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Sample records for adult brain regions

  1. Bilateral Brain Regions Associated with Naming in Older Adults

    ERIC Educational Resources Information Center

    Obler, Loraine K.; Rykhlevskaia, Elena; Schnyer, David; Clark-Cotton, Manuella R.; Spiro, Avron, III; Hyun, JungMoon; Kim, Dae-Shik; Goral, Mira; Albert, Martin L.

    2010-01-01

    To determine structural brain correlates of naming abilities in older adults, we tested 24 individuals aged 56-79 on two confrontation-naming tests (the Boston Naming Test (BNT) and the Action Naming Test (ANT)), then collected from these individuals structural Magnetic-Resonance Imaging (MRI) and Diffusion Tensor Imaging (DTI) data. Overall,…

  2. Regional distribution of neuropeptide processing endopeptidases in adult rat brain.

    PubMed

    Berman, Y L; Rattan, A K; Carr, K; Devi, L

    1994-01-01

    Many peptide hormone and neuropeptide precursors undergo post-translational processing at mono- and/or dibasic residues. An enzymatic activity capable of processing prodynorphin at a monobasic processing site designated 'dynorphin converting enzyme' has been previously reported in rat rain and bovine pituitary. In this study the distribution of dynorphin converting enzyme activity in ten regions of rat brain has been compared with the distribution of subtilisin-like processing enzymes and with the immuno-reactive dynorphin peptides. The distribution of dynorphin converting enzyme activity generally matches the distribution of immuno-reactive dynorphin B-13 in most but not all brain regions. The regions that are known to have a relatively large number of immuno-reactive dynorphin-neurons also contain high levels of dynorphin converting enzyme activity. The distribution of dynorphin converting enzyme activity does not match the distribution of subtilisin-like processing enzyme or carboxypeptidase E activities. Taken together the data support the possibility that the dynorphin converting enzyme is involved in the maturation of dynorphin, as well as other neuropeptides, and peptide hormones.

  3. Brain metabolite concentrations across cortical regions in healthy adults

    PubMed Central

    Bracken, Bethany K.; Jensen, J. Eric; Prescot, Andrew P.; Cohen, Bruce M.; Renshaw, Perry F.; Öngür, Dost

    2010-01-01

    Magnetic resonance spectroscopy (MRS) can provide in vivo information about metabolite levels across multiple brain regions. This study used MRS to examine concentrations of N-acetylaspartate (NAA), a marker of neuronal integrity and function, and choline (Cho) which is related to the amount of cell membrane per unit volume, in anterior cingulate cortex (ACC) and parieto-occipital cortex (POC) in healthy individuals. Data were drawn from two experiments which examined glutamatergic and GABAergic signaling in schizophrenia and bipolar disorder. After controlling for gray matter percentages, NAA/Creatine (Cr) was 18% higher in POC than in ACC (p<0.001); Cho/Cr was 46% lower in POC than in ACC (p<0.001). There was an effect of study (p<0.001 for both metabolites), but no region by study interaction (NAA p=0.101, Cho p=0.850). Since NAA is localized to the intracellular space, these data suggest that ACC neuronal compartment is reduced as compared with POC, or that there is a lower concentration of NAA per cell in the ACC than POC, or both. Since elevated Cho suggests more cell membrane per unit volume, reduced NAA in ACC appears to be coupled with increases in overall cell membrane compartment. These findings are consistent with a number of previous studies using proton MRS which found increasing NAA and decreasing Cho moving caudally, and with post mortem anatomical studies which found neurons in more widely spaced bundles in ACC when compared to parietal and occipital cortices. MRS may be a useful tool for studying physical properties of the living human brain. PMID:21081116

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

    PubMed Central

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

    2014-01-01

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

  5. Quantitative Expression Profile of Distinct Functional Regions in the Adult Mouse Brain

    PubMed Central

    Nagano, Mamoru; Uno, Kenichiro D.; Tsujino, Kaori; Hanashima, Carina; Shigeyoshi, Yasufumi; Ueda, Hiroki R.

    2011-01-01

    The adult mammalian brain is composed of distinct regions with specialized roles including regulation of circadian clocks, feeding, sleep/awake, and seasonal rhythms. To find quantitative differences of expression among such various brain regions, we conducted the BrainStars (B*) project, in which we profiled the genome-wide expression of ∼50 small brain regions, including sensory centers, and centers for motion, time, memory, fear, and feeding. To avoid confounds from temporal differences in gene expression, we sampled each region every 4 hours for 24 hours, and pooled the samples for DNA-microarray assays. Therefore, we focused on spatial differences in gene expression. We used informatics to identify candidate genes with expression changes showing high or low expression in specific regions. We also identified candidate genes with stable expression across brain regions that can be used as new internal control genes, and ligand-receptor interactions of neurohormones and neurotransmitters. Through these analyses, we found 8,159 multi-state genes, 2,212 regional marker gene candidates for 44 small brain regions, 915 internal control gene candidates, and 23,864 inferred ligand-receptor interactions. We also found that these sets include well-known genes as well as novel candidate genes that might be related to specific functions in brain regions. We used our findings to develop an integrated database (http://brainstars.org/) for exploring genome-wide expression in the adult mouse brain, and have made this database openly accessible. These new resources will help accelerate the functional analysis of the mammalian brain and the elucidation of its regulatory network systems. PMID:21858037

  6. Normative data for subcortical regional volumes over the lifetime of the adult human brain.

    PubMed

    Potvin, Olivier; Mouiha, Abderazzak; Dieumegarde, Louis; Duchesne, Simon

    2016-08-15

    Normative data for volumetric estimates of brain structures are necessary to adequately assess brain volume alterations in individuals with suspected neurological or psychiatric conditions. Although many studies have described age and sex effects in healthy individuals for brain morphometry assessed via magnetic resonance imaging, proper normative values allowing to quantify potential brain abnormalities are needed. We developed norms for volumetric estimates of subcortical brain regions based on cross-sectional magnetic resonance scans from 2790 healthy individuals aged 18 to 94years using 23 samples provided by 21 independent research groups. The segmentation was conducted using FreeSurfer, a widely used and freely available automated segmentation software. Models predicting subcortical regional volumes of each hemisphere were produced including age, sex, estimated total intracranial volume (eTIV), scanner manufacturer, magnetic field strength, and interactions as predictors. The mean explained variance by the models was 48%. For most regions, age, sex and eTIV predicted most of the explained variance while manufacturer, magnetic field strength and interactions predicted a limited amount. Estimates of the expected volumes of an individual based on its characteristics and the scanner characteristics can be obtained using derived formulas. For a new individual, significance test for volume abnormality, effect size and estimated percentage of the normative population with a smaller volume can be obtained. Normative values were validated in independent samples of healthy adults and in adults with Alzheimer's disease and schizophrenia. PMID:27165761

  7. Light scattering properties vary across different regions of the adult mouse brain.

    PubMed

    Al-Juboori, Saif I; Dondzillo, Anna; Stubblefield, Elizabeth A; Felsen, Gidon; Lei, Tim C; Klug, Achim

    2013-01-01

    Recently developed optogenetic tools provide powerful approaches to optically excite or inhibit neural activity. In a typical in-vivo experiment, light is delivered to deep nuclei via an implanted optical fiber. Light intensity attenuates with increasing distance from the fiber tip, determining the volume of tissue in which optogenetic proteins can successfully be activated. However, whether and how this volume of effective light intensity varies as a function of brain region or wavelength has not been systematically studied. The goal of this study was to measure and compare how light scatters in different areas of the mouse brain. We delivered different wavelengths of light via optical fibers to acute slices of mouse brainstem, midbrain and forebrain tissue. We measured light intensity as a function of distance from the fiber tip, and used the data to model the spread of light in specific regions of the mouse brain. We found substantial differences in effective attenuation coefficients among different brain areas, which lead to substantial differences in light intensity demands for optogenetic experiments. The use of light of different wavelengths additionally changes how light illuminates a given brain area. We created a brain atlas of effective attenuation coefficients of the adult mouse brain, and integrated our data into an application that can be used to estimate light scattering as well as required light intensity for optogenetic manipulation within a given volume of tissue.

  8. Light Scattering Properties Vary across Different Regions of the Adult Mouse Brain

    PubMed Central

    Stubblefield, Elizabeth A.; Felsen, Gidon

    2013-01-01

    Recently developed optogenetic tools provide powerful approaches to optically excite or inhibit neural activity. In a typical in-vivo experiment, light is delivered to deep nuclei via an implanted optical fiber. Light intensity attenuates with increasing distance from the fiber tip, determining the volume of tissue in which optogenetic proteins can successfully be activated. However, whether and how this volume of effective light intensity varies as a function of brain region or wavelength has not been systematically studied. The goal of this study was to measure and compare how light scatters in different areas of the mouse brain. We delivered different wavelengths of light via optical fibers to acute slices of mouse brainstem, midbrain and forebrain tissue. We measured light intensity as a function of distance from the fiber tip, and used the data to model the spread of light in specific regions of the mouse brain. We found substantial differences in effective attenuation coefficients among different brain areas, which lead to substantial differences in light intensity demands for optogenetic experiments. The use of light of different wavelengths additionally changes how light illuminates a given brain area. We created a brain atlas of effective attenuation coefficients of the adult mouse brain, and integrated our data into an application that can be used to estimate light scattering as well as required light intensity for optogenetic manipulation within a given volume of tissue. PMID:23874433

  9. Light scattering properties vary across different regions of the adult mouse brain

    NASA Astrophysics Data System (ADS)

    Al-Juboori, Saif I.

    Recently developed optogenetic tools provide powerful approaches to optically excite or inhibit neural activity. In a typical in-vivo experiment, light is delivered to deep nuclei via an implanted optical fiber. Light intensity attenuates with increasing distance from the fiber tip, determining the volume of tissue in which optogenetic proteins can successfully be activated. However, whether and how this volume of effective light intensity varies as a function of brain region or wavelength has not been systematically studied. The goal of this study was to measure and compare how light scatters in different areas of the mouse brain. We delivered different wavelengths of light via optical fibers to acute slices of mouse brainstem, midbrain and forebrain tissue. We measured light intensity as a function of distance from the fiber tip, and used the data to model the spread of light in specific regions of the mouse brain. We found substantial differences in effective attenuation coefficients among different brain areas, which lead to substantial differences in light intensity demands for optogenetic experiments. The use of light of different wavelengths additionally changes how light illuminates a given brain area. We created a brain atlas of effective attenuation coefficients of the adult mouse brain, and integrated our data into an application that can be used to estimate light scattering as well as required light intensity for optogenetic manipulation within a given volume of tissue.

  10. Effects of alcohol consumption on cognition and regional brain volumes among older adults.

    PubMed

    Downer, Brian; Jiang, Yang; Zanjani, Faika; Fardo, David

    2015-06-01

    This study utilized data from the Framingham Heart Study Offspring Cohort to examine the relationship between midlife and late-life alcohol consumption, cognitive functioning, and regional brain volumes among older adults without dementia or a history of abusing alcohol. The results from multiple linear regression models indicate that late life, but not midlife, alcohol consumption status is associated with episodic memory and hippocampal volume. Compared to late life abstainers, moderate consumers had larger hippocampal volume, and light consumers had higher episodic memory. The differences in episodic memory according to late life alcohol consumption status were no longer significant when hippocampal volume was included in the regression model. The findings from this study provide new evidence that hippocampal volume may contribute to the observed differences in episodic memory among older adults and late life alcohol consumption status.

  11. Functional Connectivity Abnormalities of Brain Regions with Structural Deficits in Young Adult Male Smokers

    PubMed Central

    Bu, Limei; Yu, Dahua; Su, Shaoping; Ma, Yao; von Deneen, Karen M.; Luo, Lin; Zhai, Jinquan; Liu, Bo; Cheng, Jiadong; Guan, Yanyan; Li, Yangding; Bi, Yanzhi; Xue, Ting; Lu, Xiaoqi; Yuan, Kai

    2016-01-01

    Smoking is one of the most prevalent dependence disorders. Previous studies have detected structural and functional deficits in smokers. However, few studies focused on the changes of resting state functional connectivity (RSFC) of the brain regions with structural deficits in young adult smokers. Twenty-six young adult smokers and 26 well-matched healthy non-smokers participated in our study. Voxel-based morphometry (VBM) and RSFC were employed to investigate the structural and functional changes in young adult smokers. Compared with healthy non-smokers, young smokers showed increased gray matter (GM) volume in the left putamen and decreased GM volume in the left anterior cingulate cortex (ACC). Moreover, GM volume in the left ACC has a negative correlation trend with pack-years and GM volume in the left putamen was positively correlated with pack-years. The left ACC and putamen with abnormal volumes were chosen as the regions of interest (ROIs) for the RSFC analysis. We found that smokers showed increased RSFC between the left ACC and right amygdala and between the left putamen and right anterior insula. We revealed structural and functional deficits within the frontostriatal circuits in young smokers, which may shed new insights into the neural mechanisms of smoking. PMID:27757078

  12. Comparison of Regional Brain Perfusion Levels in Chronically Smoking and Non-Smoking Adults

    PubMed Central

    Durazzo, Timothy C.; Meyerhoff, Dieter J.; Murray, Donna E.

    2015-01-01

    Chronic cigarette smoking is associated with numerous abnormalities in brain neurobiology, but few studies specifically investigated the chronic effects of smoking (compared to the acute effects of smoking, nicotine administration, or nicotine withdrawal) on cerebral perfusion (i.e., blood flow). Predominately middle-aged male (47 ± 11 years of age) smokers (n = 34) and non-smokers (n = 27) were compared on regional cortical perfusion measured by continuous arterial spin labeling magnetic resonance studies at 4 Tesla. Smokers showed significantly lower perfusion than non-smokers in the bilateral medial and lateral orbitofrontal cortices, bilateral inferior parietal lobules, bilateral superior temporal gyri, left posterior cingulate, right isthmus of cingulate, and right supramarginal gyrus. Greater lifetime duration of smoking (adjusted for age) was related to lower perfusion in multiple brain regions. The results indicated smokers showed significant perfusion deficits in anterior cortical regions implicated in the development, progression, and maintenance of all addictive disorders. Smokers concurrently demonstrated reduced blood flow in posterior brain regions that show morphological and metabolic aberrations as well as elevated beta amyloid deposition demonstrated by those with early stage Alzheimer disease. The findings provide additional novel evidence of the adverse effects of cigarette smoking on the human brain. PMID:26193290

  13. Comparison of Regional Brain Perfusion Levels in Chronically Smoking and Non-Smoking Adults.

    PubMed

    Durazzo, Timothy C; Meyerhoff, Dieter J; Murray, Donna E

    2015-07-16

    Chronic cigarette smoking is associated with numerous abnormalities in brain neurobiology, but few studies specifically investigated the chronic effects of smoking (compared to the acute effects of smoking, nicotine administration, or nicotine withdrawal) on cerebral perfusion (i.e., blood flow). Predominately middle-aged male (47 ± 11 years of age) smokers (n = 34) and non-smokers (n = 27) were compared on regional cortical perfusion measured by continuous arterial spin labeling magnetic resonance studies at 4 Tesla. Smokers showed significantly lower perfusion than non-smokers in the bilateral medial and lateral orbitofrontal cortices, bilateral inferior parietal lobules, bilateral superior temporal gyri, left posterior cingulate, right isthmus of cingulate, and right supramarginal gyrus. Greater lifetime duration of smoking (adjusted for age) was related to lower perfusion in multiple brain regions. The results indicated smokers showed significant perfusion deficits in anterior cortical regions implicated in the development, progression, and maintenance of all addictive disorders. Smokers concurrently demonstrated reduced blood flow in posterior brain regions that show morphological and metabolic aberrations as well as elevated beta amyloid deposition demonstrated by those with early stage Alzheimer disease. The findings provide additional novel evidence of the adverse effects of cigarette smoking on the human brain.

  14. Regionally distinct responses of microglia and glial progenitor cells to whole brain irradiation in adult and aging rats.

    PubMed

    Hua, Kun; Schindler, Matthew K; McQuail, Joseph A; Forbes, M Elizabeth; Riddle, David R

    2012-01-01

    Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of proliferating cells but also occurs in adults and older individuals and in non-proliferative cell populations. To better understand radiation-induced normal tissue injury and how it may be affected by aging, we exposed young adult, middle-aged, and old rats to 10 Gy of whole brain irradiation and assessed in gray- and white matter the responses of microglia, the primary cellular mediators of radiation-induced neuroinflammation, and oligodendrocyte precursor cells, the largest population of proliferating cells in the adult brain. We found that aging and/or irradiation caused only a few microglia to transition to the classically "activated" phenotype, e.g., enlarged cell body, few processes, and markers of phagocytosis, that is seen following more damaging neural insults. Microglial changes in response to aging and irradiation were relatively modest and three markers of reactivity - morphology, proliferation, and expression of the lysosomal marker CD68- were regulated largely independently within individual cells. Proliferation of oligodendrocyte precursors did not appear to be altered during normal aging but increased following irradiation. The impacts of irradiation and aging on both microglia and oligodendrocyte precursors were heterogeneous between white- and gray matter and among regions of gray matter, indicating that there are regional regulators of the neural response to brain irradiation. By several measures, the CA3 region of the hippocampus appeared to be differentially sensitive to effects of aging and irradiation. The changes assessed here likely contribute to injury following inflammatory challenges like brain irradiation and

  15. Effect of adult onset hypothyroidism on behavioral parameters and acetylcholinesterase isoforms activity in specific brain regions of male mice.

    PubMed

    Vasilopoulou, Catherine G; Constantinou, Caterina; Giannakopoulou, Dimitra; Giompres, Panagiotis; Margarity, Marigoula

    2016-10-01

    Thyroid hormones (TH) are essential for normal development and function of mammalian central nervous system (CNS); TH dysregulation has been implicated in several cognitive and behavioral deficits related to dysfunctions of neurotransmitter systems. In the present study, we investigated the effects of adult onset hypothyroidism on the activity of acetylcholinesterase (AChE) and on related behavioral parameters. For this purpose we used adult male Balb/cJ mice that were divided randomly into euthyroid and hypothyroid animal groups. Animals were rendered hypothyroid through administration of 1% w/v KClO4 in their drinking water for 8weeks. At the end of the treatment, learning/memory procedures were examined through step-through passive avoidance task while fear/anxiety was assessed using elevated plus-maze (EPM) and open-field (OF) tests. AChE activity was determined colorimetrically in two different fractions, salt-soluble fraction (SS) (containing mainly the G1 isoform) and detergent-soluble fraction (DS) (containing mainly the G4 isoform) in cerebral cortex, cerebellum, midbrain, hippocampus and striatum. Our results indicate that adult onset hypothyroidism caused significant memory impairment and increased fear/anxiety. Moreover, the activity of both isoforms of AChE was reduced in all brain regions examined in a brain region- and isoform-specific manner. PMID:27317840

  16. Effect of adult onset hypothyroidism on behavioral parameters and acetylcholinesterase isoforms activity in specific brain regions of male mice.

    PubMed

    Vasilopoulou, Catherine G; Constantinou, Caterina; Giannakopoulou, Dimitra; Giompres, Panagiotis; Margarity, Marigoula

    2016-10-01

    Thyroid hormones (TH) are essential for normal development and function of mammalian central nervous system (CNS); TH dysregulation has been implicated in several cognitive and behavioral deficits related to dysfunctions of neurotransmitter systems. In the present study, we investigated the effects of adult onset hypothyroidism on the activity of acetylcholinesterase (AChE) and on related behavioral parameters. For this purpose we used adult male Balb/cJ mice that were divided randomly into euthyroid and hypothyroid animal groups. Animals were rendered hypothyroid through administration of 1% w/v KClO4 in their drinking water for 8weeks. At the end of the treatment, learning/memory procedures were examined through step-through passive avoidance task while fear/anxiety was assessed using elevated plus-maze (EPM) and open-field (OF) tests. AChE activity was determined colorimetrically in two different fractions, salt-soluble fraction (SS) (containing mainly the G1 isoform) and detergent-soluble fraction (DS) (containing mainly the G4 isoform) in cerebral cortex, cerebellum, midbrain, hippocampus and striatum. Our results indicate that adult onset hypothyroidism caused significant memory impairment and increased fear/anxiety. Moreover, the activity of both isoforms of AChE was reduced in all brain regions examined in a brain region- and isoform-specific manner.

  17. Brain and Spinal Cord Tumors in Adults

    MedlinePlus

    ... saved articles window. My Saved Articles » My ACS » Brain and Spinal Cord Tumors in Adults Download Printable ... the topics below to get started. What Is Brain/CNS Tumors In Adults? What are adult brain ...

  18. Measuring the effects of aging and sex on regional brain stiffness with MR elastography in healthy older adults

    PubMed Central

    Arani, Arvin; Murphy, Matthew C; Glaser, Kevin J; Manduca, Armando; Lake, David S; Kruse, Scott; Jack, Clifford R; Ehman, Richard; Huston, John

    2015-01-01

    Changes in tissue composition and cellular architecture have been associated with neurological disease, and these in turn can affect biomechanical properties. Natural biological factors such as aging and an individual’s sex also affect underlying tissue biomechanics in different brain regions. Understanding the normal changes is necessary before determining the efficacy of stiffness imaging for neurological disease diagnosis and therapy monitoring. The objective of this study was to evaluate global and regional changes in brain stiffness as a function of age and sex, using improved MRE acquisition and processing that has been shown to provide median stiffness values that are typically reproducible to within 1% in global measurements and within 2% for regional measurements. Furthermore, this is the first study to report the effects of age and sex over the entire cerebrum volume and over the full frontal, occipital, parietal, temporal, deep gray matter/white matter (insula, deep gray nuclei and white matter tracts), and cerebellum volumes. In 45 volunteers, we observed a significant linear correlation between age and brain stiffness in the cerebrum (P<.0001), frontal lobes (P<.0001), occipital lobes (P=.0005), parietal lobes (P=.0002), and the temporal lobes (P<.0001) of the brain. No significant linear correlation between brain stiffness and age was observed in the cerebellum (P=.74), and the sensory-motor regions (P=.32) of the brain, and a weak linear trend was observed in the deep gray matter/white matter (P=.075). A multiple linear regression model predicted an annual decline of 0.011±0.002 kPa in cerebrum stiffness with a theoretical median age value (76 years old) of 2.56±0.08 kPa. Sexual dimorphism was observed in the temporal (P=.03) and occipital (P=.001) lobes of the brain, but no significant difference was observed in any of the other brain regions (P>.20 for all other regions). The model predicted female occipital and temporal lobes to be 0.23 k

  19. Measuring the effects of aging and sex on regional brain stiffness with MR elastography in healthy older adults.

    PubMed

    Arani, Arvin; Murphy, Matthew C; Glaser, Kevin J; Manduca, Armando; Lake, David S; Kruse, Scott A; Jack, Clifford R; Ehman, Richard L; Huston, John

    2015-05-01

    Changes in tissue composition and cellular architecture have been associated with neurological disease, and these in turn can affect biomechanical properties. Natural biological factors such as aging and an individual's sex also affect underlying tissue biomechanics in different brain regions. Understanding the normal changes is necessary before determining the efficacy of stiffness imaging for neurological disease diagnosis and therapy monitoring. The objective of this study was to evaluate global and regional changes in brain stiffness as a function of age and sex, using improved MRE acquisition and processing that have been shown to provide median stiffness values that are typically reproducible to within 1% in global measurements and within 2% for regional measurements. Furthermore, this is the first study to report the effects of age and sex over the entire cerebrum volume and over the full frontal, occipital, parietal, temporal, deep gray matter/white matter (insula, deep gray nuclei and white matter tracts), and cerebellum volumes. In 45 volunteers, we observed a significant linear correlation between age and brain stiffness in the cerebrum (P<.0001), frontal lobes (P<.0001), occipital lobes (P=.0005), parietal lobes (P=.0002), and the temporal lobes (P<.0001) of the brain. No significant linear correlation between brain stiffness and age was observed in the cerebellum (P=.74), and the sensory-motor regions (P=.32) of the brain, and a weak linear trend was observed in the deep gray matter/white matter (P=.075). A multiple linear regression model predicted an annual decline of 0.011 ± 0.002 kPa in cerebrum stiffness with a theoretical median age value (76 years old) of 2.56 ± 0.08 kPa. Sexual dimorphism was observed in the temporal (P=.03) and occipital (P=.001) lobes of the brain, but no significant difference was observed in any of the other brain regions (P>.20 for all other regions). The model predicted female occipital and temporal lobes to be 0.23 k

  20. Brain tumor - primary - adults

    MedlinePlus

    ... tumor, relieve symptoms, and improve brain function or comfort. Surgery is often needed for most primary brain ... and pressure Anticonvulsants to reduce seizures Pain medicines Comfort measures, safety measures, physical therapy, and occupational therapy ...

  1. Flow of glucose carbon into cholesterol and phospholipids in various regions of the adult rat brain: enhanced incorporation into hypothalamic phospholipids

    SciTech Connect

    Barkai, A.I.

    1981-01-01

    The contribution of glucose carbon to the biosynthesis of cholesterol and phospholipids in distinct brain regions was studied quantitatively in the adult male rat. Rates of flow of glucose carbon into the lipids in vivo were calculated from two measurements: the curve representing the decrease in plasma /sup 14/C-glucose with time and the specific activity of the cerebral lipid 180 minutes after a rapid intravenous injection of a tracer dose of D-U /sup 14/C-glucose. The following brain regions were studied: cerebral cortex, hypothalamus, medulla, and corpus callosum and cerebellum. The values for carbon flow into phospholipids were significantly higher in the hypothalamus than in the whole brain, whereas small, but insignificant, regional differences were found for carbon flow into cholesterol. The conversion of U-/sup 14/C-glucose to individual phospholipids of both hypothalamus and cerebral cortex was further investigated in vitro in order to establish whether the higher rate of carbon flow into hypothalamic phospholipids resulted from enhanced synthesis of a particular phospholipid. In agreement with the results obtained in vivo, the rate of incorporation of /sup 14/C into total phospholipids was 60% higher in hypothalamic tissue. The results indicate that the higher rate of carbon flow into hypothalamic phospholipids might be attributed to enhanced incorporation of glucose carbon to phosphatidyl-choline and phosphatidyl-ethanolamine following a faster conversion of glucose to glycerol in this brain region.

  2. Feeling Present in Arousing Virtual Reality Worlds: Prefrontal Brain Regions Differentially Orchestrate Presence Experience in Adults and Children

    PubMed Central

    Baumgartner, Thomas; Speck, Dominique; Wettstein, Denise; Masnari, Ornella; Beeli, Gian; Jäncke, Lutz

    2008-01-01

    Virtual reality (VR) is a powerful tool for simulating aspects of the real world. The success of VR is thought to depend on its ability to evoke a sense of “being there”, that is, the feeling of “Presence”. In view of the rapid progress in the development of increasingly more sophisticated virtual environments (VE), the importance of understanding the neural underpinnings of presence is growing. To date however, the neural correlates of this phenomenon have received very scant attention. An fMRI-based study with 52 adults and 25 children was therefore conducted using a highly immersive VE. The experience of presence in adult subjects was found to be modulated by two major strategies involving two homologous prefrontal brain structures. Whereas the right DLPFC controlled the sense of presence by down-regulating the activation in the egocentric dorsal visual processing stream, the left DLPFC up-regulated widespread areas of the medial prefrontal cortex known to be involved in self-reflective and stimulus-independent thoughts. In contrast, there was no evidence of these two strategies in children. In fact, anatomical analyses showed that these two prefrontal areas have not yet reached full maturity in children. Taken together, this study presents the first findings that show activation of a highly specific neural network orchestrating the experience of presence in adult subjects, and that the absence of activity in this neural network might contribute to the generally increased susceptibility of children for the experience of presence in VEs. PMID:18958209

  3. Toluene effects on oxidative stress in brain regions of young-adult, middle-age, and senescent Brown Norway rats

    SciTech Connect

    Kodavanti, Prasada Rao S.; Royland, Joyce E.; Richards, Judy E.; Besas, Jonathan; MacPhail, Robert C.

    2011-11-15

    The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound, toluene. The objective was to test whether oxidative stress (OS) plays a role in the adverse effects caused by toluene exposure, and if so, if effects are age-dependent. OS parameters were selected to measure the production of reactive oxygen species (NADPH Quinone oxidoreductase 1 (NQO1), NADH Ubiquinone reductase (UBIQ-RD)), antioxidant homeostasis (total antioxidant substances (TAS), superoxide dismutase (SOD), {gamma}-glutamylcysteine synthetase ({gamma}-GCS), glutathione transferase (GST), glutathione peroxidase (GPX), glutathione reductase (GRD)), and oxidative damage (total aconitase and protein carbonyls). In this study, Brown Norway rats (4, 12, and 24 months) were dosed orally with toluene (0, 0.65 or 1 g/kg) in corn oil. Four hours later, frontal cortex, cerebellum, striatum, and hippocampus were dissected, quick frozen on dry ice, and stored at - 80 Degree-Sign C until analysis. Some parameters of OS were found to increase with age in select brain regions. Toluene exposure also resulted in increased OS in select brain regions. For example, an increase in NQO1 activity was seen in frontal cortex and cerebellum of 4 and 12 month old rats following toluene exposure, but only in the hippocampus of 24 month old rats. Similarly, age and toluene effects on glutathione enzymes were varied and brain-region specific. Markers of oxidative damage reflected changes in oxidative stress. Total aconitase activity was increased by toluene in frontal cortex and cerebellum at 12 and 24 months, respectively. Protein carbonyls in both brain regions and in all age groups were increased by toluene, but step-down analyses indicated toluene effects were statistically significant only in 12 month old rats. These results indicate changes in OS parameters with age and toluene exposure

  4. Expression profiling of synaptic microRNAs from the adult rat brain identifies regional differences and seizure-induced dynamic modulation

    PubMed Central

    Pichardo-Casas, Israel; Goff, Loyal A; Swerdel, Mavis R; Athie, Alejandro; Davila, Jonathan; Ramos-Brossier, Mariana; Lapid-Volosin, Martha; Friedman, Wilma J; Hart, Ronald P; Vaca, Luis

    2015-01-01

    In recent years, microRNAs or miRNAs have been proposed to target neuronal mRNAs localized near the synapse, exerting a pivotal role in modulating local protein synthesis, and presumably affecting adaptive mechanisms such as synaptic plasticity. In the present study we have characterized the distribution of miRNAs in five regions of the adult mammalian brain and compared the relative abundance between total fractions and purified synaptoneurosomes (SN), using three different methodologies. The results show selective enrichment or depletion of some miRNAs when comparing total versus SN fractions. These miRNAs were different for each brain region explored. Changes in distribution could not be attributed to simple diffusion or to a targeting sequence inside the miRNAs. In silico analysis suggest that the differences in distribution may be related to the preferential concentration of synaptically localized mRNA targeted by the miRNAs. These results favor a model of co-transport of the miRNA-mRNA complex to the synapse, although further studies are required to validate this hypothesis. Using an in vivo model for increasing excitatory activity in the cortex and the hippocampus indicates that the distribution of some miRNAs can be modulated by enhanced neuronal (epileptogenic) activity. All these results demonstrate the dynamic modulation in the local distribution of miRNAs from the adult brain, which may play key roles in controlling localized protein synthesis at the synapse. PMID:22197703

  5. A brain-specific gene cluster isolated from the region of the mouse obesity locus is expressed in the adult hypothalamus and during mouse development

    SciTech Connect

    Laig-Webster, M.; Lim, M.E.; Chehab, F.F.

    1994-09-01

    The molecular defect underlying an autosomal recessive form of genetic obesity in a classical mouse model C57 BL/6J-ob/ob has not yet been elucidated. Whereas metabolic and physiological disturbances such as diabetes and hypertension are associated with obesity, the site of expression and the nature of the primary lesion responsible for this cascade of events remains elusive. Our efforts aimed at the positional cloning of the ob gene by YAC contig mapping and gene identification have resulted in the cloning of a brain-specific gene cluster from the ob critical region. The expression of this gene cluster is remarkably complex owing to the multitude of brain-specific mRNA transcripts detected on Northern blots. cDNA cloning of these transcripts suggests that they are expressed from different genes as well as by alternate splicing mechanisms. Furthermore, the genomic organization of the cluster appears to consist of at least two identical promoters displaying CpG islands characteristic of housekeeping genes, yet clearly involving tissue-specific expression. Sense and anti-sense synthetic RNA probes were derived from a common DNA sequence on 3 cDNA clones and hybridized to 8-16 days mouse embryonic stages and mouse adult brain sections. Expression in development was noticeable as of the 11th day of gestation and confined to the central nervous system mainly in the telencephalon and spinal cord. Coronal and sagittal sections of the adult mouse brain showed expression only in 3 different regions of the brain stem. In situ hybridization to mouse hypothalamus sections revealed the presence of a localized and specialized group of cells expressing high levels of mRNA, suggesting that this gene cluster may also be involved in the regulation of hypothalamic activities. The hypothalamus has long been hypothesized as a primary candidate tissue for the expression of the obesity gene mainly because of its well-established role in the regulation of energy metabolism and food intake.

  6. Thinking about Seeing: perceptual sources of knowledge are encoded in the theory of mind brain regions of sighted and blind adults

    PubMed Central

    Koster-Hale, Jorie; Bedny, Marina; Saxe, Rebecca

    2014-01-01

    Blind people's inferences about how other people see provide a window into fundamental questions about the human capacity to think about one another's thoughts. By working with blind individuals, we can ask both what kinds of representations people form about others’ minds, and how much these representations depend on the observer having had similar mental states themselves. Thinking about others’ mental states depends on a specific group of brain regions, including the right temporo-parietal junction (RTPJ). We investigated the representations of others’ mental states in these brain regions, using multivoxel pattern analyses (MVPA). We found that, first, in the RTPJ of sighted adults, the pattern of neural response distinguished the source of the mental state (did the protagonist see or hear something?) but not the valence (did the protagonist feel good or bad?). Second, these neural representations were preserved in congenitally blind adults. These results suggest that the temporo-parietal junction contains explicit, abstract representations of features of others’ mental states, including the perceptual source. The persistence of these representations in congenitally blind adults, who have no first-person experience with sight, provides evidence that these representations emerge even in the absence of first-person perceptual experiences. PMID:24960530

  7. Thinking about seeing: perceptual sources of knowledge are encoded in the theory of mind brain regions of sighted and blind adults.

    PubMed

    Koster-Hale, Jorie; Bedny, Marina; Saxe, Rebecca

    2014-10-01

    Blind people's inferences about how other people see provide a window into fundamental questions about the human capacity to think about one another's thoughts. By working with blind individuals, we can ask both what kinds of representations people form about others' minds, and how much these representations depend on the observer having had similar mental states themselves. Thinking about others' mental states depends on a specific group of brain regions, including the right temporo-parietal junction (RTPJ). We investigated the representations of others' mental states in these brain regions, using multivoxel pattern analyses (MVPA). We found that, first, in the RTPJ of sighted adults, the pattern of neural response distinguished the source of the mental state (did the protagonist see or hear something?) but not the valence (did the protagonist feel good or bad?). Second, these neural representations were preserved in congenitally blind adults. These results suggest that the temporo-parietal junction contains explicit, abstract representations of features of others' mental states, including the perceptual source. The persistence of these representations in congenitally blind adults, who have no first-person experience with sight, provides evidence that these representations emerge even in the absence of relevant first-person perceptual experiences.

  8. Short-term erythrosine B-induced inhibition of the brain regional serotonergic activity suppresses motor activity (exploratory behavior) of young adult mammals.

    PubMed

    Dalal, Arindam; Poddar, Mrinal K

    2009-06-01

    Previous studies showed that repeated ingestion of erythrosine B (artificial food color) developed behavioral hyperactivity, but nothing is known about its single administration effect as well as the neurochemical (s) involvement. The present study provides evidence that a single higher dosage (10, 100 or 200 mg/kg, p.o.) of erythrosine administration to young adult male rats reduced motor activity (MA) maximally at 2 h and brain regional (medulla-pons, hippocampus and hypothalamus) serotonergic activity (measuring steady-state levels of 5-HT and 5-HIAA, pargyline-induced 5-HT accumulation and 5-HIAA declination rate and 5-HT receptor binding) under similar experimental condition. The degree of erythrosine-induced inhibition of both MA and brain regional serotonergic activity was dosage dependent. Lower dosage (1 mg/kg, p.o.) did not affect either of the above. Erythrosine (100 or 200 mg/kg, p.o.)-induced MA suppression was also observed in the presence of specific MAO-A inhibitor, clorgyline (5 mg/kg, i.p.) or MAO-B inhibitor, deprenyl (5 mg/kg, i.p.); but their co-application (5 mg/kg, i.p., each) effectively prevented the erythrosine-induced motor suppression. Altogether these results suggest that a single higher dosage of erythrosine (10-200 mg/kg, p.o.) may reduce MA by reducing serotonergic activity with modulation of central dopaminergic activity depending on the brain regions.

  9. Stem Cell-Mediated Regeneration of the Adult Brain

    PubMed Central

    Jessberger, Sebastian

    2016-01-01

    Acute or chronic injury of the adult mammalian brain is often associated with persistent functional deficits as its potential for regeneration and capacity to rebuild lost neural structures is limited. However, the discovery that neural stem cells (NSCs) persist throughout life in discrete regions of the brain, novel approaches to induce the formation of neuronal and glial cells, and recently developed strategies to generate tissue for exogenous cell replacement strategies opened novel perspectives how to regenerate the adult brain. Here, we will review recently developed approaches for brain repair and discuss future perspectives that may eventually allow for developing novel treatment strategies in acute and chronic brain injury. PMID:27781019

  10. Extracellular proteolysis in the adult murine brain.

    PubMed

    Sappino, A P; Madani, R; Huarte, J; Belin, D; Kiss, J Z; Wohlwend, A; Vassalli, J D

    1993-08-01

    Plasminogen activators are important mediators of extracellular metabolism. In the nervous system, plasminogen activators are thought to be involved in the remodeling events required for cell migration during development and regeneration. We have now explored the expression of the plasminogen activator/plasmin system in the adult murine central nervous system. Tissue-type plasminogen activator is synthesized by neurons of most brain regions, while prominent tissue-type plasminogen activator-catalyzed proteolysis is restricted to discrete areas, in particular within the hippocampus and hypothalamus. Our observations indicate that tissue-type plasminogen activator-catalyzed proteolysis in neural tissues is not limited to ontogeny, but may also contribute to adult central nervous system physiology, for instance by influencing neuronal plasticity and synaptic reorganization. The identification of an extracellular proteolytic system active in the adult central nervous system may also help gain insights into the pathogeny of neurodegenerative disorders associated with extracellular protein deposition.

  11. Toluene effects on Oxidative Stress in Brain regions of Young-adult, Middleage,and Senescent Brown Norway Rats

    EPA Science Inventory

    The influence of aging on susceptibility to environmental contaminants is not well understood. To extend knowledge in this area, we examined effects in rat brain of the volatile organic compound toluene. The objective was to test whether oxidative stress plays a role in the adver...

  12. Adult Education Regional Planning

    ERIC Educational Resources Information Center

    California Community Colleges, Chancellor's Office, 2015

    2015-01-01

    For more than one hundred and fifty years, until 2008, California was an undisputed national leader in its commitment to adult education. The state's investment in adult learners topped $750 million, a sum greater than the combined total of every other state in the nation. However, for the past several years recession and fiscal crisis have left…

  13. Dendritic development of newly generated neurons in the adult brain.

    PubMed

    Ribak, Charles E; Shapiro, Lee A

    2007-10-01

    Ramon y Cajal described the fundamental morphology of the dendritic and axonal growth cones of neurons during development. However, technical limitations at the time prevented him from describing such growth cones from newborn neurons in the adult brain. The phenomenon of adult neurogenesis is briefly reviewed, and the structural description of dendritic and axonal outgrowth for these newly generated neurons in the adult brain is discussed. Axonal outgrowth into the hilus and CA3 region of the hippocampus occurs later than the outgrowth of dendrites into the molecular layer, and the ultrastructural analysis of axonal outgrowth has yet to be completed. In contrast, growth cones on dendrites from newborn neurons in the adult dentate gyrus have been described and this observation suggests that dendrites in adult brains grow in a similar way to those found in immature brains. However, dendrites in adult brains have to navigate through a denser neuropil and a more complex cell layer. Therefore, some aspects of dendritic outgrowth of neurons born in the adult dentate gyrus are different as compared to that found in development. These differences include the radial process of radial glial cells acting as a lattice to guide apical dendritic growth through the granule cell layer and a much thinner dendrite to grow through the neuropil of the molecular layer. Therefore, similarities and differences exist for dendritic outgrowth from newborn neurons in the developing and adult brain.

  14. Regional Myelin and Axon Damage and Neuroinflammation in the Adult Mouse Brain After Long-Term Postnatal Vanadium Exposure.

    PubMed

    Azeez, Idris A; Olopade, Funmilayo; Laperchia, Claudia; Andrioli, Anna; Scambi, Ilaria; Onwuka, Silas K; Bentivoglio, Marina; Olopade, James O

    2016-09-01

    Environmental exposure to vanadium occurs in areas of persistent burning of fossil fuels; this metal is known to induce oxidative stress and oligodendrocyte damage. Here, we determined whether vanadium exposure (3 mg/kg) in mice during the first 3 postnatal months leads to a sustained neuroinflammatory response. Body weight monitoring, and muscle strength and open field tests showed reduction of body weight gain and locomotor impairment in vanadium-exposed mice. Myelin histochemistry and immunohistochemistry for astrocytes, microglia, and nonphosphorylated neurofilaments revealed striking regional heterogeneity. Myelin damage involved the midline corpus callosum and fibers in cortical gray matter, hippocampus, and diencephalon that were associated with axonal damage. Astrocyte and microglial activation was identified in the same regions and in the internal capsule; however, no overt myelin and axon damage was observed in the latter. Double immunofluorescence revealed induction of high tumor necrosis factor (TNF) immunoreactivity in reactive astrocytes. Western blotting analysis showed significant induction of TNF and interleukin-1β expression. Together these findings show that chronic postnatal vanadium exposure leads to functional deficit and region-dependent myelin damage that does not spare axons. This injury is associated with glial cell activation and proinflammatory cytokine induction, which may reflect both neurotoxic and neuroprotective responses. PMID:27390101

  15. Adult mouse brain gene expression patterns bear an embryologic imprint.

    PubMed

    Zapala, Matthew A; Hovatta, Iiris; Ellison, Julie A; Wodicka, Lisa; Del Rio, Jo A; Tennant, Richard; Tynan, Wendy; Broide, Ron S; Helton, Rob; Stoveken, Barbara S; Winrow, Christopher; Lockhart, Daniel J; Reilly, John F; Young, Warren G; Bloom, Floyd E; Lockhart, David J; Barlow, Carrolee

    2005-07-19

    The current model to explain the organization of the mammalian nervous system is based on studies of anatomy, embryology, and evolution. To further investigate the molecular organization of the adult mammalian brain, we have built a gene expression-based brain map. We measured gene expression patterns for 24 neural tissues covering the mouse central nervous system and found, surprisingly, that the adult brain bears a transcriptional "imprint" consistent with both embryological origins and classic evolutionary relationships. Embryonic cellular position along the anterior-posterior axis of the neural tube was shown to be closely associated with, and possibly a determinant of, the gene expression patterns in adult structures. We also observed a significant number of embryonic patterning and homeobox genes with region-specific expression in the adult nervous system. The relationships between global expression patterns for different anatomical regions and the nature of the observed region-specific genes suggest that the adult brain retains a degree of overall gene expression established during embryogenesis that is important for regional specificity and the functional relationships between regions in the adult. The complete collection of extensively annotated gene expression data along with data mining and visualization tools have been made available on a publicly accessible web site (www.barlow-lockhart-brainmapnimhgrant.org).

  16. [Generation of new nerve cells in the adult human brain].

    PubMed

    Poulsen, Frantz Rom; Meyer, Morten; Rasmussen, Jens Zimmer

    2003-03-31

    Generation of new nerve cells (neurogenesis) is normally considered to be limited to the fetal and early postnatal period. Thus, damaged nerve cells are not expected to be replaced by generation of new cells. The brain is, however, more plastic than previously assumed. This also includes neurogenesis in the adult human brain. In particular two brain regions show continuous division of neural stem and progenitor cells generating neurons and glial cells, namely the subgranular zone of the dentate gyrus and the subventricular zones of the lateral ventricles. From the latter region newly generated neuroblasts (immature nerve cells) migrate toward the olfactory bulb where they differentiate into neurons. In the dentate gyrus the newly generated neurons become functionally integrated in the granule cell layer, where they are believed to be of importance to learning and memory. It is at present not known whether neurogenesis in the adult human brain can be manipulated for specific repair after brain damage.

  17. Coexpression networks identify brain region-specific enhancer RNAs in the human brain.

    PubMed

    Yao, Pu; Lin, Peijie; Gokoolparsadh, Akira; Assareh, Amelia; Thang, Mike W C; Voineagu, Irina

    2015-08-01

    Despite major progress in identifying enhancer regions on a genome-wide scale, the majority of available data are limited to model organisms and human transformed cell lines. We have identified a robust set of enhancer RNAs (eRNAs) expressed in the human brain and constructed networks assessing eRNA-gene coexpression interactions across human fetal brain and multiple adult brain regions. Our data identify brain region-specific eRNAs and show that enhancer regions expressing eRNAs are enriched for genetic variants associated with autism spectrum disorders.

  18. On Expression Patterns and Developmental Origin of Human Brain Regions

    PubMed Central

    Kirsch, Lior; Chechik, Gal

    2016-01-01

    Anatomical substructures of the human brain have characteristic cell-types, connectivity and local circuitry, which are reflected in area-specific transcriptome signatures, but the principles governing area-specific transcription and their relation to brain development are still being studied. In adult rodents, areal transcriptome patterns agree with the embryonic origin of brain regions, but the processes and genes that preserve an embryonic signature in regional expression profiles were not quantified. Furthermore, it is not clear how embryonic-origin signatures of adult-brain expression interplay with changes in expression patterns during development. Here we first quantify which genes have regional expression-patterns related to the developmental origin of brain regions, using genome-wide mRNA expression from post-mortem adult human brains. We find that almost all human genes (92%) exhibit an expression pattern that agrees with developmental brain-region ontology, but that this agreement changes at multiple phases during development. Agreement is particularly strong in neuron-specific genes, but also in genes that are not spatially correlated with neuron-specific or glia-specific markers. Surprisingly, agreement is also stronger in early-evolved genes. We further find that pairs of similar genes having high agreement to developmental region ontology tend to be more strongly correlated or anti-correlated, and that the strength of spatial correlation changes more strongly in gene pairs with stronger embryonic signatures. These results suggest that transcription regulation of most genes in the adult human brain is spatially tuned in a way that changes through life, but in agreement with development-determined brain regions. PMID:27564987

  19. Relationships between Gene Expression and Brain Wiring in the Adult Rodent Brain

    PubMed Central

    French, Leon; Pavlidis, Paul

    2011-01-01

    We studied the global relationship between gene expression and neuroanatomical connectivity in the adult rodent brain. We utilized a large data set of the rat brain “connectome” from the Brain Architecture Management System (942 brain regions and over 5000 connections) and used statistical approaches to relate the data to the gene expression signatures of 17,530 genes in 142 anatomical regions from the Allen Brain Atlas. Our analysis shows that adult gene expression signatures have a statistically significant relationship to connectivity. In particular, brain regions that have similar expression profiles tend to have similar connectivity profiles, and this effect is not entirely attributable to spatial correlations. In addition, brain regions which are connected have more similar expression patterns. Using a simple optimization approach, we identified a set of genes most correlated with neuroanatomical connectivity, and find that this set is enriched for genes involved in neuronal development and axon guidance. A number of the genes have been implicated in neurodevelopmental disorders such as autistic spectrum disorder. Our results have the potential to shed light on the role of gene expression patterns in influencing neuronal activity and connectivity, with potential applications to our understanding of brain disorders. Supplementary data are available at http://www.chibi.ubc.ca/ABAMS. PMID:21253556

  20. A brain sexual dimorphism controlled by adult circulating androgens.

    PubMed

    Cooke, B M; Tabibnia, G; Breedlove, S M

    1999-06-22

    Reports of structural differences between the brains of men and women, heterosexual and homosexual men, and male-to-female transsexuals and other men have been offered as evidence that the behavioral differences between these groups are likely caused by differences in the early development of the brain. However, a possible confounding variable is the concentration of circulating hormones seen in these groups in adulthood. Evaluation of this possibility hinges on the extent to which circulating hormones can alter the size of mammalian brain regions as revealed by Nissl stains. We now report a sexual dimorphism in the volume of a brain nucleus in rats that can be completely accounted for by adult sex differences in circulating androgen. The posterodorsal nucleus of the medial amygdala (MePD) has a greater volume in male rats than in females, but adult castration of males causes the volume to shrink to female values within four weeks, whereas androgen treatment of adult females for that period enlarges the MePD to levels equivalent to normal males. This report demonstrates that adult hormone manipulations can completely reverse a sexual dimorphism in brain regional volume in a mammalian species. The sex difference and androgen responsiveness of MePD volume is reflected in the soma size of neurons there. PMID:10377450

  1. Abnormal brain structure in adults with Van der Woude syndrome.

    PubMed

    Nopoulos, P; Richman, L; Andreasen, N C; Murray, J C; Schutte, B

    2007-06-01

    Van der Woude syndrome (VWS) is an autosomal dominant disorder manifested in cleft lip and/or palate and lip pits. Isolated clefts of the lip and/or palate (ICLP) have both genotype and phenotype overlap with VWS. Subjects with ICLP have abnormalities in brain structure and function. Given the similarities between VWS and ICLP, the current study was designed to evaluate the pattern of brain structure of adults with VWS. Fourteen adults with VWS were compared to age- and gender-matched healthy controls. Brain structure was evaluated using magnetic resonance imaging. All subjects with VWS had enlarged volumes of the anterior regions of the cerebrum. Men with VWS had reduced volumes of the posterior cerebrum. Anterior cerebrum volume was negatively correlated with intelligent quotient in the subjects with VWS indicating that the enlargement of this brain region was 'pathologic.' The pattern of brain structure in VWS is nearly identical to those seen in ICLP. In addition, men are affected more severely. Pathologic enlargement of the tissue and a gender effect with men affected more severely are common features of neurodevelopmental disorders supporting the notion that the brain structure of VWS and ICLP may be because of abnormal brain development. PMID:17539900

  2. Involvement of high plasma corticosterone status and activation of brain regional serotonin metabolism in long-term erythrosine-induced rearing motor hyper activity in young adult male rats.

    PubMed

    Dalal, Arindam; Poddar, Mrinal K

    2010-07-01

    Long-term consumption of artificial food color(s) can induce behavioral hyperactivity in human and experimental animals, but no neurobiochemical mechanism is defined. This study investigates the role of brain regional serotonin metabolism including its turnover, MAO-A activity, and plasma corticosterone status in relation to behavioral disturbances due to an artificial food color, erythrosine. Long-term (15 or 30 consecutive days) erythrosine administration with higher dosage (10 or 100 mg/kg/day, p.o.) produced optimal hyperactive state in exploratory behavior (rearing motor activity) after 2 h of last erythrosine administration, in young adult male albino rats. Erythrosine-induced stimulation in brain regional (medulla-pons, hypothalamus, hippocampus, and corpus striatum) serotonin metabolism (measuring steady state levels of 5-HT and 5-HIAA, MAO-A activity), including its turnover (pargyline-induced 5-HT accumulation and 5-HIAA declination rate), as well as plasma corticosterone were also observed depending on dosage(s) and duration(s) of erythrosine administration under similar experimental conditions. The lower dosage of erythrosine (1 mg/kg/day, p.o.) under similar conditions did not affect either of the above. These findings suggests (a) the induction as well as optimal effect of long-term erythrosine (artificial food color) on behavioral hyperactivity in parallel with increase in 5-HT level in brain regions, (b) the activation of brain regional serotonin biosynthesis in accordance with plasma corticosterone status under such behavioral hyperactivity, and (c) a possible inhibitory influence of the enhanced glucocorticoids-serotonin interaction on erythrosine-induced rearing motor hyperactivity in young adult mammals.

  3. Treatment of primary brain tumours in adults.

    PubMed

    McNamara, Shanne

    This article considers the complexities of caring for patients with primary brain tumours. The incidence, classification and clinical signs and symptoms are outlined. Adult patients experience disabling effects as a result of a brain tumour, which is often accompanied by high morbidity and mortality rates. The various treatment options available are summarised. However, for many patients, there are limited curative treatment options and the main focus is palliative care. The nurse's contribution to care and support of these patients and their families is discussed, with the aim of improving their quality of life.

  4. Histomorphological Phenotyping of the Adult Mouse Brain.

    PubMed

    Mikhaleva, Anna; Kannan, Meghna; Wagner, Christel; Yalcin, Binnaz

    2016-01-01

    This article describes a series of standard operating procedures for morphological phenotyping of the mouse brain using basic histology. Many histological studies of the mouse brain use qualitative approaches based on what the human eye can detect. Consequently, some phenotypic information may be missed. Here we describe a quantitative approach for the assessment of brain morphology that is simple and robust. A total of 78 measurements are made throughout the brain at specific and well-defined regions, including the cortex, the hippocampus, and the cerebellum. Experimental design and timeline considerations, including strain background effects, the importance of sectioning quality, measurement variability, and efforts to correct human errors are discussed. © 2016 by John Wiley & Sons, Inc. PMID:27584555

  5. Immunological regulation of neurogenic niches in the adult brain

    PubMed Central

    Gonzalez-Perez, Oscar; Gutierrez-Fernandez, Fernando; Lopez-Virgen, Veronica; Collas-Aguilar, Jorge; Quinones-Hinojosa, Alfredo; Garcia-Verdugo, Jose M.

    2012-01-01

    In mammals, neurogenesis and oligodendrogenesis are germinal processes that occur in the adult brain throughout life. The subventricular (SVZ) and subgranular (SGZ) zones are the main neurogenic regions in adult brain. Therein, it resides a subpopulation of astrocytes that act as neural stem cells. Increasing evidence indicates that pro-inflammatory and other immunological mediators are important regulators of neural precursors into the SVZ and the SGZ. There are a number of inflammatory cytokines that regulate the function of neural stem cells. Some of the most studied include: interleukin-1, interleukin-6, tumor necrosis factor-alpha, insulin-like growth factor-1, growth-regulated oncogene-alpha, leukemia inhibitory factor, cardiotrophin-1, ciliary neurotrophic factor, interferon-gamma, monocyte chemotactic protein-1 and macrophage inflammatory protein-1alpha. This plethora of immunological mediators can control the migration, proliferation, quiescence, cell-fate choices and survival of neural stem cells and their progeny. Thus, systemic or local inflammatory processes represent important regulators of germinal niches in the adult brain. In this review, we summarized the current evidence regarding the effects of pro-inflammatory cytokines involved in the regulation of adult neural stem cells under in vitro and in vivo conditions. Additionally, we described the role of proinflammatory cytokines in neurodegenerative diseases and some therapeutical approaches for the immunomodulation of neural progenitor cells. PMID:22986164

  6. Describing functional diversity of brain regions and brain networks

    PubMed Central

    Anderson, Michael L.; Kinnison, Josh; Pessoa, Luiz

    2013-01-01

    Despite the general acceptance that functional specialization plays an important role in brain function, there is little consensus about its extent in the brain. We sought to advance the understanding of this question by employing a data-driven approach that capitalizes on the existence of large databases of neuroimaging data. We quantified the diversity of activation in brain regions as a way to characterize the degree of functional specialization. To do so, brain activations were classified in terms of task domains, such as vision, attention, and language, which determined a region’s functional fingerprint. We found that the degree of diversity varied considerably across the brain. We also quantified novel properties of regions and of networks that inform our understanding of several task-positive and task-negative networks described in the literature, including defining functional fingerprints for entire networks and measuring their functional assortativity, namely the degree to which they are composed of regions with similar functional fingerprints. Our results demonstrate that some brain networks exhibit strong assortativity, whereas other networks consist of relatively heterogeneous parts. In sum, rather than characterizing the contributions of individual brain regions using task-based functional attributions, we instead quantified their dispositional tendencies, and related those to each region’s affiliative properties in both task-positive and task-negative contexts. PMID:23396162

  7. A revised dosimetric model of the adult head and brain

    SciTech Connect

    Bouchet, L.G.; Bolch, W.E.; Weber, D.A.

    1996-06-01

    During the last decade, new radiopharmaceutical have been introduced for brain imaging. The marked differences of these tracers in tissue specificity within the brain and their increasing use for diagnostic studies support the need for a more anthropomorphic model of the human brain and head. Brain and head models developed in the past have been only simplistic representations of this anatomic region. For example, the brain within the phantom of MIRD Pamphlet No. 5 Revised is modeled simply as a single ellipsoid of tissue With no differentiation of its internal structures. To address this need, the MIRD Committee established a Task Group in 1992 to construct a more detailed brain model to include the cerebral cortex, the white matter, the cerebellum, the thalamus, the caudate nucleus, the lentiform nucleus, the cerebral spinal fluid, the lateral ventricles, and the third ventricle. This brain model has been included within a slightly modified version of the head model developed by Poston et al. in 1984. This model has been incorporated into the radiation transport code EGS4 so as to calculate photon and electron absorbed fractions in the energy range 10 keV to 4 MeV for each of thirteen sources in the brain. Furthermore, explicit positron transport have been considered, separating the contribution by the positron itself and its associated annihilations photons. No differences are found between the electron and positron absorbed fractions; however, for initial energies of positrons greater than {approximately}0.5 MeV, significant differences are found between absorbed fractions from explicit transport of annihilation photons and those from an assumed uniform distribution of 0.511-MeV photons. Subsequently, S values were calculated for a variety of beta-particle and positron emitters brain imaging agents. Moreover, pediatric head and brain dosimetric models are currently being developed based on this adult head model.

  8. Mature brain tissue in the sacrococcygeal region

    PubMed Central

    Shrestha, Binod Bade; Ghimire, Pradeep; Ghartimagar, Dilasma; Jwarchan, Bishnu; Lalchan, Subita; Karmacharya, Mikesh

    2016-01-01

    Complete mature brain tissue in sacrococcygeal region is a rare congenital anomaly in a newborn, which usually is misdiagnosed for sacrococcygeal teratoma. Glial tumor-like ependymoma is also common in sacrococcygeal area but mostly appears later in life. We present a case of complete heterotopic brain tissue in the sacrococcygeal region. The patient underwent total excision of mass with coccygectomy. To our knowledge it is the second case being reported. PMID:27194682

  9. Mature brain tissue in the sacrococcygeal region.

    PubMed

    Shrestha, Binod Bade; Ghimire, Pradeep; Ghartimagar, Dilasma; Jwarchan, Bishnu; Lalchan, Subita; Karmacharya, Mikesh

    2016-01-01

    Complete mature brain tissue in sacrococcygeal region is a rare congenital anomaly in a newborn, which usually is misdiagnosed for sacrococcygeal teratoma. Glial tumor-like ependymoma is also common in sacrococcygeal area but mostly appears later in life. We present a case of complete heterotopic brain tissue in the sacrococcygeal region. The patient underwent total excision of mass with coccygectomy. To our knowledge it is the second case being reported. PMID:27194682

  10. Testosterone affects language areas of the adult human brain

    PubMed Central

    Hahn, Andreas; Kranz, Georg S.; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F.

    2016-01-01

    Abstract Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high‐dose hormone application in adult female‐to‐male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel‐based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting‐state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone‐dependent neuroplastic adaptations in adulthood within language‐specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738–1748, 2016. © 2016 Wiley Periodicals, Inc. PMID:26876303

  11. Brain network activity in monolingual and bilingual older adults.

    PubMed

    Grady, Cheryl L; Luk, Gigi; Craik, Fergus I M; Bialystok, Ellen

    2015-01-01

    Bilingual older adults typically have better performance on tasks of executive control (EC) than do their monolingual peers, but differences in brain activity due to language experience are not well understood. Based on studies showing a relation between the dynamic range of brain network activity and performance on EC tasks, we hypothesized that life-long bilingual older adults would show increased functional connectivity relative to monolinguals in networks related to EC. We assessed intrinsic functional connectivity and modulation of activity in task vs. fixation periods in two brain networks that are active when EC is engaged, the frontoparietal control network (FPC) and the salience network (SLN). We also examined the default mode network (DMN), which influences behavior through reduced activity during tasks. We found stronger intrinsic functional connectivity in the FPC and DMN in bilinguals than in monolinguals. Although there were no group differences in the modulation of activity across tasks and fixation, bilinguals showed stronger correlations than monolinguals between intrinsic connectivity in the FPC and task-related increases of activity in prefrontal and parietal regions. This bilingual difference in network connectivity suggests that language experience begun in childhood and continued throughout adulthood influences brain networks in ways that may provide benefits in later life.

  12. Brain network activity in monolingual and bilingual older adults.

    PubMed

    Grady, Cheryl L; Luk, Gigi; Craik, Fergus I M; Bialystok, Ellen

    2015-01-01

    Bilingual older adults typically have better performance on tasks of executive control (EC) than do their monolingual peers, but differences in brain activity due to language experience are not well understood. Based on studies showing a relation between the dynamic range of brain network activity and performance on EC tasks, we hypothesized that life-long bilingual older adults would show increased functional connectivity relative to monolinguals in networks related to EC. We assessed intrinsic functional connectivity and modulation of activity in task vs. fixation periods in two brain networks that are active when EC is engaged, the frontoparietal control network (FPC) and the salience network (SLN). We also examined the default mode network (DMN), which influences behavior through reduced activity during tasks. We found stronger intrinsic functional connectivity in the FPC and DMN in bilinguals than in monolinguals. Although there were no group differences in the modulation of activity across tasks and fixation, bilinguals showed stronger correlations than monolinguals between intrinsic connectivity in the FPC and task-related increases of activity in prefrontal and parietal regions. This bilingual difference in network connectivity suggests that language experience begun in childhood and continued throughout adulthood influences brain networks in ways that may provide benefits in later life. PMID:25445783

  13. Brain Network Activity in Monolingual and Bilingual Older Adults

    PubMed Central

    Grady, Cheryl L.; Luk, Gigi; Craik, Fergus I.M.; Bialystok, Ellen

    2016-01-01

    Bilingual older adults typically have better performance on tasks of executive control (EC) than do their monolingual peers, but differences in brain activity due to language experience are not well understood. Based on studies showing a relation between the dynamic range of brain network activity and performance on EC tasks, we hypothesized that life-long bilingual older adults would show increased functional connectivity relative to monolinguals in networks related to EC. We assessed intrinsic functional connectivity and modulation of activity in task vs. fixation periods in two brain networks that are active when EC is engaged, the frontoparietal control network (FPC) and the salience network (SLN). We also examined the default mode network (DMN), which influences behavior through reduced activity during tasks. We found stronger intrinsic functional connectivity in the FPC and DMN in bilinguals than in monolinguals. Although there were no group differences in the modulation of activity across tasks and fixation, bilinguals showed stronger correlations than monolinguals between intrinsic connectivity in the FPC and task-related increases of activity in prefrontal and parietal regions. This bilingual difference in network connectivity suggests that language experience begun in childhood and continued throughout adulthood influences brain networks in ways that may provide benefits in later life. PMID:25445783

  14. Restricted nature of adult neural stem cells: re-evaluation of their potential for brain repair

    PubMed Central

    Obernier, Kirsten; Tong, Cheuk Ka; Alvarez-Buylla, Arturo

    2014-01-01

    Neural stem cells (NSCs) in the walls of the lateral ventricles continue to produce new neurons and oligodendrocytes throughout life. The identification of NSCs, long-range neuronal migration, and the integration of new neurons into fully formed mature neural circuits—all in the juvenile or adult brain—has dramatically changed concepts in neurodevelopment and suggests new strategies for brain repair. Yet, the latter has to be seen in perspective: NSCs in the adult are heterogeneous and highly regionally specified; young neurons derived from these primary progenitors migrate and integrate in specific brain regions. Neurogenesis appears to have a function in brain plasticity rather than brain repair. If similar processes could be induced in regions of the brain that are normally not a target of new neurons, therapeutic neuronal replacement may one day reinstate neural circuit plasticity and possibly repair broken neural circuits. PMID:24987325

  15. Experience-Dependent Neural Plasticity in the Adult Damaged Brain

    ERIC Educational Resources Information Center

    Kerr, Abigail L.; Cheng, Shao-Ying; Jones, Theresa A.

    2011-01-01

    Behavioral experience is at work modifying the structure and function of the brain throughout the lifespan, but it has a particularly dramatic influence after brain injury. This review summarizes recent findings on the role of experience in reorganizing the adult damaged brain, with a focus on findings from rodent stroke models of chronic upper…

  16. Large scale study on the variation of RF energy absorption in the head & brain regions of adults and children and evaluation of the SAM phantom conservativeness

    NASA Astrophysics Data System (ADS)

    Keshvari, J.; Kivento, M.; Christ, A.; Bit-Babik, G.

    2016-04-01

    This paper presents the results of two computational large scale studies using highly realistic exposure scenarios, MRI based human head and hand models, and two mobile phone models. The objectives are (i) to study the relevance of age when people are exposed to RF by comparing adult and child heads and (ii) to analyze and discuss the conservativeness of the SAM phantom for all age groups. Representative use conditions were simulated using detailed CAD models of two mobile phones operating between 900 MHz and 1950 MHz including configurations with the hand holding the phone, which were not considered in most previous studies. The peak spatial-average specific absorption rate (psSAR) in the head and the pinna tissues is assessed using anatomically accurate head and hand models. The first of the two mentioned studies involved nine head-, four hand- and two phone-models, the second study included six head-, four hand- and three simplified phone-models (over 400 configurations in total). In addition, both studies also evaluated the exposure using the SAM phantom. Results show no systematic differences between psSAR induced in the adult and child heads. The exposure level and its variation for different age groups may be different for particular phones, but no correlation between psSAR and model age was found. The psSAR from all exposure conditions was compared to the corresponding configurations using SAM, which was found to be conservative in the large majority of cases.

  17. Cell type- and brain region-resolved mouse brain proteome.

    PubMed

    Sharma, Kirti; Schmitt, Sebastian; Bergner, Caroline G; Tyanova, Stefka; Kannaiyan, Nirmal; Manrique-Hoyos, Natalia; Kongi, Karina; Cantuti, Ludovico; Hanisch, Uwe-Karsten; Philips, Mari-Anne; Rossner, Moritz J; Mann, Matthias; Simons, Mikael

    2015-12-01

    Brain transcriptome and connectome maps are being generated, but an equivalent effort on the proteome is currently lacking. We performed high-resolution mass spectrometry-based proteomics for in-depth analysis of the mouse brain and its major brain regions and cell types. Comparisons of the 12,934 identified proteins in oligodendrocytes, astrocytes, microglia and cortical neurons with deep sequencing data of the transcriptome indicated deep coverage of the proteome. Cell type-specific proteins defined as tenfold more abundant than average expression represented about a tenth of the proteome, with an overrepresentation of cell surface proteins. To demonstrate the utility of our resource, we focused on this class of proteins and identified Lsamp, an adhesion molecule of the IgLON family, as a negative regulator of myelination. Our findings provide a framework for a system-level understanding of cell-type diversity in the CNS and serves as a rich resource for analyses of brain development and function. PMID:26523646

  18. Guidelines for Better Communication with Brain Impaired Adults

    MedlinePlus

    ... A You are here Home Guidelines for Better Communication with Brain Impaired Adults Printer-friendly version Communicating ... easy solutions, following some basic guidelines should ease communication, and lower levels of stress both for you ...

  19. Critical care management of severe traumatic brain injury in adults

    PubMed Central

    2012-01-01

    Traumatic brain injury (TBI) is a major medical and socio-economic problem, and is the leading cause of death in children and young adults. The critical care management of severe TBI is largely derived from the "Guidelines for the Management of Severe Traumatic Brain Injury" that have been published by the Brain Trauma Foundation. The main objectives are prevention and treatment of intracranial hypertension and secondary brain insults, preservation of cerebral perfusion pressure (CPP), and optimization of cerebral oxygenation. In this review, the critical care management of severe TBI will be discussed with focus on monitoring, avoidance and minimization of secondary brain insults, and optimization of cerebral oxygenation and CPP. PMID:22304785

  20. Cell proliferation and neurogenesis in adult mouse brain.

    PubMed

    Bordiuk, Olivia L; Smith, Karen; Morin, Peter J; Semënov, Mikhail V

    2014-01-01

    Neurogenesis, the formation of new neurons, can be observed in the adult brain of many mammalian species, including humans. Despite significant progress in our understanding of adult neurogenesis, we are still missing data about the extent and location of production of neural precursors in the adult mammalian brain. We used 5-ethynyl-2'-deoxyuridine (EdU) to map the location of proliferating cells throughout the entire adult mouse brain and found that neurogenesis occurs at two locations in the mouse brain. The larger one we define as the main proliferative zone (MPZ), and the smaller one corresponds to the subgranular zone of the hippocampus. The MPZ can be divided into three parts. The caudate migratory stream (CMS) occupies the middle part of the MPZ. The cable of proliferating cells emanating from the most anterior part of the CMS toward the olfactory bulbs forms the rostral migratory stream. The thin layer of proliferating cells extending posteriorly from the CMS forms the midlayer. We have not found any additional aggregations of proliferating cells in the adult mouse brain that could suggest the existence of other major neurogenic zones in the adult mouse brain.

  1. Cell proliferation and neurogenesis in adult mouse brain.

    PubMed

    Bordiuk, Olivia L; Smith, Karen; Morin, Peter J; Semënov, Mikhail V

    2014-01-01

    Neurogenesis, the formation of new neurons, can be observed in the adult brain of many mammalian species, including humans. Despite significant progress in our understanding of adult neurogenesis, we are still missing data about the extent and location of production of neural precursors in the adult mammalian brain. We used 5-ethynyl-2'-deoxyuridine (EdU) to map the location of proliferating cells throughout the entire adult mouse brain and found that neurogenesis occurs at two locations in the mouse brain. The larger one we define as the main proliferative zone (MPZ), and the smaller one corresponds to the subgranular zone of the hippocampus. The MPZ can be divided into three parts. The caudate migratory stream (CMS) occupies the middle part of the MPZ. The cable of proliferating cells emanating from the most anterior part of the CMS toward the olfactory bulbs forms the rostral migratory stream. The thin layer of proliferating cells extending posteriorly from the CMS forms the midlayer. We have not found any additional aggregations of proliferating cells in the adult mouse brain that could suggest the existence of other major neurogenic zones in the adult mouse brain. PMID:25375658

  2. Memory and Brain Volume in Adults Prenatally Exposed to Alcohol

    ERIC Educational Resources Information Center

    Coles, Claire D.; Goldstein, Felicia C.; Lynch, Mary Ellen; Chen, Xiangchuan; Kable, Julie A.; Johnson, Katrina C.; Hu, Xiaoping

    2011-01-01

    The impact of prenatal alcohol exposure on memory and brain development was investigated in 92 African-American, young adults who were first identified in the prenatal period. Three groups (Control, n = 26; Alcohol-related Neurodevelopmental Disorder, n = 36; and Dysmorphic, n = 30) were imaged using structural MRI with brain volume calculated for…

  3. Brain regions and genes affecting limb-clasping responses.

    PubMed

    Lalonde, R; Strazielle, C

    2011-06-24

    Adult rodents picked up by the tail and slowly descending towards a horizontal surface extend all four limbs in anticipation of contact. Mouse mutants with pathologies in various brain regions and the spinal cord display instead a flexion response, often characterized by paw-clasping and a bat-like posture. These phenotypes are observed in mice with lesions in cerebellum, basal ganglia, and neocortex, as well as transgenic models of Alzheimer's disease. The underlying mechanism appears to include cerebello-cortico-reticular and cortico-striato-pallido-reticular pathways, possibly triggered by changes in noradrenaline and serotonin transmission.

  4. Compromised quality of life in adult patients who have received a radiation dose towards the basal part of the brain. A case-control study in long-term survivors from cancer in the head and neck region

    PubMed Central

    2012-01-01

    Background Adult patients with hypothalamic-pituitary disorders have compromised quality of life (QoL). Whether this is due to their endocrine consequences (hypopituitarism), their underlying hypothalamic-pituitary disorder or both is still under debate. The aim of this trial was to measure quality of life (QoL) in long-term cancer survivors who have received a radiation dose to the basal part of the brain and the pituitary. Methods Consecutive patients (n=101) treated for oropharyngeal or epipharyngeal cancer with radiotherapy followed free of cancer for a period of 4 to10 years were identified. Fifteen patients (median age 56 years) with no concomitant illness and no hypopituitarism after careful endocrine evaluation were included in a case-control study with matched healthy controls. Doses to the hypothalamic-pituitary region were calculated. QoL was assessed using the Symptom check list (SCL)-90, Nottingham Health Profile (NHP), and Psychological Well Being (PGWB) questionnaires. Level of physical activity was assessed using the Baecke questionnaire. Results The median accumulated dose was 1.9 Gy (1.5–2.2 Gy) to the hypothalamus and 2.4 Gy (1.8–3.3 Gy) to the pituitary gland in patients with oropharyngeal cancer and 6.0–9.3 Gy and 33.5–46.1 Gy, respectively in patients with epipharyngeal cancer (n=2). The patients showed significantly more anxiety and depressiveness, and lower vitality, than their matched controls. Conclusion In a group of long time survivors of head and neck cancer who hade received a low radiation dose to the hypothalamic-pituitary region and who had no endocrine consequences of disease or its treatment QoL was compromised as compared with well matched healthy controls. PMID:23101561

  5. Microglial brain region-dependent diversity and selective regional sensitivities to ageing

    PubMed Central

    Grabert, Kathleen; Michoel, Tom; Karavolos, Michail H; Clohisey, Sara; Baillie, J Kenneth; Stevens, Mark P; Freeman, Tom C; Summers, Kim M; McColl, Barry W

    2015-01-01

    Microglia play critical roles in neural development, homeostasis and neuroinflammation and are increasingly implicated in age-related neurological dysfunction. Neurodegeneration often occurs in disease-specific spatially-restricted patterns, the origins of which are unknown. We performed the first genome-wide analysis of microglia from discrete brain regions across the adult lifespan of the mouse and reveal that microglia have distinct region-dependent transcriptional identities and age in a regionally variable manner. In the young adult brain, differences in bioenergetic and immunoregulatory pathways were the major sources of heterogeneity and suggested that cerebellar and hippocampal microglia exist in a more immune vigilant state. Immune function correlated with regional transcriptional patterns. Augmentation of the distinct cerebellar immunophenotype and a contrasting loss in distinction of the hippocampal phenotype among forebrain regions were key features during ageing. Microglial diversity may enable regionally localised homeostatic functions but could also underlie region-specific sensitivities to microglial dysregulation and involvement in age-related neurodegeneration. PMID:26780511

  6. Microglial brain region-dependent diversity and selective regional sensitivities to aging.

    PubMed

    Grabert, Kathleen; Michoel, Tom; Karavolos, Michail H; Clohisey, Sara; Baillie, J Kenneth; Stevens, Mark P; Freeman, Tom C; Summers, Kim M; McColl, Barry W

    2016-03-01

    Microglia have critical roles in neural development, homeostasis and neuroinflammation and are increasingly implicated in age-related neurological dysfunction. Neurodegeneration often occurs in disease-specific, spatially restricted patterns, the origins of which are unknown. We performed to our knowledge the first genome-wide analysis of microglia from discrete brain regions across the adult lifespan of the mouse, and found that microglia have distinct region-dependent transcriptional identities and age in a regionally variable manner. In the young adult brain, differences in bioenergetic and immunoregulatory pathways were the major sources of heterogeneity and suggested that cerebellar and hippocampal microglia exist in a more immune-vigilant state. Immune function correlated with regional transcriptional patterns. Augmentation of the distinct cerebellar immunophenotype and a contrasting loss in distinction of the hippocampal phenotype among forebrain regions were key features during aging. Microglial diversity may enable regionally localized homeostatic functions but could also underlie region-specific sensitivities to microglial dysregulation and involvement in age-related neurodegeneration.

  7. Essential role of brain-derived neurotrophic factor in adult hippocampal function

    PubMed Central

    Monteggia, Lisa M.; Barrot, Michel; Powell, Craig M.; Berton, Olivier; Galanis, Victor; Gemelli, Terry; Meuth, Sven; Nagy, Andreas; Greene, Robert W.; Nestler, Eric J.

    2004-01-01

    Brain-derived neurotrophic factor (BDNF) regulates neuronal development and function. However, it has been difficult to discern its role in the adult brain in influencing complex behavior. Here, we use a recently developed inducible knockout system to show that deleting BDNF in broad forebrain regions of adult mice impairs hippocampal-dependent learning and long-term potentiation. We use the inducible nature of this system to show that the loss of BDNF during earlier stages of development causes hyperactivity and more pronounced hippocampal-dependent learning deficits. We also demonstrate that the loss of forebrain BDNF attenuates the actions of desipramine, an antidepressant, in the forced swim test, suggesting the involvement of BDNF in antidepressant efficacy. These results establish roles for BDNF in the adult, and demonstrate the strength of this inducible knockout system in studying gene function in the adult brain. PMID:15249684

  8. Childhood Onset Schizophrenia: Cortical Brain Abnormalities as Young Adults

    ERIC Educational Resources Information Center

    Greenstein, Deanna; Lerch, Jason; Shaw, Philip; Clasen, Liv; Giedd, Jay; Gochman, Peter; Rapoport, Judith; Gogtay, Nitin

    2006-01-01

    Background: Childhood onset schizophrenia (COS) is a rare but severe form of the adult onset disorder. While structural brain imaging studies show robust, widespread, and progressive gray matter loss in COS during adolescence, there have been no longitudinal studies of sufficient duration to examine comparability with the more common adult onset…

  9. Neural stem cells in the adult human brain

    PubMed Central

    Gonzalez-Perez, Oscar

    2012-01-01

    For decades, it was believed that the adult brain was a quiescent organ unable to produce new neurons. At the beginning of the1960's, this dogma was challenged by a small group of neuroscientists. To date, it is well-known that new neurons are generated in the adult brain throughout life. Adult neurogenesis is primary confined to the subventricular zone (SVZ) of the forebrain and the subgranular zone of the dentate gyrus within the hippocampus. In both the human and the rodent brain, the primary progenitor of adult SVZ is a subpopulation of astrocytes that have stem-cell-like features. The human SVZ possesses a peculiar cell composition and displays important organizational differences when compared to the SVZ of other mammals. Some evidence suggests that the human SVZ may be not only an endogenous source of neural precursor cells for brain repair, but also a source of brain tumors. In this review, we described the cytoarchitecture and cellular composition of the SVZ in the adult human brain. We also discussed some clinical implications of SVZ, such as: stem-cell-based therapies against neurodegenerative diseases and its potential as a source of malignant cells. Understanding the biology of human SVZ and its neural progenitors is one of the crucial steps to develop novel therapies against neurological diseases in humans. PMID:23181200

  10. Brain stem auditory evoked responses in human infants and adults

    NASA Technical Reports Server (NTRS)

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  11. New Nerve Cells for the Adult Brain.

    ERIC Educational Resources Information Center

    Kempermann, Gerd; Gage, Fred H.

    1999-01-01

    Contrary to dogma, the human brain does produce new nerve cells in adulthood. The mature human brain spawns neurons routinely in the hippocampus, an area important to memory and learning. This research can make it possible to ease any number of disorders involving neurological damage and death. (CCM)

  12. Wnts in adult brain: from synaptic plasticity to cognitive deficiencies

    PubMed Central

    Oliva, Carolina A.; Vargas, Jessica Y.; Inestrosa, Nibaldo C.

    2013-01-01

    During development of the central nervous system the Wnt signaling pathway has been implicated in a wide spectrum of physiological processes, including neuronal connectivity and synapse formation. Wnt proteins and components of the Wnt pathway are expressed in the brain since early development to the adult life, however, little is known about its role in mature synapses. Here, we review evidences indicating that Wnt proteins participate in the remodeling of pre- and post-synaptic regions, thus modulating synaptic function. We include the most recent data in the literature showing that Wnts are constantly released in the brain to maintain the basal neural activity. Also, we review the evidences that involve components of the Wnt pathway in the development of neurological and mental disorders, including a special emphasis on in vivo studies that relate behavioral abnormalities to deficiencies in Wnt signaling. Finally, we include the evidences that support a neuroprotective role of Wnt proteins in Alzheimer’s disease. We postulate that deregulation in Wnt signaling might have a fundamental role in the origin of neurological diseases, by altering the synaptic function at stages where the phenotype is not yet established but when the cognitive decline starts. PMID:24348327

  13. Structural and functional rich club organization of the brain in children and adults.

    PubMed

    Grayson, David S; Ray, Siddharth; Carpenter, Samuel; Iyer, Swathi; Dias, Taciana G Costa; Stevens, Corinne; Nigg, Joel T; Fair, Damien A

    2014-01-01

    Recent studies using Magnetic Resonance Imaging (MRI) have proposed that the brain's white matter is organized as a rich club, whereby the most highly connected regions of the brain are also highly connected to each other. Here we use both functional and diffusion-weighted MRI in the human brain to investigate whether the rich club phenomena is present with functional connectivity, and how this organization relates to the structural phenomena. We also examine whether rich club regions serve to integrate information between distinct brain systems, and conclude with a brief investigation of the developmental trajectory of rich-club phenomena. In agreement with prior work, both adults and children showed robust structural rich club organization, comprising regions of the superior medial frontal/dACC, medial parietal/PCC, insula, and inferior temporal cortex. We also show that these regions were highly integrated across the brain's major networks. Functional brain networks were found to have rich club phenomena in a similar spatial layout, but a high level of segregation between systems. While no significant differences between adults and children were found structurally, adults showed significantly greater functional rich club organization. This difference appeared to be driven by a specific set of connections between superior parietal, insula, and supramarginal cortex. In sum, this work highlights the existence of both a structural and functional rich club in adult and child populations with some functional changes over development. It also offers a potential target in examining atypical network organization in common developmental brain disorders, such as ADHD and Autism.

  14. The effects of vitamin D on brain development and adult brain function.

    PubMed

    Kesby, James P; Eyles, Darryl W; Burne, Thomas H J; McGrath, John J

    2011-12-01

    A role for vitamin D in brain development and function has been gaining support over the last decade. Multiple lines of evidence suggest that this vitamin is actually a neuroactive steroid that acts on brain development, leading to alterations in brain neurochemistry and adult brain function. Early deficiencies have been linked with neuropsychiatric disorders, such as schizophrenia, and adult deficiencies have been associated with a host of adverse brain outcomes, including Parkinson's disease, Alzheimer's disease, depression and cognitive decline. This review summarises the current state of research on the actions of vitamin D in the brain and the consequences of deficiencies in this vitamin. Furthermore, we discuss specific implications of vitamin D status on the neurotransmitter, dopamine. PMID:21664231

  15. Radial glial cell-specific ablation in the adult Zebrafish brain.

    PubMed

    Shimizu, Yuki; Ito, Yoko; Tanaka, Hideomi; Ohshima, Toshio

    2015-07-01

    The zebrafish brain can continue to produce new neurons in widespread neurogenic brain regions throughout life. In contrast, neurogenesis in the adult mammalian brain is restricted to the subventricular zone (SVZ) and dentate gyrus (DG). In neurogenic regions in the adult brain, radial glial cells (RGCs) are considered to function as neural stem cells (NSCs). We generated a Tg(gfap:Gal4FF) transgenic zebrafish line, which enabled us to express specific genes in RGCs. To study the function of RGCs in neurogenesis in the adult zebrafish brain, we also generated a Tg(gfap: Gal4FF; UAS:nfsB-mcherry) transgenic zebrafish line, which allowed us to induce cell death exclusively within RGCs upon addition of metronidazole (Mtz) to the media. RGCs expressing nitroreductase were specifically ablated by the Mtz treatment, decreasing the number of proliferative RGCs. Using the Tg(gfap:Gal4FF; UAS:nfsB-mcherry) transgenic zebrafish line, we found that RGCs were specifically ablated in the adult zebrafish telencephalon. The Tg(gfap:Gal4FF) line could be useful to study the function of RGCs.

  16. Differential Expression of protocadherin-19, protocadherin-17 and cadherin-6 in Adult Zebrafish Brain

    PubMed Central

    Liu, Qin; Bhattarai, Sunil; Wang, Nan; Sochacka-Marlowe, Alicja

    2015-01-01

    Cell adhesion molecule cadherins play important roles in both development and maintenance of adult structures. Most studies on cadherin expression have been carried out in developing organisms, but information on cadherin distribution in adult vertebrate brains is limited. In this study, we used in situ hybridization to examine mRNA expression of three cadherins, protocadherin-19, protocadherin-17 and cadherin-6 in adult zebrafish brain. Each cadherin exhibits a distinct expression pattern in the fish brain, with protocadherin-19 and protocadherin-17 showing much wider and stronger expression than that of cadherin-6. Both protocadherin-19 and protocadherin-17 expressing cells occur throughout the brain with strong expression in the ventromedial telencephalon, periventricular regions of the thalamus and anterior hypothalamus, stratum periventriculare of the optic tectum, dorsal tegmental nucleus, granular regions of the cerebellar body and valvula, and superficial layers of the facial and vagal lobes. Numerous sensory structures (e.g. auditory, gustatory, lateral line, olfactory and visual nuclei) and motor nuclei (e.g. oculomotor, trochlear, trigeminal motor, abducens and vagal motor nuclei) contain protocadherin-19 and/or protocadherin-17 expressing cell. Expression of these two protocadherins is similar in the ventromedial telencephalon, thalamus, hypothalamus, facial and vagal lobes, but substantially different in the dorsolateral telencephalon, intermediate layers of the optic tectum, and cerebellar valvula. In contrast to the two protocadherins, cadherin-6 expression is much weaker and limited in the adult fish brain. PMID:25612302

  17. Differential expression of protocadherin-19, protocadherin-17, and cadherin-6 in adult zebrafish brain.

    PubMed

    Liu, Qin; Bhattarai, Sunil; Wang, Nan; Sochacka-Marlowe, Alicja

    2015-06-15

    Cell adhesion molecule cadherins play important roles in both development and maintenance of adult structures. Most studies on cadherin expression have been carried out in developing organisms, but information on cadherin distribution in adult vertebrate brains is limited. In this study we used in situ hybridization to examine mRNA expression of three cadherins, protocadherin-19, protocadherin-17, and cadherin-6 in adult zebrafish brain. Each cadherin exhibits a distinct expression pattern in the fish brain, with protocadherin-19 and protocadherin-17 showing much wider and stronger expression than that of cadherin-6. Both protocadherin-19 and protocadherin-17-expressing cells occur throughout the brain, with strong expression in the ventromedial telencephalon, periventricular regions of the thalamus and anterior hypothalamus, stratum periventriculare of the optic tectum, dorsal tegmental nucleus, granular regions of the cerebellar body and valvula, and superficial layers of the facial and vagal lobes. Numerous sensory structures (e.g., auditory, gustatory, lateral line, olfactory, and visual nuclei) and motor nuclei (e.g., oculomotor, trochlear, trigeminal motor, abducens, and vagal motor nuclei) contain protocadherin-19 and/or protocadherin-17-expressing cell. Expression of these two protocadherins is similar in the ventromedial telencephalon, thalamus, hypothalamus, facial, and vagal lobes, but substantially different in the dorsolateral telencephalon, intermediate layers of the optic tectum, and cerebellar valvula. In contrast to the two protocadherins, cadherin-6 expression is much weaker and limited in the adult fish brain.

  18. Experience induces structural and biochemical changes in the adult primate brain.

    PubMed

    Kozorovitskiy, Yevgenia; Gross, Charles G; Kopil, Catherine; Battaglia, Lisa; McBreen, Meghan; Stranahan, Alexis M; Gould, Elizabeth

    2005-11-29

    Primates exhibit complex social and cognitive behavior in the wild. In the laboratory, however, the expression of their behavior is usually limited. A large body of literature shows that living in an enriched environment alters dendrites and synapses in the brains of adult rodents. To date, no studies have investigated the influence of living in a complex environment on brain structure in adult primates. We assessed dendritic architecture, dendritic spines, and synaptic proteins in adult marmosets housed in either a standard laboratory cage or in one of two differentially complex habitats. A month-long stay in either complex environment enhanced the length and complexity of the dendritic tree and increased dendritic spine density and synaptic protein levels in the hippocampus and prefrontal cortex. No differences were detected between the brains of marmosets living in the two differentially complex environments. Our results show that the structure of the adult primate brain remains highly sensitive even to modest levels of experiential complexity. For adult primates, living in standard laboratory housing may induce reversible dendritic spine and synapse decreases in brain regions important for cognition.

  19. BDNF Expression in Larval and Adult Zebrafish Brain: Distribution and Cell Identification

    PubMed Central

    Cacialli, Pietro; Gueguen, Marie-Madeleine; Coumailleau, Pascal; D’Angelo, Livia; Kah, Olivier; Lucini, Carla; Pellegrini, Elisabeth

    2016-01-01

    Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has emerged as an active mediator in many essential functions in the central nervous system of mammals. BDNF plays significant roles in neurogenesis, neuronal maturation and/or synaptic plasticity and is involved in cognitive functions such as learning and memory. Despite the vast literature present in mammals, studies devoted to BDNF in the brain of other animal models are scarse. Zebrafish is a teleost fish widely known for developmental genetic studies and is emerging as model for translational neuroscience research. In addition, its brain shows many sites of adult neurogenesis allowing higher regenerative properties after traumatic injuries. To add further knowledge on neurotrophic factors in vertebrate brain models, we decided to determine the distribution of bdnf mRNAs in the larval and adult zebrafish brain and to characterize the phenotype of cells expressing bdnf mRNAs by means of double staining studies. Our results showed that bdnf mRNAs were widely expressed in the brain of 7 days old larvae and throughout the whole brain of mature female and male zebrafish. In adults, bdnf mRNAs were mainly observed in the dorsal telencephalon, preoptic area, dorsal thalamus, posterior tuberculum, hypothalamus, synencephalon, optic tectum and medulla oblongata. By combining immunohistochemistry with in situ hybridization, we showed that bdnf mRNAs were never expressed by radial glial cells or proliferating cells. By contrast, bdnf transcripts were expressed in cells with neuronal phenotype in all brain regions investigated. Our results provide the first demonstration that the brain of zebrafish expresses bdnf mRNAs in neurons and open new fields of research on the role of the BDNF factor in brain mechanisms in normal and brain repairs situations. PMID:27336917

  20. BDNF Expression in Larval and Adult Zebrafish Brain: Distribution and Cell Identification.

    PubMed

    Cacialli, Pietro; Gueguen, Marie-Madeleine; Coumailleau, Pascal; D'Angelo, Livia; Kah, Olivier; Lucini, Carla; Pellegrini, Elisabeth

    2016-01-01

    Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, has emerged as an active mediator in many essential functions in the central nervous system of mammals. BDNF plays significant roles in neurogenesis, neuronal maturation and/or synaptic plasticity and is involved in cognitive functions such as learning and memory. Despite the vast literature present in mammals, studies devoted to BDNF in the brain of other animal models are scarse. Zebrafish is a teleost fish widely known for developmental genetic studies and is emerging as model for translational neuroscience research. In addition, its brain shows many sites of adult neurogenesis allowing higher regenerative properties after traumatic injuries. To add further knowledge on neurotrophic factors in vertebrate brain models, we decided to determine the distribution of bdnf mRNAs in the larval and adult zebrafish brain and to characterize the phenotype of cells expressing bdnf mRNAs by means of double staining studies. Our results showed that bdnf mRNAs were widely expressed in the brain of 7 days old larvae and throughout the whole brain of mature female and male zebrafish. In adults, bdnf mRNAs were mainly observed in the dorsal telencephalon, preoptic area, dorsal thalamus, posterior tuberculum, hypothalamus, synencephalon, optic tectum and medulla oblongata. By combining immunohistochemistry with in situ hybridization, we showed that bdnf mRNAs were never expressed by radial glial cells or proliferating cells. By contrast, bdnf transcripts were expressed in cells with neuronal phenotype in all brain regions investigated. Our results provide the first demonstration that the brain of zebrafish expresses bdnf mRNAs in neurons and open new fields of research on the role of the BDNF factor in brain mechanisms in normal and brain repairs situations. PMID:27336917

  1. Theory of Mind Performance in Children Correlates with Functional Specialization of a Brain Region for Thinking about Thoughts

    ERIC Educational Resources Information Center

    Gweon, Hyowon; Dodell-Feder, David; Bedny, Marina; Saxe, Rebecca

    2012-01-01

    Thinking about other people's thoughts recruits a specific group of brain regions, including the temporo-parietal junctions (TPJ), precuneus (PC), and medial prefrontal cortex (MPFC). The same brain regions were recruited when children (N = 20, 5-11 years) and adults (N = 8) listened to descriptions of characters' mental states, compared to…

  2. Expansion of Multipotent Stem Cells from the Adult Human Brain

    PubMed Central

    Murrell, Wayne; Palmero, Emily; Bianco, John; Stangeland, Biljana; Joel, Mrinal; Paulson, Linda; Thiede, Bernd; Grieg, Zanina; Ramsnes, Ingunn; Skjellegrind, Håvard K.; Nygård, Ståle; Brandal, Petter; Sandberg, Cecilie; Vik-Mo, Einar; Palmero, Sheryl; Langmoen, Iver A.

    2013-01-01

    The discovery of stem cells in the adult human brain has revealed new possible scenarios for treatment of the sick or injured brain. Both clinical use of and preclinical research on human adult neural stem cells have, however, been seriously hampered by the fact that it has been impossible to passage these cells more than a very few times and with little expansion of cell numbers. Having explored a number of alternative culturing conditions we here present an efficient method for the establishment and propagation of human brain stem cells from whatever brain tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and Oct4 are expressed without artificial induction. For the first time multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells’ behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient’s own-derived stem cells. PMID:23967194

  3. Phylogenetic origins of early alterations in brain region proportions.

    PubMed

    Charvet, Christine J; Sandoval, Alexis L; Striedter, Georg F

    2010-01-01

    Adult galliform birds (e.g. chickens) exhibit a relatively small telencephalon and a proportionately large optic tectum compared with parrots and songbirds. We previously examined the embryonic origins of these adult species differences and found that the optic tectum is larger in quail than in parakeets and songbirds at early stages of development, prior to tectal neurogenesis onset. The aim of this study was to determine whether a proportionately large presumptive tectum is a primitive condition within birds or a derived feature of quail and other galliform birds. To this end, we examined embryonic brains of several avian species (emus, parrots, songbirds, waterfowl, galliform birds), reptiles (3 lizard species, alligators, turtles) and a monotreme (platypuses). Brain region volumes were estimated from serial Nissl-stained sections. We found that the embryos of galliform birds and lizards exhibit a proportionally larger presumptive tectum than all the other examined species. The presumptive tectum of the platypus is unusually small. The most parsimonious interpretation of these data is that the expanded embryonic tectum of lizards and galliform birds is a derived feature in both of these taxonomic groups.

  4. Inflammation is detrimental for neurogenesis in adult brain

    NASA Astrophysics Data System (ADS)

    Ekdahl, Christine T.; Claasen, Jan-Hendrik; Bonde, Sara; Kokaia, Zaal; Lindvall, Olle

    2003-11-01

    New hippocampal neurons are continuously generated in the adult brain. Here, we demonstrate that lipopolysaccharide-induced inflammation, which gives rise to microglia activation in the area where the new neurons are born, strongly impairs basal hippocampal neurogenesis in rats. The increased neurogenesis triggered by a brain insult is also attenuated if it is associated with microglia activation caused by tissue damage or lipopolysaccharide infusion. The impaired neurogenesis in inflammation is restored by systemic administration of minocycline, which inhibits microglia activation. Our data raise the possibility that suppression of hippocampal neurogenesis by activated microglia contributes to cognitive dysfunction in aging, dementia, epilepsy, and other conditions leading to brain inflammation.

  5. Brain abscess caused by Citrobacter koseri infection in an adult.

    PubMed

    Liu, Heng-Wei; Chang, Chih-Ju; Hsieh, Cheng-Ta

    2015-04-01

    Citrobacter koseri is a gram-negative bacillus that causes mostly meningitis and brain abscesses in neonates and infants. However, brain abscess caused by Citrobacter koseri infection in an adult is extremely rare, and only 2 cases have been described. Here, we reported a 73-year-old male presenting with a 3-week headache. A history of diabetes mellitus was noted. The images revealed a brain abscess in the left frontal lobe and pus culture confirmed the growth of Citrobacter koseri. The clinical symptoms improved completely postoperatively.

  6. The antidepressant tranylcypromine alters cellular proliferation and migration in the adult goldfish brain.

    PubMed

    Romanczyk, Tara B; Jacobowitz, David M; Pollard, Harvey B; Wu, Xingjia; Anders, Juanita J

    2014-10-01

    The goldfish (Carassius auratus) is a widely studied vertebrate model organism for studying cell proliferation in the adult brain, and provide the experimental advantage of growing their body and brain throughout their ∼30-year life time. Cell proliferation occurs in the teleost brain in widespread proliferation zones. Increased cell proliferation in the brain has been linked to the actions of certain antidepressants, including tranylcypromine (TCP), which is used in the treatment of depression. We hypothesized that proliferation zones in the adult goldfish brain can be used to determine the antidepressant effects on cellular proliferation. Here, we report that bromodeoxyuridine (BrdU) labeling over a 24-hr period can be used to rapidly identify the proliferation zones throughout the goldfish brain, including the telencephalon, diencephalon, optic tectal lobes, cerebellum, and facial and vagal lobes. In the first 24 hr of BrdU administration, TCP caused an approximate and significant doubling of labeled cells in the combined brain regions examined, as detected by BrdU immunohistochemistry. TCP caused the greatest increase in cell proliferation in the cerebellum. The normal migratory paths of the proliferating cells within the cerebellum were not affected by TCP treatment. These results indicate that the goldfish provide significant advantages as a vertebrate model for rapidly investigating the effects of antidepressant drugs on cellular proliferation and migration in the normal and injured brain.

  7. Identification of a set of genes showing regionally enriched expression in the mouse brain

    PubMed Central

    D'Souza, Cletus A; Chopra, Vikramjit; Varhol, Richard; Xie, Yuan-Yun; Bohacec, Slavita; Zhao, Yongjun; Lee, Lisa LC; Bilenky, Mikhail; Portales-Casamar, Elodie; He, An; Wasserman, Wyeth W; Goldowitz, Daniel; Marra, Marco A; Holt, Robert A; Simpson, Elizabeth M; Jones, Steven JM

    2008-01-01

    Background The Pleiades Promoter Project aims to improve gene therapy by designing human mini-promoters (< 4 kb) that drive gene expression in specific brain regions or cell-types of therapeutic interest. Our goal was to first identify genes displaying regionally enriched expression in the mouse brain so that promoters designed from orthologous human genes can then be tested to drive reporter expression in a similar pattern in the mouse brain. Results We have utilized LongSAGE to identify regionally enriched transcripts in the adult mouse brain. As supplemental strategies, we also performed a meta-analysis of published literature and inspected the Allen Brain Atlas in situ hybridization data. From a set of approximately 30,000 mouse genes, 237 were identified as showing specific or enriched expression in 30 target regions of the mouse brain. GO term over-representation among these genes revealed co-involvement in various aspects of central nervous system development and physiology. Conclusion Using a multi-faceted expression validation approach, we have identified mouse genes whose human orthologs are good candidates for design of mini-promoters. These mouse genes represent molecular markers in several discrete brain regions/cell-types, which could potentially provide a mechanistic explanation of unique functions performed by each region. This set of markers may also serve as a resource for further studies of gene regulatory elements influencing brain expression. PMID:18625066

  8. Localization of PPAR isotypes in the adult mouse and human brain

    PubMed Central

    Warden, Anna; Truitt, Jay; Merriman, Morgan; Ponomareva, Olga; Jameson, Kelly; Ferguson, Laura B.; Mayfield, R. Dayne; Harris, R. Adron

    2016-01-01

    Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. PPAR agonists have well-documented anti-inflammatory and neuroprotective roles in the central nervous system. Recent evidence suggests that PPAR agonists are attractive therapeutic agents for treating neurodegenerative diseases as well as addiction. However, the distribution of PPAR mRNA and protein in brain regions associated with these conditions (i.e. prefrontal cortex, nucleus accumbens, amygdala, ventral tegmental area) is not well defined. Moreover, the cell type specificity of PPARs in mouse and human brain tissue has yet to be investigated. We utilized quantitative PCR and double immunofluorescence microscopy to determine that both PPAR mRNA and protein are expressed ubiquitously throughout the adult mouse brain. We found that PPARs have unique cell type specificities that are consistent between species. PPARα was the only isotype to colocalize with all cell types in both adult mouse and adult human brain tissue. Overall, we observed a strong neuronal signature, which raises the possibility that PPAR agonists may be targeting neurons rather than glia to produce neuroprotection. Our results fill critical gaps in PPAR distribution and define novel cell type specificity profiles in the adult mouse and human brain. PMID:27283430

  9. Narrative Skills Following Traumatic Brain Injury in Children and Adults.

    ERIC Educational Resources Information Center

    Biddle, Kathleen R.; And Others

    1996-01-01

    This study used dependency analysis to document and describe the narrative discourse impairments of 10 children (mean age 12) and 10 adults (mean age 35) with traumatic brain injury (TBI), and matched controls. Individuals with TBI were significantly more disfluent than controls and their narrative performance required a significant listener…

  10. Oligodendrogenesis in the fornix of adult mouse brain; the effect of LPS-induced inflammatory stimulation.

    PubMed

    Fukushima, Shohei; Nishikawa, Kazunori; Furube, Eriko; Muneoka, Shiori; Ono, Katsuhiko; Takebayashi, Hirohide; Miyata, Seiji

    2015-11-19

    Evidence have been accumulated that continuous oligodendrogenesis occurs in the adult mammalian brain. The fornix, projection and commissure pathway of hippocampal neurons, carries signals from the hippocampus to other parts of the brain and has critical role in memory and learning. However, basic characterization of adult oligodendrogenesis in this brain region is not well understood. In the present study, therefore, we aimed to examine the proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) and the effect of acute inflammatory stimulation on oligodendrogenesis in the fornix of adult mouse. We demonstrated the proliferation of OPCs and a new generation of mature oligodendrocytes by using bromodeoxyuridine and Ki67 immunohistochemistry. Oligodendrogenesis of adult fornix was also demonstrated by using oligodendrocyte transcription factor 2 transgenic mouse. A single systemic administration of lipopolysaccharide (LPS) attenuated proliferation of OPCs in the fornix together with reduced proliferation of hippocampal neural stem/progenitor cells. Time course analysis showed that a single administration of LPS attenuated the proliferation of OPCs during 24-48 h. On the other hand, consecutive administration of LPS did not suppress proliferation of OPCs. The treatment of LPS did not affect differentiation of OPCs into mature oligodendrocytes. Treatment of a microglia inhibitor minocycline significantly attenuated basal proliferation of OPCs under normal condition. In conclusion, the present study indicates that continuous oligodendrogenesis occurs and a single administration of LPS transiently attenuates proliferation of OPCs without changing differentiation in the fornix of the adult mouse brains.

  11. Neuronal Organization of the Brain in the Adult Amphioxus (Branchiostoma lanceolatum): A Study With Acetylated Tubulin Immunohistochemistry.

    PubMed

    Castro, Antonio; Becerra, Manuela; Manso, María Jesús; Anadón, Ramón

    2015-10-15

    Amphioxus (Cephalochordata) belongs to the most basal extant chordates, and knowledge of their brain organization appears to be key to deciphering the early stages of evolution of vertebrate brains. Most comprehensive studies of the organization of the central nervous system of adult amphioxus have investigated the spinal cord. Some brain populations have been characterized via neurochemistry and electron microscopy, and the overall cytoarchitecture of the brain was studied by Ekhart et al. (2003; J. Comp. Neurol. 466:319-330) with general staining methods and retrograde transport from the spinal cord. Here, the cytoarchitecture of the brain of adult amphioxus Branchiostoma lanceolatum was reinvestigated by using acetylated tubulin immunohistochemistry, which specifically stains neurons and fibers, in combination with some ancillary methods. This method allowed reproducible staining and mapping of types of neuron, mostly in brain regions caudal to the entrance level of nerve 2, and its comparison with spinal cord populations. The brain populations studied and discussed in detail were the Retzius bipolar cells, lamellate cells, Joseph cells, various types of translumenal cells, somatic motoneurons, Rohde nucleus cells, small ventral multipolar neurons, and Edinger cells. These observations expand our knowledge of the distribution of cell types and provide additional data on the number of cells and the axonal tracts and commissural regions of the adult amphioxus brain. The results of this comprehensive study provide a framework for comparison of complex adult populations with the early brain neuronal populations revealed in developmental studies of the amphioxus.

  12. Neuronal Organization of the Brain in the Adult Amphioxus (Branchiostoma lanceolatum): A Study With Acetylated Tubulin Immunohistochemistry.

    PubMed

    Castro, Antonio; Becerra, Manuela; Manso, María Jesús; Anadón, Ramón

    2015-10-15

    Amphioxus (Cephalochordata) belongs to the most basal extant chordates, and knowledge of their brain organization appears to be key to deciphering the early stages of evolution of vertebrate brains. Most comprehensive studies of the organization of the central nervous system of adult amphioxus have investigated the spinal cord. Some brain populations have been characterized via neurochemistry and electron microscopy, and the overall cytoarchitecture of the brain was studied by Ekhart et al. (2003; J. Comp. Neurol. 466:319-330) with general staining methods and retrograde transport from the spinal cord. Here, the cytoarchitecture of the brain of adult amphioxus Branchiostoma lanceolatum was reinvestigated by using acetylated tubulin immunohistochemistry, which specifically stains neurons and fibers, in combination with some ancillary methods. This method allowed reproducible staining and mapping of types of neuron, mostly in brain regions caudal to the entrance level of nerve 2, and its comparison with spinal cord populations. The brain populations studied and discussed in detail were the Retzius bipolar cells, lamellate cells, Joseph cells, various types of translumenal cells, somatic motoneurons, Rohde nucleus cells, small ventral multipolar neurons, and Edinger cells. These observations expand our knowledge of the distribution of cell types and provide additional data on the number of cells and the axonal tracts and commissural regions of the adult amphioxus brain. The results of this comprehensive study provide a framework for comparison of complex adult populations with the early brain neuronal populations revealed in developmental studies of the amphioxus. PMID:25846052

  13. Ephrin/Eph receptor expression in brain of adult nonhuman primates: implications for neuroadaptation.

    PubMed

    Xiao, Danqing; Miller, Gregory M; Jassen, Amy; Westmoreland, Susan V; Pauley, Douglas; Madras, Bertha K

    2006-01-01

    In developing brain, Eph receptors and their ephrin ligands (Ephs/ephrins) are implicated in facilitating topographic guidance of a number of pathways, including the nigrostriatal and mesolimbic dopamine (DA) pathways. In adult rodent brain, these molecules are implicated in neuronal plasticity associated with learning and memory. Cocaine significantly alters the expression of select members of this family of axonal guidance molecules, implicating Ephs, ephrins in drug-induced neuroadaptation. The potential contribution of Ephs, ephrins to cocaine-induced reorganization of striatal circuitry brain in primates [Saka, E., Goodrich, C., Harlan, P., Madras, B.K., Graybiel, A.M., 2004. Repetitive behaviors in monkeys are linked to specific striatal activation patterns. J. Neurosci. 24, 7557-7565] is unknown because there are no documented reports of Eph/ephrin expression or function in adult primate brain. We now report that brains of adult old and new world monkeys express mRNA encoding EphA4 receptor and ephrin-B2 ligand, implicated in topographic guidance of dopamine and striatal neurons during development. Their encoded proteins distributed highly selectively in regions of adult monkey brain. EphA4 mRNA levels were prominent in the DA-rich caudate/putamen, nucleus accumbens and globus pallidus, as well as the medial and orbitofrontal cortices, hippocampus, amygdala, thalamus and cerebellum. Immunocytochemical localization of EphA4 protein revealed discrete expression in caudate/putamen, globus pallidus, substantia nigra, cerebellar Purkinje cells, pyramidal cells of frontal cortices (layers II, III and V) and the subgranular zone of the hippocampus. Evidence for EphA4 expression in dopamine neurons emerged from colocalization with tyrosine-hydroxylase-positive terminals in striatum and substantia nigra and ventral tegmental area cell bodies. The association of axonal guidance molecules with drug-induced reorganization of adult primate brain circuitry warrants

  14. Cranial irradiation induces bone marrow-derived microglia in adult mouse brain tissue.

    PubMed

    Okonogi, Noriyuki; Nakamura, Kazuhiro; Suzuki, Yoshiyuki; Suto, Nana; Suzue, Kazutomo; Kaminuma, Takuya; Nakano, Takashi; Hirai, Hirokazu

    2014-07-01

    Postnatal hematopoietic progenitor cells do not contribute to microglial homeostasis in adult mice under normal conditions. However, previous studies using whole-body irradiation and bone marrow (BM) transplantation models have shown that adult BM cells migrate into the brain tissue and differentiate into microglia (BM-derived microglia; BMDM). Here, we investigated whether cranial irradiation alone was sufficient to induce the generation of BMDM in the adult mouse brain. Transgenic mice that express green fluorescent protein (GFP) under the control of a murine stem cell virus (MSCV) promoter (MSCV-GFP mice) were used. MSCV-GFP mice express GFP in BM cells but not in the resident microglia in the brain. Therefore, these mice allowed us to detect BM-derived cells in the brain without BM reconstitution. MSCV-GFP mice, aged 8-12 weeks, received 13.0 Gy irradiation only to the cranium, and BM-derived cells in the brain were quantified at 3 and 8 weeks after irradiation. No BM-derived cells were detected in control non-irradiated MSCV-GFP mouse brains, but numerous GFP-labeled BM-derived cells were present in the brain stem, basal ganglia and cerebral cortex of the irradiated MSCV-GFP mice. These BM-derived cells were positive for Iba1, a marker for microglia, indicating that GFP-positive BM-derived cells were microglial in nature. The population of BMDM was significantly greater at 8 weeks post-irradiation than at 3 weeks post-irradiation in all brain regions examined. Our results clearly show that cranial irradiation alone is sufficient to induce the generation of BMDM in the adult mouse.

  15. Environmental Impact on Direct Neuronal Reprogramming In Vivo in the Adult Brain

    PubMed Central

    López-Juárez, Alejandro; Howard, Jennifer; Sakthivel, Bhuvaneswari; Aronow, Bruce; Campbell, Kenneth; Nakafuku, Masato

    2013-01-01

    Direct reprogramming of non-neuronal cells to generate new neurons is a promising approach to repair damaged brains. Impact of the in vivo environment on neuronal reprogramming, however, is poorly understood. Here we show that regional differences and injury conditions have significant influence on the efficacy of reprogramming and subsequent survival of newly generated neurons in the adult rodent brain. A combination of local exposure to growth factors and retrovirus-mediated overexpression of the neurogenic transcription factor Neurogenin2 (Neurog2) can induce new neurons from non-neuronal cells in the adult neocortex and striatum where neuronal turnover is otherwise very limited. These two regions respond to growth factors and Neurog2 differently and instruct new neurons to exhibit distinct molecular phenotypes. Moreover, ischemic insult differentially affects differentiation of new neurons in these regions. These results demonstrate strong environmental impact on direct neuronal reprogramming in vivo. PMID:23974433

  16. Environmental impact on direct neuronal reprogramming in vivo in the adult brain.

    PubMed

    Grande, Andrew; Sumiyoshi, Kyoko; López-Juárez, Alejandro; Howard, Jennifer; Sakthivel, Bhuvaneswari; Aronow, Bruce; Campbell, Kenneth; Nakafuku, Masato

    2013-01-01

    Direct reprogramming of non-neuronal cells to generate new neurons is a promising approach to repair damaged brains. Impact of the in vivo environment on neuronal reprogramming, however, is poorly understood. Here we show that regional differences and injury conditions have significant influence on the efficacy of reprogramming and subsequent survival of the newly generated neurons in the adult rodent brain. A combination of local exposure to growth factors and retrovirus-mediated overexpression of the neurogenic transcription factor Neurogenin2 can induce new neurons from non-neuronal cells in the adult neocortex and striatum where neuronal turnover is otherwise very limited. These two regions respond to growth factors and Neurogenin2 differently and instruct new neurons to exhibit distinct molecular phenotypes. Moreover, ischaemic insult differentially affects differentiation of new neurons in these regions. These results demonstrate strong environmental impact on direct neuronal reprogramming in vivo.

  17. Developmental Vitamin D3 deficiency alters the adult rat brain.

    PubMed

    Féron, F; Burne, T H J; Brown, J; Smith, E; McGrath, J J; Mackay-Sim, A; Eyles, D W

    2005-03-15

    There is growing evidence that Vitamin D(3) (1,25-dihydroxyvitamin D(3)) is involved in brain development. We have recently shown that the brains of newborn rats from Vitamin D(3) deficient dams were larger than controls, had increased cell proliferation, larger lateral ventricles, and reduced cortical thickness. Brains from these animals also had reduced expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor. The aim of the current study was to examine if there were any permanent outcomes into adulthood when the offspring of Vitamin D(3) deficient dams were restored to a normal diet. The brains of adult rats were examined at 10 weeks of age after Vitamin D(3) deficiency until birth or weaning. Compared to controls animals that were exposed to transient early Vitamin D(3) deficiency had larger lateral ventricles, reduced NGF protein content, and reduced expression of a number genes involved in neuronal structure, i.e. neurofilament or MAP-2 or neurotransmission, i.e. GABA-A(alpha4). We conclude that transient early life hypovitaminosis D(3) not only disrupts brain development but leads to persistent changes in the adult brain. In light of the high incidence of hypovitaminosis D(3) in women of child-bearing age, the public health implications of these findings warrant attention. PMID:15763180

  18. Pedophilic brain potential responses to adult erotic stimuli.

    PubMed

    Knott, Verner; Impey, Danielle; Fisher, Derek; Delpero, Emily; Fedoroff, Paul

    2016-02-01

    Cognitive mechanisms associated with the relative lack of sexual interest in adults by pedophiles are poorly understood and may benefit from investigations examining how the brain processes adult erotic stimuli. The current study used event-related brain potentials (ERP) to investigate the time course of the explicit processing of erotic, emotional, and neutral pictures in 22 pedophilic patients and 22 healthy controls. Consistent with previous studies, early latency anterior ERP components were highly selective for erotic pictures. Although the ERPs elicited by emotional stimuli were similar in patients and controls, an early frontal positive (P2) component starting as early as 185 ms was significantly attenuated and slow to onset in pedophilia, and correlated with a clinical measure of cognitive distortions. Failure of rapid attentional capture by erotic stimuli suggests a relative reduction in early processing in pedophilic patients which may be associated with relatively diminished sexual interest in adults. PMID:26683083

  19. [Endocrine functions of the brain in adult and developing mammals].

    PubMed

    Ugriumov, M V

    2009-01-01

    The main prerequisite for organism's viability is the maintenance of the internal environment despite changes in the external environment, which is provided by the neuroendocrine control system. The key unit in this system is hypothalamus exerting endocrine effects on certain peripheral organs and anterior pituitary. Physiologically active substances of neuronal origin enter blood vessels in the neurohemal parts of hypothalamus where no blood-brain barrier exists. In other parts of the adult brain, the arrival of physiologically active substances is blocked by the blood-brain barrier. According to the generally accepted concept, the neuroendocrine system formation in ontogeny starts with the maturation of peripheral endocrine glands, which initially function autonomously and then are controlled by the anterior pituitary. The brain is engaged in neuroendocrine control after its maturation completes, which results in a closed control system typical of adult mammals. Since neurons start to secrete physiologically active substances soon after their formation and long before interneuronal connections are formed, these cells are thought to have an effect on brain development as inducers. Considering that there is no blood-brain barrier during this period, we proposed the hypothesis that the developing brain functions as a multipotent endocrine organ. This means that tens of physiologically active substances arrive from the brain to the systemic circulation and have an endocrine effect on the whole body development. Dopamine, serotonin, and gonadotropin-releasing hormone were selected as marker physiologically active substances of cerebral origin to test this hypothesis. In adult animals, they act as neurotransmitters or neuromodulators transmitting information from neuron to neuron as well as neurohormones arriving from the hypothalamus with portal blood to the anterior pituitary. Perinatal rats--before the blood-brain barrier is formed--proved to have equally high

  20. Does acute caffeine ingestion alter brain metabolism in young adults?

    PubMed

    Xu, Feng; Liu, Peiying; Pekar, James J; Lu, Hanzhang

    2015-04-15

    Caffeine, as the most commonly used stimulant drug, improves vigilance and, in some cases, cognition. However, the exact effect of caffeine on brain activity has not been fully elucidated. Because caffeine has a pronounced vascular effect which is independent of any neural effects, many hemodynamics-based methods such as fMRI cannot be readily applied without a proper calibration. The scope of the present work is two-fold. In Study 1, we used a recently developed MRI technique to examine the time-dependent changes in whole-brain cerebral metabolic rate of oxygen (CMRO2) following the ingestion of 200mg caffeine. It was found that, despite a pronounced decrease in CBF (p<0.001), global CMRO2 did not change significantly. Instead, the oxygen extraction fraction (OEF) was significantly elevated (p=0.002) to fully compensate for the reduced blood supply. Using the whole-brain finding as a reference, we aim to investigate whether there are any regional differences in the brain's response to caffeine. Therefore, in Study 2, we examined regional heterogeneities in CBF changes following the same amount of caffeine ingestion. We found that posterior brain regions such as posterior cingulate cortex and superior temporal regions manifested a slower CBF reduction, whereas anterior brain regions including dorsolateral prefrontal cortex and medial frontal cortex showed a faster rate of decline. These findings have a few possible explanations. One is that caffeine may result in a region-dependent increase or decrease in brain activity, resulting in an unaltered average brain metabolic rate. The other is that caffeine's effect on vasculature may be region-specific. Plausibility of these explanations is discussed in the context of spatial distribution of the adenosine receptors.

  1. Does acute caffeine ingestion alter brain metabolism in young adults?

    PubMed

    Xu, Feng; Liu, Peiying; Pekar, James J; Lu, Hanzhang

    2015-04-15

    Caffeine, as the most commonly used stimulant drug, improves vigilance and, in some cases, cognition. However, the exact effect of caffeine on brain activity has not been fully elucidated. Because caffeine has a pronounced vascular effect which is independent of any neural effects, many hemodynamics-based methods such as fMRI cannot be readily applied without a proper calibration. The scope of the present work is two-fold. In Study 1, we used a recently developed MRI technique to examine the time-dependent changes in whole-brain cerebral metabolic rate of oxygen (CMRO2) following the ingestion of 200mg caffeine. It was found that, despite a pronounced decrease in CBF (p<0.001), global CMRO2 did not change significantly. Instead, the oxygen extraction fraction (OEF) was significantly elevated (p=0.002) to fully compensate for the reduced blood supply. Using the whole-brain finding as a reference, we aim to investigate whether there are any regional differences in the brain's response to caffeine. Therefore, in Study 2, we examined regional heterogeneities in CBF changes following the same amount of caffeine ingestion. We found that posterior brain regions such as posterior cingulate cortex and superior temporal regions manifested a slower CBF reduction, whereas anterior brain regions including dorsolateral prefrontal cortex and medial frontal cortex showed a faster rate of decline. These findings have a few possible explanations. One is that caffeine may result in a region-dependent increase or decrease in brain activity, resulting in an unaltered average brain metabolic rate. The other is that caffeine's effect on vasculature may be region-specific. Plausibility of these explanations is discussed in the context of spatial distribution of the adenosine receptors. PMID:25644657

  2. Delineating multiple functions of VEGF-A in the adult brain.

    PubMed

    Licht, Tamar; Keshet, Eli

    2013-05-01

    Vascular endothelial growth factor-A (abbreviated throughout this review as VEGF) is mostly known for its angiogenic activity, for its activity as a vascular permeability factor, and for its vascular survival activity [1]. There is a growing body of evidence, however, that VEGF fulfills additional less 'traditional' functions in multiple organs, both during development, as well as homeostatic functions in fully developed organs. This review focuses on the multiple roles of VEGF in the adult brain and is less concerned with the roles played by VEGF during brain development, functions described elsewhere in this review series. Most functions of VEGF that are essential for proper brain development are, in fact, dispensable in the adult brain as was clearly demonstrated using a conditional brain-specific VEGF loss-of-function (LOF) approach. Thus, in contrast to VEGF LOF in the developing brain, a process which is detrimental for the growth and survival of blood vessels and leads to massive neuronal apoptosis [2-4], continued signaling by VEGF in the mature brain is no longer required for maintaining already established cerebral vasculature and its inhibition does not cause appreciable vessel regression, hypoxia or apoptosis [4-7]. Yet, VEGF continues to be expressed in the adult brain in a constitutive manner. Moreover, VEGF is expressed in the adult brain in a region-specific manner and in distinctive spatial patterns incompatible with an angiogenic role (see below), strongly suggesting angiogenesis-independent and possibly also perfusion-independent functions. Here we review current knowledge on some of these 'non-traditional', often unexpected homeostatic VEGF functions, including those unrelated to its effects on the brain vasculature. These effects could be mediated directly (on non-vascular cells expressing cognate VEGF receptors) or indirectly (via the endothelium). Experimental approaches aimed at distinguishing between these possibilities for each particular

  3. Clonal development and organization of the adult Drosophila central brain

    PubMed Central

    Yu, Hung-Hsiang; Awasaki, Takeshi; Schroeder, Mark David; Long, Fuhui; Yang, Jacob S.; He, Yisheng; Ding, Peng; Kao, Jui-Chun; Wu, Gloria Yueh-Yi; Peng, Hanchuan; Myers, Gene; Lee, Tzumin

    2013-01-01

    Summary Background The insect brain can be divided into neuropils that are formed by neurites of both local and remote origin. The complexity of the interconnections obscures how these neuropils are established and interconnected through development. The Drosophila central brain develops from a fixed number of neuroblasts (NBs) that deposit neurons in regional clusters. Results By determining individual NB clones and pursuing their projections into specific neuropils we unravel the regional development of the brain neural network. Exhaustive clonal analysis revealed 95 stereotyped neuronal lineages with characteristic cell body locations and neurite trajectories. Most clones show complex projection patterns, but despite the complexity, neighboring clones often co-innervate the same local neuropil(s) and further target a restricted set of distant neuropils. Conclusions These observations argue for regional clonal development of both neuropils and neuropil connectivity throughout the Drosophila central brain. PMID:23541733

  4. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging

    PubMed Central

    Bell, Robert D.; Winkler, Ethan A.; Sagare, Abhay P.; Singh, Itender; LaRue, Barb; Deane, Rashid; Zlokovic, Berislav V.

    2010-01-01

    SUMMARY Pericytes play a key role in the development of cerebral microcirculation. The exact role of pericytes in the neurovascular unit in the adult brain and during brain aging remains, however, elusive. Using adult viable pericyte-deficient mice, we show that pericyte loss leads to brain vascular damage by two parallel pathways: (1) reduction in brain microcirculation causing diminished brain capillary perfusion, cerebral blood flow and cerebral blood flow responses to brain activation which ultimately mediates chronic perfusion stress and hypoxia, and (2) blood-brain barrier breakdown associated with brain accumulation of serum proteins and several vasculotoxic and/or neurotoxic macromolecules ultimately leading to secondary neuronal degenerative changes. We show that age-dependent vascular damage in pericyte-deficient mice precedes neuronal degenerative changes, learning and memory impairment and the neuroinflammatory response. Thus, pericytes control key neurovascular functions that are necessary for proper neuronal structure and function, and pericytes loss results in a progressive age-dependent vascular-mediated neurodegeneration. PMID:21040844

  5. Life satisfaction in adult survivors of childhood brain tumors.

    PubMed

    Crom, Deborah B; Li, Zhenghong; Brinkman, Tara M; Hudson, Melissa M; Armstrong, Gregory T; Neglia, Joseph; Ness, Kirsten K

    2014-01-01

    Adult survivors of childhood brain tumors experience multiple, significant, lifelong deficits as a consequence of their malignancy and therapy. Current survivorship literature documents the substantial impact such impairments have on survivors' physical health and quality of life. Psychosocial reports detail educational, cognitive, and emotional limitations characterizing survivors as especially fragile, often incompetent, and unreliable in evaluating their circumstances. Anecdotal data suggest some survivors report life experiences similar to those of healthy controls. The aim of our investigation was to determine whether life satisfaction in adult survivors of childhood brain tumors differs from that of healthy controls and to identify potential predictors of life satisfaction in survivors. This cross-sectional study compared 78 brain tumor survivors with population-based matched controls. Chi-square tests, t tests, and linear regression models were used to investigate patterns of life satisfaction and identify potential correlates. Results indicated that life satisfaction of adult survivors of childhood brain tumors was similar to that of healthy controls. Survivors' general health expectations emerged as the primary correlate of life satisfaction. Understanding life satisfaction as an important variable will optimize the design of strategies to enhance participation in follow-up care, reduce suffering, and optimize quality of life in this vulnerable population.

  6. Persistent Representation of Juvenile Experience in the Adult Songbird Brain

    PubMed Central

    Prather, JF; Peters, S; Nowicki, S; Mooney, R

    2010-01-01

    Juveniles sometimes learn behaviors that they cease to express as adults. Whether the adult brain retains a record of experiences associated with behaviors performed transiently during development remains unclear. We addressed this issue by studying neural representations of song in swamp sparrows, a species in which juveniles learn and practice many more songs than they retain in their adult vocal repertoire. We exposed juvenile swamp sparrows to a suite of tutor songs and confirmed that although many tutor songs were imitated during development, not all copied songs were retained into adulthood. We then recorded extracellularly in the sensorimotor nucleus HVC in anesthetized sparrows to assess neuronal responsiveness to songs in the adult repertoire, tutor songs, and novel songs. Individual HVC neurons almost always responded to songs in the adult repertoire and commonly responded even more strongly to a tutor song. Effective tutor songs were not simply those that were acoustically similar to songs in the adult repertoire. Moreover, the strength of tutor song responses was unrelated to the number of times that the bird sang copies of those songs in juvenile or adult life. Notably, several neurons responded most strongly to a tutor song performed only rarely and transiently during juvenile life, or even to a tutor song for which we could find no evidence of ever having been copied. Thus, HVC neurons representing songs in the adult repertoire also appear to retain a lasting record of certain tutor songs, including those imitated only transiently. PMID:20686001

  7. Does acute caffeine ingestion alter brain metabolism in young adults?

    PubMed Central

    Xu, Feng; Liu, Peiying; Pekar, James J.; Lu, Hanzhang

    2015-01-01

    Caffeine, as the most commonly used stimulant drug, improves vigilance and, in some cases, cognition. However, the exact effect of caffeine on brain activity has not been fully elucidated. Because caffeine has a pronounced vascular effect which is independent of any neural effects, many hemodynamics-based methods such as fMRI cannot be readily applied without a proper calibration. The scope of the present work is two-fold. In Study 1, we used a recently developed MRI technique to examine the time-dependent changes in whole-brain cerebral metabolic rate of oxygen (CMRO2) following the ingestion of 200mg caffeine. It was found that, despite a pronounced decrease in CBF (p<0.001), global CMRO2 did not change significantly. Instead, the oxygen extraction fraction (OEF) was significantly elevated (p=0.002) to fully compensate for the reduced blood supply. Using the whole-brain finding as a reference, we aim to investigate whether there are any regional differences in the brain’s response to caffeine. Therefore, in Study 2, we examined regional heterogeneities in CBF changes following the same amount of caffeine ingestion. We found that posterior brain regions such as posterior cingulate cortex and superior temporal regions manifested a slower CBF reduction, whereas anterior brain regions including dorsolateral prefrontal cortex and medial frontal cortex showed a faster rate of decline. These findings have a few possible explanations. One is that caffeine may result in a region-dependent increase or decrease in brain activity, resulting in an unaltered average brain metabolic rate. The other is that caffeine’s effect on vasculature may be region-specific. Plausibility of these explanations is discussed in the context of spatial distribution of the adenosine receptors. PMID:25644657

  8. Prenatal Ethanol Exposure Increases Brain Cholesterol Content in Adult Rats

    PubMed Central

    Barceló-Coblijn, Gwendolyn; Wold, Loren E.; Ren, Jun; Murphy, Eric J.

    2013-01-01

    Fetal alcohol syndrome is the most severe expression of the fetal alcohol spectrum disorders (FASD). Although alterations in fetal and neonate brain fatty acid composition and cholesterol content is known to change in animal models of FASD, the persistence of these alterations into adulthood is unknown. To address this question, we determined the effect of prenatal ethanol exposure on individual phospholipid class fatty acid composition, individual phospholipid class mass, and cholesterol mass in brains from 25-week-old rats that were exposed to ethanol during gestation beginning at gestational day 2. While total phospholipid mass was unaffected, phosphatidylinositol and cardiolipin mass was decreased 14 and 43%, respectively. Exposure to prenatal ethanol modestly altered brain phospholipid fatty acid composition, and the most consistent change was a significant 1.1-fold increase in total PUFA, in the n-3/n-6 ratio, and in the 22:6 n-3 content in ethanolamine glycerophospholipids and in phosphatidylserine. In contrast, prenatal ethanol consumption significantly increased brain cholesterol mass 1.4-fold and the phospholipid to cholesterol ratio was significantly increased 1.3-fold. These results indicate that brain cholesterol mass was significantly increased in adult rats exposed prenatally to ethanol, but changes in phospholipid mass and phospholipid fatty acid composition were extremely limited. Importantly, suppression of post-natal ethanol consumption was not sufficient to reverse the large increase in cholesterol observed in the adult rats. PMID:23996454

  9. Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain

    PubMed Central

    Duan, Xin; Chang, Jay H.; Ge, Shaoyu; Faulkner, Regina L.; Kim, Ju Young; Kitabatake, Yasuji; Liu, Xiao-bo; Yang, Chih-Hao; Jordan, J. Dedrick; Ma, Dengke K.; Liu, Cindy Y.; Ganesan, Sundar; Cheng, Hwai-Jong; Ming, Guo-li; Lu, Bai; Song, Hongjun

    2007-01-01

    Summary Adult neurogenesis occurs throughout life in discrete regions of the adult mammalian brain. Little is known about the mechanism governing the sequential developmental process that leads to integration of new neurons from adult neural stem cells into the existing circuitry. Here, we investigated roles of Disrupted-In-Schizophrenia 1 (DISC1), a schizophrenia susceptibility gene, in adult hippocampal neurogenesis. Unexpectedly, down regulation of DISC1 leads to accelerated neuronal integration, resulting in aberrant morphological development and mis-positioning of new dentate granule cells in a cell-autonomous fashion. Functionally, newborn neurons with DISC1 knockdown exhibit enhanced excitability and accelerated dendritic development and synapse formation. Furthermore, DISC1 cooperates with its binding partner Ndel1 in regulating adult neurogenesis. Taken together, our study identifies DISC1 as a key regulator that orchestrates the tempo of functional neuronal integration in the adult brain and demonstrates essential roles of a susceptibility gene for major mental illness in neuronal development, including adult neurogenesis. PMID:17825401

  10. Isolation and culture of neurospheres from the adult newt brain.

    PubMed

    Hameed, Liyakath Ali Shahul; Simon, András

    2015-01-01

    Neural stem cells (NSCs) give rise to neurons in the adult brain and are possible targets in regenerative therapies. In vitro cultures of NSCs as neurospheres have been established from cells isolated from diverse species. Newts are exceptional regenerators among vertebrates. These animals are able to efficiently replace neurons following ablation of those by activation and subsequent differentiation of NSCs. Here we describe the method for isolating and culturing of NSCs from the newt brain both during self-renewing and differentiating conditions. Newt NSC culture provides a useful tool for functional studies of NSC fate with the potential of resulting in novel regenerative strategies.

  11. Clinical review: Brain-body temperature differences in adults with severe traumatic brain injury.

    PubMed

    Childs, Charmaine; Lunn, Kueh Wern

    2013-04-22

    Surrogate or 'proxy' measures of brain temperature are used in the routine management of patients with brain damage. The prevailing view is that the brain is 'hotter' than the body. The polarity and magnitude of temperature differences between brain and body, however, remains unclear after severe traumatic brain injury (TBI). The focus of this systematic review is on the adult patient admitted to intensive/neurocritical care with a diagnosis of severe TBI (Glasgow Coma Scale score of less than 8). The review considered studies that measured brain temperature and core body temperature. Articles published in English from the years 1980 to 2012 were searched in databases, CINAHL, PubMed, Scopus, Web of Science, Science Direct, Ovid SP, Mednar and ProQuest Dissertations & Theses Database. For the review, publications of randomised controlled trials, non-randomised controlled trials, before and after studies, cohort studies, case-control studies and descriptive studies were considered for inclusion. Of 2,391 records identified via the search strategies, 37 were retrieved for detailed examination (including two via hand searching). Fifteen were reviewed and assessed for methodological quality. Eleven studies were included in the systematic review providing 15 brain-core body temperature comparisons. The direction of mean brain-body temperature differences was positive (brain higher than body temperature) and negative (brain lower than body temperature). Hypothermia is associated with large brain-body temperature differences. Brain temperature cannot be predicted reliably from core body temperature. Concurrent monitoring of brain and body temperature is recommended in patients where risk of temperature-related neuronal damage is a cause for clinical concern and when deliberate induction of below-normal body temperature is instituted.

  12. Stars from the darkest night: unlocking the neurogenic potential of astrocytes in different brain regions.

    PubMed

    Magnusson, Jens P; Frisén, Jonas

    2016-04-01

    In a few regions of the adult brain, specialized astrocytes act as neural stem cells capable of sustaining life-long neurogenesis. In other, typically non-neurogenic regions, some astrocytes have an intrinsic capacity to produce neurons when provoked by particular conditions but do not use this ability to replace neurons completely after injury or disease. Why do astrocytes display regional differences and why do they not use their neurogenic capacity for brain repair to a greater extent? In this Review, we discuss the neurogenic potential of astrocytes in different brain regions and ask what stimulates this potential in some regions but not in others. We discuss the transcriptional networks and environmental cues that govern cell identity, and consider how the activation of neurogenic properties in astrocytes can be understood as the de-repression of a latent neurogenic transcriptional program. PMID:27048686

  13. Chronic ethanol consumption profoundly alters regional brain ceramide and sphingomyelin content in rodents.

    PubMed

    Roux, Aurelie; Muller, Ludovic; Jackson, Shelley N; Baldwin, Katherine; Womack, Virginia; Pagiazitis, John G; O'Rourke, Joseph R; Thanos, Panayotis K; Balaban, Carey; Schultz, J Albert; Volkow, Nora D; Woods, Amina S

    2015-02-18

    Ceramides (CER) are involved in alcohol-induced neuroinflammation. In a mouse model of chronic alcohol exposure, 16 CER and 18 sphingomyelin (SM) concentrations from whole brain lipid extracts were measured using electrospray mass spectrometry. All 18 CER concentrations in alcohol exposed adults increased significantly (range: 25-607%); in juveniles, 6 CER decreased (range: -9 to -37%). In contrast, only three SM decreased in adult and one increased significantly in juvenile. Next, regional identification at 50 μm spatial resolution from coronal sections was obtained with matrix implanted laser desorption/ionization mass spectrometry imaging (MILDI-MSI) by implanting silver nanoparticulate matrices followed by focused laser desorption. Most of the CER and SM quantified in whole brain extracts were detected in MILDI images. Coronal sections from three brain levels show qualitative regional changes in CER-SM ion intensities, as a function of group and brain region, in cortex, striatum, accumbens, habenula, and hippocampus. Highly correlated changes in certain white matter CER-SM pairs occur in regions across all groups, including the hippocampus and the lateral (but not medial) cerebellar cortex of adult mice. Our data provide the first microscale MS evidence of regional lipid intensity variations induced by alcohol.

  14. Brain Activity in Adults Who Stutter: Similarities across Speaking Tasks and Correlations with Stuttering Frequency and Speaking Rate

    ERIC Educational Resources Information Center

    Ingham, Roger J.; Grafton, Scott T.; Bothe, Anne K.; Ingham, Janis C.

    2012-01-01

    Many differences in brain activity have been reported between persons who stutter (PWS) and typically fluent controls during oral reading tasks. An earlier meta-analysis of imaging studies identified stutter-related regions, but recent studies report less agreement with those regions. A PET study on adult dextral PWS (n = 18) and matched fluent…

  15. Regional Differences in Brain Volume Predict the Acquisition of Skill in a Complex Real-Time Strategy Videogame

    ERIC Educational Resources Information Center

    Basak, Chandramallika; Voss, Michelle W.; Erickson, Kirk I.; Boot, Walter R.; Kramer, Arthur F.

    2011-01-01

    Previous studies have found that differences in brain volume among older adults predict performance in laboratory tasks of executive control, memory, and motor learning. In the present study we asked whether regional differences in brain volume as assessed by the application of a voxel-based morphometry technique on high resolution MRI would also…

  16. Comprehensive cellular‐resolution atlas of the adult human brain

    PubMed Central

    Royall, Joshua J.; Sunkin, Susan M.; Ng, Lydia; Facer, Benjamin A.C.; Lesnar, Phil; Guillozet‐Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A.; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A.; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L.; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A.; Koch, Christof; Phillips, John W.; Sestan, Nenad; Wohnoutka, Paul; Zielke, H. Ronald; Hohmann, John G.; Jones, Allan R.; Bernard, Amy; Hawrylycz, Michael J.; Hof, Patrick R.; Fischl, Bruce

    2016-01-01

    ABSTRACT Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole‐brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high‐resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion‐weighted imaging (DWI), and 1,356 large‐format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto‐ and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127–3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27418273

  17. Comprehensive cellular-resolution atlas of the adult human brain.

    PubMed

    Ding, Song-Lin; Royall, Joshua J; Sunkin, Susan M; Ng, Lydia; Facer, Benjamin A C; Lesnar, Phil; Guillozet-Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A; Koch, Christof; Phillips, John W; Sestan, Nenad; Wohnoutka, Paul; Zielke, H Ronald; Hohmann, John G; Jones, Allan R; Bernard, Amy; Hawrylycz, Michael J; Hof, Patrick R; Fischl, Bruce; Lein, Ed S

    2016-11-01

    Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole-brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high-resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and 1,356 large-format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto- and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127-3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27418273

  18. Comprehensive cellular-resolution atlas of the adult human brain.

    PubMed

    Ding, Song-Lin; Royall, Joshua J; Sunkin, Susan M; Ng, Lydia; Facer, Benjamin A C; Lesnar, Phil; Guillozet-Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A; Koch, Christof; Phillips, John W; Sestan, Nenad; Wohnoutka, Paul; Zielke, H Ronald; Hohmann, John G; Jones, Allan R; Bernard, Amy; Hawrylycz, Michael J; Hof, Patrick R; Fischl, Bruce; Lein, Ed S

    2016-11-01

    Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole-brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high-resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and 1,356 large-format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto- and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127-3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

  19. Ketone-body utilization by homogenates of adult rat brain

    SciTech Connect

    Lopes-Cardozo, M.; Klein, W.

    1982-06-01

    The regulation of ketone-body metabolism and the quantitative importance of ketone bodies as lipid precursors in adult rat brain has been studied in vitro. Utilization of ketone bodies and of pyruvate by homogenates of adult rat brain was measured and the distribution of /sup 14/C from (3-/sup 14/C)ketone bodies among the metabolic products was analysed. The rate of ketone-body utilization was maximal in the presence of added Krebs-cycle intermediates and uncouplers of oxidative phosphorylation. The consumption of acetoacetate was faster than that of D-3-hydroxybutyrate, whereas, pyruvate produced twice as much acetyl-CoA as acetoacetate under optimal conditions. Millimolar concentrations of ATP in the presence of uncoupler lowered the consumption of ketone bodies but not of pyruvate. Indirect evidence is presented suggesting that ATP interferes specifically with the mitochondrial uptake of ketone bodies. Interconversion of ketone bodies and the accumulation of acid-soluble intermediates (mainly citrate and glutamate) accounted for the major part of ketone-body utilization, whereas only a small part was oxidized to CO/sub 2/. Ketone bodies were not incorporated into lipids or protein. We conclude that adult rat-brain homogenates use ketone bodies exclusively for oxidative purposes.

  20. Hippocampal Brain Volume Is Associated with Faster Facial Emotion Identification in Older Adults: Preliminary Results.

    PubMed

    Szymkowicz, Sarah M; Persson, Jonas; Lin, Tian; Fischer, Håkan; Ebner, Natalie C

    2016-01-01

    Quick correct identification of facial emotions is highly relevant for successful social interactions. Research suggests that older, compared to young, adults experience increased difficulty with face and emotion processing skills. While functional neuroimaging studies suggest age differences in neural processing of faces and emotions, evidence about age-associated structural brain changes and their involvement in face and emotion processing is scarce. Using structural magnetic resonance imaging (MRI), this study investigated the extent to which volumes of frontal and temporal brain structures were related to reaction time in accurate identification of facial emotions in 30 young and 30 older adults. Volumetric segmentation was performed using FreeSurfer and gray matter volumes from frontal and temporal regions were extracted. Analysis of covariances (ANCOVAs) models with response time (RT) as the dependent variable and age group and regional volume, and their interaction, as independent variables were conducted, controlling for total intracranial volume (ICV). Results indicated that, in older adults, larger hippocampal volumes were associated with faster correct facial emotion identification. These preliminary observations suggest that greater volume in brain regions associated with face and emotion processing contributes to improved facial emotion identification performance in aging. PMID:27610082

  1. Hippocampal Brain Volume Is Associated with Faster Facial Emotion Identification in Older Adults: Preliminary Results

    PubMed Central

    Szymkowicz, Sarah M.; Persson, Jonas; Lin, Tian; Fischer, Håkan; Ebner, Natalie C.

    2016-01-01

    Quick correct identification of facial emotions is highly relevant for successful social interactions. Research suggests that older, compared to young, adults experience increased difficulty with face and emotion processing skills. While functional neuroimaging studies suggest age differences in neural processing of faces and emotions, evidence about age-associated structural brain changes and their involvement in face and emotion processing is scarce. Using structural magnetic resonance imaging (MRI), this study investigated the extent to which volumes of frontal and temporal brain structures were related to reaction time in accurate identification of facial emotions in 30 young and 30 older adults. Volumetric segmentation was performed using FreeSurfer and gray matter volumes from frontal and temporal regions were extracted. Analysis of covariances (ANCOVAs) models with response time (RT) as the dependent variable and age group and regional volume, and their interaction, as independent variables were conducted, controlling for total intracranial volume (ICV). Results indicated that, in older adults, larger hippocampal volumes were associated with faster correct facial emotion identification. These preliminary observations suggest that greater volume in brain regions associated with face and emotion processing contributes to improved facial emotion identification performance in aging.

  2. Hippocampal Brain Volume Is Associated with Faster Facial Emotion Identification in Older Adults: Preliminary Results

    PubMed Central

    Szymkowicz, Sarah M.; Persson, Jonas; Lin, Tian; Fischer, Håkan; Ebner, Natalie C.

    2016-01-01

    Quick correct identification of facial emotions is highly relevant for successful social interactions. Research suggests that older, compared to young, adults experience increased difficulty with face and emotion processing skills. While functional neuroimaging studies suggest age differences in neural processing of faces and emotions, evidence about age-associated structural brain changes and their involvement in face and emotion processing is scarce. Using structural magnetic resonance imaging (MRI), this study investigated the extent to which volumes of frontal and temporal brain structures were related to reaction time in accurate identification of facial emotions in 30 young and 30 older adults. Volumetric segmentation was performed using FreeSurfer and gray matter volumes from frontal and temporal regions were extracted. Analysis of covariances (ANCOVAs) models with response time (RT) as the dependent variable and age group and regional volume, and their interaction, as independent variables were conducted, controlling for total intracranial volume (ICV). Results indicated that, in older adults, larger hippocampal volumes were associated with faster correct facial emotion identification. These preliminary observations suggest that greater volume in brain regions associated with face and emotion processing contributes to improved facial emotion identification performance in aging. PMID:27610082

  3. Restraint Stress-Induced Morphological Changes at the Blood-Brain Barrier in Adult Rats

    PubMed Central

    Sántha, Petra; Veszelka, Szilvia; Hoyk, Zsófia; Mészáros, Mária; Walter, Fruzsina R.; Tóth, Andrea E.; Kiss, Lóránd; Kincses, András; Oláh, Zita; Seprényi, György; Rákhely, Gábor; Dér, András; Pákáski, Magdolna; Kálmán, János; Kittel, Ágnes; Deli, Mária A.

    2016-01-01

    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 recognized 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, occluding, 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, 1-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, cognitive and

  4. Restraint Stress-Induced Morphological Changes at the Blood-Brain Barrier in Adult Rats.

    PubMed

    Sántha, Petra; Veszelka, Szilvia; Hoyk, Zsófia; Mészáros, Mária; Walter, Fruzsina R; Tóth, Andrea E; Kiss, Lóránd; Kincses, András; Oláh, Zita; Seprényi, György; Rákhely, Gábor; Dér, András; Pákáski, Magdolna; Kálmán, János; Kittel, Ágnes; Deli, Mária A

    2015-01-01

    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 recognized 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, occluding, 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, 1-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, cognitive and

  5. Regulation of stroke-induced neurogenesis in adult brain--recent scientific progress.

    PubMed

    Kokaia, Zaal; Thored, Pär; Arvidsson, Andreas; Lindvall, Olle

    2006-07-01

    Stroke induced by middle cerebral artery occlusion in adult rodents induces the formation of new neurons in the damaged striatum, a region that normally does not show neurogenesis. Here we describe recent findings on the regulation of neurogenesis after stroke, in particular regarding the duration of the neurogenic response and the influence of age, as well as the molecular mechanisms influencing migration and survival of the new neurons. We also discuss some crucial issues that need to be addressed in the further exploration of this potential self-repair mechanism after damage to the adult brain. PMID:16766702

  6. Area-specific migration and recruitment of new neurons in the adult songbird brain.

    PubMed

    Vellema, Michiel; van der Linden, Annemie; Gahr, Manfred

    2010-05-01

    Neuron recruitment has been implicated in morphological and functional plasticity in the adult brain. Whereas mammals restrict neuron recruitment specifically to two regions of known plasticity, the hippocampus and olfactory bulb, newborn neurons are found throughout the forebrain of adult songbirds. In order to study the area-specificity of the widespread proliferation and recruitment in the songbird brain, six adult male canaries received repetitive intraperitoneal injections of the mitotic marker BrdU (5-bromo-2-deoxyuridine) and were sacrificed after 24 hours to study proliferation or after 38 days to study recruitment. Migration and incorporation of new neurons was apparent throughout many but not all parts of the canary forebrain and was quantitatively related to mitotic levels in the most closely associated proliferative zones. Surprisingly, some areas of the vocal control system sensitive to plastic changes, such as nucleus higher vocal center (HVC) and area X, recruited similar numbers of new neurons as their surrounding brain tissues, employing no specific directional mechanisms. The distribution pattern in and around HVC could best be described by a random displacement model, where cells originating from the overlying lateral ventricle can move independently in any direction. Other plastic song control areas, such as the medial magnocellular nucleus of anterior nidopallium and the robust nucleus of arcopallium, were specifically avoided by migrating neurons, while migration toward the olfactory bulb showed high specificity, similar to the mammalian rostral migratory stream. Thus, different mechanisms appear to organize area-specific neuron recruitment in different recipients of the adult songbird brain, unrelated to global plasticity of brain regions.

  7. Transcriptional profiling of adult neural stem-like cells from the human brain.

    PubMed

    Sandberg, Cecilie Jonsgar; Vik-Mo, Einar O; Behnan, Jinan; Helseth, Eirik; Langmoen, Iver A

    2014-01-01

    There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60). Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate). We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6), foetal human neural stem cells (n = 1) and human brain tissues (n = 12). The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular fate.

  8. Transcriptional Profiling of Adult Neural Stem-Like Cells from the Human Brain

    PubMed Central

    Sandberg, Cecilie Jonsgar; Vik-Mo, Einar O.; Behnan, Jinan; Helseth, Eirik; Langmoen, Iver A.

    2014-01-01

    There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33–60). Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate). We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6), foetal human neural stem cells (n = 1) and human brain tissues (n = 12). The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular fate. PMID

  9. Functional brain connectivity and cognition: effects of adult age and task demands.

    PubMed

    Chou, Ying-Hui; Chen, Nan-Kuei; Madden, David J

    2013-08-01

    Previous neuroimaging research has documented that patterns of intrinsic (resting state) functional connectivity (FC) among brain regions covary with individual measures of cognitive performance. Here, we examined the relation between intrinsic FC and a reaction time (RT) measure of performance, as a function of age group and task demands. We obtained filtered, event-related functional magnetic resonance imaging data, and RT measures of visual search performance, from 21 younger adults (19-29 years old) and 21 healthy, older adults (60-87 years old). Age-related decline occurred in the connectivity strength in multiple brain regions, consistent with previous findings. Among 8 pairs of regions, across somatomotor, orbitofrontal, and subcortical networks, increasing FC was associated with faster responding (lower RT). Relative to younger adults, older adults exhibited a lower strength of this RT-connectivity relation and greater disruption of this relation by a salient but irrelevant display item (color singleton distractor). Age-related differences in the covariation of intrinsic FC and cognitive performance vary as a function of task demands.

  10. Eph Receptor and Ephrin Signaling in Developing and Adult Brain of the Honeybee (Apis mellifera)

    PubMed Central

    Vidovic, Maria; Nighorn, Alan; Koblar, Simon; Maleszka, Ryszard

    2007-01-01

    Roles for Eph receptor tyrosine kinase and ephrin signaling in vertebrate brain development are well established. Their involvement in the modulation of mammalian synaptic structure and physiology is also emerging. However, less is known of their effects on brain development and their function in adult invertebrate nervous systems. Here, we report on the characterization of Eph receptor and ephrin orthologs in the honeybee, Apis mellifera (Am), and their role in learning and memory. In situ hybridization for mRNA expression showed a uniform distribution of expression of both genes across the developing pupal and adult brain. However, in situ labeling with Fc fusion proteins indicated that the AmEphR and Amephrin proteins were differentially localized to cell body regions in the mushroom bodies and the developing neuropiles of the antennal and optic lobes. In adults, AmEphR protein was localized to regions of synaptic contacts in optic lobes, in the glomeruli of antennal lobes, and in the medial lobe of the mushroom body. The latter two regions are involved in olfactory learning and memory in the honeybee. Injections of EphR-Fc and ephrin-Fc proteins into the brains of adult bees, 1 h before olfactory conditioning of the proboscis extension reflex, sig-nificantly reduced memory 24 h later. Experimental amnesia in the group injected with ephrin-Fc was apparent 1 h post-training. Experimental amnesia was also induced by post-training injections with ephrin-Fc suggesting a role in recall. This is the first demonstration that Eph molecules function to regulate the formation of memory in insects. PMID:17443785

  11. Regional brain responses in nulliparous women to emotional infant stimuli.

    PubMed

    Montoya, Jessica L; Landi, Nicole; Kober, Hedy; Worhunsky, Patrick D; Rutherford, Helena J V; Mencl, W Einar; Mayes, Linda C; Potenza, Marc N

    2012-01-01

    Infant cries and facial expressions influence social interactions and elicit caretaking behaviors from adults. Recent neuroimaging studies suggest that neural responses to infant stimuli involve brain regions that process rewards. However, these studies have yet to investigate individual differences in tendencies to engage or withdraw from motivationally relevant stimuli. To investigate this, we used event-related fMRI to scan 17 nulliparous women. Participants were presented with novel infant cries of two distress levels (low and high) and unknown infant faces of varying affect (happy, sad, and neutral) in a randomized, counter-balanced order. Brain activation was subsequently correlated with scores on the Behavioral Inhibition System/Behavioral Activation System scale. Infant cries activated bilateral superior and middle temporal gyri (STG and MTG) and precentral and postcentral gyri. Activation was greater in bilateral temporal cortices for low- relative to high-distress cries. Happy relative to neutral faces activated the ventral striatum, caudate, ventromedial prefrontal, and orbitofrontal cortices. Sad versus neutral faces activated the precuneus, cuneus, and posterior cingulate cortex, and behavioral activation drive correlated with occipital cortical activations in this contrast. Behavioral inhibition correlated with activation in the right STG for high- and low-distress cries relative to pink noise. Behavioral drive correlated inversely with putamen, caudate, and thalamic activations for the comparison of high-distress cries to pink noise. Reward-responsiveness correlated with activation in the left precentral gyrus during the perception of low-distress cries relative to pink noise. Our findings indicate that infant cry stimuli elicit activations in areas implicated in auditory processing and social cognition. Happy infant faces may be encoded as rewarding, whereas sad faces activate regions associated with empathic processing. Differences in motivational

  12. Adult neurogenesis and cellular brain repair with neural progenitors, precursors and stem cells

    PubMed Central

    Shivraj Sohur, U; Emsley, Jason G; Mitchell, Bartley D; Macklis, Jeffrey D

    2006-01-01

    Recent work in neuroscience has shown that the adult central nervous system (CNS) contains neural progenitors, precursors and stem cells that are capable of generating new neurons, astrocytes and oligodendrocytes. While challenging the previous dogma that no new neurons are born in the adult mammalian CNS, these findings bring with them the future possibilities for development of novel neural repair strategies. The purpose of this review is to present the current knowledge about constitutively occurring adult mammalian neurogenesis, highlight the critical differences between ‘neurogenic’ and ‘non-neurogenic’ regions in the adult brain, and describe the cardinal features of two well-described neurogenic regions—the subventricular zone/olfactory bulb system and the dentate gyrus of the hippocampus. We also provide an overview of presently used models for studying neural precursors in vitro, mention some precursor transplantation models and emphasize that, in this rapidly growing field of neuroscience, one must be cautious with respect to a variety of methodological considerations for studying neural precursor cells both in vitro and in vivo. The possibility of repairing neural circuitry by manipulating neurogenesis is an intriguing one, and, therefore, we also review recent efforts to understand the conditions under which neurogenesis can be induced in non-neurogenic regions of the adult CNS. This work aims towards molecular and cellular manipulation of endogenous neural precursors in situ, without transplantation. We conclude this review with a discussion of what might be the function of newly generated neurons in the adult brain, and provide a summary of present thinking about the consequences of disturbed adult neurogenesis and the reaction of neurogenic regions to disease. PMID:16939970

  13. Regional brain monitoring in the neurocritical care unit.

    PubMed

    Frontera, Jennifer; Ziai, Wendy; O'Phelan, Kristine; Leroux, Peter D; Kirkpatrick, Peter J; Diringer, Michael N; Suarez, Jose I

    2015-06-01

    Regional multimodality monitoring has evolved over the last several years as a tool to understand the mechanisms of brain injury and brain function at the cellular level. Multimodality monitoring offers an important augmentation to the clinical exam and is especially useful in comatose neurocritical care patients. Cerebral microdialysis, brain tissue oxygen monitoring, and cerebral blood flow monitoring all offer insight into permutations in brain chemistry and function that occur in the context of brain injury. These tools may allow for development of individual therapeutic strategies that are mechanistically driven and goal-directed. We present a summary of the discussions that took place during the Second Neurocritical Care Research Conference regarding regional brain monitoring.

  14. Regional brain monitoring in the neurocritical care unit.

    PubMed

    Frontera, Jennifer; Ziai, Wendy; O'Phelan, Kristine; Leroux, Peter D; Kirkpatrick, Peter J; Diringer, Michael N; Suarez, Jose I

    2015-06-01

    Regional multimodality monitoring has evolved over the last several years as a tool to understand the mechanisms of brain injury and brain function at the cellular level. Multimodality monitoring offers an important augmentation to the clinical exam and is especially useful in comatose neurocritical care patients. Cerebral microdialysis, brain tissue oxygen monitoring, and cerebral blood flow monitoring all offer insight into permutations in brain chemistry and function that occur in the context of brain injury. These tools may allow for development of individual therapeutic strategies that are mechanistically driven and goal-directed. We present a summary of the discussions that took place during the Second Neurocritical Care Research Conference regarding regional brain monitoring. PMID:25832349

  15. An anatomic gene expression atlas of the adult mouse brain.

    PubMed

    Ng, Lydia; Bernard, Amy; Lau, Chris; Overly, Caroline C; Dong, Hong-Wei; Kuan, Chihchau; Pathak, Sayan; Sunkin, Susan M; Dang, Chinh; Bohland, Jason W; Bokil, Hemant; Mitra, Partha P; Puelles, Luis; Hohmann, John; Anderson, David J; Lein, Ed S; Jones, Allan R; Hawrylycz, Michael

    2009-03-01

    Studying gene expression provides a powerful means of understanding structure-function relationships in the nervous system. The availability of genome-scale in situ hybridization datasets enables new possibilities for understanding brain organization based on gene expression patterns. The Anatomic Gene Expression Atlas (AGEA) is a new relational atlas revealing the genetic architecture of the adult C57Bl/6J mouse brain based on spatial correlations across expression data for thousands of genes in the Allen Brain Atlas (ABA). The AGEA includes three discovery tools for examining neuroanatomical relationships and boundaries: (1) three-dimensional expression-based correlation maps, (2) a hierarchical transcriptome-based parcellation of the brain and (3) a facility to retrieve from the ABA specific genes showing enriched expression in local correlated domains. The utility of this atlas is illustrated by analysis of genetic organization in the thalamus, striatum and cerebral cortex. The AGEA is a publicly accessible online computational tool integrated with the ABA (http://mouse.brain-map.org/agea). PMID:19219037

  16. Decoding Brain States Based on Magnetoencephalography From Prespecified Cortical Regions.

    PubMed

    Zhang, Jinyin; Li, Xin; Foldes, Stephen T; Wang, Wei; Collinger, Jennifer L; Weber, Douglas J; Bagić, Anto

    2016-01-01

    Brain state decoding based on whole-head MEG has been extensively studied over the past decade. Recent MEG applications pose an emerging need of decoding brain states based on MEG signals originating from prespecified cortical regions. Toward this goal, we propose a novel region-of-interest-constrained discriminant analysis algorithm (RDA) in this paper. RDA integrates linear classification and beamspace transformation into a unified framework by formulating a constrained optimization problem. Our experimental results based on human subjects demonstrate that RDA can efficiently extract the discriminant pattern from prespecified cortical regions to accurately distinguish different brain states.

  17. The functional organisation of glia in the adult brain of Drosophila and other insects

    PubMed Central

    Edwards, Tara N.; Meinertzhagen, Ian A.

    2010-01-01

    This review annotates and categorises the glia of adult Drosophila and other model insects and describes the developmental origins of these in the Drosophila optic lobe. The functions of glia in the adult vary depending upon their sub-type and location in the brain. The task of annotating glia is essentially complete only for the glia of the fly's lamina, which comprise: two types of surface glia - the pseudocartridge and fenestrated glia; two types of cortex glia - the distal and proximal satellite glia; and two types of neuropile glia - the epithelial and marginal glia. We advocate that the term subretinal glia, as used to refer to both pseudocartridge and fenestrated glia, be abandoned. Other neuropiles contain similar glial subtypes, but other than the antennal lobes these have not been described in detail. Surface glia form the blood brain barrier, regulating the flow of substances into and out of the nervous system, both for the brain as a whole and the optic neuropiles in particular. Cortex glia provide a second level of barrier, wrapping axon fascicles and isolating neuronal cell bodies both from neighbouring brain regions and from their underlying neuropiles. Neuropile glia can be generated in the adult and a subtype, ensheathing glia, are responsible for cleaning up cellular debris during Wallerian degeneration. Both the neuropile ensheathing and astrocyte-like glia may be involved in clearing neurotransmitters from the extracellular space, thus modifying the levels of histamine, glutamate and possibly dopamine at the synapse to ultimately affect behaviour. PMID:20109517

  18. A revised dosimetric model of the adult head and brain

    SciTech Connect

    Bouchet, L.G.; Bolch, W.E.; Weber, D.A.; Atkins, H.L.; Poston, J.W. ||

    1996-07-01

    During the last decade, several new radiopharmaceuticals have been introduced for brain imaging. The marked differences of these tracers in tissue specificicity within the brain and their increasing use for diagnostic studies support the need for a more antihropomorphic model of the human brain and head. Brain and head models developed in the past have comprised only simplistic representations of this anatomic region. A new brain model has been developed which includes eight subregions: the caudate nucleus, the cerebellium, the cerebral cortex, the lateral ventricles, the lentiform nucleus, the thalamus, the third ventricle and the white matter. This brain model has been included within a slightly modified version of the head model developed by Poston et al. in 1984. The head model, which includes both the thyroid and eyes, was modified in this work to include the cerebrospinal fluid within the cranial and spinal regions. Absorbed fractions of energy for photon and electron sources located in thirteen source regions within the new head model were calculated using the EGS4 Monte Carlo radiation transport code for radiations in the energy range 10 keV to 4 MeV. S-values were calculated for five radionuclides used in brain imaging ({sup 11}C, {sup 15}O, {sup 18}F, {sup 99m}Tc and {sup 123}I) and for three radionuclides showing selective uptake in the thyroid ({sup 99m}Tc, {sup 123}I, and {sup 131}I). S-values were calculated using 100 discrete energy points in the beta-emission spectrum of the different radionuclides. 17 refs., 14 figs., 3 tabs.

  19. Regional deconvolution method for partial volume correction in brain PET

    NASA Astrophysics Data System (ADS)

    Rusinek, Henry; Tsui, Wai-Hon; de Leon, Mony J.

    2001-05-01

    Correction of PET images for partial volume effects (PVE) is of particular utility in studies of metabolism in brain aging and brain disorders. PVE is commonly corrected using voxel-by- voxel factors obtained from a high resolution brain mask (obtained from the coregistered MR scan), after convolution with the point spread function (PSF) of the imaging system. In a recently proposed regional deconvolution (RD) method, the observed regional activity is expressed as linear combinations of the true metabolic activity. The weights are obtained by integrating the PSF over the geometric extent of the brain regions. We have analyzed the accuracy of RD and two other PVE correction algorithms under a variety of conditions using simulated PET scans. Each of the brain regions was assigned a distribution of metabolic activity, with gray matter/white matter contrast representative of subjects in several age categories. Simulations were performed over a wide range of PET resolutions. The influence of PET/MR misregistration and heterogeneity of brain metabolism were also evaluated. Our results demonstrate the importance of correcting PET metabolic images for PVE. Without such correction, the regional brain activity values are contaminated with 30 - 40% errors. Under most conditions studied, the accuracy of RD and of the three- compartmental method were superior to the accuracy of the two- compartmental method. Our study provides the first demonstration of the feasibility of RD algorithm to provide accurate correction for a large number (n equals 109) of brain compartments. PVE correction methods appear to be promising tools in studies of metabolism in normal brain, brain aging, and brain disorders.

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

    PubMed

    Zhang, Kuan; Zhou, Yanzhao; Zhao, Tong; Wu, Liying; Huang, Xin; Wu, Kuiwu; Xu, Lun; Li, Dahu; Liu, Shuhong; Zhao, Yongqi; Fan, Ming; Zhu, Lingling

    2015-01-01

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

  1. Resting state fMRI entropy probes complexity of brain activity in adults with ADHD.

    PubMed

    Sokunbi, Moses O; Fung, Wilson; Sawlani, Vijay; Choppin, Sabine; Linden, David E J; Thome, Johannes

    2013-12-30

    In patients with attention deficit hyperactivity disorder (ADHD), quantitative neuroimaging techniques have revealed abnormalities in various brain regions, including the frontal cortex, striatum, cerebellum, and occipital cortex. Nonlinear signal processing techniques such as sample entropy have been used to probe the regularity of brain magnetoencephalography signals in patients with ADHD. In the present study, we extend this technique to analyse the complex output patterns of the 4 dimensional resting state functional magnetic resonance imaging signals in adult patients with ADHD. After adjusting for the effect of age, we found whole brain entropy differences (P=0.002) between groups and negative correlation (r=-0.45) between symptom scores and mean whole brain entropy values, indicating lower complexity in patients. In the regional analysis, patients showed reduced entropy in frontal and occipital regions bilaterally and a significant negative correlation between the symptom scores and the entropy maps at a family-wise error corrected cluster level of P<0.05 (P=0.001, initial threshold). Our findings support the hypothesis of abnormal frontal-striatal-cerebellar circuits in ADHD and the suggestion that sample entropy is a useful tool in revealing abnormalities in the brain dynamics of patients with psychiatric disorders.

  2. A detailed viscoelastic characterization of the P17 and adult rat brain.

    PubMed

    Elkin, Benjamin S; Ilankovan, Ashok I; Morrison, Barclay

    2011-11-01

    Brain is a morphologically and mechanically heterogeneous organ. Although rat brain is commonly used as an experimental neurophysiological model for various in vivo biomechanical studies, little is known about its regional viscoelastic properties. To address this issue, we have generated viscoelastic mechanical property data for specific anatomical regions of the P17 and adult rat brain. These ages are commonly used in rat experimental models. We measured mechanical properties of both white and gray matter regions in coronal slices with a custom-designed microindentation device performing stress-relaxation indentations to 10% effective strain. Shear moduli calculated for short (100?ms), intermediate (1?sec), and long (20?sec) time points, ranged from ?1?kPa for short term moduli to ?0.4?kPa for long term moduli. Both age and anatomic region were significant factors affecting the time-dependent shear modulus. White matter regions and regions of the cerebellum were much more compliant than those of the hippocampus, cortex, and thalamus. Linear viscoelastic models (Prony series, continuous phase lag, and a power law model) were fit to the time-dependent shear modulus data. All models fit the data equally with no significant differences between them (F-test; p>0.05). The F-test was also used to statistically determine that a Prony series with three time-dependent parameters accurately fit the data with no added benefit from additional terms. The age- and region-dependent rat brain viscoelastic properties presented here will help inform future biomechanical models of the rat brain with specific and accurate regional mechanical property data. PMID:21341982

  3. A Telephone Based Regional Adult Education Information Service.

    ERIC Educational Resources Information Center

    Eyler, David R.

    This report describes a cooperative project designed to inform area residents of available adult education opportunities and to establish a central information contact point. The regional Adult Education Coordinating Committee compiled a list of adult education courses and services offered by member institutions, devised newspaper and radio…

  4. Acute moderate exercise enhances compensatory brain activation in older adults.

    PubMed

    Hyodo, Kazuki; Dan, Ippeita; Suwabe, Kazuya; Kyutoku, Yasushi; Yamada, Yuhki; Akahori, Mitsuya; Byun, Kyeongho; Kato, Morimasa; Soya, Hideaki

    2012-11-01

    A growing number of reports state that regular exercise enhances brain function in older adults. Recently a functional near-infrared spectroscopy (fNIRS) study revealed that an acute bout of moderate exercise enhanced activation of the left dorsolateral prefrontal cortex (L-DLPFC) associated with Stroop interference in young adults. Whether this acute effect is also applicable to older adults was examined. Sixteen older adults performed a color-word matching Stroop task before and after 10 minutes of exercise on a cycle ergometer at a moderate intensity. Cortical hemodynamics of the prefrontal area was monitored with a fNIRS during the Stroop task. We analyzed Stroop interference (incongruent-neutral) as Stroop performance. Though activation for Stroop interference was found in the bilateral prefrontal area before the acute bout of exercise, activation of the right frontopolar area (R-FPA) was enhanced after exercise. In the majority of participants, this coincided with improved performance reflected in Stroop interference results. Thus, an acute bout of moderate exercise improved Stroop performance in older adults, and this was associated with contralateral compensatory activation. PMID:22300952

  5. Acute moderate exercise enhances compensatory brain activation in older adults.

    PubMed

    Hyodo, Kazuki; Dan, Ippeita; Suwabe, Kazuya; Kyutoku, Yasushi; Yamada, Yuhki; Akahori, Mitsuya; Byun, Kyeongho; Kato, Morimasa; Soya, Hideaki

    2012-11-01

    A growing number of reports state that regular exercise enhances brain function in older adults. Recently a functional near-infrared spectroscopy (fNIRS) study revealed that an acute bout of moderate exercise enhanced activation of the left dorsolateral prefrontal cortex (L-DLPFC) associated with Stroop interference in young adults. Whether this acute effect is also applicable to older adults was examined. Sixteen older adults performed a color-word matching Stroop task before and after 10 minutes of exercise on a cycle ergometer at a moderate intensity. Cortical hemodynamics of the prefrontal area was monitored with a fNIRS during the Stroop task. We analyzed Stroop interference (incongruent-neutral) as Stroop performance. Though activation for Stroop interference was found in the bilateral prefrontal area before the acute bout of exercise, activation of the right frontopolar area (R-FPA) was enhanced after exercise. In the majority of participants, this coincided with improved performance reflected in Stroop interference results. Thus, an acute bout of moderate exercise improved Stroop performance in older adults, and this was associated with contralateral compensatory activation.

  6. Role of astrocytes as neural stem cells in the adult brain

    PubMed Central

    Gonzalez-Perez, Oscar; Quiñones-Hinojosa, Alfredo

    2012-01-01

    In the adult mammalian brain, bona fide neural stem cells were discovered in the subventricular zone (SVZ), the largest neurogenic niche lining the striatal wall of the lateral ventricles of the brain. In this region resides a subpopulation of astrocytes that express the glial fibrillary acidic protein (GFAP), nestin and LeX. Astonishingly, these GFAP-expressing progenitors display stem-cell-like features both in vivo and in vitro. Throughout life SVZ astrocytes give rise to interneurons and oligodendrocyte precursors, which populate the olfactory bulb and the white matter, respectively. The role of the progenies of SVZ astrocytes has not been fully elucidated, but some evidence indicates that the new neurons play a role in olfactory discrimination, whereas oligodendrocytes contribute to myelinate white matter tracts. In this chapter, we describe the astrocytic nature of adult neural stem cells, their organization into the SVZ and some of their molecular and genetic characteristics. PMID:23619383

  7. Neuroimaging in adult penetrating brain injury: a guide for radiographers

    PubMed Central

    Temple, Nikki; Donald, Cortny; Skora, Amanda; Reed, Warren

    2015-01-01

    Penetrating brain injuries (PBI) are a medical emergency, often resulting in complex damage and high mortality rates. Neuroimaging is essential to evaluate the location and extent of injuries, and to manage them accordingly. Currently, a myriad of imaging modalities are included in the diagnostic workup for adult PBI, including skull radiography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, with each modality providing their own particular benefits. This literature review explores the current modalities available for investigating PBI and aims to assist in decision making for the appropriate use of diagnostic imaging when presented with an adult PBI. Based on the current literature, the authors have developed an imaging pathway for adult penetrating brain injury that functions as both a learning tool and reference guide for radiographers and other health professionals. Currently, CT is recommended as the imaging modality of choice for the initial assessment of PBI patients, while MRI is important in the sub-acute setting where it aids prognosis prediction and rehabilitation planning, Additional follow-up imaging, such as angiography, should be dependent upon clinical findings. PMID:26229677

  8. Neuroimaging in adult penetrating brain injury: a guide for radiographers

    SciTech Connect

    Temple, Nikki; Donald, Cortny; Skora, Amanda; Reed, Warren

    2015-06-15

    Penetrating brain injuries (PBI) are a medical emergency, often resulting in complex damage and high mortality rates. Neuroimaging is essential to evaluate the location and extent of injuries, and to manage them accordingly. Currently, a myriad of imaging modalities are included in the diagnostic workup for adult PBI, including skull radiography, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, with each modality providing their own particular benefits. This literature review explores the current modalities available for investigating PBI and aims to assist in decision making for the appropriate use of diagnostic imaging when presented with an adult PBI. Based on the current literature, the authors have developed an imaging pathway for adult penetrating brain injury that functions as both a learning tool and reference guide for radiographers and other health professionals. Currently, CT is recommended as the imaging modality of choice for the initial assessment of PBI patients, while MRI is important in the sub-acute setting where it aids prognosis prediction and rehabilitation planning, Additional follow-up imaging, such as angiography, should be dependent upon clinical findings.

  9. Indices of Regional Brain Atrophy: Formulae and Nomenclature.

    PubMed

    Menendez, Manuel; Arias-Carrión, Oscar

    2015-08-01

    The pattern of brain atrophy helps to discriminate normal age-related changes from neurodegenerative diseases. Albeit indices of regional brain atrophy have proven to be a parameter useful in the early diagnosis and differential diagnosis of some neurodegenerative diseases, indices of absolute regional atrophy still have some important limitations. We propose using indices of relative atrophy for representing how the volume of a given region of interest (ROI) changes over time in comparison to changes in global brain measures over the same time. A second problem in morphometric studies is terminology. There is a lack of systematization naming indices and the same measure can be named with different terms by different research groups or imaging softwares. This limits the understanding and discussion of studies. In this technological report, we provide a general description on how to compute indices of absolute and relative regional brain atrophy and propose a standardized nomenclature. PMID:26261753

  10. Indices of Regional Brain Atrophy: Formulae and Nomenclature

    PubMed Central

    Arias-Carrión, Oscar

    2015-01-01

    The pattern of brain atrophy helps to discriminate normal age-related changes from neurodegenerative diseases. Albeit indices of regional brain atrophy have proven to be a parameter useful in the early diagnosis and differential diagnosis of some neurodegenerative diseases, indices of absolute regional atrophy still have some important limitations. We propose using indices of relative atrophy for representing how the volume of a given region of interest (ROI) changes over time in comparison to changes in global brain measures over the same time. A second problem in morphometric studies is terminology. There is a lack of systematization naming indices and the same measure can be named with different terms by different research groups or imaging softwares. This limits the understanding and discussion of studies. In this technological report, we provide a general description on how to compute indices of absolute and relative regional brain atrophy and propose a standardized nomenclature. PMID:26261753

  11. Moral values are associated with individual differences in regional brain volume

    PubMed Central

    Lewis, G. J.; Kanai, R.; Bates, T. C.; Rees, G.

    2012-01-01

    Moral sentiment has been hypothesized to reflect evolved adaptations to social living. If so, individual differences in moral values may relate to regional variation in brain structure. We tested this hypothesis in a sample of 70 young, healthy adults examining whether differences on two major dimensions of moral values were significantly associated with regional gray matter volume. The two clusters of moral values assessed were “individualizing” (values of harm/care and fairness), and “binding” (deference to authority, in-group loyalty, and purity/sanctity). Individualizing was positively associated with left dorsomedial prefrontal cortex volume, and negatively associated with bilateral precuneus volume. For binding, a significant positive association was found for bilateral subcallosal gyrus and a trend to significance for the left anterior insula volume. These findings demonstrate that variation in moral sentiment reflects individual differences in brain structure and suggest a biological basis for moral sentiment, distributed across multiple brain regions. PMID:22571458

  12. REGULATION OF NETRIN-1 RECEPTORS BY AMPHETAMINE IN THE ADULT BRAIN

    PubMed Central

    YETNIKOFF, L.; LABELLE-DUMAIS, C.; FLORES, C.

    2016-01-01

    Netrin-1 is a guidance cue molecule fundamental to the organization of neuronal connectivity during development. Netrin-1 and its receptors, deleted in colorectal cancer (DCC) and UNC-5 homologues (UNC-5), continue to be expressed in the adult brain, although neither their function nor the kinds of events that activate their expression are known. Two lines of evidence suggest a role for netrin-1 in amphetamine-induced dopamine plasticity in the adult. First, DCC is highly expressed by adult dopamine neurons. Second, adult mice with reduced DCC levels do not develop amphetamine-induced behavioral sensitization. To explore the role of netrin-1 in amphetamine-induced plasticity, we examined the effects of sensitizing treatment regimens of amphetamine on DCC and/or UNC-5 protein expression in the adult rat. These treatments produced striking and enduring increases in DCC and UNC-5 expression in the cell body, but not terminal regions, of the mesocorticolimbic dopamine system. Notably, neuroadaptations in the cell body region of mesocorticolimbic dopamine neurons underlie the development of sensitization to the effects of amphetamine. Furthermore, these localized amphetamine-induced changes were prevented by co-treatment with an N-methyl-D-aspartate receptor antagonist, a treatment known to block the development of amphetamine-induced sensitization of behavioral activation, dopamine release and motivated behavior. Using immunohistochemistry, we showed that both DCC and UNC-5 receptors are highly expressed by adult mesocorticolimbic dopamine neurons. These results provide the first evidence that repeated exposure to a stimulant drug such as amphetamine affects netrin-1 receptor expression in the adult brain. Taken together, our findings suggest that changes in netrin-1 receptor expression may play a role in the lasting effects of exposure to amphetamine and other stimulant drugs. PMID:17996376

  13. Leptin replacement alters brain response to food cues in genetically leptin-deficient adults

    PubMed Central

    Baicy, Kate; London, Edythe D.; Monterosso, John; Wong, Ma-Li; Delibasi, Tuncay; Sharma, Anil; Licinio, Julio

    2007-01-01

    A missense mutation in the ob gene causes leptin deficiency and morbid obesity. Leptin replacement to three adults with this mutation normalized body weight and eating behavior. Because the neural circuits mediating these changes were unknown, we paired functional magnetic resonance imaging (fMRI) with presentation of food cues to these subjects. During viewing of food-related stimuli, leptin replacement reduced brain activation in regions linked to hunger (insula, parietal and temporal cortex) while enhancing activation in regions linked to inhibition and satiety (prefrontal cortex). Leptin appears to modulate feeding behavior through these circuits, suggesting therapeutic targets for human obesity. PMID:17986612

  14. Astaxanthin reduces ischemic brain injury in adult rats.

    PubMed

    Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N; Post, Jeremy; Woods, Amina S; Hoffer, Barry J; Wang, Yun; Harvey, Brandon K

    2009-06-01

    Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events. PMID:19218497

  15. Astaxanthin reduces ischemic brain injury in adult rats.

    PubMed

    Shen, Hui; Kuo, Chi-Chung; Chou, Jenny; Delvolve, Alice; Jackson, Shelley N; Post, Jeremy; Woods, Amina S; Hoffer, Barry J; Wang, Yun; Harvey, Brandon K

    2009-06-01

    Astaxanthin (ATX) is a dietary carotenoid of crustaceans and fish that contributes to their coloration. Dietary ATX is important for development and survival of salmonids and crustaceans and has been shown to reduce cardiac ischemic injury in rodents. The purpose of this study was to examine whether ATX can protect against ischemic injury in the mammalian brain. Adult rats were injected intracerebroventricularly with ATX or vehicle prior to a 60-min middle cerebral artery occlusion (MCAo). ATX was present in the infarction area at 70-75 min after onset of MCAo. Treatment with ATX, compared to vehicle, increased locomotor activity in stroke rats and reduced cerebral infarction at 2 d after MCAo. To evaluate the protective mechanisms of ATX against stroke, brain tissues were assayed for free radical damage, apoptosis, and excitoxicity. ATX antagonized ischemia-mediated loss of aconitase activity and reduced glutamate release, lipid peroxidation, translocation of cytochrome c, and TUNEL labeling in the ischemic cortex. ATX did not alter physiological parameters, such as body temperature, brain temperature, cerebral blood flow, blood gases, blood pressure, and pH. Collectively, our data suggest that ATX can reduce ischemia-related injury in brain tissue through the inhibition of oxidative stress, reduction of glutamate release, and antiapoptosis. ATX may be clinically useful for patients vulnerable or prone to ischemic events.

  16. Antenatal Maternal Stress Alters Functional Brain Responses In Adult Offspring During Conditioned Fear

    PubMed Central

    Sadler, Theodore R.; Nguyen, Peter T.; Yang, Jun; Givrad, Tina K.; Mayer, Emeran A.; Maarek, Jean-Michel I.; Hinton, David R.; Holschneider, Daniel P.

    2011-01-01

    Antenatal maternal stress has been shown in rodent models and in humans to result in altered behavioral and neuroendocrine responses, yet little is known about its effects on functional brain activation. Pregnant female rats received a daily foot-shock stress or sham-stress two days after testing plug-positive and continuing for the duration of their pregnancy. Adult male offspring (age 14 weeks) with and without prior maternal stress (MS) were exposed to an auditory fear conditioning (CF) paradigm. Cerebral blood flow (CBF) was assessed during recall of the tone cue in the nonsedated, nontethered animal using the 14C-iodoantipyrine method, in which the tracer was administered intravenously by remote activation of an implantable minipump. Regional CBF distribution was examined by autoradiography and analyzed by statistical parametric mapping in the three-dimensionally reconstructed brains. Presence of fear memory was confirmed by behavioral immobility (‘freezing’). Corticosterone plasma levels during the CF paradigm were measured by ELISA in a separate group of rats. Antenatal MS exposure altered functional brain responses to the fear conditioned cue in adult offspring. Rats with prior MS exposure compared to those without demonstrated heightened fear responsivity, exaggerated and prolonged corticosterone release, increased functional cerebral activation of limbic/paralimbic regions (amygdala, ventral hippocampus, insula, ventral striatum, nucleus acumbens), the locus coeruleus, and white matter, and deactivation of medial prefrontal cortical regions. Dysregulation of corticolimbic circuits may represent risk factors in the future development of anxiety disorders and associated alterations in emotional regulation. PMID:21300034

  17. Analysis of chaperone mRNA expression in the adult mouse brain by meta analysis of the Allen Brain Atlas.

    PubMed

    Tebbenkamp, Andrew T N; Borchelt, David R

    2010-10-28

    The pathology of many neurodegenerative diseases is characterized by the accumulation of misfolded and aggregated proteins in various cell types and regional substructures throughout the central and peripheral nervous systems. The accumulation of these aggregated proteins signals dysfunction of cellular protein homeostatic mechanisms such as the ubiquitin/proteasome system, autophagy, and the chaperone network. Although there are several published studies in which transcriptional profiling has been used to examine gene expression in various tissues, including tissues of neurodegenerative disease models, there has not been a report that focuses exclusively on expression of the chaperone network. In the present study, we used the Allen Brain Atlas online database to analyze chaperone expression levels. This database utilizes a quantitative in situ hybridization approach and provides data on 270 chaperone genes within many substructures of the adult mouse brain. We determined that 256 of these chaperone genes are expressed at some level. Surprisingly, relatively few genes, only 30, showed significant variations in levels of mRNA across different substructures of the brain. The greatest degree of variability was exhibited by genes of the DnaJ co-chaperone, Tetratricopeptide repeat, and the HSPH families. Our analysis provides a valuable resource towards determining how variations in chaperone gene expression may modulate the vulnerability of specific neuronal populations of mammalian brain.

  18. Regional growth and atlasing of the developing human brain.

    PubMed

    Makropoulos, Antonios; Aljabar, Paul; Wright, Robert; Hüning, Britta; Merchant, Nazakat; Arichi, Tomoki; Tusor, Nora; Hajnal, Joseph V; Edwards, A David; Counsell, Serena J; Rueckert, Daniel

    2016-01-15

    Detailed morphometric analysis of the neonatal brain is required to characterise brain development and define neuroimaging biomarkers related to impaired brain growth. Accurate automatic segmentation of neonatal brain MRI is a prerequisite to analyse large datasets. We have previously presented an accurate and robust automatic segmentation technique for parcellating the neonatal brain into multiple cortical and subcortical regions. In this study, we further extend our segmentation method to detect cortical sulci and provide a detailed delineation of the cortical ribbon. These detailed segmentations are used to build a 4-dimensional spatio-temporal structural atlas of the brain for 82 cortical and subcortical structures throughout this developmental period. We employ the algorithm to segment an extensive database of 420 MR images of the developing brain, from 27 to 45weeks post-menstrual age at imaging. Regional volumetric and cortical surface measurements are derived and used to investigate brain growth and development during this critical period and to assess the impact of immaturity at birth. Whole brain volume, the absolute volume of all structures studied, cortical curvature and cortical surface area increased with increasing age at scan. Relative volumes of cortical grey matter, cerebellum and cerebrospinal fluid increased with age at scan, while relative volumes of white matter, ventricles, brainstem and basal ganglia and thalami decreased. Preterm infants at term had smaller whole brain volumes, reduced regional white matter and cortical and subcortical grey matter volumes, and reduced cortical surface area compared with term born controls, while ventricular volume was greater in the preterm group. Increasing prematurity at birth was associated with a reduction in total and regional white matter, cortical and subcortical grey matter volume, an increase in ventricular volume, and reduced cortical surface area. PMID:26499811

  19. Injured brain regions associated with anxiety in Vietnam veterans.

    PubMed

    Knutson, Kristine M; Rakowsky, Shana T; Solomon, Jeffrey; Krueger, Frank; Raymont, Vanessa; Tierney, Michael C; Wassermann, Eric M; Grafman, Jordan

    2013-03-01

    Anxiety negatively affects quality of life and psychosocial functioning. Previous research has shown that anxiety symptoms in healthy individuals are associated with variations in the volume of brain regions, such as the amygdala, hippocampus, and the bed nucleus of the stria terminalis. Brain lesion data also suggests the hemisphere damaged may affect levels of anxiety. We studied a sample of 182 male Vietnam War veterans with penetrating brain injuries, using a semi-automated voxel-based lesion-symptom mapping (VLSM) approach. VLSM reveals significant associations between a symptom such as anxiety and the location of brain lesions, and does not require a broad, subjective assignment of patients into categories based on lesion location. We found that lesioned brain regions in cortical and limbic areas of the left hemisphere, including middle, inferior and superior temporal lobe, hippocampus, and fusiform regions, along with smaller areas in the inferior occipital lobe, parahippocampus, amygdala, and insula, were associated with increased anxiety symptoms as measured by the Neurobehavioral Rating Scale (NRS). These results were corroborated by similar findings using Neuropsychiatric Inventory (NPI) anxiety scores, which supports these regions' role in regulating anxiety. In summary, using a semi-automated analysis tool, we detected an effect of focal brain damage on the presentation of anxiety. We also separated the effects of brain injury and war experience by including a control group of combat veterans without brain injury. We compared this control group against veterans with brain lesions in areas associated with anxiety, and against veterans with lesions only in other brain areas. PMID:23328629

  20. Regional growth and atlasing of the developing human brain.

    PubMed

    Makropoulos, Antonios; Aljabar, Paul; Wright, Robert; Hüning, Britta; Merchant, Nazakat; Arichi, Tomoki; Tusor, Nora; Hajnal, Joseph V; Edwards, A David; Counsell, Serena J; Rueckert, Daniel

    2016-01-15

    Detailed morphometric analysis of the neonatal brain is required to characterise brain development and define neuroimaging biomarkers related to impaired brain growth. Accurate automatic segmentation of neonatal brain MRI is a prerequisite to analyse large datasets. We have previously presented an accurate and robust automatic segmentation technique for parcellating the neonatal brain into multiple cortical and subcortical regions. In this study, we further extend our segmentation method to detect cortical sulci and provide a detailed delineation of the cortical ribbon. These detailed segmentations are used to build a 4-dimensional spatio-temporal structural atlas of the brain for 82 cortical and subcortical structures throughout this developmental period. We employ the algorithm to segment an extensive database of 420 MR images of the developing brain, from 27 to 45weeks post-menstrual age at imaging. Regional volumetric and cortical surface measurements are derived and used to investigate brain growth and development during this critical period and to assess the impact of immaturity at birth. Whole brain volume, the absolute volume of all structures studied, cortical curvature and cortical surface area increased with increasing age at scan. Relative volumes of cortical grey matter, cerebellum and cerebrospinal fluid increased with age at scan, while relative volumes of white matter, ventricles, brainstem and basal ganglia and thalami decreased. Preterm infants at term had smaller whole brain volumes, reduced regional white matter and cortical and subcortical grey matter volumes, and reduced cortical surface area compared with term born controls, while ventricular volume was greater in the preterm group. Increasing prematurity at birth was associated with a reduction in total and regional white matter, cortical and subcortical grey matter volume, an increase in ventricular volume, and reduced cortical surface area.

  1. Doublecortin expression levels in adult brain reflect neurogenesis.

    PubMed

    Couillard-Despres, Sebastien; Winner, Beate; Schaubeck, Susanne; Aigner, Robert; Vroemen, Maurice; Weidner, Norbert; Bogdahn, Ulrich; Winkler, Jürgen; Kuhn, Hans-Georg; Aigner, Ludwig

    2005-01-01

    Progress in the field of neurogenesis is currently limited by the lack of tools enabling fast and quantitative analysis of neurogenesis in the adult brain. Doublecortin (DCX) has recently been used as a marker for neurogenesis. However, it was not clear whether DCX could be used to assess modulations occurring in the rate of neurogenesis in the adult mammalian central nervous system following lesioning or stimulatory factors. Using two paradigms increasing neurogenesis levels (physical activity and epileptic seizures), we demonstrate that quantification of DCX-expressing cells allows for an accurate measurement of modulations in the rate of adult neurogenesis. Importantly, we excluded induction of DCX expression during physiological or reactive gliogenesis and excluded also DCX re-expression during regenerative axonal growth. Our data validate DCX as a reliable and specific marker that reflects levels of adult neurogenesis and its modulation. We demonstrate that DCX is a valuable alternative to techniques currently used to measure the levels of neurogenesis. Importantly, in contrast to conventional techniques, analysis of neurogenesis through the detection of DCX does not require in vivo labelling of proliferating cells, thereby opening new avenues for the study of human neurogenesis under normal and pathological conditions. PMID:15654838

  2. Formal learning theory dissociates brain regions with different temporal integration.

    PubMed

    Gläscher, Jan; Büchel, Christian

    2005-07-21

    Learning can be characterized as the extraction of reliable predictions about stimulus occurrences from past experience. In two experiments, we investigated the interval of temporal integration of previous learning trials in different brain regions using implicit and explicit Pavlovian fear conditioning with a dynamically changing reinforcement regime in an experimental setting. With formal learning theory (the Rescorla-Wagner model), temporal integration is characterized by the learning rate. Using fMRI and this theoretical framework, we are able to distinguish between learning-related brain regions that show long temporal integration (e.g., amygdala) and higher perceptual regions that integrate only over a short period of time (e.g., fusiform face area, parahippocampal place area). This approach allows for the investigation of learning-related changes in brain activation, as it can dissociate brain areas that differ with respect to their integration of past learning experiences by either computing long-term outcome predictions or instantaneous reinforcement expectancies.

  3. Regional brain hypometabolism is unrelated to regional amyloid plaque burden.

    PubMed

    Altmann, Andre; Ng, Bernard; Landau, Susan M; Jagust, William J; Greicius, Michael D

    2015-12-01

    In its original form, the amyloid cascade hypothesis of Alzheimer's disease holds that fibrillar deposits of amyloid are an early, driving force in pathological events leading ultimately to neuronal death. Early clinicopathological investigations highlighted a number of inconsistencies leading to an updated hypothesis in which amyloid plaques give way to amyloid oligomers as the driving force in pathogenesis. Rather than focusing on the inconsistencies, amyloid imaging studies have tended to highlight the overlap between regions that show early amyloid plaque signal on positron emission tomography and that also happen to be affected early in Alzheimer's disease. Recent imaging studies investigating the regional dependency between metabolism and amyloid plaque deposition have arrived at conflicting results, with some showing regional associations and other not. We extracted multimodal neuroimaging data from the Alzheimer's disease neuroimaging database for 227 healthy controls and 434 subjects with mild cognitive impairment. We analysed regional patterns of amyloid deposition, regional glucose metabolism and regional atrophy using florbetapir ((18)F) positron emission tomography, (18)F-fluordeoxyglucose positron emission tomography and T1-weighted magnetic resonance imaging, respectively. Specifically, we derived grey matter density and standardized uptake value ratios for both positron emission tomography tracers in 404 functionally defined regions of interest. We examined the relation between regional glucose metabolism and amyloid plaques using linear models. For each region of interest, correcting for regional grey matter density, age, education and disease status, we tested the association of regional glucose metabolism with (i) cortex-wide florbetapir uptake; (ii) regional (i.e. in the same region of interest) florbetapir uptake; and (iii) regional florbetapir uptake while correcting in addition for cortex-wide florbetapir uptake. P-values for each setting

  4. ABAEnrichment: an R package to test for gene set expression enrichment in the adult and developing human brain

    PubMed Central

    Prüfer, Kay; Kelso, Janet; Dannemann, Michael

    2016-01-01

    Summary: We present ABAEnrichment, an R package that tests for expression enrichment in specific brain regions at different developmental stages using expression information gathered from multiple regions of the adult and developing human brain, together with ontologically organized structural information about the brain, both provided by the Allen Brain Atlas. We validate ABAEnrichment by successfully recovering the origin of gene sets identified in specific brain cell-types and developmental stages. Availability and Implementation: ABAEnrichment was implemented as an R package and is available under GPL (≥ 2) from the Bioconductor website (http://bioconductor.org/packages/3.3/bioc/html/ABAEnrichment.html). Contacts: steffi_grote@eva.mpg.de, kelso@eva.mpg.de or michael_dannemann@eva.mpg.de Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27354695

  5. On the relationship between cellular and hemodynamic properties of the human brain cortex throughout adult lifespan.

    PubMed

    Zhao, Yue; Wen, Jie; Cross, Anne H; Yablonskiy, Dmitriy A

    2016-06-01

    Establishing baseline MRI biomarkers for normal brain aging is significant and valuable for separating normal changes in the brain structure and function from different neurological diseases. In this paper for the first time we have simultaneously measured a variety of tissue specific contributions defining R2* relaxation of the gradient recalled echo (GRE) MRI signal in human brains of healthy adults (ages 22 to 74years) and related these measurements to tissue structural and functional properties. This was accomplished by separating tissue (R2t(⁎)) and extravascular BOLD contributions to the total tissue specific GRE MRI signal decay (R2(⁎)) using an advanced version of previously developed Gradient Echo Plural Contrast Imaging (GEPCI) approach and the acquisition and post-processing methods that allowed the minimization of artifacts related to macroscopic magnetic field inhomogeneities, and physiological fluctuations. Our data (20 healthy subjects) show that in most cortical regions R2t(⁎) increases with age while tissue hemodynamic parameters, i.e. relative oxygen extraction fraction (OEFrel), deoxygenated cerebral blood volume (dCBV) and tissue concentration of deoxyhemoglobin (Cdeoxy) remain practically constant. We also found the important correlations characterizing the relationships between brain structural and hemodynamic properties in different brain regions. Specifically, thicker cortical regions have lower R2t(⁎) and these regions have lower OEF. The comparison between GEPCI-derived tissue specific structural and functional metrics and literature information suggests that (a) regions in a brain characterized by higher R2t(⁎) contain higher concentration of neurons with less developed cellular processes (dendrites, spines, etc.), (b) regions in a brain characterized by lower R2t(⁎) represent regions with lower concentration of neurons but more developed cellular processes, and (c) the age-related increases in the cortical R2t(⁎) mostly

  6. The Ghosts of Brain States Past: Remembering Reactivates the Brain Regions Engaged during Encoding

    ERIC Educational Resources Information Center

    Danker, Jared F.; Anderson, John R.

    2010-01-01

    There is growing evidence that the brain regions involved in encoding an episode are partially reactivated when that episode is later remembered. That is, the process of remembering an episode involves literally returning to the brain state that was present during that episode. This article reviews studies of episodic and associative memory that…

  7. Evaluation of an automatic brain segmentation method developed for neonates on adult MR brain images

    NASA Astrophysics Data System (ADS)

    Moeskops, Pim; Viergever, Max A.; Benders, Manon J. N. L.; Išgum, Ivana

    2015-03-01

    Automatic brain tissue segmentation is of clinical relevance in images acquired at all ages. The literature presents a clear distinction between methods developed for MR images of infants, and methods developed for images of adults. The aim of this work is to evaluate a method developed for neonatal images in the segmentation of adult images. The evaluated method employs supervised voxel classification in subsequent stages, exploiting spatial and intensity information. Evaluation was performed using images available within the MRBrainS13 challenge. The obtained average Dice coefficients were 85.77% for grey matter, 88.66% for white matter, 81.08% for cerebrospinal fluid, 95.65% for cerebrum, and 96.92% for intracranial cavity, currently resulting in the best overall ranking. The possibility of applying the same method to neonatal as well as adult images can be of great value in cross-sectional studies that include a wide age range.

  8. Youthful Brains in Older Adults: Preserved Neuroanatomy in the Default Mode and Salience Networks Contributes to Youthful Memory in Superaging

    PubMed Central

    Sun, Felicia W.; Stepanovic, Michael R.; Andreano, Joseph

    2016-01-01

    Decline in cognitive skills, especially in memory, is often viewed as part of “normal” aging. Yet some individuals “age better” than others. Building on prior research showing that cortical thickness in one brain region, the anterior midcingulate cortex, is preserved in older adults with memory performance abilities equal to or better than those of people 20–30 years younger (i.e., “superagers”), we examined the structural integrity of two large-scale intrinsic brain networks in superaging: the default mode network, typically engaged during memory encoding and retrieval tasks, and the salience network, typically engaged during attention, motivation, and executive function tasks. We predicted that superagers would have preserved cortical thickness in critical nodes in these networks. We defined superagers (60–80 years old) based on their performance compared to young adults (18–32 years old) on the California Verbal Learning Test Long Delay Free Recall test. We found regions within the networks of interest where the cerebral cortex of superagers was thicker than that of typical older adults, and where superagers were anatomically indistinguishable from young adults; hippocampal volume was also preserved in superagers. Within the full group of older adults, thickness of a number of regions, including the anterior temporal cortex, rostral medial prefrontal cortex, and anterior midcingulate cortex, correlated with memory performance, as did the volume of the hippocampus. These results indicate older adults with youthful memory abilities have youthful brain regions in key paralimbic and limbic nodes of the default mode and salience networks that support attentional, executive, and mnemonic processes subserving memory function. SIGNIFICANCE STATEMENT Memory performance typically declines with age, as does cortical structural integrity, yet some older adults maintain youthful memory. We tested the hypothesis that superagers (older individuals with

  9. Eating disorder psychopathology, brain structure, neuropsychological correlates and risk mechanisms in very preterm young adults.

    PubMed

    Micali, Nadia; Kothari, Radha; Nam, Kie Woo; Gioroukou, Elena; Walshe, Muriel; Allin, Matthew; Rifkin, Larry; Murray, Robin M; Nosarti, Chiara

    2015-03-01

    This study investigates the prevalence of eating disorder (ED) psychopathology, neuropsychological function, structural brain correlates and risk mechanisms in a prospective cohort of very preterm (VPT) young adults. We assessed ED psychopathology and neuropsychological correlates in 143 cohort individuals born at <33 weeks of gestation. Structural brain correlates and risk factors at birth, in childhood and adolescence, were investigated using prospectively collected data throughout childhood/adolescence. VPT-born individuals had high levels of ED psychopathology at age 21 years. Executive function did not correlate with ED symptomatology. VPT adults presenting with ED psychopathology had smaller grey matter volume at age 14/15 years in the left posterior cerebellum and smaller white matter volume in the fusiform gyrus bilaterally, compared with VPT adults with no ED psychopathology. Caesarean delivery predicted engaging in compensatory behaviours, and severe eating difficulty at age 14 years predicted ED symptomatology in young adulthood. VPT individuals are at risk for ED symptomatology, with evidence of associated structural alterations in posterior brain regions. Further prospective studies are needed to clarify the pathways that lead from perinatal/obstetric complications to ED and relevant neurobiological mechanisms. © 2015 The Authors. European Eating Disorders Review published by John Wiley &Sons, Ltd.

  10. Brain changes in older adults at very low risk for Alzheimer's disease.

    PubMed

    Fjell, Anders M; McEvoy, Linda; Holland, Dominic; Dale, Anders M; Walhovd, Kristine B

    2013-05-01

    Alzheimer's disease (AD) has a slow onset, so it is challenging to distinguish brain changes in healthy elderly persons from incipient AD. One-year brain changes with a distinct frontotemporal pattern have been shown in older adults. However, it is not clear to what extent these changes may have been affected by undetected, early AD. To address this, we estimated 1-year atrophy by magnetic resonance imaging (MRI) in 132 healthy elderly persons who had remained free of diagnosed mild cognitive impairment or AD for at least 3 years. We found significant volumetric reductions throughout the brain. The sample was further divided into low-risk groups based on clinical, biomarker, genetic, or cognitive criteria. Although sample sizes varied, significant reductions were observed in all groups, with rates and topographical distribution of atrophy comparable to that of the full sample. Volume reductions were especially pronounced in the default mode network, closely matching the previously described frontotemporal pattern of changes in healthy aging. Atrophy in the hippocampus predicted change in memory, with no additional default mode network contributions. In conclusion, reductions in regional brain volumes can be detected over the course of 1 year even in older adults who are unlikely to be in a presymptomatic stage of AD.

  11. Regional distributions of brain glutamate and glutamine in normal subjects.

    PubMed

    Goryawala, Mohammed Z; Sheriff, Sulaiman; Maudsley, Andrew A

    2016-08-01

    Glutamate (Glu) and glutamine (Gln) play an important role in neuronal regulation and are of value as MRS-observable diagnostic biomarkers. In this study the relative concentrations of these metabolites have been measured in multiple regions in the normal brain using a short-TE whole-brain MRSI measurement at 3 T combined with a modified data analysis approach that used spatial averaging to obtain high-SNR spectra from atlas-registered anatomic regions or interest. By spectral fitting of high-SNR spectra this approach yielded reliable measurements across a wide volume of the brain. Spectral averaging also demonstrated increased SNR and improved fitting accuracy for the sum of Glu and Gln (Glx) compared with individual voxel fitting. Results in 26 healthy controls showed relatively constant Glu/Cr and Gln/Cr throughout the cerebrum, although with increased values in the anterior cingulum and paracentral lobule, and increased Gln/Cr in the superior motor area. The deep gray-matter regions of thalamus, putamen, and pallidum show lower Glu/Cr compared with cortical white-matter regions. Lobar measurements demonstrated reduced Glu/Cr and Gln/Cr in the cerebellum as compared with the cerebrum, where white-matter regions show significantly lower Glu/Cr and Gln/Cr as compared with gray-matter regions across multiple brain lobes. Regression analysis showed no significant effect of gender on Glu/Cr or Gln/Cr measurement; however, Glx/Cr ratio was found to be significantly negatively correlated with age in some lobar brain regions. In summary, this methodology provides the spectral quality necessary for reliable separation of Glu and Gln at 3 T from a single MRSI acquisition enabling generation of regional distributions of metabolites over a large volume of the brain, including cortical regions. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27351339

  12. Graph Theory Analysis of Functional Brain Networks and Mobility Disability in Older Adults

    PubMed Central

    Burdette, Jonathan H.; Morgan, Ashley R.; Williamson, Jeff D.; Kritchevsky, Stephen B.; Laurienti, Paul J.

    2014-01-01

    Background. The brain’s structural integrity is associated with mobility function in older adults. Changes in function may be evident earlier than changes in structure and may be more directly related to mobility. Therefore, we assessed whether functional brain networks varied with mobility function in older adults. Methods. Short Physical Performance Battery (SPPB) and resting state functional magnetic resonance imaging were collected on 24 young (mean age = 26.4±5.1) and 48 older (mean age = 72.04±5.1) participants. Older participants were divided into three groups by SPPB score: Low SPPB (score = 7–9), Mid SPPB (score = 10), High SPPB (score = 11–12).Graph theory–based methods were used to characterize and compare brain network organization. Results. Connectivity in the somatomotor cortex distinguished between groups based on SPPB score. The community structure of the somatomotor cortex was significantly less consistent in the Low SPPB group (mean = 0.097±0.05) compared with Young (mean = 0.163±0.09, p = .03) SPPB group. Striking differences were evident in second-order connections between somatomotor cortex and superior temporal gyrus and insula that reached statistical significance. The Low SPPB group (mean = 140.87±109.30) had a significantly higher number of connections than Young (mean = 45.05±33.79, p = .0003) or High (mean = 49.61±35.31, p = .002) SPPB group. Conclusions. Older adults with poorer mobility function exhibited reduced consistency of somatomotor community structure and a greater number of secondary connections with vestibular and multisensory regions of the brain. Further study is needed to fully interpret these effects, but analysis of functional brain networks adds new insights to the contribution of the brain to mobility. PMID:24717331

  13. Optimized heterologous transfection of viable adult organotypic brain slices using an enhanced gene gun

    PubMed Central

    2013-01-01

    Background Organotypic brain slices (OTBS) are an excellent experimental compromise between the facility of working with cell cultures and the biological relevance of using animal models where anatomical, morphological, and cellular function of specific brain regions can be maintained. The biological characteristics of OTBS can subsequently be examined under well-defined conditions. They do, however, have a number of limitations; most brain slices are derived from neonatal animals, as it is difficult to properly prepare and maintain adult OTBS. There are ample problems with tissue integrity as OTBS are delicate and frequently become damaged during the preparative stages. Notwithstanding these obstacles, the introduced exogenous proteins into both neuronal cells, and cells imbedded within tissues, have been consistently difficult to achieve. Results Following the ex vivo extraction of adult mouse brains, mounted inside a medium-agarose matrix, we have exploited a precise slicing procedure using a custom built vibroslicer. To transfect these slices we used an improved biolistic transfection method using a custom made low-pressure barrel and novel DNA-coated nanoparticles (40 nm), which are drastically smaller than traditional microparticles. These nanoparticles also minimize tissue damage as seen by a significant reduction in lactate dehydrogenase activity as well as propidium iodide (PI) and dUTP labelling compared to larger traditional gold particles used on these OTBS. Furthermore, following EYFP exogene delivery by gene gun, the 40 nm treated OTBS displayed a significantly larger number of viable NeuN and EYFP positive cells. These OTBS expressed the exogenous proteins for many weeks. Conclusions Our described methodology of producing OTBS, which results in better reproducibility with less tissue damage, permits the exploitation of mature fully formed adult brains for advanced neurobiological studies. The novel 40 nm particles are ideal for the viable

  14. Brain activation during visual working memory correlates with behavioral mobility performance in older adults.

    PubMed

    Kawagoe, Toshikazu; Suzuki, Maki; Nishiguchi, Shu; Abe, Nobuhito; Otsuka, Yuki; Nakai, Ryusuke; Yamada, Minoru; Yoshikawa, Sakiko; Sekiyama, Kaoru

    2015-01-01

    Functional mobility and cognitive function often decline with age. We previously found that functional mobility as measured by the Timed Up and Go Test (TUG) was associated with cognitive performance for visually-encoded (i.e., for location and face) working memory (WM) in older adults. This suggests a common neural basis between TUG and visual WM. To elucidate this relationship further, the present study aimed to examine the neural basis for the WM-mobility association. In accordance with the well-known neural compensation model in aging, we hypothesized that "attentional" brain activation for easy WM would increase in participants with lower mobility. The data from 32 healthy older adults were analyzed, including brain activation during easy WM tasks via functional Magnetic Resonance Imaging (fMRI) and mobility performance via both TUG and a simple walking test. WM performance was significantly correlated with TUG but not with simple walking. Some prefrontal brain activations during WM were negatively correlated with TUG performance, while positive correlations were found in subcortical structures including the thalamus, putamen and cerebellum. Moreover, activation of the subcortical regions was significantly correlated with WM performance, with less activation for lower WM performers. These results indicate that older adults with lower mobility used more cortical (frontal) and fewer subcortical resources for easy WM tasks. To date, the frontal compensation has been proposed separately in the motor and cognitive domains, which have been assumed to compensate for dysfunction of the other brain areas; however, such dysfunction was less clear in previous studies. The present study observed such dysfunction as degraded activation associated with lower performance, which was found in the subcortical regions. We conclude that a common dysfunction-compensation activation pattern is likely the neural basis for the association between visual WM and functional mobility.

  15. An empirical EEG analysis in brain death diagnosis for adults.

    PubMed

    Chen, Zhe; Cao, Jianting; Cao, Yang; Zhang, Yue; Gu, Fanji; Zhu, Guoxian; Hong, Zhen; Wang, Bin; Cichocki, Andrzej

    2008-09-01

    Electroencephalogram (EEG) is often used in the confirmatory test for brain death diagnosis in clinical practice. Because EEG recording and monitoring is relatively safe for the patients in deep coma, it is believed to be valuable for either reducing the risk of brain death diagnosis (while comparing other tests such as the apnea) or preventing mistaken diagnosis. The objective of this paper is to study several statistical methods for quantitative EEG analysis in order to help bedside or ambulatory monitoring or diagnosis. We apply signal processing and quantitative statistical analysis for the EEG recordings of 32 adult patients. For EEG signal processing, independent component analysis (ICA) was applied to separate the independent source components, followed by Fourier and time-frequency analysis. For quantitative EEG analysis, we apply several statistical complexity measures to the EEG signals and evaluate the differences between two groups of patients: the subjects in deep coma, and the subjects who were categorized as brain death. We report statistically significant differences of quantitative statistics with real-life EEG recordings in such a clinical study, and we also present interpretation and discussions on the preliminary experimental results.

  16. In Vivo MRI Mapping of Brain Iron Deposition across the Adult Lifespan

    PubMed Central

    Betts, Matthew J.; Cardenas-Blanco, Arturo; Yang, Shan; Nestor, Peter J.

    2016-01-01

    Disruption of iron homeostasis as a consequence of aging is thought to cause iron levels to increase, potentially promoting oxidative cellular damage. Therefore, understanding how this process evolves through the lifespan could offer insights into both the aging process and the development of aging-related neurodegenerative brain diseases. This work aimed to map, in vivo for the first time with an unbiased whole-brain approach, age-related iron changes using quantitative susceptibility mapping (QSM)—a new postprocessed MRI contrast mechanism. To this end, a full QSM standardization routine was devised and a cohort of N = 116 healthy adults (20–79 years of age) was studied. The whole-brain and ROI analyses confirmed that the propensity of brain cells to accumulate excessive iron as a function of aging largely depends on their exact anatomical location. Whereas only patchy signs of iron scavenging were observed in white matter, strong, bilateral, and confluent QSM–age associations were identified in several deep-brain nuclei—chiefly the striatum and midbrain—and across motor, premotor, posterior insular, superior prefrontal, and cerebellar cortices. The validity of QSM as a suitable in vivo imaging technique with which to monitor iron dysregulation in the human brain was demonstrated by confirming age-related increases in several subcortical nuclei that are known to accumulate iron with age. The study indicated that, in addition to these structures, there is a predilection for iron accumulation in the frontal lobes, which when combined with the subcortical findings, suggests that iron accumulation with age predominantly affects brain regions concerned with motor/output functions. SIGNIFICANCE STATEMENT This study used a whole-brain imaging approach known as quantitative susceptibility mapping (QSM) to provide a novel insight into iron accumulation in the brain across the adult lifespan. Validity of the method was demonstrated by showing concordance with ROI

  17. Gsx2 controls region-specific activation of neural stem cells and injury-induced neurogenesis in the adult subventricular zone

    PubMed Central

    López-Juárez, Alejandro; Howard, Jennifer; Ullom, Kristy; Howard, Lindsey; Grande, Andrew; Pardo, Andrea; Waclaw, Ronald; Sun, Yu-Yo; Yang, Dianer; Kuan, Chia-Yi; Campbell, Kenneth; Nakafuku, Masato

    2013-01-01

    Neural stem cells (NSCs) reside in widespread regions along the lateral ventricle and generate diverse olfactory bulb (OB) interneuron subtypes in the adult mouse brain. Molecular mechanisms underlying their regional diversity, however, are not well understood. Here we show that the homeodomain transcription factor Gsx2 plays a crucial role in the region-specific control of adult NSCs in both persistent and injury-induced neurogenesis. In the intact brain, Gsx2 is expressed in a regionally restricted subset of NSCs and promotes the activation and lineage progression of stem cells, thereby controlling the production of selective OB neuron subtypes. Moreover, Gsx2 is ectopically induced in damaged brains outside its normal expression domains and is required for injury-induced neurogenesis in the subventricular zone (SVZ). These results demonstrate that mobilization of adult NSCs is controlled in a region-specific manner and that distinct mechanisms operate in continuous and injury-induced neurogenesis in the adult brain. PMID:23723414

  18. Gsx2 controls region-specific activation of neural stem cells and injury-induced neurogenesis in the adult subventricular zone.

    PubMed

    López-Juárez, Alejandro; Howard, Jennifer; Ullom, Kristy; Howard, Lindsey; Grande, Andrew; Pardo, Andrea; Waclaw, Ronald; Sun, Yu-Yo; Yang, Dianer; Kuan, Chia-Yi; Campbell, Kenneth; Nakafuku, Masato

    2013-06-01

    Neural stem cells (NSCs) reside in widespread regions along the lateral ventricle and generate diverse olfactory bulb (OB) interneuron subtypes in the adult mouse brain. Molecular mechanisms underlying their regional diversity, however, are not well understood. Here we show that the homeodomain transcription factor Gsx2 plays a crucial role in the region-specific control of adult NSCs in both persistent and injury-induced neurogenesis. In the intact brain, Gsx2 is expressed in a regionally restricted subset of NSCs and promotes the activation and lineage progression of stem cells, thereby controlling the production of selective OB neuron subtypes. Moreover, Gsx2 is ectopically induced in damaged brains outside its normal expression domains and is required for injury-induced neurogenesis in the subventricular zone (SVZ). These results demonstrate that mobilization of adult NSCs is controlled in a region-specific manner and that distinct mechanisms operate in continuous and injury-induced neurogenesis in the adult brain.

  19. Brain regions and genes affecting postural control.

    PubMed

    Lalonde, R; Strazielle, C

    2007-01-01

    Postural control is integrated in all facets of motor commands. The role of cortico-subcortical pathways underlying postural control, including cerebellum and its afferents (climbing, mossy, and noradrenergic fibers), basal ganglia, motor thalamus, and parieto-frontal neocortex has been identified in animal models, notably through the brain lesion technique in rats and in mice with spontaneous and induced mutations. These studies are complemented by analyses of the factors underlying postural deficiencies in patients with cerebellar atrophy. With the gene deletion technique in mice, specific genes expressed in cerebellum encoding glutamate receptors (Grid2 and Grm1) and other molecules (Prkcc, Cntn6, Klf9, Syt4, and En2) have also been shown to affect postural control. In addition, transgenic mouse models of the synucleinopathies and of Huntington's disease cause deficiencies of motor coordination resembling those of patients with basal ganglia damage.

  20. Regional brain gray and white matter changes in perinatally HIV-infected adolescents.

    PubMed

    Sarma, Manoj K; Nagarajan, Rajakumar; Keller, Margaret A; Kumar, Rajesh; Nielsen-Saines, Karin; Michalik, David E; Deville, Jaime; Church, Joseph A; Thomas, M Albert

    2014-01-01

    Despite the success of antiretroviral therapy (ART), perinatally infected HIV remains a major health problem worldwide. Although advance neuroimaging studies have investigated structural brain changes in HIV-infected adults, regional gray matter (GM) and white matter (WM) volume changes have not been reported in perinatally HIV-infected adolescents and young adults. In this cross-sectional study, we investigated regional GM and WM changes in 16 HIV-infected youths receiving ART (age 17.0 ± 2.9 years) compared with age-matched 14 healthy controls (age 16.3 ± 2.3 years) using magnetic resonance imaging (MRI)-based high-resolution T1-weighted images with voxel based morphometry (VBM) analyses. White matter atrophy appeared in perinatally HIV-infected youths in brain areas including the bilateral posterior corpus callosum (CC), bilateral external capsule, bilateral ventral temporal WM, mid cerebral peduncles, and basal pons over controls. Gray matter volume increase was observed in HIV-infected youths for several regions including the left superior frontal gyrus, inferior occipital gyrus, gyrus rectus, right mid cingulum, parahippocampal gyrus, bilateral inferior temporal gyrus, and middle temporal gyrus compared with controls. Global WM and GM volumes did not differ significantly between groups. These results indicate WM injury in perinatally HIV-infected youths, but the interpretation of the GM results, which appeared as increased regional volumes, is not clear. Further longitudinal studies are needed to clarify if our results represent active ongoing brain infection or toxicity from HIV treatment resulting in neuronal cell swelling and regional increased GM volume. Our findings suggest that assessment of regional GM and WM volume changes, based on VBM procedures, may be an additional measure to assess brain integrity in HIV-infected youths and to evaluate success of current ART therapy for efficacy in the brain.

  1. Intervention-induced enhancement in intrinsic brain activity in healthy older adults

    PubMed Central

    Yin, Shufei; Zhu, Xinyi; Li, Rui; Niu, Yanan; Wang, Baoxi; Zheng, Zhiwei; Huang, Xin; Huo, Lijuan; Li, Juan

    2014-01-01

    This study examined the effects of a multimodal intervention on spontaneous brain activity in healthy older adults. Seventeen older adults received a six-week intervention that consisted of cognitive training, Tai Chi exercise, and group counseling, while 17 older adults in a control group attended health knowledge lectures. The intervention group demonstrated enhanced memory and social support compared to the control group. The amplitude of low frequency fluctuations (ALFF) in the middle frontal gyrus, superior frontal gyrus, and anterior cerebellum lobe was enhanced for the intervention group, while the control group showed reduced ALFF in these three regions. Moreover, changes in trail-making performance and well-being could be predicted by the intervention-induced changes in ALFF. Additionally, individual differences in the baseline ALFF were correlated with intervention-related changes in behavioral performance. These findings suggest that a multimodal intervention is effective in improving cognitive functions and well-being and can induce functional changes in the aging brain. The study extended previous training studies by suggesting resting-state ALFF as a marker of intervention-induced plasticity in older adults. PMID:25472002

  2. Ribosomal protein L11 is related to brain maturation during the adult phase in Apis cerana cerana (Hymenoptera, Apidae)

    NASA Astrophysics Data System (ADS)

    Meng, Fei; Lu, Wenjing; Yu, Feifei; Kang, Mingjiang; Guo, Xingqi; Xu, Baohua

    2012-05-01

    Ribosomal proteins (RPs) play pivotal roles in developmental regulation. The loss or mutation of ribosomal protein L11 ( RPL11) induces various developmental defects. However, few RPs have been functionally characterized in Apis cerana cerana. In this study, we isolated a single copy gene, AccRPL11, and characterized its connection to brain maturation. AccRPL11 expression was highly concentrated in the adult brain and was significantly induced by abiotic stresses such as pesticides and heavy metals. Immunofluorescence assays demonstrated that AccRPL11 was localized to the medulla, lobula and surrounding tissues of esophagus in the brain. The post-transcriptional knockdown of AccRPL11 gene expression resulted in a severe decrease in adult brain than in other tissues. The expression levels of other brain development-related genes, p38, ERK2, CacyBP and CREB, were also reduced. Immunofluorescence signal attenuation was also observed in AccRPL11-rich regions of the brain in ds AccRPL11-injected honeybees. Taken together, these results suggest that AccRPL11 may be functional in brain maturation in honeybee adults.

  3. Regional brain shrinkage and change in cognitive performance over two years: The bidirectional influences of the brain and cognitive reserve factors.

    PubMed

    Persson, Ninni; Ghisletta, Paolo; Dahle, Cheryl L; Bender, Andrew R; Yang, Yiqin; Yuan, Peng; Daugherty, Ana M; Raz, Naftali

    2016-02-01

    We examined relationships between regional brain shrinkage and changes in cognitive performance, while taking into account the influence of chronological age, vascular risk, Apolipoprotein E variant and socioeconomic status. Regional brain volumes and cognitive performance were assessed in 167 healthy adults (age 19-79 at baseline), 90 of whom returned for the follow-up after two years. Brain volumes were measured in six regions of interest (ROIs): lateral prefrontal cortex (LPFC), prefrontal white matter (PFw), hippocampus (Hc), parahippocampal gyrus (PhG), cerebellar hemispheres (CbH), and primary visual cortex (VC), and cognitive performance was evaluated in three domains: episodic memory (EM), fluid intelligence (Gf), and vocabulary (V). Average volume loss was observed in Hc, PhG and CbH, but reliable individual differences were noted in all examined ROIs. Average positive change was observed in EM and V performance but not in Gf scores, yet only the last evidenced individual differences in change. We observed reciprocal influences among neuroanatomical and cognitive variables. Larger brain volumes at baseline predicted greater individual gains in Gf, but differences in LPFC volume change were in part explained by baseline level of cognitive performance. In one region (PFw), individual change in volume was coupled with change in Gf. Larger initial brain volumes did not predict slower shrinkage. The results underscore the complex role of brain maintenance and cognitive reserve in adult development. PMID:26584866

  4. Regional brain shrinkage and change in cognitive performance over two years: The bidirectional influences of the brain and cognitive reserve factors.

    PubMed

    Persson, Ninni; Ghisletta, Paolo; Dahle, Cheryl L; Bender, Andrew R; Yang, Yiqin; Yuan, Peng; Daugherty, Ana M; Raz, Naftali

    2016-02-01

    We examined relationships between regional brain shrinkage and changes in cognitive performance, while taking into account the influence of chronological age, vascular risk, Apolipoprotein E variant and socioeconomic status. Regional brain volumes and cognitive performance were assessed in 167 healthy adults (age 19-79 at baseline), 90 of whom returned for the follow-up after two years. Brain volumes were measured in six regions of interest (ROIs): lateral prefrontal cortex (LPFC), prefrontal white matter (PFw), hippocampus (Hc), parahippocampal gyrus (PhG), cerebellar hemispheres (CbH), and primary visual cortex (VC), and cognitive performance was evaluated in three domains: episodic memory (EM), fluid intelligence (Gf), and vocabulary (V). Average volume loss was observed in Hc, PhG and CbH, but reliable individual differences were noted in all examined ROIs. Average positive change was observed in EM and V performance but not in Gf scores, yet only the last evidenced individual differences in change. We observed reciprocal influences among neuroanatomical and cognitive variables. Larger brain volumes at baseline predicted greater individual gains in Gf, but differences in LPFC volume change were in part explained by baseline level of cognitive performance. In one region (PFw), individual change in volume was coupled with change in Gf. Larger initial brain volumes did not predict slower shrinkage. The results underscore the complex role of brain maintenance and cognitive reserve in adult development.

  5. Structural brain correlates of associative memory in older adults.

    PubMed

    Becker, Nina; Laukka, Erika J; Kalpouzos, Grégoria; Naveh-Benjamin, Moshe; Bäckman, Lars; Brehmer, Yvonne

    2015-09-01

    Associative memory involves binding two or more items into a coherent memory episode. Relative to memory for single items, associative memory declines greatly in aging. However, older individuals vary substantially in their ability to memorize associative information. Although functional studies link associative memory to the medial temporal lobe (MTL) and prefrontal cortex (PFC), little is known about how volumetric differences in MTL and PFC might contribute to individual differences in associative memory. We investigated regional gray-matter volumes related to individual differences in associative memory in a sample of healthy older adults (n=54; age=60years). To differentiate item from associative memory, participants intentionally learned face-scene picture pairs before performing a recognition task that included single faces, scenes, and face-scene pairs. Gray-matter volumes were analyzed using voxel-based morphometry region-of-interest (ROI) analyses. To examine volumetric differences specifically for associative memory, item memory was controlled for in the analyses. Behavioral results revealed large variability in associative memory that mainly originated from differences in false-alarm rates. Moreover, associative memory was independent of individuals' ability to remember single items. Older adults with better associative memory showed larger gray-matter volumes primarily in regions of the left and right lateral PFC. These findings provide evidence for the importance of PFC in intentional learning of associations, likely because of its involvement in organizational and strategic processes that distinguish older adults with good from those with poor associative memory.

  6. Adult Community Education: A Model for Regional Policy Development.

    ERIC Educational Resources Information Center

    Jones, Peter

    1998-01-01

    The adult community education (ACE) sector in the state of Victoria provides an example of best practice in regional rural policy in Australia that may serve as a model for other areas of government effort. In 1997, 309,000 Victorians enrolled in adult and community education courses, such as business and technical skills development, literacy and…

  7. Adult Education, Social Inclusion and Cultural Diversity in Regional Communities

    ERIC Educational Resources Information Center

    Townsend, Rob

    2008-01-01

    This article presents the outcomes of recent research into adult education programs and experiences in the Shire of Campaspe, a region in northern Victoria. Research data of people from diverse cultural backgrounds reveal how individuals can utilize adult education as a space to explore their own social and cultural isolation in a regional…

  8. Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives.

    PubMed

    Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Margus, Brad; Crawford, Thomas O

    2014-06-01

    Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P < 0.001), anterior vermis (40%, P < 0.001) and fusiform gyrus (20%, P < 0.001) compared with controls or siblings, and lower metabolism in hippocampus (12%, P = 0.05) compared with controls, and showed significant intersubject variability (decreases in vermis ranged from 18% to 60%). Participants with ataxia-telangiectasia also had higher metabolism in globus pallidus (16%, P = 0.05), which correlated negatively with motor performance. Asymptomatic relatives had lower metabolism in anterior vermis (12%; P = 0.01) and hippocampus (19%; P = 0.002) than controls. Our results indicate that, in addition to the expected decrease in cerebellar metabolism, participants with ataxia-telangiectasia had widespread changes in metabolic

  9. Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives.

    PubMed

    Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Margus, Brad; Crawford, Thomas O

    2014-06-01

    Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P < 0.001), anterior vermis (40%, P < 0.001) and fusiform gyrus (20%, P < 0.001) compared with controls or siblings, and lower metabolism in hippocampus (12%, P = 0.05) compared with controls, and showed significant intersubject variability (decreases in vermis ranged from 18% to 60%). Participants with ataxia-telangiectasia also had higher metabolism in globus pallidus (16%, P = 0.05), which correlated negatively with motor performance. Asymptomatic relatives had lower metabolism in anterior vermis (12%; P = 0.01) and hippocampus (19%; P = 0.002) than controls. Our results indicate that, in addition to the expected decrease in cerebellar metabolism, participants with ataxia-telangiectasia had widespread changes in metabolic

  10. Regional brain glucose metabolism in patients with brain tumors before and after radiotherapy

    SciTech Connect

    Wang, G.J.; Volkow, N.D.; Lau, Y.H.

    1994-05-01

    This study was performed to measure regional glucose metabolism in nonaffected brain regions of patients with primary or metastatic brain tumors. Seven female and four male patients (mean age 51.5{plus_minus}14.0 years old) were compared with eleven age and sex matched normal subjects. None of the patients had hydrocephalus and/or increased intracranial pressure. Brain glucose metabolism was measured using FDG-PET scan. Five of the patients were reevaluated one week after receiving radiation treatment (RT) to the brain. Patients were on Decadron and/or Dilantin at the time of both scan. PET images were analyzed with a template of 115 nonoverlapping regions of interest and then grouped into eight gray matter regions on each hemisphere. Brain regions with tumors and edema shown in MR imaging were excluded. Z scores were used to compare individual patients` regional values with those of normal subjects. The number of regional values with Z scores of less than - 3.0 were considered abnormal and were quantified. The mean global glucose metabolic rate (mean of all regions) in nonaffected brain regions of patients was significantly lower than that of normal controls (32.1{plus_minus}9.0 versus 44.8{plus_minus}6.3 {mu}mol/100g/min, p<0.001). Analyses of individual subjects revealed that none of the controls and 8 of the 11 patients had at least one abnormal region. In these 8 patients the regions which were abnormal were most frequently localized in right (n=5) and left occipital (n=6) and right orbital frontal cortex (n=7) whereas the basal ganglia was not affected. Five of the patients who had repeated scans following RT showed decrements in tumor metabolism (41{plus_minus}20.5%) and a significant increase in whole brain metabolism (8.6{plus_minus}5.3%, p<0.001). The improvement in whole brain metabolism after RT suggests that the brain metabolic decrements in the patients were related to the presence of tumoral tissue and not just a medication effect.

  11. Analysis of Adult Neurogenesis: Evidence for a Prominent “Non-Neurogenic” DCX-Protein Pool in Rodent Brain

    PubMed Central

    Kremer, Thomas; Jagasia, Ravi; Herrmann, Annika; Matile, Hugues; Borroni, Edilio; Francis, Fiona; Kuhn, Hans Georg; Czech, Christian

    2013-01-01

    Here, we have developed a highly sensitive immunoassay for Dcx to characterize expression in brain and cerebrospinal fluid (CSF) of rodents. We demonstrate that Dcx is widely expressed during development in various brain regions and as well can be detected in cerebrospinal fluid of rats (up to 30 days postnatal). While Dcx protein level decline in adulthood and were detectable in neurogenic regions of the adult rodent brain, similar levels were also detectable in brain regions expected to bear no neurogenesis including the cerebral cortex and CA1/CA3 enriched hippocampus. We monitored DCX protein levels after paradigms to increase or severely decrease adult hippocampal neurogenesis, namely physical activity and cranial radiation, respectively. In both paradigms, Dcx protein- and mRNA-levels clearly reflected changes in neurogenesis in the hippocampus. However, basal Dcx-levels are unaffected in non-neurogenic regions (e.g. CA1/CA3 enriched hippocampus, cortex). These data suggest that there is a substantial “non-neurogenic” pool of Dcx- protein, whose regulation can be uncoupled from adult neurogenesis suggesting caution for the interpretation of such studies. PMID:23690918

  12. Region-specific growth restriction of brain following preterm birth

    PubMed Central

    Iwata, Sachiko; Katayama, Reiji; Kinoshita, Masahiro; Saikusa, Mamoru; Araki, Yuko; Takashima, Sachio; Abe, Toshi; Iwata, Osuke

    2016-01-01

    Regional brain sizes of very-preterm infants at term-equivalent age differ from those of term-born peers, which have been linked with later cognitive impairments. However, dependence of regional brain volume loss on gestational age has not been studied in detail. To investigate the spatial pattern of brain growth in neonates without destructive brain lesions, head MRI of 189 neonates with a wide range of gestational age (24–42 weeks gestation) was assessed using simple metrics measurements. Dependence of MRI findings on gestational age at birth (Agebirth) and the corrected age at MRI scan (AgeMRI) were assessed. The head circumference was positively correlated with AgeMRI, but not Agebirth. The bi-parietal width, deep grey matter area and the trans-cerebellar diameter were positively correlated with both Agebirth and AgeMRI. The callosal thickness (positive), atrial width of lateral ventricle (negative) and the inter-hemispheric distance (negative) were exclusively correlated with Agebirth. The callosal thickness and cerebral/cerebellar transverse diameters showed predominant dependence on Agebirth over AgeMRI, suggesting that brain growth after preterm-birth was considerably restricted or even became negligible compared with that in utero. Such growth restriction after preterm birth may extensively affect relatively more matured infants, considering the linear relationships observed between brain sizes and Agebirth. PMID:27658730

  13. Reproducibility of regional brain metabolic responses to lorazepam

    SciTech Connect

    Wang, G.J.; Volkow, N.D.; Overall, J. |

    1996-10-01

    Changes in regional brain glucose metabolism in response to benzodiazepine agonists have been used as indicators of benzodiazepine-GABA receptor function. The purpose of this study was to assess the reproducibility of these responses. Sixteen healthy right-handed men underwent scanning with PET and [{sup 18}F]fluorodeoxyglucose (FDG) twice: before placebo and before lorazepam (30 {mu}g/kg). The same double FDG procedure was repeated 6-8 wk later on the men to assess test-retest reproducibility. The regional absolute brain metabolic values obtained during the second evaluation were significantly lower than those obtained from the first evaluation regardless of condition (p {le} 0.001). Lorazepam significantly and consistently decreased both whole-brain metabolism and the magnitude. The regional pattern of the changes were comparable for both studies (12.3% {plus_minus} 6.9% and 13.7% {plus_minus} 7.4%). Lorazepam effects were the largest in the thalamus (22.2% {plus_minus} 8.6% and 22.4% {plus_minus} 6.9%) and occipital cortex (19% {plus_minus} 8.9% and 21.8% {plus_minus} 8.9%). Relative metabolic measures were highly reproducible both for pharmacolgic and replication condition. This study measured the test-retest reproducibility in regional brain metabolic responses, and although the global and regional metabolic values were significantly lower for the repeated evaluation, the response to lorazepam was highly reproducible. 1613 refs., 3 figs., 3 tabs.

  14. Exploratory case-control study of brain tumors in adults

    SciTech Connect

    Burch, J.D.; Craib, K.J.; Choi, B.C.; Miller, A.B.; Risch, H.A.; Howe, G.R.

    1987-04-01

    An exploratory study of brain tumors in adults was carried out using 215 cases diagnosed in Southern Ontario between 1979 and 1982, with an individually matched, hospital control series. Significantly elevated risks were observed for reported use of spring water, drinking of wine, and consumption of pickled fish, together with a significant protective effect for the regular consumption of any of several types of fruit. While these factors are consistent with a role for N-nitroso compounds in the etiology of these tumors, for several other factors related to this hypothesis, no association was observed. Occupation in the rubber industry was associated with a significant relative risk of 9.0, though no other occupational associations were seen. Two previously unreported associations were with smoking nonfilter cigarettes with a significant trend and with the use of hair dyes or sprays. The data do not support an association between physical head trauma requiring medical attention and risk of brain tumors and indicate that exposure to ionizing radiation and vinyl chloride monomer does not contribute any appreciable fraction of attributable risk in the population studied. The findings warrant further detailed investigation in future epidemiologic studies.

  15. Postnatal day 7 ethanol treatment causes persistent reductions in adult mouse brain volume and cortical neurons with sex specific effects on neurogenesis.

    PubMed

    Coleman, Leon G; Oguz, Ipek; Lee, Joohwi; Styner, Martin; Crews, Fulton T

    2012-09-01

    Ethanol treatment on postnatal day seven (P7) causes robust brain cell death and is a model of late gestational alcohol exposure (Ikonomidou et al., 2000). To investigate the long-term effects of P7 ethanol treatment on adult brain, mice received either two doses of saline or ethanol on P7 (2.5 g/kg, s.c., 2 h apart) and were assessed as adults (P82) for brain volume (using postmortem MRI) and cellular architecture (using immunohistochemistry). Adult mice that received P7 ethanol had reduced MRI total brain volume (4%) with multiple brain regions being reduced in both males and females. Immunohistochemistry indicated reduced frontal cortical parvalbumin immunoreactive (PV + IR) interneurons (18-33%) and reduced Cux1+IR layer II pyramidal neurons (15%) in both sexes. Interestingly, markers of adult hippocampal neurogenesis differed between sexes, with only ethanol treated males showing increased doublecortin and Ki67 expression (52 and 57% respectively) in the dentate gyrus, consistent with increased neurogenesis compared to controls. These findings suggest that P7 ethanol treatment causes persistent reductions in adult brain volume and frontal cortical neurons in both males and females. Increased adult neurogenesis in males, but not females, is consistent with differential adaptive responses to P7 ethanol toxicity between the sexes. One day of ethanol exposure, e.g. P7, causes persistent adult brain dysmorphology.

  16. The effects of cognitive-behavioral therapy on intrinsic functional brain networks in adults with attention-deficit/hyperactivity disorder.

    PubMed

    Wang, Xiaoli; Cao, Qingjiu; Wang, Jinhui; Wu, Zhaomin; Wang, Peng; Sun, Li; Cai, Taisheng; Wang, Yufeng

    2016-01-01

    Cognitive-behavioral therapy (CBT) is an efficacious psychological treatment for adults with attention-deficit/hyperactivity disorder (ADHD), but the neural processes underlying the benefits of CBT are not well understood. This study aims to unravel psychosocial mechanisms for treatment ADHD by exploring the effects of CBT on functional brain networks. Ten adults with ADHD were enrolled and resting-state functional magnetic resonance imaging scans were acquired before and after a 12-session CBT. Twelve age- and gender-matched healthy controls were also scanned. We constructed whole-brain functional connectivity networks using graph-theory approaches and further computed the changes of regional functional connectivity strength (rFCS) between pre- and post-CBT in ADHD for measuring the effects of CBT. The results showed that rFCS was increased in the fronto-parietal network and cerebellum, the brain regions that were most often affected by medication, in adults with ADHD following CBT. Furthermore, the enhanced functional coupling between bilateral superior parietal gyrus was positively correlated with the improvement of ADHD symptoms following CBT. Together, these findings provide evidence that CBT can selectively modulate the intrinsic network connectivity in the fronto-parietal network and cerebellum and suggest that the CBT may share common brain mechanism with the pharmacology in adults with ADHD.

  17. Reading in the brain of children and adults: a meta-analysis of 40 functional magnetic resonance imaging studies.

    PubMed

    Martin, Anna; Schurz, Matthias; Kronbichler, Martin; Richlan, Fabio

    2015-05-01

    We used quantitative, coordinate-based meta-analysis to objectively synthesize age-related commonalities and differences in brain activation patterns reported in 40 functional magnetic resonance imaging (fMRI) studies of reading in children and adults. Twenty fMRI studies with adults (age means: 23-34 years) were matched to 20 studies with children (age means: 7-12 years). The separate meta-analyses of these two sets showed a pattern of reading-related brain activation common to children and adults in left ventral occipito-temporal (OT), inferior frontal, and posterior parietal regions. The direct statistical comparison between the two meta-analytic maps of children and adults revealed higher convergence in studies with children in left superior temporal and bilateral supplementary motor regions. In contrast, higher convergence in studies with adults was identified in bilateral posterior OT/cerebellar and left dorsal precentral regions. The results are discussed in relation to current neuroanatomical models of reading and tentative functional interpretations of reading-related activation clusters in children and adults are provided.

  18. Traumatic brain injury: endocrine consequences in children and adults.

    PubMed

    Richmond, Erick; Rogol, Alan D

    2014-02-01

    Traumatic brain injury (TBI) is a common cause of death and disability in young adults with consequences ranging from physical disabilities to long-term cognitive, behavioral, psychological and social defects. Recent data suggest that pituitary hormone deficiency is not infrequent among TBI survivors; the prevalence of reported hypopituitarism following TBI varies widely among published studies. The most common cause of TBI is motor vehicle accidents, including pedestrian-car and bicycle car encounters, falls, child abuse, violence and sports injuries. Prevalence of hypopituitarism, from total to isolated pituitary deficiency, ranges from 5 to 90 %. The time interval between TBI and pituitary function evaluation is one of the major factors responsible for variations in the prevalence of hypopituitarism reported. Endocrine dysfunction after TBI in children and adolescents is common. Adolescence is a time of growth, freedom and adjustment, consequently TBI is also common in this group. Sports-related TBI is an important public health concern, but many cases are unrecognized and unreported. Sports that are associated with an increased risk of TBI include those involving contact and/or collisions such as boxing, football, soccer, ice hockey, rugby, and the martial arts, as well as high velocity sports such as cycling, motor racing, equestrian sports, skiing and roller skating. The aim of this paper is to summarize the best evidence of TBI as a cause of pituitary deficiency in children and adults. PMID:24030696

  19. Narrative skills following traumatic brain injury in children and adults.

    PubMed

    Biddle, K R; McCabe, A; Bliss, L S

    1996-01-01

    Personal narratives serve an important function in virtually all societies (Peterson & McCabe, 1991). Through narratives individuals make sense of their experiences and represent themselves to others (Bruner, 1990). The ability to produce narratives has been linked to academic success (Feagans, 1982). Persons who have sustained a traumatic brain injury (TBI) are at risk for impaired narrative ability (Dennis, 1991). However, a paucity of information exists on the discourse abilities of persons with TBI. This is partly due to a lack of reliable tools with which to assess narrative discourse. The present study utilized dependency analysis (Deese, 1984) to document and describe the narrative discourse impairments of children and adults with TBI. Ten children (mean age 12;0) and 10 adults (mean age 35;2) were compared with matched controls. Dependency analysis reliably differentiated the discourse of the individuals with TBI from their controls. Individuals with TBI were significantly more dysfluent than their matched controls. Furthermore, their performance on the narrative task revealed a striking listener burden.

  20. Extracting regional brain patterns for classification of neurodegenerative diseases

    NASA Astrophysics Data System (ADS)

    Pulido, Andrea; Rueda, Andrea; Romero, Eduardo

    2013-11-01

    In structural Magnetic Resonance Imaging (MRI), neurodegenerative diseases generally present complex brain patterns that can be correlated with di erent clinical onsets of this pathologies. An objective method that aims to determine both global and local changes is not usually available in clinical practice, thus the interpretation of these images is strongly dependent on the radiologist's skills. In this paper, we propose a strategy which interprets the brain structure using a framework that highlights discriminant brain patterns for neurodegenerative diseases. This is accomplished by combining a probabilistic learning technique, which identi es and groups regions with similar visual features, with a visual saliency method that exposes relevant information within each region. The association of such patterns with a speci c disease is herein evaluated in a classi cation task, using a dataset including 80 Alzheimer's disease (AD) patients and 76 healthy subjects (NC). Preliminary results show that the proposed method reaches a maximum classi cation accuracy of 81.39%.

  1. Differential effects of age and history of hypertension on regional brain volumes and iron

    PubMed Central

    Rodrigue, Karen M.; Haacke, E. Mark; Raz, Naftali

    2010-01-01

    Aging affects various structural and metabolic properties of the brain. However, associations among various aspects of brain aging are unclear. Moreover, those properties and associations among them may be modified by age-associated increase in vascular risk. In this study, we measured volume of brain regions that vary in their vulnerability to aging and estimated local iron content via T2* relaxometry. In 113 healthy adults (19–83 years old), we examined prefrontal cortex (PFC), primary visual cortex (VC), hippocampus (HC), entorhinal cortex (EC), caudate nucleus (Cd), and putamen (Pt). In some regions (PFC, VC, Cd, Pt) age-related differences in iron and volume followed similar patterns. However, in the medial temporal structures, volume and iron content exhibited different age trajectories. Whereas age-related volume reduction was mild in HC and absent in EC, iron content evidenced significant age-related declines. In hypertensive participants significantly greater iron content was noted in all examined regions. Thus, iron content as measured by T2* may be a sensitive index of regional brain aging and may reveal declines that are more prominent than gross anatomical shrinkage. PMID:20923707

  2. Longitudinal alterations to brain function, structure, and cognitive performance in healthy older adults: A fMRI-DTI study.

    PubMed

    Hakun, Jonathan G; Zhu, Zude; Brown, Christopher A; Johnson, Nathan F; Gold, Brian T

    2015-05-01

    Cross-sectional research has shown that older adults tend to have different frontal cortex activation patterns, poorer brain structure, and lower task performance than younger adults. However, relationships between longitudinal changes in brain function, brain structure, and cognitive performance in older adults are less well understood. Here we present the results of a longitudinal, combined fMRI-DTI study in cognitive normal (CN) older adults. A two time-point study was conducted in which participants completed a task switching paradigm while fMRI data was collected and underwent the identical scanning protocol an average of 3.3 years later (SD=2 months). We observed longitudinal fMRI activation increases in bilateral regions of lateral frontal cortex at time point 2. These fMRI activation increases were associated with longitudinal declines in WM microstructure in a portion of the corpus callosum connecting the increasingly recruited frontal regions. In addition, the fMRI activation increase in the left VLPFC was associated with longitudinal increases in response latencies. Taken together, our results suggest that local frontal activation increases in CN older adults may in part reflect a response to reduced inter-hemispheric signaling mechanisms.

  3. Longitudinal Alterations to Brain Function, Structure, and Cognitive Performance in Healthy Older Adults: a fMRI-DTI study

    PubMed Central

    Hakun, Jonathan G.; Zhu, Zude; Brown, Christopher A.; Johnson, Nathan F.; Gold, Brian T.

    2015-01-01

    Cross-sectional research has shown that older adults tend to have different frontal cortex activation patterns, poorer brain structure, and lower task performance than younger adults. However, relationships between longitudinal changes in brain function, brain structure, and cognitive performance in older adults are less well understood. Here we present the results of a longitudinal, combined fMRI-DTI study in cognitive normal (CN) older adults. A two time-point study was conducted in which participants completed a task switching paradigm while fMRI data was collected and underwent the identical scanning protocol an average of 3.3 years later (SD = 2 months). We observed longitudinal fMRI activation increases in bilateral regions of lateral frontal cortex at time point 2. These fMRI activation increases were associated with longitudinal declines in WM microstructure in a portion of the corpus callosum connecting the increasingly recruited frontal regions. In addition, the fMRI activation increase in the left VLPFC was associated with longitudinal increases in response latencies. Taken together, our results suggest that local frontal activation increases in CN older adults may in part reflect a response to reduced inter-hemispheric signaling mechanisms. PMID:25862416

  4. Cognitive Abilities Independent of IQ Correlate with Regional Brain Structure

    ERIC Educational Resources Information Center

    Johnson, Wendy; Jung, Rex E.; Colom, Roberto; Haier, Richard J.

    2008-01-01

    There is increasing evidence relating psychometric measures of general intelligence and reasoning to regional brain structure and function assessed with a variety of neuroimaging techniques. Cognitive dimensions independent of general intelligence can also be identified psychometrically and studied for any neuroanatomical correlates. Here we…

  5. Brain Regions Underlying Word Finding Difficulties in Temporal Lobe Epilepsy

    ERIC Educational Resources Information Center

    Trebuchon-Da Fonseca, Agnes; Guedj, Eric; Alario, F-Xavier; Laguitton, Virginie; Mundler, Olivier; Chauvel, Patrick; Liegeois-Chauvel, Catherine

    2009-01-01

    Word finding difficulties are often reported by epileptic patients with seizures originating from the language dominant cerebral hemisphere, for example, in temporal lobe epilepsy. Evidence regarding the brain regions underlying this deficit comes from studies of peri-operative electro-cortical stimulation, as well as post-surgical performance.…

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

    PubMed

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

    2016-05-03

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

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

    PubMed Central

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

    2016-01-01

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

  8. Distribution of branch point prenyltransferases in regions of bovine brain.

    PubMed

    Runquist, M; Parmryd, I; Thelin, A; Chojnacki, T; Dallner, G

    1995-11-01

    Bovine brains contain large amounts of isoprenoid compounds and the enzymes involved in their biosynthesis were investigated. Ten different regions were dissected from fresh bovine brains and, in addition, fractions from cerebellum, spinal cord, and hypophysis were obtained. The cholesterol concentration was found to be approximately 8 mg/g in the cortex regions and three times higher in the pons, medulla oblongata, and white matter. Dolichol concentration varied between 8 and 40 micrograms/g in the different tissues, and ubiquinone was found at a lower level, which varied between 3 and 25 micrograms/g. Farnesylpyrophosphate synthase activity in cytosolic fractions from various regions exhibited only a twofold variation, whereas geranylgeranyl pyrophosphate synthase displayed larger differences, being particularly rich in the pons, medulla oblongata, white matter, and spinal cord. Squalene synthase activity was lowest in the thalamus and threefold higher in the pons. Determination of specific activity based on cholesterol content revealed that enzyme activities in various regions are not related to the actual lipid amount present. Both cis- and trans-prenyltransferases exhibited similarities in their regional distribution showing up to 20-fold differences in activity. Thus, it appears that the mevalonate pathway lipids and the various branch point enzymes involved in their syntheses vary greatly in different brain regions and are subjected to separate regulation.

  9. Positron Emission Tomography of Brain β-Amyloid and Tau Levels in Adults With Down Syndrome

    PubMed Central

    Nelson, Linda D.; Siddarth, Prabha; Kepe, Vladimir; Scheibel, Kevin E.; Huang, S. C.; Barrio, Jorge R.; Small, Gary W.

    2012-01-01

    Objectives To determine the neuropathological load in the living brain of nondemented adults with Down syndrome using positron emission tomography with 2-(1-{6-[(2-fluorine 18–labeled fluoroethyl)methylamino]-2-napthyl}ethylidene) malononitrile ([18F]FDDNP) and to assess the influence of age and cognitive and behavioral functioning. For reference, [18F]FDDNP binding values and patterns were compared with those from patients with Alzheimer disease and cognitively intact control participants. Design Cross-sectional clinical study. Participants Volunteer sample of 19 persons with Down syndrome without dementia (mean age, 36.7 years), 10 patients with Alzheimer disease (mean age, 66.5 years), and 10 controls (mean age, 43.8 years). Main Outcome Measures Binding of [18F]FDDNP in brain regions of interest, including the parietal, medial temporal, lateral temporal, and frontal lobes and posterior cingulate gyrus, and the average of all regions (global binding). Results The [18F]FDDNP binding values were higher in all brain regions in the Down syndrome group than in controls. Compared with the Alzheimer disease group, the Down syndrome group had higher [18F]FDDNP binding values in the parietal and frontal regions, whereas binding levels in other regions were comparable. Within the Down syndrome group, age correlated with [18F]FDDNP binding values in all regions except the posterior cingulate, and several measures of behavioral dysfunction showed positive correlations with global, frontal, parietal, and posterior cingulate [18F]FDDNP binding. Conclusions Consistent with neuropathological findings from postmortem studies, [18F]FDDNP positron emission tomography shows high binding levels in Down syndrome comparable to Alzheimer disease and greater levels than in members of a control group. The positive associations between [18F]FDDNP binding levels and age as well as behavioral dysfunction in Down syndrome are consistent with the age-related progression of Alzheimer

  10. Influence of ketamine on regional brain glucose use

    SciTech Connect

    Davis, D.W.; Mans, A.M.; Biebuyck, J.F.; Hawkins, R.A.

    1988-08-01

    The purpose of this study was to determine the effect of different doses of ketamine on cerebral function at the level of individual brain structures as reflected by glucose use. Rats received either 5 or 30 mg/kg ketamine intravenously as a loading dose, followed by an infusion to maintain a steady-state level of the drug. An additional group received 30 mg/kg as a single injection only, and was studied 20 min later, by which time they were recovering consciousness (withdrawal group). Regional brain energy metabolism was evaluated with (6-/sup 14/C)glucose and quantitative autoradiography during a 5-min experimental period. A subhypnotic, steady-state dose (5 mg/kg) of ketamine caused a stimulation of glucose use in most brain areas, with an average increase of 20%. At the larger steady-state dose (30 mg/kg, which is sufficient to cause anesthesia), there was no significant effect on most brain regions; some sensory nuclei were depressed (inferior colliculus, -29%; cerebellar dentate nucleus, -18%; vestibular nucleus, -16%), but glucose use in the ventral posterior hippocampus was increased by 33%. In contrast, during withdrawal from a 30-mg/kg bolus, there was a stimulation of glucose use throughout the brain (21-78%), at a time when plasma ketamine levels were similar to the levels in the 5 mg/kg group. At each steady-state dose, as well as during withdrawal, ketamine caused a notable stimulation of glucose use by the hippocampus.

  11. Regional brain stiffness changes across the Alzheimer's disease spectrum☆

    PubMed Central

    Murphy, Matthew C.; Jones, David T.; Jack, Clifford R.; Glaser, Kevin J.; Senjem, Matthew L.; Manduca, Armando; Felmlee, Joel P.; Carter, Rickey E.; Ehman, Richard L.; Huston, John

    2015-01-01

    Magnetic resonance elastography (MRE) is an MRI-based technique to noninvasively measure tissue stiffness. Currently well established for clinical use in the liver, MRE is increasingly being investigated to measure brain stiffness as a novel biomarker of a variety of neurological diseases. The purpose of this work was to apply a recently developed MRE pipeline to measure regional brain stiffness changes in human subjects across the Alzheimer's disease (AD) spectrum, and to gain insights into the biological processes underlying those stiffness changes by correlating stiffness with existing biomarkers of AD. The results indicate that stiffness changes occur mostly in the frontal, parietal and temporal lobes, in accordance with the known topography of AD pathology. Furthermore, stiffness in those areas correlates with existing imaging biomarkers of AD including hippocampal volumes and amyloid PET. Additional analysis revealed preliminary but significant evidence that the relationship between brain stiffness and AD severity is nonlinear and non-monotonic. Given that similar relationships have been observed in functional MRI experiments, we used task-free fMRI data to test the hypothesis that brain stiffness was sensitive to structural changes associated with altered functional connectivity. The analysis revealed that brain stiffness is significantly and positively correlated with default mode network connectivity. Therefore, brain stiffness as measured by MRE has potential to provide new and essential insights into the temporal dynamics of AD, as well as the relationship between functional and structural plasticity as it relates to AD pathophysiology. PMID:26900568

  12. Regional brain stiffness changes across the Alzheimer's disease spectrum.

    PubMed

    Murphy, Matthew C; Jones, David T; Jack, Clifford R; Glaser, Kevin J; Senjem, Matthew L; Manduca, Armando; Felmlee, Joel P; Carter, Rickey E; Ehman, Richard L; Huston, John

    2016-01-01

    Magnetic resonance elastography (MRE) is an MRI-based technique to noninvasively measure tissue stiffness. Currently well established for clinical use in the liver, MRE is increasingly being investigated to measure brain stiffness as a novel biomarker of a variety of neurological diseases. The purpose of this work was to apply a recently developed MRE pipeline to measure regional brain stiffness changes in human subjects across the Alzheimer's disease (AD) spectrum, and to gain insights into the biological processes underlying those stiffness changes by correlating stiffness with existing biomarkers of AD. The results indicate that stiffness changes occur mostly in the frontal, parietal and temporal lobes, in accordance with the known topography of AD pathology. Furthermore, stiffness in those areas correlates with existing imaging biomarkers of AD including hippocampal volumes and amyloid PET. Additional analysis revealed preliminary but significant evidence that the relationship between brain stiffness and AD severity is nonlinear and non-monotonic. Given that similar relationships have been observed in functional MRI experiments, we used task-free fMRI data to test the hypothesis that brain stiffness was sensitive to structural changes associated with altered functional connectivity. The analysis revealed that brain stiffness is significantly and positively correlated with default mode network connectivity. Therefore, brain stiffness as measured by MRE has potential to provide new and essential insights into the temporal dynamics of AD, as well as the relationship between functional and structural plasticity as it relates to AD pathophysiology.

  13. Aging Effects on Whole-Brain Functional Connectivity in Adults Free of Cognitive and Psychiatric Disorders.

    PubMed

    Ferreira, Luiz Kobuti; Regina, Ana Carolina Brocanello; Kovacevic, Natasa; Martin, Maria da Graça Morais; Santos, Pedro Paim; Carneiro, Camila de Godoi; Kerr, Daniel Shikanai; Amaro, Edson; McIntosh, Anthony Randal; Busatto, Geraldo F

    2016-09-01

    Aging is associated with decreased resting-state functional connectivity (RSFC) within the default mode network (DMN), but most functional imaging studies have restricted the analysis to specific brain regions or networks, a strategy not appropriate to describe system-wide changes. Moreover, few investigations have employed operational psychiatric interviewing procedures to select participants; this is an important limitation since mental disorders are prevalent and underdiagnosed and can be associated with RSFC abnormalities. In this study, resting-state fMRI was acquired from 59 adults free of cognitive and psychiatric disorders according to standardized criteria and based on extensive neuropsychological and clinical assessments. We tested for associations between age and whole-brain RSFC using Partial Least Squares, a multivariate technique. We found that normal aging is not only characterized by decreased RSFC within the DMN but also by ubiquitous increases in internetwork positive correlations and focal internetwork losses of anticorrelations (involving mainly connections between the DMN and the attentional networks). Our results reinforce the notion that the aging brain undergoes a dedifferentiation processes with loss of functional diversity. These findings advance the characterization of healthy aging effects on RSFC and highlight the importance of adopting a broad, system-wide perspective to analyze brain connectivity.

  14. FMR1 transcript isoforms: association with polyribosomes; regional and developmental expression in mouse brain.

    PubMed

    Brackett, David M; Qing, Feng; Amieux, Paul S; Sellers, Drew L; Horner, Philip J; Morris, David R

    2013-01-01

    The primary transcript of the mammalian Fragile X Mental Retardation-1 gene (Fmr1), like many transcripts in the central nervous system, is alternatively spliced to yield mRNAs encoding multiple proteins, which can possess quite different biochemical properties. Despite the fact that the relative levels of the 12 Fmr1 transcript isoforms examined here vary by as much as two orders of magnitude amongst themselves in both adult and embryonic mouse brain, all are associated with polyribosomes, consistent with translation into the corresponding isoforms of the protein product, FMRP (Fragile X Mental Retardation Protein). Employing the RiboTag methodology developed in our laboratory, the relative proportions of the 7 most abundant transcript isoforms were measured specifically in neurons and found to be similar to those identified in whole brain. Measurements of isoform profiles across 11 regions of adult brain yielded similar distributions, with the exceptions of the hippocampus and the olfactory bulb. These two regions differ from most of the brain in relative amounts of transcripts encoding an alternate form of one of the KH RNA binding domains. A possible relationship between patterns of expression in the hippocampus and olfactory bulb and the presence of neuroblasts in these two regions is suggested by the isoform patterns in early embryonic brain and in cultured neural progenitor cells. These results demonstrate that the relative levels of the Fmr1 isoforms are modulated according to developmental stage, highlighting the complex ramifications of losing all the protein isoforms in individuals with Fragile X Syndrome. It should also be noted that, of the eight most prominent FMRP isoforms (1-3, 6-9 and 12) in mouse, only two have the major site of phosphorylation at Ser-499, which is thought to be involved in some of the regulatory interactions of this protein.

  15. Construction of brain atlases based on a multi-center MRI dataset of 2020 Chinese adults.

    PubMed

    Liang, Peipeng; Shi, Lin; Chen, Nan; Luo, Yishan; Wang, Xing; Liu, Kai; Mok, Vincent C T; Chu, Winnie C W; Wang, Defeng; Li, Kuncheng

    2015-01-01

    Despite the known morphological differences (e.g., brain shape and size) in the brains of populations of different origins (e.g., age and race), the Chinese brain atlas is less studied. In the current study, we developed a statistical brain atlas based on a multi-center high quality magnetic resonance imaging (MRI) dataset of 2020 Chinese adults (18-76 years old). We constructed 12 Chinese brain atlas from the age 20 year to the age 75 at a 5 years interval. New Chinese brain standard space, coordinates, and brain area labels were further defined. The new Chinese brain atlas was validated in brain registration and segmentation. It was found that, as contrast to the MNI152 template, the proposed Chinese atlas showed higher accuracy in hippocampus segmentation and relatively smaller shape deformations during registration. These results indicate that a population-specific time varying brain atlas may be more appropriate for studies involving Chinese populations. PMID:26678304

  16. Gene co-expression analysis identifies brain regions and cell types involved in migraine pathophysiology: a GWAS-based study using the Allen Human Brain Atlas.

    PubMed

    Eising, Else; Huisman, Sjoerd M H; Mahfouz, Ahmed; Vijfhuizen, Lisanne S; Anttila, Verneri; Winsvold, Bendik S; Kurth, Tobias; Ikram, M Arfan; Freilinger, Tobias; Kaprio, Jaakko; Boomsma, Dorret I; van Duijn, Cornelia M; Järvelin, Marjo-Riitta R; Zwart, John-Anker; Quaye, Lydia; Strachan, David P; Kubisch, Christian; Dichgans, Martin; Davey Smith, George; Stefansson, Kari; Palotie, Aarno; Chasman, Daniel I; Ferrari, Michel D; Terwindt, Gisela M; de Vries, Boukje; Nyholt, Dale R; Lelieveldt, Boudewijn P F; van den Maagdenberg, Arn M J M; Reinders, Marcel J T

    2016-04-01

    Migraine is a common disabling neurovascular brain disorder typically characterised by attacks of severe headache and associated with autonomic and neurological symptoms. Migraine is caused by an interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified over a dozen genetic loci associated with migraine. Here, we integrated migraine GWAS data with high-resolution spatial gene expression data of normal adult brains from the Allen Human Brain Atlas to identify specific brain regions and molecular pathways that are possibly involved in migraine pathophysiology. To this end, we used two complementary methods. In GWAS data from 23,285 migraine cases and 95,425 controls, we first studied modules of co-expressed genes that were calculated based on human brain expression data for enrichment of genes that showed association with migraine. Enrichment of a migraine GWAS signal was found for five modules that suggest involvement in migraine pathophysiology of: (i) neurotransmission, protein catabolism and mitochondria in the cortex; (ii) transcription regulation in the cortex and cerebellum; and (iii) oligodendrocytes and mitochondria in subcortical areas. Second, we used the high-confidence genes from the migraine GWAS as a basis to construct local migraine-related co-expression gene networks. Signatures of all brain regions and pathways that were prominent in the first method also surfaced in the second method, thus providing support that these brain regions and pathways are indeed involved in migraine pathophysiology. PMID:26899160

  17. Gene co-expression analysis identifies brain regions and cell types involved in migraine pathophysiology: a GWAS-based study using the Allen Human Brain Atlas.

    PubMed

    Eising, Else; Huisman, Sjoerd M H; Mahfouz, Ahmed; Vijfhuizen, Lisanne S; Anttila, Verneri; Winsvold, Bendik S; Kurth, Tobias; Ikram, M Arfan; Freilinger, Tobias; Kaprio, Jaakko; Boomsma, Dorret I; van Duijn, Cornelia M; Järvelin, Marjo-Riitta R; Zwart, John-Anker; Quaye, Lydia; Strachan, David P; Kubisch, Christian; Dichgans, Martin; Davey Smith, George; Stefansson, Kari; Palotie, Aarno; Chasman, Daniel I; Ferrari, Michel D; Terwindt, Gisela M; de Vries, Boukje; Nyholt, Dale R; Lelieveldt, Boudewijn P F; van den Maagdenberg, Arn M J M; Reinders, Marcel J T

    2016-04-01

    Migraine is a common disabling neurovascular brain disorder typically characterised by attacks of severe headache and associated with autonomic and neurological symptoms. Migraine is caused by an interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified over a dozen genetic loci associated with migraine. Here, we integrated migraine GWAS data with high-resolution spatial gene expression data of normal adult brains from the Allen Human Brain Atlas to identify specific brain regions and molecular pathways that are possibly involved in migraine pathophysiology. To this end, we used two complementary methods. In GWAS data from 23,285 migraine cases and 95,425 controls, we first studied modules of co-expressed genes that were calculated based on human brain expression data for enrichment of genes that showed association with migraine. Enrichment of a migraine GWAS signal was found for five modules that suggest involvement in migraine pathophysiology of: (i) neurotransmission, protein catabolism and mitochondria in the cortex; (ii) transcription regulation in the cortex and cerebellum; and (iii) oligodendrocytes and mitochondria in subcortical areas. Second, we used the high-confidence genes from the migraine GWAS as a basis to construct local migraine-related co-expression gene networks. Signatures of all brain regions and pathways that were prominent in the first method also surfaced in the second method, thus providing support that these brain regions and pathways are indeed involved in migraine pathophysiology.

  18. Regional Volume Decreases in the Brain of Pax6 Heterozygous Mutant Rats: MRI Deformation-Based Morphometry

    PubMed Central

    Hiraoka, Kotaro; Sumiyoshi, Akira; Nonaka, Hiroi; Kikkawa, Takako; Kawashima, Ryuta; Osumi, Noriko

    2016-01-01

    Pax6 is a transcription factor that pleiotropically regulates various developmental processes in the central nervous system. In a previous study, we revealed that Pax6 heterozygous mutant (rSey2/+) adult rats exhibit abnormalities in social interaction. However, the brain malformations underlying the behavioral abnormality are unknown. To elucidate the brain malformations in rSey2/+ rats, we morphometrically analyzed brains of rSey2/+ and wild type rats using small-animal magnetic resonance imaging (MRI). Sixty 10-week-old rats underwent brain MRI (29 rSey2/+ rats and 31 wild type rats). SPM8 software was used for image preprocessing and statistical image analysis. Normalized maps of the Jacobian determinant, a parameter for the expansion and/or contraction of brain regions, were obtained for each rat. rSey2/+ rats showed significant volume decreases in various brain regions including the neocortex, corpus callosum, olfactory structures, hippocampal formation, diencephalon, and midbrain compared to wild type rats. Among brain regions, the anterior commissure showed significant interaction between genotype and sex, indicating the effect of genotype difference on the anterior commissure volume was more robust in females than in males. The rSey2/+ rats exhibited decreased volume in various gray and white matter regions of the brain, which may contribute to manifestation of abnormal social behaviors. PMID:27355350

  19. Sustained Survival and Maturation of Adult Neural Stem/Progenitor Cells after Transplantation into the Injured Brain

    PubMed Central

    Gugliotta, Marinella; Rolfe, Andrew; Reid, Wendy; McQuiston, A. Rory; Hu, Wenhui; Young, Harold

    2011-01-01

    Abstract Multipotent neural stem/progenitor cells (NS/NPCs) that are capable of generating neurons and glia offer enormous potential for treating neurological diseases. Adult NS/NPCs that reside in the mature mammalian brain can be isolated and expanded in vitro, and could be a potential source for autologous transplantation to replace cells lost to brain injury or disease. When these cells are transplanted into the normal brain, they can survive and become region-specific cells. However, it has not been reported whether these cells can survive for an extended period and become functional cells in an injured heterotypic environment. In this study, we tested survival, maturation fate, and electrophysiological properties of adult NS/NPCs after transplantation into the injured rat brain. NS/NPCs were isolated from the subventricular zone of adult Fisher 344 rats and cultured as a monolayer. Recipient adult Fisher 344 rats were first subjected to a moderate fluid percussive injury. Two days later, cultured NS/NPCs were injected into the injured brain in an area between the white matter tracts and peri-cortical region directly underneath the injury impact. The animals were sacrificed 2 or 4 weeks after transplantation for immunohistochemical staining or patch-clamp recording. We found that transplanted cells survived well at 2 and 4 weeks. Many cells migrated out of the injection site into surrounding areas expressing astrocyte or oligodendrocyte markers. Whole cell patch-clamp recording at 4 weeks showed that transplanted cells possessed typical mature glial cell properties. These data demonstrate that adult NS/NPCs can survive in an injured heterotypic environment for an extended period and become functional cells. PMID:21332258

  20. Physical Activity Is Linked to Greater Moment-To-Moment Variability in Spontaneous Brain Activity in Older Adults.

    PubMed

    Burzynska, Agnieszka Z; Wong, Chelsea N; Voss, Michelle W; Cooke, Gillian E; Gothe, Neha P; Fanning, Jason; McAuley, Edward; Kramer, Arthur F

    2015-01-01

    Higher cardiorespiratory fitness (CRF) and physical activity (PA) in old age are associated with greater brain structural and functional integrity, and higher cognitive functioning. However, it is not known how different aspects of lifestyle such as sedentariness, light PA (LI-PA), or moderate-to-vigorous physical activity (MV-PA) relate to neural activity in aging. In addition, it is not known whether the effects of PA on brain function differ or overlap with those of CRF. Here, we objectively measured CRF as oxygen consumption during a maximal exercise test and measured PA with an accelerometer worn for 7 days in 100 healthy but low active older adults (aged 60-80 years). We modeled the relationships between CRF, PA, and brain functional integrity using multivariate partial least squares analysis. As an index of functional brain integrity we used spontaneous moment-to-moment variability in the blood oxygenation level-dependent signal (SDBOLD), known to be associated with better cognitive functioning in aging. We found that older adults who engaged more in LI-PA and MV-PA had greater SDBOLD in brain regions that play a role in integrating segregated functional domains in the brain and benefit from greater CRF or PA, such as precuneus, hippocampus, medial and lateral prefrontal, and temporal cortices. Our results suggest that engaging in higher intensity PA may have protective effects on neural processing in aging. Finally, we demonstrated that older adults with greater overall WM microstructure were those showing more LI-PA and MV-PA and greater SDBOLD. We conclude that SDBOLD is a promising correlate of functional brain health in aging. Future analyses will evaluate whether SDBOLD is modifiable with interventions aimed to increase PA and CRF in older adults.

  1. Physical Activity Is Linked to Greater Moment-To-Moment Variability in Spontaneous Brain Activity in Older Adults

    PubMed Central

    Burzynska, Agnieszka Z.; Wong, Chelsea N.; Voss, Michelle W.; Cooke, Gillian E.; Gothe, Neha P.; Fanning, Jason; McAuley, Edward; Kramer, Arthur F.

    2015-01-01

    Higher cardiorespiratory fitness (CRF) and physical activity (PA) in old age are associated with greater brain structural and functional integrity, and higher cognitive functioning. However, it is not known how different aspects of lifestyle such as sedentariness, light PA (LI-PA), or moderate-to-vigorous physical activity (MV-PA) relate to neural activity in aging. In addition, it is not known whether the effects of PA on brain function differ or overlap with those of CRF. Here, we objectively measured CRF as oxygen consumption during a maximal exercise test and measured PA with an accelerometer worn for 7 days in 100 healthy but low active older adults (aged 60–80 years). We modeled the relationships between CRF, PA, and brain functional integrity using multivariate partial least squares analysis. As an index of functional brain integrity we used spontaneous moment-to-moment variability in the blood oxygenation level-dependent signal (SDBOLD), known to be associated with better cognitive functioning in aging. We found that older adults who engaged more in LI-PA and MV-PA had greater SDBOLD in brain regions that play a role in integrating segregated functional domains in the brain and benefit from greater CRF or PA, such as precuneus, hippocampus, medial and lateral prefrontal, and temporal cortices. Our results suggest that engaging in higher intensity PA may have protective effects on neural processing in aging. Finally, we demonstrated that older adults with greater overall WM microstructure were those showing more LI-PA and MV-PA and greater SDBOLD. We conclude that SDBOLD is a promising correlate of functional brain health in aging. Future analyses will evaluate whether SDBOLD is modifiable with interventions aimed to increase PA and CRF in older adults. PMID:26244873

  2. Investigation of genes important in neurodevelopment disorders in adult human brain.

    PubMed

    Maussion, Gilles; Diallo, Alpha B; Gigek, Carolina O; Chen, Elizabeth S; Crapper, Liam; Théroux, Jean-Francois; Chen, Gary G; Vasuta, Cristina; Ernst, Carl

    2015-10-01

    Several neurodevelopmental disorders (NDDs) are caused by mutations in genes expressed in fetal brain, but little is known about these same genes in adult human brain. Here, we test the hypothesis that genes associated with NDDs continue to have a role in adult human brain to explore the idea that NDD symptoms may be partially a result of their adult function rather than just their neurodevelopmental function. To demonstrate adult brain function, we performed expression analyses and ChIPseq in human neural stem cell(NSC) lines at different developmental stages and adult human brain, targeting two genes associated with NDDs, SATB2 and EHMT1, and the WNT signaling gene TCF7L2, which has not been associated with NDDs. Analysis of DNA interaction sites in neural stem cells reveals high (40-50 %) overlap between proliferating and differentiating cells for each gene in temporal space. Studies in adult brain demonstrate that consensus sites are similar to NSCs but occur at different genomic locations. We also performed expression analyses using BrainSpan data for NDD-associated genes SATB2, EHMT1, FMR1, MECP2, MBD5, CTNND2, RAI1, CHD8, GRIN2A, GRIN2B, TCF4, SCN2A, and DYRK1A and find high expression of these genes in adult brain, at least comparable to developing human brain, confirming that genes associated with NDDs likely have a role in adult tissue. Adult function of genes associated with NDDs might be important in clinical disease presentation and may be suitable targets for therapeutic intervention. PMID:26194112

  3. Investigation of genes important in neurodevelopment disorders in adult human brain.

    PubMed

    Maussion, Gilles; Diallo, Alpha B; Gigek, Carolina O; Chen, Elizabeth S; Crapper, Liam; Théroux, Jean-Francois; Chen, Gary G; Vasuta, Cristina; Ernst, Carl

    2015-10-01

    Several neurodevelopmental disorders (NDDs) are caused by mutations in genes expressed in fetal brain, but little is known about these same genes in adult human brain. Here, we test the hypothesis that genes associated with NDDs continue to have a role in adult human brain to explore the idea that NDD symptoms may be partially a result of their adult function rather than just their neurodevelopmental function. To demonstrate adult brain function, we performed expression analyses and ChIPseq in human neural stem cell(NSC) lines at different developmental stages and adult human brain, targeting two genes associated with NDDs, SATB2 and EHMT1, and the WNT signaling gene TCF7L2, which has not been associated with NDDs. Analysis of DNA interaction sites in neural stem cells reveals high (40-50 %) overlap between proliferating and differentiating cells for each gene in temporal space. Studies in adult brain demonstrate that consensus sites are similar to NSCs but occur at different genomic locations. We also performed expression analyses using BrainSpan data for NDD-associated genes SATB2, EHMT1, FMR1, MECP2, MBD5, CTNND2, RAI1, CHD8, GRIN2A, GRIN2B, TCF4, SCN2A, and DYRK1A and find high expression of these genes in adult brain, at least comparable to developing human brain, confirming that genes associated with NDDs likely have a role in adult tissue. Adult function of genes associated with NDDs might be important in clinical disease presentation and may be suitable targets for therapeutic intervention.

  4. [Toxic effect of formaldehyde on mouse different brain regions].

    PubMed

    Cao, Feng-Hua; Cai, Jie; Liu, Zhi-Min; Li, Hui; You, Hui-Hui; Mei, Yu-Fei; Yang, Xu; Ding, Shu-Mao

    2015-10-25

    The aim of this study was to explore the mechanism of the nervous system lesions induced by formaldehyde (FA). Male Balb/c mice were exposed to gaseous formaldehyde for 7 days (8 h/d) with three different concentrations (0, 0.5 and 3.0 mg/m(3)). A group of animals injected with the nitric oxide synthase inhibitor L-NMMA (0.01 mL/g) was also set and exposed to 3.0 mg/m(3) FA. The concentrations of cAMP, cGMP, NO and the activity of NOS in cerebral cortex, hippocampus and brain stem were determined by corresponding assay kits. The results showed that, compared with the control (0 mg/m(3) FA) group, the cAMP contents in cerebral cortex and brain stem were significantly increased in 0.5 mg/m(3) FA group (P < 0.05), but decreased in 3.0 mg/m(3) FA group (P < 0.05); The concentration of cAMP in hippocampus was significantly decreased in 3.0 mg/m(3) FA group (P < 0.05). In comparison with the control group, L-NMMA group showed unchanged cAMP contents and NOS activities in different brain regions, but showed increased cGMP contents in hippocampus and NO contents in cerebral cortex (P < 0.05). In addition, compared with 3.0 mg/m(3) FA group, L-NMMA group showed increased contents of cAMP and reduced NOS activities in different brain regions, as well as significantly decreased cGMP contents in cerebral cortex and brain stem and NO content in brain stem. These results suggest that the toxicity of FA on mouse nervous system is related to NO/cGMP and cAMP signaling pathways. PMID:26490067

  5. [Toxic effect of formaldehyde on mouse different brain regions].

    PubMed

    Cao, Feng-Hua; Cai, Jie; Liu, Zhi-Min; Li, Hui; You, Hui-Hui; Mei, Yu-Fei; Yang, Xu; Ding, Shu-Mao

    2015-10-25

    The aim of this study was to explore the mechanism of the nervous system lesions induced by formaldehyde (FA). Male Balb/c mice were exposed to gaseous formaldehyde for 7 days (8 h/d) with three different concentrations (0, 0.5 and 3.0 mg/m(3)). A group of animals injected with the nitric oxide synthase inhibitor L-NMMA (0.01 mL/g) was also set and exposed to 3.0 mg/m(3) FA. The concentrations of cAMP, cGMP, NO and the activity of NOS in cerebral cortex, hippocampus and brain stem were determined by corresponding assay kits. The results showed that, compared with the control (0 mg/m(3) FA) group, the cAMP contents in cerebral cortex and brain stem were significantly increased in 0.5 mg/m(3) FA group (P < 0.05), but decreased in 3.0 mg/m(3) FA group (P < 0.05); The concentration of cAMP in hippocampus was significantly decreased in 3.0 mg/m(3) FA group (P < 0.05). In comparison with the control group, L-NMMA group showed unchanged cAMP contents and NOS activities in different brain regions, but showed increased cGMP contents in hippocampus and NO contents in cerebral cortex (P < 0.05). In addition, compared with 3.0 mg/m(3) FA group, L-NMMA group showed increased contents of cAMP and reduced NOS activities in different brain regions, as well as significantly decreased cGMP contents in cerebral cortex and brain stem and NO content in brain stem. These results suggest that the toxicity of FA on mouse nervous system is related to NO/cGMP and cAMP signaling pathways.

  6. Brain Pathology in Adult Rats Treated With Domoic Acid.

    PubMed

    Vieira, A C; Alemañ, N; Cifuentes, J M; Bermúdez, R; Peña, M López; Botana, L M

    2015-11-01

    Domoic acid (DA) is a neurotoxin reported to produce damage to the hippocampus, which plays an important role in memory. The authors inoculated rats intraperitoneally with an effective toxic dose of DA to study the distribution of the toxin in major internal organs by using immunohistochemistry, as well as to evaluate the induced pathology by means of histopathologic and immunohistochemical methods at different time points after toxin administration (6, 10, and 24 hours; 5 and 54 days). DA was detected by immunohistochemistry exclusively in pyramidal neurons of the hippocampus at 6 and 10 hours after dosing. Lesions induced by DA were prominent at 5 days following treatment in selected regions of the brain: hippocampus, amygdala, piriform and perirhinal cortices, olfactory tubercle, septal nuclei, and thalamus. The authors found 2 types of lesions: delayed death of selective neurons and large areas of necrosis, both accompanied by astrocytosis and microgliosis. At 54 days after DA exposure, the pathology was characterized by still-distinguishable dying neurons, calcified lesions in the thalamus, persistent astrocytosis, and pronounced microgliosis. The expression of nitric oxide synthases suggests a role for nitric oxide in the pathogenesis of neuronal degeneration and chronic inflammation induced by DA in the brain.

  7. Cortical Brain Regions Associated with Color Processing: An FMRi Study

    PubMed Central

    Bramão, Inês; Faísca, Luís; Forkstam, Christian; Reis, Alexandra; Petersson, Karl Magnus

    2010-01-01

    To clarify whether the neural pathways concerning color processing are the same for natural objects, for artifacts objects and for non-objects we examined brain responses measured with functional magnetic resonance imaging (FMRI) during a covert naming task including the factors color (color vs. black&white (B&W)) and stimulus type (natural vs. artifacts vs. non-objects). Our results indicate that the superior parietal lobule and precuneus (BA 7) bilaterally, the right hippocampus and the right fusifom gyrus (V4) make part of a network responsible for color processing both for natural objects and artifacts, but not for non-objects. When color objects (both natural and artifacts) were contrasted with color non-objects we observed activations in the right parahippocampal gyrus (BA 35/36), the superior parietal lobule (BA 7) bilaterally, the left inferior middle temporal region (BA 20/21) and the inferior and superior frontal regions (BA 10/11/47). These additional activations suggest that colored objects recruit brain regions that are related to visual semantic information/retrieval and brain regions related to visuo-spatial processing. Overall, the results suggest that color information is an attribute that can improve object recognition (behavioral results) and activate a specific neural network related to visual semantic information that is more extensive than for B&W objects during object recognition. PMID:21270939

  8. GABA regulates synaptic integration of newly generated neurons in the adult brain

    NASA Astrophysics Data System (ADS)

    Ge, Shaoyu; Goh, Eyleen L. K.; Sailor, Kurt A.; Kitabatake, Yasuji; Ming, Guo-Li; Song, Hongjun

    2006-02-01

    Adult neurogenesis, the birth and integration of new neurons from adult neural stem cells, is a striking form of structural plasticity and highlights the regenerative capacity of the adult mammalian brain. Accumulating evidence suggests that neuronal activity regulates adult neurogenesis and that new neurons contribute to specific brain functions. The mechanism that regulates the integration of newly generated neurons into the pre-existing functional circuitry in the adult brain is unknown. Here we show that newborn granule cells in the dentate gyrus of the adult hippocampus are tonically activated by ambient GABA (γ-aminobutyric acid) before being sequentially innervated by GABA- and glutamate-mediated synaptic inputs. GABA, the major inhibitory neurotransmitter in the adult brain, initially exerts an excitatory action on newborn neurons owing to their high cytoplasmic chloride ion content. Conversion of GABA-induced depolarization (excitation) into hyperpolarization (inhibition) in newborn neurons leads to marked defects in their synapse formation and dendritic development in vivo. Our study identifies an essential role for GABA in the synaptic integration of newly generated neurons in the adult brain, and suggests an unexpected mechanism for activity-dependent regulation of adult neurogenesis, in which newborn neurons may sense neuronal network activity through tonic and phasic GABA activation.

  9. Cardiovascular risks and brain function: a functional magnetic resonance imaging study of executive function in older adults.

    PubMed

    Chuang, Yi-Fang; Eldreth, Dana; Erickson, Kirk I; Varma, Vijay; Harris, Gregory; Fried, Linda P; Rebok, George W; Tanner, Elizabeth K; Carlson, Michelle C

    2014-06-01

    Cardiovascular (CV) risk factors, such as hypertension, diabetes, and hyperlipidemia are associated with cognitive impairment and risk of dementia in older adults. However, the mechanisms linking them are not clear. This study aims to investigate the association between aggregate CV risk, assessed by the Framingham general cardiovascular risk profile, and functional brain activation in a group of community-dwelling older adults. Sixty participants (mean age: 64.6 years) from the Brain Health Study, a nested study of the Baltimore Experience Corps Trial, underwent functional magnetic resonance imaging using the Flanker task. We found that participants with higher CV risk had greater task-related activation in the left inferior parietal region, and this increased activation was associated with poorer task performance. Our results provide insights into the neural systems underlying the relationship between CV risk and executive function. Increased activation of the inferior parietal region may offer a pathway through which CV risk increases risk for cognitive impairment.

  10. The association of brain structure with gait velocity in older adults: a quantitative volumetric analysis of brain MRI

    PubMed Central

    Katz, Mindy J.; Lipton, Michael L.; Lipton, Richard B.; Verghese, Joe

    2015-01-01

    Introduction While cortical processes play an important role in controlling locomotion, the underlying structural brain changes associated with slowing of gait in aging are not yet fully established. Our study aimed to examine the relationship between cortical gray matter volume (GM), white matter volume (WM), ventricular volume (VV), hippocampal and hippocampal subfield volumes, and gait velocity in older adults free of dementia. Methods Gait and cognitive performance was tested in 112 community-residing adults, age 70 years and over, participating in the Einstein Aging Study. Gait velocity (cm/s) was obtained using an instrumented walkway. Volumetric MRI measures were estimated using a FreeSurfer software. We examined the cross-sectional relationship of GM, WM, VV, and hippocampal total and subfield volumes and gait velocity using linear regression models. In complementary models, the effect of memory performance on the relationship between gait velocity and regional volumes was evaluated. Results Slower gait velocity was associated with smaller cortical GM and total hippocampal volumes. There was no association between gait velocity and WM or VV. Among hippocampal subfields, only smaller presubiculum volume was significantly associated with decrease in gait velocity. Addition of the memory performance to the models attenuated the association between gait velocity and all volumetric measures. Conclusions Our findings indicate that total GM and hippocampal volumes as well as specific hippocampal subfield volumes are inversely associated with locomotor function. These associations are probably affected by cognitive status of study population. PMID:25921321

  11. Effect of exposure to diazinon on adult rat's brain.

    PubMed

    Rashedinia, Marzieh; Hosseinzadeh, Hossein; Imenshahidi, Mohsen; Lari, Parisa; Razavi, Bibi Marjan; Abnous, Khalil

    2016-04-01

    Diazinon (DZN), a commonly used agricultural organophosphate insecticide, is one of the major concerns for human health. This study was planned to investigate neurotoxic effects of subacute exposure to DZN in adult male Wistar rats. Animals received corn oil as control and 15 and 30 mg/kg DZN orally by gastric gavage for 4 weeks. The cerebrum malondialdehyde and glutathione (GSH) contents were assessed as biomarkers of lipid peroxidation and nonenzyme antioxidants, respectively. Moreover, activated forms of caspase 3, -9, and Bax/Bcl-2 ratios were evaluated as key apoptotic proteins. Results of this study suggested that chronic administration of DZN did not change lipid peroxidation and GSH levels significantly in comparison with control. Also, the active forms of caspase 3 and caspase 9 were not significantly altered in DZN-treated rat groups. Moreover, no significant changes were observed in Bax and Bcl-2 ratios. This study indicated that generation of reactive oxygen species was probably modulated by intracellular antioxidant system. In conclusion, subacute oral administration of DZN did not alter lipid peroxidation. Moreover, apoptosis induction was not observed in rat brain.

  12. Behavioral responses to and brain distribution of morphine in mature adult and aged mice

    SciTech Connect

    Burton, C.K.; Ho, I.K.; Hoskins, B.

    1986-03-01

    Mature adult (3-6 mo old) and aged (2 yr old) male ICR mice were injected with 10 to 100 mg/kg morphine, s.c. The ED50 values for running behavior (as measured using Stoelting activity monitors and having each mouse serve as its own control) representing 5 times control activity was approximately 7.5 mg/kg for aged mice and approximately 17.5 mg/kg for the mature adults. The ED50 values for analgesia 1 hr after morphine administration using the tail-flick method (max. response time = 8 sec) were approx. 70 mg/kg for the aged mice and 15 mg/kg for the mature adults. One hour after injecting /sup 3/H-morphine at doses of 30 and 100 mg/kg, 0.13 and 0.14% of the doses appeared in brains of aged and mature adult mice, respectively. Regional distribution of the morphine was the same for both age groups. Expressed as percent of total brain morphine, it was as follows: cortex, 30%; midbrain, 18%; cerebellum, 17%; medulla, 12%; pons, 9%; striatum, 8% and periaqueductal gray, 6%. Expressed as g morphine/g tissue for the 2 doses, the distribution was; periaqueductal gray, 30 and 80; striatum, 9 and 34; medulla, 6 and 20 pons; 5 and 19; cerebellum, 4 and 13; midbrain 2.5 and 8.5 and cortex, 2 and 8. These results suggest that the differences in response to morphine by the two age groups were due to age-related differences in opioid receptor populations and/or affinities.

  13. Correlations between Brain Cortical Thickness and Cutaneous Pain Thresholds Are Atypical in Adults with Migraine

    PubMed Central

    Schwedt, Todd J.; Chong, Catherine D.

    2014-01-01

    Background/Objective Migraineurs have atypical pain processing, increased expectations for pain, and hypervigilance for pain. Recent studies identified correlations between brain structure and pain sensation in healthy adults. The objective of this study was to compare cortical thickness-to-pain threshold correlations in migraineurs to healthy controls. We hypothesized that migraineurs would have aberrant relationships between the anatomical neurocorrelates of pain processing and pain thresholds. Methods Pain thresholds to cutaneously applied heat were determined for 31 adult migraineurs and 32 healthy controls. Cortical thickness was determined from magnetic resonance imaging T1-weighted sequences. Regional cortical thickness-to-pain threshold correlations were determined for migraineurs and controls separately using a general linear model whole brain vertex-wise analysis. A pain threshold-by-group interaction analysis was then conducted to estimate regions where migraineurs show alterations in the pain threshold-to-cortical thickness correlations relative to healthy controls. Results Controls had negative correlations (p<0.01 uncorrected) between pain thresholds and cortical thickness in left posterior cingulate/precuneus, right superior temporal, right inferior parietal, and left inferior temporal regions, and a negative correlation (p<0.01 Monte Carlo corrected) with a left superior temporal/inferior parietal region. Migraineurs had positive correlations (p<0.01 uncorrected) between pain thresholds and cortical thickness in left superior temporal/inferior parietal, right precuneus, right superior temporal/inferior parietal, and left inferior parietal regions. Cortical thickness-to-pain threshold correlations differed between migraine and control groups (p<0.01 uncorrected) for right superior temporal/inferior parietal, right precentral, left posterior cingulate/precuneus, and right inferior parietal regions and (p<0.01 Monte Carlo corrected) for a left superior

  14. Environmental enrichment is associated with rapid volumetric brain changes in adult mice.

    PubMed

    Scholz, Jan; Allemang-Grand, Rylan; Dazai, Jun; Lerch, Jason P

    2015-04-01

    Environmental enrichment is a model of increased structural brain plasticity. Previous histological observations have shown molecular and cellular changes in a few pre-determined areas of the rodent brain. However, little is known about the time course of enrichment-induced brain changes and how they distribute across the whole brain. Here we expose adult mice to three weeks of environmental enrichment using a novel re-configurable maze design. In-vivo MRI shows volumetric brain changes in brain areas related to spatial memory, navigation, and sensorimotor experience, such as the hippocampal formation and the sensorimotor cortex. Evidence from a second cohort of mice indicates that these plastic changes might occur as early as 24h after exposure. This suggests that novel experiences are powerful modulators of plasticity even in the adult brain. Understanding and harnessing the underlying molecular mechanisms could advance future treatments of neurological disease.

  15. Brain activation during dual-task processing is associated with cardiorespiratory fitness and performance in older adults

    PubMed Central

    Wong, Chelsea N.; Chaddock-Heyman, Laura; Voss, Michelle W.; Burzynska, Agnieszka Z.; Basak, Chandramallika; Erickson, Kirk I.; Prakash, Ruchika S.; Szabo-Reed, Amanda N.; Phillips, Siobhan M.; Wojcicki, Thomas; Mailey, Emily L.; McAuley, Edward; Kramer, Arthur F.

    2015-01-01

    Higher cardiorespiratory fitness is associated with better cognitive performance and enhanced brain activation. Yet, the extent to which cardiorespiratory fitness-related brain activation is associated with better cognitive performance is not well understood. In this cross-sectional study, we examined whether the association between cardiorespiratory fitness and executive function was mediated by greater prefrontal cortex activation in healthy older adults. Brain activation was measured during dual-task performance with functional magnetic resonance imaging in a sample of 128 healthy older adults (59–80 years). Higher cardiorespiratory fitness was associated with greater activation during dual-task processing in several brain areas including the anterior cingulate and supplementary motor cortex (ACC/SMA), thalamus and basal ganglia, right motor/somatosensory cortex and middle frontal gyrus, and left somatosensory cortex, controlling for age, sex, education, and gray matter volume. Of these regions, greater ACC/SMA activation mediated the association between cardiorespiratory fitness and dual-task performance. We provide novel evidence that cardiorespiratory fitness may support cognitive performance by facilitating brain activation in a core region critical for executive function. PMID:26321949

  16. Encoding of mechanical nociception differs in the adult and infant brain

    PubMed Central

    Fabrizi, Lorenzo; Verriotis, Madeleine; Williams, Gemma; Lee, Amy; Meek, Judith; Olhede, Sofia; Fitzgerald, Maria

    2016-01-01

    Newborn human infants display robust pain behaviour and specific cortical activity following noxious skin stimulation, but it is not known whether brain processing of nociceptive information differs in infants and adults. Imaging studies have emphasised the overlap between infant and adult brain connectome architecture, but electrophysiological analysis of infant brain nociceptive networks can provide further understanding of the functional postnatal development of pain perception. Here we hypothesise that the human infant brain encodes noxious information with different neuronal patterns compared to adults. To test this we compared EEG responses to the same time-locked noxious skin lance in infants aged 0–19 days (n = 18, clinically required) and adults aged 23–48 years (n = 21). Time-frequency analysis revealed that while some features of adult nociceptive network activity are present in infants at longer latencies, including beta-gamma oscillations, infants display a distinct, long latency, noxious evoked 18-fold energy increase in the fast delta band (2–4 Hz) that is absent in adults. The differences in activity between infants and adults have a widespread topographic distribution across the brain. These data support our hypothesis and indicate important postnatal changes in the encoding of mechanical pain in the human brain. PMID:27345331

  17. Regional Variations in Brain Gyrification Are Associated with General Cognitive Ability in Humans.

    PubMed

    Gregory, Michael D; Kippenhan, J Shane; Dickinson, Dwight; Carrasco, Jessica; Mattay, Venkata S; Weinberger, Daniel R; Berman, Karen F

    2016-05-23

    Searching for a neurobiological understanding of human intellectual capabilities has long occupied those very capabilities. Brain gyrification, or folding of the cortex, is as highly evolved and variable a characteristic in humans as is intelligence. Indeed, gyrification scales with brain size, and relationships between brain size and intelligence have been demonstrated in humans [1-3]. However, gyrification shows a large degree of variability that is independent from brain size [4-6], suggesting that the former may independently contribute to cognitive abilities and thus supporting a direct investigation of this parameter in the context of intelligence. Moreover, uncovering the regional pattern of such an association could offer insights into evolutionary and neural mechanisms. We tested for this brain-behavior relationship in two separate, independently collected, large cohorts-440 healthy adults and 662 healthy children-using high-resolution structural neuroimaging and comprehensive neuropsychometric batteries. In both samples, general cognitive ability was significantly associated (pFDR < 0.01) with increasing gyrification in a network of neocortical regions, including large portions of the prefrontal cortex, inferior parietal lobule, and temporoparietal junction, as well as the insula, cingulate cortex, and fusiform gyrus, a regional distribution that was nearly identical in both samples (Dice similarity coefficient = 0.80). This neuroanatomical pattern is consistent with an existing, well-known proposal, the Parieto-Frontal Integration Theory of intelligence [7], and is also consistent with research in comparative evolutionary biology showing rapid neocortical expansion of these regions in humans relative to other species. These data provide a framework for understanding the neurobiology of human cognitive abilities and suggest a potential neurocellular association. PMID:27133866

  18. Regional Brain Shrinkage over Two Years: Individual Differences and Effects of Pro-Inflammatory Genetic Polymorphisms

    PubMed Central

    Persson, N.; Ghisletta, P.; Dahle, C.L.; Bender, A.R.; Yang, Y.; Yuan, P.; Daugherty, A.M.; Raz, N.

    2014-01-01

    We examined regional changes in brain volume in healthy adults (N = 167, age 19-79 years at baseline; N = 90 at follow-up) over approximately two years. With latent change score models, we evaluated mean change and individual differences in rates of change in 10 anatomically-defined and manually-traced regions of interest (ROIs): lateral prefrontal cortex (LPFC), orbital frontal cortex (OF), prefrontal white matter (PFw), hippocampus (HC), parahippocampal gyrus (PhG), caudate nucleus (Cd), putamen (Pt), insula (In), cerebellar hemispheres (CbH), and primary visual cortex (VC). Significant mean shrinkage was observed in the HC, CbH, In, OF, and the PhG, and individual differences in change were noted in all regions, except the OF. Pro-inflammatory genetic variants mediated shrinkage in PhG and CbH. Carriers of two T alleles of interleukin-1β (IL-1βC-511T, rs16944) and a T allele of methylenetetrahydrofolate reductase (MTHFRC677T, rs1801133) polymorphisms showed increased PhG shrinkage. No effects of a pro-inflammatory polymorphism for C-reactive protein (CRP-286C>A>T, rs3091244) or apolipoprotein (APOE) ε4 allele were noted. These results replicate the pattern of brain shrinkage observed in previous studies, with a notable exception of the LPFC thus casting doubt on the unique importance of prefrontal cortex in aging. Larger baseline volumes of CbH and In were associated with increased shrinkage, in conflict with the brain reserve hypothesis. Contrary to previous reports, we observed no significant linear effects of age and hypertension on regional brain shrinkage. Our findings warrant further investigation of the effects of neuroinflammation on structural brain change throughout the lifespan. PMID:25264227

  19. Identification of Differentially Expressed Genes through Integrated Study of Alzheimer’s Disease Affected Brain Regions

    PubMed Central

    Berretta, Regina; Moscato, Pablo

    2016-01-01

    Background Alzheimer’s disease (AD) is the most common form of dementia in older adults that damages the brain and results in impaired memory, thinking and behaviour. The identification of differentially expressed genes and related pathways among affected brain regions can provide more information on the mechanisms of AD. In the past decade, several studies have reported many genes that are associated with AD. This wealth of information has become difficult to follow and interpret as most of the results are conflicting. In that case, it is worth doing an integrated study of multiple datasets that helps to increase the total number of samples and the statistical power in detecting biomarkers. In this study, we present an integrated analysis of five different brain region datasets and introduce new genes that warrant further investigation. Methods The aim of our study is to apply a novel combinatorial optimisation based meta-analysis approach to identify differentially expressed genes that are associated to AD across brain regions. In this study, microarray gene expression data from 161 samples (74 non-demented controls, 87 AD) from the Entorhinal Cortex (EC), Hippocampus (HIP), Middle temporal gyrus (MTG), Posterior cingulate cortex (PC), Superior frontal gyrus (SFG) and visual cortex (VCX) brain regions were integrated and analysed using our method. The results are then compared to two popular meta-analysis methods, RankProd and GeneMeta, and to what can be obtained by analysing the individual datasets. Results We find genes related with AD that are consistent with existing studies, and new candidate genes not previously related with AD. Our study confirms the up-regualtion of INFAR2 and PTMA along with the down regulation of GPHN, RAB2A, PSMD14 and FGF. Novel genes PSMB2, WNK1, RPL15, SEMA4C, RWDD2A and LARGE are found to be differentially expressed across all brain regions. Further investigation on these genes may provide new insights into the development of AD

  20. Regeneration of central cholinergic neurones in the adult rat brain.

    PubMed

    Svendgaard, N A; Björklund, A; Stenevi, U

    1976-01-30

    The regrowth of lesioned central acetylcholinesterase (AChE)-positive axons in the adult rat was studied in irides implanted to two different brain sites: in the caudal diencephalon and hippocampus, and in the hippocampal fimbria. At both implantation sites the cholinergic septo-hippocampal pathways were transected. At 2-4 weeks after lesion, newly formed, probably sprouting fibres could be followed in abundance from the lesioned proximal axon stumps into the iris transplant. Growth of newly formed AChE-positive fibres into the transplant was also observed from lesioned axons in the anterior thalamus, and to a minor extent also from the dorsal and ventral tegmental AChE-positive pathways and the habenulo-interpeduncular tract. The regrowth process of the sprouting AChE-positive, presumed cholinergic fibres into the iris target was studied in further detail in whole-mount preparations of the transplants. For this purpose the irides were removed from the brain, unfolded, spread out on microscope slides, and then stained for AChE. During the first 2-4 weeks after transplantation the sprouting central fibres grew out over large areas of the iris. The new fibres branched profusely into a terminal plexus that covered maximally about half of the iris surface, and in some areas the patterning of the regenerated central fibres mimicked closely that of the normal autonomic cholinergic innervation of the iris. In one series of experiments the AChE-staining was combined with fluorescence histochemical visualization of regenerated adrenergic fibres in the same specimens. In many areas there was a striking congruence in the distributional patterns of the regenerated central cholinergic and adrenergic fibres in the transplant. This indicates that - as in the normal iris - the sprouting cholinergic axons (primarily originating in the lesioned septo-hippocampal pathways) and adrenergic axons (primarily originating in the lesioned axons of the locus neurones) regenerate together

  1. Sex hormones affect neurotransmitters and shape the adult female brain during hormonal transition periods

    PubMed Central

    Barth, Claudia; Villringer, Arno; Sacher, Julia

    2015-01-01

    Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination and other important mechanisms of neural plasticity. Here we review the evidence from animal experiments and human studies reporting interactions between sex hormones and the dominant neurotransmitters, such as serotonin, dopamine, GABA and glutamate. We provide an overview of accumulating data during physiological and pathological conditions and discuss currently conceptualized theories on how sex hormones potentially trigger neuroplasticity changes through these four neurochemical systems. Many brain regions have been demonstrated to express high densities for estrogen- and progesterone receptors, such as the amygdala, the hypothalamus, and the hippocampus. As the hippocampus is of particular relevance in the context of mediating structural plasticity in the adult brain, we put particular emphasis on what evidence could be gathered thus far that links differences in behavior, neurochemical patterns and hippocampal structure to a changing hormonal environment. Finally, we discuss how physiologically occurring hormonal transition periods in humans can be used to model how changes in sex hormones influence functional connectivity, neurotransmission and brain structure in vivo. PMID:25750611

  2. Automatic segmentation of brain images: selection of region extraction methods

    NASA Astrophysics Data System (ADS)

    Gong, Leiguang; Kulikowski, Casimir A.; Mezrich, Reuben S.

    1991-07-01

    In automatically analyzing brain structures from a MR image, the choice of low level region extraction methods depends on the characteristics of both the target object and the surrounding anatomical structures in the image. The authors have experimented with local thresholding, global thresholding, and other techniques, using various types of MR images for extracting the major brian landmarks and different types of lesions. This paper describes specifically a local- binary thresholding method and a new global-multiple thresholding technique developed for MR image segmentation and analysis. The initial testing results on their segmentation performance are presented, followed by a comparative analysis of the two methods and their ability to extract different types of normal and abnormal brain structures -- the brain matter itself, tumors, regions of edema surrounding lesions, multiple sclerosis lesions, and the ventricles of the brain. The analysis and experimental results show that the global multiple thresholding techniques are more than adequate for extracting regions that correspond to the major brian structures, while local binary thresholding is helpful for more accurate delineation of small lesions such as those produced by MS, and for the precise refinement of lesion boundaries. The detection of other landmarks, such as the interhemispheric fissure, may require other techniques, such as line-fitting. These experiments have led to the formulation of a set of generic computer-based rules for selecting the appropriate segmentation packages for particular types of problems, based on which further development of an innovative knowledge- based, goal directed biomedical image analysis framework is being made. The system will carry out the selection automatically for a given specific analysis task.

  3. Enhanced regional brain metabolic responses to benzodiazepines in cocaine abusers

    SciTech Connect

    Volkow, N.D.; Wang, G.J.; Fowler, J.S.

    1997-05-01

    While dopamine (DA) appears to be crucial for cocaine reinforcement, its involvement in cocaine addiction is much less clear. Using PET we have shown persistent reductions in striatal DA D2 receptors (which arc predominantly located on GABA cells) in cocaine abusers. This finding coupled to GABA`s role as an effector for DA led us to investigate if there were GABAergic abnormalities in cocaine abusers. In this study we measured regional brain metabolic responses to lorazepam, to indirectly assess GABA function (benzodiazepines facilitate GABAergic neurotransmission). Methods: The experimental subjects consisted of 12 active cocaine abusers and 32 age matched controls. Each subject underwent two PET FDG scans obtained within 1 week of each other. The first FDG scan was obtained after administration of placebo (3 cc of saline solution) given 40-50 minutes prior to FDG; and the second after administration of lorazepam (30 {mu}g/kg) given 40-50 minutes prior to FDG. The subjects were blind to the drugs received. Results: Lorazepam-induced sleepiness was significantly greater in abusers than in controls (p<0.001). Lorazepam-induced decreases in brain glucose metabolism were significantly larger in cocaine abusers than in controls. Whereas in controls whole brain metabolism decreased 13{+-}7 %, in cocaine abusers it decreased 21{+-}13 % (p < 0.05). Lorazepam-induced decrements in regional metabolism were significantly larger in striatum (p < 0.0 1), thalamus (p < 0.01) and cerebellum (p < 0.005) of cocaine abusers than of controls (ANOVA diagnosis by condition (placebo versus lorazepam) interaction effect). The only brain region for which the absolute metabolic changes-induced by lorazepam in cocaine abusers were equivalent to those in controls was the orbitofrontal cortex. These results document an accentuated sensitivity to benzodiazepines in cocaine abusers which is compatible with disrupted GABAergic function in these patients.

  4. Diversity of endurance training effects on antioxidant defenses and oxidative damage in different brain regions of adolescent male rats.

    PubMed

    Chalimoniuk, M; Jagsz, S; Sadowska-Krepa, E; Chrapusta, S J; Klapcinska, B; Langfort, J

    2015-08-01

    Studies on the effect of physical activity on brain oxidative stress, performed mostly in adult rats, have shown that moderate aerobic activity increases resistance to oxidative stress and reduces cellular damage. These effects can greatly differ between various brain regions. The postnatal period of the highest brain sensitivity to various stimuli is adolescence. We hypothesized that endurance training will modify brain antioxidant barrier differently in various regions, depending on their role in locomotion. Therefore, we studied the effect of moderate intensity endurance training on the activities of selected antioxidant enzymes (superoxide dismutase, gluthathione peroxidase and catalase and the contents of thiobarbituric acid-reactive substances (the key index of lipid peroxidation) and glutathione in several brain regions with dissimilar relationship to locomotion, as well as in circulating blood. Additionally, we investigated the effect of the training on nitric oxide synthase activity that may be a major player in exercise-related oxidative stress in brain regions that are directly involved in the locomotion control and execution (the striatum, midbrain and cerebellum). The training significantly enhanced nitric oxide synthase activity only in the latter three regions. Surprisingly, it elevated the activities of all studied antioxidant enzymes (excepting gluthathione peroxidase) in the neocortex, while no appreciable change in these activities was found in either the cerebellum (except for elevated catalase activity), or the striatum, or the midbrain. The training also elevated total glutathione content (a key protector of brain proteins under the conditions of enhanced nitric oxide production) in the cerebellum and striatum, but not in the other regions. The observed brain changes greatly differed from those in circulating blood and did not prevent the training-related increases in oxidative damage as evidenced by elevations in cerebellar and striatal

  5. Blood-brain barrier permeability is increased after acute adult stroke but not neonatal stroke in the rat.

    PubMed

    Fernández-López, David; Faustino, Joel; Daneman, Richard; Zhou, Lu; Lee, Sarah Y; Derugin, Nikita; Wendland, Michael F; Vexler, Zinaida S

    2012-07-11

    The immaturity of the CNS at birth greatly affects injury after stroke but the contribution of the blood-brain barrier (BBB) to the differential response to stroke in adults and neonates is poorly understood. We asked whether the structure and function of the BBB is disrupted differently in neonatal and adult rats by transient middle cerebral artery occlusion. In adult rats, albumin leakage into injured regions was markedly increased during 2-24 h reperfusion but leakage remained low in the neonates. Functional assays employing intravascular tracers in the neonates showed that BBB permeability to both large (70 kDa dextran) and small (3 kDa dextran), gadolinium (III)-diethyltriaminepentaacetic acid tracers remained largely undisturbed 24 h after reperfusion. The profoundly different functional integrity of the BBB was associated with the largely nonoverlapping patterns of regulated genes in endothelial cells purified from injured and uninjured adult and neonatal brain at 24 h (endothelial transcriptome, 31,042 total probe sets). Within significantly regulated 1266 probe sets in injured adults and 361 probe sets in neonates, changes in the gene expression of the basal lamina components, adhesion molecules, the tight junction protein occludin, and matrix metalloproteinase-9 were among the key differences. The protein expression of collagen-IV, laminin, claudin-5, occludin, and zonula occludens protein 1 was also better preserved in neonatal rats. Neutrophil infiltration remained low in acutely injured neonates but neutralization of cytokine-induced neutrophil chemoattractant-1 in the systemic circulation enhanced neutrophil infiltration, BBB permeability, and injury. The markedly more integrant BBB in neonatal brain than in adult brain after acute stroke may have major implications for the treatment of neonatal stroke. PMID:22787045

  6. Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases

    PubMed Central

    Liu, He; Song, Ni

    2016-01-01

    Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and brain tumors. PMID:27375363

  7. Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases.

    PubMed

    Liu, He; Song, Ni

    2016-01-01

    Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and brain tumors. PMID:27375363

  8. Extrinsic and Intrinsic Brain Network Connectivity Maintains Cognition across the Lifespan Despite Accelerated Decay of Regional Brain Activation

    PubMed Central

    Henson, Richard N.A.; Tyler, Lorraine K.; Razi, Adeel; Geerligs, Linda; Ham, Timothy E.; Rowe, James B.

    2016-01-01

    large population-based cohort (n = 602, 18–88 years), separating neural connectivity from vascular components of fMRI signals. Cognitive ability was influenced by the strength of connection within and between functional brain networks, and this positive relationship increased with age. In older adults, there was more rapid decay of intrinsic neuronal activity in multiple regions of the brain networks, which related to cognitive performance. Our data demonstrate increased reliance on network flexibility to maintain cognitive function, in the presence of more rapid decay of neural activity. These insights will facilitate the development of new strategies to maintain cognitive ability. PMID:26985024

  9. Repetitive Transcranial Magnetic Stimulation Activates Specific Regions in Rat Brain

    NASA Astrophysics Data System (ADS)

    Ji, Ru-Rong; Schlaepfer, Thomas E.; Aizenman, Carlos D.; Epstein, Charles M.; Qiu, Dike; Huang, Justin C.; Rupp, Fabio

    1998-12-01

    Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive technique to induce electric currents in the brain. Although rTMS is being evaluated as a possible alternative to electroconvulsive therapy for the treatment of refractory depression, little is known about the pattern of activation induced in the brain by rTMS. We have compared immediate early gene expression in rat brain after rTMS and electroconvulsive stimulation, a well-established animal model for electroconvulsive therapy. Our result shows that rTMS applied in conditions effective in animal models of depression induces different patterns of immediate-early gene expression than does electroconvulsive stimulation. In particular, rTMS evokes strong neural responses in the paraventricular nucleus of the thalamus (PVT) and in other regions involved in the regulation of circadian rhythms. The response in PVT is independent of the orientation of the stimulation probe relative to the head. Part of this response is likely because of direct activation, as repetitive magnetic stimulation also activates PVT neurons in brain slices.

  10. Recovery from Mild Traumatic Brain Injury in Previously Healthy Adults.

    PubMed

    Losoi, Heidi; Silverberg, Noah D; Wäljas, Minna; Turunen, Senni; Rosti-Otajärvi, Eija; Helminen, Mika; Luoto, Teemu M; Julkunen, Juhani; Öhman, Juha; Iverson, Grant L

    2016-04-15

    This prospective longitudinal study reports recovery from mild traumatic brain injury (MTBI) across multiple domains in a carefully selected consecutive sample of 74 previously healthy adults. The patients with MTBI and 40 orthopedic controls (i.e., ankle injuries) completed assessments at 1, 6, and 12 months after injury. Outcome measures included cognition, post-concussion symptoms, depression, traumatic stress, quality of life, satisfaction with life, resilience, and return to work. Patients with MTBI reported more post-concussion symptoms and fatigue than the controls at the beginning of recovery, but by 6 months after injury, did not differ as a group from nonhead injury trauma controls on cognition, fatigue, or mental health, and by 12 months, their level of post-concussion symptoms and quality of life was similar to that of controls. Almost all (96%) patients with MTBI returned to work/normal activities (RTW) within the follow-up of 1 year. A subgroup of those with MTBIs and controls reported mild post-concussion-like symptoms at 1 year. A large percentage of the subgroup who had persistent symptoms had a modifiable psychological risk factor at 1 month (i.e., depression, traumatic stress, and/or low resilience), and at 6 months, they had greater post-concussion symptoms, fatigue, insomnia, traumatic stress, and depression, and worse quality of life. All of the control subjects who had mild post-concussion-like symptoms at 12 months also had a mental health problem (i.e., depression, traumatic stress, or both). This illustrates the importance of providing evidence-supported treatment and rehabilitation services early in the recovery period.

  11. Monte Carlo simulation of light propagation in the adult brain

    NASA Astrophysics Data System (ADS)

    Mudra, Regina M.; Nadler, Andreas; Keller, Emanuella; Niederer, Peter

    2004-06-01

    When near infrared spectroscopy (NIRS) is applied noninvasively to the adult head for brain monitoring, extra-cerebral bone and surface tissue exert a substantial influence on the cerebral signal. Most attempts to subtract extra-cerebral contamination involve spatially resolved spectroscopy (SRS). However, inter-individual variability of anatomy restrict the reliability of SRS. We simulated the light propagation with Monte Carlo techniques on the basis of anatomical structures determined from 3D-magnetic resonance imaging (MRI) exhibiting a voxel resolution of 0.8 x 0.8 x 0.8 mm3 for three different pairs of T1/T2 values each. The MRI data were used to define the material light absorption and dispersion coefficient for each voxel. The resulting spatial matrix was applied in the Monte Carlo Simulation to determine the light propagation in the cerebral cortex and overlaying structures. The accuracy of the Monte Carlo Simulation was furthermore increased by using a constant optical path length for the photons which was less than the median optical path length of the different materials. Based on our simulations we found a differential pathlength factor (DPF) of 6.15 which is close to with the value of 5.9 found in the literature for a distance of 4.5cm between the external sensors. Furthermore, we weighted the spatial probability distribution of the photons within the different tissues with the probabilities of the relative blood volume within the tissue. The results show that 50% of the NIRS signal is determined by the grey matter of the cerebral cortex which allows us to conclude that NIRS can produce meaningful cerebral blood flow measurements providing that the necessary corrections for extracerebral contamination are included.

  12. Region based Brain Computer Interface for a home control application.

    PubMed

    Akman Aydin, Eda; Bay, Omer Faruk; Guler, Inan

    2015-08-01

    Environment control is one of the important challenges for disabled people who suffer from neuromuscular diseases. Brain Computer Interface (BCI) provides a communication channel between the human brain and the environment without requiring any muscular activation. The most important expectation for a home control application is high accuracy and reliable control. Region-based paradigm is a stimulus paradigm based on oddball principle and requires selection of a target at two levels. This paper presents an application of region based paradigm for a smart home control application for people with neuromuscular diseases. In this study, a region based stimulus interface containing 49 commands was designed. Five non-disabled subjects were attended to the experiments. Offline analysis results of the experiments yielded 95% accuracy for five flashes. This result showed that region based paradigm can be used to select commands of a smart home control application with high accuracy in the low number of repetitions successfully. Furthermore, a statistically significant difference was not observed between the level accuracies.

  13. Effects of Unpredictable Variable Prenatal Stress (UVPS) on Bdnf DNA Methylation and Telomere Length in the Adult Rat Brain

    NASA Technical Reports Server (NTRS)

    Blaze, Jennifer; Asok, A.; Moyer, E. L.; Roth, T. L.; Ronca, A. E.

    2015-01-01

    In utero exposure to stress can shape neurobiological and behavioral outcomes in offspring, producing vulnerability to psychopathology later in life. Animal models of prenatal stress likewise have demonstrated long-­-term alterations in brain function and behavioral deficits in offspring. For example, using a rodent model of unpredictable variable prenatal stress (UVPS), in which dams are exposed to unpredictable, variable stress across pregnancy, we have found increased body weight and anxiety-­-like behavior in adult male, but not female, offspring. DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could be responsible for the long-­-term effects of UVPS. Here, we measured methylation of brain-­-derived neurotrophic factor (bdnf), a gene important in development and plasticity, and telomere length in the brains of adult offspring from the UVPS model. Results indicate that prenatally stressed adult males have greater methylation in the medial prefrontal cortex (mPFC) compared to non-­-stressed controls, while females have greater methylation in the ventral hippocampus compared to controls. Further, prenatally stressed males had shorter telomeres than controls in the mPFC. These findings demonstrate the ability of UVPS to produce epigenetic alterations and changes in telomere length across behaviorally-­-relevant brain regions, which may have linkages to the phenotypic outcomes.

  14. IGF-I: A Key Growth Factor that Regulates Neurogenesis and Synaptogenesis from Embryonic to Adult Stages of the Brain

    PubMed Central

    Nieto-Estévez, Vanesa; Defterali, Çağla; Vicario-Abejón, Carlos

    2016-01-01

    The generation of neurons in the adult mammalian brain requires the activation of quiescent neural stem cells (NSCs). This activation and the sequential steps of neuron formation from NSCs are regulated by a number of stimuli, which include growth factors. Insulin-like growth factor-I (IGF-I) exert pleiotropic effects, regulating multiple cellular processes depending on their concentration, cell type, and the developmental stage of the animal. Although IGF-I expression is relatively high in the embryonic brain its levels drop sharply in the adult brain except in neurogenic regions, i.e., the hippocampus (HP) and the subventricular zone-olfactory bulb (SVZ-OB). By contrast, the expression of IGF-IR remains relatively high in the brain irrespective of the age of the animal. Evidence indicates that IGF-I influences NSC proliferation and differentiation into neurons and glia as well as neuronal maturation including synapse formation. Furthermore, recent studies have shown that IGF-I not only promote adult neurogenesis by regulating NSC number and differentiation but also by influencing neuronal positioning and migration as described during SVZ-OB neurogenesis. In this article we will revise and discuss the actions reported for IGF-I signaling in a variety of in vitro and in vivo models, focusing on the maintenance and proliferation of NSCs/progenitors, neurogenesis, and neuron integration in synaptic circuits. PMID:26941597

  15. Radioreceptor assay of opioid peptides in selected canine brain regions

    SciTech Connect

    Desiderio, D.M.; Takeshita, H.

    1985-09-01

    A radioreceptor assay using the opioid delta receptor-preferring ligand D-/sup 2/ala, D-/sup 5/leu leucine enkephalin (/sup 3/H-DADL) and the broader-specificity ligand /sup 3/H-etorphine was used to measure five HPLC-purified neuropeptide fractions derived from the peptide-rich fraction of tissue homogenates of nine anatomical regions of the canine brain. The receptoractive peptides studied were methionine enkephalin, alpha-neo-endorphin, dynorphin 1-8, methionine enkephalin-Arg-Phe, and leucine enkephalin. These peptides derive from two larger precursors: proenkephalin A, which contains methionine enkephalin, leucine enkephalin, methionine enkephalin-Arg-Phe; and proenkephalin B, which contains alpha-neo-endorphin and dynorphin 1-8. Receptoractive peptides were measured in the peptide-rich fraction derived from homogenates of canine hypothalamus, pituitary, caudate nucleus, amygdala, hippocampus, mid-brain, thalamus, pons-medulla, and cortex.

  16. Correlates of Depression in Adult Siblings of Persons with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Degeneffe, Charles Edmund; Lynch, Ruth Torkelson

    2006-01-01

    Using Pearlin's stress process model, this study examined correlates of depression in 170 adult siblings of persons with traumatic brain injury (TBI). Approximately 39% of adult sibling participants evinced "Center for Epidemiologic Studies-Depression" (CES-D; Radloff, 1977) scores indicating clinically significant depressive symptoms. Background…

  17. Development of a Conceptual Model to Predict Physical Activity Participation in Adults with Brain Injuries

    ERIC Educational Resources Information Center

    Driver, Simon

    2008-01-01

    The purpose was to examine psychosocial factors that influence the physical activity behaviors of adults with brain injuries. Two differing models, based on Harter's model of self-worth, were proposed to examine the relationship between perceived competence, social support, physical self-worth, affect, and motivation. Adults numbering 384 with…

  18. The Social Environment and Neurogenesis in the Adult Mammalian Brain

    PubMed Central

    Lieberwirth, Claudia; Wang, Zuoxin

    2012-01-01

    Adult neurogenesis – the formation of new neurons in adulthood – has been shown to be modulated by a variety of endogenous (e.g., trophic factors, neurotransmitters, and hormones) as well as exogenous (e.g., physical activity and environmental complexity) factors. Research on exogenous regulators of adult neurogenesis has focused primarily on the non-social environment. More recently, however, evidence has emerged suggesting that the social environment can also affect adult neurogenesis. The present review details the effects of adult–adult (e.g., mating and chemosensory interactions) and adult–offspring (e.g., gestation, parenthood, and exposure to offspring) interactions on adult neurogenesis. In addition, the effects of a stressful social environment (e.g., lack of social support and dominant–subordinate interactions) on adult neurogenesis are reviewed. The underlying hormonal mechanisms and potential functional significance of adult-generated neurons in mediating social behaviors are also discussed. PMID:22586385

  19. Abnormal Brain Connectivity Patterns in Adults with ADHD: A Coherence Study

    PubMed Central

    Sato, João Ricardo; Hoexter, Marcelo Queiroz; Castellanos, Xavier Francisco; Rohde, Luis A.

    2012-01-01

    Studies based on functional magnetic resonance imaging (fMRI) during the resting state have shown decreased functional connectivity between the dorsal anterior cingulate cortex (dACC) and regions of the Default Mode Network (DMN) in adult patients with Attention-Deficit/Hyperactivity Disorder (ADHD) relative to subjects with typical development (TD). Most studies used Pearson correlation coefficients among the BOLD signals from different brain regions to quantify functional connectivity. Since the Pearson correlation analysis only provides a limited description of functional connectivity, we investigated functional connectivity between the dACC and the posterior cingulate cortex (PCC) in three groups (adult patients with ADHD, n = 21; TD age-matched subjects, n = 21; young TD subjects, n = 21) using a more comprehensive analytical approach – unsupervised machine learning using a one-class support vector machine (OC-SVM) that quantifies an abnormality index for each individual. The median abnormality index for patients with ADHD was greater than for TD age-matched subjects (p = 0.014); the ADHD and young TD indices did not differ significantly (p = 0.480); the median abnormality index of young TD was greater than that of TD age-matched subjects (p = 0.016). Low frequencies below 0.05 Hz and around 0.20 Hz were the most relevant for discriminating between ADHD patients and TD age-matched controls and between the older and younger TD subjects. In addition, we validated our approach using the fMRI data of children publicly released by the ADHD-200 Competition, obtaining similar results. Our findings suggest that the abnormal coherence patterns observed in patients with ADHD in this study resemble the patterns observed in young typically developing subjects, which reinforces the hypothesis that ADHD is associated with brain maturation deficits. PMID:23049834

  20. Distribution of angiotensin type-1 receptor messenger RNA expression in the adult rat brain.

    PubMed

    Lenkei, Z; Palkovits, M; Corvol, P; Llorens-Cortes, C

    1998-02-01

    Angiotensin II and angiotensin III in the brain exert their various effects by acting on two pharmacologically well-defined receptors, the type-1 (AT1) and the type-2 (AT2) receptors. Receptor binding autoradiography has revealed the dominant presence of AT1 in brain nuclei involved in cardiovascular, body fluid and neuroendocrine control. The cloning of the AT1 complementary DNA has revealed the existence of two receptor subtypes in rodents, AT1A and AT1B. Using specific riboprobes for in situ hybridization, we have previously shown that the AT1A messenger RNA is predominantly expressed in the rat forebrain; in contrast the AT1B subtype predominates in the anterior pituitary. Using a similar technical approach, the aim of the present study was to establish the precise anatomical localization of cells synthetising the AT1A receptor in the adult rat brain. High AT1A messenger RNA expression was found in the vascular organ of the lamina terminalis, the median preoptic nucleus, the subfornical organ, the hypothalamic periventricular nucleus, the parvocellular parts of the paraventricular nucleus, the nucleus of the solitary tract and the area postrema, in agreement with previous autoradiographic studies, describing a high density of AT1 binding sites in these nuclei. In addition, AT1A messenger RNA expression was detected in several brain areas, where no AT1 binding was reported previously. Thus, we identify strong expression of AT1A messenger RNA expression in scattered cells of the lateral parts of the preoptic region, the lateral hypothalamus and several brainstem nuclei. In none of these structures was the AT1B messenger RNA detectable at the microscopic level. In conclusion, it is suggested that angiotensins may exert their central effects on body fluid and cardiovascular homeostasis mainly via the AT1A receptor subtype. PMID:9483539

  1. Brain Regions Associated With Internalizing and Externalizing Psychiatric Symptoms in Patients With Penetrating Traumatic Brain Injury.

    PubMed

    Huey, Edward D; Lee, Seonjoo; Lieberman, Jeffrey A; Devanand, D P; Brickman, Adam M; Raymont, Vanessa; Krueger, Frank; Grafman, Jordan

    2016-01-01

    A factor structure underlying DSM-IV diagnoses has been previously reported in neurologically intact patients. The authors determined the brain regions associated with factors underlying DSM-IV diagnoses and compared the ability of DSM-IV diagnoses, factor scores, and self-report measures to account for the neuroanatomical findings in patients with penetrating brain injuries. This prospective cohort study included 254 Vietnam War veterans: 199 with penetrating brain injuries and 55 matched control participants. Measures include DSM-IV diagnoses (from a Structured Clinical Interview for DSM), self-report measures of depression and anxiety, and CT scans. Factors underlying DSM-IV diagnoses were determined using an exploratory factor analysis and correlated with percent of brain regions affected. The ability of the factor scores, DSM-IV diagnoses, and the self-report psychiatric measures to account for the anatomical variance was compared with multiple regressions. Internalizing and externalizing factors were identified in these brain-injured patients. Damage to the left amygdala and bilateral basal ganglia was associated with lower internalizing factor scores, and damage to the left medial orbitofrontal cortex (OFC) with higher, and bilateral hippocampi with lower, externalizing factor scores. Factor scores best predicted left amygdala and bilateral hippocampal involvement, whereas DSM-IV diagnoses best predicted bilateral basal ganglia and left OFC involvement. Damage to the limbic areas involved in the processing of emotional and reward information, including structures involved in the National Institute of Mental Health's Research Domain Criteria Negative Valence Domain, influences the development of internalizing and externalizing psychiatric symptoms. Self-report measures underperformed DSM-IV and factor scores in predicting neuroanatomical findings.

  2. Brain Regions Associated With Internalizing and Externalizing Psychiatric Symptoms in Patients With Penetrating Traumatic Brain Injury.

    PubMed

    Huey, Edward D; Lee, Seonjoo; Lieberman, Jeffrey A; Devanand, D P; Brickman, Adam M; Raymont, Vanessa; Krueger, Frank; Grafman, Jordan

    2016-01-01

    A factor structure underlying DSM-IV diagnoses has been previously reported in neurologically intact patients. The authors determined the brain regions associated with factors underlying DSM-IV diagnoses and compared the ability of DSM-IV diagnoses, factor scores, and self-report measures to account for the neuroanatomical findings in patients with penetrating brain injuries. This prospective cohort study included 254 Vietnam War veterans: 199 with penetrating brain injuries and 55 matched control participants. Measures include DSM-IV diagnoses (from a Structured Clinical Interview for DSM), self-report measures of depression and anxiety, and CT scans. Factors underlying DSM-IV diagnoses were determined using an exploratory factor analysis and correlated with percent of brain regions affected. The ability of the factor scores, DSM-IV diagnoses, and the self-report psychiatric measures to account for the anatomical variance was compared with multiple regressions. Internalizing and externalizing factors were identified in these brain-injured patients. Damage to the left amygdala and bilateral basal ganglia was associated with lower internalizing factor scores, and damage to the left medial orbitofrontal cortex (OFC) with higher, and bilateral hippocampi with lower, externalizing factor scores. Factor scores best predicted left amygdala and bilateral hippocampal involvement, whereas DSM-IV diagnoses best predicted bilateral basal ganglia and left OFC involvement. Damage to the limbic areas involved in the processing of emotional and reward information, including structures involved in the National Institute of Mental Health's Research Domain Criteria Negative Valence Domain, influences the development of internalizing and externalizing psychiatric symptoms. Self-report measures underperformed DSM-IV and factor scores in predicting neuroanatomical findings. PMID:26715034

  3. Cerebroventricular Microinjection (CVMI) into Adult Zebrafish Brain Is an Efficient Misexpression Method for Forebrain Ventricular Cells

    PubMed Central

    Kizil, Caghan; Brand, Michael

    2011-01-01

    The teleost fish Danio rerio (zebrafish) has a remarkable ability to generate newborn neurons in its brain at adult stages of its lifespan-a process called adult neurogenesis. This ability relies on proliferating ventricular progenitors and is in striking contrast to mammalian brains that have rather restricted capacity for adult neurogenesis. Therefore, investigating the zebrafish brain can help not only to elucidate the molecular mechanisms of widespread adult neurogenesis in a vertebrate species, but also to design therapies in humans with what we learn from this teleost. Yet, understanding the cellular behavior and molecular programs underlying different biological processes in the adult zebrafish brain requires techniques that allow manipulation of gene function. As a complementary method to the currently used misexpression techniques in zebrafish, such as transgenic approaches or electroporation-based delivery of DNA, we devised a cerebroventricular microinjection (CVMI)-assisted knockdown protocol that relies on vivo morpholino oligonucleotides, which do not require electroporation for cellular uptake. This rapid method allows uniform and efficient knockdown of genes in the ventricular cells of the zebrafish brain, which contain the neurogenic progenitors. We also provide data on the use of CVMI for growth factor administration to the brain – in our case FGF8, which modulates the proliferation rate of the ventricular cells. In this paper, we describe the CVMI method and discuss its potential uses in zebrafish. PMID:22076157

  4. Spontaneous mentalizing captures variability in the cortical thickness of social brain regions.

    PubMed

    Rice, Katherine; Redcay, Elizabeth

    2015-03-01

    Theory of mind (ToM)--or thinking about the mental states of others--is a cornerstone of successful everyday social interaction. However, the brain bases of ToM are most frequently measured via explicit laboratory tasks that pose direct questions about mental states (e.g. "In this story, what does Steve think Julia believes?"). Neuroanatomical measures may provide a way to explore the brain bases of individual differences in more naturalistic everyday mentalizing. In the current study, we examined the relation between cortical thickness and spontaneous ToM using the novel Spontaneous Theory of Mind Protocol (STOMP), which measures participants' spontaneous descriptions of the beliefs, emotions and goals of characters in naturalistic videos. We administered standard ToM tasks and the STOMP to young adults (aged 18-26 years) and collected structural magnetic resonance imaging data from a subset of these participants. The STOMP produced robust individual variability and was correlated with performance on traditional ToM tasks. Further, unlike the traditional ToM tasks, STOMP performance was related to cortical thickness for a set of brain regions that have been functionally linked to ToM processing. These findings offer novel insight into the brain bases of variability in naturalistic mentalizing performance, with implications for both typical and atypical populations. PMID:24847726

  5. Control of adult neurogenesis by programmed cell death in the mammalian brain.

    PubMed

    Ryu, Jae Ryun; Hong, Caroline Jeeyeon; Kim, Joo Yeon; Kim, Eun-Kyoung; Sun, Woong; Yu, Seong-Woon

    2016-04-21

    The presence of neural stem cells (NSCs) and the production of new neurons in the adult brain have received great attention from scientists and the public because of implications to brain plasticity and their potential use for treating currently incurable brain diseases. Adult neurogenesis is controlled at multiple levels, including proliferation, differentiation, migration, and programmed cell death (PCD). Among these, PCD is the last and most prominent process for regulating the final number of mature neurons integrated into neural circuits. PCD can be classified into apoptosis, necrosis, and autophagic cell death and emerging evidence suggests that all three may be important modes of cell death in neural stem/progenitor cells. However, the molecular mechanisms that regulate PCD and thereby impact the intricate balance between self-renewal, proliferation, and differentiation during adult neurogenesis are not well understood. In this comprehensive review, we focus on the extent, mechanism, and biological significance of PCD for the control of adult neurogenesis in the mammalian brain. The role of intrinsic and extrinsic factors in the regulation of PCD at the molecular and systems levels is also discussed. Adult neurogenesis is a dynamic process, and the signals for differentiation, proliferation, and death of neural progenitor/stem cells are closely interrelated. A better understanding of how adult neurogenesis is influenced by PCD will help lead to important insights relevant to brain health and diseases.

  6. Age-Related Differences in the Brain Areas outside the Classical Language Areas among Adults Using Category Decision Task

    ERIC Educational Resources Information Center

    Cho, Yong Won; Song, Hui-Jin; Lee, Jae Jun; Lee, Joo Hwa; Lee, Hui Joong; Yi, Sang Doe; Chang, Hyuk Won; Berl, Madison M.; Gaillard, William D.; Chang, Yongmin

    2012-01-01

    Older adults perform much like younger adults on language. This similar level of performance, however, may come about through different underlying brain processes. In the present study, we evaluated age-related differences in the brain areas outside the typical language areas among adults using a category decision task. Our results showed that…

  7. PDYN, a gene implicated in brain/mental disorders, is targeted by REST in the adult human brain.

    PubMed

    Henriksson, Richard; Bäckman, Cristina M; Harvey, Brandon K; Kadyrova, Helena; Bazov, Igor; Shippenberg, Toni S; Bakalkin, Georgy

    2014-11-01

    The dynorphin κ-opioid receptor system is implicated in mental health and brain/mental disorders. However, despite accumulating evidence that PDYN and/or dynorphin peptide expression is altered in the brain of individuals with brain/mental disorders, little is known about transcriptional control of PDYN in humans. In the present study, we show that PDYN is targeted by the transcription factor REST in human neuroblastoma SH-SY5Y cells and that that interfering with REST activity increases PDYN expression in these cells. We also show that REST binding to PDYN is reduced in the adult human brain compared to SH-SY5Y cells, which coincides with higher PDYN expression. This may be related to MIR-9 mediated down-regulation of REST as suggested by a strong inverse correlation between REST and MIR-9 expression. Our results suggest that REST represses PDYN expression in SH-SY5Y cells and the adult human brain and may have implications for mental health and brain/mental disorders. PMID:25220237

  8. Interspecific allometry of the brain and brain regions in parrots (psittaciformes): comparisons with other birds and primates.

    PubMed

    Iwaniuk, Andrew N; Dean, Karen M; Nelson, John E

    2005-01-01

    Despite significant progress in understanding the evolution of the mammalian brain, relatively little is known of the patterns of evolutionary change in the avian brain. In particular, statements regarding which avian taxa have relatively larger brains and brain regions are based on small sample sizes and statistical analyses are generally lacking. We tested whether psittaciforms (parrots, cockatoos and lorikeets) have larger brains and forebrains than other birds using both conventional and phylogenetically based methods. In addition, we compared the psittaciforms to primates to determine if cognitive similarities between the two groups were reflected by similarities in brain and telencephalic volumes. Overall, psittaciforms have relatively larger brains and telencephala than most other non-passerine orders. No significant difference in relative brain or telencephalic volume was detected between psittaciforms and passerines. Comparisons of other brain region sizes between psittaciforms and other birds, however, exhibited conflicting results depending upon whether body mass or a brain volume remainder (total brain volume - brain region volume) was used as a scaling variable. When compared to primates, psittaciforms possessed similar relative brain and telencephalic volumes. The only exception to this was that in some analyses psittaciforms had significantly larger telencephala than primates of similar brain volume. The results therefore provide empirical evidence for previous claims that psittaciforms possess relatively large brains and telencephala. Despite the variability in the results, it is clear that psittaciforms tend to possess large brains and telencephala relative to non-passerines and are similar to primates in this regard. Although it could be suggested that this reflects the advanced cognitive abilities of psittaciforms, similar studies performed in corvids and other avian taxa will be required before this claim can be made with any certainty.

  9. Face processing in autism spectrum disorders: from brain regions to brain networks

    PubMed Central

    Nomi, Jason S.; Uddin, Lucina Q.

    2015-01-01

    Autism spectrum disorder (ASD) is characterized by reduced attention to social stimuli including the human face. This hypo-responsiveness to stimuli that are engaging to typically developing individuals may result from dysfunctioning motivation, reward, and attention systems in the brain. Here we review an emerging neuroimaging literature that emphasizes a shift from focusing on hypo-activation of isolated brain regions such as the fusiform gyrus, amygdala, and superior temporal sulcus in ASD to a more holistic approach to understanding face perception as a process supported by distributed cortical and subcortical brain networks. We summarize evidence for atypical activation patterns within brain networks that may contribute to social deficits characteristic of the disorder. We conclude by pointing to gaps in the literature and future directions that will continue to shed light on aspects of face processing in autism that are still under-examined. In particular, we highlight the need for more developmental studies and studies examining ecologically valid and naturalistic social stimuli. PMID:25829246

  10. Structural alterations of brain grey and white matter in early deaf adults.

    PubMed

    Hribar, Manja; Suput, Dušan; Carvalho, Altiere Araujo; Battelino, Saba; Vovk, Andrej

    2014-12-01

    Functional and structural brain alterations in the absence of the auditory input have been described, but the observed structural brain changes in the deaf are not uniform. Some of the previous researchers focused only on the auditory areas, while others investigated the whole brain or other selected regions of interest. Majority of studies revealed decreased white matter (WM) volume or altered WM microstructure and preserved grey matter (GM) structure of the auditory areas in the deaf. However, preserved WM and increased or decreased GM volume of the auditory areas in the deaf have also been reported. Several structural alterations in the deaf were found also outside the auditory areas, but these regions differ between the studies. The observed differences between the studies could be due to the use of different single-analysis techniques, or the diverse population sample and its size, or possibly due to the usage of hearing aids by some participating deaf subjects. To overcome the aforementioned limitations four different image-processing techniques were used to investigate changes in the brain morphology of prelingually deaf adults who have never used hearing aids. GM and WM volume of the Heschl's gyrus (HG) were measured using manual volumetry, while whole brain GM volume, thickness and surface area were assessed by voxel-based morphometry (VBM) and surface-based analysis. The microstructural properties of the WM were evaluated by diffusion tensor imaging (DTI). The data were compared between 14 congenitally deaf adults and 14 sex- and age-matched normal hearing controls. Manual volumetry revealed preserved GM volume of the bilateral HG and significantly decreased WM volume of the left HG in the deaf. VBM showed increased cerebellar GM volume in the deaf, while no statistically significant differences were observed in the GM thickness or surface area between the groups. The results of the DTI analysis showed WM microstructural alterations between the groups in

  11. Real-time fMRI brain computer interfaces: self-regulation of single brain regions to networks.

    PubMed

    Ruiz, Sergio; Buyukturkoglu, Korhan; Rana, Mohit; Birbaumer, Niels; Sitaram, Ranganatha

    2014-01-01

    With the advent of brain computer interfaces based on real-time fMRI (rtfMRI-BCI), the possibility of performing neurofeedback based on brain hemodynamics has become a reality. In the early stage of the development of this field, studies have focused on the volitional control of activity in circumscribed brain regions. However, based on the understanding that the brain functions by coordinated activity of spatially distributed regions, there have recently been further developments to incorporate real-time feedback of functional connectivity and spatio-temporal patterns of brain activity. The present article reviews the principles of rtfMRI neurofeedback, its applications, benefits and limitations. A special emphasis is given to the discussion of novel developments that have enabled the use of this methodology to achieve self-regulation of the functional connectivity between different brain areas and of distributed brain networks, anticipating new and exciting applications for cognitive neuroscience and for the potential alleviation of neuropsychiatric disorders.

  12. Cognitive function and brain structure after recurrent mild traumatic brain injuries in young-to-middle-aged adults

    PubMed Central

    List, Jonathan; Ott, Stefanie; Bukowski, Martin; Lindenberg, Robert; Flöel, Agnes

    2015-01-01

    Recurrent mild traumatic brain injuries (mTBIs) are regarded as an independent risk factor for developing dementia in later life. We here aimed to evaluate associations between recurrent mTBIs, cognition, and gray matter volume and microstructure as revealed by structural magnetic resonance imaging (MRI) in the chronic phase after mTBIs in young adulthood. We enrolled 20 young-to-middle-aged subjects, who reported two or more sports-related mTBIs, with the last mTBI > 6 months prior to study enrolment (mTBI group), and 21 age-, sex- and education matched controls with no history of mTBI (control group). All participants received comprehensive neuropsychological testing, and high resolution T1-weighted and diffusion tensor MRI in order to assess cortical thickness (CT) and microstructure, hippocampal volume, and ventricle size. Compared to the control group, subjects of the mTBI group presented with lower CT within the right temporal lobe and left insula using an a priori region of interest approach. Higher number of mTBIs was associated with lower CT in bilateral insula, right middle temporal gyrus and right entorhinal area. Our results suggest persistent detrimental effects of recurrent mTBIs on CT already in young-to-middle-aged adults. If additional structural deterioration occurs during aging, subtle neuropsychological decline may progress to clinically overt dementia earlier than in age-matched controls, a hypothesis to be assessed in future prospective trials. PMID:26052275

  13. Parcellation of the Healthy Neonatal Brain into 107 Regions Using Atlas Propagation through Intermediate Time Points in Childhood

    PubMed Central

    Blesa, Manuel; Serag, Ahmed; Wilkinson, Alastair G.; Anblagan, Devasuda; Telford, Emma J.; Pataky, Rozalia; Sparrow, Sarah A.; Macnaught, Gillian; Semple, Scott I.; Bastin, Mark E.; Boardman, James P.

    2016-01-01

    Neuroimage analysis pipelines rely on parcellated atlases generated from healthy individuals to provide anatomic context to structural and diffusion MRI data. Atlases constructed using adult data introduce bias into studies of early brain development. We aimed to create a neonatal brain atlas of healthy subjects that can be applied to multi-modal MRI data. Structural and diffusion 3T MRI scans were acquired soon after birth from 33 typically developing neonates born at term (mean postmenstrual age at birth 39+5 weeks, range 37+2–41+6). An adult brain atlas (SRI24/TZO) was propagated to the neonatal data using temporal registration via childhood templates with dense temporal samples (NIH Pediatric Database), with the final atlas (Edinburgh Neonatal Atlas, ENA33) constructed using the Symmetric Group Normalization (SyGN) method. After this step, the computed final transformations were applied to T2-weighted data, and fractional anisotropy, mean diffusivity, and tissue segmentations to provide a multi-modal atlas with 107 anatomical regions; a symmetric version was also created to facilitate studies of laterality. Volumes of each region of interest were measured to provide reference data from normal subjects. Because this atlas is generated from step-wise propagation of adult labels through intermediate time points in childhood, it may serve as a useful starting point for modeling brain growth during development. PMID:27242423

  14. Parcellation of the Healthy Neonatal Brain into 107 Regions Using Atlas Propagation through Intermediate Time Points in Childhood.

    PubMed

    Blesa, Manuel; Serag, Ahmed; Wilkinson, Alastair G; Anblagan, Devasuda; Telford, Emma J; Pataky, Rozalia; Sparrow, Sarah A; Macnaught, Gillian; Semple, Scott I; Bastin, Mark E; Boardman, James P

    2016-01-01

    Neuroimage analysis pipelines rely on parcellated atlases generated from healthy individuals to provide anatomic context to structural and diffusion MRI data. Atlases constructed using adult data introduce bias into studies of early brain development. We aimed to create a neonatal brain atlas of healthy subjects that can be applied to multi-modal MRI data. Structural and diffusion 3T MRI scans were acquired soon after birth from 33 typically developing neonates born at term (mean postmenstrual age at birth 39(+5) weeks, range 37(+2)-41(+6)). An adult brain atlas (SRI24/TZO) was propagated to the neonatal data using temporal registration via childhood templates with dense temporal samples (NIH Pediatric Database), with the final atlas (Edinburgh Neonatal Atlas, ENA33) constructed using the Symmetric Group Normalization (SyGN) method. After this step, the computed final transformations were applied to T2-weighted data, and fractional anisotropy, mean diffusivity, and tissue segmentations to provide a multi-modal atlas with 107 anatomical regions; a symmetric version was also created to facilitate studies of laterality. Volumes of each region of interest were measured to provide reference data from normal subjects. Because this atlas is generated from step-wise propagation of adult labels through intermediate time points in childhood, it may serve as a useful starting point for modeling brain growth during development.

  15. Acetamiprid Accumulates in Different Amounts in Murine Brain Regions.

    PubMed

    Terayama, Hayato; Endo, Hitoshi; Tsukamoto, Hideo; Matsumoto, Koichi; Umezu, Mai; Kanazawa, Teruhisa; Ito, Masatoshi; Sato, Tadayuki; Naito, Munekazu; Kawakami, Satoshi; Fujino, Yasuhiro; Tatemichi, Masayuki; Sakabe, Kou

    2016-01-01

    Neonicotinoids such as acetamiprid (ACE) belong to a new and widely used single class of pesticides. Neonicotinoids mimic the chemical structure of nicotine and share agonist activity with the nicotine acetylcholine receptor (nAchR). Neonicotinoids are widely considered to be safe in humans; however, they have recently been implicated in a number of human health disorders. A wide range of musculoskeletal and neuromuscular disorders associated with high doses of neonicotinoids administered to animals have also been reported. Consequently, we used a mouse model to investigate the response of the central nervous system to ACE treatment. Our results show that exposure to ACE-containing water for three or seven days (decuple and centuple of no observable adverse effect level (NOAEL)/day) caused a decrease in body weight in 10-week old A/JJmsSlc (A/J) mice. However, the treatments did not affect brain histology or expression of CD34. ACE concentrations were significantly higher in the midbrain of ACE-treated mice than that of the normal and vehicle groups. Expression levels of α7, α4, and β2 nAChRs were found to be low in the olfactory bulb and midbrain of normal mice. Furthermore, in the experimental group (centuple ACE-containing water for seven days), β2 nAChR expression decreased in many brain regions. Information regarding the amount of accumulated ACE and expression levels of the acetylcholine receptor in each region of the brain is important for understanding any clinical symptoms that may be associated with ACE exposure. PMID:27669271

  16. Acetamiprid Accumulates in Different Amounts in Murine Brain Regions

    PubMed Central

    Terayama, Hayato; Endo, Hitoshi; Tsukamoto, Hideo; Matsumoto, Koichi; Umezu, Mai; Kanazawa, Teruhisa; Ito, Masatoshi; Sato, Tadayuki; Naito, Munekazu; Kawakami, Satoshi; Fujino, Yasuhiro; Tatemichi, Masayuki; Sakabe, Kou

    2016-01-01

    Neonicotinoids such as acetamiprid (ACE) belong to a new and widely used single class of pesticides. Neonicotinoids mimic the chemical structure of nicotine and share agonist activity with the nicotine acetylcholine receptor (nAchR). Neonicotinoids are widely considered to be safe in humans; however, they have recently been implicated in a number of human health disorders. A wide range of musculoskeletal and neuromuscular disorders associated with high doses of neonicotinoids administered to animals have also been reported. Consequently, we used a mouse model to investigate the response of the central nervous system to ACE treatment. Our results show that exposure to ACE-containing water for three or seven days (decuple and centuple of no observable adverse effect level (NOAEL)/day) caused a decrease in body weight in 10-week old A/JJmsSlc (A/J) mice. However, the treatments did not affect brain histology or expression of CD34. ACE concentrations were significantly higher in the midbrain of ACE-treated mice than that of the normal and vehicle groups. Expression levels of α7, α4, and β2 nAChRs were found to be low in the olfactory bulb and midbrain of normal mice. Furthermore, in the experimental group (centuple ACE-containing water for seven days), β2 nAChR expression decreased in many brain regions. Information regarding the amount of accumulated ACE and expression levels of the acetylcholine receptor in each region of the brain is important for understanding any clinical symptoms that may be associated with ACE exposure. PMID:27669271

  17. Acetamiprid Accumulates in Different Amounts in Murine Brain Regions.

    PubMed

    Terayama, Hayato; Endo, Hitoshi; Tsukamoto, Hideo; Matsumoto, Koichi; Umezu, Mai; Kanazawa, Teruhisa; Ito, Masatoshi; Sato, Tadayuki; Naito, Munekazu; Kawakami, Satoshi; Fujino, Yasuhiro; Tatemichi, Masayuki; Sakabe, Kou

    2016-09-22

    Neonicotinoids such as acetamiprid (ACE) belong to a new and widely used single class of pesticides. Neonicotinoids mimic the chemical structure of nicotine and share agonist activity with the nicotine acetylcholine receptor (nAchR). Neonicotinoids are widely considered to be safe in humans; however, they have recently been implicated in a number of human health disorders. A wide range of musculoskeletal and neuromuscular disorders associated with high doses of neonicotinoids administered to animals have also been reported. Consequently, we used a mouse model to investigate the response of the central nervous system to ACE treatment. Our results show that exposure to ACE-containing water for three or seven days (decuple and centuple of no observable adverse effect level (NOAEL)/day) caused a decrease in body weight in 10-week old A/JJmsSlc (A/J) mice. However, the treatments did not affect brain histology or expression of CD34. ACE concentrations were significantly higher in the midbrain of ACE-treated mice than that of the normal and vehicle groups. Expression levels of α7, α4, and β2 nAChRs were found to be low in the olfactory bulb and midbrain of normal mice. Furthermore, in the experimental group (centuple ACE-containing water for seven days), β2 nAChR expression decreased in many brain regions. Information regarding the amount of accumulated ACE and expression levels of the acetylcholine receptor in each region of the brain is important for understanding any clinical symptoms that may be associated with ACE exposure.

  18. Sex, stress and the brain: interactive actions of hormones on the developing and adult brain.

    PubMed

    McEwen, B S

    2014-12-01

    The brain is a target of steroid hormone actions that affect brain architecture, molecular and neurochemical processes, behavior and neuroprotection via both genomic and non-genomic actions. Estrogens have such effects throughout the brain and this article provides an historical and current view of how this new view has come about and how it has affected the study of sex differences, as well as other areas of neuroscience, including the effects of stress on the brain.

  19. Brain Region-Specific Activity Patterns after Recent or Remote Memory Retrieval of Auditory Conditioned Fear

    ERIC Educational Resources Information Center

    Kwon, Jeong-Tae; Jhang, Jinho; Kim, Hyung-Su; Lee, Sujin; Han, Jin-Hee

    2012-01-01

    Memory is thought to be sparsely encoded throughout multiple brain regions forming unique memory trace. Although evidence has established that the amygdala is a key brain site for memory storage and retrieval of auditory conditioned fear memory, it remains elusive whether the auditory brain regions may be involved in fear memory storage or…

  20. High-resolution gene expression atlases for adult and developing mouse brain and spinal cord.

    PubMed

    Henry, Alex M; Hohmann, John G

    2012-10-01

    Knowledge of the structure, genetics, circuits, and physiological properties of the mammalian brain in both normal and pathological states is ever increasing as research labs worldwide probe the various aspects of brain function. Until recently, however, comprehensive cataloging of gene expression across the central nervous system has been lacking. The Allen Institute for Brain Science, as part of its mission to propel neuroscience research, has completed several large gene-mapping projects in mouse, nonhuman primate, and human brain, producing informative online public resources and tools. Here we present the Allen Mouse Brain Atlas, covering ~20,000 genes throughout the adult mouse brain; the Allen Developing Mouse Brain Atlas, detailing expression of approximately 2,000 important developmental genes across seven embryonic and postnatal stages of brain growth; and the Allen Spinal Cord Atlas, revealing expression for ~20,000 genes in the adult and neonatal mouse spinal cords. Integrated data-mining tools, including reference atlases, informatics analyses, and 3-D viewers, are described. For these massive-scale projects, high-throughput industrial techniques were developed to standardize and reliably repeat experimental goals. To verify consistency and accuracy, a detailed analysis of the 1,000 most viewed genes for the adult mouse brain (according to website page views) was performed by comparing our data with peer-reviewed literature and other databases. We show that our data are highly consistent with independent sources and provide a comprehensive compendium of information and tools used by thousands of researchers each month. All data and tools are freely available via the Allen Brain Atlas portal (www.brain-map.org).

  1. High-resolution gene expression atlases for adult and developing mouse brain and spinal cord.

    PubMed

    Henry, Alex M; Hohmann, John G

    2012-10-01

    Knowledge of the structure, genetics, circuits, and physiological properties of the mammalian brain in both normal and pathological states is ever increasing as research labs worldwide probe the various aspects of brain function. Until recently, however, comprehensive cataloging of gene expression across the central nervous system has been lacking. The Allen Institute for Brain Science, as part of its mission to propel neuroscience research, has completed several large gene-mapping projects in mouse, nonhuman primate, and human brain, producing informative online public resources and tools. Here we present the Allen Mouse Brain Atlas, covering ~20,000 genes throughout the adult mouse brain; the Allen Developing Mouse Brain Atlas, detailing expression of approximately 2,000 important developmental genes across seven embryonic and postnatal stages of brain growth; and the Allen Spinal Cord Atlas, revealing expression for ~20,000 genes in the adult and neonatal mouse spinal cords. Integrated data-mining tools, including reference atlases, informatics analyses, and 3-D viewers, are described. For these massive-scale projects, high-throughput industrial techniques were developed to standardize and reliably repeat experimental goals. To verify consistency and accuracy, a detailed analysis of the 1,000 most viewed genes for the adult mouse brain (according to website page views) was performed by comparing our data with peer-reviewed literature and other databases. We show that our data are highly consistent with independent sources and provide a comprehensive compendium of information and tools used by thousands of researchers each month. All data and tools are freely available via the Allen Brain Atlas portal (www.brain-map.org). PMID:22832508

  2. MRI-guided stereotaxic brain surgery in the infant and adult common marmoset.

    PubMed

    Mundinano, Inaki-Carril; Flecknell, Paul A; Bourne, James A

    2016-07-01

    In the past decade, the New World common marmoset (Callithrix jacchus) has taken a seminal position in neurobiological research, fueled in part by its smooth cortical sheet, which allows cortical areas to be easily accessed by current technologies on the dorsal surface of the brain. In this protocol, we describe a method for the precision placement of agents (e.g., tracers or neurotoxins) into small brain regions of the infant and adult marmoset, using an MRI-guided approach. This strategy uses a protocol for prolonged anesthesia without the need for intubation that we have recently developed, alongside appropriate analgesia and monitoring. The protocol can be readily adapted to be used together with advanced research techniques, such as two-photon microscopy and optical imaging. Including a 5-d postoperative care plan, this protocol takes 7 d to complete. The protocol requires a team of personnel experienced in marmoset care and handling, and small-animal neurosurgery; an assistant for monitoring the animal and assisting with anesthesia; and an MRI technician. PMID:27336707

  3. Acute brain slice methods for adult and aging animals: application of targeted patch clampanalysis and optogenetics

    PubMed Central

    Daigle, Tanya L.; Chen, Qian; Feng, Guoping

    2014-01-01

    Summary The development of the living acute brain slice preparation for analyzing synaptic function roughly a half century ago was a pivotal achievement that greatly influenced the landscape of modern neuroscience. Indeed, many neuroscientists regard brain slices as the gold-standard model system for detailed cellular, molecular, and circuitry level analysis and perturbation of neuronal function. A critical limitation of this model system is the difficulty in preparing slices from adult and aging animals, and over the past several decades few substantial methodological improvements have emerged to facilitate patch clamp analysis in the mature adult stage. In this chapter we describe a robust and practical protocol for preparing brain slices from mature adult mice that are suitable for patch clamp analysis. This method reduces swelling and damage in superficial layers of the slices and improves the success rate for targeted patch clamp recordings, including recordings from fluorescently labeled populations in slices derived from transgenic mice. This adult brain slice method is suitable for diverse experimental applications, including both monitoring and manipulating neuronal activity with genetically encoded calcium indicators and optogenetic actuators, respectively. We describe the application of this adult brain slice platform and associated methods for screening kinetic properties of Channelrhodopsin (ChR) variants expressed in genetically-defined neuronal subtypes. PMID:25023312

  4. Interactive effect of excitotoxic injury and dietary restriction on neurogenesis and neurotrophic factors in adult male rat brain.

    PubMed

    Kumar, Sushil; Parkash, Jyoti; Kataria, Hardeep; Kaur, Gurcharan

    2009-12-01

    Dietary restriction (DR) is known to have potential health benefits including enhanced resistance of neurons to excitotoxic, oxidative and metabolic insults, cancer, stress, diabetes, reduced morbidity, and increased life span. In the present study, we examined the effect of DR (alternate day feeding regimen) on neurogenesis, expression of immature neuronal marker polysialic acid neural cell adhesion molecule (PSA-NCAM) and neurotrophic factors from different brain regions such as subventricular zone (SVZ), subgranular zone (SGZ) of hippocampus, median eminence arcuate (ME-ARC) region of hypothalamus, and piriform cortex (PIR) of adult male rats and further challenged ad libitum fed (AL) and DR rats with pilocarpine to induce excitotoxic injury. The quantitative analysis of bromodeoxyuridine (BrdU) labeling revealed a significant increase in the proliferation rate of neuronal progenitor cells from discrete brain regions in DR rats with and without pilocarpine induced seizures as compared to AL rats. DR significantly enhanced the expression of PSA-NCAM and neurotrophic factors, brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). There was a marked reduction in neuronal cell death in SVZ and PIR cortex after pilocarpine administration in DR rats. These results add to the accumulating evidence that DR may be an effective intervention to enhance the resistance of brain to excitotoxic injury.

  5. Event-related brain potentials - Comparison between children and adults

    NASA Technical Reports Server (NTRS)

    Courchesne, E.

    1977-01-01

    The reported investigation shows that nontarget stimuli which are infrequently presented and deviate from the background elicit Nc and Pc waves in children. The same stimuli elicit P3 waves in adults. The scalp distribution of P3 waves in adults appears to vary with the ease of stimulus recognition or the degree of stimulus novelty. However, the Nc and Pc distributions in children do not seem to vary with these factors. The differences between children and adults in event-related potentials suggest corresponding differences in the mode of processing employed by each when rare, deviant stimuli are encountered

  6. Genetic variability in the regulation of gene expression in ten regions of the human brain.

    PubMed

    Ramasamy, Adaikalavan; Trabzuni, Daniah; Guelfi, Sebastian; Varghese, Vibin; Smith, Colin; Walker, Robert; De, Tisham; Coin, Lachlan; de Silva, Rohan; Cookson, Mark R; Singleton, Andrew B; Hardy, John; Ryten, Mina; Weale, Michael E

    2014-10-01

    Germ-line genetic control of gene expression occurs via expression quantitative trait loci (eQTLs). We present a large, exon-specific eQTL data set covering ten human brain regions. We found that cis-eQTL signals (within 1 Mb of their target gene) were numerous, and many acted heterogeneously among regions and exons. Co-regulation analysis of shared eQTL signals produced well-defined modules of region-specific co-regulated genes, in contrast to standard coexpression analysis of the same samples. We report cis-eQTL signals for 23.1% of catalogued genome-wide association study hits for adult-onset neurological disorders. The data set is publicly available via public data repositories and via http://www.braineac.org/. Our study increases our understanding of the regulation of gene expression in the human brain and will be of value to others pursuing functional follow-up of disease-associated variants.

  7. Regional Homogeneity of Intrinsic Brain Activity in Happy and Unhappy Individuals

    PubMed Central

    Luo, Yangmei; Huang, Xiting; Yang, Zhen; Li, Baolin; Liu, Jie; Wei, Dongtao

    2014-01-01

    Background Why are some people happier than others? This question has intrigued many researchers. However, limited work has addressed this question within a neuroscientific framework. Methods The present study investigated the neural correlates of trait happiness using the resting-state functional magnetic resonance imaging (rs-fMRI) approach. Specifically, regional homogeneity (ReHo) was examined on two groups of young adults: happy and unhappy individuals (N = 25 per group). Results Decreased ReHo in unhappy relative to happy individuals was observed within prefrontal cortex, medial temporal lobe, superior temporal lobe, and retrosplenial cortex. In contrast, increased ReHo in unhappy relative to happy individuals was observed within the dorsolateral prefrontal cortex, middle cingulate gyrus, putamen, and thalamus. In addition, the ReHo within the left thalamus was negatively correlated with Chinese Happiness Inventory (CHI) score within the happy group. Limitations As an exploratory study, we examined how general trait happiness is reflected in the regional homogeneity of intrinsic brain activity in a relatively small sample. Examining other types of happiness in a larger sample using a multitude of intrinsic brain activity indices are warranted for future work. Conclusions The local synchronization of BOLD signal is altered in unhappy individuals. The regions implicated in this alteration partly overlapped with previously identified default mode network, emotional circuitry, and rewarding system, suggesting that these systems may be involved in happiness. PMID:24454814

  8. Aerobic exercise reduces neuronal responses in food reward brain regions.

    PubMed

    Evero, Nero; Hackett, Laura C; Clark, Robert D; Phelan, Suzanne; Hagobian, Todd A

    2012-05-01

    Acute exercise suppresses ad libitum energy intake, but little is known about the effects of exercise on food reward brain regions. After an overnight fast, 30 (17 men, 13 women), healthy, habitually active (age = 22.2 ± 0.7 yr, body mass index = 23.6 ± 0.4 kg/m(2), Vo(2peak) = 44.2 ± 1.5 ml·kg(-1)·min(-1)) individuals completed 60 min of exercise on a cycle ergometer or 60 min of rest (no-exercise) in a counterbalanced, crossover fashion. After each condition, blood oxygen level-dependent responses to high-energy food, low-energy food, and control visual cues, were measured by functional magnetic resonance imaging. Exercise, compared with no-exercise, significantly (P < 0.005) reduced the neuronal response to food (high and low food) cues vs. control cues in the insula (-0.37 ± 0.13 vs. +0.07 ± 0.18%), putamen (-0.39 ± 0.10 vs. -0.10 ± 0.09%), and rolandic operculum (-0.37 ± 0.17 vs. 0.17 ± 0.12%). Exercise alone significantly (P < 0.005) reduced the neuronal response to high food vs. control and low food vs. control cues in the inferior orbitofrontal cortex (-0.94 ± 0.33%), insula (-0.37 ± 0.13%), and putamen (-0.41 ± 0.10%). No-exercise alone significantly (P < 0.005) reduced the neuronal response to high vs. control and low vs. control cues in the middle (-0.47 ± 0.15%) and inferior occipital gyrus (-1.00 ± 0.23%). Exercise reduced neuronal responses in brain regions consistent with reduced pleasure of food, reduced incentive motivation to eat, and reduced anticipation and consumption of food. Reduced neuronal response in these food reward brain regions after exercise is in line with the paradigm that acute exercise suppresses subsequent energy intake.

  9. aBEAT: a toolbox for consistent analysis of longitudinal adult brain MRI.

    PubMed

    Dai, Yakang; Wang, Yaping; Wang, Li; Wu, Guorong; Shi, Feng; Shen, Dinggang

    2013-01-01

    Longitudinal brain image analysis is critical for revealing subtle but complex structural and functional changes of brain during aging or in neurodevelopmental disease. However, even with the rapid increase of clinical research and trials, a software toolbox dedicated for longitudinal image analysis is still lacking publicly. To cater for this increasing need, we have developed a dedicated 4D Adult Brain Extraction and Analysis Toolbox (aBEAT) to provide robust and accurate analysis of the longitudinal adult brain MR images. Specially, a group of image processing tools were integrated into aBEAT, including 4D brain extraction, 4D tissue segmentation, and 4D brain labeling. First, a 4D deformable-surface-based brain extraction algorithm, which can deform serial brain surfaces simultaneously under temporal smoothness constraint, was developed for consistent brain extraction. Second, a level-sets-based 4D tissue segmentation algorithm that incorporates local intensity distribution, spatial cortical-thickness constraint, and temporal cortical-thickness consistency was also included in aBEAT for consistent brain tissue segmentation. Third, a longitudinal groupwise image registration framework was further integrated into aBEAT for consistent ROI labeling by simultaneously warping a pre-labeled brain atlas to the longitudinal brain images. The performance of aBEAT has been extensively evaluated on a large number of longitudinal MR T1 images which include normal and dementia subjects, achieving very promising results. A Linux-based standalone package of aBEAT is now freely available at http://www.nitrc.org/projects/abeat.

  10. Molecular profiling of the developing avian telencephalon: regional timing and brain subdivision continuities.

    PubMed

    Chen, Chun-Chun; Winkler, Candace M; Pfenning, Andreas R; Jarvis, Erich D

    2013-11-01

    In our companion study (Jarvis et al. [2013] J Comp Neurol. doi: 10.1002/cne.23404) we used quantitative brain molecular profiling to discover that distinct subdivisions in the avian pallium above and below the ventricle and the associated mesopallium lamina have similar molecular profiles, leading to a hypothesis that they may form as continuous subdivisions around the lateral ventricle. To explore this hypothesis, here we profiled the expression of 16 genes at eight developmental stages. The genes included those that define brain subdivisions in the adult and some that are also involved in brain development. We found that phyletic hierarchical cluster and linear regression network analyses of gene expression profiles implicated single and mixed ancestry of these brain regions at early embryonic stages. Most gene expression-defined pallial subdivisions began as one ventral or dorsal domain that later formed specific folds around the lateral ventricle. Subsequently a clear ventricle boundary formed, partitioning them into dorsal and ventral pallial subdivisions surrounding the mesopallium lamina. These subdivisions each included two parts of the mesopallium, the nidopallium and hyperpallium, and the arcopallium and hippocampus, respectively. Each subdivision expression profile had a different temporal order of appearance, similar in timing to the order of analogous cell types of the mammalian cortex. Furthermore, like the mammalian pallium, expression in the ventral pallial subdivisions became distinct during prehatch development, whereas the dorsal portions did so during posthatch development. These findings support the continuum hypothesis of avian brain subdivision development around the ventricle and influence hypotheses on homologies of the avian pallium with other vertebrates. PMID:23818174

  11. Laterality of mental imagery generation and operation: tests with brain-damaged patients and normal adults.

    PubMed

    Hatta, T; Koike, M; Langman, P

    1994-08-01

    The relationships between hemispheric function and components of the imagery process were examined in patients with unilateral right and left brain damage and in intact adult subjects. In the image generation condition, subjects were required to mentally generate Katakana letters corresponding to Hiragana letters displayed on a CRT. The results for the intact adults suggested a left hemisphere superiority, but the unilaterally brain-damaged subjects showed no hemispheric difference in this task. In the imagery operation task (transformation or lateral translation), subjects were asked to find a genuine Kanji among distractors (pseudo-Kanji) that were constructed from two Kanji radicals (themselves real Kanji) that were either displayed in reverse order or shifted apart. The results for both intact adults and patients with unilateral brain damage suggest the superiority of the right hemisphere. PMID:7525640

  12. Distribution and characterization of doublecortin-expressing cells and fibers in the brain of the adult pigeon (Columba livia).

    PubMed

    Melleu, F F; Santos, T S; Lino-de-Oliveira, C; Marino-Neto, J

    2013-01-01

    Doublecortin (DCX) is a microtubule-associated protein essential for the migration of immature neurons in the developing and adult vertebrate brain. Herein, the distribution of DCX-immunoreactive (DCX-ir) cells in the prosencephalon of the adult pigeon (Columba livia) is described, in order to collect the evidence of their immature neural phenotype and to investigate their putative place of origin. Bipolar and multipolar DCX-ir cells were observed to be widespread throughout the parenchyma of the adult pigeon forebrain. Small, bipolar and fusiform DCX-ir cells were especially concentrated at the tips of the lateral walls of the lateral ventricles (VZ) and sparsely distributed in the remaining ependyma. Multipolar DCX-ir cells populated the pallial regions. None of these DCX-ir cells seemed to co-express NeuN or GFAP, suggesting that they were immature neurons. Two different migratory-like routes of DCX-ir cells from the VZ toward different targets in the parenchyma were putatively identified: (i) rostral migratory-like bundle; and (ii) lateral migratory-like bundle. In addition, pial surface bundles and intra-ependymal fascicles were also observed. Pigeons treated with 5-bromo-desoxyuridine (BrdU, 3 intraperitoneal injections of 100mg/kg 2h apart, sacrificed 2h after last injection) displayed BrdU-immunoreactive cells (BrdU-ir) in VZ and ependyma whereas the parenchyma was free of such cells. Despite the regional overlapping, there was no evidence of double-labeling between BrdU and DCX. Therefore, the VZ in the brain of adult pigeons seems to have rapidly dividing cells as putative progenitors of newborn neurons populating the forebrain. The distribution of the newborn neurons in the avian prosencephalon and their migration pathways appear to be larger than in mammals, suggesting that the morphological turnover of forebrain circuits is an important mechanism for brain plasticity in avian species during adulthood.

  13. Dietary resistant starch improves selected brain and behavioral functions in adult and aged rodents

    PubMed Central

    Zhou, June; Keenan, Michael J.; Fernandez-Kim, Sun Ok; Pistell, Paul J.; Ingram, Donald K.; Li, Bing; Raggio, Anne M.; Shen, Li; Zhang, Hanjie; McCutcheon, Kathleen L; Tulley, Richard T.; Blackman, Marc R.; Keller, Jeffrey N.; Martin, Roy J.

    2013-01-01

    Resistant starch (RS) is a dietary fiber that exerts multiple beneficial effects. The current study explored the effects of dietary RS on selected brain and behavioral functions in adult and aged rodents. Because glucokinase (GK) expression in hypothalamic arcuate nucleus and area postrema of the brainstem is important for brain glucose sensing, GK mRNA was measured by brain nuclei microdissection and PCR. Adult RS-fed rats had a higher GK mRNA than controls in both brain nuclei, an indicator of improved brain glucose sensing. Next, we tested whether dietary RS improve selected behaviors in aged mice. RS-fed aged mice exhibited (1) an increased eating responses to fasting, a behavioral indicator of improvement in aged brain glucose sensing; (2) a longer latency to fall from an accelerating rotarod, a behavioral indicator of improved motor coordination; and (3) a higher serum active GLP-1. Third, GLP-1 receptor null (GLP-1RKO) mice were used to test the role of GLP-1 in brain glucose sensing, and they exhibited impaired eating responses to fasting. We conclude that in rodents (1) dietary RS improves two important indicators of brain function: glucose sensing and motor coordination, and that (2) GLP-1 is important in the optimal feeding response to a fast. PMID:23818307

  14. Dietary resistant starch improves selected brain and behavioral functions in adult and aged rodents.

    PubMed

    Zhou, June; Keenan, Michael J; Fernandez-Kim, Sun Ok; Pistell, Paul J; Ingram, Donald K; Li, Bing; Raggio, Anne M; Shen, Li; Zhang, Hanjie; McCutcheon, Kathleen L; Tulley, Richard T; Blackman, Marc R; Keller, Jeffrey N; Martin, Roy J

    2013-11-01

    Resistant starch (RS) is a dietary fiber that exerts multiple beneficial effects. The current study explored the effects of dietary RS on selected brain and behavioral functions in adult and aged rodents. Because glucokinase (GK) expression in hypothalamic arcuate nucleus and area postrema of the brainstem is important for brain glucose sensing, GK mRNA was measured by brain nuclei microdissection and PCR. Adult RS-fed rats had a higher GK mRNA than controls in both brain nuclei, an indicator of improved brain glucose sensing. Next, we tested whether dietary RS improve selected behaviors in aged mice. RS-fed aged mice exhibited (i) an increased eating responses to fasting, a behavioral indicator of improvement in aged brain glucose sensing; (ii) a longer latency to fall from an accelerating rotarod, a behavioral indicator of improved motor coordination; and (iii) a higher serum active glucagon-like peptide-1 (GLP-1). Then, GLP-1 receptor null (GLP-1RKO) mice were used to test the role of GLP-1 in brain glucose sensing, and they exhibited impaired eating responses to fasting. We conclude that in rodents (i) dietary RS improves two important indicators of brain function: glucose sensing and motor coordination, and (ii) GLP-1 is important in the optimal feeding response to a fast.

  15. Is docosahexaenoic acid synthesis from α-linolenic acid sufficient to supply the adult brain?

    PubMed

    Domenichiello, Anthony F; Kitson, Alex P; Bazinet, Richard P

    2015-07-01

    Docosahexaenoic acid (DHA) is important for brain function, and can be obtained directly from the diet or synthesized in the body from α-linolenic acid (ALA). Debate exists as to whether DHA synthesized from ALA can provide sufficient DHA for the adult brain, as measures of DHA synthesis from ingested ALA are typically <1% of the oral ALA dose. However, the primary fate of orally administered ALA is β-oxidation and long-term storage in adipose tissue, suggesting that DHA synthesis measures involving oral ALA tracer ingestion may underestimate total DHA synthesis. There is also evidence that DHA synthesized from ALA can meet brain DHA requirements, as animals fed ALA-only diets have brain DHA concentrations similar to DHA-fed animals, and the brain DHA requirement is estimated to be only 2.4-3.8 mg/day in humans. This review summarizes evidence that DHA synthesis from ALA can provide sufficient DHA for the adult brain by examining work in humans and animals involving estimates of DHA synthesis and brain DHA requirements. Also, an update on methods to measure DHA synthesis in humans is presented highlighting a novel approach involving steady-state infusion of stable isotope-labeled ALA that bypasses several limitations of oral tracer ingestion. It is shown that this method produces estimates of DHA synthesis that are at least 3-fold higher than brain uptake rates in rats.

  16. Graft derived cells with double nuclei in the penumbral region of experimental brain trauma.

    PubMed

    Horváth, Eszter M; Lacza, Zsombor; Csordás, Attila; Szabó, Csaba; Kollai, Márk; Busija, David W

    2006-04-01

    Recent in vitro studies showed that stem cells might fuse with mature cells or each other; however, there is no in vivo evidence for this phenomenon in the cerebral cortex. Our goal was to find evidence for cell fusion in a model of traumatic brain injury followed by grafting of embryonic cortical cells. Cold lesion protocol was applied to induce lesion of the motor cortex in adult male rats. Six days later we grafted a suspension of freshly isolated rat brain cortical cells of early embryonic stage (E14) into the penumbra area of the lesion. The grafted cell nuclei were labelled with bromodeoxyuridine (BrDU). Six days after transplantation 4,328 BrDU positive cells were observed in nine animals. 89.5% of these cells had cytoplasmic staining probably representing dead or phagocyted grafted cells. Ten percent of surviving BrDU positive cells had only one BrDU positive nucleus and negative cytoplasm, while 0.5% had two distinct nuclei, one was unlabelled and one was BrDU positive. These cells were similar in appearance and size to the astrocytes in the vicinity and expressed the astocyte specific glial fibrillaly acidic protein. Thus, these cells showed a possible sign of cell fusion in the penumbral region of the injured brain. PMID:16377084

  17. Extracting brain regions from rest fMRI with total-variation constrained dictionary learning.

    PubMed

    Abraham, Alexandre; Dohmatob, Elvis; Thirion, Bertrand; Samaras, Dimitris; Varoquaux, Gael

    2013-01-01

    Spontaneous brain activity reveals mechanisms of brain function and dysfunction. Its population-level statistical analysis based on functional images often relies on the definition of brain regions that must summarize efficiently the covariance structure between the multiple brain networks. In this paper, we extend a network-discovery approach, namely dictionary learning, to readily extract brain regions. To do so, we introduce a new tool drawing from clustering and linear decomposition methods by carefully crafting a penalty. Our approach automatically extracts regions from rest fMRI that better explain the data and are more stable across subjects than reference decomposition or clustering methods.

  18. Bi-parental care contributes to sexually dimorphic neural cell genesis in the adult mammalian brain.

    PubMed

    Mak, Gloria K; Antle, Michael C; Dyck, Richard H; Weiss, Samuel

    2013-01-01

    Early life events can modulate brain development to produce persistent physiological and behavioural phenotypes that are transmissible across generations. However, whether neural precursor cells are altered by early life events, to produce persistent and transmissible behavioural changes, is unknown. Here, we show that bi-parental care, in early life, increases neural cell genesis in the adult rodent brain in a sexually dimorphic manner. Bi-parentally raised male mice display enhanced adult dentate gyrus neurogenesis, which improves hippocampal neurogenesis-dependent learning and memory. Female mice display enhanced adult white matter oligodendrocyte production, which increases proficiency in bilateral motor coordination and preference for social investigation. Surprisingly, single parent-raised male and female offspring, whose fathers and mothers received bi-parental care, respectively, display a similar enhancement in adult neural cell genesis and phenotypic behaviour. Therefore, neural plasticity and behavioural effects due to bi-parental care persist throughout life and are transmitted to the next generation.

  19. Developmental, regional, and cellular expression of SFT/UbcH5A and DMT1 mRNA in brain.

    PubMed

    Knutson, Mitchell; Menzies, Sharon; Connor, James; Wessling-Resnick, Marianne

    2004-06-01

    Brain iron has marked developmental, regional, and cellular distribution patterns. To characterize better the potential mechanisms for iron transport into and within the brain, we have analyzed expression patterns of two factors: divalent metal transporter 1 (DMT1) and stimulator of Fe transport (SFT). DMT1 is known to participate in brain iron uptake although functional information is lacking. Even less clear is the possible role of SFT, which is related to a member of the ubiquitin-conjugating E2 family UbcH5A, but previous studies have found SFT/Ubc5Ha mRNA expressed abundantly in mouse brain. Like DMT1, SFT function has been implicated in transferrin and nontransferrin-bound iron uptake. Comparative Northern analysis indicates that SFT/UbcH5A mRNA levels are threefold higher in 3-day-old mice than at later ages, whereas levels of DMT1 mRNA do not change. In situ analysis of neonatal mouse brain reveals prominent SFT/UbcH5A mRNA expression in epithelial and ependymal cells in the choroid plexus and neurons of the olfactory bulb, hippocampus, and cortex. Adult mouse brain expresses SFT/UbcH5A mRNA mainly in white matter of the cerebellum and pons. Using a multiple tissue expression (MTE) array containing 20 different human brain regions, the highest levels of both SFT/UbcH5A and DMT1 mRNA are detected in the corpus callosum and cerebellum. The significantly elevated levels of SFT/UbcH5A mRNA in the neonatal mouse and its localization to choroid plexus, a major site of brain iron acquisition, suggest that this factor may contribute to the rapid rate of brain iron uptake that occurs in the early postnatal period.

  20. Bilingualism alters brain functional connectivity between "control" regions and "language" regions: Evidence from bimodal bilinguals.

    PubMed

    Li, Le; Abutalebi, Jubin; Zou, Lijuan; Yan, Xin; Liu, Lanfang; Feng, Xiaoxia; Wang, Ruiming; Guo, Taomei; Ding, Guosheng

    2015-05-01

    Previous neuroimaging studies have revealed that bilingualism induces both structural and functional neuroplasticity in the dorsal anterior cingulate cortex (dACC) and the left caudate nucleus (LCN), both of which are associated with cognitive control. Since these "control" regions should work together with other language regions during language processing, we hypothesized that bilingualism may also alter the functional interaction between the dACC/LCN and language regions. Here we tested this hypothesis by exploring the functional connectivity (FC) in bimodal bilinguals and monolinguals using functional MRI when they either performed a picture naming task with spoken language or were in resting state. We found that for bimodal bilinguals who use spoken and sign languages, the FC of the dACC with regions involved in spoken language (e.g. the left superior temporal gyrus) was stronger in performing the task, but weaker in the resting state as compared to monolinguals. For the LCN, its intrinsic FC with sign language regions including the left inferior temporo-occipital part and right inferior and superior parietal lobules was increased in the bilinguals. These results demonstrate that bilingual experience may alter the brain functional interaction between "control" regions and "language" regions. For different control regions, the FC alters in different ways. The findings also deepen our understanding of the functional roles of the dACC and LCN in language processing. PMID:25858600

  1. Bilingualism alters brain functional connectivity between "control" regions and "language" regions: Evidence from bimodal bilinguals.

    PubMed

    Li, Le; Abutalebi, Jubin; Zou, Lijuan; Yan, Xin; Liu, Lanfang; Feng, Xiaoxia; Wang, Ruiming; Guo, Taomei; Ding, Guosheng

    2015-05-01

    Previous neuroimaging studies have revealed that bilingualism induces both structural and functional neuroplasticity in the dorsal anterior cingulate cortex (dACC) and the left caudate nucleus (LCN), both of which are associated with cognitive control. Since these "control" regions should work together with other language regions during language processing, we hypothesized that bilingualism may also alter the functional interaction between the dACC/LCN and language regions. Here we tested this hypothesis by exploring the functional connectivity (FC) in bimodal bilinguals and monolinguals using functional MRI when they either performed a picture naming task with spoken language or were in resting state. We found that for bimodal bilinguals who use spoken and sign languages, the FC of the dACC with regions involved in spoken language (e.g. the left superior temporal gyrus) was stronger in performing the task, but weaker in the resting state as compared to monolinguals. For the LCN, its intrinsic FC with sign language regions including the left inferior temporo-occipital part and right inferior and superior parietal lobules was increased in the bilinguals. These results demonstrate that bilingual experience may alter the brain functional interaction between "control" regions and "language" regions. For different control regions, the FC alters in different ways. The findings also deepen our understanding of the functional roles of the dACC and LCN in language processing.

  2. In vivo electroporation to physiologically identified deep brain regions in postnatal mammals.

    PubMed

    Ohmura, Nami; Kawasaki, Kazuha; Satoh, Takemasa; Hata, Yoshio

    2015-01-01

    Genetic manipulation is widely used to research the central nervous system (CNS). The manipulation of molecular expression in a small number of neurons permits the detailed investigation of the role of specific molecules on the function and morphology of the neurons. Electroporation is a broadly used technique for gene transfer in the CNS. However, the targeting of gene transfer using electroporation in postnatal animals was restricted to the cortex, hippocampus, or the region facing the ventricle in previous reports. Electroporation targeting of deep brain structures, such as the thalamus, has been difficult. We introduce a novel electroporation technique that enables gene transfer to a physiologically identified deep brain region using a glass pipette. We recorded neural activity in young-adult mice to identify the location of the lateral geniculate nucleus (LGN) of the thalamus, using a glass pipette electrode containing the plasmid DNA encoding enhanced green fluorescent protein (EGFP). The location of the LGN was confirmed by monitoring visual responses, and the plasmid solution was pressure-injected into the recording site. Voltage pulses were delivered through the glass pipette electrode. Several EGFP-labeled somata and dendrites were observed in the LGN after a few weeks, and labeled axons were found in the visual cortex. The EGFP-expressing structures were observed in detail sufficient to reconstruct their morphology in three dimensions. We further confirmed the applicability of this technique in cats. This method should be useful for the transfer of various genes into cells in physiologically identified brain regions in rodents and gyrencephalic mammals.

  3. Educating the adult brain: How the neuroscience of learning can inform educational policy

    NASA Astrophysics Data System (ADS)

    Knowland, Victoria C. P.; Thomas, Michael S. C.

    2014-05-01

    The acquisition of new skills in adulthood can positively affect an individual's quality of life, including their earning potential. In some cases, such as the learning of literacy in developing countries, it can provide an avenue to escape from poverty. In developed countries, job retraining in adulthood contributes to the flexibility of labour markets. For all adults, learning opportunities increase participation in society and family life. However, the popular view is that adults are less able to learn for an intrinsic reason: their brains are less plastic than in childhood. This article reviews what is currently known from neuroscientific research about how brain plasticity changes with age, with a particular focus on the ability to acquire new skills in adulthood. Anchoring their review in the examples of the adult acquisition of literacy and new motor skills, the authors address five specific questions: (1) Are sensitive periods in brain development relevant to learning complex educational skills like literacy? (2) Can adults become proficient in a new skill? (3) Can everyone learn equally effectively in adulthood? (4) What is the role of the learning environment? (5) Does adult education cost too much? They identify areas where further research is needed and conclude with a summary of principles for enhancing adult learning now established on a neuroscience foundation.

  4. PCNA immunoreactivity revealing normal proliferative activity in the brain of an adult Elasmobranch, Torpedo marmorata.

    PubMed

    Margotta, Vito

    2007-01-01

    The brain of adult heterothermic vertebrates can be already provided of quiescent cells, scattered ("matrix cells") and/or clustered ("matrix areas"). These typical cells, in some regions located at or near ventricular surfaces and at peri-ependymal layers, in other territories populating their framework, maintain some embryonic properties and are responsible of normal or variously experimentally induced proliferative activities. On these topics there are a great number of reports concerning Teleostean Osteichthyes, Urodele and Anuran Amphibians, Lacertilian Reptiles. At the contrary, only few are the contributions regarding the Petromyzontidae. Involving an immunocytochemical marker, the Proliferating Cell Nuclear Antigen (PCNA), revealing proliferative events, in the last years we have undertaken a reappraisal focused on these encephalic performances in normal adult poikilothermal vertebrates. To provide a valid comparison between our results and the literature data, our choice of the specimens was based on the desire to employ organisms belonging to the same or phylogenetically close species used by previous Authors in similar studies. In our immunocytochemical panorama there is a substantial agreement between our contributions and bibliographic references concerning natural encephalic proliferative phenomena in these vertebrates. At this point of our study, the last missing piece was represented by the Chondrichthyes about which the literature data are lacking. In order to fill this gap, the aim of the present research is to investigate, involving the same PCNA test, whether proliferative events also persist in the brain of adult cartilaginous fishes. The immunostaining images obtained in the Elasmo branch Torpedo marmorata, well-known for the emission of high electrical discharges, exhibit undifferentiated cells in relationship with the ependymal epithelium lining the cavities of all cerebral districts; some other neuroblasts are scattered in the mesencephalic

  5. Vitamin D as a neurosteroid affecting the developing and adult brain.

    PubMed

    Groves, Natalie J; McGrath, John J; Burne, Thomas H J

    2014-01-01

    Vitamin D deficiency is prevalent throughout the world, and growing evidence supports a requirement for optimal vitamin D levels for the healthy developing and adult brain. Vitamin D has important roles in proliferation and differentiation, calcium signaling within the brain, and neurotrophic and neuroprotective actions; it may also alter neurotransmission and synaptic plasticity. Recent experimental studies highlight the impact that vitamin D deficiency has on brain function in health and disease. In addition, results from recent animal studies suggest that vitamin D deficiency during adulthood may exacerbate underlying brain disorders and/or worsen recovery from brain stressors. An increasing number of epidemiological studies indicate that vitamin D deficiency is associated with a wide range of neuropsychiatric disorders and neurodegenerative diseases. Vitamin D supplementation is readily available and affordable, and this review highlights the need for further research. PMID:25033060

  6. Fetal Alcohol Exposure Reduces Adult Brain Plasticity. Science Briefs

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2007

    2007-01-01

    "Science Briefs" summarize the findings and implications of a recent study in basic science or clinical research. This Brief summarizes the findings and implications of "Moderate Fetal Alcohol Exposure Impairs the Neurogenic Response to an Enriched Environment in Adult Mice" (I. Y. Choi; A. M. Allan; and L. A. Cunningham). Observations of mice…

  7. Hippocampal sub-regional shape and physical activity in older adults.

    PubMed

    Varma, Vijay R; Tang, Xiaoying; Carlson, Michelle C

    2016-08-01

    Hippocampal atrophy is a hallmark of Alzheimer's disease pathology, and a target biomarker region for testing intervention efficacy. Over the last few decades, a growing body of evidence from animal and human models suggests that physical activity (PA) is associated with structural benefits to the hippocampus in older adults. Very few human studies, however have explored hippocampal sub-regional specificity of PA; this is significant considering that sub-regions of the hippocampus are associated with distinct cognitive tasks and are differentially affected by disease pathology. This study used objective and self-reported measures of daily walking activity and exercise, and surface-based regional shape analysis using high-field hippocampal sub-regional partitions to explore sub-region specific hippocampal associations in a sample of nondemented, community-dwelling older adults at elevated sociodemographic risk for cognitive decline. Vertex-wise surface areas, which may be more sensitive than global volume measures, were calculated using shape diffeomorphometry, and PA was assessed using step activity monitors and PA questionnaires. We found that daily walking activity in a participant's environment was associated in cross-section mainly with larger surface areas of the subiculum in women. Associations remained significant when controlling for self-reported exercise. Prior studies have found that PA related to exercise and aerobic fitness may be most closely associated with the anterior hippocampus, particularly the dentate gyrus of the hippocampus. These novel findings are the first, to our knowledge, in human models to suggest that PA related to navigation that may not reach the level of moderate-intensity exercise may be associated with specific sub-regions of the hippocampus. These findings underscore the importance of better understanding the independent and related biological mechanisms and pathways by which increasing exercise as well as non

  8. Intelligence and Regional Brain Volumes in Normal Controls.

    ERIC Educational Resources Information Center

    Flashman, Laura A.; Andreasen, Nancy C.; Flaum, Michael; Swayze, Victor W., II

    1998-01-01

    The relationship between brain size and intelligence was examined in 90 normal volunteers. Results support the notion of a modest relationship between brain size and measures of global intelligence and suggest diffuse brain involvement on performance tasks that require integration and use of multiple cognitive domains. (Author/SLD)

  9. [Management of swallowing disorders after brain injuries in adults].

    PubMed

    Fichaux, Bourin P; Labrune, M

    2008-01-01

    The management of swallowing disorders after brain injury must be soon as well. The physiopathological analysis and the organization of the therapeutic project of these patients require the intervention of an interdisciplinary team. Dysphagia falls under a complex clinical context associating impairments of cognition, communication and behavioural control. The management associates speech therapist, caregivers, otolaryngolologist, phoniatrician, physiotherapist and nutritional therapist without forgetting the family circle. The fluctuations of consciousness and concentration of our patients brings us to constantly readjusting and rehabilitating the strategies of feeding. Obstacles with their evolution towards a normal feeding are akinesia, limits of motor functions, impairements of cognition and behavioural control. In the located lesions swallow recovers can be fast, instead of in severe brain-injury the challenge is to ensure safe and adequate nutrition, using a variety of strategies depending on the presenting symptoms. The purpose of this article is to relate our experience beside patients with an acute or recent cerbrovascular event.

  10. Acute effects of alcohol on brain perfusion monitored with arterial spin labeling magnetic resonance imaging in young adults.

    PubMed

    Marxen, Michael; Gan, Gabriela; Schwarz, Daniel; Mennigen, Eva; Pilhatsch, Maximilian; Zimmermann, Ulrich S; Guenther, Matthias; Smolka, Michael N

    2014-03-01

    While a number of studies have established that moderate doses of alcohol increase brain perfusion, the time course of such an increase as a function of breath alcohol concentration (BrAC) has not yet been investigated, and studies differ about regional effects. Using arterial spin labeling (ASL) magnetic resonance imaging, we investigated (1) the time course of the perfusion increase during a 15-minute linear increase of BrAC up to 0.6 g/kg followed by a steady exposure of 100 minutes, (2) the regional distribution, (3) a potential gender effect, and (4) the temporal stability of perfusion effects. In 48 young adults who participated in the Dresden longitudinal study on alcohol effects in young adults, we observed (1) a 7% increase of global perfusion as compared with placebo and that perfusion and BrAC are tightly coupled in time, (2) that the increase reaches significance in most regions of the brain, (3) that the effect is stronger in women than in men, and (4) that an acute tolerance effect is not observable on the time scale of 2 hours. Larger studies are needed to investigate the origin and the consequences of the effect, as well as the correlates of inter-subject variations.

  11. HETEROTOPICALLY TRANSPLANTED CVO NEURAL STEM CELLS GENERATE NEURONS AND MIGRATE WITH SVZ CELLS IN THE ADULT MOUSE BRAIN

    PubMed Central

    Bennett, Lori B.; Cai, Jingli; Enikolopov, Grigori; Iacovitti, Lorraine

    2010-01-01

    Production of new neurons throughout adulthood has been well characterized in two brain regions, the subventricular zone (SVZ) of the anterolateral ventricle and the subgranular zone (SGZ) of the hippocampus. The neurons produced from these regions arise from neural stem cells (NSCs) found in highly regulated stem cell niches. We recently showed that midline structures called circumventricular organs (CVOs) also contain NSCs capable of neurogenesis and/or astrogliogenesis in vitro and in situ [3]. The present study demonstrates that NSCs derived from two astrogliogenic CVOs, the median eminence and organum vasculosum of the lamina terminalis of the Nestin-GFP mouse, possess the potential to integrate into the SVZ and differentiate into cells with a neuronal phenotype. These NSCs, following expansion and BrdU-labeling in culture and heterotopic transplantation into a region proximal to the SVZ in adult mice, migrate caudally to the SVZ and express early neuronal markers (TUC-4, PSA-NCAM) as they migrate along the rostral migratory stream. CVO-derived BrdU+ cells ultimately reach the olfactory bulb where they express early (PSA-NCAM) and mature (NeuN) neuronal markers. Collectively, these data suggest that although NSCs derived from the ME and OVLT CVOs are astrogliogenic in situ, they produce cells phenotypic of neurons in vivo when placed in a neurogenic environment. These findings may have implications for neural repair in the adult brain. PMID:20298755

  12. Amphetamine modulates brain signal variability and working memory in younger and older adults.

    PubMed

    Garrett, Douglas D; Nagel, Irene E; Preuschhof, Claudia; Burzynska, Agnieszka Z; Marchner, Janina; Wiegert, Steffen; Jungehülsing, Gerhard J; Nyberg, Lars; Villringer, Arno; Li, Shu-Chen; Heekeren, Hauke R; Bäckman, Lars; Lindenberger, Ulman

    2015-06-16

    Better-performing younger adults typically express greater brain signal variability relative to older, poorer performers. Mechanisms for age and performance-graded differences in brain dynamics have, however, not yet been uncovered. Given the age-related decline of the dopamine (DA) system in normal cognitive aging, DA neuromodulation is one plausible mechanism. Hence, agents that boost systemic DA [such as d-amphetamine (AMPH)] may help to restore deficient signal variability levels. Furthermore, despite the standard practice of counterbalancing drug session order (AMPH first vs. placebo first), it remains understudied how AMPH may interact with practice effects, possibly influencing whether DA up-regulation is functional. We examined the effects of AMPH on functional-MRI-based blood oxygen level-dependent (BOLD) signal variability (SD(BOLD)) in younger and older adults during a working memory task (letter n-back). Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult SD(BOLD) levels in the presence of AMPH. Drug session order greatly moderated change-change relations between AMPH-driven SD(BOLD) and reaction time means (RT(mean)) and SDs (RT(SD)). Older adults who received AMPH in the first session tended to improve in RT(mean) and RT(SD) when SD(BOLD) was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SD(BOLD) decreased (for RT(mean)) or no effect at all (for RT(SD)). The present findings support the hypothesis that age differences in brain signal variability reflect aging-induced changes in dopaminergic neuromodulation. The observed interactions among AMPH, age, and session order highlight the state- and practice-dependent neurochemical basis of human brain dynamics.

  13. Brain tissue pressure measurements in perinatal and adult rabbits.

    PubMed

    Hornig, G W; Lorenzo, A V; Zavala, L M; Welch, K

    1987-12-01

    Brain tissue pressure (BTP) in pre- and post-natal anesthetized rabbits, held in a stereotactic head holder, was measured with a fluid filled 23 gauge open-ended cannula connected distally to a pressure transducer. By advancing the cannula step wise through a hole in the cranium it was possible to sequentially measure pressure from the cranial subarachnoid space, cortex, ventricle and basal ganglia. Separate cannulas and transducers were used to measure CSFP from the cisterna magna and arterial and/or venous pressure. Pressure recordings obtained when the tip of the BTP cannula was located in the cranial subarachnoid space or ventricle exhibited respiratory and blood pressure pulsations equivalent to and in phase with CSF pulsations recorded from the cisterna magna. When the tip was advanced into brain parenchymal sites such pulsations were suppressed or non-detectable unless communication with a CSF compartment had been established inadvertently. Although CSF pressures in the three spinal fluid compartments were equivalent, in most animals BTP was higher than CSFP. However, after momentary venting of the system BTP equilibrated at a pressure below that of CSFP. We speculate that venting of the low compliance system (1.20 x 10(-5) ml/mmHg) relieves the isometric pressure build-up due to insertion of the cannula into brain parenchyma. Under these conditions, and at all ages examined, BTP in the rabbit is consistently lower than CSFP and, as with CSFP, it increases as the animal matures.

  14. Functional Brain Network Abnormalities during Verbal Working Memory Performance in Adolescents and Young Adults with Dyslexia

    ERIC Educational Resources Information Center

    Wolf, Robert Christian; Sambataro, Fabio; Lohr, Christina; Steinbrink, Claudia; Martin, Claudia; Vasic, Nenad

    2010-01-01

    Behavioral and functional neuroimaging studies indicate deficits in verbal working memory (WM) and frontoparietal dysfunction in individuals with dyslexia. Additionally, structural brain abnormalities in dyslexics suggest a dysconnectivity of brain regions associated with phonological processing. However, little is known about the functional…

  15. Regional research priorities in brain and nervous system disorders.

    PubMed

    Ravindranath, Vijayalakshmi; Dang, Hoang-Minh; Goya, Rodolfo G; Mansour, Hader; Nimgaonkar, Vishwajit L; Russell, Vivienne Ann; Xin, Yu

    2015-11-19

    The characteristics of neurological, psychiatric, developmental and substance-use disorders in low- and middle-income countries are unique and the burden that they have will be different from country to country. Many of the differences are explained by the wide variation in population demographics and size, poverty, conflict, culture, land area and quality, and genetics. Neurological, psychiatric, developmental and substance-use disorders that result from, or are worsened by, a lack of adequate nutrition and infectious disease still afflict much of sub-Saharan Africa, although disorders related to increasing longevity, such as stroke, are on the rise. In the Middle East and North Africa, major depressive disorders and post-traumatic stress disorder are a primary concern because of the conflict-ridden environment. Consanguinity is a serious concern that leads to the high prevalence of recessive disorders in the Middle East and North Africa and possibly other regions. The burden of these disorders in Latin American and Asian countries largely surrounds stroke and vascular disease, dementia and lifestyle factors that are influenced by genetics. Although much knowledge has been gained over the past 10 years, the epidemiology of the conditions in low- and middle-income countries still needs more research. Prevention and treatments could be better informed with more longitudinal studies of risk factors. Challenges and opportunities for ameliorating nervous-system disorders can benefit from both local and regional research collaborations. The lack of resources and infrastructure for health-care and related research, both in terms of personnel and equipment, along with the stigma associated with the physical or behavioural manifestations of some disorders have hampered progress in understanding the disease burden and improving brain health. Individual countries, and regions within countries, have specific needs in terms of research priorities. PMID:26580328

  16. Adding chemo after radiation treatment improves survival for adults with a type of brain tumor

    Cancer.gov

    Adults with low-grade gliomas, a form of brain tumor, who received chemotherapy following completion of radiation therapy lived longer than patients who received radiation therapy alone, according to long-term follow-up results from a NIH-supported random

  17. Minimal Brain Dysfunction in Childhood: 1. Outcome in Late Adolescence and Early Adult Years. Final Version.

    ERIC Educational Resources Information Center

    Milman, Doris H.

    Seventy-three patients, diagnosed in childhood as having either maturational lag or organic brain syndrome, were followed for an average of 12 years into late adolescence and early adult life for the purpose of discovering the outcome with respect to ultimate psychiatric status, educational attainment, social adjustment, and global adjustment. At…

  18. Brain Mapping of Language and Auditory Perception in High-Functioning Autistic Adults: A PET Study.

    ERIC Educational Resources Information Center

    Muller, R-A.; Behen, M. E.; Rothermel, R. D.; Chugani, D. C.; Muzik, O.; Mangner, T. J.; Chugani, H. T.

    1999-01-01

    A study used positron emission tomography (PET) to study patterns of brain activation during auditory processing in five high-functioning adults with autism. Results found that participants showed reversed hemispheric dominance during the verbal auditory stimulation and reduced activation of the auditory cortex and cerebellum. (CR)

  19. Humor, Rapport, and Uncomfortable Moments in Interactions with Adults with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Kovarsky, Dana; Schiemer, Christine; Murray, Allison

    2011-01-01

    We examined uncomfortable moments that damaged rapport during group interactions between college students in training to become speech-language pathologists and adults with traumatic brain injury. The students worked as staff in a community-based program affiliated with a university training program that functioned as a recreational gathering…

  20. Radial glia-like cells persist in the adult rat brain.

    PubMed

    Gubert, Fernanda; Zaverucha-do-Valle, Camila; Pimentel-Coelho, Pedro M; Mendez-Otero, Rosalia; Santiago, Marcelo F

    2009-03-01

    During development, radial glia cells contribute to neuronal migration and neurogenesis, and differentiate into astrocytes by the end of the developmental period. Recently, it was demonstrated that during development, radial glia cells, in addition to their role in migration, also give rise to neuroblasts. Furthermore, radial glial cells remain in the adult brain as adult neural stem cells (NSC) in the subventricular zone (SVZ) around the lateral ventricles (LVs), and generate new neurons continuously throughout adulthood. In this study, we used immunohistochemical and morphological methods to investigate the presence of radial glia-like cells around the LVs during the postnatal development period until adulthood in rats. In all ages of rats studied, we identified cells with morphological and immunocytochemical features that are similar to the radial glia cells found in the embryonic brain. Similarly to the radial glia, these cells express nestin and vimentin, and have a radial morphology, extending perpendicularly as processes from the ventricle wall. These cells also express GFAP, GLAST, and Pax6, and proliferate. In the brains of adult rats, we identified cells with relatively long processes (up to 600 mum) in close apposition with migrating neuroblasts. Our results showed that the radial glia-like cells present in the adult rat brain share several morphological and functional characteristics with the embryonic radial glia. We suggest that the embryonic radial glia cells located around the LV walls do not complete their transformation into astrocytes, but rather persist in adulthood.

  1. [Specific features of rhino-sinusogenic brain abscesses in adults and children].

    PubMed

    Blagoveshchenskaia, N S; Mukhamedzhanov, N Z

    1989-01-01

    Analysis of observations of 49 patients with rhinosinusogenic brain abscesses revealed differences in their development between adults and children. This pathology occurs in adults more frequently than in children, particularly young children. In adults, brain abscesses usually develop as a result of chronic frontal- or polysinusitis, while in children they typically occur after maxillary sinusitis and in early age children also after acute suppuration in the nasal cavity. For adults, the contact pathway of infection is characteristic, whereas for children, the hematogenic-metastatic pathway is typical. Adults show single abscesses while children show both single, multiple and multichamber abscesses accompanied by separation of cranial sutures, thinning of calvaria, and protrusion and tension of the cranial fontanel. In children, abscesses may grow very large. In adults, the hypertensive syndrome is very distinct, while in children, the hydrocephalic-hypertensive syndrome comes to the foreground. In children, infectious-toxic symptoms are more significant. In adults, focal neurological symptoms become more serious than in children in whom they are also more labile.

  2. Whole-brain structural topology in adult attention-deficit/hyperactivity disorder: Preserved global - disturbed local network organization.

    PubMed

    Sidlauskaite, Justina; Caeyenberghs, Karen; Sonuga-Barke, Edmund; Roeyers, Herbert; Wiersema, Jan R

    2015-01-01

    Prior studies demonstrate altered organization of functional brain networks in attention-deficit/hyperactivity disorder (ADHD). However, the structural underpinnings of these functional disturbances are poorly understood. In the current study, we applied a graph-theoretic approach to whole-brain diffusion magnetic resonance imaging data to investigate the organization of structural brain networks in adults with ADHD and unaffected controls using deterministic fiber tractography. Groups did not differ in terms of global network metrics - small-worldness, global efficiency and clustering coefficient. However, there were widespread ADHD-related effects at the nodal level in relation to local efficiency and clustering. The affected nodes included superior occipital, supramarginal, superior temporal, inferior parietal, angular and inferior frontal gyri, as well as putamen, thalamus and posterior cerebellum. Lower local efficiency of left superior temporal and supramarginal gyri was associated with higher ADHD symptom scores. Also greater local clustering of right putamen and lower local clustering of left supramarginal gyrus correlated with ADHD symptom severity. Overall, the findings indicate preserved global but altered local network organization in adult ADHD implicating regions underpinning putative ADHD-related neuropsychological deficits. PMID:26640763

  3. Apolipoprotein ε4 is associated with lower brain volume in cognitively normal Chinese but not white older adults.

    PubMed

    Yokoyama, Jennifer S; Lee, Allen K L; Takada, Leonel T; Busovaca, Edgar; Bonham, Luke W; Chao, Steven Z; Tse, Marian; He, Jing; Schwarz, Christopher G; Carmichael, Owen T; Matthews, Brandy R; Karydas, Anna; Weiner, Michael W; Coppola, Giovanni; DeCarli, Charles S; Miller, Bruce L; Rosen, Howard J

    2015-01-01

    Studying ethnically diverse groups is important for furthering our understanding of biological mechanisms of disease that may vary across human populations. The ε4 allele of apolipoprotein E (APOE ε4) is a well-established risk factor for Alzheimer's disease (AD), and may confer anatomic and functional effects years before clinical signs of cognitive decline are observed. The allele frequency of APOE ε4 varies both across and within populations, and the size of the effect it confers for dementia risk may be affected by other factors. Our objective was to investigate the role APOE ε4 plays in moderating brain volume in cognitively normal Chinese older adults, compared to older white Americans. We hypothesized that carrying APOE ε4 would be associated with reduced brain volume and that the magnitude of this effect would be different between ethnic groups. We performed whole brain analysis of structural MRIs from Chinese living in America (n = 41) and Shanghai (n = 30) and compared them to white Americans (n = 71). We found a significant interaction effect of carrying APOE ε4 and being Chinese. The APOE ε4xChinese interaction was associated with lower volume in bilateral cuneus and left middle frontal gyrus (Puncorrected<0.001), with suggestive findings in right entorhinal cortex and left hippocampus (Puncorrected<0.01), all regions that are associated with neurodegeneration in AD. After correction for multiple testing, the left cuneus remained significantly associated with the interaction effect (PFWE = 0.05). Our study suggests there is a differential effect of APOE ε4 on brain volume in Chinese versus white cognitively normal elderly adults. This represents a novel finding that, if verified in larger studies, has implications for how biological, environmental and/or lifestyle factors may modify APOE ε4 effects on the brain in diverse populations. PMID:25738563

  4. Relationship between brain accumulation of manganese and aberration of hippocampal adult neurogenesis after oral exposure to manganese chloride in mice.

    PubMed

    Kikuchihara, Yoh; Abe, Hajime; Tanaka, Takeshi; Kato, Mizuho; Wang, Liyun; Ikarashi, Yoshiaki; Yoshida, Toshinori; Shibutani, Makoto

    2015-05-01

    We previously found persistent aberration of hippocampal adult neurogenesis, along with brain manganese (Mn) accumulation, in mouse offspring after developmental exposure to 800-ppm dietary Mn. Reduction of parvalbumin (Pvalb)(+) γ-aminobutyric acid (GABA)-ergic interneurons in the hilus of the dentate gyrus along with promoter region hypermethylation are thought to be responsible for this aberrant neurogenesis. The present study was conducted to examine the relationship between the induction of aberrant neurogenesis and brain Mn accumulation after oral Mn exposure as well as the responsible mechanism in young adult animals. We used two groups of mice with 28- or 56-day exposure periods to oral MnCl2·xH2O at 800 ppm as Mn, a dose sufficient to lead to aberrant neurogenesis after developmental exposure. A third group of mice received intravenous injections of Mn at 5-mg/kg body weight once weekly for 28 days. The 28-day oral Mn exposure did not cause aberrations in neurogenesis. In contrast, 56-day oral exposure caused aberrations in neurogenesis suggestive of reductions in type 2b and type 3 progenitor cells and immature granule cells in the dentate subgranular zone. Brain Mn accumulation in 56-day exposed cases, as well as in directly Mn-injected cases occurred in parallel with reduction of Pvalb(+) GABAergic interneurons in the dentate hilus, suggesting that this may be responsible for aberrant neurogenesis. For reduction of Pvalb(+) interneurons, suppression of brain-derived neurotrophic factor-mediated signaling of mature granule cells may occur via suppression of c-Fos-mediated neuronal plasticity due to direct Mn-toxicity rather than promoter region hypermethylation of Pvalb.

  5. Chronic lead and brain development: intraocular brain grafts as a method to reveal regional and temporal effects in the central nervous system

    SciTech Connect

    Bjoerklund, H.; Olson, L.; Seiger, A.; Hoffer, B.

    1980-06-01

    A model is presented for selective studies of regional and temporal effects of chronic lead exposure on brain development, based on intraocular brain tissue grafting. Adult rat recipients were given lead acetate (1 to 2%) in their drinking water. Controls received sodium acetate in the drinking water or tap water. One week later, developing brain tissues obtained prenatally from different regions of the central nervous system were homologously grafted to the anterior chamber of the eye. Survival, vascularization, and growth were followed in oculo by repeated measurements of graft size. Growth curves were thus obtained for grafts from isolated selected brain areas, grafted at different stages of development to recipients on different concentrations of lead. Lead treatment (1%) caused a significant and pronounced delay of growth of the substantia nigra area during the second and third week postgrafting, approximately corresponding to the first 2 weeks after birth. Grafts of the hippocampal formation showed a slight impairment of growth following lead treatment while there were no detectable effects on size of cerebellar grafts. Grafts of the developing parietal cerebral cortex were inhibited in their growth in host animals given 2% lead while there was a small but significant increase in size following 1% lead. These results demonstrate the applicability of the grafting technique for studies of chronic low level lead intoxication. The method has revealed highly significant effects of lead on growth of certain selected brain areas and will be used for further histological, biochemical, and electrophysiological analysis of chronic lead effects on development of defined brain areas.

  6. Traumatic Brain Injury Activation of the Adult Subventricular Zone Neurogenic Niche.

    PubMed

    Chang, Eun Hyuk; Adorjan, Istvan; Mundim, Mayara V; Sun, Bin; Dizon, Maria L V; Szele, Francis G

    2016-01-01

    Traumatic brain injury (TBI) is common in both civilian and military life, placing a large burden on survivors and society. However, with the recognition of neural stem cells in adult mammals, including humans, came the possibility to harness these cells for repair of damaged brain, whereas previously this was thought to be impossible. In this review, we focus on the rodent adult subventricular zone (SVZ), an important neurogenic niche within the mature brain in which neural stem cells continue to reside. We review how the SVZ is perturbed following various animal TBI models with regards to cell proliferation, emigration, survival, and differentiation, and we review specific molecules involved in these processes. Together, this information suggests next steps in attempting to translate knowledge from TBI animal models into human therapies for TBI. PMID:27531972

  7. Environment matters: synaptic properties of neurons born in the epileptic adult brain develop to reduce excitability.

    PubMed

    Jakubs, Katherine; Nanobashvili, Avtandil; Bonde, Sara; Ekdahl, Christine T; Kokaia, Zaal; Kokaia, Merab; Lindvall, Olle

    2006-12-21

    Neural progenitors in the adult dentate gyrus continuously produce new functional granule cells. Here we used whole-cell patch-clamp recordings to explore whether a pathological environment influences synaptic properties of new granule cells labeled with a GFP-retroviral vector. Rats were exposed to a physiological stimulus, i.e., running, or a brain insult, i.e., status epilepticus, which gave rise to neuronal death, inflammation, and chronic seizures. Granule cells formed after these stimuli exhibited similar intrinsic membrane properties. However, the new neurons born into the pathological environment differed with respect to synaptic drive and short-term plasticity of both excitatory and inhibitory afferents. The new granule cells formed in the epileptic brain exhibited functional connectivity consistent with reduced excitability. We demonstrate a high degree of plasticity in synaptic inputs to adult-born new neurons, which could act to mitigate pathological brain function.

  8. Traumatic Brain Injury Activation of the Adult Subventricular Zone Neurogenic Niche

    PubMed Central

    Chang, Eun Hyuk; Adorjan, Istvan; Mundim, Mayara V.; Sun, Bin; Dizon, Maria L. V.; Szele, Francis G.

    2016-01-01

    Traumatic brain injury (TBI) is common in both civilian and military life, placing a large burden on survivors and society. However, with the recognition of neural stem cells in adult mammals, including humans, came the possibility to harness these cells for repair of damaged brain, whereas previously this was thought to be impossible. In this review, we focus on the rodent adult subventricular zone (SVZ), an important neurogenic niche within the mature brain in which neural stem cells continue to reside. We review how the SVZ is perturbed following various animal TBI models with regards to cell proliferation, emigration, survival, and differentiation, and we review specific molecules involved in these processes. Together, this information suggests next steps in attempting to translate knowledge from TBI animal models into human therapies for TBI. PMID:27531972

  9. Rapid Transport of CCL11 across the Blood-Brain Barrier: Regional Variation and Importance of Blood Cells

    PubMed Central

    Erickson, Michelle A.; Morofuji, Yoichi; Owen, Joshua B.

    2014-01-01

    Increased blood levels of the eotaxin chemokine C-C motif ligand 11 (CCL11) in aging were recently shown to negatively regulate adult hippocampal neurogenesis. How circulating CCL11 could affect the central nervous system (CNS) is not clear, but one possibility is that it can cross the blood-brain barrier (BBB). Here, we show that CCL11 undergoes bidirectional transport across the BBB. Transport of CCL11 from blood into whole brain (influx) showed biphasic kinetics, with a slow phase preceding a rapid phase of uptake. We found that the slow phase was explained by binding of CCL11 to cellular components in blood, whereas the rapid uptake phase was mediated by direct interactions with the BBB. CCL11, even at high doses, did not cause BBB disruption. All brain regions except striatum showed a delayed rapid-uptake phase. Striatum had only an early rapid-uptake phase, which was the fastest of any brain region. We also observed a slow but saturable transport system for CCL11 from brain to blood. C-C motif ligand 3 (CCR3), an important receptor for CCL11, did not facilitate CCL11 transport across the BBB, although high concentrations of a CCR3 inhibitor increased brain uptake without causing BBB disruption. Our results indicate that CCL11 in the circulation can access many regions of the brain outside of the neurogenic niche via transport across the BBB. This suggests that blood-borne CCL11 may have important physiologic functions in the CNS and implicates the BBB as an important regulator of physiologic versus pathologic effects of this chemokine. PMID:24706984

  10. [Regulation of neurogenesis: factors affecting of new neurons formation in adult mammals brain].

    PubMed

    Respondek, Michalina; Buszman, Ewa

    2015-12-31

    Neurogenesis is a complex and multi-step process of generating completely functional neurons. This process in adult brain is based on pluripotentional neuronal stem cells (NSC), which are able to proliferation and differentiation into mature neurons or glial cells. NSC are located in subgranular zone inside hippocampus and in subventricular zone. The new neurons formation depends on many endo- and exogenous factors which modulate each step of neurogenesis. This article describes the most important regulators of adult neurogenesis, mainly: neurotrophins, growth factors, hormones, neurotransmitters and microenvironment of NSC. Some drugs, especially antipsychotics, antidepressants and normothymics may affect the neurogenic properties of adult brain. Moreover pathological processes such as neuroinflammation, stroke or epilepsy are able to induce proliferation of NSC. The proneurogenic effects of psychotropic drugs and pathological processes are associated with their ability to increase some hormones and neurotrophins level, as well as with rising the expression of antiapoptotic Bcl-2 protein and metalloproteinase MMP-2. Additionaly, some drugs, for example haloperidol, are able to block prolactin and dopaminergic neuroblasts receptors. Down-regulation of adult neurogenesis is associated with alcohol abuse and high stress level. Negative effect of many drugs, such as cytostatics, COX-2 inhibitors and opioides was also observed. The proneurogenic effect of described factors suggest their broad therapeutic potential and gives a new perspective on an effective and modern treatment of many neuropsychiatric disorders. This effect can also help to clarify the pathogenesis of disorders associated with proliferation and degeneration of adult brain cells.

  11. Intrinsic Functional Connectivity in the Adult Brain and Success in Second-Language Learning.

    PubMed

    Chai, Xiaoqian J; Berken, Jonathan A; Barbeau, Elise B; Soles, Jennika; Callahan, Megan; Chen, Jen-Kai; Klein, Denise

    2016-01-20

    There is considerable variability in an individual's ability to acquire a second language (L2) during adulthood. Using resting-state fMRI data acquired before training in English speakers who underwent a 12 week intensive French immersion training course, we investigated whether individual differences in intrinsic resting-state functional connectivity relate to a person's ability to acquire an L2. We focused on two key aspects of language processing--lexical retrieval in spontaneous speech and reading speed--and computed whole-brain functional connectivity from two regions of interest in the language network, namely the left anterior insula/frontal operculum (AI/FO) and the visual word form area (VWFA). Connectivity between the left AI/FO and left posterior superior temporal gyrus (STG) and between the left AI/FO and dorsal anterior cingulate cortex correlated positively with improvement in L2 lexical retrieval in spontaneous speech. Connectivity between the VWFA and left mid-STG correlated positively with improvement in L2 reading speed. These findings are consistent with the different language functions subserved by subcomponents of the language network and suggest that the human capacity to learn an L2 can be predicted by an individual's intrinsic functional connectivity within the language network. Significance statement: There is considerable variability in second-language learning abilities during adulthood. We investigated whether individual differences in intrinsic functional connectivity in the adult brain relate to success in second-language learning, using resting-state functional magnetic resonance imaging in English speakers who underwent a 12 week intensive French immersion training course. We found that pretraining functional connectivity within two different language subnetworks correlated strongly with learning outcome in two different language skills: lexical retrieval in spontaneous speech and reading speed. Our results suggest that the human

  12. Intrinsic Functional Connectivity in the Adult Brain and Success in Second-Language Learning.

    PubMed

    Chai, Xiaoqian J; Berken, Jonathan A; Barbeau, Elise B; Soles, Jennika; Callahan, Megan; Chen, Jen-Kai; Klein, Denise

    2016-01-20

    There is considerable variability in an individual's ability to acquire a second language (L2) during adulthood. Using resting-state fMRI data acquired before training in English speakers who underwent a 12 week intensive French immersion training course, we investigated whether individual differences in intrinsic resting-state functional connectivity relate to a person's ability to acquire an L2. We focused on two key aspects of language processing--lexical retrieval in spontaneous speech and reading speed--and computed whole-brain functional connectivity from two regions of interest in the language network, namely the left anterior insula/frontal operculum (AI/FO) and the visual word form area (VWFA). Connectivity between the left AI/FO and left posterior superior temporal gyrus (STG) and between the left AI/FO and dorsal anterior cingulate cortex correlated positively with improvement in L2 lexical retrieval in spontaneous speech. Connectivity between the VWFA and left mid-STG correlated positively with improvement in L2 reading speed. These findings are consistent with the different language functions subserved by subcomponents of the language network and suggest that the human capacity to learn an L2 can be predicted by an individual's intrinsic functional connectivity within the language network. Significance statement: There is considerable variability in second-language learning abilities during adulthood. We investigated whether individual differences in intrinsic functional connectivity in the adult brain relate to success in second-language learning, using resting-state functional magnetic resonance imaging in English speakers who underwent a 12 week intensive French immersion training course. We found that pretraining functional connectivity within two different language subnetworks correlated strongly with learning outcome in two different language skills: lexical retrieval in spontaneous speech and reading speed. Our results suggest that the human

  13. Analgesic use and the risk of primary adult brain tumor.

    PubMed

    Egan, Kathleen M; Nabors, Louis B; Thompson, Zachary J; Rozmeski, Carrie M; Anic, Gabriella A; Olson, Jeffrey J; LaRocca, Renato V; Chowdhary, Sajeel A; Forsyth, Peter A; Thompson, Reid C

    2016-09-01

    Glioma and meningioma are uncommon tumors of the brain with few known risk factors. Regular use of aspirin has been linked to a lower risk of gastrointestinal and other cancers, though evidence for an association with brain tumors is mixed. We examined the association of aspirin and other analgesics with the risk of glioma and meningioma in a large US case-control study. Cases were persons recently diagnosed with glioma or meningioma and treated at medical centers in the southeastern US. Controls were persons sampled from the same communities as the cases combined with friends and other associates of the cases. Information on past use of analgesics (aspirin, other anti-inflammatory agents, and acetaminophen) was collected in structured interviews. Logistic regression was used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for analgesic use adjusted for potential confounders. All associations were considered according to indication for use. A total of 1123 glioma cases, 310 meningioma cases and 1296 controls were included in the analysis. For indications other than headache, glioma cases were less likely than controls to report regular use of aspirin (OR 0.69; CI 0.56, 0.87), in a dose-dependent manner (P trend < 0.001). No significant associations were observed with other analgesics for glioma, or any class of pain reliever for meningioma. Results suggest that regular aspirin use may reduce incidence of glioma. PMID:26894804

  14. Rapid and efficient gene delivery into the adult mouse brain via focal electroporation

    PubMed Central

    Nomura, Tadashi; Nishimura, Yusuke; Gotoh, Hitoshi; Ono, Katsuhiko

    2016-01-01

    In vivo gene delivery is required for studying the cellular and molecular mechanisms of various biological events. Virus-mediated gene transfer or generation of transgenic animals is widely used; however, these methods are time-consuming and expensive. Here we show an improved electroporation technique for acute gene delivery into the adult mouse brain. Using a syringe-based microelectrode, local DNA injection and the application of electric current can be performed simultaneously; this allows rapid and efficient gene transduction of adult non-neuronal cells. Combining this technique with various expression vectors that carry specific promoters resulted in targeted gene expression in astrocytic cells. Our results constitute a powerful strategy for the genetic manipulation of adult brains in a spatio-temporally controlled manner. PMID:27430903

  15. Rapid and efficient gene delivery into the adult mouse brain via focal electroporation.

    PubMed

    Nomura, Tadashi; Nishimura, Yusuke; Gotoh, Hitoshi; Ono, Katsuhiko

    2016-01-01

    In vivo gene delivery is required for studying the cellular and molecular mechanisms of various biological events. Virus-mediated gene transfer or generation of transgenic animals is widely used; however, these methods are time-consuming and expensive. Here we show an improved electroporation technique for acute gene delivery into the adult mouse brain. Using a syringe-based microelectrode, local DNA injection and the application of electric current can be performed simultaneously; this allows rapid and efficient gene transduction of adult non-neuronal cells. Combining this technique with various expression vectors that carry specific promoters resulted in targeted gene expression in astrocytic cells. Our results constitute a powerful strategy for the genetic manipulation of adult brains in a spatio-temporally controlled manner. PMID:27430903

  16. Neuronal replacement from endogenous precursors in the adult brain after stroke.

    PubMed

    Arvidsson, Andreas; Collin, Tove; Kirik, Deniz; Kokaia, Zaal; Lindvall, Olle

    2002-09-01

    In the adult brain, new neurons are continuously generated in the subventricular zone and dentate gyrus, but it is unknown whether these neurons can replace those lost following damage or disease. Here we show that stroke, caused by transient middle cerebral artery occlusion in adult rats, leads to a marked increase of cell proliferation in the subventricular zone. Stroke-generated new neurons, as well as neuroblasts probably already formed before the insult, migrate into the severely damaged area of the striatum, where they express markers of developing and mature, striatal medium-sized spiny neurons. Thus, stroke induces differentiation of new neurons into the phenotype of most of the neurons destroyed by the ischemic lesion. Here we show that the adult brain has the capacity for self-repair after insults causing extensive neuronal death. If the new neurons are functional and their formation can be stimulated, a novel therapeutic strategy might be developed for stroke in humans. PMID:12161747

  17. Brain-specific tropomyosins TMBr-1 and TMBr-3 have distinct patterns of expression during development and in adult brain.

    PubMed Central

    Stamm, S; Casper, D; Lees-Miller, J P; Helfman, D M

    1993-01-01

    In this study we report on the developmental and regional expression of two brain-specific isoforms of tropomyosin, TMBr-1 and TMBr-3, that are generated from the rat alpha-tropomyosin gene via the use of alternative promoters and alternative RNA splicing. Western blot analysis using an exon-specific peptide polyclonal antibody revealed that the two isoforms are differentially expressed in development with TMBr-3 appearing in the embryonic brain at 16 days of gestation, followed by the expression of TMBr-1 at 20 days after birth. TMBr-3 was detected in all brain regions examined, whereas TMBr-1 was detected predominantly in brain areas that derived from the prosencephalon. Immunocytochemical studies on mixed primary cultures made from rat embryonic midbrain indicate that expression of the brain-specific epitope is restricted to neurons. The developmental pattern and neuronal localization of these forms of tropomyosin suggest that these isoforms have a specialized role in the development and plasticity of the nervous system. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:7694294

  18. AGE-DEPENDENT EFFECTS OF AROCLOR 1254 ON CALCIUM UPTAKE BY SUBCELLULAR ORGANELLES IN SELECTED BRAIN REGIONS OF RATS.

    EPA Science Inventory

    Earlier reports from our laboratory have indicated that polychlorinated biphenyls (PCBs) affect signal transduction mechanisms in brain, including Ca2+ homeostasis, phosphoinositol hydrolysis, and protein kinase C (PKC) translocation in mature neurons and adult brain homogenate p...

  19. Daily Marijuana Use Is Not Associated with Brain Morphometric Measures in Adolescents or Adults

    PubMed Central

    Thayer, Rachel E.; Depue, Brendan E.; Sabbineni, Amithrupa; Bryan, Angela D.; Hutchison, Kent E.

    2015-01-01

    Recent research has suggested that marijuana use is associated with volumetric and shape differences in subcortical structures, including the nucleus accumbens and amygdala, in a dose-dependent fashion. Replication of such results in well controlled studies is essential to clarify the effects of marijuana. To that end, this retrospective study examined brain morphology in a sample of adult daily marijuana users (n = 29) versus nonusers (n = 29) and a sample of adolescent daily users (n = 50) versus nonusers (n = 50). Groups were matched on a critical confounding variable, alcohol use, to a far greater degree than in previously published studies. We acquired high-resolution MRI scans, and investigated group differences in gray matter using voxel-based morphometry, surface-based morphometry, and shape analysis in structures suggested to be associated with marijuana use, as follows: the nucleus accumbens, amygdala, hippocampus, and cerebellum. No statistically significant differences were found between daily users and nonusers on volume or shape in the regions of interest. Effect sizes suggest that the failure to find differences was not due to a lack of statistical power, but rather was due to the lack of even a modest effect. In sum, the results indicate that, when carefully controlling for alcohol use, gender, age, and other variables, there is no association between marijuana use and standard volumetric or shape measurements of subcortical structures. PMID:25632127

  20. Neuronal Organization of Deep Brain Opsin Photoreceptors in Adult Teleosts

    PubMed Central

    Hang, Chong Yee; Kitahashi, Takashi; Parhar, Ishwar S.

    2016-01-01

    Biological impacts of light beyond vision, i.e., non-visual functions of light, signify the need to better understand light detection (or photoreception) systems in vertebrates. Photopigments, which comprise light-absorbing chromophores bound to a variety of G-protein coupled receptor opsins, are responsible for visual and non-visual photoreception. Non-visual opsin photopigments in the retina of mammals and extra-retinal tissues of non-mammals play an important role in non-image-forming functions of light, e.g., biological rhythms and seasonal reproduction. This review highlights the role of opsin photoreceptors in the deep brain, which could involve conserved neurochemical systems that control different time- and light-dependent physiologies in in non-mammalian vertebrates including teleost fish. PMID:27199680

  1. Carnosine reverses the aging-induced down regulation of brain regional serotonergic system.

    PubMed

    Banerjee, Soumyabrata; Ghosh, Tushar K; Poddar, Mrinal K

    2015-12-01

    The purpose of the present investigation was to study the role of carnosine, an endogenous dipeptide biomolecule, on brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) serotonergic system during aging. Results showed an aging-induced brain region specific significant (a) increase in Trp (except cerebral cortex) and their 5-HIAA steady state level with an increase in their 5-HIAA accumulation and declination, (b) decrease in their both 5-HT steady state level and 5-HT accumulation (except cerebral cortex). A significant decrease in brain regional 5-HT/Trp ratio (except cerebral cortex) and increase in 5-HIAA/5-HT ratio were also observed during aging. Carnosine at lower dosages (0.5-1.0μg/Kg/day, i.t. for 21 consecutive days) didn't produce any significant response in any of the brain regions, but higher dosages (2.0-2.5μg/Kg/day, i.t. for 21 consecutive days) showed a significant response on those aging-induced brain regional serotonergic parameters. The treatment with carnosine (2.0μg/Kg/day, i.t. for 21 consecutive days), attenuated these brain regional aging-induced serotonergic parameters and restored towards their basal levels that observed in 4 months young control rats. These results suggest that carnosine attenuates and restores the aging-induced brain regional down regulation of serotonergic system towards that observed in young rats' brain regions.

  2. Efficacy of 68Ga-DOTATOC Positron Emission Tomography (PET) CT in Children and Young Adults With Brain Tumors

    ClinicalTrials.gov

    2016-09-07

    Acoustic Schwannoma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Supratentorial Ependymoma; Meningeal Melanocytoma; Newly Diagnosed Childhood Ependymoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood

  3. Ultrastructural analysis of blood-brain barrier breakdown in the peri-infarct zone in young adult and aged mice.

    PubMed

    Nahirney, Patrick C; Reeson, Patrick; Brown, Craig E

    2016-02-01

    Following ischemia, the blood-brain barrier is compromised in the peri-infarct zone leading to secondary injury and dysfunction that can limit recovery. Currently, it is uncertain what structural changes could account for blood-brain barrier permeability, particularly with aging. Here we examined the ultrastructure of early and delayed changes (3 versus 72 h) to the blood-brain barrier in young adult and aged mice (3-4 versus 18 months) subjected to photothrombotic stroke. At both time points and ages, permeability was associated with a striking increase in endothelial caveolae and vacuoles. Tight junctions were generally intact although small spaces were detected in a few cases. In young mice, ischemia led to a significant increase in pericyte process area and vessel coverage whereas these changes were attenuated with aging. Stroke led to an expansion of the basement membrane region that peaked at 3 h and partially recovered by 72 h in both age groups. Astrocyte endfeet and their mitochondria were severely swollen at both times points and ages. Our results suggest that blood-brain barrier permeability in young and aged animals is mediated by transcellular pathways (caveolae/vacuoles), rather than tight junction loss. Further, our data indicate that the effects of ischemia on pericytes and basement membrane are affected by aging. PMID:26661190

  4. Species differences in behavior and cell proliferation/survival in the adult brains of female meadow and prairie voles.

    PubMed

    Pan, Y; Liu, Y; Lieberwirth, C; Zhang, Z; Wang, Z

    2016-02-19

    Microtine rodents display diverse patterns of social organization and behaviors, and thus provide a useful model for studying the effects of the social environment on physiology and behavior. The current study compared the species differences and the effects of oxytocin (OT) on anxiety-like, social affiliation, and social recognition behaviors in female meadow voles (Microtus pennsylvanicus) and prairie voles (Microtus ochrogaster). Furthermore, cell proliferation and survival in the brains of adult female meadow and prairie voles were compared. We found that female meadow voles displayed a higher level of anxiety-like behavior but lower levels of social affiliation and social recognition compared to female prairie voles. In addition, meadow voles showed lower levels of cell proliferation (measured by Ki67 staining) and cell survival (measured by BrdU staining) in the ventromedial hypothalamus (VMH) and amygdala (AMY), but not the dentate gyrus of the hippocampus (DG), than prairie voles. Interestingly, the numbers of new cells in the VMH and AMY, but not DG, also correlated with anxiety-like, social affiliation, and social recognition behaviors in a brain region-specific manner. Finally, central OT treatment (200 ng/kg, icv) did not lead to changes in behavior or cell proliferation/survival in the brain. Together, these data indicate a potential role of cell proliferation/survival in selected brain areas on different behaviors between vole species with distinct life strategies. PMID:26708743

  5. MARGA: multispectral adaptive region growing algorithm for brain extraction on axial MRI.

    PubMed

    Roura, Eloy; Oliver, Arnau; Cabezas, Mariano; Vilanova, Joan C; Rovira, Alex; Ramió-Torrentà, Lluís; Lladó, Xavier

    2014-02-01

    Brain extraction, also known as skull stripping, is one of the most important preprocessing steps for many automatic brain image analysis. In this paper we present a new approach called Multispectral Adaptive Region Growing Algorithm (MARGA) to perform the skull stripping process. MARGA is based on a region growing (RG) algorithm which uses the complementary information provided by conventional magnetic resonance images (MRI) such as T1-weighted and T2-weighted to perform the brain segmentation. MARGA can be seen as an extension of the skull stripping method proposed by Park and Lee (2009) [1], enabling their use in both axial views and low quality images. Following the same idea, we first obtain seed regions that are then spread using a 2D RG algorithm which behaves differently in specific zones of the brain. This adaptation allows to deal with the fact that middle MRI slices have better image contrast between the brain and non-brain regions than superior and inferior brain slices where the contrast is smaller. MARGA is validated using three different databases: 10 simulated brains from the BrainWeb database; 2 data sets from the National Alliance for Medical Image Computing (NAMIC) database, the first one consisting in 10 normal brains and 10 brains of schizophrenic patients acquired with a 3T GE scanner, and the second one consisting in 5 brains from lupus patients acquired with a 3T Siemens scanner; and 10 brains of multiple sclerosis patients acquired with a 1.5T scanner. We have qualitatively and quantitatively compared MARGA with the well-known Brain Extraction Tool (BET), Brain Surface Extractor (BSE) and Statistical Parametric Mapping (SPM) approaches. The obtained results demonstrate the validity of MARGA, outperforming the results of those standard techniques. PMID:24380649

  6. Molecular and behavioral aspects of the actions of alcohol on the adult and developing brain.

    PubMed

    Alfonso-Loeches, Silvia; Guerri, Consuelo

    2011-01-01

    The brain is one of the major target organs of alcohol actions. Alcohol abuse can lead to alterations in brain structure and functions and, in some cases, to neurodegeneration. Cognitive deficits and alcohol dependence are highly damaging consequences of alcohol abuse. Clinical and experimental studies have demonstrated that the developing brain is particularly vulnerable to alcohol, and that drinking during gestation can lead to a range of physical, learning and behavioral defects (fetal alcohol spectrum disorders), with the most dramatic presentation corresponding to fetal alcohol syndrome. Recent findings also indicate that adolescence is a stage of brain maturation and that heavy drinking at this stage can have a negative impact on brain structure and functions causing important short- and long-term cognitive and behavioral consequences. The effects of alcohol on the brain are not uniform; some brain areas or cell populations are more vulnerable than others. The prefrontal cortex, the hippocampus, the cerebellum, the white matter and glial cells are particularly susceptible to the effects of ethanol. The molecular actions of alcohol on the brain are complex and involve numerous mechanisms and signaling pathways. Some of the mechanisms involved are common for the adult brain and for the developing brain, while others depend on the developmental stage. During brain ontogeny, alcohol causes irreversible alterations to the brain structure. It also impairs several molecular, neurochemical and cellular events taking place during normal brain development, including alterations in both gene expression regulation and the molecules involved in cell-cell interactions, interference with the mitogenic and growth factor response, enhancement of free radical formation and derangements of glial cell functions. However, in both adult and adolescent brains, alcohol damages specific brain areas through mechanisms involving excitotoxicity, free radical formation and

  7. Homeostasis of Microglia in the Adult Brain: Review of Novel Microglia Depletion Systems.

    PubMed

    Waisman, Ari; Ginhoux, Florent; Greter, Melanie; Bruttger, Julia

    2015-10-01

    Microglia are brain macrophages that emerge from early erythro-myeloid precursors in the embryonic yolk sac and migrate to the brain mesenchyme before the blood brain barrier is formed. They seed the brain, and proliferate until they have formed a grid-like distribution in the central nervous system that is maintained throughout lifespan. The mechanisms through which these embryonic-derived cells contribute to microglia homoeostasis at steady state and upon inflammation are still not entirely clear. Here we review recent studies that provided insight into the contribution of embryonically-derived microglia and of adult 'microglia-like' cells derived from monocytes during inflammation. We examine different microglia depletion models, and discuss the origin of their rapid repopulation after depletion and outline important areas of future research.

  8. The needs of aging parents caring for an adult with acquired brain injury.

    PubMed

    Minnes, Patricia; Woodford, Lynn; Carlson, Peter; Johnston, Jane; McColl, Mary Ann

    2010-06-01

    This study focused on issues of concern to and service needs of older parents caring for an adult son or daughter with an acquired brain injury (ABI) in Ontario. Three issues were identified as particularly challenging: diagnosis of the brain injury, parents' feelings about the cause of the brain injury, and planning for long-term accommodation for their family member with a brain injury. The most frequently cited services needed for the person with ABI were social and/or recreational activities, day programs, and residential placement. The most frequently cited services needed by parents were parent education and support groups. The information gathered provides a base for further research in other sectors. Implications of these initial findings for clinical practice and policy and program development are discussed.

  9. Neuropeptide Y administration acutely increases hypothalamic corticotropin-releasing factor immunoreactivity: lack of effect in other rat brain regions

    SciTech Connect

    Haas, D.A.; George, S.R.

    1987-12-21

    The effect of acute central administration of Neuropeptide Y (NPY) to adult male rats on the brain content of corticotropin-releasing factor immunoreactivity (CRF-ir) was investigated. The brain regions studied included frontal cortex, hippocampus, medulla-pons, midbrain-thalamus, cerebellum, neurointermediate lobe of pituitary, median eminence and the remaining hypothalamus. CRF-ir was determined in each of these regions using radioimmunoassay specific for rat CRF. CRF-ir was found to be significantly increased in the major site of CRF localization in the brain, the hypothalamus, in NPY-treated rats as compared to vehicle-treated controls either 15 minutes (p<0.025) or 45 minutes (p<0.005) post-injection. This increase was localized to the median eminence (p<0.05 after 15 minutes, p<0.01 after 45 minutes). No statistically significant differences were noted in any of the other brain regions assessed. Plasma adrenocorticotropin levels were also found to increase following NPY treatment, an effect which became significant after 45 minutes (p<0.05). These data show that NPY can alter the content of hypothalamic CRF and may play a role in its regulation. 33 references, 4 figures.

  10. Evaluation of a Reading Comprehension Strategy Package to Improve Reading Comprehension of Adult College Students with Acquired Brain Injuries

    ERIC Educational Resources Information Center

    Griffiths, Gina G.

    2013-01-01

    Adults with mild to moderate acquired brain injury (ABI) often pursue post-secondary or professional education after their injuries in order to enter or re-enter the job market. An increasing number of these adults report problems with reading-to-learn. The problem is particularly concerning given the growing population of adult survivors of ABI.…

  11. Frog Virus 3 dissemination in the brain of tadpoles, but not in adult Xenopus, involves blood brain barrier dysfunction

    PubMed Central

    De Jesús Andino, Francisco; Jones, Letitia; Maggirwar, Sanjay B.; Robert, Jacques

    2016-01-01

    While increasing evidence points to a key role of monocytes in amphibian host defenses, monocytes are also thought to be important in the dissemination and persistent infection caused by ranavirus. However, little is known about the fate of infected macrophages or if ranavirus exploits immune privileged organs, such as the brain, in order to establish a reservoir. The amphibian Xenopus laevis and Frog Virus 3 (FV3) were established as an experimental platform for investigating in vivo whether ranavirus could disseminate to the brain. Our data show that the FV3 infection alters the BBB integrity, possibly mediated by an inflammatory response, which leads to viral dissemination into the central nervous system in X. laevis tadpole but not adult. Furthermore, our data suggest that the macrophages play a major role in viral dissemination by carrying the virus into the neural tissues. PMID:26931458

  12. An ERP Study of Emotional Face Processing in the Adult and Infant Brain

    ERIC Educational Resources Information Center

    Leppanen, Jukka M.; Moulson, Margaret C.; Vogel-Farley, Vanessa K.; Nelson, Charles A.

    2007-01-01

    To examine the ontogeny of emotional face processing, event-related potentials (ERPs) were recorded from adults and 7-month-old infants while viewing pictures of fearful, happy, and neutral faces. Face-sensitive ERPs at occipital-temporal scalp regions differentiated between fearful and neutral/happy faces in both adults (N170 was larger for fear)…

  13. The role of right frontal brain regions in integration of spatial relation.

    PubMed

    Han, Jiahui; Cao, Bihua; Cao, Yunfei; Gao, Heming; Li, Fuhong

    2016-06-01

    Previous studies have explored the neural mechanisms of spatial reasoning on a two-dimensional (2D) plane; however, it remains unclear how spatial reasoning is conducted in a three-dimensional (3D) condition. In the present study, we presented 3D geometric objects to 16 adult participants, and asked them to process the spatial relationship between different corners of the geometric objects. In premise-1, the first two corners of a geometric shape (e.g., A vs. B) were displayed. In premise-2, the second and third corners (e.g., B vs. C) were displayed. After integrating the two premises, participants were required to infer the spatial relationship between the first and the third corners (e.g., A and C). Finally, the participants were presented with a conclusion object, and they were required to judge whether the conclusion was true or false based on their inference. The event-related potential evoked by premise-2 revealed that (1) compared with 2D spatial reasoning, 3D reasoning elicited a smaller P3b component, and (2) in the right frontal areas, increased negativities were found in the 3D condition during the N400 and late negative components (LNC). These findings imply that higher brain activity in the right frontal brain regions were related with the integration and maintenance of spatial information in working memory for reasoning.

  14. Regional Brain Glucose Hypometabolism in Young Women with Polycystic Ovary Syndrome: Possible Link to Mild Insulin Resistance

    PubMed Central

    Castellano, Christian-Alexandre; Baillargeon, Jean-Patrice; Nugent, Scott; Tremblay, Sébastien; Fortier, Mélanie; Imbeault, Hélène; Duval, Julie; Cunnane, Stephen C.

    2015-01-01

    Objective To investigate whether cerebral metabolic rate of glucose (CMRglu) is altered in normal weight young women with polycystic ovary syndrome (PCOS) who exhibit mild insulin resistance. Materials and methods Seven women with PCOS were compared to eleven healthy female controls of similar age, education and body mass index. Regional brain glucose uptake was quantified using FDG with dynamic positron emission tomography and magnetic resonance imaging, and its potential relationship with insulin resistance assessed using the updated homeostasis model assessment (HOMA2-IR). A battery of cognitive tests was administered to evaluate working memory, attention and executive function. Results The PCOS group had 10% higher fasting glucose and 40% higher HOMA2-IR (p ≤ 0.035) compared to the Controls. The PCOS group had 9–14% lower CMRglu in specific regions of the frontal, parietal and temporal cortices (p ≤ 0.018). A significant negative relation was found between the CMRglu and HOMA2-IR mainly in the frontal, parietal and temporal cortices as well as in the hippocampus and the amygdala (p ≤ 0.05). Globally, cognitive performance was normal in both groups but scores on the PASAT test of working memory tended to be low in the PCOS group. Conclusions The PCOS group exhibited a pattern of low regional CMRglu that correlated inversely with HOMA2-IR in several brain regions and which resembled the pattern seen in aging and early Alzheimer’s disease. These results suggest that a direct association between mild insulin resistance and brain glucose hypometabolism independent of overweight or obesity can exist in young adults in their 20s. Further investigation of the influence of insulin resistance on brain glucose metabolism and cognition in younger and middle-aged adults is warranted. PMID:26650926

  15. Localization and regulation of PML bodies in the adult mouse brain.

    PubMed

    Hall, Małgorzata H; Magalska, Adriana; Malinowska, Monika; Ruszczycki, Błażej; Czaban, Iwona; Patel, Satyam; Ambrożek-Latecka, Magdalena; Zołocińska, Ewa; Broszkiewicz, Hanna; Parobczak, Kamil; Nair, Rajeevkumar R; Rylski, Marcin; Pawlak, Robert; Bramham, Clive R; Wilczyński, Grzegorz M

    2016-06-01

    PML is a tumor suppressor protein involved in the pathogenesis of promyelocytic leukemia. In non-neuronal cells, PML is a principal component of characteristic nuclear bodies. In the brain, PML has been implicated in the control of embryonic neurogenesis, and in certain physiological and pathological phenomena in the adult brain. Yet, the cellular and subcellular localization of the PML protein in the brain, including its presence in the nuclear bodies, has not been investigated comprehensively. Because the formation of PML bodies appears to be a key aspect in the function of the PML protein, we investigated the presence of these structures and their anatomical distribution, throughout the adult mouse brain. We found that PML is broadly expressed across the gray matter, with the highest levels in the cerebral and cerebellar cortices. In the cerebral cortex PML is present exclusively in neurons, in which it forms well-defined nuclear inclusions containing SUMO-1, SUMO 2/3, but not Daxx. At the ultrastructural level, the appearance of neuronal PML bodies differs from the classic one, i.e., the solitary structure with more or less distinctive capsule. Rather, neuronal PML bodies have the form of small PML protein aggregates located in the close vicinity of chromatin threads. The number, size, and signal intensity of neuronal PML bodies are dynamically influenced by immobilization stress and seizures. Our study indicates that PML bodies are broadly involved in activity-dependent nuclear phenomena in adult neurons.

  16. Prenatal exposure to permethrin influences vascular development of fetal brain and adult behavior in mice offspring.

    PubMed

    Imanishi, Satoshi; Okura, Masahiro; Zaha, Hiroko; Yamamoto, Toshifumi; Akanuma, Hiromi; Nagano, Reiko; Shiraishi, Hiroaki; Fujimaki, Hidekazu; Sone, Hideko

    2013-11-01

    Pyrethroids are one of the most widely used classes of insecticides and show neurotoxic effects that induce oxidative stress in the neonatal rat brain. However, little is still known about effects of prenatal exposure to permethrin on vascular development in fetal brain, central nervous system development, and adult offspring behaviors. In this study, the effects of prenatal exposure to permethrin on the development of cerebral arteries in fetal brains, neurotransmitter in neonatal brains, and locomotor activities in offspring mice were investigated. Permethrin (0, 2, 10, 50, and 75 mg/kg) was orally administered to pregnant females once on gestation day 10.5. The brains of permethrin-treated fetuses showed altered vascular formation involving shortened lengths of vessels, an increased number of small branches, and, in some cases, insufficient fusion of the anterior communicating arteries in the area of circle of Willis. The prenatal exposure to permethrin altered neocortical and hippocampus thickness in the mid brain and significantly increased norepinephrine and dopamine levels at postnatal day 7 mice. For spontaneous behavior, the standing ability test using a viewing jar and open-field tests showed significant decrease of the standing ability and locomotor activity in male mice at 8 or 12 weeks of age, respectively. The results suggest that prenatal exposure to permethrin may affect insufficient development of the brain through alterations of vascular development.

  17. Carnosine: effect on aging-induced increase in brain regional monoamine oxidase-A activity.

    PubMed

    Banerjee, Soumyabrata; Poddar, Mrinal K

    2015-03-01

    Aging is a natural biological process associated with several neurological disorders along with the biochemical changes in brain. Aim of the present investigation is to study the effect of carnosine (0.5-2.5μg/kg/day, i.t. for 21 consecutive days) on aging-induced changes in brain regional (cerebral cortex, hippocampus, hypothalamus and pons-medulla) mitochondrial monoamine oxidase-A (MAO-A) activity with its kinetic parameters. The results of the present study are: (1) The brain regional mitochondrial MAO-A activity and their kinetic parameters (except in Km of pons-medulla) were significantly increased with the increase of age (4-24 months), (2) Aging-induced increase of brain regional MAO-A activity including its Vmax were attenuated with higher dosages of carnosine (1.0-2.5μg/kg/day) and restored toward the activity that observed in young, though its lower dosage (0.5μg/kg/day) were ineffective in these brain regional MAO-A activity, (3) Carnosine at higher dosage in young rats, unlike aged rats significantly inhibited all the brain regional MAO-A activity by reducing their only Vmax excepting cerebral cortex, where Km was also significantly enhanced. These results suggest that carnosine attenuated the aging-induced increase of brain regional MAO-A activity by attenuating its kinetic parameters and restored toward the results of MAO-A activity that observed in corresponding brain regions of young rats.

  18. MAPK signaling determines anxiety in the juvenile mouse brain but depression-like behavior in adults.

    PubMed

    Wefers, Benedikt; Hitz, Christiane; Hölter, Sabine M; Trümbach, Dietrich; Hansen, Jens; Weber, Peter; Pütz, Benno; Deussing, Jan M; de Angelis, Martin Hrabé; Roenneberg, Till; Zheng, Fang; Alzheimer, Christian; Silva, Alcino; Wurst, Wolfgang; Kühn, Ralf

    2012-01-01

    MAP kinase signaling has been implicated in brain development, long-term memory, and the response to antidepressants. Inducible Braf knockout mice, which exhibit protein depletion in principle forebrain neurons, enabled us to unravel a new role of neuronal MAPK signaling for emotional behavior. Braf mice that were induced during adulthood showed normal anxiety but increased depression-like behavior, in accordance with pharmacological findings. In contrast, the inducible or constitutive inactivation of Braf in the juvenile brain leads to normal depression-like behavior but decreased anxiety in adults. In juvenile, constitutive mutants we found no alteration of GABAergic neurotransmission but reduced neuronal arborization in the dentate gyrus. Analysis of gene expression in the hippocampus revealed nine downregulated MAPK target genes that represent candidates to cause the mutant phenotype.Our results reveal the differential function of MAPK signaling in juvenile and adult life phases and emphasize the early postnatal period as critical for the determination of anxiety in adults. Moreover, these results validate inducible gene inactivation as a new valuable approach, allowing it to discriminate between gene function in the adult and the developing postnatal brain. PMID:22529971

  19. Path Complexity in Virtual Water Maze Navigation: Differential Associations with Age, Sex, and Regional Brain Volume.

    PubMed

    Daugherty, Ana M; Yuan, Peng; Dahle, Cheryl L; Bender, Andrew R; Yang, Yiqin; Raz, Naftali

    2015-09-01

    Studies of human navigation in virtual maze environments have consistently linked advanced age with greater distance traveled between the start and the goal and longer duration of the search. Observations of search path geometry suggest that routes taken by older adults may be unnecessarily complex and that excessive path complexity may be an indicator of cognitive difficulties experienced by older navigators. In a sample of healthy adults, we quantify search path complexity in a virtual Morris water maze with a novel method based on fractal dimensionality. In a two-level hierarchical linear model, we estimated improvement in navigation performance across trials by a decline in route length, shortening of search time, and reduction in fractal dimensionality of the path. While replicating commonly reported age and sex differences in time and distance indices, a reduction in fractal dimension of the path accounted for improvement across trials, independent of age or sex. The volumes of brain regions associated with the establishment of cognitive maps (parahippocampal gyrus and hippocampus) were related to path dimensionality, but not to the total distance and time. Thus, fractal dimensionality of a navigational path may present a useful complementary method of quantifying performance in navigation.

  20. Disruption of White Matter Integrity in Adult Survivors of Childhood Brain Tumors: Correlates with Long-Term Intellectual Outcomes

    PubMed Central

    Mao, Hui

    2015-01-01

    Background Although chemotherapy and radiation treatment have contributed to increased survivorship, treatment-induced brain injury has been a concern when examining long-term intellectual outcomes of survivors. Specifically, disruption of brain white matter integrity and its relationship to intellectual outcomes in adult survivors of childhood brain tumors needs to be better understood. Methods Fifty-four participants underwent diffusion tensor imaging in addition to structural MRI and an intelligence test (IQ). Voxel-wise group comparisons of fractional anisotropy calculated from DTI data were performed using Tract Based Spatial Statistics (TBSS) on 27 survivors (14 treated with radiation with and without chemotherapy and 13 treated without radiation treatment on average over 13 years since diagnosis) and 27 healthy comparison participants. Whole brain white matter fractional anisotropy (FA) differences were explored between each group. The relationships between IQ and FA in the regions where statistically lower FA values were found in survivors were examined, as well as the role of cumulative neurological factors. Results The group of survivors treated with radiation with and without chemotherapy had lower IQ relative to the group of survivors without radiation treatment and the healthy comparison group. TBSS identified white matter regions with significantly different mean fractional anisotropy between the three different groups. A lower level of white matter integrity was found in the radiation with or without chemotherapy treated group compared to the group without radiation treatment and also the healthy control group. The group without radiation treatment had a lower mean FA relative to healthy controls. The white matter disruption of the radiation with or without chemotherapy treated survivors was positively correlated with IQ and cumulative neurological factors. Conclusions Lower long-term intellectual outcomes of childhood brain tumor survivors are

  1. Midlife measurements of white matter microstructure predict subsequent regional white matter atrophy in healthy adults

    PubMed Central

    Ly, Martina; Canu, Elisa; Xu, Guofan; Oh, Jennifer; McLaren, Donald G; Dowling, N. Maritza; Alexander, Andrew L; Sager, Mark A; Johnson, Sterling C; Bendlin, Barbara B

    2013-01-01

    Objectives While age-related brain changes are becoming better understood, midlife patterns of change are still in need of characterization, and longitudinal studies are lacking. The aim of this study was to determine if baseline fractional anisotropy (FA), obtained from diffusion tensor imaging (DTI) predicts volume change over a four-year interval. Experimental design Forty-four cognitively healthy middle-age adults underwent baseline DTI and longitudinal T1-weighted magnetic resonance imaging. Tensor Based Morphometry methods were used to evaluate volume change over time. FA values were extracted from regions of interest that included the cingulum, entorhinal white matter, and the genu and splenium of the corpus callosum. Baseline FA was used as a predictor variable, while gray and white matter atrophy rates as indexed by Tensor Based Morphometry were the dependent variables. Principal observations Over a four-year period, participants showed significant contraction of white matter, especially in frontal, temporal, and cerebellar regions (p<0.05, corrected for multiple comparisons). Baseline FA in entorhinal white matter, genu, and splenium, was associated with longitudinal rates of atrophy in regions that included the superior longitudinal fasciculus, anterior corona radiata, temporal stem, and white matter of the inferior temporal gyrus (p<0.001, uncorrected for multiple comparisons). Conclusions Brain change with aging is characterized by extensive shrinkage of white matter. Baseline white matter microstructure as indexed by DTI was associated with some of the observed regional volume loss. The findings suggest that both white matter volume loss and microstructural alterations should be considered more prominently in models of aging and neurodegenerative diseases. PMID:23861348

  2. Project ACT (Adult Competency Training): Region VIII Adult Education Staff Development: Second-Year Report: FY '74.

    ERIC Educational Resources Information Center

    Colorado State Univ., Ft. Collins. Dept. of Education.

    The second-year report describes Project ACT (Adult Competency Training) efforts from July 1, 1973 to June 30, 1974 to develop a regional staff development system. Three elements were perceived to be essential: a regional consortium organization to effectively implement ACT programs, State-by-State and region-wide; a multi-dimensional trainer…

  3. Robert Feulgen Prize Lecture. Grenzgänger: adult bone marrow cells populate the brain.

    PubMed

    Priller, Josef

    2003-08-01

    While the brain has traditionally been considered a rather secluded site, recent studies suggest that adult bone marrow (BM)-derived stem cells can generate glia and neurons in rodents and humans. Macrophages and microglia are the first to appear in the murine brain after transplantation of genetically marked BM cells. Within weeks after transplantation, some authors have found astrocytes and cells expressing neuronal antigens. We detected cerebellar Purkinje neurons and interneurons, such as basket cells, expressing the green fluorescent protein (GFP) 10-15 months after transplantation of GFP-labeled BM cells. The results push the boundaries of our classic view of lineage restriction.

  4. Reorganization and plasticity in the adult brain during learning of motor skills.

    PubMed

    Doyon, Julien; Benali, Habib

    2005-04-01

    On the basis of brain imaging studies, Doyon and Ungerleider recently proposed a model describing the cerebral plasticity that occurs in both cortico-striatal and cortico-cerebellar systems of the adult brain during learning of new motor skilled behaviors. This theoretical framework makes several testable predictions with regards to the contribution of these neural systems based on the phase (fast, slow, consolidation, automatization, and retention) and nature of the motor learning processes (motor sequence versus motor adaptation) acquired through repeated practice. There has been recent behavioral, lesion and additional neuroimaging studies that have addressed the assumptions made in this theory that will help in the revision of this model.

  5. Robert Feulgen Prize Lecture. Grenzgänger: adult bone marrow cells populate the brain.

    PubMed

    Priller, Josef

    2003-08-01

    While the brain has traditionally been considered a rather secluded site, recent studies suggest that adult bone marrow (BM)-derived stem cells can generate glia and neurons in rodents and humans. Macrophages and microglia are the first to appear in the murine brain after transplantation of genetically marked BM cells. Within weeks after transplantation, some authors have found astrocytes and cells expressing neuronal antigens. We detected cerebellar Purkinje neurons and interneurons, such as basket cells, expressing the green fluorescent protein (GFP) 10-15 months after transplantation of GFP-labeled BM cells. The results push the boundaries of our classic view of lineage restriction. PMID:12898276

  6. An acute dose of gamma-hydroxybutyric acid alters gene expression in multiple mouse brain regions.

    PubMed

    Schnackenberg, B J; Saini, U T; Robinson, B L; Ali, S F; Patterson, T A

    2010-10-13

    Gamma-hydroxybutyric acid (GHB) is normally found in the brain in low concentrations and may function as a neurotransmitter, although the mechanism of action has not been completely elucidated. GHB has been used as a general anesthetic and is currently used to treat narcolepsy and alcoholism. Recreational use of GHB is primarily as a "club drug" and a "date rape drug," due to its amnesic effects. For this study, the hypothesis was that behavioral and neurochemical alterations may parallel gene expression changes in the brain after GHB administration. Adult male C57/B6N mice (n=5/group) were administered a single dose of 500 mg/kg GHB (i.p.) and were sacrificed 1, 2 and 4 h after treatment. Control mice were administered saline. Brains were removed and regionally dissected on ice. Total RNA from the hippocampus, cortex and striatum was extracted, amplified and labeled. Gene expression was evaluated using Agilent whole mouse genome 4x44K oligonucleotide microarrays. Microarray data were analyzed by ArrayTrack and differentially expressed genes (DEGs) were identified using P < or = 0.01 and a fold change > or = 1.7 as the criteria for significance. Principal component analysis (PCA) and Hierarchical Cluster Analysis (HCA) showed that samples from each time point clustered into distinct treatment groups with respect to sacrifice time. Ingenuity pathways analysis (IPA) was used to identify involved pathways. The results show that GHB induces gene expression alterations in hundreds of genes in the hippocampus, cortex and striatum, and the number of affected genes increases throughout a 4-h time course. Many of these DEGs are involved in neurological disease, apoptosis, and oxidative stress.

  7. Brain lesions that impair vocal imitation in adult budgerigars.

    PubMed

    Plummer, Thane K; Striedter, Georg F

    2002-11-15

    Vocal imitation is a complex form of imitative learning that is well developed only in humans, dolphins, and birds. Among birds, only some species are able to imitate sounds in adulthood. Of these, the budgerigar (Melopsittacus undulatus) has been studied in most detail. Previous studies suggested that the vocal motor system in budgerigars receives auditory information from the lateral frontal neostriatum (NFl). In the present study, we confirm this hypothesis by showing that infusions of the GABA agonist muscimol into NFl reduce the strength of auditory responses in a telencephalic vocal motor nucleus, the central nucleus of the lateral neostriatum (NLc). To test whether the auditory information conveyed from NFl to NLc plays a role in vocal imitation, we lesioned parts of NFl and the overlying ventral hyperstriatum (HVl) in seven adult male budgerigars and then examined whether the lesioned males would imitate the calls of females with whom they were paired. We found that, compared to sham-lesioned controls, the lesioned birds were significantly impaired in their imitation of female calls. Yet, the lesioned males were clearly not deaf (e.g., their previously learned calls did not degrade as they do after deafening). Therefore, the data suggest that NFl/HVl lesions impair vocal imitation by reducing the amount of auditory information that reaches the vocal motor system. Interestingly, the females that were paired with lesioned males displayed more vocal plasticity than the females in the control group, and some even imitated their male's prepairing calls.

  8. Pediatric Cancers and Brain Tumors in Adolescents and Young Adults.

    PubMed

    McCabe, Martin G; Valteau-Couanet, Dominique

    2016-01-01

    Embryonal tumors classically occur in young children, some principally within the first year of life. Prospective national and international clinical trials during recent decades have brought about progressive improvements in survival, and associated biological studies have advanced our understanding of tumor biology, in some cases allowing biological tumor characteristics to be harnessed for therapeutic benefit. Embryonal tumors continue to occur, albeit less commonly, during childhood, adolescence and throughout adulthood. These tumors are less well understood, usually not managed according to standardized protocols and rarely included in clinical trials. Survival outcomes are generally poorer than their childhood equivalents. We present here a summary of the published literature on embryonal tumors that present ectopically during adolescence and adulthood. We show that for some tumors protocol-driven treatment, supported by accurate and complete diagnostics and staging, can result in equivalent outcomes to those seen during childhood. We make the case that clinical trial eligibility criteria should be disease-based rather than age-based, and support improvements in dialogue between children's and adults' cancer clinicians to improve outcomes for these rare tumors. PMID:27595358

  9. Regional infant brain development: an MRI-based morphometric analysis in 3 to 13 month olds.

    PubMed

    Choe, Myong-Sun; Ortiz-Mantilla, Silvia; Makris, Nikos; Gregas, Matt; Bacic, Janine; Haehn, Daniel; Kennedy, David; Pienaar, Rudolph; Caviness, Verne S; Benasich, April A; Grant, P Ellen

    2013-09-01

    Elucidation of infant brain development is a critically important goal given the enduring impact of these early processes on various domains including later cognition and language. Although infants' whole-brain growth rates have long been available, regional growth rates have not been reported systematically. Accordingly, relatively less is known about the dynamics and organization of typically developing infant brains. Here we report global and regional volumetric growth of cerebrum, cerebellum, and brainstem with gender dimorphism, in 33 cross-sectional scans, over 3 to 13 months, using T1-weighted 3-dimensional spoiled gradient echo images and detailed semi-automated brain segmentation. Except for the midbrain and lateral ventricles, all absolute volumes of brain regions showed significant growth, with 6 different patterns of volumetric change. When normalized to the whole brain, the regional increase was characterized by 5 differential patterns. The putamen, cerebellar hemispheres, and total cerebellum were the only regions that showed positive growth in the normalized brain. Our results show region-specific patterns of volumetric change and contribute to the systematic understanding of infant brain development. This study greatly expands our knowledge of normal development and in future may provide a basis for identifying early deviation above and beyond normative variation that might signal higher risk for neurological disorders.

  10. Neuropsin Expression Correlates with Dendritic Marker MAP2c Level in Different Brain Regions of Aging Mice.

    PubMed

    Konar, Arpita; Thakur, M K

    2015-01-01

    Neuropsin (NP) is a serine protease, implicated in synaptic plasticity and memory acquisition through cleavage of synaptic adhesion molecule, L1CAM. However, NP has not been explored during brain aging that entails drastic deterioration of plasticity and memory with selective regional vulnerability. Therefore, we have analysed the expression of NP and correlated with its function via analysis of endogenous cleavage of L1CAM and level of dendritic marker MAP2c in different regions of the aging mouse brain. While NP expression gradually decreased in the cerebral cortex during aging, it showed a sharp rise in both olfactory bulb and hippocampus in adult and thereafter declined in old age. NP expression was moderate in young medulla, but undetectable in midbrain and cerebellum. It was positively correlated with L1CAM cleavage and MAP2c level in different brain regions during aging. Taken together, our study shows age-dependent regional variation in NP expression and its positive correlation with MAP2c level, suggesting the involvement of NP in MAP2c mediated alterations in dendritic morphology during aging. PMID:24965600

  11. Interleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain

    PubMed Central

    2012-01-01

    Background Cytokines such as interleukin 6 (IL-6) have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated. Methodology In a large sample of healthy individuals (N = 303), associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840) and brain volume (gray matter volume) were analyzed using voxel-based morphometry (VBM). Selection of single nucleotide polymorphisms (SNPs) followed a tagging SNP approach (e.g., Stampa algorigthm), yielding a capture 97.08% of the variation in the IL-6 gene using four tagging SNPs. Principal findings/results In a whole-brain analysis, the polymorphism rs1800795 (−174 C/G) showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x = 24, y = −10, z = −15; F(2,286) = 8.54, puncorrected = 0.0002; pAlphaSim-corrected = 0.002; cluster size k = 577) within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses. Conclusions/significance These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress) are warranted. PMID:22695063

  12. The brain and the braincase: a spatial analysis on the midsagittal profile in adult humans.

    PubMed

    Bruner, Emiliano; Amano, Hideki; de la Cuétara, José Manuel; Ogihara, Naomichi

    2015-09-01

    The spatial relationships between brain and braincase represent a major topic in surgery and evolutionary neuroanatomy. In paleoneurology, neurocranial landmarks are often used as references for brain areas. In this study, we analyze the variation and covariation of midsagittal brain and skull coordinates in a sample of adult modern humans in order to demonstrate spatial associations between hard and soft tissues. The correlation between parietal lobe size and parietal bone size is very low, and there is a marked individual variation. The distances between lobes and bones are partially influenced by the dimensions of the parietal lobes. The main pattern of morphological variability among individuals, associated with the size of the precuneus, apparently does not influence the position of the neurocranial sutures. Therefore, variations in precuneal size modify the distance between the paracentral lobule and bregma, and between the parietal lobe and lambda. Hence, the relative position of the cranial and cerebral landmarks can change as a function of the parietal dimensions. The slight correlation and covariation among these elements suggests a limited degree of spatial integration between soft and hard tissues. Therefore, although the brain influences the cranial size and shape during morphogenesis, the specific position of the cerebral components is sensitive to multiple effects and local factors, without a strict correspondence with the bone landmarks. This absence of correspondent change between brain and skull boundaries suggests caution when making inferences about the brain areas from the position of the cranial sutures. The fact that spatial relationships between cranial and brain areas may vary according to brain proportions must be considered in paleoneurology, when brain anatomy is inferred from cranial evidence.

  13. Elevated adult neurogenesis in brain subventricular zone following in vivo manganese exposure: roles of copper and DMT1.

    PubMed

    Fu, Sherleen; O'Neal, Stefanie; Hong, Lan; Jiang, Wendy; Zheng, Wei

    2015-02-01

    The brain subventricular zone (SVZ) is a source of neural precursor cells; these cells travel along the rostral migratory stream (RMS) to destination areas in the process of adult neurogenesis. Recent x-ray fluorescence (XRF) studies reveal an extensive accumulation of copper (Cu) in the SVZ. Earlier human and animal studies also suggest an altered Cu homeostasis after manganese (Mn) exposure. This study was designed to test the hypothesis that Mn exposure by acting on the divalent metal transporter-1 (DMT1) altered Cu levels in SVZ and RMS, thereby affecting adult neurogenesis. Adult rats received intraperitoneal (i.p.) injections of 6 mg Mn/kg as MnCl2 once daily for 4 weeks with concomitant injections of bromodeoxyuridine (BrdU) for 5 days in the last week. In control rats, Cu levels were significantly higher in the SVZ than other brain regions examined. Mn exposure significantly reduced Cu concentrations in the SVZ (P < 0.01). Immunohistochemical data showed that in vivo Mn exposure significantly increased numbers of BrdU(+) cells, which were accompanied with increased GFAP(+) astrocytic stem cells and DCX(+) neuroblasts in SVZ and RMS. Quantitative RT-PCR and Western blot confirmed the increased expression of DMT1 in SVZ following in vivo Mn exposure, which contributed to Mn accumulation in the neurogenesis pathway. Taken together, these results indicate a clear disruptive effect of Mn on adult neurogenesis; the effect appears due partly to Mn induction of DMT1 and its interference with cellular Cu regulation in SVZ and RMS. The future research directions based on these observations are also discussed. PMID:25575534

  14. Elevated Adult Neurogenesis in Brain Subventricular Zone Following In vivo Manganese Exposure: Roles of Copper and DMT1

    PubMed Central

    Fu, Sherleen; O'Neal, Stefanie; Hong, Lan; Jiang, Wendy; Zheng, Wei

    2015-01-01

    The brain subventricular zone (SVZ) is a source of neural precursor cells; these cells travel along the rostral migratory stream (RMS) to destination areas in the process of adult neurogenesis. Recent x-ray fluorescence (XRF) studies reveal an extensive accumulation of copper (Cu) in the SVZ. Earlier human and animal studies also suggest an altered Cu homeostasis after manganese (Mn) exposure. This study was designed to test the hypothesis that Mn exposure by acting on the divalent metal transporter-1 (DMT1) altered Cu levels in SVZ and RMS, thereby affecting adult neurogenesis. Adult rats received intraperitoneal (i.p.) injections of 6 mg Mn/kg as MnCl2 once daily for 4 weeks with concomitant injections of bromodeoxyuridine (BrdU) for 5 days in the last week. In control rats, Cu levels were significantly higher in the SVZ than other brain regions examined. Mn exposure significantly reduced Cu concentrations in the SVZ (P < 0.01). Immunohistochemical data showed that in vivo Mn exposure significantly increased numbers of BrdU(+) cells, which were accompanied with increased GFAP(+) astrocytic stem cells and DCX(+) neuroblasts in SVZ and RMS. Quantitative RT-PCR and Western blot confirmed the increased expression of DMT1 in SVZ following in vivo Mn exposure, which contributed to Mn accumulation in the neurogenesis pathway. Taken together, these results indicate a clear disruptive effect of Mn on adult neurogenesis; the effect appears due partly to Mn induction of DMT1 and its interference with cellular Cu regulation in SVZ and RMS. The future research directions based on these observations are also discussed. PMID:25575534

  15. Benefit of interleaved practice of motor skills is associated with changes in functional brain network topology that differ between younger and older adults.

    PubMed

    Lin, Chien-Ho Janice; Knowlton, Barbara J; Wu, Allan D; Iacoboni, Marco; Yang, Ho-Ching; Ye, Yu-Ling; Liu, Kuan-Hong; Chiang, Ming-Chang

    2016-06-01

    Practicing tasks arranged in an interleaved manner generally leads to superior retention compared with practicing tasks repetitively, a phenomenon known as the contextual interference (CI) effect. We investigated the brain network of motor learning under CI, that is, the CI network, and how it was affected by aging. Sixteen younger and 16 older adults practiced motor sequences arranged in a repetitive or an interleaved order over 2 days, followed by a retention test on day 5 to evaluate learning. Network analysis was applied to functional MRI data on retention to define the CI network by identifying brain regions with greater between-region connectivity after interleaved compared with repetitive practice. CI effects were present in both groups but stronger in younger adults. Moreover, CI networks in younger adults exhibited efficient small-world topology, with a significant association between higher network centrality and better learning after interleaved practice. Older adults did not show such favorable network properties. Our findings suggest that aging affects the efficiency of brain networks underlying enhanced motor learning after CI practice.

  16. Increased Intraregional Synchronized Neural Activity in Adult Brain After Prolonged Adaptation to High-Altitude Hypoxia: A Resting-State fMRI Study.

    PubMed

    Chen, Ji; Fan, Cunxiu; Li, Jinqiang; Han, Qiaoqing; Lin, Jianzhong; Yang, Tianhe; Zhang, Jiaxing

    2016-03-01

    The human brain is intrinsically plastic such that its functional architecture can be reorganized in response to environmental pressures and physiological changes. However, it remains unclear whether a compensatory modification of spontaneous neural activity occurs in adult brain during prolonged high-altitude (HA) adaptation. In this study, we obtained resting-state functional magnetic resonance (MR) images in 16 adults who have immigrated to Qinghai-Tibet Plateau (2300-4400 m) for 2 years and in 16 age-matched sea level (SL) controls. A validated regional homogeneity (Reho) method was employed to investigate the local synchronization of resting-state functional magnetic resonance imaging (fMRI) signals. Seed connectivity analysis was carried out subsequently. Cognitive and physiological assessments were made and correlated with the image metrics. Compared with SL controls, global mean Reho was significantly increased in HA immigrants as well as a regional increase in the right inferolateral sensorimotor cortex. Furthermore, mean z-Reho value extracted within the inferolateral sensorimotor area showed trend-level significant inverse correlation with memory search reaction time in HA immigrants. These observations, for the first time, provide evidence of adult brain resilience of spontaneous neural activity after long-term HA exposure without inherited and developmental effects. Resting-state fMRI could yield valuable information for central mechanisms underlying respiratory and cognitive compensations in adults during prolonged environmentally hypoxic adaptation, paving the way for future HA-adaptive training.

  17. Cannabis cue-induced brain activation correlates with drug craving in limbic and visual salience regions: Preliminary results

    PubMed Central

    Charboneau, Evonne J.; Dietrich, Mary S.; Park, Sohee; Cao, Aize; Watkins, Tristan J; Blackford, Jennifer U; Benningfield, Margaret M.; Martin, Peter R.; Buchowski, Maciej S.; Cowan, Ronald L.

    2013-01-01

    Craving is a major motivator underlying drug use and relapse but the neural correlates of cannabis craving are not well understood. This study sought to determine whether visual cannabis cues increase cannabis craving and whether cue-induced craving is associated with regional brain activation in cannabis-dependent individuals. Cannabis craving was assessed in 16 cannabis-dependent adult volunteers while they viewed cannabis cues during a functional MRI (fMRI) scan. The Marijuana Craving Questionnaire was administered immediately before and after each of three cannabis cue-exposure fMRI runs. FMRI blood-oxygenation-level-dependent (BOLD) signal intensity was determined in regions activated by cannabis cues to examine the relationship of regional brain activation to cannabis craving. Craving scores increased significantly following exposure to visual cannabis cues. Visual cues activated multiple brain regions, including inferior orbital frontal cortex, posterior cingulate gyrus, parahippocampal gyrus, hippocampus, amygdala, superior temporal pole, and occipital cortex. Craving scores at baseline and at the end of all three runs were significantly correlated with brain activation during the first fMRI run only, in the limbic system (including amygdala and hippocampus) and paralimbic system (superior temporal pole), and visual regions (occipital cortex). Cannabis cues increased craving in cannabis-dependent individuals and this increase was associated with activation in the limbic, paralimbic, and visual systems during the first fMRI run, but not subsequent fMRI runs. These results suggest that these regions may mediate visually cued aspects of drug craving. This study provides preliminary evidence for the neural basis of cue-induced cannabis craving and suggests possible neural targets for interventions targeted at treating cannabis dependence. PMID:24035535

  18. Cannabis cue-induced brain activation correlates with drug craving in limbic and visual salience regions: preliminary results.

    PubMed

    Charboneau, Evonne J; Dietrich, Mary S; Park, Sohee; Cao, Aize; Watkins, Tristan J; Blackford, Jennifer U; Benningfield, Margaret M; Martin, Peter R; Buchowski, Maciej S; Cowan, Ronald L

    2013-11-30

    Craving is a major motivator underlying drug use and relapse but the neural correlates of cannabis craving are not well understood. This study sought to determine whether visual cannabis cues increase cannabis craving and whether cue-induced craving is associated with regional brain activation in cannabis-dependent individuals. Cannabis craving was assessed in 16 cannabis-dependent adult volunteers while they viewed cannabis cues during a functional MRI (fMRI) scan. The Marijuana Craving Questionnaire was administered immediately before and after each of three cannabis cue-exposure fMRI runs. FMRI blood-oxygenation-level-dependent (BOLD) signal intensity was determined in regions activated by cannabis cues to examine the relationship of regional brain activation to cannabis craving. Craving scores increased significantly following exposure to visual cannabis cues. Visual cues activated multiple brain regions, including inferior orbital frontal cortex, posterior cingulate gyrus, parahippocampal gyrus, hippocampus, amygdala, superior temporal pole, and occipital cortex. Craving scores at baseline and at the end of all three runs were significantly correlated with brain activation during the first fMRI run only, in the limbic system (including amygdala and hippocampus) and paralimbic system (superior temporal pole), and visual regions (occipital cortex). Cannabis cues increased craving in cannabis-dependent individuals and this increase was associated with activation in the limbic, paralimbic, and visual systems during the first fMRI run, but not subsequent fMRI runs. These results suggest that these regions may mediate visually cued aspects of drug craving. This study provides preliminary evidence for the neural basis of cue-induced cannabis craving and suggests possible neural targets for interventions targeted at treating cannabis dependence.

  19. Mapping Individual Brain Networks Using Statistical Similarity in Regional Morphology from MRI

    PubMed Central

    Kong, Xiang-zhen; Liu, Zhaoguo; Huang, Lijie; Wang, Xu; Yang, Zetian; Zhou, Guangfu; Zhen, Zonglei; Liu, Jia

    2015-01-01

    Representing brain morphology as a network has the advantage that the regional morphology of ‘isolated’ structures can be described statistically based on graph theory. However, very few studies have investigated brain morphology from the holistic perspective of complex networks, particularly in individual brains. We proposed a new network framework for individual brain morphology. Technically, in the new network, nodes are defined as regions based on a brain atlas, and edges are estimated using our newly-developed inter-regional relation measure based on regional morphological distributions. This implementation allows nodes in the brain network to be functionally/anatomically homogeneous but different with respect to shape and size. We first demonstrated the new network framework in a healthy sample. Thereafter, we studied the graph-theoretical properties of the networks obtained and compared the results with previous morphological, anatomical, and functional networks. The robustness of the method was assessed via measurement of the reliability of the network metrics using a test-retest dataset. Finally, to illustrate potential applications, the networks were used to measure age-related changes in commonly used network metrics. Results suggest that the proposed method could provide a concise description of brain organization at a network level and be used to investigate interindividual variability in brain morphology from the perspective of complex networks. Furthermore, the method could open a new window into modeling the complexly distributed brain and facilitate the emerging field of human connectomics. PMID:26536598

  20. Automatic detection of the hippocampal region associated with Alzheimer's disease from microscopic images of mice brain

    NASA Astrophysics Data System (ADS)

    Albaidhani, Tahseen; Hawkes, Cheryl; Jassim, Sabah; Al-Assam, Hisham

    2016-05-01

    The hippocampus is the region of the brain that is primarily associated with memory and spatial navigation. It is one of the first brain regions to be damaged when a person suffers from Alzheimer's disease. Recent research in this field has focussed on the assessment of damage to different blood vessels within the hippocampal region from a high throughput brain microscopic images. The ultimate aim of our research is the creation of an automatic system to count and classify different blood vessels such as capillaries, veins, and arteries in the hippocampus region. This work should provide biologists with efficient and accurate tools in their investigation of the causes of Alzheimer's disease. Locating the boundary of the Region of Interest in the hippocampus from microscopic images of mice brain is the first essential stage towards developing such a system. This task benefits from the variation in colour channels and texture between the two sides of the hippocampus and the boundary region. Accordingly, the developed initial step of our research to locating the hippocampus edge uses a colour-based segmentation of the brain image followed by Hough transforms on the colour channel that isolate the hippocampus region. The output is then used to split the brain image into two sides of the detected section of the boundary: the inside region and the outside region. Experimental results on a sufficiently number of microscopic images demonstrate the effectiveness of the developed solution.

  1. Effect of Alzheimer Disease Risk on Brain Function During Self-Appraisal in Healthy Middle-Aged Adults

    PubMed Central

    Johnson, Sterling C.; Ries, Michele L.; Hess, Timothy M.; Carlsson, Cynthia M.; Gleason, Carey E.; Alexander, Andrew L.; Rowley, Howard A.; Asthana, Sanjay; Sager, Mark A.

    2009-01-01

    Context Recently asymptomatic middle-aged adult children of patients with Alzheimer Disease (AD) were found to exhibit fMRI deficits in the mesial temporal lobe during an encoding task. Whether this effect will be observed on other fMRI tasks is not yet known. This study examines the neural substrates of self-appraisal in people at risk for AD. Accurate appraisal of deficits is a problem for many AD patients, and prior fMRI studies of healthy young adults indicates that brain areas vulnerable to AD such as the anterior mesial temporal lobe and posterior cingulate are involved during self appraisal tasks. Objective To determine whether parental family history of AD (FH) or the ε4 allele of the Apolipoprotein E gene (APOE4) exert independent effects on brain function during self-appraisal. Design Cross-sectional factorial design in which APOE4 status (present/absent) was one factor, and FH status was the other. All participants received cognitive testing, genotyping and an fMRI task that required subjective self-appraisal (SA) decisions regarding trait adjective words in comparison to semantic decisions about the same words. Setting An academic medical center with a research-dedicated 3.0 Tesla MRI facility. Participants Cognitively normal middle-aged adults (N=110): 51 +FH; 59 −FH. Outcome measure Blood oxygen-dependent contrast measured with T2* weighted echo-planar imaging. Results FH and APOE4 status interacted in the posterior cingulate as well as left superior and medial frontal regions. There were main effects of FH (−FH > +FH) in left hippocampus, and ventral posterior cingulate. There were no main effects of APOE. Conclusion These results suggest that a parental history of AD may influence brain function during subjective self-appraisal in regions commonly affected by AD. Although these participants were asymptomatic and middle-aged, the findings suggest there may be subtle alterations in brain function attributable to AD risk factors. PMID:17909128

  2. Applications of hybrid diffuse optics for clinical management of adults after brain injury

    NASA Astrophysics Data System (ADS)

    Kim, Meeri Nam

    Information about cerebral blood flow (CBF) is valuable for clinical management of patients after severe brain injury. Unfortunately, current modalities for monitoring brain are often limited by hurdles that include high cost, low throughput, exposure to ionizing radiation, probe invasiveness, and increased risk to critically ill patients when transportation out of their room or unit is required. A further limitation of current technologies is an inability to provide continuous bedside measurements that are often desirable for unstable patients. Here we explore the clinical utility of diffuse correlation spectroscopy (DCS) as an alternative approach for bedside CBF monitoring. DCS uses the rapid intensity fluctuations of near-infrared light to derive a continuous measure of changes in blood flow without ionizing radiation or invasive probing. Concurrently, we employ another optical technique, called diffuse optical spectroscopy (DOS), to derive changes in cerebral oxyhemoglobin ( HbO2) and deoxyhemoglobin (Hb) concentrations. Our clinical studies integrate DCS with DOS into a single hybrid instrument that simultaneously monitors CBF and HbO2/Hb in the injured adult brain. The first parts of this dissertation present the motivations for monitoring blood flow in injured brain, as well as the theory underlying diffuse optics technology. The next section elaborates on details of the hybrid instrumentation. The final chapters describe four human subject studies carried out with these methods. Each of these studies investigates an aspect of the potential of the hybrid monitor in clinical applications involving adult brain. The studies include: (1) validation of DCS-measured CBF against xenon-enhanced computed tomography in brain-injured adults; (2) a study of the effects of age and gender on posture-change-induced CBF variation in healthy subjects; (3) a study of the efficacy of DCS/DOS for monitoring neurocritical care patients during various medical interventions such

  3. Central artery stiffness, baroreflex sensitivity, and brain white matter neuronal fiber integrity in older adults.

    PubMed

    Tarumi, Takashi; de Jong, Daan L K; Zhu, David C; Tseng, Benjamin Y; Liu, Jie; Hill, Candace; Riley, Jonathan; Womack, Kyle B; Kerwin, Diana R; Lu, Hanzhang; Munro Cullum, C; Zhang, Rong

    2015-04-15

    Cerebral hypoperfusion elevates the risk of brain white matter (WM) lesions and cognitive impairment. Central artery stiffness impairs baroreflex, which controls systemic arterial perfusion, and may deteriorate neuronal fiber integrity of brain WM. The purpose of this study was to examine the associations among brain WM neuronal fiber integrity, baroreflex sensitivity (BRS), and central artery stiffness in older adults. Fifty-four adults (65 ± 6 years) with normal cognitive function or mild cognitive impairment (MCI) were tested. The neuronal fiber integrity of brain WM was assessed from diffusion metrics acquired by diffusion tensor imaging. BRS was measured in response to acute changes in blood pressure induced by bolus injections of vasoactive drugs. Central artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). The WM diffusion metrics including fractional anisotropy (FA) and radial (RD) and axial (AD) diffusivities, BRS, and cfPWV were not different between the control and MCI groups. Thus, the data from both groups were combined for subsequent analyses. Across WM, fiber tracts with decreased FA and increased RD were associated with lower BRS and higher cfPWV, with many of the areas presenting spatial overlap. In particular, the BRS assessed during hypotension was strongly correlated with FA and RD when compared with hypertension. Executive function performance was associated with FA and RD in the areas that correlated with cfPWV and BRS. These findings suggest that baroreflex-mediated control of systemic arterial perfusion, especially during hypotension, may play a crucial role in maintaining neuronal fiber integrity of brain WM in older adults. PMID:25623500

  4. Regional cerebral glucose metabolism is normal in young adults with Down syndrome

    SciTech Connect

    Schapiro, M.B.; Grady, C.L.; Kumar, A.; Herscovitch, P.; Haxby, J.V.; Moore, A.M.; White, B.; Friedland, R.P.; Rapoport, S.I. )

    1990-03-01

    Regional CMRglc (rCMRglc) values were measured with ({sup 18}F)2-fluoro-2-deoxy-D-glucose ({sup 18}FDG) and positron emission tomography (PET), using a Scanditronix PC-1024-7B scanner, in 14 healthy, noninstitutionalized subjects with trisomy 21 (Down syndrome; DS) (mean age 30.0 years, range 25-38 years) and in 13 sex-matched, healthy volunteers (mean age 29.5 years, range 22-38 years). In the DS group, mean mental age on the Peabody Picture Vocabulary Test was 7.8 years and dementia was not present. Resting rCMRglc was determined with eyes covered and ears occluded in a quiet, darkened room. Global gray CMRglc equaled 8.76 +/- 0.76 mg/100 g/min (mean +/- SD) in the DS group as compared with 8.74 +/- 1.19 mg/100 g/min in the control group (p greater than 0.05). Gray matter regional measurements also did not differ between groups. The ratio of rCMRglc to global CMRglc, calculated to reduce the variance associated with absolute rCMRglc, and right/left ratios did not show any consistent differences. These results show that healthy young DS adults do not have alterations in regional or global brain glucose metabolism, as measured with 18FDG and PET, prior to an age at which the neuropathological changes in Alzheimer disease are reported to occur.

  5. The effect of methylphenidate intake on brain structure in adults with ADHD in a placebo-controlled randomized trial

    PubMed Central

    van Elst, Ludger Tebartz; Maier, Simon; Klöppel, Stefan; Graf, Erika; Killius, Carola; Rump, Marthe; Sobanski, Esther; Ebert, Dieter; Berger, Mathias; Warnke, Andreas; Matthies, Swantje; Perlov, Evgeniy; Philipsen, Alexandra

    2016-01-01

    Background Based on animal research several authors have warned that the application of methylphenidate, the first-line drug for the treatment of attention-deficit/hyperactivity disorder (ADHD), might have neurotoxic effects potentially harming the brain. We investigated whether methylphenidate application, over a 1-year period, results in cerebral volume decrease. Methods We acquired structural MRIs in a double-blind study comparing methylphenidate to placebo. Global and regional brain volumes were analyzed at baseline, after 3 months and after 12 months using diffeomorphic anatomic registration through exponentiated lie algebra. Results We included 131 adult patients with ADHD into the baseline sample, 98 into the 3-month sample (54 in the methylphenidate cohort and 44 in the placebo cohort) and 76 into the 1-year sample (37 in the methylphenidate cohort and 29 in the placebo cohort). Methylphenidate intake compared with placebo did not lead to any detectable cerebral volume loss; there was a trend toward bilateral cerebellar grey matter increase. Limitations Detecting possible neurotoxic effects of methylphenidate might require a longer observation period. Conclusion There is no evidence of grey matter volume loss after 1 year of methylphenidate treatment in adult patients with ADHD. PMID:27575717

  6. Environmental enrichment improves recent but not remote memory in association with a modified brain metabolic activation profile in adult mice.

    PubMed

    Leger, Marianne; Bouet, Valentine; Freret, Thomas; Darmaillacq, Anne-Sophie; Dacher, Matthieu; Dauphin, François; Boulouard, Michel; Schumann-Bard, Pascale

    2012-03-01

    Environmental enrichment is known to improve learning and memory in adult rodents. Whereas the morphological changes underlying these beneficial effects are well documented, few studies have addressed the influence of this housing condition on the neuronal networks underlying memory processes. We assessed the effects of environmental enrichment on behavioural performances and brain metabolic activation during a memory task in mice. Adult mice were housed in standard (SC) or enriched (EC) conditions for 3 weeks. Then, recent and remote memory performances were measured in the passive avoidance test. After testing, brain metabolic activation was assessed through cytochrome oxidase (CO) activity. EC improved recent memory, in association with an increased metabolic activation in the frontal and prefrontal cortices and a decreased activation in the baso-lateral amygdala and the hippocampus. EC did not improve remote memory, and globally decreased CO activity. Our findings suggest the involvement of regions of pivotal importance during recent memory, such as the frontal cortex, in the beneficial effects of EC.

  7. Reawakening the sleeping beauty in the adult brain: neurogenesis from parenchymal glia.

    PubMed

    Péron, Sophie; Berninger, Benedikt

    2015-10-01

    Life-long neurogenesis is highly restricted to specialized niches in the adult mammalian brain and therefore the brain's capacity for spontaneous regeneration is extremely limited. However, recent work has demonstrated that under certain circumstances parenchymal astrocytes and NG2 glia can generate neuronal progeny. In the striatum, stroke or excitotoxic lesions can reawaken in astrocytes a latent neurogenic program resulting in the genesis of new neurons. By contrast, in brain areas that fail to mount a neurogenic response following injury, such as the cerebral cortex, forced expression of neurogenic reprogramming factors can lineage convert local glia into induced neurons. Yet, injury-induced and reprogramming-induced neurogenesis exhibit intriguing commonalities, suggesting that they may converge on similar mechanisms.

  8. The robo-pigeon based on the multiple brain regions synchronization implanted microelectrodes.

    PubMed

    Huai, Rui-Tuo; Yang, Jun-Qing; Wang, Hui

    2016-07-01

    Almost all multichannel microelectrodes are only applied to the same nucleus. The multiple brain regions synchronization implanted microelectrodes can be implanted in the several brain regions at the same time, when used in the robo-animal, which can reduce the operation process, shorten animals operation time. Due to electrode position relatively fixed, errors caused by each separately implanted electrode were reduced and the animal control effect was greatly increased compared to the original electrodes. The electrode fixed time was also extended. This microelectrode provided beneficial reference function for the study of the free state of small animals in different brain regions. PMID:27459594

  9. Midsagittal brain variation and MRI shape analysis of the precuneus in adult individuals.

    PubMed

    Bruner, Emiliano; Rangel de Lázaro, Gizéh; de la Cuétara, José Manuel; Martín-Loeches, Manuel; Colom, Roberto; Jacobs, Heidi I L

    2014-04-01

    Recent analyses indicate that the precuneus is one of the main centres of integration in terms of functional and structural processes within the human brain. This neuroanatomical element is formed by different subregions, involved in visuo-spatial integration, memory and self-awareness. We analysed the midsagittal brain shape in a sample of adult humans (n = 90) to evidence the patterns of variability and geometrical organization of this area. Interestingly, the major brain covariance pattern within adult humans is strictly associated with the relative proportions of the precuneus. Its morphology displays a marked individual variation, both in terms of geometry (mostly in its longitudinal dimensions) and anatomy (patterns of convolution). No patent differences are evident between males and females, and the allometric effect of size is minimal. However, in terms of morphology, the precuneus does not represent an individual module, being influenced by different neighbouring structures. Taking into consideration the apparent involvement of the precuneus in higher-order human brain functions and evolution, its wide variation further stresses the important role of these deep parietal areas in modern neuroanatomical organization.

  10. Extremely low frequency electromagnetic fields (EMF) and brain cancer in adults and children: review and comment.

    PubMed Central

    Gurney, J. G.; van Wijngaarden, E.

    1999-01-01

    Epidemiologic and experimental research on the potential carcinogenic effects of extremely low frequency electromagnetic fields (EMF) has now been conducted for over two decades. Cancer epidemiology studies in relation to EMF have focused primarily on brain cancer and leukemia, both from residential sources of exposure in children and adults and from occupational exposure in adult men. Because genotoxic effects of EMF have not been shown, most recent laboratory research has attempted to show biological effects that could be related to cancer promotion. In this report, we briefly review residential and occupational EMF studies on brain cancer. We also provide a general review of experimental studies as they relate both to the biological plausibility of an EMF-brain cancer relation and to the insufficiency of such research to help guide exposure assessment in epidemiologic studies. We conclude from our review that no recent research, either epidemiologic or experimental, has emerged to provide reasonable support for a causal role of EMF on brain cancer. PMID:11550314

  11. Landmark-based morphometrics of the normal adult brain using MRI.

    PubMed

    Free, S L; O'Higgins, P; Maudgil, D D; Dryden, I L; Lemieux, L; Fish, D R; Shorvon, S D

    2001-05-01

    We describe the application of statistical shape analysis to homologous landmarks on the cortical surface of the adult human brain. Statistical shape analysis has a sound theoretical basis. Landmarks are identified on the surface of a 3-D reconstruction of the segmented cortical surface from magnetic resonance image (MRI) data. Using publicly available software (morphologika) the location and size dependence of the landmarks are removed and the differences in landmark distribution across subjects are analysed using principal component analysis. These differences, representing shape differences between subjects, can be visually assessed using wireframe models and transformation grids. The MRI data of 58 adult brains (27 female and 15 left handed) were examined. Shape differences in the whole brain are described which concern the relative orientation of frontal lobe sulci. Analysis of all 116 hemispheres revealed a statistically significant difference (P < 0.001) between left and right hemispheres. This finding was significant for right- but not left-handed subjects alone. No other significant age, gender, handedness, or brain-size correlations with shape differences were found.

  12. Midsagittal brain variation and MRI shape analysis of the precuneus in adult individuals

    PubMed Central

    Bruner, Emiliano; Rangel de Lázaro, Gizéh; de la Cuétara, José Manuel; Martín-Loeches, Manuel; Colom, Roberto; Jacobs, Heidi I L

    2014-01-01

    Recent analyses indicate that the precuneus is one of the main centres of integration in terms of functional and structural processes within the human brain. This neuroanatomical element is formed by different subregions, involved in visuo-spatial integration, memory and self-awareness. We analysed the midsagittal brain shape in a sample of adult humans (n = 90) to evidence the patterns of variability and geometrical organization of this area. Interestingly, the major brain covariance pattern within adult humans is strictly associated with the relative proportions of the precuneus. Its morphology displays a marked individual variation, both in terms of geometry (mostly in its longitudinal dimensions) and anatomy (patterns of convolution). No patent differences are evident between males and females, and the allometric effect of size is minimal. However, in terms of morphology, the precuneus does not represent an individual module, being influenced by different neighbouring structures. Taking into consideration the apparent involvement of the precuneus in higher-order human brain functions and evolution, its wide variation further stresses the important role of these deep parietal areas in modern neuroanatomical organization. PMID:24397462

  13. In Alzheimer's disease, hypometabolism in low-amyloid brain regions may be a functional consequence of pathologies in connected brain regions.

    PubMed

    Klupp, Elisabeth; Förster, Stefan; Grimmer, Timo; Tahmasian, Masoud; Yakushev, Igor; Sorg, Christian; Yousefi, Behrooz H; Drzezga, Alexander

    2014-06-01

    In patients with Alzheimer's disease (AD), prominent hypometabolism has been observed in brain regions with minor amyloid load. These hypometabolism-only (HO) areas cannot be explained merely as a consequence of local amyloid toxicity. The aim of this multimodal imaging study was to explore whether such HO phenomenon may be related to pathologies in functionally connected, remote brain regions. Nineteen AD patients and 15 matched controls underwent examinations with [(11)C]PiB-PET and [(18)F]FDG-PET. Voxel-based statistical group comparisons were performed to obtain maps of significantly elevated amyloid burden and reduced cerebral glucose metabolism, respectively, in patients. An HO area was identified by subtraction of equally thresholded result maps (hypometabolism minus amyloid burden). To identify the network typically functionally connected to this HO area, it was used as a seed region for a functional connectivity analysis in resting-state functional magnetic resonance imaging data of 17 elderly healthy controls. The resulting intrinsic connectivity network (HO-ICN) was retransferred into the brains of AD patients to be able to analyze pathologies within this network in the positron emission tomography (PET) datasets. The most prominent HO area was detected in the left middle frontal gyrus of AD patients. The HO-ICN in healthy controls showed a major overlap with brain areas significantly affected by both amyloid deposition and hypometabolism in patients. This association was substantiated by the results of region-of-interest-based and voxel-wise correlation analyses, which revealed strong correlations between the degree of hypometabolism within the HO region and within the HO-ICN. These results support the notion that hypometabolism in brain regions not strongly affected by locoregional amyloid pathology may be related to ongoing pathologies in remote but functionally connected regions, that is, by reduced neuronal input from these regions. PMID:24870443

  14. Brain white matter structure and COMT gene are linked to second-language learning in adults.

    PubMed

    Mamiya, Ping C; Richards, Todd L; Coe, Bradley P; Eichler, Evan E; Kuhl, Patricia K

    2016-06-28

    Adult human brains retain the capacity to undergo tissue reorganization during second-language learning. Brain-imaging studies show a relationship between neuroanatomical properties and learning for adults exposed to a second language. However, the role of genetic factors in this relationship has not been investigated. The goal of the current study was twofold: (i) to characterize the relationship between brain white matter fiber-tract properties and second-language immersion using diffusion tensor imaging, and (ii) to determine whether polymorphisms in the catechol-O-methyltransferase (COMT) gene affect the relationship. We recruited incoming Chinese students enrolled in the University of Washington and scanned their brains one time. We measured the diffusion properties of the white matter fiber tracts and correlated them with the number of days each student had been in the immersion program at the time of the brain scan. We found that higher numbers of days in the English immersion program correlated with higher fractional anisotropy and lower radial diffusivity in the right superior longitudinal fasciculus. We show that fractional anisotropy declined once the subjects finished the immersion program. The relationship between brain white matter fiber-tract properties and immersion varied in subjects with different COMT genotypes. Subjects with the Methionine (Met)/Valine (Val) and Val/Val genotypes showed higher fractional anisotropy and lower radial diffusivity during immersion, which reversed immediately after immersion ended, whereas those with the Met/Met genotype did not show these relationships. Statistical modeling revealed that subjects' grades in the language immersion program were best predicted by fractional anisotropy and COMT genotype. PMID:27298360

  15. Brain white matter structure and COMT gene are linked to second-language learning in adults.

    PubMed

    Mamiya, Ping C; Richards, Todd L; Coe, Bradley P; Eichler, Evan E; Kuhl, Patricia K

    2016-06-28

    Adult human brains retain the capacity to undergo tissue reorganization during second-language learning. Brain-imaging studies show a relationship between neuroanatomical properties and learning for adults exposed to a second language. However, the role of genetic factors in this relationship has not been investigated. The goal of the current study was twofold: (i) to characterize the relationship between brain white matter fiber-tract properties and second-language immersion using diffusion tensor imaging, and (ii) to determine whether polymorphisms in the catechol-O-methyltransferase (COMT) gene affect the relationship. We recruited incoming Chinese students enrolled in the University of Washington and scanned their brains one time. We measured the diffusion properties of the white matter fiber tracts and correlated them with the number of days each student had been in the immersion program at the time of the brain scan. We found that higher numbers of days in the English immersion program correlated with higher fractional anisotropy and lower radial diffusivity in the right superior longitudinal fasciculus. We show that fractional anisotropy declined once the subjects finished the immersion program. The relationship between brain white matter fiber-tract properties and immersion varied in subjects with different COMT genotypes. Subjects with the Methionine (Met)/Valine (Val) and Val/Val genotypes showed higher fractional anisotropy and lower radial diffusivity during immersion, which reversed immediately after immersion ended, whereas those with the Met/Met genotype did not show these relationships. Statistical modeling revealed that subjects' grades in the language immersion program were best predicted by fractional anisotropy and COMT genotype.

  16. Brain white matter structure and COMT gene are linked to second-language learning in adults

    PubMed Central

    Mamiya, Ping C.; Richards, Todd L.; Coe, Bradley P.; Eichler, Evan E.; Kuhl, Patricia K.

    2016-01-01

    Adult human brains retain the capacity to undergo tissue reorganization during second-language learning. Brain-imaging studies show a relationship between neuroanatomical properties and learning for adults exposed to a second language. However, the role of genetic factors in this relationship has not been investigated. The goal of the current study was twofold: (i) to characterize the relationship between brain white matter fiber-tract properties and second-language immersion using diffusion tensor imaging, and (ii) to determine whether polymorphisms in the catechol-O-methyltransferase (COMT) gene affect the relationship. We recruited incoming Chinese students enrolled in the University of Washington and scanned their brains one time. We measured the diffusion properties of the white matter fiber tracts and correlated them with the number of days each student had been in the immersion program at the time of the brain scan. We found that higher numbers of days in the English immersion program correlated with higher fractional anisotropy and lower radial diffusivity in the right superior longitudinal fasciculus. We show that fractional anisotropy declined once the subjects finished the immersion program. The relationship between brain white matter fiber-tract properties and immersion varied in subjects with different COMT genotypes. Subjects with the Methionine (Met)/Valine (Val) and Val/Val genotypes showed higher fractional anisotropy and lower radial diffusivity during immersion, which reversed immediately after immersion ended, whereas those with the Met/Met genotype did not show these relationships. Statistical modeling revealed that subjects’ grades in the language immersion program were best predicted by fractional anisotropy and COMT genotype. PMID:27298360

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

    PubMed

    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. PMID:17762517

  18. Gender-dependent behavioural impairment and brain metabolites in young adult rats after short term exposure to lead acetate.

    PubMed

    Mansouri, M T; Naghizadeh, B; López-Larrubia, P; Cauli, O

    2012-04-01

    We investigated the behavioural effects of short-term lead (Pb) exposure in adult rats producing blood Pb concentration (<10 μg/dL) below those associated with neurological impairment in occupationally exposed individuals. In order to assess gender differences, we performed parallel behavioural experiments in male and female rats. Exposure to Pb acetate (50 mg/L in drinking water) for 30-45 days induced behavioural alterations consisting in hyperactivity in a novel environment and impairment of spatial memory. These effects were observed only in male rats. Object recognition, motor coordination were unaffected by Pb exposure. Magnetic resonance spectroscopy allows in vivo assessment of main brain metabolites (glutamate/glutamine, creatine, myoinositol, N-acetylaspartate and choline) whose changes have been demonstrated in several central nervous system pathologies. Exposure to Pb did not affect metabolite profile in the striatum and increase myoinositol signal in the hippocampus of male rats. The increase in myoinositol in hippocampus suggests early Pb-induced alteration in glial metabolism in this brain region and may represent a potential marker of early brain dysfunction during Pb exposure. PMID:22285975

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

    PubMed

    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.

  20. Prion diseases and adult neurogenesis: how do prions counteract the brain's endogenous repair machinery?

    PubMed

    Relaño-Ginés, Aroa; Lehmann, Sylvain; Crozet, Carole

    2014-01-01

    Scientific advances in stem cell biology and adult neurogenesis have raised the hope that neurodegenerative disorders could benefit from stem cell-based therapy. Adult neurogenesis might be part of the physiological regenerative process, however it might become impaired by the disease's mechanism and therefore contribute to neurodegeneration. In prion disorders this endogenous repair system has rarely been studied. Whether adult neurogenesis plays a role or not in brain repair or in the propagation of prion pathology remains unclear. We have recently investigated the status of adult neural stem cells isolated from prion-infected mice. We were able to show that neural stem cells accumulate and replicate prions thus resulting in an alteration of their neuronal destiny. We also reproduced these results in adult neural stem cells, which were infected in vitro. The fact that endogenous adult neurogenesis could be altered by the accumulation of misfolded prion protein represents another great challenge. Inhibiting prion propagation in these cells would thus help the endogenous neurogenesis to compensate for the injured neuronal system. Moreover, understanding the endogenous modulation of the neurogenesis system would help develop effective neural stem cell-based therapies.

  1. Multiple Determinants of Whole and Regional Brain Volume among Terrestrial Carnivorans

    PubMed Central

    Swanson, Eli M.; Holekamp, Kay E.; Lundrigan, Barbara L.; Arsznov, Bradley M.; Sakai, Sharleen T.

    2012-01-01

    Mammalian brain volumes vary considerably, even after controlling for body size. Although several hypotheses have been proposed to explain this variation, most research in mammals on the evolution of encephalization has focused on primates, leaving the generality of these explanations uncertain. Furthermore, much research still addresses only one hypothesis at a time, despite the demonstrated importance of considering multiple factors simultaneously. We used phylogenetic comparative methods to investigate simultaneously the importance of several factors previously hypothesized to be important in neural evolution among mammalian carnivores, including social complexity, forelimb use, home range size, diet, life history, phylogeny, and recent evolutionary changes in body size. We also tested hypotheses suggesting roles for these variables in determining the relative volume of four brain regions measured using computed tomography. Our data suggest that, in contrast to brain size in primates, carnivoran brain size may lag behind body size over evolutionary time. Moreover, carnivore species that primarily consume vertebrates have the largest brains. Although we found no support for a role of social complexity in overall encephalization, relative cerebrum volume correlated positively with sociality. Finally, our results support negative relationships among different brain regions after accounting for overall endocranial volume, suggesting that increased size of one brain regions is often accompanied by reduced size in other regions rather than overall brain expansion. PMID:22719890

  2. Persistent production of neurons from adult brain stem cells during recovery after stroke.

    PubMed

    Thored, Pär; Arvidsson, Andreas; Cacci, Emanuele; Ahlenius, Henrik; Kallur, Therése; Darsalia, Vladimer; Ekdahl, Christine T; Kokaia, Zaal; Lindvall, Olle

    2006-03-01

    Neural stem cells in the subventricular zone of adult rodents produce new striatal neurons that may replace those that have died after stroke; however, the neurogenic response has been considered acute and transient, yielding only small numbers of neurons. In contrast, we show herein that striatal neuroblasts are generated without decline at least for 4 months after stroke in adult rats. Neuroblasts formed early or late after stroke either differentiate into mature neurons, which survive for several months, or die through caspase-mediated apoptosis. The directed migration of the new neurons toward the ischemic damage is regulated by stromal cell-derived factor-1alpha and its receptor CXCR4. These results show that endogenous neural stem cells continuously supply the injured adult brain with new neurons, which suggests novel self-repair strategies to improve recovery after stroke. PMID:16210404

  3. Distinct Pools of Non-Glycolytic Substrates Differentiate Brain Regions and Prime Region-Specific Responses of Mitochondria

    PubMed Central

    Platt, Virginia; Budworth, Helen; Canaria, Christie A.; McMurray, Cynthia T.

    2013-01-01

    Many hereditary diseases are characterized by region-specific toxicity, despite the fact that disease-linked proteins are generally ubiquitously expressed. The underlying basis of the region-specific vulnerability remains enigmatic. Here, we evaluate the fundamental features of mitochondrial and glucose metabolism in synaptosomes from four brain regions in basal and stressed states. Although the brain has an absolute need for glucose in vivo, we find that synaptosomes prefer to respire on non-glycolytic substrates, even when glucose is present. Moreover, glucose is metabolized differently in each brain region, resulting in region-specific “signature” pools of non-glycolytic substrates. The use of non-glycolytic resources increases and dominates during energy crisis, and triggers a marked region-specific metabolic response. We envision that disease-linked proteins confer stress on all relevant brain cells, but region-specific susceptibility stems from metabolism of non-glycolytic substrates, which limits how and to what extent neurons respond to the stress. PMID:23874783

  4. Neural Representations Used by Brain Regions Underlying Speech Production

    ERIC Educational Resources Information Center

    Segawa, Jennifer Anne

    2013-01-01

    Speech utterances are phoneme sequences but may not always be represented as such in the brain. For instance, electropalatography evidence indicates that as speaking rate increases, gestures within syllables are manipulated separately but those within consonant clusters act as one motor unit. Moreover, speech error data suggest that a syllable's…

  5. Project ACT (Adult Competency Training): Region VIII Adult Education Staff Development: Mid-Year Report: FY '75.

    ERIC Educational Resources Information Center

    Colorado State Univ., Ft. Collins. Dept. of Education.

    The third-year report of the regional staff development system of the Adult Competency Training Project (Project ACT) examines and evaluates the events, activities, and accomplishments of Individualized Training Programs (ITP), regional policy board meetings, staff and participant travel, and planning during FY 1974. Present and anticipated…

  6. DNA microarray analysis of functionally discrete human brain regions reveals divergent transcriptional profiles

    PubMed Central

    Evans, S.J.; Choudary, P.V.; Vawter, M.P.; Li, J.; Meador-Woodruff, J.H.; Lopez, J.F.; Burke, S.M.; Thompson, R.C.; Myers, R.M.; Jones, E.G.; Bunney, W.E.; Watson, S.J.; Akil, H.

    2010-01-01

    Transcriptional profiles within discrete human brain regions are likely to reflect structural and functional specialization. Using DNA microarray technology, this study investigates differences in transcriptional profiles of highly divergent brain regions (the cerebellar cortex and the cerebral cortex) as well as differences between two closely related brain structures (the anterior cingulate cortex and the dorsolateral prefrontal cortex). Replication of this study across three independent laboratories, to address false-positive and false-negative results using microarray technology, is also discussed. We find greater than a thousand transcripts to be differentially expressed between cerebellum and cerebral cortex and very few transcripts to be differentially expressed between the two neocortical regions. We further characterized transcripts that were found to be specifically expressed within brain regions being compared and found that ontological classes representing signal transduction machinery, neurogenesis, synaptic transmission, and transcription factors were most highly represented. PMID:14572446

  7. Distinct Brain and Behavioral Benefits from Cognitive vs. Physical Training: A Randomized Trial in Aging Adults

    PubMed Central

    Chapman, Sandra B.; Aslan, Sina; Spence, Jeffrey S.; Keebler, Molly W.; DeFina, Laura F.; Didehbani, Nyaz; Perez, Alison M.; Lu, Hanzhang; D'Esposito, Mark

    2016-01-01

    Insidious declines in normal aging are well-established. Emerging evidence suggests that non-pharmacological interventions, specifically cognitive and physical training, may counter diminishing age-related cognitive and brain functions. This randomized trial compared effects of two training protocols: cognitive training (CT) vs. physical training (PT) on cognition and brain function in adults 56–75 years. Sedentary participants (N = 36) were randomized to either CT or PT group for 3 h/week over 12 weeks. They were assessed at baseline-, mid-, and post-training using neurocognitive, MRI, and physiological measures. The CT group improved on executive function whereas PT group's memory was enhanced. Uniquely deploying cerebral blood flow (CBF) and cerebral vascular reactivity (CVR) MRI, the CT cohort showed increased CBF within the prefrontal and middle/posterior cingulate cortex (PCC) without change to CVR compared to PT group. Improvements in complex abstraction were positively associated with increased resting CBF in dorsal anterior cingulate cortex (dACC). Exercisers with higher CBF in hippocampi bilaterally showed better immediate memory. The preliminary evidence indicates that increased cognitive and physical activity improves brain health in distinct ways. Reasoning training enhanced frontal networks shown to be integral to top-down cognitive control and brain resilience. Evidence of increased resting CBF without changes to CVR implicates increased neural health rather than improved vascular response. Exercise did not improve cerebrovascular response, although CBF increased in hippocampi of those with memory gains. Distinct benefits incentivize testing effectiveness of combined protocols to strengthen brain health. PMID:27462210

  8. Promoting brain health through exercise and diet in older adults: a physiological perspective.

    PubMed

    Jackson, Philippa A; Pialoux, Vincent; Corbett, Dale; Drogos, Lauren; Erickson, Kirk I; Eskes, Gail A; Poulin, Marc J

    2016-08-15

    The rise in incidence of age-related cognitive impairment is a global health concern. Ageing is associated with a number of changes in the brain that, collectively, contribute to the declines in cognitive function observed in older adults. Structurally, the ageing brain atrophies as white and grey matter volumes decrease. Oxidative stress and inflammation promote endothelial dysfunction thereby hampering cerebral perfusion and thus delivery of energy substrates and nutrients. Further, the development of amyloid plaques and neurofibrillary tangles contributes to neuronal loss. Of interest, there are substantial inter-individual differences in the degree to which these physical and functional changes impact upon cognitive function as we grow older. This review describes how engaging in physical activity and cognitive activities and adhering to a Mediterranean style diet promote 'brain health'. From a physiological perspective, we discuss the effects of these modifiable lifestyle behaviours on the brain, and how some recent human trials are beginning to show some promise as to the effectiveness of lifestyle behaviours in combating cognitive impairment. Moreover, we propose that these lifestyle behaviours, through numerous mechanisms, serve to increase brain, cerebrovascular and cognitive reserve, thereby preserving and enhancing cognitive function for longer.

  9. Distinct Brain and Behavioral Benefits from Cognitive vs. Physical Training: A Randomized Trial in Aging Adults.

    PubMed

    Chapman, Sandra B; Aslan, Sina; Spence, Jeffrey S; Keebler, Molly W; DeFina, Laura F; Didehbani, Nyaz; Perez, Alison M; Lu, Hanzhang; D'Esposito, Mark

    2016-01-01

    Insidious declines in normal aging are well-established. Emerging evidence suggests that non-pharmacological interventions, specifically cognitive and physical training, may counter diminishing age-related cognitive and brain functions. This randomized trial compared effects of two training protocols: cognitive training (CT) vs. physical training (PT) on cognition and brain function in adults 56-75 years. Sedentary participants (N = 36) were randomized to either CT or PT group for 3 h/week over 12 weeks. They were assessed at baseline-, mid-, and post-training using neurocognitive, MRI, and physiological measures. The CT group improved on executive function whereas PT group's memory was enhanced. Uniquely deploying cerebral blood flow (CBF) and cerebral vascular reactivity (CVR) MRI, the CT cohort showed increased CBF within the prefrontal and middle/posterior cingulate cortex (PCC) without change to CVR compared to PT group. Improvements in complex abstraction were positively associated with increased resting CBF in dorsal anterior cingulate cortex (dACC). Exercisers with higher CBF in hippocampi bilaterally showed better immediate memory. The preliminary evidence indicates that increased cognitive and physical activity improves brain health in distinct ways. Reasoning training enhanced frontal networks shown to be integral to top-down cognitive control and brain resilience. Evidence of increased resting CBF without changes to CVR implicates increased neural health rather than improved vascular response. Exercise did not improve cerebrovascular response, although CBF increased in hippocampi of those with memory gains. Distinct benefits incentivize testing effectiveness of combined protocols to strengthen brain health. PMID:27462210

  10. Promoting brain health through exercise and diet in older adults: a physiological perspective.

    PubMed

    Jackson, Philippa A; Pialoux, Vincent; Corbett, Dale; Drogos, Lauren; Erickson, Kirk I; Eskes, Gail A; Poulin, Marc J

    2016-08-15

    The rise in incidence of age-related cognitive impairment is a global health concern. Ageing is associated with a number of changes in the brain that, collectively, contribute to the declines in cognitive function observed in older adults. Structurally, the ageing brain atrophies as white and grey matter volumes decrease. Oxidative stress and inflammation promote endothelial dysfunction thereby hampering cerebral perfusion and thus delivery of energy substrates and nutrients. Further, the development of amyloid plaques and neurofibrillary tangles contributes to neuronal loss. Of interest, there are substantial inter-individual differences in the degree to which these physical and functional changes impact upon cognitive function as we grow older. This review describes how engaging in physical activity and cognitive activities and adhering to a Mediterranean style diet promote 'brain health'. From a physiological perspective, we discuss the effects of these modifiable lifestyle behaviours on the brain, and how some recent human trials are beginning to show some promise as to the effectiveness of lifestyle behaviours in combating cognitive impairment. Moreover, we propose that these lifestyle behaviours, through numerous mechanisms, serve to increase brain, cerebrovascular and cognitive reserve, thereby preserving and enhancing cognitive function for longer. PMID:27524792

  11. Better Glasgow outcome score, cerebral perfusion pressure and focal brain oxygenation in severely traumatized brain following direct regional brain hypothermia therapy: A prospective randomized study

    PubMed Central

    Idris, Zamzuri; Zenian, Mohd Sofan; Muzaimi, Mustapha; Hamid, Wan Zuraida Wan Abdul

    2014-01-01

    Background: Induced hypothermia for treatment of traumatic brain injury is controversial. Since many pathways involved in the pathophysiology of secondary brain injury are temperature dependent, regional brain hypothermia is thought capable to mitigate those processes. The objectives of this study are to assess the therapeutic effects and complications of regional brain cooling in severe head injury with Glasgow coma scale (GCS) 6-7. Materials and Methods: A prospective randomized controlled pilot study involving patients with severe traumatic brain injury with GCS 6 and 7 who required decompressive craniectomy. Patients were randomized into two groups: Cooling and no cooling. For the cooling group, analysis was made by dividing the group into mild and deep cooling. Brain was cooled by irrigating the brain continuously with cold Hartmann solution for 24-48 h. Main outcome assessments were a dichotomized Glasgow outcome score (GOS) at 6 months posttrauma. Results: A total of 32 patients were recruited. The cooling-treated patients did better than no cooling. There were 63.2% of patients in cooling group attained good GOS at 6 months compared to only 15.4% in noncooling group (P = 0.007). Interestingly, the analysis at 6 months post-trauma disclosed mild-cooling-treated patients did better than no cooling (70% vs. 15.4% attained good GOS, P = 0.013) and apparently, the deep-cooling-treated patients failed to be better than either no cooling (P = 0.074) or mild cooling group (P = 0.650). Conclusion: Data from this pilot study imply direct regional brain hypothermia appears safe, feasible and maybe beneficial in treating severely head-injured patients. PMID:25685201

  12. Protein carbonylation after traumatic brain injury: cell specificity, regional susceptibility, and gender differences.

    PubMed

    Lazarus, Rachel C; Buonora, John E; Jacobowitz, David M; Mueller, Gregory P

    2015-01-01

    Protein carbonylation is a well-documented and quantifiable consequence of oxidative stress in several neuropathologies, including multiple sclerosis, Alzheimer׳s disease, and Parkinson׳s disease. Although oxidative stress is a hallmark of traumatic brain injury (TBI), little work has explored the specific neural regions and cell types in which protein carbonylation occurs. Furthermore, the effect of gender on protein carbonylation after TBI has not been studied. The present investigation was designed to determine the regional and cell specificity of TBI-induced protein carbonylation and how this response to injury is affected by gender. Immunohistochemistry was used to visualize protein carbonylation in the brains of adult male and female Sprague-Dawley rats subjected to controlled cortical impact (CCI) as an injury model of TBI. Cell-specific markers were used to colocalize the presence of carbonylated proteins in specific cell types, including astrocytes, neurons, microglia, and oligodendrocytes. Results also indicated that the injury lesion site, ventral portion of the dorsal third ventricle, and ventricular lining above the median eminence showed dramatic increases in protein carbonylation after injury. Specifically, astrocytes and limited regions of ependymal cells adjacent to the dorsal third ventricle and the median eminence were most susceptible to postinjury protein carbonylation. However, these patterns of differential susceptibility to protein carbonylation were gender dependent, with males showing significantly greater protein carbonylation at sites distant from the lesion. Proteomic analyses were also conducted and determined that the proteins most affected by carbonylation in response to TBI include glial fibrillary acidic protein, dihydropyrimidase-related protein 2, fructose-bisphosphate aldolase C, and fructose-bisphosphate aldolase A. Many other proteins, however, were not carbonylated by CCI. These findings indicate that there is both regional

  13. Protein carbonylation after traumatic brain injury: cell specificity, regional susceptibility, and gender differences.

    PubMed

    Lazarus, Rachel C; Buonora, John E; Jacobowitz, David M; Mueller, Gregory P

    2015-01-01

    Protein carbonylation is a well-documented and quantifiable consequence of oxidative stress in several neuropathologies, including multiple sclerosis, Alzheimer׳s disease, and Parkinson׳s disease. Although oxidative stress is a hallmark of traumatic brain injury (TBI), little work has explored the specific neural regions and cell types in which protein carbonylation occurs. Furthermore, the effect of gender on protein carbonylation after TBI has not been studied. The present investigation was designed to determine the regional and cell specificity of TBI-induced protein carbonylation and how this response to injury is affected by gender. Immunohistochemistry was used to visualize protein carbonylation in the brains of adult male and female Sprague-Dawley rats subjected to controlled cortical impact (CCI) as an injury model of TBI. Cell-specific markers were used to colocalize the presence of carbonylated proteins in specific cell types, including astrocytes, neurons, microglia, and oligodendrocytes. Results also indicated that the injury lesion site, ventral portion of the dorsal third ventricle, and ventricular lining above the median eminence showed dramatic increases in protein carbonylation after injury. Specifically, astrocytes and limited regions of ependymal cells adjacent to the dorsal third ventricle and the median eminence were most susceptible to postinjury protein carbonylation. However, these patterns of differential susceptibility to protein carbonylation were gender dependent, with males showing significantly greater protein carbonylation at sites distant from the lesion. Proteomic analyses were also conducted and determined that the proteins most affected by carbonylation in response to TBI include glial fibrillary acidic protein, dihydropyrimidase-related protein 2, fructose-bisphosphate aldolase C, and fructose-bisphosphate aldolase A. Many other proteins, however, were not carbonylated by CCI. These findings indicate that there is both regional

  14. Long-chain n-3 PUFAs from fish oil enhance resting state brain glucose utilization and reduce anxiety in an adult nonhuman primate, the grey mouse lemur.

    PubMed

    Pifferi, Fabien; Dorieux, Olène; Castellano, Christian-Alexandre; Croteau, Etienne; Masson, Marie; Guillermier, Martine; Van Camp, Nadja; Guesnet, Philippe; Alessandri, Jean-Marc; Cunnane, Stephen; Dhenain, Marc; Aujard, Fabienne

    2015-08-01

    Decreased brain content of DHA, the most abundant long-chain n-3 polyunsaturated fatty acid (n-3 LCPUFA) in the brain, is accompanied by severe neurosensorial impairments linked to impaired neurotransmission and impaired brain glucose utilization. In the present study, we hypothesized that increasing n-3 LCPUFA intake at an early age may help to prevent or correct the glucose hypometabolism observed during aging and age-related cognitive decline. The effects of 12 months' supplementation with n-3 LCPUFA on brain glucose utilization assessed by positron emission tomography was tested in young adult mouse lemurs (Microcebus murinus). Cognitive function was tested in parallel in the same animals. Lemurs supplemented with n-3 LCPUFA had higher brain glucose uptake and cerebral metabolic rate of glucose compared with controls in all brain regions. The n-3 LCPUFA-supplemented animals also had higher exploratory activity in an open-field task and lower evidence of anxiety in the Barnes maze. Our results demonstrate for the first time in a nonhuman primate that n-3 LCPUFA supplementation increases brain glucose uptake and metabolism and concomitantly reduces anxiety. PMID:26063461

  15. Facilitation of learning after lesions of the tuberomammillary nucleus region in adult and aged rats.

    PubMed

    Frisch, C; Hasenöhrl, R U; Haas, H L; Weiler, H T; Steinbusch, H W; Huston, J P

    1998-02-01

    The tuberomammillary nucleus (TM) located in the posterior part of the hypothalamus is the main source of neuronal histamine in the central nervous system. Recent work from our laboratories has indicated an involvement of the TM region in neuronal plasticity and reinforcement processes. In the present study, we investigated the effects of TM lesions on the performance of adult and aged Wistar rats in a set of learning tasks, which differed in terms of complexity and reward contingencies (habituation learning, inhibitory avoidance, discrimination learning, Morris water maze). An improvement was found in every test applied, indicating that TM lesions seem to generally enhance learning and memory capacities independent of the special demands of a given task. Age-related learning deficits were strongly diminished. Immunohistochemistry revealed that the excitotoxic lesions used to destroy the TM region led to a marked decrease in the number of histamine-positive neurons in the vicinity of the injection site, indicating an involvement of the brain histaminergic system in the observed behavioral changes.

  16. Effects of physical exercise on central nervous system functions: a review of brain region specific adaptations.

    PubMed

    Morgan, Julie A; Corrigan, Frances; Baune, Bernhard T

    2015-01-01

    Pathologies of central nervous system (CNS) functions are involved in prevalent conditions such as Alzheimer's disease, depression, and Parkinson's disease. Notable pathologies include dysfunctions of circadian rhythm, central metabolism, cardiovascular function, central stress responses, and movement mediated by the basal ganglia. Although evidence suggests exercise may benefit these conditions, the neurobiological mechanisms of exercise in specific brain regions involved in these important CNS functions have yet to be clarified. Here we review murine evidence about the effects of exercise on discrete brain regions involved in important CNS functions. Exercise effects on circadian rhythm, central metabolism, cardiovascular function, stress responses in the brain stem and hypothalamic pituitary axis, and movement are examined. The databases Pubmed, Web of Science, and Embase were searched for articles investigating regional brain adaptations to exercise. Brain regions examined included the brain stem, hypothalamus, and basal ganglia. We found evidence of multiple regional adaptations to both forced and voluntary exercise. Exercise can induce molecular adaptations in neuronal function in many instances. Taken together, these findings suggest that the regional physiological adaptations that occur with exercise could constitute a promising field for elucidating molecular and cellular mechanisms of recovery in psychiatric and neurological health conditions.

  17. Adult rodent neurogenic regions: the ventricular subependyma contains neural stem cells, but the dentate gyrus contains restricted progenitors.

    PubMed

    Seaberg, Raewyn M; van der Kooy, Derek

    2002-03-01

    Neurogenesis persists in two adult brain regions: the ventricular subependyma and the subgranular cell layer in the hippocampal dentate gyrus (DG). Previous work in many laboratories has shown explicitly that multipotential, self-renewing stem cells in the subependyma are the source of newly generated migrating neurons that traverse the rostral migratory stream and incorporate into the olfactory bulb as interneurons. These stem cells have been specifically isolated from the subependyma, and their properties of self-renewal and multipotentiality have been demonstrated in vitro. In contrast, it is a widely held assumption that the "hippocampal" stem cells that can be isolated in vitro from adult hippocampus reside in the neurogenic subgranular layer and represent the source of new granule cell neurons, but this has never been tested directly. Primary cell isolates derived from the precise microdissection of adult rodent neurogenic regions were compared using two very different commonly used culture methods: a clonal colony-forming (neurosphere) assay and a monolayer culture system. Importantly, both of these culture methods generated the same conclusion: stem cells can be isolated from hippocampus-adjacent regions of subependyma, but the adult DG proper does not contain a population of resident neural stem cells. Indeed, although the lateral ventricle and other ventricular subependymal regions directly adjacent to the hippocampus contain neural stem cells that exhibit long-term self-renewal and multipotentiality, separate neuronal and glial progenitors with limited self-renewal capacity are present in the adult DG, suggesting that neuron-specific progenitors and not multipotential stem cells are the source of newly generated DG neurons throughout adulthood.

  18. Regional distribution of sultopride and sulpiride in rat brain measured by radioimmunoassay.

    PubMed

    Mizuchi, A; Kitagawa, N; Miyachi, Y

    1983-01-01

    Sensitive and specific radioimmunoassays for both sultopride and sulpiride were developed. Using these radioimmunoassays, the regional distributions of sultopride and sulpiride in rat brain after intraperitoneal administration were investigated. Although relatively small amounts of both drugs were detected in the brain, sultopride appears to pass the blood-brain barrier more easily than sulpiride. Relatively high concentrations of sultopride were seen in hypothalamus, striatum, the mesolimbic area and hippocampus, while sulpiride accumulated mainly in brain areas such as hypothalamus, medulla oblongata and cerebellum, where the blood-brain barrier is less effective. Both drugs seem to be concentrated by the pituitary and pineal body. These differences between sultopride and sulpiride in penetration to the brain may depend on their different lipid solubilities, since sultopride has a higher lipid solubility compared with sulpiride.

  19. Potent, stereoselective, and brain region selective modulation of second messengers in the rat brain by (+)LY354740, a novel group II metabotropic glutamate receptor agonist.

    PubMed

    Schoepp, D D; Johnson, B G; Wright, R A; Salhoff, C R; Monn, J A

    1998-08-01

    LY354740 is a highly potent and selective agonist for recombinant Group II mGlu receptors (mGlu2 and mGlu3), which has anxiolytic and drug withdrawal alleviating properties when administered systemically in rats and mice. The modulation of second messengers by LY354740 in rat brain tissues was investigated to understand the cellular basis for the pharmacological and potential therapeutic actions of LY354740. LY354740 potently decreased forskolin-stimulated cAMP formation in slices of the adult rat hippocampus (EC50=22+/-3 nM) in a stereoselective manner. LY354740 (at 1 microM) greatly (>90%) suppressed forskolin-stimulated cAMP in the cerebral cortex, hippocampus, and striatum, while producing only partial suppression (about 50%) in midbrain regions and olfactory bulb, and no significant cAMP alterations in the cerebellum and brainstem regions. Inhibition of forskolin-stimulated cAMP formation was antagonized by (+)-alpha(-methyl-4-carboxyphenylglycine [(+)MCPG], a competitive mGlu receptor antagonist. LY354740 did not alter phosphoinositide hydrolysis in the rat hippocampus per se, but potentiated stimulation of phophoinositide hydrolysis by the Group I mGlu receptor selective agonist 3,5-dihydroxyphenylglycine (DHPG) or stimulation of cAMP formation by the adenosine receptor agonist 5'-N-ethylcarboxamideoadenosine (NECA). These data indicate that LY354740 is a highly potent, efficacious, and selective Group II mGlu receptor (mGlu 2/3) agonist in the rat brain. The potent, stereoselective, and brain region selective actions of LY354740 on mGlu receptor linked second messenger systems likely underlie the in vivo potency and stereoselectivity of this compound in animal models. PMID:9750002

  20. Perfumers' expertise induces structural reorganization in olfactory brain regions.

    PubMed

    Delon-Martin, Chantal; Plailly, Jane; Fonlupt, Pierre; Veyrac, Alexandra; Royet, Jean-Pierre

    2013-03-01

    The human brain's ability to adapt to environmental changes is obvious in specific sensory domains of experts, and olfaction is one of the least investigated senses. As we have previously demonstrated that olfactory expertise is related to functional brain modifications, we investigated here whether olfactory expertise is also coupled with structural changes. We used voxel-based morphometry to compare the gray-matter volume in student and professional perfumers, as well as untrained control subjects, and accounted for all methodological improvements that have been recently developed to limit possible errors associated with image processing. In all perfumers, we detected an increase in gray-matter volume in the bilateral gyrus rectus/medial orbital gyrus (GR/MOG), an orbitofrontal area that surrounds the olfactory sulcus. In addition, gray-matter volume in the anterior PC and left GR/MOG was positively correlated with experience in professional perfumers. We concluded that the acute olfactory knowledge acquired through extensive olfactory training leads to the structural reorganization of olfactory brain areas.

  1. Global differential expression of genes located in the Down Syndrome Critical Region in normal human brain

    PubMed Central

    Montoya, Julio Cesar; Fajardo, Dianora; Peña, Angela; Sánchez, Adalberto; Domínguez, Martha C; Satizábal, José María

    2014-01-01

    Background: The information of gene expression obtained from databases, have made possible the extraction and analysis of data related with several molecular processes involving not only in brain homeostasis but its disruption in some neuropathologies; principally in Down syndrome and the Alzheimer disease. Objective: To correlate the levels of transcription of 19 genes located in the Down Syndrome Critical Region (DSCR) with their expression in several substructures of normal human brain. Methods: There were obtained expression profiles of 19 DSCR genes in 42 brain substructures, from gene expression values available at the database of the human brain of the Brain Atlas of the Allen Institute for Brain Sciences", (http://human.brain-map.org/). The co-expression patterns of DSCR genes in brain were calculated by using multivariate statistical methods. Results: Highest levels of gene expression were registered at caudate nucleus, nucleus accumbens and putamen among central areas of cerebral cortex. Increased expression levels of RCAN1 that encode by a protein involved in signal transduction process of the CNS were recorded for PCP4 that participates in the binding to calmodulin and TTC3; a protein that is associated with differentiation of neurons. That previously identified brain structures play a crucial role in the learning process, in different class of memory and in motor skills. Conclusion: The precise regulation of DSCR gene expression is crucial to maintain the brain homeostasis, especially in those areas with high levels of gene expression associated with a remarkable process of learning and cognition. PMID:25767303

  2. Epigenetic Gene Regulation in the Adult Mammalian Brain: Multiple roles in Memory Formation

    PubMed Central

    Lubin, Farah D.

    2011-01-01

    Brain-derived neurotrophic factor (bdnf) is one of numerous gene products necessary for long-term memory formation and dysregulation of bdnf has been implicated in the pathogenesis of cognitive and mental disorders. Recent work indicates that epigenetic-regulatory mechanisms including the markings of histone proteins and associated DNA remain labile throughout the lifespan and represent an attractive molecular process contributing to gene regulation in the brain. In this review, important information will be discussed on epigenetics as a set of newly identified dynamic transcriptional mechanisms serving to regulate gene expression changes in the adult brain with particular emphasis on bdnf transcriptional readout in learning and memory formation. This review will also highlight evidence for the role of epigenetics in aberrant bdnf gene regulation in the pathogenesis of cognitive dysfunction associated with seizure disorders, Rett syndrome, Schizophrenia, and Alzheimer’s disease. Such research offers novel concepts for understanding epigenetic transcriptional mechanisms subserving adult cognition and mental health, and furthermore promises novel avenues for therapeutic approach in the clinic. PMID:21419233

  3. Acquisition of Visual Perception in Blind Adults Using the BrainPort Artificial Vision Device

    PubMed Central

    Pintar, Christine; Arnoldussen, Aimee; Fisher, Christopher

    2015-01-01

    OBJECTIVE. We sought to determine whether intensive low vision rehabilitation would confer any functional improvement in a sample of blind adults using the BrainPort artificial vision device. METHOD. Eighteen adults ages 28–69 yr (n = 10 men and n = 8 women) who had light perception only or worse vision bilaterally spent up to 6 hr per day for 1 wk undergoing structured rehabilitation interventions. The functional outcomes of object identification and word recognition were tested at baseline and after rehabilitation training. RESULTS. At baseline, participants were unable to complete the two functional assessments. After participation in the 1-wk training protocol, participants were able to use the BrainPort device to complete the two tasks with moderate success. CONCLUSION. Without training, participants were not able to perform above chance level using the BrainPort device. As artificial vision technologies become available, occupational therapy practitioners can play a key role in clients’ success or failure in using these devices. PMID:25553750

  4. Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

    SciTech Connect

    Schindler, Matthew K. Forbes, M. Elizabeth; Robbins, Mike E.; Riddle, David R.

    2008-03-01

    Purpose: To assess the impact of aging on the radiation response in the adult rat brain. Methods and Materials: Male rats 8, 18, or 28 months of age received a single 10-Gy dose of whole-brain irradiation (WBI). The hippocampal dentate gyrus was analyzed 1 and 10 weeks later for sensitive neurobiologic markers associated with radiation-induced damage: changes in density of proliferating cells, immature neurons, total microglia, and activated microglia. Results: A significant decrease in basal levels of proliferating cells and immature neurons and increased microglial activation occurred with normal aging. The WBI induced a transient increase in proliferation that was greater in older animals. This proliferation response did not increase the number of immature neurons, which decreased after WBI in young rats, but not in old rats. Total microglial numbers decreased after WBI at all ages, but microglial activation increased markedly, particularly in older animals. Conclusions: Age is an important factor to consider when investigating the radiation response of the brain. In contrast to young adults, older rats show no sustained decrease in number of immature neurons after WBI, but have a greater inflammatory response. The latter may have an enhanced role in the development of radiation-induced cognitive dysfunction in older individuals.

  5. Effects of cerebrospinal fluid proteins on brain atrophy rates in cognitively healthy older adults.

    PubMed

    Mattsson, Niklas; Insel, Philip; Nosheny, Rachel; Trojanowski, John Q; Shaw, Leslie M; Jack, Clifford R; Tosun, Duygu; Weiner, Michael

    2014-03-01

    Biomarkers associated with Alzheimer's disease (AD)-like brain atrophy in healthy individuals may identify mechanisms involved in early stage AD. Aside from cerebrospinal fluid (CSF) β-amyloid42 (Aβ42) and tau, no studies have tested associations between CSF proteins and AD-like brain atrophy. We studied 90 healthy elders, who underwent lumbar puncture at baseline, and serial magnetic resonance imaging scans for up to 4 years. We tested statistical effects of baseline CSF proteins (N = 70 proteins related to Aβ42-metabolism, microglial activity, and synaptic/neuronal function) on atrophy rates in 7 AD-related regions. Besides the effects of Aβ42 and phosphorylated tau (P-tau) that were seen in several regions, novel CSF proteins were found to have effects in inferior and middle temporal cortex (including apolipoprotein CIII, apolipoprotein D, and apolipoprotein H). Several proteins (including S100β and matrix metalloproteinase-3) had effects that depended on the presence of brain Aβ pathology, as measured by CSF Aβ42. Other proteins (including P-tau and apolipoprotein D) had effects even after adjusting for CSF Aβ42. The statistical effects in this exploratory study were mild and not significant after correction for multiple comparisons, but some of the identified proteins may be associated with brain atrophy in healthy persons. Proteins interacting with CSF Aβ42 may be related to Aβ brain pathology, whereas proteins associated with atrophy even after adjusting for CSF Aβ42 may be related to Aβ-independent mechanisms.

  6. Acute stress differentially affects aromatase activity in specific brain nuclei of adult male and female quail.

    PubMed

    Dickens, Molly J; Cornil, Charlotte A; Balthazart, Jacques

    2011-11-01

    The rapid and temporary suppression of reproductive behavior is often assumed to be an important feature of the adaptive acute stress response. However, how this suppression operates at the mechanistic level is poorly understood. The enzyme aromatase converts testosterone to estradiol in the brain to activate reproductive behavior in male Japanese quail (Coturnix japonica). The discovery of rapid and reversible modification of aromatase activity (AA) provides a potential mechanism for fast, stress-induced changes in behavior. We investigated the effects of acute stress on AA in both sexes by measuring enzyme activity in all aromatase-expressing brain nuclei before, during, and after 30 min of acute restraint stress. We show here that acute stress rapidly alters AA in the male and female brain and that these changes are specific to the brain nuclei and sex of the individual. Specifically, acute stress rapidly (5 min) increased AA in the male medial preoptic nucleus, a region controlling male reproductive behavior; in females, a similar increase was also observed, but it appeared delayed (15 min) and had smaller amplitude. In the ventromedial and tuberal hypothalamus, regions associated with female reproductive behavior, stress induced a quick and sustained decrease in AA in females, but in males, only a slight increase (ventromedial) or no change (tuberal) in AA was observed. Effects of acute stress on brain estrogen production, therefore, represent one potential way through which stress affects reproduction.

  7. Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine.

    PubMed

    Jedynak, Paulina; Kos, Tomasz; Sandi, Carmen; Kaczmarek, Leszek; Filipkowski, Robert K

    2014-09-01

    The neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression.

  8. Organization of the histaminergic system in adult zebrafish (Danio rerio) brain: neuron number, location, and cotransmitters.

    PubMed

    Sundvik, Maria; Panula, Pertti

    2012-12-01

    Histamine is an essential factor in the ascending arousal system (AAS) during motivated behaviors. Histamine and hypocretin/orexin (hcrt) are proposed to be responsible for different aspects of arousal and wakefulness, histamine mainly for cognitive and motivated behaviors. In this study we visualized the entire histaminergic neuron population in adult male and female zebrafish brain and quantified the histaminergic neuron numbers. There were 40-45 histaminergic neurons in both male and female zebrafish brain. Further, we identified cotransmitters of histaminergic neurons in the ventrocaudal hypothalamus, i.e., around the posterior recess (PR) in adult zebrafish. Galanin, γ-aminobutyric acid (GABA), and thyrotropin-releasing hormone (TRH) were colocalized with histamine in some but not all neurons, a result that was verified by intracerebroventricular injections of colchicine into adult zebrafish. Fibers immunoreactive (ir) for galanin, GABA, TRH, or methionine-enkephalin (mENK) were dense in the ventrocaudal hypothalamus around the histaminergic neurons. In histamine-ir fibers TRH and galanin immunoreactivities were also detected in the ventral telencephalon. All these neurotransmitters are involved in maintaining the equilibrium of the sleep-wake state. Our results are in accordance with results from rats, further supporting the use of zebrafish as a tool to study molecular mechanisms underlying complex behaviors.

  9. Traumatic Brain Injury among Older Adults at Level I and II Trauma Centers

    PubMed Central

    Cuthbert, Jeffrey P.; Whyte, John; Corrigan, John D.; Faul, Mark; Harrison-Felix, Cynthia

    2013-01-01

    Abstract Individuals 65 years of age and over have the highest rates of traumatic brain injury (TBI)-related hospitalizations and deaths, and older adults (defined variably across studies) have particularly poor outcomes after TBI. The factors predicting these outcomes remain poorly understood, and age-specific care guidelines for TBI do not exist. This study provides an overview of TBI in older adults using data from the National Trauma Data Bank (NTDB) gathered between 2007 and 2010, evaluates age group-specific trends in rates of TBI over time using U.S. Census data, and examines whether routinely collected information is able to predict hospital discharge status among older adults with TBI in the NTDB. Results showed a 20–25% increase in trauma center admissions for TBI among the oldest age groups (those >=75 years), relative to the general population, between 2007 and 2010. Older adults (>=65 years) with TBI tended to be white females who have incurred an injury from a fall resulting in a “severe” Abbreviated Injury Scale (AIS) score of the head. Older adults had more in-hospital procedures, such as neuroimaging and neurosurgery, tended to experience longer hospital stays, and were more likely to require continued medical care than younger adults. Older age, injury severity, and hypotension increased the odds of in-hospital death. The public health burden of TBI among older adults will likely increase as the Baby Boom generation ages. Improved primary and secondary prevention of TBI in this cohort is needed. PMID:23962046

  10. Cognitive functioning in relation to brain amyloid-β in healthy adults with Down syndrome.

    PubMed

    Hartley, Sigan L; Handen, Benjamin L; Devenny, Darlynne A; Hardison, Regina; Mihaila, Iulia; Price, Julie C; Cohen, Annie D; Klunk, William E; Mailick, Marsha R; Johnson, Sterling C; Christian, Bradley T

    2014-09-01

    Nearly all adults with Down syndrome show neuropathology of Alzheimer's disease, including amyloid-β deposition, by their fifth decade of life. In the current study, we examined the association between brain amyloid-β deposition, assessed via in vivo assessments of neocortical Pittsburgh compound B, and scores on an extensive neuropsychological battery of measures of cognitive functioning in 63 adults (31 male, 32 female) with Down syndrome aged 30-53 years who did not exhibit symptoms of dementia. Twenty-two of the adults with Down syndrome were identified as having elevated neocortical Pittsburgh compound B retention levels. There was a significant positive correlation (r = 0.62, P < 0.0001) between age and neocortical Pittsburgh compound B retention. This robust association makes it difficult to discriminate normative age-related decline in cognitive functioning from any potential effects of amyloid-β deposition. When controlling for chronological age in addition to mental age, there were no significant differences between the adults with Down syndrome who had elevated neocortical Pittsburgh compound B retention levels and those who did not on any of the neuropsychological measures. Similarly, when examining Pittsburgh compound B as a continuous variable, after controlling for mental age and chronological age, only the Rivermead Picture Recognition score was significantly negatively associated with neocortical Pittsburgh compound B retention. Our findings indicate that many adults with Down syndrome can tolerate amyloid-β deposition without deleterious effects on cognitive functioning. However, we may have obscured true effects of amyloid-β deposition by controlling for chronological age in our analyses. Moreover, our sample included adults with Down syndrome who were most 'resistant' to the effects of amyloid-β deposition, as adults already exhibiting clinical symptoms of dementia symptoms were excluded from the study.

  11. Mapping brain region activity during chewing: a functional magnetic resonance imaging study.

    PubMed

    Onozuka, M; Fujita, M; Watanabe, K; Hirano, Y; Niwa, M; Nishiyama, K; Saito, S

    2002-11-01

    Mastication has been suggested to increase neuronal activities in various regions of the human brain. However, because of technical difficulties, the fine anatomical and physiological regions linked to mastication have not been fully elucidated. Using functional magnetic resonance imaging during cycles of rhythmic gum-chewing and no chewing, we therefore examined the interaction between chewing and brain regional activity in 17 subjects (aged 20-31 years). In all subjects, chewing resulted in a bilateral increase in blood oxygenation level-dependent (BOLD) signals in the sensorimotor cortex, supplementary motor area, insula, thalamus, and cerebellum. In addition, in the first three regions, chewing of moderately hard gum produced stronger BOLD signals than the chewing of hard gum. However, the signal was higher in the cerebellum and not significant in the thalamus, respectively. These results suggest that chewing causes regional increases in brain neuronal activities which are related to biting force.

  12. Distinct representations of configural and part information across multiple face-selective regions of the human brain

    PubMed Central

    Golarai, Golijeh; Ghahremani, Dara G.; Eberhardt, Jennifer L.; Gabrieli, John D. E.

    2015-01-01

    Several regions of the human brain respond more strongly to faces than to other visual stimuli, such as regions in the amygdala (AMG), superior temporal sulcus (STS), and the fusiform face area (FFA). It is unclear if these brain regions are similar in representing the configuration or natural appearance of face parts. We used functional magnetic resonance imaging of healthy adults who viewed natural or schematic faces with internal parts that were either normally configured or randomly rearranged. Response amplitudes were reduced in the AMG and STS when subjects viewed stimuli whose configuration of parts were digitally rearranged, suggesting that these regions represent the 1st order configuration of face parts. In contrast, response amplitudes in the FFA showed little modulation whether face parts were rearranged or if the natural face parts were replaced with lines. Instead, FFA responses were reduced only when both configural and part information were reduced, revealing an interaction between these factors, suggesting distinct representation of 1st order face configuration and parts in the AMG and STS vs. the FFA. PMID:26594191

  13. Localizing Brain Regions Associated with Female Mate Preference Behavior in a Swordtail

    PubMed Central

    Wong, Ryan Y.; Ramsey, Mary E.; Cummings, Molly E.

    2012-01-01

    Female mate choice behavior is a critical component of sexual selection, yet identifying the neural basis of this behavior is largely unresolved. Previous studies have implicated sensory processing and hypothalamic brain regions during female mate choice and there is a conserved network of brain regions (Social Behavior Network, SBN) that underlies sexual behaviors. However, we are only beginning to understand the role this network has in pre-copulatory female mate choice. Using in situ hybridization, we identify brain regions associated with mate preference in female Xiphophorus nigrensis, a swordtail species with a female choice mating system. We measure gene expression in 10 brain regions (linked to sexual behavior, reward, sensory integration or other processes) and find significant correlations between female preference behavior and gene expression in two telencephalic areas associated with reward, learning and multi-sensory processing (medial and lateral zones of the dorsal telencephalon) as well as an SBN region traditionally associated with sexual response (preoptic area). Network analysis shows that these brain regions may also be important in mate preference and that correlated patterns of neuroserpin expression between regions co-vary with differential compositions of the mate choice environment. Our results expand the emerging network for female preference from one that focused on sensory processing and midbrain sexual response centers to a more complex coordination involving forebrain areas that integrate primary sensory processing and reward. PMID:23209722

  14. Evidence of altered DNA integrity in the brain regions of suicidal victims of Bipolar Depression

    PubMed Central

    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.

    2010-01-01

    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. PMID:21180406

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

    PubMed

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

    2015-01-01

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

  16. Differential oxidative stress and DNA damage in rat brain regions and blood following chronic arsenic exposure.

    PubMed

    Mishra, D; Flora, S J S

    2008-05-01

    Chronic arsenic poisoning caused by contaminated drinking water is a wide spread and worldwide problem particularly in India and Bangladesh. One of the possible mechanisms suggested for arsenic toxicity is the generation of reactive oxygen species (ROS). The present study was planned 1) to evaluate if chronic exposure to arsenic leads to oxidative stress in blood and brain - parts of male Wistar rats and 2) to evaluate which brain region of the exposed animals was more sensitive to oxidative injury. Male Wistar rats were exposed to arsenic (50A ppm sodium arsenite in drinking water) for 10A months. The brain was dissected into five major parts, pons medulla, corpus striatum, cortex, hippocampus, and cerebellum. A number of biochemical variables indicative of oxidative stress were studied in blood and different brain regions. Single-strand DNA damage using comet assay was also assessed in lymphocytes. We observed a significant increase in blood and brain ROS levels accompanied by the depletion of GSH/GSSG ratio and glucose-6-phosphate dehydrogenase (G6PD) activity in different brain regions of arsenic-exposed rats. Chronic arsenic exposure also caused significant single-strand DNA damage in lymphocytes as depicted by comet with a tail in arsenic-exposed cells compared with the control cells. On the basis of results, we concluded that the cortex region of the brain was more sensitive to oxidative injury compared with the other regions studied. The present study, thus, leads us to suggest that arsenic induces differential oxidative stress in brain regions with cortex followed by hippocampus and causes single-strand DNA damage in lymphocytes.

  17. Effect of centrophenoxine on the antioxidative enzymes in various regions of the aging rat brain.

    PubMed

    Roy, D; Pathak, D N; Singh, R

    1983-01-01

    This study investigated the effect (in vivo) of centrophenoxine (Helfergin) on the activity of antioxidant enzymes (glutathione peroxidase GSH-PER, glutathione reductase GSSG-RED, superoxide dismutase SOD and catalase) in subcellular fractions from the regions of the brain (cerebrum, cerebellum and brain stem) of rats aged 6, 9 and 12 months. In all age groups, normal (control) activity of GSH-PER, GSSG-RED and SOD in the three brain regions was higher in the soluble fractions than in the particulate fractions. The three regions of the brain showed different levels of the enzyme activities. Enzymes in soluble fractions (except GSSG-RED in cerebrum of rats aged 12 months) did not change with age. In particulate fractions, however, the enzymes showed age-related changes: GSH-PER decreased with age in cerebellum and brain stem, but showed an age-related increase in cerebrum, GSSG-RED and SOD increased with age in all the three brain regions. Catalase activity in all the three brain regions remained unchanged in all age groups. Six week administration of centrophenoxine (once a day in doses of 80 mg/Kg and 120 mg/Kg) to the experimental animals produced increases in the activity of SOD, GSH-PER and GSSG-RED in particulate fractions from all the three brain regions. In the soluble fractions, however, only SOD and GSH-PER activity was increased. In vitro also centrophenoxine stimulated the activity of GSH-PER. A dosage of 80 mg/Kg produced greater changes than a 120 mg/Kg dosage. The drug had no effect on the activity of catalase. Centrophenoxine also reduced lipofuscin deposits (studied both biochemically and histochemically) thus indicating that the drug inhibited lipofuscin accumulation by elevating the activity of the antioxidant enzymes. The data suggest that alleviation of senescence by centrophenoxine may, at least, partly be due to activation by it of antioxidant enzymes.

  18. Regional Distribution of Copper, Zinc and Iron in Brain of Wistar Rat Model for Non-Wilsonian Brain Copper Toxicosis.

    PubMed

    Pal, Amit; Prasad, Rajendra

    2016-03-01

    In previous studies, we have reported first in vivo evidence of copper deposition in the choroid plexus, cognitive impairments, astrocytes swelling (Alzheimer type II cells) and astrogliosis (increase in number of astrocytes), and degenerated neurons coupled with significant increase in the hippocampus copper and zinc content in copper-intoxicated Wistar rats. Nonetheless, hippocampus iron levels were not affected by chronic copper-intoxication. Notwithstanding information on distribution of copper, zinc and iron status in different regions of brain due to chronic copper exposure remains fragmentary. In continuation with our previous study, the aim of this study was to investigate the effects of intraperitoneally injected copper lactate (0.15 mg Cu/100 g body weight) daily for 90 days on copper, zinc and iron levels in different regions of the brain using atomic absorption spectrophotometry. Copper-intoxicated group showed significantly increased cortex, cerebellum and striatum copper content (76, 46.8 and 80.7 % increase, respectively) compared to control group. However, non-significant changes were observed for the zinc and iron content in cortex, cerebellum and striatum due to chronic copper exposure. In conclusion, the current study demonstrates that chronic copper toxicity causes differential copper buildup in cortex, cerebellum and striatum region of central nervous system of male Wistar rats; signifying the critical requirement to discretely evaluate the effect of copper neurotoxicity in different brain regions, and ensuing neuropathological and cognitive dysfunctions. PMID:26855494

  19. Non-coding-regulatory regions of human brain genes delineated by bacterial artificial chromosome knock-in mice

    PubMed Central

    2013-01-01

    Background The next big challenge in human genetics is understanding the 98% of the genome that comprises non-coding DNA. Hidden in this DNA are sequences critical for gene regulation, and new experimental strategies are needed to understand the functional role of gene-regulation sequences in health and disease. In this study, we build upon our HuGX ('high-throughput human genes on the X chromosome’) strategy to expand our understanding of human gene regulation in vivo. Results In all, ten human genes known to express in therapeutically important brain regions were chosen for study. For eight of these genes, human bacterial artificial chromosome clones were identified, retrofitted with a reporter, knocked single-copy into the Hprt locus in mouse embryonic stem cells, and mouse strains derived. Five of these human genes expressed in mouse, and all expressed in the adult brain region for which they were chosen. This defined the boundaries of the genomic DNA sufficient for brain expression, and refined our knowledge regarding the complexity of gene regulation. We also characterized for the first time the expression of human MAOA and NR2F2, two genes for which the mouse homologs have been extensively studied in the central nervous system (CNS), and AMOTL1 and NOV, for which roles in CNS have been unclear. Conclusions We have demonstrated the use of the HuGX strategy to functionally delineate non-coding-regulatory regions of therapeutically important human brain genes. Our results also show that a careful investigation, using publicly available resources and bioinformatics, can lead to accurate predictions of gene expression. PMID:24124870

  20. Beyond utterances: distributed cognition as a framework for studying discourse in adults with acquired brain injury.

    PubMed

    Duff, Melissa C; Mutlu, Bilge; Byom, Lindsey; Turkstra, Lyn S

    2012-02-01

    Considerable effort has been directed at understanding the nature of the communicative deficits observed in individuals with acquired brain injuries. Yet several theoretical, methodological, and clinical challenges remain. In this article, we examine distributed cognition as a framework for understanding interaction among communication partners, interaction of communication and cognition, and interaction with the environments and contexts of everyday language use. We review the basic principles of distributed cognition and the implications for applying this approach to the study of discourse in individuals with cognitive-communication disorders. We also review a range of protocols and findings from our research that highlight how the distributed cognition approach might offer a deeper understanding of communicative mechanisms and deficits in individuals with cognitive communication impairments. The advantages and implications of distributed cognition as a framework for studying discourse in adults with acquired brain injury are discussed. PMID:22362323

  1. Beyond Utterances: Distributed Cognition as a Framework for Studying Discourse in Adults with Acquired Brain Injury

    PubMed Central

    Duff, Melissa C.; Mutlu, Bilge; Byom, Lindsey; Turkstra, Lyn S.

    2014-01-01

    Considerable effort has been directed at understanding the nature of the communicative deficits observed in individuals with acquired brain injuries. Yet several theoretical, methodological, and clinical challenges remain. In this article, we examine distributed cognition as a framework for understanding interaction among communication partners, interaction of communication and cognition, and interaction with the environments and contexts of everyday language use. We review the basic principles of distributed cognition and the implications for applying this approach to the study of discourse in individuals with cognitive-communication disorders. We also review a range of protocols and findings from our research that highlight how the distributed cognition approach might offer a deeper understanding of communicative mechanisms and deficits in individuals with cognitive communication impairments. The advantages and implications of distributed cognition as a framework for studying discourse in adults with acquired brain injury are discussed. PMID:22362323

  2. Adult axolotls can regenerate original neuronal diversity in response to brain injury.

    PubMed

    Amamoto, Ryoji; Huerta, Violeta Gisselle Lopez; Takahashi, Emi; Dai, Guangping; Grant, Aaron K; Fu, Zhanyan; Arlotta, Paola

    2016-01-01

    The axolotl can regenerate multiple organs, including the brain. It remains, however, unclear whether neuronal diversity, intricate tissue architecture, and axonal connectivity can be regenerated; yet, this is critical for recovery of function and a central aim of cell replacement strategies in the mammalian central nervous system. Here, we demonstrate that, upon mechanical injury to the adult pallium, axolotls can regenerate several of the populations of neurons present before injury. Notably, regenerated neurons acquire functional electrophysiological traits and respond appropriately to afferent inputs. Despite the ability to regenerate specific, molecularly-defined neuronal subtypes, we also uncovered previously unappreciated limitations by showing that newborn neurons organize within altered tissue architecture and fail to re-establish the long-distance axonal tracts and circuit physiology present before injury. The data provide a direct demonstration that diverse, electrophysiologically functional neurons can be regenerated in axolotls, but challenge prior assumptions of functional brain repair in regenerative species. PMID:27156560

  3. Cellular distribution and localisation of iron in adult rat brain ( substantia nigra)

    NASA Astrophysics Data System (ADS)

    Meinecke, Ch.; Morawski, M.; Reinert, T.; Arendt, T.; Butz, T.

    2006-08-01

    Iron appears to be one of the main factors in the metal induced neurodegeneration. Quantitative information on cellular, sub-cellular and cell specific distributions of iron is therefore important to assess. The investigations reported here were carried out on a brain from an adult rat. Therefore, 6 μm thick embedded, unstained brain sections containing the midbrain (substantia nigra, SN) were analysed. Particle induced X-ray emission (PIXE) using a focussed proton beam (beam - diameter app. 1 μm) was performed to determine the quantitative iron content on a cellular and sub-cellular level. The integral analysis shows that the iron content in the SN pars reticulata is twice as high than in the SN pars compacta. The analysis of the iron content on the cellular level revealed no remarkable differences between glia cells and neurons. This is in contrast to other studies using staining techniques.

  4. Regional volumes in brain stem and cerebellum are associated with postural impairments in young brain-injured patients.

    PubMed

    Drijkoningen, David; Leunissen, Inge; Caeyenberghs, Karen; Hoogkamer, Wouter; Sunaert, Stefan; Duysens, Jacques; Swinnen, Stephan P

    2015-12-01

    Many patients with traumatic brain injury (TBI) suffer from postural control impairments that can profoundly affect daily life. The cerebellum and brain stem are crucial for the neural control of posture and have been shown to be vulnerable to primary and secondary structural consequences of TBI. The aim of this study was to investigate whether morphometric differences in the brain stem and cerebellum can account for impairments in static and dynamic postural control in TBI. TBI patients (n = 18) and healthy controls (n = 30) completed three challenging postural control tasks on the EquiTest® system (Neurocom). Infratentorial grey matter (GM) and white matter (WM) volumes were analyzed with cerebellum-optimized voxel-based morphometry using the spatially unbiased infratentorial toolbox. Volume loss in TBI patients was revealed in global cerebellar GM, global infratentorial WM, middle cerebellar peduncles, pons and midbrain. In the TBI group and across both groups, lower postural control performance was associated with reduced GM volume in the vermal/paravermal regions of lobules I-IV, V and VI. Moreover, across all participants, worse postural control performance was associated with lower WM volume in the pons, medulla, midbrain, superior and middle cerebellar peduncles and cerebellum. This is the first study in TBI patients to demonstrate an association between postural impairments and reduced volume in specific infratentorial brain areas. Volumetric measures of the brain stem and cerebellum may be valuable prognostic markers of the chronic neural pathology, which complicates rehabilitation of postural control in TBI.

  5. Regional volumes in brain stem and cerebellum are associated with postural impairments in young brain-injured patients.

    PubMed

    Drijkoningen, David; Leunissen, Inge; Caeyenberghs, Karen; Hoogkamer, Wouter; Sunaert, Stefan; Duysens, Jacques; Swinnen, Stephan P

    2015-12-01

    Many patients with traumatic brain injury (TBI) suffer from postural control impairments that can profoundly affect daily life. The cerebellum and brain stem are crucial for the neural control of posture and have been shown to be vulnerable to primary and secondary structural consequences of TBI. The aim of this study was to investigate whether morphometric differences in the brain stem and cerebellum can account for impairments in static and dynamic postural control in TBI. TBI patients (n = 18) and healthy controls (n = 30) completed three challenging postural control tasks on the EquiTest® system (Neurocom). Infratentorial grey matter (GM) and white matter (WM) volumes were analyzed with cerebellum-optimized voxel-based morphometry using the spatially unbiased infratentorial toolbox. Volume loss in TBI patients was revealed in global cerebellar GM, global infratentorial WM, middle cerebellar peduncles, pons and midbrain. In the TBI group and across both groups, lower postural control performance was associated with reduced GM volume in the vermal/paravermal regions of lobules I-IV, V and VI. Moreover, across all participants, worse postural control performance was associated with lower WM volume in the pons, medulla, midbrain, superior and middle cerebellar peduncles and cerebellum. This is the first study in TBI patients to demonstrate an association between postural impairments and reduced volume in specific infratentorial brain areas. Volumetric measures of the brain stem and cerebellum may be valuable prognostic markers of the chronic neural pathology, which complicates rehabilitation of postural control in TBI. PMID:26441014

  6. Myriocin, a serine palmitoyltransferase inhibitor, alters regional brain neurotransmitter levels without concurrent inhibition of the brain sphingolipid biosynthesis in mice.

    PubMed

    Osuchowski, Marcin F; Johnson, Victor J; He, Quanren; Sharma, Raghubir P

    2004-02-28

    Myriocin is a specific serine palmitoyltransferase (SPT) inhibitor whose effect on the brain is unknown. Brain amine metabolism and sphingolipid biosynthesis were studied in mice treated intraperitoneally with 0, 0.1, 0.3 or 1 mg/kg per day of myriocin for 5 days. Regional concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT, serotonin), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE), were determined. Sphinganine (Sa) and sphingosine (So) concentrations and SPT activity in brain and liver were used to evaluate the impact of myriocin on sphingolipid biosynthesis. Myriocin treatment increased DA in striatum and hippocampus and reduced it in cortex. NE concentration decreased in cerebellum and 5-HT levels were reduced in cortex and in medulla oblongata. Changes in ratios for DOPAC/DA and HVA/DA were observed in hippocampus, cortex and midbrain. Brain Sa, So and SPT activity remained unchanged, whereas Sa and SPT activity decreased in liver. Results showed that myriocin may alter the levels and metabolism of brain amines and this effect is not related with inhibition of sphingolipid biosynthesis in the nervous system. PMID:14700532

  7. An integrative analysis of regional gene expression profiles in the human brain.

    PubMed

    Myers, Emma M; Bartlett, Christopher W; Machiraju, Raghu; Bohland, Jason W

    2015-02-01

    Studies of the brain's transcriptome have become prominent in recent years, resulting in an accumulation of datasets with somewhat distinct attributes. These datasets, which are often analyzed only in isolation, also are often collected with divergent goals, which are reflected in their sampling properties. While many researchers have been interested in sampling gene expression in one or a few brain areas in a large number of subjects, recent efforts from the Allen Institute for Brain Sciences and others have focused instead on dense neuroanatomical sampling, necessarily limiting the number of individual donor brains studied. The purpose of the present work is to develop methods that draw on the complementary strengths of these two types of datasets for study of the human brain, and to characterize the anatomical specificity of gene expression profiles and gene co-expression networks derived from human brains using different specific technologies. The approach is applied using two publicly accessible datasets: (1) the high anatomical resolution Allen Human Brain Atlas (AHBA, Hawrylycz et al., 2012) and (2) a relatively large sample size, but comparatively coarse neuroanatomical dataset described previously by Gibbs et al. (2010). We found a relatively high degree of correspondence in differentially expressed genes and regional gene expression profiles across the two datasets. Gene co-expression networks defined in individual brain regions were less congruent, but also showed modest anatomical specificity. Using gene modules derived from the Gibbs dataset and from curated gene lists, we demonstrated varying degrees of anatomical specificity based on two classes of methods, one focused on network modularity and the other focused on enrichment of expression levels. Two approaches to assessing the statistical significance of a gene set's modularity in a given brain region were studied, which provide complementary information about the anatomical specificity of a gene

  8. The long-term side effects of radiation therapy for benign brain tumors in adults.

    PubMed

    al-Mefty, O; Kersh, J E; Routh, A; Smith, R R

    1990-10-01

    Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors (two of these also had pituitary dysfunction). One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered "safe" treatment for benign brain tumors.

  9. The long-term side effects of radiation therapy for benign brain tumors in adults

    SciTech Connect

    al-Mefty, O.; Kersh, J.E.; Routh, A.; Smith, R.R. )

    1990-10-01

    Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors. One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered safe treatment for benign brain tumors. 163 refs.

  10. Dual role of cerebral blood flow in regional brain temperature control in the healthy newborn infant.

    PubMed

    Iwata, Sachiko; Tachtsidis, Ilias; Takashima, Sachio; Matsuishi, Toyojiro; Robertson, Nicola J; Iwata, Osuke

    2014-10-01

    Small shifts in brain temperature after hypoxia-ischaemia affect cell viability. The main determinants of brain temperature are cerebral metabolism, which contributes to local heat production, and brain perfusion, which removes heat. However, few studies have addressed the effect of cerebral metabolism and perfusion on regional brain temperature in human neonates because of the lack of non-invasive cot-side monitors. This study aimed (i) to determine non-invasive monitoring tools of cerebral metabolism and perfusion by combining near-infrared spectroscopy and echocardiography, and (ii) to investigate the dependence of brain temperature on cerebral metabolism and perfusion in unsedated newborn infants. Thirty-two healthy newborn infants were recruited. They were studied with cerebral near-infrared spectroscopy, echocardiography, and a zero-heat flux tissue thermometer. A surrogate of cerebral blood flow (CBF) was measured using superior vena cava flow adjusted for cerebral volume (rSVC flow). The tissue oxygenation index, fractional oxygen extraction (FOE), and the cerebral metabolic rate of oxygen relative to rSVC flow (CMRO₂ index) were also estimated. A greater rSVC flow was positively associated with higher brain temperatures, particularly for superficial structures. The CMRO₂ index and rSVC flow were positively coupled. However, brain temperature was independent of FOE and the CMRO₂ index. A cooler ambient temperature was associated with a greater temperature gradient between the scalp surface and the body core. Cerebral oxygen metabolism and perfusion were monitored in newborn infants without using tracers. In these healthy newborn infants, cerebral perfusion and ambient temperature were significant independent variables of brain temperature. CBF has primarily been associated with heat removal from the brain. However, our results suggest that CBF is likely to deliver heat specifically to the superficial brain. Further studies are required to assess the

  11. Regional brain volumes and cognition in childhood epilepsy: Does size really matter?

    PubMed Central

    Zelko, Frank A.; Pardoe, Heath R.; Blackstone, Sarah R.; Jackson, Graeme D.; Berg, Anne T.

    2014-01-01

    Purpose Recent studies have correlated neurocognitive function and regional brain volumes in children with epilepsy. We tested whether brain volume differences between children with and without epilepsy explained differences in neurocognitive function. Methods The study sample included 108 individuals with uncomplicated nonsyndromic epilepsy (NSE) and 36 healthy age- and gender-matched controls. Participants received a standardized cognitive battery. Whole brain