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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.

    Science.gov (United States)

    Lieblein-Boff, Jacqueline C; Johnson, Elizabeth J; Kennedy, Adam D; Lai, Chron-Si; Kuchan, Matthew J

    2015-01-01

    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. 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.

  3. 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

    quantitative proteomic analysis of three functionally distinct compartments of mouse brain: cortex, hippocampus, and cerebellum. In total, 976 unique peptides corresponding to 555 unique proteins were quantified. Up to 20-fold differences in the levels of some proteins between brain areas were measured...

  4. Brain Region Specificity of Mitochondrial Biogenesis and Bioenergetics Response to Nrf2 Knockdown: A Comparison Among Hippocampus, Prefrontal Cortex and Amygdala of Male Rat Brain

    Directory of Open Access Journals (Sweden)

    Solmaz Khalifeh

    2017-08-01

    Full Text Available ABSTRACT Nuclear factor (erythroid-derived 2-like 2 (Nrf2 has been identified as the well-known coordinator of intracellular antioxidant defense system. Herein, we aimed to evaluate the effects of Nrf2 silencing on mitochondrial biogenesis markers peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α, nuclear respiratory factor-1(NRF-1, mitochondrial transcription factor A (TFAM and cytochrome c as well activities of two enzymes citrate synthase (CS and malate dehydrogenase (MDH in three brain regions hippocampus, amygdala, and prefrontal cortex of male Wistar rats. Small interfering RNA (siRNA targeting Nrf2 was injected in dorsal third ventricle. Next, western blot analysis and biochemical assays were used to evaluation of protein level of mitochondrial biogenesis factors and CS and MDH enzymes activity, respectively. Based on findings, whilst Nrf2-silencing led to notably reduction in protein level of mitochondrial biogenesis upstream PGC-1α in three brain regions compared to the control rats, the level of NRF-1, TFAM and cytochrome c remained unchanged. Furthermore, although Nrf2 silencing increased CS activity, activity of MDH significantly decreased in hippocampus and prefrontal cortex areas. Interestingly, CS and MDH activities in amygdala did not change after Nrf2 knockdown. In conclusion, the present findings highlighted complexity of interaction of Nrf2 and mitochondrial functions in a brain region-specific manner. However, by outlining the exact interaction between Nrf2 and mitochondria, it would be possible to find a new therapeutic strategies for neurological disorders related to oxidative stress.

  5. 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...

  6. Initial brain aging: heterogeneity of mitochondrial size is associated with decline in complex I-linked respiration in cortex and hippocampus.

    Science.gov (United States)

    Thomsen, Kirsten; Yokota, Takashi; Hasan-Olive, Md Mahdi; Sherazi, Niloofar; Fakouri, Nima Borhan; Desler, Claus; Regnell, Christine Elisabeth; Larsen, Steen; Rasmussen, Lene Juel; Dela, Flemming; Bergersen, Linda Hildegard; Lauritzen, Martin

    2018-01-01

    Brain aging is accompanied by declining mitochondrial respiration. We hypothesized that mitochondrial morphology and dynamics would reflect this decline. Using hippocampus and frontal cortex of a segmental progeroid mouse model lacking Cockayne syndrome protein B (CSB m/m ) and C57Bl/6 (WT) controls and comparing young (2-5 months) to middle-aged mice (13-14 months), we found that complex I-linked state 3 respiration (CI) was reduced at middle age in CSB m/m hippocampus, but not in CSB m/m cortex or WT brain. In hippocampus of both genotypes, mitochondrial size heterogeneity increased with age. Notably, an inverse correlation between heterogeneity and CI was found in both genotypes, indicating that heterogeneity reflects mitochondrial dysfunction. The ratio between fission and fusion gene expression reflected age-related alterations in mitochondrial morphology but not heterogeneity. Mitochondrial DNA content was lower, and hypoxia-induced factor 1α mRNA was greater at both ages in CSB m/m compared to WT brain. Our findings show that decreased CI and increased mitochondrial size heterogeneity are highly associated and point to declining mitochondrial quality control as an initial event in brain aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Interplay of hippocampus and prefrontal cortex in memory

    Science.gov (United States)

    Preston, Alison R.; Eichenbaum, Howard

    2013-01-01

    Recent studies on the hippocampus and the prefrontal cortex have considerably advanced our understanding of the distinct roles of these brain areas in the encoding and retrieval of memories, and of how they interact in the prolonged process by which new memories are consolidated into our permanent storehouse of knowledge. These studies have led to a new model of how the hippocampus forms and replays memories and how the prefrontal cortex engages representations of the meaningful contexts in which related memories occur, as well as how these areas interact during memory retrieval. Furthermore, they have provided new insights into how interactions between the hippocampus and prefrontal cortex support the assimilation of new memories into pre-existing networks of knowledge, called schemas, and how schemas are modified in this process as the foundation of memory consolidation. PMID:24028960

  8. Cyclic AMP response element-binding protein in post-mortem brain of teenage suicide victims: specific decrease in the prefrontal cortex but not the hippocampus.

    Science.gov (United States)

    Pandey, Ghanshyam N; Dwivedi, Yogesh; Ren, Xinguo; Rizavi, Hooriyah S; Roberts, Rosalinda C; Conley, Robert R

    2007-10-01

    Abnormalities in both adenylyl cyclase (AC) and phosphoinositide (PI) signalling systems have been observed in the post-mortem brain of suicide victims. Cyclic AMP response element-binding protein (CREB) is a transcription factor that is activated by phosphorylating enzymes such as protein kinase A (PKA) and protein kinase C (PKC), which suggests that both AC and PI signalling systems converge at the level of CREB. CREB is involved in the transcription of many neuronally expressed genes that have been implicated in the pathophysiology of depression and suicide. Since we observed abnormalities of both PKA and PKC in the post-mortem brain of teenage suicide victims, we examined if these abnormalities are also associated with abnormalities of CREB, which is activated by these phosphorylating enzymes. We determined CRE-DNA binding using the gel shift assay, as well as protein expression of CREB using the Western blot technique, and the mRNA expression of CREB using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) technique in the prefrontal cortex (PFC), and hippocampus obtained from 17 teenage suicide victims and 17 matched normal control subjects. We observed that the CRE-DNA binding and the protein expression of CREB were significantly decreased in the PFC of teenage suicide victims compared with controls. There was also a significant decrease in mRNA expression of CREB in the PFC of teenage suicide victims compared with control subjects. However, there were no significant differences in CRE-DNA binding or the protein and mRNA expression of CREB in the hippocampus of teenage suicide victims compared with control subjects. These results suggest that the abnormalities of PKA, and of PKC, observed in teenage suicide victims are also associated with abnormalities of the transcription factor CREB, and that this may also cause alterations of important neuronally expressed genes, and provide further support of the signal transduction of abnormalities

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

    Directory of Open Access Journals (Sweden)

    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

  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.

  11. Circulating IGF-1 deficiency exacerbates hypertension-induced microvascular rarefaction in the mouse hippocampus and retrosplenial cortex: implications for cerebromicrovascular and brain aging

    OpenAIRE

    Tarantini, Stefano; Tucsek, Zsuzsanna; Valcarcel-Ares, M. Noa; Toth, Peter; Gautam, Tripti; Giles, Cory B.; Ballabh, Praveen; Wei, Jeanne Y.; Wren, Jonathan D.; Ashpole, Nicole M.; Sonntag, William E.; Ungvari, Zoltan; Csiszar, Anna

    2016-01-01

    Strong epidemiological and experimental evidence indicate that both age and hypertension lead to significant functional and structural impairment of the cerebral microcirculation, predisposing to the development of vascular cognitive impairment (VCI) and Alzheimer’s disease. Preclinical studies establish a causal link between cognitive decline and microvascular rarefaction in the hippocampus, an area of brain important for learning and memory. Age-related decline in circulating IGF-1 levels r...

  12. Stress Effects on Neuronal Structure: Hippocampus, Amygdala, and Prefrontal Cortex

    National Research Council Canada - National Science Library

    McEwen, Bruce S; Nasca, Carla; Gray, Jason D

    2016-01-01

    The hippocampus provided the gateway into much of what we have learned about stress and brain structural and functional plasticity, and this initial focus has expanded to other interconnected brain...

  13. A Learning-Based Wrapper Method to Correct Systematic Errors in Automatic Image Segmentation: Consistently Improved Performance in Hippocampus, Cortex and Brain Segmentation

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    Wang, Hongzhi; Das, Sandhitsu R.; Suh, Jung Wook; Altinay, Murat; Pluta, John; Craige, Caryne; Avants, Brian; Yushkevich, Paul A.

    2011-01-01

    We propose a simple but generally applicable approach to improving the accuracy of automatic image segmentation algorithms relative to manual segmentations. The approach is based on the hypothesis that a large fraction of the errors produced by automatic segmentation are systematic, i.e., occur consistently from subject to subject, and serves as a wrapper method around a given host segmentation method. The wrapper method attempts to learn the intensity, spatial and contextual patterns associated with systematic segmentation errors produced by the host method on training data for which manual segmentations are available. The method then attempts to correct such errors in segmentations produced by the host method on new images. One practical use of the proposed wrapper method is to adapt existing segmentation tools, without explicit modification, to imaging data and segmentation protocols that are different from those on which the tools were trained and tuned. An open-source implementation of the proposed wrapper method is provided, and can be applied to a wide range of image segmentation problems. The wrapper method is evaluated with four host brain MRI segmentation methods: hippocampus segmentation using FreeSurfer (Fischl et al., 2002); hippocampus segmentation using multi-atlas label fusion (Artaechevarria et al., 2009); brain extraction using BET (Smith, 2002); and brain tissue segmentation using FAST (Zhang et al., 2001). The wrapper method generates 72%, 14%, 29% and 21% fewer erroneously segmented voxels than the respective host segmentation methods. In the hippocampus segmentation experiment with multi-atlas label fusion as the host method, the average Dice overlap between reference segmentations and segmentations produced by the wrapper method is 0.908 for normal controls and 0.893 for patients with mild cognitive impairment. Average Dice overlaps of 0.964, 0.905 and 0.951 are obtained for brain extraction, white matter segmentation and gray matter

  14. Circulating IGF-1 deficiency exacerbates hypertension-induced microvascular rarefaction in the mouse hippocampus and retrosplenial cortex: implications for cerebromicrovascular and brain aging.

    Science.gov (United States)

    Tarantini, Stefano; Tucsek, Zsuzsanna; Valcarcel-Ares, M Noa; Toth, Peter; Gautam, Tripti; Giles, Cory B; Ballabh, Praveen; Wei, Jeanne Y; Wren, Jonathan D; Ashpole, Nicole M; Sonntag, William E; Ungvari, Zoltan; Csiszar, Anna

    2016-08-01

    Strong epidemiological and experimental evidence indicate that both age and hypertension lead to significant functional and structural impairment of the cerebral microcirculation, predisposing to the development of vascular cognitive impairment (VCI) and Alzheimer's disease. Preclinical studies establish a causal link between cognitive decline and microvascular rarefaction in the hippocampus, an area of brain important for learning and memory. Age-related decline in circulating IGF-1 levels results in functional impairment of the cerebral microvessels; however, the mechanistic role of IGF-1 deficiency in impaired hippocampal microvascularization remains elusive. The present study was designed to characterize the additive/synergistic effects of IGF-1 deficiency and hypertension on microvascular density and expression of genes involved in angiogenesis and microvascular regression in the hippocampus. To achieve that goal, we induced hypertension in control and IGF-1 deficient mice (Igf1 (f/f)  + TBG-Cre-AAV8) by chronic infusion of angiotensin II. We found that circulating IGF-1 deficiency is associated with decreased microvascular density and exacerbates hypertension-induced microvascular rarefaction both in the hippocampus and the neocortex. The anti-angiogenic hippocampal gene expression signature observed in hypertensive IGF-1 deficient mice in the present study provides important clues for subsequent studies to elucidate mechanisms by which hypertension may contribute to the pathogenesis and clinical manifestation of VCI. In conclusion, adult-onset, isolated endocrine IGF-1 deficiency exerts deleterious effects on the cerebral microcirculation, leading to a significant decline in cortical and hippocampal capillarity and exacerbating hypertension-induced cerebromicrovascular rarefaction. The morphological impairment of the cerebral microvasculature induced by IGF-1 deficiency and hypertension reported here, in combination with neurovascular uncoupling, increased

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Aging without Apolipoprotein D: Molecular and cellular modifications in the hippocampus and cortex.

    Science.gov (United States)

    Sanchez, Diego; Bajo-Grañeras, Raquel; Del Caño-Espinel, Manuela; Garcia-Centeno, Rosa; Garcia-Mateo, Nadia; Pascua-Maestro, Raquel; Ganfornina, Maria D

    2015-07-01

    A detailed knowledge of the mechanisms underlying brain aging is fundamental to understand its functional decline and the baseline upon which brain pathologies superimpose. Endogenous protective mechanisms must contribute to the adaptability and plasticity still present in the healthy aged brain. Apolipoprotein D (ApoD) is one of the few genes with a consistent and evolutionarily conserved up-regulation in the aged brain. ApoD protecting roles upon stress or injury are well known, but a study of the effects of ApoD expression in the normal aging process is still missing. Using an ApoD-knockout mouse we analyze the effects of ApoD on factors contributing to the functional maintenance of the aged brain. We focused our cellular and molecular analyses in the cortex and hippocampus at an age representing the onset of senescence where mortality risks are below 25%, avoiding bias towards long-lived animals. Lack of ApoD causes a prematurely aged brain without altering lifespan. Age-dependent hyperkinesia and memory deficits are accompanied by differential molecular effects in the cortex and hippocampus. Transcriptome analyses reveal distinct effects of ApoD loss on the molecular age-dependent patterns of the cortex and hippocampus, with different cell-type contributions to age-regulated gene expression. Markers of glial reactivity, proteostasis, and oxidative and inflammatory damage reveal early signs of aging and enhanced brain deterioration in the ApoD-knockout brain. The lack of ApoD results in an age-enhanced significant reduction in neuronal calcium-dependent functionality markers and signs of early reduction of neuronal numbers in the cortex, thus impinging upon parameters clearly differentiating neurodegenerative conditions from healthy brain aging. Our data support the hypothesis that the physiological increased brain expression of ApoD represents a homeostatic anti-aging mechanism. Copyright © 2015 Elsevier Inc. All rights reserved.

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

    OpenAIRE

    Bjorvatn, B; Grønli, J; Hamre, F; Sørensen, E; Fiske, E; Bjorkum, Alvhild Alette; Portas, CM; Ursin, R.

    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...

  18. In vivo three-photon activity imaging of GCaMP6-labeled neurons in deep cortex and the hippocampus of the mouse brain

    Science.gov (United States)

    Wang, Tianyu; Ouzounov, Dimitre G.; Wang, Mengran; Feng, Danielle; Cruz-Hernandez, Jean C.; Reimer, Jacob; Tolias, Andreas; Nishimura, Nozomi; Xu, Chris

    2017-02-01

    We demonstrate that three-photon microscopy (3PM) with 1300-nm excitation enables functional imaging of GCaMP6s labeled neurons beyond the depth limit of two-photon microscopy (2PM) with 920-nm excitation. We quantitatively compared 2PM and 3PM imaging of calcium indicator GCaMP6s by measuring correlation between activity traces, absolute signal level, excitation attenuation with depth, and signal-to-background ratio (SBR). Compared to 2PM imaging of GCaMP6s-labeled neurons, 3PM imaging has increasingly larger advantages in signal strength and SBR as the imaging depth increases in densely labeled mouse brain, given the same pulse energy, pulse width, and repetition rate at the sample surface. For example, 3PM has comparable signal strength as 2PM and up to two orders of magnitude higher SBR as 2PM in mouse cortex around 700-800um. We also demonstrate 3PM activity recording of 150 neurons in the hippocampal stratum pyramidale (SP) at 1mm depth, which is inaccessible to non-invasive 2PM imaging. Our work establishes 3PM as a powerful tool for calcium imaging at the depth beyond 2PM limits.

  19. Phencyclidine administration during neurodevelopment alters network activity in prefrontal cortex and hippocampus in adult rats

    DEFF Research Database (Denmark)

    Kjaerby, Celia; Hovelsø, Nanna; Dalby, Nils Ole

    2017-01-01

    of this study was to determine how administration of the NMDAR antagonist phencyclidine (PCP) during neurodevelopment affects functional network activity within the hippocampus and medial prefrontal cortex (mPFC). We recorded field potentials in vivo after electrical brain stem stimulation and observed...... to suppressed evoked theta oscillations in ventral hippocampus in adult rats, while evoked gamma oscillations are enhanced and hypersensitive to an acute challenge with a NMDA receptor antagonist in prefrontal cortex. These observations reveal the significance of neurodevelopmental disturbances......Symptoms of schizophrenia have been linked to insults during neurodevelopment such as NMDA receptor (NMDAR) antagonist exposure. In animal models, this leads to schizophrenia-like behavioral symptoms as well as molecular and functional changes within hippocampal and prefrontal regions. The aim...

  20. The Interplay of Hippocampus and Ventromedial Prefrontal Cortex in Memory-Based Decision Making

    Directory of Open Access Journals (Sweden)

    Regina A. Weilbächer

    2016-12-01

    Full Text Available Episodic memory and value-based decision making are two central and intensively studied research domains in cognitive neuroscience, but we are just beginning to understand how they interact to enable memory-based decisions. The two brain regions that have been associated with episodic memory and value-based decision making are the hippocampus and the ventromedial prefrontal cortex, respectively. In this review article, we first give an overview of these brain–behavior associations and then focus on the mechanisms of potential interactions between the hippocampus and ventromedial prefrontal cortex that have been proposed and tested in recent neuroimaging studies. Based on those possible interactions, we discuss several directions for future research on the neural and cognitive foundations of memory-based decision making.

  1. A Computational Model for Spatial Navigation Based on Reference Frames in the Hippocampus, Retrosplenial Cortex, and Posterior Parietal Cortex.

    Science.gov (United States)

    Oess, Timo; Krichmar, Jeffrey L; Röhrbein, Florian

    2017-01-01

    Behavioral studies for humans, monkeys, and rats have shown that, while traversing an environment, these mammals tend to use different frames of reference and frequently switch between them. These frames represent allocentric, egocentric, or route-centric views of the environment. However, combinations of either of them are often deployed. Neurophysiological studies on rats have indicated that the hippocampus, the retrosplenial cortex, and the posterior parietal cortex contribute to the formation of these frames and mediate the transformation between those. In this paper, we construct a computational model of the posterior parietal cortex and the retrosplenial cortex for spatial navigation. We demonstrate how the transformation of reference frames could be realized in the brain and suggest how different brain areas might use these reference frames to form navigational strategies and predict under what conditions an animal might use a specific type of reference frame. Our simulated navigation experiments demonstrate that the model's results closely resemble behavioral findings in humans and rats. These results suggest that navigation strategies may depend on the animal's reliance in a particular reference frame and shows how low confidence in a reference frame can lead to fluid adaptation and deployment of alternative navigation strategies. Because of its flexibility, our biologically inspired navigation system may be applied to autonomous robots.

  2. Comparative density of CCK- and PV-GABA cells within the cortex and hippocampus

    Directory of Open Access Journals (Sweden)

    Paul David Whissell

    2015-09-01

    Full Text Available Cholecystokinin (CCK- and parvalbumin (PV-expressing neurons constitute the two major populations of perisomatic GABAergic neurons in the cortex and the hippocampus. As CCK- and PV-GABA neurons differ in an array of morphological, biochemical and electrophysiological features, it has been proposed that they form distinct inhibitory ensembles which differentially contribute to network oscillations and behaviour. However, the relationship and balance between CCK- and PV-GABA neurons in the inhibitory networks of the brain is currently unclear as the distribution of these cells has never been compared on a large scale. Here, we systemically investigated the distribution of CCK- and PV-GABA cells across a wide number of discrete forebrain regions using an intersectional genetic approach. Our analysis revealed several novel trends in the distribution of these cells. While PV-GABA cells were more abundant overall, CCK-GABA cells outnumbered PV-GABA cells in several subregions of the hippocampus, medial prefrontal cortex and ventrolateral temporal cortex. Interestingly, CCK-GABA cells were relatively more abundant in secondary/association areas of the cortex (V2, S2, M2, and AudD/AudV than they were in corresponding primary areas (V1, S1, M1 and Aud1. The reverse trend was observed for PV-GABA cells. Our findings suggest that the balance between CCK- and PV-GABA cells in a given cortical region is related to the type of processing that area performs; inhibitory networks in the secondary cortex tend to favour the inclusion of CCK-GABA cells more than networks in the primary cortex. The intersectional genetic labelling approach employed in the current study expands upon the ability to study molecularly defined subsets of GABAergic neurons. This technique can be applied to the investigation of neuropathologies which involve disruptions to the GABAergic system, including schizophrenia, stress, maternal immune activation and autism.

  3. Humor Appreciation Involves Parametric and Synchronized Activity in the Medial Prefrontal Cortex and Hippocampus.

    Science.gov (United States)

    Iidaka, Tetsuya

    2016-10-18

    Humor perception is a ubiquitous phenomenon in human societies. In theories of humor perception, three factors, non-seriousness, social context, and incongruity, have been implicated in humor. In another theory, however, elaboration and reinterpretation of contexts are considered to play a role in eliciting humor. Although the neural correlates of humor appreciation have been investigated using neuroimaging methods, only a few studies have conducted such experiments under natural conditions. In the present study, two functional magnetic resonance imaging experiments, using a comedy movie as a stimulus, were conducted to investigate the neural correlates of humor under natural conditions. The subjects' brain activity was measured while watching and enjoying a movie. In experiment 1, a parametric analysis showed that the medial prefrontal cortex (MPFC) and hippocampus/amygdala had a positive relationship with the subjective rating of funniness. In experiment 2, intersubject correlation was analyzed to investigate synchronized activity across all participants. Signal synchronization that paralleled increased funniness ratings was observed in the MPFC and hippocampus. Thus, it appears that both parametric and synchronized activity in the MPFC and hippocampus are important during humor appreciation. The present study has revealed the brain regions that are predominantly involved in humor sensation under natural condition. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Edible Camphor-induced Histopathological Changes in Hippocampus and Cerebral Cortex Following Oral Administration into Rats

    Directory of Open Access Journals (Sweden)

    Oluwatobi T Somade

    2017-03-01

    Full Text Available Introduction: Raw edible camphor (EC, and as component of herbal infusions are widely used to treat pile, back pain, erectile dysfunction, and as an aphrodisiac especially in preparation for sexual intercourse by men. It has been traced in umbilical cord, blood, fetal, adipose, and other tissues including brain, where it bioaccumulates. Methods: The study, therefore, investigated the possible histopathological changes in brain, heart, and spleen that may result following EC administration in rats. Thirty animals were used for the study and were divided into six groups of five rats each. Group I animals served as normal control, Group II animals served as vehicle control and were orally administered 6 mL/kg corn oil daily for 7 days, while Groups III-VI animals were orally administered 1, 2, 4, and 6 g/kg EC for 7 days daily. Results and Conclusions: Following the administrations of various doses of EC, the histopathological changes seen in the cerebral cortex of the brain include mild submeningeal spongiosis, mild diffuse spongiosis of the parenchyma, a very mild diffuse gliosis, and presences of gitter cells, while in hippocampus, there were mild diffuse gliosis and disruption of the progression of the hippocampal horns, as well as foci of spongiosis around the hippocampal horns, and neuronal cells have open faced nuclei. No effect was seen in heart and spleen except 4 g/kg of EC that revealed moderate diffuse congestion in spleen only. In conclusion, EC may not have any toxic effects on the cardiac and splenic cells, but had toxic effects on the brain hippocampus and cerebral cortex, and may lead to brain cell damage. [J Interdiscipl Histopathol 2017; 5(1.000: 7-11

  5. Repeated anodal transcranial direct current stimulation induces neural plasticity-associated gene expression in the rat cortex and hippocampus.

    Science.gov (United States)

    Kim, Min Sun; Koo, Ho; Han, Sang Who; Paulus, Walter; Nitsche, Michael A; Kim, Yun-Hee; Yoon, Jin A; Shin, Yong-Il

    2017-01-01

    Anodal transcranial direct current stimulation (A-tDCS) induces a long-lasting increase in cortical excitability that can increase gene transcription in the brain. The purpose of this study was to evaluate the expression of genes related to activity-dependent neuronal plasticity in the sensorimotor cortex and hippocampus of young Sprague-Dawley rats following A-tDCS. We applied A-tDCS over the right sensorimotor cortex epicranially with a circular electrode (3 mm diameter) at 250 μA for 20 min per day for 7 consecutive days. Levels of mRNA for brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), synapsin I, Ca2+/calmodulin-dependent protein kinase II (CaMKII), activity-regulated cytoskeleton-associated protein (Arc), and c-Fos were analyzed using SYBR Green quantitative real-time polymerase chain reaction (PCR). We found that 7 days of unilateral A-tDCS resulted in significant increases in transcription of all plasticity-related genes tested in the ipsilateral cortex. Daily A-tDCS also resulted in a significant increase in c-Fos mRNA in the ipsilateral hippocampus. These results indicate that altered expression of plasticity-associated genes in the cortex and hippocampus is a molecular substrate of A-tDCS-induced neural plasticity.

  6. Selective immunolesion of cholinergic neurons leads to long-term changes in 5-HT2A receptor levels in hippocampus and frontal cortex

    DEFF Research Database (Denmark)

    Severino, Maurizio; Pedersen, Anja F; Trajkovska, Viktorija

    2007-01-01

    ) protein levels were determined by western techniques in frontal cortex and hippocampus. A significant 70% downregulation in frontal cortex and a 100% upregulation in hippocampus of 5-HT(2A) receptor levels were observed 20 weeks after the cholinergic lesion when using the highest dose of 192 Ig......G-Saporin. Our results show that cholinergic deafferentation leads to decreased frontal cortex and increased hippocampal 5-HT(2A) receptor levels. This is probably a consequence of the interaction between the serotonergic and the cholinergic system that may vary depending on the brain region....

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Early developmental actions of endocrine disruptors on the hypothalamus, hippocampus, and cerebral cortex.

    OpenAIRE

    Parent, Anne-Simone; NAVEAU, Elise; Gerard, Arlette; Bourguignon, Jean-Pierre; Gary L Westbrook

    2011-01-01

    Sex steroids and thyroid hormones play a key role in the development of the central nervous system. The critical role of these hormonal systems may explain the sensitivity of the hypothalamus, the cerebral cortex, and the hippocampus to endocrine-disrupting chemicals (EDC). This review examines the evidence for endocrine disruption of glial-neuronal functions in the hypothalamus, hippocampus, and cerebral cortex. Focus was placed on two well-studied EDC, the insecticide dichlorodiphenyltrichl...

  9. Effects of acute phencyclidine administration on arginine metabolism in the hippocampus and prefrontal cortex in rats.

    Science.gov (United States)

    Knox, Logan T; Jing, Yu; Collie, Nicola D; Zhang, Hu; Liu, Ping

    2014-06-01

    Phencyclidine (PCP), a non-competitive N-methyl-d-aspartate glutamate receptor antagonist, induces schizophrenic symptoms in healthy individuals, and altered arginine metabolism has been implicated in schizophrenia. The present study investigated the effects of a single subcutaneous injection of PCP (2, 5 or 10 mg/kg) on arginine metabolism in the sub-regions of the hippocampus and prefrontal cortex in male young adult Sprague-Dawley rats. Animals' general behaviour was assessed in the open field apparatus 30 min after the treatment, and the brain tissues were collected at the time point of 60 min post-treatment. Behaviourally, PCP resulted in reduced exploratory activity in a dose-dependent manner, and severe stereotype behaviour and ataxia at the highest dose. Neurochemically, PCP significantly altered the nitric oxide synthase and arginase activities, the l-arginine, agmatine, spermine, glutamate and GABA levels, and the glutamine/glutamate and glutamate/GABA ratios in a dose-dependent and/or region-specific manner. Cluster analyses showed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which changed as a function of PCP mainly in the hippocampus. Multiple regression analysis revealed significant neurochemical-behavioural correlations. These results demonstrate, for the first time, that a single acute administration of PCP affects animals' behaviour and arginine metabolism in the brain. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  11. Dissociable contributions of the prefrontal cortex to hippocampus- and caudate nucleus-dependent virtual navigation strategies.

    Science.gov (United States)

    Dahmani, Louisa; Bohbot, Véronique D

    2015-01-01

    The hippocampus and the caudate nucleus are critical to spatial- and stimulus-response-based navigation strategies, respectively. The hippocampus and caudate nucleus are also known to be anatomically connected to various areas of the prefrontal cortex. However, little is known about the involvement of the prefrontal cortex in these processes. In the current study, we sought to identify the prefrontal areas involved in spatial and response learning. We used functional magnetic resonance imaging (fMRI) and voxel-based morphometry to compare the neural activity and grey matter density of spatial and response strategy users. Twenty-three healthy young adults were scanned in a 1.5 T MRI scanner while they engaged in the Concurrent Spatial Discrimination Learning Task, a virtual navigation task in which either a spatial or response strategy can be used. In addition to increased BOLD activity in the hippocampus, spatial strategy users showed increased BOLD activity and grey matter density in the ventral area of the medial prefrontal cortex, especially in the orbitofrontal cortex. On the other hand, response strategy users exhibited increased BOLD activity and grey matter density in the dorsal area of the medial prefrontal cortex. Given the prefrontal cortex's role in reward-guided decision-making, we discuss the possibility that the ventromedial prefrontal cortex, including the orbitofrontal cortex, supports spatial learning by encoding stimulus-reward associations, while the dorsomedial prefrontal cortex supports response learning by encoding action-reward associations. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  12. The Anterior Prefrontal Cortex and the Hippocampus Are Negatively Correlated during False Memories.

    Science.gov (United States)

    Jeye, Brittany M; Karanian, Jessica M; Slotnick, Scott D

    2017-01-23

    False memories commonly activate the anterior/dorsolateral prefrontal cortex (A/DLPFC) and the hippocampus. These regions are assumed to work in concert during false memories, which would predict a positive correlation between the magnitudes of activity in these regions across participants. However, the A/DLPFC may also inhibit the hippocampus, which would predict a negative correlation between the magnitudes of activity in these regions. In the present functional magnetic resonance imaging (fMRI) study, during encoding, participants viewed abstract shapes in the left or right visual field. During retrieval, participants classified each old shape as previously in the "left" or "right" visual field followed by an "unsure"-"sure"-"very sure" confidence rating. The contrast of left-hits and left-misses produced two activations in the hippocampus and three activations in the left A/DLPFC. For each participant, activity associated with false memories (right-"left"-"very sure" responses) from the two hippocampal regions was plotted as a function of activity in each A/DLPFC region. Across participants, for one region in the left anterior prefrontal cortex, there was a negative correlation between the magnitudes of activity in this region and the hippocampus. This suggests that the anterior prefrontal cortex might inhibit the hippocampus during false memories and that participants engage either the anterior prefrontal cortex or the hippocampus during false memories.

  13. The hippocampus: hub of brain network communication for memory.

    NARCIS (Netherlands)

    Battaglia, F.P.; Benchenane, K.; Sirota, A.; Pennartz, C.M.A.; Wiener, S.I.

    2011-01-01

    A complex brain network, centered on the hippocampus, supports episodic memories throughout their lifetimes. Classically, upon memory encoding during active behavior, hippocampal activity is dominated by theta oscillations (6-10Hz). During inactivity, hippocampal neurons burst synchronously,

  14. Individual Differences in Human Path Integration Abilities Correlate with Gray Matter Volume in Retrosplenial Cortex, Hippocampus, and Medial Prefrontal Cortex.

    Science.gov (United States)

    Chrastil, Elizabeth R; Sherrill, Katherine R; Aselcioglu, Irem; Hasselmo, Michael E; Stern, Chantal E

    2017-01-01

    Humans differ in their individual navigational abilities. These individual differences may exist in part because successful navigation relies on several disparate abilities, which rely on different brain structures. One such navigational capability is path integration, the updating of position and orientation, in which navigators track distances, directions, and locations in space during movement. Although structural differences related to landmark-based navigation have been examined, gray matter volume related to path integration ability has not yet been tested. Here, we examined individual differences in two path integration paradigms: (1) a location tracking task and (2) a task tracking translational and rotational self-motion. Using voxel-based morphometry, we related differences in performance in these path integration tasks to variation in brain morphology in 26 healthy young adults. Performance in the location tracking task positively correlated with individual differences in gray matter volume in three areas critical for path integration: the hippocampus, the retrosplenial cortex, and the medial prefrontal cortex. These regions are consistent with the path integration system known from computational and animal models and provide novel evidence that morphological variability in retrosplenial and medial prefrontal cortices underlies individual differences in human path integration ability. The results for tracking rotational self-motion-but not translation or location-demonstrated that cerebellum gray matter volume correlated with individual performance. Our findings also suggest that these three aspects of path integration are largely independent. Together, the results of this study provide a link between individual abilities and the functional correlates, computational models, and animal models of path integration.

  15. Early developmental actions of endocrine disruptors on the hypothalamus, hippocampus, and cerebral cortex.

    Science.gov (United States)

    Parent, Anne-Simone; Naveau, Elise; Gerard, Arlette; Bourguignon, Jean-Pierre; Westbrook, Gary L

    2011-01-01

    Sex steroids and thyroid hormones play a key role in the development of the central nervous system. The critical role of these hormonal systems may explain the sensitivity of the hypothalamus, the cerebral cortex, and the hippocampus to endocrine-disrupting chemicals (EDC). This review examines the evidence for endocrine disruption of glial-neuronal functions in the hypothalamus, hippocampus, and cerebral cortex. Focus was placed on two well-studied EDC, the insecticide dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCB). DDT is involved in neuroendocrine disruption of the reproductive axis, whereas polychlorinated biphenyls (PCB) interact with both the thyroid hormone- and sex steroid-dependent systems and disturb the neuroendocrine control of reproduction and development of hippocampus and cortex. These results highlight the impact of EDC on the developing nervous system and the need for more research in this area.

  16. Using state-trace analysis to dissociate the functions of the human hippocampus and perirhinal cortex in recognition memory.

    Science.gov (United States)

    Staresina, Bernhard P; Fell, Juergen; Dunn, John C; Axmacher, Nikolai; Henson, Richard N

    2013-02-19

    A recurring issue in neuroscience concerns evidence as to whether two or more brain regions implement qualitatively different functions. Here we introduce the application of state-trace analysis to measures of neural activity, illustrating how this analysis can furnish compelling evidence for qualitatively different functions, even when the precise "neurometric" mapping between function and brain measure is unknown. In doing so, we address a long-standing debate about the brain systems supporting human memory: whether the hippocampus and the perirhinal cortex, two key components of the medial temporal lobe memory system, provide qualitatively different contributions to recognition memory. An alternative account has been that both regions support a single shared function, such as memory strength, with the apparent dissociations obtained by previous neuroimaging studies merely reflecting different, nonlinear neurometric mappings across regions. To adjudicate between these scenarios, we analyze intracranial electroencephalographic data obtained directly from human hippocampus and perirhinal cortex during a recognition paradigm and apply state-trace analysis to responses evoked by the retrieval cue as a function of different types of memory judgment. Assuming only that the neurometric mapping in each region is monotonic, any unidimensional theory (such as the memory-strength account) will produce a monotonic state trace. Critically, results showed a nonmonotonic state trace; that is, activity levels in the two regions did not show the same relative ordering across memory conditions. This nonmonotonic state trace demonstrates that there are at least two different functions implemented across the hippocampus and perirhinal cortex, allowing formal rejection of a single-process account of medial temporal lobe contributions to recognition memory.

  17. The Role of Nicotinic Acetylcholine Receptors in the Medial Prefrontal Cortex and Hippocampus in Trace Fear Conditioning

    Science.gov (United States)

    Raybuck, J. D.; Gould, T. J.

    2010-01-01

    Acute nicotine enhances multiple types of learning including trace fear conditioning but the underlying neural substrates of these effects are not well understood. Trace fear conditioning critically involves the medial prefrontal cortex and hippocampus, which both express nicotinic acetylcholine receptors (nAChRs). Therefore, nicotine could act in either or both areas to enhance trace fear conditioning. To identify the underlying neural areas and nAChR subtypes, we examined the effects of infusion of nicotine, or nicotinic antagonists dihydro-beta-erythroidine (DHβE: high-affinity nAChRs) or methyllycaconitine (MLA: low-affinity nAChRs) into the dorsal hippocampus, ventral hippocampus, and medial prefrontal cortex (mPFC) on trace and contextual fear conditioning. We found that the effects of nicotine on trace and contextual fear conditioning vary by brain region and nAChR subtype. The dorsal hippocampus was involved in the effects of nicotine on both trace and contextual fear conditioning but each task was sensitive to different doses of nicotine. Additionally, dorsal hippocampal infusion of the antagonist DHβE produced deficits in trace but not contextual fear conditioning. Nicotine infusion into the ventral hippocampus produced deficits in both trace and contextual fear conditioning. In the mPFC, nicotine enhanced trace but not contextual fear conditioning. Interestingly, infusion of the antagonists MLA or DHβE in the mPFC also enhanced trace fear conditioning. These findings suggest that nicotine acts on different substrates to enhance trace versus contextual fear conditioning, and that nicotine-induced desensitization of nAChRs in the mPFC may contribute to the effects of nicotine on trace fear conditioning. PMID:20727979

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

    Science.gov (United States)

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

    2014-01-01

    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 tracer cholera toxin B conjugated to two fluorophores to study thalamic projections to the dorsal and ventral hippocampus and to the prelimbic and infralimbic subregions of mPFC. We also examined the feedback connections from the hippocampus to reuniens. The goal was to evaluate the anatomical basis for direct coordination between reuniens, mPFC, and hippocampus by looking for double-labeled cells in reuniens and hippocampus. In confirmation of previous reports, the nucleus reuniens was the origin of most thalamic afferents to the dorsal hippocampus, whereas both reuniens and the lateral dorsal nucleus projected to ventral hippocampus. Feedback from hippocampus to reuniens originated primarily in the dorsal and ventral subiculum. Thalamic cells with collaterals to mPFC and hippocampus were found in reuniens, across its anteroposterior axis, and represented, on average, about 8 % of the labeled cells in reuniens. Hippocampal cells with collaterals to mPFC and reuniens were less common (~1 % of the labeled subicular cells), and located in the molecular layer of the subiculum. The results indicate that a subset of reuniens cells can directly coordinate activity in mPFC and hippocampus. Cells with collaterals in the hippocampus–reuniens–mPFC network may be important for the systems consolidation of memory traces and for theta synchronization during exploratory behavior. PMID:23571778

  19. 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…

  20. 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…

  1. Contributions of the hippocampus and entorhinal cortex to rapid visuomotor learning in rhesus monkeys.

    Science.gov (United States)

    Yang, Tianming; Bavley, Rachel L; Fomalont, Kevin; Blomstrom, Kevin J; Mitz, Andrew R; Turchi, Janita; Rudebeck, Peter H; Murray, Elisabeth A

    2014-09-01

    The hippocampus and adjacent structures in the medial temporal lobe are essential for establishing new associative memories. Despite this knowledge, it is not known whether the hippocampus proper is essential for establishing such memories, nor is it known whether adjacent regions like the entorhinal cortex might contribute. To test the contributions of these regions to the formation of new associative memories, we trained rhesus monkeys to rapidly acquire arbitrary visuomotor associations, i.e., associations between visual stimuli and spatially directed actions. We then assessed the effects of reversible inactivations of either the hippocampus (Experiment 1) or entorhinal cortex (Experiment 2) on the within-session rate of learning. For comparison, we also evaluated the effects of the inactivations on performance of problems of the same type that had been well learned prior to any inactivations. We found that inactivation of the entorhinal cortex but not hippocampus produced impairments in acquiring novel arbitrary associations. The impairment did not extend to the familiar, previously established associations. These data indicate that the entorhinal cortex is causally involved in establishing new associations, as opposed to retrieving previously learned associations. Published 2014. This article is a U.S. Government work and is in the public domain in the USA. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  2. Why is there a special issue on perirhinal cortex in a journal called Hippocampus?: The perirhinal cortex in historical perspective

    Science.gov (United States)

    Murray, Elisabeth A.; Wise, Steven P.

    2014-01-01

    Despite its small size, the perirhinal cortex (PRh) plays a central role in understanding the cerebral cortex, vision and memory; it figures in discussions of cognitive capacities as diverse as object perception, semantic knowledge, feelings of familiarity and conscious recollection. Two conceptual constructs have encompassed PRh. The current orthodoxy incorporates PRh within the medial temporal lobe (MTL) as a memory area; an alternative considers PRh to be a sensory area with a role in both perception and memory. A historical perspective provides insight into both of these ideas. PRh came to be included in the MTL because of two accidents of history. In evolutionary history, the hippocampus migrated from its ancestral situation, as medial cortex, into the temporal lobe; in the history of neuropsychology, a “memory system” that originally consisted of the amygdala and hippocampus came to include PRh. These two histories explain why a part of the sensory neocortex, PRh, entered into the conceptual construct called the MTL. They also explain why some experimental results seem to exclude a perceptual function for this sensory area, while others embrace perception. The exclusion of perceptual functions results from a history of categorizing tasks as perceptual or mnemonic, often on inadequate grounds. By instead exploring the role of PRh in encoding, representing and retrieving stimulus information, it can be understood as a part of the sensory neocortex, one that has much the same relationship with the hippocampus as do other parts of the neocortex that evolved at about the same time. PMID:22987673

  3. Differential sensitivity of prefrontal cortex and hippocampus to alcohol-induced toxicity.

    Directory of Open Access Journals (Sweden)

    Anna-Kate Fowler

    Full Text Available The prefrontal cortex (PFC is a brain region responsible for executive functions including working memory, impulse control and decision making. The loss of these functions may ultimately lead to addiction. Using histological analysis combined with stereological technique, we demonstrated that the PFC is more vulnerable to chronic alcohol-induced oxidative stress and neuronal cell death than the hippocampus. This increased vulnerability is evidenced by elevated oxidative stress-induced DNA damage and enhanced expression of apoptotic markers in PFC neurons. We also found that one-carbon metabolism (OCM impairment plays a significant role in alcohol toxicity to the PFC seen from the difference in the effects of acute and chronic alcohol exposure on DNA repair and from exaggeration of the damaging effects upon additional OCM impairment in mice deficient in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR. Given that damage to the PFC leads to loss of executive function and addiction, our study may shed light on the mechanism of alcohol addiction.

  4. Myelin damage of hippocampus and cerebral cortex in rat pentylenetetrazol model.

    Science.gov (United States)

    You, Yu; Bai, Hui; Wang, Chao; Chen, Liang-Wei; Liu, Bei; Zhang, Hua; Gao, Guo-Dong

    2011-03-24

    Epilepsy is a chronic neurological disorder characterized by spontaneous recurrent seizures, which also occur in demyelinating diseases of the central nervous system (CNS) with a higher prevalence. Meanwhile, demyelination occurrings have been occasionally observed in CNS of epilepsy patients, indicating an association between demyelination and epileptic seizures by an unknown mechanism. However, no confirmative experimental evidence has yet been given. Thus, by using a rat pentylenetetrazol model, electroencephalogram (EEG), Western blotting, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, the present study provided direct evidence that myelin sheath damage in rat hippocampus and cerebral cortex started in the early stage of epileptic seizures induction and lasted with no further increase in severity in the development of epileptic seizures. It was illustrated that myelin sheath damage was not the result of oligodendrocyte destruction, but the autoantibodies against myelin basic protein (MBP) produced in peripheral circulation accompanied by increased permeability of blood-brain barrier (BBB) formed in the development of epileptic seizures. This study firstly provided experimental evidence for myelin sheath damage in PTZ-induced rat's epileptic seizures and further demonstrated that its possible cause was autoimmunoreaction. Copyright © 2011 Elsevier B.V. All rights reserved.

  5. Cortex and hippocampus DNA epigenetic response to a long-term arsenic exposure via drinking water.

    Science.gov (United States)

    Du, Xiaoyan; Tian, Meiping; Wang, Xiaoxue; Zhang, Jie; Huang, Qingyu; Liu, Liangpo; Shen, Heqing

    2018-03-01

    The neurotoxicity of arsenic is a serious health problem, especially for children. DNA epigenetic change may be an important pathogenic mechanism, but the molecular pathway remains obscure. In this study, the weaned male Sprague-Dawly (SD) rats were treated with arsenic trioxide via drinking water for 6 months, simulating real developmental exposure situation of children. Arsenic exposure impaired the cognitive abilities, and altered the expression of neuronal activity-regulated genes. Total arsenic concentrations of cortex and hippocampus tissues were significantly increased in a dose-dependent manner. The reduction in 5-methylcytosine (5 mC) and 5-hydroxymethylcytosine (5hmC) levels as well as the down-regulation of DNA methyltransferases (DNMTs) and ten-eleven translocations (TETs) expression suggested that DNA methylation/demethylation processes were significantly suppressed in brain tissues. S-adenosylmethionine (SAM) level wasn't changed, but the expression of the important indicators of oxidative/anti-oxidative balance and tricarboxylic acid (TCA) cycle was significantly deregulated. Overall, arsenic can disrupt oxidative/anti-oxidative balance, further inhibit TETs expression through TCA cycle and alpha-ketoglutarate (α-KG) pathway, and consequently cause DNA methylation/demethylation disruption. The present study implies oxidative stress but not SAM depletion may lead to DNA epigenetic alteration and arsenic neurotoxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. The vasopressin receptor of the blood-brain barrier in the rat hippocampus is linked to calcium signalling

    DEFF Research Database (Denmark)

    Hess, J.; Jensen, Claus V.; Diemer, Nils Henrik

    1991-01-01

    Neuropathology, vasopressin receptor, VI subtype, blood-brain barrier, cerebral endothelium, hippocampus, Fura-2......Neuropathology, vasopressin receptor, VI subtype, blood-brain barrier, cerebral endothelium, hippocampus, Fura-2...

  7. Multivariate pattern analysis of the human medial temporal lobe revealed representationally categorical cortex and representationally agnostic hippocampus.

    Science.gov (United States)

    Huffman, Derek J; Stark, Craig E L

    2014-11-01

    Contemporary theories of the medial temporal lobe (MTL) suggest that there are functional differences between the MTL cortex and the hippocampus. High-resolution functional magnetic resonance imaging and multivariate pattern analysis were utilized to study whether MTL subregions could classify categories of images, with the hypothesis that the hippocampus would be less representationally categorical than the MTL cortex. Results revealed significant classification accuracy for faces versus objects and faces versus scenes in MTL cortical regions-parahippocampal cortex (PHC) and perirhinal cortex (PRC)-with little evidence for category discrimination in the hippocampus. MTL cortical regions showed significantly greater classification accuracy than the hippocampus. The hippocampus showed significant classification accuracy for images compared to a nonmnemonic baseline task, suggesting that it responded to the images. Classification accuracy in a region of interest encompassing retrosplenial cortex (RSC) and the posterior cingulate cortex (PCC) posterior to RSC, showed a similar pattern of results to PHC, supporting the hypothesis that these regions are functionally related. The results suggest that PHC, PRC, and RSC/PCC are representationally categorical and the hippocampus is more representationally agnostic, which is concordant with the hypothesis of the role of the hippocampus in pattern separation. Copyright © 2014 Wiley Periodicals, Inc.

  8. Effects of Short-Term Exposure to Lithium on Antiapoptotic Bcl-xL Protein Expression in Cortex and Hippocampus of Rats after Acute Stress.

    Science.gov (United States)

    Dygalo, N N; Bannova, A V; Sukhareva, E V; Shishkina, G T; Ayriyants, K A; Kalinina, T S

    2017-03-01

    The antiapoptotic protein Bcl-xL is involved in development of neurobiological resilience to stress; hence, the possibility of use of psychotropic drugs to increase its expression in brain in response to stress is of considerable interest. Lithium is a neurotropic drug widely used in psychiatry. In work, we studied effects of lithium administration (for 2 or 7 days) on the expression of Bcl-xL mRNA and protein in the hippocampi and cortices of rats subjected to stress that induced depression-like behavior in the animals. In contrast to the brain-derived neurotrophic factor (BDNF), whose expression decreased in the hippocampus in response to acute stress, stress increased the level of Bcl-xL mRNA in the hippocampus, but decreased it in the frontal cortex. Treatment of stressed animals with lithium for 2 or 7 days increased Bcl-xL protein levels 1.5-fold in the hippocampus, but it decreased them in the cortex. Therefore, Bcl-xL expression in the brain can be modulated by both stress and psychotropic drugs, and the effects of these factors are brain region-specific: both stress exposure and lithium administration activated Bcl-xL expression in the hippocampus and suppressed it in the frontal cortex. The activation of Bcl-xL expression in the hippocampus by lithium, demonstrated for the first time in this study, suggests an important role of this protein in the therapeutic effects of lithium in the treatment of stress-induced psychoemotional disorders.

  9. Harmine and Imipramine Promote Antioxidant Activities in Prefrontal Cortex and Hippocampus

    Directory of Open Access Journals (Sweden)

    Gislaine Z. Réus

    2010-01-01

    Full Text Available A growing body of evidence has suggested that reactive oxygen species (ROS may play an important role in the physiopathology of depression. Evidence has pointed to the β-carboline harmine as a potential therapeutic target for the treatment of depression. The present study we evaluated the effects of acute and chronic administration of harmine (5, 10 and 15 mg/kg and imipramine (10, 20 and 30 mg/kg or saline in lipid and protein oxidation levels and superoxide dismutase (SOD and catalase (CAT activities in rat prefrontal cortex and hippocampus. Acute and chronic treatments with imipramine and harmine reduced lipid and protein oxidation, compared to control group in prefrontal cortex and hippocampus. The SOD and CAT activities increased with acute and chronic treatments with imipramine and harmine, compared to control group in prefrontal cortex and hippocampus. In conclusion, our results indicate positive effects of imipramine antidepressant and β-carboline harmine of oxidative stress parameters, increasing SOD and CAT activities and decreasing lipid and protein oxidation.

  10. 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...

  11. Renal ischemia reperfusion causes brain hippocampus oxidative ...

    African Journals Online (AJOL)

    Background: The acute kidney injury (AKI) may do damage to remote organs. Objective of the study is to investigate effect of seaweed extract (SE) on brain oxidative damage in kidney ischemia/reperfusion rats. Material and Methods: Animals were randomly divided into five groups. SE pre-fed to rats. Results: Kidney I/R ...

  12. Fornix deep brain stimulation enhances acetylcholine levels in the hippocampus.

    Science.gov (United States)

    Hescham, Sarah; Jahanshahi, Ali; Schweimer, Judith V; Mitchell, Stephen N; Carter, Guy; Blokland, Arjan; Sharp, Trevor; Temel, Yasin

    2016-11-01

    Deep brain stimulation (DBS) of the fornix has gained interest as a potential therapy for advanced treatment-resistant dementia, yet the mechanism of action remains widely unknown. Previously, we have reported beneficial memory effects of fornix DBS in a scopolamine-induced rat model of dementia, which is dependent on various brain structures including hippocampus. To elucidate mechanisms of action of fornix DBS with regard to memory restoration, we performed c-Fos immunohistochemistry in the hippocampus. We found that fornix DBS induced a selective activation of cells in the CA1 and CA3 subfields of the dorsal hippocampus. In addition, hippocampal neurotransmitter levels were measured using microdialysis before, during and after 60 min of fornix DBS in a next experiment. We observed a substantial increase in the levels of extracellular hippocampal acetylcholine, which peaked 20 min after stimulus onset. Interestingly, hippocampal glutamate levels did not change compared to baseline. Therefore, our findings provide first experimental evidence that fornix DBS activates the hippocampus and induces the release of acetylcholine in this region.

  13. Pharmacological differences between rat frontal cortex and hippocampus in the nicotinic modulation of noradrenaline release implicate distinct receptor subtypes.

    Science.gov (United States)

    Kennett, Alexandra; Heal, David J; Wonnacott, Susan

    2012-11-01

    Noradrenergic mechanisms in frontal cortex and hippocampus are relevant to attentional and stress-related aspects of addiction, respectively. Nicotinic receptors (nAChRs) modulate the release of noradrenaline (NA) in these tissues. This study determined if similar subtypes of nAChR regulate NA release in rat frontal cortex and hippocampus. The release of [(3)H]-NA from rat tissue prisms was characterized in a 96-well plate assay. In vivo microdialysis was used to monitor NA overflow from rat frontal cortex and hippocampus in conscious freely moving rats. [(3)H]-NA release from frontal cortex prisms was more sensitive to nicotinic agonists than release from hippocampal prisms. The β2-selective agonist 5-iodo-A-85380 was 1000-fold more potent in frontal cortex compared with hippocampus. Agonist-evoked [(3)H]-NA release was inhibited by the β2-selective antagonist dihydro-beta-erythroidine (DHβE) in frontal cortex, whereas in hippocampal tissue, DHβE had no effect. In vivo, 5-iodo-A-85380 (1, 100 μM) applied locally via the dialysis probe, significantly increased NA overflow, compared with basal release, in frontal cortex but not in hippocampus. These data support the modulation of NA release by different nAChR subtypes in frontal cortex and hippocampus. The pharmacological profile for rat hippocampus is consistent with previous studies, implicating α3β4* nAChRs in the modulation of NA release in this tissue. nAChRs having this function in frontal cortex are pharmacologically distinct and correspond to β2-containing nAChRs.

  14. Prefrontal cortex, hippocampus, and basolateral amygdala plasticity in a rat model of autism spectrum.

    Science.gov (United States)

    Sosa-Díaz, Nuvia; Bringas, Maria Elena; Atzori, Marco; Flores, Gonzalo

    2014-10-01

    We aimed to investigate the effect of prenatal administration of valproic acid (VPA) (500 mg/kg) at embryonic day 12.5 on the anatomical properties of the prefrontal cortex, hippocampus, and basolateral amygdala, at three different ages: immediately after weaning (postnatal day 21 [PD21]), prepubertal (PD35), and postpubertal (PD70) ages in a rat model of autistic spectrum disorder. Quantitative analysis of the thickness of the prefrontal cortex revealed a reduced size at all study ages in the cingulate 1 area of the prefrontal cortex and CA1 of the dorsal hippocampus in prenatally exposed animals compared to controls. At the level of the basolateral amygdala, a reduction in the size was observed at PD35 and PD70 in the VPA group. In addition, a reduced thickness was observed in the prelimbic region of the prefrontal cortex in VPA animals at PD35. Interestingly, no differences in cortical thickness were observed between control and VPA animals in the infralimbic region of the prefrontal at any age. Our results suggest that prenatal exposure to VPA differentially alters cortical limbic regions anatomical parameters, with implication in the autistic spectrum disorder. © 2014 Wiley Periodicals, Inc.

  15. Differential Acetylcholine Release in the Prefrontal Cortex and Hippocampus During Pavlovian Trace and Delay Conditioning

    Science.gov (United States)

    Flesher, M. Melissa; Butt, Allen E.; Kinney-Hurd, Brandee L.

    2011-01-01

    Pavlovian trace conditioning critically depends on the medial prefrontal cortex (mPFC) and hippocampus (HPC), whereas delay conditioning does not depend on these brain structures. Given that the cholinergic basal forebrain system modulates activity in both the mPFC and HPC, it was reasoned that the level of acetylcholine (ACh) release in these regions would show distinct profiles during testing in trace and delay conditioning paradigms. To test this assumption, microdialysis probes were implanted unilaterally into the mPFC and HPC of rats that were pre-trained in appetitive trace and delay conditioning paradigms using different conditional stimuli in the two tasks. On the day of microdialysis testing, dialysate samples were collected during a quiet baseline interval before trials were initiated, and again during performance in separate blocks of trace and delay conditioning trials in each animal. ACh levels were quantified using high performance liquid chromatography and electrochemical detection techniques. Consistent with our hypothesis, results showed that ACh release in the mPFC was greater during trace conditioning than during delay conditioning. The level of ACh released during trace conditioning in the HPC was also greater than the levels observed during delay conditioning. While ACh efflux in both the mPFC and HPC selectively increased during trace conditioning, ACh levels in the mPFC during trace conditioning testing showed the greatest increases observed. These results demonstrate a dissociation in cholinergic activation of the mPFC and HPC during performance in trace but not delay appetitive conditioning, where this cholinergic activity may contribute to attentional mechanisms, adaptive response timing, or memory consolidation necessary for successful trace conditioning. PMID:21514394

  16. Apolipoprotein-E forms dimers in human frontal cortex and hippocampus

    Directory of Open Access Journals (Sweden)

    Halliday Glenda M

    2010-02-01

    Full Text Available Abstract Background Apolipoprotein-E (apoE plays important roles in neurobiology and the apoE4 isoform increases risk for Alzheimer's disease (AD. ApoE3 and apoE2 are known to form disulphide-linked dimers in plasma and cerebrospinal fluid whereas apoE4 cannot form these dimers as it lacks a cysteine residue. Previous in vitro research indicates dimerisation of apoE3 has a significant impact on its functions related to cholesterol homeostasis and amyloid-beta peptide degradation. The possible occurrence of apoE dimers in cortical tissues has not been examined and was therefore assessed. Human frontal cortex and hippocampus from control and AD post-mortem samples were homogenised and analysed for apoE by western blotting under both reducing and non-reducing conditions. Results In apoE3 homozygous samples, ~12% of apoE was present as a homodimer and ~2% was detected as a 43 kDa heterodimer. The level of dimerisation was not significantly different when control and AD samples were compared. As expected, these dimerised forms of apoE were not detected in apoE4 homozygous samples but were detected in apoE3/4 heterozygotes at a level approximately 60% lower than seen in the apoE3 homozygous samples. Similar apoE3 dimers were also detected in lysates of SK-N-SH neuroblastoma cells and in freshly prepared rabbit brain homogenates. The addition of the thiol trapping agent, iodoacetamide, to block reactive thiols during both human and rabbit brain sample homogenisation and processing did not reduce the amount of apoE homodimer recovered. These data indicate that the apoE dimers we detected in the human brain are not likely to be post-mortem artefacts. Conclusion The identification of disulphide-linked apoE dimers in human cortical and hippocampal tissues represents a distinct structural difference between the apoE3 and apoE4 isoforms that may have functional consequences.

  17. Histopathologic Effect of Prenatal Topiramate Exposure on Rat Cerebral Cortex and Hippocampus

    Directory of Open Access Journals (Sweden)

    Hagar A Hashish

    2014-04-01

    Material and methods: 12 female pregnant rats were divided into control and treated groups, 6 rats in each group. The treated group was given topiramate dissolved in tap water, from day 0 of pregnancy till the delivery, through oral route in dose of 200mg/kg. The control group received tap water at the same time. In the end of the treatment, the cerebral cortex and the hippocampus were stained with hematoxylin and eosin (H and E and immnunohistochemically for glial fibrillary acidic protein (GFAP. Results: The control rat cerebral cortex showed that granule cells were small cell with dense cytoplasm, pyramidal cells appeared with triangular cell body, light cytoplasm and small nucleus. Strong GFAP positive immunostaining was detected in the astrocytes in both granule cell and pyramidal cell layers. The pyramidal cells in Cornu Ammonis showed characteristic palisade arrangement, with lightly stained cytoplasm and central nucleus. Granule cells of the dentate gyrus were rounded, packed, dense. Strong GFAP positive immunostaining was detected in the astrocytes in both pyramidal cell and granule cell layers. In treated rats, granule and pyramidal cells in the cerebral cortex and hippocampus were disorganized with signs of degeneration. Faint GFAP positive immunostaining was detected in the astrocytes in granule and pyramidal cell layers. Conclusion: Long-term daily use of topiramate during pregnancy can lead to noticeable pathological neurotoxic effect in the cerebral cortex and hippocampus which may be implicated in cognitive affection. Neurological effect of topiramate necessitates further investigations. [J Interdiscipl Histopathol 2014; 2(2.000: 61-68

  18. Effect of soy milk on circulating 17- β estradiol, number of neurons in cerebral cortex and hippocampus and determination of their ratio in neonatal ovariectomized rats.

    Science.gov (United States)

    Marzban Abbasabadi, Behrokh; Tadjalli, Mina

    2016-01-01

    This study was conducted to evaluate the effect of soy milk on serum 17- β estradiol level and number of neurons in cerebral cortex and hippocampus as well as determination of the ratio of neurons in cortical and hippocampal regions in neonatal ovariectomized rats. Thirty female rats (one day old) were divided into six groups of five. At day 7, ovariectomy surgery was performed in four groups and two other groups were assumed as sham and control groups. Three groups of ovareictomaized rats were fed with soy milk at the doses of 0.75, 1.50 and 3.00 mL kg -1 per day since they were 14. At day 60, the blood samples were collected to measure the17- β estradiol concentration, and then the brain of rats were prepared for histological studies. The serum 17- β estradiol level significantly increased in ovariectomized rats fed with soy milk compared to ovariectomized rats with no soy milk supplementation. In addition, the results showed that soy milk significantly increased the number of neurons in CA1, CA2 and dentate gyrus regions of hippocampus and granular layer of cerebral cortex in ovariectomized rats, whereas there was no significant change in number of neurons in CA3 zone of hippocampus and molecular, pyramidal and multiform layers of cerebral cortex in ovariectomized rats fed with soy milk. The ratio of cerebral cortex neurons to hippocampal neurons had no significant changes among the experimental groups.

  19. Antidepressant administration modulates stress-induced DNA methylation and DNA methyltransferase expression in rat prefrontal cortex and hippocampus

    DEFF Research Database (Denmark)

    Sales, Amanda J; Joca, Sâmia R L

    2018-01-01

    , we investigated the effects induced by acute and repeated antidepressant treatment on DNA methylation and DNMT expression (1, 3a and 3b isoforms) in different brain regions of rats exposed to a stress model of depression, the learned helplessness (LH). Therefore, rats were exposed to pretest......Stress and antidepressant treatment can modulate DNA methylation in promoter region of genes related to neuroplasticity and mood regulation, thus implicating this epigenetic mechanism in depression neurobiology and treatment. Accordingly, systemic administration of DNA methyltransferase (DNMT...... methylation and DNMT (1, 3a and 3b) levels were measured in the dorsal and ventral hippocampus (dHPC, vHPC) and in the prefrontal cortex (PFC) of rats exposed to stress and treatment. Stress increased DNA methylation, DNMT3a and DNMT3b expression in the dHPC and PFC. Chronic, but not acute, imipramine...

  20. Possible involvements of glutamate and adrenergic receptors on acute toxicity of methylphenidate in isolated hippocampus and cerebral cortex of adult rats.

    Science.gov (United States)

    Motaghinejad, Majid; Motevalian, Manijeh; Shabab, Behnaz

    2017-04-01

    Neurodegeneration induced by methylphenidate (MPH), as a central stimulant with unknown long-term consequences, in adult rats' brain and the possible mechanisms involved were studied. Rats were acutely treated with MPH in the presence and absence of some receptor antagonists such as ketamine, topiramate, yohimbine, and haloperidol. Motor activity and anxiety level in rats were monitored. Antioxidant and inflammatory parameters were also measured in isolated hippocampus and cerebral cortex. MPH-treated groups (10 and 20 mg/kg) demonstrated anxiety-like behavior and increased motor activity. MPH significantly increased lipid peroxidation, GSSG content, IL-1β and TNF-α levels in isolated tissues, and also significantly reduced GSH content, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) activities in hippocampus and cerebral cortex. Pretreatment of animals by receptor antagonists caused inhibition of MPH-induced motor activity disturbances and anxiety-like behavior. Pretreatment of animals by ketamine, topiramate, and yohimbine inhibited the MPH-induced oxidative stress and inflammation; it significantly decreased lipid peroxidation, GSSG level, IL-1β and TNF-α levels and increased GSH content, SOD, GPx, and GR activities in hippocampus and cerebral cortex of acutely MPH-treated rats. Pretreatment with haloperidol did not cause any change in MPH-induced oxidative stress and inflammation. In conclusion, acute administration of high doses of MPH can cause oxidative and inflammatory changes in brain cells and induce neurodegeneration in hippocampus and cerebral cortex of adult rats and these changes might probably be mediated by glutamate (NMDA or AMPA) and/or α2 -adrenergic receptors. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  1. Glutaminase and MMP-9 Downregulation in Cortex and Hippocampus of LPA1 Receptor Null Mice Correlate with Altered Dendritic Spine Plasticity

    Directory of Open Access Journals (Sweden)

    Ana Peñalver

    2017-09-01

    Full Text Available Lysophosphatidic acid (LPA is an extracellular lipid mediator that regulates nervous system development and functions acting through G protein-coupled receptors (GPCRs. Here we explore the crosstalk between LPA1 receptor and glutamatergic transmission by examining expression of glutaminase (GA isoforms in different brain areas isolated from wild-type (WT and KOLPA1 mice. Silencing of LPA1 receptor induced a severe down-regulation of Gls-encoded long glutaminase protein variant (KGA (glutaminase gene encoding the kidney-type isoforms, GLS protein expression in several brain regions, particularly in brain cortex and hippocampus. Immunohistochemical assessment of protein levels for the second type of glutaminase (GA isoform, glutaminase gene encoding the liver-type isoforms (GLS2, did not detect substantial differences with regard to WT animals. The regional mRNA levels of GLS were determined by real time RT-PCR and did not show significant variations, except for prefrontal and motor cortex values which clearly diminished in KO mice. Total GA activity was also significantly reduced in prefrontal and motor cortex, but remained essentially unchanged in the hippocampus and rest of brain regions examined, suggesting activation of genetic compensatory mechanisms and/or post-translational modifications to compensate for KGA protein deficit. Remarkably, Golgi staining of hippocampal regions showed an altered morphology of glutamatergic pyramidal cells dendritic spines towards a less mature filopodia-like phenotype, as compared with WT littermates. This structural change correlated with a strong decrease of active matrix-metalloproteinase (MMP 9 in cerebral cortex and hippocampus of KOLPA1 mice. Taken together, these results demonstrate that LPA signaling through LPA1 influence expression of the main isoenzyme of glutamate biosynthesis with strong repercussions on dendritic spines maturation, which may partially explain the cognitive and learning defects

  2. Functional autoradiography shows unaltered cannabinoid CB1 receptor signalling in hippocampus and cortex of APP/PS1 transgenic mice.

    Science.gov (United States)

    Kärkkäine, E; Tanila, H; Laitinen, J T

    2012-12-01

    The cannabinoid CB1-receptor is among the most abundant G-protein-coupled receptors in the mammalian brain. Whereas post-mortem studies in Alzheimer's disease (AD) brains compared to age-matched controls have reported decreased CB1-receptor binding but no change in their protein levels (immunoreactivity), decreased or increased CB1- receptor protein levels have been reported in APP/PS1 transgenic mice modelling AD. To complete the picture, the present study used functional autoradiography to assess CB1-receptor-dependent G(i) protein activation in the hippocampus, entorhinal cortex and medial frontal cortex of 13- to 14-month-old female APPswe/PS1dE9 transgenic and wild-type littermate control mice. The mouse brains were processed for [³⁵S]GTPλS autoradiography so that brain sections were analysed in pairs of one transgenic and one control mouse brain. The autoradiography protocol was completed for each pair both in the absence and presence of dithiotreitol (DTT) to reveal possible redox-dependent alterations in CB1 receptor function. Five treatments were used: baseline, incubation with 10 μM GTPλS to assess nonspecific binding, and CB1 receptor agonist CP55,940 in three concentrations. By and large we found no statistically significant differences between the APP/PS1 transgenic and control mice in CB1 receptor signalling. The only exception was a modest redox-dependent alteration in entorhinal cortical CB1 receptors between the genotypes. Thus, in accordance with the majority of earlier human AD findings, we did not find evidence for notable changes in the number of functional CB1 receptors in the common APPswe/PS1dE9 mouse model of AD.

  3. Anxiolytic effects of muscarinic acetylcholine receptors agonist oxotremorine in chronically stressed rats and related changes in BDNF and FGF2 levels in the hippocampus and prefrontal cortex.

    Science.gov (United States)

    Di Liberto, Valentina; Frinchi, Monica; Verdi, Vincenzo; Vitale, Angela; Plescia, Fulvio; Cannizzaro, Carla; Massenti, Maria F; Belluardo, Natale; Mudò, Giuseppa

    2017-02-01

    In depressive disorders, one of the mechanisms proposed for antidepressant drugs is the enhancement of synaptic plasticity in the hippocampus and cerebral cortex. Previously, we showed that the muscarinic acetylcholine receptor (mAChR) agonist oxotremorine (Oxo) increases neuronal plasticity in hippocampal neurons via FGFR1 transactivation. Here, we aimed to explore (a) whether Oxo exerts anxiolytic effect in the rat model of anxiety-depression-like behavior induced by chronic restraint stress (CRS), and (b) if the anxiolytic effect of Oxo is associated with the modulation of neurotrophic factors, brain-derived neurotrophic factor (BDNF) and fibroblast growth factor-2 (FGF2), and phosphorylated Erk1/2 (p-Erk1/2) levels in the dorsal or ventral hippocampus and in the medial prefrontal cortex. The rats were randomly divided into four groups: control unstressed, CRS group, CRS group treated with 0.2 mg/kg Oxo, and unstressed group treated with Oxo. After 21 days of CRS, the groups were treated for 10 days with Oxo or saline. The anxiolytic role of Oxo was tested by using the following: forced swimming test, novelty suppressed feeding test, elevated plus maze test, and light/dark box test. The hippocampi and prefrontal cortex were used to evaluate BDNF and FGF2 protein levels and p-Erk1/2 levels. Oxo treatment significantly attenuated anxiety induced by CRS. Moreover, Oxo treatment counteracted the CRS-induced reduction of BDNF and FGF2 levels in the ventral hippocampus and medial prefrontal cerebral cortex CONCLUSIONS: The present study showed that Oxo treatment ameliorates the stress-induced anxiety-like behavior and rescues FGF2 and BDNF levels in two brain regions involved in CRS-induced anxiety, ventral hippocampal formation, and medial prefrontal cortex.

  4. Dopamine D1 receptor activity modulates object recognition memory consolidation in the perirhinal cortex but not in the hippocampus.

    Science.gov (United States)

    Balderas, Israela; Moreno-Castilla, Perla; Bermudez-Rattoni, Federico

    2013-10-01

    It has been proposed that distributed neuronal networks in the medial temporal lobe process different characteristics of a recognition event; the hippocampus has been associated with contextual recollection while the perirhinal cortex has been linked with familiarity. Here we show that D1 dopamine receptor activity in these two structures participates differentially in object recognition memory consolidation. The D1 receptor antagonist SCH23390 was infused bilaterally 15 min before a 5 min sample phase in either rats' perirhinal cortex or dorsal hippocampus, and they were tested 90 min for short-term memory or 24 h later for long-term memory. SCH23390 impaired long-term memory when infused in the perirhinal cortex but not when infused in the hippocampus. Conversely, when the D1 receptor agonist SKF38393 was infused 10 min before a 3 min sample phase in the perirhinal cortex, long-term memory was enhanced, however, this was not observed when the D1 agonist was infused in the hippocampus. Short-term memory was spared when SCH23390 or SKF38393 were infused in the perirhinal cortex or the dorsal hippocampus suggesting that acquisition was unaffected. These results suggest that dopaminergic transmission in these medial temporal lobe structures have a differential involvement in object recognition memory consolidation. Copyright © 2013 Wiley Periodicals, Inc.

  5. Distinct time courses of secondary brain damage in the hippocampus following brain concussion and contusion in rats.

    Science.gov (United States)

    Nakajima, Yuko; Horiuchi, Yutaka; Kamata, Hiroshi; Yukawa, Masayoshi; Kuwabara, Masato; Tsubokawa, Takashi

    2010-07-01

    Secondary brain damage (SBD) is caused by apoptosis after traumatic brain injury that is classified into concussion and contusion. Brain concussion is temporary unconsciousness or confusion caused by a blow on the head without pathological changes, and contusion is a brain injury with hemorrhage and broad extravasations. In this study, we investigated the time-dependent changes of apoptosis in hippocampus after brain concussion and contusion using rat models. We generated the concussion by dropping a plumb on the dura from a height of 3.5 cm and the contusion by cauterizing the cerebral cortex. SBD was evaluated in the hippocampus by histopathological analyses and measuring caspase-3 activity that induces apoptotic neuronal cell death. The frequency of abnormal neuronal cells with vacuolation or nuclear condensation, or those with DNA fragmentation was remarkably increased at 1 hr after concussion (about 30% for each abnormality) from the pre-injury level (0%) and reached the highest level (about 50% for each) by 48 hrs, whereas the frequency of abnormal neuronal cells was increased at 1 hr after contusion (about 10%) and reached the highest level (about 40%) by 48 hrs. In parallel, caspase-3 activity was increased sevenfold in the hippocampus at 1 hr after concussion and returned to the pre-injury level by 48 hrs, whereas after contusion, caspase-3 activity was continuously increased to the highest level at 48 hrs (fivefold). Thus, anti-apoptotic-cell-death treatment to prevent SBD must be performed by 1 hr after concussion and at latest by 48 hrs after contusion.

  6. Low-dose ionizing radiation rapidly affects mitochondrial and synaptic signaling pathways in murine hippocampus and cortex.

    Science.gov (United States)

    Kempf, Stefan J; Moertl, Simone; Sepe, Sara; von Toerne, Christine; Hauck, Stefanie M; Atkinson, Michael J; Mastroberardino, Pier G; Tapio, Soile

    2015-05-01

    The increased use of radiation-based medical imaging methods such as computer tomography is a matter of concern due to potential radiation-induced adverse effects. Efficient protection against such detrimental effects has not been possible due to inadequate understanding of radiation-induced alterations in signaling pathways. The aim of this study was to elucidate the molecular mechanisms behind learning and memory deficits after acute low and moderate doses of ionizing radiation. Female C57BL/6J mice were irradiated on postnatal day 10 (PND10) with gamma doses of 0.1 or 0.5 Gy. This was followed by evaluation of the cellular proteome, pathway-focused transcriptome, and neurological development/disease-focused miRNAome of hippocampus and cortex 24 h postirradiation. Our analysis showed that signaling pathways related to mitochondrial and synaptic functions were changed by acute irradiation. This may lead to reduced mitochondrial function paralleled by enhanced number of dendritic spines and neurite outgrowth due to elevated long-term potentiation, triggered by increased phosphorylated CREB. This was predominately observed in the cortex at 0.1 and 0.5 Gy and in the hippocampus only at 0.5 Gy. Moreover, a radiation-induced increase in the expression of several neural miRNAs associated with synaptic plasticity was found. The early changes in signaling pathways related to memory formation may be associated with the acute neurocognitive side effects in patients after brain radiotherapy but might also contribute to late radiation-induced cognitive injury.

  7. How hippocampus and cortex contribute to recognition memory: Revisiting the Complementary Learning Systems model

    Science.gov (United States)

    Norman, Kenneth A.

    2012-01-01

    We describe how the Complementary Learning Systems neural network model of recognition memory (Norman & O’Reilly, 2003) can shed light on current debates regarding hippocampal and cortical contributions to recognition memory. We review simulation results illustrating three critical differences in how (according to the model) hippocampus and cortex contribute to recognition memory, all of which derive from the hippocampus’ use of pattern separated representations. Pattern separation makes the hippocampus especially well-suited for discriminating between studied items and related lures; it makes the hippocampus especially poorly suited for computing global match; and it imbues the hippocampal ROC curve with a Y-intercept > 0. We also describe a key boundary condition on these differences: When the average level of similarity between items in an experiment is very high, hippocampal pattern separation can fail, at which point the hippocampal model will start to behave like the cortical model. We describe the implications of these simulation results for extant debates over how to describe hippocampal vs. cortical contributions and how to measure these contributions. PMID:20857486

  8. Parallel processing of information about location in the amygdala, entorhinal cortex and hippocampus.

    Science.gov (United States)

    Gaskin, Stephane; White, Norman M

    2013-11-01

    The conditioned cue preference paradigm was used to study how rats use extra-maze cues to discriminate between 2 adjacent arms on an 8-arm radial maze, a situation in which most of the same cues can be seen from both arms but only one arm contains food. Since the food-restricted rats eat while passively confined on the food-paired arm no responses are reinforced, so the discrimination is due to Pavlovian stimulus-reward (or outcome) learning. Consistent with other evidence that rats must move around in an environment to acquire a spatial map, we found that learning the adjacent arms CCP (ACCP) required a minimum amount of active exploration of the maze with no reinforcers present prior to passive pairing of the extra-maze cues with the food reinforcer, an instance of latent learning. Temporary inactivation of the hippocampus during the pre-exposure sessions had no effect on ACCP learning, confirming other evidence that the hippocampus is not involved in latent learning. A series of experiments indentified a circuit involving fimbria-fornix and dorsal entorhinal cortex as the neural basis of latent learning in this situation. In contrast, temporary inactivation of the entorhinal cortex or hippocampus during passive training or during testing blocked ACCP learning and expression, respectively, suggesting that these two structures co-operate in using spatial information to learn the location of food on the maze during passive pairing and to express this combined information during testing. In parallel with these processes we found that the amygdala processes information leading to an equal tendency to enter both adjacent arms (even though only one was paired with food) suggesting that the stimulus information available to this structure is not sufficiently precise to discriminate between the ambiguous cues visible from the adjacent arms. Expression of the ACCP in normal rats depends on hippocampus-based learning to avoid the unpaired arm which competes with the

  9. Engaging in paced mating, but neither exploratory, anti-anxiety, nor social behavior, increases 5α-reduced progestin concentrations in midbrain, hippocampus, striatum, and cortex

    Science.gov (United States)

    Frye, Cheryl A; Paris, Jason J; Rhodes, Madeline E

    2010-01-01

    Sequential actions of 17β-estradiol (E2) and progesterone (P4) in the hypothalamus and the P4 metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP), in the midbrain ventral tegmental area (VTA) respectively mediate the initiation and intensity of lordosis of female rats and mayalso modulate anxiety and social behaviors, through actions in these, and/or other brain regions. Biosynthesis of E2, P4, and 3α,5α-THP can also occur in brain, independent of peripheral gland secretion, in response to environmental/behavioral stimuli. The extent to which engaging in tasks related to reproductive behaviors and/or mating increased E2 or progestin concentrations in brain was investigated. In Experiment 1, proestrous rats were randomly assigned to be tested in individual tasks, including the open field, elevated plus maze, partner preference, social interaction, or no test control, in conjunction with paced mating or no mating. Engaging in paced mating, but not other behaviors, significantly increased dihydroprogesterone (DHP) and 3α,5α-THP levels in midbrain, hippocampus, striatum, and cortex. In Experiment 2, proestrous rats were tested in the combinations of the above tasks (open field and elevated plus maze, partner preference, and social interaction) with or without paced mating. As in Experiment 1, only engaging in paced mating increased DHP and 3α,5α-THP concentrations in midbrain, hippocampus, striatum, and cortex. Thus, paced mating enhances concentrations of 5α-reduced progestins in brain areas associated with reproduction (midbrain), as well as exploration/anxiety (hippocampus and striatum) and social behavior (cortex). PMID:17379660

  10. 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.

  11. Neural correlates of object-in-place learning in hippocampus and prefrontal cortex.

    Science.gov (United States)

    Kim, Jangjin; Delcasso, Sébastien; Lee, Inah

    2011-11-23

    Hippocampus and prefrontal cortex (PFC) process spatiotemporally discrete events while maintaining goal-directed task demands. Although some studies have reported that neural activities in the two regions are coordinated, such observations have rarely been reported in an object-place paired-associate (OPPA) task in which animals must learn an object-in-place rule. In this study, we recorded single units and local field potentials simultaneously from the CA1 subfield of the hippocampus and PFC as rats learned that Object A, but not Object B, was rewarded in Place 1, but not in Place 2 (vice versa for Object B). Both hippocampus and PFC are required for normal performance in this task. PFC neurons fired in association with the regularity of the occurrence of a certain type of event independent of space, whereas neuronal firing in CA1 was spatially localized for representing a discrete place. Importantly, the differential firing patterns were observed in tandem with common learning-related changes in both regions. Specifically, once OPPA learning occurred and rats used an object-in-place strategy, (1) both CA1 and PFC neurons exhibited spatially more similar and temporally more synchronized firing patterns, (2) spiking activities in both regions were more phase locked to theta rhythms, and (3) CA1-medial PFC coherence in theta oscillation was maximal before entering a critical place for decision making. The results demonstrate differential as well as common neural dynamics between hippocampus and PFC in acquiring the OPPA task and strongly suggest that both regions form a unified functional network for processing an episodic event.

  12. MicroRNA expression profiling reveals miRNA families regulating specific biological pathways in mouse frontal cortex and hippocampus.

    Directory of Open Access Journals (Sweden)

    Juuso Juhila

    Full Text Available MicroRNAs (miRNAs are small regulatory molecules that cause post-transcriptional gene silencing. Although some miRNAs are known to have region-specific expression patterns in the adult brain, the functional consequences of the region-specificity to the gene regulatory networks of the brain nuclei are not clear. Therefore, we studied miRNA expression patterns by miRNA-Seq and microarrays in two brain regions, frontal cortex (FCx and hippocampus (HP, which have separate biological functions. We identified 354 miRNAs from FCx and 408 from HP using miRNA-Seq, and 245 from FCx and 238 from HP with microarrays. Several miRNA families and clusters were differentially expressed between FCx and HP, including the miR-8 family, miR-182|miR-96|miR-183 cluster, and miR-212|miR-312 cluster overexpressed in FCx and miR-34 family overexpressed in HP. To visualize the clusters, we developed support for viewing genomic alignments of miRNA-Seq reads in the Chipster genome browser. We carried out pathway analysis of the predicted target genes of differentially expressed miRNA families and clusters to assess their putative biological functions. Interestingly, several miRNAs from the same family/cluster were predicted to regulate specific biological pathways. We have developed a miRNA-Seq approach with a bioinformatic analysis workflow that is suitable for studying miRNA expression patterns from specific brain nuclei. FCx and HP were shown to have distinct miRNA expression patterns which were reflected in the predicted gene regulatory pathways. This methodology can be applied for the identification of brain region-specific and phenotype-specific miRNA-mRNA-regulatory networks from the adult and developing rodent brain.

  13. Enhanced dendritic spine number of neurons of the prefrontal cortex, hippocampus and nucleus accumbens in old rats after chronic donepezil administration

    Science.gov (United States)

    Alcantara-Gonzalez, Faviola; Juarez, Ismael; Solis, Oscar; Martinez-Tellez, Isaura; Camacho-Abrego, Israel; Masliah, Eliezer; Mena, Raul; Flores, Gonzalo

    2010-01-01

    In Alzheimer's disease brains morphological changes in the dendrites of pyramidal neurons of the prefrontal cortex (PFC) and hippocampus have been observed. These changes are particularly reflected in the decrement of both the dendritic tree and spine number. Donepezil is a potent and selective acetylcholinesterase inhibitor used in the treatment of Alzheimer's disease. We have studied the effect of oral administration of this drug on the morphology of neuronal cells from the brain of aged rats. We examined dendrites of pyramidal neurons of the PFC, dorsal or ventral hippocampus and medium spiny neurons of the nucleus accumbens (NAcc). Donepezil (1 mg/Kg, vo) was administrated every day for 60 days to rats aged 10 and 18 months. Dendritic morphology was studied by the Golgi-Cox stain procedure followed by Sholl analysis at 12 and 20 months ages, respectively. In all Donepezil treated-rats a significant increment of the dendritic spines number in pyramidal neurons of the PFC, dorsal hippocampus was observed. However, pyramidal neurons of the ventral hippocampus and medium spiny cells of the NAcc only showed an increase in the number of their spines in 12 months old-rats. Our results suggest that Donepezil prevents the alterations of the neuronal dendrite morphology caused by aging. PMID:20336627

  14. 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.)

  15. Modulation of oxidative stress, inflammation, autophagy and expression of Nrf2 in hippocampus and frontal cortex of rats fed with açaí-enriched diets.

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    Poulose, Shibu M; Bielinski, Donna F; Carey, Amanda; Schauss, Alexander G; Shukitt-Hale, Barbara

    2017-06-01

    Açaí (Euterpe spp.), an exotic palm fruit, has recently emerged as a promising source of natural antioxidants with wide pharmacological and nutritional value. In this study, two different species of açaí pulp extracts, naturally grown in two distinct regions of the Amazon, namely, Euterpe oleracea Mart. (habitat: Brazilian floodplains of the Amazon) and Euterpe precatoria Mart. (habitat: Bolivian Amazon), were studied for their effects on brain health and cognition. Neurochemical analyses were performed in critical brain regions associated with memory and cognition of 19-month-old açaí-fed rats, in whom the cognitive benefits of açaí had been established. Results indicated significant reductions (P< 0.05) in prooxidant NADPH-oxidoreductase-2 (NOX2) and proinflammatory transcription factor NF-κB in açaí-fed rats. Measurement of Nrf2 expression, a transcription factor for antioxidant enzymes, and a possible link between oxidative stress, neuroinflammation and autophagy mechanisms, indicated significant overexpression (P<0.005) in the hippocampus and frontal cortex of the açaí-fed rats. Furthermore, significant activation of endogenous antioxidant enzymes GST and SOD were also observed in the açaí-fed animals when compared to control. Analysis of autophagy markers such as p62, phospho-mTOR, beclin1 and MAP1B-LC3 revealed differential expression in frontal cortex and hippocampus, mostly indicating an upregulation in the açaí-fed rats. In general, results were more profound for EP than EO in hippocampus as well as frontal cortex. Therefore, an açaí-enriched diet could possibly modulate Nrf2, which is known to modulate the intracellular redox status, thereby regulating the ubiquitin-proteosomal pathway, ultimately affecting cognitive function in the aging brain.

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

    OpenAIRE

    Gaelle eDominguez; Pierre eFaucher; Nadia eHenkous; Ali eKrazem; Christophe ePierard; Daniel eBeracochea

    2014-01-01

    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...

  17. Integrating Spatial Working Memory and Remote Memory: Interactions between the Medial Prefrontal Cortex and Hippocampus.

    Science.gov (United States)

    Wirt, Ryan A; Hyman, James M

    2017-04-18

    In recent years, two separate research streams have focused on information sharing between the medial prefrontal cortex (mPFC) and hippocampus (HC). Research into spatial working memory has shown that successful execution of many types of behaviors requires synchronous activity in the theta range between the mPFC and HC, whereas studies of memory consolidation have shown that shifts in area dependency may be temporally modulated. While the nature of information that is being communicated is still unclear, spatial working memory and remote memory recall is reliant on interactions between these two areas. This review will present recent evidence that shows that these two processes are not as separate as they first appeared. We will also present a novel conceptualization of the nature of the medial prefrontal representation and how this might help explain this area's role in spatial working memory and remote memory recall.

  18. Field repetition and local mapping in the hippocampus and the medial entorhinal cortex.

    Science.gov (United States)

    Grieves, Roddy M; Duvelle, Éléonore; Wood, Emma R; Dudchenko, Paul A

    2017-10-01

    Hippocampal place cells support spatial cognition and are thought to form the neural substrate of a global "cognitive map." A widely held view is that parts of the hippocampus also underlie the ability to separate patterns or to provide different neural codes for distinct environments. However, a number of studies have shown that in environments composed of multiple, repeating compartments, place cells and other spatially modulated neurons show the same activity in each local area. This repetition of firing fields may reflect pattern completion and may make it difficult for animals to distinguish similar local environments. In this review we 1) highlight some of the navigation difficulties encountered by humans in repetitive environments, 2) summarize literature demonstrating that place and grid cells represent local and not global space, and 3) attempt to explain the origin of these phenomena. We argue that the repetition of firing fields can be a useful tool for understanding the relationship between grid cells in the entorhinal cortex and place cells in the hippocampus, the spatial inputs shared by these cells, and the propagation of spatially related signals through these structures. Copyright © 2017 the American Physiological Society.

  19. Tramadol Pretreatment Enhances Ketamine-Induced Antidepressant Effects and Increases Mammalian Target of Rapamycin in Rat Hippocampus and Prefrontal Cortex

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    Chun Yang

    2012-01-01

    Full Text Available Several lines of evidence have demonstrated that acute administration of ketamine elicits fast-acting antidepressant effects. Moreover, tramadol also has potential antidepressant effects. The aim of this study was to investigate the effects of pretreatment with tramadol on ketamine-induced antidepressant activity and was to determine the expression of mammalian target of rapamycin (mTOR in rat hippocampus and prefrontal cortex. Rats were intraperitoneally administrated with ketamine at the dose of 10 mg/kg or saline 1 h before the second episode of the forced swimming test (FST. Tramadol or saline was intraperitoneally pretreated 30 min before the former administration of ketamine or saline. The locomotor activity and the immobility time of FST were both measured. After that, rats were sacrificed to determine the expression of mTOR in hippocampus and prefrontal cortex. Tramadol at the dose of 5 mg/kg administrated alone did not elicit the antidepressant effects. More importantly, pretreatment with tramadol enhanced the ketamine-induced antidepressant effects and upregulated the expression of mTOR in rat hippocampus and prefrontal cortex. Pretreatment with tramadol enhances the ketamine-induced antidepressant effects, which is associated with the increased expression of mTOR in rat hippocampus and prefrontal cortex.

  20. Inactivation of the dorsal hippocampus or the medial prefrontal cortex impairs retrieval but has differential effect on spatial memory reconsolidation.

    Science.gov (United States)

    Rossato, Janine I; Köhler, Cristiano A; Radiske, Andressa; Bevilaqua, Lia R M; Cammarota, Martín

    2015-11-01

    Active memories can incorporate new information through reconsolidation. However, the notion that memory retrieval is necessary for reconsolidation has been recently challenged. Non-reinforced retrieval induces hippocampus and medial prefrontal cortex (mPFC)-dependent reconsolidation of spatial memory in the Morris water maze (MWM). We found that the effect of protein synthesis inhibition on this process is abolished when retrieval of the learned spatial preference is hindered through mPFC inactivation but not when it is blocked by deactivation of dorsal CA1. Our results do not fully agree with the hypothesis that retrieval is unneeded for reconsolidation. Instead, they support the idea that a hierarchic interaction between the hippocampus and the mPFC controls spatial memory in the MWM, and indicate that this cortex is sufficient to retrieve the information essential to reconsolidate the spatial memory trace, even when the hippocampus is inactivated. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Acute stress-induced impairment of spatial memory is associated with decreased expression of neural cell adhesion molecule in the hippocampus and prefrontal cortex.

    Science.gov (United States)

    Sandi, Carmen; Woodson, James C; Haynes, Vernon F; Park, Collin R; Touyarot, Katia; Lopez-Fernandez, Miguel A; Venero, César; Diamond, David M

    2005-04-15

    There is an extensive literature describing how stress disturbs cognitive processing and can exacerbate psychiatric disorders. There is, however, an insufficient understanding of the molecular mechanisms involved in stress effects on brain and behavior. Rats were given spatial memory training in a hippocampus-dependent water maze task. We investigated how a fear-provoking experience (predator exposure) would affect their spatial memory and neural cell adhesion molecule (NCAM) levels in the hippocampus, prefrontal cortex (PFC), amygdala, and cerebellum. Whereas the control (nonstress) group exhibited excellent memory for the hidden platform location in the water maze, the cat-exposed (stress) group exhibited a profound impairment of memory and a marked suppression of levels of the NCAM-180 isoform in the hippocampus. Predator stress produced a more global reduction of NCAM levels in the PFC but had no effect on NCAM levels in the amygdala and cerebellum. This work provides a novel perspective into dynamic and structure-specific changes in the molecular events involved in learning, memory, and stress. The selective suppression of NCAM-180 in the hippocampus and the more general suppression of NCAM in the PFC provide insight into the mechanisms underlying the great sensitivity of these two structures to be disturbed by stress.

  2. Extinction-induced "despair" in aged and adult rats: links to neurotrophins in frontal cortex and hippocampus.

    Science.gov (United States)

    Topic, Bianca; Huston, Joseph P; Namestkova, Katerina; Zhu, Shun-Wei; Mohammed, Abdul H; Schulz, Daniela

    2008-10-01

    In the search for animal models of human geriatric depression, we found that operant extinction of escape from water results in the expression of immobility in different age groups, indicative of behavioral "despair", which was also associated with the resistance-to-extinction (RTE) expressed by these animals. With respect to the neurotrophin hypothesis of depression, nerve-growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) protein levels in frontal cortex (FC) and hippocampus (HP) were examined and related to behavioral immobility and RTE in the water maze in aged and adult Wistar rats. Age-related increases in levels of NGF were found in HP and of NT-3 in FC. Indices of immobility showed relationships in the aged with NGF and, in adults, with BDNF, pointing to a dissociation of neurotrophic involvement in extinction trial-induced "despair" in aged and adult rats. The present results support the hypothesis, that extinction-induced immobility in the water maze reflects a state akin to behavioral despair and point to age-related differences of neurotrophic involvement in depressive-like symptoms. The concept of extinction-induced behavioral "despair" in the aged subsumes several aspects of human geriatric depression, such as co-morbidity of learning impairment and anxiety, and, thus could represent a useful paradigm to examine the neuronal mechanisms underlying depression, especially in aged rodents.

  3. 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.

  4. Acute treatment with doxorubicin affects glutamate neurotransmission in the mouse frontal cortex and hippocampus.

    Science.gov (United States)

    Thomas, Theresa Currier; Beitchman, Joshua A; Pomerleau, Francois; Noel, Teresa; Jungsuwadee, Paiboon; Allan Butterfield, D; Clair, Daret K St; Vore, Mary; Gerhardt, Greg A

    2017-10-01

    Doxorubicin (DOX) is a potent chemotherapeutic agent known to cause acute and long-term cognitive impairments in cancer patients. Cognitive function is presumed to be primarily mediated by neuronal circuitry in the frontal cortex (FC) and hippocampus, where glutamate is the primary excitatory neurotransmitter. Mice treated with DOX (25mg/kg i.p.) were subjected to in vivo recordings under urethane anesthesia at 24h post-DOX injection or 5 consecutive days of cognitive testing (Morris Water Maze; MWM). Using novel glutamate-selective microelectrode arrays, amperometric recordings measured parameters of extracellular glutamate clearance and potassium-evoked release of glutamate within the medial FC and dentate gyrus (DG) of the hippocampus. By 24h post-DOX injection, glutamate uptake was 45% slower in the FC in comparison to saline-treated mice. In the DG, glutamate took 48% longer to clear than saline-treated mice. Glutamate overflow in the FC was similar between treatment groups, however, it was significantly increased in the DG of DOX treated mice. MWM data indicated that a single dose of DOX impaired swim speed without impacting total length traveled. These data indicate that systemic DOX treatment changes glutamate neurotransmission in key nuclei associated with cognitive function within 24h, without a lasting impact on spatial learning and memory. Understanding the functional effects of DOX on glutamate neurotransmission may help us understand and prevent some of the debilitating side effects of chemotherapeutic treatment in cancer survivors. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Involvement of pregnane xenobiotic receptor in mating-induced allopregnanolone formation in the midbrain and hippocampus and brain-derived neurotrophic factor in the hippocampus among female rats.

    Science.gov (United States)

    Frye, C A; Koonce, C J; Walf, A A

    2014-09-01

    Given that the pregnane neurosteroid, 5α-pregnan-3α-ol-20-one (3α,5α-THP), is increased following behavioral challenges (e.g., mating), and that there is behavioral-induced biosynthesis of 3α,5α-THP in midbrain and mesocorticolimbic structures, 3α,5α-THP likely has a role in homeostasis and motivated reproduction and reproduction-related behaviors (e.g., affect, affiliation). The role of pregnane xenobiotic receptor (PXR), involved in cholesterol metabolism, for these effects is of continued interest. We hypothesized that there would be differences in brain levels of 3α,5α-THP following varied behavioral experiences, an effect abrogated by knockdown of PXR in the midbrain. Proestrous rats were infused with PXR antisense oligonucleotides (AS-ODNs) or vehicle to the ventral tegmental area before different behavioral manipulations and assessments. Endpoints were expression levels of PXR in the midbrain, 3α,5α-THP, and ovarian steroids (estradiol, progesterone, dihydroprogesterone) in the midbrain, striatum, hippocampus, hypothalamus, prefrontal cortex, and plasma. Across experiments, knocking down PXR reduced PXR expression and 3α,5α-THP levels in the midbrain and hippocampus. There were differences in terms of the behavioral manipulations, such that paced mating had the most robust effects to increase 3α,5α-THP levels and reduce open field exploration and social interaction. An additional question that was addressed is whether brain-derived neurotrophic factor (BDNF) is a downstream factor for regulating effects of behavioral-induced 3α,5α-THP biosynthesis. Rats infused with PXR AS-ODNs had lower levels of BDNF in the hippocampus. Thus, PXR may be a regulator of mating-induced 3α,5α-THP formation and behavioral changes and neural plasticity, such as BDNF.

  6. 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.

  7. 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.

  8. Early memory formation disrupted by atypical PKC inhibitor ZIP in the medial prefrontal cortex but not hippocampus.

    Science.gov (United States)

    Evuarherhe, Obaro; Barker, Gareth R I; Savalli, Giorgia; Warburton, Elizabeth C; Brown, Malcolm W

    2014-08-01

    Atypical isoforms of protein kinase C (aPKCs; particularly protein kinase M zeta: PKMζ) have been hypothesized to be necessary and sufficient for the maintenance of long-term potentiation (LTP) and long term memory by maintaining postsynaptic AMPA receptors via the GluA2 subunit. A myristoylated PKMζ pseudosubstrate peptide (ZIP) blocks PKMζ activity. We examined the actions of ZIP in medial prefrontal cortex (mPFC) and hippocampus in associative recognition memory in rats during early memory formation and memory maintenance. ZIP infusion in either hippocampus or mPFC impaired memory maintenance. However, early memory formation was impaired by ZIP in mPFC but not hippocampus; and blocking GluA2-dependent removal of AMPA receptors did not affect this impairment caused by ZIP in the mPFC. The findings indicate: (i) a difference in the actions of ZIP in hippocampus and medial prefrontal cortex, and (ii) a GluA2-independent target of ZIP (possibly PKCλ) in the mPFC during early memory formation. © 2014 Wiley Periodicals, Inc.

  9. Dendritic morphology changes in neurons from the ventral hippocampus, amygdala and nucleus accumbens in rats with neonatal lesions into the prefrontal cortex.

    Science.gov (United States)

    Lazcano, Zayda; Solis, Oscar; Díaz, Alfonso; Brambila, Eduardo; Aguilar-Alonso, Patricia; Guevara, Jorge; Flores, Gonzalo

    2015-06-01

    Neonatal prefrontal cortex (nPFC) lesions in rats could be a potential animal model to study the early neurodevelopmental abnormalities associated with the behavioral and morphological brain changes observed in schizophrenia. Morphological alterations in pyramidal neurons from the ventral hippocampus (VH) have been observed in post-mortem schizophrenic brains, mainly because of decreased dendritic arbor and spine density. We assessed the effects of nPFC-lesions on the dendritic morphology of neurons from the VH, basolateral-amygdala (BLA) and the nucleus accumbens (NAcc) in rats. nPFC lesions were made on postnatal day 7 (PD7), after dendritic morphology was studied by the Golgi-Cox stain procedure followed by Sholl analysis at PD35 (prepubertal) and PD60 (adult) ages. We also evaluated the effects of PFC-lesions on locomotor activity caused by a novel environment. Adult animals with nPFC lesions showed a decreased spine density in pyramidal neurons from the VH and in medium spiny cells from the NAcc. An increased locomotion was observed in a novel environment for adult animals with a PFC-lesion. Our results indicate that PFC-lesions alter the neuronal dendrite morphology of the NAcc and the VH, suggesting a disconnection between these limbic structures. The locomotion paradigms suggest that dopaminergic transmission is altered in the PFC lesion model. This could help to understand the consequences of an earlier PFC dysfunction in schizophrenia. To evaluate possible dendritic changes in neonatal prefrontal cortex lesions in schizophrenia-related regions including nucleus accumbens, ventral hippocampus and basolateral amygdala, we used the Golgi-Cox stain samples at PD35 and PD70. Our results suggest that neonatal prefrontal cortex damage alters dendritic parameters in limbic regions, and this has potential implications for schizophrenia. © 2015 Wiley Periodicals, Inc.

  10. Orbitofrontal cortex volume and brain reward response in obesity.

    Science.gov (United States)

    Shott, M E; Cornier, M-A; Mittal, V A; Pryor, T L; Orr, J M; Brown, M S; Frank, G K W

    2015-02-01

    What drives overconsumption of food is poorly understood. Alterations in brain structure and function could contribute to increased food seeking. Recently, brain orbitofrontal cortex (OFC) volume has been implicated in dysregulated eating but little is known how brain structure relates to function. We examined obese (n=18, age=28.7±8.3 years) and healthy control women (n=24, age=27.4±6.3 years) using a multimodal brain imaging approach. We applied magnetic resonance and diffusion tensor imaging to study brain gray and white matter volume as well as white matter (WM) integrity, and tested whether orbitofrontal cortex volume predicts brain reward circuitry activation in a taste reinforcement-learning paradigm that has been associated with dopamine function. Obese individuals displayed lower gray and associated white matter volumes (Pobese individuals in fiber tracts including the external capsule, corona radiata, sagittal stratum, and the uncinate, inferior fronto-occipital, and inferior longitudinal fasciculi. Gray matter volume of the gyrus rectus at the medial edge of the orbitofrontal cortex predicted functional taste reward-learning response in frontal cortex, insula, basal ganglia, amygdala, hypothalamus and anterior cingulate cortex in control but not obese individuals. This study indicates a strong association between medial orbitofrontal cortex volume and taste reinforcement-learning activation in the brain in control but not in obese women. Lower brain volumes in the orbitofrontal cortex and other brain regions associated with taste reward function as well as lower integrity of connecting pathways in obesity (OB) may support a more widespread disruption of reward pathways. The medial orbitofrontal cortex is an important structure in the termination of food intake and disturbances in this and related structures could contribute to overconsumption of food in obesity.

  11. Retroactive interference of object-in-context long-term memory: role of dorsal hippocampus and medial prefrontal cortex.

    Science.gov (United States)

    Martínez, María Cecilia; Villar, María Eugenia; Ballarini, Fabricio; Viola, Haydée

    2014-12-01

    Retroactive interference (RI) is a type of amnesia in which a new learning experience can impair the expression of a previous one. It has been studied in several types of memories for over a century. Here, we aimed to study in the long-term memory (LTM) formation of an object-in-context task, defined as the recognition of a familiar object in a context different to that in which it was previously encountered. We trained rats with two sample trials, each taking place in a different context in association with different objects. Test sessions were performed 24 h later, to evaluate LTM for both object-context pairs using separate groups of trained rats. Furthermore, given the involvement of hippocampus (Hp) and medial prefrontal cortex (mPFC) in several recognition memories, we also analyzed the participation of these structures in the LTM formation of this task by the local infusion of muscimol. Our results show that object-in-context LTM formation is sensitive to RI by a different either familiar or novel object-context pair trial, experienced 1 h later. This interference occurs in a restricted temporal window and works on the LTM consolidation phase, leaving intact short-term memory expression. The second sample trial did not affect the object recognition part of the memory. Besides, muscimol treatment before the second sample trial blocks its object-in-context LTM and restores the first sample trial memory. We hypothesized that LTM-RI amnesia is probably caused by resources or cellular machinery competition in these brain regions when they are engaged in memory formation of the traces. In sum, when two different object-in-context memory traces are being processed, the second trace interferes with the consolidation of the first one requiring mPFC and CA1 dorsal Hp activation. © 2014 Wiley Periodicals, Inc.

  12. 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. Copyright © 2014. Published by Elsevier B.V.

  13. Neurochemical changes in the hippocampus and prefrontal cortex associated with electroacupuncture for learning and memory impairment.

    Science.gov (United States)

    He, Jian; Zhao, Congkuai; Liu, Weilin; Huang, Jia; Liang, Shengxiang; Chen, Lidian; Tao, Jing

    2018-02-01

    Electroacupuncture (EA) has been widely used to treat cognitive impairment following cerebral ischemia. However, the functional mechanisms of EA have not been fully elucidated. The aim of the present study was to investigate whether EA at the GV 20 and DU 24 acupoints can improve the learning and memory ability via alteration of the neurochemical metabolism in the hippocampus (HPC) and prefrontal cortex (PFC) of rats with ischemia and reperfusion (I/R) injury. Sprague‑Dawley male rats were randomly divided into three groups, namely the sham group (n=12), the middle cerebral artery occlusion (MCAO) group (n=12) and the EA treatment (MCAO + EA) group (n=12). MCAO was performed to establish the left focal cerebral I/R injury model, and the GV 20 and DU 24 acupoints were then stimulated with EA for 30 min per time, once daily, for 7 consecutive days. The Morris water maze (MWM) test was used to assess learning and memory ability. T2‑weighted imaging was used to assess the cerebral infarct volume. Magnetic resonance spectroscopy was used to assess neurochemical metabolism of HPC and PFC. The neurological scores of the MCAO + EA group were significantly reduced compared with those of the MCAO group 7 days after EA treatment (Pplatform area was significantly higher in the MCAO + EA group compared with that in the MCAO group (P0.05). The ratios of NAA/Cr, Cho/Cr and Glu/Cr of left‑to‑right PFC were elevated (Plearning and memory ability, possibly through increasing the levels of NAA and Cho in the HPC and PFC of rats with I/R injury.

  14. Synaptic plasticity-related neural oscillations on hippocampus-prefrontal cortex pathway in depression.

    Science.gov (United States)

    Zheng, C; Zhang, T

    2015-04-30

    It is believed that phase synchronization facilitates neural communication and neural plasticity throughout the hippocampal-cortical network, and further supports cognition and memory. The pathway from the ventral hippocampus to the medial prefrontal cortex (mPFC) is thought to play a significant role in emotional memory processing. Therefore, the information transmission on the pathway was hypothesized to be disrupted in the depressive state, which could be related to its impaired synaptic plasticity. In this study, local field potentials (LFPs) from both ventral CA1 (vCA1) and mPFC were recorded in both normal and chronic unpredictable stress (CUS) model rats under urethane anesthesia. LFPs of all rats were recorded before and after the long-term potentiation (LTP) induced on the vCA1-mPFC pathway in order to figure out the correlation of oscillatory synchronization of LFPs and synaptic plasticity. Our results showed the vCA1-to-mPFC unidirectional phase coupling of the theta rhythm, rather than the power of either region, was significantly enhanced by LTP induction, with less enhancement in the CUS model rats compared to that in the normal rats. In addition, theta phase coupling was positively correlated with synaptic plasticity on vCA1-mPFC pathway. Moreover, the theta-slow gamma phase-amplitude coupling in vCA1 was long-term enhanced after high frequency stimulation. These results suggest that the impaired synaptic plasticity in vCA1-mPFC pathway could be reflected by the attenuated theta phase coupling and theta-gamma cross frequency coupling of LFPs in the depression state. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. 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

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

    Science.gov (United States)

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

    2014-01-01

    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 cause a

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

    Directory of Open Access Journals (Sweden)

    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

  18. Influence of cocaine self-administration on learning related to prefrontal cortex or hippocampus functioning in rats.

    Science.gov (United States)

    Kantak, Kathleen M; Udo, Tomoko; Ugalde, Francisco; Luzzo, Christopher; Di Pietro, Nina; Eichenbaum, Howard B

    2005-09-01

    Individuals who abuse cocaine have cognitive deficits, particularly in functions associated with the orbitofrontal cortex. It is not clear to what extent the impact of cocaine on cognitive functioning is related to its role as a behavioral reinforcer. A preclinical means to investigate this issue is to use a yoked-triad procedure in which sets of three animals either contingently self-administer cocaine or receive passive administration of cocaine or saline in a noncontingent manner. Using this procedure, we assessed cocaine's effect on learning that requires a functionally intact prefrontal cortex (prelimbic or insular/orbital subregions) or hippocampus. Rats self-administering 1-mg/kg unit doses of cocaine responded under a fixed-ratio 5, time-out 20-s schedule of drug delivery. Testing took place in a radial-arm maze within the first 30 min after 2-hr drug sessions ended, beginning after 2.5 months of cocaine or saline exposure. Rats self-administering cocaine earned 14-18 infusions on average throughout different phases of the study. In groupwise comparisons, learning in the visually guided delayed win-shift (prelimbic prefrontal cortex-related) and win-shift (hippocampus-related) tasks was not influenced by contingent or noncontingent cocaine exposure. Session latency, though, was shorter in both cocaine-exposed groups during the win-shift task. During the odor-guided delayed win-shift task (insular/orbital prefrontal cortex-related), learning was disrupted in rats self-administering cocaine, with no influence of noncontingent cocaine exposure. Based on these and previous findings, learning related to functioning of the insular/orbital prefrontal cortex and amygdala is the most consistently disrupted in cocaine-intoxicated rats after long-term drug exposure.

  19. 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.

  20. Pioglitazone blocks ethanol induction of microglial activation and immune responses in the hippocampus, cerebellum, and cerebral cortex in a mouse model of fetal alcohol spectrum disorders.

    Science.gov (United States)

    Drew, Paul D; Johnson, Jennifer W; Douglas, James C; Phelan, Kevin D; Kane, Cynthia J M

    2015-03-01

    Fetal alcohol spectrum disorders (FASD) result from fetal exposure to alcohol and are the leading cause of mental retardation in the United States. There is currently no effective treatment that targets the causes of these disorders. Thus, novel therapies are critically needed to limit the neurodevelopmental and neurodegenerative pathologies associated with FASD. A neonatal mouse FASD model was used to examine the role of the neuroimmune system in ethanol (EtOH)-induced neuropathology. Neonatal C57BL/6 mice were treated with EtOH, with or without pioglitazone, on postnatal days 4 through 9, and tissue was harvested 1 day post treatment. Pioglitazone is a peroxisome proliferator-activated receptor (PPAR)-γ agonist that exhibits anti-inflammatory activity and is neuroprotective. We compared the effects of EtOH with or without pioglitazone on cytokine and chemokine expression and microglial morphology in the hippocampus, cerebellum, and cerebral cortex. In EtOH-treated animals compared with controls, cytokines interleukin-1β and tumor necrosis factor-α mRNA levels were increased significantly in the hippocampus, cerebellum, and cerebral cortex. Chemokine CCL2 mRNA was increased significantly in the hippocampus and cerebellum. Pioglitazone effectively blocked the EtOH-induced increase in the cytokines and chemokine in all tissues to the level expressed in handled-only and vehicle-treated control animals. EtOH also produced a change in microglial morphology in all brain regions that was indicative of microglial activation, and pioglitazone blocked this EtOH-induced morphological change. These studies indicate that EtOH activates microglia to a pro-inflammatory stage and also increases the expression of neuroinflammatory cytokines and chemokines in diverse regions of the developing brain. Further, the anti-inflammatory and neuroprotective PPAR-γ agonist pioglitazone blocked these effects. It is proposed that microglial activation and inflammatory molecules expressed

  1. Evaluation of TrkB and BDNF transcripts in prefrontal cortex, hippocampus, and striatum from subjects with schizophrenia, bipolar disorder, and major depressive disorder.

    Science.gov (United States)

    Reinhart, Veronica; Bove, Susan E; Volfson, Dmitri; Lewis, David A; Kleiman, Robin J; Lanz, Thomas A

    2015-05-01

    Brain-derived neurotrophic factor (BDNF) signaling is integral to a range of neural functions, including synaptic plasticity and exhibits activity-dependent regulation of expression. As altered BDNF signaling has been implicated in multiple psychiatric diseases, here we report a quantitative reverse transcription polymerase chain reaction (RT-PCR) analysis of mRNAs encoding TrkB, total BDNF, and the four most abundant BDNF transcripts (I, IIc, IV, and VI) in postmortem tissue from matched tetrads of subjects with schizophrenia, bipolar disorder, or major depressive disorder (MDD) and healthy comparison subjects. In all three regions examined, dorsolateral prefrontal cortex (DLPFC), associative striatum and hippocampus, total BDNF mRNA levels did not differ in any disease state. In DLPFC, BDNF IIc was significantly lower in schizophrenia relative to healthy comparison subjects. In hippocampus, BDNF I, IIc, and VI were lower in subjects with both schizophrenia and bipolar disorder relative to comparison subjects. In striatum, TrkB mRNA was lower in bipolar disorder and MDD, while BDNF IIc was elevated in MDD, relative to comparison subjects. These data highlight potential alterations in BDNF signaling in the corticohippocampal circuit in schizophrenia, and within the striatum in mood disorders. Novel therapies aimed at improving BDNF-TrkB signaling may therefore have potential to impact on a range of psychiatric disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Prenatal choline supplementation increases NGF levels in the hippocampus and frontal cortex of young and adult rats.

    Science.gov (United States)

    Sandstrom, Noah J; Loy, Rebekah; Williams, Christina L

    2002-08-23

    Female Sprague-Dawley rats received approximately 300 mg/kg per day of choline chloride through their drinking water on days 11 of pregnancy through birth and the level of nerve growth factor (NGF) in the hippocampus and frontal cortex of their male offspring was measured at 20 and 90 days of age. Prenatal choline supplementation caused significant increases in hippocampal NGF levels at 20 and 90 days of age, while levels of NGF in the frontal cortex were elevated in choline-supplemented rats at 20 days of age, but not 90 days of age. These results suggest that increases in NGF levels during development or adulthood may be one mechanism underlying improvements in spatial and temporal memory of adult rats exposed to elevated levels of choline chloride perinatally.

  3. Chronic restraint stress promotes learning and memory impairment due to enhanced neuronal endoplasmic reticulum stress in the frontal cortex and hippocampus in male mice.

    Science.gov (United States)

    Huang, Rong-Rong; Hu, Wen; Yin, Yan-Yan; Wang, Yu-Chan; Li, Wei-Ping; Li, Wei-Zu

    2015-02-01

    Chronic stress has been implicated in many types of neurodegenerative diseases, such as Alzheimer's disease (AD). In our previous study, we demonstrated that chronic restraint stress (CRS) induced reactive oxygen species (ROS) overproduction and oxidative damage in the frontal cortex and hippocampus in mice. In the present study, we investigated the effects of CRS (over a period of 8 weeks) on learning and memory impairment and endoplasmic reticulum (ER) stress in the frontal cortex and hippocampus in male mice. The Morris water maze was used to investigate the effects of CRS on learning and memory impairment. Immunohistochemistry and immunoblot analysis were also used to determine the expression levels of protein kinase C α (PKCα), 78 kDa glucose-regulated protein (GRP78), C/EBP-homologous protein (CHOP) and mesencephalic astrocyte-derived neurotrophic factor (MANF). The results revealed that CRS significantly accelerated learning and memory impairment, and induced neuronal damage in the frontal cortex and hippocampus CA1 region. Moreover, CRS significantly increased the expression of PKCα, CHOP and MANF, and decreased that of GRP78 in the frontal cortex and hippocampus. Our data suggest that exposure to CRS (for 8 weeks) significantly accelerates learning and memory impairment, and the mechanisms involved may be related to ER stress in the frontal cortex and hippocampus.

  4. Nimodipine activates TrkB neurotrophin receptors and induces neuroplastic and neuroprotective signaling events in the mouse hippocampus and prefrontal cortex.

    Science.gov (United States)

    Koskimäki, Janne; Matsui, Nobuaki; Umemori, Juzoh; Rantamäki, Tomi; Castrén, Eero

    2015-03-01

    The L-type calcium channel blocker nimodipine improves clinical outcome produced by delayed cortical ischemia or vasospasm associated with subarachnoid hemorrhage. While vasoactive mechanisms are strongly implicated in these therapeutic actions of nimodipine, we sought to test whether nimodipine might also regulate neurotrophic and neuroplastic signaling events associated with TrkB neurotrophin receptor activation. Adult male mice were acutely treated with vehicle or nimodipine (10 mg/kg, s.c., 1.5 h) after which the phosphorylation states of TrkB, cyclic-AMP response element binding protein (CREB), protein kinase B (Akt), extracellular regulated kinase (ERK), mammalian target of rapamycin (mTor) and p70S6 kinase (p70S6k) from prefrontal cortex and hippocampus were assessed. Nimodipine increased the phosphorylation of the TrkB catalytic domain and the phosphoslipase-Cγ1 (PLCγ1) domain, whereas phosphorylation of the TrkB Shc binding site remained unaltered. Nimodipine-induced TrkB phosphorylation was associated with increased phosphorylation levels of Akt and CREB in the prefrontal cortex and the hippocampus whereas phosphorylation of ERK, mTor and p70S6k remained unaltered. Nimodipine-induced TrkB signaling was not associated with changes in BDNF mRNA or protein levels. These nimodipine-induced changes on TrkB signaling mimic those produced by antidepressant drugs and thus propose common mechanisms and long-term functional consequences for the effects of these medications. This work provides a strong basis for investigating the role of TrkB-associated signaling underlying the neuroprotective and neuroplastic effects of nimodipine in translationally relevant animal models of brain trauma or compromised synaptic plasticity.

  5. Effects of L-arginine and N(ω)-nitro-L-arginine methylester on learning and memory and α7 nAChR expression in the prefrontal cortex and hippocampus of rats.

    Science.gov (United States)

    Wei, Xiao-Ming; Yang, Wei; Liu, Li-Xia; Qi, Wen-Xiu

    2013-06-01

    Nitric oxide (NO) is a novel type of neurotransmitter that is closely associated with synaptic plasticity, learning and memory. In the present study, we assessed the effects of L-arginine and N(ω)-nitro-L-arginine methylester (L-NAME, a nitric oxide synthase inhibitor) on learning and memory. Rats were assigned to three groups receiving intracerebroventricular injections of L-Arg (the NO precursor), L-NAME, or 0.9% NaCl (control), once daily for seven consecutive days. Twelve hours after the last injection, they underwent an electric shock-paired Y maze test. Twenty-four hours later, the rats' memory of the safe illuminated arm was tested. After that, the levels of NO and α7 nicotinic acetylcholine receptor (α7 nAChR) in the prefrontal cortex and hippocampus were assessed using an NO assay kit, and immunohistochemistry and Western blots, respectively. We found that, compared to controls, L-Arg-treated rats received fewer foot shocks and made fewer errors to reach the learning criterion, and made fewer errors during the memory-testing session. In contrast, L-NAME-treated rats received more foot shocks and made more errors than controls to reach the learning criterion, and made more errors during the memory-testing session. In parallel, NO content in the prefrontal cortex and hippocampus was higher in L-Arg-treated rats and lower in L-NAME rats, compared to controls. Similarly, α7 nAChR immunoreactivity and protein expression in the prefrontal cortex and hippocampus were higher in L-Arg-treated rats and lower in L-NAME rats, compared to controls. These results suggest that the modulation of NO content in the brain correlates with α7 nAChR distribution and expression in the prefrontal cortex and hippocampus, as well as with learning and memory performance in the Y-maze.

  6. Differential role of the dorsal hippocampus, ventro-intermediate hippocampus, and medial prefrontal cortex in updating the value of a spatial goal.

    Science.gov (United States)

    De Saint Blanquat, Paul; Hok, Vincent; Save, Etienne; Poucet, Bruno; Chaillan, Franck A

    2013-05-01

    Encoding of a goal with a specific value while performing a place navigation task involves the medial prefrontal cortex (mPFC) and the dorsal hippocampus (dHPC), and depends on the coordination between mPFC and the ventro-intermediate hippocampus (vHPC).The present work investigates the contribution of mPFC, dHPC, and vHPC when the rat has to update the value of a goal. Rats were trained to navigate to an uncued goal in order to release a food pellet in a continuous place navigation task. When they had reached criterion performance level in the task, they were subjected to a single "flash session" in which they were exposed to an aversive strobe light during goal visits instead of receiving a food reward. Just before the flash session, the GABA(A) agonist muscimol was injected to temporarily inactivate mPFC, dHPC, or vHPC. The ability to recall the changed value of the goal was tested on the next day. We first demonstrate the aversive effect of the strobe light by showing that rats learn to avoid the goal much more rapidly in the flash session than during a simple extinction session in which goal visits are not rewarded. Furthermore, while dHPC inactivation had no effect on learning and recalling the new goal value, vHPC muscimol injections considerably delayed goal value updating during the flash session, which resulted in a slight deficit during recall. In contrast, mPFC muscimol injections induced faster goal value updating but the rats were markedly impaired on recalling the new goal value on the next day. These results suggest that, contrary to mPFC and dHPC, vHPC is required for updating the value of a goal. In contrast, mPFC is necessary for long-term retention of this updating. Copyright © 2013 Wiley Periodicals, Inc.

  7. Effect of 17β estradiol on hippocampus region of aging female rat brain: Ultrastructural study

    Directory of Open Access Journals (Sweden)

    Rashmi Jha

    2015-01-01

    Full Text Available Estradiol has direct membrane-mediated effects on neurons and its effects are both neuroprotective and neurotrophic. This hormone modulates brain development and aging and affects neurochemical systems which are affected in age-related cognitive decline, AD and other neuropsychiatric disorders. The aim of the present study was to determine the effect of 17β estradiol (E2 in hippocampus region of different age groups of rats. The changes in the hippocampus region of female rat brain of different age groups with and without E2 treatment were observed by transmission electron microscopy. Age dependent changes in myelin sheath, axon and cytoplasm membrane were observed with aging in control group rat brain but the E2 treated rats showed significantly stable myelin sheath, myelin axon and cytoplasm structure. Our results showed that E2 treatment significantly effects hippocampus brain region of aging rats. These analyses revealed that fundamental age-related changes in brain and estrogen have important implications when estrogen levels and hippocampus dependent functions decline.

  8. Prenatal alcohol exposure alters p35, CDK5 and GSK3β in the medial frontal cortex and hippocampus of adolescent mice

    Directory of Open Access Journals (Sweden)

    Samantha L. Goggin

    2014-01-01

    Full Text Available Fetal alcohol spectrum disorders (FASDs are the number one cause of preventable mental retardation. An estimated 2–5% of children are diagnosed as having a FASD. While it is known that children prenatally exposed to alcohol experience cognitive deficits and a higher incidence of psychiatric illness later in life, the pathways underlying these abnormalities remain uncertain. GSK3β and CDK5 are protein kinases that are converging points for a vast number of signaling cascades, including those controlling cellular processes critical to learning and memory. We investigated whether levels of GSK3β and CDK5 are affected by moderate prenatal alcohol exposure (PAE, specifically in the hippocampus and medial frontal cortex of the adolescent mouse. In the present work we utilized immunoblotting techniques to demonstrate that moderate PAE increased hippocampal p35 and β-catenin, and decreased total levels of GSK3β, while increasing GSK3β Ser9 and Tyr216 phosphorylation. Interestingly, different alterations were seen in the medial frontal cortex where p35 and CDK5 were decreased and increased total GSK3β was accompanied by reduced Tyr216 of the enzyme. These results suggest that kinase dysregulation during adolescence might be an important contributing factor to the effects of PAE on hippocampal and medial frontal cortical functioning; and by extension, that global modulation of these kinases may produce differing effects depending on brain region.

  9. Locomotion in intact and in brain cortex-ablated cats.

    Science.gov (United States)

    López Ruiz, José Roberto; Castillo Hernández, Luis; De la Torre Valdovinos, Braniff; Franco Rodríguez, Nancy Elizabeth; Dueñas Jiménez, Judith Marcela; Dueñas Jiménez, Alejandro; Rivas-Carrillo, Jorge David; Dueñas Jiménez, Sergio Horacio

    2017-09-01

    The current decerebration procedures discard the role of the thalamus in the motor control and decortication only rules out the brain cortex part, leaving a gap between the brain cortex and the subthalamic motor regions. In here we define a new preparation denominated Brain Cortex-Ablated Cat (BCAC), in which the frontal and parietal brain cortices as well as the central white matter beneath them were removed, this decerebration process may be considered as suprathalamic, since the thalamus remained intact. To characterize this preparation cat hindlimb electromyograms (EMG), kinematics and cutaneous reflexes (CR) produced by electrical stimulation of sural (SU) or saphenous (SAPH) nerves were analyzed during locomotion in intact and in BCAC. In cortex-ablated cats compared to intact cats, the hindlimb EMG amplitude was increased in the flexors, whereas in most extensors the amplitude was decreased. Bifunctional muscle EMGs presented complex and speed-dependent amplitude changes. In intact cats CR produced an inhibition of extensors, as well as excitation and inhibition of flexors, and a complex pattern of withdrawal responses in bifunctional muscles. The same stimuli applied to BCAC produced no detectable responses, but in some cats cutaneous reflexes produced by electrical stimulation of saphenous nerve reappeared when the locomotion speed increased. In BCAC, EMG and kinematic changes, as well as the absence of CR, imply that for this cat preparation there is a partial compensation due to the subcortical locomotor apparatus generating close to normal locomotion. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. 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

  11. 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 eTahmasian

    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.

  12. 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.

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

    Science.gov (United States)

    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.; Riedl, Valentin; Sorg, Christian

    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. 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. Analysis of variance was used to compare ß-maps between MDD and healthy control groups, and included covariates for age and gender as well as gray 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. PMID:24101900

  14. The hippocampus: A central node in a large-scale brain network for memory.

    Science.gov (United States)

    Huijgen, J; Samson, S

    2015-03-01

    The medial temporal lobe is a key region in the formation and consolidation of conscious or declarative memories. In this review, we will first consider the role of the hippocampus and its surrounding medial temporal lobe structures in recognition memory from a historical perspective. According to the dual process model of recognition memory, recognition judgments can be based on the recollection of details about previous presented stimuli or on the feeling of familiarity. Studies in humans, primates and rodents suggest that the hippocampus, the parahippocampal cortex and the perirhinal cortex play different roles in recollection and familiarity. Then, we will describe the role of the hippocampus and neocortex in memory consolidation: a process in which novel memories become integrated into long-term memory. After presenting possible mechanisms underlying sleep-dependent declarative memory consolidation, we will discuss the phenomenon of accelerated long-term forgetting. This type of memory deficit is often observed in epileptic patients with a hippocampal lesion, and provides a novel opportunity to investigate post-encoding and memory consolidation processes. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  15. From motor cortex to visual cortex: the application of noninvasive brain stimulation to amblyopia.

    Science.gov (United States)

    Thompson, Benjamin; Mansouri, Behzad; Koski, Lisa; Hess, Robert F

    2012-04-01

    Noninvasive brain stimulation is a technique for inducing changes in the excitability of discrete neural populations in the human brain. A current model of the underlying pathological processes contributing to the loss of motor function after stroke has motivated a number of research groups to investigate the potential therapeutic application of brain stimulation to stroke rehabilitation. The loss of motor function is modeled as resulting from a combination of reduced excitability in the lesioned motor cortex and an increased inhibitory drive from the nonlesioned hemisphere over the lesioned hemisphere. This combination of impaired neural function and pathological suppression resonates with current views on the cause of the visual impairment in amblyopia. Here, we discuss how the rationale for using noninvasive brain stimulation in stroke rehabilitation can be applied to amblyopia, review a proof-of-principle study demonstrating that brain stimulation can temporarily improve amblyopic eye function, and propose future research avenues. Copyright © 2010 Wiley Periodicals, Inc.

  16. Intact renewal after extinction of conditioned suppression with lesions of either the retrosplenial cortex or dorsal hippocampus.

    Science.gov (United States)

    Todd, Travis P; Jiang, Matthew Y; DeAngeli, Nicole E; Bucci, David J

    2017-03-01

    Extinction of fear to a Pavlovian conditioned stimulus (CS) is known to be context-specific. When the CS is tested outside the context of extinction, fear returns, or renews. Several studies have demonstrated that renewal depends upon the hippocampus, although there are also studies where renewal was not impacted by hippocampal damage, suggesting that under some conditions context encoding and/or retrieval of extinction depends upon other regions. One candidate region is the retrosplenial cortex (RSC), which is known to contribute to contextual and spatial learning and memory. Using a conditioned-suppression paradigm, Experiment 1 tested the impact of pre-training RSC lesions on renewal of extinguished fear. Consistent with previous studies, lesions of the RSC did not impact acquisition or extinction of conditioned fear to the CS. Further, there was no evidence that RSC lesions impaired renewal, indicating that contextual encoding and/or retrieval of extinction does not depend upon the RSC. In Experiment 2, post-extinction lesions of either the RSC or dorsal hippocampus (DH) also had no impact on renewal. However, in Experiment 3, both RSC and DH lesions did impair performance in an object-in-place procedure, an index of place memory. RSC and DH contributions to extinction and renewal are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Inhalation of air polluted with gasoline vapours alters the levels of amino acid neurotransmitters in the cerebral cortex, hippocampus, and hypothalamus of the rat.

    Science.gov (United States)

    Kinawy, Amal A; Ezzat, Ahmed R; Al-Suwaigh, Badryah R

    2014-08-01

    This study was designed to investigate the impact of exposure to the vapours of two kinds of gasoline, a widely used fuel for the internal combustion engines on the levels of the amino acid neurotransmitters of the rat brain. Recent studies provide strong evidence for a causative role for traffic-related air pollution on morbidity outcomes as well as premature death (Health Effects Institute, 2009; Levy et al., 2010; von Stackelberg et al., 2013). Exposure to the vapours of gasoline or its constituents may be accidental, occupational by workers at fuel stations and factories, or through abuse as a mean of mood alteration (Fortenberry, 1985; Mc Garvey et al., 1999). Two kinds of gasoline that are common in Egypt have been used in this study. The first contains octane enhancers in the form of lead derivatives (leaded gasoline; G1) and the other contains methyl-tertiary butyl ether (MTBE) as the octane enhancer (unleaded gasoline; G2). The levels of the major excitatory (aspartic acid and glutamic acid) and the inhibitory (GABA and glycine) amino acid neurotransmitters were determined in the cerebral cortex, hippocampus, and hypothalamus. The current study revealed that the acute inhalation of air polluted with the two types of gasoline vapours (1/2 LC50 for 30 min) induced elevation in the levels of aspartic and glutamic acids along with a decrease in glycine and GABA in most studied brain areas. Chronic inhalation of both types of gasoline (a single daily 30-min session of 1/5 LC50 for 60 days) caused a significant increase in the aspartic and glutamic acid concentrations of the hippocampus without affecting the levels of GABA or glycine. Acute and chronic inhalation of either one of G1 and G2 vapours induced a disturbance and fluctuation in the levels of the free amino acids that act as excitatory and inhibitory neurotransmitters in the brain areas under investigation. These neurotransmitters are fundamental for the communicative functioning of the neurons and such

  18. 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

    Within one experiment and one T-maze, we examined the consequences of (i) bilateral lesions of the anteromedial prefrontal cortex (PFC), (ii) bilateral transections of the fimbria-fornix (FF), or (iii) combined lesions of both PFC and FF (COMB) on rats' ability to perform reversal or set...

  19. Activity of the anterior cingulate cortex and ventral hippocampus underlie increases in contextual fear generalization.

    Science.gov (United States)

    Cullen, Patrick K; Gilman, T Lee; Winiecki, Patrick; Riccio, David C; Jasnow, Aaron M

    2015-10-01

    Memories for context become less specific with time resulting in animals generalizing fear from training contexts to novel contexts. Though much attention has been given to the neural structures that underlie the long-term consolidation of a context fear memory, very little is known about the mechanisms responsible for the increase in fear generalization that occurs as the memory ages. Here, we examine the neural pattern of activation underlying the expression of a generalized context fear memory in male C57BL/6J mice. Animals were context fear conditioned and tested for fear in either the training context or a novel context at recent and remote time points. Animals were sacrificed and fluorescent in situ hybridization was performed to assay neural activation. Our results demonstrate activity of the prelimbic, infralimbic, and anterior cingulate (ACC) cortices as well as the ventral hippocampus (vHPC) underlie expression of a generalized fear memory. To verify the involvement of the ACC and vHPC in the expression of a generalized fear memory, animals were context fear conditioned and infused with 4% lidocaine into the ACC, dHPC, or vHPC prior to retrieval to temporarily inactivate these structures. The results demonstrate that activity of the ACC and vHPC is required for the expression of a generalized fear memory, as inactivation of these regions returned the memory to a contextually precise form. Current theories of time-dependent generalization of contextual memories do not predict involvement of the vHPC. Our data suggest a novel role of this region in generalized memory, which should be incorporated into current theories of time-dependent memory generalization. We also show that the dorsal hippocampus plays a prolonged role in contextually precise memories. Our findings suggest a possible interaction between the ACC and vHPC controls the expression of fear generalization. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Fluoride and arsenic exposure impairs learning and memory and decreases mGluR5 expression in the hippocampus and cortex in rats.

    Science.gov (United States)

    Jiang, Shoufang; Su, Jing; Yao, Sanqiao; Zhang, Yanshu; Cao, Fuyuan; Wang, Fei; Wang, Huihui; Li, Jun; Xi, Shuhua

    2014-01-01

    Fluoride and arsenic are two common inorganic contaminants in drinking water that are associated with impairment in child development and retarded intelligence. The present study was conducted to explore the effects on spatial learning, memory, glutamate levels, and group I metabotropic glutamate receptors (mGluRs) expression in the hippocampus and cortex after subchronic exposure to fluoride, arsenic, and a fluoride and arsenic combination in rats. Weaned male Sprague-Dawley rats were assigned to four groups. The control rats drank tap water. Rats in the three exposure groups drank water with sodium fluoride (120 mg/L), sodium arsenite (70 mg/L), and a sodium fluoride (120 mg/L) and sodium arsenite (70 mg/L) combination for 3 months. Spatial learning and memory was measured in Morris water maze. mGluR1 and mGluR5 mRNA and protein expression in the hippocampus and cortex was detected using RT-PCR and Western blot, respectively. Compared with controls, learning and memory ability declined in rats that were exposed to fluoride and arsenic both alone and combined. Combined fluoride and arsenic exposure did not have a more pronounced effect on spatial learning and memory compared with arsenic and fluoride exposure alone. Compared with controls, glutamate levels decreased in the hippocampus and cortex of rats exposed to fluoride and combined fluoride and arsenic, and in cortex of arsenic-exposed rats. mGluR5 mRNA and protein expressions in the hippocampus and mGluR5 protein expression in the cortex decreased in rats exposed to arsenic alone. Interestingly, compared with fluoride and arsenic exposure alone, fluoride and arsenic combination decreased mGluR5 mRNA expression in the cortex and protein expression in the hippocampus, suggesting a synergistic effect of fluoride and arsenic. These data indicate that fluoride and arsenic, either alone or combined, can decrease learning and memory ability in rats. The mechanism may be associated with changes of glutamate level and

  1. 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.

  2. 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, Per; Vedel, J-C; Olesen, J

    2011-01-01

    . 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 h...

  3. 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

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

    Science.gov (United States)

    Gupta, Shailesh Kumar; Behera, Kumaresh; Pradhan, C. R.; Mandal, Arun Kumar; Sethy, Kamdev; Behera, Dayanidhi; Shinde, Kuladip Prakash

    2016-01-01

    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 developed

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

    Science.gov (United States)

    Gupta, Shailesh Kumar; Behera, Kumaresh; Pradhan, C R; Mandal, Arun Kumar; Sethy, Kamdev; Behera, Dayanidhi; Shinde, Kuladip Prakash

    2016-05-01

    The aim of this study was to study the anatomy of different parts of brain and histology of hippocampus of Vencobb broiler chicken. 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. 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. 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 developed, whereas optic lobes were rounded and large. The exact

  6. 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.

  7. Distinct behavioral consequences of short-term and prolonged GABAergic depletion in prefrontal cortex and dorsal hippocampus

    Directory of Open Access Journals (Sweden)

    Judith M. Reichel

    2015-01-01

    Full Text Available GABAergic interneurons are essential for a functional equilibrium between excitatory and inhibitory impulses throughout the CNS. Disruption of this equilibrium can lead to various neurological or neuropsychiatric disorders such as epileptic seizures or schizophrenia. Schizophrenia itself is clinically defined by negative- (e.g. depression and positive- (e.g. hallucinations symptoms as well as cognitive dysfunction. GABAergic interneurons are proposed to play a central role in the etiology and progression of schizophrenia; however, the specific mechanisms and the time-line of symptom development as well as the distinct involvement of cortical and hippocampal GABAergic interneurons in the etiology of schizophrenia-related symptoms are still not conclusively resolved.Previous work demonstrated that GABAergic interneurons can be selectively depleted in adult mice by means of saporin-conjugated anti-vesicular GABA transporter antibodies (SAVAs in vitro and in vivo. Given their involvement in Schizophrenia-related disease etiology, we ablated GABAergic interneurons in the medial prefrontal cortex (mPFC and dorsal hippocampus (dHPC in adult male C57BL/6N mice. Subsequently we assessed alterations in anxiety, sensory processing, hyperactivity and cognition after long-term (>14 days and short-term (< 14 days GABAergic depletion. Long-term GABAergic depletion in the mPFC resulted in a decrease in sensorimotor-gating and impairments in cognitive flexibility. Notably, the same treatment at the level of the dHPC completely abolished spatial learning capabilities. Short-term GABAergic depletion in the dHPC revealed a transient hyperactive phenotype as well as marked impairments regarding the acquisition of a spatial memory. In contrast, recall of a spatial memory was not affected by the same intervention. These findings emphasize the importance of functional local GABAergic networks for the encoding but not the recall of hippocampus-dependent spatial memories.

  8. From hippocampus to whole-brain: The role of integrative processing in episodic memory retrieval.

    Science.gov (United States)

    Geib, Benjamin R; Stanley, Matthew L; Dennis, Nancy A; Woldorff, Marty G; Cabeza, Roberto

    2017-04-01

    Multivariate functional connectivity analyses of neuroimaging data have revealed the importance of complex, distributed interactions between disparate yet interdependent brain regions. Recent work has shown that topological properties of functional brain networks are associated with individual and group differences in cognitive performance, including in episodic memory. After constructing functional whole-brain networks derived from an event-related fMRI study of memory retrieval, we examined differences in functional brain network architecture between forgotten and remembered words. This study yielded three main findings. First, graph theory analyses showed that successfully remembering compared to forgetting was associated with significant changes in the connectivity profile of the left hippocampus and a corresponding increase in efficient communication with the rest of the brain. Second, bivariate functional connectivity analyses indicated stronger interactions between the left hippocampus and a retrieval assembly for remembered versus forgotten items. This assembly included the left precuneus, left caudate, bilateral supramarginal gyrus, and the bilateral dorsolateral superior frontal gyrus. Integrative properties of the retrieval assembly were greater for remembered than forgotten items. Third, whole-brain modularity analyses revealed that successful memory retrieval was marginally significantly associated with a less segregated modular architecture in the network. The magnitude of the decreases in modularity between remembered and forgotten conditions was related to memory performance. These findings indicate that increases in integrative properties at the nodal, retrieval assembly, and whole-brain topological levels facilitate memory retrieval, while also underscoring the potential of multivariate brain connectivity approaches for providing valuable new insights into the neural bases of memory processes. Hum Brain Mapp 38:2242-2259, 2017. © 2017 Wiley

  9. Tamoxifen favoured the rat sensorial cortex regeneration after a penetrating brain injury.

    Science.gov (United States)

    Franco Rodríguez, N E; Dueñas Jiménez, J M; De la Torre Valdovinos, B; López Ruiz, J R; Hernández Hernández, L; Dueñas Jiménez, S H

    2013-09-01

    A penetrating brain injury produces a glial scar formed by astrocytes, oligodendrocytes, microglia and NG2 cells. Glial scar is a barrier preventing the extent of damage but it has deleterious effects in the regeneration of the axons. Estradiol and tamoxifen reduce gliosis and have neuroprotective effects in the hippocampus and the spinal cord. We evaluated the proliferation of glia and the electrocorticogram in the sensorial cortex in a brain injury model. At seven days post-injury, estradiol, tamoxifen and estradiol plus tamoxifen reduced the number of resident and proliferative NG2 and reactive astrocyte vimentin+ cells. Estradiol and tamoxifen effects on NG2 cells could be produced by the classical oestrogen receptors found in these cells. The glial scar was also reduced by tamoxifen. At thirty days post-injury, the amount of resident and proliferative astrocytes increased significantly, except in the estradiol plus tamoxifen group, whilst the oligodendrocytes proliferation in the glial scar was reduced in treated animals. Tamoxifen promotes the survival of FOX-3+ neurons in the injured area and a recovery in the amplitude of electrocorticogram waves. At thirty days, estradiol did not favour the survival of neurons but produced a greater number of reactive astrocytes. In contrast, the number of oligodendrocytes was reduced. Tamoxifen could favour brain repair promoting neuron survival and adjusting glial cell number. It seems to recover adequate neural communication. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. 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.

  11. Andrographolide - A promising therapeutic agent, negatively regulates glial cell derived neurodegeneration of prefrontal cortex, hippocampus and working memory impairment.

    Science.gov (United States)

    Das, Sudeshna; Mishra, K P; Ganju, Lilly; Singh, S B

    2017-12-15

    Over activation of glial cell derived innate immune factors induces neuro-inflammation that results in neurodegenerative disease, like working memory impairment. In this study, we have investigated the role of andrographolide, a major constituent of Andrographis paniculata plant, in reduction of reactive glial cell derived working memory impairment. Real time PCR, Western bloting, flow cytometric and immunofluorescence studies demonstrated that andrographolide inhibited lipopolysaccharide (LPS)-induced overexpression of HMGB1, TLR4, NFκB, COX-2, iNOS, and release of inflammatory mediators in primary mix glial culture, adult mice prefrontal cortex and hippocampus region. Active microglial and reactive astrocytic makers were also downregulated after andrographolide treatment. Andrographolide suppressed overexpression of microglial MIP-1α, P2X7 receptor and its downstream signaling mediators including-inflammasome NLRP3, caspase1 and mature IL-1β. Furthermore, in vivo maze studies suggested that andrographolide treatment reversed LPS-induced behavioural and working memory disturbances including regulation of expression of protein markers like PKC, p-CREB, amyloid beta, APP, p-tau, synapsin and PSD-95. Andrographolide, by lowering expression of pro apoptotic genes and enhancing the expression of anti-apoptotic gene showed its anti-apoptotic nature that in turn reduces neurodegeneration. Morphology studies using Nissl and FJB staining also showed the neuroprotective effect of andrographolide in the prefrontal cortex region. The above studies indicated that andrographolide prevented neuroinflammation-associated neurodegeneration and improved synaptic plasticity markers in cortical as well as hippocampal region which suggests that andrographolide could be a novel pharmacological countermeasure for the treatment of neuroinflammation and neurological disorders related to memory impairment. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    Dominguez, Gaelle; Faucher, Pierre; Henkous, Nadia; Krazem, Ali; Piérard, Christophe; Béracochéa, Daniel

    2014-01-01

    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 MRP and that corticosterone is critically involved in mediating the deleterious effects of stress on cognitive functions involving the mPFC-HPC interplay.

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

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    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

  14. Radiological distribution of brain metastases and its implication for the hippocampus avoidance in whole brain radiotherapy approach.

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    Han, Yi-Min; Cai, Gang; Chai, Wei-Min; Xu, Cheng; Cao, Lu; Ou, Dan; Chen, Jia-Yi; Kirova, Youlia M

    2017-11-01

    Hippocampus avoidance in whole brain radiotherapy (HA-WBRT) offers the feasibility of less-impaired cognitive function than conventional WBRT. The study aims to assess the radiological distribution of brain metastases (BMs) with relation to the hippocampus and peri-hippocampus region as defined by the RTOG 0933 for better understanding of margin definition in HA-WBRT treatment planning. Consecutive patients with diagnosis of BM from enhanced MRI between March 2011 and July 2016 were analysed. The pre-treatment T1 weighted, T2 weighted, T2 flair, three-dimensional spoiled gradient axial and contrast-enhanced axial cranial MR images of 226 patients are examined. The closest distances between the edge of hippocampus and the margin of tumours on different planes were measured. A total of 226 patients with 1080 visible metastatic sites were reviewed. The origin of the primary tumors was in 72.6% lung (n = 164), in 45 cases (19.9%) breast cancer and in 7.5% other malignancies (n = 17). There were 758 (70.2%) lesions situated beyond the tentorium. The median size of single lesion was 13.9 ± 14.7 mm. Impossible, it seems that more of the patients are with only one lesion, to verify. The hippocampus involvement was found in 3.1% (n = 7, 95% CI 0.01-0.05) within 5 mm, 5.7% (n = 13, 95% CI 0.03-0.09) within 10mm and 8.4% (n = 19, 95% CI 0.05-0.12) within 20 mm. In multivariate analysis, the number 6 BM or higher was found to be an independent risk factor for hippocampal involvement (HI) (OR: 5.2, 5.38 and 3.84 in 5, 10 and 20 mm). This radiological study found that the incidence of hippocampus involvement is low in patients with BM. HA-WBRT can be delivered under the context of complete radiological diagnosis after careful delineation, proper margin definition and individual planning optimization. Advances in knowledge: The incidence of HI in patients with initial diagnosis of BM from solid tumours impacts the radiotherapeutic decision. Our radiological data analysed the

  15. Recognition memory for social and non-social odors: differential effects of neurotoxic lesions to the hippocampus and perirhinal cortex.

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    Feinberg, Leila M; Allen, Timothy A; Ly, Denise; Fortin, Norbert J

    2012-01-01

    The contributions of the hippocampus (HC) and perirhinal cortex (PER) to recognition memory are currently topics of debate in neuroscience. Here we used a rapidly-learned (seconds) spontaneous novel odor recognition paradigm to assess the effects of pre-training N-methyl-D-aspartate lesions to the HC or PER on odor recognition memory. We tested memory for both social and non-social odor stimuli. Social odors were acquired from conspecifics, while non-social odors were household spices. Conspecific odor stimuli are ethologically-relevant and have a high degree of overlapping features compared to non-social household spices. Various retention intervals (5 min, 20 min, 1h, 24h, or 48 h) were used between study and test phases, each with a unique odor pair, to assess changes in novelty preference over time. Consistent with findings in other paradigms, modalities, and species, we found that HC lesions yielded no significant recognition memory deficits. In contrast, PER lesions caused significant deficits for social odor recognition memory at long retention intervals, demonstrating a critical role for PER in long-term memory for social odors. PER lesions had no effect on memory for non-social odors. The results are consistent with a general role for PER in long-term recognition memory for stimuli that have a high degree of overlapping features, which must be distinguished by conjunctive representations. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Disparate Effects of Lithium and a GSK-3 Inhibitor on Neuronal Oscillatory Activity in Prefrontal Cortex and Hippocampus

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    Tuan Nguyen

    2018-01-01

    Full Text Available Glycogen synthase kinase-3 (GSK-3 plays a critical role in cognitive dysfunction associated with Alzheimer’s disease (AD, yet the mechanism by which GSK-3 alters cognitive processes in other disorders, such as schizophrenia, remains unknown. In the present study, we demonstrated a role for GSK-3 in the direct regulation of neuronal oscillations in hippocampus (HIP and prelimbic cortex (PL. A comparison of the GSK-3 inhibitors SB 216763 and lithium demonstrated disparate effects of the drugs on spatial memory and neural oscillatory activity in HIP and PL. SB 216763 administration improved spatial memory whereas lithium treatment had no effect. Analysis of neuronal local field potentials in anesthetized animals revealed that whereas both repeated SB 216763 (2.5 mg/kg and lithium (100 mg/kg induced a theta frequency spike in HIP at approximately 10 Hz, only SB 216763 treatment induced an overall increase in theta power (4–12 Hz compared to vehicle. Acute administration of either drug suppressed slow (32–59 Hz and fast (61–100 Hz gamma power. In PL, both drugs induced an increase in theta power. Repeated SB 216763 increased HIP–PL coherence across all frequencies except delta, whereas lithium selectively suppressed delta coherence. These findings demonstrate that GSK-3 plays a direct role in the regulation of theta oscillations in regions critically involved in cognition, and highlight a potential mechanism by which GSK-3 may contribute to cognitive decline in disorders of cognitive dysfunction.

  17. Selective increases of AMPA, NMDA and kainate receptor subunit mRNAs in the hippocampus and orbitofrontal cortex but not in prefrontal cortex of human alcoholics

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    Zhe eJin

    2014-01-01

    Full Text Available Glutamate is the main excitatory transmitter in the human brain. Drugs that affect the glutamatergic signaling will alter neuronal excitability. Ethanol inhibits glutamate receptors. We examined the expression level of glutamate receptor subunit mRNAs in human post-mortem samples from alcoholics and compared the results to brain samples from control subjects. RNA from hippocampal dentate gyrus (HP-DG, orbitofrontal cortex (OFC, and dorso-lateral prefrontal cortex (DL-PFC samples from 21 controls and 19 individuals with chronic alcohol dependence were included in the study. Total RNA was assayed using quantitative RT-PCR. Out of the 16 glutamate receptor subunits, mRNAs encoding two AMPA (2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-ylpropanoic acid receptor subunits GluA2 and GluA3; three kainate receptor subunits GluK2, GluK3 and GluK5 and five NMDA (N-methyl-D-aspartate receptor subunits GluN1, GluN2A, GluN2C, GluN2D and GluN3A were significantly increased in the HP-DG region in alcoholics. In the OFC, mRNA encoding the NMDA receptor subunit GluN3A was increased, whereas in the DL-PFC, no differences in mRNA levels were observed. Our laboratory has previously shown that the expression of genes encoding inhibitory GABA-A receptors is altered in the HP-DG and OFC of alcoholics (Jin et al., 2011. Whether the changes in one neurotransmitter system drives changes in the other or if they change independently is currently not known. The results demonstrate that excessive long-term alcohol consumption is associated with altered expression of genes encoding glutamate receptors in a brain region-specific manner. It is an intriguing possibility that genetic predisposition to alcoholism may contribute to these gene expression changes.

  18. Traumatic brain injury dysregulates microRNAs to modulate cell signaling in rat hippocampus.

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    Liang Liu

    Full Text Available Traumatic brain injury (TBI is a common cause for cognitive and communication problems, but the molecular and cellular mechanisms are not well understood. Epigenetic modifications, such as microRNA (miRNA dysregulation, may underlie altered gene expression in the brain, especially hippocampus that plays a major role in spatial learning and memory and is vulnerable to TBI. To advance our understanding of miRNA in pathophysiological processes of TBI, we carried out a time-course microarray analysis of microRNA expression profile in rat ipsilateral hippocampus and examined histological changes, apoptosis and synapse ultrastructure of hippocampus post moderate TBI. We found that 10 out of 156 reliably detected miRNAs were significantly and consistently altered from one hour to seven days after injury. Bioinformatic and gene ontology analyses revealed 107 putative target genes, as well as several biological processes that might be initiated by those dysregulated miRNAs. Among those differentially expressed microRNAs, miR-144, miR-153 and miR-340-5p were confirmed to be elevated at all five time points after TBI by quantitative RT-PCR. Western blots showed three of the predicated target proteins, calcium/calmodulin-dependent serine protein kinase (CASK, nuclear factor erythroid 2-related factor 2 (NRF2 and alpha-synuclein (SNCA, were concurrently down- regulated, suggesting that miR-144, miR-153 and miR-340-5p may play important roles collaboratively in the pathogenesis of TBI-induced cognitive and memory impairments. These microRNAs might serve as potential targets for progress assessment and intervention against TBI to mitigate secondary damage to the brain.

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

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    Iraj Salehi

    2010-06-01

    Full Text Available Objective(sThe 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 GR and oxidant indexes with brain-derived neurotrophic factor (BDNF protein and its mRNA and apoptosis were measured in hippocampus of rats. ResultsA significant decrease in antioxidant enzymes activities and increased malondialdehyde (MDA level were observed in diabetic rats (P= 0.004. In response to exercise, antioxidant enzymes activities increased (P= 0.004. In contrast, MDA level decreased in diabetic rats (P= 0.004. Induction of diabetes caused an increase of BDNF protein and its mRNA expression. In response to exercise, BDNF protein and its mRNA expression reduced in hippocampus of diabetic rats. ConclusionDiabetes induced oxidative stress and increased BDNF gene expression. Exercise ameliorated oxidative stress and decreased BDNF gene expression.

  20. Prenatal stress alters Fos protein expression in hippocampus and locus coeruleus stress-related brain structures.

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    Viltart, Odile; Mairesse, Jérôme; Darnaudéry, Muriel; Louvart, Hélène; Vanbesien-Mailliot, Christel; Catalani, Assia; Maccari, Stefania

    2006-07-01

    Prenatal stress (PS) durably influences responses of rats from birth throughout life by inducing deficits of the hypothalamo-pituitary-adrenal (HPA) axis feedback. The neuronal mechanisms sustaining such alterations are still unknown. The purpose of the present study was to determine whether in PS and control rats, the exposure to a mild stressor differentially induces Fos protein in hippocampus and locus coeruleus, brain areas involved in the feedback control of the HPA axis. Moreover, Fos protein expression was also evaluated in the hypothalamic paraventricular nucleus (PVN) that reflect the magnitude of the hormonal response to stress. Basal plasma corticosterone levels were not different between the groups, while, PS rats exhibited higher number of Fos-immunoreactive neurons than controls, in the hippocampus and locus coeruleus in basal condition. A higher basal expression of a marker of GABAergic synapses, the vGAT, was also observed in the hypothalamus of PS rats. Fifteen minutes after the end of the exposure to the open arm of the elevated plus-maze (mild stress) a similar increased plasma corticosterone levels was observed in both groups in parallel with an increased number of Fos-immunoreactive neurons in the PVN. Return to basal plasma corticosterone values was delayed only in the PS rats. On the contrary, after stress, no changes in Fos-immunoreactivity were observed in the hippocampus and locus coeruleus of PS rats compared to basal condition. After stress, only PS rats presented an elevation of the number of activated catecholaminergic neurons in the locus coeruleus. In conclusion, these results suggest for the first time that PS alters the neuronal activation of hippocampus and locus coeruleus implicated in the feedback mechanism of the HPA axis. These data give anatomical substrates to sustain the HPA axis hyperactivity classically described in PS rats after stress exposure.

  1. 350-μm side-view optical probe for imaging the murine brain in vivo from the cortex to the hypothalamus

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    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.

  2. Repeated injections of D-Amphetamine evoke rapid and dynamic changesin phase synchrony between the prefrontal cortex and hippocampus

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    SUNGWOO eAHN

    2013-07-01

    Full Text Available Repeated drug use evokes a number of persistent alterations in oscillatory power and synchrony. How synchronous activity in cortico-hippocampal circuits is progressively modified with repeated drug exposure, however, remains to be characterized. Drugs of abuse induce both short-term and long-term adaptations in cortical and hippocampal circuits and these changes are likely important for the expression of the altered behavioral and neurobiological phenotype associated with addiction. The present study explores how the initial (up to one hour pharmacological response to D-Amphetamine (AMPH is altered with repeated injections in the rat. The methods employed herein allow for the progressive changes in synchronized dynamics with repeated intermittent AMPH exposure to be characterized over short time scales (minutes. Specifically, we examined the temporal variations of phase-locking strength in delta and theta bands within the prefrontal cortex (PFC and between PFC and hippocampus (HC shortly after drug injection. After the first injection of AMPH synchrony increased within the PFC in the delta band, which was followed, by an increase in theta synchrony between the PFC and HC several minutes later. This relationship switched after repeated AMPH injections, where increases in theta synchrony between the PFC and HC preceded increases in delta synchrony in the PFC. The time-course of increases in synchronous activity were negatively correlated between the PFC delta and the PFC-HC theta. Collectively these data highlight the potential role of PFC-HC circuits in the development of addiction and outline dynamic changes in the time-course that cortico-hippocampal circuits become synchronized with repeated AMPH exposure.

  3. Comparison of doses received by the hippocampus in patients treated with single isocenter– vs multiple isocenter–based stereotactic radiation therapy to the brain for multiple brain metastases

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    Algan, Ozer, E-mail: oalgan@ouhsc.edu; Giem, Jared; Young, Julie; Ali, Imad; Ahmad, Salahuddin; Hossain, Sabbir

    2015-01-01

    To investigate the doses received by the hippocampus and normal brain tissue during a course of stereotactic radiation therapy using a single isocenter (SI)–based or multiple isocenter (MI)–based treatment planning in patients with less than 4 brain metastases. In total, 10 patients with magnetic resonance imaging (MRI) demonstrating 2-3 brain metastases were included in this retrospective study, and 2 sets of stereotactic intensity-modulated radiation therapy (IMRT) treatment plans (SI vs MI) were generated. The hippocampus was contoured on SPGR sequences, and doses received by the hippocampus and the brain were calculated and compared between the 2 treatment techniques. A total of 23 lesions in 10 patients were evaluated. The median tumor volume, the right hippocampus volume, and the left hippocampus volume were 3.15, 3.24, and 2.63 mL, respectively. In comparing the 2 treatment plans, there was no difference in the planning target volume (PTV) coverage except in the tail for the dose-volume histogram (DVH) curve. The only statistically significant dosimetric parameter was the V{sub 100}. All of the other measured dosimetric parameters including the V{sub 95}, V{sub 99}, and D{sub 100} were not significantly different between the 2 treatment planning techniques. None of the dosimetric parameters evaluated for the hippocampus revealed any statistically significant difference between the MI and SI plans. The total brain doses were slightly higher in the SI plans, especially in the lower dose region, although this difference was not statistically different. The use of SI-based treatment plan resulted in a 35% reduction in beam-on time. The use of SI treatments for patients with up to 3 brain metastases produces similar PTV coverage and similar normal tissue doses to the hippocampus and the brain when compared with MI plans. SI treatment planning should be considered in patients with multiple brain metastases undergoing stereotactic treatment.

  4. Traumatic Brain Injury Causes Aberrant Migration of Adult-Born Neurons in the Hippocampus.

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    Ibrahim, Sara; Hu, Weipeng; Wang, Xiaoting; Gao, Xiang; He, Chunyan; Chen, Jinhui

    2016-02-22

    Traumatic brain injury (TBI) promotes neural stem/progenitor cell (NSC) proliferation in an attempt to initiate innate repair mechanisms. However, all immature neurons in the CNS are required to migrate from their birthplace to their final destination to develop into functional neurons. Here we assessed the destination of adult-born neurons following TBI. We found that a large percentage of immature neurons migrated past their normal stopping site at the inner granular cell layer (GCL), and became misplaced in the outer GCL of the hippocampal dentate gyrus. The aberrant migration of adult-born neurons in the hippocampus occurred 48 hours after TBI, and lasted for 8 weeks, resulting in a great number of newly generated neurons misplaced in the outer GCL in the hippocampus. Those misplaced neurons were able to become mature and differentiate into granular neurons, but located ectopically in the outer GCL with reduced dendritic complexity after TBI. The adult-born neurons at the misplaced position may make wrong connections with inappropriate nearby targets in the pre-existing neural network. These results suggest that although stimulation of endogenous NSCs following TBI might offer new avenues for cell-based therapy, additional intervention is required to further enhance successful neurogenesis for repairing the damaged brain.

  5. Propofol selectively alters GluA1 AMPA receptor phosphorylation in the hippocampus but not prefrontal cortex in young and aged mice

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    Mao, Li-Min; Hastings, James M.; Fibuch, Eugene E; Wang, John Q.

    2014-01-01

    Propofol is a commonly used general anesthetic agent which has been previously shown to enhance the inhibitory GABAergic transmission in the central nervous system. In addition to the GABAergic element, the excitatory transmission may be another central molecular site impacted by propofol. Increasing evidence implies that the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor represents an excitatory amino acid receptor subtype subjected to the regulation by propofol. Indeed, in this study, we found that a single injection of propofol at an anesthetic dose increased AMPA receptor GluA1 subunit phosphorylation in young (2–3 months old) and aged (20–21 months old) mice in vivo. Propofol caused an increase in GluA1 phosphorylation in the hippocampus but not in the prefrontal cortex. The propofol effect was also site-selective as the drug elevated GluA1 phosphorylation at serine 831 (S831) but not serine 845. Interestingly, while propofol induced a moderate and transient increase in S831 phosphorylation in young mice, the drug caused a substantial and sustained S831 phosphorylation in aged animals. Total GluA1 abundance remained stable in the hippocampus and prefrontal cortex in both young and aged mice in response to propofol. These results provide evidence supporting the sensitivity of GluA1 AMPA receptors to propofol. A single dose of propofol was able to upregulate GluA1 phosphorylation in the confined hippocampus in an age-dependent manner. PMID:24907515

  6. Porcine brain natriuretic peptide receptor in bovine adrenal cortex

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    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).

  7. Exposure to 835 MHz radiofrequency electromagnetic field induces autophagy in hippocampus but not in brain stem of mice.

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    Kim, Ju Hwan; Yu, Da-Hyeon; Kim, Hyo-Jeong; Huh, Yang Hoon; Cho, Seong-Wan; Lee, Jin-Koo; Kim, Hyung-Gun; Kim, Hak Rim

    2017-01-01

    The exploding popularity of mobile phones and their close proximity to the brain when in use has raised public concern regarding possible adverse effects from exposure to radiofrequency electromagnetic fields (RF-EMF) on the central nervous system. Numerous studies have suggested that RF-EMF emitted by mobile phones can influence neuronal functions in the brain. Currently, there is still very limited information on what biological mechanisms influence neuronal cells of the brain. In the present study, we explored whether autophagy is triggered in the hippocampus or brain stem after RF-EMF exposure. C57BL/6 mice were exposed to 835 MHz RF-EMF with specific absorption rates (SAR) of 4.0 W/kg for 12 weeks; afterward, the hippocampus and brain stem of mice were dissected and analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated that several autophagic genes, which play key roles in autophagy regulation, were significantly upregulated only in the hippocampus and not in the brain stem. Expression levels of LC3B-II protein and p62, crucial autophagic regulatory proteins, were significantly changed only in the hippocampus. In parallel, transmission electron microscopy (TEM) revealed an increase in the number of autophagosomes and autolysosomes in the hippocampal neurons of RF-EMF-exposed mice. The present study revealed that autophagy was induced in the hippocampus, not in the brain stem, in 835 MHz RF-EMF with an SAR of 4.0 W/kg for 12 weeks. These results could suggest that among the various adaptation processes to the RF-EMF exposure environment, autophagic degradation is one possible mechanism in specific brain regions.

  8. Insulin improves memory and reduces chronic neuroinflammation in the hippocampus of young but not aged brains.

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    Adzovic, Linda; Lynn, Ashley E; D'Angelo, Heather M; Crockett, Alexis M; Kaercher, Roxanne M; Royer, Sarah E; Hopp, Sarah C; Wenk, Gary L

    2015-04-02

    The role of insulin in the brain is still not completely understood. In the periphery, insulin can decrease inflammation induced by lipopolysaccharide (LPS); however, whether insulin can reduce inflammation within the brain is unknown. Experiments administrating intranasal insulin to young and aged adults have shown that insulin improves memory. In our animal model of chronic neuroinflammation, we administered insulin and/or LPS directly into the brain via the fourth ventricle for 4 weeks in young rats; we then analyzed their spatial memory and neuroinflammatory response. Additionally, we administered insulin or artificial cerebral spinal fluid (aCSF), in the same manner, to aged rats and then analyzed their spatial memory and neuroinflammatory response. Response to chronic neuroinflammation in young rats was analyzed in the presence or absence of insulin supplementation. Here, we show for the first time that insulin infused (i.c.v.) to young rats significantly attenuated the effects of LPS by decreasing the expression of neuroinflammatory markers in the hippocampus and by improving performance in the Morris water pool task. In young rats, insulin infusion alone significantly improved their performance as compared to all other groups. Unexpectedly, in aged rats, the responsiveness to insulin was completely absent, that is, spatial memory was still impaired suggesting that an age-dependent insulin resistance may contribute to the cognitive impairment observed in neurodegenerative diseases. Our data suggest a novel therapeutic effect of insulin on neuroinflammation in the young but not the aged brain.

  9. Negative effects of ultrafine particle exposure during forced exercise on the expression of Brain-Derived Neurotrophic Factor in the hippocampus of rats.

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    Bos, I; De Boever, P; Int Panis, L; Sarre, S; Meeusen, R

    2012-10-25

    Exercise improves cognitive function, and Brain-Derived Neurotrophic Factor (BDNF) plays a key role in this process. We recently reported that particulate matter (PM) exposure negatively contributed to the exercise-induced increase in human serum BDNF concentration. Furthermore, PM exposure is associated with neuroinflammation and cognitive decline. The aim of this study was to investigate the effect of exposure to ultrafine particles (UFP) during a single bout of forced exercise on the expression of inflammatory (IL1α, IL1β, TNF, IL6, NOS2, NOS3) and oxidative stress (NFE2L2)-related genes, as well as BDNF in the brain of rats. Four groups (n=6/group) of Wistar rats were exposed for 90 min to one of the following exposure regimes: UFP+exercise, UFP+rest, ambient air+exercise, ambient air+rest (control). Hippocampus, olfactory bulb and prefrontal cortex were collected 24h after exposure. Gene expression changes were analyzed with real-time PCR. In the condition ambient air+exercise, hippocampal expression of BDNF and NFE2L2 was up-regulated, while the expression of IL1α and NOS3 in the prefrontal cortex and IL1α in the olfactory bulb was down-regulated compared to the control. In contrast, gene expression in the condition UFP+exercise did not differ from the control. In the condition UFP+rest, hippocampal expression of NFE2L2 was down-regulated and there was a trend toward down-regulation of BDNF expression compared to the control. This study shows a negative effect of UFP exposure on the exercise-induced up-regulation of BDNF gene expression in the hippocampus of rats. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. 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

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    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.

  11. Cross-Generational trans Fat Consumption Favors Self-Administration of Amphetamine and Changes Molecular Expressions of BDNF, DAT, and D1/D2 Receptors in the Cortex and Hippocampus of Rats.

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    Kuhn, Fábio Teixeira; Dias, Verônica Tironi; Roversi, Karine; Vey, Luciana Taschetto; de Freitas, Daniele Leão; Pase, Camila Simonetti; Roversi, Katiane; Veit, Juliana Cristina; Emanuelli, Tatiana; Bürger, Marilise Escobar

    2015-11-01

    Amphetamine (AMPH) is an addictive psychostimulant drug whose use has been related to neurotoxicity. Experimentally, AMPH increases anxiety-like symptoms, showing addictive properties. In the last decades, the growing consumption of processed foods has provided an excess of saturated and trans fats in detriment of essential fatty acids, which may modify the lipid profile of brain membranes, thus modifying its permeability and dopaminergic neurotransmission. Here, we assessed the influence of brain incorporation of different fatty acids (FA) on AMPH self-administration. Three groups of young male rats were orally supplemented from weaning with a mixture of soybean oil (SO, rich in n-6 FA) and fish oil (FO, rich in n-3 FA), hydrogenated vegetable fat (HVF, rich in trans fatty acids--TFA), or water (control group). These animals were born from dams that were supplemented with the same fat from pregnancy to lactation. Anxiety-like symptoms and locomotor index were assessed in elevated plus maze and open-field (OF), respectively, while brain molecular expressions of dopaminergic receptors, dopamine transporter (DAT), and BDNF were determined in the cortex and hippocampus. HVF increased the frequency of AMPH self-administration and was associated with reinforcement and withdrawal signs as observed by increased anxiety-like symptoms. Contrarily, SO/FO decreased these parameters. Increased BDNF protein together with decreased DAT expression was observed in the hippocampus of HVF group. Based on these findings, our study points to a harmful influence of trans fats on drug addiction and craving symptoms, whose mechanism may be related to changes in the dopaminergic neurotransmission.

  12. 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.

  13. 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.

    Science.gov (United States)

    da Silva Medeiros, Niara; Koslowsky Marder, Roberta; Farias Wohlenberg, Mariane; Funchal, Cláudia; Dani, Caroline

    2015-01-01

    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.

  14. 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

    Science.gov (United States)

    da Silva Medeiros, Niara; Koslowsky Marder, Roberta; Farias Wohlenberg, Mariane; Funchal, Cláudia; Dani, Caroline

    2015-01-01

    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. PMID:26649198

  15. 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.

  16. The hippocampus, medial prefrontal cortex, and selective memory retrieval: evidence from a rodent model of the retrieval-induced forgetting effect.

    Science.gov (United States)

    Wu, Jade Q; Peters, Greg J; Rittner, Pedro; Cleland, Thomas A; Smith, David M

    2014-09-01

    Inhibition is an important component of many cognitive functions, including memory. For example, the retrieval-induced forgetting (RIF) effect occurs when extra practice with some items from a study list inhibits the retrieval of the nonpracticed items relative to a baseline condition that does not involve extra practice. Although counterintuitive, the RIF phenomenon may be important for resolving interference by inhibiting potentially competing retrieval targets. Neuroimaging studies suggest that the hippocampus and prefrontal cortex are involved in the RIF effect, but controlled lesion studies have not yet been performed. We developed a rodent model of the RIF training procedure and trained control rats and rats with temporary inactivation of the hippocampus or medial prefrontal cortex (mPFC). Rats were trained on a list of odor cues, presented in cups of digging medium with a buried reward, followed by additional practice trials with a subset of the cues. We then tested the rats' memories for the cues and their association with reward by presenting them with unbaited cups containing the test odorants and measuring how long they persisted in digging. Control rats exhibited a robust RIF effect in which memory for the nonpracticed odors was significantly inhibited. Thus, extra practice with some odor cues inhibited memory for the others, relative to a baseline condition that involved an identical amount of training. Inactivation of either the hippocampus or the mPFC blocked the RIF effect. We also constructed a computational model of a representational learning circuit to simulate the RIF effect. We show in this model that "sideband suppression" of similar memory representations can reproduce the RIF effect and that alteration of the suppression parameters and learning rate can reproduce the lesion effects seen in our rats. Our results suggest that the RIF effect is widespread and that inhibitory processes are an important feature of memory function. © 2014 Wiley

  17. Cell-Type and State-Dependent Synchronization among Rodent Somatosensory, Visual, Perirhinal Cortex, and Hippocampus CA1

    Science.gov (United States)

    Vinck, Martin; Bos, Jeroen J.; Van Mourik-Donga, Laura A.; Oplaat, Krista T.; Klein, Gerbrand A.; Jackson, Jadin C.; Gentet, Luc J.; Pennartz, Cyriel M. A.

    2016-01-01

    Beta and gamma rhythms have been hypothesized to be involved in global and local coordination of neuronal activity, respectively. Here, we investigated how cells in rodent area S1BF are entrained by rhythmic fluctuations at various frequencies within the local area and in connected areas, and how this depends on behavioral state and cell type. We performed simultaneous extracellular field and unit recordings in four connected areas of the freely moving rat (S1BF, V1M, perirhinal cortex, CA1). S1BF spiking activity was strongly entrained by both beta and gamma S1BF oscillations, which were associated with deactivations and activations, respectively. We identified multiple classes of fast spiking and excitatory cells in S1BF, which showed prominent differences in rhythmic entrainment and in the extent to which phase locking was modulated by behavioral state. Using an additional dataset acquired by whole-cell recordings in head-fixed mice, these cell classes could be compared with identified phenotypes showing gamma rhythmicity in their membrane potential. We next examined how S1BF cells were entrained by rhythmic fluctuations in connected brain areas. Gamma-synchronization was detected in all four areas, however we did not detect significant gamma coherence among these areas. Instead, we only found long-range coherence in the theta-beta range among these areas. In contrast to local S1BF synchronization, we found long-range S1BF-spike to CA1–LFP synchronization to be homogeneous across inhibitory and excitatory cell types. These findings suggest distinct, cell-type contributions of low and high-frequency synchronization to intra- and inter-areal neuronal interactions. PMID:26834582

  18. Is the prefrontal cortex especially enlarged in the human brain allometric relations and remapping factors.

    Science.gov (United States)

    Passingham, Richard E; Smaers, Jeroen B

    2014-01-01

    There has been no agreement as to whether the prefrontal cortex is especially enlarged in the human brain. To answer this question, we analyzed the only two datasets that provide information on total prefrontal cortex volume based on cytoarchitectonic criteria. One delineated the prefrontal cortex proper on the basis of cytoarchitectonic criteria; the other used a proxy of the prefrontal cortex based on a cytoarchitectonic delineation of the frontal lobe. To investigate whether all cortical association areas, including the prefrontal cortex, are enlarged in the human brain, we scaled the different areas to a common reference, the primary visual cortex. To investigate whether the prefrontal cortex is more enlarged than other association areas, we scaled it relative to its inputs from and outputs to other nonprimary areas. We carried out separate regression analyses using different data samples as a predictive baseline group: data for monkeys alone informs us on whether great apes are different from monkeys; data for all non-human anthropoids, including great apes, informs us on whether humans are different from all other primates. The analyses show that the value for the human prefrontal cortex is greater than expected, and that this is true even when data for the great apes are included in the analysis. They also show that the chimpanzee prefrontal cortex is greater than expected for a monkey with a similar sized cortex. We discuss possible functional consequences.

  19. The bumps on the hippocampus

    Science.gov (United States)

    Gao, Yi; Ver Hoef, Lawrence

    2016-03-01

    The hippocampus has been the focus of more imaging research than any other subcortical structure in the human brain. However a feature that has been almost universally overlooked are the bumpy ridges on the inferior aspect of the hippocampus, which we refer to as hippocampal dentation. These bumps arise from folds in the CA1 layer of Ammon's horn. Similar to the folding of the cerebral cortex, hippocampal dentation allows for greater surface area in a confined space. However, while quantitative studies of radiologic brain images have been advancing for decades, examining numerous approaches to hippocampal segmentation and morphology analysis, virtually all published 3D renderings of the hippocampus show the under surface to be quite smooth or mildly irregular; we have rarely seen the characteristic bumpy structure in the reconstructed 3D scene, one exception being the 9.4T postmortem study. This is presumably due to the fact that, based on our experience with high resolution images, there is a dramatic degree of variability in hippocampal dentation between individuals from very smooth to highly dentated. An apparent question is, does this indicate that this specific morphological signature can only be captured using expensive ultra-high field techniques? Or, is such information buried in the data we commonly acquire, awaiting a computation technique that can extract and render it clearly? In this study, we propose a super-resolution technique that captures the fine scale morphometric features of the hippocampus based on common T1-weighted 3T MR images.

  20. Lesions of entorhinal cortex produce a calpain-mediated degradation of brain spectrin in dentate gyrus. I. Biochemical studies.

    Science.gov (United States)

    Seubert, P; Ivy, G; Larson, J; Lee, J; Shahi, K; Baudry, M; Lynch, G

    1988-09-06

    Lesions of the rat entorhinal cortex cause extensive synaptic restructuring and perturbation of calcium regulation in the dentate gyrus of hippocampus. Calpain is a calcium-activated protease which has been implicated in degenerative phenomena in muscles and in peripheral nerves. In addition, calpain degrades several major structural neuronal proteins and has been proposed to play a critical role in the morphological changes observed following deafferentation. In this report we present evidence that lesions of the entorhinal cortex produce a marked increase in the breakdown of brain spectrin, a substrate for calpain, in the dentate gyrus. Two lines of evidence indicate that this effect is due to calpain activation: (i) the spectrin breakdown products observed following the lesion are indistinguishable from calpain-generated spectrin fragments in vitro; and (ii) their appearance can be reduced by prior intraventricular in fusion of leupeptin, a calpain inhibitor. Levels of spectrin breakdown products are increased as early as 4 h post-lesion, reach maximal values at 2 days, and remain above normal to some degree for at least 27 days. In addition, a small but significant increase in spectrin proteolysis is also observed in the hippocampus contralateral to the lesioned side in the first week postlesion. At 2 days postlesion the total spectrin immunoreactivity (native polypeptide plus breakdown products) increases by 40%, suggesting that denervation of the dentate gyrus produces not only an increased rate of spectrin degradation but also an increased rate of spectrin synthesis. These results indicate that calpain activation and spectrin degradation are early biochemical events following deafferentation and might well participate in the remodelling of postsynaptic structures. Finally, the magnitude of the observed effects as well as the stable nature of the breakdown products provide a sensitive assay for neuronal pathology.

  1. The brain-tumor related protein podoplanin regulates synaptic plasticity and hippocampus-dependent learning and memory.

    Science.gov (United States)

    Cicvaric, Ana; Yang, Jiaye; Krieger, Sigurd; Khan, Deeba; Kim, Eun-Jung; Dominguez-Rodriguez, Manuel; Cabatic, Maureen; Molz, Barbara; Acevedo Aguilar, Juan Pablo; Milicevic, Radoslav; Smani, Tarik; Breuss, Johannes M; Kerjaschki, Dontscho; Pollak, Daniela D; Uhrin, Pavel; Monje, Francisco J

    2016-12-01

    Podoplanin is a cell-surface glycoprotein constitutively expressed in the brain and implicated in human brain tumorigenesis. The intrinsic function of podoplanin in brain neurons remains however uncharacterized. Using an established podoplanin-knockout mouse model and electrophysiological, biochemical, and behavioral approaches, we investigated the brain neuronal role of podoplanin. Ex-vivo electrophysiology showed that podoplanin deletion impairs dentate gyrus synaptic strengthening. In vivo, podoplanin deletion selectively impaired hippocampus-dependent spatial learning and memory without affecting amygdala-dependent cued fear conditioning. In vitro, neuronal overexpression of podoplanin promoted synaptic activity and neuritic outgrowth whereas podoplanin-deficient neurons exhibited stunted outgrowth and lower levels of p-Ezrin, TrkA, and CREB in response to nerve growth factor (NGF). Surface Plasmon Resonance data further indicated a physical interaction between podoplanin and NGF. This work proposes podoplanin as a novel component of the neuronal machinery underlying neuritogenesis, synaptic plasticity, and hippocampus-dependent memory functions. The existence of a relevant cross-talk between podoplanin and the NGF/TrkA signaling pathway is also for the first time proposed here, thus providing a novel molecular complex as a target for future multidisciplinary studies of the brain function in the physiology and the pathology. Key messages Podoplanin, a protein linked to the promotion of human brain tumors, is required in vivo for proper hippocampus-dependent learning and memory functions. Deletion of podoplanin selectively impairs activity-dependent synaptic strengthening at the neurogenic dentate-gyrus and hampers neuritogenesis and phospho Ezrin, TrkA and CREB protein levels upon NGF stimulation. Surface plasmon resonance data indicates a physical interaction between podoplanin and NGF. On these grounds, a relevant cross-talk between podoplanin and NGF as well

  2. Histological study on hippocampus, amygdala and cerebellum following low lead exposure during prenatal and postnatal brain development in rats.

    Science.gov (United States)

    Barkur, Rajashekar Rao; Bairy, Laxminarayana K

    2016-06-01

    Neuropsychological studies in children who are exposed to lead during their early brain development have shown to develop behavioural and cognitive deficit. The aim of the present study was to assess the cellular damage in hippocampus, amygdala and cerebellum of rat pups exposed to lead during different periods of early brain development. Five groups of rat pups were investigated. (a) Control group (n = 8) (mothers of these rats were given normal drinking water throughout gestation and lactation), (b) pregestation lead-exposed group (n = 8) (mothers of these rats were exposed to 0.2% lead acetate in the drinking water for one month before conception), (c) gestation lead-exposed group (n = 8) (exposed to 0.2% lead acetate in the drinking water through the mother throughout gestation [gestation day 01 to day 21]), (d) lactation lead-exposed group (n = 8) (exposed to 0.2% lead acetate in the drinking water through the mother throughout lactation [postnatal day 01 to day 21]) and (e) gestation and lactation lead-exposed group (n = 8) (exposed to 0.2% lead acetate throughout gestation and lactation). On postnatal day 30, rat pups of all the groups were killed. Numbers of surviving neurons in the hippocampus, amygdala and cerebellum regions were counted using cresyl violet staining technique. Histological data indicate that lead exposure caused significant damage to neurons of hippocampus, amygdala and cerebellum regions in all lead-exposed groups except lactation lead-exposed group. The extent of damage to neurons of hippocampus, amygdala and cerebellum regions in lactation lead-exposed group was comparable to gestation and lactation groups even though the duration of lead exposure was much less in lactation lead-exposed group. To conclude, the postnatal period of brain development seems to be more vulnerable to lead neurotoxicity compared to prenatal period of brain development. © The Author(s) 2014.

  3. 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 ...

  4. Frozen fruit pulp of Euterpe oleraceae Mart. (Acai) prevents hydrogen peroxide-induced damage in the cerebral cortex, cerebellum, and hippocampus of rats.

    Science.gov (United States)

    Spada, Patricia D S; Dani, Caroline; Bortolini, Giovana V; Funchal, Claudia; Henriques, João A P; Salvador, Mirian

    2009-10-01

    Oxidative stress is implicated in several human illnesses, including neurological disorders such as Parkinson's and Alzheimer's diseases. Acai is largely consumed in Brazil and contains high levels of antioxidant compounds. This work aims to study the antioxidant activity of acai frozen fruit pulp in the cerebral cortex, hippocampus, and cerebellum of rats treated with the oxidizing agent hydrogen peroxide (H(2)O(2)). Pretreatment of tissue with acai decreased H(2)O(2)-induced damage of both lipids and proteins in all tissues tested. This fruit was also able to reduce the activities of the antioxidant enzymes superoxide dismutase and catalase to basal levels. We observed a negative correlation between the polyphenol content of acai and the levels of lipid (r = -0.689; P data suggest that acai has a positive contribution in the development of age-related neurodegenerative diseases.

  5. 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.

  6. Medial Prefrontal Cortex Updates Its Status.

    Science.gov (United States)

    Cikara, Mina; Gershman, Samuel J

    2016-12-07

    How does the brain infer social status? A new study by Kumaran et al. (2016) identifies a region of the medial prefrontal cortex that, in concert with the amygdala and hippocampus, subserves updating of probabilistic beliefs about the status of individuals in a social hierarchy. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Automatic 3D graph cuts for brain cortex segmentation in patients with focal cortical dysplasia.

    Science.gov (United States)

    Despotović, Ivana; Segers, Ief; Platisa, Ljiljana; Vansteenkiste, Ewout; Pizurica, Aleksandra; Deblaere, Karel; Philips, Wilfried

    2011-01-01

    In patients with intractable epilepsy, focal cortical dysplasia (FCD) is the most frequent malformation of cortical development. Identification of subtle FCD lesions using brain MRI scans is very often based on the cortical thickness measurement, where brain cortex segmentation is required as a preprocessing step. However, the accuracy of the selected segmentation method can highly affect the final FCD lesion detection. In this work, we propose an improved graph cuts algorithm integrating Markov random field-based energy function for more accurate brain cortex MRI segmentation. Our method uses three-label graph cuts and preforms automatic 3D MRI brain cortex segmentation integrating intensity and boundary information. The performance of the method is tested on both simulated MR brain images with different noise levels and real patients with FCD lesions. Experimental quantitative segmentation results showed that the proposed method is effective, robust to noise and achieves higher accuracy than other popular brain MRI segmentation methods. The qualitative validation, visually verified by a medical expert, showed that the FCD lesions were segmented well as a part of the cortex, indicating increased thickness and cortical deformation. The proposed technique can be successfully used in this, as well as in many other clinical applications.

  8. Prolonged maternal separation attenuates BDNF-ERK signaling correlated with spine formation in the hippocampus during early brain development.

    Science.gov (United States)

    Ohta, Ken-Ichi; Suzuki, Shingo; Warita, Katsuhiko; Kaji, Tomohiro; Kusaka, Takashi; Miki, Takanori

    2017-04-01

    Maternal separation (MS) is known to affect hippocampal function such as learning and memory, yet the molecular mechanism remains unknown. We hypothesized that these impairments are attributed to abnormities of neural circuit formation by MS, and focused on brain-derived neurotrophic factor (BDNF) as key factor because BDNF signaling has an essential role in synapse formation during early brain development. Using rat offspring exposed to MS for 6 h/day during postnatal days (PD) 2-20, we estimated BDNF signaling in the hippocampus during brain development. Our results show that MS attenuated BDNF expression and activation of extracellular signal-regulated kinase (ERK) around PD 7. Moreover, plasticity-related immediate early genes, which are transcriptionally regulated by BDNF-ERK signaling, were also reduced by MS around PD 7. Interestingly, detailed analysis revealed that MS particularly reduced expression of BDNF gene and immediate early genes in the cornu ammonis 1 (CA1) of hippocampus at PD 7. Considering that BDNF-ERK signaling is involved in spine formation, we next evaluated spine formation in the hippocampus during the weaning period. Our results show that MS particularly reduced mature spine density in proximal apical dendrites of CA1 pyramidal neurons at PD 21. These results suggest that MS could attenuate BDNF-ERK signaling during primary synaptogenesis with a region-specific manner, which is likely to lead to decreased spine formation and maturation observed in the hippocampal CA1 region. It is speculated that this incomplete spine formation during early brain development has an influence on learning capabilities throughout adulthood. © 2017 International Society for Neurochemistry.

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

    Science.gov (United States)

    Kazu, Rodrigo S.; Maldonado, José; Mota, Bruno; Manger, Paul R.; Herculano-Houzel, Suzana

    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, believed to be a relatively recent radiation from the common Eutherian ancestor. We find that artiodactyls share non-neuronal 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. PMID:25429261

  10. 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.

  11. 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.

  12. Control of a brain-computer interface using stereotactic depth electrodes in and adjacent to the hippocampus

    Science.gov (United States)

    Krusienski, D. J.; Shih, J. J.

    2011-04-01

    A brain-computer interface (BCI) is a device that enables severely disabled people to communicate and interact with their environments using their brain waves. Most research investigating BCI in humans has used scalp-recorded electroencephalography or intracranial electrocorticography. The use of brain signals obtained directly from stereotactic depth electrodes to control a BCI has not previously been explored. In this study, event-related potentials (ERPs) recorded from bilateral stereotactic depth electrodes implanted in and adjacent to the hippocampus were used to control a P300 Speller paradigm. The ERPs were preprocessed and used to train a linear classifier to subsequently predict the intended target letters. The classifier was able to predict the intended target character at or near 100% accuracy using fewer than 15 stimulation sequences in the two subjects tested. Our results demonstrate that ERPs from hippocampal and hippocampal adjacent depth electrodes can be used to reliably control the P300 Speller BCI paradigm.

  13. THC and endocannabinoids differentially regulate neuronal activity in the prefrontal cortex and hippocampus in the subchronic PCP model of schizophrenia.

    Science.gov (United States)

    Aguilar, David D; Giuffrida, Andrea; Lodge, Daniel J

    2016-02-01

    Cannabis use has been associated with an increased risk to develop schizophrenia as well as symptom exacerbation in patients. In contrast, clinical studies have revealed an inverse relationship between the cerebrospinal fluid levels of the endocannabinoid anandamide and symptom severity, suggesting a therapeutic potential for endocannabinoid-enhancing drugs. Indeed, preclinical studies have shown that these drugs can reverse distinct behavioral deficits in a rodent model of schizophrenia. The mechanisms underlying the differences between exogenous and endogenous cannabinoid administration are currently unknown. Using the phencyclidine (PCP) rat model of schizophrenia, we compared the effects on neuronal activity of systematic administration of delta-9-tetrahydrocannabinol (THC) with the fatty acid amide hydrolase inhibitor URB597. Specifically, we found that the inhibitory response in the prefrontal cortex to THC administration was absent in PCP-treated rats. In contrast, an augmented response to endocannabinoid upregulation was observed in the prefrontal cortex of PCP-treated rats. Interestingly, differential effects were also observed at the neuronal population level, as endocannabinoid upregulation induced opposite effects on coordinated activity when compared with THC. Such information is important for understanding why marijuana and synthetic cannabinoid use may be contraindicated in schizophrenia patients while endocannabinoid enhancement may provide a novel therapeutic approach. © The Author(s) 2015.

  14. The cortical connectivity of the prefrontal cortex in the monkey brain.

    Science.gov (United States)

    Yeterian, Edward H; Pandya, Deepak N; Tomaiuolo, Francesco; Petrides, Michael

    2012-01-01

    One dimension of understanding the functions of the prefrontal cortex is knowledge of cortical connectivity. We have surveyed three aspects of prefrontal cortical connections: local projections (within the frontal lobe), the termination patterns of long association (post-Rolandic) projections, and the trajectories of major fiber pathways. The local connections appear to be organized in relation to dorsal (hippocampal origin) and ventral (paleocortical origin) architectonic trends. According to the proposal of a dual origin of the cerebral cortex, cortical areas can be traced as originating from archicortex (hippocampus) on the one hand, and paleocortex, on the other hand, in a stepwise manner (e.g., Sanides, 1969; Pandya and Yeterian, 1985). Prefrontal areas within each trend are connected with less architectonically differentiated areas, and also with more differentiated areas. Such organization may allow for the systematic exchange of information within each architectonic trend. The long connections of the prefrontal cortex with post-Rolandic regions seem to be organized preferentially in relation to dorsal and ventral prefrontal architectonic trends. Prefrontal areas are connected with post-Rolandic auditory, visual and somatosensory association areas, and with multimodal and paralimbic regions. This long connectivity likely works in conjunction with local connections to serve prefrontal cortical functions. The afferent and efferent connections of the prefrontal cortex with post-Rolandic regions are conveyed by specific long association pathways. These pathways as well appear to be organized in relation to dorsal and ventral prefrontal architectonic trends. Finally, although prefrontal areas have preferential connections in relation to dual architectonic trends, it is clear that there are interconnections between and among areas in each trend, which may provide a substrate for the overall integrative function of the prefrontal cortex. Prefrontal corticocortical

  15. Investigating the neurobiology of music: brain-derived neurotrophic factor modulation in the hippocampus of young adult mice.

    Science.gov (United States)

    Angelucci, Francesco; Fiore, Marco; Ricci, Enzo; Padua, Luca; Sabino, Andrea; Tonali, Pietro Attilio

    2007-09-01

    It has been shown that music might be able to improve mood state in people affected by psychiatric disorders, ameliorate cognitive deficits in people with dementia and increase motor coordination in Parkinson patients. Robust experimental evidence explaining the central effects of music, however, is missing. This study was designed to investigate the effect of music on brain neurotrophin production and behavior in the mouse. We exposed young adult mice to music with a slow rhythm (6 h/day; mild sound pressure levels, between 50 and 60 db) for 21 consecutive days. At the end of the treatment, mice were tested for passive avoidance learning and then killed for analysis of brain-derived neurotrophic factor (BDNF) and nerve growth factor with enzyme-linked immunosorbent assay (ELISA) in selected brain regions. We found that music-exposed mice showed increased BDNF, but not nerve growth factor in the hippocampus. Furthermore, we observed that music exposure significantly enhanced learning performance, as measured by the passive avoidance test. Our results demonstrate that exposure to music can modulate the activity of the hippocampus by influencing BDNF production. Our findings also suggest that music exposure might be of help in several central nervous system pathologies.

  16. Effect of the NADPH oxidase inhibitor apocynin on ischemia-reperfusion hippocampus injury in rat brain.

    Science.gov (United States)

    Kapoor, Monika; Sharma, Neha; Sandhir, Rajat; Nehru, Bimla

    2017-10-28

    Blockage along with sudden restoration of blood following ischemia, results in several cascading events, such as a massive ROS production which plays an important role in the pathophysiology of ischemia. NADPH oxidase complex in mitochondria complex is believed to be the major source for ROS production. The present study explores the therapeutic potential of apocynin, an NADPH oxidase inhibitor in attenuating the ROS production, and the resultant neuroinflammation and mitochondrial injury during cerebral ischemia in rats. Bilateral common carotid artery occlusion (BCCAO) model was chosen for the study where intracellular ROS and NO levels as well as the NADPH oxidase activity were found to be increased significantly post 7th day of ischemic injury. Enhanced glial activation was observed and an upregulated expression of GFAP and Iba-1 in hippocampus along with that of the transcription factor NFκB and inflammatory markers iNOS, IL-1α, IL-1β and TNF-α.The activity of mitochondrial electron transport chain (ETC) complexes I, II, IV and V were significantly decreased following ischemia. Consequently, there was a decrease in mitochondrial membrane potential (MMP) while an increased release of cytochrome c and upregulated apoptotic markers Bax, caspase-3 and 9 initiated the programmed neuronal death which was also reflected by the marked increase in TUNEL positive cells in the hippocampal region. The physiological functional alterations have been observed following ischemic injury i.e memory and motor deficits. The apocynin supplementation significantly reduced the NADPH oxidase activity and resulted in declined ROS production which in-turn prevented the glial activation and downregulated the inflammatory and pro-apoptotic markers. Apocynin also restored the MMP (Δψm) and mitochondrial enzymes via inhibition of ROS vicious and relationship between NADPH oxidase and mitochondrial complexes. Apocynin treatment was also successfully reduced the behavioural deficits in

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

    Directory of Open Access Journals (Sweden)

    Tyge Dahl Hermansen

    2007-01-01

    Full Text Available 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 corticocortical afferents termination and the columns in primary sensory cortex as arguments for the existence of the cortex-module. Further, we discuss the results of experiments with Luminization Microscopy (LM colouration of myalinized fibres, in which vertical bundles of afferent/efferent fibres that could support the cortex module are identified. We conclude that sensory maps seem not to be an expression for simple specific connectivity, but rather to be functional defined. We also conclude that evidence for the existence of the postulated module or column does not exist in the discussed material. This opens up for an important discussion of the brain as functionally directed by biological information (information-directed self-organisation, and for consciousness being closely linked to the structure of the universe at large. Consciousness is thus not a local phenomena limited to the brain, but a much more global phenomena connected to the wholeness of the world.

  18. 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

    BACKGROUND: Healthy first-degree relatives of patients with major depression (rMD+) show brain structure and functional response anomalies and have elevated risk for developing depression, a disorder linked to abnormal serotonergic neurotransmission and reward processing. METHOD: In a two...... responses were not accounted for by changes in gray matter density in rMD+ individuals. CONCLUSIONS: Our study in first-degree relatives of depressive patients showed abnormal brain responses to aversive and rewarding outcomes in regions known to be dysfunctional in depression. We further confirmed...

  19. Genomic divergence and brain evolution: How regulatory DNA influences development of the cerebral cortex.

    Science.gov (United States)

    Silver, Debra L

    2016-02-01

    The cerebral cortex controls our most distinguishing higher cognitive functions. Human-specific gene expression differences are abundant in the cerebral cortex, yet we have only begun to understand how these variations impact brain function. This review discusses the current evidence linking non-coding regulatory DNA changes, including enhancers, with neocortical evolution. Functional interrogation using animal models reveals converging roles for our genome in key aspects of cortical development including progenitor cell cycle and neuronal signaling. New technologies, including iPS cells and organoids, offer potential alternatives to modeling evolutionary modifications in a relevant species context. Several diseases rooted in the cerebral cortex uniquely manifest in humans compared to other primates, thus highlighting the importance of understanding human brain differences. Future studies of regulatory loci, including those implicated in disease, will collectively help elucidate key cellular and genetic mechanisms underlying our distinguishing cognitive traits. © 2015 WILEY Periodicals, Inc.

  20. [Expression of CaMK II delta in cerebral cortex following traumatic brain injury].

    Science.gov (United States)

    Pan, Hong; Zhang, Jing-Jing; Xu, Dong-Dong; Gu, Zhen-Yong; Tao, Lu-Yang; Zhang, Ming-Yang

    2014-06-01

    To observe the time-course expression of calcium-calmodulin dependent protein kinase II delta (CaMK II delta) in cerebral cortex after traumatic brain injury (TBI). The TBI rat model was established. The expression of CaMK II delta in cerebral cortex around injured area was tested by Western blotting and immunohistochemical staining. Western blotting revealed expression of CaMK II delta in normal rat brain cortex. It gradually increased after TBI, peaked after 3 days, and then returned to normal level. The result of immunohistochemical staining was consistent with that of Western blotting. The expression of CaMK II delta around injured area after TBI increased initially and then decreased. It could be used as a new indicator for wound age determination following TBI.

  1. Deep brain stimulation in the lateral orbitofrontal cortex impairs spatial reversal learning

    NARCIS (Netherlands)

    Klanker, Marianne; Post, Ger; Joosten, Ruud; Feenstra, Matthijs; Denys, Damiaan

    2013-01-01

    Deep Brain Stimulation (DBS) is a successful novel treatment for treatment-resistant obsessive-compulsive disorder and is currently under investigation for addiction and eating disorders. Clinical and preclinical studies have shown functional changes in the orbitofrontal cortex (OFC) following DBS

  2. 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

    with 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...

  3. A Study on a Brain-Computer Interface for Motor Assist by Prefrontal Cortex

    Science.gov (United States)

    Misawa, Tadanobu; Takano, Shinya; Shimokawa, Tetsuya; Hirobayashi, Shigeki

    In recent times, considerable research has been conducted on the development of brain-computer interfaces (BCIs). Although there have been several reports on BCIs that assist motor functions by measurement of brain activity in the motor cortex, only a few studies have reported on BCI that assist motor functions by measurement of activity in areas other than the motor cortex. In this study, we experimentally develop a BCI that assists motor functions on the basis of brain activity in the prefrontal cortex. In this BCI system, subjects are shown the labyrinth problem. Concretely, brain activity is measured using fNIRS and the data are acquired in real time. The signal processing module implements low pass filtering of these signals. Further, the pattern classification module used in this system currently is a support vector machine. 22 subjects, both male and female, volunteered to participate in this experiment. 8 of these 22 subjects were able to solve the labyrinth problem. In this experiment, we could not obtain a high distinction. However, these results show that it is possible to develop BCI systems that assist motor functions using information from the prefrontal cortex.

  4. Functional segmentation of the hippocampus in the healthy human brain and in Alzheimer's disease

    NARCIS (Netherlands)

    Zarei, M.; Beckmann, Christian; Binnewijzend, M.A.; Schoonheim, M.M.; Oghabian, M.A.; Sanz-Arigita, E.J.; Scheltens, P.; Matthews, P.M.; Barkhof, F.

    2013-01-01

    In this study we segment the hippocampus according to functional connectivity assessed from resting state functional magnetic resonance images in healthy subjects and in patients with Alzheimer's disease (AD). We recorded the resting FMRI signal from 16 patients and 22 controls. We used seed-based

  5. Functional segmentation of the hippocampus in the healthy human brain and in Alzheimer's disease

    NARCIS (Netherlands)

    Zarei, M.; Beckmann, C.F.; Binnewijzend, M.A.A.; Schoonheim, M.M.; Oghabian, M.A.; Sanz-Arigita, E.J.; Scheltens, P.; Matthews, P.M.; Barkhof, F.

    2013-01-01

    In this study we segment the hippocampus according to functional connectivity assessed from resting state functional magnetic resonance images in healthy subjects and in patients with Alzheimer's disease (AD).We recorded the resting FMRI signal from 16 patients and 22 controls. We used seed-based

  6. Honey and propolis abrogate neurologic deficit and neuronal damage in the hippocampus and cerebral cortex of ischemic stroke rats

    OpenAIRE

    Mark Joseph M. Desamero; Mikaela Angelica Villablanca; Jussiaea V. Bariuan; Therese Marie A. Collantes; Delia T. Ang Gobonseng; Mary Jasmin C. Ang; Alejandro C. Fajardo Jr; Cleofas R. Cervancia; Maria Amelita C. Estacio

    2017-01-01

    Summary. The effect of honey and propolis on the neurologic deficit and neural damage in extracranial internal carotid artery occlusion ischemic stroke was investigated using male Sprague-Dawley rats which were randomly allocated into distilled water, propolis and honey treated groups. Neurologic motor assessment was performed daily during the 7-day treatment period and brain samples were processed and analyzed by histopathological approach. Oral administration of honey and propolis from the ...

  7. Sleep deprivation induces differential morphological changes in the hippocampus and prefrontal cortex in young and old rats.

    Science.gov (United States)

    Acosta-Peña, Eva; Camacho-Abrego, Israel; Melgarejo-Gutiérrez, Montserrat; Flores, Gonzalo; Drucker-Colín, René; García-García, Fabio

    2015-01-01

    Sleep is a fundamental state necessary for maintenance of physical and neurological homeostasis throughout life. Several studies regarding the functions of sleep have been focused on effects of sleep deprivation on synaptic plasticity at a molecular and electrophysiological level, and only a few studies have studied sleep function from a structural perspective. Moreover, during normal aging, sleep architecture displays some changes that could affect normal development in the elderly. In this study, using a Golgi-Cox staining followed by Sholl analysis, we evaluate the effects of 24 h of total sleep deprivation on neuronal morphology of pyramidal neurons from Layer III of the prefrontal cortex (PFC) and the dorsal hippocampal CA1 region from male Wistar rats at two different ages (3 and 22 months). We found no differences in total dendritic length and branching length in both analyzed regions after sleep deprivation. Spine density was reduced in the CA1 of young-adults, and interestingly, sleep deprivation increased spine density in PFC of aged animals. Taken together, our results show that 24 h of total sleep deprivation have different effects on synaptic plasticity and could play a beneficial role in cognition during aging. © 2014 Wiley Periodicals, Inc.

  8. Topographic organization of the cerebral cortex and brain cartography.

    Science.gov (United States)

    Eickhoff, Simon B; Constable, R Todd; Yeo, B T Thomas

    2017-02-20

    One of the most specific but also challenging properties of the brain is its topographic organization into distinct modules or cortical areas. In this paper, we first review the concept of topographic organization and its historical development. Next, we provide a critical discussion of the current definition of what constitutes a cortical area, why the concept has been so central to the field of neuroimaging and the challenges that arise from this view. A key aspect in this discussion is the issue of spatial scale and hierarchy in the brain. Focusing on in-vivo brain parcellation as a rapidly expanding field of research, we highlight potential limitations of the classical concept of cortical areas in the context of multi-modal parcellation and propose a revised interpretation of cortical areas building on the concept of neurobiological atoms that may be aggregated into larger units within and across modalities. We conclude by presenting an outlook on the implication of this revised concept for future mapping studies and raise some open questions in the context of brain parcellation. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Does Short-Term Dietary Omega-3 Fatty Acid Supplementation Influence Brain Hippocampus Gene Expression of Zinc Transporter-3?

    Directory of Open Access Journals (Sweden)

    Nur Farhana Ahmad Sopian

    2015-07-01

    Full Text Available Dietary omega-3 fatty acids have been recognized to improve brain cognitive function. Deficiency leads to dysfunctional zinc metabolism associated with learning and memory impairment. The objective of this study is to explore the effect of short-term dietary omega-3 fatty acids on hippocampus gene expression at the molecular level in relation to spatial recognition memory in mice. A total of 24 male BALB/c mice were randomly divided into four groups and fed a standard pellet as a control group (CTL, n = 6, standard pellet added with 10% (w/w fish oil (FO, n = 6, 10% (w/w soybean oil (SO, n = 6 and 10% (w/w butter (BT, n = 6. After 3 weeks on the treatment diets, spatial-recognition memory was tested on a Y-maze. The hippocampus gene expression was determined using a real-time PCR. The results showed that 3 weeks of dietary omega-3 fatty acid supplementation improved cognitive performance along with the up-regulation of α-synuclein, calmodulin and transthyretin genes expression. In addition, dietary omega-3 fatty acid deficiency increased the level of ZnT3 gene and subsequently reduced cognitive performance in mice. These results indicate that the increased the ZnT3 levels caused by the deficiency of omega-3 fatty acids produced an abnormal zinc metabolism that in turn impaired the brain cognitive performance in mice.

  10. 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.

  11. 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.

  12. Semantic strategy training increases memory performance and brain activity in patients with prefrontal cortex lesions.

    Science.gov (United States)

    Miotto, Eliane C; Savage, Cary R; Evans, Jonathan J; Wilson, Barbara A; Martin, Maria G M; Balardin, Joana B; Barros, Fabio G; Garrido, Griselda; Teixeira, Manoel J; Amaro Junior, Edson

    2013-03-01

    Memory deficit is a frequent cognitive disorder following acquired prefrontal cortex lesions. In the present study, we investigated the brain correlates of a short semantic strategy training and memory performance of patients with distinct prefrontal cortex lesions using fMRI and cognitive tests. Twenty-one adult patients with post-acute prefrontal cortex (PFC) lesions, twelve with left dorsolateral PFC (LPFC) and nine with bilateral orbitofrontal cortex (BOFC) were assessed before and after a short cognitive semantic training using a verbal memory encoding paradigm during scanning and neuropsychological tests outside the scanner. After the semantic strategy training both groups of patients showed significant behavioral improvement in verbal memory recall and use of semantic strategies. In the LPFC group, greater activity in left inferior and medial frontal gyrus, precentral gyrus and insula was found after training. For the BOFC group, a greater activation was found in the left parietal cortex, right cingulated and precuneus after training. The activation of these specific areas in the memory and executive networks following cognitive training was associated to compensatory brain mechanisms and application of the semantic strategy. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Initial brain aging

    DEFF Research Database (Denmark)

    Thomsen, Kirsten; Yokota, Takashi; Hasan-Olive, Md Mahdi

    2018-01-01

    Brain aging is accompanied by declining mitochondrial respiration. We hypothesized that mitochondrial morphology and dynamics would reflect this decline. Using hippocampus and frontal cortex of a segmental progeroid mouse model lacking Cockayne syndrome protein B (CSBm/m) and C57Bl/6 (WT) controls...... and comparing young (2–5 months) to middle-aged mice (13–14 months), we found that complex I-linked state 3 respiration (CI) was reduced at middle age in CSBm/m hippocampus, but not in CSBm/m cortex or WT brain. In hippocampus of both genotypes, mitochondrial size heterogeneity increased with age. Notably...... content was lower, and hypoxia-induced factor 1α mRNA was greater at both ages in CSBm/m compared to WT brain. Our findings show that decreased CI and increased mitochondrial size heterogeneity are highly associated and point to declining mitochondrial quality control as an initial event in brain aging....

  14. Hippocampus at 25

    Science.gov (United States)

    Eichenbaum, Howard; Amaral, David G.; Buffalo, Elizabeth A.; Buzsáki, György; Cohen, Neal; Davachi, Lila; Frank, Loren; Heckers, Stephan; Morris, Richard G. M.; Moser, Edvard I.; Nadel, Lynn; O'Keefe, John; Preston, Alison; Ranganath, Charan; Silva, Alcino; Witter, Menno

    2017-01-01

    The journal Hippocampus has passed the milestone of 25 years of publications on the topic of a highly studied brain structure, and its closely associated brain areas. In a recent celebration of this event, a Boston memory group invited 16 speakers to address the question of progress in understanding the hippocampus that has been achieved. Here we present a summary of these talks organized as progress on four main themes: (1) Understanding the hippocampus in terms of its interactions with multiple cortical areas within the medial temporal lobe memory system, (2) understanding the relationship between memory and spatial information processing functions of the hippocampal region, (3) understanding the role of temporal organization in spatial and memory processing by the hippocampus, and (4) understanding how the hippocampus integrates related events into networks of memories. PMID:27399159

  15. Complex Regional Pain Syndrome Type I Affects Brain Structure in Prefrontal and Motor Cortex

    Science.gov (United States)

    Pleger, Burkhard; Draganski, Bogdan; Schwenkreis, Peter; Lenz, Melanie; Nicolas, Volkmar; Maier, Christoph; Tegenthoff, Martin

    2014-01-01

    The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the “non-flipped” data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the “flipped” data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control. PMID:24416397

  16. Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex.

    Directory of Open Access Journals (Sweden)

    Burkhard Pleger

    Full Text Available The complex regional pain syndrome (CRPS is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1 and motor cortex (M1 contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the "non-flipped" data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the "flipped" data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control.

  17. Complex regional pain syndrome type I affects brain structure in prefrontal and motor cortex.

    Science.gov (United States)

    Pleger, Burkhard; Draganski, Bogdan; Schwenkreis, Peter; Lenz, Melanie; Nicolas, Volkmar; Maier, Christoph; Tegenthoff, Martin

    2014-01-01

    The complex regional pain syndrome (CRPS) is a rare but debilitating pain disorder that mostly occurs after injuries to the upper limb. A number of studies indicated altered brain function in CRPS, whereas possible influences on brain structure remain poorly investigated. We acquired structural magnetic resonance imaging data from CRPS type I patients and applied voxel-by-voxel statistics to compare white and gray matter brain segments of CRPS patients with matched controls. Patients and controls were statistically compared in two different ways: First, we applied a 2-sample ttest to compare whole brain white and gray matter structure between patients and controls. Second, we aimed to assess structural alterations specifically of the primary somatosensory (S1) and motor cortex (M1) contralateral to the CRPS affected side. To this end, MRI scans of patients with left-sided CRPS (and matched controls) were horizontally flipped before preprocessing and region-of-interest-based group comparison. The unpaired ttest of the "non-flipped" data revealed that CRPS patients presented increased gray matter density in the dorsomedial prefrontal cortex. The same test applied to the "flipped" data showed further increases in gray matter density, not in the S1, but in the M1 contralateral to the CRPS-affected limb which were inversely related to decreased white matter density of the internal capsule within the ipsilateral brain hemisphere. The gray-white matter interaction between motor cortex and internal capsule suggests compensatory mechanisms within the central motor system possibly due to motor dysfunction. Altered gray matter structure in dorsomedial prefrontal cortex may occur in response to emotional processes such as pain-related suffering or elevated analgesic top-down control.

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

    Directory of Open Access Journals (Sweden)

    Izabela M. Zakiewicz

    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.

  19. 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.

  20. 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...... and the change of blood flow associated with the DBS. In subjects with a low emotional impact, activity measured as blood flow rose when the electrode was turned on, while in subjects of high impact, the activity at this site in the ventromedial prefrontal cortex declined when the electrode was turned on. We...... conclude that changes of neurotransmission in the ventromedial prefrontal cortex had an effect on the tissue that depends on changes of monoamine concentration interacting with specific combinations of inhibitory and excitatory monoamine receptors....

  1. 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 eGharabaghi

    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.

  2. 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...... 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...

  3. Brain state dependent activity in the cortex and thalamus.

    Science.gov (United States)

    McCormick, David A; McGinley, Matthew J; Salkoff, David B

    2015-04-01

    Cortical and thalamocortical activity is highly state dependent, varying between patterns that are conducive to accurate sensory-motor processing, to states in which the brain is largely off-line and generating internal rhythms irrespective of the outside world. The generation of rhythmic activity occurs through the interaction of stereotyped patterns of connectivity together with intrinsic membrane and synaptic properties. One common theme in the generation of rhythms is the interaction of a positive feedback loop (e.g., recurrent excitation) with negative feedback control (e.g., inhibition, adaptation, or synaptic depression). The operation of these state-dependent activities has wide ranging effects from enhancing or blocking sensory-motor processing to the generation of pathological rhythms associated with psychiatric or neurological disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Differences in the Flexibility of Switching Learning Strategies and CREB Phosphorylation Levels in Prefrontal Cortex, Dorsal Striatum, and Hippocampus in Two Inbred Strains of Mice

    Directory of Open Access Journals (Sweden)

    Woo-Hyun Cho

    2016-09-01

    Full Text Available Flexibility in using different learning strategies was assessed in two different inbred strains of mice, the C57BL/6 and DBA/2 strains. Mice were trained sequentially in two different Morris water maze protocols that tested their ability to switch their learning strategy to complete a new task after first being trained in a different task. Training consisted either of visible platform trials (cued training followed by subsequent hidden platform trials (place training or the reverse sequence (place training followed by cued training. Both strains of mice showed equivalent performance in the type of training (cued or place that they received first. However, C57BL/6 mice showed significantly better performances than DBA/2 mice following the switch in training protocols, irrespective of the order of training. After completion of the switched training session, levels of cAMP response element-binding protein (CREB and phosphorylated CREB (pCREB were measured in the hippocampus, striatum, and prefrontal cortex of the mice. Prefrontal cortical and hippocampal pCREB levels differed by strain, with higher levels found in C57BL/6 mice than in DBA/2 mice. No strain differences were observed in the medial or lateral region of the dorsal striatum. These findings indicate that the engagement (i.e., CREB signaling of relevant neural structures may vary by the specific demands of the learning strategy, and this is closely tied to differences in the flexibility of C57BL/6 and DBA/2 mice to switch their learning strategies when given a new task.

  5. Beta-amyloid (1-42)-induced learning and memory deficits in mice: involvement of oxidative burdens in the hippocampus and cerebral cortex.

    Science.gov (United States)

    Jhoo, Jin Hyeong; Kim, Hyoung-Chun; Nabeshima, Toshitaka; Yamada, Kiyofumi; Shin, Eun-Joo; Jhoo, Wang-Kee; Kim, Wookyung; Kang, Kee-Seok; Jo, Sangmee Ahn; Woo, Jong Inn

    2004-12-06

    We have demonstrated that oxidative stress is involved, at least in part, in beta-amyloid protein (Abeta)-induced neurotoxicity in vivo [Eur. J. Neurosci. 1999;11:83-90; Neuroscience 2003;119:399-419]. However, mechanistic links between oxidative stress and memory loss in response to Abeta remain elusive. In the present study, we examined whether oxidative stress contributes to the memory deficits induced by intracerebroventricular injection of Abeta (1-42) in mice. Abeta (1-42)-induced memory impairments were observed, as measured by the water maze and passive avoidance tests, although these impairments were not found in Abeta (40-1)-treated mice. Treatment with antioxidant alpha-tocopherol significantly prevented memory impairment induced by Abeta (1-42). Increased activities of the cytosolic Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and mitochondrial Mn-superoxide dismutase (Mn-SOD) were observed in the hippocampus and cerebral cortex of Abeta (1-42)-treated animals, as compared with Abeta (40-1)-treated mice. The induction of Cu,Zn-SOD was more pronounced than that of Mn-SOD after Abeta (1-42) insult. However, the concomitant induction of glutathione peroxidase (GPX) in response to significant increases in SOD activity was not seen in animals treated with Abeta (1-42). Furthermore, glutathione reductase (GRX) activity was only increased at 2h after Abeta (1-42) injection. Production of malondialdehyde (lipid peroxidation) and protein carbonyl (protein oxidation) remained elevated at 10 days post-Abeta (1-42), but the antioxidant alpha-tocopherol significantly prevented these oxidative stresses. Therefore, our results suggest that the oxidative stress contributes to the Abeta (1-42)-induced learning and memory deficits in mice.

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

    Science.gov (United States)

    Curlik, D M; Shors, T J

    2013-01-01

    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 hippocampal formation. In contrast, mental training via skill learning increases the numbers that survive, particularly when the training goals are challenging. Both manipulations can increase cognitive performance in the future, some of which are reportedly mediated by the presence of new neurons in the adult hippocampus. Based on these data, we suggest that a combination of mental and physical training, referred to here as MAP training, is more beneficial for neuronal recruitment and overall mental health than either activity alone. This article is part of a Special Issue entitled 'Cognitive Enhancers'. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Sensorimotor Cortex Injection of Adeno-Associated Viral Vector Mediates Knockout of PTEN in Neurons of the Brain and Spinal Cord of Mice.

    Science.gov (United States)

    Yang, Ping; Qin, Yu; Zhang, Wen; Bian, Zhiqun; Wang, Ruiqi

    2015-12-01

    Cre/loxP-mediated inactivation of phosphatase and tensin homolog (PTEN) is proposed to be a promising therapeutic agent for promoting CNS and PNS regeneration. And adeno-associated virus (AAV) vector has been developed as an attractive gene delivery system with proven safety. In the present study, we investigated Cre/loxP-mediated knockout of PTEN in the sensorimotor cortex, hippocampus, and spinal cord in PTEN floxed mice by immunohistological analysis of PI3K/AKT/mTOR expression in neurons of the sensorimotor cortex, hippocampus, and spinal cord after sensorimotor cortex injection of AAV-Cre. Two weeks after injection of AAV-Cre, the sensorimotor cortex, hippocampus, and spinal cord were dissected and examined the expression of downstream molecules pAKT and pS6 of PI3K/AKT signaling pathway. The results showed that remote delivery of AAV-Cre through sensorimotor cortex injection mediated PTEN knockout in neurons of the sensorimotor cortex, hippocampus, and spinal cord. We propose sensorimotor cortex injection of AAV may provide a potential strategy of gene therapy for the CNS diseases.

  8. Toward an integrative science of the developing human mind and brain: Focus on the developing cortex ?

    OpenAIRE

    Jernigan, Terry L.; Brown, Timothy T.; Bartsch, Hauke; Dale, Anders M.

    2015-01-01

    © 2015 The Authors. Based on the Huttenlocher lecture, this article describes the need for a more integrative scientific paradigm for addressing important questions raised by key observations made over 2 decades ago. Among these are the early descriptions by Huttenlocher of variability in synaptic density in cortex of postmortem brains of children of different ages and the almost simultaneous reports of cortical volume reductions on MR imaging in children and adolescents. In spite of much pro...

  9. Insulin-Like Growth Factor I Produces an Antidepressant-Like Effect and Elicits N-Methyl-D-Aspartate Receptor Independent Long-Term Potentiation of Synaptic Transmission in Medial Prefrontal Cortex and Hippocampus.

    Science.gov (United States)

    Burgdorf, Jeffrey; Zhang, Xiao-lei; Colechio, Elizabeth M; Ghoreishi-Haack, Nayereh; Gross, Amanda; Kroes, Roger A; Stanton, Patric K; Moskal, Joseph R

    2015-09-15

    Growth factors play an important role in regulating neurogenesis and synapse formation and may be involved in regulating the antidepressant response to conventional antidepressants. To date, Insulin-like growth factor I (IGFI) is the only growth factor that has shown antidepressant properties in human clinical trials. However, its mechanism of action remains unclear. The antidepressant-like effect of a single IV dose of IGFI was determined using a chronic unpredictable stress paradigm in the rat Porsolt, sucrose preference, novelty-induced hypophagia, and ultrasonic vocalization models. The dependence of the medial prefrontal cortex for these effects was determined by direct medial prefrontal cortex injection followed by Porsolt testing as well as IGFI receptor activation in the medial prefrontal cortex following an optimal IV antidepressant-like dose of IGFI. The effect of IGFI on synaptic transmission and long-term potentiation (LTP) of synaptic strength was assessed in the hippocampus and medial prefrontal cortex. The dependence of these effects on IGFI and AMPA receptor activation and protein synthesis were also determined. IGFI produced a rapid-acting and long-lasting antidepressant-like effect in each of the depression models. These effects were blocked by IGFI and AMPA receptor antagonists, and medial prefrontal cortex was localized. IGFI robustly increased synaptic strength in the hippocampus and medial prefrontal cortex and these effects were IGFI receptor and protein synthesis-dependent but N-methyl-d-aspartate receptor independent. IGFI also robustly facilitated hippocampal metaplasticity 24 hours postdosing. These data support the conclusion that the antidepressant-like effects of IGFI are mediated by a persistent, LTP-like enhancement of synaptic strength requiring both IGFIR activation and ongoing protein synthesis. © The Author 2015. Published by Oxford University Press on behalf of CINP.

  10. Forward Prediction in the Posterior Parietal Cortex and Dynamic Brain-Machine Interface.

    Science.gov (United States)

    Cui, He

    2016-01-01

    While remarkable progress has been made in brain-machine interfaces (BMIs) over the past two decades, it is still difficult to utilize neural signals to drive artificial actuators to produce predictive movements in response to dynamic stimuli. In contrast to naturalistic limb movements largely based on forward planning, brain-controlled neuroprosthetics mainly rely on feedback without prior trajectory formation. As an important sensorimotor interface integrating multisensory inputs and efference copy, the posterior parietal cortex (PPC) might play a proactive role in predictive motor control. Here it is proposed that predictive neural activity in PPC could be decoded to provide prosthetic control signals for guiding BMI systems in dynamic environments.

  11. 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

  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. A novel approach for locating mice brain regions of Cryptococcus neoformans CNS invasion

    Directory of Open Access Journals (Sweden)

    Chunting He

    2016-04-01

    Full Text Available Aim of this study was to locate the brain regions where Cryptococcus interact with brain cells and invade into brain. After 7 days of intratracheal inocula-tion of GFP-tagged Cryptococcus neoformans strains H99, serial cryosections (10 μm from 3 C57 BL/6 J mice brains were imaged with immunofluorescence microscopy. GFP-tagged H99 were found in some brain regions such as primary motor cortex-secondary motor cortex, caudate putamen, stratum lucidum of hippocampus, field CA1 of hippocampus, dorsal lateral geniculate nucleus, lateral posterior thalamic nucleus, laterorostral part, lateral posterior thalamic nucleus, mediorostral part, retrosplenial agranular cortex, lateral area of secondary visual cortex, and lacunosum molecular layer of the hippocampus. The results will be very useful for further exploring the mechanism of C. neoformans infection of brain.

  14. 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.

  15. SNAP-25a/b Isoform Levels in Human Brain Dorsolateral Prefrontal Cortex and Anterior Cingulate Cortex.

    Science.gov (United States)

    Thompson, Peter M; Cruz, Dianne A; Fucich, Elizabeth A; Olukotun, Dianna Y; Takahashi, Masami; Itakura, Makoto

    2015-12-01

    SNAP-25 is a neurotransmitter vesicular docking protein which has been associated with brain disorders such as attention deficit hyperactivity disorder, bipolar disorder and schizophrenia. In this project, we were interested if clinical factors are associated with differential SNAP-25 expression. We examined the SNAP-25 isoform mRNA and protein levels in postmortem cortex Brodmann's area 9 (BA9) and BA24 (n = 29). Subjects were divided by psychiatric diagnosis, clinical variables including mood state in the last week of life and lifetime impulsiveness. We found affected subjects with a diagnosis of alcohol use disorder (AUD) had a lower level of SNAP-25b BA24 protein compared to those without AUD. Hispanic subjects had lower levels of SNAP-25a, b and BA9 mRNA than Anglo-American subjects. Subjects who smoked had a total pan (total) SNAP-25 BA9/BA24 ratio. Subjects in the group with a low level of anxious-psychotic symptoms had higher SNAP-25a BA24 mRNA compared to normal controls, and both the high and low symptoms groups had higher pan (total) SNAP-25 BA9/BA24 ratios than normal controls. These data expand our understanding of clinical factors associated with SNAP-25. They suggest that SNAP-25 total and isoform levels may be useful biomarkers beyond limited neurological and psychiatric diagnostic categories.

  16. The phosphodiesterase-4 inhibitor Ro 20-1724 reverses learning and memory impairments, and downregulation of CREB in the hippocampus and cortex induced by ketamine anesthesia in immature rats.

    Science.gov (United States)

    Peng, S; Yang, X; Liu, G-J; Zhang, X-Q; Wang, G-L; Sun, H-Y

    2014-12-01

    The objective of the study was to examine the effects and possible mechanisms of phosphodiesterase-4 inhibitor Ro 20-1724 on learning and memory impairments induced by ketamine anesthesia. Further, expression the cAMP response element binding proteins (CREB), transcription factors involved in long-term memory, were analyzed in conjunction with these effects of Ro 20-1724. Ninety-six immature (21-day-old) Sprague-Dawley rats were divided into eight groups. To assess the learning and memory impairments, Morris Water Maze task was used. Expression of total and phosphorylated CREB in the hippocampus and cerebral cortex was evaluated by Western blot. THE escape latency and frequency of passing the platform in Morris Water Maze task were markedly longer after ketamine anesthesia. However, treatment with Ro 20-1724 significantly (Plearning and memory performance. Further, administration of Ro 20-1724 reverted the down-regulation of total and phosphorylated CREB caused by ketamine (Phippocampus and cortex. Treatment with Ro 20-1724 improves learning and memory deficits caused by ketamine anesthesia in immature rats, possibly via increases in expression of total and phosphorylated CREB in the hippocampus and cerebral cortex.

  17. Analysis of Gene Expression Profiles in the Human Brain Stem, Cerebellum and Cerebral Cortex.

    Directory of Open Access Journals (Sweden)

    Lei Chen

    Full Text Available The human brain is one of the most mysterious tissues in the body. Our knowledge of the human brain is limited due to the complexity of its structure and the microscopic nature of connections between brain regions and other tissues in the body. In this study, we analyzed the gene expression profiles of three brain regions-the brain stem, cerebellum and cerebral cortex-to identify genes that are differentially expressed among these different brain regions in humans and to obtain a list of robust, region-specific, differentially expressed genes by comparing the expression signatures from different individuals. Feature selection methods, specifically minimum redundancy maximum relevance and incremental feature selection, were employed to analyze the gene expression profiles. Sequential minimal optimization, a machine-learning algorithm, was employed to examine the utility of selected genes. We also performed a literature search, and we discuss the experimental evidence for the important physiological functions of several highly ranked genes, including NR2E1, DAO, and LRRC7, and we give our analyses on a gene (TFAP2B that have not been investigated or experimentally validated. As a whole, the results of our study will improve our ability to predict and understand genes related to brain regionalization and function.

  18. Subvoxel segmentation and representation of brain cortex using fuzzy clustering and gradient vector diffusion

    Science.gov (United States)

    Chang, Ming-Ching; Tao, Xiaodong

    2010-03-01

    Segmentation and representation of human brain cortex from Magnetic Resonance (MR) images is an important step for visualization and analysis in many neuro imaging applications. In this paper, we propose an automatic and fast algorithm to segment the brain cortex and to represent it as a geometric surface on which analysis can be carried out. The algorithm works on T1 weighted MR brain images with extracranial tissue removed. A fuzzy clustering algorithm with a parametric bias field model is applied to assign membership values of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) to each voxel. The cortical boundaries, namely the WM-GM and GM-CSF boundary surfaces, are extracted as iso-surfaces of functions derived from these membership functions. The central surface (CS), which traces the peak values (or ridges) of the GM membership function, is then extracted using gradient vector diffusion. Our main contribution is to provide a generic, accurate, fast, yet fully-automatic approach to (i) produce a soft segmentation of the MR brain image with intensity field correction, (ii) extract both the boundary and the center of the cortex in a surface form, where the topology and geometry can be explicitly examined, and (iii) use the extracted surfaces to model the curvy, folding cortical volume, which allows an intuitive measurement of the thickness. As a demonstration, we compute cortical thickness from the surfaces and compare the results with what has been reported in the literature. The entire process from raw MR image to cortical surface reconstruction takes on average between five to ten minutes.

  19. Emotional fronto-cingulate cortex activation and brain derived neurotrophic factor polymorphism in premenstrual dysphoric disorder.

    Science.gov (United States)

    Comasco, Erika; Hahn, Andreas; Ganger, Sebastian; Gingnell, Malin; Bannbers, Elin; Oreland, Lars; Wikström, Johan; Epperson, C Neill; Lanzenberger, Rupert; Sundström-Poromaa, Inger

    2014-09-01

    Premenstrual dysphoric disorder (PMDD) is the prototypical sex-specific disorder in which symptom onset and offset require a particular hormonal milieu and for which there is moderate heritability. The present study investigated brain emotion processing in PMDD and healthy controls, as well as functional polymorphisms in two candidate genes for PMDD, the serotonin transporter (5-HTT) and brain derived neurotrophic factor (BDNF). The 5-HTT linked polymorphic region (5-HTTLPR) and BDNF Val66Met polymorphisms were genotyped in 31 patients with PMDD and 31 healthy controls. A subset of 16 patients and 15 controls participated in two functional magnetic resonance imaging-sessions performing an emotion processing task; once in the mid-follicular, and once in the late luteal phase which corresponds with maximum severity of mood symptoms. Genotypes were not directly associated with PMDD. A main effect of group was found in the whole brain analysis, with patients having lower activation of the pre-genual anterior cingulate and ventro-medial prefrontal cortex, independent of menstrual cycle phase. Post-hoc functional ROI analyses in the fronto-cingulate cluster showed no effect of 5-HTTLPR genotype but a genotype-by-group-by-phase interaction effect of BDNF Val66Met. Women with PMDD who were carriers of the Met-allele had lower fronto-cingulate cortex activation in the luteal phase compared to Met-allele carrying controls. The results provide suggestive evidence of impaired emotion-induced fronto-cingulate cortex activation in PMDD patients. Although limited by a small sample, the potential influence of BDNF Val66Met in PMDD is in line with preclinical findings. Copyright © 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.

  20. Brain tissue oxygen amperometry in behaving rats demonstrates functional dissociation of dorsal and ventral hippocampus during spatial processing and anxiety

    Science.gov (United States)

    McHugh, Stephen B; Fillenz, Marianne; Lowry, John P; Rawlins, J Nicolas P; Bannerman, David M

    2011-01-01

    Traditionally, the function of the hippocampus (HPC) has been viewed in unitary terms, but there is growing evidence that the HPC is functionally differentiated along its septotemporal axis. Lesion studies in rodents and functional brain imaging in humans suggest a preferential role for the septal HPC in spatial learning and a preferential role for the temporal HPC in anxiety. To better enable cross-species comparison, we present an in vivo amperometric technique that measures changes in brain tissue oxygen at high temporal resolution in freely-moving rats. We recorded simultaneously from the dorsal (septal; dHPC) and ventral (temporal; vHPC) HPC during two anxiety tasks and two spatial tasks on the radial maze. We found a double-dissociation of function in the HPC, with increased vHPC signals during anxiety and increased dHPC signals during spatial processing. In addition, dHPC signals were modulated by spatial memory demands. These results add a new dimension to the growing consensus for a differentiation of HPC function, and highlight tissue oxygen amperometry as a valuable tool to aid translation between animal and human research. PMID:21105915

  1. [Functional asymmetry of electric processes in the rabbit brain cortex at formation of the hunger dominant].

    Science.gov (United States)

    Rusinova, E V

    2011-01-01

    The motivational condition of hunger and formation of the hunger dominant after daily food deprivation was studied in the conditions of chronic experiments on rabbits. It was shown, that the hunger condition was accompanied by left sided interhemispher asymmetry on indicators of spectral capacity of EEG frontal and right-hand asymmetry sensorimotor areas of the cortex. A hunger dominant was accompanied by falling of spectral capacity of EEG of areas of both hemispheres. The condition of hunger and a hunger dominant were characterized by right-hand asymmetry on average level of EEG coherence of frontal and sensorimotor areas. At transition of a condition of hunger in a hunger dominant there was an average level of EEG coherence decrease in areas of the right hemisphere. Electric processes of the cortex of the brain at a motivational condition of hunger and a hunger dominant were different.

  2. Reward sensitivity modulates brain activity in the prefrontal cortex, ACC and striatum during task switching.

    Directory of Open Access Journals (Sweden)

    Paola Fuentes-Claramonte

    Full Text Available Current perspectives on cognitive control acknowledge that individual differences in motivational dispositions may modulate cognitive processes in the absence of reward contingencies. This work aimed to study the relationship between individual differences in Behavioral Activation System (BAS sensitivity and the neural underpinnings involved in processing a switching cue in a task-switching paradigm. BAS sensitivity was hypothesized to modulate brain activity in frontal regions, ACC and the striatum. Twenty-eight healthy participants underwent fMRI while performing a switching task, which elicited activity in fronto-striatal regions during the processing of the switch cue. BAS sensitivity was negatively associated with activity in the lateral prefrontal cortex, anterior cingulate cortex and the ventral striatum. Combined with previous results, our data indicate that BAS sensitivity modulates the neurocognitive processes involved in task switching in a complex manner depending on task demands. Therefore, individual differences in motivational dispositions may influence cognitive processing in the absence of reward contingencies.

  3. BIASED AGONISM OF THREE DIFFERENT CANNABINOID RECEPTOR AGONISTS IN MOUSE BRAIN CORTEX

    Directory of Open Access Journals (Sweden)

    Rebeca Diez-Alarcia

    2016-11-01

    Full Text Available Cannabinoid receptors are able to couple to different families of G-proteins when activated by an agonist drug. It has been suggested that different intracellular responses may be activated depending on the ligand. The goal of the present study was to characterize the pattern of G protein subunit stimulation triggered by three different cannabinoid ligands, THC, WIN55212-2 and ACEA in mouse brain cortex.Stimulation of the [35S]GTPS binding coupled to specific immunoprecipitation with antibodies against different subtypes of G proteins (Gαi1, Gαi2, Gαi3, Gαo, Gαz, Gαs, Gαq/11, and Gα12/13, in the presence of Δ9-THC, WIN55212-2 and ACEA (submaximal concentration 10 µM was determined by Scintillation Proximity Assay (SPA technique in mouse cortex of wild type, CB1 knock-out, CB2 knock-out and CB1/CB2 double knock-out mice. Results show that, in mouse brain cortex, cannabinoid agonists are able to significantly stimulate not only the classical inhibitory Gαi/o subunits but also other G subunits like Gαz, Gαq/11, and Gα12/13. Moreover, the specific pattern of G protein subunit activation is different depending on the ligand. In conclusion, our results demonstrate that, in mice brain native tissue, different exogenous cannabinoid ligands are able to selectively activate different inhibitory and non-inhibitory Gα protein subtypes, through the activation of CB1 and/or CB2 receptors. Results of the present study may help to understand the specific molecular pathways involved in the pharmacological effects of cannabinoid-derived drugs.

  4. Developmental patterns of DR6 in normal human hippocampus and in Down syndrome

    OpenAIRE

    Iyer, Anand; van Scheppingen, Jackelien; Anink, Jasper; Milenkovic, Ivan; Kovács, Gabor G; Aronica, Eleonora

    2013-01-01

    Background Death receptor 6 (DR6) is highly expressed in the human brain: it has been shown to induce axon pruning and neuron death via distinct caspases and to mediate axonal degeneration through binding to N-terminal ? amyloid precursor protein (N-APP). Methods We investigated the expression of DR6 during prenatal and postnatal development in human hippocampus and temporal cortex by immunocytochemistry and Western blot analysis (118 normal human brain specimens; 9 to 41 gestational weeks; 1...

  5. Epileptiform activity and spreading depolarization in the blood-brain barrier-disrupted peri-infarct hippocampus are associated with impaired GABAergic inhibition and synaptic plasticity.

    Science.gov (United States)

    Lippmann, Kristina; Kamintsky, Lyn; Kim, Soo Young; Lublinsky, Svetlana; Prager, Ofer; Nichtweiss, Julia Friederike; Salar, Seda; Kaufer, Daniela; Heinemann, Uwe; Friedman, Alon

    2017-05-01

    Peri-infarct opening of the blood-brain barrier may be associated with spreading depolarizations, seizures, and epileptogenesis as well as cognitive dysfunction. We aimed to investigate the mechanisms underlying neural network pathophysiology in the blood-brain barrier-dysfunctional hippocampus. Photothrombotic stroke within the rat neocortex was associated with increased intracranial pressure, vasogenic edema, and peri-ischemic blood-brain barrier dysfunction that included the ipsilateral hippocampus. Intrahippocampal recordings revealed electrographic seizures within the first week in two-thirds of animals, accompanied by a reduction in gamma and increase in theta frequency bands. Synaptic interactions were studied in parasagittal hippocampal slices at 24 h and seven days post-stroke. Field potential recordings in CA1 and CA3 uncovered multiple population spikes, epileptiform episodes, and spreading depolarizations at 24 h. Input-output analysis revealed that fEPSP-spike coupling was significantly enhanced at seven days. In addition, CA1 feedback and feedforward inhibition were diminished. Slices generating epileptiform activity at seven days revealed impaired bidirectional long-term plasticity following high and low-frequency stimulation protocols. Microarray and PCR data confirmed changes in expression of astrocyte-related genes and suggested downregulation in expression of GABAA-receptor subunits. We conclude that blood-brain barrier dysfunction in the peri-infarct hippocampus is associated with early disinhibition, hyperexcitability, and abnormal synaptic plasticity.

  6. 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.

    NARCIS (Netherlands)

    Bohbot, VD; Allen, JJB; Dagher, A; Dumoulin, S.O.|info:eu-repo/dai/nl/314406514; Evans, A. C.; Petrides, M.; Kalina, M; Stepankova, K; Nadel, L

    2015-01-01

    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

  7. Regionally Selective Requirement for D[subscript 1]/D[subscript 5] Dopaminergic Neurotransmission in the Medial Prefrontal Cortex in Object-in-Place Associative Recognition Memory

    Science.gov (United States)

    Savalli, Giorgia; Bashir, Zafar I.; Warburton, E. Clea

    2015-01-01

    Object-in-place (OiP) memory is critical for remembering the location in which an object was last encountered and depends conjointly on the medial prefrontal cortex, perirhinal cortex, and hippocampus. Here we examined the role of dopamine D[subscript 1]/D[subscript 5] receptor neurotransmission within these brain regions for OiP memory. Bilateral…

  8. Brain-derived Neurotrophic Factor Overexpression Induces Precocious Critical Period in Mouse Visual Cortex

    OpenAIRE

    Hanover, Jessica L.; Huang, Z. Josh; Tonegawa, Susumu; Stryker, Michael P.

    1999-01-01

    Brain-derived neurotrophic factor (BDNF) is a candidate molecule for regulating activity-dependent synaptic plasticity on the grounds of its expression pattern in developing visual cortex and that of its receptor, trkB (Castrén et al., 1992; Bozzi et al., 1995; Schoups et al., 1995; Cabelli et al., 1996), as well as the modulation of these patterns by activity (Castrén et al., 1992; Bozzi et al., 1995; Schoups et al., 1995). Infusing trkB ligands or their neutralizing agents, the trkB-IgG fus...

  9. Electrophysiological recordings from rat hippocampus slices following in vivo brain ischemia.

    Science.gov (United States)

    Jensen, M S; Lambert, J D; Johansen, F F

    1991-07-19

    Pyramidal neurons in area CA1 of the septal hippocampus degenerate 2-3 days after an episode of transient global cerebral ischemia. The purpose of this study was to investigate synaptic transmission and passive neuronal properties in the post-ischemic period prior to neuronal death. Electrophysiological recordings were made from area CA1 in hippocampal slices prepared from rats which had survived a period of 20 min of ischemia for up to 5 days. In septal slices, field responses were in area CA1 unaltered up to 24 h after the ischemic insult. Forty-eight hours after ischemia, the mean amplitude of the population spike, but not the field-EPSP, was significantly reduced. In septal slices prepared more than 48 h after ischemia field potentials were absent or strongly attenuated, whereas they were intact in slices prepared from the temporal pole. No spontaneous discharges were detected in slices prepared at any time from post-ischemic rats. Intracellular recordings were obtained from slices up to 48 h after the ischemic episode. There was no significant difference in the resting membrane potential or input resistance between these neurons and those from control slices. Action potentials followed by a fast afterhyperpolarization and spike accommodation were preserved in all post-ischemic neurons. In all neurons investigated, orthodromic stimulation evoked an EPSP followed by a fast- and then a slow-IPSP. One hour after ischemia, the slow-IPSP was reduced. Forty-eight hours after ischemia, the fast-IPSP was significantly increased. The EPSP was markedly attenuated by the non N-methyl-D-aspartate receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM). The residual depolarizing component was amplified by perfusing with Mg(2+)-free medium and blocked by the N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonovaleric acid. Paired-pulse facilitation of the EPSP was also preserved. As in control slices, the slow-IPSP and paired-pulse depression of the fast

  10. Forward prediction in the posterior parietal cortex and dynamic brain-machine interface

    Directory of Open Access Journals (Sweden)

    He Cui

    2016-10-01

    Full Text Available While remarkable progress has been made in brain-machine interfaces (BMIs over the past two decades, it is still difficult to utilize neural signals to drive artificial actuators to produce predictive movements in response to dynamic stimuli. In contrast to naturalistic limb movements largely based on forward planning, brain-controlled neuroprosthetics mainly rely on feedback without prior trajectory formation. As an important sensorimotor interface integrating multisensory inputs and efference copy, the posterior parietal cortex (PPC might play a proactive role in predictive motor control. Here it is proposed that predictive neural activity in PPC could be decoded to provide prosthetic control signals for guiding BMI systems in dynamic environments.

  11. Toward an integrative science of the developing human mind and brain: Focus on the developing cortex.

    Science.gov (United States)

    Jernigan, Terry L; Brown, Timothy T; Bartsch, Hauke; Dale, Anders M

    2016-04-01

    Based on the Huttenlocher lecture, this article describes the need for a more integrative scientific paradigm for addressing important questions raised by key observations made over 2 decades ago. Among these are the early descriptions by Huttenlocher of variability in synaptic density in cortex of postmortem brains of children of different ages and the almost simultaneous reports of cortical volume reductions on MR imaging in children and adolescents. In spite of much progress in developmental neurobiology, developmental cognitive neuroscience, and behavioral and imaging genetics, we still do not know how these early observations relate to each other. It is argued that large scale, collaborative research programs are needed to establish the associations between behavioral differences among children and imaging biomarkers, and to link the latter to cellular changes in the developing brain. Examples of progress and challenges remaining are illustrated with data from the Pediatric Imaging, Neurocognition, and Genetics Project (PING). Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Upregulation of intercellular adhesion molecule 1 (ICAM-1) on brain microvascular endothelial cells in rat ischemic cortex.

    Science.gov (United States)

    Wang, X; Siren, A L; Liu, Y; Yue, T L; Barone, F C; Feuerstein, G Z

    1994-10-01

    The expression of intercellular adhesion molecule 1 (ICAM-1) was studied in rat focal ischemic cortex. A significant increase in ICAM-1 mRNA expression in the ischemic cortex over levels in contralateral (nonischemic) site was observed by means of Northern blot analysis following either permanent or temporary occlusion with reperfusion of the middle cerebral artery (PMCAO or MCAO with reperfusion) in spontaneously hypertensive rats. In the ischemic cortex, levels of ICAM-1 mRNA increased significantly at 3 h (2.6-fold, n = 3, P hypertensive rats than in two normotensive rat strains. Immunostaining using anti-ICAM-1 antibodies indicated that upregulated ICAM-1 expression was localized to endothelial cells of intraparenchymal blood vessels in the ischemic but not contralateral cortex. The data suggest that an upregulation of ICAM-1 mRNA and protein on brain capillary endothelium may play an important role in leukocyte migration into ischemic brain tissue.

  13. The hippocampus and dorsal raphe nucleus are key brain areas associated with the antidepressant effects of lithium augmentation of desipramine.

    Science.gov (United States)

    Cussotto, Sofia; Cryan, John F; O'Leary, Olivia F

    2017-05-01

    Approximately 50% of depressed individuals fail to achieve remission with first-line antidepressant drugs and a third remain treatment-resistant. When first-line antidepressant treatment is unsuccessful, second-line strategies include dose optimisation, switching to another antidepressant, combination with another antidepressant, or augmentation with a non-antidepressant medication. Much of the evidence for the efficacy of augmentation strategies comes from studies using lithium to augment the effects of tricyclic antidepressants. The neural circuitry underlying the therapeutic effects of lithium augmentation is not yet fully understood. Recently, we reported that chronic treatment with a combination of lithium and the antidepressant desipramine, exerted antidepressant-like behavioural effects in a mouse strain (BALB/cOLaHsd) that did not exhibit an antidepressant-like behavioural response to either drug alone. In the present study, we used this model in combination with ΔFosB/FosB immunohistochemistry to identify brain regions chronically affected by lithium augmentation of desipramine when compared to either treatment alone. The data suggest that the dorsal raphe nucleus and the CA3 regions of the dorsal hippocampus are key nodes in the neural circuitry underlying antidepressant action of lithium augmentation of desipramine. These data give new insight into the neurobiology underlying the mechanism of lithium augmentation in the context of treatment-resistant depression. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Expression of S100A6 in Rat Hippocampus after Traumatic Brain Injury Due to Lateral Head Acceleration

    Directory of Open Access Journals (Sweden)

    Bo Fang

    2014-04-01

    Full Text Available In a rat model of traumatic brain injury (TBI, we investigated changes in cognitive function and S100A6 expression in the hippocampus. TBI-associated changes in this protein have not previously been reported. Rat S100A6 was studied via immunohistochemical staining, Western blot, and reverse transcription-polymerase chain reaction (RT-PCR after either lateral head acceleration or sham. Reduced levels of S100A6 protein and mRNA were observed 1 h after TBI, followed by gradual increases over 6, 12, 24, and 72 h, and then a return to sham level at 14 day. Morris water maze (MWM test was used to evaluate animal spatial cognition. TBI- and sham-rats showed an apparent learning curve, expressed as escape latency. Although TBI-rats displayed a relatively poorer cognitive ability than sham-rats, the disparity was not significant early post-injury. Marked cognitive deficits in TBI-rats were observed at 72 h post-injury compared with sham animals. TBI-rats showed decreased times in platform crossing in the daily MWM test; the performance at 72 h post-injury was the worst. In conclusion, a reduction in S100A6 may be one of the early events that lead to secondary cognitive decline after TBI, and its subsequent elevation is tightly linked with cognitive improvement. S100A6 may play important roles in neuronal degeneration and regeneration in TBI.

  15. STATUS EPILEPTICUS TRIGGERS EARLY AND LATE ALTERATIONS IN BRAIN-DERIVED NEUROTROPHIC FACTOR AND NMDA GLUTAMATE RECEPTOR GRIN2B DNA METHYLATION LEVELS IN THE HIPPOCAMPUS

    Science.gov (United States)

    Parrish, R. Ryley; Albertson, Asher J.; Buckingham, Susan C.; Hablitz, John J.; Mascia, Katherine L.; Haselden, W. Davis; Lubin, Farah D.

    2013-01-01

    Status epilepticus (SE) triggers abnormal expression of genes in the hippocampus, such as glutamate receptor subunit epsilon-2 (Grin2b/Nr2b) and brain-derived neurotrophic factor (Bdnf), that is thought to occur in temporal lobe epilepsy (TLE). We examined the underlying DNA methylation mechanisms and investigated whether these mechanisms contribute to the expression of these gene targets in the epileptic hippocampus. Experimental TLE was provoked by kainic acid-induced SE. Bisulfite sequencing analysis revealed increased Grin2b/Nr2b and decreased Bdnf DNA methylation levels that corresponded to decreased Grin2b/Nr2b and increased Bdnf mRNA and protein expression in the epileptic hippocampus. Blockade of DNA methyltransferase (DNMT) activity with zebularine decreased global DNA methylation levels and reduced Grin2b/Nr2b, but not Bdnf, DNA methylation levels. Interestingly, we found that DNMT blockade further decreased Grin2b/Nr2b mRNA expression whereas GRIN2B protein expression increased in the epileptic hippocampus, suggesting that a posttranscriptional mechanism may be involved. Using chromatin immunoprecipitation analysis we found that DNMT inhibition restored the decreases in AP2alpha transcription factor levels at the Grin2b/Nr2b promoter in the epileptic hippocampus. DNMT inhibition increased field excitatory postsynaptic potential in hippocampal slices isolated from epileptic rats. EEG monitoring confirmed that DNMT inhibition did not significantly alter disease course, but promoted the latency to seizure onset or SE. Thus, DNA methylation may be an early event triggered by SE that persists late into the epileptic hippocampus to contribute to gene expression changes in TLE. PMID:23811393

  16. Brain-derived Neurotrophic Factor Overexpression Induces Precocious Critical Period in Mouse Visual Cortex

    Science.gov (United States)

    Hanover, Jessica L.; Huang, Z. Josh; Tonegawa, Susumu; Stryker, Michael P.

    2008-01-01

    Brain-derived neurotrophic factor (BDNF) is a candidate molecule for regulating activity-dependent synaptic plasticity on the grounds of its expression pattern in developing visual cortex and that of its receptor, trkB (Castrén et al., 1992; Bozzi et al., 1995; Schoups et al., 1995; Cabelli et al., 1996), as well as the modulation of these patterns by activity (Castrén et al., 1992; Bozzi et al., 1995; Schoups et al., 1995). Infusing trkB ligands or their neutralizing agents, the trkB-IgG fusion proteins, into visual cortex alters the development and plasticity of ocular dominance columns (Cabelli et al., 1995; Riddle et al., 1995; Galuske et al., 1996; Gillespie et al., 1996; Cabelli et al., 1997). To test further the physiological role of BDNF, we studied a transgenic mouse that expresses elevated levels of BDNF in primary visual cortex (V1) postnatally (Huang et al., 1999). We found that unlike the infusion experiments, excess BDNF expressed in mouse visual cortex did not block ocular dominance plasticity. Instead, single neurons in V1 of the BDNF transgenic mice were as susceptible to the effects of monocular deprivation (MD) as neurons in wild-type mice, but only during a precocious critical period. At a time when V1 in the wild-type mouse responded maximally to a 4 d MD with a reduction in its response to deprived eye visual stimulation, the transgenic mouse V1 had already passed the peak of its precocious critical period and no longer responded maximally. This finding suggests a role for BDNF in promoting the postnatal maturation of cortical circuitry. PMID:10559430

  17. Reflectometric mapping of microregional blood flow and blood volume in the brain cortex.

    Science.gov (United States)

    Eke, A

    1982-01-01

    A reflectometric indicator-dilution method has been developed for mapping the parenchymal minute volume flow and blood content over tiny superficial areas of the brain cortex at 625 or 2500 locations, respectively. About 0.4 ml dextran-saline solution was used as nondiffusible indicator and injected into the feline cerebral circulation for each measurement. The subsequent cerebrocortical transit of the hemodiluted bolus was detected as a temporary change in the tissue optical density [OD(t)] and interpreted as indicator dilution, C(t). This gave the data necessary to calculate the microregional blood volume (mrCBV), mean transit time of the bolus (mrMTT), and the microregional blood flow (mrCBF = mrCBV/mrMTT). A two-dimensional record of the OD(t) function was made on Kodak SO 115 film by 16-mm cinematography, as a reflectometric tool, over an exposed area of the brain cortex during the bolus perfusion. Later, the microregional OD(t) functions were retrieved for analysis in a square array from the developed film by computer-controlled, frame-by-frame scanning densitometry. Maps of mrCBF, mrCBV, and mrMTT were presented as square arrays of gray-scaled pixels. The maximal spatial and temporal resolution of the method was 0.015 mm2 (mrCBF), 0.004 mm2 (mrCBV), 6 maps/min (mrCBF), and 600 maps/min (mrCBV).

  18. A Brain System for Auditory Working Memory.

    Science.gov (United States)

    Kumar, Sukhbinder; Joseph, Sabine; Gander, Phillip E; Barascud, Nicolas; Halpern, Andrea R; Griffiths, Timothy D

    2016-04-20

    The brain basis for auditory working memory, the process of actively maintaining sounds in memory over short periods of time, is controversial. Using functional magnetic resonance imaging in human participants, we demonstrate that the maintenance of single tones in memory is associated with activation in auditory cortex. In addition, sustained activation was observed in hippocampus and inferior frontal gyrus. Multivoxel pattern analysis showed that patterns of activity in auditory cortex and left inferior frontal gyrus distinguished the tone that was maintained in memory. Functional connectivity during maintenance was demonstrated between auditory cortex and both the hippocampus and inferior frontal cortex. The data support a system for auditory working memory based on the maintenance of sound-specific representations in auditory cortex by projections from higher-order areas, including the hippocampus and frontal cortex. In this work, we demonstrate a system for maintaining sound in working memory based on activity in auditory cortex, hippocampus, and frontal cortex, and functional connectivity among them. Specifically, our work makes three advances from the previous work. First, we robustly demonstrate hippocampal involvement in all phases of auditory working memory (encoding, maintenance, and retrieval): the role of hippocampus in working memory is controversial. Second, using a pattern classification technique, we show that activity in the auditory cortex and inferior frontal gyrus is specific to the maintained tones in working memory. Third, we show long-range connectivity of auditory cortex to hippocampus and frontal cortex, which may be responsible for keeping such representations active during working memory maintenance. Copyright © 2016 Kumar et al.

  19. Glucocorticoid receptor expression in the cortex of the neonatal rat brain with and without focal cerebral ischemia.

    Science.gov (United States)

    Lee, Ben H; Wen, Tong-Chun; Rogido, Marta; Sola, Augusto

    2007-01-01

    Glucocorticoid receptors (GR) mediate cellular processes which may be neuroprotective and/or neurotoxic to the neonatal rat brain. Our aim was to describe GR ontogeny in the developing rat brain cortex and changes in GR expression after permanent neonatal focal cerebral ischemia (FCI). GR Western blots and immunohistochemical stains were performed on neonatal rat cortices on P1, P3, P7, P10, P15, and P30 and on P7 at 1 h, 3 h, 6 h, 12 h, 24 h, and 72 h after FCI or sham-operation (S-O), 8 per group. Nissl staining was performed on FCI or S-O P7 cortical samples. Cortical GR expression was increased by 65.2% at P7, 110.1% at P15, and 87.0% at P30, compared to P1. On P7, GR expression decreased in the ischemic cortex after 6 h and in the non-ischemic cortex after 24 h of FCI (p cortex after 6 h and in the non-ischemic cortex after 24 h of FCI. Thus, cortical GR may play important roles in normal brain development and neonatal brain injury responses.

  20. Effects of experimental cerebral malaria in memory, brain-derived neurotrophic factor and acetylcholinesterase activity [correction for acitivity] in the hippocampus of survivor mice.

    Science.gov (United States)

    Comim, Clarissa M; Reis, Patrícia A; Frutuoso, Valber S; Fries, Gabriel R; Fraga, Daiane B; Kapczinski, Flávio; Zugno, Alexandra I; Barichello, Tatiana; Quevedo, João; Castro-Faria-Neto, Hugo C

    2012-08-15

    Malaria is the most important human parasitic disease and cerebral malaria (CM), its main neurological complication, is characterized by neurological and cognitive damage in both human and animal survivors. The brain-derived neurotrophic factor (BDNF) appears to be involved with activity-dependent synaptic plasticity. There is great interest regarding its role in learning and memory as well as acetylcholinesterase activity (AChE) that is implicated in many cognitive functions and probably plays important roles in neurodegenerative disorders. In the present work, we evaluated BDNF protein levels and AChE activity in the hippocampus and habituation in an animal model of CM using C57BL/6 mice after fifteen days of the induction. The results demonstrated that there was a decrease in BDNF levels in the hippocampus of C57BL/6 mice infected with PbA when compared with C57BL/6 non-infected mice and C57BL/6 non-infected mice that received treatment with chloroquine. However, no difference was observed in AChE activity in the hippocampus. When habituation was evaluated there was memory impairment in the C57BL/6 mice infected with Plasmodium berghei ANKA (PbA). In conclusion, we believe that the decreased BDNF levels in the hippocampus may be related with memory impairment without alterations on AChE activity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  1. 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

  2. The impact of RTOG 0614 and RTOG 0933 trials in routine clinical practice: The US Survey of Utilization of Memantine and IMRT planning for hippocampus sparing in patients receiving whole brain radiotherapy for brain metastases.

    Science.gov (United States)

    Slade, Alexander N; Stanic, Sinisa

    2016-03-01

    Two recent clinical trials, phase III RTOG 0614 and phase II RTOG 0933, showed some effectiveness of Memantine and IMRT planning for hippocampus sparing, among patients receiving whole brain radiotherapy (WBRT) for brain metastases; however, their use in routine clinical practice is unknown. A survey was sent to 1933 radiation oncologists in the US. Data collected included utilization of Memantine and hippocampus sparing, reasons for adoption and non-adoption, and demographic variables. A total of 196 radiation oncologists responded to the survey, with 64% reporting using Memantine in almost none of the patients receiving WBRT for brain metastases, and only 11% considering Memantine for trial was supported by 71% of radiation oncologists, whereas further exploration of Memantine for this purpose in a phase III trial was supported by 42%. At this time, the majority of surveyed radiation oncologists in the US do not use Memantine, or IMRT planning for hippocampus sparing in patients receiving WBRT. Further validation of the hippocampus sparing concept in a phase III trial was supported, before adopting it in routine clinical practice. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. [Hippocampus, brainstem and brain dose-volume constraints for fractionated 3-D radiotherapy and for stereotactic radiation therapy: Limits and perspectives].

    Science.gov (United States)

    Gérard, M; Jumeau, R; Pichon, B; Biau, J; Blais, E; Horion, J; Noël, G

    2017-10-01

    Cerebral radiation-induced toxicities after radiotherapy (RT) of brain tumors are frequent. The protection of organs at risk (OAR) is crucial, especially for brain tumors, to preserve cognition in cancer survivors. Dose constraints of cerebral OAR used in conventional RT, radiosurgery (SRS) and stereotactic radiotherapy (SRT) are debated. In fact, they are based on historical cohorts or calculated with old mathematical models. Values of α/β ratio of cerebral OAR are also controversial leading to misestimate the equivalent dose in 2Gy fractions or the biological equivalent dose, especially during hypofractionated RT. Although recent progresses in medical imaging, the diagnosis of radionecrosis remains difficult. In this article, we propose a large review of dose constraints used for three major cerebral OAR: the brain stem, the hippocampus and the brain. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

  4. Alterations in brain-derived neurotrophic factor in the mouse hippocampus following acute but not repeated benzodiazepine treatment.

    Science.gov (United States)

    Licata, Stephanie C; Shinday, Nina M; Huizenga, Megan N; Darnell, Shayna B; Sangrey, Gavin R; Rudolph, Uwe; Rowlett, James K; Sadri-Vakili, Ghazaleh

    2013-01-01

    Benzodiazepines (BZs) are safe drugs for treating anxiety, sleep, and seizure disorders, but their use also results in unwanted effects including memory impairment, abuse, and dependence. The present study aimed to reveal the molecular mechanisms that may contribute to the effects of BZs in the hippocampus (HIP), an area involved in drug-related plasticity, by investigating the regulation of immediate early genes following BZ administration. Previous studies have demonstrated that both brain derived neurotrophic factor (BDNF) and c-Fos contribute to memory- and abuse-related processes that occur within the HIP, and their expression is altered in response to BZ exposure. In the current study, mice received acute or repeated administration of BZs and HIP tissue was analyzed for alterations in BDNF and c-Fos expression. Although no significant changes in BDNF or c-Fos were observed in response to twice-daily intraperitoneal (i.p.) injections of diazepam (10 mg/kg + 5 mg/kg) or zolpidem (ZP; 2.5 mg/kg + 2.5 mg/kg), acute i.p. administration of both triazolam (0.03 mg/kg) and ZP (1.0 mg/kg) decreased BDNF protein levels within the HIP relative to vehicle, without any effect on c-Fos. ZP specifically reduced exon IV-containing BDNF transcripts with a concomitant increase in the association of methyl-CpG binding protein 2 (MeCP2) with BDNF promoter IV, suggesting that MeCP2 activity at this promoter may represent a ZP-specific mechanism for reducing BDNF expression. ZP also increased the association of phosphorylated cAMP response element binding protein (pCREB) with BDNF promoter I. Future work should examine the interaction between ZP and DNA as the cause for altered gene expression in the HIP, given that BZs can enter the nucleus and intercalate into DNA directly.

  5. Alterations in brain-derived neurotrophic factor in the mouse hippocampus following acute but not repeated benzodiazepine treatment.

    Directory of Open Access Journals (Sweden)

    Stephanie C Licata

    Full Text Available Benzodiazepines (BZs are safe drugs for treating anxiety, sleep, and seizure disorders, but their use also results in unwanted effects including memory impairment, abuse, and dependence. The present study aimed to reveal the molecular mechanisms that may contribute to the effects of BZs in the hippocampus (HIP, an area involved in drug-related plasticity, by investigating the regulation of immediate early genes following BZ administration. Previous studies have demonstrated that both brain derived neurotrophic factor (BDNF and c-Fos contribute to memory- and abuse-related processes that occur within the HIP, and their expression is altered in response to BZ exposure. In the current study, mice received acute or repeated administration of BZs and HIP tissue was analyzed for alterations in BDNF and c-Fos expression. Although no significant changes in BDNF or c-Fos were observed in response to twice-daily intraperitoneal (i.p. injections of diazepam (10 mg/kg + 5 mg/kg or zolpidem (ZP; 2.5 mg/kg + 2.5 mg/kg, acute i.p. administration of both triazolam (0.03 mg/kg and ZP (1.0 mg/kg decreased BDNF protein levels within the HIP relative to vehicle, without any effect on c-Fos. ZP specifically reduced exon IV-containing BDNF transcripts with a concomitant increase in the association of methyl-CpG binding protein 2 (MeCP2 with BDNF promoter IV, suggesting that MeCP2 activity at this promoter may represent a ZP-specific mechanism for reducing BDNF expression. ZP also increased the association of phosphorylated cAMP response element binding protein (pCREB with BDNF promoter I. Future work should examine the interaction between ZP and DNA as the cause for altered gene expression in the HIP, given that BZs can enter the nucleus and intercalate into DNA directly.

  6. Oscillatory patterns in hippocampus under light and deep isoflurane anesthesia closely mirror prominent brain states in awake animals.

    Science.gov (United States)

    Lustig, Brian; Wang, Yingxue; Pastalkova, Eva

    2016-01-01

    The hippocampus exhibits a variety of distinct states of activity under different conditions. For instance the rhythmic patterns of activity orchestrated by the theta oscillation during running and REM sleep are markedly different from the large irregular activity (LIA) observed during awake resting and slow wave sleep. We found that under different levels of isoflurane anesthesia activity in the hippocampus of rats displays two distinct states, which have several qualities that mirror the theta and LIA states. These data provide further evidence that the two states are intrinsic modes of the hippocampus; while also characterizing a preparation that could be useful for studying the natural activity states in hippocampus. © 2015 Wiley Periodicals, Inc.

  7. Increased motor cortex excitability during motor imagery in brain-computer interface trained subjects

    Directory of Open Access Journals (Sweden)

    Olesya eMokienko

    2013-11-01

    Full Text Available Background: Motor imagery (MI is the mental performance of movement without muscle activity. It is generally accepted that MI and motor performance have similar physiological mechanisms.Purpose: To investigate the activity and excitability of cortical motor areas during MI in subjects who were previously trained with an MI-based brain-computer interface (BCI.Subjects and methods: Eleven healthy volunteers without neurological impairments (mean age, 36 years; range: 24–68 years were either trained with an MI-based BCI (BCI-trained, n = 5 or received no BCI training (n = 6, controls. Subjects imagined grasping in a blocked paradigm task with alternating rest and task periods. For evaluating the activity and excitability of cortical motor areas we used functional MRI and navigated transcranial magnetic stimulation (nTMS.Results: fMRI revealed activation in Brodmann areas 3 and 6, the cerebellum, and the thalamus during MI in all subjects. The primary motor cortex was activated only in BCI-trained subjects. The associative zones of activation were larger in non-trained subjects. During MI, motor evoked potentials recorded from two of the three targeted muscles were significantly higher only in BCI-trained subjects. The motor threshold decreased (median = 17% during MI, which was also observed only in BCI-trained subjects.Conclusion: Previous BCI training increased motor cortex excitability during MI. These data may help to improve BCI applications, including rehabilitation of patients with cerebral palsy.

  8. [Synchronization and propagation of electrical potentials in neural networks of the brain cortex].

    Science.gov (United States)

    Marchenko, V G; Zaĭchenko, M I

    2014-01-01

    On the basis of the published data the scheme is proposed which explains the spread and synhronization of oscillatory activity in cortex. The main property of the neocortex is the existence of vertically oriented functional columns. Within and between the neuronal columns exist a feedforward and feedback morphological and functional connections. At the certain conditions inside the single module temporal windows are created using inhibitory process, and a synchronized activity can be generated of variable frequency (oscillations). The activity in the columns is enhanced by the synchronous involvement of great amount of neurons which is expressed in the form of local field potentials of high amplitude. Further the information about arisen in a single generator activity is transmitted through direct links to the nearby generator or to the group of such generators. In the nearby generator the activity increases and is transferred to the next generator. At the same time the signal is transmitted through feedback to the primary generator, and the activity is terminated until the next cycle will be initiated and so on along the cortex. The most important notion is that in the transfer of activity from one generator to another is involved a small number of elements. The major part of recorded oscillations of different frequency or epileptiform discharges, is not transmitted via the brain, but is generated in each module according to the characteristics transferred to it. The generation of epileptiform spikes occurs in cases when balance of inhibition determined by GABA A and GABA B receptors is disturbed.

  9. Analysis of ribosomal protein S6 baseline phosphorylation and effect of tau pathology in the murine brain and human hippocampus.

    Science.gov (United States)

    Klingebiel, Maria; Dinekov, Maja; Köhler, Christoph

    2017-03-15

    We examined the distribution pattern of the phosphorylated 40S ribosomal subunit protein S6, a downstream target of the mTOR pathway, in the brains of 24-months-old human tau transgenic pR5 mice, non-transgenic littermates and in human hippocampi. We studied baseline levels of phosphorylated S6 and a possible effect of tau pathology. S6 phosphorylated at Ser235/236 (pS6Ser235/236) or Ser240/244 (pS6Ser240/244) has been used as a read-out of mTOR activity in several studies. The mTOR pathway regulates a wide variety of cellular functions including cell growth, ribosome biosynthesis, translational control and autophagy. Its dysregulation might underlie the neurodegenerative pathology of Alzheimer's disease and other tauopathies. pS6Ser235/236 and pS6Ser240/244 immunoreactivity in the mouse brain were widespread and similar distributed, but intensive pS6Ser235/236 immunoreactivity was more selective, especially highlighting certain brainstem regions. In the human hippocampus mainly granulovacuolar inclusions in neurons displayed pS6Ser235/236 immunoreactivity. In contrast, a considerable number of neurons displayed pS6Ser240/244 immunoreactivity in the cytoplasm without labeling of granulovacuolar inclusions. Except for a tendency of lower numbers of intensely phosphorylated S6-positive neurons in pR5 mice, the pattern of distribution of pS6Ser235/236 and pS6Ser240/244 immunoreactivity was largely unchanged when compared with non-transgenic mice and also when human hippocampi from AD cases and controls were compared. Similar to pR5 mice most neurons with hyper-phosphorylated tau in human hippocampi displayed no or only weak labeling for phosphorylated S6, suggesting that phosphorylated S6 is not especially associated with pathological tau, but is rather a feature of unaffected neurons. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Temporal expression of brain-derived neurotrophic factor (BDNF) mRNA in the rat hippocampus after treatment with selective and mixed monoaminergic antidepressants

    DEFF Research Database (Denmark)

    Larsen, Marianne Hald; Hay-Schmidt, Anders; Rønn, Lars Christian B

    2008-01-01

    Strong evidence suggests that antidepressants work by induction of neuroplastic changes mediated through regulation of brain-derived neurotrophic factor (BDNF). This study was undertaken to investigate the time-course of the effect of three antidepressants; fluoxetine, imipramine and venlafaxine......, which differentially affect monoamine reuptake, on BDNF mRNA expression in the hippocampus. The consequences of increased BDNF in the hippocampus are still indefinite. Here, we also determined the effects on the expression of two other genes (synaptophysin and growth-associated protein-43 (GAP-43......)) known to be involved in synapse formation and axonal growth and likely regulated by BDNF. The effects were determined in rats after sub-chronic (7 days) and chronic (14 and 21 days) treatment using semi-quantitative in situ hybridisation. BDNF mRNA levels in the dentate gyrus (DG) were increased after...

  11. Behavioral, neurochemical and molecular changes after acute deep brain stimulation of the infralimbic prefrontal cortex.

    Science.gov (United States)

    Jiménez-Sánchez, Laura; Linge, Raquel; Campa, Leticia; Valdizán, Elsa M; Pazos, Ángel; Díaz, Álvaro; Adell, Albert

    2016-09-01

    Deep brain stimulation (DBS) is a treatment that has shown some efficacy in treatment-resistant depression. In particular, DBS of the subcallosal cingulate gyrus (Brodmann's area 25, Cg25) has been successfully applied to treat refractory depression. In the rat, we have demonstrated that DBS applied to infralimbic (IL) cortex elevates the levels of glutamate and monoamines in the prefrontal cortex, and requires the stimulation of cortical α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors for its antidepressant-like effects. However, the molecular targets of IL DBS are not fully known. To gain insight into these pathways, we have investigated whether IL DBS is able to reverse the behavioral, biochemical and molecular changes exhibited by the olfactory bulbectomized (OBX) rat. Our results revealed that 1 h IL DBS diminished hyperlocomotion, hyperemotionality and anhedonia, and increased social interaction shown by the OBX rats. Further, IL DBS increased prefrontal efflux of glutamate and serotonin in both sham-operated and OBX rats. With regard to molecular targets, IL DBS increases the synthesis of brain-derived neurotrophic factor (BDNF) and the GluA1 AMPA receptor subunit, and stimulates the Akt/mammalian target of rapamycin (mTOR) as well as the AMPA receptor/c-AMP response element binding (CREB) pathways. Temsirolimus, a known in vivo mTOR blocker, suppressed the antidepressant-like effect of IL DBS in naïve rats in the forced swim test, thus demonstrating for the first time that mTOR signaling is required for the antidepressant-like effects of IL DBS, which is in line with the antidepressant response of other rapid-acting antidepressant drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Preventive brain radio-chemotherapy alters plasticity associated metabolite profile in the hippocampus but seems to not affect spatial memory in young leukemia patients.

    Science.gov (United States)

    Brandt, Moritz D; Brandt, Kalina; Werner, Annett; Schönfeld, Robby; Loewenbrück, Kai; Donix, Markus; Schaich, Markus; Bornhäuser, Martin; von Kummer, Rüdiger; Leplow, Bernd; Storch, Alexander

    2015-09-01

    Neuronal plasticity leading to evolving reorganization of the neuronal network during entire lifespan plays an important role for brain function especially memory performance. Adult neurogenesis occurring in the dentate gyrus of the hippocampus represents the maximal way of network reorganization. Brain radio-chemotherapy strongly inhibits adult hippocampal neurogenesis in mice leading to impaired spatial memory. To elucidate the effects of CNS radio-chemotherapy on hippocampal plasticity and function in humans, we performed a longitudinal pilot study using 3T proton magnetic resonance spectroscopy ((1)H-MRS) and virtual water-maze-tests in 10 de-novo patients with acute lymphoblastic leukemia undergoing preventive whole brain radio-chemotherapy. Patients were examined before, during and after treatment. CNS radio-chemotherapy did neither affect recall performance in probe trails nor flexible (reversal) relearning of a new target position over a time frame of 10 weeks measured by longitudinal virtual water-maze-testing, but provoked hippocampus-specific decrease in choline as a metabolite associated with cellular plasticity in (1)H-MRS. Albeit this pilot study needs to be followed up to definitely resolve the question about the functional role of adult human neurogenesis, the presented data suggest that (1)H-MRS allows the detection of neurogenesis-associated plasticity in the human brain.

  13. Continuous exercise training and curcumin attenuate changes in brain-derived neurotrophic factor and oxidative stress induced by lead acetate in the hippocampus of male rats.

    Science.gov (United States)

    Hosseinzadeh, Somayeh; Roshan, Valiollah Dabidi; Mahjoub, Soleiman

    2013-02-01

    For many years it has been known that lead is life-threatening, not only as an air pollutant but also because of it has been associated with several conditions including neurodegenerative disease. Curcumin (the principal curcuminoid found in turmeric) has demonstrated potent antioxidant properties. We investigated neuroprotective effects of endurance exercise and/or curcumin on lead acetate-induced neurotoxicity in the rat hippocampus. Forty male Wistar rats were randomly divided into five groups: 1) lead acetate, 2) curcumin, 3) training, 4) training + curcumin, and 5) control. The rats in the training groups performed treadmill running five times a week for 8 weeks (15-22 m/min, 25-64 min). All groups except control received lead acetate (20 mg/kg), whereas the control group received curcumin solution (ethyl oleate). In addition, the curcumin and training + curcumin groups received curcumin solution (30 mg/kg) intraperioneally. Lead acetate resulted in a significantly increase in the malondialdehyde (MDA) in plasma (72%), but not significant in hippocampus (59%). In addition, it led to significantly decreased brain-derived neurotrophic factor in hippocampus (17%) and total antioxidant capacity (27%), as compared to control group. Treadmill running, curcumin supplementation or both resulted in a significant decrease in hippocampus MDA (17, 20, 31%, respectively) and plasma MDA (60, 22, 71%) and also, significantly increased brain-derived neurotrophic factor (76, 45, 94%) and total antioxidant capacity (47.13, 47.11, 61%) levels, as compared to lead acetate group. These results provide a rationale for an inhibitory role of curcumin and regular exercise in the attenuation of lead-induced neurotoxicity.

  14. Our Faces in the Dog's Brain: Functional Imaging Reveals Temporal Cortex Activation during Perception of Human Faces.

    Science.gov (United States)

    Cuaya, Laura V; Hernández-Pérez, Raúl; Concha, Luis

    2016-01-01

    Dogs have a rich social relationship with humans. One fundamental aspect of it is how dogs pay close attention to human faces in order to guide their behavior, for example, by recognizing their owner and his/her emotional state using visual cues. It is well known that humans have specific brain regions for the processing of other human faces, yet it is unclear how dogs' brains process human faces. For this reason, our study focuses on describing the brain correlates of perception of human faces in dogs using functional magnetic resonance imaging (fMRI). We trained seven domestic dogs to remain awake, still and unrestrained inside an MRI scanner. We used a visual stimulation paradigm with block design to compare activity elicited by human faces against everyday objects. Brain activity related to the perception of faces changed significantly in several brain regions, but mainly in the bilateral temporal cortex. The opposite contrast (i.e., everyday objects against human faces) showed no significant brain activity change. The temporal cortex is part of the ventral visual pathway, and our results are consistent with reports in other species like primates and sheep, that suggest a high degree of evolutionary conservation of this pathway for face processing. This study introduces the temporal cortex as candidate to process human faces, a pillar of social cognition in dogs.

  15. Our Faces in the Dog's Brain: Functional Imaging Reveals Temporal Cortex Activation during Perception of Human Faces.

    Directory of Open Access Journals (Sweden)

    Laura V Cuaya

    Full Text Available Dogs have a rich social relationship with humans. One fundamental aspect of it is how dogs pay close attention to human faces in order to guide their behavior, for example, by recognizing their owner and his/her emotional state using visual cues. It is well known that humans have specific brain regions for the processing of other human faces, yet it is unclear how dogs' brains process human faces. For this reason, our study focuses on describing the brain correlates of perception of human faces in dogs using functional magnetic resonance imaging (fMRI. We trained seven domestic dogs to remain awake, still and unrestrained inside an MRI scanner. We used a visual stimulation paradigm with block design to compare activity elicited by human faces against everyday objects. Brain activity related to the perception of faces changed significantly in several brain regions, but mainly in the bilateral temporal cortex. The opposite contrast (i.e., everyday objects against human faces showed no significant brain activity change. The temporal cortex is part of the ventral visual pathway, and our results are consistent with reports in other species like primates and sheep, that suggest a high degree of evolutionary conservation of this pathway for face processing. This study introduces the temporal cortex as candidate to process human faces, a pillar of social cognition in dogs.

  16. 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. © The Author(s) 2015.

  17. Increased intrinsic brain connectivity between pons and somatosensory cortex during attacks of migraine with aura.

    Science.gov (United States)

    Hougaard, Anders; Amin, Faisal Mohammad; Larsson, Henrik B W; Rostrup, Egill; Ashina, Messoud

    2017-05-01

    The neurological disturbances of migraine aura are caused by transient cortical dysfunction due to waves of spreading depolarization that disrupt neuronal signaling. The effects of these cortical events on intrinsic brain connectivity during attacks of migraine aura have not previously been investigated. Studies of spontaneous migraine attacks are notoriously challenging due to their unpredictable nature and patient discomfort. We investigated 16 migraine patients with visual aura during attacks and in the attack-free state using resting state fMRI. We applied a hypothesis-driven seed-based approach focusing on cortical visual areas and areas involved in migraine pain, and a data-driven independent component analysis approach to detect changes in intrinsic brain signaling during attacks. In addition, we performed the analyses after mirroring the MRI data according to the side of perceived aura symptoms. We found a marked increase in connectivity during attacks between the left pons and the left primary somatosensory cortex including the head and face somatotopic areas (peak voxel: P = 0.0096, (x, y, z) = (-54, -32, 32), corresponding well with the majority of patients reporting right-sided pain. For aura-side normalized data, we found increased connectivity during attacks between visual area V5 and the lower middle frontal gyrus in the symptomatic hemisphere (peak voxel: P = 0.0194, (x, y, z) = (40, 40, 12). The present study provides evidence of altered intrinsic brain connectivity during attacks of migraine with aura, which may reflect consequences of cortical spreading depression, suggesting a link between aura and headache mechanisms. Hum Brain Mapp 38:2635-2642, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  18. 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.

  19. Dissociable Effects on Birdsong of Androgen Signaling in Cortex-Like Brain Regions of Canaries.

    Science.gov (United States)

    Alward, Beau A; Balthazart, Jacques; Ball, Gregory F

    2017-09-06

    The neural basis of how learned vocalizations change during development and in adulthood represents a major challenge facing cognitive neuroscience. This plasticity in the degree to which learned vocalizations can change in both humans and songbirds is linked to the actions of sex steroid hormones during ontogeny but also in adulthood in the context of seasonal changes in birdsong. We investigated the role of steroid hormone signaling in the brain on distinct features of birdsong using adult male canaries (Serinus canaria), which show extensive seasonal vocal plasticity as adults. Specifically, we bilaterally implanted the potent androgen receptor antagonist flutamide in two key brain regions that control birdsong. We show that androgen signaling in the motor cortical-like brain region, the robust nucleus of the arcopallium (RA), controls syllable and trill bandwidth stereotypy, while not significantly affecting higher order features of song such syllable-type usage (i.e., how many times each syllable type is used) or syllable sequences. In contrast, androgen signaling in the premotor cortical-like brain region, HVC (proper name), controls song variability by increasing the variability of syllable-type usage and syllable sequences, while having no effect on syllable or trill bandwidth stereotypy. Other aspects of song, such as the duration of trills and the number of syllables per song, were also differentially affected by androgen signaling in HVC versus RA. These results implicate androgens in regulating distinct features of complex motor output in a precise and nonredundant manner.SIGNIFICANCE STATEMENT Vocal plasticity is linked to the actions of sex steroid hormones, but the precise mechanisms are unclear. We investigated this question in adult male canaries (Serinus canaria), which show extensive vocal plasticity throughout their life. We show that androgens in two cortex-like vocal control brain regions regulate distinct aspects of vocal plasticity. For

  20. 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.

  1. Radiation sparing of cerebral cortex in brain tumor patients using quantitative neuroimaging.

    Science.gov (United States)

    Karunamuni, Roshan A; Moore, Kevin L; Seibert, Tyler M; Li, Nan; White, Nathan S; Bartsch, Hauke; Carmona, Ruben; Marshall, Deborah; McDonald, Carrie R; Farid, Nikdokht; Krishnan, Anithapriya; Kuperman, Joshua; Mell, Loren K; Brewer, James; Dale, Anders M; Moiseenko, Vitali; Hattangadi-Gluth, Jona A

    2016-01-01

    Neurocognitive decline in brain tumor patients treated with radiotherapy (RT) may be linked to cortical atrophy. We developed models to determine radiation treatment-planning objectives for cortex, which were tested on a sample population to identify the dosimetric cost of cortical sparing. The relationship between the probability of cortical atrophy in fifteen high-grade glioma patients at 1-year post-RT and radiation dose was fit using logistic mixed effects modeling. Cortical sparing was implemented using two strategies: region-specific sparing using model parameters, and non-specific sparing of all normal brain tissue. A dose threshold of 28.6 Gy was found to result in a 20% probability of severe atrophy. Average cortical sparing at 30 Gy was greater for region-specific dose avoidance (4.6%) compared to non-specific (3.6%). Cortical sparing resulted in an increase in heterogeneity index of the planning target volume (PTV) with an average increase of 1.9% (region-specific) and 0.9% (non-specific). We found RT doses above 28.6 Gy resulted in a greater than 20% probability of cortical atrophy. Cortical sparing can be achieved using region-specific or non-specific dose avoidance strategies at the cost of an increase in the dose heterogeneity of the PTV. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Neurokinin-1 (NK-1 receptor and brain-derived neurotrophic factor (BDNF gene expression is differentially modulated in the rat spinal dorsal horn and hippocampus during inflammatory pain

    Directory of Open Access Journals (Sweden)

    McCarson Kenneth E

    2007-10-01

    Full Text Available Abstract Persistent pain produces complex alterations in sensory pathways of the central nervous system (CNS through activation of various nociceptive mechanisms. However, the effects of pain on higher brain centers, particularly the influence of the stressful component of pain on the limbic system, are poorly understood. Neurokinin-1 (NK-1 receptors and brain-derived neurotrophic factor (BDNF, known neuromediators of hyperalgesia and spinal central sensitization, have also been implicated in the plasticity and neurodegeneration occurring in the hippocampal formation during exposures to various stressors. Results of this study showed that injections of complete Freund's adjuvant (CFA into the hind paw increased NK-1 receptor and BDNF mRNA levels in the ipsilateral dorsal horn, supporting an important role for these nociceptive mediators in the amplification of ascending pain signaling. An opposite effect was observed in the hippocampus, where CFA down-regulated NK-1 receptor and BDNF gene expression, phenomena previously observed in immobilization models of stress and depression. Western blot analyses demonstrated that in the spinal cord, CFA also increased levels of phosphorylated cAMP response element-binding protein (CREB, while in the hippocampus the activation of this transcription factor was significantly reduced, further suggesting that tissue specific transcription of either NK-1 or BDNF genes may be partially regulated by common intracellular transduction mechanisms mediated through activation of CREB. These findings suggest that persistent nociception induces differential regional regulation of NK-1 receptor and BDNF gene expression and CREB activation in the CNS, potentially reflecting varied roles of these neuromodulators in the spinal cord during persistent sensory activation vs. modulation of the higher brain structures such as the hippocampus.

  3. Prior regular exercise reverses the decreased effects of sleep deprivation on brain-derived neurotrophic factor levels in the hippocampus of ovariectomized female rats.

    Science.gov (United States)

    Saadati, Hakimeh; Sheibani, Vahid; Esmaeili-Mahani, Saeed; Darvishzadeh-Mahani, Fatemeh; Mazhari, Shahrzad

    2014-11-01

    Previous studies indicated that brain-derived neurotrophic factor (BDNF) is the main candidate to mediate the beneficial effects of exercise on cognitive function in sleep deprived male rats. In addition, our previous findings demonstrate that female rats are more vulnerable to the deleterious effects of sleep deprivation on cognitive performance and synaptic plasticity. Therefore, the current study was designed to investigate the effects of treadmill exercise and/or sleep deprivation (SD) on the levels of BDNF mRNA and protein in the hippocampus of female rats. Intact and ovariectomized (OVX) female Wistar rats were used in the present experiment. The exercise protocol was four weeks treadmill running and sleep deprivation was accomplished using the multiple platform method. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblot analysis were used to evaluate the level of BDNF mRNA and protein in the rat hippocampus respectively. Our results showed that protein and mRNA expression of BDNF was significantly (prats in compared with other groups. Furthermore, sleep deprived OVX rats under exercise conditions had a significant (pexercise can exert a protective effect against hippocampus-related functions and impairments induced by sleep deprivation probably by inducing BDNF expression. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Non-invasive brain stimulation of motor cortex induces embodiment when integrated with virtual reality feedback.

    Science.gov (United States)

    Bassolino, M; Franza, M; Bello Ruiz, J; Pinardi, M; Schmidlin, T; Stephan, M A; Solca, M; Serino, A; Blanke, O

    2018-02-20

    Previous evidence highlighted the multisensory-motor origin of embodiment - i.e., the experience of having a body and of being in control of it- and the possibility of experimentally manipulating it. For instance, an illusory feeling of embodiment towards a fake hand can be triggered by providing synchronous visuo-tactile stimulation to the hand of participants and to a fake hand or by asking participants to move their hand and observe a fake hand moving accordingly (rubber hand illusion, RHI). Here we tested whether it is possible to manipulate embodiment not through stimulation of the participant's hand, but by directly tapping into the brain's hand representation via non-invasive brain stimulation. To this aim, we combined transcranial magnetic stimulation (TMS) to activate the hand corticospinal representation with virtual reality (VR) to provide matching (as contrasted to non-matching) visual feedback, mimicking involuntary hand movements evoked by TMS. We show that the illusory embodiment occurred when TMS pulses were temporally matched with VR feedback, but not when TMS was administered outside primary motor cortex, (M1, over the vertex) or when stimulating M1 at a lower intensity (that did not activate peripheral muscles). Behavioral (questionnaires) and neurophysiological (motor-evoked-potentials, TMS-evoked-movements) measures further indicated that embodiment was not explained by stimulation per se, but depended on the temporal coherence between TMS-induced activation of hand corticospinal representation and the virtual bodily feedback. This reveals that non-invasive brain stimulation may replace the application of external tactile hand cues and motor components related to volition, planning, and anticipation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  5. Effects of ketamine administration on mTOR and reticulum stress signaling pathways in the brain after the infusion of rapamycin into prefrontal cortex.

    Science.gov (United States)

    Abelaira, Helena M; Réus, Gislaine Z; Ignácio, Zuleide M; Dos Santos, Maria Augusta B; de Moura, Airam B; Matos, Danyela; Demo, Júlia P; da Silva, Júlia B I; Michels, Monique; Abatti, Mariane; Sonai, Beatriz; Dal Pizzol, Felipe; Carvalho, André F; Quevedo, João

    2017-04-01

    Recent studies show that activation of the mTOR signaling pathway is required for the rapid antidepressant actions of glutamate N-methyl-D-aspartate (NMDA) receptor antagonists. A relationship between mTOR kinase and the endoplasmic reticulum (ER) stress pathway, also known as the unfolded protein response (UPR) has been shown. We evaluate the effects of ketamine administration on the mTOR signaling pathway and proteins of UPR in the prefrontal cortex (PFC), hippocampus, amygdala and nucleus accumbens, after the inhibiton of mTOR signaling in the PFC. Male adult Wistar rats received pharmacological mTOR inhibitor, rapamycin (0.2 nmol), or vehicle into the PFC and then a single dose of ketamine (15 mg/kg, i.p.). The immunocontent of mTOR, eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), eukaryotic elongation factor 2 kinase (eEF2K) homologous protein (CHOP), PKR-like ER kinase (PERK) and inositol-requiring enzyme 1 (IRE1) - alpha were determined in the brain. The mTOR levels were reduced in the rapamycin group treated with saline and ketamine in the PFC; p4EBP1 levels were reduced in the rapamycin group treated with ketamine in the PFC and nucleus accumbens; the levels of peEF2K were increased in the PFC in the vehicle group treated with ketamine and reduced in the rapamycin group treated with ketamine. The PERK and IRE1-alpha levels were decreased in the PFC in the rapamycin group treated with ketamine. Our results suggest that mTOR signaling inhibition by rapamycin could be involved, at least in part, with the mechanism of action of ketamine; and the ketamine antidepressant on ER stress pathway could be also mediated by mTOR signaling pathway in certain brain structures. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. The Neuron-Astrocyte-Microglia Triad in Normal Brain Ageing and in a Model of Neuroinflammation in the Rat Hippocampus

    Science.gov (United States)

    Cerbai, Francesca; Lana, Daniele; Nosi, Daniele; Petkova-Kirova, Polina; Zecchi, Sandra; Brothers, Holly M.; Wenk, Gary L.; Giovannini, Maria Grazia

    2012-01-01

    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. PMID:23028880

  7. Connectivity profiles reveal the relationship between brain areas for social cognition in human and monkey temporoparietal cortex.

    Science.gov (United States)

    Mars, Rogier B; Sallet, Jérôme; Neubert, Franz-Xaver; Rushworth, Matthew F S

    2013-06-25

    The human ability to infer the thoughts and beliefs of others, often referred to as "theory of mind," as well as the predisposition to even consider others, are associated with activity in the temporoparietal junction (TPJ) area. Unlike the case of most human brain areas, we have little sense of whether or how TPJ is related to brain areas in other nonhuman primates. It is not possible to address this question by looking for similar task-related activations in nonhuman primates because there is no evidence that nonhuman primates engage in theory-of-mind tasks in the same manner as humans. Here, instead, we explore the relationship by searching for areas in the macaque brain that interact with other macaque brain regions in the same manner as human TPJ interacts with other human brain regions. In other words, we look for brain regions with similar positions within a distributed neural circuit in the two species. We exploited the fact that human TPJ has a unique functional connectivity profile with cortical areas with known homologs in the macaque. For each voxel in the macaque temporal and parietal cortex we evaluated the similarity of its functional connectivity profile to that of human TPJ. We found that areas in the middle part of the superior temporal cortex, often associated with the processing of faces and other social stimuli, have the most similar connectivity profile. These results suggest that macaque face processing areas and human mentalizing areas might have a similar precursor.

  8. Asymmetric projections of the arcuate fasciculus to the temporal cortex underlie lateralized language function in the human brain

    Science.gov (United States)

    Takaya, Shigetoshi; Kuperberg, Gina R.; Liu, Hesheng; Greve, Douglas N.; Makris, Nikos; Stufflebeam, Steven M.

    2015-01-01

    The arcuate fasciculus (AF) in the human brain has asymmetric structural properties. However, the topographic organization of the asymmetric AF projections to the cortex and its relevance to cortical function remain unclear. Here we mapped the posterior projections of the human AF in the inferior parietal and lateral temporal cortices using surface-based structural connectivity analysis based on diffusion MRI and investigated their hemispheric differences. We then performed the cross-modal comparison with functional connectivity based on resting-state functional MRI (fMRI) and task-related cortical activation based on fMRI using a semantic classification task of single words. Structural connectivity analysis showed that the left AF connecting to Broca's area predominantly projected in the lateral temporal cortex extending from the posterior superior temporal gyrus to the mid part of the superior temporal sulcus and the middle temporal gyrus, whereas the right AF connecting to the right homolog of Broca's area predominantly projected to the inferior parietal cortex extending from the mid part of the supramarginal gyrus to the anterior part of the angular gyrus. The left-lateralized projection regions of the AF in the left temporal cortex had asymmetric functional connectivity with Broca's area, indicating structure-function concordance through the AF. During the language task, left-lateralized cortical activation was observed. Among them, the brain responses in the temporal cortex and Broca's area that were connected through the left-lateralized AF pathway were specifically correlated across subjects. These results suggest that the human left AF, which structurally and functionally connects the mid temporal cortex and Broca's area in asymmetrical fashion, coordinates the cortical activity in these remote cortices during a semantic decision task. The unique feature of the left AF is discussed in the context of the human capacity for language. PMID:26441551

  9. In vivo and continuous measurement of bisulfide in the hippocampus of rat's brain by an on-line integrated microdialysis/droplet-based microfluidic system.

    Science.gov (United States)

    Gu, Feidan; Zhou, Xiaoyu; Zhu, Xiaocui; Zhao, Meiping; Hao, Jie; Yu, Ping; Mao, Lanqun

    2015-06-07

    An on-line and continuous approach was demonstrated for in vivo measurement of bisulfide in rat's brain. A modified droplet-based microfluidic system was constructed, which allowed on-line qualification of the fluorescence responses of the gold nanoparticle-glutathione-fluorescein isothiocyanate probe to the variation of bisulfide in the presence of the cerebral microdialysate background. The on-line method achieved a dynamic working range from 5.0 μM to 40 μM and a detection limit of 2.5 μM. The in vivo bisulfide concentration in the hippocampus of rat's brain was measured under different physiological conditions. The on-line method may facilitate the study of H2S biology by providing a previously unattainable continuous record of H2S variation in living animals. It also provides a practical platform for in vivo and continuous monitoring of other important species in cerebral systems.

  10. 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. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. 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.

  12. Direct measurement of free radicals in the brain cortex and the blood serum after nociceptive stimulation in rats.

    Science.gov (United States)

    Rokyta, Richard; Stopka, Pavel; Holecek, Václav; Krikava, Karel; Pekárková, Ivana

    2004-08-01

    The concentrations of ROS were measured in samples of the sensorimotor brain cortex and in the rat blood. We measured the following parameters: The six lines spectra, nitroxide radical, free hydroxyl radical and singleton oxygen. Their concentration was measured under physiological conditions, after the nociceptive stimulation and after the application of melatonin, both in normal and stimulated animals. In the brain cortex only the singleton oxygen decreased after the nociceptive stimulation, whereas the nitroxide radicals and six lines spectra increased. The free hydroxyl radicals did not change significantly. In the blood serum the six lines spectra and nitroxide radical increased, the concentration of the free hydroxyl radicals did not change. Melatonin increased both the hydroxyl and nitroxide radicals. There was a non-significant decrease in the six lines spectra. The estimation of ROS can be used as a tool for detecting metabolic changes and the consequences of different environmental influences, in our case the influence of nociception and melatonin.

  13. Effect of Banisteriopsis caapi and Psychotria viridis “ayahuasca Binomio” ingestion in the rat brain hippocampus

    OpenAIRE

    Castro, Américo; Químico Farmacéutico, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Ramos, Norma; Químico Farmacéutico, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Juárez, José; Químico Farmacéutico, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Inostroza, Luis; Estudiantes de Farmacia y Bioquímica, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Ponce, Juan; Estudiantes de Farmacia y Bioquímica, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Choquesillo, Fritz; Estudiantes de Farmacia y Bioquímica, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Félix, Luis; Estudiantes de Farmacia y Bioquímica, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Escudero, Jackeline; Estudiantes de Farmacia y Bioquímica, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Navarro, Arnaldo; Estudiantes de Farmacia y Bioquímica, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Huaman, Susan; Estudiantes de Farmacia y Bioquímica, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Machaca, Bryan; Estudiantes de Farmacia y Bioquímica, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; López, Julio; Médico Patólogo, Instituto de Investigación en Ciencias Farmacéuticas y Recursos Naturales, Facultad de Farmacia y Bioquímica, UNMSM, Lima, Perú; Ramirez, Emilio; Médico Patólogo, Escuela de Formación profesional, Farmacia y Bioquímica, Facultad de Ciencias Biológicas, Universidad Nacional San Cristóbal de Huamanga, Ayacucho, Perú; Ruiz, Julio; Médico Patólogo, Instituto de Investigación en Química Biológica, Microbiología y Biotecnología, Facultad de Farmacia y Bioquímica, UNMSM, Lima-Perú; Raez, José; Médico Patólogo, Instituto de Patología, Facultad de Medicina Humana, UNMSM, Lima-Perú

    2016-01-01

    Objective. To assess the effect of Banisteriopsis caapi and Psychotria viridis ‘binomio ayahuasca’ ingestion in rat hippocampus. Design. Experimental, descriptive, analytical, and cross-sectional study. Institution. Research Institute of Pharmaceutical Sciences and Natural Resources, Faculty of Pharmacy and Biochemistry, Universidad Nacional Mayor de San Marcos, Lima, Peru. Biological material. Rats. Interventions. Orogastric administration of ‘binomio ayahuasca’ in adult Rattus norvegicus al...

  14. Engaging in paced mating, but neither exploratory, anti-anxiety, nor social behavior, increases 5α-reduced progestin concentrations in midbrain, hippocampus, striatum, and cortex

    OpenAIRE

    Frye, Cheryl A; Paris, Jason J; Rhodes, Madeline E.

    2007-01-01

    Sequential actions of 17β-estradiol (E2) and progesterone (P4) in the hypothalamus and the P4 metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP), in the midbrain ventral tegmental area (VTA) respectively mediate the initiation and intensity of lordosis of female rats and mayalso modulate anxiety and social behaviors, through actions in these, and/or other brain regions. Biosynthesis of E2, P4, and 3α,5α-THP can also occur in brain, independent of peripheral gland secretion, in response to enviro...

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

    Science.gov (United States)

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

    2015-08-20

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

  16. Non-stationary Discharge Patterns in Motor Cortex under Subthalamic Nucleus Deep Brain Stimulation: A Review.

    Directory of Open Access Journals (Sweden)

    Sabato eSantaniello

    2012-06-01

    Full Text Available Deep Brain Stimulation (DBS of the subthalamic nucleus (STN directly modulates the basal ganglia, but how such stimulation impacts the cortex upstream is largely unknown. There is evidence of cortical activation in 6-hydroxydopamine-lesioned rats and facilitation of motor evoked potentials in Parkinson’s disease (PD patients, but the impact of the DBS settings on the cortical activity in normal vs. Parkinsonian conditions is still debated.In recent studies, we used point process models to analyze non-stationary activation patterns and inter-neuronal dependencies in the motor and sensory cortices of awake non-human primates during STN DBS. We reported that these features are enhanced after treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, which causes a consistent PD-like motor impairment, and that high-frequency DBS (i.e., >100 pulses-per-second [pps] strongly reduces the short-term patterns (3-7ms period both before and after MPTP treatment, while it elicits a consistent short-latency post-stimulus activation. Low-frequency DBS (≤50pps, instead, had negligible effects on the non-stationary features while decreased the burstiness of the spike trains.We evaluate here the impact of the DBS settings on the cortical discharge patterns by using tools from the information theory (receiver operating characteristic curve, information rate, etc. and report that the probability of spiking of the cortical neurons is significantly conditioned on the DBS settings, with such dependency being significantly larger for high- vs. low-frequency DBS. Overall, the selective suppression of non-stationary features and the increased modulation of the spike probability suggest that high-frequency STN DBS enhances the neuronal activation in motor and sensory cortices, presumably because of reinforcement mechanisms, which perhaps involve the overlap between feedback antidromic and feed-forward orthodromic responses along the basal ganglia

  17. Increased ICP promotes CaMKII-mediated phosphorylation of neuronal NOS at Ser⁸⁴⁷ in the hippocampus immediately after subarachnoid hemorrhage.

    Science.gov (United States)

    Makino, Kazushige; Osuka, Koji; Watanabe, Yasuo; Usuda, Nobuteru; Hara, Masahito; Aoyama, Masahiro; Takayasu, Masakazu; Wakabayashi, Toshihiko

    2015-08-07

    Early brain injury has recently been identified as an indicator of poor prognosis after subarachnoid hemorrhage (SAH). Calmodulin-dependent protein kinase IIα (CaMKIIα) has been shown to phosphorylate neuronal NOS (nNOS) at Ser(847), resulting in a reduction in nNOS activity. In this study, we revealed chronological changes in the phosphorylation of nNOS at Ser(847) in the hippocampus and cortex immediately after SAH. In a rat single-hemorrhage model of SAH, the hippocampus and adjacent cortex were collected up to 24h after SAH. Samples from rats that were not injected with blood were used as controls. NOS was partially purified from the crude samples using ADP-agarose affinity chromatography. Western blot analysis revealed that nNOS phosphorylated (p-nNOS) at Ser(847) was significantly increased in the hippocampus, but not in the cortex, at 1h after SAH compared with that resulting from the control treatment. Immunoreactivity of p-nNOS at Ser(847) was observed in interneurons of the hippocampus at 1h after SAH. Injection of saline instead of blood also significantly induced p-nNOS at Ser(847) levels in the hippocampus at 1h after injection. The colocalization of CaMKIIα and nNOS was transiently increased in the hippocampus at 0.5h after SAH. Our data suggest that immediately after SAH, an increase in intracranial pressure might induce transient cerebral ischemia, potentially promoting the phosphorylation of nNOS at Ser(847) by CaMKIIα in the hippocampus. The activation of p-nNOS at Ser(847) in the hippocampus may alleviate ischemic insults immediately after SAH to exert a neuroprotective effect against early brain injury. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. 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.

  19. Multi-timescale measurements of brain responses in visual cortex during functional stimulation using time-resolved spectroscopy

    Science.gov (United States)

    Lebid, Solomiya; O'Neill, Raymond; Markham, Charles; Ward, Tomás; Coyle, Shirley

    2005-06-01

    Studies of neurovascular coupling (hemodynamic changes and neuronal activation) in the visual cortex using a time-domain single photon counting system have been undertaken. The system operates in near infrared (NIR) range of spectrum and allows functional brain monitoring to be done non-invasively. The detection system employs a photomultiplier and multi-channel scaler to detect and record emerging photons with sub-microsecond resolution (the effective collection time per curve point is ~ 200 ns). Localisation of the visual evoked potentials in the brain was done using knowledge obtained from electroencephalographic (EEG) studies and previous frequency-domain optical NIR spectroscopic systems. The well-known approach of visual stimulation of the human brain, which consists of an alternating black and white checkerboard pattern used previously for the EEG study of neural responses, is applied here. The checkerboard pattern is synchronized with the multi-channel scaler system and allows the analysis of time variation in back-scattered light, at different stimulation frequencies. Slow hemodynamic changes in the human brain due to Hb-HbO2 changes in the blood flow were observed, which is evidence of the system's capability to monitor these changes. Monocular visual tests were undertaken and compared with those done with an EEG system. In some subjects a fast optical response on a time scale commensurate with the neural activity associated with the visual cortex was detected. Future work will concentrate on improved experimental protocols and apparatus to confirm the existence of this important physiological signal.

  20. Sexual experience enhances cognitive flexibility and dendritic spine density in the medial prefrontal cortex.

    Science.gov (United States)

    Glasper, Erica R; LaMarca, Elizabeth A; Bocarsly, Miriam E; Fasolino, Maria; Opendak, Maya; Gould, Elizabeth

    2015-11-01

    The medial prefrontal cortex is important for cognitive flexibility, a capability that is affected by environmental conditions and specific experiences. Aversive experience, such as chronic restraint stress, is known to impair performance on a task of cognitive flexibility, specifically attentional set-shifting, in rats. Concomitant with this performance decrement, chronic stress reduces the number of dendritic spines on pyramidal neurons in the medial prefrontal cortex. No previous studies have examined whether a rewarding experience, namely mating, affects cognitive flexibility and dendritic spines in the medial prefrontal cortex of male rats. To test this possibility, we exposed adult male rats to sexual receptive females once daily for one week, assessed attentional set-shifting performance, and then analyzed their brains for changes in dendritic spines. We found that sexual experience improved performance on extradimensional set-shifting, which is known to require the medial prefrontal cortex. Additionally, we observed increased dendritic spine density on apical and basal dendrites of pyramidal neurons in the medial prefrontal cortex, but not the orbitofrontal cortex, after sexual experience. We also found that sexual experience enhanced dendritic spine density on granule neurons of the dentate gyrus. The ventral hippocampus sends a direct projection to the medial prefrontal cortex, raising the possibility that experience-dependent changes in the hippocampus are necessary for alterations in medial prefrontal cortex structure and function. As a first attempt at investigating this, we inactivated the ventral hippocampus with the GABA agonist muscimol, after each daily bout of sexual experience to observe whether the beneficial effects on cognitive flexibility were abolished. Contrary to our hypothesis, blocking hippocampal activity after sexual experience had no impact on enhanced cognitive flexibility. Taken together, these findings indicate that sexual

  1. Physical exercise mitigates doxorubicin-induced brain cortex and cerebellum mitochondrial alterations and cellular quality control signaling.

    Science.gov (United States)

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

    2016-01-01

    Doxorubicin (DOX) is a highly effective anti-neoplastic agent, whose clinical use is limited by a dose-dependent mitochondrial toxicity in non-target tissues, including the brain. Here we analyzed the effects of distinct exercise modalities (12-week endurance treadmill-TM or voluntary free-wheel activity-FW) performed before and during sub-chronic DOX treatment on brain cortex and cerebellum mitochondrial bioenergetics, oxidative stress, permeability transition pore (mPTP), and proteins involved in mitochondrial biogenesis, apoptosis and auto(mito)phagy. Male Sprague-Dawley rats were divided into saline-sedentary (SAL+SED), DOX-sedentary (DOX+SED; 7-week DOX (2 mg · kg(-1)per week)), DOX+TM and DOX+FW. Animal behavior and post-sacrifice mitochondrial function were assessed. Oxidative phosphorylation (OXPHOS) subunits, oxidative stress markers or related proteins (SIRT3, p66shc, UCP2, carbonyls, MDA, -SH, aconitase, Mn-SOD), as well as proteins involved in mitochondrial biogenesis (PGC1α and TFAM) were evaluated. Apoptotic signaling was followed through caspases 3, 8 and 9-like activities, Bax, Bcl2, CypD, ANT and cofilin expression. Mitochondrial dynamics (Mfn1, Mfn2, OPA1 and DRP1) and auto(mito)phagy (LC3II, Beclin1, Pink1, Parkin and p62)-related proteins were measured by semi-quantitative Western blotting. DOX impaired behavioral performance, mitochondrial function, including lower resistance to mPTP and increased apoptotic signaling, decreased the content in OXPHOS complex subunits and increased oxidative stress in brain cortex and cerebellum. Molecular markers of mitochondrial biogenesis, dynamics and autophagy were also altered by DOX treatment in both brain subareas. Generally, TM and FW were able to mitigate DOX-related impairments in brain cortex and cerebellum mitochondrial activity, mPTP and apoptotic signaling. We conclude that the alterations in mitochondrial biogenesis, dynamics and autophagy markers induced by exercise performed before and during

  2. Downregulation of GNA13-ERK network in prefrontal cortex of schizophrenia brain identified by combined focused and targeted quantitative proteomics.

    Science.gov (United States)

    Hirayama-Kurogi, Mio; Takizawa, Yohei; Kunii, Yasuto; Matsumoto, Junya; Wada, Akira; Hino, Mizuki; Akatsu, Hiroyasu; Hashizume, Yoshio; Yamamoto, Sakon; Kondo, Takeshi; Ito, Shingo; Tachikawa, Masanori; Niwa, Shin-Ichi; Yabe, Hirooki; Terasaki, Tetsuya; Setou, Mitsutoshi; Ohtsuki, Sumio

    2017-03-31

    Schizophrenia is a disabling mental illness associated with dysfunction of the prefrontal cortex, which affects cognition and emotion. The purpose of the present study was to identify altered molecular networks in the prefrontal cortex of schizophrenia patients by comparing protein expression levels in autopsied brains of patients and controls, using a combination of targeted and focused quantitative proteomics. We selected 125 molecules possibly related to schizophrenia for quantification by knowledge-based targeted proteomics. Among the quantified molecules, GRIK4 and MAO-B were significantly decreased in plasma membrane and cytosolic fractions, respectively, of prefrontal cortex. Focused quantitative proteomics identified 15 increased and 39 decreased proteins. Network analysis identified "GNA13-ERK1-eIF4G2 signaling" as a downregulated network, and proteins involved in this network were significantly decreased. Furthermore, searching downstream of eIF4G2 revealed that eIF4A1/2 and CYFIP1 were decreased, suggesting that downregulation of the network suppresses expression of CYFIP1, which regulates actin remodeling and is involved in axon outgrowth and spine formation. Downregulation of this signaling seems likely to impair axon formation and synapse plasticity of neuronal cells, and could be associated with development of cognitive impairment in the pathology of schizophrenia. The present study compared the proteome of the prefrontal cortex between schizophrenia patients and healthy controls by means of targeted proteomics and global quantitative proteomics. Targeted proteomics revealed that GRIK4 and MAOB were significantly decreased among 125 putatively schizophrenia-related proteins in prefrontal cortex of schizophrenia patients. Global quantitative proteomics identified 54 differentially expressed proteins in schizophrenia brains. The protein profile indicates attenuation of "GNA13-ERK signaling" in schizophrenia brain. In particular, EIF4G2 and CYFIP1

  3. Neuronal Cholesterol Accumulation Induced by Cyp46a1 Down-Regulation in Mouse Hippocampus Disrupts Brain Lipid Homeostasis

    Directory of Open Access Journals (Sweden)

    Sophie Ayciriex

    2017-07-01

    Full Text Available Impairment in cholesterol metabolism is associated with many neurodegenerative disorders including Alzheimer's disease (AD. However, the lipid alterations underlying neurodegeneration and the connection between altered cholesterol levels and AD remains not fully understood. We recently showed that cholesterol accumulation in hippocampal neurons, induced by silencing Cyp46a1 gene expression, leads to neurodegeneration with a progressive neuronal loss associated with AD-like phenotype in wild-type mice. We used a targeted and non-targeted lipidomics approach by liquid chromatography coupled to high-resolution mass spectrometry to further characterize lipid modifications associated to neurodegeneration and cholesterol accumulation induced by CYP46A1 inhibition. Hippocampus lipidome of normal mice was profiled 4 weeks after cholesterol accumulation due to Cyp46a1 gene expression down-regulation at the onset of neurodegeneration. We showed that major membrane lipids, sphingolipids and specific enzymes involved in phosphatidylcholine and sphingolipid metabolism, were rapidly increased in the hippocampus of AAV-shCYP46A1 injected mice. This lipid accumulation was associated with alterations in the lysosomal cargoe, accumulation of phagolysosomes and impairment of endosome-lysosome trafficking. Altogether, we demonstrated that inhibition of cholesterol 24-hydroxylase, key enzyme of cholesterol metabolism leads to a complex dysregulation of lipid homeostasis. Our results contribute to dissect the potential role of lipids in severe neurodegenerative diseases like AD.

  4. The prefrontal cortex in the Göttingen minipig brain defined by neural projection criteria and cytoarchitecture

    DEFF Research Database (Denmark)

    Jelsing, J; Hay-Schmidt, Anders; Dyrby, Tim

    2006-01-01

    In an attempt to delineate the prefrontal cortex (PFC) in the Gottingen minipig brain the distribution of reciprocal thalamocortical projections was investigated using anterograde and retrograde tracing techniques and evaluated in relation to the specific cytoarchitectonic organization. Tracers...... were visualized using standard immunohistochemistry or evaluated in vivo using manganese (Mn2+) as an MRI paramagnetic tracer. The in vivo tract tracing turned out to be very sensitive with a high correspondence to the histological labelling. Tracers injected into the mediodorsal thalamus labelled...... connections to different parts of the MD nucleus. Although the granular layer IV, characteristic of primate PFC could not be identified, both cytoarchitectonic and connectional data suggests that the Gottingen minipig has a structurally divided prefrontal cortex. Stereological estimates of PFC volume showed...

  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

    with ischemic stroke to detect viable neurons in cortex that appeared structurally intact on conventional neuroimaging studies. METHODS: Fourteen patients were selected by (1) angiography within 24 hours of onset showing embolic occlusion of an intracranial artery, (2) cerebral blood flow showing ischemia...... of moderate severity in 12 cases and spontaneous reflow in 2 cases, and (3) thrombolysis with reperfusion within 24 hours in most cases. Thirty reperfused cortical areas that remained structurally intact, 7 infarcted cortical areas, and 6 contralateral cerebellar areas with reduced blood flow were selected...... was calculated. RESULTS: The mean asymmetry ratio was 0.89 +/- 0.11 (range, 0.64 to 1.05), 0.50 +/- 0.15 (range, 0.23 to 0.67), and 0.97 +/- 0.05 (range, 0.90 to 1.04) in reperfused cortex, infarcted cortex, and contralateral cerebellum, respectively. Compared with unity, both reperfused cortex and infarcted...

  6. Analysis for distinctive activation patterns of pain and itchy in the human brain cortex measured using near infrared spectroscopy (NIRS.

    Directory of Open Access Journals (Sweden)

    Chih-Hung Lee

    Full Text Available Pain and itch are closely related sensations, yet qualitatively quite distinct. Despite recent advances in brain imaging techniques, identifying the differences between pain and itch signals in the brain cortex is difficult due to continuous temporal and spatial changes in the signals. The high spatial resolution of positron emission tomography (PET and functional magnetic resonance imaging (fMRI has substantially advanced research of pain and itch, but these are uncomfortable because of expensiveness, importability and the limited operation in the shielded room. Here, we used near infrared spectroscopy (NIRS, which has more conventional usability. NIRS can be used to visualize dynamic changes in oxygenated hemoglobin and deoxyhemoglobin concentrations in the capillary networks near activated neural circuits in real-time as well as fMRI. We observed distinct activation patterns in the frontal cortex for acute pain and histamine-induced itch. The prefrontal cortex exhibited a pain-related and itch-related activation pattern of blood flow in each subject. Although it looked as though that activation pattern for pain and itching was different in each subject, further cross correlation analysis of NIRS signals between each channels showed an overall agreement with regard to prefrontal area involvement. As a result, pain-related and itch-related blood flow responses (delayed responses in prefrontal area were found to be clearly different between pain (τ = +18.7 sec and itch (τ = +0.63 sec stimulation. This is the first pilot study to demonstrate the temporal and spatial separation of a pain-induced blood flow and an itch-induced blood flow in human cortex during information processing.

  7. Analysis for distinctive activation patterns of pain and itchy in the human brain cortex measured using near infrared spectroscopy (NIRS).

    Science.gov (United States)

    Lee, Chih-Hung; Sugiyama, Takashi; Kataoka, Aiko; Kudo, Ayako; Fujino, Fukue; Chen, Yu-Wen; Mitsuyama, Yuki; Nomura, Shinobu; Yoshioka, Tohru

    2013-01-01

    Pain and itch are closely related sensations, yet qualitatively quite distinct. Despite recent advances in brain imaging techniques, identifying the differences between pain and itch signals in the brain cortex is difficult due to continuous temporal and spatial changes in the signals. The high spatial resolution of positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) has substantially advanced research of pain and itch, but these are uncomfortable because of expensiveness, importability and the limited operation in the shielded room. Here, we used near infrared spectroscopy (NIRS), which has more conventional usability. NIRS can be used to visualize dynamic changes in oxygenated hemoglobin and deoxyhemoglobin concentrations in the capillary networks near activated neural circuits in real-time as well as fMRI. We observed distinct activation patterns in the frontal cortex for acute pain and histamine-induced itch. The prefrontal cortex exhibited a pain-related and itch-related activation pattern of blood flow in each subject. Although it looked as though that activation pattern for pain and itching was different in each subject, further cross correlation analysis of NIRS signals between each channels showed an overall agreement with regard to prefrontal area involvement. As a result, pain-related and itch-related blood flow responses (delayed responses in prefrontal area) were found to be clearly different between pain (τ = +18.7 sec) and itch (τ = +0.63 sec) stimulation. This is the first pilot study to demonstrate the temporal and spatial separation of a pain-induced blood flow and an itch-induced blood flow in human cortex during information processing.

  8. 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.

  9. Increased perceived stress is related to decreased prefrontal cortex volumes among older adults.

    Science.gov (United States)

    Moreno, Georgina L; Bruss, Joel; Denburg, Natalie L

    2017-05-01

    Several of the brain regions vulnerable to increased levels of stress (i.e., hippocampus and prefrontal cortex) are also known to undergo disproportionate decline during normal aging. To date, surprisingly little research has examined the effects of stress on the brain among healthy human populations, much less in the elderly. The aim of the current study was to investigate the relationship between chronic stress and brain morphometry in regions known for their involvement in the stress response, namely the prefrontal cortex, hippocampus, and amygdala, in a sample of healthy older adults. The Perceived Stress Scale and structural magnetic resonance imaging (MRI) were collected in 28 older adult individuals aged 65 to 90 years. Gray and white matter volumes in various regions of interest in the prefrontal cortex and medial temporal lobes were calculated using semiautomated segmentation tools. Perceived stress was negatively correlated with overall prefrontal cortex (PFC) volume, specifically in overall white matter volume of the PFC. Additionally, perceived stress was negatively correlated with gray and white matter volumes in lateral regions of the PFC, specifically, in the ventrolateral and dorsolateral PFC. Perceived stress was not significantly related to medial temporal lobe volumes. These findings suggest that among healthy older adults, there is a salient relationship between prefrontal cortex volumes and levels of perceived stress. This research fills a critical gap in the current literature and provides initial groundwork for future studies investigating the relationship between perceived stress and the prefrontal cortex in the context of healthy aging.

  10. Cadherin-13 Deficiency Increases Dorsal Raphe 5-HT Neuron Density and Prefrontal Cortex Innervation in the Mouse Brain

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    Andrea Forero

    2017-09-01

    Full Text Available Background: During early prenatal stages of brain development, serotonin (5-HT-specific neurons migrate through somal translocation to form the raphe nuclei and subsequently begin to project to their target regions. The rostral cluster of cells, comprising the median and dorsal raphe (DR, innervates anterior regions of the brain, including the prefrontal cortex. Differential analysis of the mouse 5-HT system transcriptome identified enrichment of cell adhesion molecules in 5-HT neurons of the DR. One of these molecules, cadherin-13 (Cdh13 has been shown to play a role in cell migration, axon pathfinding, and synaptogenesis. This study aimed to investigate the contribution of Cdh13 to the development of the murine brain 5-HT system.Methods: For detection of Cdh13 and components of the 5-HT system at different embryonic developmental stages of the mouse brain, we employed immunofluorescence protocols and imaging techniques, including epifluorescence, confocal and structured illumination microscopy. The consequence of CDH13 loss-of-function mutations on brain 5-HT system development was explored in a mouse model of Cdh13 deficiency.Results: Our data show that in murine embryonic brain Cdh13 is strongly expressed on 5-HT specific neurons of the DR and in radial glial cells (RGCs, which are critically involved in regulation of neuronal migration. We observed that 5-HT neurons are intertwined with these RGCs, suggesting that these neurons undergo RGC-guided migration. Cdh13 is present at points of intersection between these two cell types. Compared to wildtype controls, Cdh13-deficient mice display increased cell densities in the DR at embryonic stages E13.5, E17.5, and adulthood, and higher serotonergic innervation of the prefrontal cortex at E17.5.Conclusion: Our findings provide evidence for a role of CDH13 in the development of the serotonergic system in early embryonic stages. Specifically, we indicate that Cdh13 deficiency affects the cell

  11. Spinal cord injury drives chronic brain changes

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    Ignacio Jure

    2017-01-01

    Full Text Available Only a few studies have considered changes in brain structures other than sensory and motor cortex after spinal cord injury, although cognitive impairments have been reported in these patients. Spinal cord injury results in chronic brain neuroinflammation with consequent neurodegeneration and cognitive decline in rodents. Regarding the hippocampus, neurogenesis is reduced and reactive gliosis increased. These long-term abnormalities could explain behavioral impairments exhibited in humans patients suffering from spinal cord trauma.

  12. Specific metabolomics adaptations define a differential regional vulnerability in the adult human cerebral cortex

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    Rosanna Cabré

    2016-12-01

    Full Text Available Brain neurons offer diverse responses to stresses and detrimental factors during development and aging, and as a result of both neurodegenerative and neuropsychiatric disorders. This multiplicity of responses can be ascribed to the great diversity among neuronal populations. Here we have determined the metabolomic profile of three healthy adult human brain regions—entorhinal cortex, hippocampus, and frontal cortex—using mass spectrometry-based technologies. Our results show the existence of a lessened energy demand, mitochondrial stress, and lower one-carbon metabolism (particularly restricted to the methionine cycle specifically in frontal cortex. These findings, along with the better antioxidant capacity and lower mTOR signaling also seen in frontal cortex, suggest that this brain region is especially resistant to stress compared to the entorhinal cortex and hippocampus, which are more vulnerable regions. Globally, our results show the presence of specific metabolomics adaptations in three mature, healthy human brain regions, confirming the existence of cross-regional differences in cell vulnerability in the human cerebral cortex.

  13. Molar loss and powder diet leads to memory deficit and modifies the mRNA expression of brain-derived neurotrophic factor in the hippocampus of adult mice.

    Science.gov (United States)

    Takeda, Yosuke; Oue, Hiroshi; Okada, Shinsuke; Kawano, Akira; Koretake, Katsunori; Michikawa, Makoto; Akagawa, Yasumasa; Tsuga, Kazuhiro

    2016-12-05

    It is known that tooth loss is known to be a risk factor for Alzheimer's disease and soft diet feeding induces memory impairment. Recent studies have shown that brain-derived neurotrophic factor (BDNF) is associated with tooth loss or soft diet in young animal model, and that BDNF expression is decreased in patients with Alzheimer's disease. However, single or combined effect of tooth loss and/or soft diet on brain function has not fully understood. Here we examined the effect of molar loss and powder diet on memory ability and the expression of BDNF mRNA in the hippocampus of adult C57BL/6J mice. Twenty eight-weeks-old C57BL/6J mice were divided into intact molar group and extracted molar group. They were randomly divided into the I/S group (Intact upper molar teeth/Solid diet feeding), the E/S group (Extracted upper molar teeth/Solid diet feeding), the I/P group (Intact upper molar teeth/Powder diet feeding), and the E/P group (Extracted upper molar teeth/Powder diet feeding). The observation periods were 4 and 16-week. To analyze the memory ability, the step-through passive avoidance test was conducted. BDNF-related mRNA in the hippocampus was analyzed by real-time polymerase chain reaction (RT-PCR). At 4 weeks later, we performed memory test and isolated brains to analyze. There were no differences in memory function and BDNF mRNA level between these four groups. However, at 16 weeks later, E/S and E/P group showed memory impairment, and decreased level of BDNF mRNA. Whereas, the powder diet had no effect on memory function and BDNF mRNA level even at 16 weeks later. These results suggest that the effect of molar loss and powder diet on memory function and BDNF mRNA levels were different, molar loss may have a greater long-term effect on memory ability than powder diet does.

  14. [Effect of acupuncture intervention on 14-3-3 expression in cerebral cortex of hypoxic-ischemic brain damage rats].

    Science.gov (United States)

    Li, Xing-er; Yuan, Qing; Tang, Chun-zhi; Chen, Fei; Zhao, Rong; Liu, Long-lin; Yu, Yu-tian; Cao, Yong; Wu, Jia-li; Sun, Shuo

    2014-12-01

    To observe the effect of acupuncture therapy on 14-3-3, Bcl-2 and Bax expression levels in the cerebral cortex in neonatal rats with hypoxic-ischemic brain damage(HIBD). Timed pregnant Sprague-Dawley rat dams were delivered either vaginally (normal group), or by C-section (sham-operation group) or by C-section with 5 min of global anoxia (anoxia group), with 8 rats in each group. The rat pups of the anoxia group were randomly divided into model group and acupuncture group (n =8). Acupuncture stimulation of "Naosanzhen" "Niesanzhen" and "Zhisanzhen" acupoints was given begin- ning from the 14th day after birth, once daily for 7 consecutive days. All rat pups were killed by decapitation on day 21 after birth, and then 14-3-3, Bcl-2 and Bax immunoactivity (expression) in the cerebral cortex were detected by immunohistochemistry. In comparison with the normal group, the expression level of cerebral cortical 14-3-3 was significantly decreased, and that of Bax remarkably increased in the model group (Poperation group (P0. 05). Acupuncture intervention can increase the expression of 14-3-3 and Bcl-2 in the cerebral cortex in HIBD rats.

  15. Coordinated Gene Expression of Neuroinflammatory and Cell Signaling Markers in Dorsolateral Prefrontal Cortex during Human Brain Development and Aging

    Science.gov (United States)

    Primiani, Christopher T.; Ryan, Veronica H.; Rao, Jagadeesh S.; Cam, Margaret C.; Ahn, Kwangmi; Modi, Hiren R.; Rapoport, Stanley I.

    2014-01-01

    Background Age changes in expression of inflammatory, synaptic, and neurotrophic genes are not well characterized during human brain development and senescence. Knowing these changes may elucidate structural, metabolic, and functional brain processes over the lifespan, as well vulnerability to neurodevelopmental or neurodegenerative diseases. Hypothesis Expression levels of inflammatory, synaptic, and neurotrophic genes in the human brain are coordinated over the lifespan and underlie changes in phenotypic networks or cascades. Methods We used a large-scale microarray dataset from human prefrontal cortex, BrainCloud, to quantify age changes over the lifespan, divided into Development (0 to 21 years, 87 brains) and Aging (22 to 78 years, 144 brains) intervals, in transcription levels of 39 genes. Results Gene expression levels followed different trajectories over the lifespan. Many changes were intercorrelated within three similar groups or clusters of genes during both Development and Aging, despite different roles of the gene products in the two intervals. During Development, changes were related to reported neuronal loss, dendritic growth and pruning, and microglial events; TLR4, IL1R1, NFKB1, MOBP, PLA2G4A, and PTGS2 expression increased in the first years of life, while expression of synaptic genes GAP43 and DBN1 decreased, before reaching plateaus. During Aging, expression was upregulated for potentially pro-inflammatory genes such as NFKB1, TRAF6, TLR4, IL1R1, TSPO, and GFAP, but downregulated for neurotrophic and synaptic integrity genes such as BDNF, NGF, PDGFA, SYN, and DBN1. Conclusions Coordinated changes in gene transcription cascades underlie changes in synaptic, neurotrophic, and inflammatory phenotypic networks during brain Development and Aging. Early postnatal expression changes relate to neuronal, glial, and myelin growth and synaptic pruning events, while late Aging is associated with pro-inflammatory and synaptic loss changes. Thus, comparable

  16. Retrosplenial and hippocampal brain regions in human navigation: complementary functional contributions to the formation and use of cognitive maps.

    Science.gov (United States)

    Iaria, Giuseppe; Chen, Jen-Kai; Guariglia, Cecilia; Ptito, Alain; Petrides, Michael

    2007-02-01

    The ability to orientate within familiar environments relies on the formation and use of a mental representation of the environment, namely a cognitive map. Neuropsychological and neuroimaging studies suggest that the retrosplenial and hippocampal brain regions are involved in topographical orientation. We combined functional magnetic resonance imaging with a virtual-reality paradigm to investigate the functional interaction of the hippocampus and retrosplenial cortex during the formation and utilization of cognitive maps by human subjects. We found that the anterior hippocampus is involved during the formation of the cognitive map, while the posterior hippocampus is involved when using it. In conjunction with the hippocampus, the retrosplenial cortex was active during both the formation and the use of the cognitive map. In accordance with earlier studies in non-human animals, these findings suggest that, while navigating within the environment, the retrosplenial cortex complements the hippocampal contribution to topographical orientation by updating the individual's location as the frame of reference changes.

  17. 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.

  18. 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…

  19. Prefrontal Cortex Is Critical for Contextual Processing: Evidence from Brain Lesions

    Science.gov (United States)

    Fogelson, Noa; Shah, Mona; Scabini, Donatella; Knight, Robert T.

    2009-01-01

    We investigated the role of prefrontal cortex (PFC) in local contextual processing using a combined event-related potentials and lesion approach. Local context was defined as the occurrence of a short predictive series of visual stimuli occurring before delivery of a target event. Targets were preceded by either randomized sequences of standards…

  20. Thermosensory Perceptual Learning Is Associated with Structural Brain Changes in Parietal-Opercular (SII) Cortex.

    Science.gov (United States)

    Mano, Hiroaki; Yoshida, Wako; Shibata, Kazuhisa; Zhang, Suyi; Koltzenburg, Martin; Kawato, Mitsuo; Seymour, Ben

    2017-09-27

    The location of a sensory cortex for temperature perception remains a topic of substantial debate. Both the parietal-opercular (SII) and posterior insula have been consistently implicated in thermosensory processing, but neither region has yet been identified as the locus of fine temperature discrimination. Using a perceptual learning paradigm in male and female humans, we show improvement in discrimination accuracy for subdegree changes in both warmth and cool detection over 5 d of repetitive training. We found that increases in discriminative accuracy were specific to the temperature (cold or warm) being trained. Using structural imaging to look for plastic changes associated with perceptual learning, we identified symmetrical increases in gray matter volume in the SII cortex. Furthermore, we observed distinct, adjacent regions for cold and warm discrimination, with cold discrimination having a more anterior locus than warm. The results suggest that thermosensory discrimination is supported by functionally and anatomically distinct temperature-specific modules in the SII cortex.SIGNIFICANCE STATEMENT We provide behavioral and neuroanatomical evidence that perceptual learning is possible within the temperature system. We show that structural plasticity localizes to parietal-opercular (SII), and not posterior insula, providing the best evidence to date resolving a longstanding debate about the location of putative "temperature cortex." Furthermore, we show that cold and warm pathways are behaviorally and anatomically dissociable, suggesting that the temperature system has distinct temperature-dependent processing modules. Copyright © 2017 Mano et al.

  1. Higher Brain Functions Served by the Lowly Rodent Primary Visual Cortex

    Science.gov (United States)

    Gavornik, Jeffrey P.; Bear, Mark F.

    2014-01-01

    It has been more than 50 years since the first description of ocular dominance plasticity--the profound modification of primary visual cortex (V1) following temporary monocular deprivation. This discovery immediately attracted the intense interest of neurobiologists focused on the general question of how experience and deprivation modify the brain…

  2. A novel TRH analog, Glp-Asn-Pro-D-Tyr-D-TrpNH2, binds to [3H][3-Me-His2]TRH-labelled sites in rat hippocampus and cortex but not pituitary or heterologous cells expressing TRHR1 or TRHR2.

    Science.gov (United States)

    Hogan, Nicola; O'Boyle, Kathy M; Hinkle, Patricia M; Kelly, Julie A

    2008-01-24

    Glp-Asn-Pro-D-Tyr-D-TrpNH(2) is a novel synthetic peptide that mimics and amplifies central actions of thyrotropin-releasing hormone (TRH) in rat without releasing TSH. The aim of this study was to compare the binding properties of this pentapeptide and its all-L counterpart (Glp-Asn-Pro-Tyr-TrpNH(2)) to TRH receptors in native rat brain tissue and cells expressing the two TRH receptor subtypes identified in rat to date, namely TRHR1 and TRHR2. Radioligand binding studies were carried out using [(3)H][3-Me-His(2)]TRH to label receptors in hippocampal, cortical and pituitary tissue, GH4 pituitary cells, as well as CHO cells expressing TRHR1 and/or TRHR2. In situ hybridization studies suggest that cortex expresses primarily TRHR2 mRNA, hippocampus primarily TRHR1 mRNA and pituitary exclusively TRHR1 mRNA. Competition experiments showed [3-Me-His(2)]TRH potently displaced [(3)H][3-Me-His(2)]TRH binding from all tissues/cells investigated. Glp-Asn-Pro-D-Tyr-D-TrpNH(2) in concentrations up to 10(-5)M did not displace [(3)H][3-Me-His(2)]TRH binding to membranes derived from GH4 cells or CHO-TRHR1 cells, consistent with its lack of binding to pituitary membranes and TSH-releasing activity. Similar results were obtained for the corresponding all-L peptide. In contrast, both pentapeptides displaced binding from rat hippocampal membranes (pIC(50) Glp-Asn-Pro-D-Tyr-D-TrpNH(2): 7.7+/-0.2; pIC(50) Glp-Asn-Pro-Tyr-TrpNH(2): 6.6+/-0.2), analogous to cortical membranes (pIC(50) Glp-Asn-Pro-D-Tyr-D-TrpNH(2): 7.8+/-0.2; pIC(50) Glp-Asn-Pro-Tyr-TrpNH(2): 6.6+/-0.2). Neither peptide, however, displaced [(3)H][3-Me-His(2)]TRH binding to CHO-TRHR2. Thus, this study reveals for the first time significant differences in the binding properties of native and heterologously expressed TRH receptors. Also, the results raise the possibility that Glp-Asn-Pro-D-Tyr-D-TrpNH(2) is not displacing [(3)H][3-Me-His(2)]TRH from a known TRH receptor in rat cortex, but rather a hitherto unidentified TRH

  3. mRNA expression of the lipid and mechano-gated 2P domain K+ channels during rat brain development.

    Science.gov (United States)

    Xu, Xianghua; Pan, Yaping; Wang, Xiaoliang

    2002-01-01

    mRNAs encoded by genes for the lipid-sensitive mechano-gated K(+) channels TREK-1, TREK-2, and TRAAK were detected in rat brain at different life-cycle stages: 18-day embryos, postnatal days 1, 7, 28, and 60 (adulthood). mRNA expression of TREK-1 or TREK-2 showed no appreciable changes during the development of cortex and hippocampus. TRAAK mRNA expression increased with development and reached an apparent maximum at postnatal day 28 in hippocampus and day 60 in cortex. These data suggest that TRAAK might be important in the development of rat brain.

  4. Effect of chronic aluminum exposure on the levels of conjugated dienes and enzymatic antioxidants in hippocampus and whole brain of rat

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, A.; Shukla, G.S. [Industrial Toxicology Research Centre, Lucknow (India)

    1995-11-01

    The reported association between elevated tissue levels of aluminum (Al) and certain human neurological disorders have evoked increasing attention on the neurotoxic effects of aluminum. High levels of Al have been reported in hippocampal neurons comprising neurofibrillary tangles in senile dementia of Alzheimer`s type, amyotropic lateral sclerosis and Parkinsonian dementia of Guam. Aluminum is considered to be the causal factor for a high incidence of dialysis encephalopathy. It has been shown that the incidence of Alzheimer`s disease was higher in places with a high Al content in drinking water compared to low level areas. Varied uses of Al in pharmaceutical preparations, foods, water purification and many house-hold items have increased the risk of its exposure to general population. The exposure may be as high as 500 mg/kg/day in children with uremia who are treated with Al containing phosphate binding gels. Aluminum ingestion in humans and experimental animals have been reported to produce behavioural dysfunctions. The mechanism of al neurotoxicity is not understood at present. Attempts made in this direction have reported its interaction with blood-brain barrier function, decreased membrane fluidity, glutathione depletion and increased brain lipid peroxidation. These studies indicate the possibility that oxidative stress may be one of the possible mechanisms of Al-induced neurotoxicity. Since Al has been reported to be in high concentrations in hippocampal neurons in certain neurological diseases and there is wealth of evidence implicating hippocampal impairment and memory dysfunction, we attempted to investigate the effect of chronic Al intoxication on the status of enzymatic antioxidants and the extent of peroxidative damage in hippocampus and whole brain of rat. 16 refs., 4 figs., 1 tab.

  5. Changes in brain biogenic monoamines induced by the nootropic drugs adafenoxate and meclofenoxate and by citicholine (experiments on rats).

    Science.gov (United States)

    Petkov, V D; Stancheva, S L; Tocuschieva, L; Petkov, V V

    1990-01-01

    1. The effects of Adafenoxate (Adf), meclofenoxate (Mf) and citicholine (CCh) administered at a daily dose of 100 mg/kg for 7 days on the levels of noradrenaline (NA), dopamine (DA) and serotonin (5-HT) in the frontal cerebral cortex, striatum, hippocampus and hypothalamus of rats were studied. 2. Adafenoxate increased the NA level in the striatum and decreased it in the hypothalamus; it increased the DA level in the cerebral cortex and hypothalamus and decreased it in the striatum; it increased the 5-HT level in the cerebral cortex and decreased it in the hippocampus. 3. Meclofenoxate decreased the NA level in the cerebral cortex and hypothalamus; it increased the DA level in the hippocampus and hypothalamus and the 5-HT level in the cerebral cortex, striatum, hippocampus and hypothalamus. 4. Citicholine increased the NA level in the cerebral cortex and hypothalamus; it increased the DA level in the striatum and the 5-HT level in the cerebral cortex, striatum and hippocampus. 5. An attempt is made to explain some similarities and differences in the behavioral effects of the drugs tested (and those observed in other studies) by the changes they induce in brain biogenic monoamines.

  6. Positive selection in ASPM is correlated with cerebral cortex evolution across primates but not with whole-brain size.

    Science.gov (United States)

    Ali, Farhan; Meier, Rudolf

    2008-11-01

    The rapid increase of brain size is a key event in human evolution. Abnormal spindle-like microcephaly associated (ASPM) is discussed as a major candidate gene for explaining the exceptionally large brain in humans but ASPM's role remains controversial. Here we use codon-specific models and a comparative approach to test this candidate gene that was initially identified in Homo-chimp comparisons. We demonstrate that accelerated evolution of ASPM (omega = 4.7) at 16 amino acid sites occurred in 9 primate lineages with major changes in relative cerebral cortex size. However, ASPM's evolution is not correlated with major changes in relative whole-brain or cerebellum sizes. Our results suggest that a single candidate gene such as ASPM can influence a specific component of the brain across large clades through changes in a few amino acid sites. We furthermore illustrate the power of using continuous phenotypic variability across primates to rigorously test candidate genes that have been implicated in the evolution of key human traits.

  7. Cortical representations are reinstated by the hippocampus during memory retrieval.

    Science.gov (United States)

    Tanaka, Kazumasa Z; Pevzner, Aleksandr; Hamidi, Anahita B; Nakazawa, Yuki; Graham, Jalina; Wiltgen, Brian J

    2014-10-22

    The hippocampus is assumed to retrieve memory by reinstating patterns of cortical activity that were observed during learning. To test this idea, we monitored the activity of individual cortical neurons while simultaneously inactivating the hippocampus. Neurons that were active during context fear conditioning were tagged with the long-lasting fluorescent protein H2B-GFP and the light-activated proton pump ArchT. These proteins allowed us to identify encoding neurons several days after learning and silence them with laser stimulation. When tagged CA1 cells were silenced, we found that memory retrieval was impaired and representations in the cortex (entorhinal, retrosplenial, perirhinal) and the amygdala could not be reactivated. Importantly, hippocampal inactivation did not alter the total amount of activity in most brain regions. Instead, it selectively prevented neurons that were active during learning from being reactivated during retrieval. These data provide functional evidence that the hippocampus reactivates specific memory representations during retrieval. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Analysis of microRNA expression detected by microarray of the cerebral cortex after hypoxic-ischemic brain injury.

    Science.gov (United States)

    Cui, Hong; Yang, Lijun

    2013-11-01

    Small and noncoding microRNAs (miRNAs) are known as key regulators of biological processes such as cell differentiation and tumor generation. They are also the important mediators of posttranscriptional gene silencing in both pathogenic and pathologic aspects of hypoxic-ischemic brain injury. miRNA microarray has been considered to be a high-throughput and precise analysis tool for detecting miRNA expression profiling, and it does greatly facilitate the research of the biological function of miRNAs. To investigate the changes of miRNA expression in cortex of neonatal rats with hypoxic-ischemic brain injury (HIBI) and the possible roles of miRNA in the pathogenesis of HIBI, we constructed the model of rat with HIBI and the cortex tissues were obtained 14 days after the HIBI operation. The large-scale miRNA microarrays and bioinformatics analysis were used to determine the differentially expressed miRNAs of HIBI rats compared with controls. Expression of 3 miRNAs (mir-429, mir-200b, and mir-182) was determined by quantitative real-time polymerase chain reaction. The results of miRNA expression profiles indicated that 5 miRNAs were up-regulated more than twice and 29 miRNAs were down-regulated more than twice compared with the normal control group. The results of the 3 miRNAs detected by quantitative real-time polymerase chain reaction were consistent with those detected by miRNA microarray. Hypoxic-ischemic brain injury rats have significant changes in miRNA expression, which demonstrated that miRNAs may play important roles in the pathogenesis of HIBI.

  9. 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.

  10. 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

  11. Visual maps in the adult primate cerebral cortex: some implications for brain development and evolution

    Directory of Open Access Journals (Sweden)

    M.G.P. Rosa

    2002-12-01

    Full Text Available In this paper, the topology of cortical visuotopic maps in adult primates is reviewed, with emphasis on recent studies. The observed visuotopic organisation can be summarised with reference to two basic rules. First, adjacent radial columns in the cortex represent partially overlapping regions of the visual field, irrespective of whether these columns are part of the same or different cortical areas. This primary rule is seldom, if ever, violated. Second, adjacent regions of the visual field tend to be represented in adjacent radial columns of a same area. This rule is not as rigid as the first, as many cortical areas form discontinuous, second-order representations of the visual field. A developmental model based on these physiological observations, and on comparative studies of cortical organisation, is then proposed, in order to explain how a combination of molecular specification steps and activity-driven processes can generate the variety of visuotopic organisations observed in adult cortex.

  12. [Brain Mechanism for Successful Memory Retrieval].

    Science.gov (United States)

    Takeda, Masaki

    2016-04-01

    Previous neuropsychological studies that investigated patients with brain injury have revealed the presense of multiple memory systems and the related brain regions. Recent functional imaging studies have identified a neuronal network including the temporal cortex and hippocampus that is responsible for the retrieval of semantic memory. This memory network was further investigated by electrophysiology using a simultaneous recording technique. This new technique revealed that a coupling of inter-area top-down signal within the temporal cortex with translaminar signal processing is required for successful memory retrieval of visual objects.

  13. Biophysical modeling of high field diffusion MRI demonstrates micro-structural aberration in chronic mild stress rat brain

    DEFF Research Database (Denmark)

    Khan, Ahmad Raza; Chuhutin, Andrey; Wiborg, Ove

    2016-01-01

    anhedonia is considered to be a realistic model of depression in studies of animal subjects. Stereological and neuronal tracing techniques have demonstrated persistent remodeling of microstructure in hippocampus, prefrontal cortex and amygdala of CMS brains. Recent developments in diffusion MRI (d...... microstructure in the hippocampus, prefrontal cortex, caudate putamen and amygdala regions of CMS rat brains by comparison to brains from normal controls. To validate findings of CMS induced microstructural alteration, histology was performed to determine neurite, nuclear and astrocyte density. d-MRI based...... neurite density and tensor-based mean kurtosis (MKT) were significantly higher, while mean diffusivity (MD), extracellular diffusivity (Deff) and intra-neurite diffusivity(DL) were significantly lower in the amygdala of CMS rat brains. Deff was also significantly lower in the hippocampus and caudate...

  14. Brain maturation of the adolescent rat cortex and striatum : Changes in volume and myelination

    NARCIS (Netherlands)

    Mengler, L.; Khmelinskii, A.; Diedenhofen, M.; Po, C.; Staring, M.; Lelieveldt, B.P.F.; Hoehn, M.

    2013-01-01

    Longitudinal studies on brain pathology and assessment of therapeutic strategies rely on a fully mature adult brain to exclude confounds of cerebral developmental changes. Thus, knowledge about onset of adulthood is indispensable for discrimination of developmental phase and adulthood. We have

  15. Involvement of posterior cingulate cortex in ketamine-induced psychosis relevant behaviors in rats.

    Science.gov (United States)

    Ma, Jingyi; Leung, L Stan

    2018-02-15

    The involvement of posterior cingulate cortex (PCC) on ketamine-induced psychosis relevant behaviors was investigated in rats. Bilateral infusion of muscimol, a GABA A receptor agonist, into the PCC significantly antagonized ketamine-induced deficit in prepulse inhibition of a startle reflex (PPI), deficit in gating of hippocampal auditory evoked potentials, and behavioral hyperlocomotion in a dose dependent manner. Local infusion of ketamine directly into the PCC also induced a PPI deficit. Systemic injection of ketamine (3mg/kg,s.c.) induced an increase in power of electrographic activity in the gamma band (30-100Hz) in both the PCC and the hippocampus; peak theta (4-10Hz) power was not significantly altered, but peak theta frequency was increased by ketamine. In order to exclude volume conduction from the hippocampus to PCC, inactivation of the hippocampus was made by local infusion of muscimol into the hippocampus prior to ketamine administration. Muscimol in the hippocampus effectively blocked ketamine-induced increase of gamma power in the hippocampus but not in the PCC, suggesting independent generation of gamma waves in PCC and hippocampus. It is suggested that the PCC is part of the brain network mediating ketamine-induced psychosis related behaviors. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. BDNF Expression in Perirhinal Cortex is Associated with Exercise-Induced Improvement in Object Recognition Memory

    OpenAIRE

    Hopkins, Michael E.; Bucci, David J.

    2010-01-01

    Physical exercise induces widespread neurobiological adaptations and improves learning and memory. Most research in this field has focused on hippocampus-based spatial tasks and changes in brain-derived neurotrophic factor (BDNF) as a putative substrate underlying exercise-induced cognitive improvements. Chronic exercise can also be anxiolytic and causes adaptive changes in stress reactivity. The present study employed a perirhinal cortex-dependent object recognition task as well as the eleva...

  17. Cross-generational trans fat intake facilitates mania-like behavior: oxidative and molecular markers in brain cortex.

    Science.gov (United States)

    Trevizol, F; Roversi, Kr; Dias, V T; Roversi, K; Barcelos, R C S; Kuhn, F T; Pase, C S; Golombieski, R; Veit, J C; Piccolo, J; Pochmann, D; Porciúncula, L O; Emanuelli, T; Rocha, J B T; Bürger, M E

    2015-02-12

    Since that fast food consumption have raised concerns about people's health, we evaluated the influence of trans fat consumption on behavioral, biochemical and molecular changes in the brain-cortex of second generation rats exposed to a model of mania. Two successive generations of female rats were supplemented with soybean oil (SO, rich in n-6 FA, control group), fish oil (FO, rich in n-3 FA) and hydrogenated vegetable fat (HVF, rich in trans FA) from pregnancy, lactation to adulthood, when male rats from 2nd generation received amphetamine (AMPH-4 mg/kg-i.p., once a day, for 14 days) treatment. AMPH increased locomotor index in all animals, which was higher in the HVF group. While the FO group showed increased n-3 polyunsaturated fatty acid (PUFA) incorporation and reduced n-6/n-3 PUFA ratio, HVF allowed trans fatty acid (TFA) incorporation and increased n-6/n-3 PUFA ratio in the brain-cortex. In fact, the FO group showed minor AMPH-induced hyperactivity, decreased reactive species (RS) generation per se, causing no changes in protein carbonyl (PC) levels and dopamine transporter (DAT). FO supplementation showed molecular changes, since proBDNF was increased per se and reduced by AMPH, decreasing the brain-derived neurotrophic factor (BDNF) level following drug treatment. Conversely, HVF was related to increased hyperactivity, higher PC level per se and higher AMPH-induced PC level, reflecting on DAT, whose levels were decreased per se as well as in AMPH-treated groups. In addition, while HVF increased BDNF-mRNA per se, AMPH reduced this value, acting on BDNF, whose level was lower in the same AMPH-treated experimental group. ProBDNF level was influenced by HVF supplementation, but it was not sufficient to modify BDNF level. These findings reinforce that prolonged consumption of trans fat allows TFA incorporation in the cortex, facilitating hyperactive behavior, oxidative damages and molecular changes. Our study is a warning about cross-generational consumption

  18. Bidirectional changes in water-maze learning following recombinant adenovirus-associated viral vector (rAAV)-mediated brain-derived neurotrophic factor expression in the rat hippocampus.

    Science.gov (United States)

    Pietropaolo, Susanna; Paterna, Jean-Charles; Büeler, Hansruedi; Feldon, Joram; Yee, Benjamin K

    2007-09-01

    Alterations in hippocampal brain-derived neurotrophic factor (BDNF) expression have been implicated in the pathogenesis of emotional and cognitive dysfunction. Here, we induced BDNF overexpression in the rat hippocampus using recombinant adenovirus-associated viral (rAAV) vectors, and studied its long-term (2 months postinduction) effects on anxiety-related behaviour, exploration in the open field, and spatial learning in the water maze. Although the treatment successfully led to substantial elevation of hippocampal BDNF levels, its effect on spatial learning was bidirectional: a subset of rAAV-induced BDNF-overexpressing rats performed well above control level, whereas the rest were clearly impaired. This behavioural distinction corresponded to two markedly different levels of BDNF overexpression. The increase in dorsal hippocampal BDNF content achieved in the 'water-maze-impaired' subgroup was twice that attained in the 'water-maze-improved' rats. Although neither subgroup of rAAV-induced BDNF-overexpressing rats differed from controls in the open field, the 'water-maze-impaired' subgroup also showed a significant anxiolytic effect. Our results suggest that hippocampal BDNF elevation significantly affects cognitive and emotional behaviours, but the direction and magnitude of the effects critically depend on the precise levels of overexpression. This factor must be taken into account in future studies examining the functional consequences of hippocampal BDNF overexpression.

  19. The modifying effect of diabetes mellitus on the reaction of р53-dependent proapoptotic mechanisms of hippocampus of rats in dynamic of ischemic-reperfusion damage of brain

    Directory of Open Access Journals (Sweden)

    T. M. Boychuk

    2016-12-01

    Full Text Available A few studies are devoted to mechanisms of death of hippocampal cells under conditions of complications of diabetes mellitus (DM with acute disorders of cerebral circulation, although the frequency of ischemic-reperfusion brain damage on a background of diabetes is much higher than that in the general population. The objective of research is to study the state of p53-dependent proapoptotic mechanisms in the hippocampal fields in the dynamic of ischemic-reperfusion brain damage in rats with experimental diabetes mellitus. Materials and methods. In neurons of hippocampal fields of rats with experimental DM content of p53 protein was studied by immunofluorescence using monoclonal antibodies in dynamic of incomplete global brain ischemia-reperfusion. The diabetes mellitus was modeled by single intraperitoneal injection of streptozotocin (Sigma, USA, 60 mg / kg. The results were estimated after a 20-minute carotic ischemia combined with one-hour reperfusion and on the 12th day of postischemic period. Results. After 20 minutes of ischemia / one hour reperfusion, in rats without DM and with DM, the activity of p53 proapoptotic processes increased in all the fields of hippocampus, only in the last group of rats its indices significantly exceed these are in hippocampal fields CA1, CA3, CA4 of rats without diabetes. On the 12th day of postischemic period in hippocampal fields CA1-CA3 of rats without diabetes the proapoptotic activity remains high, and in the field CA4 returns to normal level. In this period, in rats with diabetes activity of p53 proapoptotic processes remains increased in the field of CA1, returns to the level in rats with diabetes in the field of CA2, and decreases – in the fields CA3 and СA4. Conclusions. Diabetes mellitus quantitatively modifies the reaction of product of proapoptotic gene of p53 protein to the ischemic-reperfusion injury of the brain in the early postischemic period in the hippocampal fields CA1-CA3 and

  20. Brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) levels in post-mortem brain tissue from patients with depression compared to healthy individuals 

    DEFF Research Database (Denmark)

    Sheldrick, A; Camara, S; Ilieva, M

    2017-01-01

    suggests that antidepressant treatment may improve or normalise cerebral concentrations of neurotrophic factors. Therefore, we examined the concentration of brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) in different brain regions (cortex, cingulate gyrus, thalamus, hippocampus, putamen...... treatment and overall age 84.3±5 years versus 14 unaffected subjects at age 70.3±13.8. We detected significant elevation of BDNF (parietal cortex) and NT3 (parietal, temporal and occipital cortex, cingulate gyrus, thalamus, putamen and nucleus caudatus regions) in MDD patients who received antidepressant...

  1. Impact of video games on plasticity of the hippocampus.

    Science.gov (United States)

    West, G L; Konishi, K; Diarra, M; Benady-Chorney, J; Drisdelle, B L; Dahmani, L; Sodums, D J; Lepore, F; Jolicoeur, P; Bohbot, V D

    2017-08-08

    The hippocampus is critical to healthy cognition, yet results in the current study show that action video game players have reduced grey matter within the hippocampus. A subsequent randomised longitudinal training experiment demonstrated that first-person shooting games reduce grey matter within the hippocampus in participants using non-spatial memory strategies. Conversely, participants who use hippocampus-dependent spatial strategies showed increased grey matter in the hippocampus after training. A control group that trained on 3D-platform games displayed growth in either the hippocampus or the functionally connected entorhinal cortex. A third study replicated the effect of action video game training on grey matter in the hippocampus. These results show that video games can be beneficial or detrimental to the hippocampal system depending on the navigation strategy that a person employs and the genre of the game.Molecular Psychiatry advance online publication, 8 August 2017; doi:10.1038/mp.2017.155.

  2. Recurrent Moderate Hypoglycemia Suppresses Brain-Derived Neurotrophic Factor Expression in the Prefrontal Cortex and Impairs Sensorimotor Gating in the Posthypoglycemic Period in Young Rats.

    Science.gov (United States)

    Rao, Raghavendra; Ennis, Kathleen; Mitchell, Eugena P; Tran, Phu V; Gewirtz, Jonathan C

    2016-01-01

    Recurrent hypoglycemia is common in infants and children. In developing rat models, recurrent moderate hypoglycemia leads to neuronal injury in the medial prefrontal cortex. To understand the effects beyond neuronal injury, 3-week-old male rats were subjected to 5 episodes of moderate hypoglycemia (blood glucose concentration, approx. 30 mg/dl for 90 min) once daily from postnatal day 24 to 28. Neuronal injury was determined using Fluoro-Jade B histochemistry on postnatal day 29. The effects on brain-derived neurotrophic factor (BDNF) and its cognate receptor, tyrosine kinase receptor B (TrkB) expression, which is critical for prefrontal cortex development, were determined on postnatal day 29 and at adulthood. The effects on prefrontal cortex-mediated function were determined by assessing the prepulse inhibition of the acoustic startle reflex on postnatal day 29 and 2 weeks later, and by testing for fear-potentiated startle at adulthood. Recurrent hypoglycemia led to neuronal injury confined primarily to the medial prefrontal cortex. BDNF/TrkB expression in the prefrontal cortex was suppressed on postnatal day 29 and was accompanied by lower prepulse inhibition, suggesting impaired sensorimotor gating. Following the cessation of recurrent hypoglycemia, the prepulse inhibition had recovered at 2 weeks. BDNF/TrkB expression in the prefrontal cortex had normalized and fear-potentiated startle was intact at adulthood. Recurrent moderate hypoglycemia during development has significant adverse effects on the prefrontal cortex in the posthypoglycemic period. © 2016 S. Karger AG, Basel.

  3. 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.)

  4. Brain Damage and Motor Cortex Impairment in Chronic Obstructive Pulmonary Disease: Implication of Nonrapid Eye Movement Sleep Desaturation.

    Science.gov (United States)

    Alexandre, Francois; Heraud, Nelly; Sanchez, Anthony M J; Tremey, Emilie; Oliver, Nicolas; Guerin, Philippe; Varray, Alain

    2016-02-01

    Nonrapid eye movement (NREM) sleep desaturation may cause neuronal damage due to the withdrawal of cerebrovascular reactivity. The current study (1) assessed the prevalence of NREM sleep desaturation in nonhypoxemic patients with chronic obstructive pulmonary disease (COPD) and (2) compared a biological marker of cerebral lesion and neuromuscular function in patients with and without NREM sleep desaturation. One hundred fifteen patients with COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grades 2 and 3), resting PaO2 of 60-80 mmHg, aged between 40 and 80 y, and without sleep apnea (apnea-hypopnea index sleep recordings. In addition, twenty-nine patients (substudy) were assessed i) for brain impairment by serum S100B (biological marker of cerebral lesion), and ii) for neuromuscular function via motor cortex activation and excitability and maximal voluntary quadriceps strength measurement. A total of 51.3% patients (n = 59) had NREM sleep desaturation (NREMDes). Serum S100B was higher in the NREMDes patients of the substudy (n = 14): 45.1 [Q1: 37.7, Q3: 62.8] versus 32.9 [Q1: 25.7, Q3: 39.5] pg.ml(-1) (P = 0.028). Motor cortex activation and excitability were lower in NREMDes patients (both P = 0.03), but muscle strength was comparable between groups (P = 0.58). Over half the nonhypoxemic COPD patients exhibited NREM sleep desaturation associated with higher values of the cerebral lesion biomarker and lower neural drive reaching the quadriceps during maximal voluntary contraction. The lack of muscle strength differences between groups suggests a compensatory mechanism(s). Altogether, the results are consistent with an involvement of NREM sleep desaturation in COPD brain impairment. The study was registered at www.clinicaltrials.gov as NCT01679782. © 2016 Associated Professional Sleep Societies, LLC.

  5. Higher-order brain areas associated with real-time functional MRI neurofeedback training of the somato-motor cortex.

    Science.gov (United States)

    Auer, Tibor; Dewiputri, Wan Ilma; Frahm, Jens; Schweizer, Renate

    2016-04-29

    Neurofeedback (NFB) allows subjects to learn self-regulation of neuronal brain activation based on information about the ongoing activation. The implementation of real-time functional magnetic resonance imaging (rt-fMRI) for NFB training now facilitates the investigation into underlying processes. Our study involved 16 control and 16 training right-handed subjects, the latter performing an extensive rt-fMRI NFB training using motor imagery. A previous analysis focused on the targeted primary somato-motor cortex (SMC). The present study extends the analysis to the supplementary motor area (SMA), the next higher brain area within the hierarchy of the motor system. We also examined transfer-related functional connectivity using a whole-volume psycho-physiological interaction (PPI) analysis to reveal brain areas associated with learning. The ROI analysis of the pre- and post-training fMRI data for motor imagery without NFB (transfer) resulted in a significant training-specific increase in the SMA. It could also be shown that the contralateral SMA exhibited a larger increase than the ipsilateral SMA in the training and the transfer runs, and that the right-hand training elicited a larger increase in the transfer runs than the left-hand training. The PPI analysis revealed a training-specific increase in transfer-related functional connectivity between the left SMA and frontal areas as well as the anterior midcingulate cortex (aMCC) for right- and left-hand trainings. Moreover, the transfer success was related with training-specific increase in functional connectivity between the left SMA and the target area SMC. Our study demonstrates that NFB training increases functional connectivity with non-targeted brain areas. These are associated with the training strategy (i.e., SMA) as well as with learning the NFB skill (i.e., aMCC and frontal areas). This detailed description of both the system to be trained and the areas involved in learning can provide valuable information

  6. Using individualized brain network for analyzing structural covariance of the cerebral cortex in Alzheimer’s patients

    Directory of Open Access Journals (Sweden)

    Hee-Jong Kim

    2016-09-01

    Full Text Available Cortical thinning patterns in Alzheimer’s disease (AD have been widely reported through conventional regional analysis. In addition, the coordinated variance of cortical thickness in different brain regions has been investigated both at the individual and group network levels. In this study, we aim to investigate network architectural characteristics of a structural covariance network (SCN in AD, and further to show that the structural covariance connectivity becomes disorganized across the brain regions in AD, while the normal control (NC subjects maintain more clustered and consistent coordination in cortical atrophy variations. We generated SCNs directly from T1-weighted MR images of individual patients using surface-based cortical thickness data, with structural connectivity defined as similarity in cortical thickness within different brain regions. Individual SCNs were constructed using morphometric data from the Samsung Medical Center (SMC dataset. The structural covariance connectivity showed higher clustering than randomly generated networks, as well as similar minimum path lengths, indicating that the SCNs are small world. There were significant difference between NC and AD group in characteristic path lengths (z=-2.97, p<0.01 and small-worldness values (z=4.05, p<0.01. Clustering coefficients in AD was smaller than that of NC but there was no significant difference (z=1.81, not significant. We further observed that the AD patients had significantly disrupted structural connectivity. We also show that the coordinated variance of cortical thickness is distributed more randomly from one region to other regions in AD patients when compared to NC subjects. Our proposed SCN may provide surface-based measures for understanding interaction between two brain regions with co-atrophy of the cerebral cortex due to normal aging or AD. We applied our method to the AD Neuroimaging Initiative (ADNI data to show consistency in results with the SMC

  7. Endogenous ghrelin-O-acyltransferase (GOAT) acylates local ghrelin in the hippocampus.

    Science.gov (United States)

    Murtuza, Mohammad I; Isokawa, Masako

    2018-01-01

    Ghrelin is an appetite-stimulating peptide. Serine 3 on ghrelin must be acylated by octanoate via the enzyme ghrelin-O-acyltransferase (GOAT) for the peptide to bind and activate the cognate receptor, growth hormone secretagogue receptor type 1a (GHSR1a). Interest in GHSR1a increased dramatically when GHSR1a mRNA was demonstrated to be widespread in the brain, including the cortex and hippocampus, indicating that it has multifaceted functions beyond the regulation of metabolism. However, the source of octanoylated ghrelin for GHSR1a in the brain, outside of the hypothalamus, is not well understood. Here, we report the presence of GOAT and its ability to acylate non-octanoylated ghrelin in the hippocampus. GOAT immunoreactivity is aggregated at the base of the dentate granule cell layer in the rat and wild-type mouse. This immunoreactivity was not affected by the pharmacological inhibition of GHSR1a or the metabolic state-dependent fluctuation of systemic ghrelin levels. However, it was absent in the GHSR1a knockout mouse hippocampus, pointing the possibility that the expression of GHSR1a may be a prerequisite for the production of GOAT. Application of fluorescein isothiocyanate (FITC)-conjugated non-octanoylated ghrelin in live hippocampal slice culture (but not in fixed culture or in the presence of GOAT inhibitors) mimicked the binding profile of FITC-conjugated octanoylated ghrelin, suggesting that extracellularly applied non-octanoylated ghrelin was acylated by endogenous GOAT in the live hippocampus while GOAT being mobilized out of neurons. Our results will advance the understanding for the role of endogenous GOAT in the hippocampus and facilitate the search for the source of ghrelin that is intrinsic to the brain. © 2017 International Society for Neurochemistry.

  8. Brain-Wide Maps of "Fos" Expression during Fear Learning and Recall

    Science.gov (United States)

    Cho, Jin-Hyung; Rendall, Sam D.; Gray, Jesse M.

    2017-01-01

    "Fos" induction during learning labels neuronal ensembles in the hippocampus that encode a specific physical environment, revealing a memory trace. In the cortex and other regions, the extent to which "Fos" induction during learning reveals specific sensory representations is unknown. Here we generate high-quality brain-wide…

  9. Brain rhythms: towards a coherent picture of ensemble development in learning.

    Science.gov (United States)

    Rangel, L M; Eichenbaum, H

    2014-07-07

    A recent study suggests that coherence of 20-40 Hz brain oscillations in the hippocampus and upstream lateral entorhinal cortex may support encoding of task-relevant information during associative learning. Coordination of local hippocampal circuits in this frequency range could be important for encoding new information. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Increased intrinsic brain connectivity between pons and somatosensory cortex during attacks of migraine with aura

    DEFF Research Database (Denmark)

    Hougaard, Anders; Amin, Faisal Mohammad; Larsson, Henrik B W

    2017-01-01

    The neurological disturbances of migraine aura are caused by transient cortical dysfunction due to waves of spreading depolarization that disrupt neuronal signaling. The effects of these cortical events on intrinsic brain connectivity during attacks of migraine aura have not previously been......-based approach focusing on cortical visual areas and areas involved in migraine pain, and a data-driven independent component analysis approach to detect changes in intrinsic brain signaling during attacks. In addition, we performed the analyses after mirroring the MRI data according to the side of perceived......-sided pain. For aura-side normalized data, we found increased connectivity during attacks between visual area V5 and the lower middle frontal gyrus in the symptomatic hemisphere (peak voxel: P = 0.0194, (x, y, z) = (40, 40, 12). The present study provides evidence of altered intrinsic brain connectivity...

  11. Novel approach to magnetic resonance imaging of epileptic dogs - T2 relaxometry of the brain with emphasised hippocampus.

    Science.gov (United States)

    Lorincz, Borbála A; Anson, Agustina; Csébi, Péter; Bajzik, Gábor; Biró, Gergely; Tichy, Alexander; Lorincz, Balázs B; Garamvölgyi, Rita

    2017-06-01

    Hippocampal sclerosis is the most common imaging finding of intractable human epilepsy, and it may play an important role in canine and feline epileptogenesis and seizure semiology, too. The magnetic resonance imaging (MRI) criteria of hippocampal sclerosis are T2 hyperintensity, shrinkage and loss of internal structure. The detection of these changes is often challenging by subjective visual assessment of qualitative magnetic resonance (MR) images. The recognition is more reliable with quantitative MR methods, such as T2 relaxometry. In the present prospective study including 31 dogs with idiopathic epilepsy and 15 control dogs showing no seizure activity, we compared the T2 relaxation times of different brain areas. Furthermore, we studied correlations between the hippocampal T2 values and age, gender and skull formation. We found higher hippocampal T2 values in the epileptic group than in the control; however, these findings were not statistically significant. No correlations were found with age, gender or skull formation. In the individual analysis six epileptic dogs presented higher hippocampal T2 relaxation times than the cut-off value. Two of these dogs were also evaluated as abnormal in the visual assessment. Individual analysis of hippocampal T2 relaxation times may be a helpful method to understand hippocampal involvement in canine epilepsy.

  12. Brain-derived neurotrophic factor increases Ca2+/calmodulin-dependent protein kinase 2 activity in hippocampus.

    Science.gov (United States)

    Blanquet, P R; Lamour, Y

    1997-09-26

    Here we show that brain-derived neurotrophic factor (BDNF) stimulates both the phosphorylation of the Ca2+/calmodulin-dependent protein kinase 2 (CaMK2) and its kinase activity in rat hippocampal slices. In addition, we find that: (i) the time course of BDNF action is not accompanied by a change in the spectrum of either alpha- and beta-subunits of CaMK2 detected by immunoblotting; (ii) both treatment of solubilized CaMK2 with alkaline phosphatase and treatment of immunoprecipitated CaMK2 with protein phosphatase 1 reverse phosphorylation and activation of the kinase; (iii) phospholipase C inhibitor D609 and intracellular Ca2+ chelation by 1,2-bis-(o-aminophenoxy)ethane-N,N,N",N',-tetracetic acid tetra(acetoxymethyl)ester or 8-(diethylamino)octyl-3,4,5-trimethoxybenzoate but not omission of Ca2+ or Ca2+ chelation by EGTA, abolish the stimulatory effect of BDNF on phosphorylation and activation of CaMK2. These results strongly suggest that the conversion of CaMK2 into its active, autophosphorylated form, but not its concentration, is increased by BDNF via stimulation of phospholipase C and subsequent intracellular Ca2+ mobilization.

  13. Multi-template analysis of human perirhinal cortex in brain MRI: Explicitly accounting for anatomical variability

    Science.gov (United States)

    Xie, Long; Pluta, John B.; Das, Sandhitsu R.; Wisse, Laura E.M.; Wang, Hongzhi; Mancuso, Lauren; Kliot, Dasha; Avants, Brian B.; Ding, Song-Lin; Manjón, José V.; Wolk, David A.; Yushkevich, Paul A.

    2016-01-01

    Rational The human perirhinal cortex (PRC) plays critical roles in episodic and semantic memory and visual perception. The PRC consists of Brodmann areas 35 and 36 (BA35, BA36). In Alzheimer's disease (AD), BA35 is the first cortical site affected by neurofibrillary tangle pathology, which is closely linked to neural injury in AD. Large anatomical variability, manifested in the form of different cortical folding and branching patterns, makes it difficult to segment the PRC in MRI scans. Pathology studies have found that in ~97% of specimens, the PRC falls into one of three discrete anatomical variants. However, current methods for PRC segmentation and morphometry in MRI are based on single-template approaches, which may not be able to accurately model these discrete variants Methods A multi-template analysis pipeline that explicitly accounts for anatomical variability is used to automatically label the PRC and measure its thickness in T2-weighted MRI scans. The pipeline uses multi-atlas segmentation to automatically label medial temporal lobe cortices including entorhinal cortex, PRC and the parahippocampal cortex. Pairwise registration between label maps and clustering based on residual dissimilarity after registration are used to construct separate templates for the anatomical variants of the PRC. An optimal path of deformations linking these templates is used to establish correspondences between all the subjects. Experimental evaluation focuses on the ability of single-template and multi-template analyses to detect differences in the thickness of medial temporal lobe cortices between patients with amnestic mild cognitive impairment (aMCI, n=41) and age-matched controls (n=44). Results The proposed technique is able to generate templates that recover the three dominant discrete variants of PRC and establish more meaningful correspondences between subjects than a single-template approach. The largest reduction in thickness associated with aMCI, in absolute terms

  14. Regional distribution of high affinity binding of 3H-adenosine in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Traversa, U.; Puppini, P.; de Angelis, L.; Vertua, R.

    1984-06-01

    The high and low affinity adenosine binding sites with Kd values ranging respectively from 0.8 to 1.65 microM and from 3.1 to 13.86 microM were demonstrated in the following rat brain areas: cortex, hippocampus, striatum, cerebellum, diencephalon, and pons-medulla. Adenosine receptors involved in the high affinity binding seem to be mainly Ra-type. The analysis of the regional distribution of 3H-Adenosine showed the highest levels of specific binding in striatum and hippocampus; somewhat smaller values in cortex, cerebellum, and diencephalon, and even lower in pons-medulla.

  15. Aging, stress and the hippocampus.

    Science.gov (United States)

    Miller, D B; O'Callaghan, J P

    2005-05-01

    Functional loss often occurs in many body systems (e.g., endocrine, cognitive, motor) with the passage of years, but there is great individual variation in the degree of compromise shown. The current focus on brain aging will continue because demographic trends indicate that the average lifespan will show a continued increase. There is increasing emphasis on understanding how aging contributes to a decline in brain functions, cognition being a prime example. This is due in part to the fact that dementias and other losses in brain function that sometimes accompany aging cause an obvious decline in the quality of life and these deficits are of more concern as the number of elderly increase. Stress also is a ubiquitous aspect of life and there is now a greater interest in understanding the role of stress and the stress response in brain aging. The key role of the hippocampus and its related brain structures in cognition, as well as in the feedback control of the response to stress, have made this brain area a logical focus of investigation for those interested in the impact of stress on brain aging. Here, we describe how the hippocampus changes with age and we examine the idea that age-related changes in the secretion patterns of the hypothalamic-pituitary adrenal (HPA) axis can contribute to aging of this structure. We also examine the proposal that stress, perhaps due to compromised HPA axis function, can contribute to hippocampal aging through exposure to excessive levels of glucocorticoids. The aging hippocampus does not appear to suffer a generalized loss of cells or synapses, although atrophy of the structure may occur in humans. Thus, age-related cognitive impairments are likely related to other neurobiological alterations that could include changes in the signaling, information encoding, plasticity, electrophysiological or neurochemical properties of neurons or glia. Although excessive levels of glucocorticoids are able to interfere with cognition, as well as

  16. Brain On Stress: Vulnerability and Plasticity of the Prefrontal Cortex Over the Life Course

    Science.gov (United States)

    McEwen, Bruce S.; Morrison, John H.

    2013-01-01

    The prefrontal cortex (PFC) is involved in working memory, self-regulatory and goal-directed behaviors and displays remarkable structural and functional plasticity over the life course. Neural circuitry, molecular profiles and neurochemistry can be changed by experiences, which influences behavior as well as neuroendocrine and autonomic function. Such effects have a particular impact during infancy and in adolescence. Behavioral stress affects both the structure and function of PFC, though such effects are not necessarily permanent, as young animals show remarkable neuronal resilience if the stress is discontinued. During aging, neurons within the PFC become less resilient to stress. There are also sex differences in the PFC response to stressors. While such stress- and sex-hormone related alterations occur in regions mediating the highest levels of cognitive function and self regulatory control, the fact that they are not necessarily permanent has implications for future behavior-based therapies that harness neural plasticity for recovery. PMID:23849196

  17. HDAC inhibition modulates hippocampus-dependent long-term memory for object location in a CBP-dependent manner

    Science.gov (United States)

    Haettig, Jakob; Stefanko, Daniel P.; Multani, Monica L.; Figueroa, Dario X.; McQuown, Susan C.; Wood, Marcelo A.

    2011-01-01

    Transcription of genes required for long-term memory not only involves transcription factors, but also enzymatic protein complexes that modify chromatin structure. Chromatin-modifying enzymes, such as the histone acetyltransferase (HAT) CREB (cyclic-AMP response element binding) binding protein (CBP), are pivotal for the transcriptional regulation required for long-term memory. Several studies have shown that CBP and histone acetylation are necessary for hippocampus-dependent long-term memory and hippocampal long-term potentiation (LTP). Importantly, every genetically modified Cbp mutant mouse exhibits long-term memory impairments in object recognition. However, the role of the hippocampus in object recognition is controversial. To better understand how chromatin-modifying enzymes modulate long-term memory for object recognition, we first examined the role of the hippocampus in retrieval of long-term memory for object recognition or object location. Muscimol inactivation of the dorsal hippocampus prior to retrieval had no effect on long-term memory for object recognition, but completely blocked long-term memory for object location. This was consistent with experiments showing that muscimol inactivation of the hippocampus had no effect on long-term memory for the object itself, supporting the idea that the hippocampus encodes spatial information about an object (such as location or context), whereas cortical areas (such as the perirhinal or insular cortex) encode information about the object itself. Using location-dependent object recognition tasks that engage the hippocampus, we demonstrate that CBP is essential for the modulation of long-term memory via HDAC inhibition. Together, these results indicate that HDAC inhibition modulates memory in the hippocampus via CBP and that different brain regions utilize different chromatin-modifying enzymes to regulate learning and memory. PMID:21224411

  18. The predicting brain: anticipation of moving objects in human visual cortex

    NARCIS (Netherlands)

    Schellekens, W.

    2015-01-01

    The human brain is nearly constantly subjected to visual motion signals originating from a large variety of external sources. It is the job of the central nervous system to determine correspondence among visual motion input across spatially distant locations within certain time frames. In order to

  19. A brain-computer interface based on self-regulation of gamma-oscillations in the superior parietal cortex

    Science.gov (United States)

    Grosse-Wentrup, Moritz; Schölkopf, Bernhard

    2014-10-01

    Objective. Brain-computer interface (BCI) systems are often based on motor- and/or sensory processes that are known to be impaired in late stages of amyotrophic lateral sclerosis (ALS). We propose a novel BCI designed for patients in late stages of ALS that only requires high-level cognitive processes to transmit information from the user to the BCI. Approach. We trained subjects via EEG-based neurofeedback to self-regulate the amplitude of gamma-oscillations in the superior parietal cortex (SPC). We argue that parietal gamma-oscillations are likely to be associated with high-level attentional processes, thereby providing a communication channel that does not rely on the integrity of sensory- and/or motor-pathways impaired in late stages of ALS. Main results. Healthy subjects quickly learned to self-regulate gamma-power in the SPC by alternating between states of focused attention and relaxed wakefulness, resulting in an average decoding accuracy of 70.2%. One locked-in ALS patient (ALS-FRS-R score of zero) achieved an average decoding accuracy significantly above chance-level though insufficient for communication (55.8%). Significance. Self-regulation of gamma-power in the SPC is a feasible paradigm for brain-computer interfacing and may be preserved in late stages of ALS. This provides a novel approach to testing whether completely locked-in ALS patients retain the capacity for goal-directed thinking.

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

    Energy Technology Data Exchange (ETDEWEB)

    Wengenroth, Martina; Blatow, M.; Guenther, J. [University of Heidelberg Medical School, Department of Neuroradiology, Heidelberg (Germany); Akbar, M. [University of Heidelberg Medical School, Department of Orthopaedics, Heidelberg (Germany); Tronnier, V.M. [University of Schleswig-Holstein, Department of Neurosurgery, Luebeck (Germany); Stippich, C. [University Hospital Basle, Department of Diagnostic and Interventional Neuroradiology, Basle (Switzerland)

    2011-07-15

    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.)

  1. 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)

    Marine eMondino

    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.

  2. 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.

  3. Mnemonic convergence in the human hippocampus.

    Science.gov (United States)

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

    2016-06-21

    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.

  4. Functional Connectivity of Multiple Brain Regions Required for the Consolidation of Social Recognition Memory.

    Science.gov (United States)

    Tanimizu, Toshiyuki; Kenney, Justin W; Okano, Emiko; Kadoma, Kazune; Frankland, Paul W; Kida, Satoshi

    2017-04-12

    Social recognition memory is an essential and basic component of social behavior that is used to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory. Importantly, significant inductions of the CREB target immediate-early genes c-fos and Arc were observed in the hippocampus (CA1 and CA3 regions), medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and amygdala (basolateral region) when social recognition memory was generated. Pharmacological experiments using a microinfusion of the protein synthesis inhibitor anisomycin showed that protein synthesis in these brain regions is required for the consolidation of social recognition memory. These findings suggested that social recognition memory is consolidated through the activation of CREB-mediated gene expression in the hippocampus/mPFC/ACC/amygdala. Network analyses suggested that these four brain regions show functional connectivity with other brain regions and, more importantly, that the hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas the ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. We have found that a brain network composed of the hippocampus/mPFC/ACC/amygdala is required for the consolidation of social recognition memory.SIGNIFICANCE STATEMENT Here, we identify brain networks composed of multiple brain regions for the consolidation of social recognition memory. We

  5. Effects of isolation rearing and early antipsychotic intervention on oxidative stress-induced apoptosis and brain-derived neurotrophic factor in hippocampus in a rat model of schizophrenia

    Directory of Open Access Journals (Sweden)

    Szu-Nian Yang

    2017-01-01

    Full Text Available Background: Oxidative stress-induced neuronal dysfunction has been considered an essential factor for the development of schizophrenia. However, a longitudinal and causal relation between the impacts of developmental stress and oxidative stress remains unsolved. The present study aimed to examine whether the oxidative stress-relevant dysfunctions of the apoptotic index can be induced in rats of isolation rearing (IR, a rodent model of schizophrenia and to see if the intervention of antipsychotics can reverse these dysfunctions. Materials and Methods: Pharmacological manipulation (risperidone [RIS] [1 mg/kg/day], olanzapine [OLA] [2.5 mg/kg/day], or saline [SAL] vehicle was introduced 4 weeks (adolescence or 8 weeks (young adulthood after IR (i.e., rats were 7- or 11-week-old. The regime of RIS, OLA, or SAL was continued for 9 weeks. Locomotor activity was employed to validate the IR effect. Rats' hippocampus immediately after sacrifice was removed to measure messenger RNA expression of Bax, Bcl-2, brain-derived neurotrophic factor (BDNF and the plasma level of nitric oxide (NO. Results: The results showed: (i IR rats were more hyperactive. (ii RIS may exert anti-apoptotic effects on IR rats, particularly at their adolescent age (as indexed by increased Bcl-2 and decreased Bax/Bcl-2 ratio. (iii The therapeutic potential of RIS can be also observed in the change of BDNF in an age-independent manner, in which RIS effectively increased the BDNF level in IR but not social (SOC rats. (iv Plasma NO was not altered. Conclusion: The study results support the utility of the IR paradigm in exploring mental disorders with neurodevelopmental origin in which early pharmacological intervention may provide a therapeutic benefit in the overloaded oxidative stress and the dysfunction of BDNF.

  6. Concurrent calpain and caspase-3 mediated proteolysis of alpha II-spectrin and tau in rat brain after methamphetamine exposure: a similar profile to traumatic brain injury.

    Science.gov (United States)

    Warren, Matthew W; Kobeissy, Firas H; Liu, Ming Cheng; Hayes, Ronald L; Gold, Mark S; Wang, Kevin K W

    2005-12-05

    Neurotoxicity in rat cortex and hippocampus following acute methamphetamine administration was characterized and compared to changes following traumatic brain injury. Doses of 10, 20, and 40 mg/kg of methamphetamine produced significant increases in calpain- and caspase-cleaved alpha II-spectrin and tau protein fragments, suggesting cell injury or death. Changes in proteolytic products were significantly increased over vehicle controls. Use of fragment specific biomarkers detected prominent calpain-mediated protein fragments in the cortex and hippocampus while caspase-mediated protein fragments were also detected in the hippocampus. Remarkably, proteolytic product increases at the 40 mg/kg dose after 24 h were as high as those observed in experimental traumatic brain injury. Use of calpain and caspase proteolytic inhibitors may be useful in preventing methamphetamine-induced neurotoxicity.

  7. Consensus Paper: Probing Homeostatic Plasticity of Human Cortex With Non-invasive Transcranial Brain Stimulation.

    Science.gov (United States)

    Karabanov, Anke; Ziemann, Ulf; Hamada, Masashi; George, Mark S; Quartarone, Angelo; Classen, Joseph; Massimini, Marcello; Rothwell, John; Siebner, Hartwig Roman

    2015-01-01

    Homeostatic plasticity is thought to stabilize neural activity around a set point within a physiologically reasonable dynamic range. Over the last ten years, a wide range of non-invasive transcranial brain stimulation (NTBS) techniques have been used to probe homeostatic control of cortical plasticity in the intact human brain. Here, we review different NTBS approaches to study homeostatic plasticity on a systems level and relate the findings to both, physiological evidence from in vitro studies and to a theoretical framework of homeostatic function. We highlight differences between homeostatic and other non-homeostatic forms of plasticity and we examine the contribution of sleep in restoring synaptic homeostasis. Finally, we discuss the growing number of studies showing that abnormal homeostatic plasticity may be associated to a range of neuropsychiatric diseases. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  8. 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.)

  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. Resting-state oscillatory dynamics in sensorimotor cortex in benign epilepsy with centro-temporal spikes and typical brain development.

    Science.gov (United States)

    Koelewijn, Loes; Hamandi, Khalid; Brindley, Lisa M; Brookes, Matthew J; Routley, Bethany C; Muthukumaraswamy, Suresh D; Williams, Natalie; Thomas, Marie A; Kirby, Amanda; Te Water Naudé, Johann; Gibbon, Frances; Singh, Krish D

    2015-10-01

    Benign Epilepsy with Centro-Temporal Spikes (BECTS) is a common childhood epilepsy associated with deficits in several neurocognitive domains. Neurophysiological studies in BECTS often focus on centro-temporal spikes, but these correlate poorly with morphology and cognitive impairments. To better understand the neural profile of BECTS, we studied background brain oscillations, thought to be integrally involved in neural network communication, in sensorimotor areas. We used independent component analysis of temporally correlated sources on magnetoencephalography recordings to assess sensorimotor resting-state network activity in BECTS patients and typically developing controls. We also investigated the variability of oscillatory characteristics within focal primary motor cortex (M1), localized with a separate finger abduction task. We hypothesized that background oscillations would differ between patients and controls in the sensorimotor network but not elsewhere, especially in the beta band (13-30 Hz) because of its role in network communication and motor processing. The results support our hypothesis: in the sensorimotor network, patients had a greater variability in oscillatory amplitude compared to controls, whereas there was no difference in the visual network. Network measures did not correlate with age. The coefficient of variation of resting M1 peak frequency correlated negatively with age in the beta band only, and was greater than average for a number of patients. Our results point toward a "disorganized" functional sensorimotor network in BECTS, supporting a neurodevelopmental delay in sensorimotor cortex. Our findings further suggest that investigating the variability of oscillatory peak frequency may be a useful tool to investigate deficits of disorganization in neurodevelopmental disorders. © 2015 Wiley Periodicals, Inc.

  11. Induction of late LTP-like plasticity in the human motor cortex by repeated non-invasive brain stimulation.

    Science.gov (United States)

    Monte-Silva, Katia; Kuo, Min-Fang; Hessenthaler, Silvia; Fresnoza, Shane; Liebetanz, David; Paulus, Walter; Nitsche, Michael A

    2013-05-01

    Non-invasive brain stimulation enables the induction of neuroplasticity in humans, however, with so far restricted duration of the respective cortical excitability modifications. Conventional anodal transcranial direct current stimulation (tDCS) protocols including one stimulation session induce NMDA receptor-dependent excitability enhancements lasting for about 1 h. We aimed to extend the duration of tDCS effects by periodic stimulation, consisting of two stimulation sessions, since periodic stimulation protocols are able to induce neuroplastic excitability alterations stable for days or weeks, termed late phase long term potentiation (l-LTP), in animal slice preparations. Since both, l-LTP and long term memory formation, require gene expression and protein synthesis, and glutamatergic receptor activity modifications, l-LTP might be a candidate mechanism for the formation of long term memory. The impact of two consecutive tDCS sessions on cortical excitability was probed in the motor cortex of healthy humans, and compared to that of a single tDCS session. The second stimulation was applied without an interval (temporally contiguous tDCS), during the after-effects of the first stimulation (during after-effects; 3, or 20 min interval), or after the after-effects of the first stimulation had vanished (post after-effects; 3 or 24 h interval). The during after-effects condition resulted in an initially reduced, but then relevantly prolonged excitability enhancement, which was blocked by an NMDA receptor antagonist. The other conditions resulted in an abolishment, or a calcium channel-dependent reversal of neuroplasticity. Repeated tDCS within a specific time window is able to induce l-LTP-like plasticity in the human motor cortex. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Places in the Brain: Bridging Layout and Object Geometry in Scene-Selective Cortex.

    Science.gov (United States)

    Dillon, Moira R; Persichetti, Andrew S; Spelke, Elizabeth S; Dilks, Daniel D

    2017-06-13

    Diverse animal species primarily rely on sense (left-right) and egocentric distance (proximal-distal) when navigating the environment. Recent neuroimaging studies with human adults show that this information is represented in 2 scene-selective cortical regions-the occipital place area (OPA) and retrosplenial complex (RSC)-but not in a third scene-selective region-the parahippocampal place area (PPA). What geometric properties, then, does the PPA represent, and what is its role in scene processing? Here we hypothesize that the PPA represents relative length and angle, the geometric properties classically associated with object recognition, but only in the context of large extended surfaces that compose the layout of a scene. Using functional magnetic resonance imaging adaptation, we found that the PPA is indeed sensitive to relative length and angle changes in pictures of scenes, but not pictures of objects that reliably elicited responses to the same geometric changes in object-selective cortical regions. Moreover, we found that the OPA is also sensitive to such changes, while the RSC is tolerant to such changes. Thus, the geometric information typically associated with object recognition is also used during some aspects of scene processing. These findings provide evidence that scene-selective cortex differentially represents the geometric properties guiding navigation versus scene categorization. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. 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.

  14. Dietary fat induces sustained reward response in the human brain without primary taste cortex discrimination

    Directory of Open Access Journals (Sweden)

    Hélène eTzieropoulos

    2013-02-01

    Full Text Available To disentangle taste from reward responses in the human gustatory cortex, we combined high density electro-encephalography with a gustometer delivering tastant puffs to the tip of the tongue. Stimuli were pure tastants (salt solutions at two concentrations, caloric emulsions of identical taste (two milk preparations differing in fat content and a mixture of high fat milk with the lowest salt concentration. Early event-related potentials showed a dose-response effect for increased taste intensity, with higher amplitude and shorter latency for high compared to low salt concentration, but not for increased fat content. However, the amplitude and distribution of late potentials were modulated by fat content independently of reported intensity and discrimination. Neural source estimation revealed a sustained activation of reward areas to the two high-fat stimuli. The results suggest calorie detection through specific sensors on the tongue independent of perceived taste. Finally, amplitude variation of the first peak in the event-related potential to the different stimuli correlated with papilla density, suggesting a higher discrimination power for subjects with more fungiform papillae.

  15. Benefits of physical exercise on the aging brain: the role of the prefrontal cortex.

    Science.gov (United States)

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

    2013-11-01

    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 two groups based on physical exercise participation. The response times and accuracy and the premotor activity of the PFC were separately correlated with age for the two groups. The data were first fit with a linear function and then a higher order polynomial function. We observed that after 35-40 years of age, physically active individuals have faster response times than their less active peers and showed no signs of PFC hyperactivity during motor planning. The present findings show that physical exercise could speed up the response of older people and reveal that also in middle-aged people, moderate-to-high levels of physical exercise benefits the planning/execution of a response and the executive functions mediated by the PFC, counteracting the neural overactivity often observed in the elderly adults.

  16. Antioxidant effect of frankincense extract in the brain cortex of diabetic rats

    Directory of Open Access Journals (Sweden)

    Anwar Masoud

    2017-10-01

    Alloxan treatment in the DM group showed significant reductions in catalase (CAT activity and other non-enzymatic antioxidants i.e. thiol groups, concomitant with decreases in the levels of protein and albumin and increasing the level of uric acid. However, FRN administration to DM animals in DM + FRN group showed significant recovery of antioxidants, the thiol contents (total thiols, protein thiols and glutathione of DM + FRN group have been increased as compared with DM animals (p < 0.05. A recovery of CAT activity (p < 0.05 to almost the levels of control rats with the recovery in protein and albumin levels (p < 0.05 have been observed when FRN was administered. The uric acid level increased in DM group, came back to the levels of control after administration of FRN (p < 0.05. We also observed that FRN reduces the histopathological damage caused by alloxan in DM + FRN group. It is concluded that FRN shows a beneficial effects that can reduce the oxidative damage caused by alloxan induced DM in the cortex of rats.

  17. High membrane protein oxidation in the human cerebral cortex.

    Science.gov (United States)

    Granold, Matthias; Moosmann, Bernd; Staib-Lasarzik, Irina; Arendt, Thomas; Del Rey, Adriana; Engelhard, Kristin; Behl, Christian; Hajieva, Parvana

    2015-01-01

    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. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  18. 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.

  19. Homocysteine induces mitochondrial dysfunction involving the crosstalk between oxidative stress and mitochondrial pSTAT3 in rat ischemic brain

    OpenAIRE

    Chen, Shuang; Dong, Zhiping; Zhao, Yaqian; Sai, Na; Wang, Xuan; Liu, Huan; Huang, Guowei; Zhang, Xumei

    2017-01-01

    Homocysteine (Hcy) has been shown to have a neurotoxic effect on ischemic brain cells; however, the underlying mechanisms remain incompletely understood. Here, we examined whether Hcy treatment influences mitochondria injury, oxidative stress, and mitochondrial STAT3 (mitoStat3) expression in rat ischemic brain. Our results demonstrated that Hcy treatment aggravated the damage of mitochondrial ultrastructure in the brain cortex and the dentate gyrus region of the hippocampus after focal cereb...

  20. Mirror-image discrimination in the literate brain: A causal role for the left occpitotemporal cortex

    Directory of Open Access Journals (Sweden)

    Kimihiro eNakamura

    2014-05-01

    Full Text Available Previous studies show that the primate and human visual system automatically generates a common and invariant representation from a visual object image and its mirror reflection. For humans, however, this mirror-image generalization seems to be partially suppressed through literacy acquisition, since literate adults have greater difficulty in recognizing mirror images of letters than those of other visual objects. At the neural level, such category-specific effect on mirror-image processing has been associated with the left occpitotemporal cortex (L-OTC, but it remains unclear whether the apparent inhibition on mirror letters is mediated by suppressing mirror-image representations covertly generated from normal letter stimuli. Using transcranial magnetic stimulation (TMS, we examined how transient disruption of the L-OTC affects mirror-image recognition during a same-different judgment task, while varying the semantic category (letters and non-letter objects, identity (same or different and orientation (same or mirror-reversed of the first and second stimuli. We found that magnetic stimulation of the L-OTC produced a significant delay in mirror-image recognition for letter-strings but not for other objects. By contrast, this category specific impact was not observed when TMS was applied to other control sites, including the right homologous area and vertex. These results thus demonstrate a causal link between the L-OTC and mirror-image discrimination in literate people. We further suggest that left-right sensitivity for letters is not achieved by a local inhibitory mechanism in the L-OTC but probably relies on the inter-regional coupling with other orientation-sensitive occipito-parietal regions.

  1. Apelin-13 as a novel target for intervention in secondary injury after traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Hai-jun Bao

    2016-01-01

    Full Text Available The adipocytokine, apelin-13, is an abundantly expressed peptide in the nervous system. Apelin-13 protects the brain against ischemia/reperfusion injury and attenuates traumatic brain injury by suppressing autophagy. However, secondary apelin-13 effects on traumatic brain injury-induced neural cell death and blood-brain barrier integrity are still not clear. Here, we found that apelin-13 significantly decreases cerebral water content, mitigates blood-brain barrier destruction, reduces aquaporin-4 expression, diminishes caspase-3 and Bax expression in the cerebral cortex and hippocampus, and reduces apoptosis. These results show that apelin-13 attenuates secondary injury after traumatic brain injury and exerts a neuroprotective effect

  2. Hippocampus and amygdala morphology in attention-deficit/hyperactivity disorder

    DEFF Research Database (Denmark)

    Plessen, Kerstin J; Bansal, Ravi; Zhu, Hongtu

    2006-01-01

    of the hippocampus and amygdala in children with ADHD. DESIGN: A cross-sectional case-control study of the hippocampus and amygdala using anatomical magnetic resonance imaging. SETTINGS: University research institute. PATIENTS: One hundred fourteen individuals aged 6 to 18 years, 51 with combined-type ADHD and 63...... healthy controls. MAIN OUTCOME MEASURES: Volumes and measures of surface morphology for the hippocampus and amygdala. RESULTS: The hippocampus was larger bilaterally in the ADHD group than in the control group (t = 3.35; P ... suggested abnormal connectivity between the amygdala and prefrontal cortex in the ADHD group. Enlarged subregions of the hippocampus tended to accompany fewer symptoms. CONCLUSIONS: The enlarged hippocampus in children and adolescents with ADHD may represent a compensatory response to the presence...

  3. Primate phencyclidine model of schizophrenia: sex-specific effects on cognition, brain derived neurotrophic factor, spine synapses, and dopamine turnover in prefrontal cortex.

    Science.gov (United States)

    Elsworth, John D; Groman, Stephanie M; Jentsch, James D; Leranth, Csaba; Redmond, D Eugene; Kim, Jung D; Diano, Sabrina; Roth, Robert H

    2014-10-31

    Cognitive deficits are a core symptom of schizophrenia, yet they remain particularly resistant to treatment. The model provided by repeatedly exposing adult nonhuman primates to phencyclidine has generated important insights into the neurobiology of these deficits, but it remains possible that administration of this psychotomimetic agent during the pre-adult period, when the dorsolateral prefrontal cortex in human and nonhuman primates is still undergoing significant maturation, may provide a greater understanding of schizophrenia-related cognitive deficits. The effects of repeated phencyclidine treatment on spine synapse number, dopamine turnover and BDNF expression in dorsolateral prefrontal cortex, and working memory accuracy were examined in pre-adult monkeys. One week following phencyclidine treatment, juvenile and adolescent male monkeys demonstrated a greater loss of spine synapses in dorsolateral prefrontal cortex than adult male monkeys. Further studies indicated that in juvenile males, a cognitive deficit existed at 4 weeks following phencyclidine treatment, and this impairment was associated with decreased dopamine turnover, decreased brain derived neurotrophic factor messenger RNA, and a loss of dendritic spine synapses in dorsolateral prefrontal cortex. In contrast, female juvenile monkeys displayed no cognitive deficit at 4 weeks after phencyclidine treatment and no alteration in dopamine turnover or brain derived neurotrophic factor messenger RNA or spine synapse number in dorsolateral prefrontal cortex. In the combined group of male and female juvenile monkeys, significant linear correlations were detected between dopamine turnover, spine synapse number, and cognitive performance. As the incidence of schizophrenia is greater in males than females, these findings support the validity of the juvenile primate phencyclidine model and highlight its potential usefulness in understanding the deficits in dorsolateral prefrontal cortex in schizophrenia and

  4. Activation of sensory cortex by imagined genital stimulation: an fMRI analysis.

    Science.gov (United States)

    Wise, Nan J; Frangos, Eleni; Komisaruk, Barry R

    2016-01-01

    During the course of a previous study, our laboratory made a serendipitous finding that just thinking about genital stimulation resulted in brain activations that overlapped with, and differed from, those generated by physical genital stimulation. This study extends our previous findings by further characterizing how the brain differentially processes physical 'touch' stimulation and 'imagined' stimulation. Eleven healthy women (age range 29-74) participated in an fMRI study of the brain response to imagined or actual tactile stimulation of the nipple and clitoris. Two additional conditions - imagined dildo self-stimulation and imagined speculum stimulation - were included to characterize the effects of erotic versus non-erotic imagery. Imagined and tactile self-stimulation of the nipple and clitoris each activated the paracentral lobule (the genital region of the primary sensory cortex) and the secondary somatosensory cortex. Imagined self-stimulation of the clitoris and nipple resulted in greater activation of the frontal pole and orbital frontal cortex compared to tactile self-stimulation of these two bodily regions. Tactile self-stimulation of the clitoris and nipple activated the cerebellum, primary somatosensory cortex (hand region), and premotor cortex more than the imagined stimulation of these body regions. Imagining dildo stimulation generated extensive brain activation in the genital sensory cortex, secondary somatosensory cortex, hippocampus, amygdala, insula, nucleus accumbens, and medial prefrontal cortex, whereas imagining speculum stimulation generated only minimal activation. The present findings provide evidence of the potency of imagined stimulation of the genitals and that the following brain regions may participate in erogenous experience: primary and secondary sensory cortices, sensory-motor integration areas, limbic structures, and components of the 'reward system'. In addition, these results suggest a mechanism by which some individuals may

  5. Activation of sensory cortex by imagined genital stimulation: an fMRI analysis

    Directory of Open Access Journals (Sweden)

    Nan J. Wise

    2016-10-01

    Full Text Available Background: During the course of a previous study, our laboratory made a serendipitous finding that just thinking about genital stimulation resulted in brain activations that overlapped with, and differed from, those generated by physical genital stimulation. Objective: This study extends our previous findings by further characterizing how the brain differentially processes physical ‘touch’ stimulation and ‘imagined’ stimulation. Design: Eleven healthy women (age range 29–74 participated in an fMRI study of the brain response to imagined or actual tactile stimulation of the nipple and clitoris. Two additional conditions – imagined dildo self-stimulation and imagined speculum stimulation – were included to characterize the effects of erotic versus non-erotic imagery. Results: Imagined and tactile self-stimulation of the nipple and clitoris each activated the paracentral lobule (the genital region of the primary sensory cortex and the secondary somatosensory cortex. Imagined self-stimulation of the clitoris and nipple resulted in greater activation of the frontal pole and orbital frontal cortex compared to tactile self-stimulation of these two bodily regions. Tactile self-stimulation of the clitoris and nipple activated the cerebellum, primary somatosensory cortex (hand region, and premotor cortex more than the imagined stimulation of these body regions. Imagining dildo stimulation generated extensive brain activation in the genital sensory cortex, secondary somatosensory cortex, hippocampus, amygdala, insula, nucleus accumbens, and medial prefrontal cortex, whereas imagining speculum stimulation generated only minimal activation. Conclusion: The present findings provide evidence of the potency of imagined stimulation of the genitals and that the following brain regions may participate in erogenous experience: primary and secondary sensory cortices, sensory-motor integration areas, limbic structures, and components of the

  6. Evidences that maternal swimming exercise improves antioxidant defenses and induces mitochondrial biogenesis in the brain of young Wistar rats.

    Science.gov (United States)

    Marcelino, T B; Longoni, A; Kudo, K Y; Stone, V; Rech, A; de Assis, A M; Scherer, E B S; da Cunha, M J; Wyse, A T S; Pettenuzzo, L F; Leipnitz, G; Matté, C

    2013-08-29

    Physical exercise during pregnancy has been considered beneficial to mother and child. Recent studies showed that maternal swimming improves memory in the offspring, increases hippocampal neurogenesis and levels of neurotrophic factors. The objective of this work was to investigate the effect of maternal swimming during pregnancy on redox status and mitochondrial parameters in brain structures from the offspring. Adult female Wistar rats were submitted to five swimming sessions (30 min/day) prior to mating with adult male Wistar rats, and then trained during the pregnancy (five sessions of 30-min swimming/week). The litter was sacrificed when 7 days old, when cerebellum, parietal cortex, hippocampus, and striatum were dissected. We evaluated the production of reactive species and antioxidant status, measuring the activities of superoxide-dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPx), as well as non-enzymatic antioxidants. We also investigated a potential mitochondrial biogenesis regarding mitochondrion mass and membrane potential, through cytometric approaches. Our results showed that maternal swimming exercise promoted an increase in reactive species levels in cerebellum, parietal cortex, and hippocampus, demonstrated by an increase in dichlorofluorescein oxidation. Mitochondrial superoxide was reduced in cerebellum and parietal cortex, while nitrite levels were increased in cerebellum, parietal cortex, hippocampus, and striatum. Antioxidant status was improved in cerebellum, parietal cortex, and hippocampus. SOD activity was increased in parietal cortex, and was not altered in the remaining brain structures. CAT and GPx activities, as well as non-enzymatic antioxidant potential, were increased in cerebellum, parietal cortex, and hippocampus of rats whose mothers were exercised. Finally, we observed an increased mitochondrial mass and membrane potential, suggesting mitochondriogenesis, in cerebellum and parietal cortex of pups subjected to

  7. Tactile Object Familiarity in the Blind Brain Reveals the Supramodal Perceptual-Mnemonic Nature of the Perirhinal Cortex

    Science.gov (United States)

    Cacciamani, Laura; Likova, Lora T.

    2016-01-01

    This study is the first to investigate the neural underpinnings of tactile object familiarity in the blind during both perception and memory. In the sighted, the perirhinal cortex (PRC) has been implicated in the assessment of visual object familiarity—a crucial everyday task—as evidenced by reduced activation when an object becomes familiar. Here, to examine the PRC’s role in tactile object familiarity in the absence of vision, we trained blind participants on a unique memory-guided drawing technique and measured brain activity while they perceptually explored raised-line drawings, drew them from tactile memory, and scribbled (control). Functional magnetic resonance imaging (fMRI) before and after a week of training revealed a significant decrease in PRC activation from pre- to post-training (i.e., from unfamiliar to familiar) during perceptual exploration as well as memory-guided drawing, but not scribbling. This familiarity-based reduction is the first evidence that the PRC represents tactile object familiarity in the blind. Furthermore, the finding of this effect during both tactile perception and tactile memory provides the critical link in establishing the PRC as a structure whose representations are supramodal for both perception and memory. PMID:27148002

  8. Tactile object familiarity in the blind brain reveals the supramodal perceptual-mnemonic nature of the perirhinal cortex

    Directory of Open Access Journals (Sweden)

    Laura eCacciamani

    2016-04-01

    Full Text Available This study is the first to investigate the neural underpinnings of tactile object familiarity in the blind during both perception and memory. In the sighted, the perirhinal cortex (PRC has been implicated in the assessment of visual object familiarity—a crucial everyday task—as evidenced by reduced activation when an object becomes familiar. Here, to examine the PRC’s role in tactile object familiarity in the absence of vision, we trained blind subjects on a unique memory-guided drawing technique and measured brain activity while they perceptually explored raised-line drawings, drew them from tactile memory, and scribbled (control. FMRI before and after a week of training revealed a significant decrease in PRC activation from pre- to post-training (i.e., from unfamiliar to familiar during perceptual exploration as well as memory-guided drawing, but not scribbling. This familiarity-based reduction is the first evidence that the PRC represents tactile object familiarity in the blind. Furthermore, the finding of this effect during both tactile perception and tactile memory provides the critical link in establishing the PRC as a structure whose representations are supramodal for both perception and memory.

  9. Correlation-based model of artificially induced plasticity in motor cortex by a bidirectional brain-computer interface

    Science.gov (United States)

    Lajoie, Guillaume; Kalaska, John F.; Fairhall, Adrienne L.; Fetz, Eberhard E.

    2017-01-01

    Experiments show that spike-triggered stimulation performed with Bidirectional Brain-Computer-Interfaces (BBCI) can artificially strengthen connections between separate neural sites in motor cortex (MC). When spikes from a neuron recorded at one MC site trigger stimuli at a second target site after a fixed delay, the connections between sites eventually strengthen. It was also found that effective spike-stimulus delays are consistent with experimentally derived spike-timing-dependent plasticity (STDP) rules, suggesting that STDP is key to drive these changes. However, the impact of STDP at the level of circuits, and the mechanisms governing its modification with neural implants remain poorly understood. The present work describes a recurrent neural network model with probabilistic spiking mechanisms and plastic synapses capable of capturing both neural and synaptic activity statistics relevant to BBCI conditioning protocols. Our model successfully reproduces key experimental results, both established and new, and offers mechanistic insights into spike-triggered conditioning. Using analytical calculations and numerical simulations, we derive optimal operational regimes for BBCIs, and formulate predictions concerning the efficacy of spike-triggered conditioning in different regimes of cortical activity. PMID:28151957

  10. Selective increase of intention-based economic decisions by noninvasive brain stimulation to the dorsolateral prefrontal cortex.

    Science.gov (United States)

    Nihonsugi, Tsuyoshi; Ihara, Aya; Haruno, Masahiko

    2015-02-25

    The intention behind another's action and the impact of the outcome are major determinants of human economic behavior. It is poorly understood, however, whether the two systems share a core neural computation. Here, we investigated whether the two systems are causally dissociable in the brain by integrating computational modeling, functional magnetic resonance imaging, and transcranial direct current stimulation experiments in a newly developed trust game task. We show not only that right dorsolateral prefrontal cortex (DLPFC) activity is correlated with intention-based economic decisions and that ventral striatum and amygdala activity are correlated with outcome-based decisions, but also that stimulation to the DLPFC selectively enhances intention-based decisions. These findings suggest that the right DLPFC is involved in the implementation of intention-based decisions in the processing of cooperative decisions. This causal dissociation of cortical and subcortical backgrounds may indicate evolutionary and developmental differences in the two decision systems. Copyright © 2015 the authors 0270-6474/15/53412-08$15.00/0.

  11. Prenatal alcohol-induced neuroapoptosis in rat brain cerebral cortex: protective effect of folic acid and betaine.

    Science.gov (United States)

    Sogut, Ibrahim; Uysal, Onur; Oglakci, Aysegul; Yucel, Ferruh; Kartkaya, Kazim; Kanbak, Gungor

    2017-03-01

    Alcohol consumption in pregnancy may cause fetal alcohol syndrome (FAS) in the infant. This study aims to investigate prenatal alcohol exposure related neuroapoptosis on the cerebral cortex tissues of newborn rats and possible neuroprotective effects of betaine, folic acid, and combined therapy. Pregnant rats were divided into five experimental groups: control, ethanol, ethanol + betaine, ethanol + folic acid, and ethanol + betaine + folic acid combined therapy groups. We measured cytochrome c release, caspase-3, calpain and cathepsin B and L. enzyme activities. In order to observe apoptotic cells in the early stages, TUNEL method was chosen together with histologic methods such as assessing the diameters of the apoptotic cells, their distribution in unit volume and volume proportion of cortical intact neuron nuclei. Calpain, caspase-3 activities, and cytochrome c levels were significantly increased in alcohol group while cathepsin B and L. activities were also found to be elevated albeit not statistically significant. These increases were significantly reversed by folic acid and betaine + folic acid treatments. While ethanol increased the number of apoptotic cells, this increase was prevented in ethanol + betaine and ethanol + betaine + folic acid groups. Morphometric examination showed that the mean diameter of apoptotic cells was increased with ethanol administration while this increase was reduced by betaine and betaine + folic acid treatments. We observed that ethanol is capable of triggering apoptotic cell death in the newborn rat brains. Furthermore, folic acid, betaine, and combined therapy of these supplements may reduce neuroapoptosis related to prenatal alcohol consumption, and might be effective on preventing fetal alcohol syndrome in infants.

  12. Correlation-based model of artificially induced plasticity in motor cortex by a bidirectional brain-computer interface.

    Directory of Open Access Journals (Sweden)

    Guillaume Lajoie

    2017-02-01

    Full Text Available Experiments show that spike-triggered stimulation performed with Bidirectional Brain-Computer-Interfaces (BBCI can artificially strengthen connections between separate neural sites in motor cortex (MC. When spikes from a neuron recorded at one MC site trigger stimuli at a second target site after a fixed delay, the connections between sites eventually strengthen. It was also found that effective spike-stimulus delays are consistent with experimentally derived spike-timing-dependent plasticity (STDP rules, suggesting that STDP is key to drive these changes. However, the impact of STDP at the level of circuits, and the mechanisms governing its modification with neural implants remain poorly understood. The present work describes a recurrent neural network model with probabilistic spiking mechanisms and plastic synapses capable of capturing both neural and synaptic activity statistics relevant to BBCI conditioning protocols. Our model successfully reproduces key experimental results, both established and new, and offers mechanistic insights into spike-triggered conditioning. Using analytical calculations and numerical simulations, we derive optimal operational regimes for BBCIs, and formulate predictions concerning the efficacy of spike-triggered conditioning in different regimes of cortical activity.

  13. Cognitive memory and mapping in a brain-like system for robotic navigation.

    Science.gov (United States)

    Tang, Huajin; Huang, Weiwei; Narayanamoorthy, Aditya; Yan, Rui

    2017-03-01

    Electrophysiological studies in animals may provide a great insight into developing brain-like models of spatial cognition for robots. These studies suggest that the spatial ability of animals requires proper functioning of the hippocampus and the entorhinal cortex (EC). The involvement of the hippocampus in spatial cognition has been extensively studied, both in animal as well as in theoretical studies, such as in the brain-based models by Edelman and colleagues. In this work, we extend these earlier models, with a particular focus on the spatial coding properties of the EC and how it functions as an interface between the hippocampus and the neocortex, as proposed by previous work. By realizing the cognitive memory and mapping functions of the hippocampus and the EC, respectively, we develop a neurobiologically-inspired system to enable a mobile robot to perform task-based navigation in a maze environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Brain correlates of music-evoked emotions.

    Science.gov (United States)

    Koelsch, Stefan

    2014-03-01

    Music is a universal feature of human societies, partly owing to its power to evoke strong emotions and influence moods. During the past decade, the investigation of the neural correlates of music-evoked emotions has been invaluable for the understanding of human emotion. Functional neuroimaging studies on music and emotion show that music can modulate activity in brain structures that are known to be crucially involved in emotion, such as the amygdala, nucleus accumbens, hypothalamus, hippocampus, insula, cingulate cortex and orbitofrontal cortex. The potential of music to modulate activity in these structures has important implications for the use of music in the treatment of psychiatric and neurological disorders.

  15. Auto-deleting brain machine interface: Error detection using spiking neural activity in the motor cortex.

    Science.gov (United States)

    Even-Chen, Nir; Stavisky, Sergey D; Kao, Jonathan C; Ryu, Stephen I; Shenoy, Krishna V

    2015-01-01

    Brain machine interfaces (BMIs) aim to assist people with paralysis by increasing their independence and ability to communicate, e.g., by using a cursor-based virtual keyboard. Current BMI clinical trials are hampered by modest performance that causes selection of wrong characters (errors) and thus reduces achieved typing rate. If it were possible to detect these errors without explicit knowledge of the task goal, this could be used to automatically "undo" wrong selections or even prevent upcoming wrong selections. We decoded imminent or recent errors during closed-loop BMI control from intracortical spiking neural activity. In our experiment, a non-human primate controlled a neurally-driven BMI cursor to acquire targets on a grid, which simulates a virtual keyboard. In offline analyses of this closed-loop BMI control data, we identified motor cortical neural signals indicative of task error occurrence. We were able to detect task outcomes (97% accuracy) and even predict upcoming task outcomes (86% accuracy) using neural activity alone. This novel strategy may help increase the performance and clinical viability of BMIs.

  16. Variability in neural excitability and plasticity induction in the human cortex: A brain stimulation study.

    Science.gov (United States)

    Hordacre, Brenton; Goldsworthy, Mitchell R; Vallence, Ann-Maree; Darvishi, Sam; Moezzi, Bahar; Hamada, Masashi; Rothwell, John C; Ridding, Michael C

    The potential of non-invasive brain stimulation (NIBS) for both probing human neuroplasticity and the induction of functionally relevant neuroplastic change has received significant interest. However, at present the utility of NIBS is limited due to high response variability. One reason for this response variability is that NIBS targets a diffuse cortical population and the net outcome to stimulation depends on the relative levels of excitability in each population. There is evidence that the relative excitability of complex oligosynaptic circuits (late I-wave circuits) as assessed by transcranial magnetic stimulation (TMS) is useful in predicting NIBS response. Here we examined whether an additional marker of cortical excitability, MEP amplitude variability, could provide additional insights into response variability following application of the continuous theta burst stimulation (cTBS) NIBS protocol. Additionally we investigated whether I-wave recruitment was associated with MEP variability. Thirty-four healthy subjects (15 male, aged 18-35 years) participated in two experiments. Experiment 1 investigated baseline MEP variability and cTBS response. Experiment 2 determined if I-wave recruitment was associated with MEP variability. Data show that both baseline MEP variability and late I-wave recruitment are associated with cTBS response, but were independent of each other; together, these variables predict 31% of the variability in cTBS response. This study provides insight into the physiological mechanisms underpinning NIBS plasticity responses and may facilitate development of more reliable NIBS protocols. Copyright © 2016 Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ebersole, B.L.J.

    1985-01-01

    The localization of (/sup 3/H)-d-lysergic acid diethylamide ((/sup 3/H)LSD) binding sites in the mouse brain was compared in vivo and in vitro. Radioautography of brain sections incubated with (/sup 3/H)LSD in vitro revealed substantial specific (/sup 3/H)LSD binding in cortical layers III-IV and areas CA1 and dentate gyrus in hippocampus. In contrast, in brain sections from animals that received (/sup 3/H)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 (/sup 3/H)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 (/sup 3/H)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 (/sup 3/H)LSD binding sites were similar in both brain regions. Saturation binding studies in vivo showed that the lower amount of (/sup 3/H)LSD binding in hippocampus was attributable to a lower density of sites labeled by (/sup 3/H)LSD. The pharmacological identify of (/sub 3/H)LSD binding sites in vivo may be relevant to the hallucinogenic properties of LSD and of other related hallucinogens.

  18. [Morphological study of neuroprotective properties of dipeptide mimetic of nerve growth factor (GK-2h) in focal ischemic damage of rat brain prefrontal cortex].

    Science.gov (United States)

    Barskov, I V; Stelmashuk, E V; Romanova, G A; Khaspekov, L G

    2013-01-01

    The neuroprotective effects of dipeptide GK-2h, a mimetic of nerve growth factor, in bifocal photoinduced ischemia in rat brain prefrontal cortex was studied. It was shown that GK-2h, injected intraperitonealy in dose 0.1 mg/kg in 1 h or 4 h after operation and then on 2nd, 4th and 8th days, prevented significantly on 9th day from increasing volume of cortical infarction.

  19. [Effect of acute hypoxia with hypercapnia on the content of monoamines in symmetrical brain structures of the BALB/c male mice].

    Science.gov (United States)

    Karpova, I V; Mikheev, V V; Marysheva, V V; Bychkov, E R; Shabanov, P D

    2014-01-01

    The changes in activity of monoaminergic systems of both the right and the left brain hemispheres of the BALB/c male mice after an acute hypoxia with hypercapnia were studied. The concentrations of dopamine, serotonin and their metabolites dihydroxyphenylacetic, homovanilic and 5-hydroxyindolacetic acids were measured by HPLC in the brain cortex, hippocampus and striatum of the right and the left hemispheres. The more high concentration of serotonin was revealed only in the cortex of the left hemisphere in control mice without hypoxia with hypercapnia. The asymmetry in dopamine level was not registered in all structures studied. Acute hypoxia with hypercapnia decreased the dopamine level in the striatum and the serotonin level both in the hippocampus and the brain cortex. The dopamine metabolites level was reduced in the striatum and in the brain cortex of hypoxed mice: both metabolites in the right brain cortex and only dihydroxyphenylacetic acid in the left br ain cortex. Serotonin metabolism was decreased in all brain structures studied after hypoxia with hypercapnia in mice. Therefore, serotoninergic system of the brain is more sensitive to acute hypoxia with hypercapnia than dopaminergic system.

  20. 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.

  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. Chronic noise stress-induced alterations of glutamate and gamma-aminobutyric acid and their metabolism in the rat brain

    Directory of Open Access Journals (Sweden)

    Amajad Iqbal Kazi

    2014-01-01

    Full Text Available Chronic stress induces neurochemical changes that include neurotransmitter imbalance in the brain. Noise is an environmental factor inducing stress. Chronic noise stress affects monoamine neurotransmitter systems in the central nervous system. The effect on other excitatory and inhibitory neurotransmitter systems is not known. The aim was to study the role of chronic noise stress on the glutamatergic and gamma-aminobutyric acid (GABAergic systems of the brain. Female Wistar rats (155 ± 5 g were unintentionally exposed to noise due to construction (75-95 db, 3-4 hours/day, 5 days a week for 7-8 weeks in the vicinity of the animal care facility. Glutamate/GABA levels and their metabolic enzymes were evaluated in different rat brain regions (cortex, hippocampus, striatum, and cerebellum and compared with age and gender matched nonexposed rats. Chronic noise stress decreased glutamate levels and glutaminase activity 27% and 33% in the cortex, 15% and 24% in the cerebellum. Glutamate levels increased 10% in the hippocampus, 28% in striatum and glutaminase activity 15% in striatum. Glutamine synthetase activity increased significantly in all brain regions studied, that is, cortex, hippocampus, striatum, and cerebellum (P < 0.05. Noise stress-increased GABA levels and glutamate alpha decarboxylase activity 20% and 45% in the cortex, 13% and 28% in the hippocampus respectively. GABA levels and glutamate alpha decarboxylase activity decreased 15% and 14%, respectively in the striatum. GABA transaminase activity was significantly reduced in the cortex (55%, hippocampus (17%, and cerebellum (33%. Chronic noise stress differentially affected glutamatergic and GABAergic neurotransmitter systems in the rat brain, which may alter glutamate and GABA neurotransmission.

  3. Chronic noise stress-induced alterations of glutamate and gamma-aminobutyric acid and their metabolism in the rat brain.

    Science.gov (United States)

    Kazi, Amajad Iqbal; Oommen, Anna

    2014-01-01

    Chronic stress induces neurochemical changes that include neurotransmitter imbalance in the brain. Noise is an environmental factor inducing stress. Chronic noise stress affects monoamine neurotransmitter systems in the central nervous system. The effect on other excitatory and inhibitory neurotransmitter systems is not known. The aim was to study the role of chronic noise stress on the glutamatergic and gamma-aminobutyric acid (GABA)ergic systems of the brain. Female Wistar rats (155 ± 5 g) were unintentionally exposed to noise due to construction (75-95 db, 3-4 hours/day, 5 days a week for 7-8 weeks) in the vicinity of the animal care facility. Glutamate/GABA levels and their metabolic enzymes were evaluated in different rat brain regions (cortex, hippocampus, striatum, and cerebellum) and compared with age and gender matched nonexposed rats. Chronic noise stress decreased glutamate levels and glutaminase activity 27% and 33% in the cortex, 15% and 24% in the cerebellum. Glutamate levels increased 10% in the hippocampus, 28% in striatum and glutaminase activity 15% in striatum. Glutamine synthetase activity increased significantly in all brain regions studied, that is, cortex, hippocampus, striatum, and cerebellum (P Noise stress-increased GABA levels and glutamate alpha decarboxylase activity 20% and 45% in the cortex, 13% and 28% in the hippocampus respectively. GABA levels and glutamate alpha decarboxylase activity decreased 15% and 14%, respectively in the striatum. GABA transaminase activity was significantly reduced in the cortex (55%), hippocampus (17%), and cerebellum (33%). Chronic noise stress differentially affected glutamatergic and GABAergic neurotransmitter systems in the rat brain, which may alter glutamate and GABA neurotransmission.

  4. Reduced basal and novelty-induced levels of activity-regulated cytoskeleton associated protein (Arc) and c-Fos mRNA in the cerebral cortex and hippocampus of APPswe/PS1ΔE9 transgenic mice

    DEFF Research Database (Denmark)

    Christensen, Ditte Z; Thomsen, Morten Skøtt; Mikkelsen, Jens D

    2013-01-01

    in APP/PS1ΔE9 compared to wild-type mice. Novelty exposure induced an increase in Arc and c-Fos mRNA in the medial prefrontal cortex (mPFC), parietal cortex, and hippocampal formation in both APP/PS1ΔE9 transgenic and wild-type mice. However, novelty-induced IEG expression did not reach the same levels...

  5. Altered Effective Connectivity of Hippocampus-Dependent Episodic Memory Network in mTBI Survivors

    Directory of Open Access Journals (Sweden)

    Hao Yan

    2016-01-01

    Full Text Available Traumatic brain injuries (TBIs are generally recognized to affect episodic memory. However, less is known regarding how external force altered the way functionally connected brain structures of the episodic memory system interact. To address this issue, we adopted an effective connectivity based analysis, namely, multivariate Granger causality approach, to explore causal interactions within the brain network of interest. Results presented that TBI induced increased bilateral and decreased ipsilateral effective connectivity in the episodic memory network in comparison with that of normal controls. Moreover, the left anterior superior temporal gyrus (aSTG, the concept forming hub, left hippocampus (the personal experience binding hub, and left parahippocampal gyrus (the contextual association hub were no longer network hubs in TBI survivors, who compensated for hippocampal deficits by relying more on the right hippocampus (underlying perceptual memory and the right medial frontal gyrus (MeFG in the anterior prefrontal cortex (PFC. We postulated that the overrecruitment of the right anterior PFC caused dysfunction of the strategic component of episodic memory, which caused deteriorating episodic memory in mTBI survivors. Our findings also suggested that the pattern of brain network changes in TBI survivors presented similar functional consequences to normal aging.

  6. Neurogenic Effects of Ghrelin on the Hippocampus.

    Science.gov (United States)

    Kim, Chanyang; Kim, Sehee; Park, Seungjoon

    2017-03-08

    Mammalian neurogenesis continues throughout adulthood in the subventricular zone of the lateral ventricle and in the subgranular zone of the dentate gyrus in the hippocampus. It is well known that hippocampal neurogenesis is essential in mediating hippocampus-dependent learning and memory. Ghrelin, a peptide hormone mainly synthesized in the stomach, has been shown to play a major role in the regulation of energy metabolism. A plethora of evidence indicates that ghrelin can also exert important effects on neurogenesis in the hippocampus of the adult brain. The aim of this review is to discuss the current role of ghrelin on the in vivo and in vitro regulation of neurogenesis in the adult hippocampus. We will also discuss the possible role of ghrelin in dietary restriction-induced hippocampal neurogenesis and the link between ghrelin-induced hippocampal neurogenesis and cognitive functions.

  7. Evaluation of Krebs cycle enzymes in the brain of rats after chronic administration of antidepressants.

    Science.gov (United States)

    Scaini, Giselli; Santos, Patricia M; Benedet, Joana; Rochi, Natália; Gomes, Lara M; Borges, Lislaine S; Rezin, Gislaine T; Pezente, Daiana P; Quevedo, João; Streck, Emilio L

    2010-05-31

    Several works report brain impairment of metabolism as a mechanism underlying depression. Citrate synthase and succinate dehydrogenase are enzymes localized within cells in the mitochondrial matrix and are important steps of Krebs cycle. In addition, citrate synthase has been used as a quantitative enzyme marker for the presence of intact mitochondria. Thus, we investigated citrate synthase and succinate dehydrogenase activities from rat brain after chronic administration of paroxetine, nortriptiline and venlafaxine. Adult male Wistar rats received daily injections of paroxetine (10mg/kg), nortriptiline (15mg/kg), venlafaxine (10mg/kg) or saline in 1.0mL/kg volume for 15 days. Twelve hours after the last administration, the rats were killed by decapitation, the hippocampus, striatum and prefrontal cortex were immediately removed, and activities of citrate synthase and succinate dehydrogenase were measured. We verified that chronic administration of paroxetine increased citrate synthase activity in the prefrontal cortex, hippocampus, striatum and cerebral cortex of adult rats; cerebellum was not affected. Chronic administration of nortriptiline and venlafaxine did not affect the enzyme activity in these brain areas. Succinate dehydrogenase activity was increased by chronic administration of paroxetine and nortriptiline in the prefrontal cortex, hippocampus, striatum and cerebral cortex of adult rats; cerebellum was not affected either. Chronic administration of venlafaxine increased succinate dehydrogenase activity in prefrontal cortex, but did not affect the enzyme activity in cerebellum, hippocampus, striatum and cerebral cortex. Considering that metabolism impairment is probably involved in the pathophysiology of depressive disorders, an increase in these enzymes by antidepressants may be an important mechanism of action of these drugs. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  8. The brain-derived neurotrophic factor Val66Met polymorphism is associated with reduced functional magnetic resonance imaging activity in the hippocampus and increased use of caudate nucleus-dependent strategies in a human virtual navigation task.

    Science.gov (United States)

    Banner, Harrison; Bhat, Venkataramana; Etchamendy, Nicole; Joober, Ridha; Bohbot, Véronique D

    2011-03-01

    Multiple memory systems are involved in parallel processing of spatial information during navigation. A series of studies have distinguished between hippocampus-dependent 'spatial' navigation, which relies on knowledge of the relationship between landmarks in one's environment to build a cognitive map, and habit-based 'response' learning, which requires the memorization of a series of actions and is mediated by the caudate nucleus. Studies have demonstrated that people spontaneously use one of these two alternative navigational strategies with almost equal frequency to solve a given navigation task, and that strategy correlates with functional magnetic resonance imaging (fMRI) activity and grey matter density. Although there is evidence for experience modulating grey matter in the hippocampus, genetic contributions may also play an important role in the hippocampus and caudate nucleus. Recently, the Val66Met polymorphism of the brain-derived neurotrophic factor (BDNF) gene has emerged as a possible inhibitor of hippocampal function. We have investigated the role of the BDNF Val66Met polymorphism on virtual navigation behaviour and brain activation during an fMRI navigation task. Our results demonstrate a genetic contribution to spontaneous strategies, where 'Met' carriers use a response strategy more frequently than individuals homozygous for the 'Val' allele. Additionally, we found increased hippocampal activation in the Val group relative to the Met group during performance of a virtual navigation task. Our results support the idea that the BDNF gene with the Val66Met polymorphism is a novel candidate gene involved in determining spontaneous strategies during navigation behaviour. © 2011 The Authors. European Journal of Neuroscience © 2011 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  9. Temporal Changes in Cortical and Hippocampal Expression of Genes Important for Brain Glucose Metabolism Following Controlled Cortical Impact Injury in Mice

    Directory of Open Access Journals (Sweden)

    June Zhou

    2017-09-01

    Full Text Available Traumatic brain injury (TBI causes transient increases and subsequent decreases in brain glucose utilization. The underlying molecular pathways are orchestrated processes and poorly understood. In the current study, we determined temporal changes in cortical and hippocampal expression of genes important for brain glucose/lactate metabolism and the effect of a known neuroprotective drug telmisartan on the expression of these genes after experimental TBI. Adult male C57BL/6J mice (n = 6/group underwent sham or unilateral controlled cortical impact (CCI injury. Their ipsilateral and contralateral cortex and hippocampus were collected 6 h, 1, 3, 7, 14, 21, and 28 days after injury. Expressions of several genes important for brain glucose utilization were determined by qRT-PCR. In results, (1 mRNA levels of three key enzymes in glucose metabolism [hexo kinase (HK 1, pyruvate kinase, and pyruvate dehydrogenase (PDH] were all increased 6 h after injury in the contralateral cortex, followed by decreases at subsequent times in the ipsilateral cortex and hippocampus; (2 capillary glucose transporter Glut-1 mRNA increased, while neuronal glucose transporter Glut-3 mRNA decreased, at various times in the ipsilateral cortex and hippocampus; (3 astrocyte lactate transporter MCT-1 mRNA increased, whereas neuronal lactate transporter MCT-2 mRNA decreased in the ipsilateral cortex and hippocampus; (4 HK2 (an isoform of hexokinase expression increased at all time points in the ipsilateral cortex and hippocampus. GPR81 (lactate receptor mRNA increased at various time points in the ipsilateral cortex and hippocampus. These temporal alterations in gene expression corresponded closely to the patterns of impaired brain glucose utilization reported in both TBI patients and experimental TBI rodents. The observed changes in hippocampal gene expression were delayed and prolonged, when compared with those in the cortex. The patterns of alterations were specific

  10. 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

  11. Connections of the Mouse Orbitofrontal Cortex and Regulation of Goal-Directed Action Selection by Brain-Derived Neurotrophic Factor.

    Science.gov (United States)

    Zimmermann, Kelsey S; Yamin, John A; Rainnie, Donald G; Ressler, Kerry J; Gourley, Shannon L

    2017-02-15

    Distinguishing between actions that are more likely or less likely to be rewarded is a critical aspect of goal-directed decision making. However, neuroanatomic and molecular mechanisms are not fully understood. We used anterograde tracing, viral-mediated gene silencing, functional disconnection strategies, pharmacologic rescue, and designer receptors exclusively activated by designer drugs (DREADDs) to determine the anatomic and functional connectivity between the orbitofrontal cortex (OFC) and the amygdala in mice. In particular, we knocked down brain-derived neurotrophic factor (Bdnf) bilaterally in the OFC or generated an OFC-amygdala "disconnection" by pairing unilateral OFC Bdnf knockdown with lesions of the contralateral amygdala. We characterized decision-making strategies using a task in which mice selected actions based on the likelihood that they would be reinforced. Additionally, we assessed the effects of DREADD-mediated OFC inhibition on the consolidation of action-outcome conditioning. As in other species, the OFC projects to the basolateral amygdala and dorsal striatum in mice. Bilateral Bdnf knockdown within the ventrolateral OFC and unilateral Bdnf knockdown accompanied by lesions of the contralateral amygdala impede goal-directed response selection, implicating BDNF-expressing OFC projection neurons in selecting actions based on their consequences. The tyrosine receptor kinase B agonist 7,8-dihydroxyflavone rescues action selection and increases dendritic spine density on excitatory neurons in the OFC. Rho-kinase inhibition also rescues goal-directed response strategies, linking neural remodeling with outcome-based decision making. Finally, DREADD-mediated OFC inhibition weakens new action-outcome memory. Activity-dependent and BDNF-dependent neuroplasticity within the OFC coordinate outcome-based decision making through interactions with the amygdala. These interactions break reward-seeking habits, a putative factor in multiple psychopathologies

  12. Right parietal cortex and calculation processing: intraoperative functional mapping of multiplication and addition in patients affected by a brain tumor.

    Science.gov (United States)

    Della Puppa, Alessandro; De Pellegrin, Serena; d'Avella, Elena; Gioffrè, Giorgio; Munari, Marina; Saladini, Marina; Salillas, Elena; Scienza, Renato; Semenza, Carlo

    2013-11-01

    The role of parietal areas in number processing is well known. The significance of intraoperative functional mapping of these areas has been only partially explored, however, and only a few discordant data are available in the surgical literature with regard to the right parietal lobe. The purpose of this study was to evaluate the clinical impact of simple calculation in cortical electrostimulation of right-handed patients affected by a right parietal brain tumor. Calculation mapping in awake surgery was performed in 3 right-handed patients affected by high-grade gliomas located in the right parietal lobe. Preoperatively, none of the patients presented with calculation deficits. In all 3 cases, after sensorimotor and language mapping, cortical and intraparietal sulcus areas involved in single-digit multiplication and addition calculations were mapped using bipolar electrostimulation. In all patients, different sites of the right parietal cortex, mainly in the inferior lobule, were detected as being specifically related to calculation (multiplication or addition). In 2 patients the intraparietal sulcus was functionally specific for multiplication. No functional sites for language were detected. All sites functional for calculation were spared during tumor resection, which was complete in all cases without postoperative neurological deficits. These findings provide intraoperative data in support of an anatomofunctional organization for multiplication and addition within the right parietal area. Furthermore, the study shows the potential clinical relevance of intraoperative mapping of calculation in patients undergoing surgery in the right parietal area. Further and larger studies are needed to confirm these data and assess whether mapped areas are effectively essential for function.

  13. Dexamethasone Treatment Reverses Cognitive Impairment but Increases Brain Oxidative Stress in Rats Submitted to Pneumococcal Meningitis

    Directory of Open Access Journals (Sweden)

    Tatiana Barichello

    2011-01-01

    Full Text Available Pneumococcal meningitis is associated with a significant mortality rate and neurologic sequelae. The animals received either 10 μL of saline or a S. pneumoniae suspension and were randomized into different groups: sham: placebo with dexamethasone 0.7 mg/kg/1 day; placebo with dexamethasone 0.2 mg/kg/7 days; meningitis groups: dexamethasone 0.7 mg/kg/1 day and dexamethasone 0.2 mg/kg/7 days. Ten days after induction we evaluated memory and oxidative stress parameters in hippocampus and cortex. In the step-down inhibitory avoidance task, we observed memory impairment in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The lipid peroxidation was increased in hippocampus in the meningitis groups with dexamethasone and in cortex only in the meningitis group with dexamethasone 0.2 mg/kg/7 days. The protein carbonyl was increased in hippocampus in the meningitis groups with dexamethasone and in cortex in the meningitis groups with and without dexamethasone. There was a decrease in the proteins integrity in hippocampus in all groups receiving treatment with dexamethasone and in cortex in all groups with dexamethasone (0.7 mg/kg/1 day. The mitochondrial superoxide was increased in the hippocampus and cortex in the meningitis group with dexamethasone 0.2 mg/kg/7 days. Our findings demonstrate that dexamethasone reverted cognitive impairment but increased brain oxidative stress in hippocampus and cortex in Wistar rats ten days after pneumococcal meningitis induction.

  14. Brain Basics

    Medline Plus

    Full Text Available ... to change the way she thinks about and reacts to things that may trigger her depression. Several ... early brain development, and may also assist in learning and memory. hippocampus —A portion of the brain ...

  15. Brain Basics

    Medline Plus

    Full Text Available ... early brain development, and may also assist in learning and memory. hippocampus —A portion of the brain involved in creating and filing new memories. hypothalmic-pituitary-adrenal (HPA) ...

  16. Brain Basics

    Medline Plus

    Full Text Available ... doctor that she had experienced long periods of deep sadness throughout her teenage years, but had never ... early brain development, and may also assist in learning and memory. hippocampus —A portion of the brain ...

  17. Alzheimer-associated presenilin 2 gene is dysregulated in rat medial temporal lobe cortex after complete brain ischemia due to cardiac arrest.

    Science.gov (United States)

    Pluta, Ryszard; Kocki, Janusz; Ułamek-Kozioł, Marzena; Bogucka-Kocka, Anna; Gil-Kulik, Paulina; Januszewski, Sławomir; Jabłoński, Mirosław; Petniak, Alicja; Brzozowska, Judyta; Bogucki, Jacek; Furmaga-Jabłońska, Wanda; Czuczwar, Stanisław J

    2016-02-01

    Brain ischemia may be causally related with Alzheimer's disease. Probably, presenilin gene dysregulation may be associated with Alzheimer's disease neuropathology. Consequently, we have examined quantitative changes in both presenilin 1 and 2 genes in the medial temporal lobe cortex following 10-min global brain ischemia in rats. Global brain ischemia was induced by cardiac arrest in female rats that were allowed to survive for 2, 7 and 30 days. The expression of presenilin genes was evaluated in the rat medial temporal lobe cortex with the use of quantitative RT-PCR analysis. Presenilin 1 gene expression tended to be downregulated from days 2 to 7 postischemia but at day 30, there was a reverse tendency. The greatest overexpression of presenilin 2 gene was noted at 2-nd day whilst on day 7, the expression of this gene was only modestly elevated. Eventually, at day 30 expression of presenilin 2 gene was modestly downregulated. Alterations of presenilin 2 gene expression between 2 and 7 days and between 2 and 30 days were statistically significant. Thus, presented changes suggest that the significant dysregulation of presenilin 2 gene may be connected with a response of neuronal cells to transient global brain ischemia due to cardiac arrest. Finally, the ischemia-induced gene dysregulation may play a key role in the late onset of Alzheimer's-type dementia. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  18. Obesity in aging exacerbates blood-brain barrier disruption, neuroinflammation, and oxidative stress in the mouse hippocampus: effects on expression of genes involved in beta-amyloid generation and Alzheimer's disease.

    Science.gov (United States)

    Tucsek, Zsuzsanna; Toth, Peter; Sosnowska, Danuta; Gautam, Tripti; Mitschelen, Matthew; Koller, Akos; Szalai, Gabor; Sonntag, William E; Ungvari, Zoltan; Csiszar, Anna

    2014-10-01

    There is growing evidence that obesity has deleterious effects on the brain and cognitive function in the elderly population. However, the specific mechanisms through which aging and obesity interact to promote cognitive decline remain unclear. To test the hypothesis that aging exacerbates obesity-induced cerebromicrovascular damage and neuroinflammation, we compared young (7 months) and aged (24 months) high fat diet-fed obese C57BL/6 mice. Aging exacerbated obesity-induced systemic inflammation and blood-brain barrier disruption, as indicated by the increased circulating levels of proinflammatory cytokines and increased presence of extravasated immunoglobulin G in the hippocampus, respectively. Obesity-induced blood-brain barrier damage was associated with microglia activation, upregulation of activating Fc-gamma receptors and proinflammatory cytokines, and increased oxidative stress. Treatment of cultured primary microglia with sera derived from aged obese mice resulted in significantly more pronounced microglia activation and oxidative stress, as compared with treatment with young sera. Serum-induced activation and oxidative stress were also exacerbated in primary microglia derived from aged animals. Hippocampal expression of genes involved in regulation of the cellular amyloid precursor protein-dependent signaling pathways, beta-amyloid generation, and the pathogenesis of tauopathy were largely unaffected by obesity in aged mice. Collectively, obesity in aging is associated with a heightened state of systemic inflammation, which exacerbates blood-brain barrier disruption. The resulting neuroinflammation and oxidative stress in the mouse hippocampus likely contribute to the significant cognitive decline observed in aged obese animals. © The Author 2013. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. 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)

  20. Dysregulation of Amyloid-β Protein Precursor, β-Secretase, Presenilin 1 and 2 Genes in the Rat Selectively Vulnerable CA1 Subfield of Hippocampus Following Transient Global Brain Ischemia.

    Science.gov (United States)

    Kocki, Janusz; Ułamek-Kozioł, Marzena; Bogucka-Kocka, Anna; Januszewski, Sławomir; Jabłoński, Mirosław; Gil-Kulik, Paulina; Brzozowska, Judyta; Petniak, Alicja; Furmaga-Jabłońska, Wanda; Bogucki, Jacek; Czuczwar, Stanisław J; Pluta, Ryszard

    2015-01-01

    The interaction between brain ischemia and Alzheimer's disease (AD) has been intensively investigated recently. Nevertheless, we have not yet understood the nature and mechanisms of the ischemic episodes triggering the onset of AD and how they influence its slow progression. The assumed connection between brain ischemia and the accumulation of amyloid-β (Aβ) peptide awaits to be clearly explained. In our research, we employed a rat cardiac arrest model to study the changes in gene expression of amyloid-β protein precursor (AβPP) and its cleaving enzymes, β- and γ-secretases (including presenilins) in hippocampal CA1 sector, following transient 10-min global brain ischemia. The quantitative reverse-transcriptase PCR assay demonstrated that the expression of all above genes that contribute to Aβ peptide generation was dysregulated during 30 days in postischemic hippocampal CA1 area. It suggests that studied Aβ peptide generation-related genes can be involved in AβPP metabolism, following global brain ischemia and will be useful to identify the molecular mechanisms underpinning that cerebral ischemia might be an etiological cause of AD via dysregulation of AβPP and its cleaving enzymes, β- and γ-secretases genes, and subsequently, it may increase Aβ peptide production and promote the gradual and slow development of AD neuropathology. Our data demonstrate that brain ischemia activates delayed neuronal death in hippocampus in an AβPP-dependent manner, thus defining a new and important mode of ischemic cell death.

  1. Citalopram Ameliorates Synaptic Plasticity Deficits in Different Cognition-Associated Brain Regions Induced by Social Isolation in Middle-Aged Rats.

    Science.gov (United States)

    Gong, Wei-Gang; Wang, Yan-Juan; Zhou, Hong; Li, Xiao-Li; Bai, Feng; Ren, Qing-Guo; Zhang, Zhi-Jun

    2017-04-01

    Our previous experiments demonstrated that social isolation (SI) caused AD-like tau hyperphosphorylation and spatial memory deficits in middle-aged rats. However, the underlying mechanisms of SI-induced spatial memory deficits remain elusive. Middle-aged rats (10 months) were group or isolation reared for 8 weeks. Following the initial 4-week period of rearing, citalopram (10 mg/kg i.p.) was administered for 28 days. Then, pathophysiological changes were assessed by performing behavioral, biochemical, and pathological analyses. We found that SI could cause cognitive dysfunction and decrease synaptic protein (synaptophysin or PSD93) expression in different brain regions associated with cognition, such as the prefrontal cortex, dorsal hippocampus, ventral hippocampus, amygdala, and caudal putamen, but not in the entorhinal cortex or posterior cingulate. Citalopram could significantly improve learning and memory and partially restore synaptophysin or PSD93 expression in the prefrontal cortex, hippocampus, and amygdala in SI rats. Moreover, SI decreased the number of dendritic spines in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus, which could be reversed by citalopram. Furthermore, SI reduced the levels of BDNF, serine-473-phosphorylated Akt (active form), and serine-9-phosphorylated GSK-3β (inactive form) with no significant changes in the levels of total GSK-3β and Akt in the dorsal hippocampus, but not in the posterior cingulate. Our results suggest that decreased synaptic plasticity in cognition-associated regions might contribute to SI-induced cognitive deficits, and citalopram could ameliorate these deficits by promoting synaptic plasticity mainly in the prefrontal cortex, dorsal hippocampus, and ventral hippocampus. The BDNF/Akt/GSK-3β pathway plays an important role in regulating synaptic plasticity in SI rats.

  2. Glutamate Levels and Resting Cerebral Blood Flow in Anterior Cingulate Cortex Are Associated at Rest and Immediately Following Infusion of S-Ketamine in Healthy Volunteers

    OpenAIRE

    Kirsten Borup Bojesen; Kirsten Borup Bojesen; Kasper Aagaard Andersen; Kasper Aagaard Andersen; Kasper Aagaard Andersen; Sophie Nordahl Rasmussen; Sophie Nordahl Rasmussen; Sophie Nordahl Rasmussen; Lone Baandrup; Line Malmer Madsen; Birte Yding Glenthøj; Birte Yding Glenthøj; Egill Rostrup; Brian Villumsen Broberg

    2018-01-01

    Progressive loss of brain tissue is seen in some patients with schizophrenia and might be caused by increased levels of glutamate and resting cerebral blood flow (rCBF) alterations. Animal studies suggest that the normalisation of glutamate levels decreases rCBF and prevents structural changes in hippocampus. However, the relationship between glutamate and rCBF in anterior cingulate cortex (ACC) of humans has not been studied in the absence of antipsychotics and illness chronicity. Ketamine i...

  3. A neural model of normal and abnormal learning and memory consolidation: adaptively timed conditioning, hippocampus, amnesia, neurotrophins, and consciousness.

    Science.gov (United States)

    Franklin, Daniel J; Grossberg, Stephen

    2017-02-01

    How do the hippocampus and amygdala interact with thalamocortical systems to regulate cognitive and cognitive-emotional learning? Why do lesions of thalamus, amygdala, hippocampus, and cortex have differential effects depending on the phase of learning when they occur? In particular, why is the hippocampus typically needed for trace conditioning, but not delay conditioning, and what do the exceptions reveal? Why do amygdala lesions made before or immediately after training decelerate conditioning while those made later do not? Why do thalamic or sensory cortical lesions degrade trace conditioning more than delay conditioning? Why do hippocampal lesions during trace conditioning experiments degrade recent but not temporally remote learning? Why do orbitofrontal cortical lesions degrade temporally remote but not recent or post-lesion learning? How is temporally graded amnesia caused by ablation of prefrontal cortex after memory consolidation? How are attention and consciousness linked during conditioning? How do neurotrophins, notably brain-derived neurotrophic factor (BDNF), influence memory formation and consolidation? Is there a common output path for learned performance? A neural model proposes a unified answer to these questions that overcome problems of alternative memory models.

  4. Dogs Have the Most Neurons, Though Not the Largest Brain: Trade-Off between Body Mass and Number of Neurons in the Cerebral Cortex of Large Carnivoran Species.

    Science.gov (United States)

    Jardim-Messeder, Débora; Lambert, Kelly; Noctor, Stephen; Pestana, Fernanda M; de Castro Leal, Maria E; Bertelsen, Mads F; Alagaili, Abdulaziz N; Mohammad, Osama B; Manger, Paul R; Herculano-Houzel, Suzana

    2017-01-01

    Carnivorans are a diverse group of mammals that includes carnivorous, omnivorous and herbivorous, domesticated and wild species, with a large range of brain sizes. Carnivory is one of several factors expected to be cognitively demanding for carnivorans due to a requirement to outsmart larger prey. On the other hand, large carnivoran species have high hunting costs and unreliable feeding patterns, which, given the high metabolic cost of brain neurons, might put them at risk of metabolic constraints regarding how many brain neurons they can afford, especially in the cerebral cortex. For a given cortical size, do carnivoran species have more cortical neurons than the herbivorous species they prey upon? We find they do not; carnivorans (cat, mongoose, dog, hyena, lion) share with non-primates, including artiodactyls (the typical prey of large carnivorans), roughly the same relationship between cortical mass and number of neurons, which suggests that carnivorans are subject to the same evolutionary scaling rules as other non-primate clades. However, there are a few important exceptions. Carnivorans stand out in that the usual relationship between larger body, larger cortical mass and larger number of cortical neurons only applies to small and medium-sized species, and not beyond dogs: we find that the golden retriever dog has more cortical neurons than the striped hyena, African lion and even brown bear, even though the latter species have up to three times larger cortices than dogs. Remarkably, the brown bear cerebral cortex, the largest examined, only has as many neurons as the ten times smaller cat cerebral cortex, although it does have the expected ten times as many non-neuronal cells in the cerebral cortex compared to the cat. We also find that raccoons have dog-like numbers of neurons in their cat-sized brain, which makes them comparable to primates in neuronal density. Comparison of domestic and wild species suggests that the neuronal composition of carnivoran

  5. Dogs Have the Most Neurons, Though Not the Largest Brain: Trade-Off between Body Mass and Number of Neurons in the Cerebral Cortex of Large Carnivoran Species

    Science.gov (United States)

    Jardim-Messeder, Débora; Lambert, Kelly; Noctor, Stephen; Pestana, Fernanda M.; de Castro Leal, Maria E.; Bertelsen, Mads F.; Alagaili, Abdulaziz N.; Mohammad, Osama B.; Manger, Paul R.; Herculano-Houzel, Suzana

    2017-01-01

    Carnivorans are a diverse group of mammals that includes carnivorous, omnivorous and herbivorous, domesticated and wild species, with a large range of brain sizes. Carnivory is one of several factors expected to be cognitively demanding for carnivorans due to a requirement to outsmart larger prey. On the other hand, large carnivoran species have high hunting costs and unreliable feeding patterns, which, given the high metabolic cost of brain neurons, might put them at risk of metabolic constraints regarding how many brain neurons they can afford, especially in the cerebral cortex. For a given cortical size, do carnivoran species have more cortical neurons than the herbivorous species they prey upon? We find they do not; carnivorans (cat, mongoose, dog, hyena, lion) share with non-primates, including artiodactyls (the typical prey of large carnivorans), roughly the same relationship between cortical mass and number of neurons, which suggests that carnivorans are subject to the same evolutionary scaling rules as other non-primate clades. However, there are a few important exceptions. Carnivorans stand out in that the usual relationship between larger body, larger cortical mass and larger number of cortical neurons only applies to small and medium-sized species, and not beyond dogs: we find that the golden retriever dog has more cortical neurons than the striped hyena, African lion and even brown bear, even though the latter species have up to three times larger cortices than dogs. Remarkably, the brown bear cerebral cortex, the largest examined, only has as many neurons as the ten times smaller cat cerebral cortex, although it does have the expected ten times as many non-neuronal cells in the cerebral cortex compared to the cat. We also find that raccoons have dog-like numbers of neurons in their cat-sized brain, which makes them comparable to primates in neuronal density. Comparison of domestic and wild species suggests that the neuronal composition of carnivoran

  6. Dogs Have the Most Neurons, Though Not the Largest Brain: Trade-Off between Body Mass and Number of Neurons in the Cerebral Cortex of Large Carnivoran Species

    Directory of Open Access Journals (Sweden)

    Débora Jardim-Messeder

    2017-12-01

    Full Text Available Carnivorans are a diverse group of mammals that includes carnivorous, omnivorous and herbivorous, domesticated and wild species, with a large range of brain sizes. Carnivory is one of several factors expected to be cognitively demanding for carnivorans due to a requirement to outsmart larger prey. On the other hand, large carnivoran species have high hunting costs and unreliable feeding patterns, which, given the high metabolic cost of brain neurons, might put them at risk of metabolic constraints regarding how many brain neurons they can afford, especially in the cerebral cortex. For a given cortical size, do carnivoran species have more cortical neurons than the herbivorous species they prey upon? We find they do not; carnivorans (cat, mongoose, dog, hyena, lion share with non-primates, including artiodactyls (the typical prey of large carnivorans, roughly the same relationship between cortical mass and number of neurons, which suggests that carnivorans are subject to the same evolutionary scaling rules as other non-primate clades. However, there are a few important exceptions. Carnivorans stand out in that the usual relationship between larger body, larger cortical mass and larger number of cortical neurons only applies to small and medium-sized species, and not beyond dogs: we find that the golden retriever dog has more cortical neurons than the striped hyena, African lion and even brown bear, even though the latter species have up to three times larger cortices than dogs. Remarkably, the brown bear cerebral cortex, the largest examined, only has as many neurons as the ten times smaller cat cerebral cortex, although it does have the expected ten times as many non-neuronal cells in the cerebral cortex compared to the cat. We also find that raccoons have dog-like numbers of neurons in their cat-sized brain, which makes them comparable to primates in neuronal density. Comparison of domestic and wild species suggests that the neuronal

  7. Alterations in right posterior hippocampus in early blind individuals

    DEFF Research Database (Denmark)

    Chebat, Daniel-Robert; Chen, Jan-Kai; Schneider, Fabien

    2007-01-01

    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...... 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 posterior hippocampus in early blind individuals suggests the implication of this region in visual spatial memory. Udgivelsesdato: 2007-Mar-5...

  8. iTRAQ proteomic analysis of the hippocampus in a rat model of nicotine-induced conditioned place preference.

    Science.gov (United States)

    Zhu, Beibei; Li, Xiangyu; Chen, Huan; Wang, Hongjuan; Zhu, Xinchao; Hou, Hongwei; Hu, Qingyuan

    2017-05-13

    Repeated exposures to nicotine are known to result in persistent changes in proteins expression in addiction-related brain regions, such as the striatum, nucleus accumbens and prefrontal cortex, but the changes induced in the protein content of the hippocampus remain poorly studied. This study established a rat model of nicotine-induced conditioned place preference (CPP), and screened for proteins that were differentially expressed in the hippocampus of these rats using isobaric tags for relative and absolute quantitation labeling (iTRAQ) coupled with 2D-LC MS/MS. The nicotine-induced CPP was established by subcutaneously injecting rats with 0.2 mg/kg nicotine. Relative to the control (saline) group, the nicotine group showed 0.67- and 1.5-fold changes in 117 and 10 hippocampal proteins, respectively. These differentially expressed proteins are mainly involved in calcium-mediated signaling, neurotransmitter transport, GABAergic synapse function, long-term synaptic potentiation and nervous system development. Furthermore, RT-PCR was used to confirmed the results of the proteomic analysis. Our findings identify several proteins and cellular signaling pathways potentially involved in the molecular mechanisms in the hippocampus that underlie nicotine addiction. These results provide insights into the mechanisms of nicotine treatment in hippocampus. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. 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...

  10. 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

  11. 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.

  12. Hippocampus and striatum: dynamics and interaction during acquisition and sleep-related motor sequence memory consolidation.

    Science.gov (United States)

    Albouy, Geneviève; King, Bradley R; Maquet, Pierre; Doyon, Julien

    2013-11-01

    While several models of memory consolidation have previously associated hippocampal activity with declarative memory, there is now increasing evidence that the hippocampus also plays a crucial role in procedural memory. Here, we review recent human functional neuroimaging studies demonstrating that the hippocampus is involved in the acquisition and sleep-related consolidation of procedural memories, and motor sequence-based skills in particular. More specifically, we present evidence that hippocampal activity and its functional interactions with other brain structures, particularly competition with the striatum, contribute to initial learning of sequential motor behavior. Interestingly, these early cerebral representations in the hippocampus and striatum, which may interact through the prefrontal cortex, can even predict subsequent sleep-related memory consolidation processes. We propose that sleep can reorganize the activity within, as well as the functional interactions between, these structures, ultimately favoring overnight performance enhancement. Finally, we conclude by offering insights into the respective roles of these structures in procedural memory consolidation processes. We argue that, in the context of motor sequence memory consolidation, the hippocampal system triggers subsequent sleep-dependent performance enhancement whereas the striatal system is involved in the maintenance of the motor behavior over time. Copyright © 2013 Wiley Periodicals, Inc.

  13. Disruption of redox homeostasis and brain damage caused in vivo by methylmalonic acid and ammonia in cerebral cortex and striatum of developing rats.

    Science.gov (United States)

    Viegas, C M; Zanatta, Â; Grings, M; Hickmann, F H; Monteiro, W O; Soares, L E; Sitta, Â; Leipnitz, G; de Oliveira, F H; Wajner, M

    2014-06-01

    Hyperammonemia is a common finding in children with methylmalonic acidemia and propionic acidemia, but its contribution to the development of the neurological symptoms in the affected patients is poorly known. Considering that methylmalonic acid (MMA) and propionic acid (PA) predominantly accumulate in these disorders, we investigated the effects of hyperammonemia induced by urease treatment in 30-day-old rats receiving an intracerebroventricular (ICV) injection of MMA or PA on important parameters of redox homeostasis in cerebral cortex and striatum. We evaluated glutathione (GSH) concentrations, sulfhydryl content, nitrate and nitrite concentrations, 2',7'-dichlorofluorescein (DCFH) oxidation, and the activity of antioxidant enzymes. MMA decreased GSH concentrations and sulfhydryl content and increased nitrate and nitrite concentrations in cerebral cortex and striatum from hyperammonemic rats, whereas MMA or ammonia per se did not alter these parameters. MMA plus hyperammonemia also decreased glutathione reductase activity in rat cerebral cortex, but did not affect catalase, superoxide dismutase and glutathione peroxidase activities, neither DCFH oxidation. Furthermore, ICV PA administration alone or combined with hyperammonemia did not alter any of the evaluated parameters. We also found that pre-treatment with antioxidants prevented GSH reduction and sulfhydryl oxidation, whereas N(ω)-nitro-L-arginine methyl ester (L-NAME) prevented the increased nitrate and nitrite concentrations provoked by MMA plus ammonia treatments. Histological alterations, including vacuolization, ischemic neurons, and pericellular edema, were observed in brain of hyperammonemic rats injected with MMA. The data indicate a synergistic effect of MMA and ammonia disturbing redox homeostasis and causing morphological brain abnormalities in rat brain.

  14. Local structure and global connectivity in the cerebral cortex: neuroinformatics, histology and ultra high resolution diffusion MRI in the rhesus and marmoset monkey brain

    OpenAIRE

    Reveley, Colin

    2017-01-01

    This thesis concerns the cortical connectivity in Primates. The efficacy of Diffusion weighted MRI (dMRI) is examined. White matter (“WM”) systems subjacent to cortex (“superficial WM” ) are found to be a limiting factor to dMRI tractography. Superficial WM systems are examined with dMRI itself, and with analysis of histological data from the scanned brains. dMRI data was acquired ex-vivo at exceptional spatial and angular resolution (250μm in Rhesus, 150μm in Marmoset). The superficial WM wa...

  15. Analysis of transcriptional initiation and translatability of brain-derived neurotrophic factor mRNAs in the rat brain.

    Science.gov (United States)

    Timmusk, T; Persson, H; Metsis, M

    1994-08-15

    The rat brain-derived neurotrophic factor (BDNF) gene consists of four 5' exons linked to separate promoters and one 3' exon encoding the prepro-BDNF protein. In the present study, using RNase protection analysis, we show that the same major transcription initiation sites are used for each BDNF exon mRNA in different brain regions and that in addition to hippocampus and cerebral cortex, kainate differentially induces the expression of BDNF exon mRNAs in thalamus, cerebellum and striatum. The 4.2 kb transcripts, are less enriched in the polysomal fraction of rat brain than the shorter 1.6 kb transcripts suggesting their translational discrimination.

  16. 3,5,6,7,8,3′,4′-Heptamethoxyflavone, a Citrus Flavonoid, Ameliorates Corticosterone-Induced Depression-like Behavior and Restores Brain-Derived Neurotrophic Factor Expression, Neurogenesis, and Neuroplasticity in the Hippocampus

    Directory of Open Access Journals (Sweden)

    Atsushi Sawamoto

    2016-04-01

    Full Text Available We previously reported that the citrus flavonoid 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF increased the expression of brain-derived neurotrophic factor (BDNF in the hippocampus of a transient global ischemia mouse model. Since the BDNF hypothesis of depression postulates that a reduction in BDNF is directly involved in the pathophysiology of depression, we evaluated the anti-depressive effects of HMF in mice with subcutaneously administered corticosterone at a dose of 20 mg/kg/day for 25 days. We demonstrated that the HMF treatment ameliorated (1 corticosterone-induced body weight loss, (2 corticosterone-induced depression-like behavior, and (3 corticosterone-induced reductions in BDNF production in the hippocampus. We also showed that the HMF treatment restored (4 corticosterone-induced reductions in neurogenesis in the dentate gyrus subgranular zone and (5 corticosterone-induced reductions in the expression levels of phosphorylated calcium-calmodulin-dependent protein kinase II and extracellular signal-regulated kinase1/2. These results suggest that HMF exerts its effects as an anti-depressant drug by inducing the expression of BDNF.

  17. Transient inactivation of the neonatal ventral hippocampus impairs attentional set-shifting behavior

    DEFF Research Database (Denmark)

    Brooks, Julie M; Pershing, Michelle L; Thomsen, Morten Skøtt

    2012-01-01

    Cognitive deficits represent a core symptom cluster in schizophrenia that are thought to reflect developmental dysregulations within a neural system involving the ventral hippocampus (VH), nucleus accumbens (NAC), and prefrontal cortex (PFC). The present experiments determined the cognitive effects...

  18. 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…

  19. The response of cerebral cortex to haemorrhagic damage: experimental evidence from a penetrating injury model.

    Directory of Open Access Journals (Sweden)

    Sivaraman Purushothuman

    Full Text Available Understanding the response of the brain to haemorrhagic damage is important in haemorrhagic stroke and increasingly in the understanding the cerebral degeneration and dementia that follow head trauma and head-impact sports. In addition, there is growing evidence that haemorrhage from small cerebral vessels is important in the pathogenesis of age-related dementia (Alzheimer's disease. In a penetration injury model of rat cerebral cortex, we have examined the neuropathology induced by a needlestick injury, with emphasis on features prominent in the ageing and dementing human brain, particularly plaque-like depositions and the expression of related proteins. Needlestick lesions were made in neo- and hippocampal cortex in Sprague Dawley rats aged 3-5 months. Brains were examined after 1-30 d survival, for haemorrhage, for the expression of hyperphosphorylated tau, Aβ, amyloid precursor protein (APP, for gliosis and for neuronal death. Temporal cortex from humans diagnosed with Alzheimer's disease was examined with the same techniques. Needlestick injury induced long-lasting changes-haem deposition, cell death, plaque-like deposits and glial invasion-along the needle track. Around the track, the lesion induced more transient changes, particularly upregulation of Aβ, APP and hyperphosporylated tau in neurons and astrocytes. Reactions were similar in hippocampus and neocortex, except that neuronal death was more widespread in the hippocampus. In summary, experimental haemorrhagic injury to rat cerebral cortex induced both permanent and transient changes. The more permanent changes reproduced features of human senile plaques, including the formation of extracellular deposits in which haem and Aβ-related proteins co-localised, neuronal loss and gliosis. The transient changes, observed in tissue around the direct lesion, included the upregulation of Aβ, APP and hyperphosphorylated tau, not associated with cell death. The findings support the

  20. 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...

  1. Distinct functional brain regional integration of Casp3, Ascl1 and S100a6 gene expression in spatial memory.

    Science.gov (United States)

    Gruden, Marina A; Storozheva, Zinaida I; Sewell, Robert D E; Kolobov, Vitaly V; Sherstnev, Vladimir V

    2013-09-01

    Evaluating the brain structural expression of defined genes involved in basic biological processes of neurogenesis, apoptosis or neural plasticity may facilitate the understanding of genetic mechanisms underlying spatial memory. The aim of the present study was to compare Ascl1, Casp3 and S100a6 gene expression in the hippocampus, prefrontal cortex and cerebellum of adult rats in water maze spatial memory performance. After four days training, the mean platform time (memory formation. Real time PCR analysis revealed a positive inter-structural correlation for S100a6/Casp gene expression between the prefrontal cortex and the cerebellum but a negative correlation for S100a6/Ascl1 transcribed genes between the prefrontal cortex and hippocampus during swimming in the active controls. However, during spatial memory performance there was only one inter-structural correlation between the prefrontal cortex and cerebellum with respect to Casp3 expression, though there were intra-structural correlations between Casp3/Ascl1 transcriptions within the prefrontal cortex and hippocampus as well as between Ascl1/S100a6 in the cerebellum. In active learners versus naive controls, the transcrption of all genes was augmented in the prefrontal cortex but Casp3 and Ascl1 were also elevated in hippocampus whilst only S100a6 increased in the cerebellum. The findings endorsed the role of the hippocampus in memory acquisition in addition to an integrative relationship with the prefrontal cortex and cerebellum. This structural and molecular configuration is important for creation of novel neural circuitry for consolidation and reconsolidation of memory trace with an involvement of coupled processes of neurogenesis, apoptosis or neural plasticity. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Effects of caffeine on neuronal apoptosis in neonatal hypoxic-ischemic brain injury.

    Science.gov (United States)

    Kilicdag, Hasan; Daglioglu, Yusuf Kenan; Erdogan, Seyda; Zorludemir, Suzan

    2014-09-01

    Hypoxia-ischemia (HI) in rat pups leads to strong activation of apoptosis, and apoptosis contributes significantly to cerebral damage in the perinatal period. Caffeine displays a broad array of actions on the brain. The aim of this study was to investigate the effects of caffeine on neuronal apoptosis in a hypoxic-ischemic neonatal model. Twenty-four seven-day-old Wistar rat pups were subjected to right common carotid artery ligation and hypoxia for 2 h. Sham group (n = 8) had a median neck incision, but the rats were not subjected to ligation or hypoxia. The pups were treated with 20 mg/kg/day caffeine citrate (n = 8) or saline (n = 8) immediately before HI and at 0, 24, 48 and 72 h post-hypoxia. Neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) and caspase-3 in the hippocampus and parietal cortex of both hemispheres. The numbers of apoptotic cells in the hippocampus and parietal cortex were significantly higher in the saline group than they were in the sham group (p cells in the hippocampus (p caffeine-treated group than they were in the sham group, but the number of apoptotic cells decreased significantly in the caffeine-treated group compared with the saline group in the hippocampus (p caffeine administration in hypoxic-ischemic brain injury reduces neuronal apoptosis in the developing brain. We suggest that caffeine may be effective in reducing brain injury.

  3. Forebrain Ischemia-Reperfusion Simulating Cardiac Arrest in Mice Induces Edema and DNA Fragmentation in the Brain

    Directory of Open Access Journals (Sweden)

    Christina H. Liu

    2007-05-01

    Full Text Available Brain injury affects one-third of persons who survive after heart attack, even with restoration of spontaneous circulation by cardiopulmonary resuscitation. We studied brain injury resulting from transient bilateral carotid artery occlusion (BCAO and reperfusion by simulating heart attack and restoration of circulation, respectively, in live C57Black6 mice. This model is known to induce neuronal death in the hippocampus, striatum, and cortex. We report the appearance of edema after transient BCAO of 60 minutes and 1 day of reperfusion. Hyperintensity in diffusion-weighted magnetic resonance imaging (MRI was detectable in the striatum, thalamus, and cortex but not in the hippocampus. To determine whether damage to the hippocampus can be detected in live animals, we infused a T2 susceptibility magnetic resonance contrast agent (superparamagnetic iron oxide nanoparticles [SPIONs] that was linked to single-stranded deoxyribonucleic acid (DNA complementary in sequence to c-fos messenger ribonucleic acid (SPION-cfos; we acquired in vivo T2*-weighted MRI 3 days later. SPION retention was measured as T2* (milliseconds signal reduction or R2* value (s−1 elevation. We found that animals treated with 60-minute BCAO and 7-day reperfusion exhibited significantly less SPION retention in the hippocampus and cortex than sham-operated animals. These findings suggest that brain injury induced by cardiac arrest can be detected in live animals.

  4. Aluminum-Induced Cholinergic Deficits in Different Brain Parts and Its Implications on Sociability and Cognitive Functions in Mouse.

    Science.gov (United States)

    Farhat, Syeda Mehpara; Mahboob, Aamra; Iqbal, Ghazala; Ahmed, Touqeer

    2017-05-01

    Aluminum is associated with etiology of many neurodegenerative diseases specially Alzheimer's disease. Chronic exposure to aluminum via drinking water results in aluminum deposition in the brain that leads to cognitive deficits. The study aimed to determine the effects of aluminum on cholinergic biomarkers, i.e., acetylcholine level, free choline level, and choline acetyltransferase gene expression, and how cholinergic deficit affects novel object recognition and sociability in mice. Mice were treated with AlCl3 (250 mg/kg). Acetylcholine level, free choline level, and choline acetyltransferase gene expression were determined in cortex, hippocampus, and amygdala. The mice were subjected to behavior tests (novel object recognition and social novelty preference) to assess memory deficits. The acetylcholine level in cortex and hippocampus was significantly reduced in aluminum-treated animals, as compared to cortex and hippocampus of control animals. Acetylcholine level in amygdala of aluminum-treated animals remained unchanged. Free choline level in all the three brain parts was found unaltered in aluminum-treated mice. The novel object recognition memory was severely impaired in aluminum-treated mice, as compared to the control group. Similarly, animals treated with aluminum showed reduced sociability compared to the control mice group. Our study demonstrates that aluminum exposure via drinking water causes reduced acetylcholine synthesis in spite of normal free choline availability. This deficit is caused by reduced recycling of acetylcholine due to lower choline acetyltransferase level. This cholinergic hypofunction leads to cognitive and memory deficits. Moreover, hippocampus is the most affected brain part after aluminum intoxication.

  5. Activation of dominant hemisphere association cortex during naming as a function of cognitive performance in mild traumatic brain injury: Insights into mechanisms of lexical access

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    Mihai Popescu

    2017-01-01

    Full Text Available Patients with a history of mild traumatic brain injury (mTBI and objective cognitive deficits frequently experience word finding difficulties in normal conversation. We sought to improve our understanding of this phenomenon by determining if the scores on standardized cognitive testing are correlated with measures of brain activity evoked in a word retrieval task (confrontational picture naming. The study participants (n = 57 were military service members with a history of mTBI. The General Memory Index (GMI determined after administration of the Rivermead Behavioral Memory Test, Third Edition, was used to assign subjects to three groups: low cognitive performance (Group 1: GMI ≤ 87, n = 18, intermediate cognitive performance (Group 2: 88 ≤ GMI ≤ 99, n = 18, and high cognitive performance (Group 3: GMI ≥ 100, n = 21. Magnetoencephalography data were recorded while participants named eighty pictures of common objects. Group differences in evoked cortical activity were observed relatively early (within 200 ms from picture onset over a distributed network of left hemisphere cortical regions including the fusiform gyrus, the entorhinal and parahippocampal cortex, the supramarginal gyrus and posterior part of the superior temporal gyrus, and the inferior frontal and rostral middle frontal gyri. Differences were also present in bilateral cingulate cortex and paracentral lobule, and in the right fusiform gyrus. All differences reflected a lower amplitude of the evoked responses for Group 1 relative to Groups 2 and 3. These findings may indicate weak afferent inputs to and within an extended cortical network including association cortex of the dominant hemisphere in patients with low cognitive performance. The association between word finding difficulties and low cognitive performance may therefore be the result of a diffuse pathophysiological process affecting distributed neuronal networks serving a wide range of cognitive

  6. Activation of dominant hemisphere association cortex during naming as a function of cognitive performance in mild traumatic brain injury: Insights into mechanisms of lexical access.

    Science.gov (United States)

    Popescu, Mihai; Hughes, John D; Popescu, Elena-Anda; Mikola, Judy; Merrifield, Warren; DeGraba, Maria; Riedy, Gerard; DeGraba, Thomas J

    2017-01-01

    Patients with a history of mild traumatic brain injury (mTBI) and objective cognitive deficits frequently experience word finding difficulties in normal conversation. We sought to improve our understanding of this phenomenon by determining if the scores on standardized cognitive testing are correlated with measures of brain activity evoked in a word retrieval task (confrontational picture naming). The study participants (n = 57) were military service members with a history of mTBI. The General Memory Index (GMI) determined after administration of the Rivermead Behavioral Memory Test, Third Edition, was used to assign subjects to three groups: low cognitive performance (Group 1: GMI ≤ 87, n = 18), intermediate cognitive performance (Group 2: 88 ≤ GMI ≤ 99, n = 18), and high cognitive performance (Group 3: GMI ≥ 100, n = 21). Magnetoencephalography data were recorded while participants named eighty pictures of common objects. Group differences in evoked cortical activity were observed relatively early (within 200 ms from picture onset) over a distributed network of left hemisphere cortical regions including the fusiform gyrus, the entorhinal and parahippocampal cortex, the supramarginal gyrus and posterior part of the superior temporal gyrus, and the inferior frontal and rostral middle frontal gyri. Differences were also present in bilateral cingulate cortex and paracentral lobule, and in the right fusiform gyrus. All differences reflected a lower amplitude of the evoked responses for Group 1 relative to Groups 2 and 3. These findings may indicate weak afferent inputs to and within an extended cortical network including association cortex of the dominant hemisphere in patients with low cognitive performance. The association between word finding difficulties and low cognitive performance may therefore be the result of a diffuse pathophysiological process affecting distributed neuronal networks serving a wide range of cognitive processes. These

  7. Molecular size of alpha 1- and beta-adrenoceptors in rat brain cortex as determined by a radiation inactivation method.

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    Mogilnicka, E; Nielsen, M

    1986-04-02

    Frozen whole rat cerebral cortex was exposed to 10 MeV electrons from a linear accelerator. Based on the theory of target size analysis, the in situ molecular weight of alpha 1-adrenoceptors (labelled by [3H]prazosin) and beta-adrenoceptors (labelled by [3H]dihydroalprenolol) was 57 800 daltons and 42 600 daltons, respectively.

  8. Evidence of altered DNA integrity in the brain regions of suicidal victims of Bipolar Depression.

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    Mustak, Mohammed S; Hegde, Muralidhar L; Dinesh, Athira; Britton, Gabrielle B; Berrocal, Ruben; Subba Rao, K; Shamasundar, N M; Rao, K S J; Sathyanarayana Rao, T S

    2010-07-01

    Deoxyribonucleic acid (DNA) integrity plays a significant role in cell function. There are limited studies with regard to the role of DNA damage in bipolar affective disorder (BP). In the present study, we have assessed DNA integrity, conformation, and stability in the brain region of bipolar depression (BD) patients (n=10) compared to age-matched controls (n=8). Genomic DNA was isolated from 10 postmortem BD patients' brain regions (frontal cortex, Pons, medulla, thalamus, cerebellum, hypothalamus, Parietal, temporal, occipital lobe, and hippocampus) and from the age-matched control subjects. DNA from the frontal cortex, pons, medulla, and thalamus showed significantly higher number of strand breaks in BD (P<0.01) compared to the age-matched controls. However, DNA from the hippocampus region was intact and did not show any strand breaks. The stability studies also indicated that the melting temperature and ethidium bromide binding pattern were altered in the DNA of BD patients' brain regions, except in the hippocampus. The conformation studies showed B-A or secondary B-DNA conformation (instead of the normal B-DNA) in BD patients' brain regions, with the exception of the hippocampus. The levels of redox metals such as Copper (Cu) and Iron (Fe) were significantly elevated in the brain regions of the sufferers of BD, while the Zinc (Zn) level was decreased. In the hippocampus, there was no change in the Fe or Cu levels, whereas, the Zn level was elevated. There was a clear correlation between Cu and Fe levels versus strand breaks in the brain regions of the BD. To date, as far as we are aware, this is a new comprehensive database on stability and conformations of DNA in different brain regions of patients affected with BD. The biological significance of these findings is discussed here.

  9. Rapid treatment-induced brain changes in pediatric CRPS.

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    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.

  10. 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

    2014-01-01

    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 (PAG), 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

  11. Deep brain stimulation of the mediodorsal thalamic nucleus yields increases in the expression of zif-268 but not c-fos in the frontal cortex.

    Science.gov (United States)

    Ewing, Samuel G; Porr, Bernd; Pratt, Judith A

    2013-09-01

    This study explores the regions activated by deep brain stimulation of the mediodorsal thalamic nucleus through examination of immediate early genes as markers of neuronal activation. Stimulation was delivered unilaterally with constant current 100 μs duration pulses at a frequency of 130 Hz delivered at an amplitude of 200 μA for 3h. Brains were removed, sectioned and radio-labelled for the IEGs zif-268 and c-fos. In anaesthetised rats, deep brain stimulation of mediodorsal thalamic nucleus produced robust increases in the expression of zif-268 but not c-fos localised to regions that are reciprocally connected with the mediodorsal thalamic nucleus, including the prelimbic and orbitofrontal cortices, and the premotor cortex indicating an increase in synaptic activity in these regions. These findings map those brain regions that are persistently, rather than transiently, activated by high frequency electrical stimulation of the mediodorsal thalamic nucleus by a putatively antidromic mechanism which may be relevant to neuropsychiatric disorders such as schizophrenia in which thalamocortical systems are disrupted and in which DBS protocols are being considered. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Effects of acute and sustained administration of vortioxetine on the serotonin system in the hippocampus: electrophysiological studies in the rat brain.

    Science.gov (United States)

    El Mansari, Mostafa; Lecours, Maurice; Blier, Pierre

    2015-07-01

    Vortioxetine is a novel multimodal antidepressant that is a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist, an inhibitor of the serotonin (5-HT) transporter, and a 5-HT1D, 5-HT3, and 5-HT7 receptor antagonist in vitro. In vivo studies have shown that vortioxetine enhances levels of 5-HT and desensitizes 5-HT1A autoreceptors. The aim of the present study was to investigate the effects of acute and long-term administration of vortioxetine on the terminal 5-HT1B receptor and the tonic activation of 5-HT1A receptor in the rat hippocampus. These receptors were assessed following vortioxetine administration acutely or subcutaneously using minipumps for 14 days. These studies were carried out using in vivo electrophysiological recording, microiontophoresis, and stimulation of the ascending 5-HT fibers. Vortioxetine enhanced the inhibitory effect of the stimulation of the 5-HT bundle at a high, but not low frequency and reversed the inhibitory effect of the 5-HT1B receptor agonist CP 94253. These results indicate that this compound acted as a 5-HT1B receptor partial agonist. Vortioxetine inhibited 5-HT reuptake but did not dampen the sensitivity of postsynaptic 5-HT1A receptors on pyramidal neurons. Long-term administration of vortioxetine and escitalopram (both at 5 mg/kg/day) induced an increase of tonic activation of the 5-HT1A receptors in CA3 pyramidal neurons, resulting in an increase in 5-HT transmission. In addition, vortioxetine decreased the function of terminal 5-HT1B autoreceptor following its sustained administration. Desensitization of 5-HT1B autoreceptor and an increase of tonic activation of 5-HT1A receptors in the hippocampus may contribute to the antidepressant effect of vortioxetine.

  13. Neural activity in the hippocampus predicts individual visual short-term memory capacity.

    Science.gov (United States)

    von Allmen, David Yoh; Wurmitzer, Karoline; Martin, Ernst; Klaver, Peter

    2013-07-01

    Although the hippocampus had been traditionally thought to be exclusively involved in long-term memory, recent studies raised controversial explanations why hippocampal activity emerged during short-term memory tasks. For example, it has been argued that long-term memory processes might contribute to performance within a short-term memory paradigm when memory capacity has been exceeded. It is still unclear, though, whether neural activity in the hippocampus predicts visual short-term memory (VSTM) performance. To investigate this question, we measured BOLD activity in 21 healthy adults (age range 19-27 yr, nine males) while they performed a match-to-sample task requiring processing of object-location associations (delay period  =  900 ms; set size conditions 1, 2, 4, and 6). Based on individual memory capacity (estimated by Cowan's K-formula), two performance groups were formed (high and low performers). Within whole brain analyses, we found a robust main effect of "set size" in the posterior parietal cortex (PPC). In line with a "set size × group" interaction in the hippocampus, a subsequent Finite Impulse Response (FIR) analysis revealed divergent hippocampal activation patterns between performance groups: Low performers (mean capacity  =  3.63) elicited increased neural activity at set size two, followed by a drop in activity at set sizes four and six, whereas high performers (mean capacity  =  5.19) showed an incremental activity increase with larger set size (maximal activation at set size six). Our data demonstrated that performance-related neural activity in the hippocampus emerged below capacity limit. In conclusion, we suggest that hippocampal activity reflected successful processing of object-location associations in VSTM. Neural activity in the PPC might have been involved in attentional updating. Copyright © 2013 Wiley Periodicals, Inc.

  14. Cystatin C Has a Dual Role in Post-Traumatic Brain Injury Recovery

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    Marina Martinez-Vargas

    2014-04-01

    Full Text Available Cathepsin B is one of the major lysosomal cysteine proteases involved in neuronal protein catabolism. This cathepsin is released after traumatic injury and increases neuronal death; however, release of cystatin C, a cathepsin inhibitor, appears to be a self-protective brain response. Here we describe the effect of cystatin C intracerebroventricular administration in rats prior to inducing a traumatic brain injury. We observed that cystatin C injection caused a dual response in post-traumatic brain injury recovery: higher doses (350 fmoles increased bleeding and mortality, whereas lower doses (3.5 to 35 fmoles decreased bleeding, neuronal damage and mortality. We also analyzed the expression of cathepsin B and cystatin C in the brains of control rats and of rats after a traumatic brain injury. Cathepsin B was detected in the brain stem, cerebellum, hippocampus and cerebral cortex of control rats. Cystatin C was localized to the choroid plexus, brain stem and cerebellum of control rats. Twenty-four hours after traumatic brain injury, we observed changes in both the expression and localization of both proteins in the cerebral cortex, hippocampus and brain stem. An early increase and intralysosomal expression of cystatin C after brain injury was associated with reduced neuronal damage.

  15. Restraint stress-induced morphological changes at the blood-brain barrier in adult rats

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    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

  16. Proteome rearrangements after auditory learning: high-resolution profiling of synapse-enriched protein fractions from mouse brain.

    Science.gov (United States)

    Kähne, Thilo; Richter, Sandra; Kolodziej, Angela; Smalla, Karl-Heinz; Pielot, Rainer; Engler, Alexander; Ohl, Frank W; Dieterich, Daniela C; Seidenbecher, Constanze; Tischmeyer, Wolfgang; Naumann, Michael; Gundelfinger, Eckart D

    2016-07-01

    Learning and memory processes are accompanied by rearrangements of synaptic protein networks. While various studies have demonstrated the regulation of individual synaptic proteins during these processes, much less is known about the complex regulation of synaptic proteomes. Recently, we reported that