors in adulthood. Molecular mechanisms mediating these alterations are not fully understood. Disturbances in one-carbon metabolism, a source of methyl donors for epigenetic processes, contributes to alcoholic liver disease. We assessed whether PAE affects one-carbon metabolism (including Mtr, Mat2a, Mthfr, and Cbs mRNA) and programming of HPA function genes (Nr3c1, Nr3c2, and Slc6a4) in offspring from ethanol-fed (E), pair-fed (PF), and ad libitum-fed control (C) dams. At gestation day 21, plasma total homocysteine and methionine concentrations were higher in E compared with C dams, and E fetuses had higher plasma methionine concentrations and lower whole brain Mtr and Mat2a mRNA compared with C fetuses. In adulthood (55 days), hippocampal Mtr and Cbs mRNA was lower in E compared with C males, whereas Mtr, Mat2a, Mthfr, and Cbs mRNA were higher in E compared with C females. We found lower Nr3c1 mRNA and lower nerve growth factor inducible protein A (NGFI-A) protein in the hippocampus of E compared with PF females, whereas hippocampal Slc6a4 mRNA was higher in E than C males. By contrast, hypothalamic Slc6a4 mRNA was lower in E males and females compared with C offspring. This was accompanied by higher hypothalamic Slc6a4 mean promoter methylation in E compared with PF females. These findings demonstrate that PAE is associated with alterations in one-carbon metabolism and has long-term and region-specific effects on gene expression in the brain. These findings advance our understanding of mechanisms of HPA dysregulation associated with PAE.

  5. Neurobehavioral alterations and histopathological changes in brain and spinal cord of rats intoxicated with acrylamide.

    PubMed

    Jangir, Babu Lal; Mahaprabhu, R; Rahangadale, Santosh; Bhandarkar, Arun G; Kurkure, Nitin V

    2016-03-01

    The aim of this project was to study the clinical manifestations, neurobehavioral, hematobiochemical, oxidative stress, genotoxicity, and histopathological changes during acrylamide toxicity in rats. A total of 30 adult male Wistar rats were divided in 5 equal groups and received 0, 10, 15, and 20 mg/kg body weight acrylamide as oral gavage, while group 5 was micronucleus (MN) control. Functional observational battery (FOB) parameters were studied at the 28th day of post treatment. Toxicological manifestations were evident in acrylamide-treated rats from 14th day onward. FOB revealed a significant change in central nervous system, neuromuscular, and autonomic domains. The hematological changes include significant decrease in concentration of hemoglobin, total erythrocyte count, packed cell volume, and mean corpuscular volume. The biochemical parameters aspartate aminotransferases, alkaline phosphatase, and albumin showed significant increase, while the levels of serum globulin and glucose were found to decrease significantly. The MN assay revealed the significant increase in frequencies of micronuclei and number of polychromatic erythrocytes. The oxidative stress parameters revealed no significant difference as compared to control rats. Histopathological changes observed in brain include neuronal degeneration, edema, and congestion, while spinal cord revealed demyelination in low-dose group and bilateral necrosis with malacia, liquefaction of white matter, and loss of myelin from gray matter in high-dose groups. The result indicates pathological alterations in brain and spinal cord and is responsible for neurobehavioral changes in rats. The FOB changes and histopathological alterations in spinal cord are in dose dependent to acrylamide intoxication. Various toxicological effects observed in experiment direct us to focus on a deep study and evaluate the possible causes pertaining to toxicity of this chemical. It would furnish the scientists with better options that

  6. Forebrain and brain stem neural circuits contribute to altered sympathetic responses to heating in senescent rats.

    PubMed

    Kenney, Michael J; Fels, Richard J

    2003-11-01

    Acute heating in young rats increases visceral sympathetic nerve discharge (SND); however, renal and splanchnic SND responses to hyperthermia are attenuated in senescent compared with young Fischer 344 (F344) rats (Kenney MJ and Fels RJ. Am J Physiol Regul Integr Comp Physiol 283: R513-R520, 2002). Central mechanisms by which aging alters visceral SND responses to heating are unknown. We tested the hypothesis that forebrain neural circuits are involved in suppressing sympathoexcitatory responses to heating in chloralose-anesthetized, senescent F344 rats. Renal and splanchnic SND responses to increased (38 degrees C-41 degrees C) internal temperature were determined in midbrain-transected (MT) and sham-MT young (3-mo-old), mature (12-mo-old), and senescent (24-mo-old) F344 rats and in cervical-transected (CT) and sham-CT senescent rats. Renal SND remained unchanged during heating in MT and sham-MT senescent rats but was increased in CT senescent rats. Splanchnic SND responses to heating were higher in MT vs. sham-MT senescent rats and in CT vs. MT senescent rats. SND responses to heating were similar in MT and sham-MT young and mature rats. Mean arterial pressure (MAP) was increased during heating in MT but not in sham-MT senescent rats, whereas heating-induced increases in MAP were higher in sham-MT vs. MT young rats. These data suggest that in senescent rats suppression of splanchnic SND to heating involves forebrain and brain stem neural circuits, whereas renal suppression is mediated solely by brain stem neural circuits. These results support the concept that aging alters the functional organization of pathways regulating SND and arterial blood pressure responses to acute heating.

  7. Prenatal alcohol exposure alters methyl metabolism and programs serotonin transporter and glucocorticoid receptor expression in brain

    PubMed Central

    Ngai, Ying Fai; Sulistyoningrum, Dian C.; O'Neill, Ryan; Innis, Sheila M.; Weinberg, Joanne

    2015-01-01

    Prenatal alcohol exposure (PAE) programs the fetal hypothalamic-pituitary-adrenal (HPA) axis, resulting in HPA dysregulation and hyperresponsiveness to stressors in adulthood. Molecular mechanisms mediating these alterations are not fully understood. Disturbances in one-carbon metabolism, a source of methyl donors for epigenetic processes, contributes to alcoholic liver disease. We assessed whether PAE affects one-carbon metabolism (including Mtr, Mat2a, Mthfr, and Cbs mRNA) and programming of HPA function genes (Nr3c1, Nr3c2, and Slc6a4) in offspring from ethanol-fed (E), pair-fed (PF), and ad libitum-fed control (C) dams. At gestation day 21, plasma total homocysteine and methionine concentrations were higher in E compared with C dams, and E fetuses had higher plasma methionine concentrations and lower whole brain Mtr and Mat2a mRNA compared with C fetuses. In adulthood (55 days), hippocampal Mtr and Cbs mRNA was lower in E compared with C males, whereas Mtr, Mat2a, Mthfr, and Cbs mRNA were higher in E compared with C females. We found lower Nr3c1 mRNA and lower nerve growth factor inducible protein A (NGFI-A) protein in the hippocampus of E compared with PF females, whereas hippocampal Slc6a4 mRNA was higher in E than C males. By contrast, hypothalamic Slc6a4 mRNA was lower in E males and females compared with C offspring. This was accompanied by higher hypothalamic Slc6a4 mean promoter methylation in E compared with PF females. These findings demonstrate that PAE is associated with alterations in one-carbon metabolism and has long-term and region-specific effects on gene expression in the brain. These findings advance our understanding of mechanisms of HPA dysregulation associated with PAE. PMID:26180184

  8. Daily Physical Activity Is Associated with Subcortical Brain Volume and Cognition in Heart Failure.

    PubMed

    Alosco, Michael L; Brickman, Adam M; Spitznagel, Mary Beth; Sweet, Lawrence H; Josephson, Richard; Griffith, Erica Y; Narkhede, Atul; Hughes, Joel; Gunstad, John

    2015-11-01

    Cognitive impairment in heart failure (HF) is believed to in part stem from structural brain alterations, including shrinkage of subcortical regions. Fortunately, neurocognitive dysfunction in HF can be mitigated by physical activity (PA), though mechanisms for this phenomenon are unclear. PA is protective against age-related cognitive decline that may involve improved structural integrity to brain regions sensitive to aging (e.g., subcortical structures). Yet, no study has examined the benefits of PA on the brain in HF and we sought to do so and clarify related cognitive implications. Fifty older adults with HF completed a neuropsychological battery and wore an accelerometer for 7 days. All participants underwent brain MRI. This study targeted subcortical brain volume given subcortical alterations are often observed in HF and the sensitivity of PA to subcortical structures in other patient populations. Participants averaged 4348.49 (SD=2092.08) steps per day and greater daily steps predicted better attention/executive function, episodic memory, and language abilities, p's<.05. Medical and demographically adjusted regression analyses revealed higher daily steps per day predicted greater subcortical volume, with specific effects for the thalamus and ventral diencephalon, p's<.05. Greater subcortical volume was associated with better attention/executive function, p<.05. Higher daily PA was associated with increased subcortical brain volume and better cognition in older adults with HF. Longitudinal work is needed to clarify whether daily PA can attenuate brain atrophy in HF to reduce accelerated cognitive decline in this population.

  9. Ionic transporter activity in astrocytes, microglia, and oligodendrocytes during brain ischemia

    PubMed Central

    Annunziato, Lucio; Boscia, Francesca; Pignataro, Giuseppe

    2013-01-01

    Glial cells constitute a large percentage of cells in the nervous system. During recent years, a large number of studies have critically attributed to glia a new role which no longer reflects the long-held view that glia constitute solely a silent and passive supportive scaffolding for brain cells. Indeed, it has been hypothesized that glia, partnering neurons, have a much more actively participating role in brain function. Alteration of intraglial ionic homeostasis in response to ischemic injury has a crucial role in inducing and maintaining glial responses in the ischemic brain. Therefore, glial transporters as potential candidates in stroke intervention are becoming promising targets to enhance an effective and additional therapy for brain ischemia. In this review, we will describe in detail the role played by ionic transporters in influencing astrocyte, microglia, and oligodendrocyte activity and the implications that these transporters have in the progression of ischemic lesion. PMID:23549380

  10. Alterations in the sense of time, space, and body in the mindfulness-trained brain: a neurophenomenologically-guided MEG study

    PubMed Central

    Berkovich-Ohana, Aviva; Dor-Ziderman, Yair; Glicksohn, Joseph; Goldstein, Abraham

    2013-01-01

    Meditation practice can lead to what have been referred to as “altered states of consciousness.”One of the phenomenological characteristics of these states is a joint alteration in the sense of time, space, and body. Here, we set out to study the unique experiences of alteration in the sense of time and space by collaborating with a select group of 12 long-term mindfulness meditation (MM) practitioners in a neurophenomenological setup, utilizing first-person data to guide the neural analyses. We hypothesized that the underlying neural activity accompanying alterations in the sense of time and space would be related to alterations in bodily processing. The participants were asked to volitionally bring about distinct states of “Timelessness” (outside time) and “Spacelessness” (outside space) while their brain activity was recorded by MEG. In order to rule out the involvement of attention, memory, or imagination, we used control states of “Then” (past) and “There” (another place). MEG sensors evidencing alterations in power values were identified, and the brain regions underlying these changes were estimated via spatial filtering (beamforming). Particularly, we searched for similar neural activity hypothesized to underlie both the state of “Timelessness” and “Spacelessness.” The results were mostly confined to the theta band, and showed that: (1) the “Then”/“There” overlap yielded activity in regions related to autobiographic memory and imagery (right posterior parietal lobule (PPL), right precentral/middle frontal gyrus (MFG), bilateral precuneus); (2) “Timelessness”/“Spacelessness” conditions overlapped in a different network, related to alterations in the sense of the body (posterior cingulate, right temporoparietal junction (TPJ), cerebellum); and (3) phenomenologically-guided neural analyses enabled us to dissociate different levels of alterations in the sense of the body. This study illustrates the utility of employing

  11. Paracetamol (acetaminophen) administration during neonatal brain development affects cognitive function and alters its analgesic and anxiolytic response in adult male mice.

    PubMed

    Viberg, Henrik; Eriksson, Per; Gordh, Torsten; Fredriksson, Anders

    2014-03-01

    Paracetamol (acetaminophen) is one of the most commonly used drugs for the treatment of pain and fever in children, both at home and in the clinic, and is now also found in the environment. Paracetamol is known to act on the endocannabinoid system, involved in normal development of the brain. We examined if neonatal paracetamol exposure could affect the development of the brain, manifested as adult behavior and cognitive deficits, as well as changes in the response to paracetamol. Ten-day-old mice were administered a single dose of paracetamol (30 mg/kg body weight) or repeated doses of paracetamol (30 + 30 mg/kg body weight, 4h apart). Concentrations of paracetamol and brain-derived neurotrophic factor (BDNF) were measured in the neonatal brain, and behavioral testing was done when animals reached adulthood. This study shows that acute neonatal exposure to paracetamol (2 × 30 mg) results in altered locomotor activity on exposure to a novel home cage arena and a failure to acquire spatial learning in adulthood, without affecting thermal nociceptive responding or anxiety-related behavior. However, mice neonatally exposed to paracetamol (2 × 30 mg) fail to exhibit paracetamol-induced antinociceptive and anxiogenic-like behavior in adulthood. Behavioral alterations in adulthood may, in part, be due to paracetamol-induced changes in BDNF levels in key brain regions at a critical time during development. This indicates that exposure to and presence of paracetamol during a critical period of brain development can induce long-lasting effects on cognitive function and alter the adult response to paracetamol in mice.

  12. Cellular proliferation and infiltration following interstitial irradiation of normal dog brain is altered by an inhibitor of polyamine synthesis

    SciTech Connect

    Fike, J.R.; Gobbel, G.T.; Chou, D.

    1995-07-15

    The objectives of this study were to quantitatively define proliferative and infiltrative cell responses after focal {sup 125}I irradiation of normal brain, and to determine the effects of an intravenous infusion of {alpha}-defluoromethylornithine (DFMO) on those responses. Adult beagle dogs were irradiated using high activity {sup 125}I sources. Cellular responses were quantified using a histomorphometric analysis. After radiation alone, cellular events included a substantial acute inflammatory response followed by increased BrdU labeling and progressive increases in numbers of capillaries and astrocytes. {alpha}-Difluoromethylornithine treatment significantly affected the measured cell responses. As in controls, an early inflammatory response was measured, but after 2 weeks there were more PMNs/unit area than in controls. The onset of measurable BrdU labeling was delayed in DFMO-treated animals, and the magnitude of labeling was significantly reduced. Increases in astrocyte and vessel numbers/mm{sup 2} were observed after a 2-week delay. At the site of implant, astrocytes from DFMO-treated dogs were significantly smaller than those from controls. There is substantial cell proliferation and infiltration in response to interstitial irradiation of normal brain, and these responses are significantly altered by DFMO treatment. Although the precise mechanisms by which DFMO exerts its effects in this model are not known, the results from this study suggest that modification of radiation injury may be possible by manipulating the response of normal cells to injury. 57 refs., 6 figs.

  13. Craniosynostosis in 10q26 deletion patients: A consequence of brain underdevelopment or altered suture biology?

    PubMed

    Faria, Ágatha Cristhina; Rabbi-Bortolini, Eliete; Rebouças, Maria R G O; de S Thiago Pereira, Andréia L A; Frasson, Milena G Tonini; Atique, Rodrigo; Lourenço, Naila Cristina V; Rosenberg, Carla; Kobayashi, Gerson S; Passos-Bueno, Maria Rita; Errera, Flávia Imbroisi Valle

    2016-02-01

    Approximately a hundred patients with terminal 10q deletions have been described. They present with a wide range of clinical features always accompanied by delayed development, intellectual disability and craniofacial dysmorphisms. Here, we report a girl and a boy with craniosynostosis, developmental delay and other congenital anomalies. Karyotyping and molecular analysis including Multiplex Ligation dependent probe amplification (MLPA) and Array Comparative Genomic Hybridization (aCGH) were performed in both patients. We detected a 13.1 Mb pure deletion at 10q26.12-q26.3 in the girl and a 10.9 Mb pure deletion at 10q26.13-q26.3 in the boy, both encompassing about 100 genes. The clinical and molecular findings in these patients reinforce the importance of the DOCK1 smallest region of overlap I (SRO I), previously suggested to explain the clinical signs, and together with a review of the literature suggest a second 3.5 Mb region important for the phenotype (SRO II). Genotype-phenotype correlations and literature data suggest that the craniosynostosis is not directly related to dysregulated signaling in suture development, but may be secondary to alterations in brain development instead. Further, genes at 10q26 may be involved in the molecular crosstalk between brain and cranial vault.

  14. Dietary cholesterol alters memory and synaptic structural plasticity in young rat brain.

    PubMed

    Ya, Bai-liu; Liu, Wen-yan; Ge, Feng; Zhang, Yan-xia; Zhu, Bao-liang; Bai, Bo

    2013-08-01

    Cholesterol plays an important role in synaptic plasticity, learning and memory. To better explore how dietary cholesterol contributes to learning and memory and the related changes in synaptic structural plasticity, rats were categorized into a regular diet (RD) group and a cholesterol-enriched diet (CD) group, and were fed with respective diet for 2 months. Dietary cholesterol impacts on learning and memory, hippocampal synaptic ultrastructure, expression levels of postsynaptic density-95 (PSD-95), synaptophysin (SYP) and cannabinoid receptor type 1 (CB1R) were investigated. We found CD rats had better performances in learning and memory using Morris water maze and object recognition test than RD rats. The memory improvement was accompanied with alterations of synaptic ultrastructure in the CA1 area of the hippocampus evaluated by electron microscopy, enhanced immunoreactivity of SYP, a presynaptic marker in hippocampus detected by immunocytochemistry, as well as increased levels of PSD-95, SYP and decreased level of CB1R in brains of CD rats determined by Western blot. Taken together, the results suggest that the improvement of learning and memory abilities of the young adult rats induced by dietary cholesterol may be linked with changes in synaptic structural plasticity in the brain.

  15. The anabolic steroid nandrolone alters cannabinoid self-administration and brain CB1 receptor density and function.

    PubMed

    Struik, Dicky; Fadda, Paola; Zara, Tamara; Zamberletti, Erica; Rubino, Tiziana; Parolaro, Daniela; Fratta, Walter; Fattore, Liana

    2017-01-01

    Clinical and pre-clinical observations indicate that anabolic-androgenic steroids can induce neurobiological changes that alter the rewarding effects of drugs of abuse. In this study, we investigated the effect of the anabolic steroid nandrolone on the rewarding properties of the cannabinoid CB1 receptor agonist WIN55,212-2 (WIN) in rats. Lister Hooded male rats were treated intramuscularly with nandrolone (15mg/kg) or vehicle for 14 consecutive days, and then allowed to self-administer WIN (12.5μg/kg/infusion) intravenously. After reaching stable drug intake, self-administration behavior was extinguished to examine drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Other behavioral parameters presumed to influence drug-taking and drug-seeking behaviors were examined to gain more insight into the behavioral specificity of nandrolone treatment. Finally, animals were sacrificed for analysis of CB1 receptor density and function in selected brain areas. We found that nandrolone-treated rats self-administered up to 2 times more cannabinoid than vehicle-treated rats, but behaved similarly to control rats when tested for drug- and cue-induced reinstatement of cannabinoid-seeking behavior. Enhanced cannabinoid intake by nandrolone-treated rats was not accompanied by changes in locomotor activity, sensorimotor gating, or memory function. However, our molecular data show that after chronic WIN self-administration nandrolone-treated rats display altered CB1 receptor density and function in selected brain areas. We hypothesize that increased cannabinoid self-administration in nandrolone-treated rats results from a nandrolone-induced decrease in reward function, which rats seem to compensate by voluntarily increasing their cannabinoid intake. Altogether, our findings corroborate the hypothesis that chronic exposure to anabolic-androgenic steroids induces dysfunction of the reward pathway in rats and might represent a potential risk factor for abuse of

  16. Alterations in neuronal activity in basal ganglia-thalamocortical circuits in the parkinsonian state

    PubMed Central

    Galvan, Adriana; Devergnas, Annaelle; Wichmann, Thomas

    2015-01-01

    In patients with Parkinson’s disease and in animal models of this disorder, neurons in the basal ganglia and related regions in thalamus and cortex show changes that can be recorded by using electrophysiologic single-cell recording techniques, including altered firing rates and patterns, pathologic oscillatory activity and increased inter-neuronal synchronization. In addition, changes in synaptic potentials or in the joint spiking activities of populations of neurons can be monitored as alterations in local field potentials (LFPs), electroencephalograms (EEGs) or electrocorticograms (ECoGs). Most of the mentioned electrophysiologic changes are probably related to the degeneration of diencephalic dopaminergic neurons, leading to dopamine loss in the striatum and other basal ganglia nuclei, although degeneration of non-dopaminergic cell groups may also have a role. The altered electrical activity of the basal ganglia and associated nuclei may contribute to some of the motor signs of the disease. We here review the current knowledge of the electrophysiologic changes at the single cell level, the level of local populations of neural elements, and the level of the entire basal ganglia-thalamocortical network in parkinsonism, and discuss the possible use of this information to optimize treatment approaches to Parkinson’s disease, such as deep brain stimulation (DBS) therapy. PMID:25698937

  17. Supervised learning for neural manifold using spatiotemporal brain activity

    NASA Astrophysics Data System (ADS)

    Kuo, Po-Chih; Chen, Yong-Sheng; Chen, Li-Fen

    2015-12-01

    Objective. Determining the means by which perceived stimuli are compactly represented in the human brain is a difficult task. This study aimed to develop techniques for the construction of the neural manifold as a representation of visual stimuli. Approach. We propose a supervised locally linear embedding method to construct the embedded manifold from brain activity, taking into account similarities between corresponding stimuli. In our experiments, photographic portraits were used as visual stimuli and brain activity was calculated from magnetoencephalographic data using a source localization method. Main results. The results of 10 × 10-fold cross-validation revealed a strong correlation between manifolds of brain activity and the orientation of faces in the presented images, suggesting that high-level information related to image content can be revealed in the brain responses represented in the manifold. Significance. Our experiments demonstrate that the proposed method is applicable to investigation into the inherent patterns of brain activity.

  18. Cerebral blood volume changes during brain activation

    PubMed Central

    Krieger, Steffen Norbert; Streicher, Markus Nikolar; Trampel, Robert; Turner, Robert

    2012-01-01

    Cerebral blood volume (CBV) changes significantly with brain activation, whether measured using positron emission tomography, functional magnetic resonance imaging (fMRI), or optical microscopy. If cerebral vessels are considered to be impermeable, the contents of the skull incompressible, and the skull itself inextensible, task- and hypercapnia-related changes of CBV could produce intolerable changes of intracranial pressure. Because it is becoming clear that CBV may be useful as a well-localized marker of neural activity changes, a resolution of this apparent paradox is needed. We have explored the idea that much of the change in CBV is facilitated by exchange of water between capillaries and surrounding tissue. To this end, we developed a novel hemodynamic boundary-value model and found approximate solutions using a numerical algorithm. We also constructed a macroscopic experimental model of a single capillary to provide biophysical insight. Both experiment and theory model capillary membranes as elastic and permeable. For a realistic change of input pressure, a relative pipe volume change of 21±5% was observed when using the experimental setup, compared with the value of approximately 17±1% when this quantity was calculated from the mathematical model. Volume, axial flow, and pressure changes are in the expected range. PMID:22569192

  19. The impact of early aerobic exercise on brain microvascular alterations induced by cerebral hypoperfusion.

    PubMed

    Leardini-Tristão, Marina; Borges, Juliana Pereira; Freitas, Felipe; Rangel, Raquel; Daliry, Anissa; Tibiriçá, Eduardo; Estato, Vanessa

    2017-02-15

    The therapeutic potential of early exercise training following cerebral hypoperfusion was investigated on brain perfusion and inflammation in rats with permanent bilateral occlusion of the common carotid arteries (2VO). Wistar rats were subjected to 2VO or sham surgery and each group was then subdivided randomly into sedentary or exercise groups. Early exercise training was initiated after three days of 2VO or sham surgery and consisted of seven days of treadmill training (30min/day at ∼60% of maximal exercise test), composing four groups: 1) Sham sedentary (Sham-Sed), 2) Sham exercised (Sham-Ex), 3) 2VO sedentary (2VO-Sed) and 4) 2VO exercised (2VO-Ex). Microvascular cerebral blood flow (MCBF) and NADPH oxidase and eNOS gene expression were evaluated by laser speckle contrast imaging and RT-PCR, respectively, and brain functional capillary density and endothelial-leukocyte interactions were evaluated by fluorescence intravital video-microscopy. The 2VO-Sed group presented a decrease in MCBF (Sham-Sed: 230.9±12.2 vs. 2VO-Sed: 183.6±10.6 arbitrary perfusion units, P<0.05) and in functional capillary density (Sham-Sed: 336.4±25.3 vs. 2VO-Sed: 225.5±28.1capillaries/mm(2), P<0.05). Early intervention with physical exercise was able to prevent the cerebral microvascular inflammation by decreasing endothelial-leukocyte interactions (2VO-Ex: 0.9±0.3 vs. 2VO-Sed: 5±0.6cells/min/100μm, P<0.0001) and reducing brain NADPH oxidase gene expression (2VO-Ex: 1.7±0.1 arbitrary units, P<0.05). Cerebral microcirculatory and inflammatory alterations appear to be triggered during the first days after 2VO surgery, and early intervention with physical exercise may represent a means of preventing the microvascular alterations induced by chronic cerebral hypoperfusion.

  20. Abnormal brain activation during movement observation in patients with conversion paralysis.

    PubMed

    Burgmer, Markus; Konrad, Carsten; Jansen, Andreas; Kugel, Harald; Sommer, Jens; Heindel, Walter; Ringelstein, Erich B; Heuft, Gereon; Knecht, Stefan

    2006-02-15

    Dissociative paralysis in conversion disorders has variably been attributed to a lack of movement initiation or an inhibition of movement. While psychodynamic theory suggests altered movement conceptualization, brain activation associated with observation and replication of movements has so far not been assessed neurobiologically. Here, we measured brain activation by functional magnetic resonance imaging during observation and subsequent imitative execution of movements in four patients with dissociative hand paralysis. Compared to healthy controls conversion disorder patients showed decreased activation of cortical hand areas during movement observation. This effect was specific to the side of their dissociative paralysis. No brain activation compatible with movement inhibition was observed. These findings indicate that in dissociative paralysis, there is not only derangement of movement initiation but already of movement conceptualization. This raises the possibility that strategies targeted at reestablishing appropriate movement conceptualization may contribute to the therapy of dissociative paralysis.

  1. Altered sleep composition after traumatic brain injury does not affect declarative sleep-dependent memory consolidation.

    PubMed

    Mantua, Janna; Mahan, Keenan M; Henry, Owen S; Spencer, Rebecca M C

    2015-01-01

    Individuals with a history of traumatic brain injury (TBI) often report sleep disturbances, which may be caused by changes in sleep architecture or reduced sleep quality (greater time awake after sleep onset, poorer sleep efficiency, and sleep stage proportion alterations). Sleep is beneficial for memory formation, and herein we examine whether altered sleep physiology following TBI has deleterious effects on sleep-dependent declarative memory consolidation. Participants learned a list of word pairs in the morning or evening, and recall was assessed 12-h later, following an interval awake or with overnight sleep. Young adult participants (18-22 years) were assigned to one of four experimental groups: TBI Sleep (n = 14), TBI Wake (n = 12), non-TBI Sleep (n = 15), non-TBI Wake (n = 15). Each TBI participant was >1 year post-injury. Sleep physiology was measured with polysomnography. Memory consolidation was assessed by comparing change in word-pair recall over 12-h intersession intervals. The TBI group spent a significantly greater proportion of the night in SWS than the non-TBI group at the expense of NREM1. The TBI group also had marginally lower EEG delta power during SWS in the central region. Intersession changes in recall were greater for intervals with sleep than without sleep in both groups. However, despite abnormal sleep stage proportions for individuals with a TBI history, there was no difference in the intersession change in recall following sleep for the TBI and non-TBI groups. In both Sleep groups combined, there was a positive correlation between Intersession Change and the proportion of the night in NREM2 + SWS. Overall, sleep composition is altered following TBI but such deficits do not yield insufficiencies in sleep-dependent memory consolidation.

  2. Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring.

    PubMed

    Ceccanti, Mauro; Coccurello, Roberto; Carito, Valentina; Ciafrè, Stefania; Ferraguti, Giampiero; Giacovazzo, Giacomo; Mancinelli, Rosanna; Tirassa, Paola; Chaldakov, George N; Pascale, Esterina; Ceccanti, Marco; Codazzo, Claudia; Fiore, Marco

    2016-07-01

    Ethanol (EtOH) exposure during pregnancy induces cognitive and physiological deficits in the offspring. However, the role of paternal alcohol exposure (PAE) on offspring EtOH sensitivity and neurotrophins has not received much attention. The present study examined whether PAE may disrupt nerve growth factor (NGF) and/or brain-derived neurotrophic factor (BDNF) and affect EtOH preference/rewarding properties in the male offspring. CD1 sire mice were chronically addicted for EtOH or administered with sucrose. Their male offsprings when adult were assessed for EtOH preference by a conditioned place preference paradigm. NGF and BDNF, their receptors (p75(NTR) , TrkA and TrkB), dopamine active transporter (DAT), dopamine receptors D1 and D2, pro-NGF and pro-BDNF were also evaluated in brain areas. PAE affected NGF levels in frontal cortex, striatum, olfactory lobes, hippocampus and hypothalamus. BDNF alterations in frontal cortex, striatum and olfactory lobes were found. PAE induced a higher susceptibility to the EtOH rewarding effects mostly evident at the lower concentration (0.5 g/kg) that was ineffective in non-PAE offsprings. Moreover, higher ethanol concentrations (1.5 g/kg) produced an aversive response in PAE animals and a significant preference in non-PAE offspring. PAE affected also TrkA in the hippocampus and p75(NTR) in the frontal cortex. DAT was affected in the olfactory lobes in PAE animals treated with 0.5 g/kg of ethanol while no differences were found on D1/D2 receptors and for pro-NGF or pro-BDNF. In conclusion, this study shows that: PAE affects NGF and BDNF expression in the mouse brain; PAE may induce ethanol intake preference in the male offspring.

  3. Antioxidant Therapy Alters Brain MAPK-JNK and BDNF Signaling Path-ways in Experimental Diabetes Mellitus.

    PubMed

    Réus, Gislaine Zilli; Bernardini Dos Santos, Maria Augusta; Abelaira, Helena Mendes; Maciel, Amanda Luis; Arent, Camila Orlandi; Matias, Beatriz Iladi; Bruchchen, Lívia; Ignácio, Zuleide Maria; Michels, Monique; Dal-Pizzol, Felipe; Carvalho, André Ferrer; Zugno, Alexandra Ioppi; Quevedo, João

    2016-01-01

    This study was designed to investigate the effects of treatment with the antioxidants N-acetylcysteine (NAC) and deferoxamine (DFX) in intracellular pathways in the brain of diabetic rats. To conduct this study we induced diabetes in Wistar rats with a single injection of alloxan, and afterwards rats were treated with NAC or DFX for 14 days. Following treatment completion, the immunocontent of c-Jun N-terminal kinase (JNK), mitogen-activated protein kinase-38 (MAPK38), brain-derived neurotrophic factor (BDNF), and protein kinases A and C (PKA and PKC) were determined in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens (NAc). DFX treatment increased JNK content in the PFC and NAc of diabetic rats. In the amygdala, JNK was increased in diabetics treated with saline or NAC. MAPK38 was decreased in the PFC of control and in diabetic rats treated with NAC or DFX; and in the NAc in all groups. PKA was decreased in the PFC with DFX treatment. In the amygdala, PKA content was increased in diabetic rats treated with either saline or NAC, compared to controls; and it was decreased in either NAC or DFX-treated groups, compared to saline-treated diabetic animals. In the NAc, PKA was increased in NAC-treated diabetic rats. PKC was increased in the amygdala of NAC-treated diabetic rats. In the PFC, the BDNF levels were decreased following treatment with DFX in diabetic rats. In the hippocampus of diabetic rats the BDNF levels were decreased. However, treatment with DFX reversed this effect. In the amygdala the BDNF increased with DFX in non-diabetic rats. In the NAc DFX treatment increased the BDNF levels in diabetic rats. In conclusion, both diabetes and treatment with antioxidants were able to alter intracellular pathways involved in the regulation of cell survival in a brain area and treatment-dependent fashion.

  4. Brain studies may alter long-held concepts about likely causes of some voice disorders

    SciTech Connect

    Not Available

    1989-02-17

    Two voice disorders long considered to be psychological problems, stuttering and spasmodic dysphonia, have been shown in many persons to have a neurophysiological basis. Investigators at the 155th national meeting of the American Association for the Advancement of Science, in San Francisco, described their findings, which are based on new analytic techniques. The research is being done at the Dallas Center for Vocal Motor Control, Callier Center for Communication Disorders, University of Texas at Dallas Health Science Center. The technology employed to learn what's wrong with the brains, rather than the psyches, of persons with certain speech disorders includes magnetic resonance imaging (MRI), brain electrical activity mapping (BEAM), and single photon emission computerized tomography (SPECT). The results of applying these techniques are combined with quantitative behavioral measures of vocal and nonvocal motor control, language performance, and cognition to arrive at a better understanding of the problem.

  5. Brain activation associated with active and passive lower limb stepping

    PubMed Central

    Jaeger, Lukas; Marchal-Crespo, Laura; Wolf, Peter; Riener, Robert; Michels, Lars; Kollias, Spyros

    2014-01-01

    Reports about standardized and repeatable experimental procedures investigating supraspinal activation in patients with gait disorders are scarce in current neuro-imaging literature. Well-designed and executed tasks are important to gain insight into the effects of gait-rehabilitation on sensorimotor centers of the brain. The present study aims to demonstrate the feasibility of a novel imaging paradigm, combining the magnetic resonance (MR)-compatible stepping robot (MARCOS) with sparse sampling functional magnetic resonance imaging (fMRI) to measure task-related BOLD signal changes and to delineate the supraspinal contribution specific to active and passive stepping. Twenty-four healthy participants underwent fMRI during active and passive, periodic, bilateral, multi-joint, lower limb flexion and extension akin to human gait. Active and passive stepping engaged several cortical and subcortical areas of the sensorimotor network, with higher relative activation of those areas during active movement. Our results indicate that the combination of MARCOS and sparse sampling fMRI is feasible for the detection of lower limb motor related supraspinal activation. Activation of the anterior cingulate and medial frontal areas suggests motor response inhibition during passive movement in healthy participants. Our results are of relevance for understanding the neural mechanisms underlying gait in the healthy. PMID:25389396

  6. Invisible Brain: Knowledge in Research Works and Neuron Activity

    PubMed Central

    Segev, Aviv; Curtis, Dorothy; Jung, Sukhwan; Chae, Suhyun

    2016-01-01

    If the market has an invisible hand, does knowledge creation and representation have an “invisible brain”? While knowledge is viewed as a product of neuron activity in the brain, can we identify knowledge that is outside the brain but reflects the activity of neurons in the brain? This work suggests that the patterns of neuron activity in the brain can be seen in the representation of knowledge-related activity. Here we show that the neuron activity mechanism seems to represent much of the knowledge learned in the past decades based on published articles, in what can be viewed as an “invisible brain” or collective hidden neural networks. Similar results appear when analyzing knowledge activity in patents. Our work also tries to characterize knowledge increase as neuron network activity growth. The results propose that knowledge-related activity can be seen outside of the neuron activity mechanism. Consequently, knowledge might exist as an independent mechanism. PMID:27439199

  7. Sustained NMDA receptor hypofunction induces compromised neural systems integration and schizophrenia-like alterations in functional brain networks.

    PubMed

    Dawson, Neil; Xiao, Xiaolin; McDonald, Martin; Higham, Desmond J; Morris, Brian J; Pratt, Judith A

    2014-02-01

    Compromised functional integration between cerebral subsystems and dysfunctional brain network organization may underlie the neurocognitive deficits seen in psychiatric disorders. Applying topological measures from network science to brain imaging data allows the quantification of complex brain network connectivity. While this approach has recently been used to further elucidate the nature of brain dysfunction in schizophrenia, the value of applying this approach in preclinical models of psychiatric disease has not been recognized. For the first time, we apply both established and recently derived algorithms from network science (graph theory) to functional brain imaging data from rats treated subchronically with the N-methyl-D-aspartic acid (NMDA) receptor antagonist phencyclidine (PCP). We show that subchronic PCP treatment induces alterations in the global properties of functional brain networks akin to those reported in schizophrenia. Furthermore, we show that subchronic PCP treatment induces compromised functional integration between distributed neural systems, including between the prefrontal cortex and hippocampus, that have established roles in cognition through, in part, the promotion of thalamic dysconnectivity. We also show that subchronic PCP treatment promotes the functional disintegration of discrete cerebral subsystems and also alters the connectivity of neurotransmitter systems strongly implicated in schizophrenia. Therefore, we propose that sustained NMDA receptor hypofunction contributes to the pathophysiology of dysfunctional brain network organization in schizophrenia.

  8. Altered resting-state functional activity in posttraumatic stress disorder: A quantitative meta-analysis

    PubMed Central

    Wang, Ting; Liu, Jia; Zhang, Junran; Zhan, Wang; Li, Lei; Wu, Min; Huang, Hua; Zhu, Hongyan; Kemp, Graham J.; Gong, Qiyong

    2016-01-01

    Many functional neuroimaging studies have reported differential patterns of spontaneous brain activity in posttraumatic stress disorder (PTSD), but the findings are inconsistent and have not so far been quantitatively reviewed. The present study set out to determine consistent, specific regional brain activity alterations in PTSD, using the Effect Size Signed Differential Mapping technique to conduct a quantitative meta-analysis of resting-state functional neuroimaging studies of PTSD that used either a non-trauma (NTC) or a trauma-exposed (TEC) comparison control group. Fifteen functional neuroimaging studies were included, comparing 286 PTSDs, 203 TECs and 155 NTCs. Compared with NTC, PTSD patients showed hyperactivity in the right anterior insula and bilateral cerebellum, and hypoactivity in the dorsal medial prefrontal cortex (mPFC); compared with TEC, PTSD showed hyperactivity in the ventral mPFC. The pooled meta-analysis showed hypoactivity in the posterior insula, superior temporal, and Heschl’s gyrus in PTSD. Additionally, subgroup meta-analysis (non-medicated subjects vs. NTC) identified abnormal activation in the prefrontal-limbic system. In meta-regression analyses, mean illness duration was positively associated with activity in the right cerebellum (PTSD vs. NTC), and illness severity was negatively associated with activity in the right lingual gyrus (PTSD vs. TEC). PMID:27251865

  9. Altered functional brain connectivity in a non-clinical sample of young adults with attention-deficit/hyperactivity disorder.

    PubMed

    Cocchi, Luca; Bramati, Ivanei E; Zalesky, Andrew; Furukawa, Emi; Fontenelle, Leonardo F; Moll, Jorge; Tripp, Gail; Mattos, Paulo

    2012-12-05

    Attention-deficit/hyperactivity disorder (ADHD) is characterized by symptoms of inattention and hyperactivity/impulsivity that often persist in adulthood. There is a growing consensus that ADHD is associated with abnormal function of diffuse brain networks, but such alterations remain poorly characterized. Using resting-state functional magnetic resonance imaging, we characterized multivariate (complex network measures), bivariate (network-based statistic), and univariate (regional homogeneity) properties of brain networks in a non-clinical, drug-naive sample of high-functioning young men and women with ADHD (nine males, seven females) and a group of matched healthy controls. Data from our sample allowed the isolation of intrinsic functional connectivity alterations specific to ADHD diagnosis and symptoms that are not related to developmental delays, general cognitive dysfunction, or history of medication use. Multivariate results suggested that frontal, temporal, and occipital cortices were abnormally connected locally as well as with the rest of the brain in individuals with ADHD. Results from the network-based statistic support and extend multivariate results by isolating two brain networks comprising regions between which inter-regional connectivity was significantly altered in the ADHD group; namely, a frontal amygdala-occipital network and a frontal temporal-occipital network. Brain behavior correlations further highlighted the key role of altered orbitofrontal-temporal and frontal-amygdala connectivity for symptoms of inattention and hyperactivity/impulsivity. All univariate properties were similar between groups. Taken together, results from this study show that the diagnosis and the two main symptom dimensions of ADHD are related to altered intrinsic connectivity in orbitofrontal-temporal-occipital and fronto-amygdala-occipital networks. Accordingly, our findings highlight the importance of extending the conceptualization of ADHD beyond segregated fronto

  10. Thalidomide combined with irradiation alters the activity of two proteases.

    PubMed

    Şimşek, Ece; Aydemir, Esra; Korcum, Aylin Fidan; Fişkın, Kayahan

    2015-02-01

    The aim of the present study was to investigate the effects of thalidomide, a drug known for its anti‑angiogenic and antitumor properties, at its cytotoxic dose previously determined as 40 µg/ml (according to four cytotoxic test results). The effect of the drug alone and in combination with radiotherapy using Cobalt 60 (60Co) at 45 Gy on the enzymatic activity of substance‑P degrading A disintegrin and metalloproteinase (ADAM)10 and neprilysin (NEP) was investigated in the mouse breast cancer cell lines 4T1 and 4T1 heart metastases post‑capsaicin (4THMpc). Thalidomide (40 µg/ml) exerted differing effects on the activities of ADAM10 and NEP enzymes. In 4T1 cells, 40 µg/ml thalidomide alone did not alter ADAM10 enzyme activity. 60Co irradiation at 45 Gy alone caused a 42% inhibition in ADAM10 activity, however, the inhibition increased to 89% when combined therapy was used. By contrast, in the 4THMpc cell line, 40 µg/ml thalidomide alone induced a 66.6% increase in ADAM10 enzyme activity. Radiotherapy alone and thalidomide with 60Co combined therapy caused a 33.3 and 40% inhibition of ADAM10 activity, respectively. In 4T1 cells, thalidomide alone caused a 40.9% increase in NEP activity. Radiation therapy alone or in combination with the drug caused a 40.7% increase in NEP activity. In more aggressive 4THMpc cells, thalidomide alone caused a 26.6% increase in NEP activity. Radiotherapy alone and combined therapy caused a 33.3 and 37% increase in enzyme activity, respectively. To the best of our knowledge, the present study is the first to demonstrate that thalidomide alone or in combination with radiotherapy exhibits significant cytotoxic effects on 4T1 and 4THMpc mouse breast cancer cell lines indicating that this drug affects the enzymatic activity of ADAM10 and NEP in vitro.

  11. Brain-Wide Insulin Resistance, Tau Phosphorylation Changes, and Hippocampal Neprilysin and Amyloid-β Alterations in a Monkey Model of Type 1 Diabetes

    PubMed Central

    Morales-Corraliza, Jose; Wong, Harrison; Mazzella, Matthew J.; Che, Shaoli; Lee, Sang Han; Petkova, Eva; Wagner, Janice D.; Hemby, Scott E.; Ginsberg, Stephen D.

    2016-01-01

    Epidemiological findings suggest that diabetic individuals are at a greater risk for developing Alzheimer's disease (AD). To examine the mechanisms by which diabetes mellitus (DM) may contribute to AD pathology in humans, we examined brain tissue from streptozotocin-treated type 1 diabetic adult male vervet monkeys receiving twice-daily exogenous insulin injections for 8–20 weeks. We found greater inhibitory phosphorylation of insulin receptor substrate 1 in each brain region examined of the diabetic monkeys when compared with controls, consistent with a pattern of brain insulin resistance that is similar to that reported in the human AD brain. Additionally, a widespread increase in phosphorylated tau was seen, including brain areas vulnerable in AD, as well as relatively spared structures, such as the cerebellum. An increase in active ERK1/2 was also detected, consistent with DM leading to changes in tau-kinase activity broadly within the brain. In contrast to these widespread changes, we found an increase in soluble amyloid-β (Aβ) levels that was restricted to the temporal lobe, with the greatest increase seen in the hippocampus. Consistent with this localized Aβ increase, a hippocampus-restricted decrease in the protein and mRNA for the Aβ-degrading enzyme neprilysin (NEP) was found, whereas various Aβ-clearing and -degrading proteins were unchanged. Thus, we document multiple biochemical changes in the insulin-controlled DM monkey brain that can link DM with the risk of developing AD, including dysregulation of the insulin-signaling pathway, changes in tau phosphorylation, and a decrease in NEP expression in the hippocampus that is coupled with a localized increase in Aβ. SIGNIFICANCE STATEMENT Given that diabetes mellitus (DM) appears to increase the risk of developing Alzheimer's disease (AD), understanding the mechanisms by which DM promotes AD is important. We report that DM in a nonhuman primate brain leads to changes in the levels or

  12. Tumor Necrosis Factor Alpha-Induced Recruitment of Inflammatory Mononuclear Cells Leads to Inflammation and Altered Brain Development in Murine Cytomegalovirus-Infected Newborn Mice.

    PubMed

    Seleme, Maria C; Kosmac, Kate; Jonjic, Stipan; Britt, William J

    2017-04-15

    Congenital human cytomegalovirus (HCMV) infection is a significant cause of abnormal neurodevelopment and long-term neurological sequelae in infants and children. Resident cell populations of the developing brain have been suggested to be more susceptible to virus-induced cytopathology, a pathway thought to contribute to the clinical outcomes following intrauterine HCMV infection. However, recent findings in a newborn mouse model of the infection in the developing brain have indicated that elevated levels of proinflammatory mediators leading to mononuclear cell activation and recruitment could underlie the abnormal neurodevelopment. In this study, we demonstrate that treatment with tumor necrosis factor alpha (TNF-α)-neutralizing antibodies decreased the frequency of CD45(+) Ly6C(hi) CD11b(+) CCR2(+) activated myeloid mononuclear cells (MMCs) and the levels of proinflammatory cytokines in the blood and the brains of murine CMV-infected mice. This treatment also normalized neurodevelopment in infected mice without significantly impacting the level of virus replication. These results indicate that TNF-α is a major component of the inflammatory response associated with altered neurodevelopment that follows murine CMV infection of the developing brain and that a subset of peripheral blood myeloid mononuclear cells represent a key effector cell population in this model of virus-induced inflammatory disease of the developing brain.IMPORTANCE Congenital human cytomegalovirus (HCMV) infection is the most common viral infection of the developing human fetus and can result in neurodevelopmental sequelae. Mechanisms of disease leading to neurodevelopmental deficits in infected infants remain undefined, but postulated pathways include loss of neuronal progenitor cells, damage to the developing vascular system of the brain, and altered cellular positioning. Direct virus-mediated cytopathic effects cannot explain the phenotypes of brain damage in most infected infants. Using a

  13. Does pediatric post-traumatic stress disorder alter the brain? Systematic review and meta-analysis of structural and functional magnetic resonance imaging studies.

    PubMed

    Milani, Ana Carolina C; Hoffmann, Elis V; Fossaluza, Victor; Jackowski, Andrea P; Mello, Marcelo F

    2017-03-01

    Several studies have recently demonstrated that the volumes of specific brain regions are reduced in children and adolescents with post-traumatic stress disorder (PTSD) compared with those of healthy controls. Our study investigated the potential association between early traumatic experiences and altered brain regions and functions. We conducted a systematic review of the scientific literature regarding functional magnetic resonance imaging and a meta-analysis of structural magnetic resonance imaging studies that investigated cerebral region volumes in pediatric patients with PTSD. We searched for articles from 2000 to 2014 in the PsycINFO, PubMed, Medline, Lilacs, and ISI (Web of Knowledge) databases. All data regarding the amygdala, hippocampus, corpus callosum, brain, and intracranial volumes that fit the inclusion criteria were extracted and combined in a meta-analysis that assessed differences between groups. The meta-analysis found reduced total corpus callosum areas and reduced total cerebral and intracranial volumes in the patients with PTSD. The total hippocampus (left and right hippocampus) and gray matter volumes of the amygdala and frontal lobe were also reduced, but these differences were not significant. The functional studies revealed differences in brain region activation in response to stimuli in the post-traumatic stress symptoms/PTSD group. Our results confirmed that the pediatric patients with PTSD exhibited structural and functional brain abnormalities and that some of the abnormalities occurred in different brain regions than those observed in adults.

  14. Alterations in fear conditioning and amygdalar activation following chronic wheel running in rats.

    PubMed

    Burghardt, Paul R; Pasumarthi, Ravi K; Wilson, Marlene A; Fadel, Jim

    2006-06-01

    Several convergent lines of evidence point to the amygdala as a key site of plasticity underlying most forms of fear conditioning. Studies have shown that chronic physical activity, such as wheel running, can alter learning in a variety of contexts, including aversive conditioning. The ability of chronic wheel running (WR) to alter both behavioral correlates of fear conditioning and indices of amygdalar activation, however, has not been simultaneously assessed. Here, rats were given constant access to either free-turning or--as a control--locked (LC) running wheels in their home cages. After 8 weeks of housing under these conditions, animals were exposed to a series of shocks in a separate testing chamber. Twenty-four hours later, the animals were returned to the shock chamber and freezing behavior was measured as an indicator of contextual fear conditioning. The animals were then sacrificed and their brains processed for immunohistochemical detection of Fos to assess patterns of putative neuronal activation. WR rats spent significantly more time freezing than their LC counterparts upon return to the shock-paired context. The enhanced conditioned freezing response was most pronounced in animals showing high levels of nightly wheel running activity. WR animals also had significantly higher levels of neuronal activation, as indicated by Fos expression in the central nucleus of the amygdala, but less activation in the basolateral nucleus, compared to sedentary controls. These data demonstrate the ability of chronic physical activity to alter contextual fear conditioning and implicate the amygdala as a potential site of plasticity underlying this phenomenon.

  15. Alpha- and gamma- tocopherol prevent age-related transcriptional alterations in the heart and brain of mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To investigate the global effects of vitamin E supplementation on aging, we used high density oligonucleotide arrays to measure transcriptional alterations in the heart and brain (neocortex) of 30-month-old B6C3F1 mice supplemented with alpha- and gamma-tocopherol since middle age (15 months). Gene ...

  16. Nicotine Increases Codeine Analgesia Through the Induction of Brain CYP2D and Central Activation of Codeine to Morphine.

    PubMed

    McMillan, Douglas M; Tyndale, Rachel F

    2015-06-01

    CYP2D metabolically activates codeine to morphine, which is required for codeine analgesia. Permeability across the blood-brain barrier, and active efflux, suggests that initial morphine in the brain after codeine is due to brain CYP2D metabolism. Human CYP2D is higher in the brains, but not in the livers, of smokers and 7-day nicotine treatment induces rat brain, but not hepatic, CYP2D. The role of nicotine-induced rat brain CYP2D in the central metabolic activation of peripherally administered codeine and resulting analgesia was investigated. Rats received 7-day nicotine (1 mg/kg subcutaneously) and/or a single propranolol (CYP2D mechanism-based inhibitor; 20 μg intracerebroventricularly) pretreatment, and then were tested for analgesia and drug levels following codeine (20 mg/kg intraperitoneally) or morphine (3.5 mg/kg intraperitoneally), matched for peak analgesia. Nicotine increased codeine analgesia (1.59X AUC(0-30 min) vs vehicle; p<0.001), while propranolol decreased analgesia (0.56X; p<0.05); co-pretreatment was similar to vehicle controls (1.23X; p>0.1). Nicotine increased, while propranolol decreased, brain, but not plasma, morphine levels, and analgesia correlated with brain (p<0.02), but not plasma (p>0.4), morphine levels after codeine. Pretreatments did not alter baseline or morphine analgesia. Here we show that brain CYP2D alters drug response despite the presence of substantial first-pass metabolism of codeine and further that nicotine induction of brain CYP2D increases codeine response in vivo. Thus variation in brain CYP2D activity, due to genetics or environment, may contribute to individual differences in response to centrally acting substrates. Exposure to nicotine may increase central drug metabolism, not detected peripherally, contributing to altered drug efficacy, onset time, and/or abuse liability.

  17. Is meditation associated with altered brain structure? A systematic review and meta-analysis of morphometric neuroimaging in meditation practitioners.

    PubMed

    Fox, Kieran C R; Nijeboer, Savannah; Dixon, Matthew L; Floman, James L; Ellamil, Melissa; Rumak, Samuel P; Sedlmeier, Peter; Christoff, Kalina

    2014-06-01

    Numerous studies have begun to address how the brain's gray and white matter may be shaped by meditation. This research is yet to be integrated, however, and two fundamental questions remain: Is meditation associated with altered brain structure? If so, what is the magnitude of these differences? To address these questions, we reviewed and meta-analyzed 123 brain morphology differences from 21 neuroimaging studies examining ∼300 meditation practitioners. Anatomical likelihood estimation (ALE) meta-analysis found eight brain regions consistently altered in meditators, including areas key to meta-awareness (frontopolar cortex/BA 10), exteroceptive and interoceptive body awareness (sensory cortices and insula), memory consolidation and reconsolidation (hippocampus), self and emotion regulation (anterior and mid cingulate; orbitofrontal cortex), and intra- and interhemispheric communication (superior longitudinal fasciculus; corpus callosum). Effect size meta-analysis (calculating 132 effect sizes from 16 studies) suggests a global 'medium' effect size (Cohen's d¯=0.46; r¯=.19). Publication bias and methodological limitations are strong concerns, however. Further research using rigorous methods is required to definitively link meditation practice to altered brain morphology.

  18. Network-dependent modulation of brain activity during sleep.

    PubMed

    Watanabe, Takamitsu; Kan, Shigeyuki; Koike, Takahiko; Misaki, Masaya; Konishi, Seiki; Miyauchi, Satoru; Miyahsita, Yasushi; Masuda, Naoki

    2014-09-01

    Brain activity dynamically changes even during sleep. A line of neuroimaging studies has reported changes in functional connectivity and regional activity across different sleep stages such as slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. However, it remains unclear whether and how the large-scale network activity of human brains changes within a given sleep stage. Here, we investigated modulation of network activity within sleep stages by applying the pairwise maximum entropy model to brain activity obtained by functional magnetic resonance imaging from sleeping healthy subjects. We found that the brain activity of individual brain regions and functional interactions between pairs of regions significantly increased in the default-mode network during SWS and decreased during REM sleep. In contrast, the network activity of the fronto-parietal and sensory-motor networks showed the opposite pattern. Furthermore, in the three networks, the amount of the activity changes throughout REM sleep was negatively correlated with that throughout SWS. The present findings suggest that the brain activity is dynamically modulated even in a sleep stage and that the pattern of modulation depends on the type of the large-scale brain networks.

  19. [Hydrazine derivative modification of the activity of brain mitochondrial monoamine oxidases].

    PubMed

    Kalninia, I E; Baumanas, E A; Kaĭrane, Ch B; Gorkin, V Z

    1981-01-01

    Treatment of bovine brain stem mitochondria with hydrazine derivatives, which inhibited the monoamine oxidase activity (substrate: 5-hydroxytryptamine), was accompanied by appearance of the properties to deaminate histamine and cadaverine at a high rate. The same phenomenon was observed in vivo after treatment of mice with the hydrazine derivatives. The dramatic increase in histamine deaminating activity in brain was accompanied by a decrease in the tissue concentration of histamine. The hydrazine derivatives are considered as prooxidants stimulating via a free-radical mechanism lipid peroxidation in methyloleate solutions and in biomembranes (ref. 5) and causing qualitative alteration (transformation) in catalytic properties of monoamine oxidases of the tyre A, which acquire the histamine deaminating activity. A certain correlation was noted between the prooxidant effect of the hydrazine derivatives and the modification of catalytic properties of the membrane bound monoamine oxidases of brain mitochondria in vitro and in vivo.

  20. Nylon Wool Purification Alters the Activation of T Cells

    PubMed Central

    Wohler, Jillian E.; Barnum, Scott R.

    2009-01-01

    Purification of lymphocytes, particularly T cells, is commonly performed using nylon wool. This enrichment method selectively retains B cells and some myeloid cells allowing a significantly more pure T cell population to flow through a nylon wool column. T cells purified in this fashion are assumed to be unaltered and functionally naïve, however some studies have suggested aberrant in vitro T cell responses after nylon wool treatment. We found that nylon wool purification significantly altered T cell proliferation, expression of activation markers and production of cytokines. Our results suggest that nylon wool treatment modifies T cell activation responses and that caution should be used when choosing this purification method. PMID:18952296

  1. Neonatal exposure to amphetamine alters social affiliation and central dopamine activity in adult male prairie voles.

    PubMed

    Fukushiro, D F; Olivera, A; Liu, Y; Wang, Z

    2015-10-29

    The prairie vole (Microtus ochrogaster) is a socially monogamous rodent species that forms pair bonds after mating. Recent data have shown that amphetamine (AMPH) is rewarding to prairie voles as it induces conditioned place preferences. Further, repeated treatment with AMPH impairs social bonding in adult prairie voles through a central dopamine (DA)-dependent mechanism. The present study examined the effects of neonatal exposure to AMPH on behavior and central DA activity in adult male prairie voles. Our data show that neonatal exposure to AMPH makes voles less social in an affiliation test during adulthood, but does not affect animals' locomotor activity and anxiety-like behavior. Neonatal exposure to AMPH also increases the levels of tyrosine hydroxylase (TH) and DA transporter (DAT) mRNA expression in the ventral tegmental area (VTA) in the brain, indicating an increase in central DA activity. As DA has been implicated in AMPH effects on behavioral and cognitive functions, altered DA activity in the vole brain may contribute to the observed changes in social behavior.

  2. Tryptophan overloading activates brain regions involved with cognition, mood and anxiety.

    PubMed

    Silva, Luana C A; Viana, Milena B; Andrade, José S; Souza, Melyssa A; Céspedes, Isabel C; D'Almeida, Vânia

    2017-02-16

    Tryptophan is the only precursor of serotonin and mediates serotonergic activity in the brain. Previous studies have shown that the administration of tryptophan or tryptophan depletion significantly alters cognition, mood and anxiety. Nevertheless, the neurobiological alterations that follow these changes have not yet been fully investigated. The aim of this study was to verify the effects of a tryptophan-enriched diet on immunoreactivity to Fos-protein in the rat brain. Sixteen male Wistar rats were distributed into two groups that either received standard chow diet or a tryptophan-enriched diet for a period of thirty days. On the morning of the 31st day, animals were euthanized and subsequently analyzed for Fos-immunoreactivity (Fos-ir) in the dorsal and median raphe nuclei and in regions that receive serotonin innervation from these two brain areas. Treatment with a tryptophan-enriched diet increased Fos-ir in the prefrontal cortex, nucleus accumbens, paraventricular hypothalamus, arcuate and ventromedial hypothalamus, dorsolateral and dorsomedial periaqueductal grey and dorsal and median raphe nucleus. These observations suggest that the physiological and behavioral alterations that follow the administration of tryptophan are associated with the activation of brain regions that regulate cognition and mood/anxiety-related responses.

  3. Deletion of Rictor in brain and fat alters peripheral clock gene expression and increases blood pressure.

    PubMed

    Drägert, Katja; Bhattacharya, Indranil; Pellegrini, Giovanni; Seebeck, Petra; Azzi, Abdelhalim; Brown, Steven A; Georgiopoulou, Stavroula; Held, Ulrike; Blyszczuk, Przemyslaw; Arras, Margarete; Humar, Rok; Hall, Michael N; Battegay, Edouard; Haas, Elvira

    2015-08-01

    The mammalian target of rapamycin complex 2 (mTORC2) contains the essential protein RICTOR and is activated by growth factors. mTORC2 in adipose tissue contributes to the regulation of glucose and lipid metabolism. In the perivascular adipose tissue, mTORC2 ensures normal vascular reactivity by controlling expression of inflammatory molecules. To assess whether RICTOR/mTORC2 contributes to blood pressure regulation, we applied a radiotelemetry approach in control and Rictor knockout (Rictor(aP2KO)) mice generated using adipocyte protein-2 gene promoter-driven CRE recombinase expression to delete Rictor. The 24-hour mean arterial pressure was increased in Rictor(aP2KO) mice, and the physiological decline in mean arterial pressure during the dark period was impaired. In parallel, heart rate and locomotor activity were elevated during the dark period with a pattern similar to blood pressure changes. This phenotype was associated with mild cardiomyocyte hypertrophy, decreased cardiac natriuretic peptides, and their receptor expression in adipocytes. Moreover, clock gene expression was reduced or phase-shifted in perivascular adipose tissue. No differences in clock gene expression were observed in the master clock suprachiasmatic nucleus, although Rictor gene expression was also lower in brain of Rictor(aP2KO) mice. Thus, this study highlights the importance of RICTOR/mTORC2 for interactions between vasculature, adipocytes, and brain to tune physiological outcomes, such as blood pressure and locomotor activity.

  4. Epigenetic alterations in the brain associated with HIV-1 infection and methamphetamine dependence.

    PubMed

    Desplats, Paula; Dumaop, Wilmar; Cronin, Peter; Gianella, Sara; Woods, Steven; Letendre, Scott; Smith, David; Masliah, Eliezer; Grant, Igor

    2014-01-01

    HIV involvement of the CNS continues to be a significant problem despite successful use of combination antiretroviral therapy (cART). Drugs of abuse can act in concert with HIV proteins to damage glia and neurons, worsening the neurotoxicity caused by HIV alone. Methamphetamine (METH) is a highly addictive psychostimulant drug, abuse of which has reached epidemic proportions and is associated with high-risk sexual behavior, increased HIV transmission, and development of drug resistance. HIV infection and METH dependence can have synergistic pathological effects, with preferential involvement of frontostriatal circuits. At the molecular level, epigenetic alterations have been reported for both HIV-1 infection and drug abuse, but the neuropathological pathways triggered by their combined effects are less known. We investigated epigenetic changes in the brain associated with HIV and METH. We analyzed postmortem frontal cortex tissue from 27 HIV seropositive individuals, 13 of which had a history of METH dependence, in comparison to 14 cases who never used METH. We detected changes in the expression of DNMT1, at mRNA and protein levels, that resulted in the increase of global DNA methylation. Genome-wide profiling of DNA methylation in a subset of cases, showed differential methylation on genes related to neurodegeneration; dopamine metabolism and transport; and oxidative phosphorylation. We provide evidence for the synergy of HIV and METH dependence on the patterns of DNA methylation on the host brain, which results in a distinctive landscape for the comorbid condition. Importantly, we identified new epigenetic targets that might aid in understanding the aggravated neurodegenerative, cognitive, motor and behavioral symptoms observed in persons living with HIV and addictions.

  5. Reorganization of Visual Callosal Connections Following Alterations of Retinal Input and Brain Damage

    PubMed Central

    Restani, Laura; Caleo, Matteo

    2016-01-01

    Vision is a very important sensory modality in humans. Visual disorders are numerous and arising from diverse and complex causes. Deficits in visual function are highly disabling from a social point of view and in addition cause a considerable economic burden. For all these reasons there is an intense effort by the scientific community to gather knowledge on visual deficit mechanisms and to find possible new strategies for recovery and treatment. In this review, we focus on an important and sometimes neglected player of the visual function, the corpus callosum (CC). The CC is the major white matter structure in the brain and is involved in information processing between the two hemispheres. In particular, visual callosal connections interconnect homologous areas of visual cortices, binding together the two halves of the visual field. This interhemispheric communication plays a significant role in visual cortical output. Here, we will first review the essential literature on the physiology of the callosal connections in normal vision. The available data support the view that the callosum contributes to both excitation and inhibition to the target hemisphere, with a dynamic adaptation to the strength of the incoming visual input. Next, we will focus on data showing how callosal connections may sense visual alterations and respond to the classical paradigm for the study of visual plasticity, i.e., monocular deprivation (MD). This is a prototypical example of a model for the study of callosal plasticity in pathological conditions (e.g., strabismus and amblyopia) characterized by unbalanced input from the two eyes. We will also discuss the findings of callosal alterations in blind subjects. Noteworthy, we will discuss data showing that inter-hemispheric transfer mediates recovery of visual responsiveness following cortical damage. Finally, we will provide an overview of how callosal projections dysfunction could contribute to pathologies such as neglect and occipital

  6. Chronic alcohol drinking alters neuronal dendritic spines in the brain reward center nucleus accumbens.

    PubMed

    Zhou, Feng C; Anthony, Bruce; Dunn, Kenneth W; Lindquist, W Brent; Xu, Zao C; Deng, Ping

    2007-02-23

    Alcohol is known to affect glutamate transmission. However, how chronic alcohol affects the synaptic structure mediating glutamate transmission is unknown. Repeated alcohol exposure in a subject with familial alcoholic history often leads to alcohol addiction. The current study adopts alcohol-preferring rats, which are known to develop high drinking. Two-photon microscopy analysis indicates that chronic alcohol of 14 weeks either, under continuous alcohol (C-Alc) or with repeated deprivation (RD-Alc), causes dysmorphology--thickened, beaded, and disoriented dendrites that are reminiscent of reactive astrocytes--in a subpopulation of medium spiny neurons. The density of dendritic spines was found differentially lower in the nucleus accumbens of RD-Alc and C-Alc groups as compared with those of Water groups. Large-sized spines and multiple-headed spines were increased in the RD-Alc group. The NMDA receptor subunit NR1 proteins, as analyzed with Western blot, were upregulated in C-Alc, but not in RD-Alc. The upregulated NMDA receptor subunits of NR1 however, are predominantly a splice variant isoform with truncated exon 21, which is required for membrane-bound trafficking or anchoring into a spine synaptic site. These maladaptations may contribute to the transformation of spines. The changes, in density and head-size of spines and the corresponding NMDA receptors, demonstrated an alteration of microcircuitry for glutamate reception. The current study demonstrates for the first time that chronic alcohol exposure causes structural alteration of dendrites and their spines in the key reward brain region in animals that have a genetic background leading to alcohol addiction.

  7. Experimental human endotoxemia enhances brain activity during social cognition.

    PubMed

    Kullmann, Jennifer S; Grigoleit, Jan-Sebastian; Wolf, Oliver T; Engler, Harald; Oberbeck, Reiner; Elsenbruch, Sigrid; Forsting, Michael; Schedlowski, Manfred; Gizewski, Elke R

    2014-06-01

    Acute peripheral inflammation with corresponding increases in peripheral cytokines affects neuropsychological functions and induces depression-like symptoms. However, possible effects of increased immune responses on social cognition remain unknown. Therefore, this study investigated the effects of experimentally induced acute inflammation on performance and neural responses during a social cognition task assessing Theory of Mind (ToM) ability. In this double-blind randomized crossover functional magnetic resonance imaging study, 18 healthy right-handed male volunteers received an injection of bacterial lipopolysaccharide (LPS; 0.4 ng/kg) or saline, respectively. Plasma levels of pro- and anti-inflammatory cytokines as well as mood ratings were analyzed together with brain activation during a validated ToM task (i.e. Reading the Mind in the Eyes Test). LPS administration induced pronounced transient increases in pro- (IL-6, TNF-α) and anti-inflammatory (IL-10, IL-1ra) cytokines as well as decreases in mood. Social cognition performance was not affected by acute inflammation. However, altered neural activity was observed during the ToM task after LPS administration, reflected by increased responses in the fusiform gyrus, temporo-parietal junction, superior temporal gyrus and precuneus. The increased task-related neural responses in the LPS condition may reflect a compensatory strategy or a greater social cognitive processing as a function of sickness.

  8. Altered expression of tight junction proteins and matrix metalloproteinases in thiamine-deficient mouse brain.

    PubMed

    Beauchesne, Elizabeth; Desjardins, Paul; Hazell, Alan S; Butterworth, Roger F

    2009-09-01

    Wernicke's encephalopathy (WE) in humans is a metabolic disorder caused by thiamine deficiency (TD). In both humans and experimental animals, TD leads to selective neuronal cell death in diencephalic and brainstem structures. Neuropathologic features of WE include petechial hemorrhagic lesions, and blood-brain barrier (BBB) breakdown has been suggested to play an important role in the pathogenesis of TD. The goal of the present study was to examine expression of the tight junction (TJ) protein occludin, its associated scaffolding proteins zona occludens (ZO-1 and ZO-2), and to measure matrix metalloproteinase (MMP) levels as a function of regional BBB permeability changes in thiamine-deficient mice. TD was induced in 12-week-old male C57Bl/6 mice by feeding a thiamine-deficient diet and administration of the central thiamine antagonist pyrithiamine. BBB permeability was measured by IgG extravasation; expression of occludin, ZO-1 and ZO-2 was measured by Western blot analysis and RT-PCR, structural integrity of the BBB was assessed using occludin and ZO-1 immunostaining, and MMPs levels were measured by gelatin zymography and immunohistochemistry. Studies were performed in vulnerable (medial thalamus) versus spared (frontal cortex) regions of the brain. Hemorrhagic lesions, selective increases in brain IgG extravasation, a concomitant loss in protein expression of occludin, ZO-1 and ZO-2, as well as decreased and disrupted patterns of occludin and ZO-1 immunostaining were observed in the medial thalamus of thiamine-deficient mice. MMP-9 levels were also selectively increased in the medial thalamus of these animals, and were found to be localized in the vascular endothelium, as well as in cells with an apparent polymorphonuclear morphology. No changes of TJ gene expression were observed. These results indicate that alterations in TJ proteins occur in TD, and offer a plausible explanation for the selective increase in BBB permeability in thiamine-deficient animals

  9. Neurochemical alterations in lemon shark (Negaprion brevirostris) brains in association with brevetoxin exposure.

    PubMed

    Nam, Dong-Ha; Adams, Douglas H; Flewelling, Leanne J; Basu, Niladri

    2010-09-01

    Brevetoxins are persistent, bioaccumulative, lipophilic polyether neurotoxins synthesized by Karenia brevis, a harmful algal bloom (HAB) dinoflagellate. Although some marine organisms accumulate potentially harmful levels of brevetoxins, little is known about neurotoxic effects in wild populations. Here, tissue (i.e., liver, kidney, muscle, intestine, gill, brain) brevetoxin levels (as ng PbTx-3 eq/g) and four neurochemical biomarkers (monoamine oxidase, MAO; cholinesterase, ChE; muscarinic cholinergic receptor, mAChR; N-methyl-d-aspartic acid receptor, NMDAR) were compared between eleven lemon sharks collected during a K. brevis bloom and eighteen lemon sharks not exposed to a bloom (controls) in a case-control manner. Brevetoxin levels in tissues were significantly higher in HAB-exposed sharks when compared to controls, and tissue levels (e.g., 277-3112 ng/g in livers, 429-2833 ng/g in gills) in HAB-exposed sharks were comparable to levels detected in a shark (e.g., 1223 ng/g in liver, 930 ng/g in gill) that died presumably of toxin exposure. Further, there were significant correlations between brain brevetoxin levels and ChE activity (r=-0.41; p<0.05), MAO activity (r=-0.37; p<0.05), mAChR levels (r=0.55; p<0.01), and NMDAR levels (r=-0.49; p<0.01). There were no relationships between neurochemical biomarkers and metals (total mercury, methylmercury, selenium). Overall, these results in tissues from free-ranging lemon sharks indicate that ecologically relevant exposures to brevetoxins may cause significant changes in brain neurochemistry. As disruptions to neurochemistry precede structural and functional damage to the nervous system, these results suggest that relevant exposures to HABs may be causing sub-clinical effects in lemon sharks and raise further questions about the ecological and physiological impacts of HABs on marine biota.

  10. High fat diet produces brain insulin resistance, synaptodendritic abnormalities and altered behavior in mice.

    PubMed

    Arnold, Steven E; Lucki, Irwin; Brookshire, Bethany R; Carlson, Gregory C; Browne, Caroline A; Kazi, Hala; Bang, Sookhee; Choi, Bo-Ran; Chen, Yong; McMullen, Mary F; Kim, Sangwon F

    2014-07-01

    Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17days or a moderate high fat diet (HFD, 45% kcal by fat) for 8weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3β with ex-vivo insulin stimulation. Importantly, we found that expression of brain IPMK, which is necessary for mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD mouse hippocampus exhibited increased expression of serine-phosphorylated insulin receptor substrate 1 (IRS1-pS(616)), a marker of insulin resistance, as well as decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic densities, and synaptopodin, an actin-associated protein enriched in spine apparatuses. Spatial working memory was impaired as assessed by decreased spontaneous alternation in a T-maze. These findings indicate that HFD is associated with telencephalic insulin resistance and deleterious effects on synaptic integrity and cognitive behaviors.

  11. High Fat Diet Produces Brain Insulin Resistance, Synaptodendritic Abnormalities and Altered Behavior in Mice

    PubMed Central

    Arnold, Steven E.; Lucki, Irwin; Brookshire, Bethany R.; Carlson, Gregory C.; Browne, Carolyn A.; Kazi, Hala; Bang, Sookhee; Choi, Bo-Ran; Chen, Yong; McMullen, Mary F.; Kim, Sangwon F.

    2014-01-01

    Insulin resistance and other features of the metabolic syndrome are increasingly recognized for their effects on cognitive health. To ascertain mechanisms by which this occurs, we fed mice a very high fat diet (60% kcal by fat) for 17 days or a moderate high fat diet (HFD, 45% kcal by fat) for 8 weeks and examined changes in brain insulin signaling responses, hippocampal synaptodendritic protein expression, and spatial working memory. Compared to normal control diet mice, cerebral cortex tissues of HFD mice were insulin-resistant as evidenced by failed activation of Akt, S6 and GSK3β with ex-vivo insulin stimulation. Importantly, we found that expression of brain IPMK, which is necessary for mTOR/Akt signaling, remained decreased in HFD mice upon activation of AMPK. HFD mouse hippocampus exhibited increased expression of serine-phosphorylated insulin receptor substrate 1 (IRS1-pS616), a marker of insulin resistance, as well as decreased expression of PSD-95, a scaffolding protein enriched in post-synaptic densities, and synaptopodin, an actin-associated protein enriched in spine apparatuses. Spatial working memory was impaired as assessed by decreased spontaneous alternation in a T-maze. These findings indicate that HFD is associated with telencephalic insulin resistance and deleterious effects on synaptic integrity and cognitive behaviors. PMID:24686304

  12. Optical imaging of neural and hemodynamic brain activity

    NASA Astrophysics Data System (ADS)

    Schei, Jennifer Lynn

    Optical imaging technologies can be used to record neural and hemodynamic activity. Neural activity elicits physiological changes that alter the optical tissue properties. Specifically, changes in polarized light are concomitant with neural depolarization. We measured polarization changes from an isolated lobster nerve during action potential propagation using both reflected and transmitted light. In transmission mode, polarization changes were largest throughout the center of the nerve, suggesting that most of the optical signal arose from the inner nerve bundle. In reflection mode, polarization changes were largest near the edges, suggesting that most of the optical signal arose from the outer sheath. To overcome irregular cell orientation found in the brain, we measured polarization changes from a nerve tied in a knot. Our results show that neural activation produces polarization changes that can be imaged even without regular cell orientations. Neural activation expends energy resources and elicits metabolic delivery through blood vessel dilation, increasing blood flow and volume. We used spectroscopic imaging techniques combined with electrophysiological measurements to record evoked neural and hemodynamic responses from the auditory cortex of the rat. By using implantable optics, we measured responses across natural wake and sleep states, as well as responses following different amounts of sleep deprivation. During quiet sleep, evoked metabolic responses were larger compared to wake, perhaps because blood vessels were more compliant. When animals were sleep deprived, evoked hemodynamic responses were smaller following longer periods of deprivation. These results suggest that prolonged neural activity through sleep deprivation may diminish vascular compliance as indicated by the blunted vascular response. Subsequent sleep may allow vessels to relax, restoring their ability to deliver blood. These results also suggest that severe sleep deprivation or chronic

  13. Altered AMP deaminase activity may extend postmortem glycolysis.

    PubMed

    England, E M; Matarneh, S K; Scheffler, T L; Wachet, C; Gerrard, D E

    2015-04-01

    Postmortem energy metabolism drives hydrogen accumulation in muscle and results in a fairly constant ultimate pH. Extended glycolysis results in adverse pork quality and may be possible with greater adenonucleotide availability postmortem. We hypothesized that slowing adenonucleotide removal by reducing AMP deaminase activity would extend glycolysis and lower the ultimate pH of muscle. Longissimus muscle samples were incorporated into an in vitro system that mimics postmortem glycolysis with or without pentostatin, an AMP deaminase inhibitor. Pentostatin lowered ultimate pH and increased lactate and glucose 6-phosphate with time. Based on these results and that AMPK γ3(R200Q) mutated pigs (RN⁻) produce low ultimate pH pork, we hypothesized AMP deaminase abundance and activity would be lower in RN⁻ muscle than wild-type. RN⁻ muscle contained lower AMP deaminase abundance and activity. These data show that altering adenonucleotide availability postmortem can extend postmortem pH decline and suggest that AMP deaminase activity may, in part, contribute to the low ultimate pH observed in RN⁻ pork.

  14. The bile acid-sensitive ion channel (BASIC) is activated by alterations of its membrane environment.

    PubMed

    Schmidt, Axel; Lenzig, Pia; Oslender-Bujotzek, Adrienne; Kusch, Jana; Lucas, Susana Dias; Gründer, Stefan; Wiemuth, Dominik

    2014-01-01

    The bile acid-sensitive ion channel (BASIC) is a member of the DEG/ENaC family of ion channels. Channels of this family are characterized by a common structure, their physiological functions and modes of activation, however, are diverse. Rat BASIC is expressed in brain, liver and intestinal tract and activated by bile acids. The physiological function of BASIC and its mechanism of bile acid activation remain a puzzle. Here we addressed the question whether amphiphilic bile acids activate BASIC by directly binding to the channel or indirectly by altering the properties of the surrounding membrane. We show that membrane-active substances other than bile acids also affect the activity of BASIC and that activation by bile acids and other membrane-active substances is non-additive, suggesting that BASIC is sensitive for changes in its membrane environment. Furthermore based on results from chimeras between BASIC and ASIC1a, we show that the extracellular and the transmembrane domains are important for membrane sensitivity.

  15. Correspondence between resting state activity and brain gene expression

    PubMed Central

    Wang, Guang-Zhong; Belgard, T. Grant; Mao, Deng; Chen, Leslie; Berto, Stefano; Preuss, Todd M.; Lu, Hanzhang; Geschwind, Daniel H.; Konopka, Genevieve

    2015-01-01

    SUMMARY The relationship between functional brain activity and gene expression has not been fully explored in the human brain. Here, we identify significant correlations between gene expression in the brain and functional activity by comparing fractional Amplitude of Low Frequency Fluctuations (fALFF) from two independent human fMRI resting state datasets to regional cortical gene expression from a newly generated RNA-seq dataset and two additional gene expression datasets to obtain robust and reproducible correlations. We find significantly more genes correlated with fALFF than expected by chance, and identify specific genes correlated with the imaging signals in multiple expression datasets in the default mode network. Together, these data support a population-level relationship between regional steady state brain gene expression and resting state brain activity. PMID:26590343

  16. Exposure to vehicle emissions results in altered blood brain barrier permeability and expression of matrix metalloproteinases and tight junction proteins in mice

    PubMed Central

    2013-01-01

    Background Traffic-generated air pollution-exposure is associated with adverse effects in the central nervous system (CNS) in both human exposures and animal models, including neuroinflammation and neurodegeneration. While alterations in the blood brain barrier (BBB) have been implicated as a potential mechanism of air pollution-induced CNS pathologies, pathways involved have not been elucidated. Objectives To determine whether inhalation exposure to mixed vehicle exhaust (MVE) mediates alterations in BBB permeability, activation of matrix metalloproteinases (MMP) -2 and −9, and altered tight junction (TJ) protein expression. Methods Apolipoprotein (Apo) E−/− and C57Bl6 mice were exposed to either MVE (100 μg/m3 PM) or filtered air (FA) for 6 hr/day for 30 days and resulting BBB permeability, expression of ROS, TJ proteins, markers of neuroinflammation, and MMP activity were assessed. Serum from study mice was applied to an in vitro BBB co-culture model and resulting alterations in transport and permeability were quantified. Results MVE-exposed Apo E−/− mice showed increased BBB permeability, elevated ROS and increased MMP-2 and −9 activity, compared to FA controls. Additionally, cerebral vessels from MVE-exposed mice expressed decreased levels of TJ proteins, occludin and claudin-5, and increased levels of inducible nitric oxide synthase (iNOS) and interleukin (IL)-1β in the parenchyma. Serum from MVE-exposed animals also resulted in increased in vitro BBB permeability and altered P-glycoprotein transport activity. Conclusions These data indicate that inhalation exposure to traffic-generated air pollutants promotes increased MMP activity and degradation of TJ proteins in the cerebral vasculature, resulting in altered BBB permeability and expression of neuroinflammatory markers. PMID:24344990

  17. Pam (Peptidylglycine α-amidating monooxygenase) heterozygosity alters brain copper handling with region specificity

    PubMed Central

    Gaier, Eric D; Miller, Megan B; Ralle, Martina; Aryal, Dipendra; Wetsel, William C; Mains, Richard E; Eipper, Betty A

    2013-01-01

    Copper (Cu), an essential trace element present throughout the mammalian nervous system, is crucial for normal synaptic function. Neuronal handling of Cu is poorly understood. We studied the localization and expression of Atp7a, the major intracellular Cu transporter in the brain, and its relation to peptidylglycine α-amidating monooxygenase (PAM), an essential cuproenzyme and regulator of Cu homeostasis in neuroendocrine cells. Based on biochemical fractionation and immunostaining of dissociated neurons, Atp7a was enriched in postsynaptic vesicular fractions. Cu followed a similar pattern, with ~20% of total Cu in synaptosomes. A mouse model heterozygous for the Pam gene (PAM+/−) is selectively Cu deficient in the amygdala. As in cortex and hippocampus, Atp7a and PAM expression overlap in the amygdala, with highest expression in interneurons. Messenger RNA levels of Atox-1 and Atp7a, which deliver Cu to the secretory pathway, were reduced in the amygdala but not the hippocampus in PAM+/− mice, along with GABAB receptor mRNA levels. Consistent with Cu deficiency, dopamine β-monooxygenase function was impaired as evidenced by elevated dopamine metabolites in the amygdala, but not the hippocampus, of PAM+/− mice. These alterations in Cu delivery to the secretory pathway in the PAM+/− amygdala may contribute to the physiological and behavioral deficits observed. PMID:24032518

  18. Altered Amygdala Connectivity in Individuals with Chronic Traumatic Brain Injury and Comorbid Depressive Symptoms

    PubMed Central

    Han, Kihwan; Chapman, Sandra B.; Krawczyk, Daniel C.

    2015-01-01

    Depression is one of the most common psychiatric conditions in individuals with chronic traumatic brain injury (TBI). Though depression has detrimental effects in TBI and network dysfunction is a “hallmark” of TBI and depression, there have not been any prior investigations of connectivity-based neuroimaging biomarkers for comorbid depression in TBI. We utilized resting-state functional magnetic resonance imaging to identify altered amygdala connectivity in individuals with chronic TBI (8 years post-injury on average) exhibiting comorbid depressive symptoms (N = 31), relative to chronic TBI individuals having minimal depressive symptoms (N = 23). Connectivity analysis of these participant sub-groups revealed that the TBI-plus-depressive symptoms group showed relative increases in amygdala connectivity primarily in the regions that are part of the salience, somatomotor, dorsal attention, and visual networks (pvoxel < 0.01, pcluster < 0.025). Relative increases in amygdala connectivity in the TBI-plus-depressive symptoms group were also observed within areas of the limbic–cortical mood-regulating circuit (the left dorsomedial and right dorsolateral prefrontal cortices and thalamus) and the brainstem. Further analysis revealed that spatially dissociable patterns of correlation between amygdala connectivity and symptom severity according to subtypes (Cognitive and Affective) of depressive symptoms (pvoxel < 0.01, pcluster < 0.025). Taken together, these results suggest that amygdala connectivity may be a potentially effective neuroimaging biomarker for comorbid depressive symptoms in chronic TBI. PMID:26581959

  19. Revisiting Metchnikoff: Age-related alterations in microbiota-gut-brain axis in the mouse.

    PubMed

    Scott, Karen A; Ida, Masayuki; Peterson, Veronica L; Prenderville, Jack A; Moloney, Gerard M; Izumo, Takayuki; Murphy, Kiera; Murphy, Amy; Ross, R Paul; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

    2017-02-04

    Over the last decade, there has been increased interest in the role of the gut microbiome in health including brain health. This is by no means a new theory; Elie Metchnikoff proposed over a century ago that targeting the gut by consuming lactic acid bacteria such as those in yogurt, could improve or delay the onset of cognitive decline associated with ageing. However, there is limited information characterising the relationship between the behavioural and physiological sequelae of ageing and alterations in the gut microbiome. To this end, we assessed the behavioural, physiological and caecal microbiota profile of aged male mice. Older mice (20-21months old) exhibited deficits in spatial memory and increases in anxiety-like behaviours compared to younger mice (2-3months old). They also exhibited increased gut permeability, which was directly correlated with elevations in peripheral pro-inflammatory cytokines. Furthermore, stress exacerbated the gut permeability of aged mice. Examination of the caecal microbiota revealed significant increases in phylum TM7, family Porphyromonadaceae and genus Odoribacter of aged mice. This represents a shift of aged microbiota towards a profile previously associated with inflammatory disease, particularly gastrointestinal and liver disorders. Furthermore, Porphyromonadaceae, which has also been associated with cognitive decline and affective disorders, was directly correlated with anxiety-like behaviour in aged mice. These changes suggest that changes in the gut microbiota and associated increases in gut permeability and peripheral inflammation may be important mediators of the impairments in behavioural, affective and cognitive functions seen in ageing.

  20. Deep brain stimulation amplitude alters posture shift velocity in Parkinson's disease.

    PubMed

    Krishnamurthi, Narayanan; Mulligan, Stefani; Mahant, Padma; Samanta, Johan; Abbas, James J

    2012-08-01

    Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is now widely used to alleviate symptoms of Parkinson's disease (PD). The specific aim of this study was to identify posture control measures that may be used to improve selection of DBS parameters in the clinic and this was carried out by changing the DBS stimulation amplitude. A dynamic posture shift paradigm was used to assess posture control in 4 PD STN-DBS subjects. Each subject was tested at 4 stimulation amplitude settings. Movements of the center of pressure and the position of the pelvis were monitored and several quantitative indices were calculated. The presence of any statistically significant changes in several normalized indices due to reduced/no stimulation was tested using the one-sample t test. The peak velocity and the average movement velocity during the initial and mid phases of movement towards the target posture were substantially reduced. These results may be explained in terms of increased akinesia and bradykinesia due to altered stimulation conditions. Thus, the dynamic posture shift paradigm may be an effective tool to quantitatively characterize the effects of DBS on posture control and should be further investigated as a tool for selection of DBS parameters in the clinic.

  1. Response of lead-induced oxidative stress and alterations in biogenic amines in different rat brain regions to combined administration of DMSA and MiADMSA.

    PubMed

    Flora, S J S; Saxena, Geetu; Gautam, Pratibha; Kaur, Pushpinder; Gill, Kiran Dip

    2007-12-15

    The present study was planned to investigate if combined administration of meso-2,3-dimercaptosuccinic acid (DMSA) and monoisoamyl DMSA (MiADMSA) could achieve better recovery in the altered biochemical parameters suggestive of brain oxidative stress and depletion of lead from blood and brain following acute lead exposure. Male Wistar rats were exposed to lead nitrate (50 mg/kg, i.p., once daily for 5 days) followed by treatment with the above chelating agents using two different doses of 25 or 50 mg/kg (orally) either alone and in combination once daily for five consecutive days. Lead exposure resulted in the significant inhibition of delta-aminolevulinic acid dehydratase activity and depletion of glutathione (GSH) in blood. These changes were accompanied by significant reduction in blood hemoglobin, RBC levels and superoxide dismutase and catalase activities. Significant increase in blood reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) levels were noted. We observed marked increase in brain ROS level while GSH/oxidized glutathione ratio showed significant decrease accompanied by a significant increase in blood and brain lead concentration. The levels of norepinephrine, dopamine and serotonin in different brain regions were also altered on lead exposure. Co-administration of DMSA and MiADMSA particularly at the lower dose was most effective in the recovery of lead-induced changes in the hematological variables and oxidative stress and resulted in more pronounced depletion of lead from blood and brain compared to monotherapy with these chelators. On the other hand, combined administration of MiADMSA (50 mg/kg) in combination with DMSA (25 mg/kg each) had additional beneficial effect over the individual effect of chelating agent in the recovery of altered levels of brain biogenic amines. The study suggests that administration of MiADMSA is generally a better lead chelator than DMSA while combined administration of DMSA and Mi

  2. Photodynamic-therapy-induced alterations of the blood-brain barrier transfer constant of a tracer molecule in normal brain

    NASA Astrophysics Data System (ADS)

    Yeung, Ivan; Lilge, Lothar D.; Wilson, Brian C.; Lee, Ting-Yim; Stevens, Laura; Cenic, Aleksa

    1997-05-01

    Photofrin uptake studies in brain tissues using bulk sampling techniques have demonstrated up to a 10-fold higher concentration in intracranial tumors compared to normal brain structures. This selective uptake is in part attributed to the leaky blood-brain barrier (BBB) in brain tumors while intact BBB in normal brain excludes Photofrin from the extravascular space. However, in vivo preclinical studies have shown a very high sensitivity in normal brain to photodynamic therapy (PDT) despite this selective uptake. In vivo computed tomography (CT) measurement of the blood- brain transfer constant (K) and cerebral plasma volume using an x-ray dye as a tracer was used to monitor the degradation process of the BBB in normal brain during and post PDT. In these experiments, it was observed that K increased as early as 15 minutes after the onset of PDT, peaking at approximately 3 hr post PDT treatment followed by a drop close to baseline values for 3 out of 4 animals. On the other hand, the cerebral plasma volume showed a decrease also as early as 15 min post PDT onset, but its decrease continued up to 6 hrs with no apparent vascular stasis at the end of the time period. The results suggested a continuous process of BBB breakdown and vascular shutdown shortly after start of PDT.

  3. Human brain plasticity: evidence from sensory deprivation and altered language experience.

    PubMed

    Neville, Helen; Bavelier, Daphne

    2002-01-01

    The results from the language studies taken as a whole point to different developmental time courses and developmental vulnerabilities of aspects of grammatical and semantic/lexical processing. They thus provide support for conceptions of language that distinguish these subprocesses within language. Similarly, following auditory deprivation, processes associated with the dorsal visual pathway were more altered than were functions associated with the ventral pathway, providing support for conceptions of visual system organization that distinguish functions along these lines. Could the effects observed in blind and deaf adults be accounted for, at least in part, by the redundant connectivity of the immature human brain? One way we tested this hypothesis was to study the differentiation of visual and auditory sensory responses in normal development (Neville, 1995). In normal adults, auditory stimuli elicit ERP responses that are large over temporal brain regions but small or absent over occipital regions. By contrast, in 6-month-old children we observed that auditory ERPs are equally large over temporal and visual brain regions, consistent with the idea that there is less specificity and more redundancy of connections between the auditory and visual cortex at this time. Between 6 and 36 months, however, we observed a gradual decrease in the amplitude of the auditory ERP over visual areas, while the amplitude over the temporal areas was unchanged. These results suggest that early in human development, there exists a redundancy of connections between auditory and visual areas and that this overlap gradually decreases after birth. This loss of redundancy may be a boundary condition that determines when sensory deprivation can result in alterations in the organization of remaining sensory systems. The considerable variability in timing of sensitive periods may also be in part due to temporal differences in the occurrence of redundancy within different systems. Ongoing

  4. Pharmacological activity of metal binding agents that alter copper bioavailability

    PubMed Central

    Helsel, Marian E.

    2015-01-01

    Iron, copper and zinc are required nutrients for many organisms but also potent toxins if misappropriated. An overload of any of these metals can be cytotoxic and ultimately lead to organ failure, whereas deficiencies can result in anemia, weakened immune system function, and other medical conditions. Cellular metal imbalances have been implicated in neurodegenerative diseases, cancer and infection. It is therefore critical for living organisms to maintain careful control of both the total levels and subcellular distributions of these metals to maintain healthy function. This perspective explores several strategies envisioned to alter the bioavailability of metal ions by using synthetic metal-binding agents targeted for diseases where misappropriated metal ions are suspected of exacerbating cellular damage. Specifically, we discuss chemical properties that influence the pharmacological outcome of a subset of metal-binding agents known as ionophores, and review several examples that have shown multiple pharmacological activities in metal-related diseases, with a specific focus on copper. PMID:25797044

  5. Chronic imipramine treatment differentially alters the brain and plasma amino acid metabolism in Wistar and Wistar Kyoto rats.

    PubMed

    Nagasawa, Mao; Otsuka, Tsuyoshi; Yasuo, Shinobu; Furuse, Mitsuhiro

    2015-09-05

    In the present study, the amino acids which have the possibility for the therapeutic efficacy of imipramine were explored and compared between Wistar Kyoto rats, an animal model of depression, and Wistar rats as a normal model. The antidepressant-like effect caused by chronic imipramine treatment was confirmed by decreased immobility in the forced swimming test. Chronic imipramine administration altered the amino acid dynamics in the brain. In the striatum, the concentrations of asparagine, glutamine and methionine were significantly increased by chronic imipramine administration. In the thalamus and hypothalamus, chronic imipramine administration significantly decreased the valine concentration. On the other hand, no amino acid was altered by chronic imipramine administration in the hippocampus, brain stem and cerebellum. In addition, lower concentration of asparagine in the prefrontal cortex of WKY rats was improved by chronic imipramine administration. This amelioration only in WKY rats may be a specific effect of chronic imipramine administration under the depressive state. In conclusion, chronic imipramine administration altered the several amino acid dynamics in the brain. Modification of the amino acid metabolism in the brain may provide a new strategy in the development of therapeutic treatment of major depression.

  6. Linking neocortical, cognitive, and genetic variability in autism with alterations of brain plasticity: the Trigger-Threshold-Target model.

    PubMed

    Mottron, Laurent; Belleville, Sylvie; Rouleau, Guy A; Collignon, Olivier

    2014-11-01

    The phenotype of autism involves heterogeneous adaptive traits (strengths vs. disabilities), different domains of alterations (social vs. non-social), and various associated genetic conditions (syndromic vs. nonsyndromic autism). Three observations suggest that alterations in experience-dependent plasticity are an etiological factor in autism: (1) the main cognitive domains enhanced in autism are controlled by the most plastic cortical brain regions, the multimodal association cortices; (2) autism and sensory deprivation share several features of cortical and functional reorganization; and (3) genetic mutations and/or environmental insults involved in autism all appear to affect developmental synaptic plasticity, and mostly lead to its upregulation. We present the Trigger-Threshold-Target (TTT) model of autism to organize these findings. In this model, genetic mutations trigger brain reorganization in individuals with a low plasticity threshold, mostly within regions sensitive to cortical reallocations. These changes account for the cognitive enhancements and reduced social expertise associated with autism. Enhanced but normal plasticity may underlie non-syndromic autism, whereas syndromic autism may occur when a triggering mutation or event produces an altered plastic reaction, also resulting in intellectual disability and dysmorphism in addition to autism. Differences in the target of brain reorganization (perceptual vs. language regions) account for the main autistic subgroups. In light of this model, future research should investigate how individual and sex-related differences in synaptic/regional brain plasticity influence the occurrence of autism.

  7. Exposure to mercury alters early activation events in fish leukocytes.

    PubMed Central

    MacDougal, K C; Johnson, M D; Burnett, K G

    1996-01-01

    Although fish in natural populations may carry high body burdens of both organic and inorganic mercury, the effects of this divalent metal on such lower vertebrates is poorly understood. In this report, inorganic mercury in the form of mercuric chloride (HgCl2) is shown to produce both high-dose inhibition and low-dose activation of leukocytes in a marine teleost fish, Sciaenops ocellatus. Concentrations of inorganic mercury > or = 10 microM suppressed DNA synthesis and induced rapid influx of radiolabeled calcium, as well as tyrosine phosphorylation of numerous cellular proteins. Lower concentrations (0.1-1 microM) of HgCl2 that activated cell growth also induced a slow sustained rise in intracellular calcium in cells loaded with the calcium indicator dye fura-2, but did not produce detectable tyrosine phosphorylation of leukocyte proteins. These studies support the possibility that subtoxic doses of HgCl2 may inappropriately activate teleost leukocytes, potentially altering the processes that regulate the magnitude and specificity of the fish immune response to environmental pathogens. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. Figure 6. Figure 7. PMID:8930553

  8. Multiple toxic doses of methamphetamine alter neurotensin concentrations in various region of the rat brain

    SciTech Connect

    Hanson, G.R.; Merchant, K.; Gibb, J.W.; Letter, A.A.

    1986-03-05

    The authors have previously reported that multiple high doses of methamphetamine (METH) alter neuronal monoamine metabolism and release. Recently, Hokfelt et al. showed that neurotensin, a tridecapeptide, has neurotransmitter properties which may be involved with DA neuronal activity. In the present study they investigated the possible effects of METH on the CNS neurotensin system. Five doses of METH (15 mg/kg) were administered every 6 h; control and treated rats were sacrificed 18 h after the last dose and concentrations of neurotensin-like immuno-reactivity (NTLI) were measured by radioimmunoassay. NTLI was elevated 200-300% in the nucleus accumbens, neostriatum, and substantia nigra; 30-40% increases in NTLI were measured in the hippocampus and hypothalamus. No change was observed in amygdala, A-10 or periaqueductal gray. In contrast to the above measured areas, the frontal lobe and olfactory bulb showed decreases of 25-35%. These findings demonstrate that METH treatment alters the activities of several CNS neurotensin systems, possibly due to the influence of this drug on DA pathways. The variability in the type and magnitude of these responses suggests that DA and neurotensin systems interact by more than one mechanism.

  9. Altered activity of the medial prefrontal cortex and amygdala during acquisition and extinction of an active avoidance task

    PubMed Central

    Jiao, Xilu; Beck, Kevin D.; Myers, Catherine E.; Servatius, Richard J.; Pang, Kevin C. H.

    2015-01-01

    Altered medial prefrontal cortex (mPFC) and amygdala function is associated with anxiety-related disorders. While the mPFC-amygdala pathway has a clear role in fear conditioning, these structures are also involved in active avoidance. Given that avoidance perseveration represents a core symptom of anxiety disorders, the neural substrate of avoidance, especially its extinction, requires better understanding. The present study was designed to investigate the activity, particularly, inhibitory neuronal activity in mPFC and amygdala during acquisition and extinction of lever-press avoidance in rats. Neural activity was examined in the mPFC, intercalated cell clusters (ITCs) lateral (LA), basal (BA) and central (CeA) amygdala, at various time points during acquisition and extinction, using induction of the immediate early gene product, c-Fos. Neural activity was greater in the mPFC, LA, BA, and ITC during the extinction phase as compared to the acquisition phase. In contrast, the CeA was the only region that was more activated during acquisition than during extinction. Our results indicate inhibitory neurons are more activated during late phase of acquisition and extinction in the mPFC and LA, suggesting the dynamic involvement of inhibitory circuits in the development and extinction of avoidance response. Together, these data start to identify the key brain regions important in active avoidance behavior, areas that could be associated with avoidance perseveration in anxiety disorders. PMID:26441578

  10. Expression of trkB mRNA is altered in rat hippocampus after experimental brain trauma.

    PubMed

    Hicks, R R; Zhang, L; Dhillon, H S; Prasad, M R; Seroogy, K B

    1998-08-31

    Recent investigations have shown that expression of mRNAs for the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) is differentially altered in the hippocampus following traumatic brain injury. In the present study, modulation of neurotrophin receptor expression was examined in the hippocampus in a rat model of traumatic brain injury using in situ hybridization. Messenger RNA for trkB, the high-affinity receptor for BDNF and neurotrophin-4 (NT-4), was increased between 3 and 6 h bilaterally in the dentate gyrus following a lateral fluid-percussion brain injury of moderate severity (2.0-2.1 atm). No time-dependent alterations were observed for trkB mRNA in hippocampal subfields CA1 and CA3. Levels of mRNA for trkC, the high-affinity receptor for NT-3, did not change in any region of the hippocampus. These data demonstrate that lateral fluid-percussion injury modulates expression of trkB mRNA in the hippocampus and support a role for BDNF/trkB signalling mechanisms in secondary events associated with traumatic brain injury.

  11. Altered Brain Connectivity in Early Postmenopausal Women with Subjective Cognitive Impairment

    PubMed Central

    Vega, Jennifer N.; Zurkovsky, Lilia; Albert, Kimberly; Melo, Alyssa; Boyd, Brian; Dumas, Julie; Woodward, Neil; McDonald, Brenna C.; Saykin, Andrew J.; Park, Joon H.; Naylor, Magdalena; Newhouse, Paul A.

    2016-01-01

    Cognitive changes after menopause are a common complaint, especially as the loss of estradiol at menopause has been hypothesized to contribute to the higher rates of dementia in women. To explore the neural processes related to subjective cognitive complaints, this study examined resting state functional connectivity in 31 postmenopausal women (aged 50–60) in relationship to cognitive complaints following menopause. A cognitive complaint index was calculated using responses to a 120-item questionnaire. Seed regions were identified for resting state brain networks important for higher-order cognitive processes and for areas that have shown differences in volume and functional activity associated with cognitive complaints in prior studies. Results indicated a positive correlation between the executive control network and cognitive complaint score, weaker negative functional connectivity within the frontal cortex, and stronger positive connectivity within the right middle temporal gyrus in postmenopausal women who report more cognitive complaints. While longitudinal studies are needed to confirm this hypothesis, these data are consistent with previous findings suggesting that high levels of cognitive complaints may reflect changes in brain connectivity and may be a potential marker for the risk of late-life cognitive dysfunction in postmenopausal women with otherwise normal cognitive performance. PMID:27721740

  12. IMAGING BRAIN ACTIVATION: SIMPLE PICTURES OF COMPLEX BIOLOGY

    PubMed Central

    Dienel, Gerald A.; Cruz, Nancy F.

    2009-01-01

    Elucidation of biochemical, physiological, and cellular contributions to metabolic images of brain is important for interpretation of images of brain activation and disease. Discordant brain images obtained with [14C]deoxyglucose (DG) and [1- or 6-14C]glucose were previously ascribed to increased glycolysis and rapid [14C]lactate release from tissue, but direct proof of [14C]lactate release from activated brain structures is lacking. Analysis of factors contributing to images of focal metabolic activity evoked by monotonic acoustic stimulation of conscious rats reveals that labeled metabolites of [1- or 6-14C]glucose are quickly released from activated cells due to decarboxylation reactions, spreading via gap junctions, and efflux via lactate transporters. Label release from activated tissue accounts for most of the additional [14C]glucose consumed during activation compared to rest. Metabolism of [3,4-14C]glucose generates about four times more [14C]lactate compared to 14CO2 in extracellular fluid suggesting that most lactate is not locally oxidized. In brain slices, direct assays of lactate uptake from extracellular fluid demonstrate that astrocytes have faster influx and higher transport capacity than neurons. Also, lactate transfer from a single astrocyte to other gap junction-coupled astrocytes exceeds astrocyte-to-neuron lactate shuttling. Astrocytes and neurons have excess capacities for glycolysis, and oxidative metabolism in both cell types rises during sensory stimulation. The energetics of brain activation is quite complex and the proportion of glucose consumed by astrocytes and neurons, lactate generation by either cell type, and the contributions of both cell types to brain images during brain activation are likely to vary with the stimulus paradigm and activated pathways. PMID:19076439

  13. Autism as a disorder of deficiency of brain-derived neurotrophic factor and altered metabolism of polyunsaturated fatty acids.

    PubMed

    Das, Undurti N

    2013-10-01

    Autism has a strong genetic and environmental basis in which inflammatory markers and factors concerned with synapse formation, nerve transmission, and information processing such as brain-derived neurotrophic factor (BDNF), polyunsaturated fatty acids (PUFAs): arachidonic (AA), eicosapentaenoic (EPA), and docosahexaenoic acids (DHA) and their products and neurotransmitters: dopamine, serotonin, acetylcholine, γ-aminobutyric acid, and catecholamines and cytokines are altered. Antioxidants, vitamins, minerals, and trace elements are needed for the normal metabolism of neurotrophic factors, eicosanoids, and neurotransmitters, supporting reports of their alterations in autism. But, the exact relationship among these factors and their interaction with genes and proteins concerned with brain development and growth is not clear. It is suggested that maternal infections and inflammation and adverse events during intrauterine growth of the fetus could lead to alterations in the gene expression profile and proteomics that results in dysfunction of the neuronal function and neurotransmitters, alteration(s) in the metabolism of PUFAs and their metabolites resulting in excess production of proinflammatory eicosanoids and cytokines and a deficiency of anti-inflammatory cytokines and bioactive lipids that ultimately results in the development of autism. Based on these evidences, it is proposed that selective delivery of BDNF and methods designed to augment the production of anti-inflammatory cytokines and eicosanoids and PUFAs may prevent, arrest, or reverse the autism disease process.

  14. Evoked Brain Activity and Personnel Performance

    DTIC Science & Technology

    1987-10-01

    correlation suggests variability. Early papers by Travis and Gottlober (1936, 1937), Davis and Davis (1936), Rubin (1938) and Williams (1939... Gottlober , A. (1936). Do brain waves have individuality? Science, 8^, 532-533. Travis, L.E., &: Gottlober , A. (1937). How consistent are an individual’s

  15. BRAIN NETWORKS. Correlated gene expression supports synchronous activity in brain networks.

    PubMed

    Richiardi, Jonas; Altmann, Andre; Milazzo, Anna-Clare; Chang, Catie; Chakravarty, M Mallar; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Conrod, Patricia; Fauth-Bühler, Mira; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Lemaître, Hervé; Mann, Karl F; Martinot, Jean-Luc; Nees, Frauke; Paus, Tomáš; Pausova, Zdenka; Rietschel, Marcella; Robbins, Trevor W; Smolka, Michael N; Spanagel, Rainer; Ströhle, Andreas; Schumann, Gunter; Hawrylycz, Mike; Poline, Jean-Baptiste; Greicius, Michael D

    2015-06-12

    During rest, brain activity is synchronized between different regions widely distributed throughout the brain, forming functional networks. However, the molecular mechanisms supporting functional connectivity remain undefined. We show that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set. The set of 136 genes we identify is significantly enriched for ion channels. Polymorphisms in this set of genes significantly affect resting-state functional connectivity in a large sample of healthy adolescents. Expression levels of these genes are also significantly associated with axonal connectivity in the mouse. The results provide convergent, multimodal evidence that resting-state functional networks correlate with the orchestrated activity of dozens of genes linked to ion channel activity and synaptic function.

  16. Subanesthetic Ketamine Treatment Promotes Abnormal Interactions between Neural Subsystems and Alters the Properties of Functional Brain Networks

    PubMed Central

    Dawson, Neil; McDonald, Martin; Higham, Desmond J; Morris, Brian J; Pratt, Judith A

    2014-01-01

    Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia. PMID:24492765

  17. The neurobiology of brain and cognitive reserve: mental and physical activity as modulators of brain disorders.

    PubMed

    Nithianantharajah, Jess; Hannan, Anthony J

    2009-12-01

    The concept of 'cognitive reserve', and a broader theory of 'brain reserve', were originally proposed to help explain epidemiological data indicating that individuals who engaged in higher levels of mental and physical activity via education, occupation and recreation, were at lower risk of developing Alzheimer's disease and other forms of dementia. Subsequently, behavioral, cellular and molecular studies in animals (predominantly mice and rats) have revealed dramatic effects of environmental enrichment, which involves enhanced levels of sensory, cognitive and motor stimulation via housing in novel, complex environments. Furthermore, increasing levels of voluntary physical exercise, via ad libitum access to running wheels, can have significant effects on brain and behavior, thus informing the relative effects of mental and physical activity. More recently, animal models of brain disorders have been compared under environmentally stimulating and standard housing conditions, and this has provided new insights into environmental modulators and gene-environment interactions involved in pathogenesis. Here, we review animal studies that have investigated the effects of modifying mental and physical activity via experimental manipulations, and discuss their relevance to brain and cognitive reserve (BCR). Recent evidence suggests that the concept of BCR is not only relevant to brain aging, neurodegenerative diseases and dementia, but also to other neurological and psychiatric disorders. Understanding the cellular and molecular mechanisms mediating BCR may not only facilitate future strategies aimed at optimising healthy brain aging, but could also identify molecular targets for novel pharmacological approaches aimed at boosting BCR in 'at risk' and symptomatic individuals with various brain disorders.

  18. Investigation of age-related changes in brain activity during the divalent task-switching paradigm using functional MRI.

    PubMed

    Kunimi, Mitsunobu; Kiyama, Sachiko; Nakai, Toshiharu

    2016-02-01

    This study compared the brain