Science.gov

Sample records for adult brain including

  1. Brain tumor - primary - adults

    MedlinePlus

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  2. 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 ...

  3. Lung Disease Including Asthma and Adult Vaccination

    MedlinePlus

    ... Healthcare Professionals Lung Disease including Asthma and Adult Vaccination Language: English Español (Spanish) Recommend on Facebook Tweet ... more about health insurance options. Learn about adult vaccination and other health conditions Asplenia Diabetes Heart Disease, ...

  4. Brain tumor - primary - adults

    MedlinePlus

    ... are best treated by a team that includes: Neuro-oncologist Neurosurgeon Medical oncologist Radiation oncologist Other health ... pdq . Accessed January 18, 2016. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): ...

  5. 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

  6. Neural repair in the adult brain

    PubMed Central

    Jessberger, Sebastian

    2016-01-01

    Acute or chronic injury to the adult brain often results in substantial loss of neural tissue and subsequent permanent functional impairment. Over the last two decades, a number of approaches have been developed to harness the regenerative potential of neural stem cells and the existing fate plasticity of neural cells in the nervous system to prevent tissue loss or to enhance structural and functional regeneration upon injury. Here, we review recent advances of stem cell-associated neural repair in the adult brain, discuss current challenges and limitations, and suggest potential directions to foster the translation of experimental stem cell therapies into the clinic. PMID:26918167

  7. Brain size and limits to adult neurogenesis.

    PubMed

    Paredes, Mercedes F; Sorrells, Shawn F; Garcia-Verdugo, Jose M; Alvarez-Buylla, Arturo

    2016-02-15

    The walls of the cerebral ventricles in the developing embryo harbor the primary neural stem cells from which most neurons and glia derive. In many vertebrates, neurogenesis continues postnatally and into adulthood in this region. Adult neurogenesis at the ventricle has been most extensively studied in organisms with small brains, such as reptiles, birds, and rodents. In reptiles and birds, these progenitor cells give rise to young neurons that migrate into many regions of the forebrain. Neurogenesis in adult rodents is also relatively widespread along the lateral ventricles, but migration is largely restricted to the rostral migratory stream into the olfactory bulb. Recent work indicates that the wall of the lateral ventricle is highly regionalized, with progenitor cells giving rise to different types of neurons depending on their location. In species with larger brains, young neurons born in these spatially specified domains become dramatically separated from potential final destinations. Here we hypothesize that the increase in size and topographical complexity (e.g., intervening white matter tracts) in larger brains may severely limit the long-term contribution of new neurons born close to, or in, the ventricular wall. We compare the process of adult neuronal birth, migration, and integration across species with different brain sizes, and discuss how early regional specification of progenitor cells may interact with brain size and affect where and when new neurons are added. PMID:26417888

  8. 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

  9. 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

  10. 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.

  11. 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

  12. Exploration and visualization of connectivity in the adult mouse brain.

    PubMed

    Feng, David; Lau, Chris; Ng, Lydia; Li, Yang; Kuan, Leonard; Sunkin, Susan M; Dang, Chinh; Hawrylycz, Michael

    2015-02-01

    The Allen Mouse Brain Connectivity Atlas is a mesoscale whole brain axonal projection atlas of the C57Bl/6J mouse brain. All data were aligned to a common template in 3D space to generate a comprehensive and quantitative database of inter-areal and cell-type-specific projections. A suite of computational tools were developed to search and visualize the projection labeling experiments, available at http://connectivity.brain-map.org. We present three use cases illustrating how these publicly-available tools can be used to perform analyses of long range brain region connectivity. The use cases make extensive use of advanced visualization tools integrated with the atlas including projection density histograms, 3D computed anterograde and retrograde projection paths, and multi-specimen projection composites. These tools offer convenient access to detailed axonal projection information in the adult mouse brain and the ability to perform data analysis and visualization of projection fields and neuroanatomy in an integrated manner. PMID:25637033

  13. 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…

  14. 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

  15. 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.

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

    PubMed

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

    2015-06-01

    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

  17. 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.

  18. 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

  19. 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

  20. 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

  1. Testosterone affects language areas of the adult human brain.

    PubMed

    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; Lanzenberger, Rupert

    2016-05-01

    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

  2. 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

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

    PubMed

    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

  4. 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 ...

  5. Roles for Oestrogen Receptor β in Adult Brain Function

    PubMed Central

    Handa, R. J.; Ogawa, S.; Wang, J. M.; Herbison, A. E.

    2012-01-01

    Oestradiol exerts a profound influence upon multiple brain circuits. For the most part, these effects are mediated by oestrogen receptor (ER)α. We review here the roles of ERβ, the other ER isoform, in mediating rodent oestradiol-regulated anxiety, aggressive and sexual behaviours, the control of gonadotrophin secretion, and adult neurogenesis. Evidence exists for: (i) ERβ located in the paraventricular nucleus underpinning the suppressive influence of oestradiol on the stress axis and anxiety-like behaviour; (ii) ERβ expressed in gonadotrophin-releasing hormone neurones contributing to oestrogen negative-feedback control of gonadotrophin secretion; (iii) ERβ controlling the offset of lordosis behaviour; (iv) ERβ suppressing aggressive behaviour in males; (v) ERβ modulating responses to social stimuli; and (vi) ERβ in controlling adult neurogenesis. This review highlights two major themes; first, ERβ and ERα are usually tightly inter-related in the oestradiol-dependent control of a particular brain function. For example, even though oestradiol feedback to control reproduction occurs principally through ERα-dependent mechanisms, modulatory roles for ERβ also exist. Second, the roles of ERα and ERβ within a particular neural network may be synergistic or antagonistic. Examples of the latter include the role of ERα to enhance, and ERβ to suppress, anxiety-like and aggressive behaviours. Splice variants such as ERβ2, acting as dominant negative receptors, are of further particular interest because their expression levels may reflect preceeding oestradiol exposure of relevance to oestradiol replacement therapy. Together, this review highlights the predominant modulatory, but nonetheless important, roles of ERβ in mediating the many effects of oestradiol upon adult brain function. PMID:21851428

  6. EFA Includes Education and Literacy for All Adults Everywhere

    ERIC Educational Resources Information Center

    Hildebrand, Henner; Hinzen, Heribert

    2004-01-01

    The Institute for International Co-operation of the German Adult Education Association, otherwise known as the IIZ/DVV, is based in Bonn. Germany and has more than 40 years of service in various projects in different countries. The Institute is known for the publication of the journal "Adult Education and Development," the most widely disseminated…

  7. 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…

  8. Neural Correlates of Animacy Attribution Include Neocerebellum in Healthy Adults.

    PubMed

    Jack, Allison; Pelphrey, Kevin A

    2015-11-01

    Recent work suggests that biological motion perception is supported by interactions between posterior superior temporal sulcus (pSTS) and regions of the posterior lobe of the cerebellum. However, insufficient attention has been given to cerebellar contributions to most other social cognitive functions, including ones that rely upon the use of biological motion cues for making mental inferences. Here, using adapted Heider and Simmel stimuli in a passive-viewing paradigm, we present functional magnetic resonance imaging evidence detailing cerebellar contributions to animacy attribution processes in healthy adults. We found robust cerebellar activity associated with viewing animate versus random movement in hemispheric lobule VII bilaterally as well as in vermal and paravermal lobule IX. Stronger activity in left Crus I and lobule VI was associated with a greater tendency to describe the stimuli in social-affective versus motion-related terms. Psychophysiological interaction analysis indicated preferential effective connectivity between right pSTS and left Crus II during the viewing of animate than random stimuli, controlling for individual variance in social attributions. These findings indicate that lobules VI, VII, and IX participate in social functions even when no active response is required. This cerebellar activity may also partially explain individual differences in animacy attribution. PMID:24981794

  9. 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…

  10. 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

  11. Noncanonical Sites of Adult Neurogenesis in the Mammalian Brain.

    PubMed

    Feliciano, David M; Bordey, Angélique; Bonfanti, Luca

    2015-10-01

    Two decades after the discovery that neural stem cells (NSCs) populate some regions of the mammalian central nervous system (CNS), deep knowledge has been accumulated on their capacity to generate new neurons in the adult brain. This constitutive adult neurogenesis occurs throughout life primarily within remnants of the embryonic germinal layers known as "neurogenic sites." Nevertheless, some processes of neurogliogenesis also occur in the CNS parenchyma commonly considered as "nonneurogenic." This "noncanonical" cell genesis has been the object of many claims, some of which turned out to be not true. Indeed, it is often an "incomplete" process as to its final outcome, heterogeneous by several measures, including regional location, progenitor identity, and fate of the progeny. These aspects also strictly depend on the animal species, suggesting that persistent neurogenic processes have uniquely adapted to the brain anatomy of different mammals. Whereas some examples of noncanonical neurogenesis are strictly parenchymal, others also show stem cell niche-like features and a strong link with the ventricular cavities. This work will review results obtained in a research field that expanded from classic neurogenesis studies involving a variety of areas of the CNS outside of the subventricular zone (SVZ) and subgranular zone (SGZ). It will be highlighted how knowledge concerning noncanonical neurogenic areas is still incomplete owing to its regional and species-specific heterogeneity, and to objective difficulties still hampering its full identification and characterization. PMID:26384869

  12. 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.

  13. 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

  14. 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)

  15. Axonal injury and regeneration in the adult brain of Drosophila

    PubMed Central

    Ayaz, Derya; Leyssen, Maarten; Koch, Marta; Yan, Jiekun; Srahna, Mohammed; Sheeba, Vasu; Fogle, Keri J.; Holmes, Todd C.; Hassan, Bassem A.

    2009-01-01

    Drosophila melanogaster is a leading genetic model system in nervous system development and disease research. Using the power of fly genetics in traumatic axonal injury research will significantly speed up the characterization of molecular processes that control axonal regeneration in the Central Nervous System (CNS). We developed a versatile and physiologically robust preparation for the long-term culture of the whole Drosophila brain. We use this method to develop a novel Drosophila model for CNS axonal injury and regeneration. We first show that, similar to mammalian CNS axons, injured adult wild type fly CNS axons fail to regenerate, whereas adult-specific enhancement of Protein Kinase A activity increases the regenerative capacity of lesioned neurons. Combined, these observations suggest conservation of neuronal regeneration mechanisms following injury. We next exploit this model to explore pathways that induce robust regeneration and find that adult-specific activation of JNK signalling is sufficient for de novo CNS axonal regeneration after injury, including the growth of new axons past the lesion site and into the normal target area. PMID:18524906

  16. Substance use and brain reward mechanisms in older adults.

    PubMed

    Snyder, Marsha; Platt, Lois

    2013-07-01

    Substance use among older adults is on the rise, with statistics indicating this to be a growing health problem. Brain changes in the reward center of the brain that naturally occur with aging are offered as one source of these statistics. Aging is generally associated with increased prevalence of chronic disease, disability, and death, and therefore a public health goal for older adults is to maintain health, independence, and function. Psychiatric-mental health nurses are uniquely positioned to assist older adults in achievement of these goals through health assessment and promotion. The use of client-centered counseling approaches that recognize the older adult's developmental need for autonomy and choice in decision making have been shown to be effective in increasing motivation in this adult population. PMID:23758223

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

    PubMed Central

    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

    2005-01-01

    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). PMID:16002470

  18. 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

    2016-01-01

    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. PMID:27098178

  19. 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

  20. 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

  1. 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

  2. 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. PMID:23577105

  3. 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.

  4. [Chemotherapy for brain tumors in adult patients].

    PubMed

    Weller, M

    2008-02-01

    Chemotherapy has become a third major treatment option for patients with brain tumors, in addition to surgery and radiotherapy. The role of chemotherapy in the treatment of gliomas is no longer limited to recurrent disease. Temozolomide has become the standard of care in newly diagnosed glioblastoma. Several ongoing trials seek to define the role of chemotherapy in the primary care of other gliomas. Some of these studies are no longer only based on histological diagnoses, but take into consideration molecular markers such as MGMT promoter methylation and loss of genetic material on chromosomal arms 1p and 19q. Outside such clinical trials chemotherapy is used in addition to radiotherapy, e.g., in anaplastic astrocytoma, medulloblastoma or germ cell tumors, or as an alternative to radiotherapy, e.g., in anaplastic oligodendroglial tumors or low-grade gliomas. In contrast, there is no established role for chemotherapy in other tumors such as ependymomas, meningiomas or neurinomas. Primary cerebral lymphomas are probably the only brain tumors which can be cured by chemotherapy alone and only by chemotherapy. The chemotherapy of brain metastases follows the recommendations for the respective primary tumors. Further, strategies of combined radiochemotherapy using mainly temozolomide or topotecan are currently explored. Leptomeningeal metastases are treated by radiotherapy or systemic or intrathecal chemotherapy depending on their pattern of growth. PMID:18253773

  5. 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

  6. 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,…

  7. Development of a conceptual model to predict physical activity participation in adults with brain injuries.

    PubMed

    Driver, Simon

    2008-10-01

    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 brain injuries completed a series of questionnaires measuring each psychosocial variable. The structural analysis indicated a nonsignificant chi squared value and good fit indices for model two which included affect as the mediating variable. Findings indicate that affect is critical in shaping the physical activity cognitions and behaviors of adults with brain injuries. Suggestions are made on practical ways to enhance affect and subsequently physical activity participation. PMID:18955746

  8. Adult neurogenesis in the decapod crustacean brain: A hematopoietic connection?

    PubMed Central

    Beltz, Barbara S.; Zhang, Yi; Benton, Jeanne L.; Sandeman, David C.

    2011-01-01

    New neurons are produced and integrated into circuits in the adult brains of many organisms, including crustaceans. In some crustacean species, the 1st- generation neuronal precursors reside in a niche exhibiting characteristics analogous to mammalian neurogenic niches. However, unlike mammalian niches where several generations of neuronal precursors coexist, the lineage of precursor cells in crayfish is spatially separated allowing the influence of environmental and endogenous regulators on specific generations in the neuronal precursor lineage to be defined. Experiments also demonstrate that the 1st-generation neuronal precursors in the crayfish Procambarus clarkii are not self-renewing. A source external to the neurogenic niche must therefore provide cells that replenish the 1st-generation precursor pool, because although these cells divide and produce a continuous efflux of 2nd-generation cells from the niche, the population of 1st-generation niche precursors is not diminished with growth and aging. In vitro studies show that cells extracted from the hemolymph, but not other tissues, are attracted to and incorporated into the neurogenic niche, a phenomenon that appears to involve serotonergic mechanisms. We propose that in crayfish, the hematopoietic system may be a source of cells that replenish the niche cell pool. These and other studies reviewed here establish decapod crustaceans as model systems in which the processes underlying adult neurogenesis, such as stem cell origins and transformation, can be readily explored. Studies in diverse species where adult neurogenesis occurs will result in a broader understanding of fundamental mechanisms and how evolutionary processes may have shaped the vertebrate/mammalian condition. PMID:21929622

  9. 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

  10. 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

  11. That's Using Your Brain!

    ERIC Educational Resources Information Center

    Visser, Dana R.

    1996-01-01

    Discusses new adult learning theories, including those of Roger Sperry (left brain/right brain), Paul McLean (triune brain), and Howard Gardner (multiple intelligences). Relates adult learning theory to training. (JOW)

  12. A stereotaxic, population-averaged T1w ovine brain atlas including cerebral morphology and tissue volumes.

    PubMed

    Nitzsche, Björn; Frey, Stephen; Collins, Louis D; Seeger, Johannes; Lobsien, Donald; Dreyer, Antje; Kirsten, Holger; Stoffel, Michael H; Fonov, Vladimir S; Boltze, Johannes

    2015-01-01

    Standard stereotaxic reference systems play a key role in human brain studies. Stereotaxic coordinate systems have also been developed for experimental animals including non-human primates, dogs, and rodents. However, they are lacking for other species being relevant in experimental neuroscience including sheep. Here, we present a spatial, unbiased ovine brain template with tissue probability maps (TPM) that offer a detailed stereotaxic reference frame for anatomical features and localization of brain areas, thereby enabling inter-individual and cross-study comparability. Three-dimensional data sets from healthy adult Merino sheep (Ovis orientalis aries, 12 ewes and 26 neutered rams) were acquired on a 1.5 T Philips MRI using a T1w sequence. Data were averaged by linear and non-linear registration algorithms. Moreover, animals were subjected to detailed brain volume analysis including examinations with respect to body weight (BW), age, and sex. The created T1w brain template provides an appropriate population-averaged ovine brain anatomy in a spatial standard coordinate system. Additionally, TPM for gray (GM) and white (WM) matter as well as cerebrospinal fluid (CSF) classification enabled automatic prior-based tissue segmentation using statistical parametric mapping (SPM). Overall, a positive correlation of GM volume and BW explained about 15% of the variance of GM while a positive correlation between WM and age was found. Absolute tissue volume differences were not detected, indeed ewes showed significantly more GM per bodyweight as compared to neutered rams. The created framework including spatial brain template and TPM represent a useful tool for unbiased automatic image preprocessing and morphological characterization in sheep. Therefore, the reported results may serve as a starting point for further experimental and/or translational research aiming at in vivo analysis in this species. PMID:26089780

  13. A stereotaxic, population-averaged T1w ovine brain atlas including cerebral morphology and tissue volumes

    PubMed Central

    Nitzsche, Björn; Frey, Stephen; Collins, Louis D.; Seeger, Johannes; Lobsien, Donald; Dreyer, Antje; Kirsten, Holger; Stoffel, Michael H.; Fonov, Vladimir S.; Boltze, Johannes

    2015-01-01

    Standard stereotaxic reference systems play a key role in human brain studies. Stereotaxic coordinate systems have also been developed for experimental animals including non-human primates, dogs, and rodents. However, they are lacking for other species being relevant in experimental neuroscience including sheep. Here, we present a spatial, unbiased ovine brain template with tissue probability maps (TPM) that offer a detailed stereotaxic reference frame for anatomical features and localization of brain areas, thereby enabling inter-individual and cross-study comparability. Three-dimensional data sets from healthy adult Merino sheep (Ovis orientalis aries, 12 ewes and 26 neutered rams) were acquired on a 1.5 T Philips MRI using a T1w sequence. Data were averaged by linear and non-linear registration algorithms. Moreover, animals were subjected to detailed brain volume analysis including examinations with respect to body weight (BW), age, and sex. The created T1w brain template provides an appropriate population-averaged ovine brain anatomy in a spatial standard coordinate system. Additionally, TPM for gray (GM) and white (WM) matter as well as cerebrospinal fluid (CSF) classification enabled automatic prior-based tissue segmentation using statistical parametric mapping (SPM). Overall, a positive correlation of GM volume and BW explained about 15% of the variance of GM while a positive correlation between WM and age was found. Absolute tissue volume differences were not detected, indeed ewes showed significantly more GM per bodyweight as compared to neutered rams. The created framework including spatial brain template and TPM represent a useful tool for unbiased automatic image preprocessing and morphological characterization in sheep. Therefore, the reported results may serve as a starting point for further experimental and/or translational research aiming at in vivo analysis in this species. PMID:26089780

  14. Life Satisfaction in Adult Survivors of Childhood Brain Tumors

    PubMed Central

    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, life-long 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 suggests 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 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. PMID:25027187

  15. 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

  16. The adult human brain harbors multipotent perivascular mesenchymal stem cells.

    PubMed

    Paul, Gesine; Özen, Ilknur; Christophersen, Nicolaj S; Reinbothe, Thomas; Bengzon, Johan; Visse, Edward; Jansson, Katarina; Dannaeus, Karin; Henriques-Oliveira, Catarina; Roybon, Laurent; Anisimov, Sergey V; Renström, Erik; Svensson, Mikael; Haegerstrand, Anders; Brundin, Patrik

    2012-01-01

    Blood vessels and adjacent cells form perivascular stem cell niches in adult tissues. In this perivascular niche, a stem cell with mesenchymal characteristics was recently identified in some adult somatic tissues. These cells are pericytes that line the microvasculature, express mesenchymal markers and differentiate into mesodermal lineages but might even have the capacity to generate tissue-specific cell types. Here, we isolated, purified and characterized a previously unrecognized progenitor population from two different regions in the adult human brain, the ventricular wall and the neocortex. We show that these cells co-express markers for mesenchymal stem cells and pericytes in vivo and in vitro, but do not express glial, neuronal progenitor, hematopoietic, endothelial or microglial markers in their native state. Furthermore, we demonstrate at a clonal level that these progenitors have true multilineage potential towards both, the mesodermal and neuroectodermal phenotype. They can be epigenetically induced in vitro into adipocytes, chondroblasts and osteoblasts but also into glial cells and immature neurons. This progenitor population exhibits long-term proliferation, karyotype stability and retention of phenotype and multipotency following extensive propagation. Thus, we provide evidence that the vascular niche in the adult human brain harbors a novel progenitor with multilineage capacity that appears to represent mesenchymal stem cells and is different from any previously described human neural stem cell. Future studies will elucidate whether these cells may play a role for disease or may represent a reservoir that can be exploited in efforts to repair the diseased human brain. PMID:22523602

  17. 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. PMID:25740488

  18. Electrophysiological recording in the brain of intact adult zebrafish.

    PubMed

    Johnston, Lindsey; Ball, Rebecca E; Acuff, Seth; Gaudet, John; Sornborger, Andrew; Lauderdale, James D

    2013-01-01

    Previously, electrophysiological studies in adult zebrafish have been limited to slice preparations or to eye cup preparations and electrorentinogram recordings. This paper describes how an adult zebrafish can be immobilized, intubated, and used for in vivo electrophysiological experiments, allowing recording of neural activity. Immobilization of the adult requires a mechanism to deliver dissolved oxygen to the gills in lieu of buccal and opercular movement. With our technique, animals are immobilized and perfused with habitat water to fulfill this requirement. A craniotomy is performed under tricaine methanesulfonate (MS-222; tricaine) anesthesia to provide access to the brain. The primary electrode is then positioned within the craniotomy window to record extracellular brain activity. Through the use of a multitube perfusion system, a variety of pharmacological compounds can be administered to the adult fish and any alterations in the neural activity can be observed. The methodology not only allows for observations to be made regarding changes in neurological activity, but it also allows for comparisons to be made between larval and adult zebrafish. This gives researchers the ability to identify the alterations in neurological activity due to the introduction of various compounds at different life stages. PMID:24300281

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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

  4. 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

  5. Genetic Methods to Identify and Manipulate Newly Born Neurons in the Adult Brain

    PubMed Central

    Imayoshi, Itaru; Sakamoto, Masayuki; Kageyama, Ryoichiro

    2011-01-01

    Although mammalian neurogenesis is mostly completed by the perinatal period, new neurons are continuously generated in the subventricular zone of the lateral ventricle and the subgranular zone of the hippocampal dentate gyrus. Since the discovery of adult neurogenesis, many extensive studies have been performed on various aspects of adult neurogenesis, including proliferation and fate-specification of adult neural stem cells, and the migration, maturation and synaptic integration of newly born neurons. Furthermore, recent research has shed light on the intensive contribution of adult neurogenesis to olfactory-related and hippocampus-mediated brain functions. The field of adult neurogenesis progressed tremendously thanks to technical advances that facilitate the identification and selective manipulation of newly born neurons among billions of pre-existing neurons in the adult central nervous system. In this review, we introduce recent advances in the methodologies for visualizing newly generated neurons and manipulating neurogenesis in the adult brain. Particularly, the application of site-specific recombinases and Tet inducible system in combination with transgenic or gene targeting strategy is discussed in further detail. PMID:21562606

  6. Combined Cognitive-Psychological-Physical Intervention Induces Reorganization of Intrinsic Functional Brain Architecture in Older Adults

    PubMed Central

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

    2015-01-01

    Mounting evidence suggests that enriched mental, physical, and socially stimulating activities are beneficial for counteracting age-related decreases in brain function and cognition in older adults. Here, we used functional magnetic resonance imaging (fMRI) to demonstrate the functional plasticity of brain activity in response to a combined cognitive-psychological-physical intervention and investigated the contribution of the intervention-related brain changes to individual performance in healthy older adults. The intervention was composed of a 6-week program of combined activities including cognitive training, Tai Chi exercise, and group counseling. The results showed improved cognitive performance and reorganized regional homogeneity of spontaneous fluctuations in the blood oxygen level-dependent (BOLD) signals in the superior and middle temporal gyri, and the posterior lobe of the cerebellum, in the participants who attended the intervention. Intriguingly, the intervention-induced changes in the coherence of local spontaneous activity correlated with the improvements in individual cognitive performance. Taken together with our previous findings of enhanced resting-state functional connectivity between the medial prefrontal cortex and medial temporal lobe regions following a combined intervention program in older adults, we conclude that the functional plasticity of the aging brain is a rather complex process, and an effective cognitive-psychological-physical intervention is helpful for maintaining a healthy brain and comprehensive cognition during old age. PMID:25810927

  7. Astaxanthin reduces ischemic brain injury in adult rats

    PubMed Central

    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.

    2009-01-01

    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.—Shen, H., Kuo, C.-C., Chou, J., Delvolve, A., Jackson, S. N., Post, J., Woods, A. S., Hoffer, B. J., Wang, Y., Harvey, B. K. Astaxanthin reduces ischemic brain injury in adult rats. PMID:19218497

  8. 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

  9. Adult Education Literacy Instruction. Appendix: Tables of Studies Included in the Review

    ERIC Educational Resources Information Center

    National Institute for Literacy, 2010

    2010-01-01

    Included here are two appendixes to "Adult Education Literacy Instruction: A Review of the Research." Appendix A, "Adult Studies," contains: (1) Assessment Profiles; (2) Alphabetics; (3) Fluency; (4) Vocabulary; and (5) Comprehension. Appendix B, "Adolescent Studies," contains: (1) Alphabetics; (2) Fluency; (3) Vocabulary; and (4) Comprehension.…

  10. Including Adults with Intellectual Disabilities in Research: Scientists' Perceptions of Risks and Protections

    ERIC Educational Resources Information Center

    McDonald, Katherine E.; Kidney, Colleen A.; Nelms, Sandra L.; Parker, Michael R.; Kimmel, Ali; Keys, Christopher B.

    2009-01-01

    Social and cognitive characteristics of adults with intellectual disabilities (ID) place them at risk for inappropriate inclusion in or exclusion from research participation. As we grapple with how to include adults with ID in research in order to secure their right to contribute to scientific advancements and be positioned to derive benefit from…

  11. 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. PMID:26437675

  12. 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.

  13. 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

  14. 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.

  15. Rehabilitation for Adults with Traumatic Brain Injury: Where Will We Be Clinically in 2026?

    PubMed

    Turkstra, Lyn S

    2016-08-01

    In 10 years, there might be fewer adults who need rehabilitation after traumatic brain injury because of advances in injury prevention and very early treatment. For adults who do need rehabilitation, assessment might include biosensor recordings in their everyday communication contexts, and home practice might be delivered by a robot that can be programmed to mimic target characteristics of human behavior. These advances in science and technology will enhance rehabilitation, but it will always be our responsibility as speech-language pathologists to advocate for our patients and clients and support them in achieving the best possible quality of communication life. PMID:27232097

  16. Neurogenesis in the adult brain: implications for Alzheimer's disease.

    PubMed

    Galvan, Veronica; Bredesen, Dale E

    2007-10-01

    The function of neurogenesis in the adult brain is still unknown. Interventions such as environmental enrichment and exercise impinge on neurogenesis, suggesting that the process is regulated by experience. Conversely, a role for neurogenesis in learning has been proposed through 'cellular plasticity', a process akin to synaptic plasticity but operating at the network level. Although neurogenesis is stimulated by acute injury, and possibly by neurodegenerative processes such as Alzheimer's disease (AD), it does not suffice to restore function. While the role and direction of change in the neurogenic response at different stages of AD is still a matter of debate, it is possible that a deficit in neurogenesis may contribute to AD pathogenesis since at least one of the two regions ostensibly neurogenic in the adult human brain (the subgranular zone of the dentage gyrus and the ventriculo-olfactory neurogenic system) support high-level functions affected in early AD (associative memory and olfaction respectively). The age of onset and the rate of progression of sporadic forms of AD are highly variable. Sporadic AD may have a component of insufficient neurogenic replacement or insufficient neurogenic stimulation that is correlated with traits of personal history; the rate of neurogenesis and the survival of replicating progenitors is strongly modified by behavioral interventions known to impinge on the rate of neurogenesis and the probability of survival of newly born neurons--exercise, enriched experience, and learning. This view is consistent with epidemiological data suggesting that higher education and increased participation in intellectual, social and physical aspects of daily life are associated with slower cognitive decline in healthy elderly ("cognitive reserve") and may reduce the risk of AD. Although neurogenesis can be modulated exogenously by growth factors, stimulation of neurogenesis as a mean to treat neurodegeneration is still for the most part

  17. 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. PMID:25956166

  18. ChIP-Seq analysis of the adult male mouse brain after developmental exposure to arsenic.

    PubMed

    Tyler, Christina R; Weber, Jessica A; Labrecque, Matthew; Hessinger, Justin M; Edwards, Jeremy S; Allan, Andrea M

    2015-12-01

    Exposure to the common environmental contaminant arsenic impacts the epigenetic landscape, including DNA methylation and histone modifications, of several cell types. Developmental arsenic exposure (DAE) increases acetylation and methylation of histone proteins and the protein expression of several chromatin-modifying enzymes in the dentate gyrus (DG) subregion of the adult male mouse brain [26]. To complement and support these data, ChIP-Seq analysis of DNA associated with trimethylation of histone 3 lysine 4 (H3K4me3) derived from the adult male DG after DAE was performed. DAE induced differential H3K4me3 enrichment on genes in pathways associated with cellular development and growth, cell death and survival, and neurological disorders, particularly as they relate to cancer, in the adult male brain. Comparison of H3K4me3 enrichment in controls revealed mechanisms that are potentially lacking in arsenic-exposed animals, including neurotransmission, neuronal growth and development, hormonal regulation, protein synthesis, and cellular homeostasis. New pathways impacted by arsenic include cytoskeleton organization, cell signaling, and potential disruption of immune function and warrant further investigation using this DAE paradigm in the mouse brain. PMID:26543888

  19. 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

  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. PMID:25644657

  1. Diminished adult neurogenesis in the marmoset brain precedes old age

    PubMed Central

    Leuner, Benedetta; Kozorovitskiy, Yevgenia; Gross, Charles G.; Gould, Elizabeth

    2007-01-01

    With aging there is a decline in the number of newly generated neurons in the dentate gyrus of the hippocampus. In rodents and tree shrews, this age-related decrease in neurogenesis is evident long before the animals become aged. No previous studies have investigated whether primates exhibit a similar decline in hippocampal neurogenesis with aging. To investigate this possibility, young to middle aged adult common marmosets (Callithrix jacchus) were injected with BrdU and perfused 3 weeks later. The number of newly generated cells in the subgranular zone/granule cell layer of the dentate gyrus was significantly lower in older animals and decreased linearly with age. A similar age-related decline in new cells was observed in the subventricular zone but not in the hilar region of the dentate gyrus. These data demonstrate that a substantial decrease in neurogenesis occurs before the onset of old age in the adult marmoset brain, suggesting the possibility that similar alterations occur in the human brain. PMID:17940008

  2. 3D Standard Brain of the Red Flour Beetle Tribolium Castaneum: A Tool to Study Metamorphic Development and Adult Plasticity

    PubMed Central

    Dreyer, David; Vitt, Holger; Dippel, Stefan; Goetz, Brigitte; el Jundi, Basil; Kollmann, Martin; Huetteroth, Wolf; Schachtner, Joachim

    2009-01-01

    The red flour beetle Tribolium castaneum is emerging as a further standard insect model beside Drosophila. Its genome is fully sequenced and it is susceptible for genetic manipulations including RNA-interference. We use this beetle to study adult brain development and plasticity primarily with respect to the olfactory system. In the current study, we provide 3D standard brain atlases of freshly eclosed adult female and male beetles (A0). The atlases include eight paired and three unpaired neuropils including antennal lobes (ALs), optic lobe neuropils, mushroom body calyces and pedunculi, and central complex. For each of the two standard brains, we averaged brain areas of 20 individual brains. Additionally, we characterized eight selected olfactory glomeruli from 10 A0 female and male beetles respectively, which we could unequivocally recognize from individual to individual owing to their size and typical position in the ALs. In summary, comparison of the averaged neuropil volumes revealed no sexual dimorphism in any of the reconstructed neuropils in A0 Tribolium brains. Both, the female and male 3D standard brain are also used for interspecies comparisons, and, importantly, will serve as future volumetric references after genetical manipulation especially regarding metamorphic development and adult plasticity. PMID:20339482

  3. 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

  4. Stroke Incidence Following Traumatic Brain Injury in Older Adults

    PubMed Central

    Albrecht, Jennifer S.; Liu, Xinggang; Smith, Gordon S.; Baumgarten, Mona; Rattinger, Gail B.; Gambert, Steven R.; Langenberg, Patricia; Zuckerman, Ilene H.

    2015-01-01

    Objective Following traumatic brain injury (TBI), older adults are at increased risk of hemorrhagic and thromboembolic events, but it is unclear whether the increased risk continues after hospital discharge. We estimated incidence rates of hemorrhagic and ischemic stroke following hospital discharge for TBI among adults ≥65 and compared them with pre-TBI rates. Participants 16,936 Medicare beneficiaries aged ≥65 with a diagnosis of TBI in any position on an inpatient claim between 6/1/2006 and 12/31/2009 who survived to hospital discharge. Design Retrospective analysis of a random 5% sample of Medicare claims data Main Measures Hemorrhagic stroke was defined as ICD-9 codes 430.xx-432.xx. Ischemic stroke was defined as ICD-9 codes 433.xx-435.xx, 437.0x, and 437.1x. Results There was a six-fold increase in the rate of hemorrhagic stroke following TBI compared to the pre-TBI period (adjusted Rate Ratio (RR) 6.5; 95% Confidence Interval (CI) 5.3, 7.8), controlling for age and sex. A smaller increase in the rate of ischemic stroke was observed (adjusted RR 1.3; 95% CI 1.2, 1.4). Conclusion Future studies should investigate causes of increased stroke risk post-TBI as well as effective treatments to reduce stroke risk and improve outcomes post-TBI among older adults. PMID:24816156

  5. Resting-State Brain Activity in Adult Males Who Stutter

    PubMed Central

    Zhu, Chaozhe; Wang, Liang; Yan, Qian; Lin, Chunlan; Yu, Chunshui

    2012-01-01

    Although developmental stuttering has been extensively studied with structural and task-based functional magnetic resonance imaging (fMRI), few studies have focused on resting-state brain activity in this disorder. We investigated resting-state brain activity of stuttering subjects by analyzing the amplitude of low-frequency fluctuation (ALFF), region of interest (ROI)-based functional connectivity (FC) and independent component analysis (ICA)-based FC. Forty-four adult males with developmental stuttering and 46 age-matched fluent male controls were scanned using resting-state fMRI. ALFF, ROI-based FCs and ICA-based FCs were compared between male stuttering subjects and fluent controls in a voxel-wise manner. Compared with fluent controls, stuttering subjects showed increased ALFF in left brain areas related to speech motor and auditory functions and bilateral prefrontal cortices related to cognitive control. However, stuttering subjects showed decreased ALFF in the left posterior language reception area and bilateral non-speech motor areas. ROI-based FC analysis revealed decreased FC between the posterior language area involved in the perception and decoding of sensory information and anterior brain area involved in the initiation of speech motor function, as well as increased FC within anterior or posterior speech- and language-associated areas and between the prefrontal areas and default-mode network (DMN) in stuttering subjects. ICA showed that stuttering subjects had decreased FC in the DMN and increased FC in the sensorimotor network. Our findings support the concept that stuttering subjects have deficits in multiple functional systems (motor, language, auditory and DMN) and in the connections between them. PMID:22276215

  6. 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

  7. Brain activation deficit in increased-load working memory tasks among adults with ADHD using fMRI.

    PubMed

    Ko, Chih-Hung; Yen, Ju-Yu; Yen, Cheng-Fang; Chen, Cheng-Sheng; Lin, Wei-Chen; Wang, Peng-Wei; Liu, Gin-Chung

    2013-10-01

    Working memory (WM) is impaired among adults with attention-deficit hyperactivity disorder (ADHD). This study aimed to investigate the brain activation deficit for low-level or increased-load WM among adults with ADHD. A total of 20 adults with ADHD and controls were recruited according to diagnostic interviewing by a psychiatrist. Phonological and visual-spatial 2-back and 3-back tasks were performed under functional magnetic resonance scanning. The results demonstrated that both the adults with ADHD and the controls exhibited activation of the fronto-parietal network for WM, and the intensity was greater in the adult ADHD group. The ADHD group had higher brain activation over the bilateral anterior cingulate, left inferior frontal lobe, hippocampus, and supplementary motor area (SMA) for phonological WM than the control group. When the task loading increased from 2-back to 3-back tasks, the adults with ADHD perceived greater difficulty. The control group exhibited increased brain activation over the frontal-parietal network in response to increased phonological WM load. However, the ADHD group showed decreased brain activation over the left precuneus, insula, and SMA. Further analysis demonstrated that the ADHD group exhibited a greater decrease in brain activation over the left fronto-parietal network, including the precuneus, SMA, insula/inferior frontal lobe, and dorsolateral prefrontal cortex, than the control group. These results suggest that adults with ADHD pay more effort to low demanding phonological WM. On the other hand, brain activation of the left fronto-parietal network is impaired when the demands of WM exceed the capacity of adults with ADHD. PMID:23645101

  8. African American Participation in Alzheimer’s Disease Research that Includes Brain Donation

    PubMed Central

    Darnell, Kathryn R.; McGuire, Caitlin

    2012-01-01

    Historically, minority groups have been underrepresented in research and clinical trials. The lack of participation by minorities has been attributed to variety of factors including a mistrust of the predominately white research establishments and a lack of education about the purpose of research. The current study was designed to determine African-American interest in Alzheimer’s disease (AD) research and to recruit African Americans as normal controls in current AD studies with the goal of eventually gaining consent for brain donation upon death. Participants were 46 African Americans aged 65 or older who were interviewed about knowledge of medical procedures and experience with research. After initial recruitment interviews, 31.7% of participants agreed to yearly testing with eventual brain donation. Study findings suggest a moderate relationship between participants’ knowledge of medical procedures used to prolong life and willingness to donate one’s brain. PMID:22009227

  9. Segmentation of center brains and optic lobes in 3D confocal images of adult fruit fly brains.

    PubMed

    Lam, Shing Chun Benny; Ruan, Zongcai; Zhao, Ting; Long, Fuhui; Jenett, Arnim; Simpson, Julie; Myers, Eugene W; Peng, Hanchuan

    2010-02-01

    Automatic alignment (registration) of 3D images of adult fruit fly brains is often influenced by the significant displacement of the relative locations of the two optic lobes (OLs) and the center brain (CB). In one of our ongoing efforts to produce a better image alignment pipeline of adult fruit fly brains, we consider separating CB and OLs and align them independently. This paper reports our automatic method to segregate CB and OLs, in particular under conditions where the signal to noise ratio (SNR) is low, the variation of the image intensity is big, and the relative displacement of OLs and CB is substantial. We design an algorithm to find a minimum-cost 3D surface in a 3D image stack to best separate an OL (of one side, either left or right) from CB. This surface is defined as an aggregation of the respective minimum-cost curves detected in each individual 2D image slice. Each curve is defined by a list of control points that best segregate OL and CB. To obtain the locations of these control points, we derive an energy function that includes an image energy term defined by local pixel intensities and two internal energy terms that constrain the curve's smoothness and length. Gradient descent method is used to optimize this energy function. To improve both the speed and robustness of the method, for each stack, the locations of optimized control points in a slice are taken as the initialization prior for the next slice. We have tested this approach on simulated and real 3D fly brain image stacks and demonstrated that this method can reasonably segregate OLs from CBs despite the aforementioned difficulties. PMID:19698789

  10. Brain-expressed imprinted genes and adult behaviour: the example of Nesp and Grb10.

    PubMed

    Dent, Claire L; Isles, Anthony R

    2014-02-01

    Imprinted genes are defined by their parent-of-origin-specific monoallelic expression. Although the epigenetic mechanisms regulating imprinted gene expression have been widely studied, their functional importance is still unclear. Imprinted genes are associated with a number of physiologies, including placental function and foetal growth, energy homeostasis, and brain and behaviour. This review focuses on genomic imprinting in the brain and on two imprinted genes in particular, Nesp and paternal Grb10, which, when manipulated in animals, have been shown to influence adult behaviour. These two genes are of particular interest as they are expressed in discrete and overlapping neural regions, recognised as key "imprinting hot spots" in the brain. Furthermore, these two genes do not appear to influence placental function and/or maternal provisioning of offspring. Consequently, by understanding their behavioural function we may begin to shed light on the evolutionary significance of imprinted genes in the adult brain, independent of the recognised role in maternal care. In addition, we discuss the potential future directions of research investigating the function of these two genes and the behavioural role of imprinted genes more generally. PMID:23974804

  11. Neural stem cells display extensive tropism for pathology in adult brain: Evidence from intracranial gliomas

    PubMed Central

    Aboody, Karen S.; Brown, Alice; Rainov, Nikolai G.; Bower, Kate A.; Liu, Shaoxiong; Yang, Wendy; Small, Juan E.; Herrlinger, Ulrich; Ourednik, Vaclav; Black, Peter McL.; Breakefield, Xandra O.; Snyder, Evan Y.

    2000-01-01

    One of the impediments to the treatment of brain tumors (e.g., gliomas) has been the degree to which they expand, infiltrate surrounding tissue, and migrate widely into normal brain, usually rendering them “elusive” to effective resection, irradiation, chemotherapy, or gene therapy. We demonstrate that neural stem cells (NSCs), when implanted into experimental intracranial gliomas in vivo in adult rodents, distribute themselves quickly and extensively throughout the tumor bed and migrate uniquely in juxtaposition to widely expanding and aggressively advancing tumor cells, while continuing to stably express a foreign gene. The NSCs “surround” the invading tumor border while “chasing down” infiltrating tumor cells. When implanted intracranially at distant sites from the tumor (e.g., into normal tissue, into the contralateral hemisphere, or into the cerebral ventricles), the donor cells migrate through normal tissue targeting the tumor cells (including human glioblastomas). When implanted outside the CNS intravascularly, NSCs will target an intracranial tumor. NSCs can deliver a therapeutically relevant molecule—cytosine deaminase—such that quantifiable reduction in tumor burden results. These data suggest the adjunctive use of inherently migratory NSCs as a delivery vehicle for targeting therapeutic genes and vectors to refractory, migratory, invasive brain tumors. More broadly, they suggest that NSC migration can be extensive, even in the adult brain and along nonstereotypical routes, if pathology (as modeled here by tumor) is present. PMID:11070094

  12. Brain morphological changes in adolescent and adult patients with anorexia nervosa.

    PubMed

    Seitz, J; Herpertz-Dahlmann, B; Konrad, K

    2016-08-01

    Gray matter (GM) and white matter (WM) volume loss occur in the brains of patients with acute anorexia nervosa (AN) and improve again upon weight restoration. Adolescence is an important time period for AN to begin. However, little is known about the differences between brain changes in adolescents vs adults. We used a meta-analysis and a qualitative review of all MRI studies regarding acute structural brain volume changes and their recovery in adolescents and adults with AN. 29 studies with 473 acute, 121 short-term weight-recovered and 255 long-term recovered patients with AN were included in the meta-analysis. In acute AN, GM and WM were reduced compared to healthy controls. Acute adolescent patients showed a significantly greater GM reduction than adults (-8.4 vs -3.1 %), the difference in WM (-4.0 vs -2.1 %) did not reach significance. Short-term weight-recovered patients showed a remaining GM deficit of 3.6 % and a non-significant WM reduction of 0.9 % with no age differences. Following 1.5-8 years of remission, GM and WM were no longer significantly reduced in adults (GM -0.4 %, WM -0.7 %); long-term studies for adolescents were scarce. The qualitative review showed that GM volume loss was correlated with cognitive deficits and three studies found GM regions, cerebellar deficits and WM to be predictive of outcome. GM and WM are strongly reduced in acute AN and even more pronounced in adolescence. Long-term recovery appears to be complete for adults while no conclusions can be drawn for adolescents, thus caution remains. PMID:27188331

  13. Donepezil markedly potentiates memantine neurotoxicity in the adult rat brain.

    PubMed

    Creeley, Catherine E; Wozniak, David F; Nardi, Anthony; Farber, Nuri B; Olney, John W

    2008-02-01

    The NMDA antagonist, memantine (Namenda), and the cholinesterase inhibitor, donepezil (Aricept), are currently being used widely, either individually or in combination, for treatment of Alzheimer's disease (AD). NMDA antagonists have both neuroprotective and neurotoxic properties; the latter is augmented by drugs, such as pilocarpine, that increase cholinergic activity. Whether donepezil, by increasing cholinergic activity, might augment memantine's neurotoxic potential has not been investigated. In the present study, we determined that a dose of memantine (20mg/kg, i.p.), considered to be in the therapeutic (neuroprotective) range for rats, causes a mild neurotoxic reaction in the adult rat brain. Co-administration of memantine (20 or 30 mg/kg) with donepezil (2.5-10mg/kg) markedly potentiated this neurotoxic reaction, causing neuronal injury at lower doses of memantine, and causing the toxic reaction to become disseminated and lethal to neurons throughout many brain regions. These findings raise questions about using this drug combination in AD, especially in the absence of evidence that the combination is beneficial, or that either drug arrests or reverses the disease process. PMID:17112636

  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. Enhanced peripheral visual processing in congenitally deaf humans is supported by multiple brain regions, including primary auditory cortex

    PubMed Central

    Scott, Gregory D.; Karns, Christina M.; Dow, Mark W.; Stevens, Courtney; Neville, Helen J.

    2014-01-01

    Brain reorganization associated with altered sensory experience clarifies the critical role of neuroplasticity in development. An example is enhanced peripheral visual processing associated with congenital deafness, but the neural systems supporting this have not been fully characterized. A gap in our understanding of deafness-enhanced peripheral vision is the contribution of primary auditory cortex. Previous studies of auditory cortex that use anatomical normalization across participants were limited by inter-subject variability of Heschl's gyrus. In addition to reorganized auditory cortex (cross-modal plasticity), a second gap in our understanding is the contribution of altered modality-specific cortices (visual intramodal plasticity in this case), as well as supramodal and multisensory cortices, especially when target detection is required across contrasts. Here we address these gaps by comparing fMRI signal change for peripheral vs. perifoveal visual stimulation (11–15° vs. 2–7°) in congenitally deaf and hearing participants in a blocked experimental design with two analytical approaches: a Heschl's gyrus region of interest analysis and a whole brain analysis. Our results using individually-defined primary auditory cortex (Heschl's gyrus) indicate that fMRI signal change for more peripheral stimuli was greater than perifoveal in deaf but not in hearing participants. Whole-brain analyses revealed differences between deaf and hearing participants for peripheral vs. perifoveal visual processing in extrastriate visual cortex including primary auditory cortex, MT+/V5, superior-temporal auditory, and multisensory and/or supramodal regions, such as posterior parietal cortex (PPC), frontal eye fields, anterior cingulate, and supplementary eye fields. Overall, these data demonstrate the contribution of neuroplasticity in multiple systems including primary auditory cortex, supramodal, and multisensory regions, to altered visual processing in congenitally deaf

  16. Psychotherapy Interventions for Managing Anxiety and Depressive Symptoms in Adult Brain Tumor Patients: A Scoping Review

    PubMed Central

    Kangas, Maria

    2015-01-01

    Background Adult brain tumor (BT) patients and longer-term survivors are susceptible to experiencing emotional problems, including anxiety and/or depression disorders, which may further compromise their quality-of-life (QOL) and general well-being. The objective of this paper is to review psychological approaches for managing anxiety and depressive symptoms in adult BT patients. A review of psychological interventions comprising mixed samples of oncology patients, and which included BT patients is also evaluated. The review concludes with an overview of a recently developed transdiagnostic psychotherapy program, which was specifically designed to treat anxiety and/or depressive symptoms in adult BT patients. Methods Electronic databases (PsycINFO, Medline, Embase, and Cochrane) were searched to identify published studies investigating psychological interventions for managing anxiety and depressive symptoms in adult BT patients. Only four randomized controlled trials (RCTs) were identified. Results Only one of the RCTs tested a psychosocial intervention, which was specifically developed for primary BT patients, and which was found to improve QOL including existential well-being as well as reducing depressive symptoms. A second study tested a combined cognitive rehabilitation and problem-solving intervention, although was not found to significantly improve mood or QOL. The remaining two studies tested multidisciplinary psychosocial interventions in heterogeneous samples of cancer patients (included BT patients) with advanced stage disease. Maintenance of QOL was found in both studies, although no secondary gains were found for improvements in mood. Conclusion There is a notable paucity of psychological interventions for adult BT patients across the illness trajectory. Further research is required to strengthen the evidence base for psychological interventions in managing anxiety and depressive symptoms, and enhancing the QOL of distressed adults diagnosed with a BT

  17. 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

  18. Differential, regional, and cellular expression of the stathmin family transcripts in the adult rat brain.

    PubMed

    Ozon, S; El Mestikawy, S; Sobel, A

    1999-06-01

    Stathmin is a ubiquitous cytosolic phosphoprotein, preferentially expressed in the nervous system, and previously described as a relay integrating diverse intracellular signaling pathways. Stathmin is the generic element of a mammalian protein family including SCG10, SCLIP, and RB3 with its splice variants RB3' and RB3". In contrast with stathmin, SCG10, SCLIP, and RB3/RB3'/RB3" are exclusively expressed in the nervous system, stathmin and SCG10 being mostly expressed during cell proliferation and differentiation, and SCLIP and RB3 rather in mature neural cells. To further understand their specific roles in the CNS, we compared the localization of the stathmin, SCG10, SCLIP, and RB3 transcripts in adult rat brain. Northern blot analysis as well as in situ hybridization experiments showed that all stathmin-related mRNAs are expressed in a wide range of adult rat brain areas. At a regional level, SCG10 and SCLIP appear generally distributed similarly except in a few areas. The pattern of expression of the RB3 transcript is very different from that of the three other members of the stathmin family. Furthermore, unlike SCG10 and SCLIP, which were detected only in neurons, but like stathmin, RB3 was detected in neurons and also in glial cells of the white matter. Altogether, our results suggest distinct roles for each member of the stathmin-related phosphoprotein family, in regard to their specific regional and cellular localization in the rat brain. PMID:10369222

  19. 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

  20. Acute effect of a high nitrate diet on brain perfusion in older adults

    PubMed Central

    Presley, Tennille D.; Morgan, Ashley R.; Bechtold, Erika; Clodfelter, William; Dove, Robin W.; Jennings, Janine M.; Kraft, Robert A.; King, S. Bruce; Laurienti, Paul J.; Rejeski, W. Jack; Burdette, Jonathan H.; Kim-Shapiro, Daniel B.; Miller, Gary D.

    2010-01-01

    Aims Poor blood flow and hypoxia/ischemia contribute to many disease states and may also be a factor in the decline of physical and cognitive function in aging. Nitrite has been discovered to be a vasodilator that is preferentially harnessed in hypoxia. Thus, both infused and inhaled nitrite are being studied as therapeutic agents for a variety of diseases. In addition, nitrite derived from nitrate in the diet has been shown to decrease blood pressure and improve exercise performance. Thus, dietary nitrate may also be important when increased blood flow in hypoxic or ischemic areas is indicated. These conditions could include age-associated dementia and cognitive decline. The goal of this study was to determine if dietary nitrate would increase cerebral blood flow in older adults. Methods and Results In this investigation we administered a high vs. low nitrate diet to older adults (74.7 ± 6.9 years) and measured cerebral perfusion using arterial spin labeling magnetic resonance imaging. We found that the high nitrate diet did not alter global cerebral perfusion, but did lead to increased regional cerebral perfusion in frontal lobe white matter, especially between the dorsolateral prefrontal cortex and anterior cingulate cortex. Conclusion These results suggest that dietary nitrate may be useful in improving regional brain perfusion in older adults in critical brain areas known to be involved in executive functioning. PMID:20951824

  1. Biochemical effect of a ketogenic diet on the brains of obese adult rats.

    PubMed

    Mohamed, Hoda E; El-Swefy, Sahar E; Rashed, Leila A; Abd El-Latif, Sally K

    2010-07-01

    Excess weight, particularly abdominal obesity, can cause or exacerbate cardiovascular and metabolic disease. Obesity is also a proven risk factor for Alzheimer's disease (AD). Various studies have demonstrated the beneficial effects of a ketogenic diet (KD) in weight reduction and in modifying the disease activity of neurodegenerative disorders, including AD. Therefore, in this study we examined the metabolic and neurodegenerative changes associated with obesity and the possible neuroprotective effects of a KD in obese adult rats. Compared with obese rats fed a control diet, obese rats fed a KD showed significant weight loss, improvement in lipid profiles and insulin resistance, and upregulation of adiponectin mRNA expression in adipose tissue. In addition, the KD triggered significant downregulation of brain amyloid protein precursor, apolipoprotein E and caspase-3 mRNA expression, and improvement of brain oxidative stress responses. These findings suggest that a KD has anti-obesity and neuroprotective effects. PMID:20395146

  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. 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.

  4. Gestational ketogenic diet programs brain structure and susceptibility to depression & anxiety in the adult mouse offspring

    PubMed Central

    Sussman, Dafna; Germann, Jurgen; Henkelman, Mark

    2015-01-01

    Introduction The ketogenic diet (KD) has seen an increase in popularity for clinical and non-clinical purposes, leading to rise in concern about the diet's impact on following generations. The KD is known to have a neurological effect, suggesting that exposure to it during prenatal brain development may alter neuro-anatomy. Studies have also indicated that the KD has an anti-depressant effect on the consumer. However, it is unclear whether any neuro-anatomical and/or behavioral changes would occur in the offspring and persist into adulthood. Methods To fill this knowledge gap we assessed the brain morphology and behavior of 8-week-old young-adult CD-1 mice, who were exposed to the KD in utero, and were fed only a standard-diet (SD) in postnatal life. Standardized neuro-behavior tests included the Open-Field, Forced-Swim, and Exercise Wheel tests, and were followed by post-mortem Magnetic Resonance Imaging (MRI) to assess brain anatomy. Results The adult KD offspring exhibit reduced susceptibility to anxiety and depression, and elevated physical activity level when compared with controls exposed to the SD both in utero and postnatally. Many neuro-anatomical differences exist between the KD offspring and controls, including, for example, a cerebellar volumetric enlargement by 4.8%, a hypothalamic reduction by 1.39%, and a corpus callosum reduction by 4.77%, as computed relative to total brain volume. Conclusions These results suggest that prenatal exposure to the KD programs the offspring neuro-anatomy and influences their behavior in adulthood. PMID:25642385

  5. Occupational and environmental risk factors of adult primary brain cancers: a systematic review.

    PubMed

    Gomes, J; Al Zayadi, A; Guzman, A

    2011-04-01

    The incidence of brain neoplasm has been progressively increasing in recent years in the industrialized countries. One of the reasons for this increased incidence could be better access to health care and improved diagnosis in the industrialized countries. It also appears that Caucasians have a higher incidence than blacks or Hispanics or Asians. A number of risk factors have been identified and described including the genetic, ethnic and age-based factors. Certain occupational and environmental factors are also believed to influence the risk of primary adult brain tumors. Potential occupational and environmental factors include exposure to diagnostic and therapeutic radiations, electromagnetic radiation from cellular phones and other wireless devices, infectious agents, air pollution and residence near landfills and high-voltage power lines and jobs as firefighters, farmers, physician, chemists and jobs in industries such as petrochemical, power generation, synthetic rubber manufacturing, agricultural chemicals manufacturing. The purpose of this systematic review is to examine occupational and environmental risk factors of brain neoplasm. A range of occupational and environmental exposures are evaluated for significance of their relationship with adult primary brain tumors. On the basis of this review we suggest a concurrent evaluation of multiple risk factors both within and beyond occupational and environmental domains. The concurrent approach needs to consider better exposure assessment techniques, lifetime occupational exposures, genotypic and phenotypic characteristics and lifestyle and dietary habits. This approach needs to be interdisciplinary with contributions from neurologists, oncologists, epidemiologists and molecular biologists. Conclusive evidence that has eluded multitude of studies with single focus and single exposure needs to multifaceted and multidisciplinary. PMID:23022824

  6. 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. PMID:24217015

  7. 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. PMID:25202027

  8. Effects of Alcohol Consumption on Cognition and Regional Brain Volumes Among Older Adults

    PubMed Central

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

    2015-01-01

    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. PMID:25202027

  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. APOE Polymorphism Affects Brain Default Mode Network in Healthy Young Adults: A STROBE Article.

    PubMed

    Su, Yun Yan; Liang, Xue; Schoepf, U Joseph; Varga-Szemes, Akos; West, Henry C; Qi, Rongfeng; Kong, Xiang; Chen, Hui Juan; Lu, Guang Ming; Zhang, Long Jiang

    2015-12-01

    To investigate the effect of apolipoprotein E (APOE) gene polymorphism on the resting-state brain function, structure, and blood flow in healthy adults younger than 35 years, using multimodality magnetic resonance (MR) imaging.Seventy-six healthy adults (34 men, 23.7 ± 2.8 y; 31 APOE ε4/ε3 carriers, 31 ε3/ε3 carriers, and 14 ε2/ε3 carriers) were included. For resting-state functional MRI data, default mode network (DMN) and amplitude of low-frequency fluctuation maps were extracted and analyzed. Voxel-based morphometry, diffusion tensor imaging from structural imaging, and cerebral blood flow based on arterial spin labeling MR imaging were also analyzed. Correlation analysis was performed between the above mentioned brain parameters and neuropsychological tests.There were no differences in neuropsychological performances, amplitude of low-frequency fluctuation, gray/white matter volumes, fractional anisotropy, mean diffusivity, or whole brain cerebral blood flow among the 3 groups. As for DMN, the ε4/ε3 group showed increased functional connectivities (FCs) in the left medial prefrontal cortex and bilateral posterior cingulate cortices/precuneus compared with the ε3/ε3 group, and increased FCs in the left medial prefrontal cortex and right temporal lobe compared with the ε2/ε3 group (P < 0.05, Alphasim corrected). No differences of DMN FCs were found between the ε2/ε3 and ε3/ε3 groups. FCs in the right temporal lobe positively correlated with the performances of vocabulary learning, delayed recall, and graph recall in all participants (P < 0.05).APOE ε4 carriers exhibited significantly increased DMN FCs when compared with ε3 and ε2 carriers. The ε4 affects DMN FCs before brain structure and blood flow in cognitively intact young patients, suggesting DMN FC may serve as a potential biomarker for the detection of early manifestations of genetic effect. PMID:26717353

  11. 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

  12. Age-specific MRI brain and head templates for healthy adults from 20 through 89 years of age

    PubMed Central

    Fillmore, Paul T.; Phillips-Meek, Michelle C.; Richards, John E.

    2015-01-01

    This study created and tested a database of adult, age-specific MRI brain and head templates. The participants included healthy adults from 20 through 89 years of age. The templates were done in five-year, 10-year, and multi-year intervals from 20 through 89 years, and consist of average T1W for the head and brain, and segmenting priors for gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF). It was found that age-appropriate templates provided less biased tissue classification estimates than age-inappropriate reference data and reference data based on young adult templates. This database is available for use by other investigators and clinicians for their MRI studies, as well as other types of neuroimaging and electrophysiological research.1 PMID:25904864

  13. Physical performance limitations among adult survivors of childhood brain tumors

    PubMed Central

    Ness, Kirsten K.; Morris, E. Brannon; Nolan, Vikki G.; Howell, Carrie R.; Gilchrist, Laura S.; Stovall, Marilyn; Cox, Cheryl L.; Klosky, James L.; Gajjar, Amar; Neglia, Joseph P.

    2013-01-01

    Background Young adult survivors of childhood brain tumors (BT) may have late-effects that compromise physical performance and everyday task participation. Objective To evaluate muscle strength, fitness, physical performance, and task participation among adult survivors of childhood BT. Design/Method In-home evaluations and interviews were conducted for 156 participants (54% male). Results on measures of muscle strength, fitness, physical performance, and participation were compared between survivors and population-group members with chi-squared statistics and two-sample t-tests. Associations between late effects and physical performance, and physical performance and participation, were evaluated in regression models. Results BT survivors were a median age of 22 (18–58), and 14.7 (6.5–45.9) years from diagnosis. Survivors had lower estimates of grip strength (Female: 24.7±9.2 vs. 31.5±5.8, Male: 39.0±12.2 vs. 53.0±10.1 kilograms), knee extension strength (Female: 246.6±95.5 vs. 331.5±5.8, Male: 304.7±116.4 vs. 466.6±92.1 Newtons) and peak oxygen uptake (Female: 25.1±8.8 vs. 31.3±5.1, Male: 24.6±9.5 vs. 33.2±3.4 milliliters/kilogram/minute) than population-group members. Physical performance was lower among survivors and associated with not living independently (OR=5.0, 95% CI=2.0–12.2) and not attending college (OR=2.3, 95% CI 1.2–4.4). Conclusion Muscle strength and fitness values among BT survivors are similar to those among persons 60+ years, and are associated with physical performance limitations. Physical performance limitations are associated with poor outcomes in home and school environments. These data indicate an opportunity for interventions targeted at improving long-term physical function in this survivor population. PMID:20564409

  14. Brain Volumetrics, Regional Cortical Thickness and Radiographic Findings in Adults with Cyanotic Congenital Heart Disease☆

    PubMed Central

    Cordina, Rachael; Grieve, Stuart; Barnett, Michael; Lagopoulos, Jim; Malitz, Nathan; Celermajer, David S.

    2014-01-01

    Background Chronic cyanosis in adults with congenital heart disease (CHD) may cause structural brain changes that could contribute to impaired neurological functioning. The extent of these changes has not been adequately characterized. Hypothesis We hypothesized that adults with cyanotic CHD would have widespread changes including abnormal brain volumetric measures, decreased cortical thickness and an increased burden of small and large vessel ischemic changes. Methods Ten adults with chronic cyanosis from CHD (40 ± 4 years) and mean oxygen saturations of 82 ± 2% were investigated using quantitative MRI. Hematological and biochemical parameters were also assessed. All subjects were free from major physical or intellectual impairment. Brain volumetric results were compared with randomly selected age- and sex-matched controls from our database of normal subjects. Results Five of 10 cyanotic subjects had cortical lacunar infarcts. The white matter (WM) hyperintensity burden was also abnormally high (Scheltens Scale was 8 ± 2). Quantitative MRI revealed evidence of extensive generalized WM and gray matter (GM) volumetric loss; global GM volume was reduced in cyanosed subjects (630 ± 16 vs. 696 ± 14 mL in controls, p = 0.01) as was global WM volume (471 ± 10 vs. 564 ± 18 mL, p = 0.003). Ventricular cerebrospinal fluid volume was increased (35 ± 10 vs. 26 ± 5 mL, p = 0.002). There were widespread regions of local cortical thickness reduction observed across the brain. These changes included bilateral thickness reductions in the frontal lobe including the dorsolateral prefrontal cortex and precentral gyrus, the posterior parietal lobe and the middle temporal gyrus. Sub-cortical volume changes were observed in the caudate, putamen and in the thalamus (p ≤ 0.005 for all regions). Cortical GM volume negatively correlated with brain natriuretic peptide (R = − 0.89, p = 0.009), high sensitivity C-reactive protein (R = − 0

  15. 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

  16. Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype?

    PubMed

    Nugent, S; Castellano, C A; Bocti, C; Dionne, I; Fulop, T; Cunnane, S C

    2016-02-01

    Our primary objective in this study was to quantify whole brain and regional cerebral metabolic rates of glucose (CMRg) in young and older adults in order to determine age-normalized reference CMRg values for healthy older adults with normal cognition for age. Our secondary objectives were to--(i) report a broader range of metabolic and endocrine parameters including body fat composition that could form the basis for the concept of a 'metabolic phenotype' in cognitively normal, older adults, and (ii) to assess whether medications commonly used to control blood lipids, blood pressure or thyroxine affect CMRg values in older adults. Cognition assessed by a battery of tests was normal for age and education in both groups. Compared to the young group (25 years old; n = 34), the older group (72 years old; n = 41) had ~14% lower CMRg (μmol/100 g/min) specifically in the frontal cortex, and 18% lower CMRg in the caudate. Lower grey matter volume and cortical thickness was widespread in the older group. These differences in CMRg, grey matter volume and cortical thickness were present in the absence of any known evidence for prodromal Alzheimer's disease (AD). Percent total body fat was positively correlated with CMRg in many brain regions but only in the older group. Before and after controlling for body fat, HOMA2-IR was significantly positively correlated to CMRg in several brain regions in the older group. These data show that compared to a healthy younger adult, the metabolic phenotype of a cognitively-normal 72 year old person includes similar plasma glucose, insulin, cholesterol, triglycerides and TSH, higher hemoglobin A1c and percent body fat, lower CMRg in the superior frontal cortex and caudate, but the same CMRg in the hippocampus and white matter. Age-normalization of cognitive test results is standard practice and we would suggest that regional CMRg in cognitively healthy older adults should also be age-normalized. PMID:26364049

  17. Prenatal detection of 5q14.3 duplication including MEF2C and brain phenotype.

    PubMed

    Cesaretti, Claudia; Spaccini, Luigina; Righini, Andrea; Parazzini, Cecilia; Conte, Giorgio; Crosti, Francesca; Redaelli, Serena; Bulfamante, Gaetano; Avagliano, Laura; Rustico, Mariangela

    2016-05-01

    The 5q14.3 duplication is a rare condition comprising speech and developmental delay, microcephaly, and mild ventriculomegaly. The region 5q14.3 contains several genes but the predominant role for the onset of the neurodevelopmental phenotype has been attributed to MEF2C. We describe the prenatal identification of 5q14.3 duplication, including MEF2C, in a monochorionic twin pregnancy with corpus callosum anomalies, confirmed by autopsy. To the best of our knowledge, this cerebral finding has been observed for the first time in 5q14.3 duplication patients, possibly widening the neurological picture of this scarcely known syndrome. A pathogenetic role of MEF2C overexpression in brain development may be assumed, but further studies are needed. © 2016 Wiley Periodicals, Inc. PMID:26864752

  18. 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…

  19. Future Concerns of Adult Siblings of Persons with Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Degeneffe, Charles Edmund; Olney, Marjorie F.

    2008-01-01

    This study examined future concerns conveyed by adult siblings who provided regular caregiving support to their brothers and sisters with traumatic brain injury (TBI). The authors surveyed a national sample of 280 adult siblings of persons with TBI. Using a constant comparative approach to text analysis, the authors analyzed responses to the…

  20. 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

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

    PubMed

    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

  2. Schizophrenia susceptibility alleles are enriched for alleles that affect gene expression in adult human brain

    PubMed Central

    Richards, Alexander L; Jones, Lesley; Moskvina, Valentina; Kirov, George; Gejman, Pablo V; Levinson, Douglas F; Sanders, Alan R; Purcell, Shaun; Visscher, Peter M; Craddock, Nick; Owen, Michael J; Holmans, Peter; O’Donovan, Michael C

    2016-01-01

    It is widely thought that alleles that influence susceptibility to common diseases, including schizophrenia, will frequently do so through effects on gene expression. Since only a small proportion of the genetic variance for schizophrenia has been attributed to specific loci, this remains an unproven hypothesis. The International Schizophrenia Consortium (ISC) recently reported a substantial polygenic contribution to that disorder, and that schizophrenia risk alleles are enriched among SNPs selected for marginal evidence for association (p<0.5) from genome wide association studies (GWAS). It follows that if schizophrenia susceptibility alleles are enriched for those that affect gene expression, those marginally associated SNPs which are also eQTLs should carry more true association signals compared with SNPs which are not. To test this, we identified marginally associated (p<0.5) SNPs from two of the largest available schizophrenia GWAS datasets. We assigned eQTL status to those SNPs based upon an eQTL dataset derived from adult human brain. Using the polygenic score method of analysis reported by the ISC, we observed and replicated the observation that higher probability cis-eQTLs predicted schizophrenia better than those with a lower probability for being a cis-eQTL. Our data support the hypothesis that alleles conferring risk of schizophrenia are enriched among those that affect gene expression. Moreover, our data show that notwithstanding the likely developmental origin of schizophrenia, studies of adult brain tissue can in principle allow relevant susceptibility eQTLs to be identified. PMID:21339752

  3. Brain structure and cognitive correlates of body mass index in healthy older adults

    PubMed Central

    Bolzenius, Jacob D.; Laidlaw, David H.; Cabeen, Ryan P.; Conturo, Thomas E.; McMichael, Amanda R.; Lane, Elizabeth M.; Heaps, Jodi M.; Salminen, Lauren E.; Baker, Laurie M.; Scott, Staci E.; Cooley, Sarah A.; Gunstad, John; Paul, Robert H.

    2014-01-01

    Obesity, commonly measured with body mass index (BMI), is associated with numerous deleterious health conditions including alterations in brain integrity related to advanced age. Prior research has suggested that white matter integrity observed using diffusion tensor imaging (DTI) is altered in relation to high BMI, but the integrity of specific white matter tracts remains poorly understood. Additionally, no studies have examined white matter tract integrity in conjunction with neuropsychological evaluation associated with BMI among older adults. The present study examined white matter tract integrity using DTI and cognitive performance associated with BMI in 62 healthy older adults (20 males, 42 females) aged 51 to 81. Results revealed that elevated BMI was associated with lower fractional anisotropy (FA) in the uncinate fasciculus, though there was no evidence of an age by BMI interaction relating to FA in this tract. No relationships were observed between BMI and other white matter tracts or cognition after controlling for demographic variables. Findings suggest that elevated BMI is associated with lower structural integrity in a brain region connecting frontal and temporal lobes and this alteration precedes cognitive dysfunction. Future studies should examine biological mechanisms that mediate the relationships between BMI and white matter tract integrity, as well as the evolution of these abnormalities utilizing longitudinal designs. PMID:25448431

  4. Brain structure and cognitive correlates of body mass index in healthy older adults.

    PubMed

    Bolzenius, Jacob D; Laidlaw, David H; Cabeen, Ryan P; Conturo, Thomas E; McMichael, Amanda R; Lane, Elizabeth M; Heaps, Jodi M; Salminen, Lauren E; Baker, Laurie M; Scott, Staci E; Cooley, Sarah A; Gunstad, John; Paul, Robert H

    2015-02-01

    Obesity, commonly measured with body mass index (BMI), is associated with numerous deleterious health conditions including alterations in brain integrity related to advanced age. Prior research has suggested that white matter integrity observed using diffusion tensor imaging (DTI) is altered in relation to high BMI, but the integrity of specific white matter tracts remains poorly understood. Additionally, no studies have examined white matter tract integrity in conjunction with neuropsychological evaluation associated with BMI among older adults. The present study examined white matter tract integrity using DTI and cognitive performance associated with BMI in 62 healthy older adults (20 males, 42 females) aged 51-81. Results revealed that elevated BMI was associated with lower fractional anisotropy (FA) in the uncinate fasciculus, though there was no evidence of an age by BMI interaction relating to FA in this tract. No relationships were observed between BMI and other white matter tracts or cognition after controlling for demographic variables. Findings suggest that elevated BMI is associated with lower structural integrity in a brain region connecting frontal and temporal lobes and this alteration precedes cognitive dysfunction. Future studies should examine biological mechanisms that mediate the relationships between BMI and white matter tract integrity, as well as the evolution of these abnormalities utilizing longitudinal designs. PMID:25448431

  5. 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

  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. Pre-Adult MRI of Brain Cancer and Neurological Injury: Multivariate Analyses

    PubMed Central

    Levman, Jacob; Takahashi, Emi

    2016-01-01

    Brain cancer and neurological injuries, such as stroke, are life-threatening conditions for which further research is needed to overcome the many challenges associated with providing optimal patient care. Multivariate analysis (MVA) is a class of pattern recognition technique involving the processing of data that contains multiple measurements per sample. MVA can be used to address a wide variety of neuroimaging challenges, including identifying variables associated with patient outcomes; understanding an injury’s etiology, development, and progression; creating diagnostic tests; assisting in treatment monitoring; and more. Compared to adults, imaging of the developing brain has attracted less attention from MVA researchers, however, remarkable MVA growth has occurred in recent years. This paper presents the results of a systematic review of the literature focusing on MVA technologies applied to brain injury and cancer in neurological fetal, neonatal, and pediatric magnetic resonance imaging (MRI). With a wide variety of MRI modalities providing physiologically meaningful biomarkers and new biomarker measurements constantly under development, MVA techniques hold enormous potential toward combining available measurements toward improving basic research and the creation of technologies that contribute to improving patient care. PMID:27446888

  8. Neurobehavioural treatment for obsessive-compulsive disorder in an adult with traumatic brain injury.

    PubMed

    Arco, Lucius

    2008-01-01

    Although obsessive-compulsive disorder has been reported as one of many anxiety-related sequelae of brain injury, few empirical data of its responsiveness to psychological intervention are available. In this study, a single participant changing criterion experimental design was used to evaluate a neurobehavioural intervention for compulsive behaviour of an adult with severe traumatic brain injury. The participant, a man aged 24 years, had sustained frontal-temporal lobe brain trauma 12 months earlier, and presented with compulsive counting and voiding of bladder. The neurobehavioural intervention consisted of regular in-home consultations, self-regulation procedures including self-recording of compulsive behaviour, stress-coping strategies, errorless remediation, social reinforcement, and gradual fading of intervention. Baseline showed counting occurred on average 80% of daily hourly intervals, and voiding 12 times per day. Intervention produced elimination of compulsive counting, acceptable voiding at 8 times per day, and reports of the participant's satisfaction with intervention methods and outcomes. At 6 months follow-up, counting remained at zero levels, and voiding had decreased further to 7 times per day. PMID:18058389

  9. Pre-Adult MRI of Brain Cancer and Neurological Injury: Multivariate Analyses.

    PubMed

    Levman, Jacob; Takahashi, Emi

    2016-01-01

    Brain cancer and neurological injuries, such as stroke, are life-threatening conditions for which further research is needed to overcome the many challenges associated with providing optimal patient care. Multivariate analysis (MVA) is a class of pattern recognition technique involving the processing of data that contains multiple measurements per sample. MVA can be used to address a wide variety of neuroimaging challenges, including identifying variables associated with patient outcomes; understanding an injury's etiology, development, and progression; creating diagnostic tests; assisting in treatment monitoring; and more. Compared to adults, imaging of the developing brain has attracted less attention from MVA researchers, however, remarkable MVA growth has occurred in recent years. This paper presents the results of a systematic review of the literature focusing on MVA technologies applied to brain injury and cancer in neurological fetal, neonatal, and pediatric magnetic resonance imaging (MRI). With a wide variety of MRI modalities providing physiologically meaningful biomarkers and new biomarker measurements constantly under development, MVA techniques hold enormous potential toward combining available measurements toward improving basic research and the creation of technologies that contribute to improving patient care. PMID:27446888

  10. Insulin-like growth factor I is required for vessel remodeling in the adult brain

    PubMed Central

    Lopez-Lopez, C.; LeRoith, D.; Torres-Aleman, I.

    2004-01-01

    Although vascular dysfunction is a major suspect in the etiology of several important neurodegenerative diseases, the signals involved in vessel homeostasis in the brain are still poorly understood. We have determined whether insulin-like growth factor I (IGF-I), a wide-spectrum growth factor with angiogenic actions, participates in vascular remodeling in the adult brain. IGF-I induces the growth of cultured brain endothelial cells through hypoxiainducible factor 1α and vascular endothelial growth factor, a canonical angiogenic pathway. Furthermore, the systemic injection of IGF-I in adult mice increases brain vessel density. Physical exercise that stimulates widespread brain vessel growth in normal mice fails to do so in mice with low serum IGF-I. Brain injury that stimulates angiogenesis at the injury site also requires IGF-I to promote perilesion vessel growth, because blockade of IGF-I input by an anti-IGF-I abrogates vascular growth at the injury site. Thus, IGF-I participates in vessel remodeling in the adult brain. Low serum/brain IGF-I levels that are associated with old age and with several neurodegenerative diseases may be related to an increased risk of vascular dysfunction. PMID:15210967

  11. Systematic Review of the Literature on Pain in Patients with Polytrauma Including Traumatic Brain Injury

    PubMed Central

    Dobscha, Steven K.; Clark, Michael E.; Morasco, Benjamin J.; Freeman, Michele; Campbell, Rose; Helfand, Mark

    2010-01-01

    Objective To review the literature addressing the assessment and management of pain in patients with polytraumatic injuries including traumatic brain injury (TBI) and blast-related headache, and to identify patient, clinician and systems factors associated with pain-related outcomes. Design Systematic review. Methods We conducted searches in MEDLINE of literature published from 1950 through July 2008. Due to a limited number of studies using controls or comparators, we included observational and rigorous qualitative studies. We systematically rated the quality of systematic reviews, cohort, and case-control design studies. Results One systematic review, 93 observational studies, and one qualitative research study met inclusion criteria. The literature search yielded no published studies that assessed measures of pain intensity or pain-related functional interference among patients with cognitive deficits due to TBI, that compared patients with blast-related headache with patients with other types of headache, or that assessed treatments for blast-related headache pain. Studies on the association between TBI severity and pain reported mixed findings. There was limited evidence that the following factors are associated with pain among TBI patients: severity, location, and multiplicity of injuries; insomnia; fatigue; depression; and post-traumatic stress disorder. Conclusions Very little evidence is currently available to guide pain assessment and treatment approaches in patients with polytrauma. Further research employing systematic observational as well as controlled intervention designs is clearly indicated. PMID:19818031

  12. Expression of Npas4 mRNA in Telencephalic Areas of Adult and Postnatal Mouse Brain

    PubMed Central

    Damborsky, Joanne C.; Slaton, G. Simona; Winzer-Serhan, Ursula H.

    2015-01-01

    The transcription factor neuronal PAS domain-containing protein 4 (Npas4) is an inducible immediate early gene which regulates the formation of inhibitory synapses, and could have a significant regulatory role during cortical circuit formation. However, little is known about basal Npas4 mRNA expression during postnatal development. Here, postnatal and adult mouse brain sections were processed for isotopic in situ hybridization using an Npas4 specific cRNA antisense probe. In adults, Npas4 mRNA was found in the telencephalon with very restricted or no expression in diencephalon or mesencephalon. In most telencephalic areas, including the anterior olfactory nucleus (AON), piriform cortex, neocortex, hippocampus, dorsal caudate putamen (CPu), septum and basolateral amygdala nucleus (BLA), basal Npas4 expression was detected in scattered cells which exhibited strong hybridization signal. In embryonic and neonatal brain sections, Npas4 mRNA expression signals were very low. Starting at postnatal day 5 (P5), transcripts for Npas4 were detected in the AON, CPu and piriform cortex. At P8, additional Npas4 hybridization was found in CA1 and CA3 pyramidal layer, and in primary motor cortex. By P13, robust mRNA expression was located in layers IV and VI of all sensory cortices, frontal cortex and cingulate cortex. After onset of expression, postnatal spatial mRNA distribution was similar to that in adults, with the exception of the CPu, where Npas4 transcripts became gradually restricted to the most dorsal part. In conclusion, the spatial distribution of Npas4 mRNA is mostly restricted to telencephalic areas, and the temporal expression increases with developmental age during postnatal development, which seem to correlate with the onset of activity-driven excitatory transmission. PMID:26633966

  13. Analysis of adult neurogenesis: evidence for a prominent "non-neurogenic" DCX-protein pool in rodent brain.

    PubMed

    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

  14. 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

  15. 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

  16. 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

  17. Hyperbaric oxygen as an adjunctive therapy in treatment of malignancies, including brain tumours.

    PubMed

    Stępień, Katarzyna; Ostrowski, Robert P; Matyja, Ewa

    2016-09-01

    Hyperbaric oxygen (HBO) therapy is widely used as an adjunctive treatment for various pathological states, predominantly related to hypoxic and/or ischaemic conditions. It also holds promise as an approach to overcoming the problem of oxygen deficiency in the poorly oxygenated regions of the neoplastic tissue. Occurrence of local hypoxia within the central areas of solid tumours is one of the major issues contributing to ineffective medical treatment. However, in anti-cancer therapy, HBO alone gives a limited curative effect and is typically not applied by itself. More often, HBO is used as an adjuvant treatment along with other therapeutic modalities, such as radio- and chemotherapy. This review outlines the existing data regarding the medical use of HBO in cancer treatment, with a particular focus on the use of HBO in the treatment of brain tumours. We conclude that the administration of HBO can provide many clinical benefits in the treatment of tumours, including management of highly malignant gliomas. Applied immediately before irradiation, it is safe and well tolerated by patients, causing rare and limited side effects. The results obtained with a combination of HBO/radiotherapy protocol proved to be especially favourable compared to radiation treatment alone. HBO can also increase the cytostatic effect of certain drugs, which may render standard chemotherapy more effective. The currently available data support the legitimacy of conducting further research on the use of HBO in the treatment of malignancies. PMID:27485098

  18. 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

  19. Adult neurogenesis in the crayfish brain: proliferation, migration and possible origin of precursor cells

    PubMed Central

    Zhang, Y.; Allodi, S.; Sandeman, D.C.; Beltz, B.S.

    2015-01-01

    The birth of new neurons and their incorporation into functional circuits in the adult brain is a characteristic of many vertebrate and invertebrate organisms, including decapod crustaceans. Precursor cells maintaining life-long proliferation in the brains of crayfish (Procambarus clarkii, Cherax destructor) and clawed lobsters (Homarus americanus) reside within a specialized niche on the ventral surface of the brain; their daughters migrate to two proliferation zones along a stream formed by processes of the niche precursors. Here they divide again, finally producing interneurons in the olfactory pathway. The present studies in P. clarkii explore (1) differential proliferative activity among the niche precursor cells with growth and aging, (2) morphological characteristics of cells in the niche and migratory streams, and (3) aspects of the cell cycle in this lineage. Morphologically symmetrical divisions of neuronal precursor cells were observed in the niche near where the migratory streams emerge, as well as in the streams and proliferation zones. The nuclei of migrating cells elongate and undergo shape changes consistent with nucleokinetic movement. LIS1, a highly conserved dynein-binding protein, is expressed in cells in the migratory stream and neurogenic niche, implicating this protein in the translocation of crustacean brain neuronal precursor cells. Symmetrical divisions of the niche precursors and migration of both daughters raised the question of how the niche precursor pool is replenished. We present here preliminary evidence for an association between vascular cells and the niche precursors, which may relate to the life-long growth and maintenance of the crustacean neurogenic niche. PMID:19294644

  20. Adult neurogenesis in the crayfish brain: proliferation, migration, and possible origin of precursor cells.

    PubMed

    Zhang, Yi; Allodi, Silvana; Sandeman, David C; Beltz, Barbara S

    2009-06-01

    The birth of new neurons and their incorporation into functional circuits in the adult brain is a characteristic of many vertebrate and invertebrate organisms, including decapod crustaceans. Precursor cells maintaining life-long proliferation in the brains of crayfish (Procambarus clarkii, Cherax destructor) and clawed lobsters (Homarus americanus) reside within a specialized niche on the ventral surface of the brain; their daughters migrate to two proliferation zones along a stream formed by processes of the niche precursors. Here they divide again, finally producing interneurons in the olfactory pathway. The present studies in P. clarkii explore (1) differential proliferative activity among the niche precursor cells with growth and aging, (2) morphological characteristics of cells in the niche and migratory streams, and (3) aspects of the cell cycle in this lineage. Morphologically symmetrical divisions of neuronal precursor cells were observed in the niche near where the migratory streams emerge, as well as in the streams and proliferation zones. The nuclei of migrating cells elongate and undergo shape changes consistent with nucleokinetic movement. LIS1, a highly conserved dynein-binding protein, is expressed in cells in the migratory stream and neurogenic niche, implicating this protein in the translocation of crustacean brain neuronal precursor cells. Symmetrical divisions of the niche precursors and migration of both daughters raised the question of how the niche precursor pool is replenished. We present here preliminary evidence for an association between vascular cells and the niche precursors, which may relate to the life-long growth and maintenance of the crustacean neurogenic niche. PMID:19294644

  1. 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

  2. Morphological brain network assessed using graph theory and network filtration in deaf adults.

    PubMed

    Kim, Eunkyung; Kang, Hyejin; Lee, Hyekyoung; Lee, Hyo-Jeong; Suh, Myung-Whan; Song, Jae-Jin; Oh, Seung-Ha; Lee, Dong Soo

    2014-09-01

    Prolonged deprivation of auditory input can change brain networks in pre- and postlingual deaf adults by brain-wide reorganization. To investigate morphological changes in these brains voxel-based morphometry, voxel-wise correlation with the primary auditory cortex, and whole brain network analyses using morphological covariance were performed in eight prelingual deaf, eleven postlingual deaf, and eleven hearing adults. Network characteristics based on graph theory and network filtration based on persistent homology were examined. Gray matter density in the primary auditor cortex was preserved in prelingual deafness, while it tended to decrease in postlingual deafness. Unlike postlingual, prelingual deafness showed increased bilateral temporal connectivity of the primary auditory cortex compared to the hearing adults. Of the graph theory-based characteristics, clustering coefficient, betweenness centrality, and nodal efficiency all increased in prelingual deafness, while all the parameters of postlingual deafness were similar to the hearing adults. Patterns of connected components changing during network filtration were different between prelingual deafness and hearing adults according to the barcode, dendrogram, and single linkage matrix representations, while these were the same in postlingual deafness. Nodes in fronto-limbic and left temporal components were closely coupled, and nodes in the temporo-parietal component were loosely coupled, in prelingual deafness. Patterns of connected components changing in postlingual deafness were the same as hearing adults. We propose that the preserved density of auditory cortex associated with increased connectivity in prelingual deafness, and closer coupling between certain brain areas, represent distinctive reorganization of auditory and related cortices compared with hearing or postlingual deaf adults. The differential network reorganization in the prelingual deaf adults could be related to the absence of auditory speech

  3. Transsynaptic trophic effects of steroid hormones in an avian model of adult brain plasticity

    PubMed Central

    Brenowitz, Eliot A.

    2014-01-01

    The avian song control system provides an excellent model for studying transsynaptic trophic effects of steroid sex hormones. Seasonal changes in systemic testosterone (T) and its metabolites regulate plasticity of this system. Steroids interact with the neurotrophin brain-derived neurotrophic factor (BDNF) to influence cellular processes of plasticity in nucleus HVC of adult birds, including the addition of newborn neurons. This interaction may also occur transsynpatically; T increases the synthesis of BDNF in HVC, and BDNF protein is then released by HVC neurons on to postsynaptic cells in nucleus RA where it has trophic effects on activity and morphology. Androgen action on RA neurons increases their activity and this has a retrograde trophic effect on the addition of new neurons to HVC. The functional linkage of sex steroids to BDNF may be of adaptive value in regulating the trophic effects of the neurotrophin and coordinating circuit function in reproductively relevant contexts. PMID:25285401

  4. 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

  5. Environmental changes in oxygen tension reveal ROS-dependent neurogenesis and regeneration in the adult newt brain.

    PubMed

    Hameed, L Shahul; Berg, Daniel A; Belnoue, Laure; Jensen, Lasse D; Cao, Yihai; Simon, András

    2015-01-01

    Organisms need to adapt to the ecological constraints in their habitat. How specific processes reflect such adaptations are difficult to model experimentally. We tested whether environmental shifts in oxygen tension lead to events in the adult newt brain that share features with processes occurring during neuronal regeneration under normoxia. By experimental simulation of varying oxygen concentrations, we show that hypoxia followed by re-oxygenation lead to neuronal death and hallmarks of an injury response, including activation of neural stem cells ultimately leading to neurogenesis. Neural stem cells accumulate reactive oxygen species (ROS) during re-oxygenation and inhibition of ROS biosynthesis counteracts their proliferation as well as neurogenesis. Importantly, regeneration of dopamine neurons under normoxia also depends on ROS-production. These data demonstrate a role for ROS-production in neurogenesis in newts and suggest that this role may have been recruited to the capacity to replace lost neurons in the brain of an adult vertebrate. PMID:26485032

  6. Update on tetralogy of Fallot for the adult cardiologist including a brief historical and surgical perspective.

    PubMed

    Kalra, Nishant; Klewer, Scott E; Raasch, Hannah; Sorrell, Vincent L

    2010-01-01

    There has been a steady rise in the prevalence of severe congenital heart disease (CHD) in adults because of improved treatment and survival during childhood. This has resulted in a shift in CHD morbidity and mortality beyond 18 years of age. The healthcare community must be prepared to meet this new challenge. Adult cardiologists need to be aware of common CHD, such as tetralogy of Fallot (TOF), as they will encounter adults with this CHD in their practice. With routine monitoring, cardiac imaging, early intervention, and treatment as highlighted in this report, continued improvement in the long-term fitness and avoidance of late complications for adult TOF patient is anticipated. PMID:20576040

  7. 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

  8. Using Network Science to Evaluate Exercise-Associated Brain Changes in Older Adults

    PubMed Central

    Burdette, Jonathan H.; Laurienti, Paul J.; Espeland, Mark A.; Morgan, Ashley; Telesford, Qawi; Vechlekar, Crystal D.; Hayasaka, Satoru; Jennings, Janine M.; Katula, Jeffrey A.; Kraft, Robert A.; Rejeski, W. Jack

    2010-01-01

    Literature has shown that exercise is beneficial for cognitive function in older adults and that aerobic fitness is associated with increased hippocampal tissue and blood volumes. The current study used novel network science methods to shed light on the neurophysiological implications of exercise-induced changes in the hippocampus of older adults. Participants represented a volunteer subgroup of older adults that were part of either the exercise training (ET) or healthy aging educational control (HAC) treatment arms from the Seniors Health and Activity Research Program Pilot (SHARP-P) trial. Following the 4-month interventions, MRI measures of resting brain blood flow and connectivity were performed. The ET group's hippocampal cerebral blood flow (CBF) exhibited statistically significant increases compared to the HAC group. Novel whole-brain network connectivity analyses showed greater connectivity in the hippocampi of the ET participants compared to HAC. Furthermore, the hippocampus was consistently shown to be within the same network neighborhood (module) as the anterior cingulate cortex only within the ET group. Thus, within the ET group, the hippocampus and anterior cingulate were highly interconnected and localized to the same network neighborhood. This project shows the power of network science to investigate potential mechanisms for exercise-induced benefits to the brain in older adults. We show a link between neurological network features and CBF, and it is possible that this alteration of functional brain networks may lead to the known improvement in cognitive function among older adults following exercise. PMID:20589103

  9. Brain function differences in language processing in children and adults with autism.

    PubMed

    Williams, Diane L; Cherkassky, Vladimir L; Mason, Robert A; Keller, Timothy A; Minshew, Nancy J; Just, Marcel Adam

    2013-08-01

    Comparison of brain function between children and adults with autism provides an understanding of the effects of the disorder and associated maturational differences on language processing. Functional imaging (functional magnetic resonance imaging) was used to examine brain activation and cortical synchronization during the processing of literal and ironic texts in 15 children with autism, 14 children with typical development, 13 adults with autism, and 12 adult controls. Both the children and adults with autism had lower functional connectivity (synchronization of brain activity among activated areas) than their age and ability comparison group in the left hemisphere language network during irony processing, and neither autism group had an increase in functional connectivity in response to increased task demands. Activation differences for the literal and irony conditions occurred in key language-processing regions (left middle temporal, left pars triangularis, left pars opercularis, left medial frontal, and right middle temporal). The children and adults with autism differed from each other in the use of some brain regions during the irony task, with the adults with autism having activation levels similar to those of the control groups. Overall, the children and adults with autism differed from the adult and child controls in (a) the degree of network coordination, (b) the distribution of the workload among member nodes, and (3) the dynamic recruitment of regions in response to text content. Moreover, the differences between the two autism age groups may be indicative of positive changes in the neural function related to language processing associated with maturation and/or educational experience. PMID:23495230

  10. Brain Function Differences in Language Processing in Children and Adults with Autism

    PubMed Central

    Williams, Diane L.; Cherkassky, Vladimir L.; Mason, Robert A.; Keller, Timothy A.; Minshew, Nancy J.; Just, Marcel Adam

    2015-01-01

    Comparison of brain function between children and adults with autism provides an understanding of the effects of the disorder and associated maturational differences on language processing. Functional imaging (functional magnetic resonance imaging) was used to examine brain activation and cortical synchronization during the processing of literal and ironic texts in 15 children with autism, 14 children with typical development, 13 adults with autism, and 12 adult controls. Both the children and adults with autism had lower functional connectivity (synchronization of brain activity among activated areas) than their age and ability comparison group in the left hemisphere language network during irony processing, and neither autism group had an increase in functional connectivity in response to increased task demands. Activation differences for the literal and irony conditions occurred in key language-processing regions (left middle temporal, left pars triangularis, left pars opercularis, left medial frontal, and right middle temporal). The children and adults with autism differed from each other in the use of some brain regions during the irony task, with the adults with autism having activation levels similar to those of the control groups. Overall, the children and adults with autism differed from the adult and child controls in (a) the degree of network coordination, (b) the distribution of the workload among member nodes, and (3) the dynamic recruitment of regions in response to text content. Moreover, the differences between the two autism age groups may be indicative of positive changes in the neural function related to language processing associated with maturation and/or educational experience. PMID:23495230

  11. 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

  12. 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

  13. Competence in Caregivers of Adolescent and Young Adult Childhood Brain Tumor Survivors

    PubMed Central

    Deatrick, Janet A.; Hobbie, Wendy; Ogle, Sue; Fisher, Michael J.; Barakat, Lamia; Hardie, Thomas; Reilly, Maureen; Li, Yimei; Ginsberg, Jill P.

    2015-01-01

    Objective Caregivers of adolescents and young adults (AYA) with complex medical conditions, including brain tumor survivors, have protracted and often complex roles, yet a gap exists in understanding their perceived competence. The aim of this study is to test a hypothesized model based on the theoretical and empirical literature: better caregiver health, better survivor health, and better family functioning contribute directly to fewer caregiving demands, which in turn contribute to greater caregiver competence. Method Telephone interviews using structured self-report questionnaires were conducted in this cross-sectional study with a sample of 186 caregivers (mothers) of childhood brain tumor survivors aged 14–40 years old who live with at least one parent. Structural equation modeling (SEM) was used to test the hypothesized model. Results The final SEM model suggests that survivor health and family functioning directly predict caregiver competence. Caregiver health indirectly predicts caregiver competence through caregiver demands and then family functioning. Family income directly predicts family functioning. The model showed adequate fit (CFI = 0.905, TFI = 0.880, and RMSEA = 0.081). Overall, the model accounted for 45% of variance in caregiver competence. Conclusions For this sample of caregivers of AYA with medically complex conditions, family functioning and the health of survivors are both important to how they evaluate their skills as caregivers. The results of this study underscore the crucial role of care models that focus on optimizing the health of the survivor, caregiver, and family, along with supporting a family centered approach to their care. PMID:23957900

  14. Adult axolotls can regenerate original neuronal diversity in response to brain injury

    PubMed Central

    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. DOI: http://dx.doi.org/10.7554/eLife.13998.001 PMID:27156560

  15. Environmental enrichment influences neuronal stem cells in the adult crayfish brain

    PubMed Central

    Ayub, Neishay; Benton, Jeanne L.; Zhang, Yi; Beltz, Barbara S.

    2011-01-01

    New neurons are incorporated throughout life into the brains of many vertebrate and non-vertebrate species. This process of adult neurogenesis is regulated by a variety of external and endogenous factors, including environmental enrichment, which increases the production of neurons in juvenile mice and crayfish. The primary goal of the present study was to exploit the spatial separation of the neuronal precursor cell lineage in crayfish to determine which generation(s) of precursors is altered by environmental conditions. Further, in crayfish, an intimate relationship between the 1st generation neuronal precursors (stem cells) and cells circulating in the hemolymph has been proposed (Zhang et al., 2009). Therefore, a second goal was to assess whether environmental enrichment alters the numbers or types of cells circulating in the hemolymph. We find that neurogenesis in the brains of sexually differentiated procambarid crayfish is enhanced by environmental enrichment as previously demonstrated by Sandeman and Sandeman (2000) in young, sexually undifferentiated Cherax destructor. We also show that environmental enrichment increases the cell cycle rate of neuronal stem cells. While there was no effect of environment on the overall numbers of cells circulating in the hemolymph, enrichment resulted in increased expression of glutamine synthetase, a marker of the neuronal stem cells, in a small percentage of circulating cells; there was little or no expression of this enzyme in hemolymph cells extracted from deprived animals. Thus, environmental enrichment influences the rate of neuronal stem cell division in adult crayfish, as well as the composition of cells circulating in the hemolymph. PMID:21485010

  16. (/sup 125/I)endothelin-1 binding sites: Autoradiographic studies in the brain and periphery of various species including humans

    SciTech Connect

    Hoyer, D.; Waeber, C.; Palacios, J.M.

    1989-01-01

    Quantitative autoradiography with (/sup 125/I)-endothelin-1 (ET-1) has been used to localize putative ET-1 recognition sites in the brain and peripheral organs of various species including humans. High densities of high-affinity (/sup 125/I)ET-1 binding sites were observed in heart, lung, liver, kidney, blood vessels, and brain. A differential pattern of distribution of ET-1 recognition sites was observed in the periphery and in the brain, indicating that putative ET-1 receptors are not located only in blood vessels. The data are consistent with a role for ET-1 in vascular smooth muscle and nonvascular tissues, such as heart, lung, intestine, kidney, and brain.

  17. The effects of sleep deprivation on brain functioning in older adults.

    PubMed

    Almklov, Erin L; Drummond, Sean P A; Orff, Henry; Alhassoon, Omar M

    2015-01-01

    Few studies have examined the effects of total sleep deprivation (TSD) on cognitive performance and brain activation using functional MRI (fMRI) in older adults. The current study examines blood oxygen level-dependent (BOLD) activation in older adults and younger adults during the sustained attention (GO) and response inhibition (NOGO) portions of a GO-NOGO cognitive task following 36 hr of total sleep deprivation. No significant performance differences were observed between the groups on the behavioral outcome measures of total hits and false alarms. Neuroimaging results, however, revealed a significant interaction between age-group and sleep-deprivation status. Specifically, older adults showed greater BOLD activation as compared to younger adults after 36 hours total sleep deprivation in brain regions typically associated with attention and inhibitory processes. These results suggest in order for older adults to perform the GO-NOGO task effectively after sleep deprivation, they rely on compensatory recruitment of brain regions that aide in the maintenance of cognitive performance. PMID:24787041

  18. Systematic Review of Interventions to Improve the Provision of Information for Adults with Primary Brain Tumors and Their Caregivers

    PubMed Central

    Langbecker, Danette; Janda, Monika

    2014-01-01

    Background: Adults with primary brain tumors and their caregivers have significant information needs. This review assessed the effect of interventions to improve information provision for adult primary brain tumor patients and/or their caregivers. Methods: We included randomized or non-randomized trials testing educational interventions that had outcomes of information provision, knowledge, understanding, recall, or satisfaction with the intervention, for adults diagnosed with primary brain tumors and/or their family or caregivers. PubMed, MEDLINE, EMBASE, and Cochrane Reviews databases were searched for studies published between 1980 and June 2014. Results: Two randomized controlled, 1 non-randomized controlled, and 10 single group pre–post trials enrolled more than 411 participants. Five group, four practice/process change, and four individual interventions assessed satisfaction (12 studies), knowledge (4 studies), and information provision (2 studies). Nine studies reported high rates of satisfaction. Three studies showed statistically significant improvements over time in knowledge and two showed greater information was provided to intervention than control group participants, although statistical testing was not performed. Discussion: The trials assessed intermediate outcomes such as satisfaction, and only 4/13 reported on knowledge improvements. Few trials had a randomized controlled design and risk of bias was either evident or could not be assessed in most domains. PMID:25667919

  19. Seasonal regulation of structural plasticity and neurogenesis in the adult mammalian brain: focus on the sheep hypothalamus.

    PubMed

    Migaud, Martine; Butrille, Lucile; Batailler, Martine

    2015-04-01

    To cope with variations in the environment, most mammalian species exhibit seasonal cycles in physiology and behaviour. Seasonal plasticity during the lifetime contributes to seasonal physiology. Over the years, our ideas regarding adult brain plasticity and, more specifically, hypothalamic plasticity have greatly evolved. Along with the two main neurogenic regions, namely the hippocampal subgranular and lateral ventricle subventricular zones, the hypothalamus, which is the central homeostatic regulator of numerous physiological functions that comprise sexual behaviours, feeding and metabolism, also hosts neurogenic niches. Both endogenous and exogenous factors, including the photoperiod, modulate the hypothalamic neurogenic capacities. The present review describes the effects of season on adult morphological plasticity and neurogenesis in seasonal species, for which the photoperiod is a master environmental cue for the successful programming of seasonal functions. In addition, the potential functional significance of adult neurogenesis in the mediation of the seasonal control of reproduction and feeding is discussed. PMID:25462590

  20. 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

  1. Pulmonary Function After Treatment for Embryonal Brain Tumors on SJMB03 That Included Craniospinal Irradiation

    SciTech Connect

    Green, Daniel M.; Merchant, Thomas E.; Billups, Catherine A.; Stokes, Dennis C.; Broniscer, Alberto; Bartels, Ute; Chintagumpala, Murali; Hassall, Timothy E.; Gururangan, Sridharan; McCowage, Geoffrey B.; Heath, John A.; Cohn, Richard J.; Fisher, Michael J.; Srinivasan, Ashok; Robinson, Giles W.; Gajjar, Amar

    2015-09-01

    Purpose: The treatment of children with embryonal brain tumors (EBT) includes craniospinal irradiation (CSI). There are limited data regarding the effect of CSI on pulmonary function. Methods: Protocol SJMB03 enrolled patients 3 to 21 years of age with EBT. Pulmonary function tests (PFTs) (forced expiratory volume in 1 second [FEV{sub 1}] and forced vital capacity [FVC] by spirometry, total lung capacity [TLC] by nitrogen washout or plethysmography, and diffusing capacity of the lung for carbon monoxide corrected for hemoglobin [DLCO{sub corr}]) were obtained. Differences between PFTs obtained immediately after the completion of CSI and 24 or 60 months after the completion of treatment (ACT) were compared using exact Wilcoxon signed-rank tests and repeated-measures models. Results: Between June 24, 2003, and March 1, 2010, 303 eligible patients (spine dose: ≤2345 cGy, 201; >2345 cGy, 102; proton beam, 20) were enrolled, 260 of whom had at least 1 PFT. The median age at diagnosis was 8.9 years (range, 3.1-20.4 years). The median thoracic spinal radiation dose was 23.4 Gy (interquartile range [IQR], 23.4-36.0 Gy). The median cyclophosphamide dose was 16.0 g/m{sup 2} (IQR, 15.7-16.0 g/m{sup 2}). At 24 and 60 months ACT, DLCO{sub corr} was <75% predicted in 23% (27/118) and 25% (21/84) of patients, FEV{sub 1} was <80% predicted in 20% (34/170) and 29% (32/109) of patients, FVC was <80% predicted in 27% (46/172) and 28% (30/108) of patients, and TLC was <75% predicted in 9% (13/138) and 11% (10/92) of patients. DLCO{sub corr} was significantly decreased 24 months ACT (median difference [MD] in % predicted, 3.00%; P=.028) and 60 months ACT (MD in % predicted, 6.00%; P=.033) compared with the end of radiation therapy. These significant decreases in DLCO{sub corr} were also observed in repeated-measures models (P=.011 and P=.032 at 24 and 60 months ACT, respectively). Conclusions: A significant minority of EBT survivors experience PFT deficits after CSI

  2. Differential vascular permeability along the forebrain ventricular neurogenic niche in the adult murine brain.

    PubMed

    Colín-Castelán, Dannia; Ramírez-Santos, Jesús; Gutiérrez-Ospina, Gabriel

    2016-02-01

    Adult neurogenesis is influenced by blood-borne factors. In this context, greater or lesser vascular permeability along neurogenic niches would expose differentially neural stem cells (NSCs), transit amplifying cells (TACs), and neuroblasts to such factors. Here we evaluate endothelial cell morphology and vascular permeability along the forebrain neurogenic niche in the adult brain. Our results confirm that the subventricular zone (SVZ) contains highly permeable, discontinuous blood vessels, some of which allow the extravasation of molecules larger than those previously reported. In contrast, the rostral migratory stream (RMS) and the olfactory bulb core (OBc) display mostly impermeable, continuous blood vessels. These results imply that NSCs, TACs, and neuroblasts located within the SVZ are exposed more readily to blood-borne molecules, including those with very high molecular weights, than those positioned along the RMS and the OBc, subregions in which every stage of neurogenesis also takes place. These observations suggest that the existence of specialized vascular niches is not a precondition for neurogenesis to occur; specialized vascular beds might be essential for keeping high rates of proliferation and/or differential differentiation of neural precursors located at distinct domains. PMID:26492830

  3. 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…

  4. Amphetamine modulates brain signal variability and working memory in younger and older adults

    PubMed Central

    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

    2015-01-01

    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 (SDBOLD) 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 SDBOLD levels in the presence of AMPH. Drug session order greatly moderated change–change relations between AMPH-driven SDBOLD and reaction time means (RTmean) and SDs (RTSD). Older adults who received AMPH in the first session tended to improve in RTmean and RTSD when SDBOLD was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SDBOLD decreased (for RTmean) or no effect at all (for RTSD). 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. PMID:26034283

  5. 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. PMID:24505468

  6. Regulation of brain water during acute glucose-induced hyperosmolality in ovine fetuses, lambs, and adults.

    PubMed

    Stonestreet, Barbara S; Petersson, Katherine H; Sadowska, Grazyna B; Patlak, Clifford S

    2004-02-01

    We tested the hypothesis that, during acute glucose-induced hyperosmolality, the brain shrinks less than predicted on the basis of an ideal osmometer and that brain volume regulation is present in fetuses, premature and newborn lambs. Brain water responses to glucose-induced hyperosmolality were measured in the cerebral cortex, cerebellum, and medulla of fetuses at 60% of gestation, premature ventilated lambs at 90% of gestation, newborn lambs, and adult sheep. After exposure of the sheep to increases in osmolality with glucose plus NaCl, brain water and electrolytes were measured. The ideal osmometer is a system in which impermeable solutes do not enter or leave in response to an osmotic stress. In the absence of volume regulation, brain solute remains constant as osmolality changes. The osmotically active solute demonstrated direct linear correlations with plasma osmolality in the cerebral cortex of the fetuses at 60% of gestation (r = 0.72, n = 24, P = 0.0001), premature lambs (r = 0.58, n = 22, P = 0.005), newborn lambs (r = 0.57, n = 24, P = 0.004), and adult sheep (r = 0.70, n = 18, P = 0.001). Similar findings were observed in the cerebellum and medulla. Increases in the quantity of osmotically active solute over the range of plasma osmolalities indicate that volume regulation was present in the brain regions of the fetuses, premature lambs, newborn lambs, and adult sheep during glucose-induced hyperosmolality. We conclude that, during glucose-induced hyperosmolality, the brain shrinks less than predicted on the basis of an ideal osmometer and exhibits volume regulation in fetuses at 60% of gestation, premature lambs, newborn lambs, and adult sheep. PMID:14578364

  7. Regeneration, Plasticity, and Induced Molecular Programs in Adult Zebrafish Brain

    PubMed Central

    Cosacak, Mehmet Ilyas; Papadimitriou, Christos; Kizil, Caghan

    2015-01-01

    Regenerative capacity of the brain is a variable trait within animals. Aquatic vertebrates such as zebrafish have widespread ability to renew their brains upon damage, while mammals have—if not none—very limited overall regenerative competence. Underlying cause of such a disparity is not fully evident; however, one of the reasons could be activation of peculiar molecular programs, which might have specific roles after injury or damage, by the organisms that regenerate. If this hypothesis is correct, then there must be genes and pathways that (a) are expressed only after injury or damage in tissues, (b) are biologically and functionally relevant to restoration of neural tissue, and (c) are not detected in regenerating organisms. Presence of such programs might circumvent the initial detrimental effects of the damage and subsequently set up the stage for tissue redevelopment to take place by modulating the plasticity of the neural stem/progenitor cells. Additionally, if transferable, those “molecular mechanisms of regeneration” could open up new avenues for regenerative therapies of humans in clinical settings. This review focuses on the recent studies addressing injury/damage-induced molecular programs in zebrafish brain, underscoring the possibility of the presence of genes that could be used as biomarkers of neural plasticity and regeneration. PMID:26417601

  8. Canonical Genetic Signatures of the Adult Human Brain

    PubMed Central

    Hawrylycz, Michael; Miller, Jeremy A.; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L.; Jegga, Anil G.; Aronow, Bruce J.; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F.; Dierker, Donna L.; Menche, Jörge; Szafer, Aaron; Collman, Forrest; Grange, Pascal; Berman, Kenneth A.; Mihalas, Stefan; Yao, Zizhen; Stewart, Lance; Barabási, Albert-László; Schulkin, Jay; Phillips, John; Ng, Lydia; Dang, Chinh; Haynor, David R.; Jones, Allan; Van Essen, David C.; Koch, Christof; Lein, Ed

    2015-01-01

    The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure, and function. We applied a correlation-based metric of “differential stability” (DS) to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing meso-scale genetic organization. The highest DS genes are highly biologically relevant, with enrichment for brain-related biological annotations, disease associations, drug targets, and literature citations. Using high DS genes we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components, and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely-patterned genes displayed dramatic shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry. PMID:26571460

  9. Canonical genetic signatures of the adult human brain.

    PubMed

    Hawrylycz, Michael; Miller, Jeremy A; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L; Jegga, Anil G; Aronow, Bruce J; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F; Dierker, Donna L; Menche, Jörg; Szafer, Aaron; Collman, Forrest; Grange, Pascal; Berman, Kenneth A; Mihalas, Stefan; Yao, Zizhen; Stewart, Lance; Barabási, Albert-László; Schulkin, Jay; Phillips, John; Ng, Lydia; Dang, Chinh; Haynor, David R; Jones, Allan; Van Essen, David C; Koch, Christof; Lein, Ed

    2015-12-01

    The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure and function. We applied a correlation-based metric called differential stability to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing mesoscale genetic organization. The genes with the highest differential stability are highly biologically relevant, with enrichment for brain-related annotations, disease associations, drug targets and literature citations. Using genes with high differential stability, we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely patterned genes displayed marked shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry. PMID:26571460

  10. Brain Blood Flow Related to Acoustic Laryngeal Reaction Time in Adult Developmental Stutterers.

    ERIC Educational Resources Information Center

    Watson, Ben C.; And Others

    1992-01-01

    This study sought to identify patterns of impaired acoustic laryngeal reaction time as a function of response complexity parallel to metabolic measures of brain function. Findings indicated that the disruption in speech motor control for 16 adult male developmental stutterers was systematically related to metabolic asymmetry in left superior and…

  11. 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)

  12. 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…

  13. 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

  14. Neural Underpinnings of Working Memory in Adult Survivors of Childhood Brain Tumors.

    PubMed

    King, Tricia Z; Na, Sabrina; Mao, Hui

    2015-08-01

    Adult survivors of childhood brain tumors are at risk for cognitive performance deficits that require the core cognitive skill of working memory. Our goal was to examine the neural mechanisms underlying working memory performance in survivors. We studied the working memory of adult survivors of pediatric posterior fossa brain tumors using a letter n-back paradigm with varying cognitive workload (0-, 1-, 2-, and 3-back) and functional magnetic resonance imaging as well as neuropsychological measures. Survivors of childhood brain tumors evidenced lower working memory performance than demographically matched healthy controls. Whole-brain analyses revealed significantly greater blood-oxygen level dependent (BOLD) activation in the left superior / middle frontal gyri and left parietal lobe during working memory (2-back versus 0-back contrast) in survivors. Left frontal BOLD response negatively correlated with 2- and 3-back working memory performance, Auditory Consonant Trigrams (ACT), and Digit Span Backwards. In contrast, parietal lobe BOLD response negatively correlated with 0-back (vigilance task) and ACT. The results revealed that adult survivors of childhood posterior fossa brain tumors recruited additional cognitive control resources in the prefrontal lobe during increased working memory demands. This increased prefrontal activation is associated with lower working memory performance and is consistent with the allocation of latent resources theory. PMID:26234757

  15. [Regulation of neurogenesis: factors affecting of new neurons formation in adult mammals brain].

    PubMed

    Respondek, Michalina; Buszman, Ewa

    2015-01-01

    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. PMID:27259217

  16. 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

  17. 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

  18. Removing brakes on adult brain plasticity: from molecular to behavioral interventions

    PubMed Central

    Bavelier, D.; Levi, D.M.; Li, R.W.; Dan, Y.; Hensch, T.K.

    2010-01-01

    Adult brain plasticity, although possible, remains more restricted in scope than during development. Here, we address conditions under which circuit rewiring may be facilitated in the mature brain. At a cellular and molecular level, adult plasticity is actively limited. Some of these “brakes” are structural, such as peri-neuronal nets or myelin, which inhibit neurite outgrowth. Others are functional, acting directly upon excitatory-inhibitory balance within local circuits. Plasticity in adulthood can be induced either by lifting these brakes through invasive interventions or by exploiting endogenous permissive factors, such as neuromodulators. Using the amblyopic visual system as a model, we discuss genetic, pharmacological, and environmental removal of brakes to enable recovery of vision in adult rodents. Although these mechanisms remain largely uncharted in the human, we consider how they may provide a biological foundation for the remarkable increase in plasticity after action video game play by amblyopic subjects. PMID:21068299

  19. Regional Brain Volumes and ADHD Symptoms in Middle-Aged Adults: The PATH Through Life Study.

    PubMed

    Das, Debjani; Cherbuin, Nicolas; Anstey, Kaarin J; Abhayaratna, Walter; Easteal, Simon

    2014-02-24

    Objective: We investigated whether volumetric differences in ADHD-associated brain regions are related to current symptoms of inattention and hyperactivity in healthy middle-aged adults and whether co-occurring anxiety/depression symptoms moderate these relationships. Method: ADHD Self-Report Scale and Brief Patient Health Questionnaire were used to assess current symptoms of inattention, hyperactivity, anxiety, and depression in a population-based sample (n = 269). Brain volumes, measured using a semi-automated method, were analyzed using multiple regression and structural equation modeling to evaluate brain volume-inattention/hyperactivity symptom relationships for selected regions. Results: Volumes of the left nucleus accumbens and a region overlapping the dorsolateral prefrontal cortex were positively associated with inattention symptoms. Left hippocampal volume was negatively associated with hyperactivity symptoms. The brain volume-inattention/hyperactivity symptom associations were stronger when anxiety/depression symptoms were controlled for. Conclusion: Inattention and hyperactivity symptoms in middle-aged adults are associated with different brain regions and co-occurring anxiety/depression symptoms moderate these brain-behavior relationships. (J. of Att. Dis. XXXX; XX(X) XX-XX). PMID:24567365

  20. The Effects of Face Expertise Training on the Behavioral Performance and Brain Activity of Adults with High Functioning Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Faja, Susan; Webb, Sara Jane; Jones, Emily; Merkle, Kristen; Kamara, Dana; Bavaro, Joshua; Aylward, Elizabeth; Dawson, Geraldine

    2012-01-01

    The effect of expertise training with faces was studied in adults with ASD who showed initial impairment in face recognition. Participants were randomly assigned to a computerized training program involving either faces or houses. Pre- and post-testing included standardized and experimental measures of behavior and event-related brain potentials…

  1. 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. PMID:25939577

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

    PubMed Central

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

    2014-01-01

    Quantitative analysis of the cellular composition of rodent, primate, insectivore, and afrotherian brains has shown that non-neuronal scaling rules are similar across these mammalian orders that diverged about 95 million years ago, and therefore appear to be conserved in evolution, while neuronal scaling rules appear to be free to vary in a clade-specific manner. Here we analyze the cellular scaling rules that apply to the brain of artiodactyls, a group within the order Cetartiodactyla, believed to be a relatively recent radiation from the common Eutherian ancestor. We find that artiodactyls share non-neuronal scaling rules with all groups analyzed previously. Artiodactyls share with afrotherians and rodents, but not with primates, the neuronal scaling rules that apply to the cerebral cortex and cerebellum. The neuronal scaling rules that apply to the remaining brain areas are, however, distinct in artiodactyls. Importantly, we show that the folding index of the cerebral cortex scales with the number of neurons in the cerebral cortex in distinct fashions across artiodactyls, afrotherians, rodents, and primates, such that the artiodactyl cerebral cortex is more convoluted than primate cortices of similar numbers of neurons. Our findings suggest that the scaling rules found to be shared across modern afrotherians, glires, and artiodactyls applied to the common Eutherian ancestor, such as the relationship between the mass of the cerebral cortex as a whole and its number of neurons. In turn, the distribution of neurons along the surface of the cerebral cortex, which is related to its degree of gyrification, appears to be a clade-specific characteristic. If the neuronal scaling rules for artiodactyls extend to all cetartiodactyls, we predict that the large cerebral cortex of cetaceans will still have fewer neurons than the human cerebral cortex. PMID:25429261

  3. 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

  4. Rejecting familiar distracters during recognition in young adults with traumatic brain injury and in healthy older adults.

    PubMed

    Ozen, Lana J; Skinner, Erin I; Fernandes, Myra A

    2010-05-01

    The most common cognitive complaint reported by healthy older adults and young adults with traumatic brain injury (TBI) is memory difficulties. We investigated the effects of normal aging and the long-term effects of TBI in young adults on the susceptibility to incorrectly endorse distracter information on a memory test. Prior to a study phase, participants viewed a "pre-exposure" list containing distracter words, presented once or three times, and half of the target study words. Subsequently, during the study phase, all target words were presented such that, across lists, study words were viewed either once or three times. On the recognition test, TBI and older adult participants were more likely to falsely endorse "pre-exposed" distracter words viewed three times as being from the target study list, compared to non-head-injured young controls. Normal aging and head injury in young may similarly compromise one's ability to reject highly familiar, but distracting, information during recognition. Older adult and TBI participants were also slower to complete the Trail Making task and had poorer output on a Digit Span task, suggesting these two populations share a deficit in executive function and working memory. Similar changes in frontal lobe function may underlie these shared cognitive deficits. PMID:20211048

  5. 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.…

  6. Multidisciplinary management including periodontics, orthodontics, implants, and prosthetics for an adult.

    PubMed

    Pinho, Teresa; Neves, Manuel; Alves, Célia

    2012-08-01

    This article describes the complex dental treatment of an adult patient with multiple missing teeth, mild chronic periodontitis, and a malocclusion with a cant of the occlusal plane. After periodontal treatment, titanium implants and a miniscrew were placed to correct the occlusal plane canting with orthodontic treatment. Prosthodontic treatment was completed by using osseointegrated implants to replace the missing teeth. PMID:22858334

  7. Sleep and synaptic plasticity in the developing and adult brain.

    PubMed

    Frank, Marcos G

    2015-01-01

    Sleep is hypothesized to play an integral role in brain plasticity. This has traditionally been investigated using behavioral assays. In the last 10-15 years, studies combining sleep measurements with in vitro and in vivo models of synaptic plasticity have provided exciting new insights into how sleep alters synaptic strength. In addition, new theories have been proposed that integrate older ideas about sleep function and recent discoveries in the field of synaptic plasticity. There remain, however, important challenges and unanswered questions. For example, sleep does not appear to have a single effect on synaptic strength. An unbiased review of the literature indicates that the effects of sleep vary widely depending on ontogenetic stage, the type of waking experience (or stimulation protocols) that precede sleep and the type of neuronal synapse under examination. In this review, I discuss these key findings in the context of current theories that posit different roles for sleep in synaptic plasticity. PMID:24671703

  8. 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

  9. 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

  10. 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

  11. Calpain proteolysis of alpha II-spectrin in the normal adult human brain.

    PubMed

    Huh, G Y; Glantz, S B; Je, S; Morrow, J S; Kim, J H

    2001-12-01

    The proteolysis of alphaII-spectrin by calpain may be physiologically involved with synaptic remodeling, long-term potentiation, and memory formation. Calpain activation may also mediate neuronal apoptosis, responses to hypoxic insult, and excitotoxic injury. Surprisingly little is known of the activity of these calpain-mediated processes in the adult human brain. Using an antibody that specifically recognizes calpain-cleaved alphaII-spectrin, we have mapped the topographic distribution of the major alphaII-spectrin break-down product (alphaII-bdp1) in six adult brains examined post-mortem. All brains were from patients without evident neurological disease. Focally positive alphaII-bdp1 was consistently detected in the neuropil of the cortical gray matter, in occasional pyramidal neurons, and in rare reactive astrocytes in the cerebral cortex and hippocampus. Cerebellar Purkinje cells were more frequently, and more intensely, immunopositive. In all fields, staining was most intense in the soma and dendrites of neurons. There was no correlation of the frequency of positive cells with the postmortem interval or clinical condition. While these findings do not rigorously exclude contributions from postmortem calpain activation, they do suggest that a low-level of calpain processing of alphaII-spectrin is likely to be a constitutive process in the adult human brain. PMID:11720774

  12. 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

  13. 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

  14. Structural and Functional Rich Club Organization of the Brain in Children and Adults

    PubMed Central

    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. PMID:24505468

  15. Nuclear receptors of the honey bee: annotation and expression in the adult brain

    PubMed Central

    Velarde, Rodrigo A; Robinson, Gene E; Fahrbach, Susan E

    2006-01-01

    The Drosophila genome encodes 18 canonical nuclear receptors. All of the Drosophila nuclear receptors are here shown to be present in the genome of the honey bee (Apis mellifera). Given that the time since divergence of the Drosophila and Apis lineages is measured in hundreds of millions of years, the identification of matched orthologous nuclear receptors in the two genomes reveals the fundamental set of nuclear receptors required to ‘make’ an endopterygote insect. The single novelty is the presence in the A. mellifera genome of a third insect gene similar to vertebrate photoreceptor-specific nuclear receptor (PNR). Phylogenetic analysis indicates that this novel gene, which we have named AmPNR-like, is a new member of the NR2 subfamily not found in the Drosophila or human genomes. This gene is expressed in the developing compound eye of the honey bee. Like their vertebrate counterparts, arthropod nuclear receptors play key roles in embryonic and postembryonic development. Studies in Drosophila have focused primarily on the role of these transcription factors in embryogenesis and metamorphosis. Examination of an expressed sequence tag library developed from the adult bee brain and analysis of transcript expression in brain using in situ hybridization and quantitative RT-PCR revealed that several members of the nuclear receptor family (AmSVP, AmUSP, AmERR, AmHr46, AmFtz-F1, and AmHnf-4) are expressed in the brain of the adult bee. Further analysis of the expression of AmUSP and AmSVP in the mushroom bodies, the major insect brain centre for learning and memory, revealed changes in transcript abundance and, in the case of AmUSP, changes in transcript localization, during the development of foraging behaviour in the adult. Study of the honey bee therefore provides a model for understanding nuclear receptor function in the adult brain. PMID:17069634

  16. Brain Gray Matter Changes Associated with Mindfulness Meditation in Older Adults: An Exploratory Pilot Study using Voxel-based Morphometry

    PubMed Central

    Kurth, Florian; Luders, Eileen; Wu, Brian; Black, David S.

    2015-01-01

    Background Mindfulness-based interventions (MBIs) have previously been associated with structural gray matter changes in normal healthy adults. However, it remains unknown if standardized MBIs can induce similar changes in older adults and those with health complaints as well. The objective of this investigation was to examine the effect of a standardized MBI on the gray matter tissue of older adults with sleep disturbances. Methods This exploratory single-group pilot longitudinal study examined local gray matter changes over a six-week MBI period. Participants included six older adult community volunteers (M=66.5 years of age, SD=5.5, range=58–75; 66% female) with sleep disturbances recruited through advertisement in local newspapers/flyers posted at a university medical center and affiliated clinics in Los Angeles, CA. The MBI was delivered as a weekly, two-hour, six-session, group-based course in mindfulness meditation. Gray matter was measured voxel-wise pre- and post-intervention. Results A significant gray matter increase was identified within the precuneus, possibly implicating meditation-induced changes of the default mode network. In contrast, observed significant gray matter decreases may have been driven by MBI-related remediation of brain architecture subserving sleep complaints. Conclusions Exploratory findings suggest that mindfulness meditation practice is associated with a detectable alteration of cerebral gray matter in older adults. PMID:25632405

  17. Protein synthesis in the rat brain: a comparative in vivo and in vitro study in immature and adult animals

    SciTech Connect

    Shahbazian, F.M.

    1985-01-01

    Rates of protein synthesis of CNS and other organs were compared in immature and adult rats by in vivo and slice techniques with administration of flooding doses of labeled precursor. The relationship between synthesis and brain region, cell type, subcellular fraction, or MW was examined. Incorporation of (/sup 14/C)valine into protein of CNS regions in vivo was about 1.2% per hour for immature rats and 0.6% for adults. For slices, the rates decreased significantly more in adults. In adult organs, the highest synthesis rate in vivo was found in liver (2.2% per hour) followed by kidney, spleen, lung, heart, brain, and muscle (0.5% per hour). In immature animals synthesis was highest in liver and spleen (2.5% per hour) and lowest in muscle (0.9% per hour). Slices all showed lower rates than in vivo, especially in adults. In vivo, protein synthesis rates of immature neurons and astrocytes and adult neurons exceeded those of whole brain, while that in adult astrocytes was the same. These results demonstrate a developmental difference of protein synthesis (about double in immature animals) in all brain cells, cell fractions and most brain protein. Similarly the decreased synthesis in brain slices - especially in adults, affects most proteins and structural elements.

  18. 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

  19. 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

  20. In vivo imaging of endogenous neural stem cells in the adult brain

    PubMed Central

    Rueger, Maria Adele; Schroeter, Michael

    2015-01-01

    The discovery of endogenous neural stem cells (eNSCs) in the adult mammalian brain with their ability to self-renew and differentiate into functional neurons, astrocytes and oligodendrocytes has raised the hope for novel therapies of neurological diseases. Experimentally, those eNSCs can be mobilized in vivo, enhancing regeneration and accelerating functional recovery after, e.g., focal cerebral ischemia, thus constituting a most promising approach in stem cell research. In order to translate those current experimental approaches into a clinical setting in the future, non-invasive imaging methods are required to monitor eNSC activation in a longitudinal and intra-individual manner. As yet, imaging protocols to assess eNSC mobilization non-invasively in the live brain remain scarce, but considerable progress has been made in this field in recent years. This review summarizes and discusses the current imaging modalities suitable to monitor eNSCs in individual experimental animals over time, including optical imaging, magnetic resonance tomography and-spectroscopy, as well as positron emission tomography (PET). Special emphasis is put on the potential of each imaging method for a possible clinical translation, and on the specificity of the signal obtained. PET-imaging with the radiotracer 3’-deoxy-3’-[18F]fluoro-L-thymidine in particular constitutes a modality with excellent potential for clinical translation but low specificity; however, concomitant imaging of neuroinflammation is feasible and increases its specificity. The non-invasive imaging strategies presented here allow for the exploitation of novel treatment strategies based upon the regenerative potential of eNSCs, and will help to facilitate a translation into the clinical setting. PMID:25621107

  1. In vivo imaging of endogenous neural stem cells in the adult brain.

    PubMed

    Rueger, Maria Adele; Schroeter, Michael

    2015-01-26

    The discovery of endogenous neural stem cells (eNSCs) in the adult mammalian brain with their ability to self-renew and differentiate into functional neurons, astrocytes and oligodendrocytes has raised the hope for novel therapies of neurological diseases. Experimentally, those eNSCs can be mobilized in vivo, enhancing regeneration and accelerating functional recovery after, e.g., focal cerebral ischemia, thus constituting a most promising approach in stem cell research. In order to translate those current experimental approaches into a clinical setting in the future, non-invasive imaging methods are required to monitor eNSC activation in a longitudinal and intra-individual manner. As yet, imaging protocols to assess eNSC mobilization non-invasively in the live brain remain scarce, but considerable progress has been made in this field in recent years. This review summarizes and discusses the current imaging modalities suitable to monitor eNSCs in individual experimental animals over time, including optical imaging, magnetic resonance tomography and-spectroscopy, as well as positron emission tomography (PET). Special emphasis is put on the potential of each imaging method for a possible clinical translation, and on the specificity of the signal obtained. PET-imaging with the radiotracer 3'-deoxy-3'-[(18)F]fluoro-L-thymidine in particular constitutes a modality with excellent potential for clinical translation but low specificity; however, concomitant imaging of neuroinflammation is feasible and increases its specificity. The non-invasive imaging strategies presented here allow for the exploitation of novel treatment strategies based upon the regenerative potential of eNSCs, and will help to facilitate a translation into the clinical setting. PMID:25621107

  2. Brain metabolism and memory in age differentiated healthy adults

    SciTech Connect

    Riege, W.H.; Metter, E.J.; Kuhl, D.E.; Phelps, M.E.

    1984-01-01

    The (F-18)-fluorodeoxyglucose (FDG) scan method with positron emission tomography was used to determine age differences in factors underlying both the performances on 18 multivariate memory tests and the rates of cerebral glucose utilization in 9 left and 9 right hemispheric regions of 23 healthy adults in the age range of 27-78 years. Young persons below age 42 had higher scores than middle-aged (age 48-65 yrs) or old (age 66-78 yrs) persons on two of seven factors, reflecting memory for sequences of words or events together with metabolic indices of Broca's (and its mirror region) and Thalamic areas. Reliable correlations (critical r = 0.48, p<0.02) indicated that persons with high Superior Frontal and low Caudate-Thalamic metabolic measures were the same who performed well in tests of memory for sentences, story, designs, and complex patterns; while metabolic indices of Occipital and Posterior Temporal regions were correlated with the decision criteria adopted in testing. The mean metabolic ratio (b = -0.033, F = 5.47, p<0.03) and those of bilateral Broca's regions (b = -0.002, F = 13.65, p<0.001) significantly declined with age. The functional interrelation of frontal-subcortical metabolic ratios with memory processing was more prominent in younger persons under study and implicates decreasing thalamo-frontal interaction with age.

  3. 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. PMID:26200138

  4. Plasticity of Brain Networks in a Randomized Intervention Trial of Exercise Training in Older Adults

    PubMed Central

    Voss, Michelle W.; Prakash, Ruchika S.; Erickson, Kirk I.; Basak, Chandramallika; Chaddock, Laura; Kim, Jennifer S.; Alves, Heloisa; Heo, Susie; Szabo, Amanda N.; White, Siobhan M.; Wójcicki, Thomas R.; Mailey, Emily L.; Gothe, Neha; Olson, Erin A.; McAuley, Edward; Kramer, Arthur F.

    2010-01-01

    Research has shown the human brain is organized into separable functional networks during rest and varied states of cognition, and that aging is associated with specific network dysfunctions. The present study used functional magnetic resonance imaging (fMRI) to examine low-frequency (0.008 < f < 0.08 Hz) coherence of cognitively relevant and sensory brain networks in older adults who participated in a 1-year intervention trial, comparing the effects of aerobic and non-aerobic fitness training on brain function and cognition. Results showed that aerobic training improved the aging brain's resting functional efficiency in higher-level cognitive networks. One year of walking increased functional connectivity between aspects of the frontal, posterior, and temporal cortices within the Default Mode Network and a Frontal Executive Network, two brain networks central to brain dysfunction in aging. Length of training was also an important factor. Effects in favor of the walking group were observed only after 12 months of training, compared to non-significant trends after 6 months. A non-aerobic stretching and toning group also showed increased functional connectivity in the DMN after 6 months and in a Frontal Parietal Network after 12 months, possibly reflecting experience-dependent plasticity. Finally, we found that changes in functional connectivity were behaviorally relevant. Increased functional connectivity was associated with greater improvement in executive function. Therefore the study provides the first evidence for exercise-induced functional plasticity in large-scale brain systems in the aging brain, using functional connectivity techniques, and offers new insight into the role of aerobic fitness in attenuating age-related brain dysfunction. PMID:20890449

  5. 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

  6. Neurodevelopment. Live imaging of adult neural stem cell behavior in the intact and injured zebrafish brain.

    PubMed

    Barbosa, Joana S; Sanchez-Gonzalez, Rosario; Di Giaimo, Rossella; Baumgart, Emily Violette; Theis, Fabian J; Götz, Magdalena; Ninkovic, Jovica

    2015-05-15

    Adult neural stem cells are the source for restoring injured brain tissue. We used repetitive imaging to follow single stem cells in the intact and injured adult zebrafish telencephalon in vivo and found that neurons are generated by both direct conversions of stem cells into postmitotic neurons and via intermediate progenitors amplifying the neuronal output. We observed an imbalance of direct conversion consuming the stem cells and asymmetric and symmetric self-renewing divisions, leading to depletion of stem cells over time. After brain injury, neuronal progenitors are recruited to the injury site. These progenitors are generated by symmetric divisions that deplete the pool of stem cells, a mode of neurogenesis absent in the intact telencephalon. Our analysis revealed changes in the behavior of stem cells underlying generation of additional neurons during regeneration. PMID:25977550

  7. 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

  8. Brain Training Game Boosts Executive Functions, Working Memory and Processing Speed in the Young Adults: A Randomized Controlled Trial

    PubMed Central

    Nouchi, Rui; Taki, Yasuyuki; Takeuchi, Hikaru; Hashizume, Hiroshi; Nozawa, Takayuki; Kambara, Toshimune; Sekiguchi, Atsushi; Miyauchi, Carlos Makoto; Kotozaki, Yuka; Nouchi, Haruka; Kawashima, Ryuta

    2013-01-01

    Background Do brain training games work? The beneficial effects of brain training games are expected to transfer to other cognitive functions. Yet in all honesty, beneficial transfer effects of the commercial brain training games in young adults have little scientific basis. Here we investigated the impact of the brain training game (Brain Age) on a wide range of cognitive functions in young adults. Methods We conducted a double-blind (de facto masking) randomized controlled trial using a popular brain training game (Brain Age) and a popular puzzle game (Tetris). Thirty-two volunteers were recruited through an advertisement in the local newspaper and randomly assigned to either of two game groups (Brain Age, Tetris). Participants in both the Brain Age and the Tetris groups played their game for about 15 minutes per day, at least 5 days per week, for 4 weeks. Measures of the cognitive functions were conducted before and after training. Measures of the cognitive functions fell into eight categories (fluid intelligence, executive function, working memory, short-term memory, attention, processing speed, visual ability, and reading ability). Results and Discussion Our results showed that commercial brain training game improves executive functions, working memory, and processing speed in young adults. Moreover, the popular puzzle game can engender improvement attention and visuo-spatial ability compared to playing the brain training game. The present study showed the scientific evidence which the brain training game had the beneficial effects on cognitive functions (executive functions, working memory and processing speed) in the healthy young adults. Conclusions Our results do not indicate that everyone should play brain training games. However, the commercial brain training game might be a simple and convenient means to improve some cognitive functions. We believe that our findings are highly relevant to applications in educational and clinical fields. Trial

  9. Daily marijuana use is not associated with brain morphometric measures in adolescents or adults.

    PubMed

    Weiland, Barbara J; Thayer, Rachel E; Depue, Brendan E; Sabbineni, Amithrupa; Bryan, Angela D; Hutchison, Kent E

    2015-01-28

    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

  10. 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

  11. Regional specific regulation of steroid receptor coactivator-1 immunoreactivity by orchidectomy in the brain of adult male mice.

    PubMed

    Bian, Chen; Zhang, Kaiyuan; Zhao, Yangang; Guo, Qiang; Cai, Wenqin; Zhang, Jiqiang

    2014-10-01

    Androgens including testosterone and dihydrotestosterone play important roles on brain structure and function, either directly through androgen receptor or indirectly through estrogen receptors, which need coactivators for their transcription activation. Steroid receptor coactivator-1 (SRC-1) has been shown to be multifunctional potentials in the brain, but how it is regulated by androgens in the brain remains unclear. In this study, we explored the effect of orchidectomy (ORX) on the expression of SRC-1 in the adult male mice using nickel-intensified immunohistochemistry. The results showed that ORX induced dramatic decrease of SRC-1 immunoreactivity in the olfactory tubercle, piriform cortex, ventral pallidum, most parts of the septal area, hippocampus, substantia nigra (compact part), pontine nuclei and nucleus of the trapezoid body (p<0.01). Significant decrease of SRC-1 was noticed in the dorsal and lateral septal nucleus, medial preoptical area, dorsomedial and ventromedial hypothalamic nucleus and superior paraolivary nucleus (p<0.05). Whereas in other regions examined, levels of SRC-1 immunoreactivity were not obviously changed by ORX (p>0.05). The above results demonstrated ORX downregulation of SRC-1 in specific regions that have been involved in sense of smell, learning and memory, cognition, neuroendocrine, reproduction and motor control, indicating that SRC-1 play pivotal role in the mediating circulating androgenic regulation on these important brain functions. It also indicates that SRC-1 may serve as a novel target for the central disorders caused by the age-related decrease of circulating androgens. PMID:24945110

  12. Regulation of netrin-1 receptors by amphetamine in the adult brain.

    PubMed

    Yetnikoff, L; Labelle-Dumais, C; Flores, C

    2007-12-19

    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. 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

  14. A METHODOLOGY FOR ANALYZING CURVATURE IN THE DEVELOPING BRAIN FROM PRETERM TO ADULT

    PubMed Central

    PIENAAR, R.; FISCHL, B.; CAVINESS, V.; MAKRIS, N.; GRANT, P. E.

    2009-01-01

    The character and timing of gyral development is one manifestation of the complex orchestration of human brain development. The ability to quantify these changes would not only allow for deeper understanding of cortical development, but also conceivably allow for improved detection of pathologies. This paper describes a FreeSurfer based image-processing analysis “pipeline” or methodology that inputs an MRI volume, corrects possible contrast defects, creates surface reconstructions, and outputs various curvature-based function analyses. A technique of performing neonate reconstructions using FreeSurfer, which has not been possible previously due to inverted image contrast in pre-myelinated brains, is described. Once surfaces are reconstructed, the analysis component of the pipeline incorporates several surface-based curvature functions found in literature (principle curvatures, Gaussian, mean curvature, “curvedness”, and Willmore Bending Energy). We consider the problem of analyzing curvatures from different sized brains by introducing a Gaussian-curvature based variable-radius filter. Segmented volume data is also analyzed for folding measures: a gyral folding index (gyrification-white index GWI), and a gray-white matter junction folding index (WMF). A very simple curvature-based classifier is proposed that has the potential to discriminate between certain classes of subjects. We also present preliminary results of this curvature analysis pipeline on nine neonate subjects (30.4 weeks through 40.3 weeks Corrected Gestational Age), 3 children (2, 3, and 7 years) and 3 adults (33, 37, and 39 years). Initial results demonstrate that curvature measures and functions across our subjects peaked at term, with a gradual decline through early childhood and further decline continuing through to adults. We can also discriminate older neonates, children, and adults based on curvature analysis. Using a variable radius Gaussian-curvature filter, we also observed that the

  15. Eph receptor and ephrin signaling in developing and adult brain of the honeybee (Apis mellifera).

    PubMed

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

    2007-02-01

    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, significantly 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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. PMID:26296150

  2. Notch Receptor Expression in Neurogenic Regions of the Adult Zebrafish Brain

    PubMed Central

    de Oliveira-Carlos, Vanessa; Ganz, Julia; Hans, Stefan; Kaslin, Jan; Brand, Michael

    2013-01-01

    The adult zebrash brain has a remarkable constitutive neurogenic capacity. The regulation and maintenance of its adult neurogenic niches are poorly understood. In mammals, Notch signaling is involved in stem cell maintenance both in embryonic and adult CNS. To better understand how Notch signaling is involved in stem cell maintenance during adult neurogenesis in zebrafish we analysed Notch receptor expression in five neurogenic zones of the adult zebrafish brain. Combining proliferation and glial markers we identified several subsets of Notch receptor expressing cells. We found that 90 of proliferating radial glia express notch1a, notch1b and notch3. In contrast, the proliferating non-glial populations of the dorsal telencephalon and hypothalamus rarely express notch3 and about half express notch1a/1b. In the non-proliferating radial glia notch3 is the predominant receptor throughout the brain. In the ventral telencephalon and in the mitotic area of the optic tectum, where cells have neuroepithelial properties, notch1a/1b/3 are expressed in most proliferating cells. However, in the cerebellar niche, although progenitors also have neuroepithelial properties, only notch1a/1b are expressed in a high number of PCNA cells. In this region notch3 expression is mostly in Bergmann glia and at low levels in few PCNA cells. Additionally, we found that in the proliferation zone of the ventral telencephalon, Notch receptors display an apical high to basal low gradient of expression. Notch receptors are also expressed in subpopulations of oligodendrocytes, neurons and endothelial cells. We suggest that the partial regional heterogeneity observed for Notch expression in progenitor cells might be related to the cellular diversity present in each of these neurogenic niches. PMID:24039926

  3. Spatial distribution and cellular composition of adult brain proliferative zones in the teleost, Gymnotus omarorum

    PubMed Central

    Olivera-Pasilio, Valentina; Peterson, Daniel A.; Castelló, María E.

    2014-01-01

    Proliferation of stem/progenitor cells during development provides for the generation of mature cell types in the CNS. While adult brain proliferation is highly restricted in the mammals, it is widespread in teleosts. The extent of adult neural proliferation in the weakly electric fish, Gymnotus omarorum has not yet been described. To address this, we used double thymidine analog pulse-chase labeling of proliferating cells to identify brain proliferation zones, characterize their cellular composition, and analyze the fate of newborn cells in adult G. omarorum. Short thymidine analog chase periods revealed the ubiquitous distribution of adult brain proliferation, similar to other teleosts, particularly Apteronotus leptorhynchus. Proliferating cells were abundant at the ventricular-subventricular lining of the ventricular-cisternal system, adjacent to the telencephalic subpallium, the diencephalic preoptic region and hypothalamus, and the mesencephalic tectum opticum and torus semicircularis. Extraventricular proliferation zones, located distant from the ventricular-cisternal system surface, were found in all divisions of the rombencephalic cerebellum. We also report a new adult proliferation zone at the caudal-lateral border of the electrosensory lateral line lobe. All proliferation zones showed a heterogeneous cellular composition. The use of short (24 h) and long (30 day) chase periods revealed abundant fast cycling cells (potentially intermediate amplifiers), sparse slow cycling (potentially stem) cells, cells that appear to have entered a quiescent state, and cells that might correspond to migrating newborn neural cells. Their abundance and migration distance differed among proliferation zones: greater numbers and longer range and/or pace of migrating cells were associated with subpallial and cerebellar proliferation zones. PMID:25249943

  4. 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. PMID:23658162

  5. 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

  6. 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. PMID:24397462

  7. 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

  8. Arginine vasotocin neuronal development and its projection in the adult brain of the medaka.

    PubMed

    Kagawa, Nao; Honda, Akira; Zenno, Akiko; Omoto, Ryosuke; Imanaka, Saya; Takehana, Yusuke; Naruse, Kiyoshi

    2016-02-01

    The neurohypophysial peptide arginine vasotocin (AVT) and its mammalian ortholog arginine vasopressin function in a wide range of physiological and behavioral events. Here, we generated a new line of transgenic medaka (Oryzias latipes), which allowed us to monitor AVT neurons by enhanced green fluorescent protein (EGFP) and demonstrate AVT neuronal development in the embryo and the projection of AVT neurons in the adult brain of avt-egfp transgenic medaka. The onset of AVT expression manifested at 2 days postfertilization (dpf) as a pair of signals in the telencephalon of the brain. The telencephalic AVT neurons migrated and converged on the preoptic area (POA) by 4dpf. At the same stage, another onset of AVT expression manifested in the central optic tectum (OT), and they migrated to the ventral part of the hypothalamus (VH) by 6dpf. In the adult brain, the AVT somata with EGFP signals existed in the gigantocellular POA (gPOA), magnocellular POA (mPOA), and parvocellular POA (pPOA) and in the VH. Whereas the major projection of AVT fibers was found from the pPOA and VH to the posterior pituitary, it was also found that AVT neurons in the three POAs send their fibers into wide regions of the brain such as the telencephalon, mesencephalon and diencephalon. This study suggests that the avt-egfp transgenic medaka is a useful model to explore AVT neuronal development and function. PMID:26739197

  9. 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

  10. 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

  11. Long-Term Intermittent Hypoxia Elevates Cobalt Levels in the Brain and Injures White Matter in Adult Mice

    PubMed Central

    Veasey, Sigrid C.; Lear, Jessica; Zhu, Yan; Grinspan, Judith B.; Hare, Dominic J.; Wang, SiHe; Bunch, Dustin; Doble, Philip A.; Robinson, Stephen R.

    2013-01-01

    Study Objectives: Exposure to the variable oxygenation patterns in obstructive sleep apnea (OSA) causes oxidative stress within the brain. We hypothesized that this stress is associated with increased levels of redox-active metals and white matter injury. Design: Participants were randomly allocated to a control or experimental group (single independent variable). Setting: University animal house. Participants: Adult male C57BL/6J mice. Interventions: To model OSA, mice were exposed to long-term intermittent hypoxia (LTIH) for 10 hours/day for 8 weeks or sham intermittent hypoxia (SIH). Measurements and Results: Laser ablation-inductively coupled plasma-mass spectrometry was used to quantitatively map the distribution of the trace elements cobalt, copper, iron, and zinc in forebrain sections. Control mice contained 62 ± 7 ng cobalt/g wet weight, whereas LTIH mice contained 5600 ± 600 ng cobalt/g wet weight (P < 0.0001). Other elements were unchanged between conditions. Cobalt was concentrated within white matter regions of the brain, including the corpus callosum. Compared to that of control mice, the corpus callosum of LTIH mice had significantly more endoplasmic reticulum stress, fewer myelin-associated proteins, disorganized myelin sheaths, and more degenerated axon profiles. Because cobalt is an essential component of vitamin B12, serum methylmalonic acid (MMA) levels were measured. LTIH mice had low MMA levels (P < 0.0001), indicative of increased B12 activity. Conclusions: Long-term intermittent hypoxia increases brain cobalt, predominantly in the white matter. The increased cobalt is associated with endoplasmic reticulum stress, myelin loss, and axonal injury. Low plasma methylmalonic acid levels are associated with white matter injury in long-term intermittent hypoxia and possibly in obstructive sleep apnea. Citation: Veasey SC; Lear J; Zhu Y; Grinspan JB; Hare DJ; Wang S; Bunch D; Doble PA; Robinson SR. Long-term intermittent hypoxia elevates cobalt

  12. 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

  13. Noninvasive methods, including transient elastography, for the detection of liver disease in adults with cystic fibrosis

    PubMed Central

    Sadler, Matthew D; Crotty, Pam; Fatovich, Linda; Wilson, Stephanie; Rabin, Harvey R; Myers, Robert P

    2015-01-01

    BACKGROUND: Liver disease is the third leading cause of mortality in patients with cystic fibrosis (CF). However, detection of CF-associated liver disease (CFLD) is challenging. OBJECTIVE: To evaluate the diagnostic performance of noninvasive methods for the detection of CFLD with a focus on transient elastography (TE). METHODS: Patients at the Adult CF Clinic of Calgary and Southern Alberta (n=127) underwent liver stiffness measurement (LSM) by TE using the FibroScan (FS, Ecosens, France) M probe; aspartate amino-transferase to platelet ratio index (APRI) and FibroTest (FT) scores were also calculated. The diagnostic performance of these tools for the detection of CFLD (defined as two or more the following criteria: abnormal liver biochemistry, hepatomegaly or sonographic abnormalities other than steatosis) were compared using the area under ROC curves. RESULTS: Forty-seven percent of the cohort was male. The median age was 27 years (interquartile range [IQR] 22 to 37 years) and body mass index 21 kg/m2 (IQR 19 kg/m2 to 23 kg/m2); 25% of patients were on ursodeoxycholic acid and 12% had undergone lung transplantation. The prevalence of CFLD was 14% (n=18). FS was successful in all patients; one (0.8%) patient had poorly reliable results (IQR/M >30% and LSM ≥7.1kPa). Compared with patients without CFLD (n=109), individuals with CFLD had higher median LSM according to FS (3.9 kPa [IQR 3.4 to 4.9 kPa] versus 6.4 kPa [IQR 4.4 to 8.0 kPa]), APRI (0.24 [IQR 0.17 to 0.31] versus 0.50 [IQR 0.22 to 1.18]) and FT scores (0.08 [IQR 0.05 to 1.5] versus 0.18 [IQR 0.11 to 0.35]; all P<0.05). Area under ROC curve for FS, APRI and FT for the detection of CFLD were 0.78 (95% CI 0.65 to 0.92), 0.72 (95% CI 0.56 to 0.87) and 0.76 (95% CI 0.62 to 0.90) (P not significant). At a threshold of >5.2 kPa, the sensitivity, specificity, positive and negative predictive values of LSM according to FS for detecting CFLD were 67%, 83%, 40% and 94%, respectively. CONCLUSIONS: FS, APRI and FT

  14. Evaluation of use of reading comprehension strategies to improve reading comprehension of adult college students with acquired brain injury.

    PubMed

    Griffiths, Gina G; Sohlberg, McKay Moore; Kirk, Cecilia; Fickas, Stephen; Biancarosa, Gina

    2016-01-01

    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. Despite the rising need, empirical evaluation of reading comprehension interventions for adults with ABI is scarce. This study used a within-subject design to evaluate whether adult college students with ABI with no more than moderate cognitive impairments benefited from using reading comprehension strategies to improve comprehension of expository text. Integrating empirical support from the cognitive rehabilitation and special education literature, the researchers designed a multi-component reading comprehension strategy package. Participants read chapters from an introductory-level college anthropology textbook in two different conditions: strategy and no-strategy. The results indicated that reading comprehension strategy use was associated with recall of more correct information units in immediate and delayed free recall tasks; more efficient recall in the delayed free recall task; and increased accuracy recognising statements from a sentence verification task designed to reflect the local and global coherence of the text. The findings support further research into using reading comprehension strategies as an intervention approach for the adult ABI population. Future research needs include identifying how to match particular reading comprehension strategies to individuals, examining whether reading comprehension performance improves further through the incorporation of systematic training, and evaluating texts from a range of disciplines and genres. PMID:25712402

  15. 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

  16. 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

  17. The Whole-Brain N-Acetylaspartate Correlates with Education in Normal Adults

    PubMed Central

    Glodzik, Lidia; Wu, William E.; Babb, James S.; Achtnichts, Lutz; Amann, Michael; Sollberger, Marc; Monsch, Andreas U.; Gass, Achim; Gonen, Oded

    2012-01-01

    N-acetylaspartate (NAA) is an index of neuronal integrity. We hypothesized that in healthy subjects its whole brain concentration (WBNAA) may be related to formal educational attainment, a common proxy for cognitive reserve. To test this hypothesis 97 middle aged to elderly subjects (51–89 years old, 38% women) underwent brain MRI and non-localizing proton spectroscopy. Their WBNAA was obtained by dividing their whole-head NAA amount with the brain volume. Intracranial volume and fractional brain volume, a metric of brain atrophy, were also determined. Each subject’s educational attainment was the sum of their years of formal education. In the entire group higher education was associated with larger intracranial volume. The relationship between WBNAA and education was observed only in younger (51–70 years old) participants. In this group education explained 21% variance in WBNAA. More WBNAA was related to more years of formal education in adults and younger elders. Prospective studies can determine whether this relationship reflects a true advantage from years of training versus innate characteristic predisposing to higher achievements later in life. We offer that late life WBNAA may be more affected by other like factors acting at midlife and later. PMID:23177924

  18. 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

  19. An Updated Review of Interventions that Include Promotion of Physical Activity for Adult Men.

    PubMed

    Bottorff, Joan L; Seaton, Cherisse L; Johnson, Steve T; Caperchione, Cristina M; Oliffe, John L; More, Kimberly; Jaffer-Hirji, Haleema; Tillotson, Sherri M

    2015-06-01

    The marked disparity in life expectancy between men and women suggests men are a vulnerable group requiring targeted health promotion programs. As such, there is an increasing need for health promotion strategies that effectively engage men with their health and/or illness management. Programs that promote physical activity could significantly improve the health of men. Although George et al. (Sports Med 42(3):281, 30) reviewed physical activity programs involving adult males published between 1990 and 2010, developments in men's health have prompted the emergence of new sex- and gender-specific approaches targeting men. The purpose of this review was to: (1) extend and update the review undertaken by George et al. (Sports Med 42(3):281, 30) concerning the effectiveness of physical activity programs in males, and (2) evaluate the integration of gender-specific influences in the content, design, and delivery of men's health promotion programs. A search of MEDLINE, CINAHL, ScienceDirect, Web of Science, PsycINFO, the Cochrane Library, and the SPORTDiscus databases for articles published between January 2010 and August 2014 was conducted. In total, 35 studies, involving evaluations of 31 programs, were identified. Findings revealed that a variety of techniques and modes of delivery could effectively promote physical activity among men. Though the majority of programs were offered exclusively to men, 12 programs explicitly integrated gender-related influences in male-specific programs in ways that recognized men's interests and preferences. Innovations in male-only programs that focus on masculine ideals and gender influences to engage men in increasing their physical activity hold potential for informing strategies to promote other areas of men's health. PMID:25430599

  20. Retrospective Analysis of Levetiracetam Compared to Phenytoin for Seizure Prophylaxis in Adults with Traumatic Brain Injury

    PubMed Central

    Caballero, G. Christina; Hughes, Darrel W.; Maxwell, Pamela R.; Green, Kay; Gamboa, Conrado D.; Barthol, Colleen A.

    2013-01-01

    Background: Phenytoin is standard of care for seizure prophylaxis following traumatic brain injury (TBI). Levetiracetam, an alternative antiepileptic drug, is utilized for seizure prophylaxis despite limited data supporting its use. Objective: Our primary outcome was post-TBI seizure activity measured by electroencephalogram (EEG) for levetiracetam versus phenytoin. Secondary outcomes were length of intensive care unit (ICU) stay, requirement for additional antiepileptic drugs (AED), and drug and monitoring costs. Methods: A retrospective review was performed of patients admitted to neurosurgical or surgical trauma ICU. Adult patients with at least 1 day of EEG monitoring were included. Patients were excluded if they had history of epilepsy, prior TBI, less than 48 hours of AED therapy, or additional AED prior to EEG monitoring. Results: A total 90 patients met inclusion criteria, with 18 receiving levetiracetam and 72 receiving phenytoin. Prevalence of EEG-confirmed seizure activity was similar between the levetiracetam and phenytoin groups (28% vs 29%; P = .99). ICU length of stay (13 vs 18 days; P = .28), time to EEG-confirmed seizure activity (4 vs 6 days; P = .24), and duration of seizure prophylaxis (9 vs 14 days; P = .18) were also similar. The median daily cost of levetiracetam therapy was $43 compared to $55 for phenytoin therapy and monitoring (P = .08). When all anticonvulsant therapy and monitoring were included, costs were lower for the levetiracetam group ($45 vs $83; P = .02). Conclusion: Levetiracetam may provide an alternative treatment option for seizure prevention in TBI patients in the ICU. Total antiepileptic drug and monitoring costs were lower for levetiracetam patients. PMID:24421550

  1. Clinical significance of brain white matter hyperintensities in young adults with psychiatric illness.

    PubMed

    Breeze, Janis L; Hesdorffer, Dale C; Hong, Xiaoni; Frazier, Jean A; Renshaw, Perry F

    2003-01-01

    Magnetic resonance imaging (MRI) provides detailed images of brain anatomy, with especially clear definition of gray and white matter structures. Several brain MRI studies have suggested that adults with bipolar disorder (BD) are more likely to have "white matter hyperintensities" (WMH) than adults without BD. The disproportionately greater frequency of these lesions in otherwise physically healthy patients suggests that the illness itself, or treatments used to control the illness, may be risk factors for the development of white matter changes. Similarly, WMH may be an etiological factor for some types of BD. In addition to reviewing the relevant literature, this research study attempted to determine whether lithium treatment is associated with an increased prevalence of WMH in young adults with psychiatric illness. To test this hypothesis, we evaluated over 600 brain MRI scans from inpatients at McLean Hospital, Belmont, Massachusetts. We controlled for possible confounding variables such as age, vascular disease, substance abuse, and markers of illness severity. We found that individuals with BD were no more likely to have WMH than other psychiatric patients. Lithium use was nonsignificantly associated with the presence of WMH. A multivariate regression model for the presence of WMH showed that heart disease, female gender, and multiple psychiatric admissions were significant predictors of WMH. This study does not support previous findings that BD, compared to other psychiatric illnesses, was associated with increased risk of WMH. Lithium use may be subtly associated with WMH. Our results are consistent with previous research that found an association between cardiovascular disease, advanced age, and the presence of WMH, though our analysis appears to be unique in its inclusion of cardiovascular disease as a risk factor in young adults with psychiatric illness. PMID:14555427

  2. PRENATAL ALCOHOL EXPOSURE ALTERS STEADY-STATE AND ACTIVATED GENE EXPRESSION IN THE ADULT RAT BRAIN

    PubMed Central

    Stepien, Katarzyna A.; Lussier, Alexandre A.; Neumann, Sarah M.; Pavlidis, Paul; Kobor, Michael S.; Weinberg, Joanne

    2016-01-01

    Background Prenatal alcohol exposure (PAE) is associated with alterations in numerous physiological systems, including the stress and immune systems . We have previously shown that PAE increases the course and severity of arthritis in an adjuvant-induced arthritis (AA) model. While the molecular mechanisms underlying these effects are not fully known, changes in neural gene expression are emerging as important factors in the etiology of PAE effects. As the prefrontal cortex (PFC) and hippocampus (HPC) play key roles in neuroimmune function, PAE-induced alterations to their transcriptome may underlie abnormal steady-state functions and responses to immune challenge. The current study examined brains from adult PAE and control females from our recent AA study to determine whether PAE causes long-term alterations in gene expression and whether these mediate the altered severity and course of arthritis in PAE females Methods Adult females from PAE, pair-fed [PF], and ad libitum-fed control [C]) groups were injected with either saline or complete Freund’s adjuvant. Animals were terminated at the peak of inflammation or during resolution (days 16 and 39 post-injection, respectively); cohorts of saline-injected PAE, PF and C females were terminated in parallel. Gene expression was analyzed in the PFC and HPC using whole genome mRNA expression microarrays. Results Significant changes in gene expression in both the PFC and HPC were found in PAE compared to controls in response to ethanol exposure alone (saline-injected females), including genes involved in neurodevelopment, apoptosis, and energy metabolism. Moreover, in response to inflammation (adjuvant-injected females), PAE animals showed unique expression patterns, while failing to exhibit the activation of genes and regulators involved in the immune response observed in control and pair-fed animals. Conclusions These results support the hypothesis that PAE affects neuroimmune function at the level of gene expression

  3. Cyclophilin D-Sensitive Mitochondrial Permeability Transition in Adult Human Brain and Liver Mitochondria

    PubMed Central

    Morota, Saori; Chen, Li; Matsuyama, Nagahisa; Suzuki, Yoshiaki; Nakajima, Satoshi; Tanoue, Tadashi; Omi, Akibumi; Shibasaki, Futoshi; Shimazu, Motohide; Ikeda, Yukio; Uchino, Hiroyuki; Elmér, Eskil

    2011-01-01

    Abstract The mitochondrial permeability transition (mPT) is considered to be a major cause of cell death under a variety of pathophysiological conditions of the central nervous system (CNS) and other organs. Pharmacological inhibition or genetic knockout of the matrix protein cyclophilin D (CypD) prevents mPT and cell degeneration in several models of brain injury. If these findings in animal models are translatable to human disease, pharmacological inhibition of mPT offers a promising therapeutic target. The objective of this study was to validate the presence of a CypD-sensitive mPT in adult human brain and liver mitochondria. In order to perform functional characterization of human mitochondria, fresh tissue samples were obtained during hemorrhage or tumor surgery and mitochondria were rapidly isolated. Mitochondrial calcium retention capacity, a quantitative assay for mPT, was significantly increased by the CypD inhibitor cyclosporin A in both human brain and liver mitochondria, whereas thiol-reactive compounds and oxidants sensitized mitochondria to calcium-induced mPT. Brain mitochondria underwent swelling upon calcium overload, which was reversible upon calcium removal. To further explore mPT of human mitochondria, liver mitochondria were demonstrated to exhibit several classical features of the mPT phenomenon, such as calcium-induced loss of membrane potential and respiratory coupling, as well as release of the pro-apoptotic protein cytochrome c. We concluded that adult viable human brain and liver mitochondria possess an active CypD-sensitive mPT. Our findings support the rationale of CypD and mPT inhibition as pharmacological targets in acute and chronic neurodegeneration. PMID:21121808

  4. Early developmental gene enhancers affect subcortical volumes in the adult human brain.

    PubMed

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. PMID:26890892

  5. Postnatal Diagnosis of a Baby With Multiple Rare Congenital Anomalies Including Syngnathia, Brain Dysmorphism, and Skin Pigmentation.

    PubMed

    Mahgoub, Linda; Joynt, Chloe; Bhargava, Ravi; Davies, Dawn; El-Hakim, Hamdy; Dobrovolsky, Walter

    2015-11-01

    Syngnathia is a rare congenital disorder of jaw fusion with a paucity of literature from developed countries. We present a case of an infant noted to have multiple anomalies at birth including syngnathia, microcephaly with a variant of brain abnormality between holoprosencephaly and syntelencephaly, optic nerve hypoplasia, ear canal anomalies, hemi-vertebrae, and suspected hypomelanosis of Ito. To our knowledge, this patient with syngnathia and multiple anomalies is the first to be reported, but whether they are a coincidence, a pathogenetic association, or a new syndrome remains unknown. This case is discussed with a brief review of the literature. PMID:25325328

  6. Environmental changes in oxygen tension reveal ROS-dependent neurogenesis and regeneration in the adult newt brain

    PubMed Central

    Hameed, L Shahul; Berg, Daniel A; Belnoue, Laure; Jensen, Lasse D; Cao, Yihai; Simon, András

    2015-01-01

    Organisms need to adapt to the ecological constraints in their habitat. How specific processes reflect such adaptations are difficult to model experimentally. We tested whether environmental shifts in oxygen tension lead to events in the adult newt brain that share features with processes occurring during neuronal regeneration under normoxia. By experimental simulation of varying oxygen concentrations, we show that hypoxia followed by re-oxygenation lead to neuronal death and hallmarks of an injury response, including activation of neural stem cells ultimately leading to neurogenesis. Neural stem cells accumulate reactive oxygen species (ROS) during re-oxygenation and inhibition of ROS biosynthesis counteracts their proliferation as well as neurogenesis. Importantly, regeneration of dopamine neurons under normoxia also depends on ROS-production. These data demonstrate a role for ROS-production in neurogenesis in newts and suggest that this role may have been recruited to the capacity to replace lost neurons in the brain of an adult vertebrate. DOI: http://dx.doi.org/10.7554/eLife.08422.001 PMID:26485032

  7. 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

  8. 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.

  9. In vivo quantification of brain injury in adult Niemann-Pick Disease Type C.

    PubMed

    Zaaraoui, Wafaa; Crespy, Lydie; Rico, Audrey; Faivre, Anthony; Soulier, Elisabeth; Confort-Gouny, Sylviane; Cozzone, Patrick J; Pelletier, Jean; Ranjeva, Jean-Philippe; Kaphan, Elsa; Audoin, Bertrand

    2011-06-01

    Development of surrogate markers is necessary to assess the potential efficacy of new therapeutics in Niemann-Pick Disease Type C (NP-C). In the present study, magnetization transfer ratio (MTR) imaging, a quantitative MRI imaging technique sensitive to subtle brain microstructural changes, was applied in two patients suffering from adult NP-C. Statistical mapping analysis was performed to compare each patient's MTR maps with those of a group of 34 healthy controls to quantify and localize the extent of brain injury of each patient. Using this method, pathological changes were evidenced in the cerebellum, the thalami and the lenticular nuclei in both patients and also in the fronto-temporal cortices in the patient with the worse functional deficit. In addition, white matter changes were located in the midbrain, the cerebellum and the fronto-temporal lobes in the patient with the higher level of disability and in only one limited periventricular white matter region in the other patient. A 6-month follow-up was performed in the patient with the lower functional deficit and evidenced significant extension of grey matter (GM) and white matter (WM) injuries during the following period (14% of increased injury for GM and 53% for WM). This study demonstrates that significant brain injury related to clinical deficit can be assessed in vivo in adult NP-C using MTR imaging. Although preliminary, these findings suggest that MTR imaging may be a relevant candidate for the development of biomarker in NP-C. PMID:21397539

  10. 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. PMID:24931850

  11. An ultrastructural study of the phagocytic activity of astrocytes in adult rat brain.

    PubMed Central

    al-Ali, S Y; al-Hussain, S M

    1996-01-01

    The role of adult astrocytes in the removal of cell debris and foreign particles following injury to the brain is controversial. This study was undertaken to elucidate the response of adult astrocytes to needle injury of the rat cerebral cortex, using a suspension of colloidal carbon as a marker for phagocytosis. Either a single or 2 successive injections of colloidal carbon suspension were made into the cerebral cortex. The animals were allowed to survive for periods of from 1 to 30 d. Unequivocal involvement of astrocytes in the removal of carbon particles was evident only in those brains which had been subjected to 2 successive injections of carbon. The particles were located in membrane-bound vacuoles and were subsequently sequestered in lysosomes. Carbon-containing astrocytes were observed in the immediate vicinity of the lesion, in the adjacent parenchyma, around blood vessels and abutting carbon-containing macrophages. This study demonstrates that adult astrocytes are involved in phagocytosis, but only as a second line of defence. The possible significance of carbon-laden astrocytes further away from the site of the lesion is discussed. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:8621323

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

    PubMed Central

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

    2016-01-01

    Traumatic brain injury (TBI) promotes neural stem/progenitor cell (NSC) proliferation in an attempt to initiate innate repair mechanisms. However, all immature neurons in the CNS are required to migrate from their birthplace to their final destination to develop into functional neurons. Here we assessed the destination of adult-born neurons following TBI. We found that a large percentage of immature neurons migrated past their normal stopping site at the inner granular cell layer (GCL), and became misplaced in the outer GCL of the hippocampal dentate gyrus. The aberrant migration of adult-born neurons in the hippocampus occurred 48 hours after TBI, and lasted for 8 weeks, resulting in a great number of newly generated neurons misplaced in the outer GCL in the hippocampus. Those misplaced neurons were able to become mature and differentiate into granular neurons, but located ectopically in the outer GCL with reduced dendritic complexity after TBI. The adult-born neurons at the misplaced position may make wrong connections with inappropriate nearby targets in the pre-existing neural network. These results suggest that although stimulation of endogenous NSCs following TBI might offer new avenues for cell-based therapy, additional intervention is required to further enhance successful neurogenesis for repairing the damaged brain. PMID:26898165

  13. 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

  14. Expression and Regulation of the Fkbp5 Gene in the Adult Mouse Brain

    PubMed Central

    Scharf, Sebastian H.; Liebl, Claudia; Binder, Elisabeth B.

    2011-01-01

    Background Chronic stress has been found to be a major risk factor for various human pathologies. Stress activates the hypothalamic-pituitary-adrenal (HPA) axis, which is tightly regulated via, among others, the glucocorticoid receptor (GR). The activity of the GR is modulated by a variety of proteins, including the co-chaperone FK506 binding protein 51 (FKBP5). Although FKBP5 has been associated with risk for affective disorders and has been implicated in GR sensitivity, previous studies focused mainly on peripheral blood, while information about basal distribution and induction in the central nervous system are sparse. Methodology/Principal Findings In the present study, we describe the basal expression pattern of Fkbp5 mRNA in the brain of adult male mice and show the induction of Fkbp5 mRNA via dexamethasone treatment or different stress paradigms. We could show that Fkbp5 is often, but not exclusively, expressed in regions also known for GR expression, for example the hippocampus. Furthermore, we were able to induce Fkbp5 expression via dexamethasone in the CA1 and DG subregions of the hippocampus, the paraventricular nucleus (PVN) and the central amygdala (CeA). Increase of Fkbp5 mRNA was also found after restrained stress and 24 hours of food deprivation in the PVN and the CeA, while in the hippocampus only food deprivation caused an increase in Fkbp5 mRNA. Conclusions/Significance Interestingly, regions with a low basal expression showed higher increase in Fkbp5 mRNA following induction than regions with high basal expression, supporting the hypothesis that GR sensitivity is, at least partly, mediated via Fkbp5. In addition, this also supports the use of Fkbp5 gene expression as a marker for GR sensitivity. In summary, we were able to give an overview of the basal expression of fkbp5 mRNA as well as to extend the findings of induction of Fkbp5 and its regulatory influence on GR sensitivity from peripheral blood to the brain. PMID:21347384

  15. Functional mitochondrial analysis in acute brain sections from adult rats reveals mitochondrial dysfunction in a rat model of migraine

    PubMed Central

    Fried, Nathan T.; Moffat, Cynthia; Seifert, Erin L.

    2014-01-01

    Mitochondrial dysfunction has been implicated in many neurological disorders that only develop or are much more severe in adults, yet no methodology exists that allows for medium-throughput functional mitochondrial analysis of brain sections from adult animals. We developed a technique for quantifying mitochondrial respiration in acutely isolated adult rat brain sections with the Seahorse XF Analyzer. Evaluating a range of conditions made quantifying mitochondrial function from acutely derived adult brain sections from the cortex, cerebellum, and trigeminal nucleus caudalis possible. Optimization of this technique demonstrated that the ideal section size was 1 mm wide. We found that sectioning brains at physiological temperatures was necessary for consistent metabolic analysis of trigeminal nucleus caudalis sections. Oxygen consumption in these sections was highly coupled to ATP synthesis, had robust spare respiratory capacities, and had limited nonmitochondrial respiration, all indicative of healthy tissue. We demonstrate the effectiveness of this technique by identifying a decreased spare respiratory capacity in the trigeminal nucleus caudalis of a rat model of chronic migraine, a neurological disorder that has been associated with mitochondrial dysfunction. This technique allows for 24 acutely isolated sections from multiple brain regions of a single adult rat to be analyzed simultaneously with four sequential drug treatments, greatly advancing the ability to study mitochondrial physiology in adult neurological disorders. PMID:25252946

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

    PubMed Central

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

    2015-01-01

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

  17. 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. PMID:26315689

  18. Efficient Cargo Delivery into Adult Brain Tissue Using Short Cell-Penetrating Peptides

    PubMed Central

    Thomas, Alvin Kuriakose; Bhattarai, Prabesh; Zhang, Yixin; Brand, Michael

    2015-01-01

    Zebrafish brains can regenerate lost neurons upon neurogenic activity of the radial glial progenitor cells (RGCs) that reside at the ventricular region. Understanding the molecular events underlying this ability is of great interest for translational studies of regenerative medicine. Therefore, functional analyses of gene function in RGCs and neurons are essential. Using cerebroventricular microinjection (CVMI), RGCs can be targeted efficiently but the penetration capacity of the injected molecules reduces dramatically in deeper parts of the brain tissue, such as the parenchymal regions that contain the neurons. In this report, we tested the penetration efficiency of five known cell-penetrating peptides (CPPs) and identified two– polyR and Trans – that efficiently penetrate the brain tissue without overt toxicity in a dose-dependent manner as determined by TUNEL staining and L-Plastin immunohistochemistry. We also found that polyR peptide can help carry plasmid DNA several cell diameters into the brain tissue after a series of coupling reactions using DBCO-PEG4-maleimide-based Michael’s addition and azide-mediated copper-free click reaction. Combined with the advantages of CVMI, such as rapidness, reproducibility, and ability to be used in adult animals, CPPs improve the applicability of the CVMI technique to deeper parts of the central nervous system tissues. PMID:25894337

  19. 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

  20. Characterization of TLX Expression in Neural Stem Cells and Progenitor Cells in Adult Brains

    PubMed Central

    Li, Shengxiu; Sun, Guoqiang; Murai, Kiyohito; Ye, Peng; Shi, Yanhong

    2012-01-01

    TLX has been shown to play an important role in regulating the self-renewal and proliferation of neural stem cells in adult brains. However, the cellular distribution of endogenous TLX protein in adult brains remains to be elucidated. In this study, we used immunostaining with a TLX-specific antibody to show that TLX is expressed in both neural stem cells and transit-amplifying neural progenitor cells in the subventricular zone (SVZ) of adult mouse brains. Then, using a double thymidine analog labeling approach, we showed that almost all of the self-renewing neural stem cells expressed TLX. Interestingly, most of the TLX-positive cells in the SVZ represented the thymidine analog-negative, relatively quiescent neural stem cell population. Using cell type markers and short-term BrdU labeling, we demonstrated that TLX was also expressed in the Mash1+ rapidly dividing type C cells. Furthermore, loss of TLX expression dramatically reduced BrdU label-retaining neural stem cells and the actively dividing neural progenitor cells in the SVZ, but substantially increased GFAP staining and extended GFAP processes. These results suggest that TLX is essential to maintain the self-renewing neural stem cells in the SVZ and that the GFAP+ cells in the SVZ lose neural stem cell property upon loss of TLX expression.Understanding the cellular distribution of TLX and its function in specific cell types may provide insights into the development of therapeutic tools for neurodegenerative diseases by targeting TLX in neural stem/progenitors cells. PMID:22952666

  1. Netrin-5 is highly expressed in neurogenic regions of the adult brain

    PubMed Central

    Yamagishi, Satoru; Yamada, Kohei; Sawada, Masato; Nakano, Suguru; Mori, Norio; Sawamoto, Kazunobu; Sato, Kohji

    2015-01-01

    Mammalian netrin family proteins are involved in targeting of axons, neuronal migration, and angiogenesis and act as repulsive and attractive guidance molecules. Netrin-5 is a new member of the netrin family with homology to the C345C domain of netrin-1. Unlike other netrin proteins, murine netrin-5 consists of two EGF motifs of the laminin V domain (LE) and the C345C domain, but lacks the N-terminal laminin VI domain and one of the three LE motifs. We generated a specific antibody against netrin-5 to investigate its expression pattern in the rodent adult brain. Strong netrin-5 expression was observed in the olfactory bulb (OB), rostral migrate stream (RMS), the subventricular zone (SVZ), and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus, where neurogenesis occurs in the adult brain. In the SVZ and RMS, netrin-5 expression was observed in Mash1-positive transit-amplifying cells and in Doublecortin (DCX)-positive neuroblasts, but not in GFAP-positive astrocytes. In the OB, netrin-5 expression was maintained in neuroblasts, but its level was decreased in NeuN-positive mature neurons. In the hippocampal SGZ, netrin-5 was observed in Mash1-positive cells and in DCX-positive neuroblasts, but not in GFAP-positive astrocytes, suggesting that netrin-5 expression occurs from type 2a to type 3 cells. These data suggest that netrin-5 is produced by both transit-amplifying cells and neuroblasts to control neurogenesis in the adult brain. PMID:25941474

  2. Longitudinal magnetic resonance imaging studies of older adults: a shrinking brain.

    PubMed

    Resnick, Susan M; Pham, Dzung L; Kraut, Michael A; Zonderman, Alan B; Davatzikos, Christos

    2003-04-15

    Age-related loss of brain tissue has been inferred from cross-sectional neuroimaging studies, but direct measurements of gray and white matter changes from longitudinal studies are lacking. We quantified longitudinal magnetic resonance imaging (MRI) scans of 92 nondemented older adults (age 59-85 years at baseline) in the Baltimore Longitudinal Study of Aging to determine the rates and regional distribution of gray and white matter tissue loss in older adults. Using images from baseline, 2 year, and 4 year follow-up, we found significant age changes in gray (p < 0.001) and white (p < 0.001) volumes even in a subgroup of 24 very healthy elderly. Annual rates of tissue loss were 5.4 +/- 0.3, 2.4 +/- 0.4, and 3.1 +/- 0.4 cm3 per year for total brain, gray, and white volumes, respectively, and ventricles increased by 1.4 +/- 0.1 cm3 per year (3.7, 1.3, 2.4, and 1.2 cm3, respectively, in very healthy). Frontal and parietal, compared with temporal and occipital, lobar regions showed greater decline. Gray matter loss was most pronounced for orbital and inferior frontal, cingulate, insular, inferior parietal, and to a lesser extent mesial temporal regions, whereas white matter changes were widespread. In this first study of gray and white matter volume changes, we demonstrate significant longitudinal tissue loss for both gray and white matter even in very healthy older adults. These data provide essential information on the rate and regional pattern of age-associated changes against which pathology can be evaluated and suggest slower rates of brain atrophy in individuals who remain medically and cognitively healthy. PMID:12716936

  3. Adult rat brain is sensitive to thyroid hormone. Regulation of RC3/neurogranin mRNA.

    PubMed Central

    Iñiguez, M A; Rodriguez-Peña, A; Ibarrola, N; Morreale de Escobar, G; Bernal, J

    1992-01-01

    The mammalian brain is considered to be poorly responsive to thyroid hormone after the so called "critical periods" of brain development, which occur in the rat before postnatal days 15-20. In a previous work (Muñoz, A., A. Rodriguez-Peña, A. Perez-Castillo, B. Ferreiro, J.G. Sutcliffe, and J. Bernal. 1991. Mol. Endocrinol. 5:273-280) we have identified one neuronal gene, RC3, whose expression is influenced by early neonatal hypothyroidism and thyroid hormone treatment. In the present work we show that adult-onset hypothyroidism leads to a reversible decrease of RC3 mRNA. Rats thyroidectomized on postnatal day 40 and killed three months later showed a decreased RC3 mRNA concentration in the cerebral cortex and striatum. The same effect was observed in animals made hypothyroid on postnatal day 32 and killed on postnatal day 52. RC3 expression was normal when hypothyroid animals were treated with T4 five days before being killed. In contrast, the mRNA encoding myelin proteolipid protein showed no changes in either experimental situation. RC3 mRNA levels were not affected by food restriction demonstrating that the effect of hypothyroidism was not related to the lack of weight gain. The control of RC3 mRNA is so far the only molecular event known to be regulated by thyroid hormone once the critical periods of brain development are over and could represent a molecular correlate for the age-independent, reversible alterations induced by hypothyroidism in the adult brain. Images PMID:1379612

  4. Differentiation in boron distribution in adult male and female rats' normal brain: a BNCT approach.

    PubMed

    Goodarzi, Samereh; Pazirandeh, Ali; Jameie, Seyed Behnamedin; Khojasteh, Nasrin Baghban

    2012-06-01

    Boron distribution in adult male and female rats' normal brain after boron carrier injection (0.005 g Boric Acid+0.005 g Borax+10 ml distilled water, pH: 7.4) was studied in this research. Coronal sections of control and trial animal tissue samples were irradiated with thermal neutrons. Using alpha autoradiography, significant differences in boron concentration were seen in forebrain, midbrain and hindbrain sections of male and female animal groups with the highest value, four hours after boron compound injection. PMID:22484141

  5. 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

  6. Neuroinflammation and Neurodegeneration in Adult Rat Brain from Binge Ethanol Exposure: Abrogation by Docosahexaenoic Acid

    PubMed Central

    Tajuddin, Nuzhath; Moon, Kwan-Hoon; Marshall, S. Alex; Nixon, Kimberly; Neafsey, Edward J.; Kim, Hee-Yong; Collins, Michael A.

    2014-01-01

    Evidence that brain edema and aquaporin-4 (AQP4) water channels have roles in experimental binge ethanol-induced neurodegeneration has stimulated interest in swelling/edema-linked neuroinflammatory pathways leading to oxidative stress. We report here that neurotoxic binge ethanol exposure produces comparable significant effects in vivo and in vitro on adult rat brain levels of AQP4 as well as neuroinflammation-linked enzymes: key phospholipase A2 (PLA2) family members and poly (ADP-ribose) polymerase-1 (PARP-1). In adult male rats, repetitive ethanol intoxication (3 gavages/d for 4 d, ∼9 g/kg/d, achieving blood ethanol levels ∼375 mg/dl; “Majchrowicz” model) significantly increased AQP4, Ca+2-dependent PLA2 GIVA (cPLA2), phospho-cPLA2 GIVA (p-cPLA2), secretory PLA2 GIIA (sPLA2) and PARP-1 in regions incurring extensive neurodegeneration in this model—hippocampus, entorhinal cortex, and olfactory bulb—but not in two regions typically lacking neurodamage, frontal cortex and cerebellum. Also, ethanol reduced hippocampal Ca+2-independent PLA2 GVIA (iPLA2) levels and increased brain “oxidative stress footprints” (4-hydroxynonenal-adducted proteins). For in vitro studies, organotypic cultures of rat hippocampal-entorhinocortical slices of adult age (∼60 d) were ethanol-binged (100 mM or ∼450 mg/dl) for 4 d, which augments AQP4 and causes neurodegeneration (Collins et al. 2013). Reproducing the in vivo results, cPLA2, p-cPLA2, sPLA2 and PARP-1 were significantly elevated while iPLA2 was decreased. Furthermore, supplementation with docosahexaenoic acid (DHA; 22:6n-3), known to quell AQP4 and neurodegeneration in ethanol-treated slices, blocked PARP-1 and PLA2 changes while counteracting endogenous DHA reduction and increases in oxidative stress footprints (3-nitrotyrosinated proteins). Notably, the PARP-1 inhibitor PJ-34 suppressed binge ethanol-dependent neurodegeneration, indicating PARP upstream involvement. The results with corresponding models

  7. Neurons diversify astrocytes in the adult brain through sonic hedgehog signaling.

    PubMed

    Farmer, W Todd; Abrahamsson, Therése; Chierzi, Sabrina; Lui, Christopher; Zaelzer, Cristian; Jones, Emma V; Bally, Blandine Ponroy; Chen, Gary G; Théroux, Jean-Francois; Peng, Jimmy; Bourque, Charles W; Charron, Frédéric; Ernst, Carl; Sjöström, P Jesper; Murai, Keith K

    2016-02-19

    Astrocytes are specialized and heterogeneous cells that contribute to central nervous system function and homeostasis. However, the mechanisms that create and maintain differences among astrocytes and allow them to fulfill particular physiological roles remain poorly defined. We reveal that neurons actively determine the features of astrocytes in the healthy adult brain and define a role for neuron-derived sonic hedgehog (Shh) in regulating the molecular and functional profile of astrocytes. Thus, the molecular and physiological program of astrocytes is not hardwired during development but, rather, depends on cues from neurons that drive and sustain their specialized properties. PMID:26912893

  8. Regrowth of Serotonin Axons in the Adult Mouse Brain Following Injury.

    PubMed

    Jin, Yunju; Dougherty, Sarah E; Wood, Kevin; Sun, Landy; Cudmore, Robert H; Abdalla, Aya; Kannan, Geetha; Pletnikov, Mikhail; Hashemi, Parastoo; Linden, David J

    2016-08-17

    It is widely believed that damaged axons in the adult mammalian brain have little capacity to regrow, thereby impeding functional recovery after injury. Studies using fixed tissue have suggested that serotonin neurons might be a notable exception, but remain inconclusive. We have employed in vivo two-photon microscopy to produce time-lapse images of serotonin axons in the neocortex of the adult mouse. Serotonin axons undergo massive retrograde degeneration following amphetamine treatment and subsequent slow recovery of axonal density, which is dominated by new growth with little contribution from local sprouting. A stab injury that transects serotonin axons running in the neocortex is followed by local regression of cut serotonin axons and followed by regrowth from cut ends into and across the stab rift zone. Regrowing serotonin axons do not follow the pathways left by degenerated axons. The regrown axons release serotonin and their regrowth is correlated with recovery in behavioral tests. PMID:27499084

  9. Status epilepticus stimulates NDEL1 expression via the CREB/CRE pathway in the adult mouse brain.

    PubMed

    Choi, Yun-Sik; Lee, Boyoung; Hansen, Katelin F; Aten, Sydney; Horning, Paul; Wheaton, Kelin L; Impey, Soren; Hoyt, Kari R; Obrietan, Karl

    2016-09-01

    Nuclear distribution element-like 1 (NDEL1/NUDEL) is a mammalian homolog of the Aspergillus nidulans nuclear distribution molecule NudE. NDEL1 plays a critical role in neuronal migration, neurite outgrowth and neuronal positioning during brain development; however within the adult central nervous system, limited information is available regarding NDEL1 expression and functions. Here, the goal was to examine inducible NDEL1 expression in the adult mouse forebrain. Immunolabeling revealed NDEL1 within the forebrain, including the cortex and hippocampus, as well as the midbrain and hypothalamus. Expression was principally localized to perikarya. Using a combination of immunolabeling and RNA seq profiling, we detected a marked and long-lasting upregulation of NDEL1 expression within the hippocampus following a pilocarpine-evoked repetitive seizure paradigm. Chromatin immunoprecipitation (ChIP) analysis identified a cAMP response element-binding protein (CREB) binding site within the CpG island proximal to the NDEL1 gene, and in vivo transgenic repression of CREB led to a marked downregulation of seizure-evoked NDEL1 expression. Together these data indicate that NDEL1 is inducibly expressed in the adult nervous system, and that signaling via the CREB/CRE transcriptional pathway is likely involved. The role of NDEL1 in neuronal migration and neurite outgrowth during development raises the interesting prospect that inducible NDEL1 in the mature nervous system could contribute to the well-characterized structural and functional plasticity resulting from repetitive seizure activity. PMID:27298008

  10. Long-term oral methylphenidate treatment in adolescent and adult rats: differential effects on brain morphology and function.

    PubMed

    van der Marel, Kajo; Klomp, Anne; Meerhoff, Gideon F; Schipper, Pieter; Lucassen, Paul J; Homberg, Judith R; Dijkhuizen, Rick M; Reneman, Liesbeth

    2014-01-01

    Methylphenidate is a widely prescribed psychostimulant for treatment of attention deficit hyperactivity disorder (ADHD) in children and adolescents, which raises questions regarding its potential interference with the developing brain. In the present study, we investigated effects of 3 weeks oral methylphenidate (5 mg/kg) vs vehicle treatment on brain structure and function in adolescent (post-natal day [P]25) and adult (P65) rats. Following a 1-week washout period, we used multimodal magnetic resonance imaging (MRI) to assess effects of age and treatment on independent component analysis-based functional connectivity (resting-state functional MRI), D-amphetamine-induced neural activation responses (pharmacological MRI), gray and white matter tissue volumes and cortical thickness (postmortem structural MRI), and white matter structural integrity (postmortem diffusion tensor imaging (DTI)). Many age-related differences were found, including cortical thinning, white matter development, larger dopamine-mediated activation responses and increased striatal functional connectivity. Methylphenidate reduced anterior cingulate cortical network strength in both adolescents and adults. In contrast to clinical observations from ADHD patient studies, methylphenidate did not increase white matter tissue volume or cortical thickness in rat. Nevertheless, DTI-based fractional anisotropy was higher in the anterior part of the corpus callosum following adolescent treatment. Furthermore, methylphenidate differentially affected adolescents and adults as evidenced by reduced striatal volume and myelination upon adolescent treatment, although we did not observe adverse treatment effects on striatal functional activity. Our findings of small but significant age-dependent effects of psychostimulant treatment in the striatum of healthy rats highlights the importance of further research in children and adolescents that are exposed to methylphenidate. PMID:23851400

  11. Neuronal production, migration, and differentiation in a vocal control nucleus of the adult female canary brain.

    PubMed Central

    Goldman, S A; Nottebohm, F

    1983-01-01

    The vocal control nucleus designated HVc (hyperstriatum ventrale, pars caudalis) of adult female canaries expands in response to systemic testosterone administration, which also induces the females to sing in a male-like manner. We became interested in the possibility of neurogenesis as a potential basis for this phenomenon. Intact adult female canaries were injected with [3H]thymidine over a 2-day period. Some birds were given testosterone implants at various times before thymidine. The birds were sacrificed 5 wk after hormone implantation, and their brains were processed for autoradiography. In parallel control experiments, some birds were given implants of cholesterol instead of testosterone. All birds showed considerable numbers of labeled neurons, glia, endothelia, and ventricular zone cells in and around HVc. Ultrastructural analysis confirmed the identity of these labeled neurons. Cholesterol- and testosterone-treated birds had similar neuronal labeling indices, which ranged from 1.8% to 4.0% in HVc. Thus, neurogenesis occurred in these adults independently of exogenous hormone treatment. Conversely, both glial and endothelial proliferation rates were markedly stimulated by exogenous testosterone treatment. We determined the origin of the thymidine-incorporating neurons by sacrificing two thymidine-treated females soon after their thymidine injections, precluding any significant migration of newly labeled cells. Analysis of these brains revealed no cells of neuronal morphology present in HVc but a very heavily labeled ventricular zone overlying HVc. We conclude that neuronal precursors exist in the HVc ventricular zone that incorporate tritiated thymidine during the S phase preceding their mitosis; after division these cells migrate into, and to some extent beyond, HVc. This ventricular zone neurogenesis seems to be a normally occurring phenomenon in intact adult female canaries. Images PMID:6572982

  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. Chemotherapy disrupts learning, neurogenesis and theta activity in the adult brain.

    PubMed

    Nokia, Miriam S; Anderson, Megan L; Shors, Tracey J

    2012-12-01

    Chemotherapy, especially if prolonged, disrupts attention, working memory and speed of processing in humans. Most cancer drugs that cross the blood-brain barrier also decrease adult neurogenesis. Because new neurons are generated in the hippocampus, this decrease may contribute to the deficits in working memory and related thought processes. The neurophysiological mechanisms that underlie these deficits are generally unknown. A possible mediator is hippocampal oscillatory activity within the theta range (3-12 Hz). Theta activity predicts and promotes efficient learning in healthy animals and humans. Here, we hypothesised that chemotherapy disrupts learning via decreases in hippocampal adult neurogenesis and theta activity. Temozolomide was administered to adult male Sprague-Dawley rats in a cyclic manner for several weeks. Treatment was followed by training with different types of eyeblink classical conditioning, a form of associative learning. Chemotherapy reduced both neurogenesis and endogenous theta activity, as well as disrupted learning and related theta-band responses to the conditioned stimulus. The detrimental effects of temozolomide only occurred after several weeks of treatment, and only on a task that requires the association of events across a temporal gap and not during training with temporally overlapping stimuli. Chemotherapy did not disrupt the memory for previously learned associations, a memory independent of (new neurons in) the hippocampus. In conclusion, prolonged systemic chemotherapy is associated with a decrease in hippocampal adult neurogenesis and theta activity that may explain the selective deficits in processes of learning that describe the 'chemobrain'. PMID:23039863

  14. 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

  15. 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

  16. Functional Neuroanatomy of Executive Function after Neonatal Brain Injury in Adults Who Were Born Very Preterm

    PubMed Central

    Kalpakidou, Anastasia K.; Allin, Matthew P. G.; Walshe, Muriel; Giampietro, Vincent; McGuire, Philip K.; Rifkin, Larry; Murray, Robin M.; Nosarti, Chiara

    2014-01-01

    Individuals who were born very preterm (VPT; <33 gestational weeks) are at risk of experiencing deficits in tasks involving executive function in childhood and beyond. In addition, the type and severity of neonatal brain injury associated with very preterm birth may exert differential effects on executive functioning by altering its neuroanatomical substrates. Here we addressed this question by investigating with functional magnetic resonance imaging (fMRI) the haemodynamic response during executive-type processing using a phonological verbal fluency and a working memory task in VPT-born young adults who had experienced differing degrees of neonatal brain injury. 12 VPT individuals with a history of periventricular haemorrhage and ventricular dilatation (PVH+VD), 17 VPT individuals with a history of uncomplicated periventricular haemorrhage (UPVH), 13 VPT individuals with no history of neonatal brain injury and 17 controls received an MRI scan whilst completing a verbal fluency task with two cognitive loads (‘easy’ and ‘hard’ letters). Two groups of VPT individuals (PVH+VD; n = 10, UPVH; n = 8) performed an n-back task with three cognitive loads (1-, 2-, 3-back). Results demonstrated that VPT individuals displayed hyperactivation in frontal, temporal, and parietal cortices and in caudate nucleus, insula and thalamus compared to controls, as demands of the verbal fluency task increased, regardless of type of neonatal brain injury. On the other hand, during the n-back task and as working memory load increased, the PVH+VD group showed less engagement of the frontal cortex than the UPVH group. In conclusion, this study suggests that the functional neuroanatomy of different executive-type processes is altered following VPT birth and that neural activation associated with specific aspects of executive function (i.e., working memory) may be particularly sensitive to the extent of neonatal brain injury. PMID:25438043

  17. Changes in synaptic transmission and protein expression in the brains of adult offspring after prenatal inhibition of the kynurenine pathway.

    PubMed

    Forrest, C M; Khalil, O S; Pisar, M; McNair, K; Kornisiuk, E; Snitcofsky, M; Gonzalez, N; Jerusalinsky, D; Darlington, L G; Stone, T W

    2013-12-19

    During early brain development, N-methyl-d-aspartate (NMDA) receptors are involved in cell migration, neuritogenesis, axon guidance and synapse formation, but the mechanisms which regulate NMDA receptor density and function remain unclear. The kynurenine pathway of tryptophan metabolism includes an agonist (quinolinic acid) and an antagonist (kynurenic acid) at NMDA receptors and we have previously shown that inhibition of the pathway using the kynurenine-3-monoxygenase inhibitor Ro61-8048 in late gestation produces rapid changes in protein expression in the embryos and effects on synaptic transmission lasting until postnatal day 21 (P21). The present study sought to determine whether any of these effects are maintained into adulthood. After prenatal injections of Ro61-8048 the litter was allowed to develop to P60 when some offspring were euthanized and the brains removed for examination. Analysis of protein expression by Western blotting revealed significantly reduced expression of the GluN2A subunit (32%) and the morphogenetic protein sonic hedgehog (31%), with a 29% increase in the expression of doublecortin, a protein associated with neurogenesis. No changes were seen in mRNA abundance using quantitative real-time polymerase chain reaction. Neuronal excitability was normal in the CA1 region of hippocampal slices but paired-pulse stimulation revealed less inhibition at short interpulse intervals. The amount of long-term potentiation was decreased by 49% in treated pups and recovery after low-frequency stimulation was delayed. The results not only strengthen the view that basal, constitutive kynurenine metabolism is involved in normal brain development, but also show that changes induced prenatally can affect the brains of adult offspring and those changes are quite different from those seen previously at weaning (P21). Those changes may be mediated by altered expression of NMDAR subunits and sonic hedgehog. PMID:24076085

  18. Exergame and Balance Training Modulate Prefrontal Brain Activity during Walking and Enhance Executive Function in Older Adults

    PubMed Central

    Eggenberger, Patrick; Wolf, Martin; Schumann, Martina; de Bruin, Eling D.

    2016-01-01

    Different types of exercise training have the potential to induce structural and functional brain plasticity in the elderly. Thereby, functional brain adaptations were observed during cognitive tasks in functional magnetic resonance imaging studies that correlated with improved cognitive performance. This study aimed to investigate if exercise training induces functional brain plasticity during challenging treadmill walking and elicits associated changes in cognitive executive functions. Forty-two elderly participants were recruited and randomly assigned to either interactive cognitive-motor video game dancing (DANCE) or balance and stretching training (BALANCE). The 8-week intervention included three sessions of 30 min per week and was completed by 33 participants (mean age 74.9 ± 6.9 years). Prefrontal cortex (PFC) activity during preferred and fast walking speed on a treadmill was assessed applying functional near infrared spectroscopy pre- and post-intervention. Additionally, executive functions comprising shifting, inhibition, and working memory were assessed. The results showed that both interventions significantly reduced left and right hemispheric PFC oxygenation during the acceleration of walking (p < 0.05 or trend, r = 0.25–0.36), while DANCE showed a larger reduction at the end of the 30-s walking task compared to BALANCE in the left PFC [F(1, 31) = 3.54, p = 0.035, r = 0.32]. These exercise training induced modulations in PFC oxygenation correlated with improved executive functions (p < 0.05 or trend, r = 0.31–0.50). The observed reductions in PFC activity may release cognitive resources to focus attention on other processes while walking, which could be relevant to improve mobility and falls prevention in the elderly. This study provides a deeper understanding of the associations between exercise training, brain function during walking, and cognition in older adults. PMID:27148041

  19. Exergame and Balance Training Modulate Prefrontal Brain Activity during Walking and Enhance Executive Function in Older Adults.

    PubMed

    Eggenberger, Patrick; Wolf, Martin; Schumann, Martina; de Bruin, Eling D

    2016-01-01

    Different types of exercise training have the potential to induce structural and functional brain plasticity in the elderly. Thereby, functional brain adaptations were observed during cognitive tasks in functional magnetic resonance imaging studies that correlated with improved cognitive performance. This study aimed to investigate if exercise training induces functional brain plasticity during challenging treadmill walking and elicits associated changes in cognitive executive functions. Forty-two elderly participants were recruited and randomly assigned to either interactive cognitive-motor video game dancing (DANCE) or balance and stretching training (BALANCE). The 8-week intervention included three sessions of 30 min per week and was completed by 33 participants (mean age 74.9 ± 6.9 years). Prefrontal cortex (PFC) activity during preferred and fast walking speed on a treadmill was assessed applying functional near infrared spectroscopy pre- and post-intervention. Additionally, executive functions comprising shifting, inhibition, and working memory were assessed. The results showed that both interventions significantly reduced left and right hemispheric PFC oxygenation during the acceleration of walking (p < 0.05 or trend, r = 0.25-0.36), while DANCE showed a larger reduction at the end of the 30-s walking task compared to BALANCE in the left PFC [F (1, 31) = 3.54, p = 0.035, r = 0.32]. These exercise training induced modulations in PFC oxygenation correlated with improved executive functions (p < 0.05 or trend, r = 0.31-0.50). The observed reductions in PFC activity may release cognitive resources to focus attention on other processes while walking, which could be relevant to improve mobility and falls prevention in the elderly. This study provides a deeper understanding of the associations between exercise training, brain function during walking, and cognition in older adults. PMID:27148041

  20. Reading in the brain of children and adults: A meta‐analysis of 40 functional magnetic resonance imaging studies

    PubMed Central

    Martin, Anna; Schurz, Matthias; Kronbichler, Martin

    2015-01-01

    Abstract 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. Hum Brain Mapp 36:1963–1981, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.. PMID:25628041

  1. 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.

  2. Microglial Kv1.3 Channels and P2Y12 Receptors Differentially Regulate Cytokine and Chemokine Release from Brain Slices of Young Adult and Aged Mice

    PubMed Central

    Eder, Claudia

    2015-01-01

    Brain tissue damage following stroke or traumatic brain injury is accompanied by neuroinflammatory processes, while microglia play a central role in causing and regulating neuroinflammation via production of proinflammatory substances, including cytokines and chemokines. Here, we used brain slices, an established in situ brain injury model, from young adult and aged mice to investigate cytokine and chemokine production with particular focus on the role of microglia. Twenty four hours after slice preparation, higher concentrations of proinflammatory cytokines, i.e. TNF-α and IL-6, and chemokines, i.e. CCL2 and CXCL1, were released from brain slices of aged mice than from slices of young adult mice. However, maximal microglial stimulation with LPS for 24 h did not reveal age-dependent differences in the amounts of released cytokines and chemokines. Mechanisms underlying microglial cytokine and chemokine production appear to be similar in young adult and aged mice. Inhibition of microglial Kv1.3 channels with margatoxin reduced release of IL-6, but not release of CCL2 and CXCL1. In contrast, blockade of microglial P2Y12 receptors with PSB0739 inhibited release of CCL2 and CXCL1, whereas release of IL-6 remained unaffected. Cytokine and chemokine production was not reduced by inhibitors of Kir2.1 K+ channels or adenosine receptors. In summary, our data suggest that brain tissue damage-induced production of cytokines and chemokines is age-dependent, and differentially regulated by microglial Kv1.3 channels and P2Y12 receptors. PMID:26011191

  3. Brain

    MedlinePlus

    ... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

  4. Neurotoxic Methamphetamine Doses Increase LINE-1 Expression in the Neurogenic Zones of the Adult Rat Brain

    PubMed Central

    Moszczynska, Anna; Flack, Amanda; Qiu, Ping; Muotri, Alysson R.; Killinger, Bryan A.

    2015-01-01

    Methamphetamine (METH) is a widely abused psychostimulant with the potential to cause neurotoxicity in the striatum and hippocampus. Several epigenetic changes have been described after administration of METH; however, there are no data regarding the effects of METH on the activity of transposable elements in the adult brain. The present study demonstrates that systemic administration of neurotoxic METH doses increases the activity of Long INterspersed Element (LINE-1) in two neurogenic niches in the adult rat brain in a promoter hypomethylation-independent manner. Our study also demonstrates that neurotoxic METH triggers persistent decreases in LINE-1 expression and increases the LINE-1 levels within genomic DNA in the striatum and dentate gyrus of the hippocampus, and that METH triggers LINE-1 retrotransposition in vitro. We also present indirect evidence for the involvement of glutamate (GLU) in LINE-1 activation. The results suggest that LINE-1 activation might occur in neurogenic areas in human METH users and might contribute to METH abuse-induced hippocampus-dependent memory deficits and impaired performance on several cognitive tasks mediated by the striatum. PMID:26463126

  5. In-vivo RGB marking and multicolour single-cell tracking in the adult brain

    PubMed Central

    Gomez-Nicola, Diego; Riecken, Kristoffer; Fehse, Boris; Perry, V. Hugh

    2014-01-01

    In neuroscience it is a technical challenge to identify and follow the temporal and spatial distribution of cells as they differentiate. We hypothesised that RGB marking, the tagging of individual cells with unique hues resulting from simultaneous expression of the three basic colours red, green and blue, provides a convenient toolbox for the study of the CNS anatomy at the single-cell level. Using γ-retroviral and lentiviral vector sets we describe for the first time the in-vivo multicolour RGB marking of neurons in the adult brain. RGB marking also enabled us to track the spatial and temporal fate of neural stem cells in the adult brain. The application of different viral envelopes and promoters provided a useful approach to track the generation of neurons vs. glial cells at the neurogenic niche, allowing the identification of the prominent generation of new astrocytes to the striatum. Multicolour RGB marking could serve as a universal and reproducible method to study and manipulate the CNS at the single-cell level, in both health and disease. PMID:25531807

  6. Brain apoptosis signaling pathways are regulated by methylphenidate treatment in young and adult rats.

    PubMed

    Réus, Gislaine Z; Scaini, Giselli; Jeremias, Gabriela C; Furlanetto, Camila B; Morais, Meline O S; Mello-Santos, Lis Maira; Quevedo, João; Streck, Emilio L

    2014-10-01

    Methylphenidate (MPH) is commonly prescribed for children who have been diagnosed with attention deficit hyperactivity disorder (ADHD); however, the action mechanisms of methylphenidate have not been fully elucidated. Studies have shown a relationship between apoptosis signaling pathways and psychiatric disorders, as well as in therapeutic targets for such disorders. So, we investigated if chronic treatment with MPH at doses of 1, 2 and 10mg/kg could alter the levels of pro-apoptotic protein, Bax, anti-apoptotic protein, Bcl-2, caspase-3 and cytochrome c in the brain of young and adult Wistar rats. Our results showed that MPH at all doses increased Bax in the cortex; the Bcl-2 and caspase-3 were increased with MPH (1mg/kg) and were reduced with MPH (2 and 10mg/kg); the cytochrome c was reduced in the cortex after treatment with MPH at all doses; in the cerebellum there was an increase of Bax with MPH at all doses, however, there was a reduction of Bcl-2, caspase-3, and cytochrome c with MPH (2 and 10mg/kg); in the striatum the treatment with MPH (10mg/kg) decreased caspase-3 and cytochrome c; treatment with MPH (2 and 10mg/kg) increased Bax and decreased Bcl-2 in the hippocampus; and the caspase-3 and cytochrome c were reduced in the hippocampus with MPH (10mg/kg). In conclusion, our results suggest that MPH influences plasticity in the brain of young and adult rats; however, the effects were dependent of age and brain area, on the one hand activating the initial cascade of apoptosis, increasing Bax and reducing Bcl-2, but otherwise inhibiting apoptosis by reduction of caspase-3 and cytochrome c. PMID:25128604

  7. Prenatal cocaine exposure alters progenitor cell markers in the subventricular zone of the adult rat brain

    PubMed Central

    Patel, Dhyanesh Arvind; Booze, Rosemarie M.; Mactutus, Charles F.

    2013-01-01

    Long-term consequences of early developmental exposure to drugs of abuse may have deleterious effects on the proliferative plasticity of the brain. The purpose of this study was to examine the long-term effects of prenatal exposure to cocaine, using the IV route of administration and doses that mimic the peak arterial levels of cocaine use in humans, on the proliferative cell types of the subventricular zones (SVZ) in the adult (180 days-old) rat brain. Employing immunocytochemistry, the expression of GFAP+ (type B cells) and nestin+(GFAP−) (Type C and A cells) staining was quantified in the subcallosal area of the SVZ. GFAP+ expression was significantly different between the prenatal cocaine treated group and the vehicle (saline) control group. The prenatal cocaine treated group possessed significantly lower GFAP+ expression relative to the vehicle control group, suggesting that prenatal cocaine exposure significantly reduced the expression of type B neural stem cells of the SVZ. In addition, there was a significant sex difference in nestin+ expression with females showing approximately 8–13% higher nestin+ expression compared to the males. More importantly, a significant prenatal treatment condition (prenatal cocaine, control) by sex interaction in nestin+ expression was confirmed, indicating different effects of cocaine based on sex of the animal. Specifically, prenatal cocaine exposure eliminated the basal difference between the sexes. Collectively, the present findings suggest that prenatal exposure to cocaine, when delivered via a protocol designed to capture prominent features of recreational usage, can selectively alter the major proliferative cell types in the subcallosal area of the SVZ in an adult rat brain, and does so differently for males and females. PMID:22119286

  8. Self-reported electrical appliance use and risk of adult brain tumors.

    PubMed

    Kleinerman, Ruth A; Linet, Martha S; Hatch, Elizabeth E; Tarone, Robert E; Black, Peter M; Selker, Robert G; Shapiro, William R; Fine, Howard A; Inskip, Peter D

    2005-01-15

    Electrical appliances produce the highest intensity exposures to residential extremely low frequency electromagnetic fields. The authors investigated whether appliances may be associated with adult brain tumors in a hospital-based case-control study at three centers in the United States from 1994 to 1998. A total of 410 glioma, 178 meningioma, and 90 acoustic neuroma cases and 686 controls responded to a self-administered questionnaire about 14 electrical appliances. There was little evidence of association between brain tumors and curling iron, heating pad, vibrating massager, electric blanket, heated water bed, sound system, computer, television, humidifier, microwave oven, and electric stove. Ever use of hair dryers was associated with glioma (odds ratio = 1.7, 95% confidence interval: 1.1, 2.5), but there was no evidence of increasing risk with increasing amount of use. In men, meningioma was associated with electric shaver use (odds ratio = 10.9, 95% confidence interval: 2.3, 50), and odds ratios increased with cumulative minutes of use, although they were based on only two nonexposed cases. Recall bias for appliances used regularly near the head or chance may provide an alternative explanation for the observed associations. Overall, results indicate that extremely low frequency electromagnetic fields from commonly used household appliances are unlikely to increase the risk of brain tumors. PMID:15632263

  9. Physical Activity and Brain Function in Older Adults at Increased Risk for Alzheimer’s Disease

    PubMed Central

    Smith, J. Carson; Nielson, Kristy A.; Woodard, John L.; Seidenberg, Michael; Rao, Stephen M.

    2013-01-01

    Leisure-time physical activity (PA) and exercise training are known to help maintain cognitive function in healthy older adults. However, relatively little is known about the effects of PA on cognitive function or brain function in those at increased risk for Alzheimer’s disease through the presence of the apolipoproteinE epsilon4 (APOE-ε4) allele, diagnosis of mild cognitive impairment (MCI), or the presence of metabolic disease. Here, we examine the question of whether PA and exercise interventions may differentially impact cognitive trajectory, clinical outcomes, and brain structure and function among individuals at the greatest risk for AD. The literature suggests that the protective effects of PA on risk for future dementia appear to be larger in those at increased genetic risk for AD. Exercise training is also effective at helping to promote stable cognitive function in MCI patients, and greater cardiorespiratory fitness is associated with greater brain volume in early-stage AD patients. In APOE-ε4 allele carriers compared to non-carriers, greater levels of PA may be more effective in reducing amyloid burden and are associated with greater activation of semantic memory-related neural circuits. A greater research emphasis should be placed on randomized clinical trials for exercise, with clinical, behavioral, and neuroimaging outcomes in people at increased risk for AD. PMID:24961307

  10. Vascular health and longitudinal changes in brain and cognition in middle-aged and older adults.

    PubMed

    Raz, Naftali; Rodrigue, Karen M; Kennedy, Kristen M; Acker, James D

    2007-03-01

    The impact of vascular health on the relations between structural brain changes and cognition was assessed in a longitudinal study of 46 adults, 23 of whom remained healthy for 5 years and 23 of whom had hypertension at baseline or acquired vascular problems during follow-up. At both measurement occasions, the volume of white matter hyperintensities (WMH) and regional brain volumes correlated with age. In 5 years, WMH volume more than doubled in the vascular risk group but did not increase in healthy participants. The frontal lobes had the highest WMH load at baseline and follow-up; the parietal WMH showed the greatest rate of expansion. In the vascular risk group, systolic blood pressure at follow-up correlated with posterior WMH volume. The fastest cortical shrinkage was observed in the prefrontal cortex and the hippocampus. Fluid intelligence correlated with WMH burden and declined along with faster WMH progression. In the vascular risk group, WMH progression and shrinkage of the fusiform cortex correlated with decline in working memory. Thus, poor vascular health contributes to age-related declines in brain and cognition, and some of the age-related declines may be limited to persons with elevated vascular risk. PMID:17402815

  11. 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

  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. Endogenous brain erythropoietin is a potent sex-specific respiratory stimulant in adult and newborn mice.

    PubMed

    Ballot, Orlane; Joseph, Vincent; Soliz, Jorge

    2015-06-01

    We tested the hypothesis that endogenous brain Epo is a respiratory stimulant. Adult (3 mo) and newborn (10 days) male and female mice received an intracisternal (cisterna magna) injection of soluble Epo receptor (sEpoR; competes with EpoR to bind Epo; 50 μg/ml) or vehicle (0.1% BSA in PBS). Twenty-four hours after injection, we used whole body plethysmography to record minute ventilation (V̇e) tidal volume (VT), respiratory frequency (fR), O2 consumption (V̇o2), and CO2 production (V̇co2) under normoxia and progressive exposure to hypoxia (12-10-6% O2; 10 min each). In adult male and female mice sEpoR decreased normoxic V̇e (-25%), due to a decrease of VT in males and fR in females. Moreover, sEpoR injection decreased the ventilatory response to 12% O2, assessed as V̇e/V̇o2 or V̇e/V̇co2, in male but not in female mice. In newborn male and female mice sEpoR decreased V̇e (-37% in males, -59% in females) and VT (-38% in males, -47% in females) in normoxia and fR in females. During hypoxia, sEpoR decreased V̇e/V̇o2 and V̇e/V̇co2 in mice of both sexes. Upon extreme hypoxia (6% O2), the newborn mice treated with sEpoR showed respiratory depression, signs of asphyxia (gasping) and a high mortality rate in males and females. We concluded that endogenous brain Epo is a potent respiratory stimulant under normoxia and hypoxia in adult and newborn mice. Because sex-specific effects are different in newborn male and female, sex steroids secreted at different ages mice appear to modulate the effects of Epo on respiratory regulation in normoxia and in response to hypoxia. PMID:25792712

  14. Adult sports-related traumatic brain injury in United States trauma centers.

    PubMed

    Winkler, Ethan A; Yue, John K; Burke, John F; Chan, Andrew K; Dhall, Sanjay S; Berger, Mitchel S; Manley, Geoffrey T; Tarapore, Phiroz E

    2016-04-01

    OBJECTIVE Sports-related traumatic brain injury (TBI) is an important public health concern estimated to affect 300,000 to 3.8 million people annually in the United States. Although injuries to professional athletes dominate the media, this group represents only a small proportion of the overall population. Here, the authors characterize the demographics of sports-related TBI in adults from a community-based trauma population and identify predictors of prolonged hospitalization and increased morbidity and mortality rates. METHODS Utilizing the National Sample Program of the National Trauma Data Bank (NTDB), the authors retrospectively analyzed sports-related TBI data from adults (age ≥ 18 years) across 5 sporting categories-fall or interpersonal contact (FIC), roller sports, skiing/snowboarding, equestrian sports, and aquatic sports. Multivariable regression analysis was used to identify predictors of prolonged hospital length of stay (LOS), medical complications, inpatient mortality rates, and hospital discharge disposition. Statistical significance was assessed at α < 0.05, and the Bonferroni correction for multiple comparisons was applied for each outcome analysis. RESULTS From 2003 to 2012, in total, 4788 adult sports-related TBIs were documented in the NTDB, which represented 18,310 incidents nationally. Equestrian sports were the greatest contributors to sports-related TBI (45.2%). Mild TBI represented nearly 86% of injuries overall. Mean (± SEM) LOSs in the hospital or intensive care unit (ICU) were 4.25 ± 0.09 days and 1.60 ± 0.06 days, respectively. The mortality rate was 3.0% across all patients, but was statistically higher in TBI from roller sports (4.1%) and aquatic sports (7.7%). Age, hypotension on admission to the emergency department (ED), and the severity of head and extracranial injuries were statistically significant predictors of prolonged hospital and ICU LOSs, medical complications, failure to discharge to home, and death. Traumatic

  15. Measuring inhibitory control in children and adults: brain imaging and mental chronometry

    PubMed Central

    Houdé, Olivier; Borst, Grégoire

    2014-01-01

    Jean Piaget underestimated the cognitive capabilities of infants, preschoolers, and elementary schoolchildren, and overestimated the capabilities of adolescents and even adults which are often biased by illogical intuitions and overlearned strategies (i.e., “fast thinking” in Daniel Kahneman’s words). The crucial question is now to understand why, despite rich precocious knowledge about physical and mathematical principles observed over the last three decades in infants and young children, older children, adolescents and even adults are nevertheless so often bad reasoners. We propose that inhibition of less sophisticated solutions (or heuristics) by the prefrontal cortex is a domain-general executive ability that supports children’s conceptual insights associated with more advanced Piagetian stages, such as number-conservation and class inclusion. Moreover, this executive ability remains critical throughout the whole life and even adults may sometimes need “prefrontal pedagogy” in order to learn inhibiting intuitive heuristics (or biases) in deductive reasoning tasks. Here we highlight some of the discoveries from our lab in the field of cognitive development relying on two methodologies used for measuring inhibitory control: brain imaging and mental chronometry (i.e., the negative priming paradigm). We also show that this new approach opens an avenue for re-examining persistent errors in standard classroom-learning tasks. PMID:24994993

  16. Measuring inhibitory control in children and adults: brain imaging and mental chronometry.

    PubMed

    Houdé, Olivier; Borst, Grégoire

    2014-01-01

    Jean Piaget underestimated the cognitive capabilities of infants, preschoolers, and elementary schoolchildren, and overestimated the capabilities of adolescents and even adults which are often biased by illogical intuitions and overlearned strategies (i.e., "fast thinking" in Daniel Kahneman's words). The crucial question is now to understand why, despite rich precocious knowledge about physical and mathematical principles observed over the last three decades in infants and young children, older children, adolescents and even adults are nevertheless so often bad reasoners. We propose that inhibition of less sophisticated solutions (or heuristics) by the prefrontal cortex is a domain-general executive ability that supports children's conceptual insights associated with more advanced Piagetian stages, such as number-conservation and class inclusion. Moreover, this executive ability remains critical throughout the whole life and even adults may sometimes need "prefrontal pedagogy" in order to learn inhibiting intuitive heuristics (or biases) in deductive reasoning tasks. Here we highlight some of the discoveries from our lab in the field of cognitive development relying on two methodologies used for measuring inhibitory control: brain imaging and mental chronometry (i.e., the negative priming paradigm). We also show that this new approach opens an avenue for re-examining persistent errors in standard classroom-learning tasks. PMID:24994993

  17. Trajectories of brain aging in middle-aged and older adults: Regional and individual differences

    PubMed Central

    Raz, Naftali; Ghisletta, Paolo; Rodrigue, Karen M.; Kennedy, Kristen M.; Lindenberger, Ulman

    2010-01-01

    The human brain changes with age. However, the rate and the trajectories of change vary among the brain regions and among individuals, and the reasons for these differences are unclear. In a sample of healthy middle-aged and older adults, we examined mean volume change and individual differences in the rate of change in 12 regional brain volumes over approximately 30 months. In addition to the baseline assessment, there were two follow-ups, 15 months apart. We observed significant average shrinkage of the hippocampus, entorhinal cortex, orbital–frontal cortex, and cerebellum in each of the intervals. Shrinkage of the hippocampus accelerated with time, whereas shrinkage of the caudate nucleus, prefrontal subcortical white matter, and corpus callosum emerged only at the second follow-up. Throughout both assessment intervals, the mean volumes of the lateral prefrontal and primary visual cortices, putamen, and pons did not change. Significant individual differences in shrinkage rates were observed in the lateral prefrontal cortex, the cerebellum, and all the white matter regions throughout the study, whereas additional regions (medial–temporal structures, the insula, and the basal ganglia) showed significant individual variation in change during the second follow-up. No individual variability was noted in the change of orbital frontal and visual cortices. In two white matter regions, we were able to identify factors associated with individual differences in brain shrinkage. In corpus callosum, shrinkage rate was greater in persons with hypertension, and in the pons, women and carriers of the ApoEε4 allele exhibited declines not noted in the whole sample. PMID:20298790

  18. 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

  19. The relation between brain activity during memory tasks and years of education in young and older adults.

    PubMed

    Springer, Mellanie V; McIntosh, Anthony R; Winocur, Gordon; Grady, Cheryl L

    2005-03-01

    Higher education is associated with less age-related decline in cognitive function, but the mechanism of this protective effect is unknown. The authors examined the effect of age on the relation between education and brain activity by correlating years of education with activity measured using functional MRI during memory tasks in young and older adults. In young adults, education was negatively correlated with frontal activity, whereas in older adults, education was positively correlated with frontal activity. Medial temporal activity was associated with more education in young adults but less education in older adults. This suggests that the frontal cortex is engaged by older adults, particularly by the highly educated, as an alternative network that may be engaged to aid cognitive function. PMID:15769202

  20. Alzheimer’s Biomarkers are Correlated with Brain Connectivity in Older Adults Differentially during Resting and Task States

    PubMed Central

    Jiang, Yang; Huang, Haiqing; Abner, Erin; Broster, Lucas S.; Jicha, Gregory A.; Schmitt, Frederick A.; Kryscio, Richard; Andersen, Anders; Powell, David; Van Eldik, Linda; Gold, Brian T.; Nelson, Peter T.; Smith, Charles; Ding, Mingzhou

    2016-01-01

    β-amyloid (Aβ) plaques and tau-related neurodegeneration are pathologic hallmarks of Alzheimer’s disease (AD). The utility of AD biomarkers, including those measured in cerebrospinal fluid (CSF), in predicting future AD risk and cognitive decline is still being refined. Here, we explored potential relationships between functional connectivity (FC) patterns within the default-mode network (DMN), age, CSF biomarkers (Aβ42 and pTau181), and cognitive status in older adults. Multiple measures of FC were explored, including a novel time series-based measure [total interdependence (TI)]. In our sample of 27 cognitively normal older adults, no significant associations were found between levels of Aβ42 or pTau181 and cognitive scores or regional brain volumes. However, we observed several novel relationships between these biomarkers and measures of FC in DMN during both resting-state and a short-term memory task. First, increased connectivity between bilateral anterior middle temporal gyri was associated with higher levels of CSF Aβ42 and Aβ42/pTau181 ratio (reflecting lower AD risk) during both rest and task. Second, increased bilateral parietal connectivity during the short-term memory task, but not during rest, was associated with higher levels of CSF pTau181 (reflecting higher AD risk). Third, increased connectivity between left middle temporal and left parietal cortices during the active task was associated with decreased global cognitive status but not CSF biomarkers. Lastly, we found that our new TI method was more sensitive to the CSF Aβ42-connectivity relationship whereas the traditional cross-correlation method was more sensitive to levels of CSF pTau181 and cognitive status. With further refinement, resting-state connectivity and task-driven connectivity measures hold promise as non-invasive neuroimaging markers of Aβ and pTau burden in cognitively normal older adults. PMID:26903858

  1. Introduction of the Uppsala Traumatic Brain Injury register for regular surveillance of patient characteristics and neurointensive care management including secondary insult quantification and clinical outcome

    PubMed Central

    Nyholm, Lena; Howells, Tim; Enblad, Per

    2013-01-01

    Background To improve neurointensive care (NIC) and outcome for traumatic brain injury (TBI) patients it is crucial to define and monitor indexes of the quality of patient care. With this purpose we established the web-based Uppsala TBI register in 2008. In this study we will describe and analyze the data collected during the first three years of this project. Methods Data from the medical charts were organized in three columns containing: 1) Admission data; 2) Data from the NIC period including neurosurgery, type of monitoring, treatment, complications, neurological condition at discharge, and the amount of secondary insults; 3) Outcome six months after injury. Indexes of the quality of care implemented include: 1) Index of improvement; 2) Index of change; 3) The percentages of ‘Talk and die' and ‘Talk and deteriorate' patients. Results Altogether 314 patients were included 2008–2010: 66 women and 248 men aged 0–86 years. Automatic reports showed that the proportion of patients improving during NIC varied between 80% and 60%. The percentage of deteriorated patients was less than 10%. The percentage of Talk and die/Talk and deteriorate cases was <1%. The mean Glasgow Coma Score (Motor) improved from 5.04 to 5.68 during the NIC unit stay. The occurrences of secondary insults were less than 5% of good monitoring time for intracranial pressure (ICP) >25 mmHg, cerebral perfusion pressure (CPP) <50 mmHg, and systolic blood pressure <100 mmHg. Favorable outcome was achieved by 64% of adults. Conclusion The Uppsala TBI register enables the routine monitoring of NIC quality indexes. PMID:23837596

  2. Regional brain volumes changes in adult male FMR1-KO mouse on the FVB strain.

    PubMed

    Lai, J K Y; Lerch, J P; Doering, L C; Foster, J A; Ellegood, J

    2016-03-24

    Fragile X Syndrome (FXS) is the most common heritable single gene cause of autism spectrum disorder (ASD). FMR1-KO mice mimic the etiology and phenotypic manifestations of FXS. Neuroanatomical changes in specific brain regions have been reported in clinical settings and in preclinical models. FMR1-KO mice have been generated in different strains including C57Bl/6 (B6) and FVB. Mice on different genetic backgrounds have stable yet distinct behavioral phenotypes that may lead to unique gene-strain interactions on brain structure. Previous magnetic resonance imaging (MRI) studies have examined FMR1 knockout male mice on a B6 and found few differences compared to wild-type mice. Here, we examine brain volumes in FMR1 knockout male mice on a FVB background using high resolution (multi-channel 7.0Tesla) MRI. We observe multiple differences in the neuroanatomy of male FMR1-/y mice on a FVB background. Significantly larger relative volume (% total brain volume) differences were found in major white matter structures throughout the brain. In addition, there were changes in areas associated with fronto-striatal circuitry and other regions. Functional and structural connectivity differences are often seen in human ASD, and therefore, this increased white matter seen in the FMR1-KO-FVB could be highlighting a structural over-connectivity, which could lead to some of the behavioral abnormalities seen with the FMR1-KO-FVB mice. Furthermore, these results highlight the importance of genetic strain contribution to brain structure. PMID:26794591

  3. Unresolved legal and ethical issues in research of adults with severe traumatic brain injury: analysis of an ongoing protocol.

    PubMed

    Pape, Theresa Louise-Bender; Jaffe, Nancy Oddi; Savage, Teresa; Collins, Eileen; Warden, Deborah

    2004-03-01

    This paper synthesizes federal and state laws and bioethics literature with observations from an ongoing research protocol to identify, define, and clarify the unresolved legal and ethical issues regarding research involving adults with traumatic brain injury (TBI). Solutions that protect rights and minimize unnecessary impediments to valuable clinical and scientific inquiry are also illustrated using the same protocol. Research was performed at intensive care, inpatient rehabilitation, and long-term acute chronic hospitals. Our research protocol identified five areas of law impacting adults with TBI: advanced directives, healthcare surrogacy acts, probate acts, power of attorney acts, and the Health Insurance Portability and Accountability Act. The published bioethics literature and responses from local human subject institutional review boards (IRBs) suggest that some of the unresolved ethical issues in research include defining vulnerability, defining informed voluntary consent, determining competency and/or decision-making capacity, using caregivers as subjects, and conducting multisite cooperative studies. Collaboration with IRB members and administrators as well as legal and research ethic scholars developed procedures that protect rights while avoiding unnecessary impediments to research. Investigations of persons with TBI and other cognitive impairments are governed by complicated and inconsistent regulations within the Common Rule and federal and state statues. A need for clear and consistent regulatory guidance regarding multisite studies of TBI persists. In lieu of regulatory guidance, carefully researched solutions for critical peer review are needed to guide future multisite investigations of TBI. PMID:15558370

  4. Microarray analysis of thyroid hormone-induced changes in mRNA expression in the adult rat brain.

    PubMed

    Haas, Michael J; Mreyoud, Amjad; Fishman, Miriam; Mooradian, Arshag D

    2004-07-15

    To determine which genes in the adult rat brain are regulated by thyroid hormone (TH), we used microarrays to examine the effect of hyperthyroidism on neuron-specific gene expression. Four-month-old male Fisher 344 rats were rendered hyperthyroid by intraperitoneal injection of 3,5,3'-L-triiodothyronine (T3, 15 microg/100 g body weight) for 10 consecutive days. To minimize interindividual variability, pooled cerebral tissue RNA from four-control and five-hyperthyroid rats was hybridized in duplicates to the Affymetrix (Santa Clara, CA) U34N rat neurobiology microarray, which contains probes for 1224 neural-specific genes. Changes in gene expression were considered significant only if they were observed in both pair-wise comparisons as well as by Northern blot analysis. Hyperthyroidism was associated with modest changes in the expression of only 11 genes. The expression of the phosphodiesterase Enpp2, myelin oligodendrocyte glycoprotein (Mog), microtubule-associated protein 2 (MAP2), growth hormone (GH), Ca(2+)/calmodulin-dependent protein kinase beta-subunit (Camk2b), neuron-specific protein PEP-19 (Pcp4), a sodium-dependent neurotransmitter, and the myelin-associated glycoprotein (S-MAG) was significantly increased. Three genes were suppressed by hyperthyroidism, including the activity and neurotransmitter-induced early genes-1 and -7 (ANIA-1 and ANIA-7) and the guanine nucleotide-binding protein one (Gnb1). The present study underscores the paucity of TH responsive genes in adult cerebral tissue. PMID:15234464

  5. 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

  6. 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. PMID:26244873

  7. New Hippocampal Neurons Are Not Obligatory for Memory Formation; Cyclin D2 Knockout Mice with No Adult Brain Neurogenesis Show Learning

    ERIC Educational Resources Information Center

    Jaholkowski, Piotr; Kiryk, Anna; Jedynak, Paulina; Abdallah, Nada M. Ben; Knapska, Ewelina; Kowalczyk, Anna; Piechal, Agnieszka; Blecharz-Klin, Kamilla; Figiel, Izabela; Lioudyno, Victoria; Widy-Tyszkiewicz, Ewa; Wilczynski, Grzegorz M.; Lipp, Hans-Peter; Kaczmarek, Leszek; Filipkowski, Robert K.

    2009-01-01

    The role of adult brain neurogenesis (generating new neurons) in learning and memory appears to be quite firmly established in spite of some criticism and lack of understanding of what the new neurons serve the brain for. Also, the few experiments showing that blocking adult neurogenesis causes learning deficits used irradiation and various drugs…

  8. Modulating Astrocyte Transition after Stroke to Promote Brain Rescue and Functional Recovery: Emerging Targets Include Rho Kinase

    PubMed Central

    Abeysinghe, Hima Charika S.; Phillips, Ellie L.; Chin-Cheng, Heung; Beart, Philip M.; Roulston, Carli L.

    2016-01-01

    Stroke is a common and serious condition, with few therapies. Whilst previous focus has been directed towards biochemical events within neurons, none have successfully prevented the progression of injury that occurs in the acute phase. New targeted treatments that promote recovery after stroke might be a better strategy and are desperately needed for the majority of stroke survivors. Cells comprising the neurovascular unit, including blood vessels and astrocytes, present an alternative target for supporting brain rescue and recovery in the late phase of stroke, since alteration in the unit also occurs in regions outside of the lesion. One of the major changes in the unit involves extensive morphological transition of astrocytes resulting in altered energy metabolism, decreased glutamate reuptake and recycling, and retraction of astrocyte end feed from both blood vessels and neurons. Whilst globally inhibiting transitional change in astrocytes after stroke is reported to result in further damage and functional loss, we discuss the available evidence to suggest that the transitional activation of astrocytes after stroke can be modulated for improved outcomes. In particular, we review the role of Rho-kinase (ROCK) in reactive gliosis and show that inhibiting ROCK after stroke results in reduced scar formation and improved functional recovery. PMID:26927079

  9. Modulating Astrocyte Transition after Stroke to Promote Brain Rescue and Functional Recovery: Emerging Targets Include Rho Kinase.

    PubMed

    Abeysinghe, Hima Charika S; Phillips, Ellie L; Chin-Cheng, Heung; Beart, Philip M; Roulston, Carli L

    2016-01-01

    Stroke is a common and serious condition, with few therapies. Whilst previous focus has been directed towards biochemical events within neurons, none have successfully prevented the progression of injury that occurs in the acute phase. New targeted treatments that promote recovery after stroke might be a better strategy and are desperately needed for the majority of stroke survivors. Cells comprising the neurovascular unit, including blood vessels and astrocytes, present an alternative target for supporting brain rescue and recovery in the late phase of stroke, since alteration in the unit also occurs in regions outside of the lesion. One of the major changes in the unit involves extensive morphological transition of astrocytes resulting in altered energy metabolism, decreased glutamate reuptake and recycling, and retraction of astrocyte end feed from both blood vessels and neurons. Whilst globally inhibiting transitional change in astrocytes after stroke is reported to result in further damage and functional loss, we discuss the available evidence to suggest that the transitional activation of astrocytes after stroke can be modulated for improved outcomes. In particular, we review the role of Rho-kinase (ROCK) in reactive gliosis and show that inhibiting ROCK after stroke results in reduced scar formation and improved functional recovery. PMID:26927079

  10. Stability and Autolysis of Cortical Neurons in Post-Mortem Adult Rat Brains

    PubMed Central

    Sheleg, Sergey V; LoBello, Janine R; Hixon, Hugh; Coons, Stephen W; Lowry, David; Nedzved, Mikhail K

    2008-01-01

    We investigated the dynamics of autolytic damage of the cortical neurons in adult brains for 24 hours at room temperature (+20°C) after cardiac arrest. The progressive histological and ultrastructural changes were documented using routine and immunohistochemical staining as well as electron microscopy. Our results demonstrated that there were no autolytic damages in the ultrastructure of cerebral neurons in the first 6 hours after warm cardiac arrest, in agreement with previous studies in other mammals. Interestingly, the activation of caspase-3 was observed in a significant number of neurons of the cerebellum and neocortex 9 hours following cardiac arrest. No significant changes related to autolysis were observed using amnio-cupric acid and Nissl (thionine) staining. PMID:18784829

  11. Computer-based cognitive retraining for adults with chronic acquired brain injury: a pilot study.

    PubMed

    Li, Kitsum; Robertson, Julie; Ramos, Joshua; Gella, Stephanie

    2013-10-01

    This study evaluated the effectiveness of a computer-based cognitive retraining (CBCR) program on improving memory and attention deficits in individuals with a chronic acquired brain injury (ABI). Twelve adults with a chronic ABI demonstrating deficits in memory and attention were recruited from a convenience sample from the community. Using a quasi-experimental one-group pretest-posttest design, a significant improvement was found in both memory and attention scores postintervention using the cognitive screening tool. This study supported the effectiveness of CBCR programs in improving cognitive deficits in memory and attention in individuals with chronic ABI. Further research is recommended to validate these findings with a larger ABI population and to investigate transfer to improvement in occupational performance that supports daily living skills. PMID:24102589

  12. Brain-derived neurotrophic factor prevents dendritic retraction of adult mouse retinal ganglion cells.

    PubMed

    Binley, Kate E; Ng, Wai S; Barde, Yves-Alain; Song, Bing; Morgan, James E

    2016-08-01

    We used cultured adult mouse retinae as a model system to follow and quantify the retraction of dendrites using diolistic labelling of retinal ganglion cells (RGCs) following explantation. Cell death was monitored in parallel by nuclear staining as 'labelling' with RGC and apoptotic markers was inconsistent and exceedingly difficult to quantify reliably. Nuclear staining allowed us to delineate a lengthy time window during which dendrite retraction can be monitored in the absence of RGC death. The addition of brain-derived neurotrophic factor (BDNF) produced a marked reduction in dendritic degeneration, even when application was delayed for 3 days after retinal explantation. These results suggest that the delayed addition of trophic factors may be functionally beneficial before the loss of cell bodies in the course of conditions such as glaucoma. PMID:27285957

  13. Dairy intake is associated with brain glutathione concentration in older adults123

    PubMed Central

    Lee, Phil; Denney, Douglas R; Spaeth, Kendra; Nast, Olivia; Ptomey, Lauren; Roth, Alexandra K; Lierman, Jo Ann; Sullivan, Debra K

    2015-01-01

    Background: A reduction in key antioxidants such as glutathione has been noted in brain tissue undergoing oxidative stress in aging and neurodegeneration. To date, no dietary factor has been linked to a higher glutathione concentration. However, in an earlier pilot study, we showed evidence of a positive association between cerebral glutathione and dairy intake. Objective: We tested the hypothesis that dairy food consumption is associated with cerebral glutathione concentrations in older adults. Design: In this observational study, we measured cerebral glutathione concentrations in 60 healthy subjects (mean ± SD age: 68.7 ± 6.2 y) whose routine dairy intakes varied. Glutathione concentrations were measured by using a unique, noninvasive magnetic resonance chemical shift imaging technique at 3 T and compared with dairy intakes reported in 7-d food records. Results: Glutathione concentrations in the frontal [Spearman's rank-order correlation (rs) = 0.39, P = 0.013], parietal (rs = 0.50, P = 0.001), and frontoparietal regions (rs = 0.47, P = 0.003) were correlated with average daily dairy servings. In particular, glutathione concentrations in all 3 regions were positively correlated with milk servings (P ≤ 0.013), and those in the parietal region were also correlated with cheese servings (P = 0.015) and calcium intake (P = 0.039). Dairy intake was related to sex, fat-free mass, and daily intakes of energy, protein, and carbohydrates. However, when these factors were controlled through a partial correlation, correlations between glutathione concentrations and dairy and milk servings remained significant. Conclusions: Higher cerebral glutathione concentrations were associated with greater dairy consumption in older adults. One possible explanation for this association is that dairy foods may serve as a good source of substrates for glutathione synthesis in the human brain. PMID:25646325

  14. Gender, intoxication and the developing brain: Problematisations of drinking among young adults in Australian alcohol policy.

    PubMed

    Manton, Elizabeth; Moore, David

    2016-05-01

    In this article, we draw on recent scholarly work in the poststructuralist analysis of policy to consider how policy itself functions as a key site in the constitution of alcohol 'problems', and the political implications of these problematisations. We do this by examining Australian alcohol policy as it relates to young adults (18-24 years old). Our critical analysis focuses on three national alcohol policies (1990, 2001 and 2006) and two Victorian state alcohol policies (2008 and 2013), which together span a 25-year period. We argue that Australian alcohol policies have conspicuously ignored young adult men, despite their ongoing over-representation in the statistical 'evidence base' on alcohol-related harm, while increasingly problematising alcohol consumption amongst other population subgroups. We also identify the development of a new problem representation in Australian alcohol policy, that of 'intoxication' as the leading cause of alcohol-related harm and rising hospital admissions, and argue that changes in the classification and diagnosis of intoxication may have contributed to its prioritisation and problematisation in alcohol policy at the expense of other forms of harm. Finally, we draw attention to how preliminary and inconclusive research on the purported association between binge drinking and brain development in those under 25 years old has been mobilised prematurely to support calls to increase the legal purchasing age from 18 to 21 years. Our critical analysis of the treatment of these three issues - gender, intoxication, and brain development - is intended to highlight the ways in which policy functions as a key site in the constitution of alcohol 'problems'. PMID:26644026

  15. Neurogenesis in the aging brain

    PubMed Central

    Galvan, Veronica; Jin, Kunlin

    2007-01-01

    Neurogenesis, or the birth of new neural cells, was thought to occur only in the developing nervous system and a fixed neuronal population in the adult brain was believed to be necessary to maintain the functional stability of adult brain circuitry. However, recent studies have demonstrated that neurogenesis does indeed continue into and throughout adult life in discrete regions of the central nervous systems (CNS) of all mammals, including humans. Although neurogenesis may contribute to the ability of the adult brain to function normally and be induced in response to cerebral diseases for self-repair, this nevertheless declines with advancing age. Understanding the basic biology of neural stem cells and the molecular and cellular regulation mechanisms of neurogenesis in young and aged brain will allow us to modulate cell replacement processes in the adult brain for the maintenance of healthy brain tissues and for repair of disease states in the elderly. PMID:18225461

  16. Characteristics of diffusion-tensor imaging for healthy adult rhesus monkey brains

    PubMed Central

    Zhao, Xinxiang; Pu, Jun; Fan, Yaodong; Niu, Xiaoqun; Yu, Danping; Zhang, Yanglin

    2013-01-01

    Diffusion-tensor imaging can be used to observe the microstructure of brain tissue. Fractional sotropy reflects the integrity of white matter fibers. Fractional anisotropy of a young adult brain is low in gray matter, high in white matter, and highest in the splenium of the corpus callosum. Thus, we selected the anterior and posterior limbs of the internal capsule, head of the caudate nucleus, semioval center, thalamus, and corpus callosum (splenium and genu) as regions of interest when using diffusion-tensor imaging to observe fractional anisotropy of major white matter fiber tracts and the deep gray matter of healthy rhesus monkeys aged 4–8 years. Results showed no laterality ferences in fractional anisotropy values. Fractional anisotropy values were low in the head of date nucleus and thalamus in gray matter. Fractional anisotropy values were highest in the splenium of corpus callosum in the white matter, followed by genu of the corpus callosum and the posterior limb of the internal capsule. Fractional anisotropy values were lowest in the semioval center and posterior limb of internal capsule. These results suggest that fractional anisotropy values in major white matter fibers and the deep gray matter of 4–8-year-old rhesus monkeys are similar to those of healthy young people. PMID:25206616

  17. Figurative language processing after traumatic brain injury in adults: a preliminary study.

    PubMed

    Yang, Fanpei Gloria; Fuller, Jerome; Khodaparast, Navid; Krawczyk, Daniel C

    2010-06-01

    Figurative speech (e.g., proverb, irony, metaphor, and idiom) has been reported to be particularly sensitive to measurement of abstract thinking in patients who suffer from impaired abstraction and language abilities. Metaphor processing was investigated with fMRI in adults with moderate to severe post-acute traumatic brain injury (TBI) and healthy age-matched controls using a valence-judgment task. We hypothesized that TBI patients would display decreased activation of the left inferior frontal gyrus (LIFG), which is considered central to semantic memory retrieval and abstract thought, in comparison with healthy controls. We also predicted that decreased activation in TBI individuals would correlate with their behavioral response times. A whole-brain analysis across the two participant groups revealed that patients did not strongly engage frontal and temporal regions related to semantic processing for novel metaphor comprehension, whereas control participants exhibited more intensive and concentrated activation within frontal and temporal areas. A region of interest (ROI) analysis verified that the LIFG was underactivated in TBI patients compared to controls across all conditions. TBI patients' impaired abstraction of novel stimuli may stem from reduced prefrontal control of semantic memory as well as disrupted interconnectivity of prefrontal cortex with other regions. PMID:20230844

  18. Brain-derived neurotrophic factor into adult neocortex strengthens a taste aversion memory.

    PubMed

    Martínez-Moreno, Araceli; Rodríguez-Durán, Luis F; Escobar, Martha L

    2016-01-15

    Nowadays, it is known that brain derived neurotrophic-factor (BDNF) is a protein critically involved in regulating long-term memory related mechanisms. Previous studies from our group in the insular cortex (IC), a brain structure of the temporal lobe implicated in acquisition, consolidation and retention of conditioned taste aversion (CTA), demonstrated that BDNF is essential for CTA consolidation. Recent studies show that BDNF-TrkB signaling is able to mediate the enhancement of memory. However, whether BDNF into neocortex is able to enhance aversive memories remains unexplored. In the present work, we administrated BDNF in a concentration capable of inducing in vivo neocortical LTP, into the IC immediately after CTA acquisition in two different conditions: a "strong-CTA" induced by 0.2M lithium chloride i.p. as unconditioned stimulus, and a "weak-CTA" induced by 0.1M lithium chloride i.p. Our results show that infusion of BDNF into the IC converts a weak CTA into a strong one, in a TrkB receptor-dependent manner. The present data suggest that BDNF into the adult insular cortex is sufficient to increase an aversive memory-trace. PMID:26433146

  19. FGF-2 regulation of neurogenesis in adult hippocampus after brain injury

    PubMed Central

    Yoshimura, Shinichi; Takagi, Yasushi; Harada, Jun; Teramoto, Tetsuyuki; Thomas, Sunu S.; Waeber, Christian; Bakowska, Joanna C.; Breakefield, Xandra O.; Moskowitz, Michael A.

    2001-01-01

    Fibroblast growth factor-2 (FGF-2) promotes proliferation of neuroprogenitor cells in culture and is up-regulated within brain after injury. Using mice genetically deficient in FGF-2 (FGF-2−/− mice), we addressed the importance of endogenously generated FGF-2 on neurogenesis within the hippocampus, a structure involved in spatial, declarative, and contextual memory, after seizures or ischemic injury. BrdUrd incorporation was used to mark dividing neuroprogenitor cells and NeuN expression to monitor their differentiation into neurons. In the wild-type strain, hippocampal FGF-2 increased after either kainic acid injection or middle cerebral artery occlusion, and the numbers of BrdUrd/NeuN-positive cells significantly increased on days 9 and 16 as compared with the controls. In FGF-2−/− mice, BrdUrd labeling was attenuated after kainic acid or middle cerebral artery occlusion, as was the number of neural cells colabeled with both BrdUrd and NeuN. After FGF-2−/− mice were injected intraventricularly with a herpes simplex virus-1 amplicon vector carrying FGF-2 gene, the number of BrdUrd-labeled cells increased significantly to values equivalent to wild-type littermates after kainate seizures. These results indicate that endogenously synthesized FGF-2 is necessary and sufficient to stimulate proliferation and differentiation of neuroprogenitor cells in the adult hippocampus after brain insult. PMID:11320217

  20. The Wechsler Adult Intelligence Scale-III and Malingering in Traumatic Brain Injury: Classification Accuracy in Known Groups

    ERIC Educational Resources Information Center

    Curtis, Kelly L.; Greve, Kevin W.; Bianchini, Kevin J.

    2009-01-01

    A known-groups design was used to determine the classification accuracy of Wechsler Adult Intelligence Scale-III (WAIS-III) variables in detecting malingered neurocognitive dysfunction (MND) in traumatic brain injury (TBI). TBI patients were classified into the following groups: (a) mild TBI not-MND (n = 26), (b) mild TBI MND (n = 31), and (c)…

  1. 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…

  2. Atypical Brain Activation during Simple & Complex Levels of Processing in Adult ADHD: An fMRI Study

    ERIC Educational Resources Information Center

    Hale, T. Sigi; Bookheimer, Susan; McGough, James J.; Phillips, Joseph M.; McCracken, James T.

    2007-01-01

    Objective: Executive dysfunction in ADHD is well supported. However, recent studies suggest that more fundamental impairments may be contributing. We assessed brain function in adults with ADHD during simple and complex forms of processing. Method: We used functional magnetic resonance imaging with forward and backward digit spans to investigate…

  3. Post-mortem brain pathology is related to declining respiratory function in community-dwelling older adults

    PubMed Central

    Buchman, Aron S.; Yu, Lei; Wilson, Robert S.; Dawe, Robert J.; VanderHorst, Veronique; Schneider, Julie A.; Bennett, David A.

    2015-01-01

    Damage to brain structures which constitute the distributed neural network that integrates respiratory muscle and pulmonary functions, can impair adequate ventilation and its volitional control. We tested the hypothesis that the level of brain pathology in older adults is associated with declining respiratory function measured during life. 1,409 older adults had annual testing with spirometry (SPI) and respiratory muscle strength (RMS) based on maximal inspiratory and maximal expiratory pressures (MEPs). Those who died underwent structured brain autopsy. On average, during 5 years of follow-up, SPI and RMS showed progressive decline which was moderately correlated (ρ = 0.57, p < 0.001). Among decedents (N = 447), indices of brain neuropathologies showed differential associations with declining SPI and RMS. Nigral neuronal loss was associated with the person-specific decline in SPI (Estimate, −0.016 unit/year, S.E. 0.006, p = 0.009) and reduction of the slope variance was equal to 4%. By contrast, Alzheimer’s disease (AD) pathology (Estimate, −0.030 unit/year, S.E. 0.009, p < 0.001) and macroscopic infarcts (−0.033 unit/year, S.E., 0.011, p = 0.003) were associated with the person-specific decline in RMS and reduction of the slope variance was equal to 7%. These results suggest that brain pathology is associated with the rate of declining respiratory function in older adults. PMID:26539108

  4. Comparison of specific absorption rate induced in brain tissues of a child and an adult using mobile phone

    NASA Astrophysics Data System (ADS)

    Lu, Mai; Ueno, Shoogo

    2012-04-01

    The steady increase of mobile phone usage, especially mobile phones by children, has led to a rising concern about the possible adverse health effects of radio frequency electromagnetic field exposure. The objective of this work is to study whether there is a larger radio frequency energy absorption in the brain of a child compared to that of an adult. For this reason, three high-resolution models, two child head models (6 - and 11-year old) and one adult head model (34-year old) have been used in the study. A finite-difference time-domain method was employed to calculate the specific absorption rate (SAR) in the models from exposure to a generic handset at 1750 MHz. The results show that the SAR distributions in the human brain are age-dependent, and there is a deeper penetration of the absorbed SAR in the child's brain. The induced SAR can be significantly higher in subregions of the child's brain. In all of the examined cases, the SAR values in the brains of a child and an adult are well below the IEEE safety standard.

  5. Fish consumption and risk of subclinical brain abnormalities on MRI in older adults

    PubMed Central

    Virtanen, J K.; Siscovick, D S.; Longstreth, W T.; Kuller, L H.; Mozaffarian, D

    2008-01-01

    Objective: To investigate the association between fish consumption and subclinical brain abnormalities. Methods: In the population-based Cardiovascular Health Study, 3,660 participants age ≥65 underwent an MRI scan in 1992–1994. Five years later, 2,313 were scanned. Neuroradiologists assessed MRI scans in a standardized and blinded manner. Food frequency questionnaires were used to assess dietary intakes. Participants with known cerebrovascular disease were excluded from the analyses. Results: After adjustment for multiple risk factors, the risk of having one or more prevalent subclinical infarcts was lower among those consuming tuna/other fish ≥3 times/week, compared to <1/month (relative risk 0.74, 95% CI = 0.54–1.01, p = 0.06, p trend = 0.03). Tuna/other fish consumption was also associated with trends toward lower incidence of subclinical infarcts. Additionally, tuna/other fish intake was associated with better white matter grade, but not with sulcal and ventricular grades, markers of brain atrophy. No significant associations were found between fried fish consumption and any subclinical brain abnormalities. Conclusions: Among older adults, modest consumption of tuna/other fish, but not fried fish, was associated with lower prevalence of subclinical infarcts and white matter abnormalities on MRI examinations. Our results add to prior evidence that suggest that dietary intake of fish with higher eicosapentaenoic acid and docosahexaenoic acid content, and not fried fish intake, may have clinically important health benefits. GLOSSARY ARR = absolute risk reduction; BMI = body mass index; CHD = coronary heart disease; CHS = Cardiovascular Health Study; DHA = docosahexaenoic acid; EPA = eicosapentaenoic acid; FFQ = food frequency questionnaire; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; PUFA = polyunsaturated fatty acid; RR = relative risk. PMID:18678827

  6. Prevalence, associations, and predictors of apathy in adult survivors of infantile (<5 years of age) posterior fossa brain tumors†

    PubMed Central

    Carroll, Cliodhna; Watson, Peter; Spoudeas, Helen A.; Hawkins, Michael M.; Walker, David A.; Clare, Isabel C. H.; Holland, Anthony J.; Ring, Howard A.

    2013-01-01

    Background Apathy is associated with pervasive and disadvantageous effects on daily functioning. It has been observed transiently in some children after surgery for posterior fossa tumors. In this study, our objective was to examine prevalence, associations, and predictors of apathy in adult survivors of an infantile posterior fossa brain tumor (PFT). Methods One hundred seventeen adult survivors of a childhood PFT diagnosed before age 5 years and 60 of their siblings were assessed in a cross-sectional study a mean of 32 years (range, 18–53 years) after survivors' initial tumor diagnoses, using the Marin Apathy Evaluation Scale (AES), the Weschler Abbreviated Scale of Intelligence and the Composite International Diagnostic Interview for psychiatric disorders. Results Marin Apathy Evaluation Scale, the Weschler Abbreviated Scale of Intelligence reached or exceeded a criterion score for clinically significant apathy in 35% of survivors, compared with 18% in a sibling comparison group. In both siblings and survivors, apathy was associated with lower verbal and full-scale IQ and, among survivors, with having undergone partial rather than total tumor resection (independent of irradiation status). Apathy was not related to presence of concurrent International Classification of Diseases, 10th Revision, depression. Female sex was associated with late apathy after a PFT, with increased likelihood of women reaching the apathy criterion relative to men if they were survivors. Conclusions Clinically significant and potentially treatable apathy occurs relatively commonly in adult survivors of an infantile childhood PFT, particularly women. Clinicians, including those managing posterior fossa pathology in very young children, should be aware of this association, and future research should clarify whether specific treatment-related variables are implicated in increasing this risk of apathy. PMID:23502428

  7. Stab wound injury of the zebrafish adult telencephalon: a method to investigate vertebrate brain neurogenesis and regeneration.

    PubMed

    Schmidt, Rebecca; Beil, Tanja; Strähle, Uwe; Rastegar, Sepand

    2014-01-01

    Adult zebrafish have an amazing capacity to regenerate their central nervous system after injury. To investigate the cellular response and the molecular mechanisms involved in zebrafish adult central nervous system (CNS) regeneration and repair, we developed a zebrafish model of adult telencephalic injury. In this approach, we manually generate an injury by pushing an insulin syringe needle into the zebrafish adult telencephalon. At different post injury days, fish are sacrificed, their brains are dissected out and stained by immunohistochemistry and/or in situ hybridization (ISH) with appropriate markers to observe cell proliferation, gliogenesis, and neurogenesis. The contralateral unlesioned hemisphere serves as an internal control. This method combined for example with RNA deep sequencing can help to screen for new genes with a role in zebrafish adult telencephalon neurogenesis, regeneration, and repair. PMID:25146302

  8. Neuroprotective Pathways: Lifestyle activity, brain pathology and cognition in cognitively normal older adults

    PubMed Central

    Wirth, Miranka; Haase, Claudia M.; Villeneuve, Sylvia; Vogel, Jacob; Jagust, William J.

    2014-01-01

    This study used path analysis to examine effects of cognitive activity and physical activity on cognitive functioning in older adults, through pathways involving beta-amyloid (Aβ) burden, cerebrovascular lesions, and neural injury within brain regions affected in Alzheimer’s disease (AD). Ninety-two cognitively normal older adults (75.2±5.6 years) reported lifetime cognitive activity and current physical activity using validated questionnaires. For each participant, we evaluated cortical Aβ burden (using PIB-PET), cerebrovascular lesions (using MRI-defined white matter lesion (WML)), and neural integrity within AD regions (using a multimodal biomarker). Path models (adjusted for age, gender, and education) indicated that higher lifetime cognitive activity and higher current physical activity was associated with fewer WMLs. Lower WML volumes were in turn related to higher neural integrity and higher global cognitive functioning. As shown previously, higher lifetime cognitive activity was associated with lower PIB retention, which itself moderated the impact of neural integrity on cognitive functioning. Lifestyle activity may thus promote cognitive health in aging by protecting against cerebrovascular pathology and Aβ pathology thought to be relevant to AD development. PMID:24656834

  9. 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

  10. Adaptive Modulation of Adult Brain Gray and White Matter to High Altitude: Structural MRI Studies

    PubMed Central

    Zhang, Jiaxing; Zhang, Haiyan; Li, Jinqiang; Chen, Ji; Han, Qiaoqing; Lin, Jianzhong; Yang, Tianhe; Fan, Ming

    2013-01-01

    The aim of this study was to investigate brain structural alterations in adult immigrants who adapted to high altitude (HA). Voxel-based morphometry analysis of gray matter (GM) volumes, surface-based analysis of cortical thickness, and Tract-Based Spatial Statistics analysis of white matter fractional anisotropy (FA) based on MRI images were conducted on 16 adults (20–22 years) who immigrated to the Qinghai-Tibet Plateau (2300–4400 m) for 2 years. They had no chronic mountain sickness. Control group consisted of 16 matched sea level subjects. A battery of neuropsychological tests was also conducted. HA immigrants showed significantly decreased GM volumes in the right postcentral gyrus and right superior frontal gyrus, and increased GM volumes in the right middle frontal gyrus, right parahippocampal gyrus, right inferior and middle temporal gyri, bilateral inferior ventral pons, and right cerebellum crus1. While there was some divergence in the left hemisphere, surface-based patterns of GM changes in the right hemisphere resembled those seen for VBM analysis. FA changes were observed in multiple WM tracts. HA immigrants showed significant impairment in pulmonary function, increase in reaction time, and deficit in mental rotation. Parahippocampal and middle frontal GM volumes correlated with vital capacity. Superior frontal GM volume correlated with mental rotation and postcentral GM correlated with reaction time. Paracentral lobule and frontal FA correlated with mental rotation reaction time. There might be structural modifications occurred in the adult immigrants during adaptation to HA. The changes in GM may be related to impaired respiratory function and psychological deficits. PMID:23874692

  11. Long-term treatment with responsive brain stimulation in adults with refractory partial seizures

    PubMed Central

    Bergey, Gregory K.; Mizrahi, Eli M.; Goldman, Alica; King-Stephens, David; Nair, Dileep; Srinivasan, Shraddha; Jobst, Barbara; Gross, Robert E.; Shields, Donald C.; Barkley, Gregory; Salanova, Vicenta; Olejniczak, Piotr; Cole, Andrew; Cash, Sydney S.; Noe, Katherine; Wharen, Robert; Worrell, Gregory; Murro, Anthony M.; Edwards, Jonathan; Duchowny, Michael; Spencer, David; Smith, Michael; Geller, Eric; Gwinn, Ryder; Skidmore, Christopher; Eisenschenk, Stephan; Berg, Michel; Heck, Christianne; Van Ness, Paul; Fountain, Nathan; Rutecki, Paul; Massey, Andrew; O'Donovan, Cormac; Labar, Douglas; Duckrow, Robert B.; Hirsch, Lawrence J.; Courtney, Tracy; Sun, Felice T.; Seale, Cairn G.

    2015-01-01

    Objective: The long-term efficacy and safety of responsive direct neurostimulation was assessed in adults with medically refractory partial onset seizures. Methods: All participants were treated with a cranially implanted responsive neurostimulator that delivers stimulation to 1 or 2 seizure foci via chronically implanted electrodes when specific electrocorticographic patterns are detected (RNS System). Participants had completed a 2-year primarily open-label safety study (n = 65) or a 2-year randomized blinded controlled safety and efficacy study (n = 191); 230 participants transitioned into an ongoing 7-year study to assess safety and efficacy. Results: The average participant was 34 (±11.4) years old with epilepsy for 19.6 (±11.4) years. The median preimplant frequency of disabling partial or generalized tonic-clonic seizures was 10.2 seizures a month. The median percent seizure reduction in the randomized blinded controlled trial was 44% at 1 year and 53% at 2 years (p < 0.0001, generalized estimating equation) and ranged from 48% to 66% over postimplant years 3 through 6 in the long-term study. Improvements in quality of life were maintained (p < 0.05). The most common serious device-related adverse events over the mean 5.4 years of follow-up were implant site infection (9.0%) involving soft tissue and neurostimulator explantation (4.7%). Conclusions: The RNS System is the first direct brain responsive neurostimulator. Acute and sustained efficacy and safety were demonstrated in adults with medically refractory partial onset seizures arising from 1 or 2 foci over a mean follow-up of 5.4 years. This experience supports the RNS System as a treatment option for refractory partial seizures. Classification of evidence: This study provides Class IV evidence that for adults with medically refractory partial onset seizures, responsive direct cortical stimulation reduces seizures and improves quality of life over a mean follow-up of 5.4 years. PMID:25616485

  12. Atypical brain activation patterns during a face-to-face joint attention game in adults with autism spectrum disorder.

    PubMed

    Redcay, Elizabeth; Dodell-Feder, David; Mavros, Penelope L; Kleiner, Mario; Pearrow, Mark J; Triantafyllou, Christina; Gabrieli, John D; Saxe, Rebecca

    2013-10-01

    Joint attention behaviors include initiating one's own and responding to another's bid for joint attention to an object, person, or topic. Joint attention abilities in autism are pervasively atypical, correlate with development of language and social abilities, and discriminate children with autism from other developmental disorders. Despite the importance of these behaviors, the neural correlates of joint attention in individuals with autism remain unclear. This paucity of data is likely due to the inherent challenge of acquiring data during a real-time social interaction. We used a novel experimental set-up in which participants engaged with an experimenter in an interactive face-to-face joint attention game during fMRI data acquisition. Both initiating and responding to joint attention behaviors were examined as well as a solo attention (SA) control condition. Participants included adults with autism spectrum disorder (ASD) (n = 13), a mean age- and sex-matched neurotypical group (n = 14), and a separate group of neurotypical adults (n = 22). Significant differences were found between groups within social-cognitive brain regions, including dorsal medial prefrontal cortex (dMPFC) and right posterior superior temporal sulcus (pSTS), during the RJA as compared to SA conditions. Region-of-interest analyses revealed a lack of signal differentiation between joint attention and control conditions within left pSTS and dMPFC in individuals with ASD. Within the pSTS, this lack of differentiation was characterized by reduced activation during joint attention and relative hyper-activation during SA. These findings suggest a possible failure of developmental neural specialization within the STS and dMPFC to joint attention in ASD. PMID:22505330

  13. Pharmacological reduction of adult hippocampal neurogenesis modifies functional brain circuits in mice exposed to a cocaine conditioned place preference paradigm.

    PubMed

    Castilla-Ortega, Estela; Blanco, Eduardo; Serrano, Antonia; Ladrón de Guevara-Miranda, David; Pedraz, María; Estivill-Torrús, Guillermo; Pavón, Francisco Javier; Rodríguez de Fonseca, Fernando; Santín, Luis J

    2016-05-01

    We investigated the role of adult hippocampal neurogenesis in cocaine-induced conditioned place preference (CPP) behaviour and the functional brain circuitry involved. Adult hippocampal neurogenesis was pharmacologically reduced with temozolomide (TMZ), and mice were tested for cocaine-induced CPP to study c-Fos expression in the hippocampus and in extrahippocampal addiction-related areas. Correlational and multivariate analysis revealed that, under normal conditions, the hippocampus showed widespread functional connectivity with other brain areas and strongly contributed to the functional brain module associated with CPP expression. However, the neurogenesis-reduced mice showed normal CPP acquisition but engaged an alternate brain circuit where the functional connectivity of the dentate gyrus was notably reduced and other areas (the medial prefrontal cortex, accumbens and paraventricular hypothalamic nucleus) were recruited instead of the hippocampus. A second experiment unveiled that mice acquiring the cocaine-induced CPP under neurogenesis-reduced conditions were delayed in extinguishing their drug-seeking behaviour. But if the inhibited neurons were generated after CPP acquisition, extinction was not affected but an enhanced long-term CPP retention was found, suggesting that some roles of the adult-born neurons may differ depending on whether they are generated before or after drug-contextual associations are established. Importantly, cocaine-induced reinstatement of CPP behaviour was increased in the TMZ mice, regardless of the time of neurogenesis inhibition. The results show that adult hippocampal neurogenesis sculpts the addiction-related functional brain circuits, and reduction of the adult-born hippocampal neurons increases cocaine seeking in the CPP model. PMID:25870909

  14. Alternate day fasting impacts the brain insulin-signaling pathway of young adult male C57BL/6 mice.

    PubMed

    Lu, Jianghua; E, Lezi; Wang, Wenfang; Frontera, Jennifer; Zhu, Hao; Wang, Wen-Tung; Lee, Phil; Choi, In Young; Brooks, William M; Burns, Jeffrey M; Aires, Daniel; Swerdlow, Russell H

    2011-04-01

    Dietary restriction (DR) has recognized health benefits that may extend to brain. We examined how DR affects bioenergetics-relevant enzymes and signaling pathways in the brains of C57BL/6 mice. Five-month-old male mice were placed in ad libitum or one of two repeated fasting and refeeding (RFR) groups, an alternate day (intermittent fed; IF) or alternate day plus antioxidants (blueberry, pomegranate, and green tea extracts) (IF + AO) fed group. During the 24-h fast blood glucose levels initially fell but stabilized within 6 h of starting the fast, thus avoiding frank hypoglycemia. DR in general appeared to enhance insulin sensitivity. After six weeks brain AKT and glycogen synthase kinase 3 beta phosphorylation were lower in the RFR mice, suggesting RFR reduced brain insulin-signaling pathway activity. Pathways that mediate mitochondrial biogenesis were not activated; AMP kinase phosphorylation, silent information regulator 2 phosphorylation, peroxisomal proliferator-activated receptor-gamma coactivator 1 alpha levels, and cytochrome oxidase subunit 4 levels did not change. ATP levels also did not decline, which suggests the RFR protocols did not directly impact brain bioenergetics. Antioxidant supplementation did not affect the brain parameters we evaluated. Our data indicate in young adult male C57BL/6 mice, RFR primarily affects brain energy metabolism by reducing brain insulin signaling, which potentially results indirectly as a consequence of reduced peripheral insulin production. PMID:21244426

  15. Alternate Day Fasting Impacts the Brain Insulin Signaling Pathway of Young Adult Male C57BL/6 Mice

    PubMed Central

    Lu, Jianghua; Lezi, E; Wang, WenFang; Frontera, Jennifer; Zhu, Hao; Wang, Wen-Tung; Lee, Sang-Pil; Choi, In Young; Brooks, William M.; Burns, Jeffrey M.; Aires, Daniel; Swerdlow, Russell H.

    2011-01-01

    Dietary restriction (DR) has recognized health benefits that may extend to brain. We examined how DR affects bioenergetics-relevant enzymes and signaling pathways in the brains of C57BL/6 mice. Five month-old male mice were placed in ad libitum (AL) or one of two repeated fasting and refeeding (RFR) groups, an alternate day (intermittent fed; IF) or alternate day plus antioxidants (blueberry, pomegranate, and green tea extracts) (IF+AO) fed group. During the 24 hour fast blood glucose levels initially fell but stabilized within 6 hours of starting the fast, thus avoiding frank hypoglycemia. DR in general appeared to enhance insulin sensitivity. After six weeks brain AKT and GSK3β phosphorylation were lower in the RFR mice, suggesting RFR reduced brain insulin signaling pathway activity. Pathways that mediate mitochondrial biogenesis were not activated; AMPK phosphorylation, SIRT1 phosphorylation, PGC1a levels, and COX4 levels did not change. ATP levels also did not decline, which suggests the RFR protocols did not directly impact brain bioenergetics. Antioxidant supplementation did not affect the brain parameters we evaluated. Our data indicate in young adult male C57BL/6 mice, RFR primarily affects brain energy metabolism by reducing brain insulin signaling, which potentially results indirectly as a consequence of reduced peripheral insulin production. PMID:21244426

  16. Transient postnatal fluoxetine leads to decreased brain arachidonic acid metabolism and cytochrome P450 4A in adult mice

    PubMed Central

    Ramadan, Epolia; Blanchard, Helene; Cheon, Yewon; Fox, Meredith A.; Chang, Lisa; Chen, Mei; Ma, Kaizong; Rapoport, Stanley I.; Basselin, Mireille

    2014-01-01

    Fetal and perinatal exposure to selective serotonin (5-HT) reuptake inhibitors (SSRIs) has been reported to alter childhood behavior, while transient early exposure in rodents is reported to alter their behavior and decrease brain extracellular 5-HT in adulthood. Since 5-HT2A/2C receptor-mediated neurotransmission can involve G-protein coupled activation of cytosolic phospholipase A2 (cPLA2), releasing arachidonic acid (ARA) from synaptic membrane phospholipid, we hypothesized that transient postnatal exposure to fluoxetine would decrease brain ARA metabolism in adult mice. Brain ARA incorporation coefficients k* and rates Jin were quantitatively imaged following intravenous [1-14C]ARA infusion of unanesthetized adult mice that had been injected daily with fluoxetine (10 mg/kg i.p.) or saline during postnatal days P4–P21. Expression of brain ARA metabolic enzymes and other relevant markers also was measured. On neuroimaging, k* and Jin was decreased widely in early fluoxetine- compared to saline-treated adult mice. Of the enzymes measured, cPLA2 activity was unchanged, while Ca2+-independent iPLA2 activity was increased. There was a significant 74% reduced protein level of cytochrome P450 (CYP) 4A, which can convert ARA to 20-HETE. Reduced brain ARA metabolism in adult mice transiently exposed to postnatal fluoxetine, and a 74% reduction in CYP4A protein, suggest long-term effects independent of drug presence in brain ARA metabolism, and in CYP4A metabolites. Comparable changes in humans might contribute to reported altered behavior following early SSRI. PMID:24529827

  17. Long-term tracing of the BrdU label-retaining cells in adult rat brain.

    PubMed

    Zhang, Lei; Li, Haihong; Zeng, Shaopeng; Chen, Lu; Fang, Zeman; Huang, Qingjun

    2015-03-30

    Stem cells have been shown to be label-retaining, slow-cycling cells. In the adult mammalian central nervous system, the distribution of the stem cells is inconsistent among previous studies. The purpose of the present study was to determine the distribution of BrdU-LRCs and the cell types of the BrdU-LRCs in rat brain. To label BrdU-LRCs in rat brain, six newborn rats were administered intraperitoneal injections of BrdU 50mg/kg/time twice a day at 2h intervals, over four consecutive days. The BrdU-LRCs were detected by immunohistochemistry, the cell types were examined by double immunofluorescence staining for BrdU/GFAP and BrdU/MAP2, and the percentage of BrdU-LRCs was calculated following a chase period of 24 weeks post-injection. We observed that BrdU-LRCs distributed extensively in rat brain. In the LV, DG, striatum, cerebellum and neocortex, the percentage of BrdU-LRCs was 11.3 ± 2.5%, 10.9 ± 1.3%, 6.4 ± 1.2%, 5.6 ± 0.8%, and 4.9 ± 0.6%, respectively. The highest density of BrdU-LRCs was in LV and DG, the known stem cell sites in adult mammalian brain. Both BrdU/GFAP and BrdU/MAP2 double-staining cells could be detected in the above five brain subregions. Ongoing cell production was widespread in the adult mammalian brain, which would allow us to reevaluate the capacity and potentiality of the brain in homeostasis, wound repair, and regeneration. PMID:25681624

  18. 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

  19. 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. PMID:24960530

  20. Adult human dental pulp stem cells promote blood-brain barrier permeability through vascular endothelial growth factor-a expression.

    PubMed

    Winderlich, Joshua N; Kremer, Karlea L; Koblar, Simon A

    2016-06-01

    Stem cell therapy is a promising new treatment option for stroke. Intravascular administration of stem cells is a valid approach as stem cells have been shown to transmigrate the blood-brain barrier. The mechanism that causes this effect has not yet been elucidated. We hypothesized that stem cells would mediate localized discontinuities in the blood-brain barrier, which would allow passage into the brain parenchyma. Here, we demonstrate that adult human dental pulp stem cells express a soluble factor that increases permeability across an in vitro model of the blood-brain barrier. This effect was shown to be the result of vascular endothelial growth factor-a. The effect could be amplified by exposing dental pulp stem cell to stromal-derived factor 1, which stimulates vascular endothelial growth factor-a expression. These findings support the use of dental pulp stem cell in therapy for stroke. PMID:26661186

  1. New neurons in the adult brain: The role of sleep and consequences of sleep loss

    PubMed Central

    Meerlo, Peter; Mistlberger, Ralph E.; Jacobs, Barry L.; Heller, H. Craig; McGinty, Dennis

    2009-01-01

    Research over the last few decades has firmly established that new neurons are generated in selected areas of the adult mammalian brain, particularly the dentate gyrus of the hippocampal formation and the subventricular zone of the lateral ventricles. The function of adult-born neurons is still a matter of debate. In the case of the hippocampus, integration of new cells in to the existing neuronal circuitry may be involved in memory processes and the regulation of emotionality. In recent years, various studies have examined how the production of new cells and their development into neurons is affected by sleep and sleep loss. While disruption of sleep for a period shorter than one day appears to have little effect on the basal rate of cell proliferation, prolonged restriction or disruption of sleep may have cumulative effects leading to a major decrease in hippocampal cell proliferation, cell survival and neurogenesis. Importantly, while short sleep deprivation may not affect the basal rate of cell proliferation, one study in rats shows that even mild sleep restriction may interfere with the increase in neurogenesis that normally occurs with hippocampus-dependent learning. Since sleep deprivation also disturbs memory formation, these data suggest that promoting survival, maturation and integration of new cells may be an unexplored mechanism by which sleep supports learning and memory processes. Most methods of sleep deprivation that have been employed affect both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Available data favor the hypothesis that decreases in cell proliferation are related to a reduction in REM sleep, whereas decreases in the number of cells that subsequently develop into adult neurons may be related to reductions in both NREM and REM sleep. The mechanisms by which sleep loss affects different aspects of adult neurogenesis are unknown. It has been proposed that adverse effects of sleep disruption may be mediated by stress and

  2. Chelonitoxism in Andaman and Nicobar Island: A report on mass poisoning including a death of an adult.

    PubMed

    Singh, S S; Biswas, Ashok Kumar; Shirley, P; Vijayachari, Paluru

    2016-08-01

    Chelonitoxism is a type of seafood poisoning which usually occurs due to consumption of certain marine turtle flesh. As the pharmacology or chemistry of the toxin is still unknown, antidote or treatment to chelonitoxism is unavailable. The symptoms can vary from common gastro-intestinal symptoms to neurological manifestations and even death. This case report of community poisoning following consumption of turtle meat includes the death of an adult male (56 yrs.) being reported for the first time in the Great Nicobar Island, Andaman and Nicobar (A&N) Islands, India in August 2012. The patient encountered common gastrointestinal symptoms after one day of ingestion of green turtle flesh and later, he developed neurological symptoms and did not respond to symptomatic treatment and expired after four days after the consumption. However, out of 30 villagers who took the same food, six others developed symptoms and recovered within a period of 3-7 days while two pets (a dog and a cat) died within 24 hours as they were fed with the same food. In spite of several existing wildlife protection acts, catching a turtle and making them a source of food-celebration is quite common in coastal areas of the Indian Ocean and the Bay of Bengal which includes A&N Islands. A proper monitoring and follow-up of the food-borne diseases along with a wide range of explorative health education protocol should be implemented especially for the people who are not reachable via media to avoid such incidents in future. PMID:27103071

  3. 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.

  4. Migration of bone marrow progenitor cells in the adult brain of rats and rabbits.

    PubMed

    Dennie, Donnahue; Louboutin, Jean-Pierre; Strayer, David S

    2016-04-26

    Neurogenesis takes place in the adult mammalian brain in three areas: Subgranular zone of the dentate gyrus (DG); subventricular zone of the lateral ventricle; olfactory bulb. Different molecular markers can be used to characterize the cells involved in adult neurogenesis. It has been recently suggested that a population of bone marrow (BM) progenitor cells may migrate to the brain and differentiate into neuronal lineage. To explore this hypothesis, we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced cells. Long-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells, then after several months in mature neurons and microglial cells, and thus without central nervous system (CNS) lesion. Most of transgene-expressing cells expressed NeuN, a marker of mature neurons. Thus, BM-derived cells may function as progenitors of CNS cells in adult animals. The mechanism by which the cells from the BM come to be neurons remains to be determined. Although the observed gradual increase in transgene-expressing neurons over 16 mo suggests that the pathway involved differentiation of BM-resident cells into neurons, cell fusion as the principal route cannot be totally ruled out. Additional studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature neurons. Transgene-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the vector. In addition to cells expressing markers of mature neurons, transgene-positive cells were also positive for nestin and doublecortin, molecules expressed by developing neuronal cells. These cells were actively proliferating, as shown by short term BrdU incorporation studies. Inducing seizures by using kainic acid increased the number of BM progenitor cells

  5. Migration of bone marrow progenitor cells in the adult brain of rats and rabbits

    PubMed Central

    Dennie, Donnahue; Louboutin, Jean-Pierre; Strayer, David S

    2016-01-01

    Neurogenesis takes place in the adult mammalian brain in three areas: Subgranular zone of the dentate gyrus (DG); subventricular zone of the lateral ventricle; olfactory bulb. Different molecular markers can be used to characterize the cells involved in adult neurogenesis. It has been recently suggested that a population of bone marrow (BM) progenitor cells may migrate to the brain and differentiate into neuronal lineage. To explore this hypothesis, we injected recombinant SV40-derived vectors into the BM and followed the potential migration of the transduced cells. Long-term BM-directed gene transfer using recombinant SV40-derived vectors leads to expression of the genes delivered to the BM firstly in circulating cells, then after several months in mature neurons and microglial cells, and thus without central nervous system (CNS) lesion. Most of transgene-expressing cells expressed NeuN, a marker of mature neurons. Thus, BM-derived cells may function as progenitors of CNS cells in adult animals. The mechanism by which the cells from the BM come to be neurons remains to be determined. Although the observed gradual increase in transgene-expressing neurons over 16 mo suggests that the pathway involved differentiation of BM-resident cells into neurons, cell fusion as the principal route cannot be totally ruled out. Additional studies using similar viral vectors showed that BM-derived progenitor cells migrating in the CNS express markers of neuronal precursors or immature neurons. Transgene-positive cells were found in the subgranular zone of the DG of the hippocampus 16 mo after intramarrow injection of the vector. In addition to cells expressing markers of mature neurons, transgene-positive cells were also positive for nestin and doublecortin, molecules expressed by developing neuronal cells. These cells were actively proliferating, as shown by short term BrdU incorporation studies. Inducing seizures by using kainic acid increased the number of BM progenitor cells

  6. Dido mutations trigger perinatal death and generate brain abnormalities and behavioral alterations in surviving adult mice.

    PubMed

    Villares, Ricardo; Gutiérrez, Julio; Fütterer, Agnes; Trachana, Varvara; Gutiérrez del Burgo, Fernando; Martínez-A, Carlos

    2015-04-14

    Nearly all vertebrate cells have a single cilium protruding from their surface. This threadlike organelle, once considered vestigial, is now seen as a pivotal element for detection of extracellular signals that trigger crucial morphogenetic pathways. We recently proposed a role for Dido3, the main product of the death inducer-obliterator (dido) gene, in histone deacetylase 6 delivery to the primary cilium [Sánchez de Diego A, et al. (2014) Nat Commun 5:3500]. Here we used mice that express truncated forms of Dido proteins to determine the link with cilium-associated disorders. We describe dido mutant mice with high incidence of perinatal lethality and distinct neurodevelopmental, morphogenetic, and metabolic alterations. The anatomical abnormalities were related to brain and orofacial development, consistent with the known roles of primary cilia in brain patterning, hydrocephalus incidence, and cleft palate. Mutant mice that reached adulthood showed reduced life expectancy, brain malformations including hippocampus hypoplasia and agenesis of corpus callosum, as well as neuromuscular and behavioral alterations. These mice can be considered a model for the study of ciliopathies and provide information for assessing diagnosis and therapy of genetic disorders linked to the deregulation of primary cilia. PMID:25825751

  7. Cocaine-induced expression changes of axon guidance molecules in the adult rat brain.

    PubMed

    Bahi, Amine; Dreyer, Jean-Luc

    2005-02-01

    Administration of drugs of abuse induces strong molecular adaptations and plasticity within the mesolimbic dopamine (DA) system, a pathway essential for reward-seeking behavior. Little is known about the specific targets involved in this neuroadaptation process, but there are indications that cocaine and other drugs of abuse share the ability to alter the morphology of neuronal dendrites and spines, the primary site of excitatory synapses in the brain. Axon guidance molecules, the very molecular cues that regulate the formation of axon-target connections during development, may mediate these alterations. To test this hypothesis, we investigated mRNA expression changes of 39 axon guidance molecules, including 17 Semaphorins, 12 Ephs, 8 Ephrins, and 2 neuropilins in the mesolimbic dopamine system of cocaine-treated animals under different paradigms by mean of DNA-Microarray and quantitative real-time PCR. In all cases, strong changes in gene expression are observed, yielding to up or downregulation of these axon guidance molecules. Our data suggest that cocaine treatment induces activation of a complex program of synaptic rearrangements, which may partly recapitulate the plastic changes occurring during development, and may underlie the important neuroplastic adaptations that occur in the reward- and memory-related brain centers following drug action. We conclude that in some brain regions, exposure to psychomotor-stimulant drugs produce expression changes in axon guidance molecules, which may contribute to cognitive deficits associated with drug abuse. PMID:15691709

  8. Dido mutations trigger perinatal death and generate brain abnormalities and behavioral alterations in surviving adult mice

    PubMed Central

    Villares, Ricardo; Gutiérrez, Julio; Fütterer, Agnes; Trachana, Varvara; Gutiérrez del Burgo, Fernando; Martínez-A, Carlos

    2015-01-01

    Nearly all vertebrate cells have a single cilium protruding from their surface. This threadlike organelle, once considered vestigial, is now seen as a pivotal element for detection of extracellular signals that trigger crucial morphogenetic pathways. We recently proposed a role for Dido3, the main product of the death inducer-obliterator (dido) gene, in histone deacetylase 6 delivery to the primary cilium [Sánchez de Diego A, et al. (2014) Nat Commun 5:3500]. Here we used mice that express truncated forms of Dido proteins to determine the link with cilium-associated disorders. We describe dido mutant mice with high incidence of perinatal lethality and distinct neurodevelopmental, morphogenetic, and metabolic alterations. The anatomical abnormalities were related to brain and orofacial development, consistent with the known roles of primary cilia in brain patterning, hydrocephalus incidence, and cleft palate. Mutant mice that reached adulthood showed reduced life expectancy, brain malformations including hippocampus hypoplasia and agenesis of corpus callosum, as well as neuromuscular and behavioral alterations. These mice can be considered a model for the study of ciliopathies and provide information for assessing diagnosis and therapy of genetic disorders linked to the deregulation of primary cilia. PMID:25825751

  9. Optimal level activity of matrix metalloproteinases is critical for adult visual plasticity in the healthy and stroke-affected brain.

    PubMed

    Pielecka-Fortuna, Justyna; Kalogeraki, Evgenia; Fortuna, Michal G; Löwel, Siegrid

    2016-01-01

    The ability of the adult brain to undergo plastic changes is of particular interest in medicine, especially regarding recovery from injuries or improving learning and cognition. Matrix metalloproteinases (MMPs) have been associated with juvenile experience-dependent primary visual cortex (V1) plasticity, yet little is known about their role in this process in the adult V1. Activation of MMPs is a crucial step facilitating structural changes in a healthy brain; however, upon brain injury, upregulated MMPs promote the spread of a lesion and impair recovery. To clarify these seemingly opposing outcomes of MMP-activation, we examined the effects of MMP-inhibition on experience-induced plasticity in healthy and stoke-affected adult mice. In healthy animals, 7-day application of MMP-inhibitor prevented visual plasticity. Additionally, treatment with MMP-inhibitor once but not twice following stroke rescued plasticity, normally lost under these conditions. Our data imply that an optimal level of MMP-activity is crucial for adult visual plasticity to occur. PMID:26609811

  10. Optimal level activity of matrix metalloproteinases is critical for adult visual plasticity in the healthy and stroke-affected brain

    PubMed Central

    Pielecka-Fortuna, Justyna; Kalogeraki, Evgenia; Fortuna, Michal G; Löwel, Siegrid

    2015-01-01

    The ability of the adult brain to undergo plastic changes is of particular interest in medicine, especially regarding recovery from injuries or improving learning and cognition. Matrix metalloproteinases (MMPs) have been associated with juvenile experience-dependent primary visual cortex (V1) plasticity, yet little is known about their role in this process in the adult V1. Activation of MMPs is a crucial step facilitating structural changes in a healthy brain; however, upon brain injury, upregulated MMPs promote the spread of a lesion and impair recovery. To clarify these seemingly opposing outcomes of MMP-activation, we examined the effects of MMP-inhibition on experience-induced plasticity in healthy and stoke-affected adult mice. In healthy animals, 7-day application of MMP-inhibitor prevented visual plasticity. Additionally, treatment with MMP-inhibitor once but not twice following stroke rescued plasticity, normally lost under these conditions. Our data imply that an optimal level of MMP-activity is crucial for adult visual plasticity to occur. DOI: http://dx.doi.org/10.7554/eLife.11290.001 PMID:26609811

  11. (±)3,4-Methylenedioxymethamphetamine (“Ecstasy”) Treatment Modulates Expression of Neurotrophins and Their Receptors in Multiple Regions of Adult Rat Brain

    PubMed Central

    Hemmerle, Ann M.; Dickerson, Jonathan W.; Herring, Nicole R.; Schaefer, Tori L.; Vorhees, Charles V.; Williams, Michael T.; Seroogy, Kim B.

    2014-01-01

    (±)3,4-Methylenedioxymethamphetamine (MDMA), a widely used drug of abuse, rapidly reduces serotonin levels in the brain when ingested or administered in sufficient quantities, resulting in deficits in complex route-based learning, spatial learning, and reference memory. Neurotrophins are important for survival and preservation of neurons in the adult brain, including serotonergic neurons. In this study, we examined the effects of MDMA on the expression of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) and their respective high-affinity receptors, tropomyosin receptor kinase (trk)B and trkC, in multiple regions of the rat brain. A serotonergic-depleting dose of MDMA (10 mg/kg × 4 at 2-hour intervals on a single day) was administered to adult Sprague-Dawley rats, and brains were examined 1, 7, or 24 hours after the last dose. Messenger RNA levels of BDNF, NT-3, trkB, and trkC were analyzed by using in situ hybridization with cRNA probes. The prefrontal cortex was particularly vulnerable to MDMA-induced alterations in that BDNF, NT-3, trkB, and trkC mRNAs were all upregulated at multiple time points. MDMA-treated animals had increased BDNF expression in the frontal, parietal, piriform, and entorhinal cortices, increased NT-3 expression in the anterior cingulate cortex, and elevated trkC in the entorhinal cortex. In the nigrostriatal system, BDNF expression was upregulated in the substantia nigra pars compacta, and trkB was elevated in the striatum in MDMA-treated animals. Both neurotrophins and trkB were differentially regulated in several regions of the hippocampal formation. These findings suggest a possible role for neurotrophin signaling in the learning and memory deficits seen following MDMA treatment. PMID:22237931

  12. Blockage of VIP during mouse embryogenesis modifies adult behavior and results in permanent changes in brain chemistry.

    PubMed

    Hill, Joanna M; Hauser, Janet M; Sheppard, Lia M; Abebe, Daniel; Spivak-Pohis, Irit; Kushnir, Michal; Deitch, Iris; Gozes, Illana

    2007-01-01

    Vasoactive intestinal peptide (VIP) regulates growth and development during the early postimplantation period of mouse embryogenesis. Blockage of VIP with a VIP antagonist during this period results in growth restriction, microcephaly, and developmental delays. Similar treatment of neonatal rodents also causes developmental delays and impaired diurnal rhythms, and the adult brains of these animals exhibit neuronal dystrophy and increased VIP binding. These data suggest that blockage of VIP during the development of the nervous system can result in permanent changes to the brain. In the current study, pregnant mice were treated with a VIP antagonist during embryonic days 8 through 10. The adult male offspring were examined in tests of novelty, paired activity, and social recognition. Brain tissue was examined for several measures of chemistry and gene expression of VIP and related compounds. Glial cells from the cortex of treated newborn mice were plated with neurons and examined for VIP binding and their ability to enhance neuronal survival. Treated adult male mice exhibited increased anxiety-like behavior and deficits in social behavior. Brain tissue exhibited regionally specific changes in VIP chemistry and a trend toward increased gene expression of VIP and related compounds that reached statistical significance in the VIP receptor, VPAC-1, in the female cortex. When compared to control astrocytes, astrocytes from treated cerebral cortex produced further increases in neuronal survival with excess synaptic connections and reduced VIP binding. In conclusion, impaired VIP activity during mouse embryogenesis resulted in permanent changes to both adult brain chemistry/cell biology and behavior with aspects of autism-like social deficits. PMID:17726225

  13. Activation and maintenance of peripheral semantic features of unambiguous words after right hemisphere brain damage in adults

    PubMed Central

    Tompkins, Connie A.; Fassbinder, Wiltrud; Scharp, Victoria L.; Meigh, Kimberly M.

    2009-01-01

    Background The right cerebral hemisphere (RH) sustains activation of subordinate, secondary, less common, and/or distantly related meanings of words. Much of the pertinent data come from studies of homonyms, but some evidence also suggests that the RH has a unique maintenance function in relation to unambiguous nouns. In a divided visual field priming study, Atchley, Burgess, and Keeney (1999) reported that only left visual field/RH presentation yielded evidence of continuing activation of peripheral semantic features that were incompatible with the most common image or representation of their corresponding nouns (e.g., rotten for “apple”). Activation for weakly related features that were compatible with the dominant representation (e.g., crunchy) was sustained over time regardless of the visual field/hemisphere of initial stimulus input. Several studies report that unilateral right hemisphere brain damage (RHD) in adults affects the RH’s meaning maintenance function, but this work also has centred on homonyms, and/or more recently metonymic and metaphoric polysemous words. Aims The current investigation examined whether RHD deficits in processing secondary and/or distantly related meanings of words, typically observed in studies of homonyms, would extend to peripheral, weakly related semantic features of unambiguous nouns. Methods & Procedures Participants were 28 adults with unilateral RHD from cerebrovascular accident, and 38 adults without brain damage. Participants listened to spoken sentences that ended with an unambiguous noun. Each sentence was followed by a spoken target phoneme string. Targets included peripheral semantic features of the sentence-final noun that were either compatible or incompatible with the dominant mental images of the noun, and were presented at two intervals after that noun. A lexical decision task was used to gauge both the early activation and maintenance of activation for these weakly related semantic features. Outcomes

  14. 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

  15. Acute and crucial requirement for MeCP2 function upon transition from early to late adult stages of brain maturation.

    PubMed

    Du, Fang; Nguyen, Minh Vu Chuong; Karten, Ariel; Felice, Christy A; Mandel, Gail; Ballas, Nurit

    2016-05-01

    Germline mutations in the X-linked gene, methyl-CpG-binding protein 2 (MECP2), underlie most cases of Rett syndrome (RTT), an autism spectrum disorder affecting approximately one in 10 000 female live births. The disease is characterized in affected girls by a latent appearance of symptoms between 12 and 18 months of age while boys usually die before the age of two. The nature of the latency is not known, but RTT-like phenotypes are recapitulated in mouse models, even when MeCP2 is removed at different postnatal stages, including juvenile and adolescent stages. Unexpectedly, here, we show that within a very brief developmental window, between 10 (adolescent) and 15 (adult) weeks after birth, symptom initiation and progression upon removal of MeCP2 in male mice transitions from 3 to 4 months to only several days, followed by lethality. We further show that this accelerated development of RTT phenotype and lethality occur at the transition to adult stage (15 weeks of age) and persists thereafter. Importantly, within this abbreviated time frame of days, the brain acquires dramatic anatomical, cellular and molecular abnormalities, typical of classical RTT. This study reveals a new postnatal developmental stage, which coincides with full-brain maturation, where the structure/function of the brain is extremely sensitive to levels of MeCP2 and loss of MeCP2 leads to precipitous collapse of the neuronal networks and incompatibility with life within days. PMID:26908602

  16. Augmenting NMDA receptor signaling boosts experience-dependent neuroplasticity in the adult human brain

    PubMed Central

    Forsyth, Jennifer K.; Bachman, Peter; Mathalon, Daniel H.; Roach, Brian J.; Asarnow, Robert F.

    2015-01-01

    Experience-dependent plasticity is a fundamental property of the brain. It is critical for everyday function, is impaired in a range of neurological and psychiatric disorders, and frequently depends on long-term potentiation (LTP). Preclinical studies suggest that augmenting N-methyl-d-aspartate receptor (NMDAR) signaling may promote experience-dependent plasticity; however, a lack of noninvasive methods has limited our ability to test this idea in humans until recently. We examined the effects of enhancing NMDAR signaling using d-cycloserine (DCS) on a recently developed LTP EEG paradigm that uses high-frequency visual stimulation (HFvS) to induce neural potentiation in visual cortex neurons, as well as on three cognitive tasks: a weather prediction task (WPT), an information integration task (IIT), and a n-back task. The WPT and IIT are learning tasks that require practice with feedback to reach optimal performance. The n-back assesses working memory. Healthy adults were randomized to receive DCS (100 mg; n = 32) or placebo (n = 33); groups were similar in IQ and demographic characteristics. Participants who received DCS showed enhanced potentiation of neural responses following repetitive HFvS, as well as enhanced performance on the WPT and IIT. Groups did not differ on the n-back. Augmenting NMDAR signaling using DCS therefore enhanced activity-dependent plasticity in human adults, as demonstrated by lasting enhancement of neural potentiation following repetitive HFvS and accelerated acquisition of two learning tasks. Results highlight the utility of considering cellular mechanisms underlying distinct cognitive functions when investigating potential cognitive enhancers. PMID:26621715

  17. Augmenting NMDA receptor signaling boosts experience-dependent neuroplasticity in the adult human brain.

    PubMed

    Forsyth, Jennifer K; Bachman, Peter; Mathalon, Daniel H; Roach, Brian J; Asarnow, Robert F

    2015-12-15

    Experience-dependent plasticity is a fundamental property of the brain. It is critical for everyday function, is impaired in a range of neurological and psychiatric disorders, and frequently depends on long-term potentiation (LTP). Preclinical studies suggest that augmenting N-methyl-d-aspartate receptor (NMDAR) signaling may promote experience-dependent plasticity; however, a lack of noninvasive methods has limited our ability to test this idea in humans until recently. We examined the effects of enhancing NMDAR signaling using d-cycloserine (DCS) on a recently developed LTP EEG paradigm that uses high-frequency visual stimulation (HFvS) to induce neural potentiation in visual cortex neurons, as well as on three cognitive tasks: a weather prediction task (WPT), an information integration task (IIT), and a n-back task. The WPT and IIT are learning tasks that require practice with feedback to reach optimal performance. The n-back assesses working memory. Healthy adults were randomized to receive DCS (100 mg; n = 32) or placebo (n = 33); groups were similar in IQ and demographic characteristics. Participants who received DCS showed enhanced potentiation of neural responses following repetitive HFvS, as well as enhanced performance on the WPT and IIT. Groups did not differ on the n-back. Augmenting NMDAR signaling using DCS therefore enhanced activity-dependent plasticity in human adults, as demonstrated by lasting enhancement of neural potentiation following repetitive HFvS and accelerated acquisition of two learning tasks. Results highlight the utility of considering cellular mechanisms underlying distinct cognitive functions when investigating potential cognitive enhancers. PMID:26621715

  18. The turnover of myelin phospholipids in the adult and developing rat brain

    PubMed Central

    Jungalwala, F. B.; Dawson, R. M. C.

    1971-01-01

    1. Inorganic [32P]phosphate, [U-14C]glycerol and [2-14C]ethanolamine were injected into the lateral ventricles in the brains of adult rats, and the labelling of individual phospholipids was followed over 2–4 months in both a microsomal and a highly purified myelin fraction. 2. All the phospholipids in myelin became appreciably labelled, although initially the specific radioactivities of the microsomal phospholipids were somewhat higher. Eventually the specific radioactivities in microsomal and myelin phospholipids fell rapidly at a rate corresponding to the decline of radioactivity in the acid-soluble pools. 3. Equivalent experiments carried out in developing rats with [32P]phosphate administered at the start of myelination showed some persistence of phospholipid labelling in the myelin, but this could partly be attributed to the greater retention of 32P in the acid-soluble phosphorus pool and recycling. 4. It is concluded that a substantial part of the phospholipid molecules in adult myelin membranes is readily exchangeable, although a small pool of slowly exchangeable material also exists. 5. A slow incorporation into or loss of labelled precursor from myelin phospholipids does not necessarily give a good indication of the rate of renewal of the molecules in the membrane. As presumably such labelled molecules originate by exchange with those in another membrane site (not necessarily where synthesis occurs) it is only possible to calculate the turnover rate in the myelin membrane if the behaviour of the specific radioactivity with time of the phospholipid molecules in the immediate precursor pool is known. PMID:5124379

  19. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    ClinicalTrials.gov

    2015-07-27

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Recurrent Adult Brain Tumor

  20. Posterior brain white matter abnormalities in older adults with probable mild cognitive impairment

    PubMed Central

    Cooley, Sarah A.; Cabeen, Ryan P.; Laidlaw, David H.; Conturo, Thomas E.; Lane, Elizabeth M.; Heaps, Jodi M.; Bolzenius, Jacob D.; Baker, Laurie M.; Salminen, Lauren E.; Scott, Staci E.; Paul, Robert H.

    2014-01-01

    Objective Much of the mild cognitive impairment (MCI) neuroimaging literature has exclusively focused on regions associated with Alzheimer’s disease. Little research has examined white matter abnormalities of other brain regions, including those associated with visual processing, despite evidence that other brain abnormalities appear in these regions in early disease stages. Method Diffusion tensor imaging (DTI) was utilized to examine participants (n = 44) that completed baseline imaging as part of a longitudinal healthy aging study. Participants were divided into two groups based on scores from the Montreal Cognitive Assessment (MoCA), a brief screening tool for MCI. Participants who scored < 26 were defined as “probable MCI” while those who scored ≥ 26 were labled cognitively healthy. Two DTI indices were analyzed including fractional anisotropy (FA) and mean diffusivity (MD). DTI values for white matter in the lingual gyrus, cuneus, pericalcarine, fusiform gyrus and all four lobes were compared using MANOVA. Regression analyses examined the relationship between DTI indices and total MoCA score. Results Results revealed significantly lower FA in the probable MCI group in the cuneus, fusiform, pericalcarine and occipital lobe, and significantly higher MD in the temporal lobe. Fusiform FA and temporal lobe MD were significantly related to total MoCA score after accounting for age and education. Conclusions Results indicate that there are posterior white matter microstructural changes in individuals with probable MCI. These differences demonstrate that white matter abnormalities are evident among individuals with probable MCI in regions beyond those commonly associated with Alzheimer’s disease and anterior brain aging patterns. PMID:25523313

  1. Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain

    PubMed Central

    Guo, Junjie U.; Su, Yijing; Shin, Joo Heon; Shin, Jaehoon; Li, Hongda; Xie, Bin; Zhong, Chun; Hu, Shaohui; Le, Thuc; Fan, Guoping; Zhu, Heng; Chang, Qiang; Gao, Yuan; Ming, Guo-li; Song, Hongjun

    2014-01-01

    DNA methylation plays critical roles in the nervous system and has been traditionally considered to be restricted to CpG dinucleotides in metazoan genomes. Here we show that the single-base resolution DNA methylome from adult mouse dentate neurons consists of both CpG (~75%) and CpH (~25%) methylation (H = A/C/T). Neuronal CpH methylation is conserved in human brains, enriched in low CpG-density regions, depleted at protein-DNA interaction sites, and anti-correlated with gene expression. Functionally, both mCpGs and mCpHs can repress transcription in vitro and are recognized by MeCP2 in neurons in vivo. Unlike most CpG methylation, CpH methylation is established de novo during neuronal maturation and requires DNMT3A for active maintenance in post-mitotic neurons. These characteristics of CpH methylation suggest a significantly expanded proportion of the neuronal genome under cytosine methylation regulation and provide a new foundation for understanding the role of this key epigenetic modification in the nervous system. PMID:24362762

  2. Detection of Growth Hormone Deficiency in Adults with Chronic Traumatic Brain Injury.

    PubMed

    Kreber, Lisa A; Griesbach, Grace S; Ashley, Mark J

    2016-09-01

    This study examined the prevalence of growth hormone deficiency (GHD) in patients with traumatic brain injury (TBI) during the post-acute phase of recovery and whether GHD was associated with increased disability, decreased independence, and depression. A secondary objective was to determine the accuracy of insulin-like growth factor-1 (IGF-1) levels in predicting GHD in patients with TBI. Anterior pituitary function was assessed in 235 adult patients with TBI through evaluation of fasting morning hormone levels. GH levels were assessed through provocative testing, specifically the glucagon stimulation test. GHD was diagnosed in a significant number of patients, with 45% falling into the severe GHD (≤3 μg/L) category. IGF-1 levels were not predictive of GHD. Patients with GHD were more disabled and less independent compared with those patients who were not GHD. Those patients with more severe GHD also showed decreased levels of cortisol and testosterone. Symptoms of depression were also more prevalent in this group. In addition, patients with severe GHD had delayed admission to post-acute rehabilitation. This study confirms the high prevalence of GHD in patients with TBI and the necessity to monitor clinical symptoms and perform provocative testing to definitively diagnose GHD. PMID:26414093

  3. Expression of gangliosides on glial and neuronal cells in normal and pathological adult human brain.

    PubMed

    Marconi, Silvia; De Toni, Luca; Lovato, Laura; Tedeschi, Elisa; Gaetti, Luigi; Acler, Michele; Bonetti, Bruno

    2005-12-30

    Few studies have assessed the glycolipid phenotype of glial cells in the human central nervous system (CNS) in situ. We investigated by immunohistochemistry the expression and cellular distribution of a panel of gangliosides (GM1, GM2, acetyl-GM3, GD1a, GD1b, GD2, GD3, GT1b, GQ1b and the A2B5 antibody) in adult, human normal and pathological brain, namely multiple sclerosis (MS) and other neurological diseases (OND). In normal conditions, we found diffuse expression in the white matter of most gangliosides tested, with the exception of acetyl-GM3, GT1b and GQ1b. By double immunofluorescence with phenotypic markers, GM1 and GD1b were preferentially expressed on GFAP+ astrocytes, GD1a on NG2+ oligodendrocyte precursors, A2B5 immunostained both populations, while GD2 was selectively present on mature oligodendrocytes. In the gray matter, only GM1, GD2 and A2B5 were present on neuronal cells. Interestingly, those gangliosides present on astrocytes in normal conditions were preferentially expressed on NG2+ cells in chronic MS lesions and in OND. Selective expression of GT1b upon astrocytes and NG2+ cells was instead observed in MS lesions, but not in OND. The definition of the glycolipid phenotype of CNS glial cells may be useful to identify distinct biological glial subsets and provide insights on the potential autoantigenic role of gangliosides in CNS autoimmune diseases. PMID:16313974

  4. Adverse Outcomes Among Homeless Adolescents and Young Adults Who Report a History of Traumatic Brain Injury

    PubMed Central

    Harpin, Scott B.; Grubenhoff, Joseph A.; Rivara, Frederick P.

    2014-01-01

    Objectives. We examined the prevalence of self-reported traumatic brain injury (TBI) among homeless young people and explored whether sociodemographic characteristics, mental health diagnoses, substance use, exposure to violence, or difficulties with activities of daily living (ADLs) were associated with TBI. Methods. We analyzed data from the Wilder Homelessness Study, in which participants were recruited in 2006 and 2009 from streets, shelters, and locations in Minnesota that provide services to homeless individuals. Participants completed 30-minute interviews to collect information about history of TBI, homelessness, health status, exposure to violence (e.g., childhood abuse, assault), and other aspects of functioning. Results. Of the 2732 participating adolescents and young adults, 43% reported a history of TBI. Participants with TBI became homeless at a younger age and were more likely to report mental health diagnoses, substance use, suicidality, victimization, and difficulties with ADLs. The majority of participants (51%) reported sustaining their first injury prior to becoming homeless or at the same age of their first homeless episode (10%). Conclusions. TBI occurs frequently among homeless young people and is a marker of adverse outcomes such as mental health difficulties, suicidal behavior, substance use, and victimization. PMID:25122029

  5. Detection of Growth Hormone Deficiency in Adults with Chronic Traumatic Brain Injury

    PubMed Central

    Griesbach, Grace S.; Ashley, Mark J.

    2016-01-01

    Abstract This study examined the prevalence of growth hormone deficiency (GHD) in patients with traumatic brain injury (TBI) during the post-acute phase of recovery and whether GHD was associated with increased disability, decreased independence, and depression. A secondary objective was to determine the accuracy of insulin-like growth factor-1 (IGF-1) levels in predicting GHD in patients with TBI. Anterior pituitary function was assessed in 235 adult patients with TBI through evaluation of fasting morning hormone levels. GH levels were assessed through provocative testing, specifically the glucagon stimulation test. GHD was diagnosed in a significant number of patients, with 45% falling into the severe GHD (≤3 μg/L) category. IGF-1 levels were not predictive of GHD. Patients with GHD were more disabled and less independent compared with those patients who were not GHD. Those patients with more severe GHD also showed decreased levels of cortisol and testosterone. Symptoms of depression were also more prevalent in this group. In addition, patients with severe GHD had delayed admission to post-acute rehabilitation. This study confirms the high prevalence of GHD in patients with TBI and the necessity to monitor clinical symptoms and perform provocative testing to definitively diagnose GHD. PMID:26414093

  6. Fat brains, greedy genes, and parent power: a biobehavioural risk model of child and adult obesity.

    PubMed

    Carnell, Susan; Kim, Yale; Pryor, Katherine

    2012-06-01

    We live in a world replete with opportunities to overeat highly calorific, palatable foods - yet not everyone becomes obese. Why? We propose that individuals show differences in appetitive traits (e.g. food cue responsiveness, satiety sensitivity) that manifest early in life and predict their eating behaviours and weight trajectories. What determines these traits? Parental feeding restriction is associated with higher child adiposity, pressure to eat with lower adiposity, and both strategies with less healthy eating behaviours, while authoritative feeding styles coincide with more positive outcomes. But, on the whole, twin and family studies argue that nature has a greater influence than nurture on adiposity and eating behaviour, and behavioural investigations of genetic variants that are robustly associated with obesity (e.g. FTO) confirm that genes influence appetite. Meanwhile, a growing body of neuroimaging studies in adults, children and high risk populations suggests that structural and functional variation in brain networks associated with reward, emotion and control might also predict appetite and obesity, and show genetic influence. Together these different strands of evidence support a biobehavioural risk model of obesity development. Parental feeding recommendations should therefore acknowledge the powerful - but modifiable - contribution of genetic and neurological influences to children's eating behaviour. PMID:22724640

  7. The Influence of Organized Physical Activity (including Gymnastics) on Young Adult Skeletal Traits: Is Maturity Phase Important?

    PubMed Central

    Bernardoni, Brittney; Scerpella, Tamara A.; Rosenbaum, Paula F.; Kanaley, Jill A.; Raab, Lindsay N.; Li, Quefeng; Wang, Sijian; Dowthwaite, Jodi N.

    2015-01-01

    We prospectively evaluated adolescent organized physical activity (PA) as a factor in adult female bone traits. Annual DXA scans accompanied semi-annual records of anthropometry, maturity and PA for 42 participants in this preliminary analysis (criteria: appropriately timed DXA scans at ~1 year pre-menarche [predictor] and ~5 years post-menarche [dependent variable]). Regression analysis evaluated total adolescent inter-scan PA and PA over 3 maturity sub-phases as predictors of young adult bone outcomes: 1) bone mineral content (BMC), geometry and strength indices at non-dominant distal radius and femoral neck; 2) sub-head BMC; 3) lumbar spine BMC. Analyses accounted for baseline gynecological age (years pre- or post-menarche), baseline bone status, adult body size and inter-scan body size change. Gymnastics training was evaluated as a potentially independent predictor, but did not improve models for any outcomes (p<0.07). Pre-menarcheal bone traits were strong predictors of most adult outcomes (semi-partial r2 = 0.21-0.59, p≤0.001). Adult 1/3 radius and sub-head BMC were predicted by both total PA and PA 1-3 years post-menarche (p<0.03). PA 3-5 years post-menarche predicted femoral narrow neck width, endosteal diameter and buckling ratio (p<0.05). Thus, participation in organized physical activity programs throughout middle and high school may reduce lifetime fracture risk in females. PMID:25386845

  8. The Influence of Organized Physical Activity (Including Gymnastics) on Young Adult Skeletal Traits: Is Maturity Phase Important?

    PubMed

    Bernardoni, Brittney; Scerpella, Tamara A; Rosenbaum, Paula F; Kanaley, Jill A; Raab, Lindsay N; Li, Quefeng; Wang, Sijian; Dowthwaite, Jodi N

    2015-05-01

    We prospectively evaluated adolescent organized physical activity (PA) as a factor in adult female bone traits. Annual DXA scans accompanied semiannual records of anthropometry, maturity, and PA for 42 participants in this preliminary analysis (criteria: appropriately timed DXA scans at ~1 year premenarche [predictor] and ~5 years postmenarche [dependent variable]). Regression analysis evaluated total adolescent interscan PA and PA over 3 maturity subphases as predictors of young adult bone outcomes: 1) bone mineral content (BMC), geometry, and strength indices at nondominant distal radius and femoral neck; 2) subhead BMC; 3) lumbar spine BMC. Analyses accounted for baseline gynecological age (years pre- or postmenarche), baseline bone status, adult body size and interscan body size change. Gymnastics training was evaluated as a potentially independent predictor, but did not improve models for any outcomes (p > .07). Premenarcheal bone traits were strong predictors of most adult outcomes (semipartial r2 = .21-0.59, p ≤ .001). Adult 1/3 radius and subhead BMC were predicted by both total PA and PA 1-3 years postmenarche (p < .03). PA 3-5 years postmenarche predicted femoral narrow neck width, endosteal diameter, and buckling ratio (p < .05). Thus, participation in organized physical activity programs throughout middle and high school may reduce lifetime fracture risk in females. PMID:25386845

  9. Programming Hippocampal Neural Stem/Progenitor Cells into Oligodendrocytes Enhances Remyelination in the Adult Brain after Injury.

    PubMed

    Braun, Simon M G; Pilz, Gregor-Alexander; Machado, Raquel A C; Moss, Jonathan; Becher, Burkhard; Toni, Nicolas; Jessberger, Sebastian

    2015-06-23

    Demyelinating diseases are characterized by a loss of oligodendrocytes leading to axonal degeneration and impaired brain function. Current strategies used for the treatment of demyelinating disease such as multiple sclerosis largely rely on modulation of the immune system. Only limited treatment options are available for treating the later stages of the disease, and these treatments require regenerative therapies to ameliorate the consequences of oligodendrocyte loss and axonal impairment. Directed differentiation of adult hippocampal neural stem/progenitor cells (NSPCs) into oligodendrocytes may represent an endogenous source of glial cells for cell-replacement strategies aiming to treat demyelinating disease. Here, we show that Ascl1-mediated conversion of hippocampal NSPCs into mature oligodendrocytes enhances remyelination in a diphtheria-toxin (DT)-inducible, genetic model for demyelination. These findings highlight the potential of targeting hippocampal NSPCs for the treatment of demyelinated lesions in the adult brain. PMID:26074082

  10. Mammalian Target of Rapamycin: Its Role in Early Neural Development and in Adult and Aged Brain Function.

    PubMed

    Garza-Lombó, Carla; Gonsebatt, María E

    2016-01-01

    The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging. PMID:27378854

  11. Mammalian Target of Rapamycin: Its Role in Early Neural Development and in Adult and Aged Brain Function

    PubMed Central

    Garza-Lombó, Carla; Gonsebatt, María E.

    2016-01-01

    The kinase mammalian target of rapamycin (mTOR) integrates signals triggered by energy, stress, oxygen levels, and growth factors. It regulates ribosome biogenesis, mRNA translation, nutrient metabolism, and autophagy. mTOR participates in various functions of the brain, such as synaptic plasticity, adult neurogenesis, memory, and learning. mTOR is present during early neural development and participates in axon and dendrite development, neuron differentiation, and gliogenesis, among other processes. Furthermore, mTOR has been shown to modulate lifespan in multiple organisms. This protein is an important energy sensor that is present throughout our lifetime its role must be precisely described in order to develop therapeutic strategies and prevent diseases of the central nervous system. The aim of this review is to present our current understanding of the functions of mTOR in neural development, the adult brain and aging. PMID:27378854

  12. The Mediating Role of Visuospatial Planning Skills on Adaptive Function Among Young-Adult Survivors of Childhood Brain Tumor.

    PubMed

    King, Tricia Z; Smith, Kristen M; Ivanisevic, Mirjana

    2015-08-01

    The Boston Qualitative Scoring System (BQSS) was used as a method to examine executive skills on the Rey-Osterrieth complex figure (ROCF). Young-adult survivors of childhood brain tumor (N = 31) and a demographically-matched comparison group (N = 33) completed the ROCF copy version and Grooved Pegboard, and informants were administered the Scales of Independent Behavior-Revised (SIB-R) and Behavior Rating Inventory of Executive Function (BRIEF). Survivors had significantly lower BQSS planning and SIB-R community living skills and greater perseveration. Mediation analyses found that BQSS planning skills mediate the relationship between group and community living skills. Convergent findings of the BRIEF Planning, and discriminant findings with the BQSS Fragmentation, BRIEF Emotional Control, and Grooved Pegboard support the planning construct as the specific mediator in this model. Together, these findings highlight the role of planning skills in adaptive functions of young-adult survivors of childhood brain tumor. PMID:26055499

  13. Enhanced Adult Neurogenesis Increases Brain Stiffness: In Vivo Magnetic Resonance Elastography in a Mouse Model of Dopamine Depletion

    PubMed Central

    Klein, Charlotte; Hain, Elisabeth G.; Braun, Juergen; Riek, Kerstin; Mueller, Susanne

    2014-01-01

    The mechanical network of the brain is a major contributor to neural health and has been recognized by in vivo magnetic resonance elastography (MRE) to be highly responsive to diseases. However, until now only brain softening was observed and no mechanism was known that reverses the common decrement of neural elasticity during aging or disease. We used MRE in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) mouse model for dopaminergic neurodegeneration as observed in Parkinson’s disease (PD) to study the mechanical response of the brain on adult hippocampal neurogenesis as a robust correlate of neuronal plasticity in healthy and injured brain. We observed a steep transient rise in elasticity within the hippocampal region of up to over 50% six days after MPTP treatment correlating with increased neuronal density in the dentate gyrus, which could not be detected in healthy controls. Our results provide the first indication that new neurons reactively generated following neurodegeneration substantially contribute to the mechanical scaffold of the brain. Diagnostic neuroimaging may thus target on regions of the brain displaying symptomatically elevated elasticity values for the detection of neuronal plasticity following neurodegeneration. PMID:24667730

  14. Age, sex and APOE ε4 effects on memory, brain structure and β-amyloid across the adult lifespan

    PubMed Central

    Jack, Clifford R.; Wiste, Heather J.; Weigand, Stephen D.; Knopman, David S.; Vemuri, Prashanthi; Mielke, Michelle M.; Lowe, Val; Senjem, Matthew L.; Gunter, Jeffrey L.; Machulda, Mary M.; Gregg, Brian E.; Pankratz, Vernon S.; Rocca, Walter A.; Petersen, Ronald C.

    2015-01-01

    Importance Typical cognitive aging may be defined as age associated changes in cognitive performance in individuals who remain free of dementia. Ideally the full adult age spectrum should be included to assess brain imaging findings associated with typical aging. Objective To compare age, sex and Apolipoprotein E (APOE ε4) effects on memory, brain structure (adjusted hippocampal volume, HVa) and amyloid PET in cognitively normal individuals aged 30 to 95 years old. Design, Setting, and Participants Cross sectional observational study (Marc 2006 to October 2014) at an academic medical center. We studied 1246 cognitively normal subjects; 1209 participants aged 50–95 years old enrolled in a population-based study of cognitive aging and 37 self-selected volunteers aged 30–49. Main Outcomes and Measures Memory, HVa, and amyloid PET Results Overall, memory worsened from age 30 years through the 90s. HVa worsened gradually from 30 years to the mid-60s and more steeply beyond that age. The median amyloid PET was low until age 70 years and increased thereafter. Memory was worse in men than women overall (p<0.001) and more specifically beyond age 40 years. HVa was lower in men than women overall (p<0.001) and more specifically beyond age 60 years. There was no sex difference in amyloid PET at any age. Within each sex, memory performance and HVa were not different by APOE ε4 at any age. From age 70 years onward APOE ε4 carriers had significantly greater median amyloid PET load than noncarriers. However the ages at which 10% of the population were amyloid PET positive were 57 years for APOE ε4 carriers and 64 years for non-carriers. Conclusions and Relevance Male sex is associated with worse memory and HVa among cognitively normal individuals while APOE ε4 is not. In contrast, APOE ε4 is associated with greater amyloid PET values (from age 70 years onward) while sex is not. Worsening memory and HVa occur at earlier ages than abnormal amyloid PET. Therefore

  15. 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

  16. Efficacy of a combined oral formulation of derquantel-abamectin against the adult and larval stages of nematodes in sheep, including anthelmintic-resistant strains.

    PubMed

    Little, Peter R; Hodge, Andrew; Maeder, Steven J; Wirtherle, Nicole C; Nicholas, David R; Cox, George G; Conder, George A

    2011-09-27

    Derquantel (DQL), a semi-synthetic member of a novel anthelmintic class, the spiroindoles, in combination with abamectin (ABA) [as the combination product STARTECT(®)] is a new entry for the treatment and control of parasites in sheep. The 19 studies reported herein were conducted in Australia, New Zealand, South Africa and the United Kingdom to demonstrate the efficacy of derquantel-abamectin (DQL-ABA) against a broad spectrum of gastrointestinal and respiratory nematodes of sheep, and to support registration of the combination product. Eleven studies were conducted using natural or experimental parasite infections with unknown or unconfirmed resistance, while eight studies utilised isolates/strains with confirmed or well characterised resistance to one or more currently available anthelmintics, including macrocyclic lactones. All studies included DQL-ABA and negative control groups, and in selected studies one or more reference anthelmintic groups were included. In all studies the commercial formulation of DQL-ABA was administered orally at 2mg/kg DQL and 0.2mg/kg ABA; placebo was administered in the same volume as DQL-ABA; and reference anthelmintics were administered as per label recommendations, except in one instance where levamisole was administered at twice the label dose. Infection, necropsy, worm collection and worm counting procedures were performed using standard techniques. Efficacy was calculated based on the percentage reduction in geometric mean worm count relative to negative control for each nematode species and lifecycle stage targeted. Twenty-two isolates/strains used in the eight studies targeting resistant worms had proven resistance: three to one anthelmintic class, eleven to two classes and eight to three or more classes; of these resistant strains, 16 demonstrated resistance to a macrocyclic lactone anthelmintic. Regardless of resistance status in the 19 studies, DQL-ABA controlled a broad range of economically important gastrointestinal

  17. Adult Asylum Seekers from the Middle East Including Syria in Central Europe: What Are Their Health Care Problems?

    PubMed Central

    Pfortmueller, Carmen Andrea; Schwetlick, Miriam; Mueller, Thomas; Lehmann, Beat; Exadaktylos, Aristomenis Konstantinos

    2016-01-01

    Background Forced displacement related to persecution and violent conflict has reached a new peak in recent years. The primary aim of this study is to provide an initial overview of the acute and chronic health care problems of asylum seekers from the Middle East, with special emphasis on asylum seekers from Syria. Methods Our retrospective data analysis comprised adult patients presenting to our emergency department between 01.11.2011 and 30.06.2014 with the official resident status of an “asylum seeker” or “refugee” from the Middle East. Results In total, 880 patients were included in the study. Of these, 625 (71.0%) were male and 255 (29.0%) female. The median age was 34 (range 16–84). 222 (25.2%) of our patients were from Syria. The most common reason for presentation was surgical (381, 43.3%), followed by medical (321, 36.5%) and psychiatric (137, 15.6%). In patients with surgical presentations, trauma-related problems were most common (n = 196, 50.6%). Within the group of patients with medical presentation, acute infectious diseases were most common (n = 141, 43.9%), followed by neurological problems (n = 70, 21.8%) and gastrointestinal problems (n = 47, 14.6%). There were no differences between Syrian and non-Syrian refugees concerning surgical or medical admissions. The most common chronic disorder of unclear significance was chronic gastrointestinal problems (n = 132, 15%), followed by chronic musculoskeletal problems (n = 108, 12.3%) and chronic headaches (n = 78, 8.9%). Patients from Syria were significantly younger and more often suffered from a post-traumatic stress disorder than patients of other nationalities (p<0.0001, and p = 0.05, respectively). Conclusion Overall a remarkable number of our very young group of patients suffered from psychiatric disorders and unspecified somatic symptoms. Asylum seekers should be carefully evaluated when presenting to a medical facility and physicians should be aware of the high incidence of unspecified

  18. Whole-brain grey matter density predicts balance stability irrespective of age and protects older adults from falling.

    PubMed

    Boisgontier, Matthieu P; Cheval, Boris; van Ruitenbeek, Peter; Levin, Oron; Renaud, Olivier; Chanal, Julien; Swinnen, Stephan P

    2016-03-01

    Functional and structural imaging studies have demonstrated the involvement of the brain in balance control. Nevertheless, how decisive grey matter density and white matter microstructural organisation are in predicting balance stability, and especially when linked to the effects of ageing, remains unclear. Standing balance was tested on a platform moving at different frequencies and amplitudes in 30 young and 30 older adults, with eyes open and with eyes closed. Centre of pressure variance was used as an indicator of balance instability. The mean density of grey matter and mean white matter microstructural organisation were measured using voxel-based morphometry and diffusion tensor imaging, respectively. Mixed-effects models were built to analyse the extent to which age, grey matter density, and white matter microstructural organisation predicted balance instability. Results showed that both grey matter density and age independently predicted balance instability. These predictions were reinforced when the level of difficulty of the conditions increased. Furthermore, grey matter predicted balance instability beyond age and at least as consistently as age across conditions. In other words, for balance stability, the level of whole-brain grey matter density is at least as decisive as being young or old. Finally, brain grey matter appeared to be protective against falls in older adults as age increased the probability of losing balance in older adults with low, but not moderate or high grey matter density. No such results were observed for white matter microstructural organisation, thereby reinforcing the specificity of our grey matter findings. PMID:26979897

  19. Low Current-driven Micro-electroporation Allows Efficient In Vivo Delivery of Nonviral DNA into the Adult Mouse Brain

    PubMed Central

    Vry, Jochen De; Martínez-Martínez, Pilar; Losen, Mario; Bode, Gerard H; Temel, Yasin; Steckler, Thomas; Steinbusch, Harry WM; Baets, Marc De; Prickaerts, Jos

    2010-01-01

    Viral gene transfer or transgenic animals are commonly used technologies to alter gene expression in the adult brain, although these approaches lack spatial specificity and are time consuming. We delivered plasmid DNA locally into the brain of adult C57BL/6 mice in vivo by voltage- and current-controlled electroporation. The low current-controlled delivery of unipolar square wave pulses of 125 µA with microstimulation electrodes at the injection site gave 16 times higher transfection rates than a voltage-controlled electroporation protocol with plate electrodes resulting in currents of about 400 mA. Transfection was restricted to the target region and no damage due to the electric pulses was found. Our current-controlled electroporation protocol indicated that the use of very low currents resulting in applied voltages within the physiological range of the membrane potential, allows efficient transfection of nonviral plasmid DNA. In conclusion, low current-controlled electroporation is an excellent approach for electroporation in the adult brain, i.e., gene function can be influenced locally at a high level with no mortality and minimal tissue damage. PMID:20389292

  20. Long-Term Upregulation of Inflammation and Suppression of Cell Proliferation in the Brain of Adult Rats Exposed to Traumatic Brain Injury Using the Controlled Cortical Impact Model

    PubMed Central

    Acosta, Sandra A.; Tajiri, Naoki; Shinozuka, Kazutaka; Ishikawa, Hiroto; Grimmig, Bethany; Diamond, David; Sanberg, Paul R.; Bickford, Paula C.; Kaneko, Yuji; Borlongan, Cesar V.

    2013-01-01

    The long-term consequences of traumatic brain injury (TBI), specifically the detrimental effects of inflammation on the neurogenic niches, are not very well understood. In the present in vivo study, we examined the prolonged pathological outcomes of experimental TBI in different parts of the rat brain with special emphasis on inflammation and neurogenesis. Sixty days after moderate controlled cortical impact injury, adult Sprague-Dawley male rats were euthanized and brain tissues harvested. Antibodies against the activated microglial marker, OX6, the cell cycle-regulating protein marker, Ki67, and the immature neuronal marker, doublecortin, DCX, were used to estimate microglial activation, cell proliferation, and neuronal differentiation, respectively, in the subventricular zone (SVZ), subgranular zone (SGZ), striatum, thalamus, and cerebral peduncle. Stereology-based analyses revealed significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle. In parallel, significant decrements in Ki67-positive proliferating cells in SVZ and SGZ, but only trends of reduced DCX-positive immature neuronal cells in SVZ and SGZ were detected relative to sham control group. These results indicate a progressive deterioration of the TBI brain over time characterized by elevated inflammation and suppressed neurogenesis. Therapeutic intervention at the chronic stage of TBI may confer abrogation of these deleterious cell death processes. PMID:23301065

  1. A preliminary study of sex differences in brain activation during a spatial navigation task in healthy adults.

    PubMed

    Sneider, Jennifer Tropp; Sava, Simona; Rogowska, Jadwiga; Yurgelun-Todd, Deborah A

    2011-10-01

    The hippocampus plays a significant role in spatial memory processing, with sex differences being prominent on various spatial tasks. This study examined sex differences in healthy adults, using functional magnetic resonance imaging (fMRI) in areas implicated in spatial processing during navigation of a virtual analogue of the Morris water-maze. There were three conditions: learning, hidden, and visible control. There were no significant differences in performance measures. However, sex differences were found in regional brain activation during learning in the right hippocampus, right parahippocampal gyrus, and the cingulate cortex. During the hidden condition, the hippocampus, parahippocampal gyrus, and cingulate cortex were activated in both men and women. Additional brain areas involved in spatial processing may be recruited in women when learning information about the environment, by utilizing external cues (landmarks) more than do men, contributing to the observed sex differences in brain activation. PMID:22185061

  2. A comparison of different models with motor dysfunction after traumatic brain injury in adult rats.

    PubMed

    Wang, Meng; Pu, Hongjian; Liu, Yingchao; Wang, Zengtao; Wang, Bomin; Xu, Wendong

    2014-12-01

    The aim of this study was to evaluate the validity of the model that could produce reproducible and persistent motor weakness and define the accurate tasks and testing parameters for longitudinal assessment of neurological deficits after traumatic brain injury (TBI). We compared the effects of two rat models that suffered different controlled cortical impact (CCI) injury, as well as extensive motor cortex resection model, on behavior recovery and brain morphology. Behavioral tests including the skilled reaching task, limb-use asymmetry test and the grasping test were employed to evaluate neurofunctional recovery from pre- to 12 weeks after the injury. The results demonstrated that all the rats in four groups showed spontaneous functional improvement with the past of time after surgery, especially in rats with mild and moderate CCI injury. At the end of the experiment, the animals' performance reached preoperative base lines on reaching task and limb-use asymmetry test in mild and moderate groups, while severe motor weakness could be observed in rats with severe CCI injury, as well as rats with extended motor cortex resection. Overall, the results of this study indicated that both models with severe CCI injury and extended resection of the motor cortex developed reproducible and long-lasting motor weakness, comparable in severity and duration and identified skilled reaching task, as well as limb-use asymmetry test, as sensitive assessments for slight neurological deficits after brain injury. This will help to provide the basis for further research of the processes after the TBI and development of novel therapies. PMID:25385190

  3. A Novel Procedure for Rapid Imaging of Adult Mouse Brains with MicroCT Using Iodine-Based Contrast

    PubMed Central

    Anderson, Ryan; Maga, A. Murat

    2015-01-01

    High-resolution Magnetic Resonance Imaging (MRI) has been the primary modality for obtaining 3D cross-sectional anatomical information in animals for soft tissue, particularly brain. However, costs associated with MRI can be considerably high for large phenotypic screens for gross differences in the structure of the brain due to pathology and/or experimental manipulations. MicroCT (mCT), especially benchtop mCT, is becoming a common laboratory equipment with throughput rates equal or faster than any form of high-resolution MRI at lower costs. Here we explore adapting previously developed contrast based mCT to image adult mouse brains in-situ. We show that 2% weight per volume (w/v) iodine-potassium iodide solution can be successfully used to image adult mouse brains within 48 hours post-mortem when a structural support matrix is used. We demonstrate that hydrogel can be effectively used as a perfusant which limits the tissue shrinkage due to iodine. PMID:26571123

  4. Assessing blood brain barrier dynamics or identifying or measuring selected substances, including ethanol or toxins, in a subject by analyzing Raman spectrum signals

    NASA Technical Reports Server (NTRS)

    Lambert, James L. (Inventor); Borchert, Mark S. (Inventor)

    2008-01-01

    A non-invasive method for analyzing the blood-brain barrier includes obtaining a Raman spectrum of a selected portion of the eye and monitoring the Raman spectrum to ascertain a change to the dynamics of the blood brain barrier.Also, non-invasive methods for determining the brain or blood level of an analyte of interest, such as glucose, drugs, alcohol, poisons, and the like, comprises: generating an excitation laser beam at a selected wavelength (e.g., at a wavelength of about 400 to 900 nanometers); focusing the excitation laser beam into the anterior chamber of an eye of the subject so that aqueous humor, vitreous humor, or one or more conjunctiva vessels in the eye is illuminated; detecting (preferably confocally detecting) a Raman spectrum from the illuminated portion of the eye; and then determining the blood level or brain level (intracranial or cerebral spinal fluid level) of an analyte of interest for the subject from the Raman spectrum. In certain embodiments, the detecting step may be followed by the step of subtracting a confounding fluorescence spectrum from the Raman spectrum to produce a difference spectrum; and determining the blood level and/or brain level of the analyte of interest for the subject from that difference spectrum, preferably using linear or nonlinear multivariate analysis such as partial least squares analysis. Apparatus for carrying out the foregoing methods are also disclosed.

  5. Development and psychometric properties of an informant assessment scale of theory of mind for adults with traumatic brain injury.

    PubMed

    Zhang, Dengke; Pang, Yanxia; Cai, Weixiong; Fazio, Rachel L; Ge, Jianrong; Su, Qiaorong; Xu, Shuiqin; Pan, Yinan; Chen, Sanmei; Zhang, Hongwei

    2016-08-01

    Impairment of theory of mind (ToM) is a common phenomenon following traumatic brain injury (TBI) that has clear effects on patients' social functioning. A growing body of research has focused on this area, and several methods have been developed to assess ToM deficiency. Although an informant assessment scale would be useful for examining individuals with TBI, very few studies have adopted this approach. The purpose of the present study was to develop an informant assessment scale of ToM for adults with traumatic brain injury (IASToM-aTBI) and to test its reliability and validity with 196 adults with TBI and 80 normal adults. A 44-item scale was developed following a literature review, interviews with patient informants, consultations with experts, item analysis, and exploratory factor analysis (EFA). The following three common factors were extracted: social interaction, understanding of beliefs, and understanding of emotions. The psychometric analyses indicate that the scale has good internal consistency reliability, split-half reliability, test-retest reliability, inter-rater reliability, structural validity, discriminate validity and criterion validity. These results provide preliminary evidence that supports the reliability and validity of the IASToM-aTBI as a ToM assessment tool for adults with TBI. PMID:25849662

  6. Traumatic brain injury and age at onset of cognitive impairment in older adults.

    PubMed

    Li, Wei; Risacher, Shannon L; McAllister, Thomas W; Saykin, Andrew J

    2016-07-01

    There is a deficiency of knowledge regarding how traumatic brain injury (TBI) is associated with age at onset (AAO) of cognitive impairment in older adults. Participants with a TBI history were identified from the Alzheimer's disease neuroimaging initiative (ADNI 1/GO/2) medical history database. Using an analysis of covariance (ANCOVA) model, the AAO was compared between those with and without TBI, and potential confounding factors were controlled. The AAO was also compared between those with mild TBI (mTBI) and moderate or severe TBI (sTBI). Lastly, the effects of mTBI were analyzed on the AAO of participants with clinical diagnoses of either mild cognitive impairment (MCI) or Alzheimer's disease (AD). The AAO for a TBI group was 68.2 ± 1.1 years [95 % confidence interval (CI) 66.2-70.3, n = 62], which was significantly earlier than the AAO for the non-TBI group of 70.9 ± 0.2 years (95 % CI 70.5-71.4, n = 1197) (p = 0.013). Participants with mTBI history showed an AAO of 68.5 ± 1.1 years (n = 56), which was significantly earlier than the AAO for the non-TBI group (p = 0.032). Participants with both MCI and mTBI showed an AAO of 66.5 ± 1.3 years (95 % CI 63.9-69.1, n = 45), compared to 70.6 ± 0.3 years for the non-TBI MCI group (95 % CI 70.1-71.1, n = 935) (p = 0.016). As a conclusion, a history of TBI may accelerate the AAO of cognitive impairment by two or more years. These results were consistent with reports of TBI as a significant risk factor for cognitive decline in older adults, and TBI is associated with an earlier AAO found in patients with MCI or AD. PMID:27007484

  7. Transcriptome analyses of adult mouse brain reveal enrichment of lncRNAs in specific brain regions and neuronal populations

    PubMed Central

    Kadakkuzha, Beena M.; Liu, Xin-An; McCrate, Jennifer; Shankar, Gautam; Rizzo, Valerio; Afinogenova, Alina; Young, Brandon; Fallahi, Mohammad; Carvalloza, Anthony C.; Raveendra, Bindu; Puthanveettil, Sathyanarayanan V.

    2015-01-01

    Despite the importance of the long non-coding RNAs (lncRNAs) in regulating biological functions, the expression profiles of lncRNAs in the sub-regions of the mammalian brain and neuronal populations remain largely uncharacterized. By analyzing RNASeq datasets, we demonstrate region specific enrichment of populations of lncRNAs and mRNAs in the mouse hippocampus and pre-frontal cortex (PFC), the two major regions of the brain involved in memory storage and neuropsychiatric disorders. We identified 2759 lncRNAs and 17,859 mRNAs in the hippocampus and 2561 lncRNAs and 17,464 mRNAs expressed in the PFC. The lncRNAs identified correspond to ~14% of the transcriptome of the hippocampus and PFC and ~70% of the lncRNAs annotated in the mouse genome (NCBIM37) and are localized along the chromosomes as varying numbers of clusters. Importantly, we also found that a few of the tested lncRNA-mRNA pairs that share a genomic locus display specific co-expression in a region-specific manner. Furthermore, we find that sub-regions of the brain and specific neuronal populations have characteristic lncRNA expression signatures. These results reveal an unexpected complexity of the lncRNA expression in the mouse brain. PMID:25798087

  8. Energy Metabolism of the Brain, Including the Cooperation between Astrocytes and Neurons, Especially in the Context of Glycogen Metabolism.

    PubMed

    Falkowska, Anna; Gutowska, Izabela; Goschorska, Marta; Nowacki, Przemysław; Chlubek, Dariusz; Baranowska-Bosiacka, Irena

    2015-01-01

    Glycogen metabolism has important implications for the functioning of the brain, especially the cooperation between astrocytes and neurons. According to various research data, in a glycogen deficiency (for example during hypoglycemia) glycogen supplies are used to generate lactate, which is then transported to neighboring neurons. Likewise, during periods of intense activity of the nervous system, when the energy demand exceeds supply, astrocyte glycogen is immediately converted to lactate, some of which is transported to the neurons. Thus, glycogen from astrocytes functions as a kind of protection against hypoglycemia, ensuring preservation of neuronal function. The neuroprotective effect of lactate during hypoglycemia or cerebral ischemia has been reported in literature. This review goes on to emphasize that while neurons and astrocytes differ in metabolic profile, they interact to form a common metabolic cooperation. PMID:26528968

  9. Energy Metabolism of the Brain, Including the Cooperation between Astrocytes and Neurons, Especially in the Context of Glycogen Metabolism

    PubMed Central

    Falkowska, Anna; Gutowska, Izabela; Goschorska, Marta; Nowacki, Przemysław; Chlubek, Dariusz; Baranowska-Bosiacka, Irena

    2015-01-01

    Glycogen metabolism has important implications for the functioning of the brain, especially the cooperation between astrocytes and neurons. According to various research data, in a glycogen deficiency (for example during hypoglycemia) glycogen supplies are used to generate lactate, which is then transported to neighboring neurons. Likewise, during periods of intense activity of the nervous system, when the energy demand exceeds supply, astrocyte glycogen is immediately converted to lactate, some of which is transported to the neurons. Thus, glycogen from astrocytes functions as a kind of protection against hypoglycemia, ensuring preservation of neuronal function. The neuroprotective effect of lactate during hypoglycemia or cerebral ischemia has been reported in literature. This review goes on to emphasize that while neurons and astrocytes differ in metabolic profile, they interact to form a common metabolic cooperation. PMID:26528968

  10. Advanced BrainAGE in older adults with type 2 diabetes mellitus.

    PubMed

    Franke, Katja; Gaser, Christian; Manor, Brad; Novak, Vera

    2013-01-01

    Aging alters brain structure and function and diabetes mellitus (DM) may accelerate this process. This study investigated the effects of type 2 DM on individual brain aging as well as the relationships between individual brain aging, risk factors, and functional measures. To differentiate a pattern of brain atrophy that deviates from normal brain aging, we used the novel BrainAGE approach, which determines the complex multidimensional aging pattern within the whole brain by applying established kernel regression methods to anatomical brain magnetic resonance images (MRI). The "Brain Age Gap Estimation" (BrainAGE) score was then calculated as the difference between chronological age and estimated brain age. 185 subjects (98 with type 2 DM) completed an MRI at 3Tesla, laboratory and clinical assessments. Twenty-five subjects (12 with type 2 DM) also completed a follow-up visit after 3.8 ± 1.5 years. The estimated brain age of DM subjects was 4.6 ± 7.2 years greater than their chronological age (p = 0.0001), whereas within the control group, estimated brain age was similar to chronological age. As compared to baseline, the average BrainAGE scores of DM subjects increased by 0.2 years per follow-up year (p = 0.034), whereas the BrainAGE scores of controls did not change between baseline and follow-up. At baseline, across all subjects, higher BrainAGE scores were associated with greater smoking and alcohol consumption, higher tumor necrosis factor alpha (TNFα) levels, lower verbal fluency scores and more severe deprepession. Within the DM group, higher BrainAGE scores were associated with longer diabetes duration (r = 0.31, p = 0.019) and increased fasting blood glucose levels (r = 0.34, p = 0.025). In conclusion, type 2 DM is independently associated with structural changes in the brain that reflect advanced aging. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of abnormal patterns of brain aging associated with type 2 DM

  11. Brain structures and functional connectivity associated with individual differences in Internet tendency in healthy young adults.

    PubMed

    Li, Weiwei; Li, Yadan; Yang, Wenjing; Zhang, Qinglin; Wei, Dongtao; Li, Wenfu; Hitchman, Glenn; Qiu, Jiang

    2015-04-01

    Internet addiction (IA) incurs significant social and financial costs in the form of physical side-effects, academic and occupational impairment, and serious relationship problems. The majority of previous studies on Internet addiction disorders (IAD) have focused on structural and functional abnormalities, while few studies have simultaneously investigated the structural and functional brain alterations underlying individual differences in IA tendencies measured by questionnaires in a healthy sample. Here we combined structural (regional gray matter volume, rGMV) and functional (resting-state functional connectivity, rsFC) information to explore the neural mechanisms underlying IAT in a large sample of 260 healthy young adults. The results showed that IAT scores were significantly and positively correlated with rGMV in the right dorsolateral prefrontal cortex (DLPFC, one key node of the cognitive control network, CCN), which might reflect reduced functioning of inhibitory control. More interestingly, decreased anticorrelations between the right DLPFC and the medial prefrontal cortex/rostral anterior cingulate cortex (mPFC/rACC, one key node of the default mode network, DMN) were associated with higher IAT scores, which might be associated with reduced efficiency of the CCN and DMN (e.g., diminished cognitive control and self-monitoring). Furthermore, the Stroop interference effect was positively associated with the volume of the DLPFC and with the IA scores, as well as with the connectivity between DLPFC and mPFC, which further indicated that rGMV variations in the DLPFC and decreased anticonnections between the DLPFC and mPFC may reflect addiction-related reduced inhibitory control and cognitive efficiency. These findings suggest the combination of structural and functional information can provide a valuable basis for further understanding of the mechanisms and pathogenesis of IA. PMID:25698637

  12. Seasonal variation in cell proliferation and cell migration in the brain of adult red-sided garter snakes (Thamnophis sirtalis parietalis).

    PubMed

    Maine, Ashley R; Powers, Sean D; Lutterschmidt, Deborah I

    2014-01-01

    Plasticity in the adult central nervous system has been described in all vertebrate classes as well as in some invertebrate groups. However, the limited taxonomic diversity represented in the current neurogenesis literature limits our ability to assess the functional significance of adult neurogenesis for natural behaviors as well as the evolution of its regulatory mechanisms. In the present study, we used free-ranging red-sided garter snakes (Thamnophis sirtalis parietalis) to test the hypothesis that seasonal shifts in physiology and behavior are associated with seasonal variation in postembryonic neurogenesis. Specifically, we used the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) to determine if the rates of cell proliferation in the adult brain vary between male snakes collected during spring and fall at 1, 5, and 10 days post-BrdU treatment. To assess rates of cell migration within the brain, we further categorized BrdU-labeled cells according to their location within the ventricular zone or parenchymal region. BrdU-labeled cells were localized mainly within the lateral, dorsal, and medial cortex, septal nucleus, nucleus sphericus, preoptic area, and hypothalamus. In all regions, the number of BrdU-labeled cells in the ventricular zone was higher in the fall compared to spring. In the parenchymal region, a significantly higher number of labeled cells was also observed during the fall, but only within the nucleus sphericus and the combined preoptic area/hypothalamus. The immunoreactive cell number did not vary significantly with days post-BrdU treatment in either season or in any brain region. While it is possible that the higher rates of cell proliferation in the fall simply reflect increased growth of all body tissues, including the brain, our data show that seasonal changes in cell migration into the parenchyma are region specific. In red-sided garter snakes and other reptiles, the dorsal and medial cortex is important for spatial navigation and memory

  13. Brain structural deficits and working memory fMRI dysfunction in young adults who were diagnosed with ADHD in adolescence.

    PubMed

    Roman-Urrestarazu, Andres; Lindholm, Päivi; Moilanen, Irma; Kiviniemi, Vesa; Miettunen, Jouko; Jääskeläinen, Erika; Mäki, Pirjo; Hurtig, Tuula; Ebeling, Hanna; Barnett, Jennifer H; Nikkinen, Juha; Suckling, John; Jones, Peter B; Veijola, Juha; Murray, Graham K

    2016-05-01

    When adolescents with ADHD enter adulthood, some no longer meet disorder diagnostic criteria but it is unknown if biological and cognitive abnorma lities persist. We tested the hypothesis that people diagnosed with ADHD during adolescence present residual brain abnormalities both in brain structure and in working memory brain function. 83 young adults (aged 20-24 years) from the Northern Finland 1986 Birth Cohort were classified as diagnosed with ADHD in adolescence (adolescence ADHD, n = 49) or a control group (n = 34). Only one patient had received medication for ADHD. T1-weighted brain scans were acquired and processed in a voxel-based analysis using permutation-based statistics. A sub-sample of both groups (ADHD, n = 21; controls n = 23) also performed a Sternberg working memory task whilst acquiring fMRI data. Areas of structural difference were used as a region of interest to evaluate the implications that structural abnormalities found in the ADHD group might have on working memory function. There was lower grey matter volume bilaterally in adolescence ADHD participants in the caudate (p < 0.05 FWE corrected across the whole brain) at age 20-24. Working memory was poorer in adolescence ADHD participants, with associated failure to show normal load-dependent caudate activation. Young adults diagnosed with ADHD in adolescence have structural and functional deficits in the caudate associated with abnormal working memory function. These findings are not secondary to stimulant treatment, and emphasise the importance of taking a wider perspective on ADHD outcomes than simply whether or not a particular patient meets diagnostic criteria at any given point in time. PMID:26307356

  14. Predicting healthy older adult's brain age based on structural connectivity networks using artificial neural networks.

    PubMed

    Lin, Lan; Jin, Cong; Fu, Zhenrong; Zhang, Baiwen; Bin, Guangyu; Wu, Shuicai

    2016-03-01

    Brain ageing is followed by changes of the connectivity of white matter (WM) and changes of the grey matter (GM) concentration. Neurodegenerative disease is more vulnerable to an accelerated brain ageing, which is associated with prospective cognitive decline and disease severity. Accurate detection of accelerated ageing based on brain network analysis has a great potential for early interventions designed to hinder atypical brain changes. To capture the brain ageing, we proposed a novel computational approach for modeling the 112 normal older subjects (aged 50-79 years) brain age by connectivity analyses of networks of the brain. Our proposed method applied principal component analysis (PCA) to reduce the redundancy in network topological parameters. Back propagation artificial neural network (BPANN) improved by hybrid genetic algorithm (GA) and Levenberg-Marquardt (LM) algorithm is established to model the relation among principal components (PCs) and brain age. The predicted brain age is strongly correlated with chronological age (r=0.8). The model has mean absolute error (MAE) of 4.29 years. Therefore, we believe the method can provide a possible way to quantitatively describe the typical and atypical network organization of human brain and serve as a biomarker for presymptomatic detection of neurodegenerative diseases in the future. PMID:26718834

  15. Effects of Chronic Consumption of Sugar-Enriched Diets on Brain Metabolism and Insulin Sensitivity in Adult Yucatan Minipigs.

    PubMed

    Ochoa, Melissa; Malbert, Charles-Henri; Meurice, Paul; Val-Laillet, David

    2016-01-01

    Excessive sugar intake might increase the risk to develop eating disorders via an altered reward circuitry, but it remains unknown whether different sugar sources induce different neural effects and whether these effects are dependent from body weight. Therefore, we compared the effects of three high-fat and isocaloric diets varying only in their carbohydrate sources on brain activity of reward-related regions, and assessed whether brain activity is dependent on insulin sensitivity. Twenty-four minipigs underwent 18FDG PET brain imaging following 7-month intake of high-fat diets of which 20% in dry matter weight (36.3% of metabolisable energy) was provided by starch, glucose or fructose (n = 8 per diet). Animals were then subjected to a euglycemic hyperinsulinemic clamp to determine peripheral insulin sensitivity. After a 7-month diet treatment, all groups had substantial increases in body weight (from 36.02±0.85 to 63.33±0.81 kg; P<0.0001), regardless of the diet. All groups presented similar insulin sensitivity index (ISI = 1.39±0.10 mL·min-1·μUI·kg). Compared to starch, chronic exposure to fructose and glucose induced bilateral brain activations, i.e. increased basal cerebral glucose metabolism, in several reward-related brain regions including the anterior and dorsolateral prefrontal cortex, the orbitofrontal cortex, the anterior cingulate cortex, the caudate and putamen. The lack of differences in insulin sensitivity index and body weight suggests that the observed differences in basal brain glucose metabolism are not related to differences in peripheral insulin sensitivity and weight gain. The differences in basal brain metabolism in reward-related brain areas suggest the onset of cerebral functional alterations induced by chronic consumption of dietary sugars. Further studies should explore the underlying mechanisms, such as the availability of intestinal and brain sugar transporter, or the appearance of addictive-like behavioral correlates of these

  16. Effects of Open and Closed Endotracheal Suctioning on Intracranial Pressure and Cerebral Perfusion Pressure in Adult Patients With Severe Brain Injury: A Literature Review.

    PubMed

    Galbiati, Giancarlo; Paola, Cattaneo

    2015-08-01

    In neurologically impaired adult patients, endotracheal suctioning is a potentially dangerous nursing procedure because it can increase intracranial pressure (ICP) and decrease cerebral perfusion pressure (CPP). This article presents an overview of the literature relating to the appropriate techniques (open system suctioning and closed system suctioning) for minimizing variability in ICP and CPP. The research used databases such as Medline, CINAHL, Embase, Scopus, Cochrane Library, and TripDataBase. Literature published from January 1, 2002, to August 31, 2013, that involved adult patients was reviewed. The main search strings were obtained using the following keyword combinations: "suction AND intracranial pressure AND cerebrovascular circulation," "brain injuries OR craniocerebral trauma AND suction," and "brain injuries OR craniocerebral trauma AND suction AND intracranial pressure." Fourteen articles were included: two systematic reviews, two prospective nonrandomized studies, two prospective double-blind clinical trials, a crossover single-blind clinical trial, three prospective interventionist case studies, a case-control study, and three observational studies. Although most of the articles show an increased ICP above 20 mm Hg when using open system suctioning (as opposed to closed system suctioning), it is still not clear which technique is best for maintaining CPP. Therefore, further studies are needed to determine the best technique for nursing practice. PMID:25951310

  17. Deconstructing brain-derived neurotrophic factor actions in adult brain circuits to bridge an existing informational gap in neuro-cell biology.

    PubMed

    Bowling, Heather; Bhattacharya, Aditi; Klann, Eric; Chao, Moses V

    2016-03-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in neurodevelopment, synaptic plasticity, learning and memory, and in preventing neurodegeneration. Despite decades of investigations into downstream signaling cascades and changes in cellular processes, the mechanisms of how BDNF reshapes circuits in vivo remain unclear. This informational gap partly arises from the fact that the bulk of studies into the molecular actions of BDNF have been performed in dissociated neuronal cultures, while the majority of studies on synaptic plasticity, learning and memory were performed in acute brain slices or in vivo. A recent study by Bowling-Bhattacharya et al., measured the proteomic changes in acute adult hippocampal slices following treatment and reported changes in proteins of neuronal and non-neuronal origin that may in concert modulate synaptic release and secretion in the slice. In this paper, we place these findings into the context of existing literature and discuss how they impact our understanding of how BDNF can reshape the brain. PMID:27127458

  18. Deconstructing brain-derived neurotrophic factor actions in adult brain circuits to bridge an existing informational gap in neuro-cell biology

    PubMed Central

    Bowling, Heather; Bhattacharya, Aditi; Klann, Eric; Chao, Moses V.

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in neurodevelopment, synaptic plasticity, learning and memory, and in preventing neurodegeneration. Despite decades of investigations into downstream signaling cascades and changes in cellular processes, the mechanisms of how BDNF reshapes circuits in vivo remain unclear. This informational gap partly arises from the fact that the bulk of studies into the molecular actions of BDNF have been performed in dissociated neuronal cultures, while the majority of studies on synaptic plasticity, learning and memory were performed in acute brain slices or in vivo. A recent study by Bowling-Bhattacharya et al., measured the proteomic changes in acute adult hippocampal slices following treatment and reported changes in proteins of neuronal and non-neuronal origin that may in concert modulate synaptic release and secretion in the slice. In this paper, we place these findings into the context of existing literature and discuss how they impact our understanding of how BDNF can reshape the brain. PMID:27127458

  19. Pluripotent embryonic stem cells and multipotent adult germline stem cells reveal similar transcriptomes including pluripotency-related genes.

    PubMed

    Meyer, S; Nolte, J; Opitz, L; Salinas-Riester, G; Engel, W

    2010-11-01

    DNA microarray analysis was performed with mouse multipotent adult germline stem cells (maGSCs) and embryonic stem cells (ESCs) from different genetic backgrounds cultured under standard ESC-culture conditions and under differentiation-promoting conditions by the withdrawal of the leukemia inhibitory factor (LIF) and treatment with retinoic acid (RA). The analyzed undifferentiated cell lines are very similar based on their global gene expression pattern and show 97-99% identity dependent on the analyzed background. Only 621 genes are differentially expressed in cells derived from mouse 129SV-background and 72 genes show differences in expression in cells generated from transgenic Stra8-EGFP/Rosa26-LacZ-background. Both maGSCs and ESCs express the same genes involved in the regulation of pluripotency and even show no differences in the expression level of these genes. When comparing maGSCs with previously published signature genes of other pluripotent cell lines, we found that maGSCs shared a very similar gene expression pattern with embryonic germ cells (EGCs). Also after differentiation of maGSCs and ESCs the transcriptomes of the cell lines are nearly identical which suggests that both cell types differentiate spontaneously in a very similar way. This is the first study, at transcriptome level, to compare ESCs and a pluripotent cell line derived from an adult organism (maGSCs). PMID:20624824

  20. Radio-wave exposure of the human head: analytical study based on a versatile eccentric spheres model including a brain core and a pair of eyeballs.

    PubMed

    Moneda, Angela P; Ioannidou, Melina P; Chrissoulidis, Dimitris P

    2003-06-01

    A versatile eccentric-spheres model of the human head is used in this paper to investigate radio-wave absorption. Numerical results, obtained by use of an exact analytical solution, are presented for the total, percentage, and gram-specific absorption. Interest is mainly in the brain and in the eyes of an adult or an infant head. Our model comprises a host sphere and several spherical inclusions, all concentrically stratified with respect to their own center. Any number of inclusions and any number of concentric layers for the host sphere and each one of the inclusions can be considered. Excitation is provided either by a plane-wave or by a nearby electric dipole. The analytical solution is obtained by use of the indirect-mode matching method. The theory of this paper and the accompanying computer code constitute a versatile tool for analytical studies of cellular-phone interactions with the human head. Specific absorption rate maps in a horizontal cross section of the head model manifest the existence of hot spots in the eyes and near the center of the brain. PMID:12814233

  1. Heterogeneous vascular permeability and alternative diffusion barrier in sensory circumventricular organs of adult mouse brain.

    PubMed

    Morita, Shoko; Furube, Eriko; Mannari, Tetsuya; Okuda, Hiroaki; Tatsumi, Kouko; Wanaka, Akio; Miyata, Seiji

    2016-02-01

    Fenestrated capillaries of the sensory circumventricular organs (CVOs), including the organum vasculosum of the lamina terminalis, the subfornical organ and the area postrema, lack completeness of the blood-brain barrier (BBB) to sense a variety of blood-derived molecules and to convey the information into other brain regions. We examine the vascular permeability of blood-derived molecules and the expression of tight-junction proteins in sensory CVOs. The present tracer assays revealed that blood-derived dextran 10 k (Dex10k) having a molecular weight (MW) of 10,000 remained in the perivascular space between the inner and outer basement membranes, but fluorescein isothiocyanate (FITC; MW: 389) and Dex3k (MW: 3000) diffused into the parenchyma. The vascular permeability of FITC was higher at central subdivisions than at distal subdivisions. Neither FITC nor Dex3k diffused beyond the dense network of glial fibrillar acidic protein (GFAP)-positive astrocytes/tanycytes. The expression of tight-junction proteins such as occludin, claudin-5 and zonula occludens-1 (ZO-1) was undetectable at the central subdivisions of the sensory CVOs but some was expressed at the distal subdivisions. Electron microscopic observation showed that capillaries were surrounded with numerous layers of astrocyte processes and dendrites. The expression of occludin and ZO-1 was also observed as puncta on GFAP-positive astrocytes/tanycytes of the sensory CVOs. Our study thus demonstrates the heterogeneity of vascular permeability and expression of tight-junction proteins and indicates that the outer basement membrane and dense astrocyte/tanycyte connection are possible alternative mechanisms for a diffusion barrier of blood-derived molecules, instead of the BBB. PMID:26048259

  2. White matter structure in young adults with familial risk for psychosis - The Oulu Brain and Mind Study.

    PubMed

    Koivukangas, Jenni; Björnholm, Lassi; Tervonen, Osmo; Miettunen, Jouko; Nordström, Tanja; Kiviniemi, Vesa; Mäki, Pirjo; Jääskeläinen, Erika; Mukkala, Sari; Moilanen, Irma; Barnett, Jennifer H; Jones, Peter B; Nikkinen, Juha; Veijola, Juha

    2015-09-30

    According to the disconnectivity model, disruptions in neural connectivity play an essential role in the pathology of schizophrenia. The aim of this study was to determine whether these abnormalities are present in young adults with familial risk (FR) for psychosis in the general population based sample. We used diffusion tensor imaging (DTI) and tract-based spatial statistics to compare whole-brain fractional anisotropy, mean diffusivity, and axial and radial diffusion in 47 (17 males) FR subjects to 51 controls (17 males). All the participants were aged between 20 and 25 years and were members of the Northern Finland Birth Cohort 1986 (Oulu Brain and Mind Study). Region of interest analyses were conducted for 12 tracts. Separately, we analysed whole-brain FA for the subgroup with FR for schizophrenia (n=13) compared with 13 gender-matched controls. Contrary to our expectations there were no differences in any of the DTI measures between FR and control groups. This suggests that white matter abnormalities may not be a genetic feature for risk of psychosis and preceding the onset of a psychotic disorder. Our findings do not support the theory of disconnectivity as a primary sign of psychosis in young adults with FR for the illness. PMID:26231121

  3. The adult brain tissue response to hollow fiber membranes of varying surface architecture with or without cotransplanted cells

    NASA Astrophysics Data System (ADS)

    Zhang, Ning

    A variety of biomaterials have been chronically implanted into the central nervous system (CNS) for repair or therapeutic purposes. Regardless of the application, chronic implantation of materials into the CNS induces injury and elicits a wound healing response, eventually leading to the formation of a dense extracellular matrix (ECM)-rich scar tissue that is associated with the segregation of implanted materials from the surrounding normal tissue. Often this reaction results in impaired performance of indwelling CNS devices. In order to enhance the performance of biomaterial-based implantable devices in the CNS, this thesis investigated whether adult brain tissue response to implanted biomaterials could be manipulated by changing biomaterial surface properties or further by utilizing the biology of co-transplanted cells. Specifically, the adult rat brain tissue response to chronically implanted poly(acrylonitrile-vinylchloride) (PAN-PVC) hollow fiber membranes (HFMs) of varying surface architecture were examined temporally at 2, 4, and 12 weeks postimplantation. Significant differences were discovered in the brain tissue response to the PAN-PVC HFMs of varying surface architecture at 4 and 12 weeks. To extend this work, whether the soluble factors derived from a co-transplanted cellular component further affect the brain tissue response to an implanted HFM in a significant way was critically exploited. The cells used were astrocytes, whose ability to influence scar formation process following CNS injury by physical contact with the host tissue had been documented in the literature. Data indicated for the first time that astrocyte-derived soluble factors ameliorate the adult brain tissue reactivity toward HFM implants in an age-dependent manner. While immature astrocytes secreted soluble factors that suppressed the brain tissue reactivity around the implants, mature astrocytes secreted factors that enhanced the gliotic response. These findings prove the feasibility

  4. Brain aromatase (Cyp19A2) and estrogen receptors, in larvae and adult pejerrey fish Odontesthes bonariensis: Neuroanatomical and functional relations

    USGS Publications Warehouse

    Strobl-Mazzulla, P. H.; Lethimonier, C.; Gueguen, M.M.; Karube, M.; Fernandino, J.I.; Yoshizaki, G.; Patino, R.; Strussmann, C.A.; Kah, O.; Somoza, G.M.

    2008-01-01

    Although estrogens exert many functions on vertebrate brains, there is little information on the relationship between brain aromatase and estrogen receptors. Here, we report the cloning and characterization of two estrogen receptors, ?? and ??, in pejerrey. Both receptors' mRNAs largely overlap and were predominantly expressed in the brain, pituitary, liver, and gonads. Also brain aromatase and estrogen receptors were up-regulated in the brain of estradiol-treated males. In situ hybridization was performed to study in more detail, the distribution of the two receptors in comparison with brain aromatase mRNA in the brain of adult pejerrey. The estrogen receptors' mRNAs exhibited distinct but partially overlapping patterns of expression in the preoptic area and the mediobasal hypothalamus, as well as in the pituitary gland. Moreover, the estrogen receptor ??, but not ??, were found to be expressed in cells lining the preoptic recess, similarly as observed for brain aromatase. Finally, it was shown that the onset expression of brain aromatase and both estrogen receptors in the head of larvae preceded the morphological differentiation of the gonads. Because pejerrey sex differentiation is strongly influenced by temperature, brain aromatase expression was measured during the temperature-sensitive window and was found to be significantly higher at male-promoting temperature. Taken together these results suggest close neuroanatomical and functional relationships between brain aromatase and estrogen receptors, probably involved in the sexual differentiation of the brain and raising interesting questions on the origin (central or peripheral) of the brain aromatase substrate. ?? 2008 Elsevier Inc.

  5. Brain training with non-action video games enhances aspects of cognition in older adults: a randomized controlled trial.

    PubMed

    Ballesteros, Soledad; Prieto, Antonio; Mayas, Julia; Toril, Pilar; Pita, Carmen; Ponce de León, Laura; Reales, José M; Waterworth, John

    2014-01-01

    Age-related cognitive and brain declines can result in functional deterioration in many cognitive domains, dependency, and dementia. A major goal of aging research is to investigate methods that help to maintain brain health, cognition, independent living and wellbeing in older adults. This randomized controlled study investigated the effects of 20 1-h non-action video game training sessions with games selected from a commercially available package (Lumosity) on a series of age-declined cognitive functions and subjective wellbeing. Two groups of healthy older adults participated in the study, the experimental group who received the training and the control group who attended three meetings with the research team along the study. Groups were similar at baseline on demographics, vocabulary, global cognition, and depression status. All participants were assessed individually before and after the intervention, or a similar period of time, using neuropsychological tests and laboratory tasks to investigate possible transfer effects. The results showed significant improvements in the trained group, and no variation in the control group, in processing speed (choice reaction time), attention (reduction of distraction and increase of alertness), immediate and delayed visual recognition memory, as well as a trend to improve in Affection and Assertivity, two dimensions of the Wellbeing Scale. Visuospatial working memory (WM) and executive control (shifting strategy) did not improve. Overall, the current results support the idea that training healthy older adults with non-action video games will enhance some cognitive abilities but not others. PMID:25352805

  6. Brain training with non-action video games enhances aspects of cognition in older adults: a randomized controlled trial

    PubMed Central

    Ballesteros, Soledad; Prieto, Antonio; Mayas, Julia; Toril, Pilar; Pita, Carmen; Ponce de León, Laura; Reales, José M.; Waterworth, John

    2014-01-01

    Age-related cognitive and brain declines can result in functional deterioration in many cognitive domains, dependency, and dementia. A major goal of aging research is to investigate methods that help to maintain brain health, cognition, independent living and wellbeing in older adults. This randomized controlled study investigated the effects of 20 1-h non-action video game training sessions with games selected from a commercially available package (Lumosity) on a series of age-declined cognitive functions and subjective wellbeing. Two groups of healthy older adults participated in the study, the experimental group who received the training and the control group who attended three meetings with the research team along the study. Groups were similar at baseline on demographics, vocabulary, global cognition, and depression status. All participants were assessed individually before and after the intervention, or a similar period of time, using neuropsychological tests and laboratory tasks to investigate possible transfer effects. The results showed significant improvements in the trained group, and no variation in the control group, in processing speed (choice reaction time), attention (reduction of distraction and increase of alertness), immediate and delayed visual recognition memory, as well as a trend to improve in Affection and Assertivity, two dimensions of the Wellbeing Scale. Visuospatial working memory (WM) and executive control (shifting strategy) did not improve. Overall, the current results support the idea that training healthy older adults with non-action video games will enhance some cognitive abilities but not others. PMID:25352805

  7. 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

  8. An electrophysiological study of the in vitro, perfused brain stem-cerebellum of adult guinea-pig.

    PubMed Central

    Llinás, R; Mühlethaler, M

    1988-01-01

    1. We describe here a technique which allows the long-term in vitro survival of the perfused isolated brain stem-cerebellum of adult guinea-pig. The viability of this preparation was assessed by comparing the electrophysiological properties of individual neurones and of neuronal pools to those obtained in vivo or in brain slices. The areas investigated included the cerebellar cortex, the inferior olive and the pontine nuclei. 2. Cerebellar field potential and intra- and extracellular single-cell recordings could be obtained for as long as 15 h after the preparation was initially isolated. The waveforms of field potentials recorded at various depths in the cerebellar cortex following surface folial stimulation were similar to those recorded in vivo. Extracellular recordings from single Purkinje cells following white matter stimulation demonstrated antidromic as well as mossy- and climbing fibre-mediated excitation. Stimulation of the cerebellar surface elicited orthodromic parallel fibre excitation of Purkinje cells and basket-stellate and Golgi cell inhibition. 3. Intrasomatic and intradendritic recordings from Purkinje cells reproduced all the phenomenology described earlier under in vivo conditions and in vitro slice preparations. In addition, spontaneous excitatory synaptic potentials generating simple spikes (mossy fibre-parallel fibre-mediated activity) and complex spikes (climbing fibre-mediated activity) were consistently observed. 4. Extracellular field potentials and extra- and intracellular recordings from inferior olive neurones were similar to those previously shown for the mammalian inferior olive. 5. Intracellular recordings were also obtained from pontine nuclei neurones, a major source of mossy fibre afferents to the cerebellum. Stimulation of the contralateral superior cerebellar peduncle produced antidromic invasion of these neurones whereas stimulation of the ipsilateral inferior cerebral peduncle resulted in their orthodromic activation. 6. The

  9. Brain lithium, N-acetyl aspartate and myo-inositol levels in older adults with bipolar disorder treated with lithium: a lithium-7 and proton magnetic resonance spectroscopy study

    PubMed Central

    Forester, Brent P; Finn, Chelsea T; Berlow, Yosef A; Wardrop, Megan; Renshaw, Perry F; Moore, Constance M

    2014-01-01

    Objectives We investigated the relationship between brain lithium levels and the metabolites N-acetyl aspartate (NAA) and myo-inositol (myo-Ino) in the anterior cingulate cortex of a group of older adults with bipolar disorder (BD). Methods This cross-sectional assessment included nine subjects (six males and three females) with bipolar I disorder and currently treated with lithium, who were examined at McLean Hospital’s Geriatric Psychiatry Research Program and Brain Imaging Center. The subjects’ ages ranged from 56 to 85 years (66.0 ± 9.7 years) and all subjects had measurements of serum and brain lithium levels. Brain lithium levels were assessed using lithium magnetic resonance spectroscopy. All subjects also had proton magnetic resonance spectroscopy to obtain measurements of NAA and myo-Ino. Results Brain lithium levels were associated with higher NAA levels [df = (1, 8), B = 12.53, t = 4.09, p < 0.005] and higher myo-Ino levels [df = (1, 7), F = 16.81, p < 0.006]. There were no significant effects of serum lithium levels on any of the metabolites. Conclusion Our findings of a relationship between higher brain lithium levels and elevated NAA levels in older adult subjects with BD may support previous evidence of lithium’s neuroprotective, neurotrophic, and mitochondrial function-enhancing effects. Elevated myo-Ino related to elevated brain lithium levels may reflect increased inositol monophosphatase (IMPase) activity, which would lead to an increase in myo-Ino levels. This is the first study to demonstrate alterations in NAA and myo-Ino in a sample of older adults with BD treated with lithium. PMID:18837863

  10. Care of Adults With Intellectual and Developmental Disabilities: Traumatic Brain Injury.

    PubMed

    Jones, Kyle Bradford; Wilson, Benjamin; Weedon, Dean; Bilder, Deborah

    2015-12-01

    Traumatic brain injuries (TBIs) manifest in various forms and severities, and patients with TBIs can have multiple physical and psychological comorbidities. The physician should be prepared to assess effects of the injury and associated comorbidities, and provide needed social support. Common comorbidities include cognitive changes; epilepsy; chronic pain; headache; sleep disorders; neuroendocrine disorders; dizziness and balance issues; substance abuse; depression and anxiety; dementia; and behavioral disturbances, such as aggression. Early severity and cognitive assessment after TBI is key. For patients with mild TBIs, short-term management focuses on cognitive rest, symptom management, and gradual return to regular activities. Short-term management of patients with moderate to severe TBI often requires intensive care unit admission, early psychological consultation, and use of mannitol and probiotics. Long-term care includes monitoring and managing of the physical, behavioral, emotional, and psychological comorbidities that commonly occur in patients with TBIs. Assisting patients in accessing community and government resources can be crucial for improving their independence and quality of life. PMID:26669213

  11. Concurrent and Longitudinal Relationships Between Cognitive Activity, Cognitive Performance, and Brain Volume in Older Adult Women

    PubMed Central

    Erickson, Kirk I.; Espeland, Mark A.; Smith, J. Carson; Tindle, Hilary A.; Rapp, Stephen R.

    2014-01-01

    Objectives. We investigated (a) cross-sectional associations between cognitive activity, cognitive performance, and MRI measures and (b) longitudinal associations between cognitive activity and change in cognitive performance, using structural equation modeling (SEM). Method. Women’s Health Initiative Memory Study (WHIMS) Extension participants who continued annual neuropsychological assessments by telephone and completed a concurrent questionnaire of cognitive activities and MRI scans were included (mean age = 81.4 years; N = 393). Cognitive performance was measured by tests of attention, working memory, verbal fluency, executive function, and memory. Cognitive activity was measured by self-reported participation in a variety of cognitive activities (e.g., reading books, playing games, computer activities; N = 11 items) during the previous 12 months. MRI measures included gray and white matter normal and white matter lesion volumes. Results. SEM demonstrated a significant association between cognitive activity and baseline cognitive performance but not change over 2–3 years. Gray and white matter was associated with cognitive performance but not cognitive activity. All effects remained significant after modeling covariates (age, education, depressive symptoms, WHIMS intervention assignment, and intracranial volume). Conclusions. Cognitive activity benefits current cognitive performance but is not associated with change over 2–3 years. Cognitive activity and MRI volumes are independently associated with cognitive performance, suggesting distinct cognitive and brain reserve constructs. PMID:25209372

  12. Chronic Histopathological and Behavioral Outcomes of Experimental Traumatic Brain Injury in Adult Male Animals.

    PubMed

    Osier, Nicole D; Carlson, Shaun W; DeSana, Anthony; Dixon, C Edward

    2015-12-01

    The purpose of this review is to survey the use of experimental animal models for studying the chronic histopathological and behavioral consequences of traumatic brain injury (TBI). The strategies employed to study the long-term consequences of TBI are described, along with a summary of the evidence available to date from common experimental TBI models: fluid percussion injury; controlled cortical impact; blast TBI; and closed-head injury. For each model, evidence is organized according to outcome. Histopathological outcomes included are gross changes in morphology/histology, ventricular enlargement, gray/white matter shrinkage, axonal injury, cerebrovascular histopathology, inflammation, and neurogenesis. Behavioral outcomes included are overall neurological function, motor function, cognitive function, frontal lobe function, and stress-related outcomes. A brief discussion is provided comparing the most common experimental models of TBI and highlighting the utility of each model in understanding specific aspects of TBI pathology. The majority of experimental TBI studies collect data in the acute postinjury period, but few continue into the chronic period. Available evidence from long-term studies suggests that many of the experimental TBI models can lead to progressive changes in histopathology and behavior. The studies described in this review contribute to our understanding of chronic TBI pathology. PMID:25490251

  13. Circulating Omega‐3 Polyunsaturated Fatty Acids and Subclinical Brain Abnormalities on MRI in Older Adults: The Cardiovascular Health Study

    PubMed Central

    Virtanen, Jyrki K.; Siscovick, David S.; Lemaitre, Rozenn N.; Longstreth, William T.; Spiegelman, Donna; Rimm, Eric B.; King, Irena B.; Mozaffarian, Dariush

    2013-01-01

    Background Consumption of tuna or other broiled or baked fish, but not fried fish, is associated with fewer subclinical brain abnormalities on magnetic resonance imaging (MRI). We investigated the association between plasma phospholipid omega‐3 polyunsaturated fatty acids (PUFAs), objective biomarkers of exposure, and subclinical brain abnormalities on MRI. Methods and Results In the community‐based Cardiovascular Health Study, 3660 participants aged ≥65 underwent brain MRI in 1992–1994, and 2313 were rescanned 5 years later. MRIs were centrally read by neuroradiologists in a standardized, blinded manner. Participants with recognized transient ischemic attacks or stroke were excluded. Phospholipid PUFAs were measured in stored plasma collected in 1992–1993 and related to cross‐sectional and longitudinal MRI findings. After multivariable adjustment, the odds ratio for having a prevalent subclinical infarct was 0.60 (95% CI, 0.44 to 0.82; P for trend=0.001) in the highest versus lowest long‐chain omega‐3 PUFA quartile. Higher long‐chain omega‐3 PUFA content was also associated with better white matter grade, but not with sulcal or ventricular grades, markers of brain atrophy, or with incident subclinical infarcts. The phospholipid intermediate‐chain omega‐3 PUFA alpha‐linolenic acid was associated only with modestly better sulcal and ventricular grades. However, this finding was not supported in the analyses with alpha‐linolenic acid intake. Conclusions Among older adults, higher phospholipid long‐chain omega‐3 PUFA content was associated with lower prevalence of subclinical infarcts and better white matter grade on MRI. Our results support the beneficial effects of fish consumption, the major source of long‐chain omega‐3 PUFAs, on brain health in later life. The role of plant‐derived alpha‐linolenic acid in brain health requires further investigation. PMID:24113325

  14. Bafetinib in Treating Patients With Recurrent High-Grade Glioma or Brain Metastases

    ClinicalTrials.gov

    2013-03-18

    Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Oligodendroglioma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Mixed Glioma; Recurrent Adult Brain Tumor; Tumors Metastatic to Brain; Adult Anaplastic Oligoastrocytoma

  15. The Brain and Consciousness: Sources of Information for Understanding Adult Learning.

    ERIC Educational Resources Information Center

    Hill, Lilian H.

    2001-01-01

    Reviews current knowledge of the brain in the areas of neurobiology, aging, and consciousness as conceived by different cultures. Derives learning principles that take into account the brain's plasticity, ability to respond to learning throughout life, and the involvement of emotional and sensory experience. (Contains 27 references.) (SK)

  16. Structural Dissociation of Attentional Control and Memory in Adults with and without Mild Traumatic Brain Injury

    ERIC Educational Resources Information Center

    Niogi, Sumit N.; Mukherjee, Pratik; Ghajar, Jamshid; Johnson, Carl E.; Kolster, Rachel; Lee, Hana; Suh, Minah; Zimmerman, Robert D.; Manley, Geoffrey T.; McCandliss, Bruce D.

    2008-01-01

    Memory and attentional control impairments are the two most common forms of dysfunction following mild traumatic brain injury (TBI) and lead to significant morbidity in patients, yet these functions are thought to be supported by different brain networks. This 3 T magnetic resonance diffusion tensor imaging (DTI) study investigates whether…

  17. 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…

  18. 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

  19. Accumulation and turnover of the classical Folch-Lees proteolipid proteins in developing and adult rat brain.

    PubMed Central

    Agrawal, H C; Fujimoto, K; Burton, R M

    1976-01-01

    The turnover of classical Folch-Lees proteolipid proteins was studied after administration of [2,3-3H]tryptophan to both developing and adult rat brain. The animals were killed from 2h to 250 days after subcutaneous injections of [3H]tryptophan. The measured specific radioactivity in developing brain attained maximum value 24h after the administration of label, whereas the total radioactivity per brain reached a maximum 21 days after injection. The half-life of proteolipid protein from the measured specific radioactivity was 7-20 days, depending on the time-points used for the calculation, whereas calculation from total radioactivity between 28-77 and 91-257 days gave half-lives of 35-40 and 188 days respectively. In contrast, in animals injected at 40 days of age, the half-life from the whole-brain-radioactivity data was 188 days. The problem of the recycling of radioactivity for the synthesis of myelin proteins from either a general or a discrete amino acid pool is discussed. Images PLATE 1 PMID:938450

  20. 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

  1. Graphene Functionalized Scaffolds Reduce the Inflammatory Response and Supports Endogenous Neuroblast Migration when Implanted in the Adult Brain.

    PubMed

    Zhou, Kun; Motamed, Sepideh; Thouas, George A; Bernard, Claude C; Li, Dan; Parkington, Helena C; Coleman, Harold A; Finkelstein, David I; Forsythe, John S

    2016-01-01

    Electroactive materials have been investigated as next-generation neuronal tissue engineering scaffolds to enhance neuronal regeneration and functional recovery after brain injury. Graphene, an emerging neuronal scaffold material with charge transfer properties, has shown promising results for neuronal cell survival and differentiation in vitro. In this in vivo work, electrospun microfiber scaffolds coated with self-assembled colloidal graphene, were implanted into the striatum or into the subventricular zone of adult rats. Microglia and astrocyte activation levels were suppressed with graphene functionalization. In addition, self-assembled graphene implants prevented glial scarring in the brain 7 weeks following implantation. Astrocyte guidance within the scaffold and redirection of neuroblasts from the subventricular zone along the implants was also demonstrated. These findings provide new functional evidence for the potential use of graphene scaffolds as a therapeutic platform to support central nervous system regeneration. PMID:26978268

  2. Graphene Functionalized Scaffolds Reduce the Inflammatory Response and Supports Endogenous Neuroblast Migration when Implanted in the Adult Brain

    PubMed Central

    Zhou, Kun; Motamed, Sepideh; Thouas, George A.; Bernard, Claude C.; Li, Dan; Parkington, Helena C.; Coleman, Harold A.; Finkelstein, David I.; Forsythe, John S.

    2016-01-01

    Electroactive materials have been investigated as next-generation neuronal tissue engineering scaffolds to enhance neuronal regeneration and functional recovery after brain injury. Graphene, an emerging neuronal scaffold material with charge transfer properties, has shown promising results for neuronal cell survival and differentiation in vitro. In this in vivo work, electrospun microfiber scaffolds coated with self-assembled colloidal graphene, were implanted into the striatum or into the subventricular zone of adult rats. Microglia and astrocyte activation levels were suppressed with graphene functionalization. In addition, self-assembled graphene implants prevented glial scarring in the brain 7 weeks following implantation. Astrocyte guidance within the scaffold and redirection of neuroblasts from the subventricular zone along the implants was also demonstrated. These findings provide new functional evidence for the potential use of graphene scaffolds as a therapeutic platform to support central nervous system regeneration. PMID:26978268

  3. Adult-born hippocampal dentate granule cells undergoing maturation modulate learning and memory in the brain

    PubMed Central

    Deng, Wei; Saxe, Michael D.; Gallina, Iryna S.; Gage, Fred H.

    2009-01-01

    Adult-born dentate granule cells (DGCs) contribute to learning and memory, yet it remains unknown when adult-born DGCs become involved in the cognitive processes. During neurogenesis, immature dentate granule cells (DGCs) display distinctive physiological characteristics while undergoing morphological maturation before final integration into the neural circuits. The survival and activity of the adult-born DGCs can be influenced by the experience of the animal during a critical period when newborn DGCs are still immature. To assess the temporal importance of adult neurogenesis, we developed a transgenic mouse model that allowed us to transiently reduce the numbers of adult-born DGCs in a temporally regulatable manner. We found that mice with a reduced population of adult-born DGCs at the immature stage were deficient in forming robust, long-term spatial memory and displayed impaired performance in extinction tasks. These results suggest that immature DGCs that undergo maturation make important contributions to learning and memory. PMID:19864566

  4. Influence of mild traumatic brain injury during pediatric stage on short-term memory and hippocampal apoptosis in adult rats

    PubMed Central

    Park, Mi-Sook; Oh, Hyean-Ae; Ko, Il-Gyu; Kim, Sung-Eun; Kim, Sang-Hoon; Kim, Chang-Ju; Kim, Hyun-Bae; Kim, Hong

    2014-01-01

    Traumatic brain injury (TBI) is a leading cause of neurological deficit in the brain, which induces short- and long-term brain damage, cognitive impairment with/without structural alteration, motor deficits, emotional problems, and death both in children and adults. In the present study, we evaluated whether mild TBI in childhood causes persisting memory impairment until adulthood. Moreover, we investigated the influence of mild TBI on memory impairment in relation with hippocampal apoptosis. For this, step-down avoidance task, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay, and immunohistochemistry for caspase-3 were performed. Male Sprague-Dawley rats were used in the experiments. The animals were randomly divided into two groups: sham-operation group and TBI-induction group. The mild TBI model was created with an electromagnetic contusion device activated at a velocity of 3.0 m/sec. The results showed that mild TBI during the pediatric stage significantly decreased memory retention. The numbers of TUNEL-positive and caspase-3-positive cells were increased in the TBI-induction group compared to those in the sham-operation group. Defective memory retention and apoptosis sustained up to the adult stage. The present results shows that mild TBI induces long-lasting cognitive impairment from pediatric to adult stages in rats through the high level of apoptosis. The finding of this study suggests that children with mild TBI may need intensive treatments for the reduction of long-lasting cognitive impairment by secondary neuronal damage. PMID:25061593

  5. A little goes a long way: how the adult brain is shaped by musical training in childhood.

    PubMed

    Skoe, Erika; Kraus, Nina

    2012-08-22

    Playing a musical instrument changes the anatomy and function of the brain. But do these changes persist after music training stops? We probed this question by measuring auditory brainstem responses in a cohort of healthy young human adults with varying amounts of past musical training. We show that adults who received formal music instruction as children have more robust brainstem responses to sound than peers who never participated in music lessons and that the magnitude of the response correlates with how recently training ceased. Our results suggest that neural changes accompanying musical training during childhood are retained in adulthood. These findings advance our understanding of long-term neuroplasticity and have general implications for the development of effective auditory training programs. PMID:22915097

  6. Adolescent, but Not Adult, Binge Ethanol Exposure Leads to Persistent Global Reductions of Choline Acetyltransferase Expressing Neurons in Brain

    PubMed Central

    Vetreno, Ryan P.; Broadwater, Margaret; Liu, Wen; Spear, Linda P.; Crews, Fulton T.

    2014-01-01

    During the adolescent transition from childhood to adulthood, notable maturational changes occur in brain neurotransmitter systems. The cholinergic system is composed of several distinct nuclei that exert neuromodulatory control over cognition, arousal, and reward. Binge drinking and alcohol abuse are common during this stage, which might alter the developmental trajectory of this system leading to long-term changes in adult neurobiology. In Experiment 1, adolescent intermittent ethanol (AIE; 5.0 g/kg, i.g., 2-day on/2-day off from postnatal day [P] 25 to P55) treatment led to persistent, global reductions of choline acetyltransferase (ChAT) expression. Administration of the Toll-like receptor 4 agonist lipopolysaccharide to young adult rats (P70) produced a reduction in ChAT+IR that mimicked AIE. To determine if the binge ethanol-induced ChAT decline was unique to the adolescent, Experiment 2 examined ChAT+IR in the basal forebrain following adolescent (P28–P48) and adult (P70–P90) binge ethanol exposure. Twenty-five days later, ChAT expression was reduced in adolescent, but not adult, binge ethanol-exposed animals. In Experiment 3, expression of ChAT and vesicular acetylcholine transporter expression was found to be significantly reduced in the alcoholic basal forebrain relative to moderate drinking controls. Together, these data suggest that adolescent binge ethanol decreases adult ChAT expression, possibly through neuroimmune mechanisms, which might impact adult cognition, arousal, or reward sensitivity. PMID:25405505

  7. Tai Chi Chuan optimizes the functional organization of the intrinsic human brain architecture in older adults

    PubMed Central

    Wei, Gao-Xia; Dong, Hao-Ming; Yang, Zhi; Luo, Jing; Zuo, Xi-Nian

    2014-01-01

    Whether Tai Chi Chuan (TCC) can influence the intrinsic functional architecture of the human brain remains unclear. To examine TCC-associated changes in functional connectomes, resting-state functional magnetic resonance images were acquired from 40 older individuals including 22 experienced TCC practitioners (experts) and 18 demographically matched TCC-naïve healthy controls, and their local functional homogeneities across the cortical mantle were compared. Compared to the controls, the TCC experts had significantly greater and more experience-dependent functional homogeneity in the right post-central gyrus (PosCG) and less functional homogeneity in the left anterior cingulate cortex (ACC) and the right dorsal lateral prefrontal cortex. Increased functional homogeneity in the PosCG was correlated with TCC experience. Intriguingly, decreases in functional homogeneity (improved functional specialization) in the left ACC and increases in functional homogeneity (improved functional integration) in the right PosCG both predicted performance gains on attention network behavior tests. These findings provide evidence for the functional plasticity of the brain’s intrinsic architecture toward optimizing locally functional organization, with great implications for understanding the effects of TCC on cognition, behavior and health in aging population. PMID:24860494

  8. Multi- and unisensory decoding of words and nonwords result in differential brain responses in dyslexic and nondyslexic adults.

    PubMed

    Kast, Monika; Bezzola, Ladina; Jäncke, Lutz; Meyer, Martin

    2011-12-01

    The present functional magnetic resonance imaging (fMRI) study was designed, in order to investigate the neural substrates involved in the audiovisual processing of disyllabic German words and pseudowords. Twelve dyslexic and 13 nondyslexic adults performed a lexical decision task while stimuli were presented unimodally (either aurally or visually) or bimodally (audiovisually simultaneously). The behavioral data collected during the experiment evidenced more accurate processing for bimodally than for unimodally presented stimuli irrespective of group. Words were processed faster than pseudowords. Notably, no group differences have been found for either accuracy or for reaction times. With respect to brain responses, nondyslexic compared to dyslexic adults elicited stronger hemodynamic responses in the leftward supramarginal gyrus (SMG), as well as in the right hemispheric superior temporal sulcus (STS). Furthermore, dyslexic compared to nondyslexic adults showed reduced responses to only aurally presented signals and enhanced hemodynamic responses to audiovisual, as well as visual stimulation in the right anterior insula. Our behavioral results evidence that the two groups easily identified the two-syllabic proper nouns that we provided them with. Our fMRI results indicate that dyslexics show less neuronal involvement of heteromodal and extrasylvian regions, namely, the STS, SMG, and insula when decoding phonological information. We posit that dyslexic adults evidence deficient functioning of word processing, which could possibly be attributed to deficits in phoneme to grapheme mapping. This problem may be caused by impaired audiovisual processing in multimodal areas. PMID:21641022

  9. One-year age changes in MRI brain volumes in older adults.

    PubMed

    Resnick, S M; Goldszal, A F; Davatzikos, C; Golski, S; Kraut, M A; Metter, E J; Bryan, R N; Zonderman, A B

    2000-05-01

    Longitudinal studies indicate that declines in cognition and memory accelerate after age 70 years. The neuroanatomic and neurophysiologic underpinnings of cognitive change are unclear, as there is little information on longitudinal brain changes. We are conducting a longitudinal neuroimaging study of nondemented older participants in the Baltimore Longitudinal Study of Aging. This report focuses on age and sex differences in brain structure measured by magnetic resonance imaging during the first two annual evaluations. Cross-sectional results from 116 participants aged 59-85 years reveal significantly larger ventricular volumes and smaller gray and white matter volumes in older compared with younger participants and in men compared with women. Regional brain volumes show that the effects of age and sex are not uniform across brain regions. Age differences are greatest for the parietal region. Sex differences tend to be larger for frontal and temporal than parietal and occipital regions. Longitudinal analysis demonstrates an increase of 1526 mm(3) in ventricular volume over 1 year, but no detectable change in total or regional brain volumes. Definition of the pattern and rate of longitudinal brain changes will facilitate the detection of pathological brain changes, which may be predictors of dementia. PMID:10847596

  10. 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

  11. Brain activity during source memory retrieval in young, middle-aged and old adults.

    PubMed

    Cansino, Selene; Trejo-Morales, Patricia; Estrada-Manilla, Cinthya; Pasaye-Alcaraz, Erick Humberto; Aguilar-Castañeda, Erika; Salgado-Lujambio, Perla; Sosa-Ortiz, Ana Luisa

    2015-08-27

    We investigated neurofunctional changes associated with source memory decline across the adult life span using functional magnetic resonance imaging (fMRI). Young, middle-aged and old adults carried out a natural/artificial judgment of images of common objects that were randomly presented in one of the quadrants of the screen. At retrieval, the images were displayed at the center of the screen and the participants judged whether each image was new or old and, if old, they indicated in which quadrant of the screen the image had originally been presented. Comparing the items associated with correct versus incorrect source judgments revealed that no regions showed greater activity in young adults than in middle-aged adults; however, in young and middle-aged adults the activity in the left hippocampus and left anterior temporal cortex was of greater magnitude than in the older adults. Several regions also exhibited greater activity in young adults than in old adults. These results suggest that in middle age the recollection neural network, assessable by fMRI, is still preserved. PMID:26054305

  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. Design and Validation of a Novel Method to Measure Cross-Sectional Area of Neck Muscles Included during Routine MR Brain Volume Imaging

    PubMed Central

    Kilgour, Alixe H. M.; Subedi, Deepak; Gray, Calum D.; Deary, Ian J.; Lawrie, Stephen M.; Wardlaw, Joanna M.; Starr, John M.

    2012-01-01

    Introduction Low muscle mass secondary to disease and ageing is an important cause of excess mortality and morbidity. Many studies include a MR brain scan but no peripheral measure of muscle mass. We developed a technique to measure posterior neck muscle cross-sectional area (CSA) on volumetric MR brain scans enabling brain and muscle size to be measured simultaneously. Methods We performed four studies to develop and test: feasibility, inter-rater reliability, repeatability and external validity. We used T1-weighted MR brain imaging from young and older subjects, obtained on different scanners, and collected mid-thigh MR data. Results After developing the technique and demonstrating feasibility, we tested it for inter-rater reliability in 40 subjects. Intraclass correlation coefficients (ICC) between raters were 0.99 (95% confidence intervals (CI) 0.98–1.00) for the combined group (trapezius, splenius and semispinalis), 0.92 (CI 0.85–0.96) for obliquus and 0.92 (CI 0.85–0.96) for sternocleidomastoid. The first unrotated principal component explained 72.2% of total neck muscle CSA variance and correlated positively with both right (r = 0.52, p = .001) and left (r = 0.50, p = .002) grip strength. The 14 subjects in the repeatability study had had two MR brain scans on three different scanners. The ICC for between scanner variation for total neck muscle CSA was high at 0.94 (CI 0.86–0.98). The ICCs for within scanner variations were also high, with values of 0.95 (CI 0.86–0.98), 0.97 (CI 0.92–0.99) and 0.96 (CI 0.86–0.99) for the three scanners. The external validity study found a correlation coefficient for total thigh CSA and total neck CSA of 0.88. Discussion We present a feasible, valid and reliable method for measuring neck muscle CSA on T1-weighted MR brain scans. Larger studies are needed to validate and apply our technique with subjects differing in age, ethnicity and geographical location. PMID:22509305

  14. Incidence of adult brain cancers is higher in countries where the protozoan parasite Toxoplasma gondii is common

    USGS Publications Warehouse

    Thomas, Frédéric; Lafferty, Kevin D.; Brodeur, Jacques; Elguero, Eric; Gauthier-Clerc, Michel; Missé, Dorothée

    2012-01-01

    We explored associations between the common protozoan parasite Toxoplasma gondii and brain cancers in human populations. We predicted that T. gondii could increase the risk of brain cancer because it is a long-lived parasite that encysts in the brain, where it provokes inflammation and inhibits apoptosis. We used a medical geography approach based on the national incidence of brain cancers and seroprevalence of T. gondii. We corrected reports of incidence for national gross domestic product because wealth probably increases the ability to detect cancer. We also included gender, cell phone use and latitude as variables in our initial models. Prevalence of T. gondii explained 19 per cent of the residual variance in brain cancer incidence after controlling for the positive effects of gross domestic product and latitude among nations. Infection with T. gondii was associated with a 1.8-fold increase in the risk of brain cancers across the range of T. gondii prevalence in our dataset (4–67%). These results, though correlational, suggest that T. gondii should be investigated further as a possible oncogenic pathogen of humans.

  15. Normal Neurochemistry in the Prefrontal and Cerebellar Brain of Adults with Attention-Deficit Hyperactivity Disorder

    PubMed Central

    Endres, Dominique; Perlov, Evgeniy; Maier, Simon; Feige, Bernd; Nickel, Kathrin; Goll, Peter; Bubl, Emanuel; Lange, Thomas; Glauche, Volkmar; Graf, Erika; Ebert, Dieter; Sobanski, Esther; Philipsen, Alexandra; Tebartz van Elst, Ludger

    2015-01-01

    Attention-deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. In an attempt to extend earlier neurochemical findings, we organized a magnetic resonance spectroscopy (MRS) study as part of a large, government-funded, prospective, randomized, multicenter clinical trial comparing the effectiveness of specific psychotherapy with counseling and stimulant treatment with placebo treatment (Comparison of Methylphenidate and Psychotherapy Study). We report the baseline neurochemical data for the anterior cingulate cortex (ACC) and the cerebellum in a case–control setting. For the trial, 1,480 adult patients were contacted for participation, 518 were assessed for eligibility, 433 were randomized, and 187 were potentially eligible for neuroimaging. The control group included 119 healthy volunteers. Single-voxel proton MRS was performed. In the patient group, 113 ACC and 104 cerebellar spectra fulfilled all quality criteria for inclusion in statistical calculations, as did 82 ACC and 78 cerebellar spectra in the control group. We did not find any significant neurometabolic differences between the ADHD and control group in the ACC (Wilks’ lambda test: p = 0.97) or in the cerebellum (p = 0.62). Thus, we were unable to replicate earlier findings in this methodologically sophisticated study. We discuss our findings in the context of a comprehensive review of other MRS studies on ADHD and a somewhat skeptical neuropsychiatric research perspective. As in other neuropsychiatric disorders, the unclear nosological status of ADHD might be an explanation for false-negative findings. PMID:26441572

  16. Cytochrome c oxidase response to changes in cerebral oxygen delivery in the adult brain shows higher brain-specificity than haemoglobin☆

    PubMed Central

    Kolyva, Christina; Ghosh, Arnab; Tachtsidis, Ilias; Highton, David; Cooper, Chris E.; Smith, Martin; Elwell, Clare E.

    2014-01-01

    The redox state of cerebral mitochondrial cytochrome c oxidase monitored with near-infrared spectroscopy (Δ[oxCCO]) is a signal with strong potential as a non-invasive, bedside biomarker of cerebral metabolic status. We hypothesised that the higher mitochondrial density of brain compared to skin and skull would lead to evidence of brain-specificity of the Δ[oxCCO] signal when measured with a multi-distance near-infrared spectroscopy (NIRS) system. Measurements of Δ[oxCCO] as well as of concentration changes in oxygenated (Δ[HbO2]) and deoxygenated haemoglobin (Δ[HHb]) were taken at multiple source-detector distances during systemic hypoxia and hypocapnia (decrease in cerebral oxygen delivery), and hyperoxia and hypercapnia (increase in cerebral oxygen delivery) from 15 adult healthy volunteers. Increasing source-detector spacing is associated with increasing light penetration depth and thus higher sensitivity to cerebral changes. An increase in Δ[oxCCO] was observed during the challenges that increased cerebral oxygen delivery and the opposite was observed when cerebral oxygen delivery decreased. A consistent pattern of statistically significant increasing amplitude of the Δ[oxCCO] response with increasing light penetration depth was observed in all four challenges, a behaviour that was distinctly different from that of the haemoglobin chromophores, which did not show this statistically significant depth gradient. This depth-dependence of the Δ[oxCCO] signal corroborates the notion of higher concentrations of CCO being present in cerebral tissue compared to extracranial components and highlights the value of NIRS-derived Δ[oxCCO] as a brain-specific signal of cerebral metabolism, superior in this aspect to haemoglobin. PMID:23707584

  17. Cytochrome c oxidase response to changes in cerebral oxygen delivery in the adult brain shows higher brain-specificity than haemoglobin.

    PubMed

    Kolyva, Christina; Ghosh, Arnab; Tachtsidis, Ilias; Highton, David; Cooper, Chris E; Smith, Martin; Elwell, Clare E

    2014-01-15

    The redox state of cerebral mitochondrial cytochrome c oxidase monitored with near-infrared spectroscopy (Δ[oxCCO]) is a signal with strong potential as a non-invasive, bedside biomarker of cerebral metabolic status. We hypothesised that the higher mitochondrial density of brain compared to skin and skull would lead to evidence of brain-specificity of the Δ[oxCCO] signal when measured with a multi-distance near-infrared spectroscopy (NIRS) system. Measurements of Δ[oxCCO] as well as of concentration changes in oxygenated (Δ[HbO2]) and deoxygenated haemoglobin (Δ[HHb]) were taken at multiple source-detector distances during systemic hypoxia and hypocapnia (decrease in cerebral oxygen delivery), and hyperoxia and hypercapnia (increase in cerebral oxygen delivery) from 15 adult healthy volunteers. Increasing source-detector spacing is associated with increasing light penetration depth and thus higher sensitivity to cerebral changes. An increase in Δ[oxCCO] was observed during the challenges that increased cerebral oxygen delivery and the opposite was observed when cerebral oxygen delivery decreased. A consistent pattern of statistically significant increasing amplitude of the Δ[oxCCO] response with increasing light penetration depth was observed in all four challenges, a behaviour that was distinctly different from that of the haemoglobin chromophores, which did not show this statistically significant depth gradient. This depth-dependence of the Δ[oxCCO] signal corroborates the notion of higher concentrations of CCO being present in cerebral tissue compared to extracranial components and highlights the value of NIRS-derived Δ[oxCCO] as a brain-specific signal of cerebral metabolism, superior in this aspect to haemoglobin. PMID:23707584

  18. Inhibition of acetylcholinesterase activity in brain and behavioral analysis in adult rats after chronic administration of fenproporex.

    PubMed

    Rezin, Gislaine T; Scaini, Giselli; Ferreira, Gabriela K; Cardoso, Mariane R; Gonçalves, Cinara L; Constantino, Larissa S; Deroza, Pedro F; Ghedim, Fernando V; Valvassori, Samira S; Resende, Wilson R; Quevedo, João; Zugno, Alexandra I; Streck, Emilio L

    2012-12-01

    Fenproporex is an amphetamine-based anorectic and it is rapidly converted in vivo into amphetamine. It elevates the levels of extracellular dopamine in the brain. Acetylcholinesterase is a regulatory enzyme which is involved in cholinergic synapses and may indirectly modulate the release of dopamine. Thus, we investigated whether the effects of chronic administration of fenproporex in adult rats alters acquisition and retention of avoidance memory and acetylcholinesterase activity. Adult male Wistar rats received repeated (14 days) intraperitoneal injection of vehicle or fenproporex (6.25, 12.5 or 25 mg/kg i.p.). For behavioral assessment, animals were submitted to inhibitory avoidance (IA) tasks and continuous multiple trials step-down inhibitory avoidance (CMIA). Acetylcholinesterase activity was measured in the prefrontal cortex, hippocampus, hypothalamus and striatum. The administration of fenproporex (6.25, 12.5 and 25 mg/kg) did not induce impairment in short and long-term IA or CMIA retention memory in rats. In addition, longer periods of exposure to fenproporex administration decreased acetylcholinesterase activity in prefrontal cortex and striatum of rats, but no alteration was verified in the hippocampus and hypothalamus. In conclusion, the present study showed that chronic fenproporex administration decreased acetylcholinesterase activity in the rat brain. However, longer periods of exposure to fenproporex did not produce impairment in short and long-term IA or CMIA retention memory in rats. PMID:22832793

  19. Environmental Circadian Disruption Worsens Neurologic Impairment and Inhibits Hippocampal Neurogenesis in Adult Rats After Traumatic Brain Injury.

    PubMed

    Li, Dongpeng; Ma, Shanshan; Guo, Dewei; Cheng, Tian; Li, Hongwei; Tian, Yi; Li, Jianbin; Guan, Fangxia; Yang, Bo; Wang, Jian

    2016-10-01

    Circadian rhythms modulate many physiologic processes and behaviors. Therefore, their disruption causes a variety of potential adverse effects in humans and animals. Circadian disruption induced by constant light exposure has been discovered to produce pathophysiologic consequences after brain injury. However, the underlying mechanisms that lead to more severe impairment and disruption of neurophysiologic processes are not well understood. Here, we evaluated the effect of constant light exposure on the neurobehavioral impairment and survival of neurons in rats after traumatic brain injury (TBI). Sixty adult male Sprague-Dawley rats were subjected to a weight-drop model of TBI and then exposed to either a standard 12-/12-h light/dark cycle or a constant 24-h light/light cycle for 14 days. Our results showed that 14 days of constant light exposure after TBI significantly worsened the sensorimotor and cognitive deficits, which were associated with decreased body weight, impaired water and food intake, increased cortical lesion volume, and decreased neuronal survival. Furthermore, environmental circadian disruption inhibited cell proliferation and newborn cell survival and decreased immature cell production in rats subjected to the TBI model. We conclude that circadian disruption induced by constant light exposure worsens histologic and neurobehavioral impairment and inhibits neurogenesis in adult TBI rats. Our novel findings suggest that light exposure should be decreased and circadian rhythm reestablished in hospitalized TBI patients and that drugs and strategies that maintain circadian rhythm would offer a novel therapeutic option. PMID:26886755

  20. Training-related changes in early visual processing of functionally illiterate adults: evidence from event-related brain potentials

    PubMed Central

    2013-01-01

    Background Event-related brain potentials (ERPs) were used to investigate training-related changes in fast visual word recognition of functionally illiterate adults. Analyses focused on the left-lateralized occipito-temporal N170, which represents the earliest processing of visual word forms. Event-related brain potentials were recorded from 20 functional illiterates receiving intensive literacy training for adults, 10 functional illiterates not participating in the training and 14 regular readers while they read words, pseudowords or viewed symbol strings. Subjects were required to press a button whenever a stimulus was immediately repeated. Results Attending intensive literacy training was associated with improvements in reading and writing skills and with an increase of the word-related N170 amplitude. For untrained functional illiterates and regular readers no changes in literacy skills or N170 amplitude were observed. Conclusions Results of the present study suggest that the word-related N170 can still be modulated in adulthood as a result of the improvements in literacy skills. PMID:24330622

  1. Follistatin-like 5 is expressed in restricted areas of the adult mouse brain: Implications for its function in the olfactory system.

    PubMed

    Masuda, Tomoyuki; Sakuma, Chie; Nagaoka, Atsuko; Yamagishi, Toshiyuki; Ueda, Shuichi; Nagase, Takahiro; Yaginuma, Hiroyuki

    2014-02-01

    Follistatin-like 5 (Fstl5), a member of the follistatin family of genes, encodes a secretory glycoprotein. Previous studies revealed that other members of this family including Fstl1 and Fstl3 play an essential role in development, homeostasis, and congenital disorders. However, the in vivo function of Fstl5 is poorly understood. To gain insight into the function of Fstl5 in the mouse central nervous system, we examined the Fstl5 expression pattern in the adult mouse brain. The results of in situ hybridization analysis showed a highly restricted pattern of Fstl5, namely, with localization in the olfactory system, hippocampal CA3 area and granular cell layer of the cerebellum. Restricted expression in the olfactory system suggests a possible role for Fstl5 in maintaining odor perception. PMID:24588779

  2. The DSM-5 Dimensional Anxiety Scales in a Dutch non-clinical sample: psychometric properties including the adult separation anxiety disorder scale.

    PubMed

    Möller, Eline L; Bögels, Susan M

    2016-09-01

    With DSM-5, the American Psychiatric Association encourages complementing categorical diagnoses with dimensional severity ratings. We therefore examined the psychometric properties of the DSM-5 Dimensional Anxiety Scales, a set of brief dimensional scales that are consistent in content and structure and assess DSM-5-based core features of anxiety disorders. Participants (285 males, 255 females) completed the DSM-5 Dimensional Anxiety Scales for social anxiety disorder, generalized anxiety disorder, specific phobia, agoraphobia, and panic disorder that were included in previous studies on the scales, and also for separation anxiety disorder, which is included in the DSM-5 chapter on anxiety disorders. Moreover, they completed the Screen for Child Anxiety Related Emotional Disorders Adult version (SCARED-A). The DSM-5 Dimensional Anxiety Scales demonstrated high internal consistency, and the scales correlated significantly and substantially with corresponding SCARED-A subscales, supporting convergent validity. Separation anxiety appeared present among adults, supporting the DSM-5 recognition of separation anxiety as an anxiety disorder across the life span. To conclude, the DSM-5 Dimensional Anxiety Scales are a valuable tool to screen for specific adult anxiety disorders, including separation anxiety. Research in more diverse and clinical samples with anxiety disorders is needed. © 2016 The Authors International Journal of Methods in Psychiatric Research Published by John Wiley & Sons Ltd. PMID:27378317

  3. 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

  4. Botulinum toxin assessment, intervention and aftercare for paediatric and adult niche indications including pain: international consensus statement.

    PubMed

    Rawicki, B; Sheean, G; Fung, V S C; Goldsmith, S; Morgan, C; Novak, I

    2010-08-01

    Evidence is emerging for the use of botulinum neurotoxin type-A (BoNT-A) for niche indications including pain independent of spasticity. Pain indications such as chronic nociceptive back pain, piriformis syndrome, chronic myofascial pain, pelvic pain, complex regional pain syndrome, facial pain and neuropathic pain are outlined in this paper. Of these, class I evidence is available for the treatment of chronic nociceptive low back pain, piriformis syndrome, myofascial pain, facial pain, neuropathic pain and plantar fasciitis. Peri-operative use of BoNT-A is emerging, with indications including planning for surgery and facilitating surgery, as well as healing and improving analgesia post-operatively. Evidence is limited, although there are some reports that clinicians are successfully using BoNT-A peri-operatively. There is class I evidence showing pre-operative use of BoNT-A has a beneficial effect on outcomes following adductor-release surgery. The use of BoNT for treatment of tremor, other than neck tremor in the setting of cervical dystonia, including evidence for upper limb tremor, cranial tremor and non-dystonic neck tremor is reviewed. The evidence is variable at this stage, and further study is required to develop definitive recommendations for the clinical utility of BoNT-A for these indications. PMID:20633183

  5. Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

    SciTech Connect

    Gondi, Vinai; Hermann, Bruce P.; Mehta, Minesh P.; Tome, Wolfgang A.

    2012-07-15

    Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation of the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients

  6. Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

    SciTech Connect

    Gondi, Vinai; Hermann, Bruce P.; Mehta, Minesh P.; Tome, Wolfgang A.

    2013-02-01

    Purpose: To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). Methods and Materials: Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score {<=}-1.5. After delineation of the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD{sub 2}) assuming an {alpha}/{beta} ratio of 2 Gy were computed. Fisher's exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. Results: Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD{sub 2} to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD{sub 2} to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD{sub 2} to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients

  7. In Vivo Neural Tissue Engineering: Cylindrical Biocompatible Hydrogels That Create New Neural Tracts in the Adult Mammalian Brain.

    PubMed

    Clark, Amanda R; Carter, Arrin B; Hager, Lydia E; Price, Elmer M

    2016-08-01

    Individuals with neurodegenerative disorders or brain injury have few treatment options and it has been proposed that endogenous adult neural stem cells can be harnessed to repopulate dysfunctional nonneurogenic regions of the brain. We have accomplished this through the development of rationally designed hydrogel implants that recruit endogenous cells from the adult subventricular zone to create new relatively long tracts of neuroblasts. These implants are biocompatible and biodegradable cylindrical hydrogels consisting of fibrin and immobilized neurotrophic factors. When implanted into rat brain such that the cylinder intersected the migratory path of endogenous neural progenitors (the rostral migratory stream) and led into the nonneurogenic striatum, we observed a robust neurogenic response in the form of migrating neuroblasts with long (>100 μm) complex neurites. The location of these new neural cells in the striatum was directly coincident with the original track of the fibrin implant, which itself had completely degraded, and covered a significant area and distance (>2.5 mm). We also observed a significant number of neuroblasts in the striatal region between the implant track and the lateral ventricle. When these fibrin cylinders were implanted into hemiparkinson rats, correction of parkinsonian behavior was observed. There were no obvious behavioral, inflammatory or tumorigenic sequelae as a consequence of the implants. In conclusion, we have successfully engineered neural tissue in vivo, using neurogenic biomaterials cast into a unique cylindrical architecture. These results represent a novel approach to efficiently induce neurogenesis in a controlled and targeted manner, which may lead toward a new therapeutic modality for neurological disorders. PMID:27295980

  8. Brain lateralization and self-reported symptoms of ADHD in a population sample of adults: a dimensional approach

    PubMed Central

    Mohamed, Saleh M. H.; Börger, Norbert A.; Geuze, Reint H.; van der Meere, Jaap J.

    2015-01-01

    Many clinical studies reported a compromised brain lateralization in patients with Attention-Deficit/Hyperactivity Disorder (ADHD) without being conclusive about whether the deficit existed in the left or right hemisphere. It is well-recognized that studying ADHD dimensionally is more controlled for comorbid problems and medication effects, and provides more accurate assessment of the symptoms. Therefore, the present study applied the dimensional approach to test the relationship between brain lateralization and self-reported ADHD symptoms in a population sample. Eighty-five right-handed university students filled in the Conners’ Adult ADHD Rating Scales and performed a lateralization reaction time task. The task consists of two matching conditions: one condition requires nominal identification for letters tapping left hemisphere specialization (Letter Name-Identity condition) and the other one requires physical and visuospatial identification for shapes tapping right hemisphere specialization (Shape Physical-Identity condition). The letters or shapes to be matched are presented in left or right visual field of a fixation cross. For both task conditions, brain lateralization was indexed as the difference in mean reaction time between left and right visual field. Linear regression analyses, controlled for mood symptoms reported by a depression, anxiety, and stress scale, showed no relationship between the variables. These findings from a population sample of adults do not support the dimensionality of lateralized information processing deficit in ADHD symptomatology. However, group comparison analyses showed that subjects with high level of inattention symptoms close to or above the clinical cut-off had a reduced right hemisphere processing in the Shape Physical-Identity condition. PMID:26441789

  9. Prenatal restraint stress decreases the expression of alpha-7 nicotinic receptor in the brain of adult rat offspring.

    PubMed

    Baier, Carlos J; Pallarés, María E; Adrover, Ezequiela; Monteleone, Melisa C; Brocco, Marcela A; Barrantes, Francisco J; Antonelli, Marta C

    2015-01-01

    Prenatal stress (PS) strongly impacts fetal brain development and function in adulthood. In normal aging and Alzheimer's disease, there is hypothalamic-pituitary-adrenal axis dysfunction and loss of cholinergic neurons and neuronal nicotinic acetylcholine receptors (nAChRs). This study investigated whether prenatal restraint stress affects nAChR expression in the brain of adult offspring. For PS, pregnant dams were placed in a plastic restrainer for 45 min, three times daily during the last week of pregnancy; controls were undisturbed. Male offspring were analyzed at postnatal day (PND) 60 (n = 4 rats per group). Western blot (WB) and fluorescence microscopy showed that PS decreased α7-AChR subunit expression (∼50%) in the frontal cortex in the adult offspring. PS decreased significantly the number of α7-AChR-expressing cells in the medial prefrontal cortex (by ∼25%) and in the sensory-motor cortex (by ∼20%) without affecting the total cell number in those areas. No alterations were found in the hippocampus by quantitative polymerase chain reaction (qPCR), or WB analysis, but a detailed fluorescence microscopy analysis showed that PS affected α7-AChR mainly in the CA3 and dentate gyrus subfields: PS decreased α7-AChR subunit expression by ∼25 and ∼30%, respectively. Importantly, PS decreased the number of α7-AChR-expressing cells and the total cell number (by ∼15 and 20%, respectively) in the dentate gyrus. PS differently affected α4-AChR: PS impaired its mRNA expression in the frontal cortex (by ∼50%), without affecting protein levels. These results demonstrate that disturbances during gestation produce long-term alterations in the expression pattern of α7-AChR in rat brain. PMID:25798813

  10. The Cell Birth Marker BrdU Does Not Affect Recruitment of Subsequent Cell Divisions in the Adult Avian Brain

    PubMed Central

    Cattan, Anat

    2015-01-01

    BrdU is commonly used to quantify neurogenesis but also causes mutation and has mitogenic, transcriptional, and translational effects. In mammalian studies, attention had been given to its dosage, but in birds such examination was not conducted. Our previous study suggested that BrdU might affect subsequent cell divisions and neuronal recruitment in the brain. Furthermore, this effect seemed to increase with time from treatment. Accordingly, we examined whether BrdU might alter neurogenesis in the adult avian brain. We compared recruitment of [3H]-thymidine+ neurons in brains of zebra finches (Taeniopygia guttata) when no BrdU was involved and when BrdU was given 1 or 3 months prior to [3H]-thymidine. In nidopallium caudale, HVC, and hippocampus, no differences were found between groups in densities and percentages of [3H]-thymidine+ neurons. The number of silver grains per [3H]-thymidine+ neuronal nucleus and their distribution were similar across groups. Additionally, time did not affect the results. The results indicate that the commonly used dosage of BrdU in birds has no long-term effects on subsequent cell divisions and neuronal recruitment. This conclusion is also important in neuronal replacement experiments, where BrdU and another cell birth marker are given, with relatively long intervals between them. PMID:25759813

  11. 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

  12. The cell birth marker BrdU does not affect recruitment of subsequent cell divisions in the adult avian brain.

    PubMed

    Cattan, Anat; Ayali, Amir; Barnea, Anat

    2015-01-01

    BrdU is commonly used to quantify neurogenesis but also causes mutation and has mitogenic, transcriptional, and translational effects. In mammalian studies, attention had been given to its dosage, but in birds such examination was not conducted. Our previous study suggested that BrdU might affect subsequent cell divisions and neuronal recruitment in the brain. Furthermore, this effect seemed to increase with time from treatment. Accordingly, we examined whether BrdU might alter neurogenesis in the adult avian brain. We compared recruitment of [(3)H]-thymidine(+) neurons in brains of zebra finches (Taeniopygia guttata) when no BrdU was involved and when BrdU was given 1 or 3 months prior to [(3)H]-thymidine. In nidopallium caudale, HVC, and hippocampus, no differences were found between groups in densities and percentages of [(3)H]-thymidine(+) neurons. The number of silver grains per [(3)H]-thymidine(+) neuronal nucleus and their distribution were similar across groups. Additionally, time did not affect the results. The results indicate that the commonly used dosage of BrdU in birds has no long-term effects on subsequent cell divisions and neuronal recruitment. This conclusion is also important in neuronal replacement experiments, where BrdU and another cell birth marker are given, with relatively long intervals between them. PMID:25759813

  13. 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

  14. Gender and age related expression of Oct-6--a POU III domain transcription factor, in the adult mouse brain.