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Sample records for brain cortex hippocampus

  1. Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain.

    Directory of Open Access Journals (Sweden)

    Jacqueline C Lieblein-Boff

    Full Text Available Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510 were excluded. In addition, moderate correlations with xenobiotic relationships (2 or those driven by single outliers (3 were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region-specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development.

  2. Effects of static magnetic field and cadmium on oxidative stress and DNA damage in rat cortex brain and hippocampus.

    Science.gov (United States)

    Amara, Salem; Douki, Thierry; Garrel, Catherine; Favier, Alain; Ben Rhouma, Khémais; Sakly, Mohsen; Abdelmelek, Hafedh

    2011-03-01

    The present study was undertaken to determine the effect of co-exposure to static magnetic field (SMF) and cadmium (Cd) on the antioxidant enzymes activity and DNA integrity in rat brain. Sub-chronic exposure to CdCl (CdCl(2), 40 mg/L, per os) for 30 days resulted in a significant reduction in antioxidant enzyme activity such as the glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) in frontal cortex and hippocampus. Total GSH were decreased in the frontal cortex of the Cd-exposed group. Cd exposure induced an increase in malondialdehyde (MDA) concentration in the frontal cortex and hippocampus. Moreover, the same exposure increased 8-oxo-7,8-dihydro-2-desoxyguanosine (8-oxodGuo) level in rat brain. Interestingly, the combined effect of SMF (128 mT, 1 hour/day for 30 consecutive days) and CdCl (40 mg/L, per os) decreased the SOD activity and glutathione level in frontal cortex as compared with the Cd group. Moreover, the association between SMF and Cd increased MDA concentration in frontal cortex as compared with Cd-exposed rats. DNA analysis revealed that SMF exposure failed to alter 8-oxodGuo concentration in Cd-exposed rats. Our data showed that Cd exposure altered the antioxidant enzymes activity and induced oxidative DNA lesions in rat brain. The combined effect of SMF and Cd increased oxidative damage in rat brain as compared with Cd-exposed rats. PMID:20837562

  3. A concussive-like brain injury model in mice (II): selective neuronal loss in the cortex and hippocampus.

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    Tang, Y P; Noda, Y; Hasegawa, T; Nabeshima, T

    1997-11-01

    A novel concussive-like brain injury (CLBI) model characterized by transient neurobehavioral depression, short duration of brain edema, and long-lasting memory deficits has been reported in our companion paper. This was achieved by dropping a 21-g weight from a height of 25 cm onto the head of a mouse. In the present study, we examined the histopathological changes in this model. Male ddY mice were subjected to either the trauma or sham injury. Gross pathological examination of the brain 1 h posttrauma did not demonstrate subdural, subarachnoid, intraventricular, periventricular, and intraparenchymatous hemorrhage, focal lesions or contusions. Microscopic examination 24 h posttrauma with Nissl staining (cresyl violet), however, revealed a selective bilateral neuronal cell loss in the cerebral cortex and hippocampus but not in the regions of the thalamus, cerebellum, and brain stem. The characteristics of neuronal cell loss in the cortex suggested that this pathology was related in part, to the head impact dynamics, since the cell loss was noted in the central portion of the supraventricular cerebral cortex (p < 0.001), the site of the weight impact, gradually decreasing peripheral to this site, and disappearing in the areas remote from this locus. In contrast, neuronal cell loss seen in the hippocampus did not suggest that this pathology was directly associated with the impact site. Neuronal cell loss was concentrated in the pyramidal cell layer of CA2 (p < 0.01) and CA3 (p < 0.01), and a lesser degree was noted in the subfields of CA3c (p < 0.05) and the hilar region (p < 0.05) but not in the subfields of CA1 and the dentate gyrus layers. The present study characterized the histopathological change seen in the CLBI model, demonstrating the selective neuronal cell loss following weight-drop concussion in mice. PMID:9421457

  4. Exploratory metabolomic analyses reveal compounds correlated with lutein concentration in frontal cortex, hippocampus, and occipital cortex of human infant brain

    Science.gov (United States)

    Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with...

  5. Reduced brain-derived neurotrophic factor expression in cortex and hippocampus involved in the learning and memory deficit in molarless SAMP8 mice

    Institute of Scientific and Technical Information of China (English)

    JIANG Qing-song; LIANG Zi-liang; WU Min-Jie; FENG Lin; LIU Li-li; ZHANG Jian-jun

    2011-01-01

    Background The molarless condition has been reported to compromise learning and memory functions. However, it remains unclear how the molarless condition directly affects the central nervous system, and the functional consequences on the brain cortex and hippocampus have not been described in detail. The aim of this study was to find the molecular mechanism related with learning and memory deficit after a bilateral molarless condition having been surgically induced in senescence-accelerated mice/prone8 (SAMP8) mice, which may ultimately provide an experimental basis for clinical prevention of senile dementia.Methods Mice were either sham-operated or subjected to complete molar removal. The animals' body weights were monitored every day. Learning ability and memory were measured in a water maze test at the end of the 1 st, 2nd, and 3rd months after surgery. As soon as significantly prolonged escape latency in the molarless group was detected, the locomotor activity was examined in an open field test. Subsequently, the animals were decapitated and the cortex and hippocampus were dissected for Western blotting to measure the expression levels of brain-derived neurotrophic factor (BDNF) and the tropomyosin related kinase B (TrkB), the high affinity receptor of BDNF.Results Slightly lower weights were consistently observed in the molarless group, but there was no significant difference in weights between the two groups (P>0.05). Compared with the sham group, the molarless group exhibited lengthened escape latency in the water maze test three months after surgery, whereas no difference in locomotor activity was observed. Meanwhile, in the cortex and hippocampus, BDNF levels were significantly decreased in the molarless group (P<0.05); but the expression of its receptor, TrkB, was not significantly affected.Conclusion These results suggested that the molarless condition impaired learning and memory abilities in SAMP8mice three months after teeth extraction, and this

  6. Age-related differences in metabolites in the posterior cingulate cortex and hippocampus of normal ageing brain: A 1H-MRS study

    International Nuclear Information System (INIS)

    Objective: To study age-related metabolic changes in N-acetylaspartate (NAA), total creatine (tCr), choline (Cho) and myo-inositol (Ins). Materials and methods: Proton magnetic resonance spectroscopy (1H-MRS) was performed in the posterior cingulate cortex (PCC) and the left hippocampus (HC) of 90 healthy subjects (42 women and 48 men aged 18–76 years, mean ± SD, 48.4 ± 16.8 years). Both metabolite ratios and absolute metabolite concentrations were evaluated. Analysis of covariance (ANCOVA) and linear regression were used for statistical analysis. Results: Metabolite ratios Ins/tCr and Ins/H2O were found significantly increased with age in the PCC (P 2O was only observed in the PCC (P 1H-MRS results in these specific brain regions can be important to differentiate normal ageing from age-related pathologies such as mild cognitive impairment (MCI) and Alzheimer's disease.

  7. Early network activity propagates bidirectionally between hippocampus and cortex.

    Science.gov (United States)

    Barger, Zeke; Easton, Curtis R; Neuzil, Kevin E; Moody, William J

    2016-06-01

    Spontaneous activity in the developing brain helps refine neuronal connections before the arrival of sensory-driven neuronal activity. In mouse neocortex during the first postnatal week, waves of spontaneous activity originating from pacemaker regions in the septal nucleus and piriform cortex propagate through the neocortex. Using high-speed Ca(2+) imaging to resolve the spatiotemporal dynamics of wave propagation in parasagittal mouse brain slices, we show that the hippocampus can act as an additional source of neocortical waves. Some waves that originate in the hippocampus remain restricted to that structure, while others pause at the hippocampus-neocortex boundary and then propagate into the neocortex. Blocking GABAergic neurotransmission decreases the likelihood of wave propagation into neocortex, whereas blocking glutamatergic neurotransmission eliminates spontaneous and evoked hippocampal waves. A subset of hippocampal and cortical waves trigger Ca(2+) waves in astrocytic networks after a brief delay. Hippocampal waves accompanied by Ca(2+) elevation in astrocytes are more likely to propagate into the neocortex. Finally, we show that two structures in our preparation that initiate waves-the hippocampus and the piriform cortex-can be electrically stimulated to initiate propagating waves at lower thresholds than the neocortex, indicating that the intrinsic circuit properties of those regions are responsible for their pacemaker function. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 661-672, 2016. PMID:26385616

  8. Gene expression in cortex and hippocampus during acute pneumococcal meningitis

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    Wittwer Matthias

    2006-06-01

    Full Text Available Abstract Background Pneumococcal meningitis is associated with high mortality (~30% and morbidity. Up to 50% of survivors are affected by neurological sequelae due to a wide spectrum of brain injury mainly affecting the cortex and hippocampus. Despite this significant disease burden, the genetic program that regulates the host response leading to brain damage as a consequence of bacterial meningitis is largely unknown. We used an infant rat model of pneumococcal meningitis to assess gene expression profiles in cortex and hippocampus at 22 and 44 hours after infection and in controls at 22 h after mock-infection with saline. To analyze the biological significance of the data generated by Affymetrix DNA microarrays, a bioinformatics pipeline was used combining (i a literature-profiling algorithm to cluster genes based on the vocabulary of abstracts indexed in MEDLINE (NCBI and (ii the self-organizing map (SOM, a clustering technique based on covariance in gene expression kinetics. Results Among 598 genes differentially regulated (change factor ≥ 1.5; p ≤ 0.05, 77% were automatically assigned to one of 11 functional groups with 94% accuracy. SOM disclosed six patterns of expression kinetics. Genes associated with growth control/neuroplasticity, signal transduction, cell death/survival, cytoskeleton, and immunity were generally upregulated. In contrast, genes related to neurotransmission and lipid metabolism were transiently downregulated on the whole. The majority of the genes associated with ionic homeostasis, neurotransmission, signal transduction and lipid metabolism were differentially regulated specifically in the hippocampus. Of the cell death/survival genes found to be continuously upregulated only in hippocampus, the majority are pro-apoptotic, while those continuously upregulated only in cortex are anti-apoptotic. Conclusion Temporal and spatial analysis of gene expression in experimental pneumococcal meningitis identified potential

  9. ACETYLCHOLINE RELEASE IN THE HIPPOCAMPUS AND PRELIMBIC CORTEX DURING ACQUISITION OF A SOCIALLY TRANSMITTED FOOD PREFERENCE

    OpenAIRE

    Gold, P E; Countryman, R.A.; Dukala, D.; Chang, Q.

    2011-01-01

    Interference with cholinergic functions in hippocampus and prefrontal cortex impairs learning and memory for social transmission of food preference, suggesting that acetylcholine (ACh) release in the two brain regions may be important for acquiring the food preference. This experiment examined release of ACh in the hippocampus and prefrontal cortex of rats during training for social transmission of food preference. After demonstrator rats ate a food with novel flavor and odor, a social transm...

  10. Cerebral Oedema, Blood-Brain Barrier Breakdown and the Decrease in Na(+),K(+)-ATPase Activity in the Cerebral Cortex and Hippocampus are Prevented by Dexamethasone in an Animal Model of Maple Syrup Urine Disease.

    Science.gov (United States)

    Rosa, Luciana; Galant, Leticia S; Dall'Igna, Dhébora M; Kolling, Janaina; Siebert, Cassiana; Schuck, Patrícia F; Ferreira, Gustavo C; Wyse, Angela T S; Dal-Pizzol, Felipe; Scaini, Giselli; Streck, Emilio L

    2016-08-01

    Maple syrup urine disease (MSUD) is a rare metabolic disorder associated with acute and chronic brain dysfunction. This condition has been shown to lead to macroscopic cerebral alterations that are visible on imaging studies. Cerebral oedema is widely considered to be detrimental for MSUD patients; however, the mechanisms involved are still poorly understood. Therefore, we investigated whether acute administration of branched-chain amino acids (BCAA) causes cerebral oedema, modifies the Na(+),K(+)-ATPase activity, affects the permeability of the blood-brain barrier (BBB) and alters the levels of cytokines in the hippocampus and cerebral cortex of 10-day-old rats. Additionally, we investigated the influence of concomitant administration of dexamethasone on the alterations caused by BCAA. Our results showed that the animals submitted to the model of MSUD exhibited an increase in the brain water content, both in the cerebral cortex and in the hippocampus. By investigating the mechanism of cerebral oedema, we discovered an association between H-BCAA and the Na(+),K(+)-ATPase activity and the permeability of the BBB to small molecules. Moreover, the H-BCAA administration increases Il-1β, IL-6 and TNF-α levels in the hippocampus and cerebral cortex, whereas IL-10 levels were decreased in the hippocampus. Interestingly, we showed that the administration of dexamethasone successfully reduced cerebral oedema, preventing the inhibition of Na(+),K(+)-ATPase activity, BBB breakdown and the increase in the cytokines levels. In conclusion, these findings suggest that dexamethasone can improve the acute cerebral oedema and brain injury associated with high levels of BCAA, either through a direct effect on brain capillary Na(+),K(+)-ATPase or through a generalized effect on the permeability of the BBB to all compounds. PMID:26133302

  11. Novel experience induces persistent sleep-dependent plasticity in the cortex but not in the hippocampus

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    Sidarta Ribeiro

    2007-10-01

    Full Text Available Episodic and spatial memories engage the hippocampus during acquisition but migrate to the cerebral cortex over time. We have recently proposed that the interplay between slow-wave (SWS and rapid eye movement (REM sleep propagates recent synaptic changes from the hippocampus to the cortex. To test this theory, we jointly assessed extracellular neuronal activity, local field potentials (LFP, and expression levels of plasticity-related immediate-early genes (IEG arc and zif-268 in rats exposed to novel spatio-tactile experience. Post-experience firing rate increases were strongest in SWS and lasted much longer in the cortex (hours than in the hippocampus (minutes. During REM sleep, firing rates showed strong temporal dependence across brain areas: cortical activation during experience predicted hippocampal activity in the first post-experience hour, while hippocampal activation during experience predicted cortical activity in the third post-experience hour. Four hours after experience, IEG expression was specifically upregulated during REM sleep in the cortex, but not in the hippocampus. Arc gene expression in the cortex was proportional to LFP amplitude in the spindle-range (10-14 Hz but not to firing rates, as expected from signals more related to dendritic input than to somatic output. The results indicate that hippocampo-cortical activation during waking is followed by multiple waves of cortical plasticity as full sleep cycles recur. The absence of equivalent changes in the hippocampus may explain its mnemonic disengagement over time.

  12. Effects of sleep deprivation on extracellular serotonin in hippocampus and frontal cortex of the rat

    OpenAIRE

    2002-01-01

    Sleep deprivation improves the mood of depressed patients, but the exact mechanism behind this effect is unclear. An enhancement of serotonergic neurotransmission has been suggested. In this study, we used in vivo microdialysis to monitor extracellular serotonin in the hippocampus and the frontal cortex of rats during an 8 h sleep deprivation period. These brain regions were selected since both have been implicated in depression. The behavioral state of the animal was continuously monitored b...

  13. Glutamine synthetase activity and glutamate uptake in hippocampus and frontal cortex in portal hypertensive rats

    Institute of Scientific and Technical Information of China (English)

    Gabriela Beatriz Acosta; María Alejandra Fernández; Diego Martín Roselló; María Luján Tomaro; Karina Balestrasse; Abraham Lemberg

    2009-01-01

    AIM: To study glutamine synthetase (GS) activity and glutamate uptake in the hippocampus and frontal cortex (FC) from rats with prehepatic portal vein hypertension. METHODS: Male Wistar rats were divided into shamoperated group and a portal hypertension (PH) group with a regulated stricture of the portal vein. Animals were sacrificed by decapitation 14 d after portal vein stricture. GS activity was determined in the hippocampus and FC. Specific uptake of radiolabeled L-glutamate was studied using synaptosome-enriched fractions that were freshly prepared from both brain areas. RESULTS: We observed that the activity of GS increased in the hippocampus of PH rats, as compared to control animals, and decreased in the FC. A significant decrease in glutamate uptake was found in both brain areas, and was more marked in the hippocampus. The decrease in glutamate uptake might have been caused by a deficient transport function, significantly and persistent increase in this excitatory neurotransmitter activity. CONCLUSION: The presence of moderate ammonia blood levels may add to the toxicity of excitotoxic glutamate in the brain, which causes alterations in brain function. Portal vein stricture that causes portal hypertension modifies the normal function in some brain regions.

  14. Effects of insulin-induced hypoglycemia on somatostatin level and binding in rat cerebral cortex and hippocampus

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    Rodríguez Sánchez, María Nelly; Colás Escudero, Begoña; Prieto Villapún, Juan Carlos; Arilla Ferreiro, Eduardo

    1989-01-01

    The effects of severe insulin-induced hypoglycemia on somatostatin level and specific binding in the cerebral cortex and hippocampus were examined using 125I-Tyr11-somatostatin as a ligand. Severe insulin-induced hypoglycemia did not affect the level of somatostatin-like immunoreactivity in the brain areas studied. However, the number (but not the affinity) of specific somatostatin receptors was significantly decreased in membrane preparation from the hippocampus but not in the cerebral corte...

  15. Brain-Derived Neurotrophic Factor Transgenic Mice Exhibit Passive Avoidance Deficits, Increased Seizure Severity and In Vitro Hyperexcitability in the Hippocampus and Entorhinal Cortex

    OpenAIRE

    Croll, S. D.; Suri, C; Compton, D. L.; Simmons, M. V.; Yancopoulos, G D; Lindsay, R M; Wiegand, S. J.; RUDGE, J. S.; Scharfman, H. E.

    1999-01-01

    Transgenic mice overexpressing brain-derived neurotrophic factor from the β-actin promoter were tested for behavioral, gross anatomical and physiological abnormalities. Brain-derived neurotrophic factor messenger RNA overexpression was widespread throughout brain. Overexpression declined with age, such that levels of overexpression decreased sharply by nine months. Brain-derived neurotrophic factor transgenic mice had no gross deformities or behavioral abnormalities. However, they showed a si...

  16. The hippocampus as a stable memory allocator for cortex.

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    Valiant, Leslie G

    2012-11-01

    It is suggested here that mammalian hippocampus serves as an allocator of neurons in cortex for memorizing new items. A construction of a shallow feedforward network with biologically plausible parameters is given that possesses the characteristics needed for such an allocator. In particular, the construction is stabilizing in that for inputs within a range of activity levels spanning more than an order of magnitude, the output will have activity levels differing as little as 1%. It is also noise tolerant in that pairs of input patterns that differ little will generate output patterns that differ little. Further, pairs of inputs that differ by much will be mapped to outputs that also differ sufficiently that they can be treated by cortex as distinct. PMID:22920849

  17. Quantitative proteomic profiling of membrane proteins from the mouse brain cortex, hippocampus, and cerebellum using the HysTag reagent: mapping of neurotransmitter receptors and ion channels

    DEFF Research Database (Denmark)

    Olsen, Jesper V; Nielsen, Peter Aa; Andersen, Jens R;

    2007-01-01

    Analysis of the brain proteome and studying brain diseases through clinical biopsies and animal disease models require methods of quantitative proteomics that are sensitive and allow identification and quantification of low abundant membrane proteins from minute amount of tissue. Taking advantage...

  18. Expression of cFos and brain-derived neurotrophic factor in cortex and hippocampus of ethanol-withdrawn male and female rats

    OpenAIRE

    Alele, Paul E.; Devaud, Leslie L.

    2013-01-01

    Objective: To map areas of brain activation (cFos) alongside changes in levels of brain-derived neurotrophic factor (BDNF) to provide insights into neuronal mechanisms contributing to previously observed sex differences in behavioral measures of ethanol withdrawal (EW). Materials and Methods: Immunohistochemical analysis of cFos and BDNF levels using protein-specific antibodies and visualization with nickel-enhanced DAB staining in 3 cortical and 4 hippocampal regions was used to assess EW-in...

  19. The influence of chronic nicotine treatment on proteins expressed in the mouse hippocampus and cortex.

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    Matsuura, Kenji; Otani, Mieko; Takano, Masaoki; Kadoyama, Keiichi; Matsuyama, Shogo

    2016-06-01

    Chronic treatment with nicotine, the primary psychoactive substance in tobacco smoke, affects central nervous system functions, such as synaptic plasticity. Here, to clarify the effects of chronic nicotine treatment on the higher brain functions, proteomic analysis of the hippocampus and cortex of mice treated for 6 months with nicotine was performed using two-dimensional gel electrophoresis (2-DE) followed by mass spectrometry. There was significant change in the expression of 16 proteins and one phosphoprotein in the hippocampus (increased tubulin β-5, atp5b, MDH1, cytochrome b-c1 complex subunit 1, Hsc70, dynamin, profilin-2, 4-aminobutyrate aminotransferase, mitochondrial isoform 1 precursor, calpain small subunit 1, and vacuolar adenosine triphosphatase subunit B and decreased γ-actin, α-tubulin isotype M-α-2, putative β-actin, tubulin β-2A, NDUFA10, and G6PD) and 24 proteins and two phosphoproteins in the cortex (increased spectrin α chain, non-erythrocytic 1 isoform 1, tubulin β-5, γ-actin, creatine kinase B-type, LDH-B, secernin-1, UCH-L1, 14-3-3 γ, type II peroxiredoxin 1, PEBP-1, and unnamed protein product and decreased tubulin α-1C, α-internexin, γ-enolase, PDHE1-B, DPYL2, vacuolar adenosine triphosphatase subunit A, vacuolar adenosine triphosphatase subunit B, TCTP, NADH dehydrogenase Fe-S protein 1, protein disulfide-isomerase A3, hnRNP H2, γ-actin, atp5b, and unnamed protein product). Additionally, Western blotting validated the changes in dynamin, Hsc70, MDH1, NDUFA10, α-internexin, tubulin β-5 chain, and secernin-1. Thus, these findings indicate that chronic nicotine treatment changes the expression of proteins and phosphoproteins in the hippocampus and cortex. We propose that effect of smoking on higher brain functions could be mediated by alterations in expression levels of these proteins. PMID:26988295

  20. Mitochondria controlled by UCP2 determine hypoxia-induced synaptic remodeling in the cortex and hippocampus.

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    Varela, Luis; Schwartz, Michael L; Horvath, Tamas L

    2016-06-01

    We have established that mitochondrial dynamics, under metabolic control, play crucial roles in the regulation of systemic metabolism by hypothalamic circuits. The role of mitochondrial dynamics in neurons in higher brain regions is, however, ill-defined. Here we show that early postnatal exposure of animals to temporal hypoxia followed by normoxia, a major metabolic challenge on brain cells, resulted in adaptive responses of neuronal mitochondria. The number and oxygen consumption of mitochondria in cortical and hippocampal neurons were altered, while mitochondria-endoplasmic reticulum (ER) interactions were preserved. These changes coincided with increased synaptic input of neurons in the cortex and hippocampus. We identified that the changing oxygen tension triggered mitochondrial uncoupling protein 2 (UCP2) expression and showed that UCP2 is crucial for these adaptive mitochondrial responses. In UCP2 KO mice, changing oxygen tension did not induce changes in mitochondrial parameters and function but decreased mitochondria-ER contacts and resulted in loss of synapses both in the cortex and hippocampus. These observations establish that mitochondrial location controlled by UCP2 is relevant for adaptive responses of neurons in cortical and hippocampal neurons and are relevant to perinatal hypoxia-triggered circuit adaptations. PMID:26777666

  1. Higher density of serotonin-1A receptors in the hippocampus and cerebral cortex of alcohol-preferring P rats

    International Nuclear Information System (INIS)

    Saturable [3H]-80HDPAT binding to 5HT-1A receptors in membranes prepared from hippocampus and frontal cerebral cortex of alcohol-preferring (P) rats and of alcohol-nonpreferring (NP) rats has been compared. The Bmax values or densities of recognition sites for 5HT-1A receptors in both brain areas of the P rats are 38 and 44 percent lower in the P rats than in the NP rats. The corresponding KD values are 38 and 44 percent lower in the P rats than in the NP rats, indicating higher affinities of the recognition sites for the 5HT-1A receptors in hippocampus and cerebral cortex of the P rats. These findings indicate either an enrichment of 5HT-1A receptor density during selective breeding for alcohol preference or an upregulation of 5HT-1A receptors of 5HT found in these brain areas of P rats as compared with the NP rats

  2. Independent delta/theta rhythms in the human hippocampus and entorhinal cortex

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    Florian Mormann

    2008-05-01

    Full Text Available Theta oscillations in the medial temporal lobe (MTL of mammals are involved in various functions such as spatial navigation, sensorimotor integration, and cognitive processing. While the theta rhythm was originally assumed to originate in the medial septum, more recent studies suggest autonomous theta generation in the MTL. Although coherence between entorhinal and hippocampal theta activity has been found to influence memory formation, it remains unclear whether these two structures can generate theta independently. In this study we analyzed intracranial electroencephalographic (EEG recordings from 22 patients with unilateral hippocampal sclerosis undergoing presurgical evaluation prior to resection of the epileptic focus. Using a wavelet-based, frequency-band-specific measure of phase synchronization, we quantified synchrony between 10 different recording sites along the longitudinal axis of the hippocampal formation in the non-epileptic brain hemisphere. We compared EEG synchrony between adjacent recording sites (i within the entorhinal cortex, (ii within the hippocampus, and (iii between the hippocampus and entorhinal cortex. We observed a significant interregional gap in synchrony for the delta and theta band, indicating the existence of independent delta/theta rhythms in different subregions of the human MTL. The interaction of these rhythms could represent the temporal basis for the information processing required for mnemonic encoding and retrieval.

  3. Hippocampus, Perirhinal Cortex, and Complex Visual Discriminations in Rats and Humans

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    Hales, Jena B.; Broadbent, Nicola J.; Velu, Priya D.; Squire, Larry R.; Clark, Robert E.

    2015-01-01

    Structures in the medial temporal lobe, including the hippocampus and perirhinal cortex, are known to be essential for the formation of long-term memory. Recent animal and human studies have investigated whether perirhinal cortex might also be important for visual perception. In our study, using a simultaneous oddity discrimination task, rats with…

  4. Altered gene expression profiles in the hippocampus and prefrontal cortex of type 2 diabetic rats

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    Abdul-Rahman Omar

    2012-02-01

    Full Text Available Abstract Background There has been an increasing body of epidemiologic and biochemical evidence implying the role of cerebral insulin resistance in Alzheimer-type dementia. For a better understanding of the insulin effect on the central nervous system, we performed microarray-based global gene expression profiling in the hippocampus, striatum and prefrontal cortex of streptozotocin-induced and spontaneously diabetic Goto-Kakizaki rats as model animals for type 1 and type 2 diabetes, respectively. Results Following pathway analysis and validation of gene lists by real-time polymerase chain reaction, 30 genes from the hippocampus, such as the inhibitory neuropeptide galanin, synuclein gamma and uncoupling protein 2, and 22 genes from the prefrontal cortex, e.g. galanin receptor 2, protein kinase C gamma and epsilon, ABCA1 (ATP-Binding Cassette A1, CD47 (Cluster of Differentiation 47 and the RET (Rearranged During Transfection protooncogene, were found to exhibit altered expression levels in type 2 diabetic model animals in comparison to non-diabetic control animals. These gene lists proved to be partly overlapping and encompassed genes related to neurotransmission, lipid metabolism, neuronal development, insulin secretion, oxidative damage and DNA repair. On the other hand, no significant alterations were found in the transcriptomes of the corpus striatum in the same animals. Changes in the cerebral gene expression profiles seemed to be specific for the type 2 diabetic model, as no such alterations were found in streptozotocin-treated animals. Conclusions According to our knowledge this is the first characterization of the whole-genome expression changes of specific brain regions in a diabetic model. Our findings shed light on the complex role of insulin signaling in fine-tuning brain functions, and provide further experimental evidence in support of the recently elaborated theory of type 3 diabetes.

  5. AGE-RELATED CHANGES IN NEUTRAL SPHINGOMYELIN-SPECIFIC PHOSPHOLIPASE C ACTIVITY IN STRIATUM, HIPPOCAMPUS, AND FRONTAL CORTEX: IMPLICATION FOR SENSITIVITY TO STRESS AND INFLAMMATION

    Science.gov (United States)

    Previous studies show the enrichment of mammalian brain with neutral sphingomyelin specific phospholipase C (ceramide-phosphocholine phosphodiesterase, EC 3.1.4.12; N-Sase). The objective of this study was to evaluate the subcellular N-Sase activity in striatum, hippocampus, and frontal cortex. Resu...

  6. Context conditioning and extinction in humans: differential contribution of the hippocampus, amygdala and prefrontal cortex

    OpenAIRE

    Lang, Simone; Kroll, Alexander; Lipinski, Slawomira J; Wessa, Michèle; Ridder, Stephanie; Christmann, Christoph; Schad, Lothar R.; Flor, Herta

    2009-01-01

    Functional magnetic resonance imaging was used to investigate the role of the hippocampus, amygdala and medial prefrontal cortex (mPFC) in a contextual conditioning and extinction paradigm provoking anxiety. Twenty-one healthy persons participated in a differential context conditioning procedure with two different background colours as contexts. During acquisition increased activity to the conditioned stimulus (CS+) relative to the CS− was found in the left hippocampus and anterior cingulate ...

  7. Anatomical substrates for direct interactions between hippocampus, medial prefrontal cortex, and the thalamic nucleus reuniens

    OpenAIRE

    Varela, C.; Kumar, S.; Yang, J. Y.; Wilson, M A

    2013-01-01

    The reuniens nucleus in the midline thalamus projects to the medial prefrontal cortex (mPFC) and the hippocampus, and has been suggested to modulate interactions between these regions, such as spindle–ripple correlations during sleep and theta band coherence during exploratory behavior. Feedback from the hippocampus to the nucleus reuniens has received less attention but has the potential to influence thalamocortical networks as a function of hippocampal activation. We used the retrograde tra...

  8. Disruption of the Perineuronal Net in the Hippocampus or Medial Prefrontal Cortex Impairs Fear Conditioning

    Science.gov (United States)

    Hylin, Michael J.; Orsi, Sara A.; Moore, Anthony N.; Dash, Pramod K.

    2013-01-01

    The perineuronal net (PNN) surrounds neurons in the central nervous system and is thought to regulate developmental plasticity. A few studies have shown an involvement of the PNN in hippocampal plasticity and memory storage in adult animals. In addition to the hippocampus, plasticity in the medial prefrontal cortex (mPFC) has been demonstrated to…

  9. Hippocampus and Medial Prefrontal Cortex Contributions to Trace and Contextual Fear Memory Expression over Time

    Science.gov (United States)

    Beeman, Christopher L.; Bauer, Philip S.; Pierson, Jamie L.; Quinn, Jennifer J.

    2013-01-01

    Previous work has shown that damage to the dorsal hippocampus (DH) occurring at recent, but not remote, timepoints following acquisition produces a deficit in trace conditioned fear memory expression. The opposite pattern has been observed with lesions to the medial prefrontal cortex (mPFC). The present studies address: (1) whether these lesion…

  10. Temporal and spatial distribution of metabotropic glutamate receptor 5 during development in the rat cortex and hippocampus

    Institute of Scientific and Technical Information of China (English)

    Xinli Xiao; Ming Hu; Pengbo Yang; Lin Zhang; Xinlin Chen; Yong Liu

    2011-01-01

    Metabotropic glutamate receptor 5 (mGluR5) is expressed by neurons in zones of active neurogenesis and is involved in the development of neural stem cells in vivo and in vitro. We examined the expression of mGluR5 in the cortex and hippocampus of rats during various prenatal and postnatal periods using immunohistochemistry. During prenatal development, mGluR5 was primarily localized to neuronal somas in the forebrain. During early postnatal periods, the receptor was mainly present on somas in the cortex. mGluR5 immunostaining was visible in apical dendrites and in the neuropil of neurons and persisted throughout postnatal development. During this period, pyramidal neurons were strongly labeled for the receptor. In the hippocampal CA1 region, mGluR5 immunoreactivity was more intense in the stratum oriens, stratum radiatum, and lacunosum moleculare at P0, P5 and P10 relative to P60. mGluR5 expression increased significantly in the molecular layer and decreased significantly in the granule cell layer of the dentate gyrus at P5, P10 and P60 in comparison with P0. Furthermore, some mGluR5-positive cells were also bromodeoxyuridine- or NeuroD-positive in the dentate gyrus at P14. These results demonstrate that mGluR5 has a differential expression pattern in the cortex and hippocampus during early growth, suggesting a role for this receptor in the control of domain specific brain developmental events.

  11. Reactivation of Tert in the medial prefrontal cortex and hippocampus rescues aggression and depression of Tert(-/-) mice.

    Science.gov (United States)

    Zhou, Q-G; Wu, H-Y; Zhou, H; Liu, M-Y; Lee, H-W; Liu, X; Devkota, S; Ro, E J; Zhu, D-Y; Suh, H

    2016-01-01

    The role of telomerase reverse transcriptase (TERT) has been extensively investigated in the contexts of aging and cancer. Interestingly, Tert(-/-) mice exhibit additional but unexpected aggressive and depressive behaviors, implying the potential involvement of TERT function in mood control. Our conditional rescue experiments revealed that the depressive and aggressive behaviors of Tert(-/-) mice originate from Tert deficiency in two distinct brain structures. Reactivation of Tert in the hippocampus was sufficient to normalize the depressive but not the aggressive behaviors of Tert(-/-) mice. Conversely, re-expression of Tert in the medial prefrontal cortex (mPFC) reversed the aggressive but not the depressive behavior of Tert(-/-) mice. Mechanistically, decreased serotonergic signaling and increased nitric oxide (NO) transmission in the hippocampus transduced Tert deficiency into depression as evidenced by our observation that the infusion of a pharmacological agonist for serotonin receptor 1a (5-HTR1A) and a selective antagonist for neuronal NO synthase into the hippocampus successfully normalized the depressive behavior of Tert(-/-) mice. In addition, increased serotonergic transmission by the 5-HTR1A agonist in the mPFC was sufficient to rescue the aggressive behavior of Tert(-/-) mice. Thus, our studies revealed a novel function of TERT in the pathology of depression and aggression in a brain structure-specific manner, providing direct evidence for the contribution of TERT to emotional control. PMID:27300262

  12. Spatial memory deficits in patients with lesions to the right hippocampus and to the right parahippocampal cortex.

    Science.gov (United States)

    Bohbot, V D; Kalina, M; Stepankova, K; Spackova, N; Petrides, M; Nadel, L

    1998-11-01

    Spatial memory tasks, performance of which is known to be sensitive to hippocampal lesions in the rat, or to medial temporal lesions in the human, were administered in order to investigate the effects of selective damage to medial temporal lobe structures of the human brain. The patients had undergone thermo-coagulation with a single electrode along the amygdalo-hippocampal axis in an attempt to alleviate their epilepsy. With this surgical technique, lesions to single medial temporal lobe structures can be carried out. The locations of the lesions were assessed by means of digital high-resolution magnetic resonance imaging and software allowing a 3-D reconstruction of the brain. A break in the collateral sulcus, dividing it into the anterior collateral sulcus and the posterior collateral sulcus is reported. This division may correspond to the end of the entorhinal/perirhinal cortex and the start of the parahippocampal cortex. The results confirmed the role of the right hippocampus in visuo-spatial memory tasks (object location, Rey-Osterrieth Figure with and without delay) and the left for verbal memory tasks (Rey Auditory Verbal Learning Task with delay). However, patients with lesions either to the right or to the left hippocampus were unimpaired on several memory tasks, including a spatial one, with a 30 min delay, designed to be analogous to the Morris water maze. Patients with lesions to the right parahippocampal cortex were impaired on this task with a 30 min delay, suggesting that the parahippocampal cortex itself may play an important role in spatial memory. PMID:9842767

  13. Toxic effect of aflatoxin B1 and the role of recovery on the rat cerebral cortex and hippocampus.

    Science.gov (United States)

    Bahey, Noha Gamal; Abd Elaziz, Hekmat Osman; Gadalla, Kamal Kamal El Sayed

    2015-12-01

    Aflatoxin B1 (AFB1) is the most toxic and well-known mycotoxin that exists in many food stuff. Exposure to AFB1 has been reported to produce serious biochemical and structural alterations in human and animal organs, however, its effect on the brain is not well studied. Therefore, this study was aimed to investigate the possible histopathological effect of AFB1 and its withdrawal on the cerebral cortex and hippocampus. Fifteen adult female Wistar rats were divided into 3 equal groups: control, AFB1 (15.75 μg/kg/orally, once weekly, for 8 weeks) and recovery groups. Brain sections were processed for hematoxylin and eosin staining as well as for NeuN and GFAP immunostaining. AFB1 administration resulted in several histopathological alterations including; cellular degeneration, dilatation of the blood vessels and significant decrease in the thickness of the frontal cortex and the hippocampal CA1 pyramidal cell layer. In the frontal cortex, there was a significant reduction in the percentage of astrocyte distribution without changes in neuronal numbers. On the other hand, in the hippocampal CA1 region, there was a significant reduction of neuronal number and a significant increase in the percentage of astrocyte distribution. Importantly, AFB1-induced structural alterations were rescued following AFB1 withdrawal. In conclusion, AFB1 induce histological alterations in the rat brain which are potentially reversible upon withdrawal. PMID:26380901

  14. Intrinsic connectivity between the hippocampus and posteromedial cortex predicts memory performance in cognitively intact older individuals

    OpenAIRE

    Wang, Liang; LaViolette, Peter; O’Keefe, Kelly; Putcha, Deepti; Bakkour, Akram; Dijk, Koene R.A.Van; Pihlajamäki, Maija; Dickerson, Bradford C.; Sperling, Reisa A.

    2010-01-01

    Coherent fluctuations of spontaneous brain activity are present in distinct functional-anatomic brain systems during undirected wakefulness. However, the behavioral significance of this spontaneous activity has only begun to be investigated. Our previous studies have demonstrated that successful memory formation requires coordinated neural activity in a distributed memory network including the hippocampus and posteromedial cortices, specifically the precuneus and posterior cingulate (PPC), th...

  15. G9a/GLP Histone Lysine Dimethyltransferase Complex Activity in the Hippocampus and the Entorhinal Cortex is Required for Gene Activation and Silencing during Memory Consolidation

    OpenAIRE

    Gupta-Agarwal, Swati; Franklin, Aimee V.; DeRamus, Thomas; Wheelock, Muriah; Davis, Robin L.; McMahon, Lori L.; Lubin, Farah D.

    2012-01-01

    Learning triggers alterations in gene transcription in brain regions such as the hippocampus and the entorhinal cortex (EC) that are necessary for long-term memory (LTM) formation. Here, we identify an essential role for the G9a/GLP lysine dimethyltransferase complex and the histone H3 lysine 9 di-methylation (H3K9me2) marks it catalyzes, in the transcriptional regulation of genes in area CA1 of the rat hippocampus and the EC during memory consolidation. Contextual fear learning increased glo...

  16. Low incidence of melanoma brain metastasis in the hippocampus

    International Nuclear Information System (INIS)

    Aims: ANZMTG 01.07 WBRTMel is a phase 3 randomized trial to address the role of whole brain radiation therapy (WBRT) after local treatment of 1–3 melanoma brain metastases. Modern radiation therapy technologies can now conformally spare the hippocampus during WBRT and therefore potentially reduce the risk of neurocognitive deficit. The aims of this study were to report the prevalence of melanoma metastases within the hippocampal sparing region and to identify variables that correlate with the presence of metastases within the hippocampal sparing region. Methods: The pre-local treatment MRI scans of 77 eligible WBRTMel patients were used to contour the individual metastasis and the hippocampus. The volume, location and closest distance of each metastasis to the hippocampus were recorded. Binary logistic regression was performed to assess the influence of factors on the location of a metastasis within 5 mm of the hippocampus. Results: The median age was 61 and 66% were male. The distribution of the 115 metastases was frontal (50, 43.5%), parietal (23, 20.0%), temporal (13, 11.2%), occipital (18, 15.7%), cerebellum (10, 8.6%) and pineal gland (1, 1.0%). The median aggregate volume of the metastasis was 3516 mm3. None of the metastases were within the hippocampus. Four patients (5.2%) had metastases within 5 mm of the hippocampus. The median distance from metastasis to the nearest hippocampus was 37.2 mm. Only the total volume of metastases was a significant predictor for the risk of a metastasis within the hippocampal sparing region (OR 1.071, 95% CI: 1.003–1.144, p = 0.040). Conclusions: This study confirmed a low incidence of melanoma metastasis in the hippocampal sparing region at diagnosis. Given the lack of randomized data on the safety and benefit of hippocampal sparing WBRT, the current WBRTMel trial provides the opportunity to explore the feasibility of this technique

  17. Motor cortex and hippocampus are the two main cortical targets in LGI1-antibody encephalitis.

    Science.gov (United States)

    Navarro, Vincent; Kas, Aurélie; Apartis, Emmanuelle; Chami, Linda; Rogemond, Véronique; Levy, Pierre; Psimaras, Dimitri; Habert, Marie-Odile; Baulac, Michel; Delattre, Jean-Yves; Honnorat, Jérome

    2016-04-01

    . Cognitive impairment, either anterograde amnesia or confusion was evident in 30 of 34 patients (88%). Brain imaging was normal in patients with isolated tonic-dystonic seizures; in patients with limbic symptoms it revealed initially a hippocampal hyperintensity in 8 of 19 patients (42%) and 17 of 24 patients (70%) at later stages. Our data suggest that the major signs of LGI1-antibody encephalitis can be linked to involvement of motor cortex and hippocampus. They occur in parallel with striatum involvement. One of these cortical targets is involved, often unilaterally at disease onset. As the encephalitis progresses, in the absence of immunomodulatory treatment, the second cortical target is affected and effects become bilateral. Progression to the second cortical target occurs with a variable delay of days to several months. PMID:26945884

  18. DEVELOPMENTAL HYPOTHYROIDISM REDUCES PARVALBUMIN EXPRESSION IN GABAERGIC NEURONS OF CORTEX AND HIPPOCAMPUS: IMMUNOHISTOCHEMICAL FINDINGS AND FUNCTIONAL CORRELATES.

    Science.gov (United States)

    GABAergic interneurons comprise the bulk of local inhibitory neuronal circuitry in cortex and hippocampus and a subpopulation of these interneurons contain the calcium binding protein, parvalbumin (PV). A previous report indicated that severe hypothyroidism reduced PV immunoreact...

  19. Dissociable roles for histone acetyltransferases p300 and PCAF in hippocampus and perirhinal cortex-mediated object memory.

    Science.gov (United States)

    Mitchnick, K A; Creighton, S D; Cloke, J M; Wolter, M; Zaika, O; Christen, B; Van Tiggelen, M; Kalisch, B E; Winters, B D

    2016-07-01

    The importance of histone acetylation for certain types of memory is now well established. However, the specific contributions of the various histone acetyltransferases to distinct memory functions remain to be determined; therefore, we employed selective histone acetyltransferase protein inhibitors and short-interference RNAs to evaluate the roles of CREB-binding protein (CBP), E1A-binding protein (p300) and p300/CBP-associated factor (PCAF) in hippocampus and perirhinal cortex (PRh)-mediated object memory. Rats were tested for short- (STM) and long-term memory (LTM) in the object-in-place task, which relies on the hippocampus and PRh for spatial memory and object identity processing, respectively. Selective inhibition of these histone acetyltransferases by small-interfering RNA and pharmacological inhibitors targeting the HAT domain produced dissociable effects. In the hippocampus, CBP or p300 inhibition impaired long-term but not short-term object memory, while inhibition of PCAF impaired memory at both delays. In PRh, HAT inhibition did not impair STM, and only CBP and PCAF inhibition disrupted LTM; p300 inhibition had no effects. Messenger RNA analyses revealed findings consistent with the pattern of behavioral effects, as all three enzymes were upregulated in the hippocampus (dentate gyrus) following learning, whereas only CBP and PCAF were upregulated in PRh. These results demonstrate, for the first time, the necessity of histone acetyltransferase activity for PRh-mediated object memory and indicate that the specific mnemonic roles of distinctive histone acetyltransferases can be dissociated according to specific brain regions and memory timeframe. PMID:27251651

  20. Transitive inference: distinct contributions of rostrolateral prefrontal cortex and the hippocampus.

    Science.gov (United States)

    Wendelken, Carter; Bunge, Silvia A

    2010-05-01

    The capacity to reason about complex information is a central characteristic of human cognition. An important component of many reasoning tasks is the need to integrate multiple mental relations. Several researchers have argued that rostrolateral prefrontal cortex (RLPFC) plays a key role in relational integration. If this hypothesis is correct, then RLPFC should play a key role in transitive inference, which requires the integration of multiple relations to reach a conclusion. Thus far, however, neuroscientific research on transitive inference has focused primarily on the hippocampus. In this fMRI study, we sought to compare the roles of RLPFC and the hippocampus on a novel transitive inference paradigm. Four relations between colored balls were presented on the screen together with a target relation. Participants were asked to decide whether the target relation was correct, given the other indicated relations between balls. RLPFC, but not the hippocampus, exhibited stronger activation on trials that required relational integration as compared with trials that involved relational encoding without integration. In contrast, the hippocampus exhibited a pattern consistent with a role in relational encoding, with stronger activation on trials requiring encoding of relational predicate-argument structure as compared with trials requiring encoding of item-item associations. Functional connectivity analyses give rise to the hypothesis that RLPFC draws on hippocampal representations of mental relations during the process of relational integration. PMID:19320546

  1. Hippocampus sparing in whole-brain radiotherapy. A review

    International Nuclear Information System (INIS)

    Radiation treatment techniques for whole-brain radiation therapy (WBRT) have not changed significantly since development of the procedure. However, the recent development of novel techniques such as intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT) and helical tomotherapy, as well as an increasing body of evidence concerning neural stem cells (NSCs) have altered the conventional WBRT treatment paradigm. In this regard, hippocampus-sparing WBRT is a novel technique that aims to spare critical hippocampus regions without compromising tumour control. Published data on this new technique are limited to planning and feasibility studies; data on patient outcome are still lacking. However, several prospective trials to analyse the feasibility of this technique and to document clinical outcome in terms of reduced neurotoxicity are ongoing. (orig.)

  2. Inorganic Arsenic Induces NRF2-Regulated Antioxidant Defenses in Both Cerebral Cortex and Hippocampus in Vivo.

    Science.gov (United States)

    Zhang, Yang; Duan, Xiaoxu; Li, Jinlong; Zhao, Shuo; Li, Wei; Zhao, Lu; Li, Wei; Nie, Huifang; Sun, Guifang; Li, Bing

    2016-08-01

    Inorganic arsenic is reported to induce the reactive oxygen species-mediated oxidative stress, which is supposed to be one of the main mechanisms of arsenic-related neurological diseases. Nuclear factor erythroid 2-related factor 2 (NRF2), a master regulator of antioxidant defense systems, up-regulates the expression of target genes to fight against oxidative damages caused by harmful substances, including metals. In the present study, mice were used as a model to investigate the oxidative stress levels and the expressions of NRF2-regulated antioxidant substances in both cerebral cortex and hippocampus with 5, 10 and 20 mg/kg NaAsO2 exposure intra-gastrically. Our results showed that acute NaAsO2 treatment resulted in decreased total anti-oxidative capacity (T-AOC) and increased maleic dialdehyde production in the nervous system. We also detected rapidly elevation of NRF2 protein levels by enhancement of Nrf2 transcription, especially at 20 mg/kg NaAsO2 exposure group. In the meantime, mRNA and protein levels of Nrf2 encoding antioxidant enzymes heme oxygenase-1 (HO-1), NAD(P)H: quinine oxidoreductase 1 (NQO1) and glutathione S-transferase (GST) were consistently elevated time- and dose-dependently both in the cerebral cortex and hippocampus. Taken together, the presence study demonstrated the activation of NRF2 pathway, an early antioxidant defensive response, in both cerebral cortex and hippocampus upon inorganic arsenic (iAs) exposure in vivo. A better knowledge on the roles of NRF2 pathway in maintaining cellular redox homeostasis would be helpful for the strategies on improvement of neurotoxicity related to this metalloid. PMID:27165637

  3. Metabolomic analysis reveals metabolic disturbance in the cortex and hippocampus of subchronic MK-801 treated rats.

    Directory of Open Access Journals (Sweden)

    Liya Sun

    Full Text Available BACKGROUND: Although a number of proteins and genes relevant to schizophrenia have been identified in recent years, few are known about the exact metabolic pathway involved in this disease. Our previous proteomic study has revealed the energy metabolism abnormality in subchronic MK-801 treated rat, a well-established animal model for schizophrenia. This prompted us to further investigate metabolite levels in the same rat model to better delineate the metabolism dysfunctions and provide insights into the pathology of schizophrenia. METHODS: Metabolomics, a high-throughput investigatory strategy developed in recent years, can offer comprehensive metabolite-level insights that complement protein and genetic findings. In this study, we employed a nondestructive metabolomic approach (1H-MAS-NMR to investigate the metabolic traits in cortex and hippocampus of MK-801 treated rats. Multivariate statistics and ingenuity pathways analyses (IPA were applied in data processing. The result was further integrated with our previous proteomic findings by IPA analysis to obtain a systematic view on our observations. RESULTS: Clear distinctions between the MK-801 treated group and the control group in both cortex and hippocampus were found by OPLS-DA models (with R(2X = 0.441, Q(2Y = 0.413 and R(2X = 0.698, Q(2Y = 0.677, respectively. The change of a series of metabolites accounted for the separation, such as glutamate, glutamine, citrate and succinate. Most of these metabolites fell in a pathway characterized by down-regulated glutamate synthesis and disturbed Krebs cycle. IPA analysis further confirmed the involvement of energy metabolism abnormality induced by MK-801 treatment. CONCLUSIONS: Our metabolomics findings reveal systematic changes in pathways of glutamate metabolism and Krebs cycle in the MK-801 treated rats' cortex and hippocampus, which confirmed and improved our previous proteomic observation and served as a valuable reference to

  4. Role of parietal cortex and hippocampus during avoidance of a moving object in rats

    Czech Academy of Sciences Publication Activity Database

    Svoboda, Jan; Telenský, Petr; Blahna, Karel; Bureš, Jan

    Fyziologický ústav AV ČR, v. v. i.. Roč. 56, č. 3 (2007), 34P-34P ISSN 0862-8408. [Fyziologické dny /83./. 06.02.2007-08.02.2007, Brno] R&D Projects: GA ČR(CZ) GA309/06/1231; GA ČR(CZ) GD206/05/H012; GA MŠk(CZ) 1M0517; GA ČR(CZ) GA309/07/0341 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * hippocampus * parietal cortex * rat Subject RIV: FH - Neurology

  5. Traumatic brain injury impairs synaptic plasticity in hippocampus in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bao-liang; CHEN Xin; TAN Tao; YANG Zhuo; CARLOS Dayao; JIANG Rong-cai; ZHANG Jian-ning

    2011-01-01

    Background Traumatic brain injury (TBl) often causes cognitive deficits and remote symptomatic epilepsy.Hippocampal regional excitability is associated with the cognitive function. However, little is known about injury-induced neuronal loss and subsequent alterations of hippocampal regional excitability. The present study was designed to determine whether TBl may impair the cellular circuit in the hippocampus.Methods Forty male Wistar rats were randomized into control (n=20) and TBl groups (n=20). Long-term potentiation,extracellular input/output curves, and hippocampal parvalbumin-immunoreactive and cholecystokinin-immunoreactive interneurons were compared between the two groups.Results TBI resulted in a significantly increased excitability in the dentate gyrus (DG), but a significantly decreased excitability in the cornu ammonis 1 (CA1) area. Using design-based stereological injury procedures, we induced interneuronal loss in the DG and CA3 subregions in the hippocampus, but not in the CA1 area.Conclusions TBl leads to the impairment of hippocampus synaptic plasticity due to the changing of interneuronal interaction. The injury-induced disruption of synaptic efficacy within the hippocampal circuit may underlie the observed cognitive deficits and symptomatic epilepsy.

  6. Postnatal BDNF Expression Profiles in Prefrontal Cortex and Hippocampus of a Rat Schizophrenia Model Induced by MK-801 Administration

    Directory of Open Access Journals (Sweden)

    Chunmei Guo

    2010-01-01

    Full Text Available Neonatal blockade of N-methyl-D-aspartic acid (NMDA receptors represents one of experimental animal models for schizophrenia. This study is to investigate the long-term brain-derived neurotrophic factor (BDNF expression profiles in different regions and correlation with “schizophrenia-like” behaviors in the adolescence and adult of this rat model. The NMDA receptor antagonist MK801 was administered to female Sprague-Dawley rats on postnatal days (PND 5 through 14. Open-field test was performed on PND 42, and PND 77 to examine the validity of the current model. BDNF protein levels in hippocampus and prefrontal cortex (PFC were analyzed on PND 15, PND 42, and PND 77. Results showed that neonatal challenge with MK-801 persistently elevated locomotor activity as well as BDNF expression; the alterations in BDNF expression varied at different developing stages and among brain regions. However, these findings provide neurochemical evidence that the blockade of NMDA receptors during brain development results in long-lasting alterations in BDNF expression and might contribute to neurobehavioral pathology of the present animal model for schizophrenia. Further study in the mechanisms and roles of the BDNF may lead to better understanding of the pathophysiology of schizophrenia.

  7. Expression of constitutively active erythropoietin receptor in pyramidal neurons of cortex and hippocampus boosts higher cognitive functions in mice

    Directory of Open Access Journals (Sweden)

    Hassouna Imam

    2011-04-01

    Full Text Available Abstract Background Erythropoietin (EPO and its receptor (EPOR are expressed in the developing brain and their transcription is upregulated in adult neurons and glia upon injury or neurodegeneration. We have shown neuroprotective effects and improved cognition in patients with neuropsychiatric diseases treated with EPO. However, the critical EPO targets in brain are unknown, and separation of direct and indirect effects has remained difficult, given the role of EPO in hematopoiesis and brain oxygen supply. Results Here we demonstrate that mice with transgenic expression of a constitutively active EPOR isoform (cEPOR in pyramidal neurons of cortex and hippocampus exhibit enhancement of spatial learning, cognitive flexibility, social memory, and attentional capacities, accompanied by increased impulsivity. Superior cognitive performance is associated with augmented long-term potentiation of cEPOR expressing neurons in hippocampal slices. Conclusions Active EPOR stimulates neuronal plasticity independent of any hematopoietic effects and in addition to its neuroprotective actions. This property of EPOR signaling should be exploited for defining novel strategies to therapeutically enhance cognitive performance in disease conditions.

  8. Pharmacokinetics of ginsenoside Rg1 in rat medial prefrontal cortex, hippocampus, and lateral ventricle after subcutaneous administration.

    Science.gov (United States)

    Xue, Wei; Liu, Yang; Qi, Wen-Yuan; Gao, Yan; Li, Min; Shi, Ai-Xin; Li, Ke-Xin

    2016-06-01

    The present study aimed to investigate pharmacokinetics of Rg1 in rat medial prefrontal cortex (mPFC), hippocampus (HIP), and lateral ventricle (LV) after subcutaneous injection. For the first time, intracerebral pharmacokinetics of Rg1 was studied in freely moving rats by microdialysis technique. Rg1 concentrations in dialysates were detected by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method and were revised using in vivo probe-recovery in HIP and LV. The pharmacokinetic parameters were then determined using non-compartmental models. Since the in vivo recoveries remained stable in HIP and LV during 9 h dialysis, average recoveries were used to revise dialysate concentrations. After dosing, Rg1 was soon detected in brain extracellular fluid (bECF) and cerebrospinal fluid (CSF). The elimination of Rg1 was significantly slower in mPFC than in HIP and LV, and significantly greater AUC was obtained in mPFC than in HIP. Rg1 kinetics in bECF and CSF indicate that Rg1 can go across the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), and then immediately distribute to learning and memory-related regions in brain, which may lead to rapid pharmacological onset. There may be active transport and target-mediated disposition of Rg1 in the CNS, which need to be further clarified. PMID:27324597

  9. Hippocampus sparing in whole-brain radiotherapy. A review

    Energy Technology Data Exchange (ETDEWEB)

    Oskan, F. [University of Munich, Department of Radiation Oncology and CCC Neuro-Oncology, Munich (Germany); Saarland University Medical Center, Department of Radiation Oncology, Homburg/Saar (Germany); Ganswindt, U.; Schwarz, S.B.; Manapov, F.; Belka, C.; Niyazi, M. [University of Munich, Department of Radiation Oncology and CCC Neuro-Oncology, Munich (Germany)

    2014-04-15

    Radiation treatment techniques for whole-brain radiation therapy (WBRT) have not changed significantly since development of the procedure. However, the recent development of novel techniques such as intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT) and helical tomotherapy, as well as an increasing body of evidence concerning neural stem cells (NSCs) have altered the conventional WBRT treatment paradigm. In this regard, hippocampus-sparing WBRT is a novel technique that aims to spare critical hippocampus regions without compromising tumour control. Published data on this new technique are limited to planning and feasibility studies; data on patient outcome are still lacking. However, several prospective trials to analyse the feasibility of this technique and to document clinical outcome in terms of reduced neurotoxicity are ongoing. (orig.) [German] Die Technik der Ganzhirnbestrahlung (''whole-brain radiation therapy'', WBRT) hat sich seit der Entwicklung nicht wesentlich veraendert. Allerdings stellten die Neuentwicklung von Techniken wie die intensitaetsmodulierte Strahlentherapie (IMRT), die volumenmodulierte Arc-Therapie (VMAT) oder die helikale Tomotherapie sowie immer groesseres Wissen ueber das neurale Stammzellkompartiment (NSCs) das herkoemmliche Ganzhirn-Paradigma in Frage. Die hippocampusschonende Ganzhirnbestrahlung ist eine neuartige Technik, welche die kritische Region des Hippocampus schont, ohne die Tumorkontrolle zu gefaehrden. Ueber diese Technik gibt es bisher nur eine begrenzte Datenlage im Sinne von Planungs- und Machbarkeitsstudien. Klinische Daten bzgl. der Behandlungsergebnisse fehlen nach wie vor, aber einige prospektive Studien sind im Gange, um nicht nur die Machbarkeit zu belegen, sondern auch das klinische Outcome im Sinne einer verringerten Neurotoxizitaet nachzuweisen. (orig.)

  10. Differences between seizure-prone and non-seizure-prone mice with regard to glutamate and GABA receptor binding in the hippocampus and other regions of the brain

    DEFF Research Database (Denmark)

    Frandsen, A; Belhage, B; Schousboe, A

    1987-01-01

    Quisqualate-preferring glutamate receptors were determined in membranes from frontal cortex, occipital cortex, hippocampus and cerebellum, from seizure-prone DBA/2J BOM and seizure-resistant C57/BL mice. The animals were studied 21, 27 and 40 days postnatally, i.e., before, during and after the age...... at which DBA mice are most susceptible to seizures. Radio-binding assays were performed using [3H]AMPA in the presence of 100 nM glutamate. Except for the occipital cortex, where no significant differences between the two strains were observed, all areas of the brain of DBA mice exhibited...... significantly (P less than 0.001, t test) higher AMPA binding than the corresponding areas of C57/BL mice at 27 days of age. At pre- and post-susceptible ages, the two strains showed no significant differences in the hippocampus and occipital cortex. A significant difference was observed, however, in the...

  11. 妊娠早期暴露低浓度毒死蜱对子代鼠海马脑区及体觉皮层的影响%Effects of low concentration of chlorpyrifos prenatal exposure on generation mouse brain hippocam-pus and somatosensory cortex

    Institute of Scientific and Technical Information of China (English)

    陈晓萍; 金建龙; 李传武; 王飞石

    2009-01-01

    目的 探讨小鼠妊娠早期暴露低浓度有机磷农药毒死蜱对子代鼠脑结构发育的影响.方法 在母鼠妊娠7.5~11.5 d时,以每天皮下注射5 mg/kg毒死蜱,连续5 d,将子代鼠在出生第35天处死,取脑作定位切片,HE及尼氏染色,显微镜下测量海马CA1、CA3区、DG区厚度,计数大脑皮层S1区神经元和胶质细胞数量及比例.结果 出生35 d的子代鼠海马CA 1区平均厚度下降22.37%,CA3区平均厚度下降25.66%,而DG区平均厚度增加24.14%,与对照组比较,差异均有统计学意义(P<0.01).S1区神经元,胶质细胞比值由81.77%下降至74.61%.结论 小鼠妊娠早期低浓度有机磷农药毒死蜱持续暴露可导致子代鼠脑结构细微损伤.%Objective To observe the effects of low concentration of organophosphate pesticide chlor-pyrifos(CPF) prenatal exposure on generation mouse brain development. Methods 5 mg/kg CPF was admin-istered daily on gestation days (GD) 7.5~11.5. On postnatal clay (PD) 35, quantitative morphologic examines were measured in CA1, CA3, dentate gyrus regions of the hippocampus and somatosensory cortex. Results After CPF prenatal exposure, selective morphology impairments were observed, showing 22.37%, 25.66 % thinning of the CA1 and CA3 layers, 24.14% enlargement of the dentate guys and 81.77% to 74.61% decreas-ing of the ratio of neuron/glial of the somatosensory cortex. Conclusion There maybe slight morphological changes after prenatal low concentration pesticide exposure even without obviously systemic toxicity.

  12. Differential neuregulin 1 cleavage in the prefrontal cortex and hippocampus in schizophrenia and bipolar disorder: preliminary findings.

    Directory of Open Access Journals (Sweden)

    Ketan Marballi

    Full Text Available BACKGROUND: Neuregulin 1 (NRG1 is a key candidate susceptibility gene for both schizophrenia (SCZ and bipolar disorder (BPD. The function of the NRG1 transmembrane proteins is regulated by cleavage. Alteration of membrane bound-NRG1 cleavage has been previously shown to be associated with behavioral impairments in mouse models lacking expression of NRG1-cleavage enzymes such as BACE1 and gamma secretase. We sought to determine whether alterations in NRG1 cleavage and associated enzymes occur in patients with SCZ and BPD. METHODOLOGY/PRINCIPAL FINDINGS: Using human postmortem brain, we evaluated protein expression of NRG1 cleavage products and enzymes that cleave at the external (BACE1, ADAM17, ADAM19 and internal (PS1-gamma secretase sides of the cell membrane. We used three different cohorts (Controls, SCZ and BPD and two distinct brain regions: BA9-prefrontal cortex (Controls (n = 6, SCZ (n = 6 and BPD (n = 6 and hippocampus (Controls (n = 5, SCZ (n = 6 and BPD (n = 6. In BA9, the ratio of the NRG1 N-terminal fragment relative to full length was significantly upregulated in the SCZ cohort (Bonferroni test, p = 0.011. ADAM17 was negatively correlated with full length NRG1 levels in the SCZ cohort (r = -0.926, p = 0.008. In the hippocampus we found significantly lower levels of a soluble 50 kDa NRG1 fragment in the two affected groups compared the control cohort (Bonferroni test, p = 0.0018. We also examined the relationship of specific symptomatology criteria with measures of NRG1 cleavage using the Bipolar Inventory of Signs and Symptoms Scale (BISS and the Montgomery Åsberg Depression Rating Scale (MADRS. Our results showed a positive correlation between ADAM19 and psychosis (r = 0.595 p = 0.019; PS1 and mania (r = 0.535, p = 0.040; PS1 and depression (r = 0.567, p = 0.027 in BA9, and BACE1 with anxiety (r = 0.608, p = 0.03 in the hippocampus. CONCLUSION/SIGNIFICANCE: Our preliminary findings suggest region-specific alterations in NRG1

  13. Representations of specific acoustic patterns in the auditory cortex and hippocampus.

    Science.gov (United States)

    Kumar, Sukhbinder; Bonnici, Heidi M; Teki, Sundeep; Agus, Trevor R; Pressnitzer, Daniel; Maguire, Eleanor A; Griffiths, Timothy D

    2014-09-22

    Previous behavioural studies have shown that repeated presentation of a randomly chosen acoustic pattern leads to the unsupervised learning of some of its specific acoustic features. The objective of our study was to determine the neural substrate for the representation of freshly learnt acoustic patterns. Subjects first performed a behavioural task that resulted in the incidental learning of three different noise-like acoustic patterns. During subsequent high-resolution functional magnetic resonance imaging scanning, subjects were then exposed again to these three learnt patterns and to others that had not been learned. Multi-voxel pattern analysis was used to test if the learnt acoustic patterns could be 'decoded' from the patterns of activity in the auditory cortex and medial temporal lobe. We found that activity in planum temporale and the hippocampus reliably distinguished between the learnt acoustic patterns. Our results demonstrate that these structures are involved in the neural representation of specific acoustic patterns after they have been learnt. PMID:25100695

  14. Social attachment in juvenile monkeys with neonatal lesion of the hippocampus, amygdala and orbital frontal cortex.

    Science.gov (United States)

    Goursaud, Anne-Pierre S; Bachevalier, Jocelyne

    2007-01-10

    Non-human primates, like humans, develop and maintain social relationships and attachments throughout their life. The first and most crucial relationship in a primate life is that with its mother. Yet, in absence of their biological mother, infant primates form attachment to surrogate mothers. Although, this early attachment is critical for the development of normal species-typical social and emotional skills, the neural substrates underlying the formation of social relationships in primates are still unclear. The present study assessed, in infant rhesus monkeys (Macaca mulatta) reared by human caregivers and social interactions with peers, the effects of bilateral neonatal (1-2 weeks of age) ibotenic acid lesions of the amygdala and hippocampus (N=6 in each group), aspiration lesions of the orbital frontal cortex (N=6) or sham lesions (N=5) on the development of a social attachment with the principal human caregiver. A specific preference for the later was assessed at 11 months of age, in a two-choice discrimination task, opposing the principal human caregiver to another familiar human, in a familiar environment. None of the lesions impaired the expression of preferential responses toward the principal human caregiver. Nevertheless, lesions of the orbital frontal cortex led to a weaker preference, suggesting that this structure may play a role in the quality and/or strength of the infant/mother relationships. The present non-human primate findings are discussed in terms of their relevance for autism. PMID:17084912

  15. Hypobaric Hypoxia Imbalances Mitochondrial Dynamics in Rat Brain Hippocampus

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    Khushbu Jain

    2015-01-01

    Full Text Available Brain is predominantly susceptible to oxidative stress and mitochondrial dysfunction during hypobaric hypoxia, and therefore undergoes neurodegeneration due to energy crisis. Evidences illustrate a high degree of association for mitochondrial fusion/fission imbalance and mitochondrial dysfunction. Mitochondrial fusion/fission is a recently reported dynamic mechanism which frequently occurs among cellular mitochondrial network. Hence, the study investigated the temporal alteration and involvement of abnormal mitochondrial dynamics (fusion/fission along with disturbed mitochondrial functionality during chronic exposure to hypobaric hypoxia (HH. The Sprague-Dawley rats were exposed to simulated high altitude equivalent to 25000 ft for 3, 7, 14, 21, and 28 days. Mitochondrial morphology, distribution within neurons, enzyme activity of respiratory complexes, Δψm, ADP: ATP, and expression of fission/fusion key proteins were determined. Results demonstrated HH induced alteration in mitochondrial morphology by damaged, small mitochondria observed in neurons with disturbance of mitochondrial functionality and reduced mitochondrial density in neuronal processes manifested by excessive mitochondrial fragmentation (fission and decreased mitochondrial fusion as compared to unexposed rat brain hippocampus. The study suggested that imbalance in mitochondrial dynamics is one of the noteworthy mechanisms occurring in hippocampal neurons during HH insult.

  16. Methylphenidate induces lipid and protein damage in prefrontal cortex, but not in cerebellum, striatum and hippocampus of juvenile rats.

    Science.gov (United States)

    Schmitz, Felipe; Scherer, Emilene B S; Machado, Fernanda R; da Cunha, Aline A; Tagliari, Bárbara; Netto, Carlos A; Wyse, Angela T S

    2012-12-01

    The use of psychostimulant methylphenidate has increased in recent years for the treatment of attention-deficit hyperactivity disorder in children and adolescents. However, the behavioral and neurochemical changes promoted by its use are not yet fully understood, particularly when used for a prolonged period during stages of brain development. Thus, the aim of this study was to determine some parameters of oxidative stress in encephalic structures of juvenile rats subjected to chronic methylphenidate treatment. Wistar rats received intraperitoneal injections of methylphenidate (2.0 mg/kg) once a day, from the 15th to the 45th day of age or an equivalent volume of 0.9% saline solution (controls). Two hours after the last injection, animals were euthanized and the encephalic structures obtained for determination of oxidative stress parameters. Results showed that methylphenidate administration increased the activities of superoxide dismutase and catalase, but did not alter the levels of reactive species, thiobarbituric acid reactive substances levels and sulfhydryl group in cerebellum of rats. In striatum and hippocampus, the methylphenidate-treated rats presented a decrease in the levels of reactive species and thiobarbituric acid reactive substances, but did not present changes in the sulfhydryl groups levels. In prefrontal cortex, methylphenidate promoted an increase in reactive species formation, SOD/CAT ratio, and increased the lipid peroxidation and protein damage. These findings suggest that the encephalic structures respond differently to methylphenidate treatment, at least, when administered chronically to young rats. Notably, the prefrontal cortex of juvenile rats showed greater sensitivity to oxidative effects promoted by methylphenidate in relation to other encephalic structures analyzed. PMID:22968482

  17. Expressions of Neuregulin 1β and ErbB4 in Prefrontal Cortex and Hippocampus of a Rat Schizophrenia Model Induced by Chronic MK-801 Administration

    Directory of Open Access Journals (Sweden)

    Yu Feng

    2010-01-01

    Full Text Available Recent human genetic studies and postmortem brain examinations of schizophrenia patients strongly indicate that dysregulation of NRG1 and ErbB4 may be important pathogenic factors of schizophrenia. However, this hypothesis has not been validated and fully investigated in animal models of schizophrenia. In this study we quantitatively examined NRG1 and ErbB4 protein expressions by immunohistochemistry and Western blot in the brain of a rat schizophrenia model induced by chronic administration of MK-801 (a noncompetitive NMDA receptor antagonist. Our data showed that NRG1β and ErbB4 expressions were significantly increased in the rat prefrontal cortex and hippocampus but in different subregions. These findings suggest that altered expressions of NRG1 and ErbB4 might be attributed to the schizophrenia. Further study in the role and mechanism of NRG1 and ErbB4 may lead to better understanding of the pathophysiology for this disorder.

  18. GLT-1 promoter activity in astrocytes and neurons of mouse hippocampus and somatic sensory cortex

    Directory of Open Access Journals (Sweden)

    Luisa De Vivo

    2010-01-01

    Full Text Available GLT-1 eGFP BAC reporter transgenic adult mice were used to detect GLT-1 gene expression in individual cells of CA1, CA3 and SI, and eGFP fluorescence was measured to analyze quantitatively GLT-1 promoter activity in different cells of neocortex and hippocampus. Virtually all GFAP+ astrocytes were eGFP+; we also found that about 80% of neurons in CA3 pyramidal layer, 10-70% of neurons in I-VI layers of SI and rare neurons in all strata of CA1 and in strata oriens and radiatum of CA3 were eGFP+. Analysis of eGFP intensity showed that astrocytes had a higher GLT-1 promoter activity in SI than in CA1 and CA3, and that neurons had the highest levels of GLT-1 promoter activity in CA3 stratum pyramidale and in layer VI of SI. Finally, we observed that the intensity of GLT-1 promoter activity in neurons is 1-20% of that measured in astrocytes. These results showed that in the hippocampus and neocortex GLT-1 promoter activity is observed in astrocytes and neurons, detailed the distribution of GLT-1 expressing neurons, and indicated that GLT-1 promoter activity in both astrocytes and neurons varies in different brain regions.

  19. Role of the thalamic nucleus reuniens in mediating interactions between the hippocampus and medial prefrontal cortex during spatial working memory

    Directory of Open Access Journals (Sweden)

    Amy L Griffin

    2015-03-01

    Full Text Available Despite decades of research, the neural mechanisms of spatial working memory remain poorly understood. Although the dorsal hippocampus is known to be critical for memory-guided behavior, experimental evidence suggests that spatial working memory depends not only on the hippocampus itself, but also on the circuit comprised of the hippocampus and the medial prefrontal cortex (mPFC. Disruption of hippocampal-mPFC interactions may result in failed transfer of spatial and contextual information processed by the hippocampus to the circuitry in mPFC responsible for decision making and goal-directed behavior. Oscillatory synchrony between the hippocampus and mPFC has been shown to increase in tasks with high spatial working memory demand. However, the mechanisms and circuitry supporting hippocampal-mPFC interactions during these tasks is unknown. The midline thalamic nucleus reuniens (RE is reciprocally connected to both the hippocampus and the mPFC and has been shown to be critical for a variety of working memory tasks. Therefore, it is likely that hippocampal-mPFC oscillatory synchrony is modulated by RE activity. This article will review the anatomical connections between the hippocampus, mPFC and RE along with the behavioral studies that have investigated the effects of RE disruption on working memory task performance. The article will conclude with suggestions for future directions aimed at identifying the specific role of the RE in regulating functional interactions between the hippocampus and the PFC and investigating the degree to which these interactions contribute to spatial working memory.

  20. Antioxidant Activity of Grapevine Leaf Extracts against Oxidative Stress Induced by Carbon Tetrachloride in Cerebral Cortex, Hippocampus and Cerebellum of Rats

    Science.gov (United States)

    Wohlenberg, Mariane; Almeida, Daniela; Bokowski, Liane; Medeiros, Niara; Agostini, Fabiana; Funchal, Cláudia; Dani, Caroline

    2014-01-01

    In recent years, it has become increasingly important to study the beneficial properties of derivatives of grapes and grapevine. The objective of this study was to determine the antioxidant activity of Vitis labrusca leaf extracts, comparing conventional and organic grapevines, in different brain areas of rats. We used male Wistar rats treated with grapevine leaf extracts for a period of 14 days, and on the 15th day, we administered in half of the rats, mineral oil and the other half, carbon tetrachloride (CCl4). The animals were euthanized by decapitation and the cerebral cortex, hippocampus and cerebellum were removed to assess oxidative stress parameters and the activity of antioxidant enzymes. Lipid peroxidation levels (TBARS) were unchanged. However, CCl4 induced oxidative damage to proteins in all tissues studied, and this injury was prevented by both extracts. Superoxide dismutase (SOD) activity was increased by CCl4 in the cerebral cortex and decreased in other tissues. However, CCl4 increased catalase (CAT) activity in the cerebellum and decreased it in the cerebral cortex. The SOD/CAT ratio was restored in the cerebellum by both extracts and only in the cerebral cortex by the organic extract. PMID:26784867

  1. Antioxidant Activity of Grapevine Leaf Extracts against Oxidative Stress Induced by Carbon Tetrachloride in Cerebral Cortex, Hippocampus and Cerebellum of Rats

    Directory of Open Access Journals (Sweden)

    Mariane Wohlenberg

    2014-04-01

    Full Text Available In recent years, it has become increasingly important to study the beneficial properties of derivatives of grapes and grapevine. The objective of this study was to determine the antioxidant activity of Vitis labrusca leaf extracts, comparing conventional and organic grapevines, in different brain areas of rats. We used male Wistar rats treated with grapevine leaf extracts for a period of 14 days, and on the 15th day, we administered in half of the rats, mineral oil and the other half, carbon tetrachloride (CCl4. The animals were euthanized by decapitation and the cerebral cortex, hippocampus and cerebellum were removed to assess oxidative stress parameters and the activity of antioxidant enzymes. Lipid peroxidation levels (TBARS were unchanged. However, CCl4 induced oxidative damage to proteins in all tissues studied, and this injury was prevented by both extracts. Superoxide dismutase (SOD activity was increased by CCl4 in the cerebral cortex and decreased in other tissues. However, CCl4 increased catalase (CAT activity in the cerebellum and decreased it in the cerebral cortex. The SOD/CAT ratio was restored in the cerebellum by both extracts and only in the cerebral cortex by the organic extract.

  2. Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

    International Nuclear Information System (INIS)

    Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD). In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS) and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD

  3. Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

    Directory of Open Access Journals (Sweden)

    C. Yang

    2014-03-01

    Full Text Available Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD. In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD.

  4. Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

    Energy Technology Data Exchange (ETDEWEB)

    Yang, C.; Guo, X. [Wuhan University, Renmin Hospital, Department of Psychiatry, Wuhan, China, Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan (China); Wang, G.H. [Wuhan University, Renmin Hospital, Department of Psychiatry, Wuhan, China, Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan (China); Wuhan University, Institute of Neuropsychiatry, Wuhan, China, Institute of Neuropsychiatry, Wuhan University, Wuhan (China); Wang, H.L.; Liu, Z.C.; Liu, H.; Zhu, Z.X.; Li, Y. [Wuhan University, Renmin Hospital, Department of Psychiatry, Wuhan, China, Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan (China)

    2014-03-03

    Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD). In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS) and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD.

  5. Effects of sericin on heme oxygenase-1 expression in the hippocampus and cerebral cortex of type 2 diabetes mellitus rats

    Institute of Scientific and Technical Information of China (English)

    Zhihona Chen; Yaqiang He; Wenliang Fu; Jingfeng Xue

    2011-01-01

    Previous studies have demonstrated that sericin effectively reduces blood glucose, and protects islet cells, as well as the gonads and kidneys. However, whether sericin improves diabetes mellitus-induced structural and functional problems in the central nervous system remains poorly understood. Rat models of type 2 diabetes mellitus were established by intraperitoneal injection of streptozotocin. The present study observed histological changes in the hippocampus and cerebral cortex, as well as heme oxygenase-1 expression, and explored sericin effects on the central nervous system in diabetic rats. Pathological damage to neural cells in the rat hippocampus and cerebral cortex was relieved following intragastric administration of sericin at a dose of 2.4 g/kg for 35 consecutive days. Heme oxygenase-1 protein and mRNA expressions were decreased in the hippocampus and cerebral cortex of diabetes mellitus rats after sericin treatment. The results suggest that sericin plays a protective effect on the nervous system by decreasing the high expression of heme oxygenase-1 following diabetes mellitus.

  6. Three-dimensional microtomographic imaging of human brain cortex

    CERN Document Server

    Mizutania, Ryuta; Uesugi, Kentaro; Ohyama, Masami; Takekoshi, Susumu; Osamura, R Yoshiyuki; Suzuki, Yoshio

    2016-01-01

    This paper describes an x-ray microtomographic technique for imaging the three-dimensional structure of the human cerebral cortex. Neurons in the brain constitute a neural circuit as a three-dimensional network. The brain tissue is composed of light elements that give little contrast in a hard x-ray transmission image. The contrast was enhanced by staining neural cells with metal compounds. The obtained structure revealed the microarchitecture of the gray and white matter regions of the frontal cortex, which is responsible for the higher brain functions.

  7. Valproic acid effects in the hippocampus and prefrontal cortex in an animal model of post-traumatic stress disorder.

    Science.gov (United States)

    Wilson, C Brad; McLaughlin, Leslie D; Ebenezer, Philip J; Nair, Anand R; Francis, Joseph

    2014-07-15

    Reactive oxygen species (ROS) and pro-inflammatory cytokines (PIC) are upregulated in post-traumatic stress disorder (PTSD). Histone deacetylase inhibitors (HDACi) modify genetic transcription and can diminish ROS and PIC escalation. They can also modulate levels of neurotransmitters such as catecholamines and serotonin (5-HT). Thus, this study sought to analyze the effects of the HDACi valproic acid (VA) on oxidative stress, inflammation, and neurotransmitter modulation via a predator exposure/psychosocial stress animal model of PTSD. PTSD-like effects were induced in male Sprague-Dawley rats (n=6/group×4 groups). The rats were secured in Plexiglas cylinders and placed in a cage with a cat for 1h on days 1, 11, and 40 of a 40-day stress regimen. PTSD rats were also subjected to psychosocial stress via daily cage cohort changes. At the conclusion of the stress regimen, the treatment group (PTSD+VA) and control group (Control+VA) rats were given VA in their drinking water for 30 days. The rats were then euthanized and their brains were dissected to remove the hippocampus and prefrontal cortex (PFC). Whole blood was collected to assess systemic oxidative stress. ROS and PIC mRNA and protein elevation in the PTSD group were normalized with VA. Anxiety decreased in this group via improved performance on the elevated plus-maze (EPM). No changes were attributed to VA in the control group, and no improvements were noted in the vehicle groups. Results indicate VA can attenuate oxidative stress and inflammation, enhance fear extinction, and correct neurotransmitter aberrancies in a rat model of PTSD. PMID:24675160

  8. Predator exposure/psychosocial stress animal model of post-traumatic stress disorder modulates neurotransmitters in the rat hippocampus and prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    C Brad Wilson

    Full Text Available Post-Traumatic Stress Disorder (PTSD can develop in response to a traumatic event involving a threat to life. To date, no diagnostic biomarkers have been identified for PTSD. Recent research points toward physiological abnormalities in the hypothalamic-pituitary-adrenal (HPA axis, sympathoadrenal medullary and immune system that may be implicated in the disorder. The modulation of neurotransmitters is another possible mechanism, but their role in the progression of PTSD is poorly understood. Low serotonin (5-HT may be a factor, but it may not be the only neurotransmitter affected as modulation affects levels of other neurotransmitters. In this study, we hypothesized the predator exposure/psychosocial stress rodent model of PTSD may alter levels of 5-HT and other neurotransmitters in the rat hippocampus and prefrontal cortex (PFC. Male Sprague-Dawley rats were used in this experiment. We induced PTSD via a predator exposure/psychosocial stress model, whereby rats were placed in a cage with a cat for 1 hour on days 1 and 11 of the 31-day experiment. Rats also received psychosocial stress via daily cage cohort changes. On day 32, the rats were sacrificed and the brains dissected to remove the hippocampus and PFC. Norepinephrine (NE, 5-Hydroxyindoleacetic acid (5-HIAA, homovanillic acid (HVA, dopamine (DA, and 3,4-Dihydroxyphenylacetic acid (DOPAC, and 5-HT levels in the hippocampus and PFC were measured with high-performance liquid chromatography (HPLC. In the hippocampus, 5-HT and HVA were lower, while NE and DOPAC were higher, in the PTSD group vs. controls. In the PFC, only 5-HT was lower, while NE, DA, and DOPAC were higher, in the PTSD group vs. controls. The rate limiting enzymes tyrosine hydroxylase and tryptophan hydroxylase were also examined and confirmed our findings. These results demonstrate that the predator exposure/psychosocial stress model of PTSD produces neurotransmitter changes similar to those seen in human patients and may

  9. Comparison of the Effects of Adenosine A1 Receptors Activity in CA1 Region of the Hippocampus on Entorhinal Cortex and Amygdala Kindled Seizures in Rats

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    A. Heidarianpour

    2008-10-01

    Full Text Available Introduction & Objective: In the CNS, adenosine is known to suppress repetitive neuronal Firing, suggesting a role as an endogenous modifier of seizures. Indeed, intracerebral adenosine concentrations rise acutely during seizure activity and are thought to be responsible for terminating seizures and establishing a period of post-ictal refractoriness. However, it is unclear whether this suppression results from a general depression of brain excitability or through action on particular sites critical for the control of after discharge generation and/or seizure development and propagation. In this regard, comparison of the effects of adenosine A1 receptors of CA1 (region of the ‎hippocampus on entorhinal cortex and amygdala kindled seizures was ‎investigated in this study. Materials & Methods: In this experimental study, Animals were kindled by daily electrical stimulation of amygdale (group A or entorhinal cortex (group B. In the fully kindled animals, N6-‎cyclohexyladenosine (CHA;1 and 10 M; a selective adenosine A1 receptor ‎agonist and 1,3-dimethyl-8-cyclohexylxanthine(CPT;1 ‎µ‎M; a selective ‎adenosine A1 receptors antagonist were microinfused bilaterally into the CA1 ‎region of hippocampus (1l/2min and animals were stimulated at 5 and 15 minutes after drug ‎injection. All animals were received artificial cerebrospinal fluid, 24 h before ‎each drug injection and this result were used as control. Results: The seizure parameters were measured at 5 and 15min post injection. Obtained data showed that CHA at concentrations of 10 ‎µ‎M reduced ‎entorhinal cortex and amygdala after discharge and stage5 seizure durations and ‎increased stage4 latency. CHA at concentration 1‎µ‎M significantly alters ‎seizure parameters of group A but not effect on group B. Intrahippocampal (CA1 region pretreatment of CPT (1 ‎µ‎M before CHA abolished the effects of CHA on seizure parameters.Conclusion: It ‎may be

  10. Initialisation of 3D level set for hippocampus segmentation from volumetric brain MR images

    Science.gov (United States)

    Hajiesmaeili, Maryam; Dehmeshki, Jamshid; Bagheri Nakhjavanlo, Bashir; Ellis, Tim

    2014-04-01

    Shrinkage of the hippocampus is a primary biomarker for Alzheimer's disease and can be measured through accurate segmentation of brain MR images. The paper will describe the problem of initialisation of a 3D level set algorithm for hippocampus segmentation that must cope with the some challenging characteristics, such as small size, wide range of intensities, narrow width, and shape variation. In addition, MR images require bias correction, to account for additional inhomogeneity associated with the scanner technology. Due to these inhomogeneities, using a single initialisation seed region inside the hippocampus is prone to failure. Alternative initialisation strategies are explored, such as using multiple initialisations in different sections (such as the head, body and tail) of the hippocampus. The Dice metric is used to validate our segmentation results with respect to ground truth for a dataset of 25 MR images. Experimental results indicate significant improvement in segmentation performance using the multiple initialisations techniques, yielding more accurate segmentation results for the hippocampus.

  11. Learned helplessness is independent of levels of brain-derived neurotrophic factor in the hippocampus

    OpenAIRE

    Greenwood, Benjamin N.; Strong, Paul V; Foley, Teresa E.; Thompson, Robert; Fleshner, Monika

    2006-01-01

    Reduced levels of brain-derived neurotrophic factor (BDNF) in the hippocampus have been implicated in human affective disorders and behavioral stress responses. The current studies examined the role of BDNF in the behavioral consequences of inescapable stress, or learned helplessness. Inescapable stress decreased BDNF mRNA and protein in the hippocampus of sedentary rats. Rats allowed voluntary access to running wheels for either 3 or 6 weeks prior to exposure to stress were protected against...

  12. Elevation of Brain Magnesium Potentiates Neural Stem Cell Proliferation in the Hippocampus of Young and Aged Mice.

    Science.gov (United States)

    Jia, Shanshan; Liu, Yunpeng; Shi, Yang; Ma, Yihe; Hu, Yixin; Wang, Meiyan; Li, Xue

    2016-09-01

    In the adult brain, neural stem cells (NSCs) can self-renew and generate all neural lineage types, and they persist in the sub-granular zone (SGZ) of the hippocampus and the sub-ventricular zone (SVZ) of the cortex. Here, we show that dietary-supplemented - magnesium-L-threonate (MgT), a novel magnesium compound designed to elevate brain magnesium regulates the NSC pool in the adult hippocampus. We found that administration of both short- and long-term regimens of MgT, increased the number of hippocampal NSCs. We demonstrated that in young mice, dietary supplementation with MgT significantly enhanced NSC proliferation in the SGZ. Importantly, in aged mice that underwent long-term (12-month) supplementation with MgT, MgT did not deplete the hippocampal NSC reservoir but rather curtailed the age-associated decline in NSC proliferation. We further established an association between extracellular magnesium concentrations and NSC self-renewal in vitro by demonstrating that elevated Mg(2+) concentrations can maintain or increase the number of cultured hippocampal NSCs. Our study also suggests that key signaling pathways for cell growth and proliferation may be candidate targets for Mg(2+) 's effects on NSC self-renewal. J. Cell. Physiol. 231: 1903-1912, 2016. © 2016 Wiley Periodicals, Inc. PMID:26754806

  13. Dosimetric analysis of the alopecia preventing effect of hippocampus sparing whole brain radiation therapy

    International Nuclear Information System (INIS)

    Whole brain radiation therapy (WBRT) is widely used for the treatment of brain metastases. Cognitive decline and alopecia are recognized adverse effects of WBRT. Recently hippocampus sparing whole brain radiation therapy (HS-WBRT) has been shown to reduce the incidence of memory loss. In this study, we found that multi-field intensity modulated radiation therapy (IMRT), with strict constraints to the brain parenchyma and to the hippocampus, reduces follicular scalp dose and prevents alopecia. Suitable patients befitting the inclusion criteria of the RTOG 0933 trial received Hippocampus sparing whole brain radiation. On follow up, they were noticed to have full scalp hair preservation. 5 mm thickness of follicle bearing scalp in the radiation field was outlined in the planning CT scans. Conventional opposed lateral WBRT radiation fields were applied to these patient-specific image sets and planned with the same nominal dose of 30 Gy in 10 fractions. The mean and maximum dose to follicle bearing skin and Dose Volume Histogram (DVH) data were analyzed for conventional and HS-WBRT. Paired t-test was used to compare the means. All six patients had fully preserved scalp hair and remained clinically cognitively intact 1–3 months after HS-WBRT. Compared to conventional WBRT, in addition to the intended sparing of the Hippocampus, HS-WBRT delivered significantly lower mean dose (22.42 cGy vs. 16.33 cGy, p < 0.0001), V24 (9 cc vs. 44 cc, p < 0.0000) and V30 (9 cc vs. 0.096 cc, p = 0.0106) to follicle hair bearing scalp and prevented alopecia. There were no recurrences in the Hippocampus area. HS-WBRT, with an 11-field set up as described, while attempting to conserve hippocampus radiation and maintain radiation dose to brain inadvertently spares follicle-bearing scalp and prevents alopecia

  14. Changes in the default mode network in the prefrontal lobe, posterior cingulated cortex and hippocampus of heroin users

    Institute of Scientific and Technical Information of China (English)

    Wenfu Hu; Xiangming Fu; Ruobing Qian; Xiangpin Wei; Xuebing Ji; Chaoshi Niu

    2012-01-01

    The default mode network is associated with senior cognitive functions in humans. In this study, we performed independent component analysis of blood oxygenation signals from 14 heroin users and 13 matched normal controls in the resting state through functional MRI scans. Results showed that the default mode network was significantly activated in the prefrontal lobe, posterior cingulated cortex and hippocampus of heroin users, and an enhanced activation signal was observed in the right inferior parietal lobule (P < 0.05, corrected for false discovery rate). Experimental findings indicate that the default mode network is altered in heroin users.

  15. Neuronal degeneration in the hippocampus and dorsolateral prefrontal cortex in depressive disorder Correlation between 1H-MRS and Minnesota Multiphasic Personality Inventory

    Institute of Scientific and Technical Information of China (English)

    Jun Xia; Minjie Yang; Yi Lei; Yicheng Zhou

    2010-01-01

    Previous studies using magnetic resonance imaging(MRI)and functional MRI to study depression have primarily focused on proton magnetic resonance spectroscopy(1H-MRS)appearance in various areas of the brain and volume measurements in the limbic system.However,results have not been consistent.To the best of our knowledge,very little is known about the relationship between 1H-MRS appearance and depression inventory.In the present study,the relationship between 1H-MRS appearance in depressive patients and Minnesota Multiphasic Personality Inventory-2 scale was analyzed.MRI and 1H-MRS exhibited widened sulci and cisterns,as well as an absence of abnormal signals in depressive patients.In addition,N-acetyl aspartate/total creatine ratios in bilateral hippocampi and dorsolateral prefrontal cortex were significantly less in depressive patients than in control subjects(P < 0.01).In contrast,choline-containing compounds/total creatine ratios in the dorsolateral prefrontal cortex were significantly greater in depressive patients than in control subjects(P < 0.01).These ratios significantly and positively correlated with patient total depression scores as assessed using the Minnesota Multiphasic Personality Inventory-2 scale(r=0.934 7,0.878 7,P < 0.01).These results suggested that 1H-MRS could be used to reveal a reduced number of neurons in the hippocampus and dorsolateral prefrontal cortex,as well as altered membrane phospholipid metabolism in the dorsolateral prefrontal cortex,in patients with depressive disorder.Abnormal mechanisms partially reflected severity of depressive disorder.

  16. Expression of GFAP MRNA in rat hippocampus after whole-brain irradiation

    International Nuclear Information System (INIS)

    Objective: To discuss the role of GFAP in brain irradiation injury by observing the expression changes of GFAPmRNA in the hippocampus region of rat after whole-brain irradiation. Methods: The model was established in the rat after whole-brain irradiation with the single dose of 4 MeV electron beam. The dynamic expression of GFAPmRNA in the hippocampus was analyzed semi-quantitatively at different times (1 and 30 days) and doses (2 Gy, 10 Gy and 30 Gy) points with RT-PCR. Results: The level of GFAPmRNA was elevated significantly 1 day after whole-brain irradiation in 10 Gy and 30 Gy groups (P0.05). Conclusions: the up-regulation of GFAPmRNA is time and radiation dose dependent. GFAP plays an important role in protective and imparative mechanism of brain irradiation injury. (authors)

  17. Differential Local Connectivity and Neuroinflammation Profiles in the Medial Prefrontal Cortex and Hippocampus in the Valproic Acid Rat Model of Autism.

    Science.gov (United States)

    Codagnone, Martín Gabriel; Podestá, María Fernanda; Uccelli, Nonthué Alejandra; Reinés, Analía

    2015-01-01

    Autism spectrum disorders (ASD) are a group of developmental disabilities characterized by impaired social interaction, communication deficit and repetitive and stereotyped behaviors. Neuroinflammation and synaptic alterations in several brain areas have been suggested to contribute to the physiopathology of ASD. Although the limbic system plays an important role in the functions found impaired in ASD, reports on these areas are scarce and results controversial. In the present study we searched in the medial prefrontal cortex (mPFC) and hippocampus of rats exposed to the valproic acid (VPA) model of ASD for early structural and molecular changes, coincident in time with the behavioral alterations. After confirming delayed growth and maturation in VPA rats, we were able to detect decreased exploratory activity and social interaction at an early time point (postnatal day 35). In mPFC, although typical cortical column organization was preserved in VPA animals, we found that interneuronal space was wider than in controls. Hippocampal CA3 (cornu ammonis 3) pyramidal layer and the granular layer of the dentate gyrus both showed a disorganized spatial arrangement in VPA animals. Neuronal alterations were accompanied with increased tomato lectin and glial fibrillary acidic protein (GFAP) immunostainings both in the mPFC and hippocampus. In the latter region, the increased GFAP immunoreactivity was CA3 specific. At the synaptic level, while mPFC from VPA animals showed increased synaptophysin (SYN) immunostaining, a SYN deficit was found in all hippocampal subfields. Additionally, both the mPFC and the hippocampus of VPA rats showed increased neuronal cell adhesion molecule (NCAM) immunostaining together with decreased levels of its polysialylated form (PSA-NCAM). Interestingly, these changes were more robust in the CA3 hippocampal subfield. Our results indicate that exploratory and social deficits correlate with region-dependent neuronal disorganization and reactive

  18. Changes of CREB in rat hippocampus, prefrontal cortex and nucleus accumbens during three phases of morphine induced conditioned place preference in rats

    Institute of Scientific and Technical Information of China (English)

    ZHOU Lian-fang; ZHU Yong-ping

    2006-01-01

    Objective: To investigate the changes in CREB (cAMP response element binding protein) in hippocampus, PFC(prefrontal cortex) and NAc (nucleus accumbens) during three phases of morphine induced CPP (conditioned place preference) in rats, and to elucidate the role of CREB during the progress of conditioned place preference. Methods: Morphine induced CPP acquisition, extinction and drug primed reinstatement model was established, and CREB expression in each brain area was measured by Western Blot methods. Results: Eight alternating injections of morphine (10 mg/kg) induced CPP, and 8 d saline extinction training that extinguished CPP. CPP was reinstated following a priming injection of morphine (2.5 mg/kg). During the phases of CPP acquisition and reinstatement, the level of CREB expression was significantly changed in different brain areas.Conclusion: It was proved that CPP model can be used as an effective tool to investigate the mechanisms underlying drug-induced reinstatement of drug seeking after extinction, and that morphine induced CPP and drug primed reinstatement may involve activation of the transcription factor CREB in several brain areas, suggesting that the CREB and its target gene regulation pathway may mediate the basic mechanism underlying opioid dependence and its drug seeking behavior.

  19. Beneficial effects of hyperbaric oxygen on edema in rat hippocampus following traumatic brain injury.

    Science.gov (United States)

    Liu, Su; Liu, Ying; Deng, Shukun; Guo, Aisong; Wang, Xiubing; Shen, Guangyu

    2015-12-01

    Hyperbaric oxygen (HBO) therapy helps alleviate secondary injury following brain trauma [traumatic brain injury (TBI)], although the mechanisms remain unclear. In this study, we assessed recovery of post-TBI spatial learning and memory in rats using the Morris water maze (MWM) and measured changes in apparent diffusion coefficient in the hippocampus by diffusion-weighted imaging (DWI) to evaluate possible therapeutic effects of HBO on TBI-associated brain edema. DWIs were obtained 8, 24, 48 h, 7 days, and 14 days post-TBI. Daily HBO therapy significantly improved post-TBI MWM performance and reduced edema in the ipsilateral hippocampus, suggesting that the therapeutic efficacy of HBO is mediated, at least in part, by a reduction in brain edema. PMID:26267487

  20. Energy Drink Administration in Combination with Alcohol Causes an Inflammatory Response and Oxidative Stress in the Hippocampus and Temporal Cortex of Rats

    Directory of Open Access Journals (Sweden)

    Alfonso Díaz

    2016-01-01

    Full Text Available Energy drinks (EDs are often consumed in combination with alcohol because they reduce the depressant effects of alcohol. However, different researches suggest that chronic use of these psychoactive substances in combination with alcohol can trigger an oxidative and inflammatory response. These processes are regulated by both a reactive astrogliosis and an increase of proinflammatory cytokines such as IL-1β, TNF-α, and iNOS, causing cell death (apoptosis at the central and peripheral nervous systems. Currently, mechanisms of toxicity caused by mixing alcohol and ED in the brain are not well known. In this study, we evaluated the effect of chronic alcohol consumption in combination with ED on inflammatory response and oxidative stress in the temporal cortex (TCx and hippocampus (Hp of adult rats (90 days old. Our results demonstrated that consuming a mixture of alcohol and ED for 60 days induced an increase in reactive gliosis, IL-1β, TNF-α, iNOS, reactive oxygen species, lipid peroxidation, and nitric oxide, in the TCx and Hp. We also found immunoreactivity to caspase-3 and a decrease of synaptophysin in the same brain regions. The results suggested that chronic consumption of alcohol in combination with ED causes an inflammatory response and oxidative stress, which induced cell death via apoptosis in the TCx and Hp of the adult rats.

  1. Aberrant intrinsic connectivity of hippocampus and amygdala overlap in the fronto-insular and dorsomedial-prefrontal cortex in major depressive disorder

    Directory of Open Access Journals (Sweden)

    Masoud Tahmasian

    2013-10-01

    Full Text Available Neuroimaging studies of major depressive disorder (MDD have consistently observed functional and structural changes of the hippocampus (HP and amygdale (AY. Thus, these brain regions appear to be critical elements of the pathophysiology of MDD. The HP and AY directly interact and show broad and overlapping intrinsic functional connectivity (iFC to other brain regions. Therefore, we hypothesized the HP and AY would show a corresponding pattern of aberrant intrinsic connectivity in MDD. Resting-state functional MRI was acquired from 21 patients with MDD and 20 healthy controls. ß-maps of region-of-interest-based FC for bilateral body of the HP and basolateral AY were used as surrogates for iFC of the HP and AY. ANOVA was used to compare ß-maps between MDD and healthy control groups, and included covariates for age and gender as well as grey matter volume of the HP and AY. The HP and AY of MDD patient’s showed an overlapping pattern of reduced FC to the dorsomedial prefrontal cortex and fronto-insular operculum. Both of these regions are known to regulate the interactions among intrinsic networks (i.e. default mode, central executive, and salience networks that are disrupted in MDD. These results provide the first evidence of overlapping aberrant HP and AY intrinsic connectivity in MDD. Our findings suggest that aberrant HP and AY connectivity may interact with dysfunctional intrinsic network activity in MDD.

  2. Energy Drink Administration in Combination with Alcohol Causes an Inflammatory Response and Oxidative Stress in the Hippocampus and Temporal Cortex of Rats

    Science.gov (United States)

    Díaz, Alfonso; Treviño, Samuel; Guevara, Jorge; Muñoz-Arenas, Guadalupe; Brambila, Eduardo; Espinosa, Blanca; Moreno-Rodríguez, Albino; Lopez-Lopez, Gustavo; Peña-Rosas, Ulises; Venegas, Berenice; Handal-Silva, Anabella; Morán-Perales, José Luis; Flores, Gonzalo; Aguilar-Alonso, Patricia

    2016-01-01

    Energy drinks (EDs) are often consumed in combination with alcohol because they reduce the depressant effects of alcohol. However, different researches suggest that chronic use of these psychoactive substances in combination with alcohol can trigger an oxidative and inflammatory response. These processes are regulated by both a reactive astrogliosis and an increase of proinflammatory cytokines such as IL-1β, TNF-α, and iNOS, causing cell death (apoptosis) at the central and peripheral nervous systems. Currently, mechanisms of toxicity caused by mixing alcohol and ED in the brain are not well known. In this study, we evaluated the effect of chronic alcohol consumption in combination with ED on inflammatory response and oxidative stress in the temporal cortex (TCx) and hippocampus (Hp) of adult rats (90 days old). Our results demonstrated that consuming a mixture of alcohol and ED for 60 days induced an increase in reactive gliosis, IL-1β, TNF-α, iNOS, reactive oxygen species, lipid peroxidation, and nitric oxide, in the TCx and Hp. We also found immunoreactivity to caspase-3 and a decrease of synaptophysin in the same brain regions. The results suggested that chronic consumption of alcohol in combination with ED causes an inflammatory response and oxidative stress, which induced cell death via apoptosis in the TCx and Hp of the adult rats. PMID:27069534

  3. Energy Drink Administration in Combination with Alcohol Causes an Inflammatory Response and Oxidative Stress in the Hippocampus and Temporal Cortex of Rats.

    Science.gov (United States)

    Díaz, Alfonso; Treviño, Samuel; Guevara, Jorge; Muñoz-Arenas, Guadalupe; Brambila, Eduardo; Espinosa, Blanca; Moreno-Rodríguez, Albino; Lopez-Lopez, Gustavo; Peña-Rosas, Ulises; Venegas, Berenice; Handal-Silva, Anabella; Morán-Perales, José Luis; Flores, Gonzalo; Aguilar-Alonso, Patricia

    2016-01-01

    Energy drinks (EDs) are often consumed in combination with alcohol because they reduce the depressant effects of alcohol. However, different researches suggest that chronic use of these psychoactive substances in combination with alcohol can trigger an oxidative and inflammatory response. These processes are regulated by both a reactive astrogliosis and an increase of proinflammatory cytokines such as IL-1β, TNF-α, and iNOS, causing cell death (apoptosis) at the central and peripheral nervous systems. Currently, mechanisms of toxicity caused by mixing alcohol and ED in the brain are not well known. In this study, we evaluated the effect of chronic alcohol consumption in combination with ED on inflammatory response and oxidative stress in the temporal cortex (TCx) and hippocampus (Hp) of adult rats (90 days old). Our results demonstrated that consuming a mixture of alcohol and ED for 60 days induced an increase in reactive gliosis, IL-1β, TNF-α, iNOS, reactive oxygen species, lipid peroxidation, and nitric oxide, in the TCx and Hp. We also found immunoreactivity to caspase-3 and a decrease of synaptophysin in the same brain regions. The results suggested that chronic consumption of alcohol in combination with ED causes an inflammatory response and oxidative stress, which induced cell death via apoptosis in the TCx and Hp of the adult rats. PMID:27069534

  4. Afferent Drive of Medial Prefrontal Cortex by Hippocampus and Amygdala is Altered in MAM-Treated Rats: Evidence for Interneuron Dysfunction

    OpenAIRE

    Esmaeili, Behnaz; Grace, Anthony A.

    2013-01-01

    Evidence indicates that the prefrontal cortex and its regulation by afferent inputs are disrupted in schizophrenia. Using a validated rat model of schizophrenia based on prenatal administration of the mitotoxin methyl azoxymethanol acetate (MAM), we examined the convergent projections from the ventral hippocampus (vHipp) and the basolateral amygdala (BLA) in the medial prefrontal cortex (mPFC). In vivo extracellular recordings were done in anesthetized rats to assess how prior stimulation of ...

  5. Effects of the Brain Derived Neurotrophic Growth Factor Val66Met Variation on Hippocampus Morphology in Bipolar Disorder

    OpenAIRE

    Chepenik, Lara G.; Fredericks, Carolyn; Papademetris, Xenophon; Spencer, Linda; Lacadie, Cheryl; Wang, Fei; Pittman, Brian; Duncan, James S.; Staib, Lawrence H.; Duman, Ronald S.; Gelernter, Joel; Blumberg, Hilary P.

    2008-01-01

    Histological and behavioral research in bipolar disorder (BD) implicates structural abnormalities in the hippocampus. Brain-derived neurotrophic growth factor (BDNF) protein is associated with hippocampal development and plasticity, and in mood disorder pathophysiology. We tested the hypotheses both the BDNF val66met polymorphism and BD diagnosis are associated with decreased hippocampus volume, and individuals with BD who carry the met allele have the smallest hippocampus volumes compared to...

  6. Effects of the Bee Venom Herbal Acupuncture on the Neurotransmitters of the Rat Brain Cortex

    Directory of Open Access Journals (Sweden)

    Hyoung-Seok Yun

    2001-02-01

    Full Text Available In order to study the effects of bee venom Herbal Acupuncture on neurotransmitters in the rat brain cortex, herbal acupuncture with bee venom group and normal saline group was performed at LI4 bilaterally of the rat. the average optical density of neurotransmitters from the cerebral cortex was analysed 30 minutes after the herbal aqupuncture, by the immunohistochemistry. The results were as follows: 1. The density of NADPH-diaphorase in bee venom group was increased significantly at the motor cortex, visual cortex, auditory cortex, cingulate cortex, retrosplenial cortex and perirhinal cortex compared to the normal saline group. 2. The average optical density of vasoactive intestinal peptide in bee venom group had significant changes at the insular cortex, retrosplenial cortex and perirhinal cortex, compared to the normal saline group. 3. The average optical density of neuropeptide-Y in bee venom group increased significantly at the visual cortex and cingulate cortex, compared to the normal saline group.

  7. Altered reward processing in the orbitofrontal cortex and hippocampus in healthy first-degree relatives of patients with depression

    DEFF Research Database (Denmark)

    Macoveanu, J; Knorr, U; Skimminge, A;

    2014-01-01

    trial we investigated whether a 4-week intervention with the selective serotonergic reuptake inhibitor (SSRI) escitalopram had a normalizing effect on behavior and brain responses of the rMD+ individuals. RESULTS: Negative outcomes increased the probability of risk-averse choices in the subsequent trial...... escitalopram intervention compared to placebo. Conversely, for positive outcomes, the left hippocampus showed attenuated response to high wins in the rMD+ compared to the rMD- group. The SSRI intervention reinforced the hippocampal response to large wins. A subsequent structural analysis revealed that the...

  8. Learning-related representational changes reveal dissociable integration and separation signatures in the hippocampus and prefrontal cortex.

    Science.gov (United States)

    Schlichting, Margaret L; Mumford, Jeanette A; Preston, Alison R

    2015-01-01

    The episodic memory system enables accurate retrieval while maintaining flexibility by representing both specific episodes and generalizations across events. Although theories suggest that the hippocampus (HPC) is dedicated to represent specific episodes while the medial prefrontal cortex (MPFC) generalizes, other accounts posit that HPC can also integrate related memories. Here we use high-resolution functional magnetic resonance imaging in humans to examine how representations of memory elements change to either differentiate or generalize across related events. We show that while posterior HPC and anterior MPFC maintain distinct memories for individual events, anterior HPC and posterior MPFC integrate across memories. Integration is particularly likely for established memories versus those encoded simultaneously, highlighting the greater impact of prior knowledge on new encoding. We also show dissociable coding signatures in ventrolateral PFC, a region previously implicated in interference resolution. These data highlight how memory elements are represented to simultaneously promote generalization across memories and protect from interference. PMID:26303198

  9. Hippocampus, caudate nucleus and entorhinal cortex volumetric MRI measurements in discrimination between Alzheimer’s disease, mild cognitive impairment, and normal aging

    Directory of Open Access Journals (Sweden)

    Rasha Elshafey

    2014-06-01

    Conclusion: Semi-automated MR volumetric measurements can be used to determine atrophy in hippocampus, caudate nucleus and entorhinal cortex which aided in discrimination of healthy elderly control subjects from subjects with AD and MCI and predict clinical decline of MCI leading to increase the efficiency of clinical treatments, delay institutionalization and improve cognition and behavioral symptoms.

  10. Localization of glucocorticoid receptor messenger ribonucleic acid in hippocampus of rat brain using in situ hybridization

    International Nuclear Information System (INIS)

    An in situ hybridization procedure was applied to quantify glucocorticoid receptor (GR) mRNAs in the hippocampus of rat brain. Hybridization was carried out using a radiolabeled antisense probe complementary to the rat liver GR gene. The specificity of the method was validated by showing: 1) a high cellular grain density in sections hybridized with an antisense but not a sense probe; 2) agreement between the experimental and theoretical temperature at which 50% of the hybrids melted, and 3) a high signal distribution of GR mRNA in the hippocampus, a region of brain known to preferentially concentrate steroid hormones. Within the hippocampus, however, subregional differences in hybridization densities were observed. Quantitative autoradiography indicated that the average neuronal silver grain number was highest in the pyramidal cell layers of CA2 and CA4 and lowest in those of CA1 and CA3. Also, there was a significant difference in the average grain number between all of the cell fields except for that between CA2 and CA4. These results show that contiguous but neuroanatomically distinct cell fields of the hippocampus express different levels of GR transcripts, and indicate that differential regulation of GR expression occurs in subpopulations of hippocampal neurons

  11. Apoptosis and morphological changes in hippocampus of rat brain after hemisphere irradiation

    International Nuclear Information System (INIS)

    Objective: To study the apoptosis, the expression of bcl-2 and the morphological changes of various tissue components in the rat hippocampus after hemisphere irradiation. Methods: The DNA contents and the quantities of bcl-2 protein were analyzed by flow cytometry. The histological sections were examined by electron and light microscopy. Results: The apoptosis of hippocampal cells in the irradiated brain increased in most of the rats, the expression of bcl-2 decreased in the meantime,and those changes were significant only in the groups irradiated within 1 month. Necrosis was observed in some of the 30 Gy-3-month-period group. Different levels of morphological changes in blood vessels, neuro-glia cells and neurons were found in rats of all other groups. Conclusion: After hemisphere irradiation, apoptosis increases, bcl-2 protein decreases, and various components in the hippocampus change. These data suggest a possible association between the damage of various components and development of radiation-induced brain toxicity

  12. Effects of visual deprivation during brain development on expression of AMPA receptor subunits in rat’s hippocampus

    Directory of Open Access Journals (Sweden)

    Sayyed Alireza Talaei

    2015-06-01

    Conclusion: Dark rearing of rats during critical period of brain development changes the relative expression and also arrangement of both AMPA receptor subunits, GluR1 and GluR2 in the hippocampus, age dependently.

  13. Implication of Tryptophan 2,3-Dioxygenase and its Novel Variants in the Hippocampus and Cerebellum During the Developing and Adult Brain

    Directory of Open Access Journals (Sweden)

    Masaaki Kanai

    2010-07-01

    Full Text Available Tryptophan 2,3-dioxygenase (TDO is a first and rate-limiting enzyme for the kynurenine pathway of tryptophan metabolism. Using Tdo-/-mice, we have recently shown that TDO plays a pivotal role in systemic tryptophan metabolism and brain serotonin synthesis as well as emotional status and adult neurogenesis. However, the expression of TDO in the brain has not yet been well characterized, in contrast to its predominant expression in the liver. To further examine the possible role of local TDO in the brain, we quantified the levels of tdo mRNA in various nervous tissues, using Northern blot and quantitative real-time RT-PCR. Higher levels of tdo mRNA expression were detected in the cerebellum and hippocampus. We also identified two novel variants of the tdo gene, termed tdo variant1 and variant2, in the brain. Similar to the known TDO form (TDO full-form, tetramer formation and enzymatic activity were obtained when these variant forms were expressed in vitro. While quantitative real-time RT-PCR revealed that the tissue distribution of these variants was similar to that of tdo full-form, the expression patterns of these variants during early postnatal development in the hippocampus and cerebellum differed. Our findings indicate that in addition to hepatic TDO, TDO and its variants in the brain might function in the developing and adult nervous system. Given the previously reported associations of tdo gene polymorphisms in the patients with autism and Tourette syndrome, the expression of TDO in the brain suggests the possible influence of TDO on psychiatric status. Potential functions of TDOs in the cerebellum, hippocampus and cerebral cortex under physiological and pathological conditions are discussed.

  14. Moderate traumatic brain injury promotes proliferation of quiescent neural progenitors in the adult hippocampus

    OpenAIRE

    Gao, Xiang; Enikolopov, Grigori; Chen, Jinhui

    2009-01-01

    Recent evidence shows that traumatic brain injury (TBI) regulates proliferation of neural stem/progenitor cells in the dentate gyrus (DG) of adult hippocampus. There are distinct classes of neural stem/progenitor cells in the adult DG, including quiescent neural progenitors (QNPs), which carry stem cell properties, and their progeny, amplifying neural progenitors (ANPs). The response of each class of progenitors to TBI is not clear. We here used a transgenic reporter Nestin-GFP mouse line, in...

  15. Studies of the macroscopic and microscopic morphology (hippocampus of brain in Vencobb broiler

    Directory of Open Access Journals (Sweden)

    Shailesh Kumar Gupta

    2016-05-01

    Full Text Available Aim: The aim of this study was to study the anatomy of different parts of brain and histology of hippocampus of Vencobb broiler chicken. Materials and Methods: A 12 adult experimental birds were sacrificed by cervical dislocation. After separation of the brain, gross anatomy features were studied. Brain tissue was fixed in 10% buffered neutral formalin for 2-3 days, and then routine dehydration process in ascending grades of ethyl alcohol was done. After xylene cleaning, paraffin impregnation was prepared. Paraffin blocks were cut, and slides were stained by Harris hematoxylin and eosin. Photography was carried out both under lower (×10 and higher (×40 magnifications. Results: The brain structure (dorsal view of Vencobb bird resembled the outline of a playing card symbol of a “spade.” The brain subdivisions are cerebrum, cerebellum, and medulla oblongata. Cerebrum was devoid of usual convolutions (elevations, gyri, depressions (grooves, and sulci. The cerebral hemispheres were tightly apposed along a median sulcus called interhemispheric fissure and cerebrum and cerebellum were separated by a small transverse fissure. The olfactory bulb was small structures, and the pineal body was clearly visible. The optic lobes were partially hidden under cerebral hemispheres, but laterally, it was large, prominent rounded or spherical bodies of the midbrain. The hippocampal area appeared as dorso-medial protrusion. Different types of neurons were distinguished in the hippocampus were pyramidal neurons, pyramidal-like neurons, and multipolar neurons, etc. There was rich vascularization in the form of blood capillaries throughout the hippocampus. Conclusion: Cerebrum was pear shaped and largest part of the brain. Cerebrum hemisphere was smooth devoid of convolutions, gyri, and depressions, but in the surface of cerebellum, there was the presence of a number of transverse depression (grooves and sulci subdividing into many folds. Olfactory bulb was poorly

  16. Functional differentiation of the premotor cortex: Behavioural and brain imaging studies in humans

    OpenAIRE

    Potgieser, Adriaan Remco Ewoud

    2015-01-01

    The premotor cortex is a brain structure that is involved in the preparation of movements. It has an important role in the final integration of task-related information and to funnel this to the primary motor cortex, which subsequently causes the execution of a movement. Premotor areas can also influence motor output through their direct interactions with both the spinal cord. Within the premotor cortex, the ventral premotor cortex (PMv), dorsal premotor cortex (PMd) and supplementary motor a...

  17. Amygdala, Hippocampus, and Ventral Medial Prefrontal Cortex Volumes Differ in Maltreated Youth with and without Chronic Posttraumatic Stress Disorder.

    Science.gov (United States)

    Morey, Rajendra A; Haswell, Courtney C; Hooper, Stephen R; De Bellis, Michael D

    2016-02-01

    Posttraumatic stress disorder (PTSD) is considered a disorder of recovery where individuals fail to learn and retain extinction of the traumatic fear response. In maltreated youth, PTSD is common, chronic, and associated with comorbidity. Studies of extinction-related structural volumes (amygdala, hippocampus, anterior cingulate cortex (ACC), and ventral medial prefrontal cortex (vmPFC)) and this stress diathesis, in maltreated youth were not previously investigated. In this cross-sectional study, neuroanatomical volumes associated with extinction in maltreated youth with PTSD (N=31), without PTSD (N=32), and in non-maltreated healthy volunteers (n=57) were examined using magnetic resonance imaging. Groups were sociodemographically similar. Participants underwent extensive assessments for strict inclusion/exclusion criteria and DSM-IV disorders. Maltreated youth with PTSD demonstrated decreased right vmPFC volumes compared with both maltreated youth without PTSD and non-maltreated controls. Maltreated youth without PTSD demonstrated larger left amygdala and right hippocampal volumes compared with maltreated youth with PTSD and non-maltreated control youth. PTSD symptoms inversely correlated with right and left hippocampal and left amygdala volumes. Confirmatory masked voxel base morphometry analyses demonstrated greater medial orbitofrontal cortex gray matter intensity in controls than maltreated youth with PTSD. Volumetric results were not influenced by psychopathology or maltreatment variables. We identified volumetric differences in extinction-related structures between maltreated youth with PTSD from those without PTSD. Alterations of the vmPFC may be one mechanism that mediates the pathway from PTSD to comorbidity. Further longitudinal work is needed to determine neurobiological factors related to chronic and persistent PTSD, and to PTSD resilience despite maltreatment. PMID:26171720

  18. Linking pattern completion in the hippocampus to predictive coding in visual cortex.

    Science.gov (United States)

    Hindy, Nicholas C; Ng, Felicia Y; Turk-Browne, Nicholas B

    2016-05-01

    Models of predictive coding frame perception as a generative process in which expectations constrain sensory representations. These models account for expectations about how a stimulus will move or change from moment to moment, but do not address expectations about what other, distinct stimuli are likely to appear based on prior experience. We show that such memory-based expectations in human visual cortex are related to the hippocampal mechanism of pattern completion. PMID:27065363

  19. Prefrontal cortex and hippocampus in behavioural flexibility and posttraumatic functional recovery

    DEFF Research Database (Denmark)

    Rytter, Hana Malá; Andersen, Lykke Grønbech; Christensen, Rie Friis;

    2015-01-01

    -shifting. Postoperatively, the animals were trained to perform a spatial discrimination go-right task. This was followed by (1) a spatial reversal go-left task (reversal learning), or (2) a visual pattern discrimination task (set-shift). Neither single (PFC or FF) lesion nor combined (COMB) lesions affected the animals......' ability to acquire the original spatial discrimination task. Regarding the reversal learning, the performance of the PFC and the FF groups was not significantly different from that of the sham operated control animals (Sham). In contrast, animals with combined lesion of both structures were impaired on....... We conclude that both the PFC and the hippocampus contributed to the mediation of the reversal learning and set-shifting. During functional recovery of reversal learning, these two structures exhibited a mutual dependency, whilst the functional recovery of set-shifting was mediated by a substrate...

  20. Protection of Cactus Polysaccharide against H2O2-induced damage in the rat cerebral cortex and hippocampus Differences In time of administration

    Institute of Scientific and Technical Information of China (English)

    Xianju Huang; Qin Li; Lianjun Guo; Zankai Yan

    2008-01-01

    BACKGROUND: Pharmacological research has shown that cactus polysaccharide (CP) has anti-oxidant, anti-inflammatory, antitumor, anti-aging, and immune-stimulating activities. It may also provide protective effects against oxidative stress injuries in the rat brain.OBJECTIVE: To validate the effects of CP on H2O2-induced oxidative stress injuries in the ratcerebral cortex and hippocampal slices 30 minutes prior to injury, as well as 30 minutes and 2.5 hours after injury.DESIGN: A randomized controlled experiment.SETTINGS: Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology; Department of Pharmacology, College of Medical Science, Yangtze University.MATERIALS: A total of 50 male Sprague Dawley (SD) rats, normal grade and weighing 200-300 g, were provided by the Laboratory Animal Center of Tongji Medical College, Huazhong University of Science and Technology. The protocol was performed in accordance with ethical guidelines for the use and care of ani-mals. Cactus polysaccharide, a dried needle crystal, was extracted from Opuntia milpa alta at the Chemistry and Environment Engineering School of Yangtze University. The following chemicals and instruments were used: 2,3,5-triphenyl tetrazolium chloride (Sigma, St Louis, Missouri, USA); lactate dehydrogenase (LDH), superoxide dismutase (SOD), glutathione (GSH), and total antioxidant competence (T-AOC) assays (Jiancheng-Bioeng Institute, Nanjing); McIllwain tissue chopper (Mickle Laboratory Engineering, USA); and ELISA reader and Magellan software (TECAN, Austria).METHODS: This experiment was performed at the Department of Pharmacology, Medical College of Yangtze University, between March and June 2006. All rats were sacrificed after anesthesia. The cerebral cortex and hippocampus were dissected. Several cerebral cortex and hippocampus slices were selected as controls, while other sections were co-incubated with H2O2 for 30 minutes to induce an oxidative stress injury. The

  1. Brain polyphosphoinositide metabolism during focal ischemia in rat cortex

    International Nuclear Information System (INIS)

    Using a rat model of stroke, we examined the effects of focal cerebral ischemia on the metabolism of polyphosphoinositides by injecting 32Pi into both the left and right cortices. After equilibration of the label for 2-3 hours, ischemia induced a significant decrease (p less than 0.001) in the concentrations of labeled phosphatidyl 4,5-bisphosphates (66-78%) and phosphatidylinositol 4-phosphate (64-67%) in the right middle cerebral artery cortex of four rats. The phospholipid labeling pattern in the left middle cerebral artery cortex, which sustained only mild ischemia and no permanent tissue damage, was not different from that of two sham-operated controls. However, when 32Pi was injected 1 hour after the ischemic insult, there was a significant decrease (p less than 0.01) in the incorporation of label into the phospholipids in both cortices of four ischemic rats compared with four sham-operated controls. Furthermore, differences in the phospholipid labeling pattern were observed in the left cortex compared with the sham-operated controls. The change in labeling pattern was attributed to the partial reduction in blood flow following ligation of the common carotid arteries. We provide a sensitive procedure for probing the effects of focal cerebral ischemia on the polyphosphoinositide signaling pathway in the brain, which may play an important role in the pathogenesis of tissue injury

  2. 350-μm side-view optical probe for imaging the murine brain in vivo from the cortex to the hypothalamus

    Science.gov (United States)

    Kim, Jun Ki; Choi, Jin Woo; Yun, Seok Hyun

    2013-05-01

    Miniature endoscopic probes offer a solution for deep brain imaging by overcoming the limited depth of intravital microscopy. We describe a small-diameter (350 μm) graded-index optical probe with a side-view design for in vivo cellular imaging of the mammalian brain. The side-view probe provides a unique view of the vertical network of neurons and penetrating blood vessels. At a given insertion site, the translational and rotational scanning of the probe provides access to a large tissue area (>) across the cortex, hippocampus, thalamus, and hypothalamus.

  3. Stress induced a shift from dorsal hippocampus to prefrontal cortex-dependent memory retrieval: role of regional corticosterone.

    Directory of Open Access Journals (Sweden)

    Gaelle eDominguez

    2014-05-01

    Full Text Available Most of the deleterious effects of stress on memory retrieval are due to a dysfunction of the hippocampo-prefrontal cortex interplay. The role of the stress-induced regional corticosterone increase in such dysfunction remains however unclear, since there is no published study as yet dedicated to measuring corticosterone concentrations simultaneously in both the prefrontal cortex (mPFC and the hippocampus (dHPC in relation with memory impairments. To that aim, we first showed in Experiment 1 that an acute stress (3 electric footschocks; 0.9 mA each delivered before memory testing reversed the memory retrieval pattern (MRP in a serial discrimination task in which mice learned two successive discriminations. More precisely, whereas non-stressed animals remembered accurately the first learned discrimination and not the second one, stressed mice remembered more accurately the second discrimination but not the first one. We demonstrated that local inactivation of dHPC or mPFC with the anesthetic lidocaine recruited the dHPC activity in non-stress conditions whereas the stress-induced MRP inversion recruited the mPFC activity. In a second experiment, we showed that acute stress induced a very similar time-course evolution of corticosterone rises within both the mPFC and dHPC. In a 3rd experiment, we found however that in situ injections of corticosterone either within the mPFC or the dHPC before memory testing favored the emergence of the mPFC-dependent MRP but blocked the emergence of the dHPC-dependent one. Overall, our study evidences that the simultaneous increase of corticosterone after stress in both areas induces a shift from dHPC (non stress condition to mPFC-dependent memory retrieval pattern and that corticosterone is critically involved in mediating the deleterious effects of stress on cognitive functions involving the mPFC-HPC interplay.

  4. Learning an operant conditioning task differentially induces gliogenesis in the medial prefrontal cortex and neurogenesis in the hippocampus.

    Directory of Open Access Journals (Sweden)

    Maximiliano Rapanelli

    Full Text Available Circuit modification associated with learning and memory involves multiple events, including the addition and remotion of newborn cells trough adulthood. Adult neurogenesis and gliogenesis were mainly described in models of voluntary exercise, enriched environments, spatial learning and memory task; nevertheless, it is unknown whether it is a common mechanism among different learning paradigms, like reward dependent tasks. Therefore, we evaluated cell proliferation, neurogenesis, astrogliogenesis, survival and neuronal maturation in the medial prefrontal cortex (mPFC and the hippocampus (HIPP during learning an operant conditioning task. This was performed by using endogenous markers of cell proliferation, and a bromodeoxiuridine (BrdU injection schedule in two different phases of learning. Learning an operant conditioning is divided in two phases: a first phase when animals were considered incompletely trained (IT, animals that were learning the task when they performed between 50% and 65% of the responses, and a second phase when animals were considered trained (Tr, animals that completely learned the task when they reached 100% of the responses with a latency time lower than 5 seconds. We found that learning an operant conditioning task promoted cell proliferation in both phases of learning in the mPFC and HIPP. Additionally, the results presented showed that astrogliogenesis was induced in the medial prefrontal cortex (mPFC in both phases, however, the first phase promoted survival of these new born astrocytes. On the other hand, an increased number of new born immature neurons was observed in the HIPP only in the first phase of learning, whereas, decreased values were observed in the second phase. Finally, we found that neuronal maturation was induced only during the first phase. This study shows for the first time that learning a reward-dependent task, like the operant conditioning, promotes neurogenesis, astrogliogenesis, survival and

  5. 1H-MR spectroscopy of the rat hippocampus after whole brain irradiation: an in vivo study

    International Nuclear Information System (INIS)

    Objective: To study the relationships between dynamic changes of the hippocampus metabolites, cognitive impairment and ultrastructural changes of hippocampus in rats during the initial 4 weeks after 6 MV X-ray whole-brain irradiation. Methods: 65 rats were randomly divided into foul groups as sham control (n=5), 10 Gy, 20 Gy and 30 Gy groups (n=20). The learning and memory ability was measured with the Y maze test 4, 8 weeks, 2, 6 months after irradiation. 1H-MRS was performed after 2 or 4 weeks' brain irradiation. The ultrastructural changes of the hippocampus were observed by electronic microscope. Results: The learning and memorizing ability of irradiation groups was significantly different from that of control group. Compared with control group, the NAA/Ct and Cho/Cr ratio in the left hippocampus in 10 Gy, 20 Gy and 30 Gy groups at 2 weeks and 4 weeks decreased significantly. Neuronal mitochondria edema, endothelial cells swelling and lamina dissociation in myelin sheath were demonstrated in various degrees by electromicroscope at 4 weeks following whole brain irradiation. Conclusions: 1H-MRS can be used to non-invasively monitor the metabolic changes, both quantitatively and dynamically, of the irradiated rat brain, 1H-MRS is superior to MRI in detecting early abnormality of the brain. The NAA/Cr and Cho/Cr ratio in irradiated hippocampus could reflect the severity of the brain injury to some extent. (authors)

  6. Age-related decreases in SYN levels associated with increases in MAP-2, apoE, and GFAP levels in the rhesus macaque prefrontal cortex and hippocampus

    OpenAIRE

    Haley, Gwendolen E.; Kohama, Steven G.; Urbanski, Henryk F.; Raber, Jacob

    2010-01-01

    Loss of synaptic integrity in the hippocampus and prefrontal cortex (PFC) may play an integral role in age-related cognitive decline. Previously, we showed age-related increases in the dendritic marker microtubule associated protein 2 (MAP-2) and the synaptic marker synaptophysin (SYN) in mice. Similarly, apolipoprotein E (apoE), involved in lipid transport and metabolism, and glial fibrillary acidic protein (GFAP), a glia specific marker, increase with age in rodents. In this study, we asses...

  7. Effects of Chloroquine on GFAP, PCNA and Cyclin D1 in Hippocampus and Cerebral Cortex of Rats with Seizures Induced by Pentylenetetrazole

    Institute of Scientific and Technical Information of China (English)

    ZHANG Shuhua; ZHU Changgeng; LIU Qingying; WANG Wei

    2005-01-01

    The effects of chloroquine on glial fibrillary acidic protein (GFAP), proliferation cell nuclear antigen (PCNA) and Cyclin D1 in hippocampus and cerebral cortex of rats with seizures induced by pentylenetetrazole (PTZ) were observed in the present study. Forty-eight male adult Sprague-Dawley (SD) rats were randomly divided into control group, chloroquine intervening group, and PTZ group. The behavior and electroencephalogram (EEG) were observed and recor ded. GFAP and PCNA were examined with immunohistochemistry. The content of Cyclin D1 in hippocampus and cerebral cortex was inspected with Western blot. The results showed no seizure activity in the control group, severe seizure activity in the PTZ group (Ⅳ-Ⅴ degree), and slight seizure activity ( Ⅰ - Ⅲ degree) in the chloroquine intervening group (P<0. 05). EEG recordings showed no epileptic spikes in the control group, high amplitude with fast frequency in the PTZ group, low-amplitude and slow frequency in the chloroquine intervening group. The expression of GFAP and the positive index of PCNA in the PTZ group were higher than those of control group (P <0.05 and P<0.01, respectively). No differences in GFAP expression and PCNA index were observed between chloroquine intervening and control groups (P>0.05). The content of Cyclin D1 in hippocampus and cerebral cortex was significantly higher in the PTZ group than in control and chloroquine intervening groups (P< 0.05). Therefore, it is considered that chloroquine, by inhibiting the functions and proliferation of glial cells in the hippocampus and cerebral cortex, can alleviate the seizure activities. These results suggest that chloroquine may be an ideal anticonvulsant in preventing and treating epilepsy.

  8. Overexpression of brain-derived neurotrophic factor in the hippocampus protects against post-stroke depression

    Institute of Scientific and Technical Information of China (English)

    Hao-hao Chen; Ning Zhang; Wei-yun Li; Ma-rong Fang; Hui Zhang; Yuan-shu Fang; Ming-xing Ding; Xiao-yan Fu

    2015-01-01

    Post-stroke depression is associated with reduced expression of brain-derived neurotrophic factor (BDNF). In this study, we evaluated whether BDNF overexpression affects depression-like behavior in a rat model of post-stroke depression. The middle cerebral artery was occluded to produce a model of focal cerebral ischemia. These rats were then subjected to isolation-housing combined with chronic unpredictable mild stress to generate a model of post-stroke depression. ABDNF gene lentiviral vector was injected into the hippocampus. At 7 days after injection, western blot assay and real-time quantitative PCR revealed that BDNF expression in the hippo-campus was increased in depressive rats injected with BDNF lentivirus compared with depressive rats injected with control vector. Furthermore, sucrose solution consumption was higher, and horizontal and vertical movement scores were increased in the open ifeld test in these rats as well. These ifndings suggest that BDNF overexpression in the hippocampus of post-stroke depressive rats alleviates depression-like behaviors.

  9. Porcine brain natriuretic peptide receptor in bovine adrenal cortex

    International Nuclear Information System (INIS)

    The action of porcine brain natriuretic peptide (pBNP) on the steroidogenesis was investigated in cultured bovine adrenocortical cells. Porcine BNP induced a significant dose-dependent inhibition of both ACTH- and A II-stimulated aldosterone secretion. 10/sup /minus/8/M and 10/sup /minus/7/M pBNP also significantly inhibited ACTH-stimulated cortisol and dehydroepiandrosterone (DHEA) secretions. Binding studies of [125I]-pBNP to bovine adrenocortical membrane fractions showed that adrenal cortex had high-affinity and low-capacity pBNP binding sites, with a dissociation constant (Kd) of 1.70 x 10/sup /minus/10/M and a maximal binding capacity (Bmax) of 19.9 fmol/mg protein. Finally, the 135 Kd radioactive band was specially visualized in the affinity labeling of bovine adrenal cortex with disuccinimidyl suberate (DSS). These results suggest that pBNP may have receptor-mediated suppressive actions on bovine adrenal steroidogenesis, similar to that in atrial natriuretic peptide

  10. Porcine brain natriuretic peptide receptor in bovine adrenal cortex

    Energy Technology Data Exchange (ETDEWEB)

    Higuchi, K.; Hashiguchi, T.; Ohashi, M.; Takayanagi, R.; Haji, M.; Matsuo, H.; Nawata, H.

    1989-01-01

    The action of porcine brain natriuretic peptide (pBNP) on the steroidogenesis was investigated in cultured bovine adrenocortical cells. Porcine BNP induced a significant dose-dependent inhibition of both ACTH- and A II-stimulated aldosterone secretion. 10/sup /minus/8/M and 10/sup /minus/7/M pBNP also significantly inhibited ACTH-stimulated cortisol and dehydroepiandrosterone (DHEA) secretions. Binding studies of (/sup 125/I)-pBNP to bovine adrenocortical membrane fractions showed that adrenal cortex had high-affinity and low-capacity pBNP binding sites, with a dissociation constant (Kd) of 1.70 x 10/sup /minus/10/M and a maximal binding capacity (Bmax) of 19.9 fmol/mg protein. Finally, the 135 Kd radioactive band was specially visualized in the affinity labeling of bovine adrenal cortex with disuccinimidyl suberate (DSS). These results suggest that pBNP may have receptor-mediated suppressive actions on bovine adrenal steroidogenesis, similar to that in atrial natriuretic peptide (ANP).

  11. Thymoquinone and vitamin C attenuates pentylenetetrazole-induced seizures via activation of GABAB1 receptor in adult rats cortex and hippocampus.

    Science.gov (United States)

    Ullah, Ikram; Badshah, Haroon; Naseer, Muhammad Imran; Lee, Hae Young; Kim, Myeong Ok

    2015-03-01

    Epilepsy is a common neurological disorder that leads to neuronal excitability and provoke various forms of cellular reorganization in the brain. In this study, we investigate the anti-convulsant and neuroprotective effects of thymoquinone (TQ) and vitamin C against pentylenetetrazole (PTZ)-induced generalized seizures. Epileptic seizures were induced in adult rats using systemic intraperitoneal injections of PTZ (50 mg/kg) for 7 days. Animals pretreated with either TQ or vitamin C or in combination attenuated PTZ-induced seizures and mortality in rats as well neurodegeneration in the cells. Compared to PTZ, TQ and vitamin C significantly prolonged the onset of seizures (p > 0.05) as well decrease the high-grade seizures. Analysis of electroencephalogram (EEG) recordings revealed that TQ or vitamin C supplementation significantly reduced polyspike and epileptiform discharges. Epileptic seizures caused a decline in expression of gamma-aminobutyric acid B1 receptor (GABAB1R) (p > 0.05), unchanged expression of protein kinase A (PKA), decreased calcium/calmodulin-dependent protein kinase II (CaMKII) (p > 0.05) and inhibit the phosphorylation of cAMP response element-binding protein (CREB) (p > 0.05) in cortex and hippocampus, respectively, compared with control. Changes in expression of GABAB1R, CaMKII and CREB by PTZ were reversed by TQ and vitamin C supplementation. Moreover, PTZ significantly increased Bax, decreased Bcl-2 expression and finally the activation of caspase-3. TQ and vitamin C pretreatment reversed all these deleterious effects induced by PTZ. TQ and vitamin C showed anticonvulsant effects via activation of GABAB1R/CaMKII/CREB pathway and suggest a potential therapeutic role in epilepsy. PMID:25429759

  12. Aberrant Intrinsic Connectivity of Hippocampus and Amygdala Overlap in the Fronto-Insular and Dorsomedial-Prefrontal Cortex in Major Depressive Disorder

    OpenAIRE

    Tahmasian, Masoud; Knight, David C.; Manoliu, Andrei; Schwerthöffer, Dirk; Scherr, Martin; Meng, Chun; Shao, Junming; Peters, Henning; Doll, Anselm; Khazaie, Habibolah; Drzezga, Alexander; Bäuml, Josef; Zimmer, Claus; Förstl, Hans; Wohlschläger, Afra M.

    2013-01-01

    Neuroimaging studies of major depressive disorder (MDD) have consistently observed functional and structural changes of the hippocampus (HP) and amygdale (AY). Thus, these brain regions appear to be critical elements of the pathophysiology of MDD. The HP and AY directly interact and show broad and overlapping intrinsic functional connectivity (iFC) to other brain regions. Therefore, we hypothesized the HP and AY would show a corresponding pattern of aberrant intrinsic connectivity in MDD. Res...

  13. In humans IL-6 is released from the brain during and after exercise and paralleled by enhanced IL-6 mRNA expression in the hippocampus of mice

    DEFF Research Database (Denmark)

    Rasmussen, P; Vedel, J-C; Olesen, J; Adser, Helle; Pedersen, M V; Hart, E; Secher, N H; Pilegaard, H

    2011-01-01

    Aim: Plasma interleukin-6 (IL-6) increases during exercise by release from active muscles and during prolonged exercise also from the brain. The IL-6 release from muscles continues into recovery and we tested whether the brain also releases IL-6 in recovery from prolonged exercise in humans....... Additionally, it was evaluated in mice whether brain release of IL-6 reflected enhanced IL-6 mRNA expression in the brain as modulated by brain glycogen levels. Methods: Nine healthy male subjects completed 4 h of ergometer rowing while the arterio-jugular venous difference (a-v diff) for IL-6 was determined....... The IL-6 mRNA and the glycogen content were determined in mouse hippocampus, cerebellum and cortex before and after 2 h treadmill running (N = 8). Results: At rest, the IL-6 a-v diff was negligible but decreased to -2.2 ± 1.9 pg ml(-1) at the end of exercise and remained low (-2.1 ± 2.1 pg ml(-1) ) 1...

  14. Effect of zinc supplementation on neuronal precursor proliferation in the rat hippocampus after traumatic brain injury.

    Science.gov (United States)

    Cope, Elise C; Morris, Deborah R; Gower-Winter, Shannon D; Brownstein, Naomi C; Levenson, Cathy W

    2016-05-01

    There is great deal of debate about the possible role of adult-born hippocampal cells in the prevention of depression and related mood disorders. We first showed that zinc supplementation prevents the development of the depression-like behavior anhedonia associated with an animal model of traumatic brain injury (TBI). This work then examined the effect of zinc supplementation on the proliferation of new cells in the hippocampus that have the potential to participate in neurogenesis. Rats were fed a zinc adequate (ZA, 30ppm) or zinc supplemented (ZS, 180ppm) diet for 4wk followed by TBI using controlled cortical impact. Stereological counts of EdU-positive cells showed that TBI doubled the density of proliferating cells 24h post-injury (p<0.05), and supplemental zinc significantly increased this by an additional 2-fold (p<0.0001). While the survival of these proliferating cells decreased at the same rate in ZA and in ZS rats after injury, the total density of newly born cells was approximately 60% higher in supplemented rats 1wk after TBI. Furthermore, chronic zinc supplementation resulted in significant increases in the density of new doublecortin-positive neurons one week post-TBI that were maintained for 4wk after injury (p<0.01). While the effect of zinc supplementation on neuronal precursor cells in the hippocampus was robust, use of targeted irradiation to eliminate these cells after zinc supplementation and TBI revealed that these cells are not the sole mechanism through which zinc acts to prevent depression associated with brain injury, and suggest that other zinc dependent mechanisms are needed for the anti-depressant effect of zinc in this model of TBI. PMID:26902472

  15. Comparison of Metabolite Concentrations in the Left Dorsolateral Prefrontal Cortex, the Left Frontal White Matter, and the Left Hippocampus in Patients in Stable Schizophrenia Treated with Antipsychotics with or without Antidepressants. 1H-NMR Spectroscopy Study

    Directory of Open Access Journals (Sweden)

    Dominik Strzelecki

    2015-10-01

    Full Text Available Managing affective, negative, and cognitive symptoms remains the most difficult therapeutic problem in stable phase of schizophrenia. Efforts include administration of antidepressants. Drugs effects on brain metabolic parameters can be evaluated by means of proton nuclear magnetic resonance (1H-NMR spectroscopy. We compared spectroscopic parameters in the left prefrontal cortex (DLPFC, the left frontal white matter (WM and the left hippocampus and assessed the relationship between treatment and the spectroscopic parameters in both groups. We recruited 25 patients diagnosed with schizophrenia (DSM-IV-TR, with dominant negative symptoms and in stable clinical condition, who were treated with antipsychotic and antidepressive medication for minimum of three months. A group of 25 patients with schizophrenia, who were taking antipsychotic drugs but not antidepressants, was matched. We compared metabolic parameters (N-acetylaspartate (NAA, myo-inositol (mI, glutamatergic parameters (Glx, choline (Cho, and creatine (Cr between the two groups. All patients were also assessed with the Positive and Negative Syndrome Scale (PANSS and the Calgary Depression Scale for Schizophrenia (CDSS. In patients receiving antidepressants we observed significantly higher NAA/Cr and NAA/Cho ratios within the DLPFC, as well as significantly higher mI/Cr within the frontal WM. Moreover, we noted significantly lower values of parameters associated with the glutamatergic transmission—Glx/Cr and Glx/Cho in the hippocampus. Doses of antipsychotic drugs in the group treated with antidepressants were also significantly lower in the patients showing similar severity of psychopathology.

  16. Comparison of Metabolite Concentrations in the Left Dorsolateral Prefrontal Cortex, the Left Frontal White Matter, and the Left Hippocampus in Patients in Stable Schizophrenia Treated with Antipsychotics with or without Antidepressants. ¹H-NMR Spectroscopy Study.

    Science.gov (United States)

    Strzelecki, Dominik; Grzelak, Piotr; Podgórski, Michał; Kałużyńska, Olga; Stefańczyk, Ludomir; Kotlicka-Antczak, Magdalena; Gmitrowicz, Agnieszka

    2015-01-01

    Managing affective, negative, and cognitive symptoms remains the most difficult therapeutic problem in stable phase of schizophrenia. Efforts include administration of antidepressants. Drugs effects on brain metabolic parameters can be evaluated by means of proton nuclear magnetic resonance (¹H-NMR) spectroscopy. We compared spectroscopic parameters in the left prefrontal cortex (DLPFC), the left frontal white matter (WM) and the left hippocampus and assessed the relationship between treatment and the spectroscopic parameters in both groups. We recruited 25 patients diagnosed with schizophrenia (DSM-IV-TR), with dominant negative symptoms and in stable clinical condition, who were treated with antipsychotic and antidepressive medication for minimum of three months. A group of 25 patients with schizophrenia, who were taking antipsychotic drugs but not antidepressants, was matched. We compared metabolic parameters (N-acetylaspartate (NAA), myo-inositol (mI), glutamatergic parameters (Glx), choline (Cho), and creatine (Cr)) between the two groups. All patients were also assessed with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). In patients receiving antidepressants we observed significantly higher NAA/Cr and NAA/Cho ratios within the DLPFC, as well as significantly higher mI/Cr within the frontal WM. Moreover, we noted significantly lower values of parameters associated with the glutamatergic transmission--Glx/Cr and Glx/Cho in the hippocampus. Doses of antipsychotic drugs in the group treated with antidepressants were also significantly lower in the patients showing similar severity of psychopathology. PMID:26501256

  17. Differential expression of immediate early genes Zif268 and c-Fos in the hippocampus and prefrontal cortex following spatial learning and glutamate receptor antagonism.

    Science.gov (United States)

    Farina, Francesca R; Commins, Sean

    2016-07-01

    The objective of this study was to examine the effects of NMDAR and AMPAR antagonism on the expression of Zif268 and c-Fos in the hippocampus and medial prefrontal cortex during spatial memory encoding in rats trained in the Morris water maze. NMDAR inhibition impaired navigation and significantly attenuated expression of Zif268, but not c-Fos, in area CA1. AMPAR channel blockade had little effect on learning or IEG expression. Overall, Zif268 and c-Fos displayed markedly different patterns of hippocampal and prefrontal expression, with Zif268 being more closely linked to spatial learning. PMID:27071329

  18. Sparing of the hippocampus and limbic circuit during whole brain radiation therapy: a dosimetric study using helical tomotherapy

    International Nuclear Information System (INIS)

    Full text: The study aims to assess the feasibility of dosimetrically sparing the limbic circuit during whole brain radiation therapy (WBRT) and prophylactic cranial irradiation (PCI). Methods and Materials: We contoured the brain/brainstem on fused MRI and CT as the target volume (PTV) in 11 patients, excluding the hippocampus and the rest of the limbic circuit, which were considered organs at risk (OARs). PCI and WBRT helical tomotherapy plans were prepared for each patient with a 1.0-cm field width, pitch 0.285, initial modulation factor = 2.5. We attempted to spare the hippocampus and the rest of the limbic circuit while treating the rest of the brain to 30 Gy in 15 fractions (PCI) or 35 Gy in 14 fractions (WBRT) with VlOO ∼ 95%. The quality of the plans was assessed by calculating mean dose and equivalent uniform dose (EUD) for OARs and the % volume of the PTV receiving the prescribed dose, V 100. Results: In the PCI plans, mean doses/EUD were: hippocampus 12.5 Gy/ 14.23 Gy, rest of limbic circuit 17.0 Gy/19.02 Gy. In the WBRT plans, mean doses/EUD were: hippocampus 14.3 Gy/16.07 Gy, rest of limbic circuit 17.9 Gy/20.74 Gy. The mean VlOO for the rest of the brain (PTV) were 94.7% (PCl) and 95.1 % (WBRT). Mean PCI and WBRT treatment times were essentially identical (mean 15.23 min, range 14.27-17.5). Conclusions: It is dosimetrically feasible to spare the hippocampus and the rest of the limbic circuit using helical tomotherapy while treating the rest of the brain to full dose.

  19. Induction of brain CYP2E1 by chronic ethanol treatment and related oxidative stress in hippocampus, cerebellum, and brainstem

    International Nuclear Information System (INIS)

    Ethanol is one of the most commonly abused substances, and oxidative stress is an important causative factor in ethanol-induced neurotoxicity. Cytochrome P450 2E1 (CYP2E1) is involved in ethanol metabolism in the brain. This study investigates the role of brain CYP2E1 in the susceptibility of certain brain regions to ethanol neurotoxicity. Male Wistar rats were intragastrically treated with ethanol (3.0 g/kg, 30 days). CYP2E1 protein, mRNA expression, and catalytic activity in various brain regions were respectively assessed by immunoblotting, quantitative quantum dot immunohistochemistry, real-time RT-PCR, and LC–MS. The generation of reactive oxygen species (ROS) was analyzed using a laser confocal scanning microscope. The hippocampus, cerebellum, and brainstem were selectively damaged after ethanol treatment, indicated by both lactate dehydrogenase (LDH) activity and histopathological analysis. Ethanol markedly increased the levels of CYP2E1 protein, mRNA expression, and activity in the hippocampus and cerebellum. CYP2E1 protein and activity were significantly increased by ethanol in the brainstem, with no change in mRNA expression. ROS levels induced by ethanol paralleled the enhanced CYP2E1 proteins in the hippocampus, granular layer and white matter of cerebellum as well as brainstem. Brain CYP2E1 activity was positively correlated with the damage to the hippocampus, cerebellum, and brainstem. These results suggest that the selective sensitivity of brain regions to ethanol neurodegeneration may be attributed to the regional and cellular-specific induction of CYP2E1 by ethanol. The inhibition of CYP2E1 levels may attenuate ethanol-induced oxidative stress via ROS generation.

  20. Total Phenolic Content and Antioxidant Activity of Different Types of Chocolate, Milk, Semisweet, Dark, and Soy, in Cerebral Cortex, Hippocampus, and Cerebellum of Wistar Rats

    Directory of Open Access Journals (Sweden)

    Niara da Silva Medeiros

    2015-01-01

    Full Text Available Chocolate is a product consumed worldwide and it stands out for presenting an important amount of phenolic compounds. In this study, the total phenolic content and antioxidant activity in the cerebral cortex, hippocampus, and cerebellum of male Wistar rats when consuming different types of chocolate, including milk, semisweet, dark, and soy, was evaluated. The total polyphenols concentration and antioxidant activity in vitro by the method of DPPH radical-scavenging test were evaluated in chocolate samples. Lipid peroxidation (TBARS, protein oxidation (carbonyl, sulfhydryl groups, and activity of SOD enzyme in cerebral cortex, hippocampus, and cerebellum of rats treated or not with hydrogen peroxide and/or chocolate were also evaluated. The dark chocolate demonstrated higher phenolic content and antioxidant activity, followed by semisweet, soy, and milk chocolates. The addition of chocolate in the diet of the rats reduced lipid peroxidation and protein oxidation caused by hydrogen peroxide. In the sulfhydryl assay, we observed that the levels of nonenzymatic defenses only increased with the chocolate treatments The SOD enzyme activity was modulated in the tissues treated with the chocolates. We observed in the samples of chocolate a significant polyphenol content and an important antioxidant activity; however, additional studies with different chocolates and other tissues are necessary to further such findings.

  1. Ganoderma lucidum spore powder modulates Bcl-2 and Bax expression in the hippocampus and cerebral cortex, and improves learning and memory in pentylenetetrazole-kindled rats

    Institute of Scientific and Technical Information of China (English)

    Shuang Zhao; Shengchang Zhang; Shuqiu Wang

    2011-01-01

    We studied the effects of Ganoderma lucidum spore powder on Bax and Bcl-2 expression and neuronal apoptosis in pentylenetetrazole-kindled epileptic rats. Sixty adult rats were randomly divided into a control group, an epileptic group (kindled) and three medication groups ( 150, 300,450 mg/kg given to kindled rats). Bax and Bcl-2 immunohistochemistry and TUNEL labeling show ed that the number of Bax- and TUNEL-positive cells in the hippocampus and cerebral cortex decreased significantly in the high-dose medication group, while the number of Bcl-2immunoreactive cells increased. The Morris water maze test showed that high-dose treatment significantly shortened escape latency and increased spatial probe trial performance. Our findings indicate that a high dose of Ganoderma lucidum spore powder upregulates the expressionof antiapoptotic Bcl-2 protein in the hippocampus and cerebral cortex, inhibits proapoptotic Bax expression, and decreases seizure-induced neuronal apoptosis. Further,Ganoderma lucidum appears to protect against epilepsy-related learning and memory impairments.

  2. Differential expression of postsynaptic NMDA and AMPA receptor subunits in the hippocampus and prefrontal cortex of the flinders sensitive line rat model of depression.

    Science.gov (United States)

    Treccani, Giulia; Gaarn du Jardin, Kristian; Wegener, Gregers; Müller, Heidi Kaastrup

    2016-11-01

    Glutamatergic abnormalities have recently been implicated in the pathophysiology of depression, and the ionotropic glutamate receptors in particular have been suggested as possible underlying molecular determinants. The Flinders Sensitive Line (FSL) rats constitute a validated model of depression with dysfunctional regulation of glutamate transmission relatively to their control strain Flinders Resistant Line (FRL). To gain insight into how signaling through glutamate receptors may be altered in the FSL rats, we investigated the expression and phosphorylation of AMPA and NMDA receptor subunits in an enriched postsynaptic fraction of the hippocampus and prefrontal cortex. Compared to the hippocampal postsynaptic fractions of FRL rats, FSL rats exhibited decreased and increased levels of the NMDA receptor subunits GluN2A and GluN2B, respectively, causing a lower ratio of GluN2A/GluN2B. The GluA2/GluA3 AMPA receptor subunit ratio was significantly decreased while the expression of the individual GluA1, GluA2, and GluA3 subunits were unaltered including phosphorylation levels of GluA1 at S831 and S845. There were no changes in the prefrontal cortex. These results support altered expression of postsynaptic glutamate receptors in the hippocampus of FSL rats, which may contribute to the depressive-like phenotype of these rats. PMID:27262028

  3. Assessing Competence of Broccoli Consumption on Inflammatory and Antioxidant Pathways in Restraint-Induced Models: Estimation in Rat Hippocampus and Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    Leila Khalaj

    2013-01-01

    Full Text Available A growing body of evidence advocated the protective and therapeutic potential of natural compounds and phytochemicals used in diets against pathological conditions. Herein, the outcome of dietary whole broccoli consumption prior to restraint stress has been investigated in the hippocampus and prefrontal cortex of male rats, two important regions involved in the processing of responses to stressful events. Interestingly, a region-specific effect was detected regarding some of antioxidant defense system factors: nuclear factor erythroid-derived 2-related factor 2 (Nrf-2 antioxidant pathway, mitochondrial prosurvival proteins involved in mitochondrial biogenesis, and apoptotic cell death proteins. Dietary broccoli supplementation modulated the restraint-induced changes towards a consistent overall protection in the hippocampus. In the prefrontal cortex, however, despite activation of most of the protective factors, presumably as an attempt to save the system against the stress insult, some detrimental outcomes such as induced malate dehydrogenase (MDA level and cleaved form of caspase-3 were detectable. Such diversity may be attributed in one hand to the different basic levels and/or availability of defensive mechanisms within the two studied cerebral regions, and on the other hand to the probable dose-dependent and hormetic effects of whole broccoli. More experiments are essential to demonstrate these assumptions.

  4. The formation of recent and remote memory is associated with time-dependent formation of dendritic spines in the hippocampus and anterior cingulate cortex.

    Science.gov (United States)

    Restivo, Leonardo; Vetere, Gisella; Bontempi, Bruno; Ammassari-Teule, Martine

    2009-06-24

    Although hippocampal-cortical interactions are crucial for the formation of enduring declarative memories, synaptic events that govern long-term memory storage remain mostly unclear. We present evidence that neuronal structural changes, i.e., dendritic spine growth, develop sequentially in the hippocampus and anterior cingulate cortex (aCC) during the formation of recent and remote contextual fear memory. We found that mice placed in a conditioning chamber for one 7 min conditioning session and exposed to five footshocks (duration, 2 s; intensity, 0.7 mA; interstimulus interval, 60 s) delivered through the grid floor exhibited robust fear response when returned to the experimental context 24 h or 36 d after the conditioning. We then observed that their fear response at the recent, but not the remote, time point was associated with an increase in spine density on hippocampal neurons, whereas an inverse temporal pattern of spine density changes occurred on aCC neurons. At each time point, hippocampal or aCC structural alterations were achieved even in the absence of recent or remote memory tests, thus suggesting that they were not driven by retrieval processes. Furthermore, ibotenic lesions of the hippocampus impaired remote memory and prevented dendritic spine growth on aCC neurons when they were performed immediately after the conditioning, whereas they were ineffective when performed 24 d later. These findings reveal that gradual structural changes modifying connectivity in hippocampal-cortical networks underlie the formation and expression of remote memory, and that the hippocampus plays a crucial but time-limited role in driving structural plasticity in the cortex. PMID:19553460

  5. Effects of divalproex and atypical antipsychotic drugs on dopamine and acetylcholine efflux in rat hippocampus and prefrontal cortex.

    Science.gov (United States)

    Huang, Mei; Li, Zhu; Ichikawa, Junji; Dai, Jin; Meltzer, Herbert Y

    2006-07-12

    Mood stabilizers (e.g., valproic acid) and antipsychotic drugs (APDs) are commonly co-administered in the treatment of bipolar disorder and schizophrenia. The basis for any synergism between these classes of drugs in either group of disorders has been little studied. Previous studies have shown that atypical APDs (e.g., clozapine) preferentially increases dopamine (DA) and acetylcholine (ACh) efflux in rat medial prefrontal cortex (mPFC) and hippocampus (HIP), both of which have been suggested to contribute to their ability to improve cognition in patients with schizophrenia. We have recently reported that the anticonvulsant mood stabilizers (AMS), valproic acid, carbamazepine, and zonisamide, but not lithium, also preferentially increase DA efflux in the rat mPFC, and that, at subthreshold doses, the AMS also augment the ability of the atypical APDs clozapine and risperidone to increase DA but not ACh efflux in the mPFC. The present study examined the ability of divalproex (DVX), which is chemically related to valproic acid, to enhance DA and ACh efflux in the HIP and to augment the effect of atypical APDs on ACh efflux in the HIP and mPFC. DVX, 500 mg/kg, significantly increased DA and ACh efflux in the HIP, and DA, but not ACh, efflux in the mPFC, whereas a lower dose of DVX, 50 mg/kg, had no effect on DA or ACh in either region. However, DVX, 50 mg/kg, combined with the atypical APDs olanzapine (1.0 mg/kg) or aripiprazole (0.3 mg/kg) significantly potentiated the effect of both APDs on DA, but not ACh efflux in the HIP and mPFC. Pretreatment of olanzapine or aripiprazole with the selective serotonin 5-HT(1A) antagonist, WAY100635 (1.0 mg/kg) partially but significantly blocked the effect of the combination of DVX, 50 mg/kg, and olanzapine or aripiprazole, on DA efflux in both the HIP and mPFC. WAY100635 did not affect the ability of the combination of olanzapine or aripiprazole and DVX to enhance ACh efflux in the HIP or mPFC. Subchronic administration of the

  6. Concurrent assessment of memory for object and place: Evidence for different preferential importance of perirhinal cortex and hippocampus and for promnestic effect of a neurokinin-3 R agonist.

    Science.gov (United States)

    Chao, Owen Y; Huston, Joseph P; Nikolaus, Susanne; de Souza Silva, Maria A

    2016-04-01

    We here explore the utility of a paradigm that allows the simultaneous assessment of memory for object (what) and object location (where) and their comparative predominance. Two identical objects are presented during a familiarity trial; during the test trial one of these is displaced, and a new object is presented in a familiar location. When tested 5 or 80min later, rats explored both the novel and the displaced objects more than two familiar stationary objects, indicating intact memory for both, object and place. When tested 24h later rats explored the novel object more than the displaced familiar one, suggesting that forgetting differently influenced object and place memory, with memory for object being more robust than memory for place. Animals that received post-trial administration of the neurokinin-3 receptor agonist senktide and were tested 24h later, now explored the novel and displaced objects equally, suggesting that the treatment prevented the selective decay of memory for location. Next, animals received NMDA lesions in either the perirhinal cortex or the hippocampus, which are hypothesized to be preferentially involved in memory for objects and memory for place, respectively. When tested 5 or 80min later, the perirhinal cortex lesion group explored the displaced object more, indicating relatively deficient object memory, while the hippocampal lesion led to the opposite pattern, demonstrating comparatively deficient place memory. These results suggest different preferential engagement of the perirhinal cortex and hippocampus in their processing of memory for object and place. This preference test lends itself to application in the comparison of selective lesions of neural sites and projection systems as well as to the assessment of possible preferential action of pharmacological agents on neurochemical processes that subserve object vs place learning. PMID:26899993

  7. Pivotal role of anterior cingulate cortex in working memory after traumatic brain injury in youth

    Directory of Open Access Journals (Sweden)

    Fabienne eCazalis

    2011-01-01

    Full Text Available In this fMRI study, the functions of the Anterior Cingulate Cortex were studied in a group of adolescents who had sustained a moderate to severe Traumatic Brain Injury. A spatial working memory task with varying working memory loads, representing experimental conditions of increasing difficulty, was administered.In a cross-sectional comparison between the patients and a matched control group, patients performed worse than Controls, showing longer reaction times and lower response accuracy on the spatial working memory task. Brain imaging findings suggest a possible double-dissociation: activity of the Anterior Cingulate Cortex in the Traumatic Brain Injury group, but not in the Control group, was associated with task difficulty; conversely, activity of the left Sensorimotor Cortex in the Control group, but not in the TBI group, was correlated with task difficulty.In addition to the main cross-sectional study, a longitudinal study of a group of adolescent patients with moderate to severe Traumatic Brain Injury was done using fMRI and the same spatial working memory task. The patient group was studied at two time points: one time point during the post-acute phase and one time point 12 months later, during the chronic phase. Results indicated that patients' behavioral performance improved over time, suggesting cognitive recovery. Brain imaging findings suggest that, over this 12 month period, patients recruited less of the Anterior Cingulate Cortex and more of the left Sensorimotor Cortex in response to increasing task difficulty.The role of Anterior Cingulate Cortex in executive functions following a moderate to severe brain injury in adolescence is discussed within the context of conflicting models of the Anterior Cingulate Cortex functions in the existing literature.

  8. Expression of Glutamatergic Genes in Healthy Humans across 16 Brain Regions; Altered Expression in the Hippocampus after Chronic Exposure to Alcohol or Cocaine

    OpenAIRE

    Enoch, Mary-Anne; Rosser, Alexandra A.; Zhou, Zhifeng; Mash, Deborah C; Yuan, Qiaoping; Goldman, David

    2014-01-01

    We analyzed global patterns of expression in genes related to glutamatergic neurotransmission (glutamatergic genes) in healthy human adult brain before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus.

  9. Training your brain: Do mental and physical (MAP) training enhance cognition through the process of neurogenesis in the hippocampus?

    OpenAIRE

    Curlik, D.M.; Shors, T. J.

    2012-01-01

    New neurons are produced each day in the hippocampus through the process of neurogenesis. Both mental and physical training can modify this process by increasing the number of new cells that mature into functional neurons in the adult brain. However, the mechanisms whereby these increases occur are not necessarily the same. Physical activity, especially aerobic exercise greatly increases the number of new neurons that are produced in the hippocamal formation. In contrast, mental training via ...

  10. To What Extent is Blood a Reasonable Surrogate for Brain in Gene Expression Studies: Estimation from Mouse Hippocampus and Spleen

    OpenAIRE

    Davies, Matthew N; Lawn, Sarah; Whatley, Steven; Fernandes, Cathy; Robert W Williams; Schalkwyk, Leonard C

    2009-01-01

    Microarrays are designed to measure genome-wide differences in gene expression. In cases where a tissue is not accessible for analysis (e.g. human brain), it is of interest to determine whether a second, accessible tissue could be used as a surrogate for transcription profiling. Surrogacy has applications in the study of behavioural and neurodegenerative disorders. Comparison between hippocampus and spleen mRNA obtained from a mouse recombinant inbred panel indicates a high degree of correlat...

  11. An Overview of Brain-Derived Neurotrophic Factor and Implications for Excitotoxic Vulnerability in the Hippocampus

    Directory of Open Access Journals (Sweden)

    Patrick S. Murray

    2011-01-01

    Full Text Available The present paper examines the nature and function of brain-derived neurotrophic factor (BDNF in the hippocampal formation and the consequences of changes in its expression. The paper focuses on literature describing the role of BDNF in hippocampal development and neuroplasticity. BDNF expression is highly sensitive to developmental and environmental factors, and increased BDNF signaling enhances neurogenesis, neurite sprouting, electrophysiological activity, and other processes reflective of a general enhancement of hippocampal function. Such increases in activity may mediate beneficial effects such as enhanced learning and memory. However, the increased activity also comes at a cost: BDNF plasticity renders the hippocampus more vulnerable to hyperexcitability and/or excitotoxic damage. Exercise dramatically increases hippocampal BDNF levels and produces behavioral effects consistent with this phenomenon. In analyzing the literature regarding exercise-induced regulation of BDNF, this paper provides a theoretical model for how the potentially deleterious consequences of BDNF plasticity may be modulated by other endogenous factors. The peptide galanin may play such a role by regulating hippocampal excitability.

  12. Human Development XI: The Structure of the Cerebral Cortex. Are There Really Modules in the Brain?

    OpenAIRE

    Tyge Dahl Hermansen; Søren Ventegodt; Isack Kandel

    2007-01-01

    The structure of human consciousness is thought to be closely connected to the structure of cerebral cortex. One of the most appreciated concepts in this regard is the Szanthagothei model of a modular building of neo-cortex. The modules are believed to organize brain activity pretty much like a computer. We looked at examples in the literature and argue that there is no significant evidence that supports Szanthagothei's model. We discuss the use of the limited genetic information, the cortico...

  13. Study on cognition disorder and morphologic change of neurons in hippocampus area following traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    洪军; 崔建忠; 周云涛; 高俊玲

    2002-01-01

    Objective: To explore the correlation between cognition disorder and morphologic change of hippocampal neurons after traumatic brain injury (TBI).   Methods: Wistar rat models with severe TBI were made by Marmarous method. The histopathological change of the neurons in the hippocampus area were studied with hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated X-dUPT nick end labeling (TUNEL), respectively. The cognitive function was evaluated with the Morris water maze test.   Results: The comprehensive neuronal degeneration and necrosis could be observed in CA2-3 regions of hippocampus at 3 days after injury. Apoptotic positive neurons in CA2-4 regions of hippocampus and dentate gyrus increased in the injured group at 24 hours following TBI. They peaked at 7 days and then declined. Significant impairment of spatial learning and memory was observed after injury in the rats.   Conclusions: The rats have obvious disorders in spatial learning and memory after severe TBI. Meanwhile, delayed neuronal necrosis and apoptosis can be observed in the neurons in the hippocampus area. It suggests that delayed hippocampal cell death may contribute to the functional deficit.

  14. Functional MRI of the brain: localisation of eloquent cortex in focal brain lesion therapy

    Energy Technology Data Exchange (ETDEWEB)

    Dymarkowski, S.; Sunaert, S.; Oostende, S. van; Hecke, P. van; Wilms, G.; Demaerel, P.; Marchal, G. [Department of Radiology, University Hospitals, Leuven (Belgium); Nuttin, B.; Plets, C. [Department of Neurosurgery, University Hospitals, Leuven (Belgium)

    1998-12-01

    The aim of this study was to assess the feasibility of functional MRI (fMRI) in a clinical environment on a large patient group, and to evaluate the pretherapeutic value of localisation of eloquent cortex. Forty patients with focal brain lesions of different origin were studied using fMRI. Functional information was obtained using motor, somatosensory, auditory and phonological stimuli depending on the localisation of the lesions. To obtain information about the spatial accuracy of fMRI, the results were compared with postoperative electrocortical stimulation. Two patients with secondary trigeminal neuralgia were scanned using a motor protocol and were implanted with an extradural plate electrode. Imaging was successful in 40 of 42 patients (including the 2 with trigeminal neuralgia). These patients were analysed for strength of activation, the relation of the lesion to activation sites and the presence of mass effect. The correlation between these data and surgical findings provided significant additional clinical information. Functional MRI can be accurately performed in patients with focal brain lesions using a dedicated approach. Functional MRI offers important clinical information as a contribution to a decrease in posttherapeutic morbidity. The accuracy of the technique can be confirmed by other modalities, including invasive cortical electrostimulation. (orig.) With 7 figs., 2 tabs., 25 refs.

  15. Awake brain mapping of cortex and subcortical pathways in brain tumor surgery.

    Science.gov (United States)

    Freyschlag, C F; Duffau, H

    2014-12-01

    Awake surgery is not a new technique: this is a new philosophy. Indeed, in surgery for diffuse gliomas performed in awake patients, the goal is not anymore to remove a "tumor mass" according to oncological boundaries (which in essence do not exist in infiltrating neoplasms), but to resect a part of the brain invaded by a chronic tumoral disease, according to functional limits both at cortical and subcortical levels. Therefore, intraoperative electrical mapping is accepted as the gold standard in order to gain information about the functionality of the underlying tissue when performing neuro-oncological surgery. This review should give the reader an overview of principles and indications of mapping of eloquent cortex and subcortical pathways with practical considerations for cerebral tumors. In gliomas, awake mapping has been demonstrated as increasing the surgical indications in so-called "critical areas" with nonetheless a significant decrease of postoperative morbidity‑while maximizing the extent of resection. Beyond clinical implications, awake surgery represents a unique opportunity to study neural networks underpinning sensorimotor, visuospatial, language, executive and even behavioral functions in humans. This led to propose new models of connectomics, breaking with the localizationist view of brain processing, and opening the window to the concept of neuroplasticity. In summary, awake mapping enables to make a link between surgical neurooncology and cognitive neurosciences, to improve both survival and quality of life of glioma patients. PMID:25418274

  16. Functional MRI of the brain: localisation of eloquent cortex in focal brain lesion therapy

    International Nuclear Information System (INIS)

    The aim of this study was to assess the feasibility of functional MRI (fMRI) in a clinical environment on a large patient group, and to evaluate the pretherapeutic value of localisation of eloquent cortex. Forty patients with focal brain lesions of different origin were studied using fMRI. Functional information was obtained using motor, somatosensory, auditory and phonological stimuli depending on the localisation of the lesions. To obtain information about the spatial accuracy of fMRI, the results were compared with postoperative electrocortical stimulation. Two patients with secondary trigeminal neuralgia were scanned using a motor protocol and were implanted with an extradural plate electrode. Imaging was successful in 40 of 42 patients (including the 2 with trigeminal neuralgia). These patients were analysed for strength of activation, the relation of the lesion to activation sites and the presence of mass effect. The correlation between these data and surgical findings provided significant additional clinical information. Functional MRI can be accurately performed in patients with focal brain lesions using a dedicated approach. Functional MRI offers important clinical information as a contribution to a decrease in posttherapeutic morbidity. The accuracy of the technique can be confirmed by other modalities, including invasive cortical electrostimulation. (orig.)

  17. Constructing morphometric profiles along the human brain cortex using in vivo Magnetic Resonance Imaging (MRI)

    OpenAIRE

    Pérez Santonja, Javier

    2015-01-01

    The geometry of the brain cortex is comprised of gyri (outward folds) and sulci (inward folds). Several biological properties about the anatomy and physiology of the brain cortex have been measured at the top of the sulci and at the bottom of the gyri; however, no one has yet measured how the values of these properties (called biomarkers) change along the path joining the top of the sulci and the bottom of the gyri. In this work, a methodology to display that information is shown, using diffe...

  18. Kainate receptors in the rat hippocampus: A distribution and time course of changes in response to unilateral lesions of the entorhinal cortex

    International Nuclear Information System (INIS)

    The response of kainate receptors to deafferentation and subsequent reinnervation following unilateral entorhinal cortex lesions was studied in the rat hippocampus using quantitative in vitro autoradiography. The binding levels of [3H]kainic acid (KA) and changes in the distribution of KA sites were investigated in the dentate gyrus molecular layer (ML) and in various terminal zones in the CA1 field at 1, 3, 7, 14, 21, 30, and 60 d postlesion. The data from both the ipsilateral and contralateral hippocampus were compared with those from unoperated controls. The first changes in KA receptor distribution were observed 21 d postlesion when the dense band of KA receptors occupying the inner one-third of the ML expanded into the denervated outer two-thirds of the ipsilateral ML. The spreading of the KA receptor field into previously unoccupied zones continued 30 and 60 d postlesion. At these time points, the zone enriched in [3H]KA binding sites became significantly (on average 50%) wider than in unoperated controls. No changes were observed in either the distribution or binding levels in other hippocampal areas or in the contralateral hippocampus at any studied time point. Saturation analysis of binding in the ipsilateral ML 60 d postlesion revealed changes in the maximum number of receptor sites (Bmax) without changes in KA receptor affinity (Kd). The data suggest that the elevation of the [3H]KA binding in the outer two-thirds of the ML reflects an increase in the number of both low and high affinity receptor binding sites. The pattern of KA receptor redistribution was similar to the well-characterized pattern of sprouting of commissural/associational systems from the inner one-third into the outer two-thirds of the ML after entorhinal lesions

  19. Cellular scaling rules for the brain of Artiodactyla include a highly folded cortex with few neurons

    Directory of Open Access Journals (Sweden)

    Rodrigo eSiqueira Kazu

    2014-11-01

    Full Text Available Quantitative analysis of the cellular composition of rodent, primate, insectivore and afrotherian brains has shown that nonneuronal scaling rules are similar across these mammalian orders that diverged about 95 million years ago, and therefore appear to be conserved in evolution, while neuronal scaling rules appear to be free to vary in a clade-specific manner. Here we analyze the cellular scaling rules that apply to the brain of artiodactyls, a group within the order Cetartiodactyla, believed to be a relatively recent radiation from the common Eutherian ancestor. We find that artiodactyls share nonneuronal scaling rules with all groups analyzed previously. Artiodactyls share with afrotherians and rodents, but not with primates, the neuronal scaling rules that apply to the cerebral cortex and cerebellum. The neuronal scaling rules that apply to the remaining brain areas are however distinct in artiodactyls. Importantly, we show that the folding index of the cerebral cortex scales with the number of neurons in the cerebral cortex in distinct fashions across artiodactyls, afrotherians, rodents, and primates, such that the artiodactyl cerebral cortex is more convoluted than primate cortices of similar numbers of neurons. Our findings suggest that the scaling rules found to be shared across modern afrotherians, glires and artiodactyls applied to the common Eutherian ancestor, such as the relationship between the mass of the cerebral cortex as a whole and its number of neurons. In turn, the distribution of neurons along the surface of the cerebral cortex, which is related to its degree of gyrification, appears to be a clade-specific characteristic. If the neuronal scaling rules for artiodactyls extend to all cetartiodactyls, we predict that the large cerebral cortex of cetaceans will still have fewer neurons than the human cerebral cortex.

  20. Drosophila cortex and neuropile glia influence secondary axon tract growth, pathfinding, and fasciculation in the developing larval brain

    OpenAIRE

    Spindler, Shana R; Ortiz, Irma; Fung, Siaumin; Takashima, Shigeo; Hartenstein, Volker

    2009-01-01

    Glial cells play important roles in the developing brain during axon fasciculation, growth cone guidance, and neuron survival. In the Drosophila brain, three main classes of glia have been identified including surface, cortex, and neuropile glia. While surface glia ensheaths the brain and is involved in the formation of the blood-brain-barrier and the control of neuroblast proliferation, the range of functions for cortex and neuropile glia is less well understood. In this study, we use the ni...

  1. The bilingual brain: Flexibility and control in the human cortex

    Science.gov (United States)

    Buchweitz, Augusto; Prat, Chantel

    2013-12-01

    The goal of the present review is to discuss recent cognitive neuroscientific findings concerning bilingualism. Three interrelated questions about the bilingual brain are addressed: How are multiple languages represented in the brain? how are languages controlled in the brain? and what are the real-world implications of experience with multiple languages? The review is based on neuroimaging research findings about the nature of bilingual processing, namely, how the brain adapts to accommodate multiple languages in the bilingual brain and to control which language should be used, and when. We also address how this adaptation results in differences observed in the general cognition of bilingual individuals. General implications for models of human learning, plasticity, and cognitive control are discussed.

  2. Effects of lindane on the glucose metabolism in rat brain cortex cells

    International Nuclear Information System (INIS)

    The influence of 0.5 mM γ-hexachlorocyclohexane (γ-HCH, lindane) on glucose transport has been investigated using the analog 3-O-methyl-D(U-14C) glucose. The glucose uptake was lineal for at least 10 sec. Preincubation of dissociated brain cortex cells with lindane decreased the transport of glucose with respect to the controls. The treatment of brain cortex cells with other organochlorine compounds indicated that the α-, δ-HCH isomers and dieldrin reproduced the same inhibitory pattern, while β-HCH and endrin were inactive. The total radioactivity incorporated into CO2 from (U-14C) glucose in the cerebral cortex is also inhibited by lindane in a time dependent manner

  3. Effects of lindane on the glucose metabolism in rat brain cortex cells

    Energy Technology Data Exchange (ETDEWEB)

    Pulido, J.A.; del Hoyo, N.; Perez-Albarsanz, M.A. (Univ. of Alcala, Madrid (Spain))

    1990-01-01

    The influence of 0.5 mM {gamma}-hexachlorocyclohexane ({gamma}-HCH, lindane) on glucose transport has been investigated using the analog 3-O-methyl-D(U-{sup 14}C) glucose. The glucose uptake was lineal for at least 10 sec. Preincubation of dissociated brain cortex cells with lindane decreased the transport of glucose with respect to the controls. The treatment of brain cortex cells with other organochlorine compounds indicated that the {alpha}-, {delta}-HCH isomers and dieldrin reproduced the same inhibitory pattern, while {beta}-HCH and endrin were inactive. The total radioactivity incorporated into CO{sub 2} from (U-{sup 14}C) glucose in the cerebral cortex is also inhibited by lindane in a time dependent manner.

  4. Expression of PHB2 in Rat Brain Cortex Following Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Ting Xu

    2014-02-01

    Full Text Available Prohibitin2 (PHB2 is a ubiquitous, evolutionarily strongly conserved protein. It is one of the components of the prohibitin complex, which comprises two highly homologous subunits, PHB1 and PHB2. PHB2 is present in various cellular compartments including the nucleus and mitochondria. Recent studies have identified PHB2 as a multifunctional protein that controls cell proliferation, apoptosis, cristae morphogenesis and the functional integrity of mitochondria. However its distribution and function in the central nervous system (CNS are not well understood. In this study, we examined PHB2 expression and cellular localization in rats after acute traumatic brain injury (TBI. Western Blot analysis showed PHB2 level was significantly enhanced at five days after injury compared to control, and then declined during the following days. The protein expression of PHB2 was further analyzed by immunohistochemistry. In comparison to contralateral cerebral cortex, we observed a highly significant accumulation of PHB2 at the ipsilateral brain. Immunofluorescence double-labeling showed that PHB2 was co-expressed with NeuN, GFAP. Besides, PHB2 also colocalized with activated caspase-3 and PCNA. To further investigate the function of PHB2, primary cultured astrocytes and the neuronal cell line PC12 were employed to establish a proliferation model and an apoptosis model, respectively, to simulate the cell activity after TBI to a certain degree. Knocking down PHB2 by siRNA partly increased the apoptosis level of PC12 stimulated by H2O2. While the PHB2 was interrupted by siRNA, the proliferation level of primary cultured astrocytes was inhibited notably than that in the control group. Together with our data, we hypothesized that PHB2 might play an important role in CNS pathophysiology after TBI.

  5. Alterations of motor performance and brain cortex mitochondrial function during ethanol hangover.

    Science.gov (United States)

    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 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. PMID:22608205

  6. Does progesterone show neuroprotective effects on traumatic brain injury through increasing phosphorylation of Akt in the hippocampus?

    Institute of Scientific and Technical Information of China (English)

    Richard Justin Garling; Lora Talley Watts; Shane Sprague; Lauren Fletcher; David F Jimenez; Murat Digicaylioglu

    2014-01-01

    There are currently no federally approved neuroprotective agents to treat traumatic brain injury. Progesterone, a hydrophobic steroid hormone, has been shown in recent studies to exhibit neu-roprotective effects in controlled cortical impact rat models. Akt is a protein kinase known to play a role in cell signaling pathways that reduce edema, inlfammation, apoptosis, and promote cell growth in the brain. This study aims to determine if progesterone modulates the phosphor-ylation of Aktvia its threonine 308 phosphorylation site. Phosphorylation at the threonine 308 site is one of several sites responsible for activating Akt and enabling the protein kinase to carry out its neuroprotective effects. To assess the effects of progesterone on Akt phosphorylation, C57BL/6 mice were treated with progesterone (8 mg/kg) at 1 (intraperitonally), 6, 24, and 48 hours (subcutaneously) post closed-skull traumatic brain injury. The hippocampus was harvest-ed at 72 hours post injury and prepared for western blot analysis. Traumatic brain injury caused a signiifcant decrease in Akt phosphorylation compared to sham operation. However, mice treat-ed with progesterone following traumatic brain injury had an increase in phosphorylation of Akt compared to traumatic brain injury vehicle. Our ifndings suggest that progesterone is a viable treatment option for activating neuroprotective pathways after traumatic brain injury.

  7. Vulnerability versus resilience to prenatal stress in male and female rats; implications from gene expression profiles in the hippocampus and frontal cortex.

    Science.gov (United States)

    Van den Hove, D L A; Kenis, G; Brass, A; Opstelten, R; Rutten, B P F; Bruschettini, M; Blanco, C E; Lesch, K P; Steinbusch, H W M; Prickaerts, J

    2013-10-01

    Adverse life events during pregnancy may impact upon the developing fetus, predisposing prenatally stressed offspring to the development of psychopathology. In the present study, we examined the effects of prenatal restraint stress (PS) on anxiety- and depression-related behavior in both male and female adult Sprague-Dawley rats. In addition, gene expression profiles within the hippocampus and frontal cortex (FC) were examined in order to gain more insight into the molecular mechanisms that mediate the behavioral effects of PS exposure. PS significantly increased anxiety-related behavior in male, but not female offspring. Likewise, depression-related behavior was increased in male PS rats only. Further, male PS offspring showed increased basal plasma corticosterone levels in adulthood, whereas both PS males and females had lower stress-induced corticosterone levels when compared to controls. Microarray-based profiling of the hippocampus and FC showed distinct sex-dependent changes in gene expression after PS. Biological processes and/or signal transduction cascades affected by PS included glutamatergic and GABAergic neurotransmission, mitogen-activated protein kinase (MAPK) signaling, neurotrophic factor signaling, phosphodiesterase (PDE)/ cyclic nucleotide signaling, glycogen synthase kinase 3 (GSK3) signaling, and insulin signaling. Further, the data indicated that epigenetic regulation is affected differentially in male and female PS offspring. These sex-specific alterations may, at least in part, explain the behavioral differences observed between both sexes, i.e. relative vulnerability versus resilience to PS in male versus female rats, respectively. These data reveal novel potential targets for antidepressant and mood stabilizing drug treatments including PDE inhibitors and histone deacetylase (HDAC) inhibitors. PMID:23199416

  8. Severe cell reduction in the future brain cortex in human growth-restricted fetuses and infants

    DEFF Research Database (Denmark)

    Samuelsen, Grethe B; Pakkenberg, Bente; Bogdanović, Nenad;

    2007-01-01

    controls. The daily increase in brain cells in the future cortex was only half of that of the controls. In the 3 other developmental zones, no significant differences in cell numbers could be demonstrated. CONCLUSIONS: IUGR in humans is associated with a severe reduction in cortical growth and a...... estimated in 9 severely affected IUGR fetuses and 15 controls using the optical fractionator. Cell numbers were estimated within 4 developmental zones. The gestational ages were 19-41 weeks. RESULTS: The total cell number in the future cortex was significantly reduced in the IUGR fetuses, compared with...

  9. Determination of hyperactive areas of Cortex Cerebri with using brain SPECT study

    International Nuclear Information System (INIS)

    The aim of this study was the assessment of the ability to apply of SPECT technique to determination of hyperactive areas of cortex cerebri. Analysis included 50 patients (mean aged 44 - 58). Brain SPECT scanning was performed after 1 hour after the intravenous injection of 740 MBq of ethylcisteinate dimmer labeled 99m Technetium (99mTc-ECD) with the use one-head gamma camera with a low-energy, ultra-high resolution collimator. Qualitative and quantitative analysis was performed using specialised software. In 20 cases normal biodistribution of the radiotracer was observed (hyperactive areas in cerebellum and occiput). In patients with psychiatric and neurological disturbances hyperactive areas were visualized in 25 cases in temporal lobes, in 4 cases in parietal lobes and in 1 patient in frontal area and basal ganglia. It is concluded that a number of factors limit the wide-scale use of SPECT, including the sophistication of imaging equipment (single-head cameras are inferior to the newer multihead units) and the experience of the physicians interpreting the scans and utilizing the data. In many diseases physicians do not know which areas of the patient's brain according disorders. Brain SPECT study can be a very useful tool to evaluation of hyperactive areas of cortex cerebri. This technique visualization of cortex cerebri completes standard analysis of disorders of brain activity

  10. Coupling brain-machine interfaces with cortical stimulation for brain-state dependent stimulation: enhancing motor cortex excitability for neurorehabilitation

    Directory of Open Access Journals (Sweden)

    Alireza Gharabaghi

    2014-03-01

    Full Text Available Motor recovery after stroke is an unsolved challenge despite intensive rehabilitation training programs. Brain stimulation techniques have been explored in addition to traditional rehabilitation training to increase the excitability of the stimulated motor cortex. This modulation of cortical excitability augments the response to afferent input during motor exercises, thereby enhancing skilled motor learning by long-term potentiation-like plasticity. Recent approaches examined brain stimulation applied concurrently with voluntary movements to induce more specific use-dependent neural plasticity during motor training for neurorehabilitation. Unfortunately, such approaches are not applicable for the many severely affected stroke patients lacking residual hand function. These patients require novel activity-dependent stimulation paradigms based on intrinsic brain activity. Here, we report on such brain state-dependent stimulation (BSDS combined with haptic feedback provided by a robotic hand orthosis. Transcranial magnetic stimulation of the motor cortex and haptic feedback to the hand were controlled by sensorimotor desynchronization during motor-imagery and applied within a brain-machine interface environment in one healthy subject and one patient with severe hand paresis in the chronic phase after stroke. BSDS significantly increased the excitability of the stimulated motor cortex in both healthy and post-stroke conditions, an effect not observed in non-BSDS protocols. This feasibility study suggests that closing the loop between intrinsic brain state, cortical stimulation and haptic feedback provides a novel neurorehabilitation strategy for stroke patients lacking residual hand function, a proposal that warrants further investigation in a larger cohort of stroke patients.

  11. Brain-wide map of efferent projections from rat barrel cortex

    Directory of Open Access Journals (Sweden)

    Trygve B. Leergaard

    2014-02-01

    Full Text Available The somatotopically organized whisker barrel field of the rat primary somatosensory (S1 cortex is a commonly used model system for anatomical and physiological investigations of sensory processing. The neural connections of the barrel cortex have been extensively mapped. But most investigations have focused on connections to limited regions of the brain, and overviews in the literature of the connections across the brain thus build on a range of material from different laboratories, presented in numerous publications. Furthermore, given the limitations of the conventional journal article format, analyses and interpretations are hampered by lack of access to the underlying experimental data. New opportunities for analyses have emerged with the recent release of an online resource of experimental data consisting of collections of high-resolution images from 6 experiments in which anterograde tracers were injected in S1 whisker or forelimb representations. Building on this material, we have conducted a detailed analysis of the brain wide distribution of the efferent projections of the rat barrel cortex. We compare our findings with the available literature and reports accumulated in the Brain Architecture Management System (BAMS2 database. We report well-known and less known intracortical and subcortical projections of the barrel cortex, as well as distinct differences between S1 whisker and forelimb related projections. Our results correspond well with recently published overviews, but provide additional information about relative differences among S1 projection targets. Our approach demonstrates how collections of shared experimental image data are suitable for brain-wide analysis and interpretation of connectivity mapping data.

  12. Brain-wide map of efferent projections from rat barrel cortex.

    Science.gov (United States)

    Zakiewicz, Izabela M; Bjaalie, Jan G; Leergaard, Trygve B

    2014-01-01

    The somatotopically organized whisker barrel field of the rat primary somatosensory (S1) cortex is a commonly used model system for anatomical and physiological investigations of sensory processing. The neural connections of the barrel cortex have been extensively mapped. But most investigations have focused on connections to limited regions of the brain, and overviews in the literature of the connections across the brain thus build on a range of material from different laboratories, presented in numerous publications. Furthermore, given the limitations of the conventional journal article format, analyses and interpretations are hampered by lack of access to the underlying experimental data. New opportunities for analyses have emerged with the recent release of an online resource of experimental data consisting of collections of high-resolution images from 6 experiments in which anterograde tracers were injected in S1 whisker or forelimb representations. Building on this material, we have conducted a detailed analysis of the brain wide distribution of the efferent projections of the rat barrel cortex. We compare our findings with the available literature and reports accumulated in the Brain Architecture Management System (BAMS2) database. We report well-known and less known intracortical and subcortical projections of the barrel cortex, as well as distinct differences between S1 whisker and forelimb related projections. Our results correspond well with recently published overviews, but provide additional information about relative differences among S1 projection targets. Our approach demonstrates how collections of shared experimental image data are suitable for brain-wide analysis and interpretation of connectivity mapping data. PMID:24550819

  13. Rapid and long-term induction of effector immediate early genes (BDNF, Neuritin and Arc) in peri-infarct cortex and dentate gyrus after ischemic injury in rat brain

    DEFF Research Database (Denmark)

    Rickhag, Karl Mattias; Teilum, Maria; Wieloch, Tadeusz

    2007-01-01

    The genomic response following brain ischemia is very complex and involves activation of both protective and detrimental signaling pathways. Immediate early genes (IEGs) represent the first wave of gene expression following ischemia and are induced in extensive regions of the ischemic brain...... including cerebral cortex and hippocampus. Brain-derived neurotrophic factor (BDNF), Neuritin and Activity-regulated cytoskeleton-associated protein (Arc) belong to a subgroup of immediate early genes implicated in synaptic plasticity known as effector immediate early genes. Here, we investigated the...... at 0-6 h of reperfusion for Neuritin and 0-12 h of reperfusion for Arc while BDNF was induced 0-9 h of reperfusion. Our study demonstrates a rapid and long-term activation of effector immediate early genes in distinct brain areas following ischemic injury in rat. Effector gene activation may be part...

  14. Evidence of extensive RNA oxidation in normal appearing cortex of multiple sclerosis brain.

    Science.gov (United States)

    Kharel, Prakash; McDonough, Jennifer; Basu, Soumitra

    2016-01-01

    The role of reactive oxygen species (ROS) in the progression of neurodegenerative and neuroinflammatory disorders such as multiple sclerosis (MS) has been highlighted in recent years. Due to the debilitated cellular antioxidant defense mechanism in the neurons in MS, and their vulnerability to ROS effects, the cellular components in neuronal cells are susceptible to oxidative damage. The damage due to ROS in various biomolecules including proteins and DNA has already been shown in MS lesions. Using an in situ approach we have detected hitherto unidentified RNA oxidative damage in the neuronal cells of normal appearing cortex of postmortem MS brains. We analyzed the presence of oxidative damage marker nucleoside 8-hydroxyguanosine (8-OHG) to determine the presence of oxidized RNA in MS brain. Immunohistochemical analyses with anti 8-OHG antibody showed significant oxidation in the cytoplasm and to a conspicuously lesser extent in the nucleus of neuronal cells within the normal appearing cortex of MS brain, whereas similar areas were weakly immunopositive in control brain tissues. Pretreatment with RNase 1 greatly reduced the immune reaction with anti 8-OHG antibody while it was only slightly diminished by DNase I pre-treatment, indicating extensive oxidative damage in the RNA pool of MS brain. The abundance of 8-OHG, hence the high extent of RNA oxidative damage was further confirmed by immunoprecipitation and HPLC analyses of total RNA isolated from MS brain. To our knowledge, this is the first evidence of increased RNA oxidation in normal appearing cortex of MS brain. The current study begins to define the link of RNA oxidation to MS pathophysiology. PMID:26706235

  15. To what extent is blood a reasonable surrogate for brain in gene expression studies: estimation from mouse hippocampus and spleen

    Directory of Open Access Journals (Sweden)

    MatthewNDavies

    2009-10-01

    Full Text Available Microarrays are designed to measure genome-wide differences in gene expression. In cases where a tissue is not accessible for analysis (e.g. human brain, it is of interest to determine whether a second, accessible tissue could be used as a surrogate for transcription profiling. Surrogacy has applications in the study of behavioural and neurodegenerative disorders. Comparison between hippocampus and spleen mRNA obtained from a mouse recombinant inbred panel indicates a high degree of correlation between the tissues for genes that display a high heritability of expression level. This correlation is not limited to apparent expression differences caused by sequence polymorphisms in the target sequences and includes both cis and trans genetic effects. A tissue such as blood could therefore give surrogate information on expression in brain for a subset of genes, in particular those co-expressed between the two tissues, which have heritably varying expression.

  16. Prolonged rote learning produces delayed memory facilitation and metabolic changes in the hippocampus of the ageing human brain.

    LENUS (Irish Health Repository)

    Roche, Richard Ap

    2009-01-01

    BACKGROUND: Repeated rehearsal is one method by which verbal material may be transferred from short- to long-term memory. We hypothesised that extended engagement of memory structures through prolonged rehearsal would result in enhanced efficacy of recall and also of brain structures implicated in new learning. Twenty-four normal participants aged 55-70 (mean = 60.1) engaged in six weeks of rote learning, during which they learned 500 words per week every week (prose, poetry etc.). An extensive battery of memory tests was administered on three occasions, each six weeks apart. In addition, proton magnetic resonance spectroscopy (1H-MRS) was used to measure metabolite levels in seven voxels of interest (VOIs) (including hippocampus) before and after learning. RESULTS: Results indicate a facilitation of new learning that was evident six weeks after rote learning ceased. This facilitation occurred for verbal\\/episodic material only, and was mirrored by a metabolic change in left posterior hippocampus, specifically an increase in NAA\\/(Cr+Cho) ratio. CONCLUSION: Results suggest that repeated activation of memory structures facilitates anamnesis and may promote neuronal plasticity in the ageing brain, and that compliance is a key factor in such facilitation as the effect was confined to those who engaged fully with the training.

  17. Prolonged rote learning produces delayed memory facilitation and metabolic changes in the hippocampus of the ageing human brain

    Directory of Open Access Journals (Sweden)

    Prendergast Julie

    2009-11-01

    Full Text Available Abstract Background Repeated rehearsal is one method by which verbal material may be transferred from short- to long-term memory. We hypothesised that extended engagement of memory structures through prolonged rehearsal would result in enhanced efficacy of recall and also of brain structures implicated in new learning. Twenty-four normal participants aged 55-70 (mean = 60.1 engaged in six weeks of rote learning, during which they learned 500 words per week every week (prose, poetry etc.. An extensive battery of memory tests was administered on three occasions, each six weeks apart. In addition, proton magnetic resonance spectroscopy (1H-MRS was used to measure metabolite levels in seven voxels of interest (VOIs (including hippocampus before and after learning. Results Results indicate a facilitation of new learning that was evident six weeks after rote learning ceased. This facilitation occurred for verbal/episodic material only, and was mirrored by a metabolic change in left posterior hippocampus, specifically an increase in NAA/(Cr+Cho ratio. Conclusion Results suggest that repeated activation of memory structures facilitates anamnesis and may promote neuronal plasticity in the ageing brain, and that compliance is a key factor in such facilitation as the effect was confined to those who engaged fully with the training.

  18. Role of the hippocampus in contextual modulation of fear extinction

    Institute of Scientific and Technical Information of China (English)

    Lingzhi Kong; Xihong Wu; Liang Li

    2008-01-01

    Fear extinction is an important form of emotional learning, and affects neural plasticity. Cue fear extinction is a classical form of inhibitory learning that can be used as an exposure-based treatment for phobia, because the long-term extinction memory produced during cue fear extinction can limit the over-expression of fear. The expression of this inhibitory memory partly depends on the context in which the extinction learning occurs. Studies such as transient inhibition, electrophysiology and brain imaging have proved that the hippocampus - an important structure in the limbic system - facilitates memory retrieval by contextual cues.Mediation of the hippocampus-medial prefrontal lobe circuit may be the neurobiological basis of this process.This article has reviewed the role of the hippocampus in the learning and retrieval of fear extinction.Contextual modulation of fear extinction may rely on a neural network consisting of the hippocampus, the medial prefrontal cortex and the amygdala.

  19. A dynamic gradient of Wnt signaling controls initiation of neurogenesis in the mammalian cortex and cellular specification in the hippocampus

    Czech Academy of Sciences Publication Activity Database

    Machoň, Ondřej; Backman, M.; Machonova, O.; Kozmik, Zbyněk; Vacík, Tomáš; Andersen, L.; Krauss, S.

    2007-01-01

    Roč. 311, č. 1 (2007), s. 223-237. ISSN 0012-1606 R&D Projects: GA MŠk(CZ) 1M0520 Institutional research plan: CEZ:AV0Z50520514 Keywords : Wnt * beta-catenin * gene * brain Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.714, year: 2007

  20. Effects of Dopamine and Serotonin Systems on Modulating Neural Oscillations in Hippocampus-Prefrontal Cortex Pathway in Rats.

    Science.gov (United States)

    Xu, Xiaxia; Zheng, Chenguang; An, Lei; Wang, Rubin; Zhang, Tao

    2016-07-01

    Theta and gamma oscillations are believed to play an important role in cognition and memory, and their phase coupling facilitates the information transmission in hippocampal-cortex network. In a rat model of chronic stress, the phase coupling of both theta and gamma oscillations between ventral hippocampal CA1 (vCA1) and medial prefrontal cortex (mPFC) was found to be disrupted, which was associated with the impaired synaptic plasticity in the pathway. However, little was known about the mechanisms underlying the process. In order to address this issue, both dopamine and serotonin as monoaminergic neurotransmitters were involved in this study, since they were crucial factors in pathological basis of depressive disorder. Local field potentials (LFPs) were recorded simultaneously at both vCA1 and mPFC regions under anesthesia, before and after the injection of dopamine D1 receptor antagonist and 5-HT1A receptor agonist, respectively. The results showed that the blockage of D1 receptor could lead to depression-like decrement on theta phase coupling. In addition, the activation of 5-HT1A receptor enhanced vCA1-mPFC coupling on gamma oscillations, and attenuated CA1 theta-fast gamma cross frequency coupling. These data suggest that the theta phase coupling between vCA1 and mPFC may be modulated by dopamine system that is an underlying mechanism of the cognitive dysfunction in depression. Besides, the serotonergic system is probably involved in the regulation of gamma oscillations coupling in vCA1-mPFC network. PMID:26969669

  1. Endurance training effects on 5-HT(1B) receptors mRNA expression in cerebellum, striatum, frontal cortex and hippocampus of rats.

    Science.gov (United States)

    Chennaoui, M; Drogou, C; Gomez-Merino, D; Grimaldi, B; Fillion, G; Guezennec, C Y

    2001-07-01

    The 5-HT(1B) receptors are the predominant auto- and heteroreceptors located on serotonergic and non-serotonergic terminals where they regulate the neuronal release of neurotransmitters. The present study investigated the effects of a 7 week period of physical training on the expression of cerebral 5-HT(1B) receptors by measuring corresponding mRNA levels in rat. Using RNase protection assay technique, we have observed no change in 5-HT(1B) receptor mRNA levels in the striatum and in the hippocampus after moderate as well as after intensive training. In contrast, a significant decrease in 5-HT(1B) receptor mRNA levels was observed in cerebellum of intensively trained rats. Moreover, in frontal cortex, a significant decrease in 5-HT(1B) receptors mRNA level occurred in both groups of trained rats. These data suggest the existence of regional differences in the effect of physical exercise on the expression of 5-HT(1B) receptors. PMID:11516568

  2. Activation of a ventral hippocampus-medial prefrontal cortex pathway is both necessary and sufficient for an antidepressant response to ketamine.

    Science.gov (United States)

    Carreno, F R; Donegan, J J; Boley, A M; Shah, A; DeGuzman, M; Frazer, A; Lodge, D J

    2016-09-01

    A single sub-anesthetic dose of ketamine exerts rapid and sustained antidepressant effects. Here, we examined the role of the ventral hippocampus (vHipp)-medial prefrontal cortex (mPFC) pathway in ketamine's antidepressant response. Inactivation of the vHipp with lidocaine prevented the sustained, but not acute, antidepressant-like effect of ketamine as measured by the forced swim test (FST). Moreover, optogenetic as well as pharmacogenetic specific activation of the vHipp-mPFC pathway using DREADDs (designer receptors exclusively activated by designer drugs) mimicked the antidepressant-like response to ketamine; importantly, this was pathway specific, in that activation of a vHipp to nucleus accumbens circuit did not do this. Furthermore, optogenetic inactivation of the vHipp/mPFC pathway at the time of FST completely reversed ketamine's antidepressant response. In addition, we found that a transient increase in TrkB receptor phosphorylation in the vHipp contributes to ketamine's sustained antidepressant response. These data demonstrate that activity in the vHipp-mPFC pathway is both necessary and sufficient for the antidepressant-like effect of ketamine. PMID:26619811

  3. Postnatal BDNF Expression Profiles in Prefrontal Cortex and Hippocampus of a Rat Schizophrenia Model Induced by MK-801 Administration

    OpenAIRE

    Chunmei Guo; Yang Yang; Yun'ai Su; Tianmei Si

    2010-01-01

    Neonatal blockade of N-methyl-D-aspartic acid (NMDA) receptors represents one of experimental animal models for schizophrenia. This study is to investigate the long-term brain-derived neurotrophic factor (BDNF) expression profiles in different regions and correlation with “schizophrenia-like” behaviors in the adolescence and adult of this rat model. The NMDA receptor antagonist MK801 was administered to female Sprague-Dawley rats on postnatal days (PND) 5 through 14. Open-field test was perfo...

  4. Functional gradients through the cortex, multisensory integration and scaling laws in brain dynamics

    OpenAIRE

    Gonzalo-Fonrodona, Isabel

    2008-01-01

    In the context of the increasing number of works on multisensory and cross-modal effects in cerebral processing, a review is made on the functional model of human brain proposed by Justo Gonzalo (1910-1986), in relation to what he called central syndrome (caused by unilateral lesion in the parieto-occipital cortex, equidistant from the visual, tactile and auditory projection areas). The syndrome is featured by a bilateral, symmetric and multisensory involvement, and by a functional depression...

  5. Melatonin reduces traumatic brain injur y-induced oxidative stress in the cerebral cortex and blood of rats

    Institute of Scientific and Technical Information of China (English)

    Nilgnenol; Mustafa Nazrolu

    2014-01-01

    Free radicals induced by traumatic brain injury have deleterious effects on the function and antioxidant vitamin levels of several organ systems including the brain. Melatonin possesses antioxidant effect on the brain by maintaining antioxidant enzyme and vitamin levels. We in-vestigated the effects of melatonin on antioxidant ability in the cerebral cortex and blood of traumatic brain injury rats. Results showed that the cerebral cortex β-carotene, vitamin C, vita-min E, reduced glutathione, and erythrocyte reduced glutathione levels, and plasma vitamin C level were decreased by traumatic brain injury whereas they were increased following melatonin treatment. In conclusion, melatonin seems to have protective effects on traumatic brain inju-ry-induced cerebral cortex and blood toxicity by inhibiting free radical formation and supporting antioxidant vitamin redox system.

  6. Deep brain stimulation reveals emotional impact processing in ventromedial prefrontal cortex

    DEFF Research Database (Denmark)

    Gjedde, Albert; Geday, Jacob

    2009-01-01

    We tested the hypothesis that modulation of monoaminergic tone with deep-brain stimulation (DBS) of subthalamic nucleus would reveal a site of reactivity in the ventromedial prefrontal cortex that we previously identified by modulating serotonergic and noradrenergic mechanisms by blocking serotonin......-noradrenaline reuptake sites. We tested the hypothesis in patients with Parkinson's disease in whom we had measured the changes of blood flow everywhere in the brain associated with the deep brain stimulation of the subthalamic nucleus. We determined the emotional reactivity of the patients as the average impact of...... emotive images rated by the patients off the DBS. We then searched for sites in the brain that had significant correlation of the changes of blood flow with the emotional impact rated by the patients. The results indicate a significant link between the emotional impact when patients are not stimulated and...

  7. Laser technique for anatomical-functional study of the medial prefrontal cortex of the brain

    Science.gov (United States)

    Sanchez-Huerta, Laura; Hernandez, Adan; Ayala, Griselda; Marroquin, Javier; Silva, Adriana B.; Khotiaintsev, Konstantin S.; Svirid, Vladimir A.; Flores, Gonzalo; Khotiaintsev, Sergei N.

    1999-05-01

    The brain represents one of the most complex systems that we know yet. In its study, non-destructive methods -- in particular, behavioral studies play an important role. By alteration of brain functioning (e.g. by pharmacological means) and observation of consequent behavior changes an important information on brain organization and functioning is obtained. For inducing local alterations, permanent brain lesions are employed. However, for correct results this technique has to be quasi-non-destructive, i.e. not to affect the normal brain function. Hence, the lesions should be very small, accurate and applied precisely over the structure (e.g. the brain nucleus) of interest. These specifications are difficult to meet with the existing techniques for brain lesions -- specifically, neurotoxical, mechanical and electrical means because they result in too extensive damage. In this paper, we present new laser technique for quasi-non- destructive anatomical-functional mapping in vivo of the medial prefrontal cortex (MPFC) of the rat. The technique is based on producing of small-size, well-controlled laser- induced lesions over some areas of the MPFC. The anesthetized animals are subjected to stereotactic surgery and certain points of the MPFC are exposed the confined radiation of the 10 W cw CO2 laser. Subsequent behavioral changes observed in neonatal and adult animals as well as histological data prove effectiveness of this technology for anatomical- functional studies of the brain by areas, and as a treatment method for some pathologies.

  8. Optimizing sample preparation for anatomical determination in the hippocampus of rodent brain by ToF-SIMS analysis.

    Science.gov (United States)

    Angerer, Tina B; Mohammadi, Amir Saeid; Fletcher, John S

    2016-06-01

    Lipidomics has been an expanding field since researchers began to recognize the signaling functions of lipids and their involvement in disease. Time-of-flight secondary ion mass spectrometry is a valuable tool for studying the distribution of a wide range of lipids in multiple brain regions, but in order to make valuable scientific contributions, one has to be aware of the influence that sample treatment can have on the results. In this article, the authors discuss different sample treatment protocols for rodent brain sections focusing on signal from the hippocampus and surrounding areas. The authors compare frozen hydrated analysis to freeze drying, which is the standard in most research facilities, and reactive vapor exposure (trifluoroacetic acid and NH3). The results show that in order to preserve brain chemistry close to a native state, frozen hydrated analysis is the most suitable, but execution can be difficult. Freeze drying is prone to produce artifacts as cholesterol migrates to surface, masking other signals. This effect can be partially reversed by exposing freeze dried sections to reactive vapor. When analyzing brain sections in negative ion mode, exposing those sections to NH3 vapor can re-establish the diversity in lipid signal found in frozen hydrated analyzed sections. This is accomplished by removing cholesterol and uncovering sulfatide signals, allowing more anatomical regions to be visualized. PMID:26856332

  9. Why and how to spare the hippocampus during brain radiotherapy: the developing role of hippocampal avoidance in cranial radiotherapy

    International Nuclear Information System (INIS)

    The goal of this review is to summarize the rationale for and feasibility of hippocampal sparing techniques during brain irradiation. Radiotherapy is the most effective non-surgical treatment of brain tumors and with the improvement in overall survival for these patients over the last few decades, there is an effort to minimize potential adverse effects leading to possible worsening in quality of life, especially worsening of neurocognitive function. The hippocampus and associated limbic system have long been known to be important in memory formation and pre-clinical models show loss of hippocampal stem cells with radiation as well as changes in architecture and function of mature neurons. Cognitive outcomes in clinical studies are beginning to provide evidence of cognitive effects associated with hippocampal dose and the cognitive benefits of hippocampal sparing. Numerous feasibility planning studies support the feasibility of using modern radiotherapy systems for hippocampal sparing during brain irradiation. Although results of the ongoing phase II and phase III studies are needed to confirm the benefit of hippocampal sparing brain radiotherapy on neurocognitive function, it is now technically and dosimetrically feasible to create hippocampal sparing treatment plans with appropriate irradiation of target volumes. The purpose of this review is to provide a brief overview of studies that provide a rationale for hippocampal avoidance and provide summary of published feasibility studies in order to help clinicians prepare for clinical usage of these complex and challenging techniques

  10. Influence of brain-derived neurotrophic factor (BDNF) on serotonin neurotransmission in the hippocampus of adult rodents.

    Science.gov (United States)

    Benmansour, Saloua; Deltheil, Thierry; Piotrowski, Jonathan; Nicolas, Lorelei; Reperant, Christelle; Gardier, Alain M; Frazer, Alan; David, Denis J

    2008-06-10

    Whereas SSRIs produce rapid blockade of the serotonin transporter (SERT) in vitro and in vivo, the onset of an observable clinical effect takes longer to occur and a variety of pharmacological effects caused by antidepressants have been speculated to be involved either in initiating antidepressant effects and/or enhancing their effects on serotonergic transmission so as to cause clinical improvement. Among such secondary factors is increased activity of brain-derived neurotrophic factor (BDNF), which requires the Tropomyosine-related kinase B receptor (TrkB) for its effects. To begin an analysis of the influence of BDNF on serotonergic activity, we studied the acute effects of BDNF on SERT activity. A single BDNF injection (either intracerebroventricularly or directly into the CA3 region of hippocampus) decreased the signal amplitude and clearance rate produced by exogenously applied 5-HT compared to what was measured in control rats, shown using in vivo chronoamperometry. It also reduced the ability of a locally applied SSRI to block the clearance of 5-HT. In awake freely moving mice, acute intrahippocampal injection of BDNF decreased extracellular levels of 5-HT in the hippocampus, as measured using microdialysis. In addition, perfusion with BDNF decreased KCl-evoked elevations of 5-HT. These effects of BDNF were blocked by the non-selective antagonist of TrkB receptors, K252a. Overall, it may be inferred that in the hippocampus, through TrkB activation, a single injection of BDNF enhances SERT function. Such acute effects of BDNF would be expected to counter early effects of SSRIs, which might, in part, account for some delay in therapeutic effect. PMID:18474368

  11. Stress leads to contrasting effects on the levels of brain derived neurotrophic factor in the hippocampus and amygdala.

    Directory of Open Access Journals (Sweden)

    Harini Lakshminarasimhan

    Full Text Available Recent findings on stress induced structural plasticity in rodents have identified important differences between the hippocampus and amygdala. The same chronic immobilization stress (CIS, 2 h/day causes growth of dendrites and spines in the basolateral amygdala (BLA, but dendritic atrophy in hippocampal area CA3. CIS induced morphological changes also differ in their temporal longevity--BLA hypertrophy, unlike CA3 atrophy, persists even after 21 days of stress-free recovery. Furthermore, a single session of acute immobilization stress (AIS, 2 h leads to a significant increase in spine density 10 days, but not 1 day, later in the BLA. However, little is known about the molecular correlates of the differential effects of chronic and acute stress. Because BDNF is known to be a key regulator of dendritic architecture and spines, we investigated if the levels of BDNF expression reflect the divergent effects of stress on the hippocampus and amygdala. CIS reduces BDNF in area CA3, while it increases it in the BLA of male Wistar rats. CIS-induced increase in BDNF expression lasts for at least 21 days after the end of CIS in the BLA. But CIS-induced decrease in area CA3 BDNF levels, reverses to normal levels within the same period. Finally, BDNF is up regulated in the BLA 1 day after AIS and this increase persists even 10 days later. In contrast, AIS fails to elicit any significant change in area CA3 at either time points. Together, these findings demonstrate that both acute and chronic stress trigger opposite effects on BDNF levels in the BLA versus area CA3, and these divergent changes also follow distinct temporal profiles. These results point to a role for BDNF in stress-induced structural plasticity across both hippocampus and amygdala, two brain areas that have also been implicated in the cognitive and affective symptoms of stress-related psychiatric disorders.

  12. Occurrence of new neurons in the piriform cortex

    Directory of Open Access Journals (Sweden)

    Ti-Fei eYuan

    2015-01-01

    Full Text Available Adult neurogenesis has been well studied in hippocampus and subventricular zone; while this is much less appreciated in other brain regions, including amygdala, hypothalamus and piriform cortex. The present review aims at summarizing recent advances on the occurrence of new neurons in the piriform cortex, their potential origin and migration route from the subventricular zone. We further discuss the relevant implications in olfactory dysfunction accompanying the neuro-degenerative diseases.

  13. Traumatic stress: effects on the brain

    OpenAIRE

    Bremner, J Douglas

    2006-01-01

    Brain areas implicated in the stress response include the amygdala, hippocampus, and prefrontal cortex. Traumatic stress can be associated with lasting changes in these brain areas. Traumatic stress is associated with increased cortisol and norepinephrine responses to subsequent stressors. Antidepressants have effets on the hippocampus that counteract the effects of stress. Findings from animal studies have been extended to patients with post-traumatic stress disorder (PTSD) showing smaller h...

  14. Effects of ionizing radiation on hippocampus

    International Nuclear Information System (INIS)

    The present situation in studying effects of ionizing radiation on hippocampus of brain was reviewed in these topics, such as the kinetics of hippocampus, influences of ionizing radiation, on neutrons, biochemistry, enzymes, transmitters and synapses in hippocampus and on its electrophysiology, and the neuro-behavior after irradiation of hippocampus of brain, in order to provide information for clarifying the mechanism is radiation effect on hippocampus and for protection of human

  15. The Pattern of Brain-Derived Neurotrophic Factor Gene Expression in the Hippocampus of Diabetic Rats

    OpenAIRE

    Iraj Salehi; Safar Farajnia; Mustafa Mohammadi; Masoud Sabouri Ghannad

    2010-01-01

    Objective(s)The aim of this study was to evaluate the effects of regular exercise in preventing diabetes complication in the hippocampus of streptozotocin (STZ)-induced diabetic rat.Materials and MethodsA total of 48 male wistar rats were divided into four groups (control, control exercise, diabetic and diabetic exercise). Diabetes was induced by injection of single dose of STZ. Exercise was performed for one hr every day, over a period of 8 weeks. The antioxidant enzymes (SOD, GPX, CAT and G...

  16. The importance of the context in the hippocampus and brain related areas throughout the performance of a fear conditioning task.

    Science.gov (United States)

    Arias, Natalia; Méndez, Marta; Arias, Jorge L

    2015-11-01

    The importance context has been broadly studied in the management of phobias and in the drug addiction literature. The way in which changes to a context influence behavior after the simple acquisition of a passive avoidance task remains unclear. The hippocampus has long been implicated in the contextual and spatial processing required for contextual fear, but its role in encoding the aversive component of a contextual fear memory is still inconclusive. Our work tries to elucidate whether a change in context, represented as differences in the load of the stimuli, is critical for learning about the context-shock association and whether this manipulation of the context could be linked to any change in metabolic brain activity requirements. For this purpose, we used an avoidance conditioning task. Animals were divided into three different experimental conditions. In one group, acquisition was performed in an enriched stimuli environment and retention was performed in a typically lit chamber (the PA-ACQ-CONTX group). In another group, acquisition was performed in the typically lit chamber and retention was undertaken in the highly enriched chamber (the PA-RET-CONTX group). Finally, for the control group, PA-CN-CONTX, acquisition, and retention were performed in the enriched stimuli environment. Our results showed that the PA-ACQ-CONTX group had longer escape latencies and poorer retention than the PA-RET-CONTX and PA-CN-CONTX groups after 24 h of acquisition under contextual changes. To study metabolic brain activity, histochemical labelling of cytochrome c-oxidase (CO) was performed. CO results suggested a neural circuit including the hippocampus, amygdala, thalamus, parahippocampal cortices, and mammillary nuclei that is involved in the learning and memory processes that enable context-dependent behavior. These results highlight how dysfunction in this network may be involved in the contextualization of fear associations that underlie several forms of psychopathology

  17. A Critical Role for the Hippocampus and Perirhinal Cortex in Perceptual Learning of Scenes and Faces: Complementary Findings from Amnesia and fMRI

    Science.gov (United States)

    Mundy, Matthew E.; Downing, Paul E.; Dwyer, Dominic M.; Honey, Robert C.

    2013-01-01

    It is debated whether subregions within the medial temporal lobe (MTL), in particular the hippocampus (HC) and perirhinal cortex (PrC), play domain-sensitive roles in learning. In the present study, two patients with differing degrees of MTL damage were first exposed to pairs of highly similar scenes, faces, and dot patterns and then asked to make repeated same/different decisions to preexposed and nonexposed (novel) pairs from the three categories (Experiment 1). We measured whether patients would show a benefit of prior exposure (preexposed > nonexposed) and whether repetition of nonexposed (and preexposed) pairs at test would benefit discrimination accuracy. Although selective HC damage impaired learning of scenes, but not faces and dot patterns, broader MTL damage involving the HC and PrC compromised discrimination learning of scenes and faces but left dot pattern learning unaffected. In Experiment 2, a similar task was run in healthy young participants in the MRI scanner. Functional region-of-interest analyses revealed that posterior HC and posterior parahippocampal gyrus showed greater activity during scene pattern learning, but not face and dot pattern learning, whereas PrC, anterior HC, and posterior fusiform gyrus were recruited during discrimination learning for faces, but not scenes and dot pattern learning. Critically, activity in posterior HC and PrC, but not the other functional region-of-interest analyses, was modulated by accuracy (correct > incorrect within a preferred category). Therefore, both approaches revealed a key role for the HC and PrC in discrimination learning, which is consistent with representational accounts in which subregions in these MTL structures store complex spatial and object representations, respectively. PMID:23785161

  18. Oxytocin via its receptor affects restraint stress-induced methamphetamine CPP reinstatement in mice: Involvement of the medial prefrontal cortex and dorsal hippocampus glutamatergic system.

    Science.gov (United States)

    Han, Wen-Yan; Du, Ping; Fu, Shi-Yuan; Wang, Fang; Song, Ming; Wu, Chun-Fu; Yang, Jing-Yu

    2014-04-01

    Our previous study revealed that intracerebroventricular oxytocin (OT) markedly inhibited the restraint stress-priming conditioned place preference (CPP) reinstatement induced by methamphetamine (MAP) via the glutamatergic system. In this study, the effect of microinjection with OT into mesocorticolimbic regions, the medial prefrontal cortex (mPFC) and the dorsal hippocampus (DHC), on the restraint stress-priming CPP reinstatement were further studied. The results showed that a 15-min restraint stress significantly reinstated MAP-induced CPP, which was inhibited by the microinjection of OT (0.5 and 2.5μg/μl/mouse) into the mPFC. Atosiban (Ato), a selective inhibitor of OT receptor, could absolutely block the effect of OT (2.5μg/μl/mouse). The reinstatement was inhibited by microinjecting with OT (2.5 but not 0.5μg/μl/mouse) into the DHC, which could not be reversed by Ato. Western blotting results showed that the levels of GLT1, VGLUT2, NR2B, p-ERK1/2 and p-CREB expressions in the mPFC were increased and CaMKII was decreased markedly after the stress-priming MAP-induced CPP reinstatement test. OT blocked the changing levels of GLT1, VGLUT2, NR2B, p-CREB and CaMK II, which were reversed by Ato, but failed to affect the elevated expression of p-ERK1/2. In DHC, the levels of VGLUT2, p-ERK1/2 and CREB expressions were reduced during the stress-induced reinstatement, which could be reversed by OT and further abolished by Ato. The present results suggest that mPFC and DHC play differential roles in restraint stress-priming CPP reinstatement induced by MAP and OT via OT receptor affects the reinstatement in which the glutamatergic system is involved. PMID:24269543

  19. Protective effects of chronic treatment with a standardized extract of Ginkgo biloba L. in the prefrontal cortex and dorsal hippocampus of middle-aged rats.

    Science.gov (United States)

    Ribeiro, Marcelo L; Moreira, Luciana M; Arçari, Demetrius P; Dos Santos, Letícia França; Marques, Antônio Cezar; Pedrazzoli, José; Cerutti, Suzete M

    2016-10-15

    This study assessed the effects of chronic treatment with a standardized extract of Ginkgo biloba L. (EGb) on short-term and long-term memory as well as on anxiety-like and locomotor activity using the plus-maze discriminative avoidance task (PM-DAT). Additionally, we evaluated the antioxidant and neuroprotective effects of EGb on the prefrontal cortex (PFC) and dorsal hippocampus (DH) of middle-aged rats using the comet assay. Twelve-month-old male Wistar rats were administered vehicle or EGb (0.5mgkg(-1) or 1.0gkg(-1)) for 30days. Behavioural data showed that EGb treatment improved short-term memory. Neither an anti-anxiety effect nor a change in locomotor activity was observed. Twenty-four hours after the behavioural tests, the rats were decapitated, and the PFC and DH were quickly dissected out and prepared for the comet assay. The levels of DNA damage in the PFC were significantly lower in rats that were treated with 1.0gkg(-1) EGb. Both doses of EGb decreased H2O2-induced DNA breakage in cortical cells, whereas the levels of DNA damage in the EGb-treated animals were significantly lower than those in the control animals. No significant differences in the level of DNA damage in hippocampal cells were observed among the experimental groups. EGb treatment was not able to reduce H2O2-induced DNA damage in hippocampal cells. Altogether, our data provide the first demonstration that chronic EGb treatment improved the short-term memory of middle-aged rats, an effect that could be associated with a reduction in free radical production in the PFC. These data suggest that EGb treatment might increase the survival of cortical neurons and corroborate and extend the view that EGb has protective and therapeutic properties. PMID:27424157

  20. Imaging of copper, zinc, and other elements in thin section of human brain samples (hippocampus) by laser ablation inductively coupled plasma mass spectrometry.

    Science.gov (United States)

    Becker, J S; Zoriy, M V; Pickhardt, C; Palomero-Gallagher, N; Zilles, K

    2005-05-15

    Laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) was used to produce images of element distribution in 20-microm thin sections of human brain tissue. The sample surface was scanned (raster area approximately 80 mm(2)) with a focused laser beam (wavelength 213 nm, diameter of laser crater 50 microm, and laser power density 3 x 10(9) W cm(-2)) in a cooled laser ablation chamber developed for these measurements. The laser ablation system was coupled to a double-focusing sector field ICPMS. Ion intensities of 31P+, 32S+, 56Fe+, 63Cu+, 64Zn+, 232Th+, and 238U+ were measured within the area of interest of the human brain tissue (hippocampus) by LA-ICPMS. The quantitative determination of copper, zinc, uranium, and thorium distribution in thin slices of the human hippocampus was performed using matrix-matched laboratory standards. In addition, a new arrangement in solution-based calibration using a micronebulizer, which was inserted directly into the laser ablation chamber, was applied for validation of synthetic laboratory standard. The mass spectrometric analysis yielded an inhomogeneous distribution (layered structure) for P, S, Cu, and Zn in thin brain sections of the hippocampus. In contrast, Th and U are more homogeneously distributed at a low-concentration level with detection limits in the low-nanogram per gram range. The unique analytical capability and the limits of LA-ICPMS will be demonstrated for the imaging of element distribution in thin cross sections of brain tissue from the hippocampus. LA-ICPMS provides new information on the spatial element distribution of the layered structure in thin sections of brain tissues from the hippocampus. PMID:15889910

  1. Two-dimensional electrophoretogram of acute brain injury-associated proteins Comparison between Injured and normal cerebral cortex

    Institute of Scientific and Technical Information of China (English)

    Xuejun Li; Xianrui Yuan; Cui Li; Zefeng Peng; Dun Yuan

    2008-01-01

    BACKGROUND:To this date,specific molecular markers for early diagnosis and prognosis monitoring ofcraniocerebral injury in clinical medicine do not exist.Therefore,differential detection of specific proteinsmight play an important role in diagnosis and treatment of this type of brain injury.OBJECTIVE:To compare differential cerebral cortical protein expression of craniocerebral injury patientsand normal subjects through the use of proteomics.DESIGN:Contrast observation.SETTING:Department of Neurosurgery,Xiangya Hospital of Central South University.PARTICIPANTS:Ten patients(6 males and 4 females,20-58 years old),with severe craniocerebral injury,were selected at the Department of Neurosurgery,Xiangya Hospital of Central South University,from June2004 to December 2006.All patients were diagnosed with CT test and Glasgow test(scores <8).Surgery was performed 4-12 hours after craniocerebral injury,and injured cortical tissues of the frontal and temporal lobes were resected for sampling.At the same time,control cortical tissues were collected from frontal and temporal lobes of 2 epileptic patients who underwent hippocampus-nucleus amygdala resection,and 2 lateral ventricular tumor patients who underwent tumor resection.The participants and their relatives provided confirmed consent,and this study received confirmed consent from the local ethics committee. METHODS:Ten samples from injured patients and 4 normal samples were compared through the use of proteomics.Total protein was separated by using two-dimensional electrophoresis with immobilized pH gradients,and the differential protein expressions were compared using image analysis after blue-sliver staining. Differential protein spot expressions were analyzed with a matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI/TOF MS) and electrospray ionization-quadrupole time of flight mass spectrometry(ESI-Qq TOF MS).MAIN OUTCOME MEASURES: ①Two-dimensional electrophoresis of protein from

  2. Increases in mature brain-derived neurotrophic factor protein in the frontal cortex and basal forebrain during chronic sleep restriction in rats: possible role in initiating allostatic adaptation.

    Science.gov (United States)

    Wallingford, J K; Deurveilher, S; Currie, R W; Fawcett, J P; Semba, K

    2014-09-26

    Chronic sleep restriction (CSR) has various negative consequences on cognitive performance and health. Using a rat model of CSR that uses alternating cycles of 3h of sleep deprivation (using slowly rotating activity wheels) and 1h of sleep opportunity continuously for 4 days ('3/1' protocol), we previously observed not only homeostatic but also allostatic (adaptive) sleep responses to CSR. In particular, non-rapid eye movement sleep (NREMS) electroencephalogram (EEG) delta power, an index of sleep intensity, increased initially and then declined gradually during CSR, with no rebound during a 2-day recovery period. To study underlying mechanisms of these allostatic responses, we examined the levels of brain-derived neurotrophic factor (BDNF), which is known to regulate NREMS EEG delta activity, during the same CSR protocol. Mature BDNF protein levels were measured in the frontal cortex and basal forebrain, two brain regions involved in sleep and EEG regulation, and the hippocampus, using Western blot analysis. Adult male Wistar rats were housed in motorized activity wheels, and underwent the 3/1 CSR protocol for 27 h, for 99 h, or for 99 h followed by 24h of recovery. Additional rats were housed in either locked wheels (locked wheel controls [LWCs]) or unlocked wheels that rats could rotate freely (wheel-running controls [WRCs]). BDNF levels did not differ between WRC and LWC groups. BDNF levels were increased, compared to the control levels, in all three brain regions after 27 h, and were increased less strongly after 99 h, of CSR. After 24h of recovery, BDNF levels were at the control levels. This time course of BDNF levels parallels the previously reported changes in NREMS delta power during the same CSR protocol. Changes in BDNF protein levels in the cortex and basal forebrain may be part of the molecular mechanisms underlying allostatic sleep responses to CSR. PMID:25010399

  3. Characterization of 5-HT1D receptor binding sites in post-mortem human brain cortex.

    OpenAIRE

    Martial, J; de Montigny, C; Cecyre, D; Quirion, R

    1991-01-01

    The present study provides further evidence for the presence of serotonin1D (5-HT1D) receptors in post-mortem human brain. Receptor binding parameters in temporal cortex homogenates were assessed using [3H]5-HT in the presence of 100 nM 8-OH-DPAT, 1 microM propranolol and 1 microM mesulergine to prevent labelling of the 5-HT1A, 5-HT1B and 5-HT1C sites, respectively. Under these conditions, [3H]5-HT apparently bound to a class of high affinity (Kd = 5.0 +/- 1.0 nM) low capacity (Bmax = 96 +/- ...

  4. Where do the photons collapse - in the retina or in the brain cortex?

    CERN Document Server

    Georgiev, D D

    2002-01-01

    While looking for evidence of quantum coherent states within the brain many quantum mind advocates proposed experiments based on the assumption that the coherence state of natural light could somehow be preserved thorough the neural processing, or in other words they suppose that photons collapse not in the retina, but in the brain cortex. In this paper I show that photons collapse within the retina and subsequent processing of information at the level of neural membranes proceeds. The changes of the membrane potential of the neurons in the primary sensory cortical regions are shown to be relevant to inputting sensory information, which is converted into microtubule subunits pattern and specific quantum states. The role of the associative cortical regions in the conscious experience is thoroughly revised. One of the strangest observations, namely the existence of the so called grandmother cells, is explained by quantum state processing. The question why classical computing is needed at all gets unexpected ans...

  5. BDNF Meditated trkB and Synapsin I Changes within the Hippocampus after Mild Traumatic Brain Injury in Rat:Reflections of Injury-induced Neuroplasticity

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    1 IntroductionTraumatic brain injury (TBI) can produce chronic cognitive learning/memory deficits that are thought to be mediated, in part, by impaired hippocampal function. Brain-derived neurotrophic factor (BDNF), its signal transduction receptor trkB and its downstream effector synapsin I are involved in this period. BDNF, trkB and the slope of field excitatory post-synaptic potential(fEPSP) were measured in the hippocampus of rat after fluid percussion brain injury (FPI). Isofluorane anaesthe- tizeed 50...

  6. Sparing of the hippocampus, limbic circuit and neural stem cell compartment during partial brain radiotherapy for glioma: a dosimetric feasibility study

    International Nuclear Information System (INIS)

    The aim of this study was to assess the feasibility of sparing contralateral or bilateral neural stem cell (NSC) compartment, hippocampus and limbic circuit during partial brain radiotherapy (PBRT). Treatment plans were generated for five hemispheric high-grade gliomas, five hemispheric low-grade gliomas and two brainstem gliomas (12 patients). For each, standard intensity-modulated radiotherapy (IMRT) plans were generated, as well as IMRT plans which spared contralateral (hemispheric cases) or bilateral (brainstem cases) limbic circuit, hippocampus, and NSC. Biologically equivalent dose for late effects (BEDlate effects) was generated for limbic circuit, hippocampus and NSC. Per cent relative reduction in mean physical dose and BED was calculated for each plan (standard vs. sparing). We were able to reduce physical dose and BEDlate effects to these critical structures by 23.5–56.8% and 23.6–66%, respectively. It is possible to spare contralateral limbic circuit, NSC and hippocampus during PBRT for both high- and low-grade gliomas using IMRT, and to spare the hippocampus bilaterally during PBRT for brainstem low-grade gliomas. This approach may reduce late cognitive sequelae of cranial radiotherapy.

  7. SU-E-T-79: Comparison of Doses Received by the Hippocampus in Patients Treated with Single Vs Multiple Isocenter Based Stereotactic Radiation Therapy to the Brain for Multiple Brain Metastases

    Energy Technology Data Exchange (ETDEWEB)

    Algan, O; Giem, J; Young, J; Ali, I; Ahmad, S; Hossain, S [University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

    2014-06-01

    Purpose: To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiotherapy utilizing a single isocenter (SI) versus multiple isocenter (MI) in patients with multiple intracranial metastases. Methods: Seven patients imaged with MRI including SPGR sequence and diagnosed with 2–3 brain metastases were included in this retrospective study. Two sets of stereotactic IMRT treatment plans, (MI vs SI), were generated. The hippocampus was contoured on SPGR sequences and doses received by the hippocampus and whole brain were calculated. The prescribed dose was 25Gy in 5 fractions. The two groups were compared using t-test analysis. Results: There were 17 lesions in 7 patients. The median tumor, right hippocampus, left hippocampus and brain volumes were: 3.37cc, 2.56cc, 3.28cc, and 1417cc respectively. In comparing the two treatment plans, there was no difference in the PTV coverage except in the tail of the DVH curve. All tumors had V95 > 99.5%. The only statistically significant parameter was the V100 (72% vs 45%, p=0.002, favoring MI). All other evaluated parameters including the V95 and V98 did not reveal any statistically significant differences. None of the evaluated dosimetric parameters for the hippocampus (V100, V80, V60, V40, V20, V10, D100, D90, D70, D50, D30, D10) revealed any statistically significant differences (all p-values > 0.31) between MI and SI plans. The total brain dose was slightly higher in the SI plans, especially in the lower dose regions, although this difference was not statistically significant. Utilizing brain-sub-PTV volumes did not change these results. Conclusion: The use of SI treatment planning for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain compared to MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.

  8. SU-E-T-79: Comparison of Doses Received by the Hippocampus in Patients Treated with Single Vs Multiple Isocenter Based Stereotactic Radiation Therapy to the Brain for Multiple Brain Metastases

    International Nuclear Information System (INIS)

    Purpose: To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiotherapy utilizing a single isocenter (SI) versus multiple isocenter (MI) in patients with multiple intracranial metastases. Methods: Seven patients imaged with MRI including SPGR sequence and diagnosed with 2–3 brain metastases were included in this retrospective study. Two sets of stereotactic IMRT treatment plans, (MI vs SI), were generated. The hippocampus was contoured on SPGR sequences and doses received by the hippocampus and whole brain were calculated. The prescribed dose was 25Gy in 5 fractions. The two groups were compared using t-test analysis. Results: There were 17 lesions in 7 patients. The median tumor, right hippocampus, left hippocampus and brain volumes were: 3.37cc, 2.56cc, 3.28cc, and 1417cc respectively. In comparing the two treatment plans, there was no difference in the PTV coverage except in the tail of the DVH curve. All tumors had V95 > 99.5%. The only statistically significant parameter was the V100 (72% vs 45%, p=0.002, favoring MI). All other evaluated parameters including the V95 and V98 did not reveal any statistically significant differences. None of the evaluated dosimetric parameters for the hippocampus (V100, V80, V60, V40, V20, V10, D100, D90, D70, D50, D30, D10) revealed any statistically significant differences (all p-values > 0.31) between MI and SI plans. The total brain dose was slightly higher in the SI plans, especially in the lower dose regions, although this difference was not statistically significant. Utilizing brain-sub-PTV volumes did not change these results. Conclusion: The use of SI treatment planning for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain compared to MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment

  9. The role of hippocampus in the pathophysiology of bipolar disorder.

    Science.gov (United States)

    Frey, Benicio N; Andreazza, Ana C; Nery, Fabiano G; Martins, Marcio R; Quevedo, João; Soares, Jair C; Kapczinski, Flávio

    2007-09-01

    Bipolar disorder (BD) is thought to be associated with abnormalities within discrete brain regions associated with emotional regulation, particularly in fronto-limbic-subcortical circuits. Several reviews have addressed the involvement of the prefrontal cortex in the pathophysiology of BD, whereas little attention has been given to the role of the hippocampus. This study critically reviews data from brain imaging, postmortem, neuropsychological, and preclinical studies, which suggested hippocampal abnormalities in BD. Most of the structural brain imaging studies did not find changes in hippocampal volume in BD, although a few studies suggested that anatomical changes might be restricted to the psychotic, pediatric, or unmedicated BD subgroups. Functional imaging studies showed abnormal brain activation in the hippocampus and its closely related regions during emotional, attentional, and memory tasks. This is consistent with neuropsychological findings that revealed a wide range of cognitive disturbances during acute mood episodes and a significant impairment in declarative memory during remission. Postmortem studies indicate abnormal glutamate and GABA transmission in the hippocampus of BD patients, whereas data from preclinical studies suggest that the regulation of hippocampal plasticity and survival might be associated with the therapeutic effects of mood stabilizers. In conclusion, the available evidence suggests that the hippocampus plays an important role in the pathophysiology of BD. PMID:17762510

  10. Functional connectivity between brain areas estimated by analysis of gamma waves

    OpenAIRE

    F. Kheiri; Bragin, A.; Jr, EJ

    2013-01-01

    The goal of this study is to investigate functional connectivity between different brain regions by analyzing the temporal relationship of the maxima of gamma waves recorded in multiple brain areas. Local field potentials were recorded from motor cortex, hippocampus, entorhinal cortex and piriform cortex of rats. Gamma activity was filtered and separated into two bands; high (65–90Hz) and low (30–55Hz) gamma. Maxima for gamma activity waves were detected and functional connectivity between di...

  11. Oral administration of curcumin relieves behavioral alterations and oxidative stress in the frontal cortex, hippocampus, and striatum of ovariectomized Wistar rats.

    Science.gov (United States)

    Da Silva Morrone, Maurilio; Schnorr, Carlos Eduardo; Behr, Guilherme Antônio; Gasparotto, Juciano; Bortolin, Rafael Calixto; Moresco, Karla Suzana; Bittencourt, Leonardo; Zanotto-Filho, Alfeu; Gelain, Daniel Pens; Moreira, José Cláudio Fonseca

    2016-06-01

    Menopause occurs gradually and is characterized by increased susceptibility to developing mood disorders. Several studies have suggested treatments based on the antioxidant properties of vitamins and herbal compounds as an alternative to hormone replacement therapies, with few or none reporting toxicity. The present study was performed to explore the effects of curcumin oral supplementation on anxiety-like behavior and oxidative stress parameters in different central nervous system (CNS) areas of ovariectomized (OVX) rats. Female Wistar rats were randomly divided into either sham-operated or OVX groups. Sham-operated group (n=8) and an OVX group (n=11) were treated with vehicle, and the other two OVX groups received curcumin at 50 or 100mg/kg/day doses (n=8/group). Elevated plus maze (EPM) test was performed on the 28th day of treatment. On the 30th day, animals were killed and the dissected brain regions were removed and stored at-80°C until analysis. Ovariectomy induced deficit in the locomotor activity and increased anxiety-like behavior. Moreover, OVX rats showed increased lipid oxidized in the frontal cortex and striatum, increased hippocampal and striatal carbonylated protein level, and decreased striatal thiol content of non-protein fraction indicative of a glutathione (GSH) pool. Curcumin oral treatment for 30days reduced oxidative stress in the CNS areas as well as the behavior alterations resulting from ovariectomy. Curcumin supplementation attenuated most of these parameters to sham comparable values, suggesting that curcumin could have positive effects against anxiety-like disturbances and brain oxidative damage due to hormone deprivation. PMID:27142750

  12. Estimation of kinetic parameters for glucose transport in human brain cortex

    International Nuclear Information System (INIS)

    3-O-C-11-methyl-D-glucose (CMG), F-18-3-deoxy-3-fluoro D-glucose (3FDG), and dynamic positron-emission-tomography (dPET) were used to measure the rate constants for glucose transport across the blood brain barrier (BBB) in human cortex. The assay takes advantage of CMG or 3FDG being practically not metabolized in brain and being transported back from the tissue into the circulation. The simultaneous registration of tracer concentration in blood and tissue by dPET at 1 min intervals for 40 min yields time activity curves, which permit the in vivo determination of the rate constants for CMG or 3FDG transport across the BBB. In the present study, 4 healthy volunteers and 10 patients suffering from a single-sided ischemic brain disease were examined. In all cases the CMG/3FDG measurements were carried out at two different glucose plasma concentrations i.e. at normoglycemia and hyperglycemia after i.v. application of 10 g glucose. The determination of glucose plasma concentration was performed just before and immediately after the CMG/3FDG study. Using these data and a new mathematical model the Michaelis-Menten constant (K/sub M/) and maximal velocity (V/sub M/) for CMG, 3FDG and glucose transport across the BBB in normal and non-affected human cortex were determined. K/sub M CMG/ was 7.21 μmol/g; K/sub M 3FDG/ was 3.93 μmol/g and K/sub M gluc/ was 6.31 μmol/g. V/sub M/ was found in all cases to be 2.1 μmol/min g. The data obtained suggest that the CMG/3FDG method might provide a powerful tool for studying the mechanisms involved in the pathological alterations of glucose carrier system

  13. Chronic type 2 diabetes reduces the integrity of the blood-brain barrier by reducing tight junction proteins in the hippocampus.

    Science.gov (United States)

    Yoo, Dae Young; Yim, Hee Sun; Jung, Hyo Young; Nam, Sung Min; Kim, Jong Whi; Choi, Jung Hoon; Seong, Je Kyung; Yoon, Yeo Sung; Kim, Dae Won; Hwang, In Koo

    2016-07-01

    In the present study, we investigated the effects of type 2 diabetes-induced hyperglycemia on the integrity of the blood-brain barrier and tight junction markers in the rat hippocampus. Forty-week-old diabetic (Zucker diabetic fatty, ZDF) rats and littermate control (Zucker lean control, ZLC) rats were used in this study. We evaluated the integrity of the blood-brain barrier by measuring sodium fluorescein extravasation and blood vessel ultrastructure. In addition, tight junction markers, such as zona occludens-1, occludin and claudin-5, were quantified by western blot analysis. ZDF rats showed significantly increased sodium fluorescein leakage in the hippocampus. Tight junction markers, such as occludin and claudin-5, were significantly decreased in the hippocampi of ZDF rats compared to those of ZLC rats. In addition, ZDF rats showed ultrastructural changes with phagocytic findings in the blood vessels. These results suggest that chronic untreated diabetes impairs the permeability of the hippocampal blood-brain barrier by down-regulating occludin and claudin-5, indicating that chronic untreated diabetes may cause hippocampus-dependent dysfunction. PMID:26876499

  14. Quantitative analysis of neuronal mosaic formation in the mouse neocortex and hippocampus

    International Nuclear Information System (INIS)

    The authors obtain mathematical confirmation of the nonrandomness of mosaic formation of neuronal groups in the cerebral cortex, characterize this process quantitatively, and compare its scale with the formation of the modular organization of the cortex. Mice were used in the experiments and were injected with 3H-thymidine while pregnant. Mapping in the neocortex was carried out on frontal semithin brain sections from mice receiving 3H-thymidine from E15 through E17, whereas mapping in the hippocampus was carried out on paraffin and semithin frontal brain sections from animals receiving the isotope from E13 through E17

  15. Expression of glutamatergic genes in healthy humans across 16 brain regions; altered expression in the hippocampus after chronic exposure to alcohol or cocaine.

    Science.gov (United States)

    Enoch, M-A; Rosser, A A; Zhou, Z; Mash, D C; Yuan, Q; Goldman, D

    2014-11-01

    We analyzed global patterns of expression in genes related to glutamatergic neurotransmission (glutamatergic genes) in healthy human adult brain before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus. RNA-Seq data from 'BrainSpan' was obtained across 16 brain regions from nine control adults. We also generated RNA-Seq data from postmortem hippocampus from eight alcoholics, eight cocaine addicts and eight controls. Expression analyses were undertaken of 28 genes encoding glutamate ionotropic (AMPA, kainate, NMDA) and metabotropic receptor subunits, together with glutamate transporters. The expression of each gene was fairly consistent across the brain with the exception of the cerebellum, the thalamic mediodorsal nucleus and the striatum. GRIN1, encoding the essential NMDA subunit, had the highest expression across all brain regions. Six factors accounted for 84% of the variance in global gene expression. GRIN2B (encoding GluN2B), was up-regulated in both alcoholics and cocaine addicts (FDR corrected P = 0.008). Alcoholics showed up-regulation of three genes relative to controls and cocaine addicts: GRIA4 (encoding GluA4), GRIK3 (GluR7) and GRM4 (mGluR4). Expression of both GRM3 (mGluR3) and GRIN2D (GluN2D) was up-regulated in alcoholics and down-regulated in cocaine addicts relative to controls. Glutamatergic genes are moderately to highly expressed throughout the brain. Six factors explain nearly all the variance in global gene expression. At least in the hippocampus, chronic alcohol use largely up-regulates glutamatergic genes. The NMDA GluN2B receptor subunit might be implicated in a common pathway to addiction, possibly in conjunction with the GABAB1 receptor subunit. PMID:25262781

  16. Expression of receptor for advanced glycation endproducts and nuclear factor κB in brain hippocampus of rat with chronic fluorosis

    Institute of Scientific and Technical Information of China (English)

    张凯琳

    2014-01-01

    Objective To investigate the expressions of receptor for advanced glycation endproducts(RAGE)and nuclear factorκB(NF-κB)in brain hippocampus of rat with chronic fluorosis,and to reveal the mechanism of brain damage resulted from chronic fluorosis.Methods Sixty clean grade SD rats were randomly divided to three groups(20 rats in each group,10 female and 10 male)fed with different contents of fluoride,control group with normal tap-water(<0.5 mg/L fluoride),

  17. SU-E-T-589: Optimization of Patient Head Angle Position to Spare Hippocampus During the Brain Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Cheon, G; Kang, Y [Radiation Oncology, Seoul St. Mary’s Hospital, Seoul (Korea, Republic of); Kang, S; Kim, T; Kim, D; Suh, T [The Catholic University of Korea, Seoul (Korea, Republic of)

    2015-06-15

    Purpose: Hippocampus is one of the important organs which controls emotions, behaviors, movements the memorizing and learning ability. In the conventional head & neck therapy position, it is difficult to perform the hippocampal-sparing brain radiation therapy. The purpose of this study is to investigate optimal head angle which can save the hippocampal-sparing and organ at risk (OAR) in conformal radiation therapy (CRT), Intensity modulation radiation therapy (IMRT) and helical tomotherapy (HT). Methods: Three types of radiation treatment plans, CRT, IMRT and Tomotherapy plans, were performed for 10 brain tumor patients. The image fusion between CT and MRI data were used in the contour due to the limited delineation of the target and OAR in the CT scan. The optimal condition plan was determined by comparing the dosimetric performance of the each plan with the use of various parameters which include three different techniques (CRT, IMRT, HT) and 4 angle (0, 15, 30, 40 degree). The each treatment plans of three different techniques were compared with the following parameters: conformity index (CI), homogeneity index (HI), target coverage, dose in the OARs, monitor units (MU), beam on time and the normal tissue complication probability (NTCP). Results: HI, CI and target coverage was most excellent in head angle 30 degree among all angle. When compared by modality, target coverage and CI showed good results in IMRT and TOMO than compared to the CRT. HI at the head angle 0 degrees is 1.137±0.17 (CRT), 1.085±0.09 (IMRT) and 1.077±0.06 (HT). HI at the head angle 30 degrees is 1.056±0.08 (CRT), 1.020±0.05 (IMRT) and 1.022±0.07 (HT). Conclusion: The results of our study show that when head angle tilted at 30 degree, target coverage, HI, CI were improved, and the dose delivered to OAR was reduced compared with conventional supine position in brain radiation therapy. This work was supported by the Radiation Technology R&D program (No. 2013M2A2A7043498) and the Mid

  18. GluA1 Phosphorylation Contributes to Postsynaptic Amplification of Neuropathic Pain in the Insular Cortex

    OpenAIRE

    Qiu, Shuang; Zhang, Ming; Yan LIU; Guo, Yanyan; Zhao, Huan; Song, Qian; Zhao, Minggao; Huganir, Richard L.; Luo, Jianhong; Xu, Hui; Zhuo, Min

    2014-01-01

    Long-term potentiation of glutamatergic transmission has been observed after physiological learning or pathological injuries in different brain regions, including the spinal cord, hippocampus, amygdala, and cortices. The insular cortex is a key cortical region that plays important roles in aversive learning and neuropathic pain. However, little is known about whether excitatory transmission in the insular cortex undergoes plastic changes after peripheral nerve injury. Here, we found that peri...

  19. Evidence that brain glucose availability influences exercise-enhanced extracellular 5-HT level in hippocampus: a microdialysis study in exercising rats.

    Science.gov (United States)

    Béquet, F; Gomez-Merino, D; Berthelot, M; Guezennec, C Y

    2002-09-01

    The relationship between brain glucose and serotonin is still unclear and no direct evidence of an action of brain glucose on serotonergic metabolism in central fatigue phenomena has been shown yet. In order to determine whether or not brain glucose could influence the brain 5-hydroxytryptamine (5-HT) system, we have monitored in microdialysis the effects of a direct injection of glucose in rat brain hippocampus on serotonergic metabolism [i.e. 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and tryptophan (TRP)], during high intensive treadmill running. The injection was performed just before and after exercise. We have shown that glucose induced a decrease of brain 5-HT levels to a minimum of 73.0 +/- 3.5% of baseline after the first injection (P exercise-induced 5-HT enhanced levels. We have observed the same phenomenon concerning the 5-HIAA, but brain TRP levels were not decreased by the injections. In conclusion, this study demonstrates that brain glucose can act on serotonergic metabolism and thus can prevent exercise-induced increase of 5-HT levels. The results also suggest that extracellular brain glucose does not act on the synthesis way of 5-HT, but probably on the release/reuptake system. PMID:12193220

  20. The fuzzy brain. Vagueness and mapping connectivity of the human cerebral cortex

    Science.gov (United States)

    Haueis, Philipp

    2012-01-01

    While the past century of neuroscientific research has brought considerable progress in defining the boundaries of the human cerebral cortex, there are cases in which the demarcation of one area from another remains fuzzy. Despite the existence of clearly demarcated areas, examples of gradual transitions between areas are known since early cytoarchitectonic studies. Since multi-modal anatomical approaches and functional connectivity studies brought renewed attention to the topic, a better understanding of the theoretical and methodological implications of fuzzy boundaries in brain science can be conceptually useful. This article provides a preliminary conceptual framework to understand this problem by applying philosophical theories of vagueness to three levels of neuroanatomical research. For the first two levels (cytoarchitectonics and fMRI studies), vagueness will be distinguished from other forms of uncertainty, such as imprecise measurement or ambiguous causal sources of activation. The article proceeds to discuss the implications of these levels for the anatomical study of connectivity between cortical areas. There, vagueness gets imported into connectivity studies since the network structure is dependent on the parcellation scheme and thresholds have to be used to delineate functional boundaries. Functional connectivity may introduce an additional form of vagueness, as it is an organizational principle of the brain. The article concludes by discussing what steps are appropriate to define areal boundaries more precisely. PMID:22973199

  1. The fuzzy brain. Vagueness and the mapping connectivity of the human cortex.

    Directory of Open Access Journals (Sweden)

    Philipp Haueis

    2012-09-01

    Full Text Available While the past century of neuroscientific research has brought considerable progress in defining the boundaries of the human cerebral cortex, there are cases in which the demarcation of one area from another remains fuzzy. Despite the existence of clearly demarcated areas, examples of gradual transitions between areas are known since early cytoarchitectonic studies. Since multi-modal anatomical approaches and functional connectivity studies brought renewed attention to the topic, a better understanding of the theoretical and methodological implications of fuzzy boundaries in brain science can be conceptually useful. This article provides a preliminary conceptual framework to understand this problem by applying philosophical theories of vagueness to three levels neuroanatomical research. For the first two levels (cytoarchitectonics and fMRI studies, vagueness will be distinguished from other forms of uncertainty, such as imprecise measurement or ambiguous causal sources of activation. The article proceeds to discuss the implications of these levels for the anatomical study of connectivity between cortical areas. There, vagueness gets imported into connectivity studies since the network structure is dependent on the parcellation scheme thresholds have to be used to delineate functional boundaries. Functional connectivity may introduce an additional form of vagueness, as it is an organizational principle of the brain. The article concludes by discussing what steps are appropriate to define areal boundaries more precisely.

  2. Human umbilical cord blood cells restore brain damage induced changes in rat somatosensory cortex.

    Directory of Open Access Journals (Sweden)

    Maren Geissler

    Full Text Available Intraperitoneal transplantation of human umbilical cord blood (hUCB cells has been shown to reduce sensorimotor deficits after hypoxic ischemic brain injury in neonatal rats. However, the neuronal correlate of the functional recovery and how such a treatment enforces plastic remodelling at the level of neural processing remains elusive. Here we show by in-vivo recordings that hUCB cells have the capability of ameliorating the injury-related impairment of neural processing in primary somatosensory cortex. Intact cortical processing depends on a delicate balance of inhibitory and excitatory transmission, which is disturbed after injury. We found that the dimensions of cortical maps and receptive fields, which are significantly altered after injury, were largely restored. Additionally, the lesion induced hyperexcitability was no longer observed in hUCB treated animals as indicated by a paired-pulse behaviour resembling that observed in control animals. The beneficial effects on cortical processing were reflected in an almost complete recovery of sensorimotor behaviour. Our results demonstrate that hUCB cells reinstall the way central neurons process information by normalizing inhibitory and excitatory processes. We propose that the intermediate level of cortical processing will become relevant as a new stage to investigate efficacy and mechanisms of cell therapy in the treatment of brain injury.

  3. Effects of imipramine treatment on delta-opioid receptors of the rat brain cortex and striatum.

    Science.gov (United States)

    Varona, Adolfo; Gil, Javier; Saracibar, Gonzalo; Maza, Jose Luis; Echevarria, Enrique; Irazusta, Jon

    2003-01-01

    Imipramine (CAS 113-52-0) is being utilized widely for the treatment of major depression. In recent years, there has been evidence of the involvement of the endogenous opioid system in major depression and its treatment. There is some evidence indicating that opioid receptors could be involved in the antidepressant mechanism of action. Regarding this topic, mood-related behavior of endogenous enkephalins seems to be mediated by delta-opioid receptors. In this work, the effects of subacute (5 day) and chronic (15 day) treatments of imipramine on the density and the affinity of the delta-receptors in the striatum and in the parietal and frontal cortices of the rat brain are described. Studied parameters (Bmax and Kd) were calculated by a saturation binding assay with the delta-opioid agonists [3H]-DPDPE (tyrosyl-2,6-3H(N)-(2-D-penicillamine-5-D-penicillamine)-enkephalin) as specific ligand and DSLET ([D-serine2]-D-leucine-enkephalin-threonine) as non-radioactive competing ligand. It was found that 15 days treatment significantly decreased the delta-opioid receptor density,without changing the affinity, in the frontal cortex of the rat brain. That decrease was confirmed by delta-opioid receptor immunostaining. These results suggest that delta-opioid receptors could play a role in the chronic action mechanism of imipramine. PMID:12608010

  4. Brain-computer interfaces: an overview of the hardware to record neural signals from the cortex.

    Science.gov (United States)

    Stieglitz, Thomas; Rubehn, Birthe; Henle, Christian; Kisban, Sebastian; Herwik, Stanislav; Ruther, Patrick; Schuettler, Martin

    2009-01-01

    Brain-computer interfaces (BCIs) record neural signals from cortical origin with the objective to control a user interface for communication purposes, a robotic artifact or artificial limb as actuator. One of the key components of such a neuroprosthetic system is the neuro-technical interface itself, the electrode array. In this chapter, different designs and manufacturing techniques will be compared and assessed with respect to scaling and assembling limitations. The overview includes electroencephalogram (EEG) electrodes and epicortical brain-machine interfaces to record local field potentials (LFPs) from the surface of the cortex as well as intracortical needle electrodes that are intended to record single-unit activity. Two exemplary complementary technologies for micromachining of polyimide-based arrays and laser manufacturing of silicone rubber are presented and discussed with respect to spatial resolution, scaling limitations, and system properties. Advanced silicon micromachining technologies have led to highly sophisticated intracortical electrode arrays for fundamental neuroscientific applications. In this chapter, major approaches from the USA and Europe will be introduced and compared concerning complexity, modularity, and reliability. An assessment of the different technological solutions comparable to a strength weaknesses opportunities, and threats (SWOT) analysis might serve as guidance to select the adequate electrode array configuration for each control paradigm and strategy to realize robust, fast, and reliable BCIs. PMID:19660664

  5. THE EFFECT OF UNFAVOURABLE FACTORS ON PERUVATE KINASE ACTIVITY IN BRAIN CORTEX OF WHITE RATS IN POSTNATAL ONTOGENESIS

    Directory of Open Access Journals (Sweden)

    L. M. Guseynova

    2012-12-01

    Full Text Available The effect of unionizated electromagnetic radiation (EMI of different intensity and hypoxia on pyruvate kinase activity (PK; EC 2.7.1.40 in the tissues of right and left hemispheres of white rats has been studied during postnatal ontogenesis. The highest hyperactivity of PK was revealed in the left hemisphere of brain cortex both in the control animals and after the influence of extremal environmental factors. It was stated that hypoxia induces higher changes in the dynamics of changes in the dynamics of changes in the PK-activity in the tissues of brain cortex than EMI, which leads to changes in energy supply of brain. The changes in the PK-activity are supposed to be caused by involving decay products and activation of biosynthetic processes into energy supply of cells.

  6. Hippocampus-Sparing Whole-Brain Radiotherapy and Simultaneous Integrated Boost for Multiple Brain Metastases From Lung Adenocarcinoma: Early Response and Dosimetric Evaluation.

    Science.gov (United States)

    Kim, Kyung Hwan; Cho, Byoung Chul; Lee, Chang Geol; Kim, Hye Ryun; Suh, Yang Gun; Kim, Jun Won; Choi, Chihwan; Baek, Jong Geal; Cho, Jaeho

    2016-02-01

    In this study, the volume response and treatment outcome after hippocampus-sparing whole-brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) using tomotherapy were evaluated. Patients with primary lung adenocarcinoma and multiple brain metastases who had a Karnofsky performance status ≥ 70 and exhibited well-controlled extracranial disease were treated. The prescribed dose was administered in 10 to 14 fractions as 25 to 28 Gy to whole-brain parenchyma, as 40 to 48 Gy to the gross metastatic lesion, and as 30 to 42 Gy to a 5-mm margin to the metastatic lesion. Double-dose gadolinium contrast-enhanced magnetic resonance imaging at 1-mm slice thickness was performed before treatment and at 1, 4, and 7 months post-treatment. The tumor volume reduction ratio was calculated for each follow-up. Between July 2011 and September 2012, 11 patients with 70 lesions were included in this analysis. The median number of lesions per patient was 4 (range, 2-15). The median initial tumor volume was 0.235 cm(3) (range, 0.020-10.140 cm(3)). The treatment plans were evaluated regarding conformation number (CN), target coverage (TC), and homogeneity index (HI). The median follow-up duration was 14 months (range, 3-25 months) and the 1-year intracranial control rate was 67%. The tumor volume reduction was most prominent during the first month with a median reduction rate of 0.717 (range, -0.190 to 1.000). Complete remission was seen in 22 (33%) lesions, and 45 (64%) lesions showed more than 65% reduction in tumor volume. The CN, TC, and HI values were comparable to that of previous studies, and the mean hippocampal dose was 13.65 Gy. No treatment breaks or ≥ G3 acute toxicities were observed during or after treatment. The HS-WBRT with SIB in patients with multiple brain metastases was effective and feasible for volume reduction and showed excellent intracranial control. PMID:25601853

  7. Laser-induced accurate frontal cortex damage: a new tool for brain study

    Science.gov (United States)

    Flores, Gonzalo; Khotiaintsev, Sergei N.; Sanchez-Huerta, Maria L.; Ibanes, Osvaldo; Hernandez, Adan; Silva, Adriana B.; Calderon, Rafael; Ayala, Griselda; Marroquin, Javier; Svirid, Vladimir; Khotiaintsev, Yuri V.

    1999-01-01

    New laser-based technique for anatomical-functional study of the medial prefrontal cortex (MPFC) of the brain of experimental animals (rats) is presented. The technique is based on making accurate well-controlled lesions to small MPFC and subsequent observing behavioral alterations in the lesioned animals relative to control ones. Laser produces smaller and more accurate lesions in comparison to those obtained by traditional methods, such as: mechanical action, chemical means, and electrical currents. For producing the brain lesions, a 10 W CO2 CW laser is employed for reasons of its sufficiently high power, which is combined with relatively low cost-per-Watt ratio. In our experience, such power rating is sufficient for making MPFC lesions. The laser radiation is applied in a form of pulse series via hollow circular metallic waveguide made of stainless steel. The waveguide is of inner diameter 1.3 mm and 95 mm long. The anesthetized animals are placed in stereotaxic instrument. Via perforations made in the skull bone, the MPFC is exposed to the laser radiation. Several weeks later (after animal recuperation), standard behavioral tests are performed. They reveal behavioral changes, which point to a damage of some small regions of the MPFC. These results correlate with the histological data, which reveal the existence of small and accurate MPFC lesions. The present technique has good prospects for use in anatomical- functional studies of brain by areas. In addition, this technique appears to have considerable promise as a treatment method for some pathologies, e.g. the Parkinson's disease.

  8. Sevoflurane effects on cyclic adenosine monophosphate response element binding protein, phosphorylated cyclic adenosine monophosphate response element binding protein, and Livin expression in the cortex and hippocampus of a vascular cognitive impairment rat model

    Institute of Scientific and Technical Information of China (English)

    Bin Wu; Ling Dan; Xianlin Zhu

    2009-01-01

    BACKGROUND: Neuronal necrosis and apoptosis play important roles in the pathophysiology of cerebral ischemia and resulting cognitive impairment. However, inhibition of neuronal necrosis and apoptosis has been shown to attenuate cognitive impairment following cerebral ischemia.OBJECTIVE: To investigate the effects of sevoflurane on cyclic adenosine monophosphate response element binding protein (CREB), phosphorylated CREB (pCREB), and Livin expression in the cortex and hippocampus of a rat model of vascular cognitive impairment.DESIGN, TIME AND SETTING: A randomized, controlled experiment was performed in the Chongqing Key Laboratory of Neurology between June 2007 and July 2008.MATERIALS: Sevoflurane was provided by Abbott Laboratory, UK; Morris water maze was provided by Chinese Academy of Medical Sciences, China; goat anti-rat CREB, goat anti-rat pCREB and goat anti-rat Livin antibodies were provided by Biosource International, USA.METHODS: A total of 42 female, Wistar rats were randomly assigned to the following groups: sham operation, vascular cognitive impairment, and sevoflurane treatment. The vascular cognitive impairment rat model was established by permanent bilateral occlusion of both common carotid arteries, and 1.0 MAC sevoflurane was immediately administered by inhalation for 2 hours.MAIN OUTCOME MEASURES: CREB, pCREB, and Livin expression was measured in the cortex and hippocampus by Western blot and reverse transcription-polymerase chain reaction. Behavior was evaluated with Morris water maze.RESULTS: CREB, pCREB, and Livin expression in the sevoflurane treatment group was significantly greater than the vascular cognitive impairment group (P<0.01). However, expression of CREB and pCREB was significantly less in the sevoflurane treatment and vascular cognitive impairment groups, compared with the sham operation group (P<0.01). Livin expression in the sevoflurane treatment and vascular cognitive impairment groups was significantly greater than the sham

  9. Drosophila cortex and neuropile glia influence secondary axon tract growth, pathfinding, and fasciculation in the developing larval brain.

    Science.gov (United States)

    Spindler, Shana R; Ortiz, Irma; Fung, Siaumin; Takashima, Shigeo; Hartenstein, Volker

    2009-10-15

    Glial cells play important roles in the developing brain during axon fasciculation, growth cone guidance, and neuron survival. In the Drosophila brain, three main classes of glia have been identified including surface, cortex, and neuropile glia. While surface glia ensheaths the brain and is involved in the formation of the blood-brain-barrier and the control of neuroblast proliferation, the range of functions for cortex and neuropile glia is less well understood. In this study, we use the nirvana2-GAL4 driver to visualize the association of cortex and neuropile glia with axon tracts formed by different brain lineages and selectively eliminate these glial populations via induced apoptosis. The larval central brain consists of approximately 100 lineages. Each lineage forms a cohesive axon bundle, the secondary axon tract (SAT). While entering and traversing the brain neuropile, SATs interact in a characteristic way with glial cells. Some SATs are completely invested with glial processes; others show no particular association with glia, and most fall somewhere in between these extremes. Our results demonstrate that the elimination of glia results in abnormalities in SAT fasciculation and trajectory. The most prevalent phenotype is truncation or misguidance of axon tracts, or abnormal fasciculation of tracts that normally form separate pathways. Importantly, the degree of glial association with a given lineage is positively correlated with the severity of the phenotype resulting from glial ablation. Previous studies have focused on the embryonic nerve cord or adult-specific compartments to establish the role of glia. Our study provides, for the first time, an analysis of glial function in the brain during axon formation and growth in larval development. PMID:19646433

  10. Analysis of neural activity in human motor cortex -- Towards brain machine interface system

    Science.gov (United States)

    Secundo, Lavi

    The discovery of directional tuned neurons in the primary motor cortex has advanced motor research in several domains. For instance, in the area of brain machine interface (BMI), researchers have exploited the robust characteristic of tuned motor neurons to allow monkeys to learn control of various machines. In the first chapter of this work we examine whether this phenomena can be observed using the less invasive method of recording electrocorticographic signals (ECoG) from the surface of a human's brain. Our findings reveal that individual ECoG channels contain complex movement information about the neuronal population. While some ECoG channels are tuned to hand movement direction (direction specific channels), others are associated to movement but do not contain information regarding movement direction (non-direction specific channels). More specifically, directionality can vary temporally and by frequency within one channel. In addition, a handful of channels contain no significant information regarding movement at all. These findings strongly suggest that directional and non-directional regions of cortex can be identified with ECoG and provide solutions to decoding movement at the signal resolution provided by ECoG. In the second chapter we examine the influence of movement context on movement reconstruction accuracy. We recorded neuronal signals recorded from electro-corticography (ECoG) during performance of cued- and self-initiated movements. ECoG signals were used to train a reconstruction algorithm to reconstruct continuous hand movement. We found that both cued- and self-initiated movements could be reconstructed with similar accuracy from the ECoG data. However, while an algorithm trained on the cued task could reconstruct performance on a subsequent cued trial, it failed to reconstruct self-initiated arm movement. The same task-specificity was observed when the algorithm was trained with self-initiated movement data and tested on the cued task. Thus

  11. Role of the parahippocampal cortex in memory for the configuration but not the identity of objects: converging evidence from patients with selective thermal lesions and fMRI

    Directory of Open Access Journals (Sweden)

    Veronique D Bohbot

    2015-08-01

    Full Text Available The parahippocampal cortex and hippocampus are brain structures known to be involved in memory. However, the unique contribution of the parahippocampal cortex remains unclear. The current study investigates memory for object identity and memory of the configuration of objects in patients with small thermo-coagulation lesions to the hippocampus or the parahippocampal cortex. Results showed that in contrast to control participants and patients with damage to the hippocampus leaving the parahippocampal cortex intact, patients with lesions that included the right parahippocampal cortex were severely impaired on a task that required learning the spatial configuration of objects on a computer screen; these patients, however, were not impaired at learning the identity of objects. Conversely, we found that patients with lesions to the right hippocampus or left hippocampus, sparing the parahippocampal cortex, performed just as well as the control participants. Furthermore, they were not impaired on the object identity task. In the fMRI experiment, healthy young adults performed the same tasks. Consistent with the findings of the lesion study, the fMRI results showed significant activity in the right parahippocampal cortex in the memory for the spatial configuration condition, but not memory for object identity. Furthermore, the pattern of fMRI activity measured in the baseline control conditions decreased specifically in the parahippocampal cortex as a result of the experimental task, providing evidence for task specific repetition suppression. In summary, while our previous studies demonstrated that the hippocampus is critical to the construction of a cognitive map, both the lesion and fMRI studies have shown an involvement of the right parahippocampal cortex for learning spatial configurations of objects but not object identity, and that this takes place independent of the hippocampus.

  12. Neural patterns in the hippocampus

    OpenAIRE

    Alme, Charlotte Boermeester

    2015-01-01

    Summary: Memories make us who we are. Personal memories are tightly coupled to space – we often remember what happened where and when. Accordingly, by investigating how spatial memories are represented in the rodent brain we can begin to increase our knowledge about higher cognitive brain functions, specifically and in general. The hippocampus is crucial for storing and retrieving memories for experiences as well as locations. Place specific neurons in the hippocampus are invo...

  13. A 'complex' of brain metabolites distinguish altered chemistry in the cingulate cortex of episodic migraine patients.

    Science.gov (United States)

    Becerra, L; Veggeberg, R; Prescot, A; Jensen, J E; Renshaw, P; Scrivani, S; Spierings, E L H; Burstein, R; Borsook, D

    2016-01-01

    Despite the prevalence of migraine, the pathophysiology of the disease remains unclear. Current understanding of migraine has alluded to the possibility of a hyperexcitable brain. The aim of the current study is to investigate human brain metabolite differences in the anterior cingulate cortex (ACC) during the interictal phase in migraine patients. We hypothesized that there may be differences in levels of excitatory neurotransmitters and/or their derivatives in the migraine cohort in support of the theory of hyperexcitability in migraine. 2D J-resolved proton magnetic resonance spectroscopy ((1)H-MRS) data were acquired on a 3 Tesla (3 T) MRI from a voxel placed over the ACC of 32 migraine patients (MP; 23 females, 9 males, age 33 ± 9.6 years) and 33 healthy controls (HC; 25 females, 8 males, age 32 ± 9.6 years). Amplitude correlation matrices were constructed for each subject to evaluate metabolite discriminability. ProFit-estimated metabolite peak areas were normalized to a water reference signal to assess subject differences. The initial analysis of variance (ANOVA) was performed to test for group differences for all metabolites/creatine (Cre) ratios between healthy controls and migraineurs but showed no statistically significant differences. In addition, we used a multivariate approach to distinguish migraineurs from healthy subjects based on the metabolite/Cre ratio. A quadratic discriminant analysis (QDA) model was used to identify 3 metabolite ratios sufficient to minimize minimum classification error (MCE). The 3 selected metabolite ratios were aspartate (Asp)/Cre, N-acetyl aspartate (NAA)/Cre, and glutamine (Gln)/Cre. These findings are in support of a 'complex' of metabolite alterations, which may underlie changes in neuronal chemistry in the migraine brain. Furthermore, the parallel changes in the three-metabolite 'complex' may confer more subtle but biological processes that are ongoing. The data also support the current theory that the

  14. Changes in the biogenic amine content of the prefrontal cortex, amygdala, dorsal hippocampus, and nucleus accumbens of rats submitted to single and repeated sessions of the elevated plus-maze test

    Directory of Open Access Journals (Sweden)

    Carvalho M.C.

    2005-01-01

    Full Text Available It has been demonstrated that exposure to a variety of stressful experiences enhances fearful reactions when behavior is tested in current animal models of anxiety. Until now, no study has examined the neurochemical changes during the test and retest sessions of rats submitted to the elevated plus maze (EPM. The present study uses a new approach (HPLC by looking at the changes in dopamine and serotonin levels in the prefrontal cortex, amygdala, dorsal hippocampus, and nucleus accumbens in animals upon single or double exposure to the EPM (one-trial tolerance. The study involved two experiments: i saline or midazolam (0.5 mg/kg before the first trial, and ii saline or midazolam before the second trial. For the biochemical analysis a control group injected with saline and not tested in the EPM was included. Stressful stimuli in the EPM were able to elicit one-trial tolerance to midazolam on re-exposure (61.01%. Significant decreases in serotonin contents occurred in the prefrontal cortex (38.74%, amygdala (78.96%, dorsal hippocampus (70.33%, and nucleus accumbens (73.58% of the animals tested in the EPM (P < 0.05 in all cases in relation to controls not exposed to the EPM. A significant decrease in dopamine content was also observed in the amygdala (54.74%, P < 0.05. These changes were maintained across trials. There was no change in the turnover rates of these monoamines. We suggest that exposure to the EPM causes reduced monoaminergic neurotransmission activity in limbic structures, which appears to underlie the "one-trial tolerance" phenomenon.

  15. Activation of AMPA Receptors Mediates the Antidepressant Action of Deep Brain Stimulation of the Infralimbic Prefrontal Cortex.

    Science.gov (United States)

    Jiménez-Sánchez, Laura; Castañé, Anna; Pérez-Caballero, Laura; Grifoll-Escoda, Marc; López-Gil, Xavier; Campa, Leticia; Galofré, Mireia; Berrocoso, Esther; Adell, Albert

    2016-06-01

    Although deep brain stimulation (DBS) has been used with success in treatment-resistant depression, little is known about its mechanism of action. We examined the antidepressant-like activity of short (1 h) DBS applied to the infralimbic prefrontal cortex in the forced swim test (FST) and the novelty-suppressed feeding test (NSFT). We also used in vivo microdialysis to evaluate the release of glutamate, γ-aminobutyric acid, serotonin, dopamine, and noradrenaline in the prefrontal cortex and c-Fos immunohistochemistry to determine the brain regions activated by DBS. One hour of DBS of the infralimbic prefrontal cortex has antidepressant-like effects in FST and NSFT, and increases prefrontal efflux of glutamate, which would activate AMPA receptors (AMPARs). This effect is specific of the infralimbic area since it is not observed after DBS of the prelimbic subregion. The activation of prefrontal AMPARs would result in a stimulation of prefrontal output to the brainstem, thus increasing serotonin, dopamine, and noradrenaline in the prefrontal cortex. Further, the activation of prefrontal AMPARs is necessary and sufficient condition for the antidepressant response of 1 h DBS. PMID:26088969

  16. Astroglial Control of the Antidepressant-Like Effects of Prefrontal Cortex Deep Brain Stimulation

    Directory of Open Access Journals (Sweden)

    A. Etiévant

    2015-08-01

    Full Text Available Although deep brain stimulation (DBS shows promising efficacy as a therapy for intractable depression, the neurobiological bases underlying its therapeutic action remain largely unknown. The present study was aimed at characterizing the effects of infralimbic prefrontal cortex (IL-PFC DBS on several pre-clinical markers of the antidepressant-like response and at investigating putative non-neuronal mechanism underlying DBS action. We found that DBS induced an antidepressant-like response that was prevented by IL-PFC neuronal lesion and by adenosine A1 receptor antagonists including caffeine. Moreover, high frequency DBS induced a rapid increase of hippocampal mitosis and reversed the effects of stress on hippocampal synaptic metaplasticity. In addition, DBS increased spontaneous IL-PFC low-frequency oscillations and both raphe 5-HT firing activity and synaptogenesis. Unambiguously, a local glial lesion counteracted all these neurobiological effects of DBS. Further in vivo electrophysiological results revealed that this astrocytic modulation of DBS involved adenosine A1 receptors and K+ buffering system. Finally, a glial lesion within the site of stimulation failed to counteract the beneficial effects of low frequency (30 Hz DBS. It is proposed that an unaltered neuronal–glial system constitutes a major prerequisite to optimize antidepressant DBS efficacy. It is also suggested that decreasing frequency could heighten antidepressant response of partial responders.

  17. Brain cortex muscarinic transmission is impaired in young adult transgenic Appswe/Ps1de9 female mice

    Czech Academy of Sciences Publication Activity Database

    Machová, Eva; Jakubík, Jan; Michal, Pavel; Oksman, M.; Iivonen, H.; Tanila, H.; Doležal, Vladimír

    2007-01-01

    Roč. 4, Suppl.1 (2007), s. 281-281. ISSN 1660-2854. [International conference Alzheimer´s diseases/Parkinson´s diseases /8./. 14.03.2007-18.03.2007, Salzburg] R&D Projects: GA AV ČR(CZ) IAA5011206; GA MŠk(CZ) LC554 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpr1 * brain cortex * muscarinic transmission * Alzheimer´s disease Subject RIV: FH - Neurology

  18. 反复力竭游泳运动对小鼠前脑皮层和海马的影响%Effects of repeated exhaustive swimming exercise on the prefrontal cortex and hippocampus in mice

    Institute of Scientific and Technical Information of China (English)

    蔡成法; 李亚

    2014-01-01

    Acute stress and chronic stress can damage the brain prefrontal cortex( PFC)and hippo-campus( HP)function,then reduce learning and memory abilities of animal or human. Model of exhaustive exercise mice was set up by the way of repeatedly( four weeks)exhausted swimming. Membrane fluidity and free calcium concentrations([ Ca2+]i)of prefrontal cortical and hippocam-pal synaptosomes in mice were detected. The results show that,compared with control group mice, the membrane fluidity of synaptosomes in PFC and HP of exhaustive exercise group mice were signif-icantly decreased at 0 h and 12 h,after repeatedly exhausted exercise. The synaptosomal[ Ca2+]i in PFC and HP were significantly increased at 0 h,12 h and 24 h in exhaustive exercise group mice. The[ Ca2+]i in PFC and HP at 1 week were remarkably reduced than the exhaustive exercise 0 h group mice,respectively. The generation and recovery of exercise-induced central fatigue in mice after exhausted exercise which may be nearly related to the changes of membrane fluidity and [ Ca2+]i of synaptosomes.%急性应激和长期慢性应激均可损伤脑内的海马和前额叶,继而降低动物或人的学习记忆能力。采用4周反复力竭游泳运动方式建立力竭运动小鼠模型。在反复性力竭游泳运动后即刻(0 h)、12 h、24 h和1周,检测小鼠前脑皮层和海马突触体膜流动性变化,以及突触体内游离Ca2+浓度。结果表明,反复性力竭游泳运动后,与对照组小鼠比较,力竭运动组小鼠前脑皮层和海马突触体膜流动性在0 h、12 h显著降低,24 h有所恢复,1周后基本恢复到正常水平。力竭运动组小鼠前脑皮层和海马突触体内游离Ca2+浓度在0 h、12 h和24 h后显著增加,1周后前脑皮层和海马突触体内游离Ca2+浓度明显回落。力竭游泳运动所致小鼠运动性中枢疲劳的产生和恢复可能与突触体膜流动性和突触体内游离Ca2+浓度的变化密切相关。

  19. Cortex-, Hippocampus-, Thalamus-, Hypothalamus-, Lateral Septal Nucleus- and Striatum-specific In Utero Electroporation in the C57BL/6 Mouse.

    Science.gov (United States)

    Baumgart, Jan; Baumgart, Nadine

    2016-01-01

    In utero electroporation is a widely used technique for fast and efficient spatiotemporal manipulation of various genes in the rodent central nervous system. Overexpression of desired genes is just as possible as shRNA mediated loss-of-function studies. Therefore it offers a wide range of applications. The feasibility to target particular cells in a distinct area further increases the range of potential applications of this very useful method. For efficiently targeting specific regions knowledge about the subtleties, such as the embryonic stage, the voltage to apply and most importantly the position of the electrodes, is indispensable. Here, we provide a detailed protocol that allows for specific and efficient in utero electroporation of several regions of the C57BL/6 mouse central nervous system. In particular it is shown how to transfect regions the develop into the retrosplenial cortex, the motor cortex, the somatosensory cortex, the piriform cortex, the cornu ammonis 1-3, the dentate gyrus, the striatum, the lateral septal nucleus, the thalamus and the hypothalamus. For this information about the appropriate embryonic stage, the appropriate voltage for the corresponding embryonic stage is provided. Most importantly an angle-map, which indicates the appropriate position of the positive pole, is depicted. This standardized protocol helps to facilitate efficient in utero electroporation, which might also lead to a reduced number of animals. PMID:26862715

  20. Effects of pentoxifylline, 7-nitroindazole, and imipramine on tumor necrosis factor-α and indoleamine 2,3-dioxygenase enzyme activity in the hippocampus and frontal cortex of chronic mild-stress-exposed rats

    Directory of Open Access Journals (Sweden)

    Mohamed BMSA

    2013-05-01

    Full Text Available Bassim MSA Mohamed,1,6 Sawsan Aboul-Fotouh,2,5 Eman A Ibrahim,3 Hanan Shehata,4 Amal A Mansour,4 Nemat AZ Yassin,1 Wafaa El-Eraky,1 Ahmed M Abdel-Tawab2,5 1Department of Pharmacology, National Research Centre, Cairo, Egypt; 2Department of Pharmacology, 3Department of Pathology, 4Department of Medical Biochemistry and Molecular Biology, 5Clinical Pharmacology Unit, Ain Shams University, Cairo, Egypt; 6Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada Objectives: This study aimed to investigate the role of tumor necrosis factor (TNF-α and the neuronal nitric oxide synthase enzyme in dysregulation of indoleamine 2,3-dioxygenase (IDO enzyme, and hence serotonin availability in chronic mild stress (CMS, an animal model of depression. Methods: Rats were divided into five groups: two control and CMS-exposed for 6 weeks, and another three groups exposed to CMS and administered pentoxifylline 50 mg/kg/day intraperitoneally, 7-nitroindazole 40 mg/kg/day subcutaneously, or imipramine 20 mg/kg/day intraperitoneally for the previous 3 CMS weeks. Rats were assessed for neurochemical and immunohistochemical abnormalities. Results: Pentoxifylline-, 7-nitroindazole-, and imipramine-treated rats showed amelioration of CMS-induced behavioral deficits that was accompanied by significant reduction in kynurenine/serotonin molar ratio and nitrates/nitrites in frontal cortex and hippocampus. In the pentoxifylline and 7-nitroindazole groups, serum TNF-α was reduced relative to the CMS group (18.54 ± 0.85 and 19.16 ± 1.54 vs 26.20 ± 1.83 pg/mL, respectively; P < 0.05. Exposure to CMS increased TNF-α and IDO immunohistochemical staining scores in both hippocampus and midbrain raphe nuclei. 7-Nitroindazole and pentoxifylline significantly (P < 0.05 reduced TNF-α immunostaining in hippocampus and raphe nuclei, with significant (P < 0.01 reduction of IDO immunostaining in raphe nuclei. Likewise, imipramine reduced TNF

  1. Three-dimensional visualization of functional brain tissue and functional magnetic resonance imaging-integrated neuronavigation in the resection of brain tumor adjacent to motor cortex

    International Nuclear Information System (INIS)

    Objective: To assess the value of three -dimensional visualization of functional brain tissue and the functional magnetic resonance imaging (fMRI)-integrated neuronavigation in the resection of brain tumor adjacent to motor cortex. Method: Sixty patients with tumor located in the central sulcus were enrolled. Thirty patients were randomly assigned to function group and 30 to control group. Patients in function group underwent fMRI to localize the functional brain tissues. Then the function information was transferred to the neurosurgical navigator. The patients in control group underwent surgery with navigation without function information. The therapeutic effect, excision rate. improvement of motor function, and survival quality during follow-up were analyzed. Result: All patients in function group were accomplished visualization of functional brain tissues and fMRI-integrated neuronavigation. The locations of tumors, central sulcus and motor cortex were marked during the operation. The fMRI -integrated information played a great role in both pre- and post-operation. Pre-operation: designing the location of the skin flap and window bone, determining the relationship between the tumor and motor cortex, and designing the pathway for the resection. Post- operation: real-time navigation of relationship between the tumor and motor cortex, assisting to localize the motor cortex using interoperation ultra-sound for correcting the displacement by the CSF outflow and collapsing tumor. The patients in the function group had better results than the patients in the control group in therapeutic effect (u=2.646, P=0.008), excision rate (χ=7.200, P<0.01), improvement of motor function (u=2.231, P=0.026), and survival quality (KPS uc= 2.664, P=0.008; Zubrod -ECOG -WHO uc=2.135, P=0.033). Conclusions: Using preoperative three -dimensional visualization of cerebral function tissue and the fMRI-integrated neuronavigation technology, combining intraoperative accurate positioning

  2. The neuron-astrocyte-microglia triad in normal brain ageing and in a model of neuroinflammation in the rat hippocampus.

    Directory of Open Access Journals (Sweden)

    Francesca Cerbai

    Full Text Available Ageing is accompanied by a decline in cognitive functions; along with a variety of neurobiological changes. The association between inflammation and ageing is based on complex molecular and cellular changes that we are only just beginning to understand. The hippocampus is one of the structures more closely related to electrophysiological, structural and morphological changes during ageing. In the present study we examined the effect of normal ageing and LPS-induced inflammation on astroglia-neuron interaction in the rat hippocampus of adult, normal aged and LPS-treated adult rats. Astrocytes were smaller, with thicker and shorter branches and less numerous in CA1 Str. radiatum of aged rats in comparison to adult and LPS-treated rats. Astrocyte branches infiltrated apoptotic neurons of aged and LPS-treated rats. Cellular debris, which were more numerous in CA1 of aged and LPS-treated rats, could be found apposed to astrocytes processes and were phagocytated by reactive microglia. Reactive microglia were present in the CA1 Str. Radiatum, often in association with apoptotic cells. Significant differences were found in the fraction of reactive microglia which was 40% of total in adult, 33% in aged and 50% in LPS-treated rats. Fractalkine (CX3CL1 increased significantly in hippocampus homogenates of aged and LPS-treated rats. The number of CA1 neurons decreased in aged rats. In the hippocampus of aged and LPS-treated rats astrocytes and microglia may help clearing apoptotic cellular debris possibly through CX3CL1 signalling. Our results indicate that astrocytes and microglia in the hippocampus of aged and LPS-infused rats possibly participate in the clearance of cellular debris associated with programmed cell death. The actions of astrocytes may represent either protective mechanisms to control inflammatory processes and the spread of further cellular damage to neighboring tissue, or they may contribute to neuronal damage in pathological conditions.

  3. Cholesterol metabolism changes under long-term dietary restrictions while the cholesterol homeostasis remains unaffected in the cortex and hippocampus of aging rats

    OpenAIRE

    Smiljanic, Kosara; Vanmierlo, Tim; Djordjevic, Aleksandra Mladenovic; Perovic, Milka; Ivkovic, Sanja; Luetjohann, Dieter; Kanazir, Selma

    2014-01-01

    Maintaining cholesterol homeostasis in the brain is vital for its proper functioning. While it is well documented that dietary restriction modulates the metabolism of cholesterol peripherally, little is known as to how it can affect cholesterol metabolism in the brain. The present study was designed to elucidate the impact of long-term dietary restriction on brain cholesterol metabolism. Three-month-old male Wistar rats were exposed to long-term dietary restriction until 12 and 24 months of a...

  4. Indicaxanthin from Opuntia ficus-indica Crosses the Blood-Brain Barrier and Modulates Neuronal Bioelectric Activity in Rat Hippocampus at Dietary-Consistent Amounts.

    Science.gov (United States)

    Allegra, Mario; Carletti, Fabio; Gambino, Giuditta; Tutone, Marco; Attanzio, Alessandro; Tesoriere, Luisa; Ferraro, Giuseppe; Sardo, Pierangelo; Almerico, Anna Maria; Livrea, Maria Antonia

    2015-08-26

    Indicaxanthin is a bioactive and bioavailable betalain pigment from the Opuntia ficus-indica fruits. In this in vivo study, kinetic measurements showed that indicaxanthin is revealed in the rat brain within 1 h from oral administration of 2 μmol/kg, an amount compatible with a dietary consumption of cactus pear fruits in humans. A peak (20 ± 2.4 ng of indicaxanthin per whole brain) was measured after 2.5 h; thereafter the molecule disappeared with first order kinetics within 4 h. The potential of indicaxanthin to affect neural activities was in vivo investigated by a microiontophoretic approach. Indicaxanthin, administered in a range between 0.085 ng and 0.34 ng per neuron, dose-dependently modulated the rate of discharge of spontaneously active neurons of the hippocampus, with reduction of the discharge and related changes of latency and duration of the effect. Indicaxanthin (0.34 ng/neuron) showed inhibitory effects on glutamate-induced excitation, indicating activity at the level of glutamatergic synapses. A molecular target of indicaxanthin is suggested by in silico molecular modeling of indicaxanthin with N-methyl-D-aspartate receptor (NMDAR), the most represented of the glutamate receptor family in hippocampus. Therefore, at nutritionally compatible amounts indicaxanthin (i) crosses the rat BBB and accumulates in brain; (ii) can affect the bioelectric activity of hippocampal neurons locally treated with amounts comparable with those measured in the brain; and (iii) modulates glutamate-induced neuronal excitation. The potential of dietary indicaxanthin as a natural neuromodulatory agent deserves further mechanistic and neurophysiologic investigation. PMID:26227670

  5. Distinct proteins in cortex of rats with closed traumatic brain injury detected by a WCX-2 protein chip

    Institute of Scientific and Technical Information of China (English)

    Li Zhan; Lin Liang; Qingming Shu; Shuwang Yang; Yongliang Zhang

    2007-01-01

    BACKGROUND: Mechanical injury can cause the changes of polygene expression spectrum in rat cerebral cortical nerve cells, and then result in the changes of intracellular protein expression. At present, dielectrophoresis is combined with mass spectrum technique to detect the expression of different proteins in rat cortex after brain injury, but the protein chip technique requires further investigation. OBJECTIVE: To analyze the differences of protein expression spectrum in rat cerebral cortex before and after closed traumatic brain injury using WCX-2 protein chip technique. DESIGN: A randomized controlled animal experiment.SETTING: Training Division of the Medical College of Chinese People's Armed Police Force. MATERIALS: Seventy-two male SD rats of clean degree, 350 - 450 g, were provided by the Experimental Animal Center, Academy of Military Medical Sciences of Chinese PLA. Urea, trifluoroacetic acid, CHAPS and Tris (Sigma, USA); WCX-2 (Ciphergen, USA). Ultra-high speed hypothermia centrifuger (Bechman, USA); Rotary tissue microtome (Keuca, Germany); Biochip processor and PBS II-C protein chip reader (Ciphergen, USA).METHODS: The experiments were carried out in the Institute of Molecular Pathology, Central Laboratory, and Department of Pathology, Medical College of Chinese People's Armed Police Force from June 2005 to March 2006.①Grouping and treatment: The experiments were completed in molecular pathological institute, central laboratory and pathological department.①The rats were randomly divided into control group (n =12) and brain injury group (n =60). Marmarou's weight-dropping models were duplicated at different time points in the brain injury group. In the control group, the rats were only treated by incising the skin of head top, without fixing the stainless steel hitting backup plate at the vault of skull, and obtain brain cortex for pathological and protein chip research, and they were killed after 24 hours. The rats in the brain injury group were

  6. Gene expression in the rat brain: High similarity but unique differences between frontomedial-, temporal- and occipital cortex

    Directory of Open Access Journals (Sweden)

    Ersland Kari M

    2011-01-01

    Full Text Available Abstract Background The six-layered neocortex of the mammalian brain may appear largely homologous, but is in reality a modular structure of anatomically and functionally distinct areas. However, global gene expression seems to be almost identical across the cerebral cortex and only a few genes have so far been reported to show regional enrichment in specific cortical areas. Results In the present study on adult rat brain, we have corroborated the strikingly similar gene expression among cortical areas. However, differential expression analysis has allowed for the identification of 30, 24 and 11 genes enriched in frontomedial -, temporal- or occipital cortex, respectively. A large proportion of these 65 genes appear to be involved in signal transduction, including the ion channel Fxyd6, the neuropeptide Grp and the nuclear receptor Rorb. We also find that the majority of these genes display increased expression levels around birth and show distinct preferences for certain cortical layers and cell types in rodents. Conclusions Since specific patterns of expression often are linked to equally specialised biological functions, we propose that these cortex sub-region enriched genes are important for proper functioning of the cortical regions in question.

  7. Dynamic changes of glial fibrillary acidic protein and nestin in the hippocampus of adult rat brain following ischemic vascular dementia

    Institute of Scientific and Technical Information of China (English)

    Tianping Yu; Peng Zhang; Xiong Zhang; Linhui Wang; Mingyuan Tian; Yu Li

    2011-01-01

    Vascular dementia produced by permanent ligation of bilateral common carotid arteries involves progressive deterioration of intellectual and cognitive function in rats, which are closely associated with the hippocampus. This study used immunohistochemical analysis to detect the expression of glial fibrillary acidic protein and nestin in the hippocampus in a vascular dementia model. The results revealed that both glial fibrillary acidic protein and nestin expression were increased 1 day after permanent ligation of the bilateral common carotid arteries, compared with a sham-operated group. The expression of glial fibrillary acidic protein peaked at 7 days post-surgery. The expression of nestin was a little weaker than that of glial fibrillary acidic protein, and peaked at 14 days (P<0.01). The expression of both proteins slightly decreased at 21 and 28 days, accompanied by recovery of cerebral blood flow. In conclusion, this study demonstrated that glial fibrillary acidic protein and nestin exhibited dynamic expression in the rat hippocampus after permanent ligation of bilateral common carotid arteries. This finding suggests that dynamic alterations in protein expression play an important role in the pathogenesis of vascular dementia.

  8. Inhibition of injury-induced cell proliferation in the dentate gyrus of the hippocampus impairs spontaneous cognitive recovery after traumatic brain injury.

    Science.gov (United States)

    Sun, Dong; Daniels, Teresa E; Rolfe, Andrew; Waters, Michael; Hamm, Robert

    2015-04-01

    Neurogenesis persists throughout life in the neurogenic regions of the mature mammalian brain, and this response is enhanced after traumatic brain injury (TBI). In the hippocampus, adult neurogenesis plays an important role in hippocampal-dependent learning and memory functions and is thought to contribute to the spontaneous cognitive recovery observed after TBI. Utilizing an antimitotic agent, arabinofuranosyl cytidine (Ara-C), the current study investigated the direct association of injury-induced hippocampal neurogenesis with cognitive recovery. In this study, adult rats received a moderate lateral fluid percussion injury followed by a 7-day intraventricular infusion of 2% Ara-C or vehicle. To examine the effect of Ara-C on cell proliferation, animals received intraperitoneal injections of 5-bromo-2-deoxyuridine (BrdU), to label dividing cells, and were sacrificed at 7 days after injury. Brain sections were immunostained for BrdU or doublecortin (DCX), and the total number of BrdU(+) or DCX(+) cells in the hippocampus was quantified. To examine the outcome of inhibiting the injury-induced cell proliferative response on cognitive recovery, animals were assessed on Morris water maze (MWM) tasks at 21-25 or 56-60 days postinjury. We found that a 7-day infusion of Ara-C significantly reduced the total number of BrdU(+) and DCX(+) cells in the dentate gyrus (DG) in both hemispheres. Moreover, inhibition of the injury-induced cell proliferative response in the DG completely abolished the innate cognitive recovery on MWM performance at 56-60 days postinjury. These results support the causal relationship of injury-induced hippocampal neurogenesis on cognitive functional recovery and suggest the importance of this endogenous repair mechanism on restoration of hippocampal function. PMID:25242459

  9. Expressions of Neuregulin 1β and ErbB4 in Prefrontal Cortex and Hippocampus of a Rat Schizophrenia Model Induced by Chronic MK-801 Administration

    OpenAIRE

    Yu Feng; Xiao-Dong Wang; Chun-Mei Guo; Yang Yang; Ji-Tao Li; Yun-Ai Su; Tian-Mei Si

    2010-01-01

    Recent human genetic studies and postmortem brain examinations of schizophrenia patients strongly indicate that dysregulation of NRG1 and ErbB4 may be important pathogenic factors of schizophrenia. However, this hypothesis has not been validated and fully investigated in animal models of schizophrenia. In this study we quantitatively examined NRG1 and ErbB4 protein expressions by immunohistochemistry and Western blot in the brain of a rat schizophrenia model induced by chronic administration ...

  10. Insulin Like Growth Factor 2 Expression in the Rat Brain Both in Basal Condition and following Learning Predominantly Derives from the Maternal Allele

    OpenAIRE

    Xiaojing Ye; Amy Kohtz; Gabriella Pollonini; Andrea Riccio; Alberini, Cristina M

    2015-01-01

    Insulin like growth factor 2 (Igf2) is known as a maternally imprinted gene involved in growth and development. Recently, Igf2 was found to also be regulated and required in the adult rat hippocampus for long-term memory formation, raising the question of its allelic regulation in adult brain regions following experience and in cognitive processes. We show that, in adult rats, Igf2 is abundantly expressed in brain regions involved in cognitive functions, like hippocampus and prefrontal cortex...

  11. Optogenetic fMRI in the mouse hippocampus: Hemodynamic response to brief glutamatergic stimuli.

    Science.gov (United States)

    Lebhardt, Philipp; Hohenberg, Christian Clemm von; Weber-Fahr, Wolfgang; Kelsch, Wolfgang; Sartorius, Alexander

    2016-03-01

    The combination of optogenetics with functional magnetic resonance imaging is a promising tool to study the causal relationship between specific neuronal populations and global brain activity. We employed this technique to study the brain response to recruitment of glutamatergic neurons in the mouse hippocampus. The light-sensitive protein channelrhodopsin-2 was expressed in α-CamKII-positive glutamatergic neurons in the left hippocampus (N = 10). Functional magnetic resonance imaging was performed during local laser stimulation, with stimulus duration of 1 second. The hemodynamic response to these stimuli was analyzed on a whole-brain level. In a secondary analysis, we examined the impact of the stimulation locus on the dorso-ventral axis within the hippocampal formation. The hemodynamic response in the mouse hippocampus had an earlier peak and a shorter duration compared to those observed in humans. Photostimulation was associated with significantly increased blood oxygen level-dependent signal in group statistics: bilaterally in the hippocampus, frontal lobe and septum, ipsilaterally in the nucleus accumbens and contralaterally in the striatum. More dorsal position of the laser fiber was associated with a stronger activation in projection regions (insular cortex and striatum). The characterization of brain-region-specific hemodynamic response functions may enable more precise interpretation of future functional magnetic resonance imaging experiments. PMID:26661158

  12. How Two Brains Make One Synchronized Mind in the Inferior Frontal Cortex: fNIRS-Based Hyperscanning During Cooperative Singing.

    Science.gov (United States)

    Osaka, Naoyuki; Minamoto, Takehiro; Yaoi, Ken; Azuma, Miyuki; Shimada, Yohko Minamoto; Osaka, Mariko

    2015-01-01

    One form of communication that is common in all cultures is people singing together. Singing together reflects an index of cognitive synchronization and cooperation of human brains. Little is known about the neural synchronization mechanism, however. Here, we examined how two brains make one synchronized behavior using cooperated singing/humming between two people and hyperscanning, a new brain scanning technique. Hyperscanning allowed us to observe dynamic cooperation between interacting participants. We used functional near-infrared spectroscopy (fNIRS) to simultaneously record the brain activity of two people while they cooperatively sang or hummed a song in face-to-face (FtF) or face-to-wall (FtW) conditions. By calculating the inter-brain wavelet transform coherence between two interacting brains, we found a significant increase in the neural synchronization of the left inferior frontal cortex (IFC) for cooperative singing or humming regardless of FtF or FtW compared with singing or humming alone. On the other hand, the right IFC showed an increase in neural synchronization for humming only, possibly due to more dependence on musical processing. PMID:26635703

  13. Overall biological activity of sensorimotor and visual brain cortex of rabbits with early neurological disorders induced by high doses of γ-radiation

    International Nuclear Information System (INIS)

    The overall bioelectrical activity of the sensorimotor and visual brain cortex of rabbits was estimated during early neurological impairment caused by 120 Gy gamma irradiation. The characteristic changes were revealed in the amplitude, form, energy spectrum and spatial biopotential synchronization. The changes in the bioelectrical activity of the brain were associated with the clinically displayed stages of the neurological process development

  14. Cocaine-induced reduction of brain neuropeptide Y synthesis dependent on medial prefrontal cortex.

    OpenAIRE

    Wahlestedt, C; Karoum, F; Jaskiw, G; Wyatt, R. J.; Larhammar, D; Ekman, R.; Reis, D J

    1991-01-01

    Repeated administration of cocaine elicits substantial, long-lasting, but reversible reductions in neuropeptide Y (NPY) and NPY mRNA in the rat cerebral cortex and nucleus accumbens. The NPY reduction appears to be mediated through a decrease in NPY biosynthesis, occurring transneuronally, perhaps in response to changes in synaptic dopamine associated with mesolimbic and mesocortical dopamine neurons. The medial prefrontal cortex appears necessary for maintenance of cocaine's action on this n...

  15. Roles of the Insular Cortex in the Modulation of Pain: Insights from Brain Lesions

    OpenAIRE

    Starr, Christopher J.; Sawaki, Lumy; Wittenberg, George F.; Burdette, Jonathan H.; Oshiro, Yoshitetsu; Quevedo, Alexandre S.; Coghill, Robert C.

    2009-01-01

    Subjective sensory experiences are constructed by the integration of afferent sensory information with information about the uniquely personal internal cognitive state. The insular cortex is anatomically positioned to serve as one potential interface between afferent processing mechanisms and more cognitively-oriented modulatory systems. However, the role of the insular cortex in such modulatory processes remain poorly understood. Two individuals with extensive lesions to the insula were exam...

  16. A Heuristic Image Search Algorithm for Active Shape Model Segmentation of the Caudate Nucleus and Hippocampus in Brain MR Images of Children with FASD

    Directory of Open Access Journals (Sweden)

    A A Eicher

    2012-09-01

    Full Text Available Magnetic Resonance Imaging provides a non-invasive means to study the neural correlates of Fetal Alcohol Spectrum Disorder (FASD - the most common form of preventable mental retardation worldwide. One approach aims to detect brain abnormalities through an assessment of volume and shape of two sub-cortical structures, the caudate nucleus and hippocampus. We present a method for automatically segmenting these structures from high-resolution MR images captured as part of an ongoing study into the neural correlates of FASD. Our method incorporates an Active Shape Model, which is used to learn shape variation from manually segmented training data. A modified discrete Geometrically Deformable Model is used to generate point correspondence between training models. An ASM is then created from the landmark points. Experiments were conducted on the image search phase of ASM segmentation, in order to find the technique best suited to segmentation of the hippocampus and caudate nucleus. Various popular image search techniques were tested, including an edge detection method and a method based on grey profile Mahalanobis distance measurement. A novel heuristic image search method was also developed and tested. This heuristic method improves image segmentation by taking advantage of characteristics specific to the target data, such as a relatively homogeneous tissue colour in target structures. Results show that ASMs that use the heuristic image search technique produce the most accurate segmentations. An ASM constructed using this technique will enable researchers to quickly, reliably, and automatically segment test data for use in the FASD study.

  17. 慢性应激损害大鼠学习记忆且抑制海马及额叶FGF2蛋白表达%Chronic Stress Impairs Learning and Memory and Down-Regulates Expression of FGF2 in Hippocampus and Prefrontal Cortex of Rats

    Institute of Scientific and Technical Information of China (English)

    汤明明; 侯公林

    2011-01-01

    It is well documented that chronic stress can produce cognitive impairment, and that the hippocampus and prefrontal cortex play an important role in the process of learning and memory. The present study investigated the effects of chronic stress through examination of the modulation tone of FGF2 protein in hippocampus and prefrontal cortex. The fibroblast growth factor-2 (FGF2), a mitogen that is involved in brain development and regeneration, has been shown to facilitate neurogenesis and synaptic plasticity, as well as be involved in the mechanism of neurodegenerative disorders.In the experiment, sixteen male Sprague-Dawley rats were randomly assigned into control group and stress group and the chronic unpredictable mild stress (CUMS) model was performed to construct chronic stress model of rats. The stress group received 35 days CUMS which were consisted of food deprivation, water deprivation, clip tail, feet shock, forced swimming in cold water, wet bedding, and disturbed light-dark cycle. Following the last stressor, stressed and non-stressed rats began training in the Morris Water Maze (MWM) and Y Maze to test the change of the ability of learning and memory about space clue fixed position and conditioned escape response. The changes of protein level of FGF2 in hippocampus and prefrontal cortex were observed by Westernblot analysis and Immunohistochemistry analysis.Compared with the rats of control group, the rats of stress group have obvious impairments in learning and memory. In the MWM, the rats exposed to stress had longer latencies to reach the hidden platform during training phase (p<0.01), and passed fewer times through the platform location (p<0.01). In the Y maze test, stressed rats needed more learning performances (p<0.05) and had less precision rate (p<0.05). The protein level of FGF2 was downregulated in hippocampus of rats (p<0.001), especially the dentate gyms, CA1 neurons and CA3 pyramidal neurons. The same changes also happened in prefrontal

  18. Voluntary exercise prior to traumatic brain injury alters miRNA expression in the injured mouse cerebral cortex

    OpenAIRE

    Miao, W.; T.H. Bao; Han, J. H.; Yin, M.; Yan, Y.; Wang, W. W.; Zhu, Y. H.

    2015-01-01

    MicroRNAs (miRNAs) may be important mediators of the profound molecular and cellular changes that occur after traumatic brain injury (TBI). However, the changes and possible roles of miRNAs induced by voluntary exercise prior to TBI are still not known. In this report, the microarray method was used to demonstrate alterations in miRNA expression levels in the cerebral cortex of TBI mice that were pretrained on a running wheel (RW). Voluntary RW exercise prior to TBI: i) significantly decrease...

  19. Rosemary extract improves cognitive deficits in a rats model of repetitive mild traumatic brain injury associated with reduction of astrocytosis and neuronal degeneration in hippocampus.

    Science.gov (United States)

    Song, Hai; Xu, Lincheng; Zhang, Rongping; Cao, Zhenzhen; Zhang, Huan; Yang, Li; Guo, Zeyun; Qu, Yongqiang; Yu, Jianyun

    2016-05-27

    In this study, we investigated whether Rosemary extract (RE) improved cognitive deficits in repetitive mild Traumatic brain injury (rmTBI) rats and its potential mechanisms. The present results showed that rmTBI caused cognitive deficits, such as increased latency to find platform and decreased time spent in target quadrant in Morris water maze (MWM). These behavioral alterations were accompanying with the increased neuronal degeneration and glial fibrillary acidic protein (GFAP)-positive cells, increased Reactive oxygen species (ROS) generation, decreased activity of Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx) and Catalase (CAT), elevated protein level of IL-1β, IL-6 and TNF-α in hippocampus. Treatment with RE prevented these changes above. Our findings confirmed the effect of rosemary extract on improvement of cognitive deficits and suggested its mechanisms might be mediated by anti-oxidative and anti-inflammatory. Therefore, rosemary extract may be a potential treatment to improve cognitive deficits in rmTBI patients. PMID:27113205

  20. Effects of Mood Stabilizers on Brain Energy Metabolism in Mice Submitted to an Animal Model of Mania Induced by Paradoxical Sleep Deprivation.

    Science.gov (United States)

    Streck, Emilio L; Scaini, Giselli; Jeremias, Gabriela C; Rezin, Gislaine T; Gonçalves, Cinara L; Ferreira, Gabriela K; Réus, Gislaine Z; Resende, Wilson R; Valvassori, Samira S; Kapczinski, Flávio; Andersen, Mônica L; Quevedo, João

    2015-06-01

    There is a body of evidence suggesting that mitochondrial dysfunction is involved in bipolar disorder (BD) pathogenesis. Studies suggest that abnormalities in circadian cycles are involved in the pathophysiology of affective disorders; paradoxical sleep deprivation (PSD) induces hyperlocomotion in mice. Thus, the present study aims to investigate the effects of lithium (Li) and valproate (VPA) in an animal model of mania induced by PSD for 96 h. PSD increased exploratory activity, and mood stabilizers prevented PSD-induced behavioral effects. PSD also induced a significant decrease in the activity of complex II-III in hippocampus and striatum; complex IV activity was decreased in prefrontal cortex, cerebellum, hippocampus, striatum and cerebral cortex. Additionally, VPA administration was able to prevent PSD-induced inhibition of complex II-III and IV activities in prefrontal cortex, cerebellum, hippocampus, striatum and cerebral cortex, whereas Li administration prevented PSD-induced inhibition only in prefrontal cortex and hippocampus. Regarding the enzymes of Krebs cycle, only citrate synthase activity was increased by PSD in prefrontal cortex. We also found a similar effect in creatine kinase, an important enzyme that acts in the buffering of ATP levels in brain; its activity was increased in prefrontal cortex, hippocampus and cerebral cortex. These results are consistent with the connection of mitochondrial dysfunction and hyperactivity in BD and suggest that the present model fulfills adequate face, construct and predictive validity as an animal model of mania. PMID:25894682

  1. Decreased levels of pNR1 S897 protein in the cortex of neonatal Sprague Dawley rats with hypoxic-ischemic or NMDA-induced brain damage

    International Nuclear Information System (INIS)

    Our objective was to investigate the protein level of phosphorylated N-methyl-D-aspartate (NMDA) receptor-1 at serine 897 (pNR1 S897) in both NMDA-induced brain damage and hypoxic-ischemic brain damage (HIBD), and to obtain further evidence that HIBD in the cortex is related to NMDA toxicity due to a change of the pNR1 S897 protein level. At postnatal day 7, male and female Sprague-Dawley rats (13.12 ± 0.34 g) were randomly divided into normal control, phosphate-buffered saline (PBS) cerebral microinjection, HIBD, and NMDA cerebral microinjection groups. Immunofluorescence and Western blot (N = 10 rats per group) were used to examine the protein level of pNR1 S897. Immunofluorescence showed that control and PBS groups exhibited significant neuronal cytoplasmic staining for pNR1 S897 in the cortex. Both HIBD and NMDA-induced brain damage markedly decreased pNR1 S897 staining in the ipsilateral cortex, but not in the contralateral cortex. Western blot analysis showed that at 2 and 24 h after HIBD, the protein level of pNR1 S897 was not affected in the contralateral cortex (P > 0.05), whereas it was reduced in the ipsilateral cortex (P < 0.05). At 2 h after NMDA injection, the protein level of pNR1 S897 in the contralateral cortex was also not affected (P > 0.05). The levels in the ipsilateral cortex were decreased, but the change was not significant (P > 0.05). The similar reduction in the protein level of pNR1 S897 following both HIBD and NMDA-induced brain damage suggests that HIBD is to some extent related to NMDA toxicity possibly through NR1 phosphorylation of serine 897

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

    Science.gov (United States)

    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. PMID:16045502

  3. The Brain Prize 2011

    Science.gov (United States)

    Soltesz, Ivan

    2012-01-01

    The Grete Lundbeck European Brain Research Foundation awarded the inaugural Brain Prize 2011 to Péter Somogyi, Tamás Freund and György Buzsáki ‘for their wide-ranging, technically and conceptually brilliant research on the functional organization of neuronal circuits in the cerebral cortex, especially in the hippocampus, a region that is crucial for certain forms of memory’. The present article highlights key findings and major conceptual contributions by these three scientists that were recognized by the award. PMID:21917323

  4. Persistent Angiogenesis in the Autism Brain: An Immunocytochemical Study of Postmortem Cortex, Brainstem and Cerebellum

    Science.gov (United States)

    Azmitia, E. C.; Saccomano, Z. T.; Alzoobaee, M. F.; Boldrini, M.; Whitaker-Azmitia, P. M.

    2016-01-01

    In the current work, we conducted an immunocytochemical search for markers of ongoing neurogenesis (e.g. nestin) in auditory cortex from postmortem sections of autism spectrum disorder (ASD) and age-matched control donors. We found nestin labeling in cells of the vascular system, indicating blood vessels plasticity. Evidence of angiogenesis was…

  5. Incomplete brain infarction of reperfused cortex may be quantitated with iomazenil

    DEFF Research Database (Denmark)

    Nakagawara, J; Sperling, B; Lassen, N A

    1997-01-01

    BACKGROUND AND PURPOSE: [123I]Iomazenil is a specific radioligand for the central benzodiazepine receptor that may be useful as an indicator of the intactness of cortical neurons after focal cerebral ischemia. We evaluated the binding of this receptor in reperfused cortex among patients with isch...

  6. The functional organization of human epileptic hippocampus.

    Science.gov (United States)

    Klimes, Petr; Duque, Juliano J; Brinkmann, Ben; Van Gompel, Jamie; Stead, Matt; St Louis, Erik K; Halamek, Josef; Jurak, Pavel; Worrell, Gregory

    2016-06-01

    The function and connectivity of human brain is disrupted in epilepsy. We previously reported that the region of epileptic brain generating focal seizures, i.e., the seizure onset zone (SOZ), is functionally isolated from surrounding brain regions in focal neocortical epilepsy. The modulatory effect of behavioral state on the spatial and spectral scales over which the reduced functional connectivity occurs, however, is unclear. Here we use simultaneous sleep staging from scalp EEG with intracranial EEG recordings from medial temporal lobe to investigate how behavioral state modulates the spatial and spectral scales of local field potential synchrony in focal epileptic hippocampus. The local field spectral power and linear correlation between adjacent electrodes provide measures of neuronal population synchrony at different spatial scales, ∼1 and 10 mm, respectively. Our results show increased connectivity inside the SOZ and low connectivity between electrodes in SOZ and outside the SOZ. During slow-wave sleep, we observed decreased connectivity for ripple and fast ripple frequency bands within the SOZ at the 10 mm spatial scale, while the local synchrony remained high at the 1 mm spatial scale. Further study of these phenomena may prove useful for SOZ localization and help understand seizure generation, and the functional deficits seen in epileptic eloquent cortex. PMID:27030735

  7. Brain banks as key part of biochemical and molecular studies on cerebral cortex involvement in Parkinson's disease.

    Science.gov (United States)

    Ravid, Rivka; Ferrer, Isidro

    2012-04-01

    Exciting developments in basic and clinical neuroscience and recent progress in the field of Parkinson's disease (PD) are partly a result of the availability of human specimens obtained through brain banks. These banks have optimized the methodological, managerial and organizational procedures; standard operating procedures; and ethical, legal and social issues, including the code of conduct for 21st Century brain banking and novel protocols. The present minireview focuses on current brain banking organization and management, as well as the likely future direction of the brain banking field. We emphasize the potentials and pitfalls when using high-quality specimens of the human central nervous system for advancing PD research. PD is a generalized disease in which α-synuclein is not a unique component but, instead, is only one of the players accounting for the complex impairment of biochemical/molecular processes involved in metabolic pathways. This is particularly important in the cerebral cortex, where altered cognition has a complex neurochemical substrate. Mitochondria and energy metabolism impairment, abnormal RNA, microRNA, protein synthesis, post-translational protein modifications and alterations in the lipid composition of membranes and lipid rafts are part of these complementary factors. We have to be alert to the possible pitfalls of each specimen and its suitability for a particular study. Not all samples qualify for the study of DNA, RNA, proteins, post-translational modifications, lipids and metabolomes, although the use of carefully selected samples and appropriate methods minimizes pitfalls and errors and guarantees high-quality reserach. PMID:22313511

  8. Manipulation of Dysfunctional Spinal Joints Affects Sensorimotor Integration in the Prefrontal Cortex: A Brain Source Localization Study.

    Science.gov (United States)

    Lelic, Dina; Niazi, Imran Khan; Holt, Kelly; Jochumsen, Mads; Dremstrup, Kim; Yielder, Paul; Murphy, Bernadette; Drewes, Asbjørn Mohr; Haavik, Heidi

    2016-01-01

    Objectives. Studies have shown decreases in N30 somatosensory evoked potential (SEP) peak amplitudes following spinal manipulation (SM) of dysfunctional segments in subclinical pain (SCP) populations. This study sought to verify these findings and to investigate underlying brain sources that may be responsible for such changes. Methods. Nineteen SCP volunteers attended two experimental sessions, SM and control in random order. SEPs from 62-channel EEG cap were recorded following median nerve stimulation (1000 stimuli at 2.3 Hz) before and after either intervention. Peak-to-peak amplitude and latency analysis was completed for different SEPs peak. Dipolar models of underlying brain sources were built by using the brain electrical source analysis. Two-way repeated measures ANOVA was used to assessed differences in N30 amplitudes, dipole locations, and dipole strengths. Results. SM decreased the N30 amplitude by 16.9 ± 31.3% (P = 0.02), while no differences were seen following the control intervention (P = 0.4). Brain source modeling revealed a 4-source model but only the prefrontal source showed reduced activity by 20.2 ± 12.2% (P = 0.03) following SM. Conclusion. A single session of spinal manipulation of dysfunctional segments in subclinical pain patients alters somatosensory processing at the cortical level, particularly within the prefrontal cortex. PMID:27047694

  9. Manipulation of Dysfunctional Spinal Joints Affects Sensorimotor Integration in the Prefrontal Cortex: A Brain Source Localization Study

    Directory of Open Access Journals (Sweden)

    Dina Lelic

    2016-01-01

    Full Text Available Objectives. Studies have shown decreases in N30 somatosensory evoked potential (SEP peak amplitudes following spinal manipulation (SM of dysfunctional segments in subclinical pain (SCP populations. This study sought to verify these findings and to investigate underlying brain sources that may be responsible for such changes. Methods. Nineteen SCP volunteers attended two experimental sessions, SM and control in random order. SEPs from 62-channel EEG cap were recorded following median nerve stimulation (1000 stimuli at 2.3 Hz before and after either intervention. Peak-to-peak amplitude and latency analysis was completed for different SEPs peak. Dipolar models of underlying brain sources were built by using the brain electrical source analysis. Two-way repeated measures ANOVA was used to assessed differences in N30 amplitudes, dipole locations, and dipole strengths. Results. SM decreased the N30 amplitude by 16.9±31.3% (P=0.02, while no differences were seen following the control intervention (P=0.4. Brain source modeling revealed a 4-source model but only the prefrontal source showed reduced activity by 20.2±12.2% (P=0.03 following SM. Conclusion. A single session of spinal manipulation of dysfunctional segments in subclinical pain patients alters somatosensory processing at the cortical level, particularly within the prefrontal cortex.

  10. Manipulation of Dysfunctional Spinal Joints Affects Sensorimotor Integration in the Prefrontal Cortex: A Brain Source Localization Study

    Science.gov (United States)

    Lelic, Dina; Niazi, Imran Khan; Holt, Kelly; Jochumsen, Mads; Dremstrup, Kim; Yielder, Paul; Murphy, Bernadette; Drewes, Asbjørn Mohr; Haavik, Heidi

    2016-01-01

    Objectives. Studies have shown decreases in N30 somatosensory evoked potential (SEP) peak amplitudes following spinal manipulation (SM) of dysfunctional segments in subclinical pain (SCP) populations. This study sought to verify these findings and to investigate underlying brain sources that may be responsible for such changes. Methods. Nineteen SCP volunteers attended two experimental sessions, SM and control in random order. SEPs from 62-channel EEG cap were recorded following median nerve stimulation (1000 stimuli at 2.3 Hz) before and after either intervention. Peak-to-peak amplitude and latency analysis was completed for different SEPs peak. Dipolar models of underlying brain sources were built by using the brain electrical source analysis. Two-way repeated measures ANOVA was used to assessed differences in N30 amplitudes, dipole locations, and dipole strengths. Results. SM decreased the N30 amplitude by 16.9 ± 31.3% (P = 0.02), while no differences were seen following the control intervention (P = 0.4). Brain source modeling revealed a 4-source model but only the prefrontal source showed reduced activity by 20.2 ± 12.2% (P = 0.03) following SM. Conclusion. A single session of spinal manipulation of dysfunctional segments in subclinical pain patients alters somatosensory processing at the cortical level, particularly within the prefrontal cortex. PMID:27047694

  11. Experimental study on alteration of adrenergic receptors activity in neuronal membranes protein of cerebral cortex following brain trauma in rats

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xin-wei; XU Ru-xiang; QI Yi-long; CHEN Chang-cai

    2001-01-01

    Objective: To define the course of changes taken by α1 and β adrenergic receptors (AR) activity after traumatic brain injury (TBI) and explore the approach for secondary brain injury (SBI) management. Methods: The neuronal membrane protein of cortex were extracted from the rats subject to traumatic brain injury, and the changes of α1- and β-AR activities in the neuronal membranes were examined by radio ligand binding assay (RLBA). Results: α1- and β-AR activities underwent obvious changes, reaching their peak values at 24 h after TBI. α1-AR binding density (Bmax) reduced by 22.6%while the ligand affinity increased by 66.7%, and for β-AR, however, Bmax increased by 116.9% and the ligand affinity reduced by 50.7%. Their antagonists could counteract the changes ofα1- and β-AR activity. Conclusion: The patterns of changes varies between α1- and β-AR activity after TBI, suggesting their different roles in the neuronal membranes after brain trauma, and timely administration of AR antagonists is potentially beneficial in TBI management.

  12. The brain's code and its canonical computational motifs. From sensory cortex to the default mode network: A multi-scale model of brain function in health and disease.

    Science.gov (United States)

    Turkheimer, Federico E; Leech, Robert; Expert, Paul; Lord, Louis-David; Vernon, Anthony C

    2015-08-01

    A variety of anatomical and physiological evidence suggests that the brain performs computations using motifs that are repeated across species, brain areas, and modalities. The computational architecture of cortex, for example, is very similar from one area to another and the types, arrangements, and connections of cortical neurons are highly stereotyped. This supports the idea that each cortical area conducts calculations using similarly structured neuronal modules: what we term canonical computational motifs. In addition, the remarkable self-similarity of the brain observables at the micro-, meso- and macro-scale further suggests that these motifs are repeated at increasing spatial and temporal scales supporting brain activity from primary motor and sensory processing to higher-level behaviour and cognition. Here, we briefly review the biological bases of canonical brain circuits and the role of inhibitory interneurons in these computational elements. We then elucidate how canonical computational motifs can be repeated across spatial and temporal scales to build a multiplexing information system able to encode and transmit information of increasing complexity. We point to the similarities between the patterns of activation observed in primary sensory cortices by use of electrophysiology and those observed in large scale networks measured with fMRI. We then employ the canonical model of brain function to unify seemingly disparate evidence on the pathophysiology of schizophrenia in a single explanatory framework. We hypothesise that such a framework may also be extended to cover multiple brain disorders which are grounded in dysfunction of GABA interneurons and/or these computational motifs. PMID:25956253

  13. Effects of unpredictable chronic stress on behavior and brain-derived neurotrophic factor expression in CA3 subfield and dentate gyrus of the hippocampus in different aged rats

    Institute of Scientific and Technical Information of China (English)

    LI Ying; JI Yong-juan; JIANG Hong; LIU De-xiang; ZHANG Qian; FAN Shu-jian; PAN Fang

    2009-01-01

    Background Brain-derived neurotrophic factor (BDNF) is a stress-responsive intercellular messenger modifying hypothalamic-pituitary-adrenal (HPA) axis activity. The interaction between stress and age in BDNF expression is currently not fully understood. This study was conducted to observe unpredictable stress effect on behavior and BDNF expression in CA3 subfield (CA3) and dentate gyrus of hippocampus in different aged rats. Methods Forty-eight Wistar rats of two different ages (2 months and 15 months) were randomly assigned to six groups: two control groups and four stress groups. The rats in the stress group received three weeks of unpredictable mild stress. The depression state and the stress level of the animals were determined by sucrose preference test and observation of exploratory behavior in an open field (OF) test. The expressions of BDNF in CA3 and dentate gyrus of the hippocampus were measured using immunohistochemistry. Results Age and stress had different effects on the behavior of different aged animals (age: F=6.173, P <0.05, stress: F=6.056, P <0.05). Stress was the main factor affecting sucrose preference (F=123.608, P <0.05). Decreased sucrose preference and suppressed behavior emerged directly following stress, lasting to at least the eighth day after stress in young animals (P <0.05). The older stress rats showed a lower sucrose preference than young stress rats (P <0.05). Older control rats behaved differently from the younger control animals in the OF test, spending more time in the central square (P <0.05), exhibiting fewer vertical movements (P <0.05) and less grooming (P <0.05). Following exposure to stress, older-aged rats showed no obvious changes in vertical movement and grooming. This indicates that aged rats were in an unexcited state before the stress period, and responded less to stressful stimuli than younger rats. There was significantly lower BDNF expression in the CA3 and dentate gyrus regions of the hippocampus following stress

  14. A Cognição Social e o Córtex Cerebral Social Cognition and the Brain Cortex

    Directory of Open Access Journals (Sweden)

    Judith Butman

    2001-01-01

    Full Text Available A cognição social é o processo que orienta condutas frente a outros indivíduos da mesma espécie. Várias estruturas cerebrais têm um papel chave para controlar as condutas sociais: o córtex pré-frontal ventromedial, a amígdala, o córtex somatosensorial direito e a ínsula. O córtex pré-frontal ventromedial está comprometido com o raciocínio social e com a tomada de decisões; a amígdala com o julgamento social de faces; o córtex somatosensorial direito, com a empatia e com a simulação; enquanto que a insula, com a resposta autonômica. Estes achados estão de acordo com a hipótese do marcador somático, um mecanismo específico por meio do qual adquirimos, representamos ou memorizamos os valores de nossas ações. Estas estruturas cerebrais atuam como mediadores entre as representações perceptuais dos estímulos sensoriais e a recuperação do conhecimento que o estímulo pode ativar. O sistema límbico é a zona limítrofe; nela, a psicologia se encontra com a neurologia. A correta sincronização destas zonas e estruturas, no adulto, é a chave para uma situação livre de patologia.Social cognition refers to the processes that subserve behavior in response to other individuals of the same species. Several brain structures play a key role in guiding social behaviors: ventromedial prefrontal cortex, amygdala, right somatosensory cortex and insula. The ventromedial prefrontal cortex is most directly involved in social reasoning and decision making; the amygdala in social judgment of faces, the right somatosensory cortex in empathy and simulation and the insula in autonomic responses. These findings are corresponding to the somatic marker hypothesis, particular mechanism by which we acquire, represent and retrieve the values of our actions. These brain structures appear to mediate between perceptual representation of social stimuli and retrieval of knowledge that such stimuli can trigger. The limbic system is the border zone

  15. Induction and requirement of gene expression in the anterior cingulate cortex and medial prefrontal cortex for the consolidation of inhibitory avoidance memory

    Directory of Open Access Journals (Sweden)

    Zhang Yue

    2011-01-01

    Full Text Available Abstract Background Memory consolidation is a process to stabilize short-term memory, generating long-term memory. A critical biochemical feature of memory consolidation is a requirement for gene expression. Previous studies have shown that fear memories are consolidated through the activation of gene expression in the amygdala and hippocampus, indicating essential roles of these brain regions in memory formation. However, it is still poorly understood whether gene expression in brain regions other than the amygdala/hippocampus is required for the consolidation of fear memory; however, several brain regions are known to play modulatory roles in fear memory formation. Results To further understand the mechanisms underlying the formation of fear memory, we first identified brain regions where gene expression is activated after learning inhibitory avoidance (IA by analyzing the expression of the immediately early genes c-fos and Arc as markers. Similarly with previous findings, the induction of c-fos and Arc expression was observed in the amygdala and hippocampus. Interestingly, we also observed the induction of c-fos and Arc expression in the medial prefrontal cortex (mPFC: prelimbic (PL and infralimbic (IL regions and Arc expression in the anterior cingulate cortex (ACC. We next examined the roles of these brain regions in the consolidation of IA memory. Consistent with previous findings, inhibiting protein synthesis in the hippocampus blocked the consolidation of IA memory. More importantly, inhibition in the mPFC or ACC also blocked the formation of IA memory. Conclusion Our observations indicated that the formation of IA memory requires gene expression in the ACC and mPFC as well as in the amygdala and hippocampus, suggesting essential roles of the ACC and mPFC in IA memory formation.

  16. Benefits of Physical Exercise on the Aging Brain: The Role of the Prefrontal Cortex

    OpenAIRE

    Berchicci, Marika; Lucci, Giuliana; Di Russo, Francesco

    2013-01-01

    Motor planning in older adults likely relies on the overengagement of the prefrontal cortex (PFC) and is associated with slowness of movement and responses. Does a physically active lifestyle counteract the overrecruitment of the PFC during action preparation? This study used high-resolution electroencephalography to measure the effect of physical exercise on the executive functions of the PFC preceding a visuomotor discriminative task. A total of 130 participants aged 15–86 were divided into...

  17. Brain region-specificity of palmitic acid-induced abnormalities associated with Alzheimer's disease

    OpenAIRE

    Melrose Joseph; Balu Deebika; Patil Sachin; Chan Christina

    2008-01-01

    Abstract Background Alzheimer's disease (AD) is a progressive, neurodegenerative disease mostly affecting the basal forebrain, cortex and hippocampus whereas the cerebellum is relatively spared. The reason behind this region-specific brain damage in AD is not well understood. Here, we report our data suggesting "differential free fatty acid metabolism in the different brain areas" as a potentially important factor in causing the region-specific damage observed in AD brain. Findings The astrog...

  18. Differential erbB signaling in astrocytes from the cerebral cortex and the hypothalamus of the human brain. : ErbB signaling in human astrocytes

    OpenAIRE

    Sharif, Ariane; Duhem-Tonnelle, Véronique; Allet, Cécile; Baroncini, Marc; Loyens, Anne; Kerr-Conte, Julie; Collier, Francis; Blond, Serge; Ojeda, Sergio; Junier, Marie-Pierre; Prévot, Vincent

    2009-01-01

    Studies in rodents have shown that astroglial erbB tyrosine kinase receptors are key regulatory elements in neuron-glia communication. Although both astrocytes and deregulation of erbB functions have been implicated in the pathogenesis of many common human brain disorders, erbB signaling in native human brain astrocytes has never been explored. Taking advantage of our ability to perform primary cultures from the cortex and the hypothalamus of human fetuses, we conducted a thorough analysis of...

  19. Cellular scaling rules for the brain of Artiodactyla include a highly folded cortex with few neurons

    OpenAIRE

    Rodrigo eSiqueira Kazu; Jose eMaldonado; Bruno eMota; Paul eManger; Suzana eHerculano-Houzel

    2014-01-01

    Quantitative analysis of the cellular composition of rodent, primate, insectivore, and afrotherian brains has shown that non-neuronal scaling rules are similar across these mammalian orders that diverged about 95 million years ago, and therefore appear to be conserved in evolution, while neuronal scaling rules appear to be free to vary in a clade-specific manner. Here we analyze the cellular scaling rules that apply to the brain of artiodactyls, a group within the order Cetartiodactyla, belie...

  20. Voluntary Running in Young Adult Mice Reduces Anxiety-Like Behavior and Increases the Accumulation of Bioactive Lipids in the Cerebral Cortex

    OpenAIRE

    Santos-Soto, Iván J.; Chorna, Nataliya; Carballeira, Néstor M.; Vélez-Bartolomei, José G.; Méndez-Merced, Ana T.; Chornyy, Anatoliy P.; de Ortiz, Sandra Peña

    2013-01-01

    Combinatorial therapies using voluntary exercise and diet supplementation with polyunsaturated fatty acids have synergistic effects benefiting brain function and behavior. Here, we assessed the effects of voluntary exercise on anxiety-like behavior and on total FA accumulation within three brain regions: cortex, hippocampus, and cerebellum of running versus sedentary young adult male C57/BL6J mice. The running group was subjected to one month of voluntary exercise in their home cages, while t...

  1. Effect of propofol pretreatment on apoptosis in rat brain cortex after focal cerebral ischemia and reperfusion

    Institute of Scientific and Technical Information of China (English)

    Haiyan Xu; Chengwei Zhang; Chunxiao Zhang

    2011-01-01

    The present study aimed to observe cortical expression of Bcl-2 and Bax, cysteine-dependent aspartate directed proteases-3 activity and apoptotic cell death in a rat model of middle cerebral artery occlusion pretreated with propofol. Results showed that, propofol pretreatment significantly reduced oxidative stress levels and attenuated neuronal apoptosis in the cortex of rats. Propofol pretreatment upregulated Bcl-2 expression, and downregulated Bax expression and cysteine-dependent aspartate directed proteases-3 activity. These findings indicate that propofol pretreatment inhibits cell apoptosis during focal cerebral ischemia/reperfusion injury. This neuroprotective effect is most likely achieved through the Bcl-2/Bax/cysteine-dependent aspartate directed proteases-3 pathway.

  2. Stromal derived factor-1α in hippocampus radial glial cells in vitro regulates the migration of neural progenitor cells.

    Science.gov (United States)

    Ding, Hui; Jin, Guo-Hua; Zou, Lin-Qing; Zhang, Xiao-Qing; Li, Hao-Ming; Tao, Xue-Lei; Zhang, Xin-Hua; Qin, Jian-Bing; Tian, Mei-Ling

    2015-06-01

    Stromal derived factor-1α (SDF-1α), a critical chemokine that promotes cell homing to target tissues, was presumed to be involved in the traumatic brain injury cortex. In this study, we determined the expression of SDF-1α in the hippocampus after transection of the fimbria fornix (FF). Realtime PCR and ELISA showed that mRNA transcription and SDF-1α proteins increased significantly after FF transection. In vitro, the expression of SDF-1α in radial glial cells (RGCs) incubated with deafferented hippocampus extracts was observed to be greater than in those incubated with normal hippocampus extracts. The co-culture of neural progenitor cells (NPCs) and RGCs indicated that the extracts of deafferented hippocampus induced more NPCs migrating toward RGCs than the normal extracts. Suppression or overexpression of SDF-1α in RGCs markedly either decreased or increased, respectively, the migration of NPCs. These results suggest that after FF transection, SDF-1α in the deafferented hippocampus was upregulated and might play an important role in RGC induction of NPC migration; therefore, SDF-1α is a target for additional research for determining new therapy for brain injuries. PMID:25604551

  3. Distribution of vesicular glutamate transporters in the human brain

    Directory of Open Access Journals (Sweden)

    Erika eVigneault

    2015-03-01

    Full Text Available Glutamate is the major excitatory transmitter in the brain. Vesicular glutamate transporters (VGLUT1-3 are responsible for uploading glutamate into synaptic vesicles. VGLUT1 and VGLUT2 are considered as specific markers of canonical glutamatergic neurons, while VGLUT3 is found in neurons previously shown to use other neurotransmitters than glutamate. Although there exists a rich literature on the localization of these glutamatergic markers in the rodent brain, little is currently known about the distribution of VGLUT1-3 in the human brain. In the present study, using subtype specific probes and antisera, we examined the localization of the three vesicular glutamate transporters in the human brain by in situ hybridization, immunoautoradiography and immunohistochemistry. We found that the VGLUT1 transcript was highly expressed in the cerebral cortex, hippocampus and cerebellum, whereas VGLUT2 mRNA was mainly found in the thalamus and brainstem. VGLUT3 mRNA was localized in scarce neurons within the cerebral cortex, hippocampus, striatum and raphe nuclei. Following immunoautoradiographic labeling, intense VGLUT1- and VGLUT2-immunoreactivities were observed in all regions investigated (cerebral cortex, hippocampus, caudate-putamen, cerebellum, thalamus, amygdala, substantia nigra, raphe while VGLUT3 was absent from the thalamus and cerebellum. This extensive mapping of VGLUT1-3 in human brain reveals distributions that correspond for the most part to those previously described in rodent brains.

  4. Sources of the spatial code within the hippocampus

    OpenAIRE

    Brandon, Mark P.; Michael E Hasselmo

    2009-01-01

    Neurons in the hippocampus are thought to provide information on an animal's location within its environment. Input to the hippocampus comes via afferents from the entorhinal cortex, which are separated into several major pathways serving different hippocampal regions. Recent studies show the significance of individual afferent pathways in location perception, enhancing our understanding of hippocampal function.

  5. Does noninvasive brain stimulation applied over the dorsolateral prefrontal cortex nonspecifically influence mood and emotional processing in healthy individuals?

    Directory of Open Access Journals (Sweden)

    François Thiffault

    2015-10-01

    Full Text Available The dorsolateral prefrontal cortex (DLPFC is often targeted with noninvasive brain stimulation (NIBS to modulate in vivo human behaviors. This brain region plays a key role in mood, emotional processing and attentional processing of emotional information. In this article, we ask the question: when we target the DLPFC with NIBS, do we modulate these processes altogether, nonspecifically, or can we modulate them selectively? We thus review articles investigating the effects of NIBS applied over the DLPFC on mood, emotional processing and attentional processing of emotional stimuli in healthy subjects. We discuss that NIBS over the DLPFC can modulate emotional processing and attentional processing of emotional stimuli, without specifically influencing mood. Indeed, there seems to be a lack of evidence that NIBS over the DLPFC influence on mood in healthy individuals. Finally, there appears to be a hemispheric lateralization: when applied over the left DLPFC, NIBS improved processing of positive stimuli and reduced selective attention for stimuli expressing anger, whereas when applied over the right DLPFC, it increased selective attention for stimuli expressing anger.

  6. Age-related differences in functional nodes of the brain cortex - a high model order group ICA study

    Directory of Open Access Journals (Sweden)

    Harri Littow

    2010-08-01

    Full Text Available Functional MRI measured with blood oxygen dependent (BOLD contrast in the absence of intermittent tasks reflects spontaneous activity of so called resting state networks (RSN of the brain. Group level independent component analysis (ICA of BOLD data can separate the human brain cortex into 42 independent RSNs. In this study we evaluated age related effects from primary motor and sensory, and, higher level control RSNs. 168 healthy subjects were scanned and divided into three groups: 55 adolescents (ADO, 13.2 ± 2.4 yrs, 59 young adults (YA, 22.2 ± 0.6yrs , and 54 older adults (OA, 42.7 ± 0.5 yrs, all with normal IQ. High model order group probabilistic ICA components (70 were calculated and dual regression analysis was used to compare 21 RSN’s spatial differences between groups. The power spectra were derived from individual ICA mixing matrix time series of the group analyses for frequency domain analysis. We show that primary sensory and motor networks tend to alter more in younger age groups, whereas associative and higher level cognitive networks consolidate and re-arrange until older adulthood. The change has a common trend: both spatial extent and the low frequency power of the RSN’s reduce with increasing age. We interpret these result as a sign of normal pruning via focusing of activity to less distributed local hubs.

  7. Issues in Localization of brain function: The case of lateralized frontal cortex in cognition, emotion, and psychopathology

    Directory of Open Access Journals (Sweden)

    Gregory A. Miller

    2013-01-01

    Full Text Available The appeal of simple, sweeping portraits of large-scale brain mechanisms relevant to psychological phenomena competes with a rich, complex research base. As a prominent example, two views of frontal brain organization have emphasized dichotomous lateralization as a function of either emotional valence (positive/negative or approach/avoidance motivation. Compelling findings support each. The literature has struggled to choose between them for three decades, without success. Both views are proving untenable as comprehensive models. Recent evidence indicates that positive valence and approach motivation are associated with different areas in the left hemisphere. Evidence of other frontal lateralizations, involving distinctions among dimensions of depression and anxiety, make a dichotomous view even more problematic. Hemodynamic and electromagnetic neuroimaging studies suggest considerable functional differentiation, in specialization and activation, of subregions of frontal cortex, including their connectivity to each other and to other regions. Such findings contribute to a more nuanced understanding of functional localization that accommodates aspects of multiple theoretical perspectives.

  8. Diagnostic benefits of presurgical fMRI in patients with brain tumours in the primary sensorimotor cortex

    International Nuclear Information System (INIS)

    Reliable imaging of eloquent tumour-adjacent brain areas is necessary for planning function-preserving neurosurgery. This study evaluates the potential diagnostic benefits of presurgical functional magnetic resonance imaging (fMRI) in comparison to a detailed analysis of morphological MRI data. Standardised preoperative functional and structural neuroimaging was performed on 77 patients with rolandic mass lesions at 1.5 Tesla. The central region of both hemispheres was allocated using six morphological and three functional landmarks. fMRI enabled localisation of the motor hand area in 76/77 patients, which was significantly superior to analysis of structural MRI (confident localisation of motor hand area in 66/77 patients; p < 0.002). FMRI provided additional diagnostic information in 96% (tongue representation) and 97% (foot representation) of patients. FMRI-based presurgical risk assessment correlated in 88% with a positive postoperative clinical outcome. Routine presurgical FMRI allows for superior assessment of the spatial relationship between brain tumour and motor cortex compared with a very detailed analysis of structural 3D MRI, thus significantly facilitating the preoperative risk-benefit assessment and function-preserving surgery. The additional imaging time seems justified. FMRI has the potential to reduce postoperative morbidity and therefore hospitalisation time. (orig.)

  9. Experimental Traumatic Brain Injury Results in Long-Term Recovery of Functional Responsiveness in Sensory Cortex but Persisting Structural Changes and Sensorimotor, Cognitive, and Emotional Deficits.

    Science.gov (United States)

    Johnstone, Victoria P A; Wright, David K; Wong, Kendrew; O'Brien, Terence J; Rajan, Ramesh; Shultz, Sandy R

    2015-09-01

    Traumatic brain injury (TBI) is a leading cause of death worldwide. In recent studies, we have shown that experimental TBI caused an immediate (24-h post) suppression of neuronal processing, especially in supragranular cortical layers. We now examine the long-term effects of experimental TBI on the sensory cortex and how these changes may contribute to a range of TBI morbidities. Adult male Sprague-Dawley rats received either a moderate lateral fluid percussion injury (n=14) or a sham surgery (n=12) and 12 weeks of recovery before behavioral assessment, magnetic resonance imaging, and electrophysiological recordings from the barrel cortex. TBI rats demonstrated sensorimotor deficits, cognitive impairments, and anxiety-like behavior, and this was associated with significant atrophy of the barrel cortex and other brain structures. Extracellular recordings from ipsilateral barrel cortex revealed normal neuronal responsiveness and diffusion tensor MRI showed increased fractional anisotropy, axial diffusivity, and tract density within this region. These findings suggest that long-term recovery of neuronal responsiveness is owing to structural reorganization within this region. Therefore, it is likely that long-term structural and functional changes within sensory cortex post-TBI may allow for recovery of neuronal responsiveness, but that this recovery does not remediate all behavioral deficits. PMID:25739059

  10. Characterization and distribution of [125I]epidepride binding to dopamine D2 receptors in basal ganglia and cortex of human brain

    International Nuclear Information System (INIS)

    The distribution and pharmacology of the binding of 125I-epidepride, a substituted benzamide with high affinity and selectivity for dopamine (DA) D2 receptors in rat brain is described in human brain. Saturation analysis of the binding of 125I-epidepride to membranes derived from striatum and regions of cortex demonstrated similar Kd values (34 and 28-33 pM, respectively) but differing maximum density of binding site values (152 and 3-8 fmol/mg of protein, respectively). The pharmacological profile of binding in cortex was also similar to striatum (epidepride greater than spiperone greater than butaclamol = flupenthixol greater than clozapine) except that an additional low-affinity site, blocked by the alpha-2 adrenergic antagonist idazoxan, was present in cortex. Quantification by autoradiography also demonstrated the greatest binding in the basal ganglia, with the striatum exhibiting greater binding than the pallidal complex or midbrain regions. For the pallidum, binding in the external segment was higher than the internal segment. Within the midbrain the binding of 125I-epidepride correlated well with the known distribution of DA-containing cell bodies, with the substantia nigra (pars compacta and pars lateralis) and ventral tegmental area (A10) higher than area A8 and central gray. Binding in frontal and parietal cortex was highest in the internal layers (layers V and VI). Temporal cortex showed a 2-fold higher density of binding than other cortical regions and a trilaminar pattern; binding was greater in the external (layers I and II) and internal layers than in the middle layers (III and IV). This pattern changed in the parahippocampal complex. Within the lateral occipitotemporal cortex, binding was densest in layers I to III and very low in layers IV to VI, but binding was almost nonexistent in the adjacent entorhinal cortex

  11. Characterization and distribution of (125I)epidepride binding to dopamine D2 receptors in basal ganglia and cortex of human brain

    Energy Technology Data Exchange (ETDEWEB)

    Joyce, J.N.; Janowsky, A.; Neve, K.A. (Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia (USA))

    1991-06-01

    The distribution and pharmacology of the binding of {sup 125}I-epidepride, a substituted benzamide with high affinity and selectivity for dopamine (DA) D2 receptors in rat brain is described in human brain. Saturation analysis of the binding of {sup 125}I-epidepride to membranes derived from striatum and regions of cortex demonstrated similar Kd values (34 and 28-33 pM, respectively) but differing maximum density of binding site values (152 and 3-8 fmol/mg of protein, respectively). The pharmacological profile of binding in cortex was also similar to striatum (epidepride greater than spiperone greater than butaclamol = flupenthixol greater than clozapine) except that an additional low-affinity site, blocked by the alpha-2 adrenergic antagonist idazoxan, was present in cortex. Quantification by autoradiography also demonstrated the greatest binding in the basal ganglia, with the striatum exhibiting greater binding than the pallidal complex or midbrain regions. For the pallidum, binding in the external segment was higher than the internal segment. Within the midbrain the binding of {sup 125}I-epidepride correlated well with the known distribution of DA-containing cell bodies, with the substantia nigra (pars compacta and pars lateralis) and ventral tegmental area (A10) higher than area A8 and central gray. Binding in frontal and parietal cortex was highest in the internal layers (layers V and VI). Temporal cortex showed a 2-fold higher density of binding than other cortical regions and a trilaminar pattern; binding was greater in the external (layers I and II) and internal layers than in the middle layers (III and IV). This pattern changed in the parahippocampal complex. Within the lateral occipitotemporal cortex, binding was densest in layers I to III and very low in layers IV to VI, but binding was almost nonexistent in the adjacent entorhinal cortex.

  12. Brain metabolites in the hippocampus-amygdala region and cerebellum in autism: an {sup 1}H-MR spectroscopy study

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, H.; Harada, M.; Hisaoka, S.; Nishitani, H. [Dept. of Radiology, Univ. of Tokushima, Tokushima City (Japan); Mori, K. [Dept. of Pediatrics, Univ. of Tokushima (Japan)

    1999-07-01

    Histological abnormalities of the brain in autism have been investigated extensively. We studied metabolites in the hippocampusamygdala (HA) region and cerebellum. We examined the right HA region and left cerebellar hemisphere of 27 autistic patients 2-18 years old, 21 boys and 6 girls and 10 normal children 6-14 years old, 4 boys and 6 girls, using the STEAM sequence. This sequence was used to minimise the influence of relaxation times. The N-acetyl aspartate (NAA) concentration was significantly lower (P=0.042) in autistic patients than in normal children (9.37 and 10.95 mM, respectively). There was no significant difference in other metabolites. The correlation coefficient (r value) of NAA between the HA region and cerebellum was 0.616. The decreased NAA concentration may be due to neuronal hypofunction or immature neurons. The NAA concentration in the HA region and cerebellum may be related, because of neuronal circuits or networks. (orig.)

  13. Brain metabolites in the hippocampus-amygdala region and cerebellum in autism: an 1H-MR spectroscopy study

    International Nuclear Information System (INIS)

    Histological abnormalities of the brain in autism have been investigated extensively. We studied metabolites in the hippocampusamygdala (HA) region and cerebellum. We examined the right HA region and left cerebellar hemisphere of 27 autistic patients 2-18 years old, 21 boys and 6 girls and 10 normal children 6-14 years old, 4 boys and 6 girls, using the STEAM sequence. This sequence was used to minimise the influence of relaxation times. The N-acetyl aspartate (NAA) concentration was significantly lower (P=0.042) in autistic patients than in normal children (9.37 and 10.95 mM, respectively). There was no significant difference in other metabolites. The correlation coefficient (r value) of NAA between the HA region and cerebellum was 0.616. The decreased NAA concentration may be due to neuronal hypofunction or immature neurons. The NAA concentration in the HA region and cerebellum may be related, because of neuronal circuits or networks. (orig.)

  14. Gender and brain regions specific differences in brain derived neurotrophic factor protein levels of depressed individuals who died through suicide.

    Science.gov (United States)

    Hayley, Shawn; Du, Lisheng; Litteljohn, Darcy; Palkovits, Miklós; Faludi, Gábor; Merali, Zul; Poulter, Michael O; Anisman, Hymie

    2015-07-23

    Considerable evidence supports the view that depressive illness and suicidal behaviour stem from perturbations of neuroplasticity. Presently, we assessed whether depressed individuals who died by suicide displayed brain region-specific changes in brain derived neurotrophic factor (BDNF) and whether such effects varied by gender. Using postmortem samples from non-psychiatric controls and depressed individuals who died by suicide, BDNF protein levels were assessed within the hippocampus and frontopolar prefrontal cortex using Western blot. As expected, BDNF levels were reduced within the frontopolar prefrontal cortex among female depressed suicides; however, males showed no such effect. Contrastingly, within the hippocampus, depressed male but not female suicides displayed significant reductions of BDNF protein levels. Although the mechanisms driving the gender and brain region specific BDNF changes are unclear, our data do support the notion that complex alterations of neuroplasticity may be fundamentally involved in the illness. PMID:26033186

  15. Subarachnoid blood converts neurally evoked vasodilation to vasoconstriction in rat brain cortex

    OpenAIRE

    Koide, Masayo; Bonev, Adrian D.; Nelson, Mark T.; Wellman, George C.

    2013-01-01

    The matching of blood flow to regional brain function, called functional hyperemia or neurovascular coupling, involves the coordinated activity of neurons, astrocytes and parenchymal arterioles. Under physiological conditions, localized neuronal activation leads to elevated astrocyte endfoot Ca2+ and vasodilation, resulting in an increase in cerebral blood flow. In this study, we examined the impact of subarachnoid hemorrhage (SAH) on neurovascular coupling. SAH model rats received two inject...

  16. Region-specific maturation of cerebral cortex in human fetal brain: diffusion tensor imaging and histology

    International Nuclear Information System (INIS)

    In this study, diffusion tensor imaging (DTI) and glial fibrillary acidic protein (GFAP) immunohistochemical analysis in different cortical regions in fetal brains at different gestational age (GA) were performed. DTI was performed on 50 freshly aborted fetal brains with GA ranging from 12 to 42 weeks to compare age-related fractional anisotropy (FA) changes in different cerebral cortical regions that include frontal, parietal, occipital, and temporal lobes at the level of thalami. GFAP immunostaining was performed and the percentage of GFAP-positive areas was quantified. The cortical FA values in the frontal lobe peaked at around 26 weeks of GA, occipital and temporal lobes at around 20 weeks, and parietal lobe at around 23 weeks. A significant, but modest, positive correlation (r=0.31, p=0.02) was observed between cortical FA values and percentage area of GFAP expression in cortical region around the time period during which the migrational events are at its peak, i.e., GA ≤ 28 weeks for frontal cortical region and GA≤22 weeks for rest of the lobes. The DTI-derived FA quantification with its GFAP immunohistologic correlation in cortical regions of the various lobes of the cerebral hemispheres supports region-specific migrational and maturational events in human fetal brain. (orig.)

  17. Region-specific maturation of cerebral cortex in human fetal brain: diffusion tensor imaging and histology

    Energy Technology Data Exchange (ETDEWEB)

    Trivedi, Richa; Gupta, Rakesh K.; Saksena, Sona [Sanjay Gandhi Post Graduate Institute of Medical Sciences, Department of Radiodiagnosis, Lucknow, UP (India); Husain, Nuzhat; Srivastava, Savita [CSM Medical University, Department of Pathology, Lucknow (India); Rathore, Ram K.S.; Sarma, Manoj K. [Indian Institute of Technology, Department of Mathematics and Statistics, Kanpur (India); Malik, Gyanendra K. [CSM Medical University, Department of Pediatrics, Lucknow (India); Das, Vinita [CSM Medical University, Department of Obstetrics and Gynecology, Lucknow (India); Pradhan, Mandakini [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Medical Genetics, Lucknow (India); Pandey, Chandra M. [Sanjay Gandhi Postgraduate Institute of Medical Sciences, Department of Biostatistics, Lucknow (India); Narayana, Ponnada A. [University of Texas Medical School at Houston, Department of Diagnostic and Interventional Imaging, Houston, TX (United States)

    2009-09-15

    In this study, diffusion tensor imaging (DTI) and glial fibrillary acidic protein (GFAP) immunohistochemical analysis in different cortical regions in fetal brains at different gestational age (GA) were performed. DTI was performed on 50 freshly aborted fetal brains with GA ranging from 12 to 42 weeks to compare age-related fractional anisotropy (FA) changes in different cerebral cortical regions that include frontal, parietal, occipital, and temporal lobes at the level of thalami. GFAP immunostaining was performed and the percentage of GFAP-positive areas was quantified. The cortical FA values in the frontal lobe peaked at around 26 weeks of GA, occipital and temporal lobes at around 20 weeks, and parietal lobe at around 23 weeks. A significant, but modest, positive correlation (r=0.31, p=0.02) was observed between cortical FA values and percentage area of GFAP expression in cortical region around the time period during which the migrational events are at its peak, i.e., GA {<=} 28 weeks for frontal cortical region and GA{<=}22 weeks for rest of the lobes. The DTI-derived FA quantification with its GFAP immunohistologic correlation in cortical regions of the various lobes of the cerebral hemispheres supports region-specific migrational and maturational events in human fetal brain. (orig.)

  18. Brain cells in the avian 'prefrontal cortex' code for features of slot-machine-like gambling.

    Directory of Open Access Journals (Sweden)

    Damian Scarf

    Full Text Available Slot machines are the most common and addictive form of gambling. In the current study, we recorded from single neurons in the 'prefrontal cortex' of pigeons while they played a slot-machine-like task. We identified four categories of neurons that coded for different aspects of our slot-machine-like task. Reward-Proximity neurons showed a linear increase in activity as the opportunity for a reward drew near. I-Won neurons fired only when the fourth stimulus of a winning (four-of-a-kind combination was displayed. I-Lost neurons changed their firing rate at the presentation of the first nonidentical stimulus, that is, when it was apparent that no reward was forthcoming. Finally, Near-Miss neurons also changed their activity the moment it was recognized that a reward was no longer available, but more importantly, the activity level was related to whether the trial contained one, two, or three identical stimuli prior to the display of the nonidentical stimulus. These findings not only add to recent neurophysiological research employing simulated gambling paradigms, but also add to research addressing the functional correspondence between the avian NCL and primate PFC.

  19. Association between serotonin transporter genotype, brain structure and adolescent-onset major depressive disorder: a longitudinal prospective study

    OpenAIRE

    Little, K.; Olsson, C. A.; Whittle, S; Youssef, G J; Byrne, M L; J.G. Simmons; Yücel, M; Foley, D L; Allen, N. B.

    2014-01-01

    The extent to which brain structural abnormalities might serve as neurobiological endophenotypes that mediate the link between the variation in the promoter of the serotonin transporter gene (5-HTTLPR) and depression is currently unknown. We therefore investigated whether variation in hippocampus, amygdala, orbitofrontal cortex (OFC) and anterior cingulate cortex volumes at age 12 years mediated a putative association between 5-HTTLPR genotype and first onset of major depressive disorder (MDD...

  20. Enduring Consequences of Early-Life Infection on Glial and Neural Cell Genesis Within Cognitive Regions of the Brain

    OpenAIRE

    Bland, Sondra T.; Beckley, Jacob T; Young, Sarah; Tsang, Verne; Watkins, Linda R; Steven F. Maier; Staci D. Bilbo

    2009-01-01

    Systemic infection with Escherichia coli on postnatal day (P) 4 in rats results in significantly altered brain cytokine responses and behavioral changes in adulthood, but only in response to a subsequent immune challenge with lipopolysaccharide [LPS]. The basis for these changes may be long-term changes in glial cell function. We assessed glial and neural cell genesis in the hippocampus, parietal cortex (PAR), and pre-frontal cortex (PFC), in neonates just after the infection, as well as in a...

  1. High membrane protein oxidation in the human cerebral cortex

    Directory of Open Access Journals (Sweden)

    Matthias Granold

    2015-04-01

    Full Text Available Oxidative stress is thought to be one of the main mediators of neuronal damage in human neurodegenerative disease. Still, the dissection of causal relationships has turned out to be remarkably difficult. Here, we have analyzed global protein oxidation in terms of carbonylation of membrane proteins and cytoplasmic proteins in three different mammalian species: aged human cortex and cerebellum from patients with or without Alzheimer's disease, mouse cortex and cerebellum from young and old animals, and adult rat hippocampus and cortex subjected or not subjected to cerebral ischemia. Most tissues showed relatively similar levels of protein oxidation. However, human cortex was affected by severe membrane protein oxidation, while exhibiting lower than average cytoplasmic protein oxidation. In contrast, ex vivo autooxidation of murine cortical tissue primarily induced aqueous protein oxidation, while in vivo biological aging or cerebral ischemia had no major effect on brain protein oxidation. The unusually high levels of membrane protein oxidation in the human cortex were also not predicted by lipid peroxidation, as the levels of isoprostane immunoreactivity in human samples were considerably lower than in rodent tissues. Our results indicate that the aged human cortex is under steady pressure from specific and potentially detrimental membrane protein oxidation. The pronounced difference between humans, mice and rats regarding the primary site of cortical oxidation might have contributed to the unresolved difficulties in translating into therapies the wealth of data describing successful antioxidant neuroprotection in rodents.

  2. A Depth-Focusing Collimator for the Investigation of the Brain Cortex

    International Nuclear Information System (INIS)

    A detector is described which consists of a 5-in diam. by 1/2 in thick sodium iodide crystal and a depth-focusing collimator. The collimator was designed initially for use in brain cortical blood-flow investigations using Xe133 but may be used with other soft gamma-emitting isotopes such as I125. The collimator, which is constructed of lead, is 1/2-in thick and is of multichannel design. The focus is at 1.75 cm from the face of the collimator. The response in air to a point source on the central axis of the collimator falls to 10% of the maximum at ± 0.75 cm from the focus. The far field response in tissue is considerably better than in air due to high tissue attenuation of the soft gamma radiation. The response of the collimator to a point source in air and inside a skull is presented. The collimator has been used to measure local cortical blood flow in the brain using Xe133. However, using I125-tagged chemicals, the detection of cortical tumours and haemorrhages is possible using this apparatus. (author)

  3. Brain polarization of parietal cortex augments training-induced improvement of visual exploratory and attentional skills.

    Science.gov (United States)

    Bolognini, Nadia; Fregni, Felipe; Casati, Carlotta; Olgiati, Elena; Vallar, Giuseppe

    2010-08-19

    Recent evidence suggests that behavioural gains induced by behavioural training are maximized when combined with techniques of cortical neuromodulation, such as transcranial Direct Current Stimulation (tDCS). Here we address the validity of this appealing approach by investigating the effect of coupling a multisensory visual field exploration training with tDCS of the posterior parietal cortex (PPC). The multisensory visual field exploration training consisted in the practice of visual search through the systematic audio-visual stimulation of the visual field. Neurologically unimpaired participants performed a bimodal exploration training for 30 min, while simultaneously receiving anodal-excitatory PPC tDCS or sham tDCS. In two different experiments, the left and the right hemisphere were stimulated. Outcome measures included visual exploration speed at different time intervals during the training, and the post-training effects on tests assessing visual scanning and visuo-spatial orienting. Results show that PPC tDCS applied to the right, but not to the left, hemisphere increases the training-induced behavioural improvement of visual exploration, as compared to sham tDCS. In addition, right PPC tDCS brings about an improvement of covert visual orienting, in a task different from the visual search practice. In an additional experiment, we confirm that right parietal tDCS by itself, even without the associated training, can lead to enhancement of visual search. Overall, anodal PPC tDCS is a promising technique to enhance visuo-spatial abilities, when combined to a visual field exploration training task. PMID:20599813

  4. The Piriform Cortex and Human Focal Epilepsy

    OpenAIRE

    Vaughan, David N.; Graeme D. Jackson

    2014-01-01

    It is surprising that the piriform cortex, when compared to the hippocampus, has been given relatively little significance in human epilepsy. Like the hippocampus, it has a phylogenetically preserved three-layered cortex that is vulnerable to excitotoxic injury, has broad connections to both limbic and cortical areas, and is highly epileptogenic – being critical to the kindling process. The well-known phenomenon of early olfactory auras in temporal lobe epilepsy highlights its clinical releva...

  5. Role of Nitric Oxide in Radioinduced Effects in Developing Brain Cortex

    International Nuclear Information System (INIS)

    Nowadays, prenatal exposure is a very important topic in radiopathology.Unfortunately, pregnant women have been sometimes exposed or have to expose to ionising radiation, for example, during a medical treatment.There are lots of studies made by the International Commission of Radiation Protection (ICRP) about the effects of ionising radiation and the consequences that are suffered by the exposed foetus.Hence, it has been argued that developing mammalian brain is substantially more susceptible to teratogenic insult than most other embryonic and foetal structures.Presumably, this reflects its architectural complexity, its long developmental period, the vulnerability of the undifferentiated neural cell and the inability of the brain to replace lost neurones.Furthermore, there is abundant information on the biological effects caused by prenatal exposure of mammals to ionising radiation.Only two conspicuous effects on brain growth and development have emerged thus far in the study of atomic bomb survivors exposed prenatally in Hiroshima and Nagasaki.These are some cases of severe mental retardation and some of small head size without apparent metal retardation. Additionally, groups within the survivors have shown significantly reduced IQ scores.This increase would be dose-related and, if the shift of IQ had no clear dose threshold, might, in turn, show no threshold.Besides, it has been studied that ionising radiation implies molecular ionisation and excitation in the biological systems.When radiation has a high linear transfer energy (LET) damage may be produce trough energy absorbed directly by the target molecule (direct mechanism).However, when radiation has a low LET (like γ and X radiation), and without forgetting that biological systems are basically aqueous, damage may be produce trough generation of species highly reactive (like free radicals and reactive oxygen species - ROS) by molecules of water which has adsorbed energy radiation (indirect mechanism

  6. Interaction of D-LSD with binding sites in brain: a study in vivo and in vitro

    International Nuclear Information System (INIS)

    The localization of [3H]-d-lysergic acid diethylamide ([3H]LSD) binding sites in the mouse brain was compared in vivo and in vitro. Radioautography of brain sections incubated with [3H]LSD in vitro revealed substantial specific [3H]LSD binding in cortical layers III-IV and areas CA1 and dentate gyrus in hippocampus. In contrast, in brain sections from animals that received [3H]LSD in vivo, binding in hippocampus was scant and diffuse, although the pattern of labeling in cortex was similar to that seen in vitro. The low specific binding in hippocampus relative to cortex was confirmed by homogenate filtration studies of brain areas from mice that received injections of [3H]LSD. Time-course studies established that peak specific binding at ten minutes was the same in cortex and hippocampus. At all times, binding in hippocampus was about one-third of that in cortex; in contrast, the concentration of free [3H]LSD did not vary between regions. This finding was unexpected, because binding studies in vitro in membrane preparations indicated that the density and affinity of [3H]LSD binding sites were similar in both brain regions. Saturation binding studies in vivo showed that the lower amount of [3H]LSD binding in hippocampus was attributable to a lower density of sites labeled by [3H]LSD. The pharmacological identify of [3H]LSD binding sites in vivo may be relevant to the hallucinogenic properties of LSD and of other related hallucinogens

  7. Mnemonic convergence in the human hippocampus

    Science.gov (United States)

    Backus, Alexander R.; Bosch, Sander E.; Ekman, Matthias; Grabovetsky, Alejandro Vicente; Doeller, Christian F.

    2016-01-01

    The ability to form associations between a multitude of events is the hallmark of episodic memory. Computational models have espoused the importance of the hippocampus as convergence zone, binding different aspects of an episode into a coherent representation, by integrating information from multiple brain regions. However, evidence for this long-held hypothesis is limited, since previous work has largely focused on representational and network properties of the hippocampus in isolation. Here we identify the hippocampus as mnemonic convergence zone, using a combination of multivariate pattern and graph-theoretical network analyses of functional magnetic resonance imaging data from humans performing an associative memory task. We observe overlap of conjunctive coding and hub-like network attributes in the hippocampus. These results provide evidence for mnemonic convergence in the hippocampus, underlying the integration of distributed information into episodic memory representations. PMID:27325442

  8. The activities of six exo-and endopeptidases in the substantia nigra, neostriatum, and cortex of the rat brain.

    Science.gov (United States)

    Gallegos, M E; Zannatha, M M; Osornio, E G; Sánchez, A S; Posadas del rio, F A

    1999-12-01

    We determined the enzymatic activity and crude subcellular distribution of four exopeptidases: Dipeptidylaminopeptidase IV (DAP-IV), Alanyl aminopeptidase (AAP), Prolyl aminopeptidase (PAP) and gamma-Glutamyl transpeptidase (gammaGTP), and two endopeptidases: Postproline endopeptidase (PEP) and "Trypsin-like" peptidase ("T-L" P) in pars compacta (SNPC) and pars reticulata (SNPR) of substantia nigra, caudate-putamen (CAU) and cerebral cortex (CC) of the rat brain. We found: 1) DAP-IV activity is comparatively higher in SNPC and it is equally distributed in the postmitochondrial precipitate (PR) and supernatant (SN) fractions of SNPC, CAU and CC but higher in the SN from SNPR. 2) CC shows the highest activity of AAP and its activity is mainly located in the SN from all areas. 3) The activity of PAP is comparatively higher in SNPC and it is exclusively located in the SN from all areas. 4) gammaGTP activity is similar in all areas but its predominance is in the SN for SNPC and SNPR, and in the PR for CAU and CC. 5) CAU has higher PEP activity (higher in the PR) than CC (higher in the SN); no activity is detected in the substantia nigra. 6) The activity of a "Trypsin-like" peptidase is the highest in SNPC and SNPR; this activity have some predominance in the SN and higher predominance in the same fraction from CAU and CC. PMID:10591406

  9. The Role of Hippocampus in the Pathophysiology of Depression

    Directory of Open Access Journals (Sweden)

    Özlem Donat Eker

    2009-06-01

    Full Text Available Hippocampus, as a part of the limbic cortex, has a variety of functions ranging from mating behavior to memory besides its role in the regulation of emotions. The hippocampus has reciprocal interactions of with other brain regions which act in the pathophysiology of major depressive disorder (MDD. Moreover, since the hippocampus is a scene for the neurogenesis, which can be seen as a response to antidepressant treatment, the hippocampus became a focus of attention in neuroimaging studies of MDD. It has been shown that brain derived neurotrophic factor (BDNF, that is responsible from the neurogenesis, is associated with the response to the antidepressants and antidepressant drugs are ineffective if neurogenesis is hindered.Hippocampal atrophy is expected with the decrease of neurogenesis as a result of the lower BDNF levels with the deleterious effects of glucocorticoids in depression. Recurrent and severe depression seems to cause such a volume reduction though first episode MDD subjects do not differ from healthy individuals in respect to their hippocampal volumes (HCVs measured by magnetic resonance imaging methods. One may argue regarding these findings that the atrophy in the hippocampus may be observed in the long term and the decrease in BDNF levels may predispose the volume reduction. Although it has been postulated that smaller HCV as a result of genetic and environmental factors and prior to the illness, may cause a vulnerability to MDD, sufficient evidence has not been accumulated yet and the view that HCV loss develops as depression progresses is widely accepted. Findings that serum BDNF (sBDNF is lower in MDD patients though HCVs of patients do not differ from healthy individuals and the positive correlation of sBDNF with HCV seen only in the patient group support this view. It can be assumed that depressed patients have sensitivity for the fluctuations in BDNF levels. Follow-up studies which consider effects of hipotalamo

  10. Propofol-Induced Frontal Cortex Disconnection: A Study of Resting-State Networks, Total Brain Connectivity, and Mean BOLD Signal Oscillation Frequencies.

    Science.gov (United States)

    Guldenmund, Pieter; Gantner, Ithabi S; Baquero, Katherine; Das, Tushar; Demertzi, Athena; Boveroux, Pierre; Bonhomme, Vincent; Vanhaudenhuyse, Audrey; Bruno, Marie-Aurélie; Gosseries, Olivia; Noirhomme, Quentin; Kirsch, Muriëlle; Boly, Mélanie; Owen, Adrian M; Laureys, Steven; Gómez, Francisco; Soddu, Andrea

    2016-04-01

    Propofol is one of the most commonly used anesthetics in the world, but much remains unknown about the mechanisms by which it induces loss of consciousness. In this resting-state functional magnetic resonance imaging study, we examined qualitative and quantitative changes of resting-state networks (RSNs), total brain connectivity, and mean oscillation frequencies of the regional blood oxygenation level-dependent (BOLD) signal, associated with propofol-induced mild sedation and loss of responsiveness in healthy subjects. We found that detectability of RSNs diminished significantly with loss of responsiveness, and total brain connectivity decreased strongly in the frontal cortex, which was associated with increased mean oscillation frequencies of the BOLD signal. Our results suggest a pivotal role of the frontal cortex in propofol-induced loss of responsiveness. PMID:26650183

  11. Effect of hyperbaric oxygenation on mitochondrial function of neuronal cells in the cortex of neonatal rats after hypoxic-ischemic brain damage

    OpenAIRE

    Yang, L.; Hei, M.Y.; Dai, J.J.; Hu, N.; Xiang, X.Y.

    2016-01-01

    The timing and mechanisms of protection by hyperbaric oxygenation (HBO) in hypoxic-ischemic brain damage (HIBD) have only been partially elucidated. We monitored the effect of HBO on the mitochondrial function of neuronal cells in the cerebral cortex of neonatal rats after HIBD. Neonatal Sprague-Dawley rats (total of 360 of both genders) were randomly divided into normal control, HIBD, and HIBD+HBO groups. The HBO treatment began immediately after hypoxia-ischemia (HI) and continued once a da...

  12. Proteomic analysis of post-nuclear supernatant fraction and percoll-purified membranes prepared from brain cortex of rats exposed to increasing doses of morphine

    Czech Academy of Sciences Publication Activity Database

    Ujčíková, Hana; Eckhardt, Adam; Kagan, Dmytro; Roubalová, Lenka; Svoboda, Petr

    2014-01-01

    Roč. 12, Feb 14 (2014), s. 11. ISSN 1477-5956 R&D Projects: GA ČR(CZ) GAP207/12/0919; GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : morphine * long-term exposure * rat brain cortex * isolated plasma membranes * post-nuclear supernatant * 2D electrophoresis Subject RIV: CE - Biochemistry Impact factor: 1.725, year: 2014

  13. HPLC determination of brain biogenic amines following treatment with bispyridinium aldoxime K203.

    Science.gov (United States)

    Hashemi, F; Laufer, R; Szegi, P; Csomor, V; Kalász, H; Tekes, Kornélia

    2014-03-01

    Effect of a new acetylcholine-esterase reactivator, K203 as a new potential antidote in organophosphate intoxications was studied on dopamine (DA), homovanillic acid (HVA), serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) levels in seven brain regions (cerebellum, spinal cord, hippocampus, hypothalamus, striatum, medulla oblongata and frontal cortex) of rats by an optimized and validated HPLC method. No significant change in brain level of these neurotransmitters was found either 15 or 60 min following treatment. However, when 5-HIAA/5-HT ratios were calculated as measure of turnover, significant decreases were found in the cerebellum, hippocampus, hypothalamus and the frontal cortex 15 min following K203 administration, but after 60 min only in the frontal cortex. PMID:24631794

  14. Phenotypic Heterogeneity and Plasticity of Isocortical and Hippocampal Astrocytes in the Human Brain

    OpenAIRE

    Sosunov, Alexander A.; Wu, Xiaoping; Tsankova, Nadejda M.; Guilfoyle, Eileen; Guy M McKhann; Goldman, James E.

    2014-01-01

    To examine the diversity of astrocytes in the human brain, we immunostained surgical specimens of temporal cortex and hippocampus and autopsy brains for CD44, a plasma membrane protein and extracellular matrix receptor. CD44 antibodies outline the details of astrocyte morphology to a degree not possible with glial fibrillary acidic protein (GFAP) antibodies. CD44+ astrocytes could be subdivided into two groups. First, CD44+ astrocytes with long processes were consistently found in the subpial...

  15. Downstream targets of methyl CpG binding protein 2 and their abnormal expression in the frontal cortex of the human Rett syndrome brain

    Directory of Open Access Journals (Sweden)

    Minchenko Dimitri

    2010-04-01

    Full Text Available Abstract Background The Rett Syndrome (RTT brain displays regional histopathology and volumetric reduction, with frontal cortex showing such abnormalities, whereas the occipital cortex is relatively less affected. Results Using microarrays and quantitative PCR, the mRNA expression profiles of these two neuroanatomical regions were compared in postmortem brain tissue from RTT patients and normal controls. A subset of genes was differentially expressed in the frontal cortex of RTT brains, some of which are known to be associated with neurological disorders (clusterin and cytochrome c oxidase subunit 1 or are involved in synaptic vesicle cycling (dynamin 1. RNAi-mediated knockdown of MeCP2 in vitro, followed by further expression analysis demonstrated that the same direction of abnormal expression was recapitulated with MeCP2 knockdown, which for cytochrome c oxidase subunit 1 was associated with a functional respiratory chain defect. Chromatin immunoprecipitation (ChIP analysis showed that MeCP2 associated with the promoter regions of some of these genes suggesting that loss of MeCP2 function may be responsible for their overexpression. Conclusions This study has shed more light on the subset of aberrantly expressed genes that result from MECP2 mutations. The mitochondrion has long been implicated in the pathogenesis of RTT, however it has not been at the forefront of RTT research interest since the discovery of MECP2 mutations. The functional consequence of the underexpression of cytochrome c oxidase subunit 1 indicates that this is an area that should be revisited.

  16. Correlation of brain-derived neurotrophic factor to cognitive impairment following traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    Dezhi Kang; Zhang Guo

    2008-01-01

    BACKGROUND: In vitro and in vivo studies have confirmed that brain-derived neurotrophic factor (BDNF) can promote survival and differentiation of cholinergic, dopaminergic and motor neurons, and axonal regeneration. BDNF has neuroprotective effects on the nervous system. OBJECTIVE: To explore changes in BDNF expression and cognitive function in rats after brain injury DESIGN, TIME AND SETTING: The neuropathology experiment was performed at the Second Research Room, Department of Neurosurgery, Fujian Medical University (China) from July 2007 to July 2008. MATERIALS: A total of 72 healthy, male, Sprague Dawley, rats were selected for this study. METHODS: Rat models of mild and moderate traumatic brain injury were created by percussion, according to Feeney's method (n = 24, each group). A bone window was made in rats from the sham operation group (n = 24), but no attack was conducted. MAIN OUTCOME MEASURES: At days 1,2, 4 and 7 following injury, BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was examined by immunohistochemistry (streptavidin-biotin-peroxidase complex method). Changes in rat cognitive function were assessed by the walking test, balance-beam test and memory function detection. RESULTS: Cognitive impairment was aggravated at day 2, and recovered to normal at days 3 and 7 in rats from the mild and moderate traumatic brain injury groups. BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain was increased at 1 day, decreased at day 2, and then gradually increased in the mild and moderate traumatic brain injury groups. BDNF expression was greater in rats from the moderate traumatic brain injury group than in the sham operation and mild traumatic brain injury groups (P < 0.05). CONCLUSION: BDNF expression in the rat frontal lobe cortex, hippocampus and basal forebrain is correlated to cognitive impairment after traumatic brain injury. BDNF has a protective effect on cognitive function in rats

  17. Expression of c-fos in Rat Brain as a Prelude Marker of Central Nervous System Injury in Response to Methylmercury-stimulation

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective To probe into the prelude marker of central nervous system injury in response to methyl mercury chloride (MMC) stimulation and the signal transduction molecular mechanism of injury in rat brain induced by MMC. Methods The expression of c-fos mRNA in brain and the expression of c-FOS protein in cortex, hippocampus and ependyma were observed using reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemical methods. The control group was injected with physiological saline of 0.9%, while the concentrations for the exposure groups were 0.05 and 0.5,5 mg/kg MMC respectively, and the sampling times points were 20, 60, 240, 1440 min. Results The expression of c-FOS protein in cortex and hippocampus increased significantly, the accumulation of mercury in the brain induced by 0.05 mg/Kg MMC for 20 min had no significant difference compared with the control group. The mean value was 0.0044 mg/Kg, while the protein c-FOS expression had significant difference compared with the control group (P<0.01). More sensitive expression occurred in hippocampus and cortex, but not in ependyma. Conclusion The expression of c-FOS protein in cortex and hippocampus can predict the neurotoxicity of MMC in the early time, and immediately early gene (IEG) c-fos participates in the process of brain injury induced by MMC.

  18. Metabolic demand stimulates CREB signaling in the limbic cortex: implication for the induction of hippocampal synaptic plasticity by intrinsic stimulus for survival

    Directory of Open Access Journals (Sweden)

    Nelly M Estrada

    2009-06-01

    Full Text Available Caloric restriction by fasting has been implicated to facilitate synaptic plasticity and promote contextual learning. However, cellular and molecular mechanisms underlying the effect of fasting on memory consolidation are not completely understood. We hypothesized that fasting-induced enhancement of synaptic plasticity was mediated by the increased signaling mediated by CREB (c-AMP response element binding protein, an important nuclear protein and the transcription factor that is involved in the consolidation of memories in the hippocampus. In the in vivo rat model of 18 h fasting, the expression of phosphorylated CREB (pCREB was examined using anti-phospho-CREB (Ser133 in cardially-perfused and cryo-sectioned rat brain specimens. When compared with control animals, the hippocampus exhibited up to a two-fold of increase in pCREB expression in fasted animals. The piriform cortex, the entorhinal cortex, and the cortico-amygdala transitional zone also significantly increased immunoreactivities to pCREB. In contrast, the amygdala did not show any change in the magnitude of pCREB expression in response to fasting. The arcuate nucleus in the medial hypothalamus, which was previously reported to up-regulate CREB phosphorylation during fasting of up to 48 h, was also strongly immunoreactive and provided a positive control in the present study. Our findings demonstrate a metabolic demand not only stimulates cAMP-dependent signaling cascades in the hypothalamus, but also signals to various limbic brain regions including the hippocampus by activating the CREB signaling mechanism. The hippocampus is a primary brain structure for learning and memory. It receives hypothalamic and arcuate projections directly from the fornix. The hippocampus is also situated centrally for functional interactions with other limbic cortexes by establishing reciprocal synaptic connections. We suggest that hippocampal neurons and those in the surrounding limbic cortexes are

  19. Hippocampus in health and disease: An overview

    Directory of Open Access Journals (Sweden)

    Kuljeet Singh Anand

    2012-01-01

    Full Text Available Hippocampus is a complex brain structure embedded deep into temporal lobe. It has a major role in learning and memory. It is a plastic and vulnerable structure that gets damaged by a variety of stimuli. Studies have shown that it also gets affected in a variety of neurological and psychiatric disorders. In last decade or so, lot has been learnt about conditions that affect hippocampus and produce changes ranging from molecules to morphology. Progresses in radiological delineation, electrophysiology, and histochemical characterization have made it possible to study this archicerebral structure in greater detail. Present paper attempts to give an overview of hippocampus, both in health and diseases.

  20. Proteomic profiling of brain cortex tissues in a Tau transgenic mouse model of Alzheimer’s disease

    International Nuclear Information System (INIS)

    Highlights: ► A transgenic mouse model expressing NSE-htau23 was used. ► 2D-gel electrophoresis to analyze the cortex proteins of transgenic mice was used. ► Differentially expressed spots in different stages of AD were identified. ► GSTP1 and CAII were downregulated with the progression of AD. ► SCRN1 and ATP6VE1 were up regulated and down regulated differentially. -- Abstract: Alzheimer’s disease (AD) involves regionalized neuronal death, synaptic loss, and an accumulation of intracellular neurofibrillary tangles and extracellular senile plaques. Although there have been numerous studies on tau proteins and AD in various stages of neurodegenerative disease pathology, the relationship between tau and AD is not yet fully understood. A transgenic mouse model expressing neuron-specific enolase (NSE)-controlled human wild-type tau (NSE-htau23), which displays some of the typical Alzheimer-associated pathological features, was used to analyze the brain proteome associated with tau tangle deposition. Two-dimensional electrophoresis was performed to compare the cortex proteins of transgenic mice (6- and 12-month-old) with those of control mice. Differentially expressed spots in different stages of AD were identified with ESI-Q-TOF (electrospray ionization quadruple time-of-flight) mass spectrometry and liquid chromatography/tandem mass spectrometry. Among the identified proteins, glutathione S-transferase P 1 (GSTP1) and carbonic anhydrase II (CAII) were down-regulated with the progression of AD, and secerin-1 (SCRN1) and V-type proton ATPase subunit E 1 (ATP6VE1) were up-regulated only in the early stages, and down-regulated in the later stages of AD. The proteins, which were further confirmed by RT-PCR at the mRNA level and with western blotting at the protein level, are expected to be good candidates as drug targets for AD. The study of up- and down-regulation of proteins during the progression of AD helps to explain the mechanisms associated with neuronal

  1. Proteomic profiling of brain cortex tissues in a Tau transgenic mouse model of Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Seong-Hun; Jung, In-Soo; Han, Gi-Yeon; Kim, Nam-Hee; Kim, Hyun-Jung [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of); Kim, Chan-Wha, E-mail: cwkim@korea.ac.kr [School of Life Sciences and Biotechnology, Korea University, Seoul 136-701 (Korea, Republic of)

    2013-01-11

    Highlights: Black-Right-Pointing-Pointer A transgenic mouse model expressing NSE-htau23 was used. Black-Right-Pointing-Pointer 2D-gel electrophoresis to analyze the cortex proteins of transgenic mice was used. Black-Right-Pointing-Pointer Differentially expressed spots in different stages of AD were identified. Black-Right-Pointing-Pointer GSTP1 and CAII were downregulated with the progression of AD. Black-Right-Pointing-Pointer SCRN1 and ATP6VE1 were up regulated and down regulated differentially. -- Abstract: Alzheimer's disease (AD) involves regionalized neuronal death, synaptic loss, and an accumulation of intracellular neurofibrillary tangles and extracellular senile plaques. Although there have been numerous studies on tau proteins and AD in various stages of neurodegenerative disease pathology, the relationship between tau and AD is not yet fully understood. A transgenic mouse model expressing neuron-specific enolase (NSE)-controlled human wild-type tau (NSE-htau23), which displays some of the typical Alzheimer-associated pathological features, was used to analyze the brain proteome associated with tau tangle deposition. Two-dimensional electrophoresis was performed to compare the cortex proteins of transgenic mice (6- and 12-month-old) with those of control mice. Differentially expressed spots in different stages of AD were identified with ESI-Q-TOF (electrospray ionization quadruple time-of-flight) mass spectrometry and liquid chromatography/tandem mass spectrometry. Among the identified proteins, glutathione S-transferase P 1 (GSTP1) and carbonic anhydrase II (CAII) were down-regulated with the progression of AD, and secerin-1 (SCRN1) and V-type proton ATPase subunit E 1 (ATP6VE1) were up-regulated only in the early stages, and down-regulated in the later stages of AD. The proteins, which were further confirmed by RT-PCR at the mRNA level and with western blotting at the protein level, are expected to be good candidates as drug targets for AD. The

  2. Dysfunction of mitochondrial dynamics in the brains of scrapie-infected mice

    International Nuclear Information System (INIS)

    Highlights: • Mfn1 and Fis1 are significantly increased in the hippocampal region of the ME7 prion-infected brain, whereas Dlp1 is significantly decreased in the infected brain. • Dlp1 is significantly decreased in the cytosolic fraction of the hippocampus in the infected brain. • Neuronal mitochondria in the prion-infected brains are enlarged and swollen compared to those of control brains. • There are significantly fewer mitochondria in the ME7-infected brain compared to the number in control brain. - Abstract: Mitochondrial dysfunction is a common and prominent feature of many neurodegenerative diseases, including prion diseases; it is induced by oxidative stress in scrapie-infected animal models. In previous studies, we found swelling and dysfunction of mitochondria in the brains of scrapie-infected mice compared to brains of controls, but the mechanisms underlying mitochondrial dysfunction remain unclear. To examine whether the dysregulation of mitochondrial proteins is related to the mitochondrial dysfunction associated with prion disease, we investigated the expression patterns of mitochondrial fusion and fission proteins in the brains of ME7 prion-infected mice. Immunoblot analysis revealed that Mfn1 was up-regulated in both whole brain and specific brain regions, including the cerebral cortex and hippocampus, of ME7-infected mice compared to controls. Additionally, expression levels of Fis1 and Mfn2 were elevated in the hippocampus and the striatum, respectively, of the ME7-infected brain. In contrast, Dlp1 expression was significantly reduced in the hippocampus in the ME7-infected brain, particularly in the cytosolic fraction. Finally, we observed abnormal mitochondrial enlargement and histopathological change in the hippocampus of the ME7-infected brain. These observations suggest that the mitochondrial dysfunction, which is presumably caused by the dysregulation of mitochondrial fusion and fission proteins, may contribute to the

  3. Dysfunction of mitochondrial dynamics in the brains of scrapie-infected mice

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hong-Seok [Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702 (Korea, Republic of); Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Choi, Yeong-Gon; Shin, Hae-Young; Oh, Jae-Min [Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Park, Jeong-Ho [Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702 (Korea, Republic of); Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Kim, Jae-Il [Department of Food Science and Nutrition, Pukyong National University, 599-1 Daeyeon-3-dong, Nam-gu, Busan 608-737 (Korea, Republic of); Carp, Richard I. [New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY 10314 (United States); Choi, Eun-Kyoung, E-mail: ekchoi@hallym.ac.kr [Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of); Kim, Yong-Sun, E-mail: yskim@hallym.ac.kr [Department of Microbiology, College of Medicine, Hallym University, 1 Okcheon-dong, Chuncheon, Gangwon-do 200-702 (Korea, Republic of); Ilsong Institute of Life Science, Hallym University, 1605-4 Gwanyang-dong, Dongan-gu, Anyang, Gyeonggi-do 431-060 (Korea, Republic of)

    2014-05-30

    Highlights: • Mfn1 and Fis1 are significantly increased in the hippocampal region of the ME7 prion-infected brain, whereas Dlp1 is significantly decreased in the infected brain. • Dlp1 is significantly decreased in the cytosolic fraction of the hippocampus in the infected brain. • Neuronal mitochondria in the prion-infected brains are enlarged and swollen compared to those of control brains. • There are significantly fewer mitochondria in the ME7-infected brain compared to the number in control brain. - Abstract: Mitochondrial dysfunction is a common and prominent feature of many neurodegenerative diseases, including prion diseases; it is induced by oxidative stress in scrapie-infected animal models. In previous studies, we found swelling and dysfunction of mitochondria in the brains of scrapie-infected mice compared to brains of controls, but the mechanisms underlying mitochondrial dysfunction remain unclear. To examine whether the dysregulation of mitochondrial proteins is related to the mitochondrial dysfunction associated with prion disease, we investigated the expression patterns of mitochondrial fusion and fission proteins in the brains of ME7 prion-infected mice. Immunoblot analysis revealed that Mfn1 was up-regulated in both whole brain and specific brain regions, including the cerebral cortex and hippocampus, of ME7-infected mice compared to controls. Additionally, expression levels of Fis1 and Mfn2 were elevated in the hippocampus and the striatum, respectively, of the ME7-infected brain. In contrast, Dlp1 expression was significantly reduced in the hippocampus in the ME7-infected brain, particularly in the cytosolic fraction. Finally, we observed abnormal mitochondrial enlargement and histopathological change in the hippocampus of the ME7-infected brain. These observations suggest that the mitochondrial dysfunction, which is presumably caused by the dysregulation of mitochondrial fusion and fission proteins, may contribute to the

  4. The occurrence of diffuse axonal injury in the brain:associated with the accumulation and clearance of myelin debris

    Institute of Scientific and Technical Information of China (English)

    Liang Wen; Jun Xu; Tianxiang Zhan; Hao Wang; Xin Huang; Wenchao Liu; Xiaofeng Yang; Renya Zhan

    2014-01-01

    The accumulation of myelin debris may be a major contributor to the inlfammatory response after diffuse axonal injury. In this study, we examined the accumulation and clearance of myelin debris in a rat model of diffuse axonal injury. Oil Red O staining was performed on sections from the cerebral cortex, hippocampus and brain stem to identify the myelin debris. Seven days after diffuse axonal injury, many Oil Red O-stained particles were observed in the cerebral cortex, hippocampus and brain stem. In the cerebral cortex and hippocampus, the amount of myelin debris peaked at 14 days after injury, and decreased signiifcantly at 28 days. In the brain stem, the amount of myelin debris peaked at 7 days after injury, and decreased signiifcantly at 14 and 28 days. In the cortex and hippocampus, some myelin debris could still be observed at 28 days after diffuse axonal injury. Our ifndings suggest that myelin debris may persist in the rat central ner-vous system after diffuse axonal injury, which would hinder recovery.

  5. Brain Basics

    Medline Plus

    Full Text Available ... medications could reduce the amount of trial and error and frustration that many people with depression experience ... early brain development, and may also assist in learning and memory. hippocampus —A portion of the brain ...

  6. Cognitive improvement following transvenous adipose-derived mesenchymal stem cell transplantation in a rat model of traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    Dongfei Li; Chun Yang; Rongmei Qu; Huiying Yang; Meichun Yu; Hui Tao; Jingxing Dai; Lin Yuan

    2011-01-01

    The effects of adipose-derived mesenchymal stem cell (ADMSC) transplantation for the repair of traumatic brain injury remain poorly understood. The present study observed neurological functional changes in a rat model of traumatic brain injury following ADMSC transplantation via the tail vein.Cell transplants were observed in injured cerebral cortex, and expression of brain-derived nerve growth factor was significantly increased in the injured hippocampus following transplantation. Results demonstrated that transvenous ADMSC transplants migrated to the injured cerebral cortex and significantly improved cognitive function.

  7. Distribution of beta-amyloid in the canine brain.

    Science.gov (United States)

    Hou, Y; White, R G; Bobik, M; Marks, J S; Russell, M J

    1997-03-01

    The distribution of amyloid-beta protein (A beta) in the canine brain was demonstrated by immunochemistry on serially sectioned tissues from 10 aged mixed breed dogs. Summation of quantitative data and relegation to anatomical sites for the 10 dogs showed A beta to be widely distributed in the cortex and hippocampus while completely absent in the brain stem and cerebellum. The highest density of A beta was in the dentate gyrus of the hippocampus. Cortical areas exhibiting the greatest A beta deposition were the posterior and medial suprasylvius gyrus and the proreus gyrus of the frontal lobe. Unlike humans the canine entorhinal cortex, amygdala, basal ganglia and olfactory bulbs were rarely affected. This suggested that the highly developed olfactory pathways of the canine are generally spared from A beta deposition. PMID:9141082

  8. [Functional characteristics of the hippocampus after switching off visual afferentation in early ontogenesis].

    Science.gov (United States)

    Nikitina, G M; Boravova, A I

    1977-01-01

    EEG reactions to afferent stimuli and the driving responses (DR) to photic flickering with 1-15 sec frequency were studied in different brain structures of rabbits lacking visual experience (from the 8th to the 23rd and from the 57th to the 90th day of life). The orienting reaction in the first few days of the light regime is characterized by enhanced motor and respiratory components and is not extinguished for a long time when the stimulus is repeated. It is attended with theta-rhythm in the hippocampus EEG and desynchronized activity in the neocortical areas. DR is characterized by spatial-temporal dissociation; its development is markedly retarded in the cortical projection zone of the visual system, and of the archicortex structures, in the dentate fascia, as compared with the hippocampus proper, the midbrain reticular formation and the auditory cortex. The DR index equals the level of that of the control animals after nine to twelve days of their life in the light. The results obtained attest that the observed differences in the changes of the functional characteristics of the hippocampus and other brain structures depend on the mode of the central organization of the reaction, whose correlate is the studied EEG-parameter. PMID:899266

  9. Brain fat embolism

    International Nuclear Information System (INIS)

    Recently CT and MR imaging have demonstrated that cerebral edema is present in cases of fat embolism syndrome. To simulate this we have made a model of brain-fat embolism in rats under MR imaging. In 20 rats, we did intravenous injection of heparinized blood, 1.5 ml·kg-1 taken from femoral bone marrow cavity. Twenty four hours after the injection, we examined the MR images (1.5 tesla, spin-echo method) of brains and histologic findings of brains and lungs were obtained. In 5 of 20 rats, high signal intensity on T2-weighted images and low signal intensity on T1-weighted images were observed in the area of the unilateral cerebral cortex or hippocampus. These findings showed edema of the brains. They disappeared, however, one week later. Histologic examinations showed massive micro-fat emboli in capillaries of the deep cerebral cortex and substantia nigra, but no edematous findings of the brain were revealed in HE staining. In pulmonary arteries, we also found large fat emboli. We conclude that our model is a useful one for the study of brain fat embolism. (author)

  10. PET study of cholinergic system in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Shinotoh, Hitoshi [Chiba Univ. (Japan). School of Medicine

    1999-01-01

    Recently, we have developed a method to measure acetylcholinesterase (AChE) activity, a functional marker for cholinergic system, by positron emission tomography (PET) and carbon-11 labeled N-methyl-4-piperidyl acetate. Kinetic analysis of the radioactivity in the brain and the plasma yielded a rate constant ``k 3`` as an index of AChE activity. The ratios for the k 3 values for the cerebral cortex/thalamus/cerebellum/striatum found in healthy participants were 1/ 3/ 8/ 10, respectively, corresponding well with AChE activity ratios in the brain at necropsy (1/ 3/ 8/ 38), except for the striatum. In 23 healthy volunteers (age range: 24-89 years), there was no age-related decline of k 3 values in the cerebral cortex, suggesting AChE activity is preserved in aged cerebral cortex. In 11 patients with Alzheimer`s disease, there was a significant reduction (-24%) of k 3 values in the cerebral cortex and hippocampus, suggesting a loss of ascending cholinergic system from the basal forebrain to the cerebral cortex and hippocampus. In 16 patients with Parkinson`s disease, there was a significant reduction (-18%) of k 3 values in the cerebral cortex. In 10 patients with progressive supra nuclear palsy, there was a significant reduction (-38%) of k 3 values in the thalamus. This technique is useful for investigating central cholinergic system in neuro degenerative disorders with dementia. (author)

  11. PET study of cholinergic system in the brain

    International Nuclear Information System (INIS)

    Recently, we have developed a method to measure acetylcholinesterase (AChE) activity, a functional marker for cholinergic system, by positron emission tomography (PET) and carbon-11 labeled N-methyl-4-piperidyl acetate. Kinetic analysis of the radioactivity in the brain and the plasma yielded a rate constant ''k 3'' as an index of AChE activity. The ratios for the k 3 values for the cerebral cortex/thalamus/cerebellum/striatum found in healthy participants were 1/ 3/ 8/ 10, respectively, corresponding well with AChE activity ratios in the brain at necropsy (1/ 3/ 8/ 38), except for the striatum. In 23 healthy volunteers (age range: 24-89 years), there was no age-related decline of k 3 values in the cerebral cortex, suggesting AChE activity is preserved in aged cerebral cortex. In 11 patients with Alzheimer's disease, there was a significant reduction (-24%) of k 3 values in the cerebral cortex and hippocampus, suggesting a loss of ascending cholinergic system from the basal forebrain to the cerebral cortex and hippocampus. In 16 patients with Parkinson's disease, there was a significant reduction (-18%) of k 3 values in the cerebral cortex. In 10 patients with progressive supra nuclear palsy, there was a significant reduction (-38%) of k 3 values in the thalamus. This technique is useful for investigating central cholinergic system in neuro degenerative disorders with dementia. (author)

  12. The determination of trace metals by INAA in cortex cerebellum and putamen of human brain and in their neuromelanins

    International Nuclear Information System (INIS)

    Instrumental Neutron Activation Analysis (INAA) was used for all the measurements. Irradiations were performed at the Triga Mark II (General Atomic - USA) research reactor of the University of Pavia. Depending on the elements to be determined, two different irradiation procedures were followed: Short irradiations were performed in the pneumatic irradiation facility at a neutron flux of 5x1012 n x cm-2 x s-1 . Samples and standards sealed in plastic vials were irradiated for 5 minutes. Long irradiations were carried out in the central thimble facility at a nominal neutron flux of 1013 n x cm-2 x s-1. Samples and standards were sealed in quartz vials and then neutron irradiated for 40 h. For the gamma spectra evaluation HPGe (gamma -x) detectors (ORTEC - USA) coupled to computerized multichannel analysers (ORTEC ADCAM - USA) were used. The concentrations of trace elements in Cortex, Cerebellum, Putamen and in their Neuromelanins are reported. Fe is the most abundant element in tissues, followed by Zinc. The ability of NMs to sequestrate metals is well shown, being their concentrations in NMs much higher than in their respective tissues, where some of them (Hg, Mo) were not even detectable. Strong differences are shown between the different pigments in interaction with metals. NM from SN shows a higher affinity for iron than all the other pigments isolated from other brain areas; nevertheless, the tissue that contains the highest concentration of this metal is PU and not SN. These results would confirm that NM from SN plays a protective role in neurons by quenching Fenton's reaction, so far considered the cause of the pathogenesis of PD. A protective role could be played by the other pigments as well, as the concentrations of analysed elements show that they bind large amounts of potentially toxic metals different from iron. This might be explained as the need of the neurons to defend themselves from the toxicity of this metal by the development of a specific pigment

  13. Calretinin and parvalbumin immunoreactive interneurons in the retrosplenial cortex of the rat brain: Qualitative and quantitative analyses

    Czech Academy of Sciences Publication Activity Database

    Salaj, M.; Druga, Rastislav; Cerman, J.; Kubová, Hana; Barinka, F.

    2015-01-01

    Roč. 1627, Nov 19 (2015), s. 201-215. ISSN 0006-8993 R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : retrosplenial cortex * calretinin * parvalbumin * interneurons * calcium-binding proteins * perirhinal cortex Subject RIV: FH - Neurology Impact factor: 2.843, year: 2014

  14. A central role for the retrosplenial cortex in de novo environmental learning.

    Science.gov (United States)

    Auger, Stephen D; Zeidman, Peter; Maguire, Eleanor A

    2015-01-01

    With experience we become accustomed to the types of environments that we normally encounter as we navigate in the world. But how does this fundamental knowledge develop in the first place and what brain regions are involved? To examine de novo environmental learning, we created an 'alien' virtual reality world populated with landmarks of which participants had no prior experience. They learned about this environment by moving within it during functional MRI (fMRI) scanning while we tracked their evolving knowledge. Retrosplenial cortex (RSC) played a central and highly selective role by representing only the most stable, permanent features in this world. Subsequently, increased coupling was noted between RSC and hippocampus, with hippocampus then expressing knowledge of permanent landmark locations and overall environmental layout. Studying how environmental representations emerge from scratch provided a new window into the information processing underpinning the brain's navigation system, highlighting the key influence of the RSC. PMID:26284602

  15. Tyrosine depletion lowers in vivo DOPA synthesis in ventral hippocampus.

    Science.gov (United States)

    Bongiovanni, Rodolfo; Kyser, Abby N; Jaskiw, George E

    2012-12-01

    In vivo dopamine synthesis in the medial prefrontal cortex of the rat is sensitive to the availability of tyrosine. Whether other limbic cortical dopamine terminal regions are similarly tyrosine-dependent is not known. In this study we examined the effects of tyrosine depletion on dopamine synthesis and catecholamine levels in the ventral hippocampus. A tyrosine- and phenylalanine-free neutral amino acid mixture was used to lower brain tyrosine levels in rats undergoing in vivo microdialysis. In one group, NSD-1015 was included in perfusate to permit measurement of DOPA levels. In a second group, NSD-1015 was not included in perfusate so that catecholamine levels could be assayed. Tyrosine depletion significantly lowered DOPA levels in the NSD-1015 treated group and lowered DOPAC but not dopamine or noradrenaline levels in the group not exposed to NSD-1015. We conclude that while catecholamine synthesis in the ventral hippocampus declines when tyrosine availability is lowered, under basal conditions, compensatory mechanisms are able to maintain stable extracellular catecholamine levels. PMID:23022716

  16. A novel cognitive impairment mechanism that astrocytic p-connexin 43 promotes neuronic autophagy via activation of P2X7R and down-regulation of GLT-1 expression in the hippocampus following traumatic brain injury in rats.

    Science.gov (United States)

    Sun, Liqian; Gao, Junling; Zhao, Manman; Cui, Jianzhong; Li, Youxiang; Yang, Xinjian; Jing, Xiaobin; Wu, Zhongxue

    2015-09-15

    Connexin 43 (Cx43) is one of the major gap junction proteins in astrocytes. Our previous studies reported that astrocytic phosphorylated Cx43 (p-CX43) regulated neuronic autophagy levels in the rat hippocampus after traumatic brain injury (TBI). In this study, we explored the underlying molecular mechanism by which gap junctional intercellular communication influenced neuronic autophagy and therefore initiated cognitive and memory impairments after TBI. The gap junctional blocker carbenoxolone (CBX) or autophagy inhibitor 3-methyladenine (3-MA) reduced latencies, as compared to TBI rats. Similarly, CBX or 3-MA restored long-term potentiation (LTP), relative to TBI hippocampal slices. Immunoblotting analysis showed that the expression of autophagy-related gene Beclin-1 in the hippocampus post-TBI were decreased in response to treatment with CBX, the P2X7 receptor (P2X7R) antagonist Oxidized ATP (OxATP) or ceftriaxone (Cef) which increased the expression and activity of the glutamate transporter (GLT-1) in the central nervous system (CNS). Moreover, CBX or OxATP pretreatment increased GLT-1 level in the rat hippocampus after TBI. However, CBX pretreatment suppressed P2X7R expression whereas maintained P2X7 level post-TBI. Confocal images revealed that p-CX43, P2X7 and GLT-1 strongly colocalized with glial fibrillary acidic protein (GFAP). Taken together, these results implied that Cx43, might induce neuronic autophagy by activation of P2X7R and reduce the expression of GLT-1 in the hippocampus, promoting TBI-induced cognitive deficits repair. Therefore, control of this communication may be serve as therapeutic strategies for intervention against TBI. PMID:26031379

  17. Navigating the auditory scene: an expert role for the hippocampus.

    Science.gov (United States)

    Teki, Sundeep; Kumar, Sukhbinder; von Kriegstein, Katharina; Stewart, Lauren; Lyness, C Rebecca; Moore, Brian C J; Capleton, Brian; Griffiths, Timothy D

    2012-08-29

    Over a typical career piano tuners spend tens of thousands of hours exploring a specialized acoustic environment. Tuning requires accurate perception and adjustment of beats in two-note chords that serve as a navigational device to move between points in previously learned acoustic scenes. It is a two-stage process that depends on the following: first, selective listening to beats within frequency windows, and, second, the subsequent use of those beats to navigate through a complex soundscape. The neuroanatomical substrates underlying brain specialization for such fundamental organization of sound scenes are unknown. Here, we demonstrate that professional piano tuners are significantly better than controls matched for age and musical ability on a psychophysical task simulating active listening to beats within frequency windows that is based on amplitude modulation rate discrimination. Tuners show a categorical increase in gray matter volume in the right frontal operculum and right superior temporal lobe. Tuners also show a striking enhancement of gray matter volume in the anterior hippocampus, parahippocampal gyrus, and superior temporal gyrus, and an increase in white matter volume in the posterior hippocampus as a function of years of tuning experience. The relationship with gray matter volume is sensitive to years of tuning experience and starting age but not actual age or level of musicality. Our findings support a role for a core set of regions in the hippocampus and superior temporal cortex in skilled exploration of complex sound scenes in which precise sound "templates" are encoded and consolidated into memory over time in an experience-dependent manner. PMID:22933806

  18. Effect ofXl Feng capsule on expression of MRP1of hippocampus and cortex in epileptic rats induced by lithium-pilocarpine%熄风胶囊对氯化锂-匹罗卡品癫痫大鼠皮质和海马多药耐药相关蛋白1表达影响的研究

    Institute of Scientific and Technical Information of China (English)

    李新民; 任艳艳; 陈会; 路岩莉

    2012-01-01

    [目的]研究熄风胶囊对氯化锂-匹罗卡品癫痫大鼠皮质和海马多药耐药相关蛋白1( MRP1)表达的影响.[方法]1)利用氯化锂-匹罗卡品制作癫痫大鼠模型.2)实验大鼠按随机数字表法随机分为正常组、模型组、熄风胶囊高剂量组(熄高组)、熄风胶囊中剂量组(熄中组)、熄风胶囊低剂量组(熄低组)、熄风胶囊大剂量+卡马西平(CBZ)组(联高组)、熄风胶囊大剂量+CBZ1/2剂量(联低组)和CBZ组.3)通过Western-blot方法检测癫痫大鼠海马和皮质MRP1的表达程度.[结果]实验结果显示治疗组与模型组之间比较差异有统计学意义(P<0.05).[结论]熄风胶囊能有效抑制MRP1的过度表达.%[Objective] To sludy the intervention effect of Xi Feng capsule on medicine-related protein 1 (MRP1) of hippocampus and cortex in epileptic rats induced by Lithium-Pilocarpine. [Methods] 1 (Epilepsy was duplicated in rats with lithium-pilocarpine chemical ignition. 2)A1I the experimental rats were randomly divided into eight groups: normal control group, model group, Xi Feng intervention group(Xi Feng high-dose group), Xi Feng intervention group(Xi Feng middle-dose group), Xi Feng intervention group(Xi Feng low-dose group), Xi Feng high-dose+CBZ group, Xi Feng high-dose+CBZ 1/2 dose group, CBZ group. 3)The expression of MKP1 of hippocampus and cortex in epileptic rats was observed by Western-blot. [Results] The result of Westem-blol method suggested that there was a significant difference between intervention group of Xi Feng capsule and model group (P<0.05). [Conclusion] Xi Feng capsule single and combined with CBZ could efficiently depress the overexpression of MRP1 of the hippocampus and cortex in epileptic rats induced by Lithium-Pilocarpine.

  19. Ⅱ型糖尿病兔大脑皮质和海马神经元的神经丝蛋白表达%THE EXPRESSION OF NEUROFILAMENT PROTEINS IN CEREBRAL CORTEX AND HIPPOCAMPUS IN TYPE Ⅱ DIABETES IN RABBITS

    Institute of Scientific and Technical Information of China (English)

    马志健; 刘正清; 张秋菊; 蔡维君; 李明波; 刘小丹; 陈二云

    2002-01-01

    Objective:To investigate the morphological changes of the neuronal neurites in diabetic rabbit brain. Methods: Twenty- four New Zealand White rabbits were divided into 2 groups: control group and type Ⅱ diabetic group induced by high - carbohydrate and high- fat diet. The levels of blood sugar and insulin were detected at week 0(w0), w4, w8, w13, w18, w23 and w28. Brain tissue was stained by Nissl staining and immunolistochemistry with a specific antibody to neurofilament proteins. Result: In diabetic rabbits, the amount of large pyramidal neuron was significantly reduced, and neuronal neurites became swollen, whorled, disrupted and changed in caliber. In hippocampus CA1 region neurofilament staining was very weak. Conclusion: Neurotoxicity of chronic hyperglycemia might be relevant to vascular chronic complications, which affected the expression of NF and led to neurophysiological and structural changes in the brain of rabbits with type Ⅱ diabetes.

  20. Intra-Amniotic LPS Induced Region-Specific Changes in Presynaptic Bouton Densities in the Ovine Fetal Brain

    Directory of Open Access Journals (Sweden)

    Eveline Strackx

    2015-01-01

    Full Text Available Rationale. Chorioamnionitis has been associated with increased risk for fetal brain damage. Although, it is now accepted that synaptic dysfunction might be responsible for functional deficits, synaptic densities/numbers after a fetal inflammatory challenge have not been studied in different regions yet. Therefore, we tested in this study the hypothesis that LPS-induced chorioamnionitis caused profound changes in synaptic densities in different regions of the fetal sheep brain. Material and Methods. Chorioamnionitis was induced by a 10 mg intra-amniotic LPS injection at two different exposure intervals. The fetal brain was studied at 125 days of gestation (term = 150 days either 2 (LPS2D group or 14 days (LPS14D group after LPS or saline injection (control group. Synaptophysin immunohistochemistry was used to quantify the presynaptic density in layers 2-3 and 5-6 of the motor cortex, somatosensory cortex, entorhinal cortex, and piriforme cortex, in the nucleus caudatus and putamen and in CA1/2, CA3, and dentate gyrus of the hippocampus. Results. There was a significant reduction in presynaptic bouton densities in layers 2-3 and 5-6 of the motor cortex and in layers 2-3 of the entorhinal and the somatosensory cortex, in the nucleus caudate and putamen and the CA1/2 and CA3 of the hippocampus in the LPS2D compared to control animals. Only in the motor cortex and putamen, the presynaptic density was significantly decreased in the LPS14 D compared to the control group. No changes were found in the dentate gyrus of the hippocampus and the piriforme cortex. Conclusion. We demonstrated that LPS-induced chorioamnionitis caused a decreased density in presynaptic boutons in different areas in the fetal brain. These synaptic changes seemed to be region-specific, with some regions being more affected than others, and seemed to be transient in some regions.

  1. Ventromedial prefrontal cortex drives hippocampal theta oscillations induced by mismatch computations.

    Science.gov (United States)

    Garrido, Marta I; Barnes, Gareth R; Kumaran, Dharshan; Maguire, Eleanor A; Dolan, Raymond J

    2015-10-15

    Detecting environmental change is fundamental for adaptive behavior in an uncertain world. Previous work indicates the hippocampus supports the generation of novelty signals via implementation of a match-mismatch detector that signals when an incoming sensory input violates expectations based on past experience. While existing work has emphasized the particular contribution of the hippocampus, here we ask which other brain structures also contribute to match-mismatch detection. Furthermore, we leverage the fine-grained temporal resolution of magnetoencephalography (MEG) to investigate whether mismatch computations are spectrally confined to the theta range, based on the prominence of this range of oscillations in models of hippocampal function. By recording MEG activity while human subjects perform a task that incorporates conditions of match-mismatch novelty we show that mismatch signals are confined to the theta band and are expressed in both the hippocampus and ventromedial prefrontal cortex (vmPFC). Effective connectivity analyses (dynamic causal modeling) show that the hippocampus and vmPFC work as a functional circuit during mismatch detection. Surprisingly, our results suggest that the vmPFC drives the hippocampus during the generation and processing of mismatch signals. Our findings provide new evidence that the hippocampal-vmPFC circuit is engaged during novelty processing, which has implications for emerging theories regarding the role of vmPFC in memory. PMID:26187453

  2. Providing and optimizing functional MR (Magnetic Resonance) of motor cortex of human brain by MRI ( Magnetic Resonance Imaging) facilities of Imam Khomeinie Hospital

    CERN Document Server

    Khosravie, H R

    2000-01-01

    During the stimulation, an observable increased signal (%2-%5)in respective sensory-motor cortex was obtained after correcting for partial volume effects, optimizing S/N,and incorporating small vowels. The 2 D F A S T functional image obtained by this method, showed an anatomical association of the increased signal with gray matter of sensory-motor cortex(in T 1 weighted image). The resultant data showed the feasibility of functional magnetic resonance imaging using optimized gradient echo sequences on a standard 1.5 T imager. Display of human brain cortical activity is accomplished using various techniques, by them different spatial and temporal resolution may be obtained. F MRI technique with proper spatial and temporal resolution due to its noninvasivity is one of the promising techniques for detection of brain activities. This can be used as an important tool by neurologists, since a great development has been achieved for display different brain function. This thesis report the results of simulation effe...

  3. A silicon based implantable microelectrode array for electrophysiological and dopamine recording from cortex to striatum in the non-human primate brain.

    Science.gov (United States)

    Zhang, Song; Song, Yilin; Wang, Mixia; Zhang, Zhiming; Fan, Xinyi; Song, Xianteng; Zhuang, Ping; Yue, Feng; Chan, Piu; Cai, Xinxia

    2016-11-15

    Dual-mode, multielectrode recordings have become routine in rodent neuroscience research and have recently been adapted to the non-human primate. However, robust and reliable application of acute, multielectrode recording methods in monkeys especially for deep brain nucleus research remains a challenge. In this paper, We described a low cost silicon based 16-site implantable microelectrode array (MEA) chip fabricated by standard lithography technology for in vivo test. The array was 25mm long and designed to use in non-human primate models, for electrophysiological and electrochemical recording. We presented a detailed protocol for array fabrication, then showed that the device can record Spikes, LFPs and dopamine (DA) variation continuously from cortex to striatum in an esthetized monkey. Though our experiment, high-quality electrophysiological signals were obtained from the animal. Across any given microelectrode, spike amplitudes ranged from 70 to 300μV peak to peak, with a mean signal-to-noise ratio of better than 5:1. Calibration results showed the MEA probe had high sensitivity and good selectivity for DA. The DA concentration changed from 42.8 to 481.6μM when the MEA probe inserted from cortex into deep brain nucleus of striatum, which reflected the inhomogeneous distribution of DA in brains. Compared with existing methods allowing single mode (electrophysiology or electrochemistry) recording. This system is designed explicitly for dual-mode recording to meet the challenges of recording in non-human primates. PMID:27155116

  4. Providing and optimizing functional MR (Magnetic Resonance) of motor cortex of human brain by MRI ( Magnetic Resonance Imaging) facilities of Imam Khomeinie Hospital

    International Nuclear Information System (INIS)

    Display of human brain cortical activity is accomplished using various techniques, by them different spatial and temporal resolution may be obtained. F MRI technique with proper spatial and temporal resolution due to its noninvasivity is one of the promising techniques for detection of brain activities. This can be used as an important tool by neurologists, since a great development has been achieved for display different brain function. This thesis report the results of simulation effects of thumb motor cortex of normal volunteer by using conventional standard 1.5 T imager and optimized gradient echo techniques. Activating sensory and motor stimulations can be led to, respective cortical area of that stimulation by which oxygenated blood flow is increased in that area (Bold contrast). By designing of a T 2* sensitized gradient echo protocol, thumb's sensory and motor cortex activation is evaluated. A protocol known as FASTin picker system with the following specifications was used for F MRI: Band Width:24 Hz/Pixel, Tr=101 m Sec , T E=49 m Sec , Flip Angle= 10 deg., N E X=1 ,Slice thickness=5-7 mm F O V=250 mm ,Matrix=128*128 and total scan time= 14 Sec. Stimulation of the motor cortex was performed by periodic movement of dominant thumb in up-down and right-left direction within a Lshape trajectory of plastic sheet with a frequency about 2 Hz. Then, acquired images in rest and stimulation period were evaluated by S P M 97, S P M 99 b software. During the stimulation, an observable increased signal (%2-%5)in respective sensory-motor cortex was obtained after correcting for partial volume effects, optimizing S/N,and incorporating small vowels. The 2 D F A S T functional image obtained by this method, showed an anatomical association of the increased signal with gray matter of sensory-motor cortex(in T 1 weighted image). The resultant data showed the feasibility of functional magnetic resonance imaging using optimized gradient echo sequences on a standard 1.5 T

  5. Brain networks underlying navigation in the Cincinnati water maze with external and internal cues.

    Science.gov (United States)

    Arias, Natalia; Méndez, Marta; Arias, Jorge L

    2014-07-25

    The present study investigated the behavioural performance and the contributions of different brain regions on a spatial task performed by Wistar rats in the Cincinnati water maze (CWM) in two conditions: one where both distal and proximal visual cues were available (CWM-light group, n=7) and another where visual cues were eliminated by testing in complete darkness (CWM-dark group, n=7). There were differences in the behavioural performance. Energetic brain metabolism revealed significant differences in the infralimbic, orbitofrontal cortex and anterodorsal striatum. At the same time different brain networks were found. The CWM-light group showed a relationship between the orbitofrontal cortex and medial septum, whereas the CWM-dark group revealed three different networks involving the prefrontal cortex, ventral striatum, hippocampus and amygdala nuclei. The study shows that brain activation differs in these two conditions. PMID:24915295

  6. Investigation of Higher Brain Functions in Music Composition Using Models of the Cortex Based on Physical System Analogies.

    Science.gov (United States)

    Leng, Xiaodan

    The trion model was developed using the Mountcastle organizational principle for the column as the basic neuronal network in the cortex and the physical system analogy of Fisher's ANNNI spin model. An essential feature is that it is highly structured in time and in spatial connections. Simulations of a network of trions have shown that large numbers of quasi-stable, periodic spatial-temporal firing patterns can be excited. Characteristics of these patterns include the quality of being readily enhanced by only a small change in connection strengths, and that the patterns evolve in certain natural sequences from one to another. With only somewhat different parameters than used for studying memory and pattern recognition, much more flowing and intriguing patterns emerged from the simulations. The results were striking when these probabilistic evolutions were mapped onto pitches and instruments to produce music: For example different simple mappings of the same evolution give music having the "flavor" of a minuet, a waltz, folk music, or styles of specific periods. A theme can be learned so that evolutions have this theme and its variations reoccurring more often. That the trion model is a viable model for the coding of musical structure in human composition and perception is suggested. It is further proposed that model is relevant for examining creativity in the higher cognitive functions of mathematics and chess, which are similar to music. An even higher level of cortical organization was modeled by coupling together several trion networks. Further, one of the crucial features of higher brain function, especially in music composition or appreciation, is the role of emotion and mood as controlled by the many neuromodulators or neuropeptides. The MILA model whose underlying basis is zero-level representation of Kac-Moody algebra is used to modulate periodically the firing threshold of each network. Our preliminary results show that the introduction of "neuromodulation

  7. Perinatal exposure to lead induces morphological, ultrastructural and molecular alterations in the hippocampus

    International Nuclear Information System (INIS)

    Highlights: ► Pre- and neonatal Pb exposure decreased the number of hippocampal neurons. ► Lead caused ultrastructural alterations in CA1 region of hippocampus. ► Hippocampus is highly vulnerable to low level perinatal Pb exposure. ► Lead decreased BDNF level in the developing brain. ► Decreased Bax/Bcl2 ratio may protect hippocampus against Pb-induced apoptosis. -- Abstract: The aim of this paper is to examine if pre- and neonatal exposure to lead (Pb) may intensify or inhibit apoptosis or necroptosis in the developing rat brain. Pregnant experimental females received 0.1% lead acetate (PbAc) in drinking water from the first day of gestation until weaning of the offspring; the control group received distilled water. During the feeding of pups, mothers from the experimental group were still receiving PbAc. Pups were weaned at postnatal day 21 and the young rats of both groups then received only distilled water until postnatal day 28. This treatment protocol resulted in a concentration of Pb in rat offspring whole blood (Pb-B) below the threshold of 10 μg/dL, considered safe for humans.We studied Casp-3 activity and expression, AIF nuclear translocation, DNA fragmentation, as well as Bax, Bcl-2 mRNA and protein expression as well as BDNF concentration in selected structures of the rat brain: forebrain cortex (FC), cerebellum (C) and hippocampus (H). The microscopic examinations showed alterations in hippocampal neurons.Our data shows that pre- and neonatal exposure of rats to Pb, leading to Pb-B below 10 μg/dL, can decrease the number of hippocampus neurons, occurring concomitantly with ultrastructural alterations in this region. We observed no morphological or molecular features of severe apoptosis or necrosis (no active Casp-3 and AIF translocation to nucleus) in young brains, despite the reduced levels of BDNF. The potential protective factor against apoptosis was probably the decreased Bax/Bcl-2 ratio, which requires further investigation. Our

  8. Gene expression of fatty acid transport and binding proteins in the blood-brain barrier and the cerebral cortex of the rat: differences across development and with different DHA brain status.

    Science.gov (United States)

    Pélerin, Hélène; Jouin, Mélanie; Lallemand, Marie-Sylvie; Alessandri, Jean-Marc; Cunnane, Stephen C; Langelier, Bénédicte; Guesnet, Philippe

    2014-11-01

    Specific mechanisms for maintaining docosahexaenoic acid (DHA) concentration in brain cells but also transporting DHA from the blood across the blood-brain barrier (BBB) are not agreed upon. Our main objective was therefore to evaluate the level of gene expression of fatty acid transport and fatty acid binding proteins in the cerebral cortex and at the BBB level during the perinatal period of active brain DHA accretion, at weaning, and until the adult age. We measured by real time RT-PCR the mRNA expression of different isoforms of fatty acid transport proteins (FATPs), long-chain acyl-CoA synthetases (ACSLs), fatty acid binding proteins (FABPs) and the fatty acid transporter (FAT)/CD36 in cerebral cortex and isolated microvessels at embryonic day 18 (E18) and postnatal days 14, 21 and 60 (P14, P21 and P60, respectively) in rats receiving different n-3 PUFA dietary supplies (control, totally deficient or DHA-supplemented). In control rats, all the genes were expressed at the BBB level (P14 to P60), the mRNA levels of FABP5 and ACSL3 having the highest values. Age-dependent differences included a systematic decrease in the mRNA expressions between P14-P21 and P60 (2 to 3-fold), with FABP7 mRNA abundance being the most affected (10-fold). In the cerebral cortex, mRNA levels varied differently since FATP4, ACSL3 and ACSL6 and the three FABPs genes were highly expressed. There were no significant differences in the expression of the 10 genes studied in n-3 deficient or DHA-supplemented rats despite significant differences in their brain DHA content, suggesting that brain DHA uptake from the blood does not necessarily require specific transporters within cerebral endothelial cells and could, under these experimental conditions, be a simple passive diffusion process. PMID:25123062

  9. Acute exercise increases brain region-specific expression of MCT1, MCT2, MCT4, GLUT1, and COX IV proteins.

    Science.gov (United States)

    Takimoto, Masaki; Hamada, Taku

    2014-05-01

    The brain is capable of oxidizing lactate and ketone bodies through monocarboxylate transporters (MCTs). We examined the protein expression of MCT1, MCT2, MCT4, glucose transporter 1 (GLUT1), and cytochrome-c oxidase subunit IV (COX IV) in the rat brain within 24 h after a single exercise session. Brain samples were obtained from sedentary controls and treadmill-exercised rats (20 m/min, 8% grade). Acute exercise resulted in an increase in lactate in the cortex, hippocampus, and hypothalamus, but not the brainstem, and an increase in β-hydroxybutyrate in the cortex alone. After a 2-h exercise session MCT1 increased in the cortex and hippocampus 5 h postexercise, and the effect lasted in the cortex for 24 h postexercise. MCT2 increased in the cortex and hypothalamus 5-24 h postexercise, whereas MCT2 increased in the hippocampus immediately after exercise, and remained elevated for 10 h postexercise. Regional upregulation of MCT2 after exercise was associated with increases in brain-derived neurotrophic factor and tyrosine-related kinase B proteins, but not insulin-like growth factor 1. MCT4 increased 5-10 h postexercise only in the hypothalamus, and was associated with increased hypoxia-inducible factor-1α expression. However, none of the MCT isoforms in the brainstem was affected by exercise. Whereas GLUT 1 in the cortex increased only at 18 h postexercise, COX IV in the hippocampus increased 10 h after exercise and remained elevated for 24 h postexercise. These results suggest that acute prolonged exercise induces the brain region-specific upregulation of MCT1, MCT2, MCT4, GLUT1, and COX IV proteins. PMID:24610532

  10. Effect of Kangxin Capsule(康欣胶囊) on the Expression of Nerve Growth Factors in Parietal Lobe of Cortex and Hippocampus CA1 Area of Vascular Dementia Model Rats

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To observe the effect of Kangxin Capsule (康欣胶囊, KXC) on the expression of nerve growth factor (NGF) as well as the morphology and amount of nerve synapse in the cortical parietal lobe and hippocampus CA1 area of vascular dementia (VD) model rats. Methods: The model rats of VD made by photochemical reaction technique were randomly divided into five groups: the model group (MG), the high-dose, middle-dose and low-dose KXC groups (HDG, MDG and LDG), and the Western medicine hydergin control group (WMG). They were treated respectively with distilled water, high, middle and low dosage of KXC suspended liquid, and hydergin for a month. Besides, a blank group consisting of normal (non-model)rats was set up for control (CG). The ultrastructure of nerve synapse in the cortical parietal lobe and hippocampus CA1 area of the rats were observed and its density estimated. The condition of NGF positive neurons in the above-mentioned two regions were also observed by immunohistochemical stain. Results: All the KXC or hydergin treated groups demonstrated a normal amount of nerve synapse with integral structure in the cortical parietal lobe and hippocampus CA1 area, which approached that in the CG and was superior to that in the MG. Also, the NGF positive neuron in all the treated groups was much more than that in MG with significant difference ( P<0.01 ), approaching to that in the CG. Conclusion: KXC could elevate the expression of NGF in the cortical parietal lobe and hippocampus CA1 area, preserve the number and morphology of synapse,thus to protect the function of nerve system from ischemic injury.

  11. Cerebral cortex: a target and source of insulin?

    Science.gov (United States)

    Csajbók, Éva A; Tamás, Gábor

    2016-08-01

    Recent results suggest that insulin is synthesised by a subpopulation of neurons in the cerebral cortex and neural progenitor cells of the hippocampus. Supplementing the slow supply of insulin to the brain by pancreatic beta cells, the insulin locally released by neurons provides a rapid means of regulating local microcircuits, effectively modulating synaptic transmission and on-demand energy homeostasis of neural networks. Modulation of insulin production by brain neurons via glucagon-like peptide 1 (GLP-1) agonists might be useful in counteracting diabetes, obesity and neurodegenerative diseases. Replacement of lost pancreatic beta cells by autologous transplantation of insulin-producing neural progenitor cells could be a viable therapy for diabetes. PMID:27207082

  12. 3'-5' cyclic-guanosine monophosphate increase in rat brain hippocampus after gamma-hydroxybutyrate administration. Prevention by valproate and naloxone

    Energy Technology Data Exchange (ETDEWEB)

    Vayer, P.; Gobaille, S.; Mandel, P.; Maitre, M.

    1987-08-03

    An increase (123%) of cyclic GMP (cGMP) was observed in the hippocampus of the rat killed by microwave irradiation 45 min after administration of 500 mg/kg el-hydroxybutyrate (GHB) IP. This increase is time and dose dependent. No modification in cyclic nucleotide content was observed in striatum and in cerebellum. As the role of GHB has been implicated in neurotransmission, the fact that this compound increases cyclic GMP accumulation in hippocampus in vivo may represent a mechanism by which the actions of GHB are mediated at the cellular level. Valproate (400 mg/kg) or naloxone (10 mg/kg) pretreatment completely abolish the cGMP increase due to GHB. A GABAergic and/or opiate phenomenon may be involved in the mechanism of GHB induced increase of cGMP. 34 references, 4 figures.

  13. Why avoid the hippocampus? A comprehensive review

    International Nuclear Information System (INIS)

    In this review article, we provide a detailed and comprehensive discussion of the rationale for using modern IMRT techniques to spare the subgranular zone of the hippocampus during cranial irradiation. We review the literature on neurocognitive effects of cranial irradiation; discuss clinical and preclinical data associating damage to neural progrenitor cells located in subgranular zone of the hippocampus with radiation-induced neurocognitive decline, specifically in terms of short-term memory formation and recall; and present a review of our pilot investigations into the feasibility and risks of sparing the subgranular zone of the hippocampus during whole-brain radiotherapy for brain metastases. We also introduce our phase II cooperative group clinical trial (RTOG 0933) designed to prospectively evaluate the postulated neurocognitive benefit of hippocampal subgranular zone sparing and scheduled to open in 2010.

  14. Integral dose delivered to normal brain with conventional intensity-modulated radiotherapy (IMRT) and helical tomotherapy IMRT during partial brain radiotherapy for high-grade gliomas with and without selective sparing of the hippocampus, limbic circuit and neural stem cell compartment

    International Nuclear Information System (INIS)

    We compared integral dose with uninvolved brain (IDbrain) during partial brain radiotherapy (PBRT) for high-grade glioma patients using helical tomotherapy (HT) and seven field traditional inverse-planned intensity-modulated radiotherapy (IMRT) with and without selective sparing (SPA) of contralateral hippocampus, neural stem cell compartment (NSC) and limbic circuit. We prepared four PBRT treatment plans for four patients with high-grade gliomas (60Gy in 30 fractions delivered to planning treatment volume (PTV60Gy)). For all plans, a structure denoted 'uninvolved brain' was created, which included all brain tissue not part of PTV or standard (STD) organs at risk (OAR). No dosimetric constraints were included for uninvolved brain. Selective SPA plans were prepared with IMRT and HT; contralateral hippocampus, NSC and limbic circuit were contoured; and dosimetric constraints were entered for these structures without compromising dose to PTV or STD OAR. We compared V100 and D95 for PTV46Gy and PTV60Gy, and IDbrain for all plans. There were no significant differences in V100 and D95 for PTV46Gy and PTV60Gy. IDbrain was lower in traditional IMRT versus HT plans for STD and SPA plans (mean IDbrain 23.64Gy vs. 28Gy and 18.7Gy vs. 24.5Gy, respectively) and in SPA versus STD plans both with IMRT and HT (18.7Gy vs. 23.64Gy and 24.5Gy vs. 28Gy, respectively). n the setting of PBRT for high-grade gliomas, IMRT reduces IDbrain compared with HT with or without selective SPA of contralateral hippocampus, limbic circuit and NSC, and the use of selective SPA reduces IDbrain compared with STD PBRT delivered with either traditional IMRT or HT.

  15. Alterations in right posterior hippocampus in early blind individuals

    DEFF Research Database (Denmark)

    Chebat, Daniel-Robert; Chen, Jan-Kai; Schneider, Fabien;

    2007-01-01

    between groups and there were no within-group differences for left versus right hippocampus. Sex, age and total brain grey matter volume had no effect on hippocampal volumes. Although extensive navigational training results in structural enhancement of the hippocampus for the sighted, the reduction of the......This study compares hippocampal volumes of early blind and sex/age-matched sighted controls through volumetric and localization analyses. Early blind individuals showed a significantly smaller right posterior hippocampus compared with controls. No differences in total hippocampal volumes were found...... posterior hippocampus in early blind individuals suggests the implication of this region in visual spatial memory. Udgivelsesdato: 2007-Mar-5...

  16. Lack of potassium channel induces proliferation and survival causing increased neurogenesis and two-fold hippocampus enlargement

    DEFF Research Database (Denmark)

    Almgren, Malin; Persson, Ann-Sophie; Fenghua, Chen;

    2007-01-01

    The megencephaly mice show dramatic progressive increase in brain size and seizures. The overgrowth affects primarily the hippocampus and ventral cortex. The phenotype originates from a mutation in the Shaker-like voltage-gated potassium channel Kv1.1 brain, which results in a malfunctioning...... protein. A key question in elucidating the mechanism behind the unique brain overgrowth is whether it is caused by an increase in cell number. By applying stereological techniques, we found that the number of both neurons and astrocytes, as well as structure volume, was increased approximately two...... lower in mceph/mceph supporting additional overgrowth mechanism than induced by seizures. In conclusion, lack of a functional Kv1.1 ion channel subunit in the mceph/mceph mice causes a unique neuronal hyperplasia in distinct hippocampal regions and consequently hippocampal enlargement from 2 to 3 weeks...

  17. Structural organization of long-range GABAergic projection system of the hippocampus

    Directory of Open Access Journals (Sweden)

    Shozo Jinno

    2009-07-01

    Full Text Available GABA is a key mediator of neural activity in the mammalian central nervous system, and a diverse set of GABAergic neurons utilize GABA as transmitter. It has been widely accepted that GABAergic neurons typically serve as interneurons while glutamatergic principal cells send excitatory signals to remote areas. In general, glutamatergic projection neurons monosynaptically innervate both principal cells and local GABAergic interneurons in each target area, and these GABAergic cells play a vital role in modulation of the activity of principal cells. The formation and recall of sensory, motor and cognitive representations require coordinated fast communication among multiple areas of the cerebral cortex, which are thought to be mostly mediated by glutamatergic neurons. However, there is an increasing body of evidence showing that specific subpopulations of cortical GABAergic neurons send long-range axonal projections to subcortical and other cortical areas. In particular, a variety of GABAergic neurons in the hippocampus project to neighboring and remote areas. Using anatomical, molecular and electrophysiological approaches, several types of GABAergic projection neurons have been shown to exist in the hippocampus. The target areas of these cells are the subiculum and other retrohippocampal areas, the medial septum and the contralateral dentate gyrus. The long-range GABAergic projection system of the hippocampus may serve to coordinate precisely the multiple activity patterns of widespread cortical cell assemblies in different brain states and among multiple functionally related areas.

  18. Impairment of learning and memory after photothrombosis of the prefrontal cortex in rat brain: effects of Noopept.

    Science.gov (United States)

    Romanova, G A; Shakova, F M; Gudasheva, T A; Ostrovskaya, R U

    2002-12-01

    Experiments were performed on rats trained conditioned passive avoidance response. Acquisition and retention of memory traces were impaired after photothrombosis of the prefrontal cortex. The acyl-prolyl-containing dipeptide Noopept facilitated retention and retrieval of a conditioned passive avoidance response, normalized learning capacity in animals with ischemic damage to the cerebral cortex, and promoted finish training in rats with hereditary learning deficit. These results show that Noopept improves all three stages of memory. It should be emphasized that the effect of Noopept was most pronounced in animals with impaired mnesic function. PMID:12660828

  19. A Single Brain-Derived Neurotrophic Factor Infusion into the Dorsomedial Prefrontal Cortex Attenuates Cocaine Self-Administration-Induced Phosphorylation of Synapsin in the Nucleus Accumbens during Early Withdrawal

    OpenAIRE

    Sun, Wei-Lun; Eisenstein, Sarah A.; Zelek-Molik, Agnieszka; McGinty, Jacqueline F.

    2015-01-01

    Background: Dysregulation in the prefrontal cortex-nucleus accumbens pathway has been implicated in cocaine addiction. We have previously demonstrated that one intra-dorsomedial prefrontal cortex brain-derived neurotrophic factor (BDNF) infusion immediately following the last cocaine self-administration session caused a long-lasting inhibition of cocaine-seeking and normalized the cocaine-induced disturbance of glutamate transmission in the nucleus accumbens after extinction and a cocaine pri...

  20. Rapid treatment-induced brain changes in pediatric CRPS.

    Science.gov (United States)

    Erpelding, Nathalie; Simons, Laura; Lebel, Alyssa; Serrano, Paul; Pielech, Melissa; Prabhu, Sanjay; Becerra, Lino; Borsook, David

    2016-03-01

    To date, brain structure and function changes in children with complex regional pain syndrome (CRPS) as a result of disease and treatment remain unknown. Here, we investigated (a) gray matter (GM) differences between patients with CRPS and healthy controls and (b) GM and functional connectivity (FC) changes in patients following intensive interdisciplinary psychophysical pain treatment. Twenty-three patients (13 females, 9 males; average age ± SD = 13.3 ± 2.5 years) and 21 healthy sex- and age-matched controls underwent magnetic resonance imaging. Compared to controls, patients had reduced GM in the primary motor cortex, premotor cortex, supplementary motor area, midcingulate cortex, orbitofrontal cortex, dorsolateral prefrontal cortex (dlPFC), posterior cingulate cortex, precuneus, basal ganglia, thalamus, and hippocampus. Following treatment, patients had increased GM in the dlPFC, thalamus, basal ganglia, amygdala, and hippocampus, and enhanced FC between the dlPFC and the periaqueductal gray, two regions involved in descending pain modulation. Accordingly, our results provide novel evidence for GM abnormalities in sensory, motor, emotional, cognitive, and pain modulatory regions in children with CRPS. Furthermore, this is the first study to demonstrate rapid treatment-induced GM and FC changes in areas implicated in sensation, emotion, cognition, and pain modulation. PMID:25515312

  1. Changes in brain oxidative metabolism induced by water maze training.

    Science.gov (United States)

    Conejo, N M; González-Pardo, H; Vallejo, G; Arias, J L

    2007-03-16

    Although the hippocampus has been shown to be essential for spatial memory, the contribution of associated brain regions is not well established. Wistar rats were trained to find a hidden escape platform in the water maze during eight days. Following training, the oxidative metabolism in different brain regions was evaluated using cytochrome oxidase histochemistry. Metabolic activations were found in the prelimbic cortex, cornu ammonis (CA) 1 subfield of the dorsal hippocampus and the anterior thalamic nuclei, relative to yoked swim controls and naïve rats. In addition, many cross-correlations in brain metabolism were observed among the latter regions. These results support the implication of a hippocampal-prefrontal-thalamic system to spatial memory in rats. PMID:17222984

  2. Effect of Electromagnetic Radiation Exposure on Histology and DNA Content of the Brain Cortex and Hypothalamus of Young and Adult Male Albino Rats

    International Nuclear Information System (INIS)

    Concerns have been raised regarding the potential adverse effects of exposure to electromagnetic radiation (EMR) arising from mobile phone. The present study investigates the effect of the daily exposure of adult and young rats to EMR for 1 hour (at a frequency of 900 MHz, a power density of 0.02 mW/cm2 and an average specific absorption rate of 1.165 W/kg) on the DNA content and tissue architecture of the cortex and hypothalamus of the rat brain. Both young and adult rats were sacrificed at two intervals, after 4 months of daily EMR exposure and after 1 month of stopping the exposure. The present results showed a significant increase in the DNA intensity of young and adult rats in both areas after 4 months of daily EMR exposure. However, decreased DNA content around the normal level was observed after one month of stopping the exposure. Light microscopic examination of irradiated rats revealed edema, vacuolation, necrosis and proliferated glial cells. Stopping EMR exposure showed mild amelioration in the structural damage of the cerebral cortex of young animals, however, most drastic changes still persisted in the other animals. In conclusion, these data may confirm the neurotoxic risks arising from the extensive use of mobile phones that may alter the brain histology and impair its function

  3. Synchronous changes of cortical thickness and corresponding white matter microstructure during brain development accessed by diffusion MRI tractography from parcellated cortex

    Directory of Open Access Journals (Sweden)

    Tina Jeon

    2015-12-01

    Full Text Available Cortical thickness (CT changes during normal brain development is associated with complicated cellular and molecular processes including synaptic pruning and apoptosis. In parallel, the microstructural enhancement of developmental white matter (WM axons with their neuronal bodies in the cerebral cortex has been widely reported with measurements of metrics derived from diffusion tensor imaging (DTI, especially fractional anisotropy (FA. We hypothesized that the changes of CT and microstructural enhancement of corresponding axons are highly interacted during development. DTI and T1-weighted images of 50 healthy children and adolescents between the ages of 7 to 25 years were acquired. With the parcellated cortical gyri transformed from T1-weighted images to DTI space as the tractography seeds, probabilistic tracking was performed to delineate the WM fibers traced from specific parcellated cortical regions. CT was measured at certain cortical regions and FA was measured from the WM fibers traced from same cortical regions. The CT of all frontal cortical gyri, includeing Brodmann areas 4, 6, 8, 9, 10, 11, 44, 45, 46 and 47, decreased significantly and heterogeneously; concurrently, significant and heterogeneous increases of FA of WM traced from corresponding regions were found. We further revealed significant correlation between the slopes of the CT decrease and the slopes of corresponding WM FA increase in all frontal cortical gyri, suggesting coherent cortical pruning and corresponding WM microstructural enhancement. Such correlation was not found in cortical regions other than frontal cortex. The molecular and cellular mechanisms of these synchronous changes may be associated with overlapping signaling pathways of axonal guidance, synaptic pruning, neuronal apoptosis and more prevalent interstitial neurons in the prefrontal cortex. Revealing the coherence of cortical and WM structural changes during development may open a new window for

  4. Restraint stress-induced morphological changes at the blood-brain barrier in adult rats

    Directory of Open Access Journals (Sweden)

    Petra eSántha

    2016-01-01

    Full Text Available Stress is well known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognised in the development of neurodegenerative disorders, such as Alzheimer’s disease, dysfunction of the blood-brain barrier has been linked to stress-related psychiatric diseases only recently. In the present study the effects of restraint stress with different duration (1, 3 and 21 days were investigated on the morphology of the blood-brain barrier in male adult Wistar rats. Frontal cortex and hippocampus sections were immunostained for markers of brain endothelial cells (claudin-5, occludin and glucose transporter-1 and astroglia (GFAP. Staining pattern and intensity were visualized by confocal microscopy and evaluated by several types of image analysis. The ultrastructure of brain capillaries was investigated by electron microscopy. Morphological changes and intensity alterations in brain endothelial tight junction proteins claudin-5 and occludin were induced by stress. Following restraint stress significant increases in the fluorescence intensity of glucose transporter-1 were detected in brain endothelial cells in the frontal cortex and hippocampus. Significant reductions in GFAP fluorescence intensity were observed in the frontal cortex in all stress groups. As observed by electron microscopy, one-day acute stress induced morphological changes indicating damage in capillary endothelial cells in both brain regions. After 21 days of stress thicker and irregular capillary basal membranes in the hippocampus and edema in astrocytes in both regions were seen. These findings indicate that stress exerts time-dependent changes in the staining pattern of tight junction proteins occludin, claudin-5 and glucose transporter-1 at the level of brain capillaries and in the ultrastructure of brain endothelial cells and astroglial endfeet, which may contribute to neurodegenerative processes

  5. Brain Basics

    Medline Plus

    Full Text Available ... ADHD , schizophrenia , and depression . Hippocampus —Helps create and file new memories. When the hippocampus is damaged, a ... portion of the brain involved in creating and filing new memories. hypothalmic-pituitary-adrenal (HPA) axis —A ...

  6. Excitotoxic increase of xanthine dehydrogenase and xanthine oxidase in the rat olfactory cortex.

    Science.gov (United States)

    Battelli, M G; Buonamici, L; Abbondanza, A; Virgili, M; Contestabile, A; Stirpe, F

    1995-05-26

    Excitotoxic lesions induced by systemic injection of kainic acid, resulted in 2-3-fold increase of xanthine dehydrogenase and xanthine oxidase activities in the rat olfactory cortex 48-72 h after drug administration. A significant increase of the xanthine oxidase/dehydrogenase ratio was also observed at 4 and 48 h post-injection. No similar changes were noticed in the hippocampus. The enhancement of enzyme activity seems to be primarily a consequence of the altered cell composition in damaged area. Free radicals produced by the increased oxygen-dependent form of the enzyme could in turn aggravate the excitotoxic brain injury. PMID:7656426

  7. Brain metabolism and extracellular space diffusion parameters during and after transient global hypoxia in the rat cortex

    Czech Academy of Sciences Publication Activity Database

    Zoremba, N.; Homola, Aleš; Rossaint, R.; Syková, Eva

    2007-01-01

    Roč. 203, - (2007), s. 34-41. ISSN 0014-4886 R&D Projects: GA MŠk 1M0538; GA MŠk LC554 Institutional research plan: CEZ:AV0Z50390512 Keywords : Hypoxia * Cortex * Recovery Subject RIV: FH - Neurology Impact factor: 3.982, year: 2007

  8. Brain glycogen supercompensation following exhaustive exercise.

    Science.gov (United States)

    Matsui, Takashi; Ishikawa, Taro; Ito, Hitoshi; Okamoto, Masahiro; Inoue, Koshiro; Lee, Min-Chul; Fujikawa, Takahiko; Ichitani, Yukio; Kawanaka, Kentaro; Soya, Hideaki

    2012-02-01

    Brain glycogen localized in astrocytes, a critical energy source for neurons, decreases during prolonged exhaustive exercise with hypoglycaemia. However, it is uncertain whether exhaustive exercise induces glycogen supercompensation in the brain as in skeletal muscle. To explore this question, we exercised adult male rats to exhaustion at moderate intensity (20 m min(-1)) by treadmill, and quantified glycogen levels in several brain loci and skeletal muscles using a high-power (10 kW) microwave irradiation method as a gold standard. Skeletal muscle glycogen was depleted by 82-90% with exhaustive exercise, and supercompensated by 43-46% at 24 h after exercise. Brain glycogen levels decreased by 50-64% with exhaustive exercise, and supercompensated by 29-63% (whole brain 46%, cortex 60%, hippocampus 33%, hypothalamus 29%, cerebellum 63% and brainstem 49%) at 6 h after exercise. The brain glycogen supercompensation rates after exercise positively correlated with their decrease rates during exercise. We also observed that cortical and hippocampal glycogen supercompensation were sustained until 24 h after exercise (long-lasting supercompensation), and their basal glycogen levels increased with 4 weeks of exercise training (60 min day(-1) at 20 m min(-1)). These results support the hypothesis that, like the effect in skeletal muscles, glycogen supercompensation also occurs in the brain following exhaustive exercise, and the extent of supercompensation is dependent on that of glycogen decrease during exercise across brain regions. However, supercompensation in the brain preceded that of skeletal muscles. Further, the long-lasting supercompensation of the cortex and hippocampus is probably a prerequisite for their training adaptation (increased basal levels), probably to meet the increased energy demands of the brain in exercising animals. PMID:22063629

  9. Studies on the influence of high power microwave radiation on energy metabolism of brain in rats

    International Nuclear Information System (INIS)

    Objective: To investigate the effect of high power microwave (HPM) radiation on energy metabolism of brains in Wistar rats. Methods: 120 Wistar rats were exposed to HPM of which the average power densities were respectively 3, 10, 30 and 100 mW/cm2. Toluidine blue staining, method of Wachstein-Meisel's magnesium activating enzyme, method of Nachlas's nitroblue tetrazolium and electron telescope were used to study the change of Nissel body, adenosine triphosphatase (ATPase), succinate dehydrogenase (SDH), and ultrastructure of cerebral cortex, hippocampus and thalamencephalon. Results: 3-100 mW/cm2 HPM radiation caused the decrease, even the disappearance of Nissel body of cerebral cortex, hippocampus and thalamencephalon in 6h-3d after radiation (P2 HPM radiation can induce the disorder of energy metabolism of brains, represented the decrease of Nissel body and SDH, injuries of ATPase, injuries of mitochondrion and rough endoplasmic reticulum. (authors)

  10. Hippocampus: Remembering the Choices

    OpenAIRE

    Eichenbaum, Howard

    2013-01-01

    The hippocampus is said to be involved in “navigation” and “memory” as if these were distinct functions. In this issue of Neuron, Singer et al. (2013) provide evidence that the hippocampus retrieves spatial sequences in support of memory, strengthening a convergence between the two perspectives on hippocampal function.

  11. Neurotransmission in the hippocampus

    International Nuclear Information System (INIS)

    This book contains the following five chapters: introduction; neuronal elements in the hippocampus and their synaptic connections; Membrane properties and postsynaptic responses of hippocampal neurons; The enzyme histochemistry of neurotransmitter metabolism; and Receptor autoradiography in the hippocampus of man and rat

  12. Endurance training increases brain lactate uptake during hypoglycemia by up regulation of brain lactate transporters.

    Science.gov (United States)

    Aveseh, Malihe; Nikooie, Rohollah; Sheibani, Vahid; Esmaeili-Mahani, Saeed

    2014-08-25

    The capacity of the brain to metabolize non-glucose substrates under hypoglycemic state maintains its energy requirements. We hypothesized that exercise-induced increase in capacity for brain utilization of lactate by up regulation of the monocarboxylate transporters (MCTs) may contribute metabolic substrates during hypoglycemia in diabetic rats induced by streptozotocin. The induced diabetes increased MCT1 and MCT2 expression in the cortex and the hippocampus in the sedentary diabetic animals. There were exercise-induced increases in MCT1 in the cortex and the hippocampus and MCT2 expression in the cortex in trained diabetic animals; whereas, no changes were found in the healthy trained animals. Both diabetic and healthy trained animals showed higher values for brain lactate uptake during insulin-induced hypoglycemia when animals were intraperitoneally injected by L(+)-lactic acid. However, the response of counterregulatory hormones during hypoglycemia were blunted in the diabetic trained animals which indicates to carefully monitoring of glycemic targets both during and following prolonged exercise. PMID:25004253

  13. Adult Onset-hypothyroidism has Minimal Effects on Synaptic Transmission in the Hippocampus of Rats Independent of Hypothermia

    Science.gov (United States)

    Introduction: Thyroid hormones (TH) influence central nervous system (CNS) function during development and in adulthood. The hippocampus, a brain area critical for learning and memory is sensitive to TH insufficiency. Synaptic transmission in the hippocampus is impaired following...

  14. Recognition Memory and the Hippocampus: A Test of the Hippocampal Contribution to Recollection and Familiarity

    Science.gov (United States)

    Jeneson, Annette; Kirwan, C. Brock; Hopkins, Ramona O.; Wixted, John T.; Squire, Larry R.

    2010-01-01

    It has been suggested that the hippocampus selectively supports recollection and that adjacent cortex in the medial temporal lobe can support familiarity. Alternatively, it has been suggested that the hippocampus supports both recollection and familiarity. We tested these suggestions by assessing the performance of patients with hippocampal…

  15. Cathepsin L Plays a Major Role in Cholecystokinin Production in Mouse Brain Cortex and in Pituitary AtT-20 Cells: Protease Gene Knockout and Inhibitor Studies

    Science.gov (United States)

    Beinfeld, Margery C.; Funkelstein, Lydiane; Foulon, Thierry; Cadel, Sandrine; Kitagawa, Kouki; Toneff, Thomas; Reinheckel, Thomas; Peters, Christoph; Hook, Vivian

    2009-01-01

    Cholecystokinin (CCK) is a peptide neurotransmitter whose production requires proteolytic processing of the proCCK precursor to generate active CCK8 neuropeptide in brain. This study demonstrates the significant role of the cysteine protease cathepsin L for CCK8 production. In cathepsin L knockout (KO) mice, CCK8 levels were substantially reduced in brain cortex by an average of 75%. To evaluate the role of cathepsin L in producing CCK in the regulated secretory pathway of neuroendocrine cells, pituitary AtT-20 cells that stably produce CCK were treated with the specific cathepsin L inhibitor, CLIK-148. CLIK-148 inhibitor treatment resulted in decreased amounts of CCK secreted from the regulated secretory pathway of AtT-20 cells. CLIK-148 also reduced cellular levels of CCK9 (Arg-CCK8), consistent with CCK9 as an intermediate product of cathepsin L, shown by the decreased ratio of CCK9/CCK8. The decreased CCK0/CCK8 ratio also suggests a shift in the production to CCK8 over CCK9 during inhibition of cathepsin L. During reduction of the PC1/3 processing enzyme by siRNA, the ratio of CCK9/CCK8 was increased, suggesting a shift to the cathepsin L pathway for production of CCK9. The changes in ratios of CCK9 compared to CCK8 are consistent with dual roles of the cathepsin L protease pathway that includes aminopeptidase B to remove NH2-terminal Arg or Lys, and the PC1/3 protease pathway. These results suggest that cathepsin L functions as a major protease responsible for CCK8 production in mouse brain cortex, and participates with PC1/3 for CCK8 production in pituitary cells. PMID:19589362

  16. Superficial cortical landmarks for localization of the hippocampus: Application for temporal lobectomy and amygdalohippocampectomy

    OpenAIRE

    R. Shane Tubbs; Marios Loukas; Barbaro, Nicholas M.; Aaron A Cohen-Gadol

    2015-01-01

    Background: Accessing the hippocampus for amygdalohippocampectomy and procedures such as depth electrode placement requires accurate knowledge regarding the location of the hippocampus. Methods: The authors removed 10 human cadaveric brains (20 sides) from their crania, noted relationships between the lateral temporal neocortex and underlying hippocampus, and measured the distance between the hippocampus and superficial landmarks. Results: Mean distances were as follows: 3.8 cm from t...

  17. Total anesthesia, rats brain surgery, nitric oxide (NO and free radicals

    Directory of Open Access Journals (Sweden)

    Jelenković Ankica V.

    2005-01-01

    Full Text Available It is expected that clinical recovery after surgically induced brain trauma is followed by molecular and biochemical restitution. Seven days after surgery, we investigated whether the plastic cannula implanted in the left brain ventricle of adult Wistar rats (n = 6-7, performed in pentobarbital anesthesia, could influence oxidative stress elements (superoxide anion and lipid peroxidation, as well as the antioxidative system (superoxide dismuthase-SOD. Also, we investigated whether nitric oxide (NO is involved in these processes. Biochemical analyses was performed in the forebrain cortex, striatum and hippocampus. Clinical recovery was complete seven days after surgery. Thereafter, thirty minutes before decapitation, through the cannula, one group of rats received saline intracerebroventricularly (control group, and the treated group received Nω-nitro-L-arginine methyl ester (L-NAME. The third group was left unoperated and untreated. Before and after the treatments, rectal body temperature was measured. Compared to the untreated group the index of lipid peroxidation was increased in all three brain structures in the group that received saline (p<0.05 to 0.01. Application of L-NAME deteriorated it in the striatum and hippocampus (p<0.01 compared to the both other groups, but the value in the forebrain cortex was similar to the untreated group. Supeoxide anion level was decreased in the L-NAME treated group only in the striatum (p<0.01 compared to control and untreated groups, but SOD was increased in the hippocampus compared to the saline treated group (p<0.05. Seven days after brain surgery in pentobarbital anesthesia, recovery of biochemical disturbances was not parallel to clinical recovery. Long lasting biochemical changes are rather the consequence of brain injury than to pentobarbital anesthesia. In this experimental model, NO had protective effects, acting against lipid per oxidation in the striatum and hippocampus, but not in the

  18. Threat visibility modulates the defensive brain circuit underlying fear and anxiety

    OpenAIRE

    Rigoli, Francesco; Ewbank, Michael; Dalgleish, Tim; Calder, Andrew

    2016-01-01

    Highlights • We used human fMRI and a novel computer-based task to study the effects of visual threat uncertainty on brain activity. • Lack of visual threat information increased activity in hippocampus, ventromedial prefrontal cortex and amygdala (regions involved in anxiety). • Presence of visual threat information increased activity in periaqueductal gray (involved in fear). • High trait-anxiety participants anticipated hippocampal activation when visual threat information was not provided...

  19. Maternal separation produces alterations of forebrain brain-derived neurotrophic factor expression in differently aged rats

    OpenAIRE

    Wang, Qiong; Shao, Feng; Wang, Weiwen

    2015-01-01

    Early life adversity, such as postnatal maternal separation (MS), play a central role in the development of psychopathologies during individual ontogeny. In this study, we investigated the effects of repeated MS (4 h per day from postnatal day (PND) 1–21) on the brain-derived neurotrophic factor (BDNF) expression in the medial prefrontal cortex (mPFC), the nucleus accumbens (NAc) and the hippocampus of male and female juvenile (PND 21), adolescent (PND 35) and young adult (PND 56) Wistar rats...

  20. Oxidative Stress Biomarkers in Some Rat Brain Structures and Peripheral Organs Underwent Cocaine

    OpenAIRE

    Pomierny-Chamioło, Lucyna; Moniczewski, Andrzej; Wydra, Karolina; Suder, Agata; Filip, Małgorzata

    2012-01-01

    Oxidative stress (OS) generates or intensifies cocaine-evoked toxicity in the brain and peripheral organs. The aim of this study was to examine superoxide dismutase (SOD) activity and lipid peroxidation [measured by malondialdehyde (MDA) levels] in rats during maintenance of cocaine self-administration and after withdrawal by a yoked-triad procedure. Our results indicate that repeated cocaine self-administration provoked an elevation of SOD activity in the hippocampus, frontal cortex, dorsal ...

  1. Dynamics of endogenous Hsp70 synthesis in the brain of olfactory bulbectomized mice

    OpenAIRE

    Bobkova, Natalia; Guzhova, Irina; Margulis, Boris; Nesterova, Inna; Medvedinskaya, Natalia; Samokhin, Alexander; Alexandrova, Irina; Garbuz, David; Nudler, Evgeny; Evgen’ev, Michael

    2012-01-01

    Numerous epidemiological studies have established acute brain injury as one of the major risk factors for the Alzheimer's disease (AD). However, the lack of animal models of AD-like degeneration triggered by a defined injury hampered the development of adequate therapies. Here we report that the surgical damage of the olfactory bulbs triggers the development of several pathologies, including amyloid-β accumulation and strong decrease of neuron density in the cortex and hippocampus as well as ...

  2. Abnormal Brain Default-Mode Network Functional Connectivity in Drug Addicts

    OpenAIRE

    Ma, Ning; Liu, Ying; Fu, Xian-ming; Li, Nan; Wang, Chang-Xin; Zhang, Hao; Qian, Ruo-Bing; Xu, Hu-Sheng; Hu, Xiaoping; Zhang, Da-Ren

    2011-01-01

    Background The default mode network (DMN) is a set of brain regions that exhibit synchronized low frequency oscillations at resting-state, and is believed to be relevant to attention and self-monitoring. As the anterior cingulate cortex and hippocampus are impaired in drug addiction and meanwhile are parts of the DMN, the present study examined addiction-related alteration of functional connectivity of the DMN. Methodology Resting-state functional magnetic resonance imaging data of chronic he...

  3. Brain Basics

    Medline Plus

    Full Text Available ... producing dopamine can result in Parkinson's disease, a disorder that affects a person's ability to move as they want ... the brain. The hippocampus may be involved in mood disorders through its control of a major mood circuit ...

  4. Comparative anatomy of the pig brain : an integrative magnetic resonance imaging (MRI) study of the porcine brain with special emphasis on the external morphology of the cerebral cortex

    OpenAIRE

    Schmidt, Verena

    2015-01-01

    For this study the healthy brains of the domestic pigs are examined post mortem. MRI (magnetic resonance imaging) scans in transverse, sagittal and dorsal orientation (native and formalin fixed) are produced with a 1.0 Tesla scanner. 12 sagittal, 13 dorsal and 22 transverse scans are selected and labelled to produce a MRI picture atlas of the porcine brain. With the aid of the graphical software programs AMIRA® and AVIZO® (Mercury Computer Systems Inc.) it was possible to identify brain s...

  5. 柴胡疏肝散对抑郁模型大鼠海马乙酰胆碱代谢的影响%Effect of Chaihu Shugan Powderon metabolism of ach in brain hippocampus tissue of depressive rats

    Institute of Scientific and Technical Information of China (English)

    董海影; 张晓杰

    2011-01-01

    Objective: To observe the changes of acetylcholine metabolism of hippocampal of depression models on rats and the effect of Chaihu Shugan Powder on it.Method: 60 male Sprague-Dawley rats of 4 - 5 month were randomly divided into four groups and 15 rats in 4 groups: normal control group, model group, western medicine group and Chinese medicine group.The depressed modle was reduced by single feed combined with CUMS.After twenty-one days,behavior changes in rats were detected through open-field test, sugar consumption test and body weight;expression changes of acetylcholine transferase and acetylcholinesterase in hippocampus of rats brain were observed with immunochemistry method; ChAT mRNA expression was detected with RT-PCR; the activity of AChE in hippocampus of rats brain tissue was measured with colorimetric method.Results:On the 21st day of model replication, compared with normal control group, the scores of horizontal activity and vertical activity,weight and sugar preference degrees in model group decreased significantly (P<0.01-0.001); Compared with model group,western medicine group and Chinese medicine group got significantly higher scores of horizontal activity and vertical activity, weight and sugar preference degrees (P<0.05-0.001).The results of immunochemistry staining showed that ChAT, AChEprotein expression was significantly increased in hippocampus of model group compared with that of normal control group (P<0.05);Compared with model group, western medicine group and Chinese medicine group had significantly lower ChAT, AChE protein expression in hippocampus (P<0.05).RT-PCR results showed that expression levels of ChAT mRNA in hippocampus of rats of model group were significantly raised compared with those of normal control group (P<0.05); Compared with those of model group,expression levels of ChAT mRNA in hippocampus of rats of western medicine group and Chinese medicine group was significantly reduced (P<0.05); The results of

  6. Acute iron overload and oxidative stress in brain

    International Nuclear Information System (INIS)

    An in vivo model in rat was developed by intraperitoneally administration of Fe-dextran to study oxidative stress triggered by Fe-overload in rat brain. Total Fe levels, as well as the labile iron pool (LIP) concentration, in brain from rats subjected to Fe-overload were markedly increased over control values, 6 h after Fe administration. In this in vivo Fe overload model, the ascorbyl (A·)/ascorbate (AH−) ratio, taken as oxidative stress index, was assessed. The A·/AH− ratio in brain was significantly higher in Fe-dextran group, in relation to values in control rats. Brain lipid peroxidation indexes, thiobarbituric acid reactive substances (TBARS) generation rate and lipid radical (LR·) content detected by Electron Paramagnetic Resonance (EPR), in Fe-dextran supplemented rats were similar to control values. However, values of nuclear factor-kappaB deoxyribonucleic acid (NFκB DNA) binding activity were significantly increased (30%) after 8 h of Fe administration, and catalase (CAT) activity was significantly enhanced (62%) 21 h after Fe administration. Significant enhancements in Fe content in cortex (2.4 fold), hippocampus (1.6 fold) and striatum (2.9 fold), were found at 6 h after Fe administration. CAT activity was significantly increased after 8 h of Fe administration in cortex, hippocampus and striatum (1.4 fold, 86, and 47%, respectively). Fe response in the whole brain seems to lead to enhanced NF-κB DNA binding activity, which may contribute to limit oxygen reactive species-dependent damage by effects on the antioxidant enzyme CAT activity. Moreover, data shown here clearly indicate that even though Fe increased in several isolated brain areas, this parameter was more drastically enhanced in striatum than in cortex and hippocampus. However, comparison among the net increase in LR· generation rate, in different brain areas, showed enhancements in cortex lipid peroxidation, without changes in striatum and hippocampus LR· generation rate after 6 h

  7. Acute iron overload and oxidative stress in brain.

    Science.gov (United States)

    Piloni, Natacha E; Fermandez, Virginia; Videla, Luis A; Puntarulo, Susana

    2013-12-01

    An in vivo model in rat was developed by intraperitoneally administration of Fe-dextran to study oxidative stress triggered by Fe-overload in rat brain. Total Fe levels, as well as the labile iron pool (LIP) concentration, in brain from rats subjected to Fe-overload were markedly increased over control values, 6h after Fe administration. In this in vivo Fe overload model, the ascorbyl (A)/ascorbate (AH(-)) ratio, taken as oxidative stress index, was assessed. The A/AH(-) ratio in brain was significantly higher in Fe-dextran group, in relation to values in control rats. Brain lipid peroxidation indexes, thiobarbituric acid reactive substances (TBARS) generation rate and lipid radical (LR) content detected by Electron Paramagnetic Resonance (EPR), in Fe-dextran supplemented rats were similar to control values. However, values of nuclear factor-kappaB deoxyribonucleic acid (NFκB DNA) binding activity were significantly increased (30%) after 8h of Fe administration, and catalase (CAT) activity was significantly enhanced (62%) 21h after Fe administration. Significant enhancements in Fe content in cortex (2.4 fold), hippocampus (1.6 fold) and striatum (2.9 fold), were found at 6h after Fe administration. CAT activity was significantly increased after 8h of Fe administration in cortex, hippocampus and striatum (1.4 fold, 86, and 47%, respectively). Fe response in the whole brain seems to lead to enhanced NF-κB DNA binding activity, which may contribute to limit oxygen reactive species-dependent damage by effects on the antioxidant enzyme CAT activity. Moreover, data shown here clearly indicate that even though Fe increased in several isolated brain areas, this parameter was more drastically enhanced in striatum than in cortex and hippocampus. However, comparison among the net increase in LR generation rate, in different brain areas, showed enhancements in cortex lipid peroxidation, without changes in striatum and hippocampus LR generation rate after 6h of Fe overload

  8. Dopamine D4 receptors modulate brain metabolic activity in the prefrontal cortex and cerebellum at rest and in response to methylphenidate

    Energy Technology Data Exchange (ETDEWEB)

    Michaelides, M.; Wang, G.; Michaelides, M.; Pascau, J.; Gispert, J.-D.; Delis, F.; Grandy, D.K.; Wang, G.-J.; Desco, M.; Rubinstein, M.; Volkow, N.D.; Thanos, P.K.

    2010-07-16

    Methylphenidate (MP) is widely used to treat attention deficit hyperactivity disorder (ADHD). Variable number of tandem repeats polymorphisms in the dopamine D4 receptor (D{sub 4}) gene have been implicated in vulnerability to ADHD and the response to MP. Here we examined the contribution of dopamine D4 receptors (D4Rs) to baseline brain glucose metabolism and to the regional metabolic responses to MP. We compared brain glucose metabolism (measured with micro-positron emission tomography and [{sup 18}F]2-fluoro-2-deoxy-D-glucose) at baseline and after MP (10 mg/kg, i.p.) administration in mice with genetic deletion of the D{sub 4}. Images were analyzed using a novel automated image registration procedure. Baseline D{sub 4}{sup -/-} mice had lower metabolism in the prefrontal cortex (PFC) and greater metabolism in the cerebellar vermis (CBV) than D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice; when given MP, D{sub 4}{sup -/-} mice increased metabolism in the PFC and decreased it in the CBV, whereas in D{sub 4}{sup +/+} and D{sub 4}{sup +/-} mice, MP decreased metabolism in the PFC and increased it in the CBV. These findings provide evidence that D4Rs modulate not only the PFC, which may reflect the activation by dopamine of D4Rs located in this region, but also the CBV, which may reflect an indirect modulation as D4Rs are minimally expressed in this region. As individuals with ADHD show structural and/or functional abnormalities in these brain regions, the association of ADHD with D4Rs may reflect its modulation of these brain regions. The differential response to MP as a function of genotype could explain differences in brain functional responses to MP between patients with ADHD and healthy controls and between patients with ADHD with different D{sub 4} polymorphisms.

  9. Brain Aging and AD-Like Pathology in Streptozotocin-Induced Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Jian-Qin Wang

    2014-01-01

    Full Text Available Objective. Numerous epidemiological studies have linked diabetes mellitus (DM with an increased risk of developing Alzheimer’s disease (AD. However, whether or not diabetic encephalopathy shows AD-like pathology remains unclear. Research Design and Methods. Forebrain and hippocampal volumes were measured using stereology in serial coronal sections of the brain in streptozotocin- (STZ- induced rats. Neurodegeneration in the frontal cortex, hypothalamus, and hippocampus was evaluated using Fluoro-Jade C (FJC. Aβ aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA. Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin. Cognitive ability was evaluated through the Morris water maze and inhibitory avoidant box. Results. Rats are characterized by insulin deficiency accompanied with polydipsia, polyphagia, polyuria, and weight loss after STZ injection. The number of FJC-positive cells significantly increased in discrete brain regions of the diabetic rats compared with the age-matched control rats. Hippocampal atrophy, Aβ aggregation, and synapse loss were observed in the diabetic rats compared with the control rats. The learning and memory of the diabetic rats decreased compared with those of the age-matched control rats. Conclusions. Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies.

  10. [Cognitive and brain development of memory from infancy to early adulthood].

    Science.gov (United States)

    Dégeilh, Fanny; Eustache, Francis; Guillery-Girard, Bérengère

    2015-01-01

    Cognitive and brain development are closely linked from infancy to adulthood. The purpose of this article is to review the current state of knowledge on behavioral and brain substrates of memory development. First, we will review cognitive development of different memory systems, from procedural to autobiographical memory. We will discuss how the development of other cognitive functions (language, attention, executive functions and metamemory) participates in memory development. Second, we will describe how structural and functional changes in two core brain regions of memory, i.e. the hippocampus and the prefrontal cortex, impact the protracted development of memory throughout childhood. PMID:26820831

  11. Effect of hyperbaric oxygenation on mitochondrial function of neuronal cells in the cortex of neonatal rats after hypoxic-ischemic brain damage

    Directory of Open Access Journals (Sweden)

    L. Yang

    2016-01-01

    Full Text Available The timing and mechanisms of protection by hyperbaric oxygenation (HBO in hypoxic-ischemic brain damage (HIBD have only been partially elucidated. We monitored the effect of HBO on the mitochondrial function of neuronal cells in the cerebral cortex of neonatal rats after HIBD. Neonatal Sprague-Dawley rats (total of 360 of both genders were randomly divided into normal control, HIBD, and HIBD+HBO groups. The HBO treatment began immediately after hypoxia-ischemia (HI and continued once a day for 7 consecutive days. Animals were euthanized 0, 2, 4, 6, and 12 h post-HI to monitor the changes in mitochondrial membrane potential (ΔΨm occurring soon after a single dose of HBO treatment, as well as 2, 3, 4, 5, 6, and 7 days post-HI to study ΔΨm changes after a series of HBO treatments. Fluctuations in ΔΨm were observed in the ipsilateral cortex in both HIBD and HIBD+HBO groups. Within 2 to 12 h after HI insult, the ΔΨm of the HIBD and HIBD+HBO groups recovered to some extent. A secondary drop in ΔΨm was observed in both groups during the 1-4 days post-HI period, but was more severe in the HIBD+HBO group. There was a secondary recovery of ΔΨm observed in the HIBD+HBO group, but not in the HIBD group, during the 5-7 days period after HI insult. HBO therapy may not lead to improvement of neural cell mitochondrial function in the cerebral cortex in the early stage post-HI, but may improve it in the sub-acute stage post-HI.

  12. Effect of hyperbaric oxygenation on mitochondrial function of neuronal cells in the cortex of neonatal rats after hypoxic-ischemic brain damage.

    Science.gov (United States)

    Yang, L; Hei, M Y; Dai, J J; Hu, N; Xiang, X Y

    2016-01-01

    The timing and mechanisms of protection by hyperbaric oxygenation (HBO) in hypoxic-ischemic brain damage (HIBD) have only been partially elucidated. We monitored the effect of HBO on the mitochondrial function of neuronal cells in the cerebral cortex of neonatal rats after HIBD. Neonatal Sprague-Dawley rats (total of 360 of both genders) were randomly divided into normal control, HIBD, and HIBD+HBO groups. The HBO treatment began immediately after hypoxia-ischemia (HI) and continued once a day for 7 consecutive days. Animals were euthanized 0, 2, 4, 6, and 12 h post-HI to monitor the changes in mitochondrial membrane potential (ΔΨm) occurring soon after a single dose of HBO treatment, as well as 2, 3, 4, 5, 6, and 7 days post-HI to study ΔΨm changes after a series of HBO treatments. Fluctuations in ΔΨm were observed in the ipsilateral cortex in both HIBD and HIBD+HBO groups. Within 2 to 12 h after HI insult, the ΔΨm of the HIBD and HIBD+HBO groups recovered to some extent. A secondary drop in ΔΨm was observed in both groups during the 1-4 days post-HI period, but was more severe in the HIBD+HBO group. There was a secondary recovery of ΔΨm observed in the HIBD+HBO group, but not in the HIBD group, during the 5-7 days period after HI insult. HBO therapy may not lead to improvement of neural cell mitochondrial function in the cerebral cortex in the early stage post-HI, but may improve it in the sub-acute stage post-HI. PMID:27119428

  13. Elemental concentration analysis in brain of young, adult and old wistar rats by X-ray total reflection fluorescence with synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Serpa, Renata F.B.; Jesus, Edgar F.O. de; Lopes, Ricardo T. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia. Lab. de Instrumentacao Nuclear]. E-mail: renata@lin.ufrj.br; Anjos, Marcelino J. dos [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Fisica]. E-mail: marcelin@lin.ufrj.br; Carmo, Maria da Graca T. do [Universidade Federal, Rio de Janeiro, RJ (Brazil). Inst. de Nutricao]. E-mail: tcarmo@editema.com.br; Rocha, Monica S. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Dept. de Farmacologia]. E-mail: mrocha@farmaco.ufrj.br; Moreira, Silvana [Universidade Estadual de Campinas, SP (Brazil). Faculdade de Engenharia Civil]. E-mail: silvana@fec.unicamp.br; Martinez, Ana Maria B. [Universidade Federal, Rio de Janeiro, RJ (Brazil). Dept. de Histologia]. E-mail: martinez@histo.ufrj.br

    2005-07-01

    The mainly goal of this work is to compare the elemental concentrations with different postnatal ages (2, 8, 20, 48 and 72 weeks) at three different regions of the rat brain, namely temporal cortex, entorhinal cortex and hippocampus by X-Ray Total Reflection Fluorescence with Synchrotron Radiation (SR-TXRF). The advantages for this analytical multielemental technique are: low background, linear relation in the quantification analysis and low detection limit (ngg{sup -1}). The fluorescence measurements were carried out at XRF beamline at the Brazilian Light Synchrotron Laboratory (Campinas, Brazil). It was possible to determine the following elements: Ti, Mn, Fe, Cu, Zn, Br, Rb and Sr (at trace level) and P, S, Cl, K and Ca (at major levels) were determined in the brain. In general, Fe levels were more pronounced in entorhinal cortex. There was also observed that the hippocampus of the old female rat presented the highest concentrations for Al, P, S, K, and Zn. In contrast to this, the hippocampus and entorhinal cortex presented the less levels for Al and K in the young animals. On the other hand, Cl levels were more conspicuous in the entorhinal cortex of the oldest male animal studied. (author)

  14. The change of pathology and expression of caspase-3 in cerebral cortex and hippocampus and cerebellum of alcoholism rats%大鼠酒精中毒后大脑皮质、海马、小脑的病理学改变及caspase-3的异常表达

    Institute of Scientific and Technical Information of China (English)

    贾明月; 朱丹; 陈嘉峰

    2012-01-01

    目的 探讨大鼠慢性酒精中毒后大脑皮质、海马、小脑的病理学改变及caspase-3的异常表达.方法 选用健康雄性Wistar大鼠随机分为两组,其中酒精中毒组30只;盐水对照组20只.酒精中毒组每日每只大鼠分别按8ml/kg灌胃2w,随后再按照10ml/kg灌胃1w,按12ml/kg灌胃1w,共灌胃4w.每日灌胃两次,其间隔均为6h,酒精浓度为50%.对照组用等量的生理盐水灌胃.并对两组大鼠进行体重、一般生物学特征、HE染色、TUNEL染色、免疫组化caspase-3的检测.结果 造模成功后,两组大鼠的体重存在的统计学差异;HE染色后酒精组大鼠大脑皮质、海马、小脑锥体细胞数目减少,部分神经元变性、坏死;TUNEL法测定酒精组大鼠凋亡细胞数量明显多于对照组(P<0.05),酒精组大鼠大脑皮质、海马、小脑的caspase-3表达明显高于对照组(P<0.05).结论 慢性酒精中毒可引起大鼠大脑皮质、海马及小脑的病理学改变,出现神经细胞凋亡,引起与凋亡相对应部位caspase-3阳性表达,并参与大鼠酒精中毒后凋亡机制的发生、发展.%Objective To discuse the change of pathology and expression of caspase-3 in cerebral cortex, hippocampus and cerebellum of alcoholism rats. Methods There were 50 male healthy Wistar rats divided into 2 groups randomly, alcoholism group,30 rats,saline control group,20 rats. Alcoholic group;every rat was fed with 8ml/kg50% alcohol twice a day, and two weeks later, increased to 10ml/kg for one week, then 12ml/kg for one week. The interval of time was 6 hours of all. Control group: every rat was fed with the same dosage of 0.9% sodium chloride at the same time for four weeks. During the experiment, we measured their weight, observed their general condition, HE dyes, TUNEL dying and expression of caspase-3 by SP dying method. Results After 4 weeks,the alcoholic group rats appeared malnutrition,emaciated,moreover,some also appeared the performance of

  15. Histomorphological Phenotyping of the Adult Mouse Brain.

    Science.gov (United States)

    Mikhaleva, Anna; Kannan, Meghna; Wagner, Christel; Yalcin, Binnaz

    2016-01-01

    This article describes a series of standard operating procedures for morphological phenotyping of the mouse brain using basic histology. Many histological studies of the mouse brain use qualitative approaches based on what the human eye can detect. Consequently, some phenotypic information may be missed. Here we describe a quantitative approach for the assessment of brain morphology that is simple and robust. A total of 78 measurements are made throughout the brain at specific and well-defined regions, including the cortex, the hippocampus, and the cerebellum. Experimental design and timeline considerations, including strain background effects, the importance of sectioning quality, measurement variability, and efforts to correct human errors are discussed. © 2016 by John Wiley & Sons, Inc. PMID:27584555

  16. Persimmon leaf flavonoid induces brain ischemic tolerance in mice

    Institute of Scientific and Technical Information of China (English)

    Mingsan Miao; Xuexia Zhang; Linan Wang

    2013-01-01

    The persimmon leaf has been shown to improve cerebral ischemic outcomes; however, its mechanism of action remains unclear. In this study, mice were subjected to 10 minutes of ischemic preconditioning, and persimmon leaf flavonoid was orally administered for 5 days. Results showed that the persimmon leaf flavonoid significantly improved the content of tissue type plasminogen activator and 6-keto prostaglandin-F1 α in the cerebral cortex, decreased the content of thromboxane B2, and reduced the content of plasminogen activator inhibitor-1 in mice. Following optical microscopy, persimmon leaf flavonoid was also shown to reduce cell swelling and nuclear hyperchromatism in the cerebral cortex and hippocampus of mice. These results suggested that persimmon leaf flavonoid can effectively inhibit brain thrombosis, improve blood supply to the brain, and relieve ischemia-induced pathological damage, resulting in brain ischemic tolerance.

  17. Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.

    Science.gov (United States)

    Banerjee, Soumyabrata; Ghosh, Tushar K; Poddar, Mrinal K

    2015-12-01

    The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions. PMID:26364584

  18. Issues in localization of brain function: The case of lateralized frontal cortex in cognition, emotion, and psychopathology

    OpenAIRE

    Miller, Gregory A.; Crocker, Laura D.; Spielberg, Jeffrey M.; Zachary P. Infantolino; Wendy eHeller

    2013-01-01

    The appeal of simple, sweeping portraits of large-scale brain mechanisms relevant to psychological phenomena competes with a rich, complex research base. As a prominent example, two views of frontal brain organization have emphasized dichotomous lateralization as a function of either emotional valence (positive/negative) or approach/avoidance motivation. Compelling findings support each. The literature has struggled to choose between them for three decades, without success. Both views are pro...

  19. A role for dorsal and ventral hippocampus in response learning.

    Science.gov (United States)

    Fidalgo, C; Conejo, N M; González-Pardo, H; Lazo, P S; Arias, J L

    2012-07-01

    The hippocampus and the striatum have been traditionally considered as part of different and independent memory systems despite growing evidence supporting that both brain regions may even compete for behavioral control in particular learning tasks. In this regard, it has been reported that the hippocampus could be necessary for the use of idiothetic cues in several types of spatial learning tasks. Accordingly, the ventral striatum receives strong anatomical projections from the hippocampus, suggesting a participation of both regions in goal-directed behavior. Our work examined the role of the dorsal and ventral hippocampus on a response learning task. Cytochrome c oxidase (C.O.) quantitative histochemistry was used as an index of brain oxidative metabolism. In addition, determination of C.O. subunit I levels in the hippocampus by western blot analysis was performed to assess the contribution of this subunit to overall C.O. activity. Increased brain oxidative metabolism was found in most of the studied hippocampal subregions when experimental group was compared with a swim control group. However, no differences were found in the amount of C.O. subunit I expressed in the hippocampus by western blot analysis. Our results support that both the dorsal and ventral hippocampus are associated with the use of response strategies during response learning. PMID:22507525

  20. Human brain activity patterns beyond the isoelectric line of extreme deep coma.

    Directory of Open Access Journals (Sweden)

    Daniel Kroeger

    Full Text Available The electroencephalogram (EEG reflects brain electrical activity. A flat (isoelectric EEG, which is usually recorded during very deep coma, is considered to be a turning point between a living brain and a deceased brain. Therefore the isoelectric EEG constitutes, together with evidence of irreversible structural brain damage, one of the criteria for the assessment of brain death. In this study we use EEG recordings for humans on the one hand, and on the other hand double simultaneous intracellular recordings in the cortex and hippocampus, combined with EEG, in cats. They serve to demonstrate that a novel brain phenomenon is observable in both humans and animals during coma that is deeper than the one reflected by the isoelectric EEG, and that this state is characterized by brain activity generated within the hippocampal formation. This new state was induced either by medication applied to postanoxic coma (in human or by application of high doses of anesthesia (isoflurane in animals leading to an EEG activity of quasi-rhythmic sharp waves which henceforth we propose to call ν-complexes (Nu-complexes. Using simultaneous intracellular recordings in vivo in the cortex and hippocampus (especially in the CA3 region we demonstrate that ν-complexes arise in the hippocampus and are subsequently transmitted to the cortex. The genesis of a hippocampal ν-complex depends upon another hippocampal activity, known as ripple activity, which is not overtly detectable at the cortical level. Based on our observations, we propose a scenario of how self-oscillations in hippocampal neurons can lead to a whole brain phenomenon during coma.

  1. Ethanolic Extract of Astragali Radix and Salviae Radix Prohibits Oxidative Brain Injury by Psycho-Emotional Stress in Whisker Removal Rat Model

    Science.gov (United States)

    Kim, Hyeong-Geug; Lee, Jin-Seok; Choi, Min-Kyung; Han, Jong-Min; Son, Chang-Gue

    2014-01-01

    Myelophil, an ethanolic extract of Astragali Radix and Salviae Radix, has been clinically used to treat chronic fatigue and stress related disorders in South Korea. In this study, we investigated the protective effects of Myelophil on a whisker removal-induced psycho-emotional stress model. SD rats were subjected to whisker removal after oral administration of Myelophil or ascorbic acid for consecutive 4 days. Whisker removal considerably increased total reactive oxygen species in serum levels as well as cerebral cortex and hippocampal regions in brain tissues. Lipidperoxidation levels were also increased in the cerebral cortex, hippocampus regions, and brain tissue injuries as shown in histopathology and immunohistochemistry. However, Myelophil significantly ameliorated these alterations, and depletion of glutathione contents in both cerebral cortex and hippocampus regions respectively. Serum levels of corticosterone and adrenaline were notably altered after whisker removal stress, whereas these abnormalities were significantly normalized by pre-treatment with Myelophil. The NF-κB was notably activated in both cerebral cortex and hippocampus after whisker removal stress, while it was efficiently blocked by pre-treatment with Myelophil. Myelophil also significantly normalizes alterations of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and interferon-γ in both gene expressions and protein levels. These results suggest that Myelophil has protective effects on brain damages in psycho-emotional stress, and the underlying mechanisms involve regulation of inflammatory proteins, especially NF-κB modulation. PMID:24870587

  2. Serotonin Receptors in Hippocampus

    OpenAIRE

    Laura Cristina Berumen; Angelina Rodríguez; Ricardo Miledi; Guadalupe García-Alcocer

    2012-01-01

    Serotonin is an ancient molecular signal and a recognized neurotransmitter brainwide distributed with particular presence in hippocampus. Almost all serotonin receptor subtypes are expressed in hippocampus, which implicates an intricate modulating system, considering that they can be localized as autosynaptic, presynaptic, and postsynaptic receptors, even colocalized within the same cell and being target of homo- and heterodimerization. Neurons and glia, including immune cells, integrate a fu...

  3. Elemental concentration analysis in brain structures from young, adult and old Wistar rats by total reflection X-ray fluorescence with synchrotron radiation

    Energy Technology Data Exchange (ETDEWEB)

    Serpa, R.F.B. [Federal University of Rio de Janeiro/COPPE, Nuclear Instrumentation Laboratory, P.O. Box: 68509, Zip Code: 21941-972, Rio de Janeiro (Brazil)]. E-mail: renata@lin.ufrj.br; Jesus, E.F.O. de [Federal University of Rio de Janeiro/COPPE, Nuclear Instrumentation Laboratory, P.O. Box: 68509, Zip Code: 21941-972, Rio de Janeiro (Brazil); Anjos, M.J. [Federal University of Rio de Janeiro/COPPE, Nuclear Instrumentation Laboratory, P.O. Box: 68509, Zip Code: 21941-972, Rio de Janeiro (Brazil); University of Rio de Janeiro State, Physics Institute, RJ (Brazil); Carmo, M.G.T. do [Federal University of Rio de Janeiro, Nutrition Institute, RJ (Brazil); Moreira, S. [University of Campinas State, Civil Engineering Department, SP (Brazil); Rocha, M.S. [Federal University of Rio de Janeiro, Department of Basics and Clinic Pharmacy, RJ (Brazil); Martinez, A.M.B. [Federal University of Rio de Janeiro, Department of Histology and Embryology, RJ (Brazil); Lopes, R.T. [Federal University of Rio de Janeiro/COPPE, Nuclear Instrumentation Laboratory, P.O. Box: 68509, Zip Code: 21941-972, Rio de Janeiro (Brazil)

    2006-11-15

    The knowledge of the spatial distribution and the local concentration of trace elements in tissues are of great importance since trace elements are involved in a number of metabolic and physiological processes in the human body, and their deficiency and excess may lead to different metabolic disorders. In this way, the main goal of this work is to compare the elemental concentration in different brain structures, namely temporal cortex, entorhinal cortex, visual cortex and hippocampus, from Wistar female rats (n = 15) with different ages: 2, 8 and 48 weeks. The measurements were performed at the Synchrotron Light Brazilian Laboratory, Campinas, Sao Paulo, Brazil. In the entorhinal cortex, the following elements decreased with age: Zn, S, Cl, K, Ca and Br. In the temporal cortex, Ca, Fe and Br levels increased with aging and on the other hand, P, S, Cl, K and Rb levels decreased with aging. In the visual cortex almost all the elements decreased with aging: Cl, Ca, Fe, Ni and Zn. In the hippocampus, in turn, most of the elements identified, increased with aging: Al, P, S, K, Fe, Cu, Zn and Rb. The increase of Fe with aging in the hippocampus is an important fact that will be studied, since it is involved in oxidative stress. It is believed that oxidative stress is the one of the main causes responsible for neuronal death in Parkinson's disease.

  4. Ethinyl estradiol and levonorgestrel alter cognition and anxiety in rats concurrent with a decrease in tyrosine hydroxylase expression in the locus coeruleus and brain-derived neurotrophic factor expression in the hippocampus.

    Science.gov (United States)

    Simone, Jean; Bogue, Elizabeth A; Bhatti, Dionnet L; Day, Laura E; Farr, Nathan A; Grossman, Anna M; Holmes, Philip V

    2015-12-01

    In the United States, more than ten million women use contraceptive hormones. Ethinyl estradiol and levonorgestrel have been mainstay contraceptive hormones for the last four decades. Surprisingly, there is scant information regarding their action on the central nervous system and behavior. Intact female rats received three weeks of subcutaneous ethinyl estradiol (10 or 30μg/rat/day), levonorgestrel (20 or 60μg/rat/day), a combination of both (10/20μg/rat/day and 30/60μg/rat/day), or vehicle. Subsequently, the rats were tested in three versions of the novel object recognition test to assess learning and memory, and a battery of tests for anxiety-like behavior. Serum estradiol and ovarian weights were measured. All treatment groups exhibited low endogenous 17β-estradiol levels at the time of testing. Dose-dependent effects of drug treatment manifested in both cognitive and anxiety tests. All low dose drugs decreased anxiety-like behavior and impaired performance on novel object recognition. In contrast, the high dose ethinyl estradiol increased anxiety-like behavior and improved performance in cognitive testing. In the cell molecular analyses, low doses of all drugs induced a decrease in tyrosine hydroxylase mRNA and protein in the locus coeruleus. At the same time, low doses of ethinyl estradiol and ethinyl estradiol/levonorgestrel increased galanin protein in this structure. Consistent with the findings above, the low dose treatments of ethinyl estradiol and combination ethinyl estradiol/levonorgestrel reduced brain-derived neurotrophic factor mRNA in the hippocampus. These effects of ethinyl estradiol 10μg alone and in combination with levonorgestrel 20μg suggest a diminution of norepinephrine input into the hippocampus resulting in a decline in learning and memory. PMID:26352480

  5. Inhibition of aminoacylase 3 protects rat brain cortex neuronal cells from the toxicity of 4-hydroxy-2-nonenal mercapturate and 4-hydroxy-2-nonenal

    Energy Technology Data Exchange (ETDEWEB)

    Tsirulnikov, Kirill; Abuladze, Natalia [Department of Medicine, University of California at Los Angeles, CA 90095 (United States); Bragin, Anatol [Department of Neurology, University of California at Los Angeles, CA 90095 (United States); Brain Research Institute, University of California at Los Angeles, CA 90095 (United States); Faull, Kym [Brain Research Institute, University of California at Los Angeles, CA 90095 (United States); Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, CA 90095 (United States); Pasarow Mass Spectrometry Laboratory, University of California at Los Angeles, CA 90095 (United States); Cascio, Duilio [Institute of Genomics and Proteomics, University of California at Los Angeles, CA 90095 (United States); Damoiseaux, Robert; Schibler, Matthew J. [California NanoSystems Institute, University of California at Los Angeles, CA 90095 (United States); Pushkin, Alexander, E-mail: apushkin@mednet.ucla.edu [Department of Medicine, University of California at Los Angeles, CA 90095 (United States)

    2012-09-15

    4-Hydroxy-2-nonenal (4HNE) and acrolein (ACR) are highly reactive neurotoxic products of lipid peroxidation that are implicated in the pathogenesis and progression of Alzheimer's and Parkinson's diseases. Conjugation with glutathione (GSH) initiates the 4HNE and ACR detoxification pathway, which generates the mercapturates of 4HNE and ACR that can be excreted. Prior work has shown that the efficiency of the GSH-dependent renal detoxification of haloalkene derived mercapturates is significantly decreased upon their deacetylation because of rapid transformation of the deacetylated products into toxic compounds mediated by β-lyase. The enzymes of the GSH-conjugation pathway and β-lyases are expressed in the brain, and we hypothesized that a similar toxicity mechanism may be initiated in the brain by the deacetylation of 4HNE- and ACR-mercapturate. The present study was performed to identify an enzyme(s) involved in 4HNE- and ACR-mercapturate deacetylation, characterize the brain expression of this enzyme and determine whether its inhibition decreases 4HNE and 4HNE-mercapturate neurotoxicity. We demonstrated that of two candidate deacetylases, aminoacylases 1 (AA1) and 3 (AA3), only AA3 efficiently deacetylates both 4HNE- and ACR-mercapturate. AA3 was further localized to neurons and blood vessels. Using a small molecule screen we generated high-affinity AA3 inhibitors. Two of them completely protected rat brain cortex neurons expressing AA3 from the toxicity of 4HNE-mercapturate. 4HNE-cysteine (4HNE-Cys) was also neurotoxic and its toxicity was mostly prevented by a β-lyase inhibitor, aminooxyacetate. The results suggest that the AA3 mediated deacetylation of 4HNE-mercapturate may be involved in the neurotoxicity of 4HNE.

  6. Inhibition of aminoacylase 3 protects rat brain cortex neuronal cells from the toxicity of 4-hydroxy-2-nonenal mercapturate and 4-hydroxy-2-nonenal

    International Nuclear Information System (INIS)

    4-Hydroxy-2-nonenal (4HNE) and acrolein (ACR) are highly reactive neurotoxic products of lipid peroxidation that are implicated in the pathogenesis and progression of Alzheimer's and Parkinson's diseases. Conjugation with glutathione (GSH) initiates the 4HNE and ACR detoxification pathway, which generates the mercapturates of 4HNE and ACR that can be excreted. Prior work has shown that the efficiency of the GSH-dependent renal detoxification of haloalkene derived mercapturates is significantly decreased upon their deacetylation because of rapid transformation of the deacetylated products into toxic compounds mediated by β-lyase. The enzymes of the GSH-conjugation pathway and β-lyases are expressed in the brain, and we hypothesized that a similar toxicity mechanism may be initiated in the brain by the deacetylation of 4HNE- and ACR-mercapturate. The present study was performed to identify an enzyme(s) involved in 4HNE- and ACR-mercapturate deacetylation, characterize the brain expression of this enzyme and determine whether its inhibition decreases 4HNE and 4HNE-mercapturate neurotoxicity. We demonstrated that of two candidate deacetylases, aminoacylases 1 (AA1) and 3 (AA3), only AA3 efficiently deacetylates both 4HNE- and ACR-mercapturate. AA3 was further localized to neurons and blood vessels. Using a small molecule screen we generated high-affinity AA3 inhibitors. Two of them completely protected rat brain cortex neurons expressing AA3 from the toxicity of 4HNE-mercapturate. 4HNE-cysteine (4HNE-Cys) was also neurotoxic and its toxicity was mostly prevented by a β-lyase inhibitor, aminooxyacetate. The results suggest that the AA3 mediated deacetylation of 4HNE-mercapturate may be involved in the neurotoxicity of 4HNE.

  7. Brain Basics

    Medline Plus

    Full Text Available ... may help improve treatments for anxiety disorders like phobias or post-traumatic stress disorder (PTSD) . Prefrontal cortex ( ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as ...

  8. Association between the fMRI manifestations of activated brain areas and muscle strength in patients with space-occupying lesions in motor cortex

    Institute of Scientific and Technical Information of China (English)

    Wenbin Zheng; Xiaoke Chen; Guorui Liu; Renhua Wu

    2006-01-01

    simple active finger-tapping movements, and for the 3 cases whose clinical symptoms were severe in the patient group, the simple passive finger-tapping movements were used. The manifestations in the activated brain areas were analyzed in the patients with brain tumor of different muscle strength and the controls. The motor deficit and activation of contralateral primary motor cortex (M1) in simple finger-tapping movements were observed in the patient group.MAIN OUTCOME MEASURES: ① Brain areas activated by finger-tapping movements in each group; ② Activated volumes in hemisphere by finger-tapping movements between groups.RESULTS: The contralateral M1 area could not be activated in 1 case in the patient group,, all the other 22 patients and 9 healthy subjects were involved in the analysis of results. ① In the control group, unilateral finger tapping movement activated the contralateral primary motor cortex (M1), bilateral SMA and bilateral PMC. The activation volume was the largest in contralateral primary motor cortex (M1), smaller in the SMA,and the smallest in PMC. The finger tapping movement in healthy subjects could activate contralateral primary motor cortex (M1), bilateral SMA and bilateral PMC, which had no obvious differences from the manifestations of brain functional area activated by active finger tapping. There was no significant difference in the volume of activated functional areas between right and left hands. In the patient group, the central sulcus around the tumor in the activated M1 area displaced towards dorsal or ventral side, also extended. The distance of displacement in the functional area was determined as compared with the contralateral central sulcus, and the results suggested the M1 displacement, including that there were 10 cases with the M1 displacement larger than 10 mm in the patients with motor deficit, which were obviously more than in those without motor deficit (n =1, P < 0.01), and the activated volume in contralateral M1 area

  9. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer’s disease

    OpenAIRE

    Nagahara, Alan H.; Merrill, David A.; Coppola, Giovanni; Tsukada, Shingo; Schroeder, Brock E; Shaked, Gideon M.; Wang, Ling; Blesch, Armin; Kim, Albert; Conner, James M; Rockenstein, Edward; Chao, Moses V.; Koo, Edward H.; Geschwind, Daniel; Masliah, Eliezer

    2009-01-01

    Profound neuronal dysfunction in the entorhinal cortex contributes to early loss of short-term memory in Alzheimer’s disease1–3. Here we show broad neuroprotective effects of entorhinal brain-derived neurotrophic factor (BDNF) administration in several animal models of Alzheimer’s disease, with extension of therapeutic benefits into the degenerating hippocampus. In amyloid-transgenic mice, BDNF gene delivery, when administered after disease onset, reverses synapse loss, partially normalizes a...

  10. Post-conditioning exacerbates the MnSOD immune-reactivity after experimental cerebral global ischemia and reperfusion in the rat brain hippocampus.

    Science.gov (United States)

    Nemethova, Miroslava; Danielisova, Viera; Gottlieb, Miroslav; Burda, Jozef

    2008-01-01

    This study monitored the effects of sub-lethal ischemia (post-conditioning) applied after a previous ischemic attack by way of the MnSOD immune-reactivity examined in CA1 and dentate gyrus of the rat hippocampus. The experimental 10 min transient cerebral ischemia was followed by 2 days of reperfusion, the rats then underwent a second ischemia (4 or 6 min post-conditioning). MnSOD immune-reactivity was evaluated after 5 h, 1 and 2 days. Results obtained by computer microdensitometric image analysis indicated that 4 min of ischemic post-conditioning caused higher MnSOD immune-reactivity than 6 min. However, higher viability of CA1 neurons after stronger (6 min) post-conditioning when production of MnSOD is lower, as well as differences between MnSOD in CA1 and dentate gyrus indicates another mechanism switching pro-apoptotic destination of CA1 neurons to anti-apoptotic. PMID:17936646

  11. Brain glycogen decreases during prolonged exercise

    Science.gov (United States)

    Matsui, Takashi; Soya, Shingo; Okamoto, Masahiro; Ichitani, Yukio; Kawanaka, Kentaro; Soya, Hideaki

    2011-01-01

    Abstract Brain glycogen could be a critical energy source for brain activity when the glucose supply from the blood is inadequate (hypoglycaemia). Although untested, it is hypothesized that during prolonged exhaustive exercise that induces hypoglycaemia and muscular glycogen depletion, the resultant hypoglycaemia may cause a decrease in brain glycogen. Here, we tested this hypothesis and also investigated the possible involvement of brain monoamines with the reduced levels of brain glycogen. For this purpose, we exercised male Wistar rats on a treadmill for different durations (30–120 min) at moderate intensity (20 m min−1) and measured their brain glycogen levels using high-power microwave irradiation (10 kW). At the end of 30 and 60 min of running, the brain glycogen levels remained unchanged from resting levels, but liver and muscle glycogen decreased. After 120 min of running, the glycogen levels decreased significantly by ∼37–60% in five discrete brain loci (the cerebellum 60%, cortex 48%, hippocampus 43%, brainstem 37% and hypothalamus 34%) compared to those of the sedentary control. The brain glycogen levels in all five regions after running were positively correlated with the respective blood and brain glucose levels. Further, in the cortex, the levels of methoxyhydroxyphenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA), potential involved in degradation of the brain glycogen, increased during prolonged exercise and negatively correlated with the glycogen levels. These results support the hypothesis that brain glycogen could decrease with prolonged exhaustive exercise. Increased monoamines together with hypoglycaemia should be associated with the development of decreased brain glycogen, suggesting a new clue towards the understanding of central fatigue during prolonged exercise. PMID:21521757

  12. Regional Distribution of Copper, Zinc and Iron in Brain of Wistar Rat Model for Non-Wilsonian Brain Copper Toxicosis.

    Science.gov (United States)

    Pal, Amit; Prasad, Rajendra

    2016-03-01

    In previous studies, we have reported first in vivo evidence of copper deposition in the choroid plexus, cognitive impairments, astrocytes swelling (Alzheimer type II cells) and astrogliosis (increase in number of astrocytes), and degenerated neurons coupled with significant increase in the hippocampus copper and zinc content in copper-intoxicated Wistar rats. Nonetheless, hippocampus iron levels were not affected by chronic copper-intoxication. Notwithstanding information on distribution of copper, zinc and iron status in different regions of brain due to chronic copper exposure remains fragmentary. In continuation with our previous study, the aim of this study was to investigate the effects of intraperitoneally injected copper lactate (0.15 mg Cu/100 g body weight) daily for 90 days on copper, zinc and iron levels in different regions of the brain using atomic absorption spectrophotometry. Copper-intoxicated group showed significantly increased cortex, cerebellum and striatum copper content (76, 46.8 and 80.7 % increase, respectively) compared to control group. However, non-significant changes were observed for the zinc and iron content in cortex, cerebellum and striatum due to chronic copper exposure. In conclusion, the current study demonstrates that chronic copper toxicity causes differential copper buildup in cortex, cerebellum and striatum region of central nervous system of male Wistar rats; signifying the critical requirement to discretely evaluate the effect of copper neurotoxicity in different brain regions, and ensuing neuropathological and cognitive dysfunctions. PMID:26855494

  13. In vivo phosphorylation following [32P]orthophosphate injection into neostriatum or hippocampus: selective and rapid labeling of electrophoretically separated brain proteins

    International Nuclear Information System (INIS)

    Intracranial injections of [32P]orthophosphate readily label a number of brain phosphoproteins as resolved by polyacrylamide gel electrophoresis. The majority of these in vivo labeled phosphoproteins co-migrate with phosphoproteins that are labeled in vitro by incubation of brain membranes with [32P]ATP. Two of the major in vitro labeled phosphoproteins with apparent molecular weights of 47,000 (band F1) and 41,000 (band F2) are rapidly labeled in vivo. Since they are rapidly dephosphorylated in vitro, this suggests a high rate of phosphate turnover. (Auth.)

  14. Brain region-specific decrease in the activity and expression of protein kinase A in the frontal cortex of regressive autism.

    Directory of Open Access Journals (Sweden)

    Lina Ji

    Full Text Available Autism is a severe neurodevelopmental disorder that is characterized by impaired language, communication, and social skills. In regressive autism, affected children first show signs of normal social and language development but eventually lose these skills and develop autistic behavior. Protein kinases are essential in G-protein-coupled, receptor-mediated signal transduction and are involved in neuronal functions, gene expression, memory, and cell differentiation. We studied the activity and expression of protein kinase A (PKA, a cyclic AMP-dependent protein kinase, in postmortem brain tissue samples from the frontal, temporal, parietal, and occipital cortices, and the cerebellum of individuals with regressive autism; autistic subjects without a clinical history of regression; and age-matched developmentally normal control subjects. The activity of PKA and the expression of PKA (C-α, a catalytic subunit of PKA, were significantly decreased in the frontal cortex of individuals with regressive autism compared to control subjects and individuals with non-regressive autism. Such changes were not observed in the cerebellum, or the cortices from the temporal, parietal, and occipital regions of the brain in subjects with regressive autism. In addition, there was no significant difference in PKA activity or expression of PKA (C-α between non-regressive autism and control groups. These results suggest that regression in autism may be associated, in part, with decreased PKA-mediated phosphorylation of proteins and abnormalities in cellular signaling.

  15. Repetitive sensorimotor events modulate the magnitude and functional coupling of brain rhythmicity in human temporal cortex: a SEEG coherence study

    Czech Academy of Sciences Publication Activity Database

    Vecchio, F.; Babiloni, C.; Bareš, M.; Brázdil, M.; Moretti, D. V.; Nestrašil, I.; Jurák, Pavel; Cola, B.; Rossini, P. M.; Rektor, I.

    Budapest: HBM, 2005, TH243:1-3. [Annual Meeting of the Organization for Human Brain Mapping /10./ (HMB 2004). Budapest (HU), 13.06.2004-17.06.2004] R&D Projects: GA ČR GA102/05/0402 Keywords : intracerebral * ERD/ERS * coherency Subject RIV: FH - Neurology

  16. Electroacupuncture stimulation of the brachial plexus trunk on the healthy side promotes brain-derived neurotrophic factor mRNA expression in the ischemic cerebral cortex of a rat model of cerebral ischemia/reperfusion injury

    Institute of Scientific and Technical Information of China (English)

    Zongjun Guo; Lumin Wang

    2012-01-01

    A rat model of cerebral ischemia/reperfusion was established by suture occlusion of the left middle cerebral artery. In situ hybridization results showed that the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic rat cerebral cortex increased after cerebral ischemia/ reperfusion injury. Low frequency continuous wave electroacupuncture (frequency 2-6 Hz, current intensity 2 mA) stimulation of the brachial plexus trunk on the healthy (right) side increased the number of brain-derived neurotrophic factor mRNA-positive cells in the ischemic cerebral cortex 14 days after cerebral ischemia/reperfusion injury. At the same time, electroacupuncture stimulation of the healthy brachial plexus truck significantly decreased neurological function scores and alleviated neurological function deficits. These findings suggest that electroacupuncture stimulation of the brachial plexus trunk on the healthy (right) side can greatly increase brain-derived neurotrophic factor mRNA expression and improve neurological function.

  17. Functional neurogenesis in the adult hippocampus

    Science.gov (United States)

    van Praag, Henriette; Schinder, Alejandro F.; Christie, Brian R.; Toni, Nicolas; Palmer, Theo D.; Gage, Fred H.

    2002-02-01

    There is extensive evidence indicating that new neurons are generated in the dentate gyrus of the adult mammalian hippocampus, a region of the brain that is important for learning and memory. However, it is not known whether these new neurons become functional, as the methods used to study adult neurogenesis are limited to fixed tissue. We use here a retroviral vector expressing green fluorescent protein that only labels dividing cells, and that can be visualized in live hippocampal slices. We report that newly generated cells in the adult mouse hippocampus have neuronal morphology and can display passive membrane properties, action potentials and functional synaptic inputs similar to those found in mature dentate granule cells. Our findings demonstrate that newly generated cells mature into functional neurons in the adult mammalian brain.

  18. The hippocampus - pictorial essay

    International Nuclear Information System (INIS)

    Full text: We aim to demonstrate the anatomy and pathology of the hippocampus. It is important that radiologists distinguish normal and abnormal hippocampal hippocampal MR appearances, since hippocampal sclerosis is the commonest cause of surgically treatable temporal lobe epilepsy. The detailed anatomy of the hippocampus is reviewed and correlated with normal MR appearances. Our radiology database was reviewed to determine both common and unusual pathologies affecting the hippocampus. Most scans were performed for our large Comprehensive Epilepsy Program, for investigation of epilepsy of possible seizures. Less frequent indications included memory loss (acute or chronic), stroke, headache, and altered conscious state. Hippocampal sclerosis was the commonest MR abnormality. This was occasionally bilateral or associated with other pathology. Other common findings included mild hippocampal asymmetry, bilateral atrophy, or normal variants such as choroid fissure cysts. Other pathologies included cortical developmental malformations, infarction, posttraumatic gliosis, herpes, simplex encephalitis, paraneoplastic limbic encephalitis, vascular malformations, sarcoidosis, benign tumours such as gangliogliomas and dysembyoplastic neuroepithelial tumours (DNET) and malignant tumours. The hippocampus has a complex anatomy visible on high resolution MRI. In the clinical context of epilepsy, hippocampal sclerosis is an important pathology, but a range of conditions may affect the hippocampus, readily demonstrated by MRI. Copyright (2002) Blackwell Science Pty Ltd

  19. Egocentric spatial orientation in a water maze by rats subjected to transection of the fimbria-fornix and/or ablation of the prefrontal cortex

    DEFF Research Database (Denmark)

    Mogensen, Jesper; Moustgaard, Anette; Khan, Usman;

    2005-01-01

    prefrontal cortex, hippocampus, fimbria-fornix, egocentrisk spatial orientering, vandlabyrint, adfærdsstrategier, kognitive strategier, funktionel genopretning, rehabilitering, problemløsning, rotter...

  20. Adult Neurogenesis in the Mammalian Hippocampus: Why the Dentate Gyrus?

    Science.gov (United States)

    Drew, Liam J.; Fusi, Stefano; Hen, René

    2013-01-01

    In the adult mammalian brain, newly generated neurons are continuously incorporated into two networks: interneurons born in the subventricular zone migrate to the olfactory bulb, whereas the dentate gyrus (DG) of the hippocampus integrates locally born principal neurons. That the rest of the mammalian brain loses significant neurogenic capacity…

  1. Early correlation of microglial activation with enhanced tumor necrosis factor-alpha and monocyte chemoattractant protein-1 expression specifically within the entorhinal cortex of triple transgenic Alzheimer's disease mice

    Directory of Open Access Journals (Sweden)

    LaFerla Frank M

    2005-10-01

    Full Text Available Abstract Background Alzheimer's disease is a complex neurodegenerative disorder characterized pathologically by a temporal and spatial progression of beta-amyloid (Aβ deposition, neurofibrillary tangle formation, and synaptic degeneration. Inflammatory processes have been implicated in initiating and/or propagating AD-associated pathology within the brain, as inflammatory cytokine expression and other markers of inflammation are pronounced in individuals with AD pathology. The current study examines whether inflammatory processes are evident early in the disease process in the 3xTg-AD mouse model and if regional differences in inflammatory profiles exist. Methods Coronal brain sections were used to identify Aβ in 2, 3, and 6-month 3xTg-AD and non-transgenic control mice. Quantitative real-time RT-PCR was performed on microdissected entorhinal cortex and hippocampus tissue of 2, 3, and 6-month 3xTg-AD and non-transgenic mice. Microglial/macrophage cell numbers were quantified using unbiased stereology in 3xTg-AD and non-transgenic entorhinal cortex and hippocampus containing sections. Results We observed human Aβ deposition at 3 months in 3xTg-AD mice which is enhanced by 6 months of age. Interestingly, we observed a 14.8-fold up-regulation of TNF-α and 10.8-fold up-regulation of MCP-1 in the entorhinal cortex of 3xTg-AD mice but no change was detected over time in the hippocampus or in either region of non-transgenic mice. Additionally, this increase correlated with a specific increase in F4/80-positive microglia and macrophages in 3xTg-AD entorhinal cortex. Conclusion Our data provide evidence for early induction of inflammatory processes in a model that develops amyloid and neurofibrillary tangle pathology. Additionally, our results link inflammatory processes within the entorhinal cortex, which represents one of the earliest AD-affected brain regions.

  2. Segregation of the human medial prefrontal cortex in social cognition

    Directory of Open Access Journals (Sweden)

    Danilo eBzdok

    2013-05-01

    Full Text Available While the human medial prefrontal cortex (mPFC is widely believed to be a key node of neural networks relevant for socio-emotional processing, its functional subspecialization is still poorly understood. We thus revisited the often assumed differentiation of the mPFC in social cognition along its ventral-dorsal axis. Our neuroinformatic analysis was based on a neuroimaging meta-analysis of perspective-taking that yielded two separate clusters in the ventral and dorsal mPFC, respectively. We determined each seed region’s brain-wide interaction pattern by two complementary measures of functional connectivity: co-activation across a wide range of neuroimaging studies archived in the BrainMap database and correlated signal fluctuations during unconstrained (resting cognition. Furthermore, we characterized the functions associated with these two regions using the BrainMap database. Across methods, the ventral mPFC was more strongly connected with the nucleus accumbens, hippocampus, posterior cingulate cortex, and retrosplenial cortex, while the dorsal mPFC was more strongly connected with the inferior frontal gyrus, temporo-parietal junction, and middle temporal gyrus. Further, the ventral mPFC was selectively associated with action execution, olfaction, and reward related tasks, while the dorsal mPFC was selectively associated with perspective-taking and episodic memory retrieval. The ventral mPFC is therefore predominantly involved in sensory-driven, approach/avoidance-modulating, and evaluation-related processing, whereas the dorsal mPFC is predominantly involved in internally driven, memory-informed, and metacognition-related processing in social cognition.

  3. Manipulation of Dysfunctional Spinal Joints Affects Sensorimotor Integration in the Prefrontal Cortex: A Brain Source Localization Study

    OpenAIRE

    Dina Lelic; Imran Khan Niazi; Kelly Holt; Mads Jochumsen; Kim Dremstrup; Paul Yielder; Bernadette Murphy; Asbjørn Mohr Drewes; Heidi Haavik

    2016-01-01

    Objectives. Studies have shown decreases in N30 somatosensory evoked potential (SEP) peak amplitudes following spinal manipulation (SM) of dysfunctional segments in subclinical pain (SCP) populations. This study sought to verify these findings and to investigate underlying brain sources that may be responsible for such changes. Methods. Nineteen SCP volunteers attended two experimental sessions, SM and control in random order. SEPs from 62-channel EEG cap were recorded following median nerve ...

  4. Use of functional MRI to evaluate correlation between acupoints and brain cortex activites: comparison between conventional and electrical acupuncture

    OpenAIRE

    Wong, KKK; Leung, MCT; Ma, QY; Chan, JHM; Li, R; Yang, ES; Wong, V; Li, G.

    2000-01-01

    The use of acupuncture therapy in various functional disorders goes back several thousand years in China. Recendy, acupuncture becomes a 'hot' topic in the functional Magnetic Resonance (MR) imaging research studies [1-4]. A majority of these research projects is to study die correlation between the acupuncture points (acupoints) and die corresponding brain cortices, either by conventional acupuncture, electro-acupuncture or laser acupuncture. Cho et al reported mat by stimulating die vision-...

  5. The noninvasive dissection of the human visual cortex: using FMRI and TMS to study the organization of the visual brain.

    Science.gov (United States)

    McKeefry, Declan J; Gouws, Andre; Burton, Mark P; Morland, Antony B

    2009-10-01

    The development of brain imaging techniques, such as fMRI, has given modern neuroscientists unparalleled access to the inner workings of the living human brain. Visual processing in particular has proven to be particularly amenable to study with fMRI. Studies using this technique have revealed the existence of multiple representations of visual space with differing functional roles across many cortical locations. Yet, although fMRI provides an excellent means by which we can localize and map different areas across the visual brain, it is less well suited to providing information as to whether activation within a particular cortical region is directly related to perception or behavior. These kinds of causal links can be made, however, when fMRI is combined with transcranial magnetic stimulation (TMS). TMS is a noninvasive technique that can bring about localized, transient disruption of cortical function and can induce functional impairments in the performance of specific tasks. When guided by the detailed localizing and mapping capabilities of fMRI, TMS can be used as a means by which the functional roles of different visual areas can be investigated. This review highlights recent insights that the techniques of fMRI and TMS have given us with regard to the function and contributions of the many different visual areas to human visual perception. PMID:19826171

  6. Effect of tricyclic antidepressants on transmitter-stimulated inositol phosphate production in rat brain cortex in vitro

    International Nuclear Information System (INIS)

    Tricyclic antidepressants (TCAs) have anticholinergic and α-adrenergic blocking properties. The present study was undertaken to examine the effects of amitriptyline, imipramine, and desipramine on inositol phosphate accumulation, a brain second messenger system associated with cholinergic and adrenergic receptors. Whereas the TCAs were 28 to 400-fold weaker than atropine as inhibitors of 3H-QNB binding to brain cholinergic receptors, they were 600 to 2000-fold less active than atropine as inhibitors of carbachol-stimulated IP accumulation in brain. In contrast, the relative potencies of the TCAs and prazosin to inhibit norepinephrine-stimulated IP accumulation and 3H-prazosin binding appeared to be similar in the two assays. The results suggest pharmacological differences between the cholinergic receptors labeled in the ONB binding assay and those mediating the IP response, whereas the α1-adrenergic receptors appear to be similar in the two systems. Since atropine is considered a nonselective muscarinic antagonist, it is possible that the TCAs may differentiate between cholinergic receptor subtypes, which may be an important component of their clinical response

  7. Parcellation of parietal cortex: convergence between lesion-symptom mapping and mapping of the intact functioning brain.

    Science.gov (United States)

    Vandenberghe, Rik; Gillebert, Céline R

    2009-05-16

    Spatial-attentional deficits are highly prevalent following stroke. They can be clinically detected by means of conventional bedside tests such as target cancellation, line bisection and the visual extinction test. Until recently, lesion mapping studies and functional imaging of the intact brain did not agree very well on exactly which parietal areas play a key role in selective attention: the inferior parietal lobule or the intraparietal sulcus. Recently, the use of a contrastive approach in patients akin to that commonly used in functional imaging studies in healthy volunteers together with voxel-based lesion-symptom mapping have allowed to bring the patient lesion mapping much closer to the functional imaging results obtained in healthy controls. In this review we focus on converging evidence obtained from patient lesion studies and from fMRI studies in the intact brain in humans. This has yielded novel insights into the functional segregation between the middle third of the intraparietal sulcus, the superior parietal lobule and the temporoparietal junction in the intact brain and also enhanced our understanding of the pathogenetic mechanisms underlying deficits arising in patients. PMID:19118580

  8. Long-Term Effects of Maternal Deprivation on Cholinergic System in Rat Brain

    Directory of Open Access Journals (Sweden)

    Branka Marković

    2014-01-01

    Full Text Available Numerous clinical studies have demonstrated an association between early stressful life events and adult life psychiatric disorders including schizophrenia. In rodents, early life exposure to stressors such as maternal deprivation (MD produces numerous hormonal, neurochemical, and behavioral changes and is accepted as one of the animal models of schizophrenia. The stress induces acetylcholine (Ach release in the forebrain and the alterations in cholinergic neurotransmitter system are reported in schizophrenia. The aim of this study was to examine long-term effects of maternal separation on acetylcholinesterase (AChE activity in different brain structures and the density of cholinergic fibers in hippocampus and retrosplenial (RS cortex. Wistar rats were separated from their mothers on the postnatal day (P 9 for 24 h and sacrificed on P60. Control group of rats was bred under the same conditions, but without MD. Brain regions were collected for AChE activity measurements and morphometric analysis. Obtained results showed significant decrease of the AChE activity in cortex and increase in the hippocampus of MD rats. Density of cholinergic fibers was significantly increased in CA1 region of hippocampus and decreased in RS cortex. Our results indicate that MD causes long-term structure specific changes in the cholinergic system.

  9. Rod microglia: elongation, alignment, and coupling to form trains across the somatosensory cortex after experimental diffuse brain injury

    Directory of Open Access Journals (Sweden)

    Ziebell Jenna M

    2012-10-01

    Full Text Available Abstract Background Since their discovery, the morphology of microglia has been interpreted to mirror their function, with ramified microglia constantly surveying the micro-environment and rapidly activating when changes occur. In 1899, Franz Nissl discovered what we now recognize as a distinct microglial activation state, microglial rod cells (Stäbchenzellen, which he observed adjacent to neurons. These rod-shaped microglia are typically found in human autopsy cases of paralysis of the insane, a disease of the pre-penicillin era, and best known today from HIV-1-infected brains. Microglial rod cells have been implicated in cortical ‘synaptic stripping’ but their exact role has remained unclear. This is due at least in part to a scarcity of experimental models. Now we have noted these rod microglia after experimental diffuse brain injury in brain regions that have an associated sensory sensitivity. Here, we describe the time course, location, and surrounding architecture associated with rod microglia following experimental diffuse traumatic brain injury (TBI. Methods Rats were subjected to a moderate midline fluid percussion injury (mFPI, which resulted in transient suppression of their righting reflex (6 to 10 min. Multiple immunohistochemistry protocols targeting microglia with Iba1 and other known microglia markers were undertaken to identify the morphological activation of microglia. Additionally, labeling with Iba1 and cell markers for neurons and astrocytes identified the architecture that surrounds these rod cells. Results We identified an abundance of Iba1-positive microglia with rod morphology in the primary sensory barrel fields (S1BF. Although present for at least 4 weeks post mFPI, they developed over the first week, peaking at 7 days post-injury. In the absence of contusion, Iba1-positive microglia appear to elongate with their processes extending from the apical and basal ends. These cells then abut one another and lay adjacent

  10. Effects of Rhizoma Acori Tatarinowii extracts on gamma-aminobutyric acid type A receptor alpha 1 subunit brain expression during development in a recurrent seizure rat model

    Institute of Scientific and Technical Information of China (English)

    Liqun Liu; Ding'an Mao; Keqiang Chi; Xingfang Li; Tao Bo; Jinming Guo; Zhuwen Yi

    2011-01-01

    Extracts from Rhizoma Acori Tatarinowii (Grassleaf Sweetflag Rhizome, Shichangpu) have been shown to improve learning and memory, reduce anxiety, allay excitement, and suppress seizures. Rhizoma Acori Tatarinowii extracts interact with γ-aminobutyric acid and activate the γ-aminobutyric acid type A receptor, although few studies have addressed the precise effects of γ-aminobutyric acid type A receptor α1 subunit. In the present study, γ-aminobutyric acid type A receptor α1 subunit protein expression in the cerebral cortex and hippocampus, and pathological scores of brain injury, were significantly greater following recurrent seizures, but significantly decreased following treatment with Rhizoma Acori Tatarinowii extracts. These results indicated that Rhizoma Acori Tatarinowii extracts down-regulated γ-aminobutyric acid type A receptor α1 subunit protein expression in the cerebral cortex and hippocampus and protected seizure-induced brain injury during development.

  11. What does spatial alternation tell us about retrosplenial cortex function?

    OpenAIRE

    Andrew John Dudley Nelson

    2015-01-01

    The retrosplenial cortex supports navigation, but there are good reasons to suppose that the retrosplenial cortex has a very different role in spatial memory from that of the hippocampus and anterior thalamic nuclei. For example, retrosplenial lesions appear to have little or no effect on standard tests of spatial alternation. To examine these differences, the current study sought to determine whether the retrosplenial cortex is important for just one spatial cue type (e.g. allocentric, direc...

  12. What does spatial alternation tell us about retrosplenial cortex function?

    OpenAIRE

    Nelson, Andrew J.D.; Powell, Anna L.; Holmes, Joshua D.; Vann, Seralynne D.; Aggleton, John. P.

    2015-01-01

    The retrosplenial cortex supports navigation, but there are good reasons to suppose that the retrosplenial cortex has a very different role in spatial memory from that of the hippocampus and anterior thalamic nuclei. For example, retrosplenial lesions appear to have little or no effect on standard tests of spatial alternation. To examine these differences, the current study sought to determine whether the retrosplenial cortex is important for just one spatial cue type (e.g., allocentric, dire...

  13. Food related processes in the insular cortex

    OpenAIRE

    Frank, Sabine; Kullmann, Stephanie; Veit, Ralf

    2013-01-01

    The insular cortex is a multimodal brain region with regional cytoarchitectonic differences indicating various functional specializations. As a multisensory neural node, the insular cortex integrates perception, emotion, interoceptive awareness, cognition, and gustation. Regarding the latter, predominantly the anterior part of the insular cortex is regarded as the primary taste cortex. In this review, we will specifically focus on the involvement of the insula in food processing and on multim...

  14. Food related processes in the insular cortex

    OpenAIRE

    Sabine eFrank; Stephanie eKullmann; Ralf eVeit

    2013-01-01

    The insular cortex is a multimodal brain region with regional cytoarchitectonic differences indicating various functional specializations. As a multisensory neural node, the insular cortex integrates perception, emotion, interoceptive awareness, cognition, and gustation. Regarding the latter, predominantly the anterior part of the insular cortex is regarded as the primary taste cortex.In this review, we will specifically focus on the involvement of the insula in food processing and on multimo...

  15. 力竭运动后小鼠前脑皮层和海马神经元功能的变化及其机制%Effects of exhausted exercise on the prefrontal cortex and hippocampus function in mice and its mechanism

    Institute of Scientific and Technical Information of China (English)

    蔡成法; 李亚

    2014-01-01

    目的:研究力竭游泳运动对小鼠前脑皮层和海马神经元功能的影响及其作用机制。方法:采用力竭游泳运动小鼠模型,检测反复(4周)力竭游泳运动后即刻(0小时)、12小时、24小时和1周小鼠前脑皮层、海马突触体膜流动性和突触体内游离 Ca2+浓度的变化,通过 Morris 水迷宫测试小鼠空间学习记忆能力。结果:反复力竭游泳运动后,与正常对照组小鼠比较,力竭运动组在12 h 和24 h 小鼠的逃避潜伏期(训练周期1)明显增加,第一象限停留时间明显减少,其空间学习记忆能力显著降低(P <0.01,P <0.05);力竭运动组小鼠前脑皮层和海马突触体膜流动性在0 h、12 h 显著降低(P <0.01,P <0.05);前脑皮层和海马突触体内游离 Ca2+浓度在0 h、12 h 和24 h 显著增加(P <0.05,P <0.01),力竭运动后1周前脑皮层和海马突触体内游离 Ca2+浓度明显恢复(P <0.05)。结论:力竭游泳运动所致小鼠空间学习记忆功能损伤以及运动性中枢疲劳的产生和恢复可能与突触体膜流动性和突触体内游离 Ca2+浓度的变化密切相关。%Objective:To study the effect of exhausted exercise on the prefrontal cortex( PFC) and hippocampus( HP)function and its mechanism. Methods:The repeatedly(4 weeks) exhausted exercise model mice were applied. The spatial learning - memory abilities of mice were tested,using Morris water maze task. The changes of synaptosomal membrane fluidity and [Ca2 + ]i of the PFC and HP in exhausted exercise mice brain were examined,at 0 h (immediately),12 h,24 h,respectively. Results:After repeatedly exhausted exercise,the escape latency was significantly increased and the swimming time of first quadrants were significantly decreased at 12 h,24 h in exhaustive exercise group mice(P < 0. 01,P < 0. 05). Compared with control mice,the ability of spatial learning and memory of the exhaustive exercise group mice were

  16. Mapping Prefrontal Cortex Functions in Human Infancy

    Science.gov (United States)

    Grossmann, Tobias

    2013-01-01

    It has long been thought that the prefrontal cortex, as the seat of most higher brain functions, is functionally silent during most of infancy. This review highlights recent work concerned with the precise mapping (localization) of brain activation in human infants, providing evidence that prefrontal cortex exhibits functional activation much…

  17. Tunicamycin-induced unfolded protein response in the developing mouse brain

    International Nuclear Information System (INIS)

    Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress, resulting in the activation of the unfolded protein response (UPR). ER stress and UPR are associated with many neurodevelopmental and neurodegenerative disorders. The developing brain is particularly susceptible to environmental insults which may cause ER stress. We evaluated the UPR in the brain of postnatal mice. Tunicamycin, a commonly used ER stress inducer, was administered subcutaneously to mice of postnatal days (PDs) 4, 12 and 25. Tunicamycin caused UPR in the cerebral cortex, hippocampus and cerebellum of mice of PD4 and PD12, which was evident by the upregulation of ATF6, XBP1s, p-eIF2α, GRP78, GRP94 and MANF, but failed to induce UPR in the brain of PD25 mice. Tunicamycin-induced UPR in the liver was observed at all stages. In PD4 mice, tunicamycin-induced caspase-3 activation was observed in layer II of the parietal and optical cortex, CA1–CA3 and the subiculum of the hippocampus, the cerebellar external germinal layer and the superior/inferior colliculus. Tunicamycin-induced caspase-3 activation was also shown on PD12 but to a much lesser degree and mainly located in the dentate gyrus of the hippocampus, deep cerebellar nuclei and pons. Tunicamycin did not activate caspase-3 in the brain of PD25 mice and the liver of all stages. Similarly, immature cerebellar neurons were sensitive to tunicamycin-induced cell death in culture, but became resistant as they matured in vitro. These results suggest that the UPR is developmentally regulated and the immature brain is more susceptible to ER stress. - Highlights: • Tunicamycin caused a development-dependent UPR in the mouse brain. • Immature brain was more susceptible to tunicamycin-induced endoplasmic reticulum stress. • Tunicamycin caused more neuronal death in immature brain than mature brain. • Tunicamycin-induced neuronal death is region-specific

  18. Tunicamycin-induced unfolded protein response in the developing mouse brain

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Haiping; Wang, Xin [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Ke, Zun-Ji [Department of Biochemistry, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203 (China); Comer, Ashley L.; Xu, Mei; Frank, Jacqueline A. [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Zhang, Zhuo; Shi, Xianglin [Graduate Center for Toxicology, University of Kentucky College of Medicine, Lexington, KY 40536 (United States); Luo, Jia, E-mail: jialuo888@uky.edu [Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY 40536 (United States)

    2015-03-15

    Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) causes ER stress, resulting in the activation of the unfolded protein response (UPR). ER stress and UPR are associated with many neurodevelopmental and neurodegenerative disorders. The developing brain is particularly susceptible to environmental insults which may cause ER stress. We evaluated the UPR in the brain of postnatal mice. Tunicamycin, a commonly used ER stress inducer, was administered subcutaneously to mice of postnatal days (PDs) 4, 12 and 25. Tunicamycin caused UPR in the cerebral cortex, hippocampus and cerebellum of mice of PD4 and PD12, which was evident by the upregulation of ATF6, XBP1s, p-eIF2α, GRP78, GRP94 and MANF, but failed to induce UPR in the brain of PD25 mice. Tunicamycin-induced UPR in the liver was observed at all stages. In PD4 mice, tunicamycin-induced caspase-3 activation was observed in layer II of the parietal and optical cortex, CA1–CA3 and the subiculum of the hippocampus, the cerebellar external germinal layer and the superior/inferior colliculus. Tunicamycin-induced caspase-3 activation was also shown on PD12 but to a much lesser degree and mainly located in the dentate gyrus of the hippocampus, deep cerebellar nuclei and pons. Tunicamycin did not activate caspase-3 in the brain of PD25 mice and the liver of all stages. Similarly, immature cerebellar neurons were sensitive to tunicamycin-induced cell death in culture, but became resistant as they matured in vitro. These results suggest that the UPR is developmentally regulated and the immature brain is more susceptible to ER stress. - Highlights: • Tunicamycin caused a development-dependent UPR in the mouse brain. • Immature brain was more susceptible to tunicamycin-induced endoplasmic reticulum stress. • Tunicamycin caused more neuronal death in immature brain than mature brain. • Tunicamycin-induced neuronal death is region-specific.

  19. N-methyl-D-aspartate receptor - nitric oxide synthase pathway in the cortex of Nogo-A-deficient rats in relation to brain laterality and schizophrenia

    Directory of Open Access Journals (Sweden)

    Zdena eKristofikova

    2013-08-01

    Full Text Available It has been suggested that Nogo-A, a myelin-associated protein, could play a role in the pathogenesis of schizophrenia and that Nogo-A-deficient rodents could serve as an animal model for schizophrenic symptoms. Since changes in brain laterality are typical of schizophrenia, we investigated whether Nogo-A-deficient rats showed any signs of disturbed asymmetry in cortical N-methyl-D-aspartate (NMDA receptor–nitric oxide synthase (NOS pathway, which is reported as dysfunctional in schizophrenia. In particular, we measured separately in the right and left hemisphere of young and old Nogo-A-deficient male rats the expression of NMDA receptor subunits (NR1, NR2A and NR2B in the frontal cortex and activities of NOS isoforms (neuronal (nNOS, endothelial (eNOS and inducible (iNOS in the parietal cortex. In young controls, we observed right/left asymmetry of iNOS activity and three positive correlations (between NR1 in the left and NR2B laterality, between NR2B in the right and left sides, and between NR1 in the right side and nNOS laterality. In old controls, we found bilateral decreases in NR1, an increase in NR2B in the right side and two changes in correlations in the NR1–nNOS pathway. In young Nogo-A-deficient rats, we observed an increase in iNOS activity in the left hemisphere and two changes in correlations in NR1–nNOS and NR2A–eNOS, compared to young controls. Finally, we revealed in old Nogo-A-deficient animals, bilateral decreases in NR1 and one change in correlation between eNOS–iNOS, compared to old controls. Although some findings from schizophrenic brains did not manifest in Nogo-A-deficient rats (e.g., no alterations in NR2B, others did (e.g., alterations demonstrating accelerated ageing in young but not old animals, those occurring exclusively in the right hemisphere in young and old animals and those suggesting abnormal frontoparietal cortical interactions in young animals.

  20. Chronic methamphetamine treatment reduces the expression of synaptic plasticity genes and changes their DNA methylation status in the mouse brain.

    Science.gov (United States)

    Cheng, Min-Chih; Hsu, Shih-Hsin; Chen, Chia-Hsiang

    2015-12-10

    Methamphetamine (METH) is a highly addictive psychostimulant that may cause long-lasting synaptic dysfunction and abnormal gene expression. We aimed to explore the differential expression of synaptic plasticity genes in chronic METH-treated mouse brain. We used the RT(2) Profiler PCR Array and the real-time quantitative PCR to characterize differentially expressed synaptic plasticity genes in the frontal cortex and the hippocampus of chronic METH-treated mice compared with normal saline-treated mice. We further used pyrosequencing to assess DNA methylation changes in the CpG region of the five immediate early genes (IEGs) in chronic METH-treated mouse brain. We detected six downregulated genes in the frontal cortex and the hippocampus of chronic METH-treated mice, including five IEGs (Arc, Egr2, Fos, Klf10, and Nr4a1) and one neuronal receptor gene (Grm1), compared with normal saline-treated group, but only four genes (Arc, Egr2, Fos, and Nr4a1) were confirmed to be different. Furthermore, we found several CpG sites of the Arc and the Fos that had significant changes in DNA methylation status in the frontal cortex of chronic METH-treated mice, while the klf10 and the Nr4a1 that had significant changes in the hippocampus. Our results show that chronic administration of METH may lead to significant downregulation of the IEGs expression in both the frontal cortex and the hippocampus, which may partly account for the molecular mechanism of the action of METH. Furthermore, the changes in DNA methylation status of the IEGs in the brain indicate that an epigenetic mechanism-dependent transcriptional regulation may contribute to METH addiction, which warrants additional study. PMID:26496011

  1. Imaging of Copper, Zinc and other Elements in Thin Section of Human Brain Samples (Hippocampus) by Laser Ablation Inductively Coupled Plasma Mass Spectrometry

    OpenAIRE

    Becker, J. S.; Zoriy, M. V.; Pickhardt, C.; Palomero-Gallagher, N.; Zilles, K.

    2005-01-01

    Laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) was used to produce images of element distribution in 20-microm thin sections of human brain tissue. The sample surface was scanned (raster area approximately 80 mm(2)) with a focused laser beam (wavelength 213 nm, diameter of laser crater 50 microm, and laser power density 3 x 10(9) W cm(-2)) in a cooled laser ablation chamber developed for these measurements. The laser ablation system was coupled to a double-focusing sec...

  2. Glutamate (mGluR-5 gene expression in brain regions of streptozotocin induced diabetic rats as a function of age: role in regulation of calcium release from the pancreatic islets in vitro

    Directory of Open Access Journals (Sweden)

    Paulose CS

    2009-11-01

    Full Text Available Abstract Metabotrophic glutamate receptors (mGluRs modulate cellular activities involved in the processes of differentiation and degeneration. In this study, we have analysed the expression pattern of group-I metabotropic glutamate receptor (mGlu-5 in cerebral cortex, corpus striatum, brainstem and hippocampus of streptozotocin induced and insulin treated diabetic rats (D+I as a function of age. Also, the functional role of glutamate receptors in intra cellular calcium release from the pancreatic islets was studied in vitro. The gene expression studies showed that mGlu-5 mRNA in the cerebral cortex increased siginficantly in 7 weeks old diabetic rats whereas decreased expression was observed in brainstem, corpus striatum and hippocampus when compared to control. 90 weeks old diabetic rats showed decreased expression in cerebral cortex, corpus striatum and hippocampus whereas in brainstem the expression increased significantly compared to their respective controls. In 7 weeks old D+I group, mGlu-5 mRNA expression was significantly decreased in cerebral cortex and corpus striatum whereas the expression increased significantly in brainstem and hippocampus. 90 weeks old D+I group showed an increased expression in cerebral cortex, while it was decreased significantly in corpus striatum, brainstem and hippocampus compared to their respective controls. In vitro studies showed that glutamate at lower concentration (10-7 M stimulated calcium release from the pancreatic islets. Our results suggest that mGlu-5 receptors have differential expression in brain regions of diabetes and D+I groups as a function of age. This will have clinical significance in management of degeneration in brain function and memory enhancement through glutamate receptors. Also, the regulatory role of glutamate receptors in calcium release has immense therapeutic application in insulin secretion and function.

  3. Involvement of brain-derived neurotrophic factor (BDNF) on malathion induced depressive-like behavior in subacute exposure and protective effects of crocin

    OpenAIRE

    Somaye Ardebili Dorri; Hossein Hosseinzadeh; Khalil Abnous; Faezeh Vahdati Hasani; Rezvan Yazdian Robati; Bibi Marjan Razavi

    2015-01-01

    Objective(s): In this study the effect of crocin, a carotenoid isolated from saffron, on malathion (an organophosphate insecticide) induced depressive- like behavior in subacute exposure was investigated. Moreover the molecular mechanism of malathion induced depressive- like behavior and its decreasing effect on the level of brain derived neurotrophic factor (BDNF) in rat hippocampus and cerebral cortex were evaluated. Materials and Methods: Male Wistar rats were exposed to malathion (50 m...

  4. Effect of fentanyl on 125I-β-CIT uptake in mice brain

    International Nuclear Information System (INIS)

    Objective: To investigate the effect of fentanyl on 125I-2β-carbomethoxy-3β-(4-iodophenyl) tropane (125I-β-CIT) uptake in mice brain. Methods: 1) KM mice groups of five were given different doses of fentanyl, and 10 min or 1 h later were given a dose of 125I-β-CIT. 2)Two groups of animals were killed at 2 h after injection of 125I-β-CIT. 3)One group of animals were killed at 1 h after injection of 125I-β-CIT. Results: 1)In the striatum, frontal cortex, hippocampus, brain stem, cerebellum and whole brain, a dose-dependent increase in uptake (%ID/g or %ID) of 125I-β-CIT was detected at the fentanyl doses ranging from 125 to 300 μg/kg, and the uptakes of hippocampus and cerebellum were higher than that of the controls. There was a great difference in the value of %ID/g or %ID between the group treated with 250 μg/kg fentanyl and the control group; while at the doses from 12.5 to 100 μg/kg, a dose-dependent decrease in uptake in the same regions was observed and all the uptake levels were lower (hippocampus: except 62.5 and 12.5 μg/kg groups; brain stem: except 62.5 μg/kg group) than that of the controls. 2)The uptakes of 125I-β-CIT in the striatum, frontal cortex, hippocampus, brain stem, cerebellum and whole brain in the groups injected with 125I-β-CIT 10 min after fentanyl treatment were higher than that in the groups injected with 125I-β-CIT 1 h after fentanyl treatment. 3)The binding of 125I-β-CIT in the striatum, frontal cortex, hippocampus, brain stem, cerebellum and whole brain in the groups killed at 1 h after injection of 125I-β-CIT was higher than that in the control group, but without significant difference. Conclusion: Fentanyl may have different effects on 125I-β-CIT at various time points and doses

  5. Fluid-percussion brain injury induces changes in aquaporin channel expression.

    Science.gov (United States)

    Oliva, A A; Kang, Y; Truettner, J S; Sanchez-Molano, J; Furones, C; Yool, A J; Atkins, C M

    2011-04-28

    Edema, the accumulation of excess fluid, is a major pathological change in the brain that contributes significantly to pathology and mortality after moderate to severe brain injury. Edema is regulated by aquaporin (AQP) channels which transport water across cellular membranes. Six AQPs are found in the brain (1, 3, 4, 5, 8, and 9), and previous studies have found that AQP4 is regulated after traumatic brain injury (TBI). To further understand how AQPs contribute to brain edema, we investigated whether expression of AQP1, 3, and 9 are also regulated after TBI. Adult male Sprague Dawley rats received moderate parasagittal fluid-percussion brain injury (FPI) or sham surgery. After induction of FPI, the injured, ipsilateral parietal cortex and hippocampus were dissected and analyzed by Western blotting. We observed a small decrease in AQP3 and 4 levels at 7 days after FPI in the ipsilateral, parietal cortex. Both AQP1 and 9 significantly increased within 30 min post-injury and remained elevated for up to 6 h in the ipsilateral, parietal cortex. Aqp1 and 9 mRNA levels were also significantly increased at 30 min post-FPI. Administration of an AQP1 and 4 antagonist, AqB013, non-significantly increased brain water content in sham, non-injured animals, and did not prevent edema formation 24 h after trauma in either the parietal cortex or hippocampus. These results indicate that Aqp1 and 9 mRNA and protein levels increase after moderate parasagittal FPI and that an inhibitor of AQP1 and 4 does not decrease edema after moderate parasagittal FPI. PMID:21329742

  6. Outcome Uncertainty and Brain Activity Aberrance in the Insula and Anterior Cingulate Cortex Are Associated with Dysfunctional Impulsivity in Borderline Personality Disorder.

    Science.gov (United States)

    Mortensen, Jørgen Assar; Evensmoen, Hallvard Røe; Klensmeden, Gunilla; Håberg, Asta Kristine

    2016-01-01

    Uncertainty is recognized as an important component in distress, which may elicit impulsive behavior in patients with borderline personality disorder (BPD). These patients are known to be both impulsive and distress intolerant. The present study explored the connection between outcome uncertainty and impulsivity in BPD. The prediction was that cue primes, which provide incomplete information of subsequent target stimuli, led BPD patients to overrate the predictive value of these cues in order to reduce distress related to outcome uncertainty. This would yield dysfunctional impulsive behavior detected as commission errors to incorrectly primed targets. We hypothesized that dysfunctional impulsivity would be accompanied by aberrant brain activity in the right insula and anterior cingulate cortex (ACC), previously described to be involved in uncertainty processing, attention-/cognitive control and BPD pathology. 14 female BPD patients and 14 healthy matched controls (HCs) for comparison completed a Posner task during fMRI at 3T. The task was modified to limit the effect of spatial orientation and enhance the effect of conscious expectations. Brain activity was monitored in the priming phase where the effects of cue primes and neutral primes were compared. As predicted, the BPD group made significantly more commission errors to incorrectly primed targets than HCs. Also, the patients had faster reaction times to correctly primed targets relative to targets preceded by neutral primes. The BPD group had decreased activity in the right mid insula and increased activity in bilateral dorsal ACC during cue primes. The results indicate that strong expectations induced by cue primes led to reduced uncertainty, increased response readiness, and ultimately, dysfunctional impulsivity in BPD patients. We suggest that outcome uncertainty may be an important component in distress related impulsivity in BPD. PMID:27199724

  7. Outcome Uncertainty and Brain Activity Aberrance in the Insula and Anterior Cingulate Cortex Are Associated with Dysfunctional Impulsivity in Borderline Personality Disorder

    Science.gov (United States)

    Mortensen, Jørgen Assar; Evensmoen, Hallvard Røe; Klensmeden, Gunilla; Håberg, Asta Kristine

    2016-01-01

    Uncertainty is recognized as an important component in distress, which may elicit impulsive behavior in patients with borderline personality disorder (BPD). These patients are known to be both impulsive and distress intolerant. The present study explored the connection between outcome uncertainty and impulsivity in BPD. The prediction was that cue primes, which provide incomplete information of subsequent target stimuli, led BPD patients to overrate the predictive value of these cues in order to reduce distress related to outcome uncertainty. This would yield dysfunctional impulsive behavior detected as commission errors to incorrectly primed targets. We hypothesized that dysfunctional impulsivity would be accompanied by aberrant brain activity in the right insula and anterior cingulate cortex (ACC), previously described to be involved in uncertainty processing, attention-/cognitive control and BPD pathology. 14 female BPD patients and 14 healthy matched controls (HCs) for comparison completed a Posner task during fMRI at 3T. The task was modified to limit the effect of spatial orientation and enhance the effect of conscious expectations. Brain activity was monitored in the priming phase where the effects of cue primes and neutral primes were compared. As predicted, the BPD group made significantly more commission errors to incorrectly primed targets than HCs. Also, the patients had faster reaction times to correctly primed targets relative to targets preceded by neutral primes. The BPD group had decreased activity in the right mid insula and increased activity in bilateral dorsal ACC during cue primes. The results indicate that strong expectations induced by cue primes led to reduced uncertainty, increased response readiness, and ultimately, dysfunctional impulsivity in BPD patients. We suggest that outcome uncertainty may be an important component in distress related impulsivity in BPD. PMID:27199724

  8. A quantitative transcriptome reference map of the normal human hippocampus.

    Science.gov (United States)

    Caracausi, Maria; Rigon, Vania; Piovesan, Allison; Strippoli, Pierluigi; Vitale, Lorenza; Pelleri, Maria Chiara

    2016-01-01

    We performed an innovative systematic meta-analysis of 41 gene expression profiles of normal human hippocampus to provide a quantitative transcriptome reference map of it, i.e. a reference typical value of expression for each of the 30,739 known mapped and the 16,258 uncharacterized (unmapped) transcripts. For this aim, we used the software called TRAM (Transcriptome Mapper), which is able to generate transcriptome maps based on gene expression data from multiple sources. We also analyzed differential expression by comparing the hippocampus with the whole brain transcriptome map to identify a typical expression pattern of this subregion compared with the whole organ. Finally, due to the fact that the hippocampus is one of the main brain region to be severely affected in trisomy 21 (the best known genetic cause of intellectual disability), a particular attention was paid to the expression of chromosome 21 (chr21) genes. Data were downloaded from microarray databases, processed, and analyzed using TRAM software. Among the main findings, the most over-expressed loci in the hippocampus are the expressed sequence tag cluster Hs.732685 and the member of the calmodulin gene family CALM2. The tubulin folding cofactor B (TBCB) gene is the best gene at behaving like a housekeeping gene. The hippocampus vs. the whole brain differential transcriptome map shows the over-expression of LINC00114, a long non-coding RNA mapped on chr21. The hippocampus transcriptome map was validated in vitro by assaying gene expression through several magnitude orders by "Real-Time" reverse transcription polymerase chain reaction (RT-PCR). The highly significant agreement between in silico and experimental data suggested that our transcriptome map may be a useful quantitative reference benchmark for gene expression studies related to human hippocampus. Furthermore, our analysis yielded biological insights about those genes that have an intrinsic over-/under-expression in the hippocampus. PMID

  9. Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

    Directory of Open Access Journals (Sweden)

    Jintanaporn Wattanathorn

    2011-01-01

    Full Text Available Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect of Zingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO. Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA, superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GSH-Px in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia.

  10. The effect of heart-and kidney-Benefiting Chinese Herbal Medicine on the function of cholinergic M-and Gamma amino-butyric acid (GABA) receptor in brain tissues of analogue dementia rats

    International Nuclear Information System (INIS)

    3H-QNB and 3H-GABA were used as radioactive ligand for M-and GABA receptors respectively. M-and GABA receptors were assayed by radioligand binding assay (RBA) in cerebral cortex, hippocampus and cerebellum of analogue dementia rats. It was found that Rt of M receptor was decreased in cerebral cortex and hippocampus and Rt of GABA receptor was decreased in cerebellum of analogue dementia rats. The dissociation constant (KD) of M-receptor was decreased significantly in cerebral cortex and KD value of (GABA) receptor was decreased in cerebellum of analogue dementia rats. The decreased Rt of M-and GABA receptor in brain tissue of analogue dementia rats was raised by Heart- and Kidney-Benefiting Chinese Herbs as well as hydergin

  11. Brain

    Science.gov (United States)

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  12. Frontopolar cortex and decision-making efficiency: comparing brain activity of experts with different professional background during an exploration-exploitation task

    Directory of Open Access Journals (Sweden)

    Daniella eLaureiro-Martínez

    2014-01-01

    Full Text Available An optimal balance between efficient exploitation of available resources and creative exploration of alternatives is critical for adaptation and survival. Previous studies associated these behavioral drives with, respectively, the dopaminergic mesocorticolimbic system and frontopolar-intraparietal networks. We study the activation of these systems in two age and gender-matched groups of experienced decision-makers differing in prior professional background, with the aim to understand the neural bases of individual differences in decision-making efficiency (performance divided by response time. We compare brain activity of entrepreneurs (who currently manage the organization they founded based on their venture idea and managers (who are constantly involved in making strategic decisions but have no venture experience engaged in a gambling-task assessing exploitative vs. explorative decision-making. Compared with managers, entrepreneurs showed higher decision-making efficiency, and a stronger activation in regions of frontopolar cortex previously associated with explorative choice. Moreover, activity across a network of regions previously linked to explore/exploit tradeoffs explained individual differences in choice efficiency. These results suggest new avenues for the study of individual differences in the neural antecedents of efficient decision-making.

  13. Use of functional near-infrared spectroscopy to evaluate the effects of anodal transcranial direct current stimulation on brain connectivity in motor-related cortex

    Science.gov (United States)

    Yan, Jiaqing; Wei, Yun; Wang, Yinghua; Xu, Gang; Li, Zheng; Li, Xiaoli

    2015-04-01

    Transcranial direct current stimulation (tDCS) is a noninvasive, safe and convenient neuro-modulatory technique in neurological rehabilitation, treatment, and other aspects of brain disorders. However, evaluating the effects of tDCS is still difficult. We aimed to evaluate the effects of tDCS using hemodynamic changes using functional near-infrared spectroscopy (fNIRS). Five healthy participants were employed and anodal tDCS was applied to the left motor-related cortex, with cathodes positioned on the right dorsolateral supraorbital area. fNIRS data were collected from the right motor-related area at the same time. Functional connectivity (FC) between intracortical regions was calculated between fNIRS channels using a minimum variance distortion-less response magnitude squared coherence (MVDR-MSC) method. The levels of Oxy-HbO change and the FC between channels during the prestimulation, stimulation, and poststimulation stages were compared. Results showed no significant level difference, but the FC measured by MVDR-MSC significantly decreased during tDCS compared with pre-tDCS and post-tDCS, although the FC difference between pre-tDCS and post-tDCS was not significant. We conclude that coherence calculated from resting state fNIRS may be a useful tool for evaluating the effects of anodal tDCS and optimizing parameters for tDCS application.

  14. The Role of Neonatal Carnitine Palmitoyl Transferase Deficiency Type II on Proliferation of Neuronal Progenitor Cells and Layering of the Cerebral Cortex in the Developing Brain

    Directory of Open Access Journals (Sweden)

    Heepeel Chang

    2007-06-01

    Full Text Available Neonatal Carnitine Palmitoyl Transferase Deficiency Type II, characterized by the absence of CPT II enzyme, is one of the lethal disorders of mitochondrial fatty acid oxidation. CPT II regulates the conversion of long chain fatty acids, so that its product, acyl-CoA esters, can enter the Krebs cycle and generate energy. Neonatal mutations of CPT II lead to severe disruption of the metabolism of long-chain fatty acids and result in dysmorphic features, cystic renal dysplasia, and neuronal migration defects. Examination of the brain from an approximately 15-week gestation human fetus with CPT II deficiency revealed premature formation of cerebral cortical gyri and sulci and significantly lower levels of neuronal cell proliferation in the ventricular and subventricular zones as compared to the reference cases. We used immunohistochemical markers to further characterize the effect of CPT II deficiency on progenitor cell proliferation and layering of neurons. These studies demonstrated a premature generation of layer 5 cortical neurons. In addition, both the total number and percentage of progenitor cells proliferating in the ventricular zone were markedly reduced in the CPT II case in comparison to a reference case. Our results indicate that CPT II deficiency alters the normal program of cellular proliferation and differentiation in the cortex, with early differentiation of progenitor cells associated with premature cortical maturation.

  15. Motor cortex stimulation(MCS) for intractable complex regional pain syndrome (CRPS) type II: PSM analysis of Tc-99m ECD brain perfusion SPECT

    International Nuclear Information System (INIS)

    We had experienced a patient with intractable CRPS in whom statistical parametric mapping (SPM) analysis of cerebral perfusion explained the mechanism of pain control by MCS. A 43-year-old man presented spontaneous severe burning pain in his left hand and forearm and allodynia over the left arm and left hemibody. After the electrodes for neuromodulation therapy were inserted in the central sulcus, the baseline and stimulation brain perfusion SPECT using Tc-99m ECD were obtained within two days. The differences between the baseline and stimulation SPECT images, estimated at every voxel using t-statistics using SPM-99 software, were considered significant at a threshold of uncorrected P values less than 0.01. Among several areas significantly activated following pain relief with MCS, ipsilateral pyramidal tract in the cerebral peduncle might be related to the mechanism of pain control with MCS through efferent motor pathway. The result suggested that corticospinal neurons themselves or motor cortex efferent pathway maintained by the presence of intact corticospinal neurons could play an important role in producing pain control after MCS. This study would helpful in understanding of neurophysiology

  16. Effects of white spirits on rat brain 5-HT receptor functions and synaptic remodeling

    DEFF Research Database (Denmark)

    Lam, Henrik Rye; Plenge, P.; Jørgensen, O.S.

    2001-01-01

    ratio in forebrain, whereas NCAM increased in hippocampus and the NCAM/SNAP-25 ratio decreased in entorhinal cortex. Dearomatized white spirit did not affect NCAM, SNAP-25, or NCAM/SNAP-25 ratio in any brain region. The affected 5-HT receptor expression and synaptic plasticity marker proteins indicate......Previously, inhalation exposure to different types of white spirit (i.e. complex mixtures of aliphatic, aromatic, alkyl aromatic, and naphthenic hydrocarbons) has been shown to induce neurochemical effects in rat brains. Especially, the serotonergic system was involved at the global, regional, and...

  17. Measuring cell-type specific differential methylation in human brain tissue.

    Science.gov (United States)

    Montaño, Carolina M; Irizarry, Rafael A; Kaufmann, Walter E; Talbot, Konrad; Gur, Raquel E; Feinberg, Andrew P; Taub, Margaret A

    2013-01-01

    The behavior of epigenetic mechanisms in the brain is obscured by tissue heterogeneity and disease-related histological changes. Not accounting for these confounders leads to biased results. We develop a statistical methodology that estimates and adjusts for celltype composition by decomposing neuronal and non-neuronal differential signal. This method provides a conceptual framework for deconvolving heterogeneous epigenetic data from postmortem brain studies. We apply it to find cell-specific differentially methylated regions between prefrontal cortex and hippocampus. We demonstrate the utility of the method on both Infinium 450k and CHARM data. PMID:24000956

  18. Genetic Variation in the Catechol-O-Methyl Transferase Val108/158Met Is Linked to the Caudate and Posterior Cingulate Cortex Volume in Healthy Subjects: Voxel-Based Morphometry Analysis of Brain Magnetic Resonance Imaging.

    Directory of Open Access Journals (Sweden)

    Keita Watanabe

    Full Text Available The effect of the catechol-O-methyltransferase (COMT Val158Met polymorphism on brain morphology has been investigated but remains controversial. We hypothesized that a comparison between Val/Val and Val/Met individuals, which may represent the most different combinations concerning the effects of the COMT genotype, may reveal new findings. We investigated the brain morphology using 3-Tesla magnetic resonance imaging in 27 Val/Val and 22 Val/Met individuals. Voxel-based morphometry revealed that the volumes of the bilateral caudate and posterior cingulate cortex were significantly smaller in Val/Val individuals than in Val/Met individuals [right caudate: false discovery rate (FDR-corrected p = 0.048; left caudate: FDR-corrected p = 0.048; and bilateral posterior cingulate cortex: FDR-corrected p = 0.048]. This study demonstrates that interacting functional variants of COMT affect gray matter regional volumes in healthy subjects.

  19. The effect of heart-and kidney-benefiting Chinese herbal medicines on the function of adrenergic receptors in brain tissues of analogue dementia rats

    International Nuclear Information System (INIS)

    Analogue dementia model of rats was produced by electrolytic lesion of brain. α-adrenergic receptors were assayed by radioligand binding assay (RRBA). It was found that Bmax of α1 receptors was decreased obviously in cerebral cortex, hippocampus and cerebellum of analogue dementia rats and was raised obviously by Heart-and Kidney-Benefiting Chinese Herbs as well as by Hydergin. The electrolytic lesion did not change the activity of MAO-B in model rat brains. Neither Heart-and Kidney-Benefiting Chinese Herb Medicines nor Hydergin showed marked effect on brain MAO-B activity of the model rats

  20. Progesterone mediates brain functional connectivity changes during the menstrual cycle - A pilot resting state MRI study

    Directory of Open Access Journals (Sweden)

    Katrin eArelin

    2015-02-01

    Full Text Available The growing interest in intrinsic brain organization has sparked various innovative approaches to generating comprehensive connectivity-based maps of the human brain. Prior reports point to a sexual dimorphism of the structural and functional human connectome. However, it is uncertain whether subtle changes in sex hormones, as occur during the monthly menstrual cycle, substantially impact the functional architecture of the female brain. Here, we performed eigenvector centrality (EC mapping in 32 longitudinal resting state fMRI scans of a single healthy subject without oral contraceptive use, across four menstrual cycles, and assessed estrogen and progesterone levels. To investigate associations between cycle-dependent hormones and brain connectivity, we performed correlation analyses between the EC maps and the respective hormone levels. On the whole brain level, we found a significant positive correlation between progesterone and EC in the bilateral DLPFC and bilateral sensorimotor cortex. In a secondary region-of-interest analysis, we detected a progesterone-modulated increase in functional connectivity of both bilateral DLPFC and bilateral sensorimotor cortex with the hippocampus. Our results suggest that the menstrual cycle substantially impacts intrinsic functional connectivity, particularly in brain areas associated with contextual memory-regulation, such as the hippocampus. These findings are the first to link the subtle hormonal fluctuations that occur during the menstrual cycle, to significant changes in regional functional connectivity in the hippocampus in a longitudinal design, given the limitation of data acquisition in a single subject. Our study demonstrates the feasibility of such a longitudinal rs-fMRI design and illustrates a means of creating a personalized map of the human brain by integrating potential mediators of brain states, such as menstrual cycle phase.

  1. Plasma Membrane Density of GABA(B)-R1a, GABA(B)-R1b, GABA-R2 and Trimeric G-proteins in the Course of Postnatal Development of Rat Brain Cortex

    Czech Academy of Sciences Publication Activity Database

    Dlouhá, Kateřina; Kagan, Dmytro; Roubalová, Lenka; Ujčíková, Hana; Svoboda, Petr

    2013-01-01

    Roč. 62, č. 5 (2013), s. 547-559. ISSN 0862-8408 R&D Projects: GA ČR(CZ) GAP207/12/0919; GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : GABAB-receptors * postnatal development * rat brain cortex * G-proteins * Na, K-ATPase Subject RIV: CE - Biochemistry Impact factor: 1.487, year: 2013

  2. Regional brain morphometry predicts memory rehabilitation outcome after traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Gary E Strangman

    2010-10-01

    Full Text Available Cognitive deficits following traumatic brain injury (TBI commonly include difficulties with memory, attention, and executive dysfunction. These deficits are amenable to cognitive rehabilitation, but optimally selecting rehabilitation programs for individual patients remains a challenge. Recent methods for quantifying regional brain morphometry allow for automated quantification of tissue volumes in numerous distinct brain structures. We hypothesized that such quantitative structural information could help identify individuals more or less likely to benefit from memory rehabilitation. Fifty individuals with TBI of all severities who reported having memory difficulties first underwent structural MRI scanning. They then participated in a 12 session memory rehabilitation program emphasizing internal memory strategies (I-MEMS. Primary outcome measures (HVLT, RBMT were collected at the time of the MRI scan, immediately following therapy, and again at one month post-therapy. Regional brain volumes were used to predict outcome, adjusting for standard predictors (e.g., injury severity, age, education, pretest scores. We identified several brain regions that provided significant predictions of rehabilitation outcome, including the volume of the hippocampus, the lateral prefrontal cortex, the thalamus, and several subregions of the cingulate cortex. The prediction range of regional brain volumes were in some cases nearly equal in magnitude to prediction ranges provided by pretest scores on the outcome variable. We conclude that specific cerebral networks including these regions may contribute to learning during I-MEMS rehabilitation, and suggest that morphometric measures may provide substantial predictive value for rehabilitation outcome in other cognitive interventions as well.

  3. Quantified distribution of the noradrenaline innervation in the hippocampus of adult rat

    International Nuclear Information System (INIS)

    A recently developed radioautographic technique, based on the uptake labeling of monoamine terminals in vitro, was used to quantify the noradrenaline (NA) innervation in adult rat hippocampus. After incubation of brain slices with 1 microM 3H-NA, the NA varicosities were visualized as small aggregates of silver grains, in light microscope radioautographs prepared at 3 equidistant horizontal levels across the ventral 2/3 of the hippocampus. Using a computer-assisted image analyzer, counts were obtained from the subiculum (SUB), 3 sectors of Ammon's horn (CA1, CA3-a, CA3-b) and 3 sectors of the dentate gyrus (DG-medial blade, crest, and lateral blade), every lamina being sampled in each region. After a double correction for duration of radioautographic exposure and section thickness, and following measurement of varicosity diameter in electron microscope radioautographs, it was possible to express these results in number of terminals per volumetric unit of tissue. It was thus found that the overall density of hippocampal NA innervation averages 2.1 million varicosities/mm3 of tissue, a value almost twice as high as that in cerebral cortex. This innervation is 20% denser ventrally than dorsally and is heterogeneous both in terms of regional and laminar distribution. SUB and DG are more strongly innervated than Ammon's horn, wherein CA1 has the lowest overall density. In SUB and CA1, there is a clear predilection of NA varicosities for the stratum moleculare. In CA3, there is a narrow band of even stronger innervation in the stratum radiatum, near the apical border of the stratum pyramidale, contrasting with a 3 times lower density in this cell layer and the stratum oriens. In DG, the NA innervation is again the weakest in the cell body layer and exhibits an almost 3-fold greater density in the polymorph layer, the highest of all hippocampus

  4. Sensibility about prefrontal cortex and hippocampus of rat depressive model affected by the inflammatory factor in cerebrospinal fluid:a magnetic resonance spectrum study%抑郁模型大鼠额叶及海马对脑脊液炎症因子敏感性的磁共振质子波谱研究

    Institute of Scientific and Technical Information of China (English)

    朱彦; 王冬青; 李月峰; 赵天; 赵亮; 殷瑞根

    2013-01-01

    Objective To explore the sensibility of the encephalic region affected by the inflammatory factor of cerebrospinal fluid(CSF) and the role of the inflammatory factor in the development of the depression.Methods Based on the evaluation of ethology,forty SD rats were randomly and equally divided into control group and model group which was exposed to chronic unpredictable mild stress for 4 weeks.Using analyzing technology 1 H-MRS to detect prefrontal cortex and hippocampus of each group and detecting the levels of interlukin 6(IL-6),interlukin 2 (IL-2),interlukin 10 (IL-10) in CSF at the beginning and 4 weeks later,and the correlation was analyzed between them.Results Compared with the control group,the values of Glx/ Cr and NAA/ Cr in bilateral prefrontal cortex were reduced which did not reach statistically significance (P > 0.05),and the value of Cho/ Cr had no significant difference.The values of Glx/Cr and NAA/Cr in left hippocampus reduced significantly(Glx/Cr:(1.16 ±0.07),t =2.50,P<0.05 ;NAA/Cr:(1.30 ±0.09),t=5.94,P<0.01),and the value of Cho/Cr was increased which did not reach statistically significance(P> 0.05).The values of Glx/Cr and NAA/Cr were reduced and the value of Cho/Cr was increased in right hippocampus which did not reach statistical significance(P>0.05).The depressive group had the significantly higher levels of IL-6,IL-2 in CSF(IL-6:(32.41 ± 3.52),t =11.46,P < 0.01 ; IL-2:(18.89 ± 2.56),t =7.42,P < 0.01),but no significant difference was found in the IL-10 level in CSF.The Glx/Cr of left hippocampus level was negatively correlated to the IL-6 and IL-2 level in CSF (IL-6:r =-0.555,P< 0.05 ; IL-2:r=-0.582,P< 0.05) ; the NAA/Cr of left hippocampus level was negatively correlated to the IL-6 and IL-2 level in CSF(IL-6:r=-0.582,P<0.05;IL-2:r=-0.607,P<0.05).Conclusion The development of inchoate depression has a correlation with the high sensibility of the left hippocampus affected by the inflammatory factor levels

  5. Brain-derived neurotrophic factor--a major player in stimulation-induced homeostatic metaplasticity of human motor cortex?

    DEFF Research Database (Denmark)

    Mastroeni, Claudia; Bergmann, Til Ole; Rizzo, Vincenzo;

    2013-01-01

    Repetitive transcranial magnetic stimulation (rTMS) of the human motor hand area (M1HAND) can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter-individual......Repetitive transcranial magnetic stimulation (rTMS) of the human motor hand area (M1HAND) can induce lasting changes in corticospinal excitability as indexed by a change in amplitude of the motor-evoked potential. The plasticity-inducing effects of rTMS in M1HAND show substantial inter......-individual variability which has been partially attributed to the val(66)met polymorphism in the brain-derived neurotrophic factor (BDNF) gene. Here we used theta burst stimulation (TBS) to examine whether the BDNF val(66)met genotype can be used to predict the expression of TBS-induced homeostatic metaplasticity in...... effects was modulated by the BDNF val(66)met polymorphism, our results do not support the notion that the BDNF val(66)met genotype is a major player with regard to TBS-induced plasticity and metaplasticity in the human M1HAND....

  6. Acute Sleep Deprivation Induces a Local Brain Transfer Information Increase in the Frontal Cortex in a Widespread Decrease Context

    Directory of Open Access Journals (Sweden)

    Joan F. Alonso

    2016-04-01

    Full Text Available Sleep deprivation (SD has adverse effects on mental and physical health, affecting the cognitive abilities and emotional states. Specifically, cognitive functions and alertness are known to decrease after SD. The aim of this work was to identify the directional information transfer after SD on scalp EEG signals using transfer entropy (TE. Using a robust methodology based on EEG recordings of 18 volunteers deprived from sleep for 36 h, TE and spectral analysis were performed to characterize EEG data acquired every 2 h. Correlation between connectivity measures and subjective somnolence was assessed. In general, TE showed medium- and long-range significant decreases originated at the occipital areas and directed towards different regions, which could be interpreted as the transfer of predictive information from parieto-occipital activity to the rest of the head. Simultaneously, short-range increases were obtained for the frontal areas, following a consistent and robust time course with significant maps after 20 h of sleep deprivation. Changes during sleep deprivation in brain network were measured effectively by TE, which showed increased local connectivity and diminished global integration. TE is an objective measure that could be used as a potential measure of sleep pressure and somnolence with the additional property of directed relationships.

  7. Acute Sleep Deprivation Induces a Local Brain Transfer Information Increase in the Frontal Cortex in a Widespread Decrease Context.

    Science.gov (United States)

    Alonso, Joan F; Romero, Sergio; Mañanas, Miguel A; Alcalá, Marta; Antonijoan, Rosa M; Giménez, Sandra

    2016-01-01

    Sleep deprivation (SD) has adverse effects on mental and physical health, affecting the cognitive abilities and emotional states. Specifically, cognitive functions and alertness are known to decrease after SD. The aim of this work was to identify the directional information transfer after SD on scalp EEG signals using transfer entropy (TE). Using a robust methodology based on EEG recordings of 18 volunteers deprived from sleep for 36 h, TE and spectral analysis were performed to characterize EEG data acquired every 2 h. Correlation between connectivity measures and subjective somnolence was assessed. In general, TE showed medium- and long-range significant decreases originated at the occipital areas and directed towards different regions, which could be interpreted as the transfer of predictive information from parieto-occipital activity to the rest of the head. Simultaneously, short-range increases were obtained for the frontal areas, following a consistent and robust time course with significant maps after 20 h of sleep deprivation. Changes during sleep deprivation in brain network were measured effectively by TE, which showed increased local connectivity and diminished global integration. TE is an objective measure that could be used as a potential measure of sleep pressure and somnolence with the additional property of directed relationships. PMID:27089346

  8. Acute Sleep Deprivation Induces a Local Brain Transfer Information Increase in the Frontal Cortex in a Widespread Decrease Context

    Science.gov (United States)

    Alonso, Joan F.; Romero, Sergio; Mañanas, Miguel A.; Alcalá, Marta; Antonijoan, Rosa M.; Giménez, Sandra

    2016-01-01

    Sleep deprivation (SD) has adverse effects on mental and physical health, affecting the cognitive abilities and emotional states. Specifically, cognitive functions and alertness are known to decrease after SD. The aim of this work was to identify the directional information transfer after SD on scalp EEG signals using transfer entropy (TE). Using a robust methodology based on EEG recordings of 18 volunteers deprived from sleep for 36 h, TE and spectral analysis were performed to characterize EEG data acquired every 2 h. Correlation between connectivity measures and subjective somnolence was assessed. In general, TE showed medium- and long-range significant decreases originated at the occipital areas and directed towards different regions, which could be interpreted as the transfer of predictive information from parieto-occipital activity to the rest of the head. Simultaneously, short-range increases were obtained for the frontal areas, following a consistent and robust time course with significant maps after 20 h of sleep deprivation. Changes during sleep deprivation in brain network were measured effectively by TE, which showed increased local connectivity and diminished global integration. TE is an objective measure that could be used as a potential measure of sleep pressure and somnolence with the additional property of directed relationships. PMID:27089346

  9. Increase in serotonin 5-HT1A receptors in prefrontal and temporal cortices of brains from patients with chronic schizophrenia

    International Nuclear Information System (INIS)

    Binding studies with [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT), a specific serotonin1A (5-HT1A) receptor agonist, were done on the autopsied brains from control subjects and from patients with chronic schizophrenia. In the controls, representative Scatchard plots for the specific [3H]8-OH-DPAT bindings in the prefrontal cortex and hippocampus revealed a single component of high affinity binding site. The [3H]8-OH-DPAT bindings to the prefrontal cortex and hippocampus were potently inhibited by serotonin and 5-HT1A agonists, while other neurotransmitters, 5-HT2 and 5-HT3 related compounds did not inhibit the binding. The bindings were decreased in the presence of 0.1mM GTP and 0.1mM GppNHp but not in the presence of 0.1mM GMP. In the prefrontal and temporal cortices of schizophrenics, there was a significant increase in the specific [3H]8-OH-DPAT binding, by 40% and 60%, respectively, with no change in the hippocampus, amygdala, cingulum, motor cortex, parietal or occipital cortex, as compared to findings in the controls

  10. Expression of BDNF and TrkB Phosphorylation in the Rat Frontal Cortex During Morphine Withdrawal are NO Dependent.

    Science.gov (United States)

    Peregud, Danil I; Yakovlev, Alexander A; Stepanichev, Mikhail Yu; Onufriev, Mikhail V; Panchenko, Leonid F; Gulyaeva, Natalia V

    2016-08-01

    Nitric oxide (NO) mediates pharmacological effects of opiates including dependence and abstinence. Modulation of NO synthesis during the induction phase of morphine dependence affects manifestations of morphine withdrawal syndrome, though little is known about mechanisms underlying this phenomenon. Neurotrophic and growth factors are involved in neuronal adaptation during opiate dependence. NO-dependent modulation of morphine dependence may be mediated by changes in expression and activity of neurotrophic and/or growth factors in the brain. Here, we studied the effects of NO synthesis inhibition during the induction phase of morphine dependence on the expression of brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and insulin-like growth factor 1 (IGF1) as well as their receptors in rat brain regions after spontaneous morphine withdrawal in dependent animals. Morphine dependence in rats was induced within 6 days by 12 injections of morphine in increasing doses (10-100 mg/kg), and NO synthase inhibitor L-N(G)-nitroarginine methyl ester (L-NAME) (10 mg/kg) was given 1 h before each morphine injection. The expression of the BDNF, GDNF, NGF, IGF1, and their receptors in the frontal cortex, striatum, hippocampus, and midbrain was assessed 40 h after morphine withdrawal. L-NAME treatment during morphine intoxication resulted in an aggravation of the spontaneous morphine withdrawal severity. Morphine withdrawal was accompanied by upregulation of BDNF, IGF1, and their receptors TrkB and IGF1R, respectively, on the mRNA level in the frontal cortex, and only BDNF in hippocampus and midbrain. L-NAME administration during morphine intoxication decreased abstinence-induced upregulation of these mRNAs in the frontal cortex, hippocampus and midbrain. L-NAME prevented from abstinence-induced elevation of mature but not pro-form of BDNF polypeptide in the frontal cortex. While morphine abstinence did not affect Trk

  11. Region-specific vulnerability to endoplasmic reticulum stress-induced neuronal death in rat brain after status epilepticus

    Indian Academy of Sciences (India)

    Jing Chen; Hu Guo; Guo Zheng; Zhong-Nan Shi

    2013-12-01

    We sought to clarify the involvement and the intra-cerebral distribution variability of C/EBP homologous protein (CHOP), a representative molecule related to endoplasmic reticulum (ER) stress-induced cell death signalling pathways, in neuronal death resulting from status epilepticus in rats. The expression patterns of CHOP and glucose-regulated protein (GRP) 78, a good marker of ER stress, were assessed by Western blotting, real-time PCR, Hoechst and immunohistochemistry in the hippocampus, cortex and striatum on a status epilepticus (SE) model. Double-fluorescent staining of CHOP and the terminal deoxynucleotidyl transferase-mediated DNA nick-end labelling (TUNEL) method were performed to clarify the involvement of CHOP in cell death. SE resulted in a time-dependent increase in the expression of GRP78 and CHOP. The expression of GRP78 protein was increased at 3, 6 and 12 h after SE and no brain region variability was found. The expression of CHOP protein was also increased, reached its peak at 24 h and remained high at 48 h. CHOP protein expression, however, showed brain region variability with highest expression noted in the hippocampus followed by the striatum, and lowest in the cortex. The up-regulation of CHOP occurring at the transcriptional level was demonstrated by real-time PCR. Double fluorescence showed that CHOP expression strongly correlated with neurons undergoing apoptosis. The results indicated that SE compromises the function of the ER and that the hippocampus is more vulnerable than the cortex and the striatum.

  12. Memory consolidation of fear conditioning: bi-stable amygdala connectivity with dorsal anterior cingulate and medial prefrontal cortex.

    Science.gov (United States)

    Feng, Pan; Feng, Tingyong; Chen, Zhencai; Lei, Xu

    2014-11-01

    Investigations of fear conditioning in rodents and humans have illuminated the neural mechanisms of fear acquisition and extinction. However, the neural mechanism of memory consolidation of fear conditioning is not well understood. To address this question, we measured brain activity and the changes in functional connectivity following fear acquisition using resting-state functional magnetic resonance imaging. The amygdala-dorsal anterior cingulate cortex (dACC) and hippocampus-insula functional connectivity were enhanced, whereas the amygdala-medial prefrontal cortex (mPFC) functional coupling was decreased during fear memory consolidation. Furthermore, the amygdala-mPFC functional connectivity was negatively correlated with the subjective fear ratings. These findings suggest the amygdala functional connectivity with dACC and mPFC may play an important role in memory consolidation of fear conditioning. The change of amygdala-mPFC functional connectivity could predict the subjective fear. Accordingly, this study provides a new perspective for understanding fear memory consolidation. PMID:24194579

  13. Neuronal and inducible nitric oxide synthase upregulation in the rat medial prefrontal cortex following acute restraint stress: A dataset.

    Science.gov (United States)

    Spiers, Jereme G; Chen, Hsiao-Jou Cortina; Lee, Johnny K; Sernia, Conrad; Lavidis, Nickolas A

    2016-03-01

    This data article provides additional evidence on gene expression changes in the neuronal and inducible isoforms of nitric oxide synthase in the medial prefrontal cortex following acute stress. Male Wistar rats aged 6-8 weeks were exposed to control or restraint stress conditions for up to four hours in the dark cycle after which the brain was removed and the medial prefrontal cortex isolated by cryodissection. Following RNA extraction and cDNA synthesis, gene expression data were measured using quantitative real-time PCR. The mRNA levels of the neuronal and inducible nitric oxide synthase isoforms, and the inhibitory subunit of NF-κB, I kappa B alpha were determined using the ΔΔCT method relative to control animals. This data article presents complementary results related to the research article entitled 'Acute restraint stress induces specific changes in nitric oxide production and inflammatory markers in the rat hippocampus and striatum' [1]. PMID:26909371

  14. Transient and persistent expression of NT-3/HDNF mRNA in the rat brain during postnatal development.

    Science.gov (United States)

    Friedman, W J; Ernfors, P; Persson, H

    1991-06-01

    Neurotrophin-3 (NT-3) is closely related to two known neurotrophic agents, NGF and brain-derived neurotrophic factor (BDNF), and acts upon overlapping, yet distinct, populations of peripheral ganglia. NT-3 mRNA expression in the adult rat brain is largely confined to the hippocampus. In this study, we have used in situ hybridization to examine expression of this novel neurotrophic factor during postnatal development. The striking observation was made that NT-3 mRNA was transiently expressed at high levels in the cingulate cortex during the first 2 weeks of age. In the hippocampus, the adult pattern of expression, in the CA2, medial CA1, and granule layer of the dentate gyrus, was detected at all ages examined. However, there were two major differences in NT-3 mRNA expression in the developing hippocampus: Labeled cells were detected in the hilar region of the dentate gyrus at postnatal day 1 (P1) and 1 week that were absent by 2 weeks of age. Further, the caudal hippocampus, which has a lower intensity of labeling than the rostral region in the adult, was devoid of NT-3-expressing cells in the P1 and 1-week-old rat brain. These data indicate a substantial plasticity in NT-3 mRNA expression and suggest that the spectrum of neurons supported by NT-3 during development is partially different from that in the mature rat brain. PMID:2045877

  15. The role of the medial prefrontal cortex in the conditioning and extinction of fear

    Directory of Open Access Journals (Sweden)

    Thomas Francis Giustino

    2015-11-01

    Full Text Available Once acquired, a fearful memory can persist for a lifetime. Although learned fear can be extinguished, extinction memories are fragile. The resilience of fear memories to extinction may contribute to the maintenance of disorders of fear and anxiety, including post-traumatic stress disorder (PTSD. As such, considerable effort has been placed on understanding the neural circuitry underlying the acquisition, expression, and extinction of emotional memories in rodent models as well as in humans. A triad of brain regions, including the prefrontal cortex, hippocampus, and amygdala, form an essential brain circuit involved in fear conditioning and extinction. Within this circuit, the prefrontal cortex is thought to exert top-down control over subcortical structures to regulate appropriate behavioral responses. Importantly, a division of labor has been proposed in which the prelimbic (PL and infralimbic (IL subdivisions of the medial prefrontal cortex (mPFC regulate the expression and suppression of fear in rodents, respectively. Here we critically review the anatomical and physiological evidence that has led to this proposed dichotomy of function within mPFC. We propose that under some conditions, the PL and IL act in concert, exhibiting similar patterns of neural activity in response to aversive conditioned stimuli and during the expression or inhibition of conditioned fear. This may stem from common synaptic inputs, parallel downstream outputs, or cortico-cortical interactions. Despite this functional covariation, these mPFC subdivisions may still be coding for largely opposing behavioral outcomes, with PL biased towards fear expression and IL towards suppression.

  16. Properties of doublecortin-(DCX-expressing cells in the piriform cortex compared to the neurogenic dentate gyrus of adult mice.

    Directory of Open Access Journals (Sweden)

    Friederike Klempin

    Full Text Available The piriform cortex receives input from the olfactory bulb and (via the entorhinal cortex sends efferents to the hippocampus, thereby connecting the two canonical neurogenic regions of the adult rodent brain. Doublecortin (DCX is a cytoskeleton-associated protein that is expressed transiently in the course of adult neurogenesis. Interestingly, the adult piriform cortex, which is usually considered non-neurogenic (even though some reports exist that state otherwise, also contains an abundant population of DCX-positive cells. We asked how similar these cells would be to DCX-positive cells in the course of adult hippocampal neurogenesis. Using BAC-generated transgenic mice that express GFP under the DCX promoter, we studied DCX-expression and electrophysiological properties of DCX-positive cells in the mouse piriform cortex in comparison with the dentate gyrus. While one class of cells in the piriform cortex indeed showed features similar to newly generated immature granule neurons, the majority of DCX cells in the piriform cortex was mature and revealed large Na+ currents and multiple action potentials. Furthermore, when proliferative activity was assessed, we found that all DCX-expressing cells in the piriform cortex were strictly postmitotic, suggesting that no DCX-positive "neuroblasts" exist here as they do in the dentate gyrus. We conclude that DCX in the piriform cortex marks a unique population of postmitotic neurons with a subpopulation that retains immature characteristics associated with synaptic plasticity. DCX is thus, per se, no marker of neurogenesis but might be associated more broadly with plasticity.

  17. Molecular signatures of neurodegeneration in the cortex of PS1/PS2 double knockout mice

    Directory of Open Access Journals (Sweden)

    Choi Se

    2008-10-01

    Full Text Available Abstract Background Familial Alzheimer's disease-linked variants of presenilin (PSEN1 and PSEN2 contribute to the pathophysiology of disease by both gain-of-function and loss-of-function mechanisms. Deletions of PSEN1 and PSEN2 in the mouse forebrain result in a strong and progressive neurodegenerative phenotype which is characterized by both anatomical and behavioral changes. Results To better understand the molecular changes associated with these morphological and behavioral phenotypes, we performed a DNA microarray transcriptome profiling of the hippocampus and the frontal cortex of the PSEN1/PSEN2 double knock-out mice and littermate controls at five different ages ranging from 2–8 months. Our data suggest that combined deficiencies of PSEN1 and PSEN2 results in a progressive, age-dependent transcriptome signature related to neurodegeneration and neuroinflammation. While these events may progress differently in the hippocampus and frontal cortex, the most critical expression signatures are common across the two brain regions, and involve a strong upregulation of cathepsin and complement system transcripts. Conclusion The observed neuroinflammatory expression changes are likely to be causally linked to the neurodegenerative phenotype observed in mice with compound deletions of PSEN1 and PSEN2. Furthermore, our results suggest that the evaluation of inhibitors of PS/γ-secretase activity for treatment of Alzheimer's Disease must include close monitoring for signs of calpain-cathepsin system activation.

  18. Neurons of the Dentate Molecular Layer in the Rabbit Hippocampus

    OpenAIRE

    Sancho-Bielsa, Francisco J.; Navarro-López, Juan D.; Gregori Alonso-Llosa; Asunción Molowny; Xavier Ponsoda; Javier Yajeya; Carlos López-García

    2012-01-01

    The molecular layer of the dentate gyrus appears as the main entrance gate for information into the hippocampus, i.e., where the perforant path axons from the entorhinal cortex synapse onto the spines and dendrites of granule cells. A few dispersed neuronal somata appear intermingled in between and probably control the flow of information in this area. In rabbits, the number of neurons in the molecular layer increases in the first week of postnatal life and then stabilizes to appear permanent...

  19. Effects of long-term, low-dose sex hormone replacement therapy on hippocampus and cognition of postmenopausal women of different apoE genotypes

    Institute of Scientific and Technical Information of China (English)

    Yun YUE; Ping-ping ZUO; Ling HU; Qin-jie TIAN; Jing-mei JIANG; Yi-long DONG; Zheng-yu JIN; Yu-hang CHENG; Xia HONG; Qin-sheng GE

    2007-01-01

    Aim: To study the effects of long-term, low-dose sex hormone replacement therapy (HRT) on the volume and biochemical changes of the hippocampus in postmeno-pausal women carrying apolipoprotein E (apoE) gene ε3 or ε4. Methods: Eighty-three postmenopausal women who had used a low dose of HRT for over 4 years were selected as the HRT group, and 99 postmenopausal women with matched age and education were enrolled as the control group. ApoE alleles were analyzed by PCR. Magnetic resonance imaging was performed to determine the volume of the brain hippocampus. Proton magnetic resonance spectroscopy was used to detect the biochemical changes in the anterior cingulate cortex and hippocampus in apoE ε4 and ε3 carriers. Six common cognitive tests were used to make an overall evaluation of cognitive function. Results: Analysis with the apoE ε4 carriers showed that the volume of the hippocampus of the control group were significantly lower than those of the HRT group. The biochemical analysis showed that there was an increase of N-acetylaspartate (NAA)/total creatine (tCr) and a decrease of myoinositol (mI)/tCr in the hippocampus of apoE ε4 carriers in the HRT group, compared with the control group. For the apoE ε3 carriers, the least squares means (LSMEAN) of the HRT group was higher than that of the control group. Conclusion: This study showed that long-term, low dose HRT might be beneficial for reducing the risk of AD development in vulnerable postmenopausal women. Meanwhile, HRT could increase the LSMEAN of apoE ε3 carriers.

  20. NADPH oxidase 2-derived reactive oxygen species in the hippocampus might contribute to microglial activation in postoperative cognitive dysfunction in aged mice.

    Science.gov (United States)

    Qiu, Li-Li; Ji, Mu-Huo; Zhang, Hui; Yang, Jiao-Jiao; Sun, Xiao-Ru; Tang, Hui; Wang, Jing; Liu, Wen-Xue; Yang, Jian-Jun

    2016-01-01

    Microglial activation plays a key role in the development of postoperative cognitive dysfunction (POCD). Nox2, one of the main isoforms of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the central nervous system, is a predominant source of reactive oxygen species (ROS) overproduction in phagocytes including microglia. We therefore hypothesized that Nox2-induced microglial activation is involved in the development of POCD. Sixteen-month-old C57BL/6 mice were subjected to exploratory laparotomy with isoflurane anesthesia to mimic the clinical human abdominal surgery. Behavioral tests were performed at 6 and 7 d post-surgery with open field and fear conditioning tests, respectively. The levels of Nox2, 8-hydroxy-2'-deoxyguanosine (8-OH-dG, a marker of DNA oxidation), CD11b (a marker of microglial activation), interleukin-1β (IL-1β), and brain-derived neurotrophic factor (BDNF) were determined in the hippocampus and prefrontal cortex at 1 d and 7 d post-surgery, respectively. For the interventional study, mice were treated with a NADPH oxidase inhibitor apocynin (APO). Our results showed that exploratory laparotomy with isoflurane anesthesia impaired the contextual fear memory, increased expression of Nox2, 8-OH-dG, CD11b, and IL-1β, and down-regulated BDNF expression in the hippocampus at 7 d post-surgery. The surgery-induced microglial activation and neuroinflammation persisted to 7 d after surgery in the hippocampus, but only at 1 d in the prefrontal cortex. Notably, administration with APO could rescue these surgery-induced cognitive impairments and associated brain pathology. Together, our data suggested that Nox2-derived ROS in hippocampal microglia, at least in part, contributes to subsequent neuroinflammation and cognitive impairments induced by surgery in aged mice. PMID:26254234

  1. REM sleep, hippocampus, and memory processing: insights from functional neuroimaging studies.

    Science.gov (United States)

    Spoormaker, Victor I; Czisch, Michael; Holsboer, Florian

    2013-12-01

    Neuroimaging studies show that episodic memory encoding is associated with increased activity in hippocampus and lateral prefrontal cortex; however, the latter structure shows decreased activity in rapid eye movement (REM) sleep. Together with few episodic memory traces in REM sleep, and REM sleep deprivation affecting hippocampus-independent emotional processes, this argues for generic information processing in REM sleep rather than linking episodic memory traces. PMID:24304771

  2. Gender and environmental effects on regional brain-derived neurotrophic factor expression after experimental traumatic brain injury.

    Science.gov (United States)

    Chen, X; Li, Y; Kline, A E; Dixon, C E; Zafonte, R D; Wagner, A K

    2005-01-01

    Alterations in brain-derived neurotrophic factor expression have been reported in multiple brain regions acutely after traumatic brain injury, however neither injury nor post-injury environmental enrichment has been shown to affect hippocampal brain-derived neurotrophic factor gene expression in male rats chronically post-injury. Studies have demonstrated hormone-related neuroprotection for female rats after traumatic brain injury, and estrogen and exercise both influence brain-derived neurotrophic factor levels. Despite recent studies suggesting that exposure post-traumatic brain injury to environmental enrichment improves cognitive recovery in male rats, we have shown that environmental enrichment mediated improvements with spatial learning are gender specific and only positively affect males. Therefore the purpose of this study was to evaluate the effect of gender and environmental enrichment on chronic post-injury cortical and hippocampal brain-derived neurotrophic factor protein expression. Sprague-Dawley male and cycling female rats were placed into environmental enrichment or standard housing after controlled cortical impact or sham surgery. Four weeks post-surgery, hippocampal and frontal cortex brain-derived neurotrophic factor expression were examined using Western blot. Results revealed significant increases in brain-derived neurotrophic factor expression in the frontal cortex ipsilateral to injury for males (P=0.03). Environmental enrichment did not augment this effect. Neither environmental enrichment nor injury significantly affected cortical brain-derived neurotrophic factor expression for females. In the hippocampus ipsilateral to injury brain-derived neurotrophic factor expression for both males and females was half (49% and 51% respectively) of that observed in shams housed in the standard environment. For injured males, there was a trend in this region for environmental enrichment to restore brain-derived neurotrophic factor levels to sham values

  3. Methylphenidate treatment induces oxidative stress in young rat brain.

    Science.gov (United States)

    Martins, Márcio R; Reinke, Adalisa; Petronilho, Fabrícia C; Gomes, Karin M; Dal-Pizzol, Felipe; Quevedo, João

    2006-03-17

    Methylphenidate (MPH) is frequently prescribed for the treatment of attention deficit/hyperactivity disorder. Psychostimulants can cause long-lasting neurochemical and behavioral adaptations. Here, we evaluated oxidative damage in the rat brain and the differential age-dependent response to MPH after acute and chronic exposure. We investigated the oxidative damage, assessed by the thiobarbituric acid reactive species (TBARS), and the protein carbonyl assays in cerebellum, prefrontal cortex, hippocampus, striatum, and cerebral cortex of young (25 days old) and adult (60 days old) male Wistar rats after acute and chronic exposure to MPH. Chronic MPH-treated young rats presented a dose-dependent increase in TBARS content and protein carbonyls formation in specific rat brain regions. In the acute exposure, only MPH highest dose increased lipid peroxidation in the hippocampus. No difference in protein carbonylation was observed among groups in all structures analyzed. In adult rats, we did not find oxidative damage in both acute and chronic treatment. Chronic exposure to MPH in induces oxidative damage in young rat brain, differentially from chronic exposure during adulthood. These findings highlight the need for further research to improve understanding of MPH effects on developing nervous system and the potential consequences in adulthood resulting from early-life drug exposure. PMID:16494852

  4. Increase in brain 125I-cholecystokinin (CCK) receptor binding following chronic haloperidol treatment, intracisternal 6-hydroxydopamine or ventral tegmental lesions

    International Nuclear Information System (INIS)

    Specific 125I-CCK receptor binding was significantly increased in brain tissue taken from guinea pig or mouse following chronic (2-3 week) daily administration of haloperidol (2-3 mg/kg/day). Scatchard analysis indicated the increase in CCK binding was due to an increased receptor number (B max) with no change in affinity (Kd). In guinea pigs, the increased CCK binding was observed in the mesolimbic regions and frontal cortex, but not in striatum, hippocampus nor posterior cortex. In mice, however, the increases occurred in both pooled cerebral cortical-hippocampal tissue, and in the remainder of the brain. Enhanced CCK receptor binding was also observed in membranes prepared from whole brain of mice one month following intracisternal injection of 6-hydroxydopamine. Additionally, an increase in CCK binding was observed in mesolimbic regions and frontal cortex, but not striatum or hippocampus, of guinea pigs 3 weeks after an unilateral radiofrequency lesions of the ipsilateral ventral tegmentum. The present studies demonstrate that three different procedures which reduce dopaminergic function in the brain enhance CCK receptor binding. The data provide further support for a functional interrelationship between dopaminergic systems and CCK in some brain regions and raise the possibility that CCK may play a role in the antipsychotic action of neuroleptics

  5. Influence of an alcoholic diet prescribed to the dams during lactation period in the mineral concentration on pup's brain

    Energy Technology Data Exchange (ETDEWEB)

    Marins, Luciano A.; Serpa, Renata F.B.; Jesus, Edgar F.O. de; Lopes, Ricardo T. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Coordenacao dos Programas de Pos-graduacao de Engenharia (COPPE). Nuclear Instrumentation Lab.]. E-mail: renata@lin.ufrj.br; Anjos, Marcelino J. dos [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Physics Inst.]. E-mail: marcelin@lin.ufrj.br; Carmo, Maria G.T. do [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Nutrition Inst.; Rocha, Monica S. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Dept. of Basics and Clinic Pharmacy; Moreira, Silvana [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Civil Engineering Dept.

    2007-07-01

    It is known that during lactation, the ingestion of a diet that has obtained approximately one third of its calories from ethanol may reduce milk production, alter milk composition and retard offspring's body and central nervous system growth. In this way, the aim of this work was to study the elemental concentrations changes in the hippocampus, temporal cortex and entorhinal cortex of female pups Wistar rats related to dam's ethanol intake during lactation. On the 20 days after birth (n=6) the pups were killed. The pups from the control group were also killed on the 20 days after birth (n=6). The analysis of the elemental concentration was performed by Total Reflection X-ray Fluorescence Spectrometry with Synchrotron Radiation (SR-TXRF). These measurements were carried out at XRF beam line at Light Synchrotron Brazilian laboratory, Campinas, Brazil. The alcohol administration increased P, S and Cl levels in all brain areas studied. The K, Ca, Ti and Cu were also higher in the entorhinal cortex in the alcohol group than in the control group. Furthermore, K concentrations were also increased in the temporal cortex of the alcohol group in relation to the control group. However, the alcohol administration reduced Ca, Ti, Cu, Br and Rb levels in the temporal cortex and in the hippocampus. Therefore, the ethanol intake for the dams during lactation period leads to several changes in the brain mineral concentrations of their pups. (author)

  6. Antidepressant actions of lateral habenula deep brain stimulation differentially correlate with CaMKII/GSK3/AMPK signaling locally and in the infralimbic cortex.

    Science.gov (United States)

    Kim, Yesul; Morath, Brooke; Hu, Chunling; Byrne, Linda K; Sutor, Shari L; Frye, Mark A; Tye, Susannah J

    2016-06-01

    High frequency deep brain stimulation (DBS) of the lateral habenula (LHb) reduces symptoms of depression in severely treatment-resistant individuals. Despite the observed therapeutic effects, the molecular underpinnings of DBS are poorly understood. This study investigated the efficacy of high frequency LHb DBS (130Hz; 200μA; 90μs) in an animal model of tricyclic antidepressant resistance. Further, we reported DBS mediated changes in Ca(2+)/calmodulin-dependent protein kinase (CaMKIIα/β), glycogen synthase kinase 3 (GSK3α/β) and AMP-activated protein kinase (AMPK) both locally and in the infralimbic cortex (IL). Protein expressions were then correlated to immobility time during the forced swim test (FST). Antidepressant actions were quantified via FST. Treatment groups comprised of animals treated with adrenocorticotropic hormone alone (ACTH; 100μg/day, 14days, n=7), ACTH with active DBS (n=7), sham DBS (n=8), surgery only (n=8) or control (n=8). Active DBS significantly reduced immobility in ACTH-treated animals (p<0.05). For this group, western blot results demonstrated phosphorylation status of LHb CaMKIIα/β and GSK3α/β significantly correlated to immobility time in the FST. Concurrently, we observed phosphorylation status of CaMKIIα/β, GSK3α/β, and AMPK in the IL to be negatively correlated with antidepressant actions of DBS. These findings suggest that activity dependent phosphorylation of CaMKIIα/β, and GSK3α/β in the LHb together with the downregulation of CaMKIIα/β, GSK3α/β, and AMPK in the IL, contribute to the antidepressant actions of DBS. PMID:26956153

  7. The Stressed Female Brain: Neuronal activity in the prelimbic but not infralimbic region of the medial prefrontal cortex suppresses learning after acute stress

    Directory of Open Access Journals (Sweden)

    Lisa Y. Maeng

    2013-12-01

    Full Text Available Women are nearly twice as likely as men to suffer from anxiety and post-traumatic stress disorder (PTSD, indicating that many females are especially vulnerable to stressful life experience. A profound sex difference in the response to stress is also observed in laboratory animals. Acute exposure to an uncontrollable stressful event disrupts associative learning during classical eyeblink conditioning in female rats but enhances this same type of learning process in males. These sex differences in response to stress are dependent on neuronal activity in similar but also different brain regions. Neuronal activity in the basolateral nucleus of the amygdala (BLA is necessary in both males and females. However, neuronal activity in the medial prefrontal cortex (mPFC during the stressor is necessary to modify learning in females but not in males. The mPFC is often divided into its prelimbic (PL and infralimbic (IL subregions, which differ both in structure and function. Through its connections to the BLA, we hypothesized that neuronal activity within the PL, but not IL, during the stressor is necessary to suppress learning in females. To test this hypothesis, either the PL or IL of adult female rats was bilaterally inactivated with GABAA agonist muscimol during acute inescapable swim stress. 24h later, all subjects were trained with classical eyeblink conditioning. Though stressed, females without neuronal activity in the PL learned well. In contrast, females with IL inactivation during the stressor did not learn well, behaving similar to stressed vehicle-treated females. These data suggest that exposure to a stressful event critically engages the PL, but not IL, to disrupt associative learning in females. Together with previous studies, these data indicate that the PL communicates with the BLA to suppress learning after a stressful experience in females. This circuit may be similarly engaged in women who become cognitively impaired after stressful

  8. Brain perfusion ratios by 99mTc HMPAO SPECT utilizing a mean value of the visual cortex to the cerebellum ratio derived from normal subjects

    International Nuclear Information System (INIS)

    Aim: Previous results shows that the cerebellum (CER) is the best reference to calculate relative indexes of perfusion (IP) by brain SPECT. However, it can not be used on patients with bilateral cerebellar hypoperfusion. In such cases visual cortex (VC) or an average of the whole brain activity is recommended (WB). VC and WB are less reliable than CER, making it difficult to compare SPECT scans that have been normalized with different values. Materials and Methods: To overcome this difficulty, we developed a method to calculate IP utilizing a reference value defined as (VC / ), where is the mean value of the VC/CER ratio derived from a normal database which was assumed to be constant. We called the value VC/ the 'Pseudocerebellum' (PCER). For clinical validation, we first tested statistically the VC/CER ratio on a group of 60 [99mTc]-HMPAO SPECT scans of 20 normal subjects and 40 neurological patients with positive SPECT but without involvement of VC and CER. To demonstrate that IPPCER approx. IPCER, we calculated the mean value of the absolute differences CER - IPPCER vertical bar> on two groups of scans from subjects without involvement of VC and CER: 10 normal subjects (GI); and 40 patients (GII). Finally, using an indirect procedure the method was tested on a third group of SPECT scans of 30 patients with bilateral cerebellar hypoperfusion (G III). Results: The VC/CER ratio was approximately constant with gender and age at a 95% confidence level; CER - IPPCER vertical bar> was 1.22%±0.35 and 1.20%±0.42 for GI and GII, respectively. This is less than the within-subject replicability of the HMPAO SPECT studies; and thus demonstrated by an indirect approach that IPPCER is a valid procedure by which to evaluate relative perfusion on patients with bilateral cerebellar hypoperfusion and quantitatively comparable to using CER as reference region. Conclusion: The VC/CER ratio has very little inter-subject variability in individuals where these regions are not

  9. Association between income and the hippocampus.

    Directory of Open Access Journals (Sweden)

    Jamie L Hanson

    Full Text Available Facets of the post-natal environment including the type and complexity of environmental stimuli, the quality of parenting behaviors, and the amount and type of stress experienced by a child affects brain and behavioral functioning. Poverty is a type of pervasive experience that is likely to influence biobehavioral processes because children developing in such environments often encounter high levels of stress and reduced environmental stimulation. This study explores the association between socioeconomic status and the hippocampus, a brain region involved in learning and memory that is known to be affected by stress. We employ a voxel-based morphometry analytic framework with region of interest drawing for structural brain images acquired from participants across the socioeconomic spectrum (n = 317. Children from lower income backgrounds had lower hippocampal gray matter density, a measure of volume. This finding is discussed in terms of disparities in education and health that are observed across the socioeconomic spectrum.

  10. DHA Depletion in Rat Brain Is Associated With Impairment on Spatial Learning and Memory

    Institute of Scientific and Technical Information of China (English)

    YING XIAO; LING WANG; RUO-JUN XU; ZHEN-YU CHEN

    2006-01-01

    Objective To examine the effect of docosahexaenoic acid (DHA) deficiency in brain on spatial learning and memory in rats. Methods Sprague Dawley rats were fed with an n-3 fatty acid deficient diet for two generations to induce DHA depletion in brain. DHA in seven brain regions was analyzed using the gas-liquid chromatography. Morris water maze (MWM) was employed as an assessing index of spatial learning and memory in the n-3 fatty acid deficient adult rats of second generation. Results Feeding an n-3 deficient diet for two generations depleted DHA differently by 39%-63% in the seven brain regions including cerebellum, medulla, hypothalamus, striatum, hippocampus, cortex and midbrain. The MWM test showed that the n-3 deficient rats took a longer time and swam a longer distance to find the escape platform than the n-3 Adq group. Conclusion The spatial learning and memory in adult rats are partially impaired by brain DHA depletion.

  11. Differential changes of metabolic brain activity and interregional functional coupling in prefronto-limbic pathways during different stress conditions: Functional imaging in freely behaving rodent pups

    Directory of Open Access Journals (Sweden)

    Joerg Bock

    2012-05-01

    Full Text Available The trumpet-tailed rat or degu (Octodon degus is an established model to investigate the consequences of early stress on the development of emotional brain circuits and behaviour. The aim of this study was to identify brain circuits, that respond to different stress conditions and to test if acute stress alters functional coupling of brain activity among prefrontal and limbic regions. Using functional imaging (2-Fluoro-deoxyglucose method in 8 day old male degu pups the following stress conditions were compared: (A pups together with parents and siblings (control, (B separation of the litter from the parents, (C individual separation from parents and siblings, (D individual separation and presentation of maternal calls. Condition (B significantly downregulated brain activity in the prefrontal cortex, hippocampus, nucleus accumbens and sensory areas compared to controls. Activity decrease was even more pronounced during condition (C, where, in contrast to all other regions, activity in the PAG was increased. Interestingly, brain activity in stress-associated brain regions such as the amygdala and habenula was not affected. In condition (D maternal vocalizations reactivated brain activity in the cingulate and precentral medial cortex, nucleus accumbens and striatum and in sensory areas. In contrast, reduced activity was measured in the prelimbic and infralimbic cortex and in the hippocampus and amygdala. Correlation analysis revealed complex, region- and situation-specific changes of interregional functional coupling among prefrontal and limbic brain regions during stress exposure. We show here for the first time that early life stress results in a widespread reduction of brain activity in the infant brain and changes interregional functional coupling. Moreover, maternal vocalizations can partly buffer stress-induced decrease in brain activity in some regions and evoked very different functional coupling patterns compared to the three other

  12. Effects of brain focal ischemia or chronic stress on the hippocampus-dependent learning and memory function%脑缺血与慢性应激对依赖海马的学习记忆的影响

    Institute of Scientific and Technical Information of China (English)

    毛琳; 李德强; 罗本燕

    2011-01-01

    目的 对比脑缺血与慢性应激所致认知损害及海马病变的强弱,为临床改善脑卒中后认知障碍(poststroke cognitive impairment,PSCI)提供参考.方法 40只成年雄性SD大鼠平均分为4组:对照组、应激组、缺血组与缺血加应激组,缺血手术采用改良的选择性大脑中动脉栓塞术;应激处理采用连续3周的慢性不可预见性温和应激;Moms水迷宫实验评价依赖海马的学习记忆功能;免疫组织化学染色及半定量RT-PCR观察海马CA3区脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)的表达变化.结果 应激或缺血均可使大鼠学习功能明显下降,表现为与同时点对照组比较,逃避潜伏期显著延长,二者的综合作用更明显.慢性应激对学习功能的影响强于脑缺血损伤.应激或缺血均减弱记忆功能,但二者的作用差异无统计学意义.与对照相比,缺血显著增加海马CA3区BDNF的表达(27.0±2.5与20.1±2.1),应激降低BDNF的表达(15.2±1.8与20.1±2.1),二者综合作用仍显著降低BDNF的表达(8.2±1.5),差异均具有统计学意义(F=52.87,P<0.05).结论 缺血与应激均降低大鼠学习记忆功能,应激对认知功能的损害高于缺血,而缺血与应激的综合作用对认知功能损害与抑制BDNF表达作用更明显,提示进行PSCI的综合治疗时,要重视心理社会应激干预和抑郁状态的改善.%Objective To compare the intensity of cognitive impairment and the level of pathological lesion in hippocampus induced by ischemia or chronic stress for a more valuable guidance in the treatment of post-stroke cognitive impairment(PSCI).Methods Forty male adult SD rats were divided medially into 4 groups:control,stress,ischemia and ischemia plus stress.Animals in 3 treatment groups were subjected respectively to an operation of modified selective middle cerebral artery occlusion or a procedure of continuous 3-week chronic unpredictable mild stress or a combined program of

  13. Magnesium regulates neural stem cell proliferation in the mouse hippocampus by altering mitochondrial function.

    Science.gov (United States)

    Jia, Shanshan; Mou, Chengzhi; Ma, Yihe; Han, Ruijie; Li, Xue

    2016-04-01

    In the adult brain, neural stem cells from the subgranular zone (SGZ) of the hippocampus and the subventricular zone (SVZ) of the cortex progress through the following five developmental stages: radial glia-like cells, neural progenitor cells, neuroblasts, immature neurons, and mature neurons. These developmental stages are linked to both neuronal microenvironments and energy metabolism. Neurogenesis is restricted and has been demonstrated to arise from tissue microenvironments. We determined that magnesium, a key nutrient in cellular energy metabolism, affects neural stem cell (NSC) proliferation in cells derived from the embryonic hippocampus by influencing mitochondrial function. Densities of proliferating cells and NSCs both showed their highest values at 0.8 mM [Mg(2+) ]o , whereas lower proliferation rates were observed at 0.4 and 1.4 mM [Mg(2+) ]o . The numbers and sizes of the neurospheres reached the maximum at 0.8 mM [Mg(2+) ]o and were weaker under both low (0.4 mM) and high (1.4 mM) concentrations of magnesium. In vitro experimental evidence demonstrates that extracellular magnesium regulates the number of cultured hippocampal NSCs, affecting both magnesium homeostasis and mitochondrial function. Our findings indicate that the effect of [Mg(2+) ]o on NSC proliferation may lie downstream of alterations in mitochondrial function because mitochondrial membrane potential was highest in the NSCs in the moderate [Mg(2+) ]o (0.8 mM) group and lower in both the low (0.4 mM) and high (1.4 mM) [Mg(2+) ]o groups. Overall, these findings demonstrate a new function for magnesium in the brain in the regulation of hippocampal neural stem cells: affecting their cellular energy metabolism. PMID:26634890

  14. Gestational stress and fluoxetine treatment differentially affect plasticity, methylation and serotonin levels in the PFC and hippocampus of rat dams.

    Science.gov (United States)

    Gemmel, Mary; Rayen, Ine; van Donkelaar, Eva; Loftus, Tiffany; Steinbusch, Harry W; Kokras, Nikolaos; Dalla, Christina; Pawluski, Jodi L

    2016-07-01

    Women are more likely to develop depression during childbearing years with up to 20% of women suffering from depression during pregnancy and in the postpartum period. Increased prevalence of depression during the perinatal period has resulted in frequent selective serotonin reuptake inhibitor (SSRI) antidepressant treatment; however the effects of such medications on the maternal brain remain limited. Therefore, the aim of the present study is to investigate the effects of the SSRI medication, fluoxetine, on neurobiological differences in the maternal brain. To model aspects of maternal depression, gestational stress was used. Sprague-Dawley rat dams were exposed to either gestational stress and/or fluoxetine (5mg/kg/day) to form the following four groups: 1. Control+Vehicle, 2. Stress+Vehicle, 3. Control+Fluoxetine, and 4. Stress+Fluoxetine. At weaning maternal brains were collected. Main findings show that gestational stress alone increased synaptophysin and serotonin metabolism in the cingulate cortex2 region of the cortex while fluoxetine treatment after stress normalized these effects. In the hippocampus, fluoxetine treatment, regardless of gestational stress exposure, decreased both global measures of methylation in the dentate gyrus, as measured by Dnmt3a immunoreactivity, as well as serotonin metabolism. No further changes in synaptophysin, PSD-95, or Dnmt3a immunoreactivity were seen in the cortical or hippocampal areas investigated. These findings show that gestational stress and SSRI medication affect the neurobiology of the maternal brain in a region-specific manner. This work adds to a much needed area of research aimed at understanding neurobiological changes associated with maternal depression and the role of SSRI treatment in altering these changes in the female brain. PMID:27060483

  15. Memory and brain-derived neurotrophic factor after subchronic or chronic amphetamine treatment in an animal model of mania.

    Science.gov (United States)

    Fries, Gabriel R; Valvassori, Samira S; Bock, Hugo; Stertz, Laura; Magalhães, Pedro Vieira da Silva; Mariot, Edimilson; Varela, Roger B; Kauer-Sant'Anna, Marcia; Quevedo, João; Kapczinski, Flávio; Saraiva-Pereira, Maria Luiza

    2015-09-01

    Progression of bipolar disorder (BD) has been associated with cognitive impairment and changes in neuroplasticity, including a decrease in serum brain-derived neurotrophic factor (BDNF). However, no study could examine BDNF levels directly in different brain regions after repeated mood episodes to date. The proposed animal model was designed to mimic several manic episodes and evaluate whether the performance in memory tasks and BDNF levels in hippocampus, prefrontal cortex, and amygdala would change after repeated amphetamine (AMPH) exposure. Adult male Wistar rats were divided into subchronic (AMPH for 7 days) and chronic groups (35 days), mimicking manic episodes at early and late stages of BD, respectively. After open field habituation or inhibitory avoidance test, rats were killed, brain regions were isolated, and BDNF mRNA and protein levels were measured by quantitative real-time PCR and ELISA, respectively. AMPH impaired habituation memory in both subchronic and chronic groups, and the impairment was worse in the chronic group. This was accompanied by increased Bdnf mRNA levels in the prefrontal cortex and amygdala region, as well as reduced BDNF protein in the hippocampus. In the inhibitory avoidance, AMPH significantly decreased the change from training to test when compared to saline. No difference was observed between subchronic and chronic groups, although chronically AMPH-treated rats presented increased Bdnf mRNA levels and decreased protein levels in hippocampus when compared to the subchronic group. Our results suggest that the cognitive impairment related to BD neuroprogression may be associated with BDNF alterations in hippocampus, prefrontal cortex, and amygdala. PMID:26026487

  16. Aging-induced changes in brain regional serotonin receptor binding: Effect of Carnosine.

    Science.gov (United States)

    Banerjee, S; Poddar, M K

    2016-04-01

    Monoamine neurotransmitter, serotonin (5-HT) has its own specific receptors in both pre- and post-synapse. In the present study the role of carnosine on aging-induced changes of [(3)H]-5-HT receptor binding in different brain regions in a rat model was studied. The results showed that during aging (18 and 24 months) the [(3)H]-5-HT receptor binding was reduced in hippocampus, hypothalamus and pons-medulla with a decrease in their both Bmax and KD but in cerebral cortex the [(3)H]-5-HT binding was increased with the increase of its only Bmax. The aging-induced changes in [(3)H]-5-HT receptor binding with carnosine (2.0 μg/kg/day, intrathecally, for 21 consecutive days) attenuated in (a) 24-month-aged rats irrespective of the brain regions with the attenuation of its Bmax except hypothalamus where both Bmax and KD were significantly attenuated, (b) hippocampus and hypothalamus of 18-month-aged rats with the attenuation of its Bmax, and restored toward the [(3)H]-5-HT receptor binding that observed in 4-month-young rats. The decrease in pons-medullary [(3)H]-5-HT binding including its Bmax of 18-month-aged rats was promoted with carnosine without any significant change in its cerebral cortex. The [(3)H]-5-HT receptor binding with the same dosages of carnosine in 4-month-young rats (a) increased in the cerebral cortex and hippocampus with the increase in their only Bmax whereas (b) decreased in hypothalamus and pons-medulla with a decrease in their both Bmax and KD. These results suggest that carnosine treatment may (a) play a preventive role in aging-induced brain region-specific changes in serotonergic activity (b) not be worthy in 4-month-young rats in relation to the brain regional serotonergic activity. PMID:26808776

  17. Cyclosporine, a P-glycoprotein modulator, increases [18F]MPPF uptake in rat brain and peripheral tissues: microPET and ex vivo studies

    International Nuclear Information System (INIS)

    Pretreatment with cyclosporine, a P-glycoprotein (P-gp) modulator increases brain uptake of 4-(2'-methoxyphenyl)-1-[2'-(N-2''-pyridinyl)-p-[18F] fluorobenzamido] ethylpiper azine ([18F]MPPF) for binding to hydroxytryptamine1A (5-HT1A) receptors. Those increases were quantified in rat brain with in vivo microPET and ex vivo tissue studies. Each Sprague-Dawley rat (n=4) received a baseline [18F]MPPF microPET scan followed by second scan 2-3 weeks later that included cyclosporine pretreatment (50 mg/kg, i.p.). Maximum a posteriori reconstructed images and volumetric ROIs were used to generate dynamic radioactivity concentration measurements for hippocampus, striatum, and cerebellum, with simplified reference tissue method (SRTM) analysis. Western blots were used to semiquantify P-gp regional distribution in brain. MicroPET studies showed that hippocampus uptake of [18F]MPPF was increased after cyclosporine; ex vivo studies showed similar increases in hippocampus and frontal cortex at 30 min, and for heart and kidney at 2.5 and 5 min, without concomitant increases in [18F]MPPF plasma concentration. P-gp content in cerebellum was twofold higher than in hippocampus or frontal cortex. These studies confirm and extend prior ex vivo results (J. Passchier, et al., Eur J Pharmacol, 2000) that showed [18F]MPPF as a substrate for P-gp. Our microPET results showed that P-gp modulation of [18F]MPPF binding to 5-HT1A receptors can be imaged in rat hippocampus. The heterogeneous brain distribution of P-gp appeared to invalidate the use of cerebellum as a nonspecific reference region for SRTM modeling. Regional quantitation of P-gp may be necessary for accurate PET assessment of 5-HT1A receptor density when based on tracer uptake sensitive to P-gp modulation. (orig.)

  18. Hippocampal damage and kainic acid injection induce a rapid increase in mRNA for BDNF and NGF in the rat brain.

    Science.gov (United States)

    Ballarín, M; Ernfors, P; Lindefors, N; Persson, H

    1991-10-01

    In situ hybridization and Northern blots were used to study expression of mRNAs for members of the nerve growth factor family in the rat brain following an excitatory stimulus. One hour after a unilateral needle insertion or saline injection into the dorsal hippocampus, the level of brain-derived neurotrophic factor (BDNF) mRNA increased markedly in granular neurons of the dentate gyrus and in the piriform cortex ipsilateral to the injection. The same treatment also increased the level of NGF mRNA in granular neurons of the ipsilateral dentate gyrus. The rapid increase in BDNF and NGF mRNA after a needle insertion or injection of saline was transient and preceded by an increase in c-fos mRNA in the same brain regions. In contrast to a needle insertion per se or a saline injection, 7 h after a unilateral injection of kainic acid into the dorsal hippocampus, the level of BDNF mRNA was dramatically increased in the ipsilateral hippocampus, as well as in the ipsilateral frontoparietal, piriform and perihinal cortex, the amygdaloid complex, claustrum, and ventromedial hypothalamus. A less pronounced increase was also seen in these brain areas on the contralateral side. Northern blots revealed that the level of BDNF mRNA increased 5- and 40-fold in the contra- and ipsilateral hippocampus, respectively, compared to sham-operated control animals. In contrast to BDNF and NGF, the level of hippocampus-derived neurotrophic factor/neurotrohin-3 (HDNF/NT-3) mRNA was not altered by either needle insertion or injection of saline or kainic acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1915733

  19. Glucose transport in brain - effect of inflammation.

    Science.gov (United States)

    Jurcovicova, J

    2014-01-01

    Glucose is transported across the cell membrane by specific saturable transport system, which includes two types of glucose transporters: 1) sodium dependent glucose transporters (SGLTs) which transport glucose against its concentration gradient and 2) sodium independent glucose transporters (GLUTs), which transport glucose by facilitative diffusion in its concentration gradient. In the brain, both types of transporters are present with different function, affinity, capacity, and tissue distribution. GLUT1 occurs in brain in two isoforms. The more glycosylated GLUT1 is produced in brain microvasculature and ensures glucose transport across the blood brain barrier (BBB). The less glycosylated form is localized in astrocytic end-feet and cell bodies and is not present in axons, neuronal synapses or microglia. Glucose transported to astrocytes by GLUT1 is metabolized to lactate serving to neurons as energy source. Proinflammatory cytokine interleukin (IL)-1β upregulates GLUT1 in endothelial cells and astrocytes, whereas it induces neuronal death in neuronal cell culture. GLUT2 is present in hypothalamic neurons and serves as a glucose sensor in regulation of food intake. In neurons of the hippocampus, GLUT2 is supposed to regulate synaptic activity and neurotransmitter release. GLUT3 is the most abundant glucose transporter in the brain having five times higher transport capacity than GLUT1. It is present in neuropil, mostly in axons and dendrites. Its density and distribution correlate well with the local cerebral glucose demands. GLUT5 is predominantly fructose transporter. In brain, GLUT5 is the only hexose transporter in microglia, whose regulation is not yet clear. It is not present in neurons. GLUT4 and GLUT8 are insulin-regulated glucose transporters in neuronal cell bodies in the cortex and cerebellum, but mainly in the hippocampus and amygdala, where they maintain hippocampus-dependent cognitive functions. Insulin translocates GLUT4 from cytosol to plasma

  20. Magnetic micelles for DNA delivery to rat brains after mild traumatic brain injury.

    Science.gov (United States)

    Das, Mahasweta; Wang, Chunyan; Bedi, Raminder; Mohapatra, Shyam S; Mohapatra, Subhra

    2014-10-01

    Traumatic brain injury (TBI) causes significant mortality, long term disability and psychological symptoms. Gene therapy is a promising approach for treatment of different pathological conditions. Here we tested chitosan and polyethyleneimine (PEI)-coated magnetic micelles (CP-mag micelles or CPMMs), a potential MRI contrast agent, to deliver a reporter DNA to the brain after mild TBI (mTBI). CPMM-tomato plasmid (ptd) conjugate expressing a red-fluorescent protein (RFP) was administered intranasally immediately after mTBI or sham surgery in male SD rats. Evans blue extravasation following mTBI suggested CPMM-ptd entry into the brain via the compromised blood-brain barrier. Magnetofection increased the concentration of CPMMs in the brain. RFP expression was observed in the brain (cortex and hippocampus), lung and liver 48 h after mTBI. CPMM did not evoke any inflammatory response by themselves and were excreted from the body. These results indicate the possibility of using intranasally administered CPMM as a theranostic vehicle for mTBI. From the clinical editor: In this study, chitosan and PEI-coated magnetic micelles (CPMM) were demonstrated as potentially useful vehicles in traumatic brain injury in a rodent model. Magnetofection increased the concentration of CPMMs in the brain and, after intranasal delivery, CPMM did not evoke any inflammatory response and were excreted from the body. PMID:24486465

  1. Proteomic analysis of hippocampus in the rat

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bo; WANG Ren-zhi; LIAN Zhi-gang; YAO Yong

    2004-01-01

    Objective To analyze the protein expression in the rat hippocampus by the proteomic approach.Methods Proteins from hippocampal tissue homogenates of the rat were separated by two-dimensional gel electrophoresis(2-DE),and stained with colloidal Coomassie blue to produce a high-resolution map of the rat hippocampus proteome.Selected proteins from this map were digested with trypsin,and the resulting tryptic peptides were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS).The mass spectrometric data were used to identify the proteins through searches of the NCBI protein sequence database.Results 37 prominent proteins with various functional characteristics were identified.The identified brain protein classes covered metabolism enzymes,cytoskeleton proteins,heat shock proteins,antioxidant proteins,signalling proteins,proteasome-related proteins,neuron-specific proteins and glial-associated proteins.Furthermore,3 hypothetical proteins,unknown proteins so far only proposed from their nucleic acid structure,were identified.Conclusion This study provides the first unbiased characterization of proteins of the rat hippocampus and will be used for future studies of differential protein expression in rat models of neurological disorders.

  2. Tributyltin induces oxidative damage, inflammation and apoptosis via disturbance in blood–brain barrier and metal homeostasis in cerebral cortex of rat brain: An in vivo and in vitro study

    International Nuclear Information System (INIS)

    Highlights: • Sustainable blood–brain barrier disruption was found by single acute dose of TBTC (up to 1 week). • Imbalance in essential metal homeostasis in the cortical tissue may lead to oxidative stress. • Astroglial activation and inflammation resulted in neuronal loss. • TBTC primarily induced apoptosis as found in in-vitro study via activation of calcium, p38 signaling, ROS and caspases. • Calcium inhibitors and anti-oxidants showed protective efficacy in TBTC induced cell death. - Abstract: Tributyltin (TBT), a member of the organotin family, is primarily used for its biocidal activity. Persistent environmental levels of TBT pose threat to the ecosystem. Since neurotoxic influence of TBT remains elusive, we therefore, studied its effect on cerebral cortex of male Wistar rats. A single oral dose of Tributyltin-Chloride (TBTC) (10, 20, 30 mg/kg) was administered and the animals were sacrificed on day 3 and day 7. Blood–brain barrier permeability remained disrupted significantly till day 7 with all the doses of TBTC. Pro-oxidant metal levels (Fe, Cu) were increased with a concomitant decrease in Zn. ROS generation was substantially raised resulting in oxidative damage (increased protein carbonylation and lipid peroxidation) with marked decline in tissue antioxidant status (GSH/GSSG levels). Protein expression studies indicated astrocyte activation, upregulation of inflammatory molecules (IL-6, Cox-2 and NF-κB) and simultaneous elevation in the apoptotic index (Bax/Bcl2). Neurodegeneration was evident by reduced neurofilament expression and increased calpain cleaved Tau levels. The in-vitro study demonstrated involvement of calcium and signaling molecules (p38), with downstream activation of caspase-3 and -8, and apoptotic cell death was evident by nuclear fragmentation, DNA laddering and Annexin V binding experiments. Ca2+ inhibitors (BAPTA-AM, EGTA, and RR) and free radical scavengers (NAC and biliprotein [C-PC]) increased cell viability (MTT