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Sample records for adult rodent brains

  1. In Vivo Targeted Magnetic Resonance Imaging of Endogenous Neural Stem Cells in the Adult Rodent Brain

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    Xiao-Mei Zhong

    2015-01-01

    Full Text Available Neural stem cells in the adult mammalian brain have a significant level of neurogenesis plasticity. In vivo monitoring of adult endogenous NSCs would be of great benefit to the understanding of the neurogenesis plasticity under normal and pathological conditions. Here we show the feasibility of in vivo targeted MR imaging of endogenous NSCs in adult mouse brain by intraventricular delivery of monoclonal anti-CD15 antibody conjugated superparamagnetic iron oxide nanoparticles. After intraventricular administration of these nanoparticles, the subpopulation of NSCs in the anterior subventricular zone and the beginning of the rostral migratory stream could be in situ labeled and were in vivo visualized with 7.0-T MR imaging during a period from 1 day to 7 days after the injection. Histology confirmed that the injected targeted nanoparticles were specifically bound to CD15 positive cells and their surrounding extracellular matrix. Our results suggest that in vivo targeted MR imaging of endogenous neural stem cells in adult rodent brain could be achieved by using anti-CD15-SPIONs as the molecular probe; and this targeting imaging strategy has the advantage of a rapid in vivo monitoring of the subpopulation of endogenous NSCs in adult brains.

  2. Antidepressant drugs transactivate TrkB neurotrophin receptors in the adult rodent brain independently of BDNF and monoamine transporter blockade.

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    Tomi Rantamäki

    Full Text Available BACKGROUND: Antidepressant drugs (ADs have been shown to activate BDNF (brain-derived neurotrophic factor receptor TrkB in the rodent brain but the mechanism underlying this phenomenon remains unclear. ADs act as monoamine reuptake inhibitors and after prolonged treatments regulate brain bdnf mRNA levels indicating that monoamine-BDNF signaling regulate AD-induced TrkB activation in vivo. However, recent findings demonstrate that Trk receptors can be transactivated independently of their neurotrophin ligands. METHODOLOGY: In this study we examined the role of BDNF, TrkB kinase activity and monoamine reuptake in the AD-induced TrkB activation in vivo and in vitro by employing several transgenic mouse models, cultured neurons and TrkB-expressing cell lines. PRINCIPAL FINDINGS: Using a chemical-genetic TrkB(F616A mutant and TrkB overexpressing mice, we demonstrate that ADs specifically activate both the maturely and immaturely glycosylated forms of TrkB receptors in the brain in a TrkB kinase dependent manner. However, the tricyclic AD imipramine readily induced the phosphorylation of TrkB receptors in conditional bdnf⁻/⁻ knock-out mice (132.4±8.5% of control; P = 0.01, indicating that BDNF is not required for the TrkB activation. Moreover, using serotonin transporter (SERT deficient mice and chemical lesions of monoaminergic neurons we show that neither a functional SERT nor monoamines are required for the TrkB phosphorylation response induced by the serotonin selective reuptake inhibitors fluoxetine or citalopram, or norepinephrine selective reuptake inhibitor reboxetine. However, neither ADs nor monoamine transmitters activated TrkB in cultured neurons or cell lines expressing TrkB receptors, arguing that ADs do not directly bind to TrkB. CONCLUSIONS: The present findings suggest that ADs transactivate brain TrkB receptors independently of BDNF and monoamine reuptake blockade and emphasize the need of an intact tissue context for the

  3. Brain tumor - primary - adults

    Science.gov (United States)

    ... 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, ...

  4. Cellular scaling rules for rodent brains

    OpenAIRE

    Herculano-Houzel, Suzana; Mota, Bruno; Lent, Roberto

    2006-01-01

    How do cell number and size determine brain size? Here, we show that, in the order Rodentia, increased size of the cerebral cortex, cerebellum, and remaining areas across six species is achieved through greater numbers of neurons of larger size, and much greater numbers of nonneuronal cells of roughly invariant size, such that the ratio between total neuronal and nonneuronal mass remains constant across species. Although relative cerebellar size remains stable among rodents, the number of cer...

  5. Comparative transcriptome analysis in induced neural stem cells reveals defined neural cell identities in vitro and after transplantation into the adult rodent brain

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    Anna-Lena Hallmann

    2016-05-01

    Full Text Available Reprogramming technology enables the production of neural progenitor cells (NPCs from somatic cells by direct transdifferentiation. However, little is known on how neural programs in these induced neural stem cells (iNSCs differ from those of alternative stem cell populations in vitro and in vivo. Here, we performed transcriptome analyses on murine iNSCs in comparison to brain-derived neural stem cells (NSCs and pluripotent stem cell-derived NPCs, which revealed distinct global, neural, metabolic and cell cycle-associated marks in these populations. iNSCs carried a hindbrain/posterior cell identity, which could be shifted towards caudal, partially to rostral but not towards ventral fates in vitro. iNSCs survived after transplantation into the rodent brain and exhibited in vivo-characteristics, neural and metabolic programs similar to transplanted NSCs. However, iNSCs vastly retained caudal identities demonstrating cell-autonomy of regional programs in vivo. These data could have significant implications for a variety of in vitro- and in vivo-applications using iNSCs.

  6. A Novel Rodent Model of Autism: Intraventricular Infusions of Propionic Acid Increase Locomotor Activity and Induce Neuroinflammation and Oxidative Stress in Discrete Regions of Adult Rat Brain

    OpenAIRE

    Derrick F. MacFabe; Karina Rodríguez-Capote; Jennifer E.  Franklin; Martin Kavaliers; Fred Possmayer; Klaus-Peter Ossenkopp; Andrew E. Franklin

    2008-01-01

    Innate neuroinflammatory changes, increased oxidative stress and disorders of glutathione metabolism may be involved in the pathophysiology of autism spectrum disorders (ASD). Propionic acid (PPA) is a dietary and gut bacterial short chain fatty acid which can produce brain and behavioral changes reminiscent of ASD following intraventricular infusion in rats. Adult Long-Evans rats were given intraventricular infusions of either PPA (500ug uL-1, 4µl anima-1) or phosphate buffered saline (PBS) ...

  7. A Novel Rodent Model of Autism: Intraventricular Infusions of Propionic Acid Increase Locomotor Activity and Induce Neuroinflammation and Oxidative Stress in Discrete Regions of Adult Rat Brain

    Directory of Open Access Journals (Sweden)

    Derrick F. MacFabe

    2008-01-01

    Full Text Available Innate neuroinflammatory changes, increased oxidative stress and disorders of glutathione metabolism may be involved in the pathophysiology of autism spectrum disorders (ASD. Propionic acid (PPA is a dietary and gut bacterial short chain fatty acid which can produce brain and behavioral changes reminiscent of ASD following intraventricular infusion in rats. Adult Long-Evans rats were given intraventricular infusions of either PPA (500ug uL-1, 4µl anima-1 or phosphate buffered saline (PBS vehicle, twice daily for 7 days. Immediately following the second daily infusion, the locomotor activity of each rat was assessed in an automated open field (Versamax for 30 min. PPA-treated rats showed significant increases in locomotor activity compared to PBS vehicle controls. Following the last treatment day, specific brain regions were assessed for neuroinflammatory or oxidative stress markers. Immunohistochemical analyses revealed reactive astrogliosis (GFAP, activated microglia (CD68, Iba1 without apoptotic cell loss (Caspase 3 and NeuN in hippocampus and white matter (external capsule of PPA treated rats. Biomarkers of protein and lipid peroxidation, total glutathione (GSH as well as the activity of the antioxidant enzymes superoxide dismutase (SOD, catalase, glutathione peroxidase (GPx, glutathione reductase (GR and glutathione S-transferase (GST were examined in brain homogenates. Some brain regions of PPA treated animals (neocortex, hippocampus, thalamus, striatum showed increased lipid and protein oxidation accompanied by decreased total GSH in neocortex. Catalase activity was decreased in most brain regions of PPA treated animals suggestive of reduced antioxidant enzymatic activity. GPx and GR activity was relatively unaffected by PPA treatment while GST was increased perhaps indicating involvement of GSH in the removal of PPA or related catabolites. Impairments in GSH and catalase levels may render CNS cells more susceptible to oxidative stress

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

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    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…

  9. Anatomical Location of LPA1 Activation and LPA Phospholipid Precursors in Rodent and Human Brain

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    González de San Román, E; Manuel, I; Giralt, MT; Chun, J; Estivill-Torrús, G; Rodriguez de Fonseca, F; Santín, LJ; Ferrer, I; Rodriguez-Puertas, R

    2016-01-01

    Lysophosphatidic acid (LPA) is a signaling molecule that binds to six known G protein-coupled receptors (GPCRs): LPA1–LPA6. LPA evokes several responses in the CNS including cortical development and folding, growth of the axonal cone and its retraction process. Those cell processes involve survival, migration, adhesion proliferation, differentiation and myelination. The anatomical localization of LPA1 is incompletely understood, particularly with regard to LPA binding. Therefore, we have used functional [35S]GTPγS autoradiography to verify the anatomical distribution of LPA1 binding sites in adult rodent and human brain. The greatest activity was observed in myelinated areas of the white matter such as corpus callosum, internal capsule and cerebellum. MaLPA1-null mice (a variant of LPA1-null) lack [35S]GTPγS basal binding in white matter areas, where the LPA1 receptor is expressed at high levels, suggesting a relevant role of the activity of this receptor in the most myelinated brain areas. In addition, phospholipid precursors of LPA were localized by MALDI-IMS in both rodent and human brain slices identifying numerous species of phosphatides (PA) and phosphatidylcholines (PC). Both PA and PC species represent potential LPA precursors. The anatomical distribution of these precursors in rodent and human brain may indicate a metabolic relationship between LPA and LPA1 receptors. PMID:25857358

  10. Experience-dependent neural plasticity in the adult damaged brain

    OpenAIRE

    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 extremity (hand and arm) impairments. A prolonged and widespread process of repair and reorganization of surviving neural circuits is instigated by in...

  11. Rodent Brain Microinjection to Study Molecular Substrates of Motivated Behavior.

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    Poland, Ryan S; Bull, Cecilia; Syed, Wahab A; Bowers, M Scott

    2015-01-01

    Brain microinjection can aid elucidation of the molecular substrates of complex behaviors, such as motivation. For this purpose rodents can serve as appropriate models, partly because the response to behaviorally relevant stimuli and the circuitry parsing stimulus-action outcomes is astonishingly similar between humans and rodents. In studying molecular substrates of complex behaviors, the microinjection of reagents that modify, augment, or silence specific systems is an invaluable technique. However, it is crucial that the microinjection site is precisely targeted in order to aid interpretation of the results. We present a method for the manufacture of surgical implements and microinjection needles that enables accurate microinjection and unlimited customizability with minimal cost. Importantly, this technique can be successfully completed in awake rodents if conducted in conjunction with other JoVE articles that covered requisite surgical procedures. Additionally, there are many behavioral paradigms that are well suited for measuring motivation. The progressive ratio is a commonly used method that quantifies the efficacy of a reinforcer to maintain responding despite an (often exponentially) increasing work requirement. This assay is sensitive to reinforcer magnitude and pharmacological manipulations, which allows reinforcing efficacy and/ or motivation to be determined. We also present a straightforward approach to program operant software to accommodate a progressive ratio reinforcement schedule. PMID:26437131

  12. Expensive brains: ‘brainy’ rodents have higher metabolic rate

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    Raúl eSobrero

    2011-07-01

    Full Text Available Brains are the centers of the nervous system of animals, controlling the organ systems of the body and coordinating responses to changes in the ecological and social environment. The evolution traits that correlate with cognitive ability, such as relative brain size is thus of broad interest. Brain mass relative to body mass varies among mammals, and diverse factors have been proposed to explain this variation. A recent study provided evidence that energetics play an important role in brain evolution (Isler and van Schaik, 2006. Using composite phylogenies and data drawn from multiple sources, these authors showed that basal metabolic rate (BMR correlates with brain mass across mammals. However, no such relationship was found within rodents. Here we re-examined the relationship between BMR and brain mass within Rodentia using a novel species-level phylogeny. Our results are sensitive to parameter evaluation; in particular how species mass is estimated. We detect no pattern when applying an approach used by previous studies, where each species body mass is represented by two different numbers, one being the individual that happened to be used for BMR estimates of that species. However, this approach may compromise the analysis. When using a single value of body mass for each species, whether representing a single individual, or available species mean, our findings provide evidence that brain mass (independent of body mass and BMR are correlated. These findings are thus consistent with the hypothesis that large brains evolve when the payoff for increased brain mass is greater than the energetic cost they incur.

  13. Clinical spectrum associated with MOG autoimmunity in adults: significance of sharing rodent MOG epitopes.

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    Sepúlveda, Maria; Armangue, Thaís; Martinez-Hernandez, Eugenia; Arrambide, Georgina; Sola-Valls, Nuria; Sabater, Lidia; Téllez, Nieves; Midaglia, Luciana; Ariño, Helena; Peschl, Patrick; Reindl, Markus; Rovira, Alex; Montalban, Xavier; Blanco, Yolanda; Dalmau, Josep; Graus, Francesc; Saiz, Albert

    2016-07-01

    The aim of this study was to report the clinical spectrum associated with antibodies to myelin oligodendrocyte glycoprotein (MOG) in adult patients, and to assess whether phenotypic variants are dependent on recognition of rodent MOG epitopes. We retrospectively analyzed the features, course and outcome of 56 patients whose samples were investigated by brain tissue immunohistochemistry and cell-based assays using human and rodent MOG. The median age at symptom onset was 37 years (range 18-70); 35 patients (63 %) were female. After a median follow-up of 43 months (range 4-554), only 14 patients (25 %) developed a neuromyelitis optica spectrum disorder (NMOSD), 27 patients (47 %) retained the initial diagnosis of isolated optic neuritis, 7 (12 %) of longitudinally extensive transverse myelitis, and 2 (4 %) of acute disseminated encephalomyelitis; 6 patients (11 %) developed atypical demyelinating syndromes (4 had relapsing episodes of short myelitis lesions which in one occurred with optic neuritis; 1 had relapsing brainstem symptoms, and 1 relapsing demyelinating encephalomyelitis). The course was frequently associated with relapses (71 %) and good outcome. Twenty-seven patients (49 %) had antibodies that recognized rodent MOG epitopes, and 9 of them (16 %) showed a myelin staining pattern in rodent tissue. Only the myelin staining pattern was linked to NMOSD (p = 0.005). In conclusion, MOG autoimmunity in adult patients associates with a clinical spectrum wider than the one expected for patients with suspected NMOSD and overall good outcome. Antibodies to rodent MOG epitopes do not associate with any phenotypic variant. PMID:27147513

  14. Adult brain tumors

    International Nuclear Information System (INIS)

    Radiotherapy plays an important role in the management of adults with brain tumors. This refresher course will focus on a variety of benign and malignant brain neoplasms and how contemporary radiotherapy affects outcome. Successful outcome after radiotherapy requires that (1) there is no tumor extension beyond the selected target volume, (2) adequate dose is delivered to the target volume, and (3) normal tissue tolerance dose is not exceeded. For many neoplasms serial post-treatment scans may show little change, and success is often measured more by absence of tumor progression than by scan normalization. Three-dimensional treatment planning based on MRI or CT makes it possible to guarantee delivery of the full prescription dose to gross tumor while minimizing the volume of normal tissue receiving high dose. Acceptable dose conformity can often be achieved with 2-4 static beams or arcs, which is usually preferable to opposed lateral fields. Protocols involving substantial dose escalation require a large number of non-coplanar x-ray beams or particle therapy. This course will cover important concepts and techniques which relate to the treatment of brain tumors, including conformal radiotherapy, brachytherapy, radiosurgery, fractionated stereotactic radiotherapy, altered fractionation, inverse treatment planning, re-irradiation, and biologically effective dose (BED). Examples of planning solutions for a variety of tumor types, size and anatomical locations will be given. Note: I will incorporate examples of interesting, difficult and unusual cases from other practices as time permits, provided slides and descriptive materials are sent to me in advance of the course

  15. Corticolimbic expression of TRPC4 and TRPC5 channels in the rodent brain.

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    Melissa A Fowler

    Full Text Available The canonical transient receptor potential (TRPC channels are a family of non-selective cation channels that are activated by increases in intracellular Ca(2+ and G(q/phospholipase C-coupled receptors. We used quantitative real-time PCR, in situ hybridization, immunoblots and patch-clamp recording from several brain regions to examine the expression of the predominant TRPC channels in the rodent brain. Quantitative real-time PCR of the seven TRPC channels in the rodent brain revealed that TRPC4 and TRPC5 channels were the predominant TRPC subtypes in the adult rat brain. In situ hybridization histochemistry and immunoblotting further resolved a dense corticolimbic expression of the TRPC4 and TRPC5 channels. Total protein expression of HIP TRPC4 and 5 proteins increased throughout development and peaked late in adulthood (6-9 weeks. In adults, TRPC4 expression was high throughout the frontal cortex, lateral septum (LS, pyramidal cell layer of the hippocampus (HIP, dentate gyrus (DG, and ventral subiculum (vSUB. TRPC5 was highly expressed in the frontal cortex, pyramidal cell layer of the HIP, DG, and hypothalamus. Detailed examination of frontal cortical layer mRNA expression indicated TRPC4 mRNA is distributed throughout layers 2-6 of the prefrontal cortex (PFC, motor cortex (MCx, and somatosensory cortex (SCx. TRPC5 mRNA expression was concentrated specifically in the deep layers 5/6 and superficial layers 2/3 of the PFC and anterior cingulate. Patch-clamp recording indicated a strong metabotropic glutamate-activated cation current-mediated depolarization that was dependent on intracellular Ca(2+and inhibited by protein kinase C in brain regions associated with dense TRPC4 or 5 expression and absent in regions lacking TRPC4 and 5 expression. Overall, the dense corticolimbic expression pattern suggests that these Gq/PLC coupled nonselective cation channels may be involved in learning, memory, and goal-directed behaviors.

  16. Brain and Spinal Cord Tumors in Adults

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    ... 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 ...

  17. Effects of early life adverse experiences on brain activity: Implications from maternal separation models in rodents

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    Mayumi eNishi

    2014-06-01

    Full Text Available During postnatal development, adverse early life experiences can affect the formation of neuronal circuits and exert long-lasting influences on neural function. Many studies have shown that daily repeated MS, an animal model of early life stress, can modulate the hypothalamic-pituitary-adrenal axis (HPA axis and can affect subsequent brain function and emotional behavior during adulthood. However, the molecular basis of the long-lasting effects of early life stress on brain function has not been completely elucidated. In this review, we introduce various cases of MS in rodents and illustrate the alterations in HPA axis activity by focusing on corticosterone (CORT, an end product of the HPA axis in rodents. We then present a characterization of the brain regions affected by various patterns of MS, including repeated MS and single time MS at various stages before weaning, by investigating c-Fos expression, a biological marker of neuronal activity. These CORT and c-Fos studies suggest that repeated early life stress may affect neuronal function in region- and temporal-specific manners, indicating a critical period for habituation to early life stress. Next, we discuss how early life stress can impact behavior, namely by inducing depression, anxiety or eating disorders. Furthermore, alterations in gene expression in adult mice exposed to MS, especially epigenetic changes of DNA methylation, are discussed.

  18. Traumatic brain injury–Modeling neuropsychiatric symptoms in rodents

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    Oz eMalkesman

    2013-10-01

    Full Text Available Each year in the United States, approximately 1.5 million people sustain a traumatic brain injury (TBI. Victims of TBI can suffer from chronic post-TBI symptoms, such as sensory and motor deficits, cognitive impairments including problems with memory, learning, and attention, and neuropsychiatric symptoms such as depression, anxiety, irritability, aggression, and suicidal rumination. Although partially associated with the site and severity of injury, the biological mechanisms associated with many of these symptoms—and why some patients experience differing assortments of persistent maladies—are largely unknown. The use of animal models is a promising strategy for elucidation of the mechanisms of impairment and treatment, and learning, memory, sensory and motor tests have widespread utility in rodent models of TBI and psychopharmacology. Comparatively, behavioral tests for the evaluation of neuropsychiatric symptomatology are rarely employed in animal models of TBI and, as determined in this review, the results have been inconsistent. Animal behavioral studies contribute to the understanding of the biological mechanisms by which TBI is associated with neurobehavioral symptoms and offer a powerful means for pre-clinical treatment validation. Therefore, further exploration of the utility of animal behavioral tests for the study of injury mechanisms and therapeutic strategies for the alleviation of emotional symptoms are relevant and essential.

  19. Updated Neuronal Scaling Rules for the Brains of Glires (Rodents/Lagomorphs)

    OpenAIRE

    Herculano-Houzel, Suzana; Ribeiro, Pedro; Campos, Leandro; Valotta da Silva, Alexandre; Torres, Laila B.; Catania, Kenneth C.; Kaas, Jon H.

    2011-01-01

    Brain size scales as different functions of its number of neurons across mammalian orders such as rodents, primates, and insectivores. In rodents, we have previously shown that, across a sample of 6 species, from mouse to capybara, the cerebral cortex, cerebellum and the remaining brain structures increase in size faster than they gain neurons, with an accompanying decrease in neuronal density in these structures [Herculano-Houzel et al.: Proc Natl Acad Sci USA 2006;103:12138–12143]. Importan...

  20. Intracranial microcapsule chemotherapy delivery for the localized treatment of rodent metastatic breast adenocarcinoma in the brain.

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    Upadhyay, Urvashi M; Tyler, Betty; Patta, Yoda; Wicks, Robert; Spencer, Kevin; Scott, Alexander; Masi, Byron; Hwang, Lee; Grossman, Rachel; Cima, Michael; Brem, Henry; Langer, Robert

    2014-11-11

    Metastases represent the most common brain tumors in adults. Surgical resection alone results in 45% recurrence and is usually accompanied by radiation and chemotherapy. Adequate chemotherapy delivery to the CNS is hindered by the blood-brain barrier. Efforts at delivering chemotherapy locally to gliomas have shown modest increases in survival, likely limited by the infiltrative nature of the tumor. Temozolomide (TMZ) is first-line treatment for gliomas and recurrent brain metastases. Doxorubicin (DOX) is used in treating many types of breast cancer, although its use is limited by severe cardiac toxicity. Intracranially implanted DOX and TMZ microcapsules are compared with systemic administration of the same treatments in a rodent model of breast adenocarcinoma brain metastases. Outcomes were animal survival, quantified drug exposure, and distribution of cleaved caspase 3. Intracranial delivery of TMZ and systemic DOX administration prolong survival more than intracranial DOX or systemic TMZ. Intracranial TMZ generates the more robust induction of apoptotic pathways. We postulate that these differences may be explained by distribution profiles of each drug when administered intracranially: TMZ displays a broader distribution profile than DOX. These microcapsule devices provide a safe, reliable vehicle for intracranial chemotherapy delivery and have the capacity to be efficacious and superior to systemic delivery of chemotherapy. Future work should include strategies to improve the distribution profile. These findings also have broader implications in localized drug delivery to all tissue, because the efficacy of a drug will always be limited by its ability to diffuse into surrounding tissue past its delivery source.

  1. High-resolution in vivo Wistar rodent brain atlas based on T1 weighted image

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    Huang, Su; Lu, Zhongkang; Huang, Weimin; Seramani, Sankar; Ramasamy, Boominathan; Sekar, Sakthivel; Guan, Cuntai; Bhakoo, Kishore

    2016-03-01

    Image based atlases for rats brain have a significant impact on pre-clinical research. In this project we acquired T1-weighted images from Wistar rodent brains with fine 59μm isotropical resolution for generation of the atlas template image. By applying post-process procedures using a semi-automatic brain extraction method, we delineated the brain tissues from source data. Furthermore, we applied a symmetric group-wise normalization method to generate an optimized template of T1 image of rodent brain, then aligned our template to the Waxholm Space. In addition, we defined several simple and explicit landmarks to corresponding our template with the well known Paxinos stereotaxic reference system. Anchoring at the origin of the Waxholm Space, we applied piece-wise linear transformation method to map the voxels of the template into the coordinates system in Paxinos' stereotoxic coordinates to facilitate the labelling task. We also cross-referenced our data with both published rodent brain atlas and image atlases available online, methodologically labelling the template to produce a Wistar brain atlas identifying more than 130 structures. Particular attention was paid to the cortex and cerebellum, as these areas encompass the most researched aspects of brain functions. Moreover, we adopted the structure hierarchy and naming nomenclature common to various atlases, so that the names and hierarchy structure presented in the atlas are readily recognised for easy use. It is believed the atlas will present a useful tool in rodent brain functional and pharmaceutical studies.

  2. Metabolic Profiling of Dividing Cells in Live Rodent Brain by Proton Magnetic Resonance Spectroscopy (1HMRS) and LCModel Analysis

    DEFF Research Database (Denmark)

    Park, June-Hee; Lee, Hedok; Makaryus, Rany;

    2014-01-01

    shock in the live rodent brain via spectral signatures representing mobile lipids resonating at ∼1.30 ppm. In addition, we also apply the same 1HMRS methodology to metabolically profile glioblastomas with actively dividing cells growing in RCAS-PDGF mice. METHODS: 1HMRS metabolic profiles were acquired...... on a 9.4T MRI instrument in combination with LCModel spectral analysis of: 1) rat brains before and after ECS or sham treatments and 2) RCAS-PDGF mice with glioblastomas and wild-type controls. Quantified 1HMRS data were compared to post-mortem histology. RESULTS: Dividing cells in the rat hippocampus......-PDGF mice, when compared to normal brain tissue in the control mice. CONCLUSIONS: Metabolic profiling using 1HMRS in combination with LCModel analysis did not reveal correlation between Lip13a+Lip13b spectral signatures and an increase in neurogenesis in adult rat hippocampus after ECS. However, increases...

  3. Enhanced cortical thickness measurements for rodent brains via Lagrangian-based RK4 streamline computation

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    Lee, Joohwi; Kim, Sun Hyung; Oguz, Ipek; Styner, Martin

    2016-03-01

    The cortical thickness of the mammalian brain is an important morphological characteristic that can be used to investigate and observe the brain's developmental changes that might be caused by biologically toxic substances such as ethanol or cocaine. Although various cortical thickness analysis methods have been proposed that are applicable for human brain and have developed into well-validated open-source software packages, cortical thickness analysis methods for rodent brains have not yet become as robust and accurate as those designed for human brains. Based on a previously proposed cortical thickness measurement pipeline for rodent brain analysis,1 we present an enhanced cortical thickness pipeline in terms of accuracy and anatomical consistency. First, we propose a Lagrangian-based computational approach in the thickness measurement step in order to minimize local truncation error using the fourth-order Runge-Kutta method. Second, by constructing a line object for each streamline of the thickness measurement, we can visualize the way the thickness is measured and achieve sub-voxel accuracy by performing geometric post-processing. Last, with emphasis on the importance of an anatomically consistent partial differential equation (PDE) boundary map, we propose an automatic PDE boundary map generation algorithm that is specific to rodent brain anatomy, which does not require manual labeling. The results show that the proposed cortical thickness pipeline can produce statistically significant regions that are not observed in the previous cortical thickness analysis pipeline.

  4. Cyberinfrastructure for the digital brain: spatial standards for integrating rodent brain atlases

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    Ilya eZaslavsky

    2014-09-01

    Full Text Available Biomedical research entails capture and analysis of massive data volumes and new discoveries arise from data-integration and mining. This is only possible if data can be mapped onto a common framework such as the genome for genomic data. In neuroscience, the framework is intrinsically spatial and based on a number of paper atlases. This cannot meet today’s data-intensive analysis and integration challenges. A scalable and extensible software infrastructure that is standards based but open for novel data and resources, is required for integrating information such as signal distributions, gene-expression, neuronal connectivity, electrophysiology, anatomy, and developmental processes. Therefore, the International Neuroinformatics Coordinating Facility (INCF initiated the development of a spatial framework for neuroscience data integration with an associated Digital Atlasing Infrastructure (DAI. A prototype implementation of this infrastructure for the rodent brain is reported here. The infrastructure is based on a collection of reference spaces to which data is mapped at the required resolution, such as the Waxholm Space (WHS, a 3D reconstruction of the brain generated using high-resolution, multi-channel microMRI. The core standards of the digital atlasing service-oriented infrastructure include Waxholm Markup Language (WaxML: XML schema expressing a uniform information model for key elements such as coordinate systems, transformations, points of interest (POIs, labels, and annotations; and Atlas Web Services: interfaces for querying and updating atlas data. The services return WaxML-encoded documents with information about capabilities, spatial reference systems and structures, and execute coordinate transformations and POI-based requests. Key elements of INCF-DAI cyberinfrastructure have been prototyped for both mouse and rat brain atlas sources, including the Allen Mouse Brain Atlas, UCSD Cell-Centered Database, and Edinburgh Mouse Atlas

  5. Mechanism of Chronic Pain in Rodent Brain Imaging

    Science.gov (United States)

    Chang, Pei-Ching

    Chronic pain is a significant health problem that greatly impacts the quality of life of individuals and imparts high costs to society. Despite intense research effort in understanding of the mechanism of pain, chronic pain remains a clinical problem that has few effective therapies. The advent of human brain imaging research in recent years has changed the way that chronic pain is viewed. To further extend the use of human brain imaging techniques for better therapies, the adoption of imaging technique onto the animal pain models is essential, in which underlying brain mechanisms can be systematically studied using various combination of imaging and invasive techniques. The general goal of this thesis is to addresses how brain develops and maintains chronic pain in an animal model using fMRI. We demonstrate that nucleus accumbens, the central component of mesolimbic circuitry, is essential in development of chronic pain. To advance our imaging technique, we develop an innovative methodology to carry out fMRI in awake, conscious rat. Using this cutting-edge technique, we show that allodynia is assoicated with shift brain response toward neural circuits associated nucleus accumbens and prefrontal cortex that regulate affective and cognitive component of pain. Taken together, this thesis provides a deeper understanding of how brain mediates pain. It builds on the existing body of knowledge through maximizing the depth of insight into brain imaging of chronic pain.

  6. Structural plasticity of the adult brain

    OpenAIRE

    Gage, Fred H.

    2004-01-01

    The adult brain has long been considered stable and unchanging, except for the inevitable decline that occurs with aqinq. This view is now being challenged with clear evidence that structural changes occur in the brain throughout life, including the generation of new neurons and other brain cells, and connections between and among neurons. What is as remarkable is that the changes that occur in the adult brain are influenced by the behaviors an individual engages in, as well as the environmen...

  7. Molecular basis of thyroid hormone regulation of myelin basic protein gene expression in rodent brain.

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    Farsetti, A; Mitsuhashi, T; Desvergne, B; Robbins, J; Nikodem, V M

    1991-12-01

    Regulation of myelin basic protein (MBP) gene expression by thyroid hormone has been investigated in rodent brain. Quantitation of the 4 major alternatively spliced transcripts by RNase protection assay showed that the individual mRNAs, corresponding to MBP isoforms 21.5, 18.5, 17, and 14 kDa, were decreased from 2- to 17-fold at all ages studied (4-60 days) in hypothyroid animals when compared to euthyroid, but the timing of onset of expression was not altered. MBP mRNA was also reduced in young adult rats thyroidectomized at the age of 5-6 weeks and was restored to normal by thyroxine administration. Nuclear run-off assays showed that the rate of MBP gene transcription is dependent on thyroid state. Co-transfection of MBP (-256/+1)-chloramphenicol acetyltransferase chimeric gene with a plasmid expressing thyroid hormone receptor alpha, and in the presence of 3,5,3'-triiodothyronine, into NIH3T3 or NG108-15, increased chloramphenicol acetyltransferase expression 4-fold. Using a footprinting technique and Spodoptera frugiperda 9 (Sf9) nuclear extract infected with baculovirus expressing TR alpha, we have identified a single DNA-binding site (-186/-163) for the receptor. A part of this region contains the AGGACA sequence found in thyroid hormone-responsive elements of other 3,5,3'-triiodothyronine-regulated genes. Our finding of a specific hormone-receptor interaction with the MBP promoter region is the first direct demonstration of a thyroid hormone-responsive element in a brain-specific gene. PMID:1720778

  8. Habitat-Specific Shaping of Proliferation and Neuronal Differentiation in Adult Hippocampal Neurogenesis of Wild Rodents

    Directory of Open Access Journals (Sweden)

    Nicole eCavegn

    2013-04-01

    Full Text Available Daily life of wild mammals is characterized by a multitude of attractive and aversive stimuli. The hippocampus processes complex polymodal information associated with such stimuli and mediates adequate behavioral responses. How newly generated hippocampal neurons in wild animals contribute to hippocampal function is still a subject of debate. Here, we test the relationship between adult hippocampal neurogenesis and habitat types. To this end, we compare wild Muridae species of southern Africa (Namaqua rock mouse (Micaelamys namaquensis, red veld rat (Aethomys chrysophilus, highveld gerbil (Tatera brantsii and spiny mouse (Acomys spinosissimus with data from wild European Muridae (long-tailed wood mice (Apodemus sylvaticus, pygmy field mice (Apodemus microps, yellow-necked wood mice (Apodemus flavicollis, and house mice (Mus musculus domesticus from previous studies. The pattern of neurogenesis, expressed in normalized numbers of Ki67- and DCX-positive cells to total granule cells, is similar for the species from a southern African habitat. However, we found low proliferation, but high neuronal differentiation in rodents from the southern African habitat compared to rodents from the European environment. Within the African rodents, we observe additional regulatory and morphological traits in the hippocampus. Namaqua rock mice with previous pregnancies showed lower adult hippocampal neurogenesis compared to males and nulliparous females. The phylogenetically closely related species (Namaqua rock mouse and red veld rat show a CA4, which is not usually observed in murine rodents. The specific features of the southern environment that may be associated with the high number of young neurons in African rodents still remain to be elucidated. This study provides the first evidence that a habitat can shape adult neurogenesis in rodents across phylogenetic groups.

  9. Functional connectivity of the rodent brain using optical imaging

    Science.gov (United States)

    Guevara Codina, Edgar

    The aim of this thesis is to apply functional connectivity in a variety of animal models, using several optical imaging modalities. Even at rest, the brain shows high metabolic activity: the correlation in slow spontaneous fluctuations identifies remotely connected areas of the brain; hence the term "functional connectivity". Ongoing changes in spontaneous activity may provide insight into the neural processing that takes most of the brain metabolic activity, and so may provide a vast source of disease related changes. Brain hemodynamics may be modified during disease and affect resting-state activity. The thesis aims to better understand these changes in functional connectivity due to disease, using functional optical imaging. The optical imaging techniques explored in the first two contributions of this thesis are Optical Imaging of Intrinsic Signals and Laser Speckle Contrast Imaging, together they can estimate the metabolic rate of oxygen consumption, that closely parallels neural activity. They both have adequate spatial and temporal resolution and are well adapted to image the convexity of the mouse cortex. In the last article, a depth-sensitive modality called photoacoustic tomography was used in the newborn rat. Optical coherence tomography and laminar optical tomography were also part of the array of imaging techniques developed and applied in other collaborations. The first article of this work shows the changes in functional connectivity in an acute murine model of epileptiform activity. Homologous correlations are both increased and decreased with a small dependence on seizure duration. These changes suggest a potential decoupling between the hemodynamic parameters in resting-state networks, underlining the importance to investigate epileptic networks with several independent hemodynamic measures. The second study examines a novel murine model of arterial stiffness: the unilateral calcification of the right carotid. Seed-based connectivity analysis

  10. Hippocampal deep brain stimulation reverses physiological and behavioural deficits in a rodent model of schizophrenia.

    Science.gov (United States)

    Perez, Stephanie M; Shah, Amiksha; Asher, Amber; Lodge, Daniel J

    2013-07-01

    Subcortical dopamine system dysregulation has been suggested to underlie the positive symptoms of schizophrenia. Recent preclinical investigations and human imaging studies have proposed that the augmented dopamine system function observed in schizophrenia patients may be secondary to aberrant hippocampal activity. Thus, we posit that the hippocampus represents a novel therapeutic target for the treatment of schizophrenia. Here we provide evidence of the effectiveness of a unique approach aimed at decreasing hippocampal function in a rodent model of schizophrenia. Specifically, in a rodent model of schizophrenia, we demonstrate that ventral hippocampal (vHipp) deep brain stimulation (DBS) can normalize aberrant dopamine neuron activity and behaviours associated with positive symptoms. In addition, we provide evidence that this approach may also be effective in restoring deficits in cognitive function, often left unaltered by conventional antipsychotic medications. Therefore, we have provided initial preclinical evidence demonstrating the feasibility of hippocampal DBS as a potential novel approach for the treatment of schizophrenia.

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

    Science.gov (United States)

    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

  12. 3D segmentation of rodent brain structures using hierarchical shape priors and deformable models.

    Science.gov (United States)

    Zhang, Shaoting; Huang, Junzhou; Uzunbas, Mustafa; Shen, Tian; Delis, Foteini; Huang, Xiaolei; Volkow, Nora; Thanos, Panayotis; Metaxas, Dimitris N

    2011-01-01

    In this paper, we propose a method to segment multiple rodent brain structures simultaneously. This method combines deformable models and hierarchical shape priors within one framework. The deformation module employs both gradient and appearance information to generate image forces to deform the shape. The shape prior module uses Principal Component Analysis to hierarchically model the multiple structures at both global and local levels. At the global level, the statistics of relative positions among different structures are modeled. At the local level, the shape statistics within each structure is learned from training samples. Our segmentation method adaptively employs both priors to constrain the intermediate deformation result. This prior constraint improves the robustness of the model and benefits the segmentation accuracy. Another merit of our prior module is that the size of the training data can be small, because the shape prior module models each structure individually and combines them using global statistics. This scheme can preserve shape details better than directly applying PCA on all structures. We use this method to segment rodent brain structures, such as the cerebellum, the left and right striatum, and the left and right hippocampus. The experiments show that our method works effectively and this hierarchical prior improves the segmentation performance. PMID:22003750

  13. Organotypic tissue culture of adult rodent retina followed by particle-mediated acute gene transfer in vitro.

    Directory of Open Access Journals (Sweden)

    Satoru Moritoh

    Full Text Available BACKGROUND: Organotypic tissue culture of adult rodent retina with an acute gene transfer that enables the efficient introduction of variable transgenes would greatly facilitate studies into retinas of adult rodents as animal models. However, it has been a difficult challenge to culture adult rodent retina. The purpose of this present study was to develop organotypic tissue culture of adult rodent retina followed by particle-mediated acute gene transfer in vitro. METHODOLOGY/PRINCIPAL FINDINGS: We established an interphase organotypic tissue culture for adult rat retinas (>P35 of age which was optimized from that used for adult rabbit retinas. We implemented three optimizations: a greater volume of Ames' medium (>26 mL per retina, a higher speed (constant 55 rpm of agitation by rotary shaker, and a greater concentration (10% of horse serum in the medium. We also successfully applied this method to adult mouse retina (>P35 of age. The organotypic tissue culture allowed us to keep adult rodent retina morphologically and structurally intact for at least 4 days. However, mouse retinas showed less viability after 4-day culture. Electrophysiologically, ganglion cells in cultured rat retina were able to generate action potentials, but exhibited less reliable light responses. After transfection of EGFP plasmids by particle-mediated acute gene transfer, we observed EGFP-expressing retinal ganglion cells as early as 1 day of culture. We also introduced polarized-targeting fusion proteins such as PSD95-GFP and melanopsin-EYFP (hOPN4-EYFP into rat retinal ganglion cells. These fusion proteins were successfully transferred into appropriate locations on individual retinal neurons. CONCLUSIONS/SIGNIFICANCE: This organotypic culture method is largely applicable to rat retinas, but it can be also applied to mouse retinas with a caveat regarding cell viability. This method is quite flexible for use in acute gene transfection in adult rodent retina, replacing

  14. Effects of prenatal cocaine exposure on early postnatal rodent brain structure and diffusion properties.

    Science.gov (United States)

    McMurray, Matthew S; Oguz, Ipek; Rumple, Ashley M; Paniagua, Beatriz; Styner, Martin A; Johns, Josephine M

    2015-01-01

    Prenatal cocaine exposure has been associated with numerous behavioral phenotypes in clinical populations, including impulsivity, reduced attention, alterations in social behaviors, and delayed language and sensory-motor development. Detecting associated changes in brain structure in these populations has proven difficult, and results have been inconclusive and inconsistent. Due to their more controlled designs, animal models may shed light on the neuroanatomical changes caused by prenatal cocaine; however, to maximize clinical relevance, data must be carefully collected using translational methods. The goal of this study was two-fold: (1) to determine if prenatal cocaine alters developmental neuroanatomy using methods that are available to human researchers, specifically structural MRI and diffusion tensor imaging, and (2) to determine the feasibility of rodent in vivo neuroimaging for usage in longitudinal studies of developmental disorders. Cocaine-exposed (prenatal days 1-20, 30mg/kg/day) rat pups were sedated and imaged live using diffusion tensor imaging and postmortem (fixed) using magnetic resonance histology on postnatal day 14. Volume and diffusion properties in whole brain as well as specific regions of interest were then assessed from the resulting images. Whole brain analyses revealed that cocaine-exposed animals showed no change in whole brain volume. Additionally, we found alterations in fractional anisotropy across regions associated with reward processing and emotional regulation, especially in the thalamus and globus pallidus, as well as sex-dependent effects of cocaine in the right cortex. Reductions in fractional anisotropy were paired with reductions only in axial diffusivity, which preliminarily suggests that the changes observed here may be due to axonal damage, as opposed to reductions in myelination of the affected regions/pathways. Our data indicate that prenatal cocaine may target a number of developing brain structures but does not

  15. Modulation of NMDA receptor function by inhibition of D-amino acid oxidase in rodent brain.

    Science.gov (United States)

    Strick, Christine A; Li, Cheryl; Scott, Liam; Harvey, Brian; Hajós, Mihály; Steyn, Stefanus J; Piotrowski, Mary A; James, Larry C; Downs, James T; Rago, Brian; Becker, Stacey L; El-Kattan, Ayman; Xu, Youfen; Ganong, Alan H; Tingley, F David; Ramirez, Andres D; Seymour, Patricia A; Guanowsky, Victor; Majchrzak, Mark J; Fox, Carol B; Schmidt, Christopher J; Duplantier, Allen J

    2011-01-01

    Observations that N-Methyl-D-Aspartate (NMDA) antagonists produce symptoms in humans that are similar to those seen in schizophrenia have led to the current hypothesis that schizophrenia might result from NMDA receptor hypofunction. Inhibition of D-amino acid oxidase (DAAO), the enzyme responsible for degradation of D-serine, should lead to increased levels of this co-agonist at the NMDA receptor, and thereby provide a therapeutic approach to schizophrenia. We have profiled some of the preclinical biochemical, electrophysiological, and behavioral consequences of administering potent and selective inhibitors of DAAO to rodents to begin to test this hypothesis. Inhibition of DAAO activity resulted in a significant dose and time dependent increase in D-serine only in the cerebellum, although a time delay was observed between peak plasma or brain drug concentration and cerebellum D-serine response. Pharmacokinetic/pharmacodynamic (PK/PD) modeling employing a mechanism-based indirect response model was used to characterize the correlation between free brain drug concentration and D-serine accumulation. DAAO inhibitors had little or no activity in rodent models considered predictive for antipsychotic activity. The inhibitors did, however, affect cortical activity in the Mescaline-Induced Scratching model, produced a modest but significant increase in NMDA receptor-mediated synaptic currents in primary neuronal cultures from rat hippocampus, and resulted in a significant increase in evoked hippocampal theta rhythm, an in vivo electrophysiological model of hippocampal activity. These findings demonstrate that although DAAO inhibition did not cause a measurable increase in D-serine in forebrain, it did affect hippocampal and cortical activity, possibly through augmentation of NMDA receptor-mediated currents.

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

    Directory of Open Access Journals (Sweden)

    Gloria K Mak

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

  17. Fatigue in adults with traumatic brain injury

    DEFF Research Database (Denmark)

    Mollayeva, Tatyana; Kendzerska, Tetyana; Mollayeva, Shirin;

    2013-01-01

    BACKGROUND: Despite strong indications that fatigue is the most common and debilitating symptom after traumatic brain injury, little is known about its frequency, natural history, or relation to other factors. The current protocol outlines a strategy for a systematic review that will identify......, assess, and critically appraise studies that assessed predictors for fatigue and the consequences of fatigue on at least two separate time points following traumatic brain injury. METHODS/DESIGN: MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, CINAHL, and PsycINFO will be systematically...... searched for relevant peer-reviewed studies. Reference lists of eligible papers will also be searched. All English language studies with a longitudinal design that focus on fatigue in adults with primary-impact traumatic brain injury will be included. Studies on fatigue following brain injury due...

  18. Robert Feulgen Prize Lecture. Grenzgänger: adult bone marrow cells populate the brain.

    Science.gov (United States)

    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

  19. Robert Feulgen Prize Lecture. Grenzgänger: adult bone marrow cells populate the brain.

    Science.gov (United States)

    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.

  20. Traumatic Brain Injury Activation of the Adult Subventricular Zone Neurogenic Niche

    Science.gov (United States)

    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

  1. Extracellular proteolysis in the adult murine brain.

    Science.gov (United States)

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

    1993-08-01

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

  2. Experimental evidence for sex-specific plasticity in adult brain

    OpenAIRE

    Herczeg, Gábor; Gonda, Abigél; Balázs, Gergely; Noreikiene, Kristina; Merilä, Juha

    2015-01-01

    Background Plasticity in brain size and the size of different brain regions during early ontogeny is known from many vertebrate taxa, but less is known about plasticity in the brains of adults. In contrast to mammals and birds, most parts of a fish’s brain continue to undergo neurogenesis throughout adulthood, making lifelong plasticity in brain size possible. We tested whether maturing adult three-spined sticklebacks (Gasterosteus aculeatus) reared in a stimulus-poor environment exhibited br...

  3. New Experimental Model of Brain Tumors in Brains of Adult Immunocompetent Rats

    OpenAIRE

    Baklaushev, Vladimir P.; Kavsan, Vadym M.; Balynska, Olena V; Yusubalieva, Gaukhar M.; Abakumov, Maxim A.; Chekhonin, Vladimir P.

    2012-01-01

    Aims: Xenograft models, namely heterotransplantation of human cancer cells or tumor biopsies into immunodeficient rodents are the major preclinical approach for the development of novel cancer therapeutics. However, in these models the animals must be used only after the severe systemic immune suppression in order to ensure graft survival. Thus, additional new human brain tumor models without immune suppression of the recipient rodent may be required. Place and Duration of Study: Laboratory o...

  4. Transplantation of human neural stem cells restores cognition in an immunodeficient rodent model of traumatic brain injury

    OpenAIRE

    Haus, DL; Lopez-Velazquez, L; Gold, EM; Cunningham, KM; Perez, H; Anderson, AJ; Cummings, BJ

    2016-01-01

    Traumatic brain injury (TBI) in humans can result in permanent tissue damage and has been linked to cognitive impairment that lasts years beyond the initial insult. Clinically effective treatment strategies have yet to be developed. Transplantation of human neural stem cells (hNSCs) has the potential to restore cognition lost due to injury, however, the vast majority of rodent TBI/hNSC studies to date have evaluated cognition only at early time points, typically

  5. From Child to Young Adult, the Brain Changes Its Connections

    OpenAIRE

    Kaustubh Supekar; Mark Musen; Vinod Menon

    2009-01-01

    The ontogeny of large-scale functional organization of the human brain is not well understood. Here we use network analysis of intrinsic functional connectivity to characterize the organization of brain networks in 23 children (ages 7-9 y) and 22 young-adults (ages 19-22 y). Comparison of network properties, including path-length, clustering-coefficient, hierarchy, and regional connectivity, revealed that although children and young-adults' brains have similar "small-world" organization at th...

  6. [18F]FPEB and [18F]FDEGPECO comparative study of mGlu5 quantification in rodent brain

    International Nuclear Information System (INIS)

    The aim of this study is to compare [18F]FPEB and [18F]FDEGPECO for the quantification of mGlu5 receptors in rodent brains. After preparation of radioligands, dynamic PET data was acquired for 90 min. Estimated non-displaceable binding potential (BPND) values were calculated from the non-invasive Logan’s graphical analysis method. Although both radioligands showed similar radiochemical amenability, [18F]FPEB PET showed higher brain uptake and superior binding potential values than those of [18F]FDEGPECO PET (peak brain uptakes in the hippocampus and the striatum: 7.2–8.7 vs. 5.0–6.2, BPND: 7.3–9.6 vs. 0.3–0.4 for [18F]FPEB and [18F]FDEGPECO, respectively). In addition, the target-to-reference ratios for [18F]FPEB is >4 fold than those of [18F]FDEGPECO. From this evidence, we conclude that [18F]FPEB is a superior radioligand for mGlu5 imaging in preclinical studies. - Highlights: • [18F]FPEB and [18F]FDEGPECO had similar radiochemical yields and specific activities. • Although both radioligands have similar initial uptake patterns, the kinetics and behavior at later time phase are different. • Compared with [18F]FDEGPECO PET, [18F]FPEB PET showed remarkably high brain uptake and binding potentials. • [18F]FPEB is a better PET radioligand than [18F]FDEGPECO for imaging mGluR5 in the rodent brains

  7. Material characterization and computer model simulation of low density polyurethane foam used in a rodent traumatic brain injury model.

    Science.gov (United States)

    Zhang, Liying; Gurao, Manish; Yang, King H; King, Albert I

    2011-05-15

    Computer models of the head can be used to simulate the events associated with traumatic brain injury (TBI) and quantify biomechanical response within the brain. Marmarou's impact acceleration rodent model is a widely used experimental model of TBI mirroring axonal pathology in humans. The mechanical properties of the low density polyurethane (PU) foam, an essential piece of energy management used in Marmarou's impact device, has not been fully characterized. The foam used in Marmarou's device was tested at seven strain rates ranging from quasi-static to dynamic (0.014-42.86 s⁻¹) to quantify the stress-strain relationships in compression. Recovery rate of the foam after cyclic compression was also determined through the periods of recovery up to three weeks. The experimentally determined stress-strain curves were incorporated into a material model in an explicit Finite Element (FE) solver to validate the strain rate dependency of the FE foam model. Compression test results have shown that the foam used in the rodent impact acceleration model is strain rate dependent. The foam has been found to be reusable for multiple impacts. However the stress resistance of used foam is reduced to 70% of the new foam. The FU_CHANG_FOAM material model in an FE solver has been found to be adequate to simulate this rate sensitive foam.

  8. Cell proliferation and neurogenesis in adult mouse brain.

    Directory of Open Access Journals (Sweden)

    Olivia L Bordiuk

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

  9. An anatomically comprehensive atlas of the adult human brain transcriptome

    NARCIS (Netherlands)

    Hawrylycz, M.J.; Beckmann, C.F.; et al., et al.

    2012-01-01

    Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising

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

    Science.gov (United States)

    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…

  11. Transplantation of human neural stem cells restores cognition in an immunodeficient rodent model of traumatic brain injury.

    Science.gov (United States)

    Haus, Daniel L; López-Velázquez, Luci; Gold, Eric M; Cunningham, Kelly M; Perez, Harvey; Anderson, Aileen J; Cummings, Brian J

    2016-07-01

    Traumatic brain injury (TBI) in humans can result in permanent tissue damage and has been linked to cognitive impairment that lasts years beyond the initial insult. Clinically effective treatment strategies have yet to be developed. Transplantation of human neural stem cells (hNSCs) has the potential to restore cognition lost due to injury, however, the vast majority of rodent TBI/hNSC studies to date have evaluated cognition only at early time points, typically human cell engraftment and long-term survival in rodent models of TBI has been difficult to achieve due to host immunorejection of the transplanted human cells, which confounds conclusions pertaining to transplant-mediated behavioral improvement. To overcome these shortfalls, we have developed a novel TBI xenotransplantation model that utilizes immunodeficient athymic nude (ATN) rats as the host recipient for the post-TBI transplantation of human embryonic stem cell (hESC) derived NSCs and have evaluated cognition in these animals at long-term (≥2months) time points post-injury. We report that immunodeficient ATN rats demonstrate hippocampal-dependent spatial memory deficits (Novel Place, Morris Water Maze), but not non-spatial (Novel Object) or emotional/anxiety-related (Elevated Plus Maze, Conditioned Taste Aversion) deficits, at 2-3months post-TBI, confirming that ATN rats recapitulate some of the cognitive deficits found in immunosufficient animal strains. Approximately 9-25% of transplanted hNSCs survived for at least 5months post-transplantation and differentiated into mature neurons (NeuN, 18-38%), astrocytes (GFAP, 13-16%), and oligodendrocytes (Olig2, 11-13%). Furthermore, while this model of TBI (cortical impact) targets primarily cortex and the underlying hippocampus and generates a large lesion cavity, hNSC transplantation facilitated cognitive recovery without affecting either lesion volume or total spared cortical or hippocampal tissue volume. Instead, we have found an overall increase in

  12. Visible rodent brain-wide networks at single-neuron resolution

    Directory of Open Access Journals (Sweden)

    Jing eYuan

    2015-05-01

    Full Text Available There are some unsolvable fundamental questions, such as cell type classification, neural circuit tracing and neurovascular coupling, though great progresses are being made in neuroscience. Because of the structural features of neurons and neural circuits, the solution of these questions needs us to break through the current technology of neuroanatomy for acquiring the exactly fine morphology of neuron and vessels and tracing long-distant circuit at axonal resolution in the whole brain of mammals. Combined with fast-developing labeling techniques, efficient whole-brain optical imaging technology emerging at the right moment presents a huge potential in the structure and function research of specific-function neuron and neural circuit. In this review, we summarize brain-wide optical tomography techniques, review the progress on visible brain neuronal/vascular networks benefit from these novel techniques, and prospect the future technical development.

  13. Effects of early life adverse experiences on the brain: implications from maternal separation models in rodents

    OpenAIRE

    Mayumi eNishi; Noriko eHorii-Hayashi; Takayo eSasagawa

    2014-01-01

    During postnatal development, adverse early life experiences can affect the formation of neuronal circuits and exert long-lasting influences on neural function. Many studies have shown that daily repeated MS, an animal model of early life stress, can modulate the hypothalamic-pituitary-adrenal axis (HPA axis) and can affect subsequent brain function and emotional behavior during adulthood. However, the molecular basis of the long-lasting effects of early life stress on brain function has not ...

  14. Histomorphological Phenotyping of the Adult Mouse Brain.

    Science.gov (United States)

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

    2016-01-01

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

  15. Mapping brain response to social stress in rodents with c-fos expression: a review.

    Science.gov (United States)

    Martinez, M; Calvo-Torrent, A; Herbert, J

    2002-02-01

    Social defeat is an important event in the life of many animals, and forms part of the process of social control. Adapting to social defeat is thus an intrinsic part of social "homeostasis", and mal-adaptation may have pathological sequelae. Experimental models of social defeat (e.g. inter-male aggression) have existed for many years. However, very few studies have investigated the changes in brain activity in male animals exposed to the social stress of being defeated by another conspecific male, and in all these studies the expression of the immediate-early gene c-fos has been used as the marker of neuronal activity. In general, the results obtained inform that many areas of the brain, especially those involved in the general stress response, increase their activity when animals are exposed to an acute defeat. However, when animals are defeated repeatedly over many consecutive days, the level of activation of the brain shows different patterns of adaptation depending on the brain areas (varying from complete habituation to persistent activation). Discrepancies between studies may be due to differences in the experimental procedure. On the other hand, further research has to be conducted in order to understand what these changes in the brain activity mean in relation to the other stress responses to social defeat. Furthermore, knowing that the corresponding protein products of many immediate-early genes are transcription factors that can promote or inhibit the expression of target genes, research following this approach is also necessary.

  16. Pre-frontal control of closed-loop limbic neurostimulation by rodents using a brain-computer interface

    Science.gov (United States)

    Widge, Alik S.; Moritz, Chet T.

    2014-04-01

    Objective. There is great interest in closed-loop neurostimulators that sense and respond to a patient's brain state. Such systems may have value for neurological and psychiatric illnesses where symptoms have high intraday variability. Animal models of closed-loop stimulators would aid preclinical testing. We therefore sought to demonstrate that rodents can directly control a closed-loop limbic neurostimulator via a brain-computer interface (BCI). Approach. We trained rats to use an auditory BCI controlled by single units in prefrontal cortex (PFC). The BCI controlled electrical stimulation in the medial forebrain bundle, a limbic structure involved in reward-seeking. Rigorous offline analyses were performed to confirm volitional control of the neurostimulator. Main results. All animals successfully learned to use the BCI and neurostimulator, with closed-loop control of this challenging task demonstrated at 80% of PFC recording locations. Analysis across sessions and animals confirmed statistically robust BCI control and specific, rapid modulation of PFC activity. Significance. Our results provide a preliminary demonstration of a method for emotion-regulating closed-loop neurostimulation. They further suggest that activity in PFC can be used to control a BCI without pre-training on a predicate task. This offers the potential for BCI-based treatments in refractory neurological and mental illness.

  17. Multi-object model-based multi-atlas segmentation for rodent brains using dense discrete correspondences

    Science.gov (United States)

    Lee, Joohwi; Kim, Sun Hyung; Styner, Martin

    2016-03-01

    The delineation of rodent brain structures is challenging due to low-contrast multiple cortical and subcortical organs that are closely interfacing to each other. Atlas-based segmentation has been widely employed due to its ability to delineate multiple organs at the same time via image registration. The use of multiple atlases and subsequent label fusion techniques has further improved the robustness and accuracy of atlas-based segmentation. However, the accuracy of atlas-based segmentation is still prone to registration errors; for example, the segmentation of in vivo MR images can be less accurate and robust against image artifacts than the segmentation of post mortem images. In order to improve the accuracy and robustness of atlas-based segmentation, we propose a multi-object, model-based, multi-atlas segmentation method. We first establish spatial correspondences across atlases using a set of dense pseudo-landmark particles. We build a multi-object point distribution model using those particles in order to capture inter- and intra- subject variation among brain structures. The segmentation is obtained by fitting the model into a subject image, followed by label fusion process. Our result shows that the proposed method resulted in greater accuracy than comparable segmentation methods, including a widely used ANTs registration tool.

  18. Does Inflammation after Stroke Affect the Developing Brain Differently than Adult Brain?

    OpenAIRE

    Vexler, Zinaida S.; Yenari, Midori A.

    2009-01-01

    The immature brain is prone to hypoxic-ischemic encephalopathy and stroke. The incidence of arterial stroke in newborns is similar to that in the elderly. However, the pathogenesis of ischemic brain injury is profoundly affected by age at the time of the insult. Necrosis is a dominant type of neuronal cell death in adult brain, whereas widespread neuronal apoptosis is unique for the early postnatal synaptogenesis period. The inflammatory response, in conjunction with excitotoxic and oxidative...

  19. In vivo two-photon imaging measuring the blood-brain barrier permeability during early postnatal brain development in rodent

    Science.gov (United States)

    Shi, Lingyan; Rodríguez-Contreras, Adrián.

    2016-03-01

    The blood-brain barrier (BBB) is a unique structure between the cerebral blood circulation and the delicate neural environment that is important in regulating the movement of molecules and ions involved in brain development and function. However, little is known about the physiological permeability of molecules and ions across the BBB during brain development. In this study we applied an innovative approach to examine the development of BBB properties quantitatively. Two-photon microscopy was employed to measure BBB permeability in real time in vivo. Vascular growth and specific interactions between astrocyte end feet and microvessels were studied by using a combination of IB4 histochemistry, immunohistochemistry, confocal microscopy and 3D analysis.

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

    OpenAIRE

    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.

    2009-01-01

    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 gene...

  1. Extracellular matrix molecules and synaptic plasticity: immunomapping of intracellular and secreted Reelin in the adult rat brain.

    Science.gov (United States)

    Ramos-Moreno, Tania; Galazo, Maria J; Porrero, Cesar; Martínez-Cerdeño, Verónica; Clascá, Francisco

    2006-01-01

    Reelin, a large extracellular matrix glycoprotein, is secreted by several neuron populations in the developing and adult rodent brain. Secreted Reelin triggers a complex signaling pathway by binding lipoprotein and integrin membrane receptors in target cells. Reelin signaling regulates migration and dendritic growth in developing neurons, while it can modulate synaptic plasticity in adult neurons. To identify which adult neural circuits can be modulated by Reelin-mediated signaling, we systematically mapped the distribution of Reelin in adult rat brain using sensitive immunolabeling techniques. Results show that the distribution of intracellular and secreted Reelin is both very widespread and specific. Some interneuron and projection neuron populations in the cerebral cortex contain Reelin. Numerous striatal neurons are weakly immunoreactive for Reelin and these cells are preferentially located in striosomes. Some thalamic nuclei contain Reelin-immunoreactive cells. Double-immunolabeling for GABA and Reelin reveals that the Reelin-immunoreactive cells in the visual thalamus are the intrinsic thalamic interneurons. High local concentrations of extracellular Reelin selectively outline several dendrite spine-rich neuropils. Together with previous mRNA data, our observations suggest abundant axoplasmic transport and secretion in pathways such as the retino-collicular tract, the entorhino-hippocampal ('perforant') path, the lateral olfactory tract or the parallel fiber system of the cerebellum. A preferential secretion of Reelin in these neuropils is consistent with reports of rapid, activity-induced structural changes in adult brain circuits.

  2. Low-Radiation Cellular Inductive Powering of Rodent Wireless Brain Interfaces: Methodology and Design Guide.

    Science.gov (United States)

    Soltani, Nima; Aliroteh, Miaad S; Salam, M Tariqus; Perez Velazquez, Jose Luis; Genov, Roman

    2016-08-01

    This paper presents a general methodology of inductive power delivery in wireless chronic rodent electrophysiology applications. The focus is on such systems design considerations under the following key constraints: maximum power delivery under the allowable specific absorption rate (SAR), low cost and spatial scalability. The methodology includes inductive coil design considerations within a low-frequency ferrite-core-free power transfer link which includes a scalable coil-array power transmitter floor and a single-coil implanted or worn power receiver. A specific design example is presented that includes the concept of low-SAR cellular single-transmitter-coil powering through dynamic tracking of a magnet-less receiver spatial location. The transmitter coil instantaneous supply current is monitored using a small number of low-cost electronic components. A drop in its value indicates the proximity of the receiver due to the reflected impedance of the latter. Only the transmitter coil nearest to the receiver is activated. Operating at the low frequency of 1.5 MHz, the inductive powering floor delivers a maximum of 15.9 W below the IEEE C95 SAR limit, which is over three times greater than that in other recently reported designs. The power transfer efficiency of 39% and 13% at the nominal and maximum distances of 8 cm and 11 cm, respectively, is maintained. PMID:26960227

  3. Development of neural stem cell in the adult brain

    OpenAIRE

    Duan, Xin; Kang, Eunchai; Liu, Cindy Y.; Ming, Guo-li; Song, Hongjun

    2008-01-01

    New neurons are continuously generated in the dentate gyrus of the mammalian hippocampus and in the subventricular zone of the lateral ventricles throughout life. The origin of these new neurons is believed to be from multipotent adult neural stem cells. Aided by new methodologies, significant progress has been made in the characterization of neural stem cells and their development in the adult brain. Recent studies have also begun to reveal essential extrinsic and intrinsic molecular mechani...

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

    Science.gov (United States)

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

    2015-04-01

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

  5. A Valuable and Promising Method for Recording Brain Activity in Behaving Newborn Rodents

    OpenAIRE

    Blumberg, Mark S.; Sokoloff, Greta; Tiriac, Alexandre; Del Rio-Bermudez, Carlos

    2015-01-01

    Neurophysiological recording of brain activity has been critically important to the field of neuroscience, but has contributed little to the field of developmental psychobiology. The reasons for this can be traced largely to methodological difficulties associated with recording neural activity in behaving newborn rats and mice. Over the last decade, however, the evolution of methods for recording from head-fixed newborns has heralded a new era in developmental neurophysiology. Here, we review...

  6. Peripheral obestatin has no effect on feeding behavior and brain Fos expression in rodents

    OpenAIRE

    Kobelt, Peter; Wisser, Anna-Sophia; Stengel, Andreas; Goebel, Miriam; Bannert, Norbert; Gourcerol, Guillaume; Inhoff, Tobias; Noetzel, Steffen; Wiedenmann, Bertram; Klapp, Burghard F; Taché, Yvette; Mönnikes, Hubert

    2008-01-01

    Obestatin is produced in the stomach from proghrelin by post-translational cleavage. The initial report claimed anorexigenic effects of obestatin in mice. Contrasting studies indicated no effect of obestatin on food intake (FI). We investigated influences of metabolic state (fed/fasted), environmental factors (dark/light phase) and brain Fos response to intraperitoneal (ip) obestatin in rats, and used the protocol from the original study assessing obestatin effects in mice. FI was determined ...

  7. Adult Brain Plasticity Elicited by Anomia Treatment

    OpenAIRE

    Cornelissen, Katri; Laine, Matti; Tarkiainen, Antti; Järvensivu, Tiina; Martin, Nadine; Salmelin, Riitta

    2003-01-01

    We describe a study where a specific treatment method for word-finding difficulty (so-called contextual priming technique, which combines massive repetition priming with semantic priming) was applied with three chronic left hemisphere-damaged aphasics. Both before and after treatment, which focused on naming of a series of pictures, naming-related brain activity was measured by magnetoencephalography (MEG). Due to its excellent temporal resolution and good spatial resolution, we were able to ...

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

    Directory of Open Access Journals (Sweden)

    Satoru eYamagishi

    2015-04-01

    Full Text Available 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, 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 olfactory bulb, 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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  11. Structure Expression and Function of kynurenine Aminotransferases in Human and Rodent Brains

    Energy Technology Data Exchange (ETDEWEB)

    Q Han; T Cai; D Tagle; J Li

    2011-12-31

    Kynurenine aminotransferases (KATs) catalyze the synthesis of kynurenic acid (KYNA), an endogenous antagonist of N-methyl-D: -aspartate and alpha 7-nicotinic acetylcholine receptors. Abnormal KYNA levels in human brains are implicated in the pathophysiology of schizophrenia, Alzheimer's disease, and other neurological disorders. Four KATs have been reported in mammalian brains, KAT I/glutamine transaminase K/cysteine conjugate beta-lyase 1, KAT II/aminoadipate aminotransferase, KAT III/cysteine conjugate beta-lyase 2, and KAT IV/glutamic-oxaloacetic transaminase 2/mitochondrial aspartate aminotransferase. KAT II has a striking tertiary structure in N-terminal part and forms a new subgroup in fold type I aminotransferases, which has been classified as subgroup Iepsilon. Knowledge regarding KATs is vast and complex; therefore, this review is focused on recent important progress of their gene characterization, physiological and biochemical function, and structural properties. The biochemical differences of four KATs, specific enzyme activity assays, and the structural insights into the mechanism of catalysis and inhibition of these enzymes are discussed.

  12. Assessment of an experimental rodent model of pediatric mild traumatic brain injury.

    Science.gov (United States)

    Mychasiuk, Richelle; Farran, Allyson; Esser, Michael J

    2014-04-15

    Childhood is one the highest risk periods for experiencing a mild traumatic brain injury (mTBI) from sports-related concussions, motor vehicle accidents, and falls. In addition, many children experience lingering symptomology (post-concussion syndrome) from these closed head injuries. Although the negative sequel of mTBI has been described, a clinically reliable animal model of mild pediatric brain injury has not. The purpose of this study was to examine the validity of a modified weight-drop technique as a model for the induction of mTBI/concussion in juvenile rats following a single impact. Male and female rats (P30) were exposed to a single mTBI or a sham injury followed by a behavioral test battery. Juvenile rats who experienced a single mTBI displayed significant motor/balance impairments when tested on the beam walking task and in the open field, as well as deficits of executive functioning as measured with the novel context mismatch task and the probe trial of the Morris water task. In addition, both male and female rats showed depression-like behavior in the forced swim task, with male rats also exhibiting decreased anxiety-related behaviors in the elevated plus maze. The results from this study suggest that the modified weight-drop technique induces a clinically relevant behavioral phenotype in juvenile rats, and may provide researchers with a reliable animal model of mTBI/concussion from which clinical therapeutic strategies could be developed. PMID:24283269

  13. Salubrinal reduces oxidative stress, neuroinflammation and impulsive-like behavior in a rodent model of traumatic brain injury.

    Science.gov (United States)

    Logsdon, Aric F; Lucke-Wold, Brandon P; Nguyen, Linda; Matsumoto, Rae R; Turner, Ryan C; Rosen, Charles L; Huber, Jason D

    2016-07-15

    Traumatic brain injury (TBI) is the leading cause of trauma related morbidity in the developed world. TBI has been shown to trigger secondary injury cascades including endoplasmic reticulum (ER) stress, oxidative stress, and neuroinflammation. The link between secondary injury cascades and behavioral outcome following TBI is poorly understood warranting further investigation. Using our validated rodent blast TBI model, we examined the interaction of secondary injury cascades following single injury and how these interactions may contribute to impulsive-like behavior after a clinically relevant repetitive TBI paradigm. We targeted these secondary pathways acutely following single injury with the cellular stress modulator, salubrinal (SAL). We examined the neuroprotective effects of SAL administration on significantly reducing ER stress: janus-N-terminal kinase (JNK) phosphorylation and C/EBP homology protein (CHOP), oxidative stress: superoxide and carbonyls, and neuroinflammation: nuclear factor kappa beta (NFκB) activity, inducible nitric oxide synthase (iNOS) protein expression, and pro-inflammatory cytokines at 24h post-TBI. We then used the more clinically relevant repeat injury paradigm and observed elevated NFκB and iNOS activity. These injury cascades were associated with impulsive-like behavior measured on the elevated plus maze. SAL administration attenuated secondary iNOS activity at 72h following repetitive TBI, and most importantly prevented impulsive-like behavior. Overall, these results suggest a link between secondary injury cascades and impulsive-like behavior that can be modulated by SAL administration. PMID:27131989

  14. Pedophilic brain potential responses to adult erotic stimuli.

    Science.gov (United States)

    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

  15. DNA synthesis and cell division in the adult primate brain

    International Nuclear Information System (INIS)

    It is generally accepted that the adult human brain is incapable of producing new neuron. Even cursory examination of neurologic, neuropathologic, or neurobiological textbooks published during the past 50 years will testify that this belief is deeply entrenched. In his classification of cell populations on the basis of their proliferative behavior, Leblond regarded neurons of the central nervous system as belonging to a category of static, nonrenewing epithelial tissue incapable of expanding or replenishing itself. This belief, however needs to re reexamined for two major reasons: First, as reviewed below, a number of reports have provided evidence of neurogenesis in adult brain of several vertebrate species. Second, the capacity for neurogenesis in the adult primate central nervous system has never been examined by modern methods. In this article the author described recent results from an extensive autoradiographic analysis performed on twelve rhesus monkeys injected with the specific DNA precursor [3H] thymidine at ages ranging from 6 postnatal months to 17 years

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

    Science.gov (United States)

    Ugriumov, M V

    2009-01-01

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

  17. Moxidectin causes adult worm mortality of human lymphatic filarial parasite Brugia malayi in rodent models.

    Science.gov (United States)

    Verma, Meenakshi; Pathak, Manisha; Shahab, Mohd; Singh, Kavita; Mitra, Kalyan; Misra-Bhattacharya, Shailja

    2014-12-01

    Moxidectin is a macrocyclic lactone belonging to milbemycin family closely related to ivermectin and is currently progressing towards Phase III clinical trial against human infection with the filaria Onchocerca volvulus (Leuckart, 1894). There is a single report on the microfilaricidal and embryostatic activity of moxidectin in case of the human lymphatic filarial parasite Brugia malayi (Brug, 1927) in Mastomys coucha (Smith) but without any adulticidal action. In the present study, the in vitro and in vivo antifilarial efficacy of moxidectin was evaluated on, B. malayi. In vitro moxidectin showed 100% reduction in adult female worm motility at 0.6 μM concentration within 7 days with 68% inhibition in the reduction of MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide dye) (which is used to detect viability of worms). A 50% inhibitory concentration (IC50) of moxidectin for adult female parasite was 0.242 μM, for male worm 0.186 μM and for microfilaria IC50 was 0.813 μM. In adult B. malayi-transplanted primary screening model (Meriones unguiculatus Milne-Edwards), moxidectin at a single optimal dose of 20 mg/kg by oral and subcutaneous route was found effective on both adult parasites and microfilariae. In secondary screening (M coucha, subcutaneously inoculated with infective larvae), moxidectin at the same dose by subcutaneous route brought about death of 49% of adult worms besides causing sterilisation in 54% of the recovered live female worms. The treated animals exhibited a continuous and sustained reduction in peripheral blood microfilaraemia throughout the observation period of 90 days. The mechanism of action of moxidectin is suggested to be similar to avermectins. The in silico studies were also designed to explore the interaction of moxidectin with glutamate-gated chloride channels of B. malayi. The docking results revealed a close interaction of moxidectin with various GluCl ligand sites of B. malayi. PMID:25651699

  18. Development of NMR imaging using CEST agents: application to brain tumor in a rodent model

    International Nuclear Information System (INIS)

    The study aimed at developing saturation transfer imaging of lipoCEST contrast agents for the detection of angiogenesis in a U87 mouse brain tumor model. A lipoCEST with a sensitivity threshold of 100 pM in vitro was optimized in order to make it compatible with CEST imaging in vivo. Thanks to the development of an experimental setup dedicated to CEST imaging, we evaluated lipoCEST to detect specifically tumor angiogenesis. We demonstrated for the first time that lipoCEST visualization was feasible in vivo in a mouse brain after intravenous injection. Moreover, the integrin αvβ3 over expressed during tumor angiogenesis can be specifically targeted using a functionalized lipoCEST with RGD peptide. The specific association between the RGD-lipoCEST and its target αvβ3 was confirmed by immunohistochemical data and fluorescence microscopy. Finally, in order to tend to a molecular imaging protocol by CEST-MRI, we developed a quantification tool of lipoCEST contrast agents. This tool is based on modeling of proton exchange processes in vivo. By taking into account both B0 and B1 fields inhomogeneities which can dramatically alter CEST contrast, we showed that the accuracy of our quantification tool was 300 pM in vitro. The tool was applied on in vivo data acquired on the U87 mouse model and the maximum concentration of RGD-lipoCEST linked to their molecular targets was evaluated to 1.8 nM. (author)

  19. File list: InP.Neu.50.AllAg.Adult_brains [Chip-atlas[Archive

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

    Science.gov (United States)

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

    2014-01-01

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

  13. Synergist Ablation as a Rodent Model to Study Satellite Cell Dynamics in Adult Skeletal Muscle.

    Science.gov (United States)

    Kirby, Tyler J; McCarthy, John J; Peterson, Charlotte A; Fry, Christopher S

    2016-01-01

    In adult skeletal muscles, satellite cells are the primary myogenic stem cells involved in myogenesis. Normally, they remain in a quiescent state until activated by a stimulus, after which they proliferate, differentiate, and fuse into an existing myofiber or form a de novo myofiber. To study satellite cell dynamics in adult murine models, most studies utilize regeneration models in which the muscle is severely damaged and requires the participation from satellite cells in order to repair. Here, we describe a model to study satellite cell behavior in muscle hypertrophy that is independent of muscle regeneration.Synergist ablation surgery involves the surgical removal of the gastrocnemius and soleus muscles resulting in functional overload of the remaining plantaris muscle. This functional overload results in myofiber hypertrophy, as well as the activation, proliferation, and fusion of satellite cells into the myofibers. Within 2 weeks of functional overload, satellite cell content increases approximately 275 %, an increase that is accompanied with a ~60 % increase in the number of myonuclei. Therefore, this can be used as an alternative model to study satellite cell behavior in adulthood that is different from regeneration, and capable of revealing new satellite cell functions in regulating muscle adaptation. PMID:27492164

  14. Detrimental psychophysiological effects of early maternal deprivation in adolescent and adult rodents: altered responses to cannabinoid exposure.

    Science.gov (United States)

    Marco, Eva M; Adriani, Walter; Llorente, Ricardo; Laviola, Giovanni; Viveros, María-Paz

    2009-04-01

    Environmental rearing conditions during the neonatal period are critical for the establishment of neurobiological factors controlling behavior and stress responsiveness. Early maternal deprivation (MD), consisting of a single 24-h maternal deprivation episode during early neonatal life, has been proposed as an animal model for certain psychopathologies including anxiety, depression and schizophrenic-related disorders. Despite first onset of mental disorders usually occur during adolescence, characterization of MD has been mostly developed in adult animals. We review here a series of experiments that were conducted on rats and mice, in which we analyzed the psychoimmunoendocrine outcomes of MD at both adolescence and adulthood. As a whole our results indicate that MD might promote a depressive-like trait that may be present from adolescence to maturity. Maternally deprived adolescent animals also displayed altered locomotor responses, a reduced interest for social investigation and seemed prone for impulsive behavior. Therefore, MD in rodents is further confirmed as a suitable animal model for the study of neuropsychiatric disorders that might become evident during adolescence. Given the increasing consumption of cannabis derivatives among the juvenile population and the reported comorbidity of neuropsychiatric symptoms with cannabis abuse, we also discuss our results indicating altered responses of maternally deprived adolescent animals to cannabinoid compounds.

  15. Discordant localization of WFA reactivity and brevican/ADAMTS-derived fragment in rodent brain

    Directory of Open Access Journals (Sweden)

    Hamel Michelle G

    2008-01-01

    Full Text Available Abstract Background Proteoglycan (PG in the extracellular matrix (ECM of the central nervous system (CNS may act as a barrier for neurite elongation in a growth tract, and regulate other characteristics collectively defined as structural neural plasticity. Proteolytic cleavage of PGs appears to alter the environment to one favoring plasticity and growth. Brevican belongs to the lectican family of aggregating, chondroitin sulfate (CS-bearing PGs, and it modulates neurite outgrowth and synaptogenesis. Several ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs are glutamyl-endopeptidases that proteolytically cleave brevican. The purpose of this study was to localize regions of adult CNS that contain a proteolytic-derived fragment of brevican which bears the ADAMTS-cleaved neoepitope sequence. These regions were compared to areas of Wisteria floribunda agglutin (WFA reactivity, a common reagent used to detect "perineuronal nets" (PNNs of intact matrix and a marker which is thought to label regions of relative neural stability. Results WFA reactivity was found primarily as PNNs, whereas brevican and the ADAMTS-cleaved fragment of brevican were more broadly distributed in neuropil, and in particular regions localized to PNNs. One example is hippocampus where the ADAMTS-cleaved brevican fragment is found surrounding pyramidal neurons, in neuropil of stratum oriens/radiatum and the lacunosum moleculare. The fragment was less abundant in the molecular layer of the dentate gyrus. Mostly PNNs of scattered interneurons along the pyramidal layer were identified by WFA. In lateral thalamus, the reticular thalamic nucleus stained abundantly with WFA whereas ventral posterior nuclei were markedly immunopositive for ADAMTS-cleaved brevican. Using Western blotting techniques, no common species were reactive for brevican and WFA. Conclusion In general, a marked discordance was observed in the regional localization between WFA and brevican or

  16. Juvenile ferric iron prevents microbiota dysbiosis and colitis in adult rodents

    Institute of Scientific and Technical Information of China (English)

    Chourouk Ettreiki; Pascale Gadonna-Widehem; Irène Mangin; Mo(i)se Co(e)ffier; Carine Delayre-Orthez; Pauline M Anton

    2012-01-01

    AIM:To assess whether juvenile chronic ferric iron ingestion limit colitis and dysbiosis at adulthood in rats and mice.METHODS:Two sets of experiments were designed.In the first set,recently weaned mice were either orally administered ferrous (Fe2+) iron salt or ferric (Fe3+) microencapsulated iron for 6 wk.The last week of experiments trinitrobenzene sulfonic acid (TNBS) colitis was induced.In the second set,juvenile rats received the microencapsulated ferric iron for 6 wk and were also submitted to TNBS colitis during the last week of experiments.In both sets of experiments,animals were sacrificed 7 d after TNBS instillation.Severity of the inflammation was assessed by scoring macroscopic lesions and quantifying colonic myeloperoxidase (MPO) activity.Alteration of the microflora profile was estimated using quantitative polymerase chain reaction (qPCR) by measuring the evolution of total caecal microflora,Bacteroidetes,Firmicutes and enterobacteria.RESULTS:Neither ferrous nor ferric iron daily exposures at the juvenile period result in any effect in control animals at adulthood although ferrous iron repeated administration in infancy limited weight gain.Ferrous iron was unable to limit the experimental colitis (1.71 ± 0.27MPO U/mg protein vs 2.47 ± 0.22 MPO U/mg protein in colitic mice).In contrast,ferric iron significantly prevented the increase of MPO activity (1.64 ± 0.14 MPO U/mg protein) in TNBS-induced colitis.Moreover,this positive effect was observed at both the doses of ferric iron used (75 and 150 mg/kg per day po-6 wk).In the study we also compared,in both rats and mice,the consequences of chronic repeated low level exposure to ferric iron (75 mg/kg per day po-6 wk) on TNBS-induced colitis and its related dysbiosis.We confirmed that ferric iron limited the TNBS-induced increase of MPO activity in both the rodent species.Furthermore,we assessed the ferric iron incidence on TNBS-induced intestinal microbiota dysbiosis.At first,we needed to optimize the

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2016-11-01

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

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

    OpenAIRE

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

    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. Despite Wnt proteins and components of the Wnt pathway are expressed in the brain since early development to the adult life, little is known about its role in mature synapses. Here, we review evidences indicating that Wnt proteins participate in the remodeling of pre- and postsynaptic regions, thus ...

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

    Science.gov (United States)

    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

  1. Regional genome transcriptional response of adult mouse brain to hypoxia

    Directory of Open Access Journals (Sweden)

    Lu Aigang

    2011-10-01

    Full Text Available Abstract Background Since normal brain function depends upon continuous oxygen delivery and short periods of hypoxia can precondition the brain against subsequent ischemia, this study examined the effects of brief hypoxia on the whole genome transcriptional response in adult mouse brain. Result Pronounced changes of gene expression occurred after 3 hours of hypoxia (8% O2 and after 1 hour of re-oxygenation in all brain regions. The hypoxia-responsive genes were predominantly up-regulated in hindbrain and predominantly down-regulated in forebrain - possibly to support hindbrain survival functions at the expense of forebrain cognitive functions. The up-regulated genes had a significant role in cell survival and involved both shared and unshared signaling pathways among different brain regions. Up-regulation of transcriptional signaling including hypoxia inducible factor, insulin growth factor (IGF, the vitamin D3 receptor/retinoid X nuclear receptor, and glucocorticoid signaling was common to many brain regions. However, many of the hypoxia-regulated target genes were specific for one or a few brain regions. Cerebellum, for example, had 1241 transcripts regulated by hypoxia only in cerebellum but not in hippocampus; and, 642 (54% had at least one hepatic nuclear receptor 4A (HNF4A binding site and 381 had at least two HNF4A binding sites in their promoters. The data point to HNF4A as a major hypoxia-responsive transcription factor in cerebellum in addition to its known role in regulating erythropoietin transcription. The genes unique to hindbrain may play critical roles in survival during hypoxia. Conclusion Differences of forebrain and hindbrain hypoxia-responsive genes may relate to suppression of forebrain cognitive functions and activation of hindbrain survival functions, which may coordinately mediate the neuroprotection afforded by hypoxia preconditioning.

  2. Intraparenchymal ultrasound application and improved distribution of infusate with convection-enhanced delivery in rodent and nonhuman primate brain.

    Science.gov (United States)

    Mano, Yui; Saito, Ryuta; Haga, Yoichi; Matsunaga, Tadao; Zhang, Rong; Chonan, Masashi; Haryu, Shinya; Shoji, Takuhiro; Sato, Aya; Sonoda, Yukihiko; Tsuruoka, Noriko; Nishiyachi, Keisuke; Sumiyoshi, Akira; Nonaka, Hiroi; Kawashima, Ryuta; Tominaga, Teiji

    2016-05-01

    OBJECT Convection-enhanced delivery (CED) is an effective drug delivery method that delivers high concentrations of drugs directly into the targeted lesion beyond the blood-brain barrier. However, the drug distribution attained using CED has not satisfactorily covered the entire targeted lesion in tumors such as glioma. Recently, the efficacy of ultrasound assistance was reported for various drug delivery applications. The authors developed a new ultrasound-facilitated drug delivery (UFD) system that enables the application of ultrasound at the infusion site. The purpose of this study was to demonstrate the efficacy of the UFD system and to examine effective ultrasound profiles. METHODS The authors fabricated a steel bar-based device that generates ultrasound and enables infusion of the aqueous drug from one end of the bar. The volume of distribution (Vd) after infusion of 10 ml of 2% Evans blue dye (EBD) into rodent brain was tested with different frequencies and applied voltages: 252 kHz/30 V; 252 kHz/60 V; 524 kHz/13 V; 524 kHz/30 V; and 524 kHz/60 V. In addition, infusion of 5 mM gadopentetate dimeglumine (Gd-DTPA) was tested with 260 kHz/60 V, the distribution of which was evaluated using a 7-T MRI unit. In a nonhuman primate (Macaca fascicularis) study, 300 μl of 1 mM Gd-DTPA/EBD was infused. The final distribution was evaluated using MRI. Two-sample comparisons were made by Student t-test, and 1-way ANOVA was used for multiple comparisons. Significance was set at p < 0.05. RESULTS After infusion of 10 μl of EBD into the rat brain using the UFD system, the Vds of EBD in the UFD groups were significantly larger than those of the control group. When a frequency of 252 kHz was applied, the Vd of the group in which 60 V was applied was significantly larger than that of the group in which 30 V was used. When a frequency of 524 kHz was applied, the Vd tended to increase with application of a higher voltage; however, the differences were not significant (1-way

  3. The effects of aging on dopaminergic neurotransmission: a microPET study of [11C]-raclopride binding in the aged rodent brain.

    Science.gov (United States)

    Hoekzema, E; Herance, R; Rojas, S; Pareto, D; Abad, S; Jiménez, X; Figueiras, F P; Popota, F; Ruiz, A; Torrent, È; Fernández-Soriano, F J; Rocha, M; Rovira, M; Víctor, V M; Gispert, J D

    2010-12-29

    Rodent models are frequently used in aging research to investigate biochemical age effects and aid in the development of therapies for pathological and non-pathological age-related degenerative processes. In order to validate the use of animal models in aging research and pave the way for longitudinal intervention-based animal studies, the consistency of cerebral aging processes across species needs to be evaluated. The dopaminergic system seems particularly susceptible to the aging process, and one of the most consistent findings in human brain aging research is a decline in striatal D2-like receptor (D2R) availability, quantifiable by positron emission tomography (PET) imaging. In this study, we aimed to assess whether similar age effects can be discerned in rat brains, using in vivo molecular imaging with the radioactive compound [(11)C]-raclopride. We observed a robust decline in striatal [(11)C]-raclopride uptake in the aged rats in comparison to the young control group, comprising a 41% decrement in striatal binding potential. In accordance with human studies, these results indicate that substantial reductions in D2R availability can be measured in the aged striatal complex. Our findings suggest that rat and human brains exhibit similar biochemical alterations with age in the striatal dopaminergic system, providing support for the pertinence of rodent models in aging research.

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

    Science.gov (United States)

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

    2012-11-01

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

  5. Effects of NOS inhibitor on dentate gyrus neurogenesis after diffuse brain injury in the adult rats

    Institute of Scientific and Technical Information of China (English)

    SunLi-Sha; XuJiang-ping

    2004-01-01

    Objective To investigate the effects of selective nitric oxide synthase (NOS) inhibitors on dentate gyrus neurogenesis after diffuse brain injury (DBI) in the adult rat brain. Methods Adult male SD rats were subjected to diffuse brain injury (DBI) model. By using systemic bromodeoxyuridine (BrdU) to label dividing cells, we compared the proliferation rate of

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

    Energy Technology Data Exchange (ETDEWEB)

    Temple, Nikki; Donald, Cortny; Skora, Amanda [Discipline of Medical Radiation Sciences, The University of Sydney, Lidcombe, New South Wales (Australia); Reed, Warren, E-mail: warren.reed@sydney.edu.au [Medical Image Optimisation and Perception Group, Discipline of Medical Radiation Sciences, The University of Sydney, Lidcombe, New South Wales (Australia)

    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.

  7. Morphological brain differences between adult stutterers and non-stutterers

    Directory of Open Access Journals (Sweden)

    Hänggi Jürgen

    2004-12-01

    Full Text Available Abstract Background The neurophysiological and neuroanatomical foundations of persistent developmental stuttering (PDS are still a matter of dispute. A main argument is that stutterers show atypical anatomical asymmetries of speech-relevant brain areas, which possibly affect speech fluency. The major aim of this study was to determine whether adults with PDS have anomalous anatomy in cortical speech-language areas. Methods Adults with PDS (n = 10 and controls (n = 10 matched for age, sex, hand preference, and education were studied using high-resolution MRI scans. Using a new variant of the voxel-based morphometry technique (augmented VBM the brains of stutterers and non-stutterers were compared with respect to white matter (WM and grey matter (GM differences. Results We found increased WM volumes in a right-hemispheric network comprising the superior temporal gyrus (including the planum temporale, the inferior frontal gyrus (including the pars triangularis, the precentral gyrus in the vicinity of the face and mouth representation, and the anterior middle frontal gyrus. In addition, we detected a leftward WM asymmetry in the auditory cortex in non-stutterers, while stutterers showed symmetric WM volumes. Conclusions These results provide strong evidence that adults with PDS have anomalous anatomy not only in perisylvian speech and language areas but also in prefrontal and sensorimotor areas. Whether this atypical asymmetry of WM is the cause or the consequence of stuttering is still an unanswered question.

  8. Tai Ji Quan, the brain, and cognition in older adults

    Directory of Open Access Journals (Sweden)

    Yu-Kai Chang

    2014-03-01

    Full Text Available The relationship between physical activity (PA and cognition has received much attention recently. While evidence of improved cognition following PA has consistently been observed, the majority of studies have spotlighted aerobic exercise and the effects of other modes of PA, such as Tai Ji Quan, on cognition have received limited attention. This article provides a brief review of the literature concerning the influence of Tai Ji Quan on cognition in older adults, including those with intact cognition and those with cognitive impairment. In addition, this review proposes potential mechanisms (cardiovascular fitness, motor fitness, movement coordination, social interaction, and meditation statuses as well brain structure and function evaluated from a neuroimaging perspective that may explain the Tai Ji Quan–cognition relationship. Finally, we present suggestions for future research. In conclusion, Tai Ji Quan, with its multi-faceted characteristics, shows promise as a mode of PA for enhancing cognition, as well as brain health, in older adults. Based on the findings in this review, further exploration of the effects of Tai Ji Quan on cognition in older adults is warranted.

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

    International Nuclear Information System (INIS)

    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

  10. Prevalence of abnormal findings on brain magnetic resonance (MR examinations in adult participants of brain docking

    Directory of Open Access Journals (Sweden)

    Taketomi-Takahashi Ayako

    2005-10-01

    Full Text Available Abstract Background To determine the prevalence of abnormal findings on brain magnetic resonance (MR examinations in adult participants of brain docking in order to assess its usefulness. Methods We analyzed screening brain MR examinations for 1113 adults (age, 52.6+/-8.5 years; range, 22–84; 761 male and 352 female performed during 6-year period from April 1998 to March 2004. All participants voluntarily sought a brain MR examination at their own expense. All subjects were studied using the same 1.0-T MR scanner, on axial T1-weighted spin echo (SE images, proton-density-weighted and T2-weighted fast SE images, and intracranial MR angiography (MRA. All abnormal findings were classified into three basic categories: (1 findings with no referral necessary; (2 findings not requiring further evaluation, but which needed to be reported to the referring physician; (3 findings requiring further evaluation. Results Participants with abnormal MR findings requiring further evaluation accounted for 1.3 %, but five of seven suspected intracranial aneurysms were not confirmed by other imaging modalities (false positive. No malignant tumors or other life-threatening pathology was detected, and only three participants (0.27 % with abnormalities underwent surgical treatment. No participant groups were identified from our data as being high risk for MR abnormal findings requiring further evaluation. Conclusion Brain-docking participants had a variety of abnormalities on brain MR examinations, but only a small percentage of these findings required further evaluation. The usefulness of the brain docking with MRI and MRA has yet to be proven, and at this time we cannot approve this screening procedure.

  11. Validated methods for determination of neurotransmitters and metabolites in rodent brain tissue and extracellular fluid by reversed phase UHPLC-MS/MS.

    Science.gov (United States)

    Bergh, Marianne Skov-Skov; Bogen, Inger Lise; Lundanes, Elsa; Øiestad, Åse Marit Leere

    2016-08-15

    Fast and sensitive methods for simultaneous determination of dopamine (DA), the two DA-metabolites homovanillic acid (HVA) and 3-methoxytyramine (3-MT), serotonin (5-HT) and the 5-HT-metabolite 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine (NE), acetylcholine (ACh), glutamic acid (Glu) and γ-aminobutyric acid (GABA) in rodent brain tissue (1.0-4000nM) and extracellular fluid (ECF) (0.5-2000nM) based on ultra high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) have been developed. Of the three different sample preparation methods for brain tissue samples tested, a simple and rapid protein precipitation procedure with formic acid was found to give the best results. The neurotransmitters (NTs) and NT metabolites were separated using UHPLC with an Acquity UPLC HSS T3 C18 column (2.1×100mm, 1.8μm particle size) with acidic mobile phase. Gradient elution with methanol was used and quantification was performed using multiple reaction monitoring (MRM). The total run time was 5.2min including equilibration time. The methods were validated by determining calibration model, intra- and inter-day precision and accuracy, limit of detection (LOD), lower limit of quantification (LLOQ), matrix effects (ME), carry-over and stability. Surrogate analytes were used to enable determination of the recovery and ME of the endogenous analytes in brain tissue. The methods were applied for determination of NTs at basal levels in rodent brain ECF and brain tissue homogenate. The developed methods are valuable tools in the studies of mechanisms of drugs of abuse, and neurologic and psychiatric disease. PMID:27336704

  12. Brain micro-ecologies: neural stem cell niches in the adult mammalian brain

    OpenAIRE

    Riquelme, Patricio A; Drapeau, Elodie; Doetsch, Fiona

    2007-01-01

    Neurogenesis persists in two germinal regions in the adult mammalian brain, the subventricular zone of the lateral ventricles and the subgranular zone in the hippocampal formation. Within these two neurogenic niches, specialized astrocytes are neural stem cells, capable of self-renewing and generating neurons and glia. Cues within the niche, from cell–cell interactions to diffusible factors, are spatially and temporally coordinated to regulate proliferation and neurogenesis, ultimately affect...

  13. P-glycoprotein Function in the Rodent Brain Displays a Daily Rhythm, a Quantitative In Vivo PET Study

    NARCIS (Netherlands)

    Savolainen, Heli; Meerlo, Peter; Elsinga, Philip H.; Windhorst, Albert D.; Dierckx, Rudi; Colabufo, Nicola A.; van Waarde, Aren; Luurtsema, Geert

    2016-01-01

    Abstract. The blood-brain barrier (BBB) contributes to brain homeostasis by protecting the brain from harmful compounds. P-glycoprotein (P-gp) is one of the major efflux transporters at the BBB. In the present study, we assessed whether (1) P-gp function in the brain is constant or fluctuates across

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

    Science.gov (United States)

    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

  15. Risk of thyroid cancer, brain cancer, and non-Hodgkin lymphoma after adult leukemia

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Birgens, Henrik S;

    2011-01-01

    Patients with childhood leukemia surviving into adulthood have elevated risk of developing thyroid cancer, brain cancer, and non-Hodgkin lymphoma (NHL); these risks cannot automatically be extrapolated to patients surviving adult leukemia. We tested whether survivors of adult leukemia...

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

    Science.gov (United States)

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

    2008-09-01

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

  17. Clinical Feature And Pathogeny Analysis Of Brain Hemorrhage In Young Adult Group

    Institute of Scientific and Technical Information of China (English)

    Wang Jianming; Zeng Xiaoyun

    2000-01-01

    Objection: The trend of brain hemorrhage cases of young adults have increased recently. In this article, We studied brain hemorrhage clinical feature and pathogenic causes of 72 young adults, Whose ages are all beneath 45Y. We found That the major pathogen reasons of young adult brain hemorrhage are blood system diseases、 arteriovenous malformation of cerebral blood vessel、 hypertension arteriosclerosis、 arteritis and rheumatic heart disease et. We also found that the trend can be related to hard work、 tense life、 drinking too much alcohol and eating high lipid food, and cercbral vascular disease family history. So in order to reduce the incidence of young adult brain hemorrhage, Young adults should not drink and smoke heavily, should not eat too much high lipid food. Young adults who have hypertension and brain vessel disease family history should be regularly measured blood pressure and blood lipid. If they had hypertension, should be treated regularly.

  18. Reaction with glutathione. A possible mechanism involved in rodent brain retention of a 99mTc SNS/S complex containing a pendant ester functionality

    International Nuclear Information System (INIS)

    The synthesis, characterization of MvO([CH3CH2N(CH2CH2S)2](p-S-Ph-COOCH2-CH3)) (M:99mTc: I, Re: II) is presented in this work, where a pendant ester function is attached to the monothiolate ligand. Chemical structure of I is established after chromatographic comparison with II, synthesized in macroscopic amounts. Complex II is fully characterized by classical methods of analysis showing that the compound adopts a distorted trigonal bipyramidal configuration around the metal. The two sulfur atoms of the tridentate ligand and the oxo group form the basal plane, while the remaining nitrogen atom of the tridentate ligand and the sulfur atom of the monothiolate ligand occupy the apices of the bipyramid. In vitro challenge experiments with glutathione (GSH) in neutral aqueous medium demonstrate, that I suffers nucleophilic attack by GSH and thereby transformation to a more hydrophilic daughter metal compound. Formation of the latter depends on time and GSH concentration. Tissue distribution in mice shows minor retention in brain. As rodent brain presents no esterases to hydrolyze the ester group of I, while the intracerebral content in GSH amounts to 2 mM, the above described mechanism is suspected for the observed brain retention. However, in primate brain cells retention of I may additionally involve the hydrolysis of the ester function to the corresponding acid, as already revealed by preliminary in vitro experiments using esterase incubates. (author)

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

    Science.gov (United States)

    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

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

    International Nuclear Information System (INIS)

    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

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

    OpenAIRE

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

    2013-01-01

    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 an...

  2. Intravenous multipotent adult progenitor cell therapy attenuates activated microglial/macrophage response and improves spatial learning after traumatic brain injury.

    Science.gov (United States)

    Bedi, Supinder S; Hetz, Robert; Thomas, Chelsea; Smith, Philippa; Olsen, Alex B; Williams, Stephen; Xue, Hasen; Aroom, Kevin; Uray, Karen; Hamilton, Jason; Mays, Robert W; Cox, Charles S

    2013-12-01

    We previously demonstrated that the intravenous delivery of multipotent adult progenitor cells (MAPCs) after traumatic brain injury (TBI) in rodents provides neuroprotection by preserving the blood-brain barrier and systemically attenuating inflammation in the acute time frame following cell treatment; however, the long-term behavioral and anti-inflammatory effects of MAPC administration after TBI have yet to be explored. We hypothesized that the intravenous injection of MAPCs after TBI attenuates the inflammatory response (as measured by microglial morphology) and improves performance at motor tasks and spatial learning (Morris water maze [MWM]). MAPCs were administered intravenously 2 and 24 hours after a cortical contusion injury (CCI). We tested four groups at 120 days after TBI: sham (uninjured), injured but not treated (CCI), and injured and treated with one of two concentrations of MAPCs, either 2 million cells per kilogram (CCI-2) or 10 million cells per kilogram (CCI-10). CCI-10 rats showed significant improvement in left hind limb deficit on the balance beam. On the fifth day of MWM trials, CCI-10 animals showed a significant decrease in both latency to platform and distance traveled compared with CCI. Probe trials revealed a significant decrease in proximity measure in CCI-10 compared with CCI, suggesting improved memory retrieval. Neuroinflammation was quantified by enumerating activated microglia in the ipsilateral hippocampus. We observed a significant decrease in the number of activated microglia in the dentate gyrus in CCI-10 compared with CCI. Our results demonstrate that intravenous MAPC treatment after TBI in a rodent model offers long-term improvements in spatial learning as well as attenuation of neuroinflammation.

  3. Neurogenesis in the embryonic and adult brain: same regulators, different roles.

    Directory of Open Access Journals (Sweden)

    Noelia eUrban

    2014-11-01

    Full Text Available Neurogenesis persists in adult mammals in specific brain areas, known as neurogenic niches. Adult neurogenesis is highly dynamic and is modulated by multiple physiological stimuli and pathological states. There is a strong interest in understanding how this process is regulated, particularly since active neuronal production has been demonstrated in both the hippocampus and the subventricular zone of adult humans.The molecular mechanisms that control neurogenesis have been extensively studied during embryonic development. Therefore, we have a broad knowledge of the intrinsic factors and extracellular signalling pathways driving proliferation and differentiation of embryonic neural precursors. Many of these factors also play important roles during adult neurogenesis, but essential differences exist in the biological responses of neural precursors in the embryonic and adult contexts. Because adult neural stem cells are normally found in a quiescent state, regulatory pathways can affect adult neurogenesis in ways that have no clear counterpart during embryogenesis. BMP signalling, for instance, regulates neural stem cell behaviour both during embryonic and adult neurogenesis. However, this pathway maintains stem cell proliferation in the embryo, while it promotes quiescence to prevent stem cell exhaustion in the adult brain. In this review, we will compare and contrast the functions of transcription factors and other regulatory molecules in the embryonic brain and in adult neurogenic regions of the adult brain in the mouse, with a special focus on the hippocampal niche and on the regulation of the balance between quiescence and activation of adult neural stem cells in this region.

  4. Inhibition of Large Neutral Amino Acid Transporters Suppresses Kynurenic Acid Production Via Inhibition of Kynurenine Uptake in Rodent Brain.

    Science.gov (United States)

    Sekine, Airi; Kuroki, Yusuke; Urata, Tomomi; Mori, Noriyuki; Fukuwatari, Tsutomu

    2016-09-01

    The tryptophan metabolite, kynurenic acid (KYNA), is a preferential antagonist of the α7 nicotinic acetylcholine receptor and N-methyl-D-aspartic acid receptor at endogenous brain concentrations. Recent studies have suggested that increases of brain KYNA levels are involved in psychiatric disorders such as schizophrenia and depression, and regulation of KYNA production has become a new target for treatment of these diseases. Kynurenine (KYN), the immediate precursor of KYNA, is transported into astrocytes via large neutral amino acid transporters (LATs). In the present study, the effect of LATs regulation on KYN uptake and KYNA production was investigated in vitro and in vivo using an LATs inhibitor, 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH). In the in vitro study, cortical slices of rat brain were incubated with a physiological concentration of KYN and 3 µmol/L-3 mmol/L BCH. BCH inhibited KYNA production and KYN uptake in a dose-dependent manner, and their IC50 values were 90.7 and 97.4 µmol/L, respectively. In the in vivo study, mice were administered KYN (50 mg/kg BW) orally and BCH (200 mg/kg BW) intravenously. Administration of KYN increased brain KYN and KYNA levels compared with the mice treated with vehicle, whereas additional administration of BCH suppressed KYN-induced elevations in KYN and KYNA levels to 50 and 70 % in the brain. These results suggest that inhibition of LATs prevented the increase of KYNA production via blockade of KYN uptake in the brain in vitro and in vivo. LATs can be a target to modulate brain function by regulation of KYNA production in the brain. PMID:27161376

  5. Specific accumulation of {sup 18}F-deoxyglucose in three-dimensional long-term cultures of human and rodent brain tissue

    Energy Technology Data Exchange (ETDEWEB)

    Hocke, C.; Prante, O.; Kuwert, T. [Clinic of Nuclear Medicine, Univ. of Erlangen-Nuernberg (Germany); Bluemcke, I.; Jeske, I. [Dept. of Neuropathology, Univ. of Erlangen-Nuernberg (Germany); Romstoeck, J. [Dept. of Neurosurgery, Univ. of Erlangen-Nuernberg (Germany); Stefan, H. [Dept. of Neurology, Univ. of Erlangen-Nuernberg (Germany)

    2007-07-01

    Aim: Organotypic slice cultures (OSC) of human brain specimens represent an intriguing experimental model for translational studies addressing, e.g., stem cell transplantation in neurodegenerative diseases or targeting invasion by malignant glioma ex vivo. However, long-term viability and phenomena of structural reorganization of human OSC remain to be further characterized. Here, we report the use of {sup 18}F-deoxyglucose (FDG) for evaluating the viability of brain slice preparations obtained either from postnatal rats or human hippocampal specimens. Methods: Anatomically well preserved human hippocampi obtained from epilepsy surgery and rat hippocampus slice cultures obtained from six day old Wistar rats were dissected into horizontal slices. The slices were incubated with FDG in phosphate buffered saline up to 1 h, either with or without supplementation of glucose at a concentration of 2.5 mg/ml. Radioactivity within the medium or slice cultures was measured using a gamma-counter. In addition, distribution of radioactivity was autoradiographically visualized and quantified as counts per mm{sup 2}. Results: In rat hippocampal slices, FDG accumulated with 1 300 000 {+-} 68 000 counts/mm{sup 2}, whereas the incorporation of the radioactive label in human slices was in the order of 1 500 000 {+-} 370 000 counts/mm{sup 2}. The elevation of glucose concentration within the medium led to a significant three-fold decrease of FDG accumulation in rat slices and to a 2.4-fold decrease in human specimens. Conclusions: FDG accumulated in organotypic brain cultures of human or rodent origin. FDG is thus suited to investigate the viability of OSC. Furthermore, these preparations open new ways to study the factors governing cerebral FDG uptake in brain tissue ex vivo. (orig.)

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

    Science.gov (United States)

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

    2015-10-01

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

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

    Science.gov (United States)

    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.

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

    OpenAIRE

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

    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 analo...

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  11. The Effect of Prenatal Hypoxia on Brain Development: Short- and Long-Term Consequences Demonstrated in Rodent Models

    Science.gov (United States)

    Golan, Hava; Huleihel, Mahmoud

    2006-01-01

    Hypoxia (H) and hypoxia-ischemia (HI) are major causes of foetal brain damage with long-lasting behavioral implications. The effect of hypoxia has been widely studied in human and a variety of animal models. In the present review, we summarize the latest studies testing the behavioral outcomes following prenatal hypoxia/hypoxia-ischemia in rodent…

  12. Age-related changes of normal adult brain structure: analysed with diffusion tensor imaging

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yun-ting; ZHANG Chun-yan; ZHANG Jing; LI Wei

    2005-01-01

    Background It is known that the brain structure changes with normal aging. The objective of this study was to quantify the anisotropy and average diffusion coefficient (DCavg) of the brain in normal adults to demonstrate the microstructure changes of brain with aging.Methods One hundred and six normal adults were examined with diffusion tensor imaging (DTI). The fractional anisotropy (FA), 1-volume ratio (1-VR), relative anisotropy (RA) and average diffusion coefficient (DCavg) of different anatomic sites of brain were measured, correlated with age and compared among three broad age groups.Results Except in lentiform nucleus, the anisotropy increased and DCavg decreased with aging. Both anisotropy and DCavg of lentiform nucleus increased with aging. The normal reference values of DTI parameters of normal Chinese adult in major anatomic sites were acquired. Conclusions DTI data obtained noninvasively can reflect the microstructural changes with aging. The normal reference values acquired can serve as reference standards in differentiation of brain white matter diseases.

  13. THE SOCIAL ENVIRONMENT AND NEUROGENESIS IN THE ADULT MAMMALIAN BRAIN

    Directory of Open Access Journals (Sweden)

    Claudia eLieberwirth

    2012-05-01

    Full Text Available 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. Most 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, conspecific, and chemosensory signal exposure 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.

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

    Science.gov (United States)

    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

  15. Decreases in energy and increases in phase locking of event-related oscillations to auditory stimuli occur during adolescence in human and rodent brain.

    Science.gov (United States)

    Ehlers, Cindy L; Wills, Derek N; Desikan, Anita; Phillips, Evelyn; Havstad, James

    2014-01-01

    Synchrony of phase (phase locking) of event-related oscillations (EROs) within and between different brain areas has been suggested to reflect communication exchange between neural networks and as such may be a sensitive and translational measure of changes in brain remodeling that occur during adolescence. This study sought to investigate developmental changes in EROs using a similar auditory event-related potential (ERP) paradigm in both rats and humans. Energy and phase variability of EROs collected from 38 young adult men (aged 18-25 years), 33 periadolescent boys (aged 10-14 years), 15 male periadolescent rats [at postnatal day (PD) 36] and 19 male adult rats (at PD103) were investigated. Three channels of ERP data (frontal cortex, central cortex and parietal cortex) were collected from the humans using an 'oddball plus noise' paradigm that was presented under passive (no behavioral response required) conditions in the periadolescents and under active conditions (where each subject was instructed to depress a counter each time he detected an infrequent target tone) in adults and adolescents. ERPs were recorded in rats using only the passive paradigm. In order to compare the tasks used in rats to those used in humans, we first studied whether three ERO measures [energy, phase locking index (PLI) within an electrode site and phase difference locking index (PDLI) between different electrode sites] differentiated the 'active' from 'passive' ERP tasks. Secondly, we explored our main question of whether the three ERO measures differentiated adults from periadolescents in a similar manner in both humans and rats. No significant changes were found in measures of ERO energy between the active and passive tasks in the periadolescent human participants. There was a smaller but significant increase in PLI but not PDLI as a function of active task requirements. Developmental differences were found in energy, PLI and PDLI values between the periadolescents and adults in

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

    Science.gov (United States)

    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

  17. Relationships between choline acetyl-transferase and muscarinic binding in aging rodent brain and in Alzheimers disease

    International Nuclear Information System (INIS)

    This paper examines how the relation between ChAT and muscarinic binding might be affected by aging in mouse and rat brains. Preliminary data are presented regarding this relation in postmortem cerebral cortex samples from human subjects who died with Alzheimer's disease (AD) and from age-matched controls. The effect of acetyl coenzme A (1- C 14-acetyl coenzyme A concentration on enzyme activity was determined by varying the concentration of the coenzyme in the assay medium. Assays of muscarinic binding were performed on tissue sonicates diluted with Tris-HC1 buffer using tritium-quinuclidinyl benzilate tritium-QNB as the ligand. For brain regions obtained from rats, significance of age differences were assessed by one-way analysis of variance and Bonferroni t statistics. Differences in ChAT activity and binding site density from human postmortem samples between diagnostic groups were assessed separately by region using an analysis of covariance

  18. Simultaneous fluorometric measurement of histamine and tele-methylhistamine levels in rodent brain by high-performance liquid chromatography.

    Science.gov (United States)

    Miyamoto, Yasuhisa; Yoshimoto, Ryo; Yumoto, Mariko; Ishihara, Akane; Takahashi, Kazuhiko; Kotani, Hidehito; Kanatani, Akio; Tokita, Shigeru

    2004-11-01

    An improved high-performance liquid chromatography (HPLC) method was developed for simultaneous analysis of histamine (HA) and tele-methylhistamine (tele-MHA) levels in mouse and rat brain. The method consists of a solid-phase extraction (SPE) and subsequent HPLC with postcolumn derivatization of the amines with o-phthalaldehyde. The recovery rates of HA and tele-MHA during the SPE procedure were 82.8+/-3.4 and 86.0+/-1.7%, respectively. The detection limits for HA and tele-MHA were 8 and 12pg, respectively, with sufficient linearity up to 30pg. Using this newly developed system, we observed that the brain tele-MHA levels in H3 receptor knockout mice were significantly higher than those of wild-type mice by 2.1-fold. Furthermore, we also observed that the brain HA and tele-MHA levels in Zucker rats were significantly lower than those of lean rats by 76.6+/-5.3 and 77.8+/-5.0%, respectively. These observations coincided well with those of previous studies using radioimmunoassay or HPLC with precolumn OPA derivatization, confirming the utilization of the assay system. PMID:15464956

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

    Science.gov (United States)

    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…

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

    NARCIS (Netherlands)

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

    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 ma

  1. Canonical Genetic Signatures of the Adult Human Brain

    OpenAIRE

    Hawrylycz, Michael; Miller, Jeremy A.; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L.; Anil G. Jegga; Aronow, Bruce J.; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F.; Dierker, Donna L; Menche, Jörge; Szafer, Aaron; Collman, Forrest

    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 ann...

  2. Migrating neuroblasts in the adult human brain: a stream reduced to a trickle

    Institute of Scientific and Technical Information of China (English)

    Miriam E van Strien; Simone A van den Berge; Elly M Hol

    2011-01-01

    It has long been thought that neurogenesis (birth of neurons) in the mammalian brain only occurs while the central nervous system is still developing.Although the first indications to the contrary already appeared in the 1960s,it took more than 30 years for the neuroscience community to accept that the mammalian adult brain also generates new neurons.Today it is completely accepted that neurogenesis occurs in two mammalian adult brain areas,the subventricular zone (SVZ) near the lateral ventricles and the subgranular zone in the hippocampus.

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

    OpenAIRE

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

    2014-01-01

    This study examined the effects of a multimodal intervention on spontaneous brain activity in healthy older adults. Seventeen older adults received a six-week intervention that consisted of cognitive training, Tai Chi exercise, and group counseling, while 17 older adults in a control group attended health knowledge lectures. The intervention group demonstrated enhanced memory and social support compared to the control group. The amplitude of low frequency fluctuations (ALFF) in the middle fro...

  4. Neurogenesis in the embryonic and adult brain: same regulators, different roles

    OpenAIRE

    Urbán, Noelia; Guillemot, François

    2014-01-01

    Neurogenesis persists in adult mammals in specific brain areas, known as neurogenic niches. Adult neurogenesis is highly dynamic and is modulated by multiple physiological stimuli and pathological states. There is a strong interest in understanding how this process is regulated, particularly since active neuronal production has been demonstrated in both the hippocampus and the subventricular zone (SVZ) of adult humans. The molecular mechanisms that control neurogenesis have been extensively s...

  5. Neurogenesis in the embryonic and adult brain: same regulators, different roles.

    OpenAIRE

    Noelia eUrban; François eGuillemot

    2014-01-01

    Neurogenesis persists in adult mammals in specific brain areas, known as neurogenic niches. Adult neurogenesis is highly dynamic and is modulated by multiple physiological stimuli and pathological states. There is a strong interest in understanding how this process is regulated, particularly since active neuronal production has been demonstrated in both the hippocampus and the subventricular zone of adult humans.The molecular mechanisms that control neurogenesis have been extensively studied ...

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

    Science.gov (United States)

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

    2016-04-21

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

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

    Science.gov (United States)

    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…

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

    OpenAIRE

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

    2016-01-01

    Mild traumatic brain injury (mTBI) produces symptoms similar to those typifying posttraumatic stress disorder (PTSD) in humans. We sought to determine whether a rodent model of stress concurrent with mTBI produces characteristics of PTSD such as impaired contextual fear extinction, while also examining concurrent alterations to limbic monoamine activity in brain regions relevant to fear and anxiety states. Male rats were exposed to social stress or control conditions immediately prior to mTBI...

  9. Mild traumatic brain injury with social defeat stress alters anxiety, contextual fear extinction, and limbic monoamines in adult rats

    OpenAIRE

    Daniel eDavies; Dawne eOlson; Danielle eMeyer; Jamie eScholl; Michael eWatt; Pasquale eManzerra; Kenneth eRenner; Forster, Gina L.

    2016-01-01

    Mild traumatic brain injury (mTBI) produces symptoms similar to those typifying posttraumatic stress disorder (PTSD) in humans. We sought to determine whether a rodent model of stress concurrent with mTBI produces characteristics of PTSD such as impaired contextual fear extinction, while also examining concurrent alterations to limbic monoamine activity in brain regions relevant to fear and anxiety states. Male rats were exposed to social stress or control conditions immediately prior to mT...

  10. Brain ventricular dimensions and relationship to outcome in adult patients with bacterial meningitis

    DEFF Research Database (Denmark)

    Sporrborn, Janni L; Knudsen, Gertrud B; Sølling, Mette;

    2015-01-01

    BACKGROUND: Experimental studies suggest that changes in brain ventricle size are key events in bacterial meningitis. This study investigated the relationship between ventricle size, clinical condition and risk of poor outcome in patients with bacterial meningitis. METHODS: Adult patients diagnosed...... with bacterial meningitis admitted to two departments of infectious diseases from 2003 through 2010 were identified. Clinical and biochemical data as well as cerebral computed tomographic images were collected. The size of the brain ventricles were presented as a Ventricle to Brain Ratio (VBR). Normal range...... changes in size as a consequence of meningitis. Increased brain ventricle size in the acute phase of bacterial meningitis was associated with increased mortality....

  11. Positron Emission Tomography studies with [C-11]PBR28 in the Healthy Rodent Brain : Validating SUV as an Outcome Measure of Neuroinflammation

    NARCIS (Netherlands)

    Toth, Miklos; Doorduin, Janine; Haggkvist, Jenny; Varrone, Andrea; Amini, Nahid; Halldin, Christer; Gulyas, Balazs

    2015-01-01

    Molecular imaging of the 18 kD Translocator protein (TSPO) with positron emission tomography (PET) is of great value for studying neuroinflammation in rodents longitudinally. Quantification of the TSPO in rodents is, however, quite challenging. There is no suitable reference region and the use of pl

  12. Astrogliosis in the neonatal and adult murine brain post-trauma

    DEFF Research Database (Denmark)

    Rostworowski, M; Balasingam, V; Chabot, S;

    1997-01-01

    The relevance of astrogliosis remains controversial, especially with respect to the beneficial or detrimental influence of reactive astrocytes on CNS recovery. This dichotomy can be resolved if the mediators of astrogliosis are identified. We have measured the levels of transcripts encoding......, and because its exogenous administration to rodents enhanced astrogliosis after adult or neonatal insults. A lack of requirement for endogenous IFN-gamma was demonstrated by three lines of evidence. First, no increase in IFN-gamma transcripts could be found at injury. Second, the administration...

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

    Science.gov (United States)

    McEwen, B S

    2014-12-01

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

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

    OpenAIRE

    Mehmet Ilyas Cosacak; Christos Papadimitriou; Caghan Kizil

    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 c...

  15. A brain sexual dimorphism controlled by adult circulating androgens

    OpenAIRE

    Cooke, Bradley M.; Tabibnia, Golnaz; Breedlove, S. Marc

    1999-01-01

    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 circulatin...

  16. Expression of nestin by neural cells in the adult rat and human brain.

    Directory of Open Access Journals (Sweden)

    Michael L Hendrickson

    Full Text Available Neurons and glial cells in the developing brain arise from neural progenitor cells (NPCs. Nestin, an intermediate filament protein, is thought to be expressed exclusively by NPCs in the normal brain, and is replaced by the expression of proteins specific for neurons or glia in differentiated cells. Nestin expressing NPCs are found in the adult brain in the subventricular zone (SVZ of the lateral ventricle and the subgranular zone (SGZ of the dentate gyrus. While significant attention has been paid to studying NPCs in the SVZ and SGZ in the adult brain, relatively little attention has been paid to determining whether nestin-expressing neural cells (NECs exist outside of the SVZ and SGZ. We therefore stained sections immunocytochemically from the adult rat and human brain for NECs, observed four distinct classes of these cells, and present here the first comprehensive report on these cells. Class I cells are among the smallest neural cells in the brain and are widely distributed. Class II cells are located in the walls of the aqueduct and third ventricle. Class IV cells are found throughout the forebrain and typically reside immediately adjacent to a neuron. Class III cells are observed only in the basal forebrain and closely related areas such as the hippocampus and corpus striatum. Class III cells resemble neurons structurally and co-express markers associated exclusively with neurons. Cell proliferation experiments demonstrate that Class III cells are not recently born. Instead, these cells appear to be mature neurons in the adult brain that express nestin. Neurons that express nestin are not supposed to exist in the brain at any stage of development. That these unique neurons are found only in brain regions involved in higher order cognitive function suggests that they may be remodeling their cytoskeleton in supporting the neural plasticity required for these functions.

  17. Adult brain abscess associated with patent foramen ovale: a case report

    Directory of Open Access Journals (Sweden)

    Stathopoulos Georgios T

    2007-08-01

    Full Text Available Abstract Brain abscess results from local or metastatic septic spread to the brain. The primary infectious site is often undetected, more commonly so when it is distant. Unlike pediatric congenital heart disease, minor intracardiac right-to-left shunting due to patent foramen ovale has not been appreciated as a cause of brain abscess in adults. Here we present a case of brain abscess associated with a patent foramen ovale in a 53-year old man with dental-gingival sepsis treated in the intensive care unit. Based on this case and the relevant literature we suggest a link between a silent patent foramen ovale, paradoxic pathogen dissemination to the brain, and development of brain abscess.

  18. Arrested neuronal proliferation and impaired hippocampal function following fractionated brain irradiation in the adult rat

    DEFF Research Database (Denmark)

    Madsen, Torsten Meldgaard; Kristjansen, P.E.G.; Bolwig, Tom Gert;

    2003-01-01

    The generation of new neurons in the adult mammalian brain has been documented in numerous recent reports. Studies undertaken so far indicate that adult hippocampal neurogenesis is related in a number of ways to hippocampal function.Here, we report that subjecting adult rats to fractionated brain...... days after irradiation, the animals with blocked neurogenesis performed poorer than controls in a hippocampus-dependent place-recognition task, indicating that the presence of newly generated neurons may be necessary for the normal function of this brain area. The animals were never impaired...... irradiation blocked the formation of new neurons in the dentate gyrus of the hippocampus. At different time points after the termination of the irradiation procedure, the animals were tested in two tests of short-term memory that differ with respect to their dependence on hippocampal function. Eight and 21...

  19. Exploration and visualization of gene expression with neuroanatomy in the adult mouse brain

    Directory of Open Access Journals (Sweden)

    Pathak Sayan

    2008-03-01

    Full Text Available Abstract Background Spatially mapped large scale gene expression databases enable quantitative comparison of data measurements across genes, anatomy, and phenotype. In most ongoing efforts to study gene expression in the mammalian brain, significant resources are applied to the mapping and visualization of data. This paper describes the implementation and utility of Brain Explorer, a 3D visualization tool for studying in situ hybridization-based (ISH expression patterns in the Allen Brain Atlas, a genome-wide survey of 21,000 expression patterns in the C57BL6J adult mouse brain. Results Brain Explorer enables users to visualize gene expression data from the C57Bl/6J mouse brain in 3D at a resolution of 100 μm3, allowing co-display of several experiments as well as 179 reference neuro-anatomical structures. Brain Explorer also allows viewing of the original ISH images referenced from any point in a 3D data set. Anatomic and spatial homology searches can be performed from the application to find data sets with expression in specific structures and with similar expression patterns. This latter feature allows for anatomy independent queries and genome wide expression correlation studies. Conclusion These tools offer convenient access to detailed expression information in the adult mouse brain and the ability to perform data mining and visualization of gene expression and neuroanatomy in an integrated manner.

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

    Science.gov (United States)

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

    2014-07-01

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

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

    OpenAIRE

    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 h...

  2. Neurobiological markers of exercise-related brain plasticity in older adults

    OpenAIRE

    Voss, Michelle W.; Erickson, Kirk I.; Prakash, Ruchika Shaurya; Chaddock, Laura; Kim, Jennifer S; Alves, Heloisa; Szabo, Amanda; White, Siobhan M.; Wójcicki, Thomas R.; Mailey, Emily L; Olson, Erin A.; Gothe, Neha; Potter, Vicki V.; Martin, Stephen A.; Pence, Brandt D.

    2012-01-01

    The current study examined how a randomized one-year aerobic exercise program for healthy older adults would affect serum levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor type 1 (IGF-1), and vascular endothelial growth factor (VEGF) - putative markers of exercise-induced benefits on brain function. The study also examined whether (a) change in the concentration of these growth factors was associated with alterations in functional connectivity following exercise, ...

  3. A rapid and versatile method for the isolation, purification and cryogenic storage of Schwann cells from adult rodent nerves.

    Science.gov (United States)

    Andersen, Natalia D; Srinivas, Shruthi; Piñero, Gonzalo; Monje, Paula V

    2016-08-23

    We herein developed a protocol for the rapid procurement of adult nerve-derived Schwann cells (SCs) that was optimized to implement an immediate enzymatic dissociation of fresh nerve tissue while maintaining high cell viability, improving yields and minimizing fibroblast and myelin contamination. This protocol introduces: (1) an efficient method for enzymatic cell release immediately after removal of the epineurium and extensive teasing of the nerve fibers; (2) an adaptable drop-plating method for selective cell attachment, removal of myelin debris, and expansion of the initial SC population in chemically defined medium; (3) a magnetic-activated cell sorting purification protocol for rapid and effective fibroblast elimination; and (4) an optional step of cryopreservation for the storage of the excess of cells. Highly proliferative SC cultures devoid of myelin and fibroblast growth were obtained within three days of nerve processing. Characterization of the initial, expanded, and cryopreserved cell products confirmed maintenance of SC identity, viability and growth rates throughout the process. Most importantly, SCs retained their sensitivity to mitogens and potential for differentiation even after cryopreservation. To conclude, this easy-to-implement and clinically relevant protocol allows for the preparation of expandable homogeneous SC cultures while minimizing time, manipulation of the cells, and exposure to culture variables.

  4. A rapid and versatile method for the isolation, purification and cryogenic storage of Schwann cells from adult rodent nerves

    Science.gov (United States)

    Andersen, Natalia D.; Srinivas, Shruthi; Piñero, Gonzalo; Monje, Paula V.

    2016-01-01

    We herein developed a protocol for the rapid procurement of adult nerve-derived Schwann cells (SCs) that was optimized to implement an immediate enzymatic dissociation of fresh nerve tissue while maintaining high cell viability, improving yields and minimizing fibroblast and myelin contamination. This protocol introduces: (1) an efficient method for enzymatic cell release immediately after removal of the epineurium and extensive teasing of the nerve fibers; (2) an adaptable drop-plating method for selective cell attachment, removal of myelin debris, and expansion of the initial SC population in chemically defined medium; (3) a magnetic-activated cell sorting purification protocol for rapid and effective fibroblast elimination; and (4) an optional step of cryopreservation for the storage of the excess of cells. Highly proliferative SC cultures devoid of myelin and fibroblast growth were obtained within three days of nerve processing. Characterization of the initial, expanded, and cryopreserved cell products confirmed maintenance of SC identity, viability and growth rates throughout the process. Most importantly, SCs retained their sensitivity to mitogens and potential for differentiation even after cryopreservation. To conclude, this easy-to-implement and clinically relevant protocol allows for the preparation of expandable homogeneous SC cultures while minimizing time, manipulation of the cells, and exposure to culture variables. PMID:27549422

  5. Using network science to evaluate exercise-associated brain changes in older adults

    Directory of Open Access Journals (Sweden)

    Jonathan H Burdette

    2010-06-01

    Full Text Available 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 four-month interventions, MRI measures of resting brain blood flow and connectivity were performed. The ET group’s hippocampal 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 cerebral blood flow, 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.

  6. Adult Pilomyxoid Astrocytoma Mimicking a Cortical Brain Tumor: MR Imaging Findings

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Jong Chang; Weon, Young Cheol; Suh, Jae Hee; Kim, Young; Hwang, Jae Cheol [Ulsan University Hospital, Ulsan (Korea, Republic of)

    2010-08-15

    A pilomyxoid astrocytoma (PMA) is a recently identified low-grade neoplasm that was previously classified as a pilocytic astrocytoma (PA), yet demonstrates unique histological features and more aggressive behavior. Although a PMA is generally a tumor of early childhood and typically occurs in the hypothalamic/chiasmatic region, it can mimic cortical tumors, especially in adults. We report the MR findings of a PMA presenting as a cortical brain tumor in an adult with neurofibromatosis 1 (NF1)

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

    OpenAIRE

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

    2008-01-01

    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 year...

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

    OpenAIRE

    Gao, Xiang; Enikolopov, Grigori; Chen, Jinhui

    2009-01-01

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

  9. Systematic review of the prognosis after mild traumatic brain injury in adults

    DEFF Research Database (Denmark)

    Carroll, Linda J; Cassidy, John David; Cancelliere, Carol;

    2014-01-01

    OBJECTIVE: To synthesize the best available evidence on objective outcomes after adult mild traumatic brain injury (MTBI). DATA SOURCES: MEDLINE and other databases were searched (2001-2012) for studies related to MTBI. Inclusion criteria included published, peer-reviewed articles in English...... in adults. DATA EXTRACTION: Eligible studies were critically appraised using a modification of the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Two reviewers independently reviewed each study and extracted data from accepted articles into evidence tables. DATA SYNTHESIS: Evidence...

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

    Science.gov (United States)

    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

  11. Early life stress differentially modulates distinct forms of brain plasticity in young and adult mice.

    Directory of Open Access Journals (Sweden)

    Inga Herpfer

    Full Text Available BACKGROUND: Early life trauma is an important risk factor for many psychiatric and somatic disorders in adulthood. As a growing body of evidence suggests that brain plasticity is disturbed in affective disorders, we examined the short-term and remote effects of early life stress on different forms of brain plasticity. METHODOLOGY/PRINCIPAL FINDINGS: Mice were subjected to early deprivation by individually separating pups from their dam in the first two weeks after birth. Distinct forms of brain plasticity were assessed in the hippocampus by longitudinal MR volumetry, immunohistochemistry of neurogenesis, and whole-cell patch-clamp measurements of synaptic plasticity. Depression-related behavior was assessed by the forced swimming test in adult animals. Neuropeptides and their receptors were determined by real-time PCR and immunoassay. Early maternal deprivation caused a loss of hippocampal volume, which returned to normal in adulthood. Adult neurogenesis was unaffected by early life stress. Long-term synaptic potentiation, however, was normal immediately after the end of the stress protocol but was impaired in adult animals. In the forced swimming test, adult animals that had been subjected to early life stress showed increased immobility time. Levels of substance P were increased both in young and adult animals after early deprivation. CONCLUSION: Hippocampal volume was affected by early life stress but recovered in adulthood which corresponded to normal adult neurogenesis. Synaptic plasticity, however, exhibited a delayed impairment. The modulation of synaptic plasticity by early life stress might contribute to affective dysfunction in adulthood.

  12. Educating the adult brain: How the neuroscience of learning can inform educational policy

    Science.gov (United States)

    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.

  13. Fetal Alcohol Exposure Reduces Adult Brain Plasticity. Science Briefs

    Science.gov (United States)

    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…

  14. [Management of swallowing disorders after brain injuries in adults].

    Science.gov (United States)

    Fichaux, Bourin P; Labrune, M

    2008-01-01

    The management of swallowing disorders after brain injury must be soon as well. The physiopathological analysis and the organization of the therapeutic project of these patients require the intervention of an interdisciplinary team. Dysphagia falls under a complex clinical context associating impairments of cognition, communication and behavioural control. The management associates speech therapist, caregivers, otolaryngolologist, phoniatrician, physiotherapist and nutritional therapist without forgetting the family circle. The fluctuations of consciousness and concentration of our patients brings us to constantly readjusting and rehabilitating the strategies of feeding. Obstacles with their evolution towards a normal feeding are akinesia, limits of motor functions, impairements of cognition and behavioural control. In the located lesions swallow recovers can be fast, instead of in severe brain-injury the challenge is to ensure safe and adequate nutrition, using a variety of strategies depending on the presenting symptoms. The purpose of this article is to relate our experience beside patients with an acute or recent cerbrovascular event.

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

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    David S Grayson

    Full Text Available 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.

  16. Canonical genetic signatures of the adult human brain.

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  18. Brain tissue pressure measurements in perinatal and adult rabbits.

    Science.gov (United States)

    Hornig, G W; Lorenzo, A V; Zavala, L M; Welch, K

    1987-12-01

    Brain tissue pressure (BTP) in pre- and post-natal anesthetized rabbits, held in a stereotactic head holder, was measured with a fluid filled 23 gauge open-ended cannula connected distally to a pressure transducer. By advancing the cannula step wise through a hole in the cranium it was possible to sequentially measure pressure from the cranial subarachnoid space, cortex, ventricle and basal ganglia. Separate cannulas and transducers were used to measure CSFP from the cisterna magna and arterial and/or venous pressure. Pressure recordings obtained when the tip of the BTP cannula was located in the cranial subarachnoid space or ventricle exhibited respiratory and blood pressure pulsations equivalent to and in phase with CSF pulsations recorded from the cisterna magna. When the tip was advanced into brain parenchymal sites such pulsations were suppressed or non-detectable unless communication with a CSF compartment had been established inadvertently. Although CSF pressures in the three spinal fluid compartments were equivalent, in most animals BTP was higher than CSFP. However, after momentary venting of the system BTP equilibrated at a pressure below that of CSFP. We speculate that venting of the low compliance system (1.20 x 10(-5) ml/mmHg) relieves the isometric pressure build-up due to insertion of the cannula into brain parenchyma. Under these conditions, and at all ages examined, BTP in the rabbit is consistently lower than CSFP and, as with CSFP, it increases as the animal matures.

  19. Fluoxetine targets early progenitor cells in the adult brain

    OpenAIRE

    Encinas, Juan M.; Vaahtokari, Anne; Enikolopov, Grigori

    2006-01-01

    Chronic treatment with antidepressants increases neurogenesis in the adult hippocampus. This increase in the production of new neurons may be required for the behavioral effects of antidepressants. However, it is not known which class of cells within the neuronal differentiation cascade is targeted by the drugs. We have generated a reporter mouse line, which allows identification and classification of early neuronal progenitors. It also allows accurate quantitation of changes induced by neuro...

  20. Adding chemo after radiation treatment improves survival for adults with a type of brain tumor

    Science.gov (United States)

    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

  1. Genetic Methods to Identify and Manipulate Newly born Neurons in the Adult Brain

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    Itaru eImayoshi

    2011-05-01

    Full Text Available 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.

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

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    Zhiwei Zheng

    2015-01-01

    Full Text Available 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.

  3. Strategies for Regenerating Striatal Neurons in the Adult Brain by Using Endogenous Neural Stem Cells

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    Kanako Nakaguchi

    2011-01-01

    Full Text Available Currently, there is no effective treatment for the marked neuronal loss caused by neurodegenerative diseases, such as Huntington's disease (HD or ischemic stroke. However, recent studies have shown that new neurons are continuously generated by endogenous neural stem cells in the subventricular zone (SVZ of the adult mammalian brain, including the human brain. Because some of these new neurons migrate to the injured striatum and differentiate into mature neurons, such new neurons may be able to replace degenerated neurons and improve or repair neurological deficits. To establish a neuroregenerative therapy using this endogenous system, endogenous regulatory mechanisms that can be co-opted for efficient regenerative interventions must be understood, along with any potential drawbacks. Here, we review current knowledge on the generation of new neurons in the adult brain and discuss their potential for use in replacing striatal neurons lost to neurodegenerative diseases, including HD, and to ischemic stroke.

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

    Science.gov (United States)

    Respondek, Michalina; Buszman, Ewa

    2015-12-31

    Neurogenesis is a complex and multi-step process of generating completely functional neurons. This process in adult brain is based on pluripotentional neuronal stem cells (NSC), which are able to proliferation and differentiation into mature neurons or glial cells. NSC are located in subgranular zone inside hippocampus and in subventricular zone. The new neurons formation depends on many endo- and exogenous factors which modulate each step of neurogenesis. This article describes the most important regulators of adult neurogenesis, mainly: neurotrophins, growth factors, hormones, neurotransmitters and microenvironment of NSC. Some drugs, especially antipsychotics, antidepressants and normothymics may affect the neurogenic properties of adult brain. Moreover pathological processes such as neuroinflammation, stroke or epilepsy are able to induce proliferation of NSC. The proneurogenic effects of psychotropic drugs and pathological processes are associated with their ability to increase some hormones and neurotrophins level, as well as with rising the expression of antiapoptotic Bcl-2 protein and metalloproteinase MMP-2. Additionaly, some drugs, for example haloperidol, are able to block prolactin and dopaminergic neuroblasts receptors. Down-regulation of adult neurogenesis is associated with alcohol abuse and high stress level. Negative effect of many drugs, such as cytostatics, COX-2 inhibitors and opioides was also observed. The proneurogenic effect of described factors suggest their broad therapeutic potential and gives a new perspective on an effective and modern treatment of many neuropsychiatric disorders. This effect can also help to clarify the pathogenesis of disorders associated with proliferation and degeneration of adult brain cells.

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

    Science.gov (United States)

    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

  6. Efficacy of 68Ga-DOTATOC Positron Emission Tomography (PET) CT in Children and Young Adults With Brain Tumors

    Science.gov (United States)

    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

  7. Molecular and behavioral aspects of the actions of alcohol on the adult and developing brain.

    Science.gov (United States)

    Alfonso-Loeches, Silvia; Guerri, Consuelo

    2011-01-01

    The brain is one of the major target organs of alcohol actions. Alcohol abuse can lead to alterations in brain structure and functions and, in some cases, to neurodegeneration. Cognitive deficits and alcohol dependence are highly damaging consequences of alcohol abuse. Clinical and experimental studies have demonstrated that the developing brain is particularly vulnerable to alcohol, and that drinking during gestation can lead to a range of physical, learning and behavioral defects (fetal alcohol spectrum disorders), with the most dramatic presentation corresponding to fetal alcohol syndrome. Recent findings also indicate that adolescence is a stage of brain maturation and that heavy drinking at this stage can have a negative impact on brain structure and functions causing important short- and long-term cognitive and behavioral consequences. The effects of alcohol on the brain are not uniform; some brain areas or cell populations are more vulnerable than others. The prefrontal cortex, the hippocampus, the cerebellum, the white matter and glial cells are particularly susceptible to the effects of ethanol. The molecular actions of alcohol on the brain are complex and involve numerous mechanisms and signaling pathways. Some of the mechanisms involved are common for the adult brain and for the developing brain, while others depend on the developmental stage. During brain ontogeny, alcohol causes irreversible alterations to the brain structure. It also impairs several molecular, neurochemical and cellular events taking place during normal brain development, including alterations in both gene expression regulation and the molecules involved in cell-cell interactions, interference with the mitogenic and growth factor response, enhancement of free radical formation and derangements of glial cell functions. However, in both adult and adolescent brains, alcohol damages specific brain areas through mechanisms involving excitotoxicity, free radical formation and

  8. Homeostasis of Microglia in the Adult Brain: Review of Novel Microglia Depletion Systems.

    Science.gov (United States)

    Waisman, Ari; Ginhoux, Florent; Greter, Melanie; Bruttger, Julia

    2015-10-01

    Microglia are brain macrophages that emerge from early erythro-myeloid precursors in the embryonic yolk sac and migrate to the brain mesenchyme before the blood brain barrier is formed. They seed the brain, and proliferate until they have formed a grid-like distribution in the central nervous system that is maintained throughout lifespan. The mechanisms through which these embryonic-derived cells contribute to microglia homoeostasis at steady state and upon inflammation are still not entirely clear. Here we review recent studies that provided insight into the contribution of embryonically-derived microglia and of adult 'microglia-like' cells derived from monocytes during inflammation. We examine different microglia depletion models, and discuss the origin of their rapid repopulation after depletion and outline important areas of future research.

  9. Evaluation of a Reading Comprehension Strategy Package to Improve Reading Comprehension of Adult College Students with Acquired Brain Injuries

    Science.gov (United States)

    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.…

  10. Restraint stress-induced morphological changes at the blood-brain barrier in adult rats

    Directory of Open Access Journals (Sweden)

    Petra eSántha

    2016-01-01

    Full Text Available Stress is well known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognised in the development of neurodegenerative disorders, such as Alzheimer’s disease, dysfunction of the blood-brain barrier has been linked to stress-related psychiatric diseases only recently. In the present study the effects of restraint stress with different duration (1, 3 and 21 days were investigated on the morphology of the blood-brain barrier in male adult Wistar rats. Frontal cortex and hippocampus sections were immunostained for markers of brain endothelial cells (claudin-5, occludin and glucose transporter-1 and astroglia (GFAP. Staining pattern and intensity were visualized by confocal microscopy and evaluated by several types of image analysis. The ultrastructure of brain capillaries was investigated by electron microscopy. Morphological changes and intensity alterations in brain endothelial tight junction proteins claudin-5 and occludin were induced by stress. Following restraint stress significant increases in the fluorescence intensity of glucose transporter-1 were detected in brain endothelial cells in the frontal cortex and hippocampus. Significant reductions in GFAP fluorescence intensity were observed in the frontal cortex in all stress groups. As observed by electron microscopy, one-day acute stress induced morphological changes indicating damage in capillary endothelial cells in both brain regions. After 21 days of stress thicker and irregular capillary basal membranes in the hippocampus and edema in astrocytes in both regions were seen. These findings indicate that stress exerts time-dependent changes in the staining pattern of tight junction proteins occludin, claudin-5 and glucose transporter-1 at the level of brain capillaries and in the ultrastructure of brain endothelial cells and astroglial endfeet, which may contribute to neurodegenerative processes

  11. Brain transcriptional stability upon prion protein-encoding gene invalidation in zygotic or adult mouse

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    Béringue Vincent

    2010-07-01

    Full Text Available Abstract Background The physiological function of the prion protein remains largely elusive while its key role in prion infection has been expansively documented. To potentially assess this conundrum, we performed a comparative transcriptomic analysis of the brain of wild-type mice with that of transgenic mice invalidated at this locus either at the zygotic or at the adult stages. Results Only subtle transcriptomic differences resulting from the Prnp knockout could be evidenced, beside Prnp itself, in the analyzed adult brains following microarray analysis of 24 109 mouse genes and QPCR assessment of some of the putatively marginally modulated loci. When performed at the adult stage, neuronal Prnp disruption appeared to sequentially induce a response to an oxidative stress and a remodeling of the nervous system. However, these events involved only a limited number of genes, expression levels of which were only slightly modified and not always confirmed by RT-qPCR. If not, the qPCR obtained data suggested even less pronounced differences. Conclusions These results suggest that the physiological function of PrP is redundant at the adult stage or important for only a small subset of the brain cell population under classical breeding conditions. Following its early reported embryonic developmental regulation, this lack of response could also imply that PrP has a more detrimental role during mouse embryogenesis and that potential transient compensatory mechanisms have to be searched for at the time this locus becomes transcriptionally activated.

  12. Comparison of normal adult and children brain SPECT imaging using statistical parametric mapping(SPM)

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    Lee, Myoung Hoon; Yoon, Seok Nam; Joh, Chul Woo; Lee, Dong Soo [Ajou University School of Medicine, Suwon (Korea, Republic of); Lee, Jae Sung [Seoul national University College of Medicine, Seoul (Korea, Republic of)

    2002-07-01

    This study compared rCBF pattern in normal adult and normal children using statistical parametric mapping (SPM). The purpose of this study was to determine distribution pattern not seen visual analysis in both groups. Tc-99m ECD brain SPECT was performed in 12 normal adults (M:F=11:1, average age 35 year old) and 6 normal control children (M:F=4:2, 10.5{+-}3.1y) who visited psychiatry clinic to evaluate ADHD. Their brain SPECT revealed normal rCBF pattern in visual analysis and they were diagnosed clinically normal. Using SPM method, we compared normal adult group's SPECT images with those of 6 normal children subjects and measured the extent of the area with significant hypoperfusion and hyperperfusion (p<0.001, extent threshold=16). The areas of both angnlar gyrus, both postcentral gyrus, both superior frontal gyrus, and both superior parietal lobe showed significant hyperperfusion in normal adult group compared with normal children group. The areas of left amygdala gyrus, brain stem, both cerebellum, left globus pallidus, both hippocampal formations, both parahippocampal gyrus, both thalamus, both uncus, both lateral and medial occipitotemporal gyrus revealed significantly hyperperfusion in the children. These results demonstrated that SPM can say more precise anatomical area difference not seen visual analysis.

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

    Science.gov (United States)

    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

  14. Role of hemocytes in invertebrate adult neurogenesis and brain repair

    Directory of Open Access Journals (Sweden)

    PG Chaves da Silva

    2015-05-01

    Full Text Available The repair of lesions of the central nervous system (CNS varies widely throughout the animal kingdom. At the level of neuronal replacement lie the major differences in CNS regeneration. At one extreme are the amniote vertebrates (reptile, avian and mammalian groups, which have very limited capacity for neuronal replacement, and therefore for neural regeneration; at the other extreme, animals such as planarians (flatworms and colonial tunicates can repair their entire CNS after major injuries. These differences can be attributed to the abundance of multipotent and/or pluripotent stem cells and/or undifferentiated precursors among the general cell population. In this review we discuss recent advancements in knowledge of regeneration of the CNS of invertebrates. We focus on ascidians, which are a sister group of vertebrates, but we also address other invertebrate groups. Because neurogenesis is central to the events that allow regeneration of the adult CNS, we address this issue focusing on crustaceans, which have provided a paradigm to study the mechanisms underlying this phenomenon. The attraction of hemocytes toward a neurogenic niche and respecification of these cells toward a neural fate has been strongly suggested. Based on recent and emerging research, we suggest that cells of the blood lineage are not only associated with the roles that are generally attributed to them, but are the cells that either signal other cell types to differentiate into neural cells, or even eventually themselves transdifferentiate into neural cells.

  15. Pediatric Cancers and Brain Tumors in Adolescents and Young Adults.

    Science.gov (United States)

    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

  16. Vascular regulation of adult neurogenesis under physiological and pathological conditions

    Directory of Open Access Journals (Sweden)

    Masato eSawada

    2014-03-01

    Full Text Available Neural stem cells in the mammalian adult brain continuously produce new neurons throughout life. Accumulating evidence in rodents suggests that various aspects of adult neurogenesis, including the genesis, migration, and maturation of new neurons, are regulated by factors derived from blood vessels and their microenvironment. Brain injury enhances both neurogenesis and angiogenesis, thereby promoting the cooperative regeneration of neurons and blood vessels. In this paper, we briefly review the mechanisms for the vascular regulation of adult neurogenesis in the ventricular-subventricular zone under physiological and pathological conditions, and discuss their clinical potential for brain regeneration strategies.

  17. Hypoperfusion in baseline and cognitively activated brain SPECT imaging of adult and elderly patients with depression

    International Nuclear Information System (INIS)

    Objective: To evaluate the rCBF abnormalities of the baseline and cognitively activated rCBF imaging in unmedicated adult and elderly patients with depression. Methods: The subjects were divided into four groups: depressed adults, normal adult controls, depressed elders and normal elderly controls. All depressed patients were unmedicated and the diagnoses (depression of moderate degree with accompanying somatization) were confirmed by the ICD-10 criteria. Age range of the 39 depressed adult patients was 17 - 55 years. 17 age-matched normal adult controls (age range 21 - 50 years) were studied under identical conditions. The age range of 18 depressed elderly patients was 62 - 76 years. 21 age-matched normal elderly controls (age range 60 - 72 years) were studied under identical conditions. Baseline and cognitively activated 99Tcm-ECD SPECT were performed on 25 of the 39 adult patients with depression and 17 normal adult controls. Baseline 99Tcm-ECD SPECT only was performed on the remaining 14 patients with depression. Baseline and cognitively activated 99Tcm-ECD SPECT were performed on 12 of the 18 elderly patients with depression and 18 of the 21 normal elderly controls. Baseline 99Tcm-ECD SPECT only was performed on the remaining elderly patients and 3 normal elderly controls. Results: 1) The characteristic abnormalities of baseline and cognitively activated brain SPECT imaging of depression in adults: the baseline rCBF values of frontal and temporal lobe decreased significantly and the activated rCBF values of frontal, temporal lobe decreased more evidently than that in the baseline imaging and additionally decreased activated rCBF values in parietal lobe were found. 2) The characteristic abnormalities of baseline and cognitively activated brain SPECT imaging of elderly patients with depression: the baseline rCBF values of frontal, temporal lobe and right basal ganglia decreased significantly and the activated rCBF values of frontal, temporal, right parietal lobe

  18. Interleukin-6 gene (IL-6: a possible role in brain morphology in the healthy adult brain

    Directory of Open Access Journals (Sweden)

    Baune Bernhard T

    2012-07-01

    Full Text Available Abstract 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.

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

    Science.gov (United States)

    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

  20. Adult Human Neurogenesis: from Microscopy to Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Amanda eSierra

    2011-04-01

    Full Text Available Neural stem cells reside in well-defined areas of the adult human brain and are capable of gene-rating new neurons throughout the life span. In rodents, it is well established that the new born neurons are involved in olfaction as well as in certain forms of memory and learning. In humans, the functional relevance of adult human neurogenesis is being investigated, in particular its implication in the etiopathology of a variety of brain disorders. Adult neurogenesis in the human brain was discovered by utilizing methodologies directly imported from the rodent research, such as immunohistological detection of proliferation and cell-type specific biomarkers in postmortem or biopsy tissue. However, in the vast majority of cases, these methods do not support longitudinal studies; thus, the capacity of the putative stem cells to form new neurons under different disease conditions cannot be tested. More recently, new technologies have been specifically developed for the detection and quantification of neural stem cells in the living human brain. These technologies rely on the use of magnetic resonance imaging, available in hospitals worldwide. Although they require further validation in rodents and primates, these new methods hold the potential to test the contribution of adult human neurogenesis to brain function in both health and disease. This review reports on the current knowledge on adult human neurogenesis. We first review the different methods available to assess human neurogenesis, both ex vivo and in vivo and then appraise the changes of adult neurogenesis in human diseases.

  1. Expression of caspase-3 in rodent and monkey brain: a species- and age-related study%胱天蛋白酶3在啮齿类动物和猕猴脑中的表达:种系和年龄相关研究

    Institute of Scientific and Technical Information of China (English)

    张爱群; 高丽杰; 武艳; 赖惠玲

    2006-01-01

    presented in 3 brain regions of monkeys through immunohistochemistry. MAIN OUTCOME MEATURES: ①Detection of caspase-3 protein with immunoblot in the brain of rodents and monkeys; ② Distribution patterns of caspase-3-immunoreactive cells in 3 brain regions of monkeys. RESULTS: ① Result of detection with immunoblot: The same pattern of caspase-3 protein expression in brain of three kinds of 2-week-old rodents. But the expression was not seen in any other brains of older ages. Caspase 3 was expressed in a relatively high level inboth adult and aged monkey brains, and the amount did not attain to the level in 2-week-old rodents. Caspase-3 Was expressed in the pattern of zymogen (Mr 32 000). The ex pressions of caspase-3 in brains of monkey were not different in ages and brain regions. ②Result of Immunohistochemistry: It was showed that most neurons in the frontal cortex lack detectable caspase-3 immunoreactivity, whereas low to moderate caspase-3 immunostaining be found mainly in pyramidal cells in CA1, CA3 and CA4 subfields of hippocampus. And in the cerebellum, a small number of Purkinje cells were strongly stained in their cytosol and dendrites. Age-related expression pattern of caspase-3 were not found except that in the motor cortex of aged monkeys in which there were a limited number of large pyramidal cells in layer Ⅴ that were strongly stained with caspase-3 antibody.③ Immunoblot procedure revealed that the caspase-3 protein expressed in monkey brains is in the form of zymogen (Mr 32 000) and there is no significant difference in caspase-3 expression level as a function of either brain region or age of animals.CONCLUSION: Unlike rodents in which caspase-3 protein rapidly drops to an undetectable level since animals grow up, the primate expresses caspase-3 constitutively in brain until the late period of lifetime. But there are no significant brain region- or age-related differences in the protein levels in monkey brain.%背景:有研究显示,凋亡

  2. The Effect of Pro-Neurogenic Gene Expression on Adult Subventricular Zone Precursor Cell Recruitment and Fate Determination After Excitotoxic Brain Injury

    Science.gov (United States)

    Jones, Kathryn S; Connor, Bronwen J

    2016-01-01

    Despite the presence of on-going neurogenesis in the adult mammalian brain, neurons are generally not replaced after injury. Using a rodent model of excitotoxic cell loss and retroviral (RV) lineage tracing, we previously demonstrated transient recruitment of precursor cells from the subventricular zone (SVZ) into the lesioned striatum. In the current study we determined that these cells included migratory neuroblasts and oligodendrocyte precursor cells (OPC), with the predominant response from glial cells. We attempted to override this glial response by ectopic expression of the pro-neurogenic genes Pax6 or Dlx2 in the adult rat SVZ following quinolinic acid lesioning. RV-Dlx2 over-expression stimulated repair at a previously non-neurogenic time point by enhancing neuroblast recruitment and the percentage of cells that retained a neuronal fate within the lesioned area, compared to RV-GFP controls. RV-Pax6 expression was unsuccessful at inhibiting glial fate and intriguingly, increased OPC cell numbers with no change in neuronal recruitment. These findings suggest that gene choice is important when attempting to augment endogenous repair as the lesioned environment can overcome pro-neurogenic gene expression. Dlx2 over-expression however was able to partially overcome an anti-neuronal environment and therefore is a promising candidate for further study of striatal regeneration.

  3. Brain training game boosts executive functions, working memory and processing speed in the young adults: a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Rui Nouchi

    Full Text Available 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

  4. Applications of hybrid diffuse optics for clinical management of adults after brain injury

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  6. Cell proliferation in the Drosophila adult brain revealed by clonal analysis and bromodeoxyuridine labelling

    OpenAIRE

    Brand Andrea H; Egger Boris; von Trotha Jakob W

    2009-01-01

    Abstract Background The production of new neurons during adulthood and their subsequent integration into a mature central nervous system have been shown to occur in all vertebrate species examined to date. However, the situation in insects is less clear and, in particular, it has been reported that there is no proliferation in the Drosophila adult brain. Results We report here, using clonal analysis and 5'-bromo-2'-deoxyuridine (BrdU) labelling, that cell proliferation does occur in the Droso...

  7. Brain Infarction and Hemorrhage in Young and Middle-aged Adults

    OpenAIRE

    Lacy, Joseph R.; Filley, Christopher M.; Earnest, Michael P.; Graff-Radford, Neill R

    1984-01-01

    Of 131 young (17 to 44 years) and middle-aged (45 to 55 years) adults who had brain infarction or hemorrhage, the most common etiologic factors were rheumatic heart disease, migraine and oral contraceptive use among the younger group. In contrast, atherosclerotic, hypertensive and diabetes-associated cerebrovascular were the most common causes in the middle-aged group. Patients who have a stroke before age 45 should have prompt, complete laboratory and radiologic testing to define a possible ...

  8. Reawakening the sleeping beauty in the adult brain: neurogenesis from parenchymal glia.

    Science.gov (United States)

    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

  9. Reawakening the sleeping beauty in the adult brain: neurogenesis from parenchymal glia.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  11. Notch receptor expression in neurogenic regions of the adult zebrafish brain.

    Directory of Open Access Journals (Sweden)

    Vanessa de Oliveira-Carlos

    Full Text Available 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 [Formula: see text] 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 [Formula: see text] cells. In this region notch3 expression is mostly in Bergmann glia and at low levels in few PCNA [Formula: see text] 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.

  12. Extremely low frequency electromagnetic fields (EMF) and brain cancer in adults and children: review and comment.

    Science.gov (United States)

    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

  13. Landmark-based morphometrics of the normal adult brain using MRI.

    Science.gov (United States)

    Free, S L; O'Higgins, P; Maudgil, D D; Dryden, I L; Lemieux, L; Fish, D R; Shorvon, S D

    2001-05-01

    We describe the application of statistical shape analysis to homologous landmarks on the cortical surface of the adult human brain. Statistical shape analysis has a sound theoretical basis. Landmarks are identified on the surface of a 3-D reconstruction of the segmented cortical surface from magnetic resonance image (MRI) data. Using publicly available software (morphologika) the location and size dependence of the landmarks are removed and the differences in landmark distribution across subjects are analysed using principal component analysis. These differences, representing shape differences between subjects, can be visually assessed using wireframe models and transformation grids. The MRI data of 58 adult brains (27 female and 15 left handed) were examined. Shape differences in the whole brain are described which concern the relative orientation of frontal lobe sulci. Analysis of all 116 hemispheres revealed a statistically significant difference (P < 0.001) between left and right hemispheres. This finding was significant for right- but not left-handed subjects alone. No other significant age, gender, handedness, or brain-size correlations with shape differences were found.

  14. Plasticity of brain networks in a randomized intervention trial of exercise training in older adults

    Directory of Open Access Journals (Sweden)

    Michelle W Voss

    2010-08-01

    Full Text Available 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 (.008<.08 Hz coherence of cognitively relevant and sensory brain networks in older adults who participated in a one-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 six months. A non-aerobic stretching and toning group also showed increased functional connectivity in the DMN after six 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.

  15. Brain white matter structure and COMT gene are linked to second-language learning in adults.

    Science.gov (United States)

    Mamiya, Ping C; Richards, Todd L; Coe, Bradley P; Eichler, Evan E; Kuhl, Patricia K

    2016-06-28

    Adult human brains retain the capacity to undergo tissue reorganization during second-language learning. Brain-imaging studies show a relationship between neuroanatomical properties and learning for adults exposed to a second language. However, the role of genetic factors in this relationship has not been investigated. The goal of the current study was twofold: (i) to characterize the relationship between brain white matter fiber-tract properties and second-language immersion using diffusion tensor imaging, and (ii) to determine whether polymorphisms in the catechol-O-methyltransferase (COMT) gene affect the relationship. We recruited incoming Chinese students enrolled in the University of Washington and scanned their brains one time. We measured the diffusion properties of the white matter fiber tracts and correlated them with the number of days each student had been in the immersion program at the time of the brain scan. We found that higher numbers of days in the English immersion program correlated with higher fractional anisotropy and lower radial diffusivity in the right superior longitudinal fasciculus. We show that fractional anisotropy declined once the subjects finished the immersion program. The relationship between brain white matter fiber-tract properties and immersion varied in subjects with different COMT genotypes. Subjects with the Methionine (Met)/Valine (Val) and Val/Val genotypes showed higher fractional anisotropy and lower radial diffusivity during immersion, which reversed immediately after immersion ended, whereas those with the Met/Met genotype did not show these relationships. Statistical modeling revealed that subjects' grades in the language immersion program were best predicted by fractional anisotropy and COMT genotype.

  16. Brain white matter structure and COMT gene are linked to second-language learning in adults.

    Science.gov (United States)

    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

  17. Reduced brain resting-state network specificity in infants compared with adults

    Directory of Open Access Journals (Sweden)

    Wylie KP

    2014-07-01

    Full Text Available Korey P Wylie,1,* Donald C Rojas,1,* Randal G Ross,1 Sharon K Hunter,1 Keeran Maharajh,1 Marc-Andre Cornier,2 Jason R Tregellas1,3 1Department of Psychiatry, 2Division of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; 3Denver Veterans Affairs Medical Center, Denver, CO, USA *These authors contributed equally to this work Purpose: Infant resting-state networks do not exhibit the same connectivity patterns as those of young children and adults. Current theories of brain development emphasize developmental progression in regional and network specialization. We compared infant and adult functional connectivity, predicting that infants would exhibit less regional specificity and greater internetwork communication compared with adults.Patients and methods: Functional magnetic resonance imaging at rest was acquired in 12 healthy, term infants and 17 adults. Resting-state networks were extracted, using independent components analysis, and the resulting components were then compared between the adult and infant groups.Results: Adults exhibited stronger connectivity in the posterior cingulate cortex node of the default mode network, but infants had higher connectivity in medial prefrontal cortex/anterior cingulate cortex than adults. Adult connectivity was typically higher than infant connectivity within structures previously associated with the various networks, whereas infant connectivity was frequently higher outside of these structures. Internetwork communication was significantly higher in infants than in adults.Conclusion: We interpret these findings as consistent with evidence suggesting that resting-state network development is associated with increasing spatial specificity, possibly reflecting the corresponding functional specialization of regions and their interconnections through experience. Keywords: functional connectivity magnetic resonance imaging

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

    Science.gov (United States)

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

    2013-08-01

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

  19. Cognitive functioning in relation to brain amyloid-β in healthy adults with Down syndrome.

    Science.gov (United States)

    Hartley, Sigan L; Handen, Benjamin L; Devenny, Darlynne A; Hardison, Regina; Mihaila, Iulia; Price, Julie C; Cohen, Annie D; Klunk, William E; Mailick, Marsha R; Johnson, Sterling C; Christian, Bradley T

    2014-09-01

    Nearly all adults with Down syndrome show neuropathology of Alzheimer's disease, including amyloid-β deposition, by their fifth decade of life. In the current study, we examined the association between brain amyloid-β deposition, assessed via in vivo assessments of neocortical Pittsburgh compound B, and scores on an extensive neuropsychological battery of measures of cognitive functioning in 63 adults (31 male, 32 female) with Down syndrome aged 30-53 years who did not exhibit symptoms of dementia. Twenty-two of the adults with Down syndrome were identified as having elevated neocortical Pittsburgh compound B retention levels. There was a significant positive correlation (r = 0.62, P Down syndrome who had elevated neocortical Pittsburgh compound B retention levels and those who did not on any of the neuropsychological measures. Similarly, when examining Pittsburgh compound B as a continuous variable, after controlling for mental age and chronological age, only the Rivermead Picture Recognition score was significantly negatively associated with neocortical Pittsburgh compound B retention. Our findings indicate that many adults with Down syndrome can tolerate amyloid-β deposition without deleterious effects on cognitive functioning. However, we may have obscured true effects of amyloid-β deposition by controlling for chronological age in our analyses. Moreover, our sample included adults with Down syndrome who were most 'resistant' to the effects of amyloid-β deposition, as adults already exhibiting clinical symptoms of dementia symptoms were excluded from the study.

  20. Prion diseases and adult neurogenesis: how do prions counteract the brain's endogenous repair machinery?

    Science.gov (United States)

    Relaño-Ginés, Aroa; Lehmann, Sylvain; Crozet, Carole

    2014-01-01

    Scientific advances in stem cell biology and adult neurogenesis have raised the hope that neurodegenerative disorders could benefit from stem cell-based therapy. Adult neurogenesis might be part of the physiological regenerative process, however it might become impaired by the disease's mechanism and therefore contribute to neurodegeneration. In prion disorders this endogenous repair system has rarely been studied. Whether adult neurogenesis plays a role or not in brain repair or in the propagation of prion pathology remains unclear. We have recently investigated the status of adult neural stem cells isolated from prion-infected mice. We were able to show that neural stem cells accumulate and replicate prions thus resulting in an alteration of their neuronal destiny. We also reproduced these results in adult neural stem cells, which were infected in vitro. The fact that endogenous adult neurogenesis could be altered by the accumulation of misfolded prion protein represents another great challenge. Inhibiting prion propagation in these cells would thus help the endogenous neurogenesis to compensate for the injured neuronal system. Moreover, understanding the endogenous modulation of the neurogenesis system would help develop effective neural stem cell-based therapies.

  1. Elevated brain lesion volumes in older adults who use calcium supplements: a cross sectional clinical observational study

    OpenAIRE

    Payne, Martha E.; McQuoid, Douglas R.; Steffens, David C.; Anderson, John J. B.

    2014-01-01

    Recent studies have implicated calcium supplements with elevated vascular risk, and therefore these supplements may also relate to the occurrence of brain lesions (or hyperintensities) in older adults. These lesions represent damage to brain tissue that is caused by ischaemia. This cross sectional clinical observational study examined the association between use of calcium-containing dietary supplements and lesion volumes in a sample of 227 older adults (60 years and older). Food and suppleme...

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

    OpenAIRE

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

    2013-01-01

    Cardiovascular (CV) risk factors, such as hypertension, diabetes, and hyperlipidemia are associated with cognitive impairment and risk of dementia in older adults. However, the mechanisms linking them are not clear. This study aims to investigate the association between aggregate CV risk, assessed by the Framingham general cardiovascular risk profile, and functional brain activation in a group of community-dwelling older adults. Sixty participants (mean age: 64.6 years) from the Brain Health ...

  3. Promoting brain health through exercise and diet in older adults: a physiological perspective.

    Science.gov (United States)

    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

  4. Distinct Brain and Behavioral Benefits from Cognitive vs. Physical Training: A Randomized Trial in Aging Adults.

    Science.gov (United States)

    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

  5. Distinct Brain and Behavioral Benefits from Cognitive vs. Physical Training: A Randomized Trial in Aging Adults

    Science.gov (United States)

    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

  6. Diffusion-weighted MRI and proton MR spectroscopy in adult hypoxic brain injury

    International Nuclear Information System (INIS)

    Full text: The clinical and imaging assessment of patients with severe hypoxic brain injury is difficult, especially in the first few days after the insult. Proton spectroscopy has shown promise in the assessment of neonatal hypoxic brain injury, but there has been little experience with it in adults with such injury. The high sensitivity of diffusion-weighted imaging (DWI) for early stroke suggests that it may be more sensitive to hypoxic injury than conventional sequences. Patients with documented acute hypoxic episodes (cardiac arrest, hanging, measured severe arterial hypotension) and clinical evidence of hypoxic brain injury were included. MRI was not performed until sedation had been ceased for at least 24 hours. In addition to conventional T2-weighted and FLAIR imaging, six patients underwent DWI. A further ten patients underwent conventional imaging plus DWI and proton spectroscopy (PRESS TE 135, 2 x 2 x 2 cm voxel in parasagittal occipital cortex antero-inferiorly). Three of these patients were examined twice because of ongoing radiological and clinical uncertainty. In acute hypoxic insults, a negative diffusion-weighted study does not exclude significant brain injury. Proton spectroscopy is more sensitive to hypoxic brain injury, at least from 48 hours post-ictus, and may provide an index of severity. The findings suggest that acute hypoxia can trigger ongoing neuronal loss (over at least a week) without evidence of macroscopic infarction. Copyright (2002) Blackwell Science Pty Ltd

  7. Progressive gender differences of structural brain networks in healthy adults: a longitudinal, diffusion tensor imaging study.

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    Yu Sun

    Full Text Available Sexual dimorphism in the brain maturation during childhood and adolescence has been repeatedly documented, which may underlie the differences in behaviors and cognitive performance. However, our understanding of how gender modulates the development of structural connectome in healthy adults is still not entirely clear. Here we utilized graph theoretical analysis of longitudinal diffusion tensor imaging data over a five-year period to investigate the progressive gender differences of brain network topology. The brain networks of both genders showed prominent economical "small-world" architecture (high local clustering and short paths between nodes. Additional analysis revealed a more economical "small-world" architecture in females as well as a greater global efficiency in males regardless of scan time point. At the regional level, both increased and decreased efficiency were found across the cerebral cortex for both males and females, indicating a compensation mechanism of cortical network reorganization over time. Furthermore, we found that weighted clustering coefficient exhibited significant gender-time interactions, implying different development trends between males and females. Moreover, several specific brain regions (e.g., insula, superior temporal gyrus, cuneus, putamen, and parahippocampal gyrus exhibited different development trajectories between males and females. Our findings further prove the presence of sexual dimorphism in brain structures that may underlie gender differences in behavioral and cognitive functioning. The sex-specific progress trajectories in brain connectome revealed in this work provide an important foundation to delineate the gender related pathophysiological mechanisms in various neuropsychiatric disorders, which may potentially guide the development of sex-specific treatments for these devastating brain disorders.

  8. Disruption of White Matter Integrity in Adult Survivors of Childhood Brain Tumors: Correlates with Long-Term Intellectual Outcomes

    OpenAIRE

    King, Tricia Z.; Liya Wang; Hui Mao

    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 in...

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

    OpenAIRE

    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....

  10. Oligodendrogenesis after Cerebral Ischaemia and Traumatic Brain Injury

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    Zheng Gang Zhang

    2013-08-01

    Full Text Available Stroke and traumatic brain injury (TBI damage white and grey matter. Loss of oligodendrocytes and their myelin, impairs axonal function. Remyelination involves oligodendrogenesis during which new myelinating oligodendrocytes are generated by differentiated oligodendrocyte progenitor cells (OPCs. This article briefly reviews the processes of oligodendrogenesis in adult rodent brains, and promising experimental therapies targeting the neurovascular unit that reduce oligodendrocyte damage and amplify endogenous oligodendrogenesis after stroke and TBI.

  11. Growth Factors Released from Gelatin Hydrogel Microspheres Increase New Neurons in the Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    Kanako Nakaguchi

    2012-01-01

    Full Text Available Recent studies have shown that new neurons are continuously generated by endogenous neural stem cells in the subventricular zone (SVZ of the adult mammalian brain. Some of these new neurons migrate to injured brain tissues and differentiate into mature neurons, suggesting that such new neurons may be able to replace neurons lost to degenerative disease or injury and improve or repair neurological deficits. Here, we tested whether delivering growth factors via gelatin hydrogel microspheres would support neurogenesis in the SVZ. Insulin-like growth factor-1 (IGF-1-containing microspheres increased the number of new neurons in the SVZ. Hepatocyte growth factor (HGF-containing microspheres increased the number of new neurons migrating from the SVZ towards the injured striatum in a stroke model in mouse. These results suggest that the strategy of using gelatin hydrogel microspheres to achieve the sustained release of growth factors holds promise for the clinical regeneration of damaged brain tissues from endogenous neural stem cells in the adult SVZ.

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ezzati, Ali [Albert Einstein College of Medicine of Yeshiva University, Saul B. Korey Department of Neurology, Bronx, NY (United States); Montefiore Medical Center, Department of Neurology, Bronx, NY (United States); Katz, Mindy J. [Albert Einstein College of Medicine of Yeshiva University, Saul B. Korey Department of Neurology, Bronx, NY (United States); Lipton, Michael L. [Albert Einstein College of Medicine of Yeshiva University, The Gruss Magnetic Resonance Research Center and Departments of Radiology, Psychiatry and Behavioral Sciences and the Dominick P. Purpura Department of Neuroscience, Bronx, NY (United States); Montefiore Medical Center, The Department of Radiology, Bronx, NY (United States); Lipton, Richard B. [Albert Einstein College of Medicine of Yeshiva University, Saul B. Korey Department of Neurology, Bronx, NY (United States); Albert Einstein College of Medicine of Yeshiva University, Department of Epidemiology and Population Health, Bronx, NY (United States); Verghese, Joe [Albert Einstein College of Medicine of Yeshiva University, Saul B. Korey Department of Neurology, Bronx, NY (United States); Albert Einstein College of Medicine, Division of Cognitive and Motor Aging, Bronx, NY (United States)

    2015-08-15

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

  14. Differential changes of metabolic brain activity and interregional functional coupling in prefronto-limbic pathways during different stress conditions: Functional imaging in freely behaving rodent pups

    Directory of Open Access Journals (Sweden)

    Joerg Bock

    2012-05-01

    Full Text Available The trumpet-tailed rat or degu (Octodon degus is an established model to investigate the consequences of early stress on the development of emotional brain circuits and behaviour. The aim of this study was to identify brain circuits, that respond to different stress conditions and to test if acute stress alters functional coupling of brain activity among prefrontal and limbic regions. Using functional imaging (2-Fluoro-deoxyglucose method in 8 day old male degu pups the following stress conditions were compared: (A pups together with parents and siblings (control, (B separation of the litter from the parents, (C individual separation from parents and siblings, (D individual separation and presentation of maternal calls. Condition (B significantly downregulated brain activity in the prefrontal cortex, hippocampus, nucleus accumbens and sensory areas compared to controls. Activity decrease was even more pronounced during condition (C, where, in contrast to all other regions, activity in the PAG was increased. Interestingly, brain activity in stress-associated brain regions such as the amygdala and habenula was not affected. In condition (D maternal vocalizations reactivated brain activity in the cingulate and precentral medial cortex, nucleus accumbens and striatum and in sensory areas. In contrast, reduced activity was measured in the prelimbic and infralimbic cortex and in the hippocampus and amygdala. Correlation analysis revealed complex, region- and situation-specific changes of interregional functional coupling among prefrontal and limbic brain regions during stress exposure. We show here for the first time that early life stress results in a widespread reduction of brain activity in the infant brain and changes interregional functional coupling. Moreover, maternal vocalizations can partly buffer stress-induced decrease in brain activity in some regions and evoked very different functional coupling patterns compared to the three other

  15. Organization of the histaminergic system in adult zebrafish (Danio rerio) brain: neuron number, location, and cotransmitters.

    Science.gov (United States)

    Sundvik, Maria; Panula, Pertti

    2012-12-01

    Histamine is an essential factor in the ascending arousal system (AAS) during motivated behaviors. Histamine and hypocretin/orexin (hcrt) are proposed to be responsible for different aspects of arousal and wakefulness, histamine mainly for cognitive and motivated behaviors. In this study we visualized the entire histaminergic neuron population in adult male and female zebrafish brain and quantified the histaminergic neuron numbers. There were 40-45 histaminergic neurons in both male and female zebrafish brain. Further, we identified cotransmitters of histaminergic neurons in the ventrocaudal hypothalamus, i.e., around the posterior recess (PR) in adult zebrafish. Galanin, γ-aminobutyric acid (GABA), and thyrotropin-releasing hormone (TRH) were colocalized with histamine in some but not all neurons, a result that was verified by intracerebroventricular injections of colchicine into adult zebrafish. Fibers immunoreactive (ir) for galanin, GABA, TRH, or methionine-enkephalin (mENK) were dense in the ventrocaudal hypothalamus around the histaminergic neurons. In histamine-ir fibers TRH and galanin immunoreactivities were also detected in the ventral telencephalon. All these neurotransmitters are involved in maintaining the equilibrium of the sleep-wake state. Our results are in accordance with results from rats, further supporting the use of zebrafish as a tool to study molecular mechanisms underlying complex behaviors.

  16. Testes and brain gene expression in precocious male and adult maturing Atlantic salmon (Salmo salar

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    Houeix Benoit

    2010-03-01

    Full Text Available Abstract Background The male Atlantic salmon generally matures in fresh water upon returning after one or several years at sea. Some fast-growing male parr develop an alternative life strategy where they sexually mature before migrating to the oceans. These so called 'precocious' parr or 'sneakers' can successfully fertilise adult female eggs and so perpetuate their line. We have used a custom-built cDNA microarray to investigate gene expression changes occurring in the salmon gonad and brain associated with precocious maturation. The microarray has been populated with genes selected specifically for involvement in sexual maturation (precocious and adult and in the parr-smolt transformation. Results Immature and mature parr collected from a hatchery-reared stock in January were significantly different in weight, length and condition factor. Changes in brain expression were small - never more than 2-fold on the microarray, and down-regulation of genes was much more pronounced than up-regulation. Significantly changing genes included isotocin, vasotocin, cathepsin D, anamorsin and apolipoprotein E. Much greater changes in expression were seen in the testes. Among those genes in the testis with the most significant changes in expression were anti-Mullerian hormone, collagen 1A, and zinc finger protein (Zic1, which were down-regulated in precocity and apolipoproteins E and C-1, lipoprotein lipase and anti-leukoproteinase precursor which were up-regulated in precocity. Expression changes of several genes were confirmed in individual fish by quantitative PCR and several genes (anti-Mullerian hormone, collagen 1A, beta-globin and guanine nucleotide binding protein (G protein beta polypeptide 2-like 1 (GNB2L1 were also examined in adult maturing testes. Down-regulation of anti-Mullerian hormone was judged to be greater than 160-fold for precocious males and greater than 230-fold for November adult testes in comparison to July testes by this method. For

  17. Restoration of stressor-induced calcium dysregulation and autophagy inhibition by polyphenol-rich acai (Euterpe sps.) fruit pulp extracts in rodent brain cells in vitro

    Science.gov (United States)

    Oxidative damage to lipids, proteins and nucleic acids in brain often causes progressive neuronal degeneration and death which are the focal traits of chronic and acute pathologies in the brain, including those involving cognitive decline. It has been postulated that at least part of the loss of cog...

  18. Brain-derived neurotrophic factor (BDNF) induces sustained intracellular Ca2+ elevation through the up-regulation of surface transient receptor potential 3 (TRPC3) channels in rodent microglia.

    Science.gov (United States)

    Mizoguchi, Yoshito; Kato, Takahiro A; Seki, Yoshihiro; Ohgidani, Masahiro; Sagata, Noriaki; Horikawa, Hideki; Yamauchi, Yusuke; Sato-Kasai, Mina; Hayakawa, Kohei; Inoue, Ryuji; Kanba, Shigenobu; Monji, Akira

    2014-06-27

    Microglia are immune cells that release factors, including proinflammatory cytokines, nitric oxide (NO), and neurotrophins, following activation after disturbance in the brain. Elevation of intracellular Ca(2+) concentration ([Ca(2+)]i) is important for microglial functions such as the release of cytokines and NO from activated microglia. There is increasing evidence suggesting that pathophysiology of neuropsychiatric disorders is related to the inflammatory responses mediated by microglia. Brain-derived neurotrophic factor (BDNF) is a neurotrophin well known for its roles in the activation of microglia as well as in pathophysiology and/or treatment of neuropsychiatric disorders. In this study, we sought to examine the underlying mechanism of BDNF-induced sustained increase in [Ca(2+)]i in rodent microglial cells. We observed that canonical transient receptor potential 3 (TRPC3) channels contribute to the maintenance of BDNF-induced sustained intracellular Ca(2+) elevation. Immunocytochemical technique and flow cytometry also revealed that BDNF rapidly up-regulated the surface expression of TRPC3 channels in rodent microglial cells. In addition, pretreatment with BDNF suppressed the production of NO induced by tumor necrosis factor α (TNFα), which was prevented by co-adiministration of a selective TRPC3 inhibitor. These suggest that BDNF induces sustained intracellular Ca(2+) elevation through the up-regulation of surface TRPC3 channels and TRPC3 channels could be important for the BDNF-induced suppression of the NO production in activated microglia. We show that TRPC3 channels could also play important roles in microglial functions, which might be important for the regulation of inflammatory responses and may also be involved in the pathophysiology and/or the treatment of neuropsychiatric disorders.

  19. Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain

    Science.gov (United States)

    Rivera, Patricia; Blanco, Eduardo; Bindila, Laura; Alen, Francisco; Vargas, Antonio; Rubio, Leticia; Pavón, Francisco J.; Serrano, Antonia; Lutz, Beat; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence. PMID:26483633

  20. Large-Scale Identification of Coregulated Enhancer Networks in the Adult Human Brain

    Directory of Open Access Journals (Sweden)

    Marit W. Vermunt

    2014-10-01

    Full Text Available Understanding the complexity of the human brain and its functional diversity remain a major challenge. Distinct anatomical regions are involved in an array of processes, including organismal homeostasis, cognitive functions, and susceptibility to neurological pathologies, many of which define our species. Distal enhancers have emerged as key regulatory elements that acquire histone modifications in a cell- and species-specific manner, thus enforcing specific gene expression programs. Here, we survey the epigenomic landscape of promoters and cis-regulatory elements in 136 regions of the adult human brain. We identify a total of 83,553 promoter-distal H3K27ac-enriched regions showing global characteristics of brain enhancers. We use coregulation of enhancer elements across many distinct regions of the brain to uncover functionally distinct networks at high resolution and link these networks to specific neuroglial functions. Furthermore, we use these data to understand the relevance of noncoding genomic variations previously linked to Parkinson’s disease incidence.

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

    Directory of Open Access Journals (Sweden)

    Caghan Kizil

    Full Text Available 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.

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

    Science.gov (United States)

    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.

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

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    Kuan Zhang

    Full Text Available 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 (NSCsin 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.

  4. Cellular distribution and localisation of iron in adult rat brain (substantia nigra)

    International Nuclear Information System (INIS)

    Iron appears to be one of the main factors in the metal induced neurodegeneration. Quantitative information on cellular, sub-cellular and cell specific distributions of iron is therefore important to assess. The investigations reported here were carried out on a brain from an adult rat. Therefore, 6 μm thick embedded, unstained brain sections containing the midbrain (substantia nigra, SN) were analysed. Particle induced X-ray emission (PIXE) using a focussed proton beam (beam - diameter app. 1 μm) was performed to determine the quantitative iron content on a cellular and sub-cellular level. The integral analysis shows that the iron content in the SN pars reticulata is twice as high than in the SN pars compacta. The analysis of the iron content on the cellular level revealed no remarkable differences between glia cells and neurons. This is in contrast to other studies using staining techniques

  5. Cellular distribution and localisation of iron in adult rat brain (substantia nigra)

    Energy Technology Data Exchange (ETDEWEB)

    Meinecke, Ch. [Institute for Experimental Physics II, Faculty for Physics and Geosciences, University of Leipzig, Linnestr. 5, D-04103 Leipzig (Germany)]. E-mail: meinecke@physik.uni-leipzig.de; Morawski, M. [Paul-Flechsig-Institute for Brain research, University of Leipzig, Jahnallee 59, D-04109 Leipzig (Germany); Reinert, T. [Institute for Experimental Physics II, Faculty for Physics and Geosciences, University of Leipzig, Linnestr. 5, D-04103 Leipzig (Germany); Arendt, T. [Paul-Flechsig-Institute for Brain research, University of Leipzig, Jahnallee 59, D-04109 Leipzig (Germany); Butz, T. [Institute for Experimental Physics II, Faculty for Physics and Geosciences, University of Leipzig, Linnestr. 5, D-04103 Leipzig (Germany)

    2006-08-15

    Iron appears to be one of the main factors in the metal induced neurodegeneration. Quantitative information on cellular, sub-cellular and cell specific distributions of iron is therefore important to assess. The investigations reported here were carried out on a brain from an adult rat. Therefore, 6 {mu}m thick embedded, unstained brain sections containing the midbrain (substantia nigra, SN) were analysed. Particle induced X-ray emission (PIXE) using a focussed proton beam (beam - diameter app. 1 {mu}m) was performed to determine the quantitative iron content on a cellular and sub-cellular level. The integral analysis shows that the iron content in the SN pars reticulata is twice as high than in the SN pars compacta. The analysis of the iron content on the cellular level revealed no remarkable differences between glia cells and neurons. This is in contrast to other studies using staining techniques.

  6. The long-term side effects of radiation therapy for benign brain tumors in adults

    Energy Technology Data Exchange (ETDEWEB)

    al-Mefty, O.; Kersh, J.E.; Routh, A.; Smith, R.R. (Univ. of Mississippi Medical Center, Jackson (USA))

    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.

  7. The long-term side effects of radiation therapy for benign brain tumors in adults.

    Science.gov (United States)

    al-Mefty, O; Kersh, J E; Routh, A; Smith, R R

    1990-10-01

    Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors (two of these also had pituitary dysfunction). One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered "safe" treatment for benign brain tumors.

  8. Identification and characterization of neuroblasts in the subventricular zone and rostral migratory stream of the adult human brain

    Institute of Scientific and Technical Information of China (English)

    Congmin Wang; Qiangqiang Zhang; Yue Zhang; Rui Chen; Hongjun Song; Zhengang Yang; Fang Liu; Ying-Ying Liu; Cai-Hong Zhao; Yan You; Lei Wang; Jingxiao Zhang; Bin Wei; Tong Ma

    2011-01-01

    It is of great interest to identify new neurons in the adult human brain,but the persistence of neurogenesis in the subventricular zone (SVZ) and the existence of the rostral migratory stream (RMS)-like pathway in the adult human forebrain remain highly controversial.In the present study,we have described the general configuration of the RMS in adult monkey,fetal human and adult human brains.We provide evidence that neuroblasts exist continuously in the anterior ventral SVZ and RMS of the adult human brain.The neuroblasts appear singly or in pairs without forming chains; they exhibit migratory morphologies and co-express the immature neuronal markers doublecortin,polysialylated neural cell adhesion molecule and βI-tubulin.Few of these neuroblasts appear to be actively proliferating in the anterior ventral SVZ but none in the RMS,indicating that neuroblasts distributed along the RMS are most likely derived from the ventral SVZ.Interestingly,no neuroblasts are found in the adult human olfactory bulb.Taken together,our data suggest that the SVZ maintains the ability to produce neuroblasts in the adult human brain.

  9. In vivo brain anatomy of adult males with Fragile X syndrome: an MRI study.

    LENUS (Irish Health Repository)

    Hallahan, Brian P

    2011-01-01

    Fragile X Syndrome (FraX) is caused by the expansion of a single trinucleotide gene sequence (CGG) on the X chromosome, and is a leading cause of learning disability (mental retardation) worldwide. Relatively few studies, however, have examined the neuroanatomical abnormalities associated with FraX. Of those that are available many included mixed gender populations, combined FraX children and adults into one sample, and employed manual tracing techniques which measures bulk volume of particular regions. Hence, there is relatively little information on differences in grey and white matter content across whole brain. We employed magnetic resonance imaging to investigate brain anatomy in 17 adult males with FraX and 18 healthy controls that did not differ significantly in age. Data were analysed using stereology and VBM to compare (respectively) regional brain bulk volume, and localised grey\\/white matter content. Using stereology we found that FraX males had a significant increase in bulk volume bilaterally of the caudate nucleus and parietal lobes and of the right brainstem, but a significant decrease in volume of the left frontal lobe. Our complimentary VBM analysis revealed an increased volume of grey matter in fronto-striatal regions (including bilaterally in the caudate nucleus), and increased white matter in regions extending from the brainstem to the parahippocampal gyrus, and from the left cingulate cortex extending into the corpus callosum. People with FraX have regionally specific differences in brain anatomy from healthy controls with enlargement of the caudate nuclei that persists into adulthood.

  10. Occupational and Environmental Risk Factors of Adult Primary Brain Cancers: A Systematic Review

    Directory of Open Access Journals (Sweden)

    A Guzman

    2011-03-01

    Full Text Available 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 highvoltage 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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  13. Age-related decreased inhibitory versus excitatory gene expression in the adult autistic brain

    Directory of Open Access Journals (Sweden)

    Louie Nathan van de Lagemaat

    2014-12-01

    Full Text Available Autism spectrum disorders (ASDs are neurodevelopmental disorders characterised by impaired social interaction and communication, and restricted behaviour and interests. A disruption in the balance of excitatory and inhibitory neurotransmission has been hypothesised to underlie these disorders. Here we demonstrate that genes of both pathways are affected by ASD, and that gene expression of inhibitory and excitatory genes is altered in the cerebral cortex of adult but not younger autistic individuals. We have developed a measure for the difference in the level of excitation and inhibition based on gene expression and observe that in this measure inhibition is decreased relative to excitation in adult ASD compared to control. This difference was undetectable in young autistic brains. Given that many psychiatric features of autism are already present at an early age, this suggests that the observed imbalance in gene expression is an ageing phenomenon in ASD rather than its underlying cause.

  14. Evidence of cognitive decline in older adults after remote traumatic brain injury: an exploratory study.

    Science.gov (United States)

    Ozen, Lana J; Fernandes, Myra A; Clark, Amanda J; Roy, Eric A

    2015-01-01

    Separate bodies of literature indicate that a history of a traumatic brain injury (TBI) and natural aging may result in overlapping cognitive profiles, yet little is known about their combined effect. We predicted that a remote TBI would compound normal age-related cognitive decline, particularly affecting executive function. Neuropsychological task performance was compared between a group of older adults who sustained a TBI in their distant past (N = 9) and a group of older adults with no history of head injury (N = 15). While all participants scored in the normal range on the Mini-Mental State Examination, the TBI group scored lower than the non-TBI group. Also, in line with predictions, the TBI group made more errors on measures of executive functioning compared to the non-TBI group (the Trail Making B test and the incongruent condition of the Stroop Test), but performed similarly on all tasks with little executive requirements. Findings from this exploratory study indicate that a past TBI may put older adults at a higher risk for exacerbated age-related cognitive decline compared to older adults with no history of TBI. PMID:25532692

  15. Juvenile antioxidant treatment prevents adult deficits in a developmental model of schizophrenia

    OpenAIRE

    Cabungcal, Jan Harry; Counotte, Danielle S.; Lewis, Eastman; Tejeda, Hugo A.; Piantadosi, Patrick; Pollock, Cameron; Calhoon, Gwendolyn G.; Sullivan, Elyse; Presgraves, Echo; Kil, Jonathan; Hong, L. Elliot; Cuenod, Michel; Kim Q Do; O'Donnell, Patricio

    2014-01-01

    Abnormal development can lead to deficits in adult brain function, a trajectory likely underlying adolescent-onset psychiatric conditions such as schizophrenia. Developmental manipulations yielding adult deficits in rodents provide an opportunity to explore mechanisms involved in a delayed emergence of anomalies driven by developmental alterations. Here we assessed whether oxidative stress during presymptomatic stages causes adult anomalies in rats with a neonatal ventral hippocampal lesion, ...

  16. [18F]FDG is not transported by P-glycoprotein and breast cancer resistance protein at the rodent blood–brain barrier

    International Nuclear Information System (INIS)

    Introduction: Transport of 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG) by the multidrug efflux transporters P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) at the blood–brain barrier (BBB) may confound the interpretation of [18F]FDG brain PET data. Aim of this study was to assess the influence of ABCB1 and ABCG2 at the BBB on brain distribution of [18F]FDG in vivo by performing [18F]FDG PET scans in wild-type and transporter knockout mice and by evaluating changes in [18F]FDG brain distribution after transporter inhibition. Methods: Dynamic small-animal PET experiments (60 min) were performed with [18F]FDG in groups of wild-type and transporter knockout mice (Abcb1a/b(−/−), Abcg2(−/−) and Abcb1a/b(−/−)Abcg2(−/−)) and in wild-type rats without and with i.v. pretreatment with the known ABCB1 inhibitor tariquidar (15 mg/kg, given at 2 h before PET). Blood was sampled from animals from the orbital sinus vein at the end of the PET scans and measured in a gamma counter. Brain uptake of [18F]FDG was expressed as the brain-to-blood radioactivity concentration ratio in the last PET time frame (Kb,brain). Results: Kb,brain values of [18F]FDG were not significantly different between different mouse types both without and with tariquidar pretreatment. The blood-to-brain transfer rate constant of [18F]FDG was significantly lower in tariquidar-treated as compared with vehicle-treated rats (0.350 ± 0.025 mL/min/g versus 0.416 ± 0.024 mL/min/g, p = 0.026, paired t-test) but Kb,brain values were not significantly different between both rat groups. Conclusion: Our results show that [18F]FDG is not transported by Abcb1 at the mouse and rat BBB in vivo. In addition we found no evidence for Abcg2 transport of [18F]FDG at the mouse BBB. Advances in knowledge and implications for patient care: Our findings imply that functional activity of ABCB1 and ABCG2 at the BBB does not need to be taken into account when interpreting brain [18F]FDG PET data

  17. Adult hippocampal neurogenesis of mammals: evolution and life history

    OpenAIRE

    Amrein, I.; Lipp, H. P.

    2009-01-01

    Substantial production of new neurons in the adult mammalian brain is restricted to the olfactory system and the hippocampal formation. Its physiological and behavioural role is still debated. By comparing adult hippocampal neurogenesis (AHN) across many mammalian species, one might recognize a common function. AHN is most prominent in rodents, but shows considerable variability across species, being lowest or missing in primates and bats. The latter finding argues against a critical role of ...

  18. Low-intensity treadmill exercise and/or bright light promote neurogenesis in adult rat brain

    Institute of Scientific and Technical Information of China (English)

    Sung Jin Kwon; Jeongsook Park; So Yun Park; Kwang Seop Song; Sun Tae Jung; So Bong Jung; Ik Ryeul Park; Wan Sung Choi; Sun Ok Kwon

    2013-01-01

    The hippocampus is a brain region responsible for learning and memory functions. The purpose of this study was to investigate the effects of low-intensity exercise and bright light exposure on neurogenesis and brain-derived neurotrophic factor expression in adult rat hippocampus. Male Sprague-Dawley rats were randomly assigned to control, exercise, light, or exercise + light groups (n = 9 per group). The rats in the exercise group were subjected to treadmill exercise (5 days per week, 30 minutes per day, over a 4-week period), the light group rats were irradiated (5 days per week, 30 minutes per day, 10 000 lx, over a 4-week period), the exercise + light group rats were subjected to treadmill exercise in combination with bright light exposure, and the control group rats remained sedentary over a 4-week period. Compared with the control group, there was a significant increase in neurogenesis in the hippocampal dentate gyrus of rats in the exercise, light, and exercise + light groups. Moreover, the expression level of brain-derived neurotrophic factor in the rat hippocampal dentate gyrus was significantly higher in the exercise group and light group than that in the control group. Interestingly, there was no significant difference in brain-derived neurotrophic factor expression between the control group and exercise + light group. These results indicate that low-intensity treadmill exercise (first 5 minutes at a speed of 2 m/min, second 5 minutes at a speed of 5 m/min, and the last 20 minutes at a speed of 8 m/min) or bright-light exposure therapy induces positive biochemical changes in the brain. In view of these findings, we propose that moderate exercise or exposure to sunlight during childhood can be beneficial for neural development.

  19. Functional neuroanatomy of executive function after neonatal brain injury in adults who were born very preterm.

    Directory of Open Access Journals (Sweden)

    Anastasia K Kalpakidou

    Full Text Available 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.

  20. Brain

    Science.gov (United States)

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

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

    Science.gov (United States)

    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. 3D standard brain of the red flour beetle Tribolium castaneum: a tool to study metamorphic development and adult plasticity

    Directory of Open Access Journals (Sweden)

    David Dreyer

    2010-03-01

    Full Text Available 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, 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 antennal lobes. 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, very importantly, will serve as future volumetric references after genetical manipulation especially regarding metamorphic development and adult plasticity.

  3. GSK-3beta is required for memory reconsolidation in adult brain.

    Directory of Open Access Journals (Sweden)

    Tetsuya Kimura

    Full Text Available Activation of GSK-3beta is presumed to be involved in various neurodegenerative diseases, including Alzheimer's disease (AD, which is characterized by memory disturbances during early stages of the disease. The normal function of GSK-3beta in adult brain is not well understood. Here, we analyzed the ability of heterozygote GSK-3beta knockout (GSK+/- mice to form memories. In the Morris water maze (MWM, learning and memory performance of GSK+/- mice was no different from that of wild-type (WT mice for the first 3 days of training. With continued learning on subsequent days, however, retrograde amnesia was induced in GSK+/- mice, suggesting that GSK+/- mice might be impaired in their ability to form long-term memories. In contextual fear conditioning (CFC, context memory was normally consolidated in GSK+/- mice, but once the original memory was reactivated, they showed reduced freezing, suggesting that GSK+/- mice had impaired memory reconsolidation. Biochemical analysis showed that GSK-3beta was activated after memory reactivation in WT mice. Intraperitoneal injection of a GSK-3 inhibitor before memory reactivation impaired memory reconsolidation in WT mice. These results suggest that memory reconsolidation requires activation of GSK-3beta in the adult brain.

  4. Cortical neurogenesis in adult rats after ischemic brain injury:most new neurons fail to mature

    Institute of Scientific and Technical Information of China (English)

    Qing-quan Li; Guan-qun Qiao; Jun Ma; Hong-wei Fan; Ying-bin Li

    2015-01-01

    The present study examines the hypothesis that endogenous neural progenitor cells isolated from the neocortex of ischemic brain can differentiate into neurons or glial cells and contribute to neural regeneration. We performed middle cerebral artery occlusion to establish a model of cerebral ischemia/reperfusion injury in adult rats. Immunohistochemical staining of the cortex 1, 3, 7, 14 or 28 days after injury revealed that neural progenitor cells double-positive for nestin and sox-2 appeared in the injured cortex 1 and 3 days post-injury, and were also positive for glial ifbrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identiifed using doublecortin, microtubule-associated protein 2 and neuronal nuclei antigen immunohistochemistry. Immature new neurons coexpressing doublecortin and bromodeoxyuridine were observed in the cortex at 3 and 7 days post-injury, and semi-mature and mature new neurons double-positive for microtubule-associated protein 2 and bromode-oxyuridine were found at 14 days post-injury. A few mature new neurons coexpressing neuronal nuclei antigen and bromodeoxyuridine were observed in the injured cortex 28 days post-injury. Glial ifbrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our ifndings suggest that neural progenitor cells are present in the damaged cortex of adult rats with cerebral ischemic brain injury, and that they differentiate into astrocytes and immature neurons, but most neurons fail to reach the mature stage.

  5. The studies on neurogenesis indufced by brain injury in adult ring dove

    Institute of Scientific and Technical Information of China (English)

    ZUOMINGXUE

    1998-01-01

    It was the first time demonstrated by us that the number of newborn neurons was increased after making lesion in forebrain of adult ring dove(Streptopelia risoria) by means of autoradiography and imunohistochemistry,Neurogensis in the adult avian is restricted to the telencephalon.In doves with bilateral electrolytic lesion of nucleus ectostriatum(E),the mean mumber of proliferating cells in the lateral ventricular zone(LVZ) and newborn neurons in the forebrain increased by 1.95 times and 2.38 times respectively as compared with that in intact doves.The most remarkable incresase of neurogenesis induced by nucleus ectostriatum lesions was found at the anteriorposterior level 3(L3),where the lesion site was located.These results showed that the electrolytic brain lesion al tered the distribution pattern of proliferating cells in the LVZ and resulted in increase of the number of newborn neureons in the non-VZ areas of forebrain.The changes in number and distribution pattern of proliferating cells in LVZ and newbon neurons in forebrain may be dependent on site of lesion.Studies on the relationship between proliferating cells in LVZ and newly generated neurons in non-VZ aresa may help to understand the mechanism of brain plasticity and development.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Claudia eBarth

    2015-02-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Jonathan eList

    2015-05-01

    Full Text Available 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 grey 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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Olivier eHoudé

    2014-06-01

    Full Text Available 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.

  15. Immunocytochemical localization of a chondroitin sulfate proteoglycan in nervous tissue. I. Adult brain, retina, and peripheral nerve

    OpenAIRE

    1984-01-01

    Monospecific antibodies were prepared to a previously characterized chondroitin sulfate proteoglycan of brain and used in conjunction with the peroxidase-antiperoxidase technique to localize the proteoglycan by immunoelectron microscopy. The proteoglycan was found to be exclusively intracellular in adult cerebellum, cerebrum, brain stem, and spinal cord. Some neurons and astrocytes (including Golgi epithelial cells and Bergmann fibers) showed strong cytoplasmic staining. Although in the centr...

  16. The influence of intermittent hypobaric hypoxia on the brain iron metabolism in adult Sprague dawley rats

    Institute of Scientific and Technical Information of China (English)

    Wu Qiong; Li Yaru; Chang Yanzhong

    2015-01-01

    Objective:Iron is an essential element in all living organisms and is required as a cofactor for oxygen-binding proteins. Iron metabolism, oxygen homeostasis and erythropoiesis are consequently strongly inter-connected. In mammalian cells, exposure to a low-oxygen environment triggers a hypoxic response pathway cen-tered on the regulated expression of the hypoxia-inducible transcription factor ( HIF) . Hypoxia has been shown to increase the expression of a variety of proteins involved in iron homeostasis. However, little is known about brain iron metabolism after intermittent hypobaric hypoxia ( IHH) treatment. In this study, adult Sprague dawley ( SD) rats were treated with IHH for 28 days, 8h per day and then we detected iron homeostasis in different brain areas of SD rats. Results:The protein level of hippocampus transferrin receptor 1 ( TfR1 ) , divalent metal transporter 1 (DMT1) with IRE, DMT1 (-IRE), ferritin-H, iron regulatory protein (IRP) 2 and ceruloplasmin (CP) is ele-vated significantly while ferritin-L decreased. We have also found the down regulation of IRP1. We observe the same results in the cerebral cortex in the brain. Conclusions:We first discover that IHH has an influence on the brain iron homeostasis and the decreased ferritin-L corresponds to the down regulation of IRP1 indicating hypoxia can affect the expression of ferritin-L through IRE/IRP system. Although there is a marked increase in TfR1 ex-pression that would lead to the raised level of LIP in cells. It can finally result in the higher ROS which can damage the cells. The concerned mechanisms involved in it remain to be deliberated.

  17. Dopamine D1 receptor imaging in the rodent and primate brain using the isoquinoline (+)-[{sup 11}C]A-69024 and positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Besret, L.; Herard, A.S.; Guillermier, M.; Hantraye, P. [CNRS, URA 2210, F-91406 Orsay (France); Dolle, F.; Demphel, S.; Hinnen, F.; Coulon, C.; Ottaviani, M.; Bottlaender, M. [CEA, DSV, I2BM, SHFJ, Lab Imagerie Mol Expt, F-91406 Orsay (France); Herard, A.S.; Guillermier, M.; Hantraye, P. [CEA, DSV, I2BM, Mol Imaging Res Ctr, F-92265 Fontenay Aux Roses (France); Kassiou, M. [Univ Sydney, Discipline Med Radiat Sci, Sydney, NSW 2006 (Australia); Kassiou, M. [Univ Sydney, Brain and Mind Res Inst, Sydney, NSW 2050 (Australia); Kassiou, M. [Univ Sydney, Sch Chem, Sydney, NSW 2006 (Australia)

    2008-07-01

    In vivo pharmacokinetic and brain binding characteristics of (+)-[{sup 11}C]A-69024, a high-affinity-D1-selective dopamine receptor antagonist, were assessed with micro-PET and {beta}-microprobes in the rat and PET in the baboon. The biodistribution of (+)-[{sup 11}C]A-69024 in rats and baboons showed a rapid brain uptake (reaching a maximal value at 5 and 15 min postinjection in rats and baboons, respectively), followed by a slow wash out. The region/cerebellum concentration ratio was characterized by a fourfold higher uptake in striatum and a twofold higher uptake in cortical regions, consistent with in vivo specific binding of the radiotracer in these cerebral regions. Furthermore, this specific (+)-[{sup 11}C]A-69024 binding significantly correlated with the reported in vitro distribution of dopamine D1-receptors. Finally, the specific uptake of the tracer in the striatum and cortical regions was completely prevented by either a pretreatment with large doses of nonradioactive {+-}A-69024 or of the D1-selective antagonist SCH23390, resulting in a similar uptake in the reference region (cerebellum) and in other brain regions. Thus, (+)-[{sup 11}C]A-69024 appears to be a specific and enantioselective radioligand to visualize and quantify brain dopamine D1 receptors in vivo using positron emission tomography. (authors)

  18. In vivo imaging of neuroinflammation in the rodent brain with [{sup 11}C]SSR180575, a novel indoleacetamide radioligand of the translocator protein (18 kDa)

    Energy Technology Data Exchange (ETDEWEB)

    Chauveau, Fabien [CEA, DSV, IBM, Service Hospitalier Frederic Joliot, Orsay (France); Universite Paris Sud, INSERM U1023, Orsay (France); Universite Lyon 1, Creatis, CNRS UMR 5220, INSERM U630, INSA Lyon, Lyon (France); Boutin, Herve [CEA, DSV, IBM, Service Hospitalier Frederic Joliot, Orsay (France); Universite Paris Sud, INSERM U1023, Orsay (France); University of Manchester, Faculty of Life Sciences, Manchester (United Kingdom); Camp, Nadja van; Tavitian, Bertrand [CEA, DSV, IBM, Service Hospitalier Frederic Joliot, Orsay (France); Universite Paris Sud, INSERM U1023, Orsay (France); Thominiaux, Cyrille; Dolle, Frederic [CEA, DSV, IBM, Service Hospitalier Frederic Joliot, Orsay (France); Hantraye, Philippe [CEA, DSV, IBM, MIRCEN, Fontenay-aux-Roses (France); Rivron, Luc [Sanofi-Aventis, GMPK-Global Isotope Chemistry and Metabolite Synthesis Department (ICMS), Paris (France); Marguet, Frank; Castel, Marie-Noelle; Rooney, Thomas; Benavides, Jesus [Sanofi-Aventis, CNS Department, Paris (France)

    2011-03-15

    Neuroinflammation is involved in neurological disorders through the activation of microglial cells. Imaging of neuroinflammation with radioligands for the translocator protein (18 kDa) (TSPO) could prove to be an attractive biomarker for disease diagnosis and therapeutic evaluation. The indoleacetamide-derived 7-chloro-N,N,5-trimethyl-4-oxo-3-phenyl-3,5-dihydro-4H-pyridazino[4,5-b]indole-1-acetamide, SSR180575, is a selective high-affinity TSPO ligand in human and rodents with neuroprotective effects. Here we report the radiolabelling of SSR180575 with {sup 11}C and in vitro and in vivo imaging in an acute model of neuroinflammation in rats. The image contrast and the binding of [{sup 11}C]SSR180575 are higher than that obtained with the isoquinoline-based TSPO radioligand, [{sup 11}C]PK11195. Competition studies demonstrate that [{sup 11}C]SSR180575 has high specific binding for the TSPO. [{sup 11}C]SSR180575 is the first PET radioligand for the TSPO based on an indoleacetamide scaffold designed for imaging neuroinflammation in animal models and in the clinic. (orig.)

  19. Evaluation of the binding of the radiolabeled antidepressant drug, {sup 18}F-fluoxetine in the rodent brain: an in vitro and in vivo study

    Energy Technology Data Exchange (ETDEWEB)

    Mukherjee, Jogeshwar E-mail: jogeshwar_mukherjee@ketthealth.com; Das, Malay K.; Yang Zhiying; Lew, Robert

    1998-10-01

    We have developed {sup 18}F-fluoxetine as a radiotracer analog of the antidepressant drug fluoxetine (Prozac). In vitro saturation experiments of {sup 18}F-fluoxetine were carried out on rat midbrain tissue and citalopram was used for measuring nonspecific binding. A saturation curve for the binding of {sup 18}F-fluoxetine was not obtained. Even when fluoxetine (10 {mu}M) was used for measurements of nonspecific binding, a saturation curve was difficult to obtain. Other compounds, such as deprenyl, clorgyline, amphetamine, and reserpine were also not able to reduce the binding of {sup 18}F-fluoxetine. Ex vivo autoradiographic experiments with {sup 18}F-fluoxetine did not reveal any specific uptake in various brain regions. In vivo administration of {sup 18}F-fluoxetine in rats showed similar uptake in all the brain regions with little regional selectivity. A subcellular analysis of rat brain tissue after intravenous (IV) administration of {sup 18}F-fluoxetine indicated significant amounts of binding in mitochondria and synaptosomes. In summary, in vitro experiments with {sup 18}F-fluoxetine indicate little specific binding. Binding to the serotonin transporter was not identifiable. High nonspecific binding of the tracer resulting from its subcellular nature in the brain masks the ability to detect binding to the serotonin uptake sites in vivo. These findings indicate that a large portion of the binding of {sup 18}F-fluoxetine in rat brains is subcellular and clears slowly out of the cells. Other sites, such as monoamine oxidase, may also play a significant role in the action of fluoxetine.

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

    Science.gov (United States)

    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 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 brain injury during aquatic sports was similarly associated with prolonged ICU and hospital LOSs, medical complications, and failure to be discharged to

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

    Science.gov (United States)

    Prüfer, Kay; Kelso, Janet; Dannemann, Michael

    2016-01-01

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

  2. Effect of Synthetic Matrix Metalloproteinase Inhibitors on Lipopolysaccharide-Induced Blood-Brain Barrier Opening in Rodents: Differences in Response Based on Strains and Solvents

    OpenAIRE

    Rosenberg, Gary A; Estrada, Eduardo Y.; Mobashery, Shahriar

    2006-01-01

    Matrix metalloproteinase inhibitors (MMPIs) reduce blood-brain barrier (BBB) disruption and prevent cell death. Animal models of multiple sclerosis, cerebral ischemia and hemorrhage, and bacterial meningitis respond to treatment with MMPIs. We have used the intracerebral injection of lipopolysaccharide (LPS) in rat, which induces MMP production and results in a delayed opening of the BBB, to screen MMPIs to identify therapeutic agents. We hypothesized that the mouse would respond similarly to...

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

    Science.gov (United States)

    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. The evidence for increased L1 activity in the site of human adult brain neurogenesis.

    Directory of Open Access Journals (Sweden)

    Alexey A Kurnosov

    Full Text Available Retroelement activity is a common source of polymorphisms in human genome. The mechanism whereby retroelements contribute to the intraindividual genetic heterogeneity by inserting into the DNA of somatic cells is gaining increasing attention. Brain tissues are suspected to accumulate genetic heterogeneity as a result of the retroelements somatic activity. This study aims to expand our understanding of the role retroelements play in generating somatic mosaicism of neural tissues. Whole-genome Alu and L1 profiling of genomic DNA extracted from the cerebellum, frontal cortex, subventricular zone, dentate gyrus, and the myocardium revealed hundreds of somatic insertions in each of the analyzed tissues. Interestingly, the highest concentration of such insertions was detected in the dentate gyrus-the hotspot of adult neurogenesis. Insertions of retroelements and their activity could produce genetically diverse neuronal subsets, which can be involved in hippocampal-dependent learning and memory.

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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'.

  7. Species differences in brain gene expression profiles associated with adult behavioral maturation in honey bees

    Directory of Open Access Journals (Sweden)

    Robinson Gene E

    2007-06-01

    Full Text Available Abstract Background Honey bees are known for several striking social behaviors, including a complex pattern of behavioral maturation that gives rise to an age-related colony division of labor and a symbolic dance language, by which successful foragers communicate the location of attractive food sources to their nestmates. Our understanding of honey bees is mostly based on studies of the Western honey bee, Apis mellifera, even though there are 9–10 other members of genus Apis, showing interesting variations in social behavior relative to A. mellifera. To facilitate future in-depth genomic and molecular level comparisons of behavior across the genus, we performed a microarray analysis of brain gene expression for A. mellifera and three key species found in Asia, A. cerana, A. florea and A. dorsata. Results For each species we compared brain gene expression patterns between foragers and adult one-day-old bees on an A. mellifera cDNA microarray and calculated within-species gene expression ratios to facilitate cross-species analysis. The number of cDNA spots showing hybridization fluorescence intensities above the experimental threshold was reduced by an average of 16% in the Asian species compared to A. mellifera, but an average of 71% of genes on the microarray were available for analysis. Brain gene expression profiles between foragers and one-day-olds showed differences that are consistent with a previous study on A. mellifera and were comparable across species. Although 1772 genes showed significant differences in expression between foragers and one-day-olds, only 218 genes showed differences in forager/one-day-old expression between species (p Conclusion We conclude that the A. mellifera cDNA microarray can be used effectively for cross-species comparisons within the genus. Our results indicate that there is a widespread conservation of the molecular processes in the honey bee brain underlying behavioral maturation. Species differences in

  8. TAM receptors affect adult brain neurogenesis by negative regulation of microglial cell activation.

    Science.gov (United States)

    Ji, Rui; Tian, Shifu; Lu, Helen J; Lu, Qingjun; Zheng, Yan; Wang, Xiaomin; Ding, Jixiang; Li, Qiutang; Lu, Qingxian

    2013-12-15

    TAM tyrosine kinases play multiple functional roles, including regulation of the target genes important in homeostatic regulation of cytokine receptors or TLR-mediated signal transduction pathways. In this study, we show that TAM receptors affect adult hippocampal neurogenesis and loss of TAM receptors impairs hippocampal neurogenesis, largely attributed to exaggerated inflammatory responses by microglia characterized by increased MAPK and NF-κB activation and elevated production of proinflammatory cytokines that are detrimental to neuron stem cell proliferation and neuronal differentiation. Injection of LPS causes even more severe inhibition of BrdU incorporation in the Tyro3(-/-)Axl(-/-)Mertk(-/-) triple-knockout (TKO) brains, consistent with the LPS-elicited enhanced expression of proinflammatory mediators, for example, IL-1β, IL-6, TNF-α, and inducible NO synthase, and this effect is antagonized by coinjection of the anti-inflammatory drug indomethacin in wild-type but not TKO brains. Conditioned medium from TKO microglia cultures inhibits neuron stem cell proliferation and neuronal differentiation. IL-6 knockout in Axl(-/-)Mertk(-/-) double-knockout mice overcomes the inflammatory inhibition of neurogenesis, suggesting that IL-6 is a major downstream neurotoxic mediator under homeostatic regulation by TAM receptors in microglia. Additionally, autonomous trophic function of the TAM receptors on the proliferating neuronal progenitors may also promote progenitor differentiation into immature neurons.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  12. Expression of Bcl-2 in adult human brain regions with special reference to neurodegenerative disorders.

    Science.gov (United States)

    Vyas, S; Javoy-Agid, F; Herrero, M T; Strada, O; Boissiere, F; Hibner, U; Agid, Y

    1997-07-01

    The expression of the protooncogene bcl-2, an inhibitor of apoptosis in various cells, was examined in the adult human brain. Several experimental criteria were used to verify its presence; mRNA was analyzed by northern blot with parallel experiments in mouse tissues, by RNase protection, and by in situ hybridization histochemistry. Bcl-2 protein was detected by western blot analysis and immunohistochemistry. Two bcl-2 mRNA species were identified in the human brain. The pattern of distribution of bcl-2 mRNA at the cellular level showed labeling in neurons but not glia. The in situ hybridization signal was stronger in the pyramidal neurons of the cerebral cortex and in the cholinergic neurons of the nucleus basalis of Meynert than in the Purkinje neurons of the cerebellum. Both melanized and nonmelanized neurons were labeled in the substantia nigra. In the striatum, bcl-2 mRNA was detected in some but not all neurons. In the regions examined for Bcl-2 protein, the expression pattern correlated with the mRNA results. In patients with Alzheimer's and Parkinson's diseases, quantification of bcl-2 mRNA in the nucleus basalis of Meynert and substantia nigra, respectively, showed that the expression was unaltered compared with controls, raising the possibility that the expression of other components of apoptosis is modulated.

  13. Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population

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    Walker Peter A

    2012-09-01

    Full Text Available Abstract Introduction We have demonstrated previously that the intravenous delivery of multipotent adult progenitor cells (MAPC after traumatic brain injury affords neuroprotection via interaction with splenocytes, leading to an increase in systemic anti-inflammatory cytokines. We hypothesize that the observed modulation of the systemic inflammatory milieu is related to T regulatory cells and a subsequent increase in the locoregional neuroprotective M2 macrophage population. Methods C57B6 mice were injected with intravenous MAPC 2 and 24 hours after controlled cortical impact injury. Animals were euthanized 24, 48, 72, and 120 hours after injury. In vivo, the proportion of CD4+/CD25+/FOXP3+ T-regulatory cells were measured in the splenocyte population and plasma. In addition, the brain CD86+ M1 and CD206+ M2 macrophage populations were quantified. A series of in vitro co-cultures were completed to investigate the need for direct MAPC:splenocyte contact as well as the effect of MAPC therapy on M1 and M2 macrophage subtype apoptosis and proliferation. Results Significant increases in the splenocyte and plasma T regulatory cell populations were observed with MAPC therapy at 24 and 48 hours, respectively. In addition, MAPC therapy was associated with an increase in the brain M2/M1 macrophage ratio at 24, 48 and 120 hours after cortical injury. In vitro cultures of activated microglia with supernatant derived from MAPC:splenocyte co-cultures also demonstrated an increase in the M2/M1 ratio. The observed changes were secondary to an increase in M1 macrophage apoptosis. Conclusions The data show that the intravenous delivery of MAPC after cortical injury results in increases in T regulatory cells in splenocytes and plasma with a concordant increase in the locoregional M2/M1 macrophage ratio. Direct contact between the MAPC and splenocytes is required to modulate activated microglia, adding further evidence to the central role of the spleen in MAPC

  14. Diurnal microstructural variations in healthy adult brain revealed by diffusion tensor imaging.

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    Chunxiang Jiang

    Full Text Available Biorhythm is a fundamental property of human physiology. Changes in the extracellular space induced by cell swelling in response to the neural activity enable the in vivo characterization of cerebral microstructure by measuring the water diffusivity using diffusion tensor imaging (DTI. To study the diurnal microstructural alterations of human brain, fifteen right-handed healthy adult subjects were recruited for DTI studies in two repeated sessions (8∶30 AM and 8∶30 PM within a 24-hour interval. Fractional anisotropy (FA, apparent diffusion coefficient (ADC, axial (λ// and radial diffusivity (λ⊥ were compared pixel by pixel between the sessions for each subject. Significant increased morning measurements in FA, ADC, λ// and λ⊥ were seen in a wide range of brain areas involving frontal, parietal, temporal and occipital lobes. Prominent evening dominant λ⊥ (18.58% was detected in the right inferior temporal and ventral fusiform gyri. AM-PM variation of λ⊥ was substantially left side hemisphere dominant (p<0.05, while no hemispheric preference was observed for the same analysis for ADC (p = 0.77, λ// (p = 0.08 or FA (p = 0.25. The percentage change of ADC, λ//, λ⊥, and FA were 1.59%, 2.15%, 1.20% and 2.84%, respectively, for brain areas without diurnal diffusivity contrast. Microstructural variations may function as the substrates of the phasic neural activities in correspondence to the environment adaptation in a light-dark cycle. This research provided a baseline for researches in neuroscience, sleep medicine, psychological and psychiatric disorders, and necessitates that diurnal effect should be taken into account in following up studies using diffusion tensor quantities.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

    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)…

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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.

  19. DCC Expression by Neurons Regulates Synaptic Plasticity in the Adult Brain

    Directory of Open Access Journals (Sweden)

    Katherine E. Horn

    2013-01-01

    Full Text Available The transmembrane protein deleted in colorectal cancer (DCC and its ligand, netrin-1, regulate synaptogenesis during development, but their function in the mature central nervous system is unknown. Given that DCC promotes cell-cell adhesion, is expressed by neurons, and activates proteins that signal at synapses, we hypothesized that DCC expression by neurons regulates synaptic function and plasticity in the adult brain. We report that DCC is enriched in dendritic spines of pyramidal neurons in wild-type mice, and we demonstrate that selective deletion of DCC from neurons in the adult forebrain results in the loss of long-term potentiation (LTP, intact long-term depression, shorter dendritic spines, and impaired spatial and recognition memory. LTP induction requires Src activation of NMDA receptor (NMDAR function. DCC deletion severely reduced Src activation. We demonstrate that enhancing NMDAR function or activating Src rescues LTP in the absence of DCC. We conclude that DCC activation of Src is required for NMDAR-dependent LTP and certain forms of learning and memory.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  2. Adaptive modulation of adult brain gray and white matter to high altitude: structural MRI studies.

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    Jiaxing Zhang

    Full Text Available 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.

  3. Dietary choline supplementation to dams during pregnancy and lactation mitigates the effects of in utero stress exposure on adult anxiety-related behaviors

    OpenAIRE

    Schulz, Kalynn M.; Pearson, Jennifer N.; Gasparrini, Mary E.; Brooks, Kayla F.; Drake-Frazier, Chakeer; Zajkowski, Megan E.; Kreisler, Alison D.; Adams, Catherine E.; Leonard, Sherry; Stevens, Karen E.

    2014-01-01

    Brain cholinergic dysfunction is associated with neuropsychiatric illnesses such as depression, anxiety, and schizophrenia. Maternal stress exposure is associated with these same illnesses in adult offspring, yet the relationship between prenatal stress and brain cholinergic function is largely unexplored. Thus, using a rodent model, the current study implemented an intervention aimed at buffering the potential effects of prenatal stress on the developing brain cholinergic system. Specificall...

  4. Association of Metabolic Dysregulation With Volumetric Brain Magnetic Resonance Imaging and Cognitive Markers of Subclinical Brain Aging in Middle-Aged Adults

    OpenAIRE

    Beiser, Alexa S; Au, Rhoda; Himali, Jayandra J.; Debette, Stephanie; DeCarli, Charles; Vasan, Ramachandran S.; Wolf, Philip A.; Seshadri, Sudha; Tan, Zaldy S.; Fox, Caroline

    2011-01-01

    Objective: Diabetic and prediabtic states, including insulin resistance, fasting hyperglycemia, and hyperinsulinemia, are associated with metabolic dysregulation. These components have been individually linked to increased risks of cognitive decline and Alzheimer’s disease. We aimed to comprehensively relate all of the components of metabolic dysregulation to cognitive function and brain magnetic resonance imaging (MRI) in middle-aged adults. Research Design and Methods: Framingham Offspring ...

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

    Science.gov (United States)

    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

  6. Age-specific MRI brain and head templates for healthy adults from twenty through eighty-nine years of age

    Directory of Open Access Journals (Sweden)

    Paul T Fillmore

    2015-04-01

    Full Text Available 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 5-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 GM, WM, and 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 (http://jerlab.psych.sc.edu/NeurodevelopmentalMRIDatabase/.

  7. Mild traumatic brain injury with social defeat stress alters anxiety, contextual fear extinction, and limbic monoamines in adult rats

    Directory of Open Access Journals (Sweden)

    Daniel eDavies

    2016-04-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  9. Isoflurane anesthesia induced persistent, progressive memory impairment, caused a loss of neural stem cells, and reduced neurogenesis in young, but not adult, rodents

    OpenAIRE

    Zhu, Changlian; Gao, Jianfeng; Karlsson, Niklas; Li, Qian; Zhang, Yu; Huang, Zhiheng; Li, Hongfu; Kuhn, H. Georg; Blomgren, Klas

    2010-01-01

    Isoflurane and related anesthetics are widely used to anesthetize children, ranging from premature babies to adolescents. Concerns have been raised about the safety of these anesthetics in pediatric patients, particularly regarding possible negative effects on cognition. The purpose of this study was to investigate the effects of repeated isoflurane exposure of juvenile and mature animals on cognition and neurogenesis. Postnatal day 14 (P14) rats and mice, as well as adult (P60) rats, were an...

  10. Reduced linoleic acid intake in early postnatal life improves metabolic outcomes in adult rodents following a Western-style diet challenge.

    Science.gov (United States)

    Oosting, Annemarie; Kegler, Diane; van de Heijning, Bert J M; Verkade, Henkjan J; van der Beek, Eline M

    2015-09-01

    The global increase in dietary n-6 polyunsaturated fatty acid (PUFA) intake has been suggested to contribute to the rise in obesity incidence. We hypothesized that reduced n-6 PUFA intake during early postnatal life improves adult body composition and metabolic phenotype upon a Western diet challenge. Male offspring of C57Bl/6j mice and Wistar rats were subjected to a control diet (CTRL; 3.16 En% linoleic acid [LA]) or a low n-6 PUFA diet (low LA; 1.36 En% LA) from postnatal days (PNs) 2 to 42. Subsequently, all animals were switched to a Western-style diet (2.54 En% LA) until PN98. We monitored body composition by dual-energy x-ray absorptiometry and glucose homeostasis by an intravenous glucose and insulin tolerance test in rats and by the homeostasis model assessment of insulin resistance (HOMA-IR) in mice. At PN98, plasma lipids, glucose, insulin, and adipokines were measured and adipocyte number and size were analyzed. In mice, the postnatal low-LA diet decreased fat accumulation during the adult Western-style diet challenge (-27% compared with CTRL, P rats, the low-LA diet did not affect adult body composition, but decreased the number of retroperitoneal adipocytes and increased the number of large adipocytes. In conclusion, lowering dietary n-6 PUFA intake in early life protected against detrimental effects of an obesogenic diet in adulthood on metabolic homeostasis and fat mass accumulation. PMID:26239950

  11. Temporal features of adult neurogenesis: differences and similarities across mammalian species

    Directory of Open Access Journals (Sweden)

    Frederic eLevy

    2013-08-01

    Full Text Available Production of new neurons continues throughout life in most invertebrates and vertebrates like crustaceans, fishes, reptiles, birds, and mammals including humans. Most studies have been carried out on rodent models and demonstrated that adult neurogenesis is located mainly in two structures, the dentate gyrus (DG of the hippocampus and the sub-ventricular zone (SVZ. If adult neurogenesis is well preserved throughout evolution, yet there are however some features which differ between species. The present review proposes to target similarities and differences in the mechanism of mammalian adult neurogenesis by comparing selected species including humans. We will highlight the cellular composition and morphological organization of the SVZ in primates which differs from that of rodents and may be of functional relevance. We will particularly focus on the dynamic of neuronal maturation in rodents, primates and humans but also in sheep which appears to be an interesting model due to its similarities with the primate brain.

  12. Characterization of Aromatase Expression in the Adult Male and Female Mouse Brain. I. Coexistence with Oestrogen Receptors α and β, and Androgen Receptors

    OpenAIRE

    Davor Stanić; Sydney Dubois; Hui Kheng Chua; Bruce Tonge; Nicole Rinehart; Malcolm K Horne; Wah Chin Boon

    2014-01-01

    Aromatase catalyses the last step of oestrogen synthesis. There is growing evidence that local oestrogens influence many brain regions to modulate brain development and behaviour. We examined, by immunohistochemistry, the expression of aromatase in the adult male and female mouse brain, using mice in which enhanced green fluorescent protein (EGFP) is transcribed following the physiological activation of the Cyp19A1 gene. EGFP-immunoreactive processes were distributed in many brain regions, in...

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

    Science.gov (United States)

    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

  14. IGF-I: A key growth factor that regulates neurogenesis and synaptogenesis from embryonic to adult stages of the brain

    Directory of Open Access Journals (Sweden)

    Vanesa eNieto-Estévez

    2016-02-01

    Full Text Available 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.

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

    Science.gov (United States)

    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

  16. Effects of methylphenidate on resting-state brain activity in normal adults: an fMRI study

    Institute of Scientific and Technical Information of China (English)

    Yihong Zhu; Bin Gao; Jianming Hua; Weibo Liu; Yichao Deng; Lijie Zhang; Biao Jiang

    2013-01-01

    Methylphenidate (MPH) is one of the most commonly used stimulants for the treatment of attention deficit hyperactivity disorder (ADHD).Although several studies have evaluated the effects of MPH on human brain activation during specific cognitive tasks using functional magnetic resonance imaging (fMRI),few studies have focused on spontaneous brain activity.In the current study,we investigated the effect of MPH on the intra-regional synchronization of spontaneous brain activity during the resting state in 18normal adult males.A handedness questionnaire and the Wechsler Adult Intelligence Scale were applied before medication,and a resting-state fMRI scan was obtained 1 h after medication (20 mg MPH or placebo,order counterbalanced between participants).We demonstrated that:(1) there were no significant differences in the performance of behavioral tasks between the MPH and placebo groups; (2) the left middle and superior temporal gyri had stronger MPH-related regional homogeneity (ReHo); and (3) the left lingual gyrus had weaker MPH-related ReHo.Our findings showed that the ReHo in some brain areas changes with MPH compared to placebo in normal adults,even though there are no behavioral differences.This method can be applied to patients with mental illness who may be treated with MPH,and be used to compare the difference between patients taking MPH and normal participants,to help reveal the mechanism of how MPH works.

  17. Objectively measured physical activity, brain atrophy, and white matter lesions in older adults with mild cognitive impairment.

    Science.gov (United States)

    Doi, Takehiko; Makizako, Hyuma; Shimada, Hiroyuki; Tsutsumimoto, Kota; Hotta, Ryo; Nakakubo, Sho; Park, Hyuntae; Suzuki, Takao

    2015-02-01

    Physical activity may help to prevent or delay brain atrophy. Numerous studies have shown associations between physical activity and age-related changes in the brain. However, most of these studies involved self-reported physical activity, not objectively measured physical activity. Therefore, the aim of this study was to examine the association between objectively measured physical activity, as determined using accelerometers, and brain magnetic resonance imaging (MRI) measures in older adults with mild cognitive impairment (MCI). We analyzed 323 older subjects with MCI (mean age 71.4 years) who were recruited from the participants of the Obu Study of Health Promotion for the Elderly. We recorded demographic data and measured physical activity using a tri-axial accelerometer. Physical activity was classified as light-intensity physical activity (LPA) or moderate-to-vigorous physical activity (MVPA). Brain atrophy and the severity of white matter lesions (WML) were determined by MRI. Low levels of LPA and MVPA were associated with severe WML. Subjects with severe WML were older, had lower mobility, and had greater brain atrophy than subjects with mild WML (all Pbrain atrophy, even after adjustment for WML (β=-0.126, P=0.015), but LPA was not (β=-0.102, P=0.136). Our study revealed that objectively measured physical activity, especially MVPA, was associated with brain atrophy in MCI subjects, even after adjusting for WML. These findings support the hypothesis that physical activity plays a crucial role in maintaining brain health.

  18. Visual landmarks facilitate rodent spatial navigation in virtual reality environments

    OpenAIRE

    Youngstrom, Isaac A.; Strowbridge, Ben W.

    2012-01-01

    Because many different sensory modalities contribute to spatial learning in rodents, it has been difficult to determine whether spatial navigation can be guided solely by visual cues. Rodents moving within physical environments with visual cues engage a variety of nonvisual sensory systems that cannot be easily inhibited without lesioning brain areas. Virtual reality offers a unique approach to ask whether visual landmark cues alone are sufficient to improve performance in a spatial task. We ...

  19. Rodent Models of Depression: Neurotrophic and Neuroinflammatory Biomarkers

    OpenAIRE

    Mikhail Stepanichev; Nikolay N Dygalo; Grigory Grigoryan; Shishkina, Galina T.; Natalia Gulyaeva

    2014-01-01

    Rodent models are an indispensable tool for studying etiology and progress of depression. Since interrelated systems of neurotrophic factors and cytokines comprise major regulatory mechanisms controlling normal brain plasticity, impairments of these systems form the basis for development of cerebral pathologies, including mental diseases. The present review focuses on the numerous experimental rodent models of depression induced by different stress factors (exteroceptive and interoceptive) du...

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

    Science.gov (United States)

    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

  1. Intrinsic Functional Connectivity in the Adult Brain and Success in Second-Language Learning.

    Science.gov (United States)

    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

  2. Intrinsic Functional Connectivity in the Adult Brain and Success in Second-Language Learning.

    Science.gov (United States)

    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

  3. Influence of environmental stimulation on neurogenesis in the adult insect brain.

    Science.gov (United States)

    Scotto Lomassese, S; Strambi, C; Strambi, A; Charpin, P; Augier, R; Aouane, A; Cayre, M

    2000-11-15

    Mushroom bodies are the main integrative structures of insect brain. They receive sensory information from the eyes, the palps, and the antennae. In the house cricket, Acheta domesticus, a cluster of mushroom body neuroblasts keeps producing new interneurons during an insect's life span. The aim of the present work is to study the impact of environmental stimuli on mushroom body neurogenesis during adulthood. Crickets were reared either in an enriched environment, where they received complex environmental and congeneric stimulations or isolated in small cages and deprived of most visual, auditory, and olfactory stimuli. They then were injected with a S-phase marker, 5-bromo, 2'-deoxyuridine (BrdU) and sacrificed at different periods of their life. Neurogenesis and cell survival were estimated by counting the number of BrdU-labeled cells in the mushroom bodies. Environmentally enriched crickets were found to have an increased number of newborn cells in their mushroom bodies compared with crickets housed in cages with an impoverished environment. This effect of external factors on neurogenesis seems to be limited to the beginning of imaginal life. Furthermore, no cell loss could be detected among the newborn neurons in either environmental situation, suggesting that cell survival was not affected by the quality of the environment. Considering vertebrate studies which showed that enriched environment increases hippocampal cell survival and improves animal performances in spatial learning tests, we suggest that the increased number of interneurons produced in an integrative brain structure after exposure to enriched environment could contribute to adaptive behavioral performances in adult insects.

  4. Voluntary running prevents progressive memory decline and increases adult hippocampal neurogenesis and growth factor expression after whole-brain irradiation.

    Science.gov (United States)

    Wong-Goodrich, Sarah J E; Pfau, Madeline L; Flores, Catherine T; Fraser, Jennifer A; Williams, Christina L; Jones, Lee W

    2010-11-15

    Whole-brain irradiation (WBI) therapy produces progressive learning and memory deficits in patients with primary or secondary brain tumors. Exercise enhances memory and adult hippocampal neurogenesis in the intact brain, so we hypothesized that exercise may be an effective treatment to alleviate consequences of WBI. Previous studies using animal models to address this issue have yielded mixed results and have not examined potential molecular mechanisms. We investigated the short- and long-term effects of WBI on spatial learning and memory retention and determined whether voluntary running after WBI aids recovery of brain and cognitive function. Forty adult female C57Bl/6 mice given a single dose of 5 Gy or sham WBI were trained 2.5 weeks and up to 4 months after WBI in a Barnes maze. Half of the mice received daily voluntary wheel access starting 1 month after sham or WBI. Daily running following WBI prevented the marked decline in spatial memory retention observed months after irradiation. Bromodeoxyuridine (BrdUrd) immunolabeling and enzyme-linked immunosorbent assay indicated that this behavioral rescue was accompanied by a partial restoration of newborn BrdUrd+/NeuN+ neurons in the dentate gyrus and increased hippocampal expression of brain-derived vascular endothelial growth factor and insulin-like growth factor-1, and occurred despite irradiation-induced elevations in hippocampal proinflammatory cytokines. WBI in adult mice produced a progressive memory decline consistent with what has been reported in cancer patients receiving WBI therapy. Our findings show that running can abrogate this memory decline and aid recovery of adult hippocampal plasticity, thus highlighting exercise as a potential therapeutic intervention.

  5. Maternal folic acid supplementation to dams on marginal protein level alters brain fatty acid levels of their adult offspring.

    Science.gov (United States)

    Rao, Shobha; Joshi, Sadhana; Kale, Anvita; Hegde, Mahabaleshwar; Mahadik, Sahebarao

    2006-05-01

    Studies on fetal programming of adult diseases have highlighted the importance of maternal nutrition during pregnancy. Folic acid and long-chain essential polyunsaturated fatty acids (LC-PUFAs) have independent effects on fetal growth. However, folic acid effects may also involve alteration of LC-PUFA metabolism. Because marginal deficiency of LC-PUFAs during critical periods of brain growth and development is associated with risks for adult diseases, it is highly relevant to investigate how maternal supplementation of such nutrients can alter brain fatty acid levels. We examined the impact of folic acid supplementation, conventionally used in maternal intervention, on brain essential fatty acid levels and plasma corticosterone concentrations in adult offspring at 11 months of age. Pregnant female rats from 4 groups (6 in each) were fed with casein diets either with 18 g protein/100 g diet (control diet) or treatment diets that were marginal in protein (MP), such as 12 g protein/100 g diet supplemented with 8 mg folic acid (FAS/MP), 12 g protein/100 g diet without folic acid (FAD/MP), or 12 g protein/100 g diet (MP) with 2 mg folic acid. Pups were weaned to a standard laboratory diet with 18 g protein/100 g diet. All male adult offspring in the FAS/MP group showed lower docosahexaenoic acid (Pacids) and higher n-6/n-3 ratio (Pacid levels in FAS/MP adult offspring were also lower (Pfolic acid supplementation at MP intake decreased brain docosahexaenoic acid levels probably involving corticosterone increase. PMID:16631439

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

    Directory of Open Access Journals (Sweden)

    Chelsea N Wong

    2015-08-01

    Full Text Available 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.

  7. Changes in metabotropic glutamate receptor 4 expression and the effects of L-2-amino-4-phosphonobutyrate in a rodent model of diffuse brain injury

    Institute of Scientific and Technical Information of China (English)

    白红民; 王伟民; 李天栋; 费舟

    2004-01-01

    Objective: To examine the changes in the expression of mGluR4 after diffuse brain injury (DBI) and to determine the role of its specific agonist L-2-amino-4phosphonobutyrate (L-AP4) in vivo. Methods: A total of 161 male SD rats were randomized into the following groups. Group A included normal control, sham-operated control and DBI group. DBI was produced according to Marmarou's diffuse head injury model. mRNA expression of mGluR4 was detected by hybridization in situ. Group B included DBI alone, DBI treated with normal saline and DBI treated with L-AP4. All DBI rats were trained in a series of performance tests, following which they were subjected to DBI. At 1 and 12 hours, animals were injected intraventricularly with L-AP4 (100 mmol/L, 10 μl) or normal saline. Motor and cognitive performances were tested at 1,3, 7, 14 days after injury and the damaged neurons were also detected. Results: There was no significant difference between normal control group and sham-operated group in the expression of mGluR4 (P > 0.05 ). The animals exposed to DBI showed significantly increased expression of mRNA of mGluR4 compared with the sham-operated animals 1 h after injury (P < 0.05 ). At 6 hours, the evolution of neuronal expression of mGluR4 in the trauma alone group was relatively static. Compared with saline-treated control animals, rats treated with L-AP4 showed an effective result of decreased number of damaged neurons and better motor and cognitive performances. Conclusions: Increased expression of mGluR4 is important in the pathophysiological process of DBI and its specific agonist L -AP4 can provide remarkable neuroprotection against DBI not only at the histopathological level but also in the motor and cognitive performance.

  8. Xenogeneic transfer of fetal liver and adult bone marrow-derived haemopoietic cells in rodents: changes in spleen colony differentials with increased doses of cells.

    Science.gov (United States)

    Gulya, E; Gábor Szabó, L; Kelemen, E

    1997-01-01

    The effect of very high haemopoietic cell doses were investigated on the composition of splenic cell colonies/clusters in irradiated animals under xenogeneic circumstances. Differential cluster/colony counts from serial histological sections of the spleen were investigated before, and 9-12 days after transplantation of fetal liver- or adult bone marrow-derived haemopoietic cells following 5.0 to 8.5 Gy total body irradiation. Syngeneic as well as xenogeneic (mouse to rat and rat to mouse) transplantations were carried out. Cluster/colony differentials changed with the increase of the injected cell mass from 10(5) to 10(6) and 10(7) or more, i.e. the overwhelming erythroid pattern became trilinear even with xenogeneic transplants.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  12. Progressive mental deterioration after radiotherapy in adult patients with brain tumors

    International Nuclear Information System (INIS)

    We report a study on changes of mental function in twenty five adult patients with cerebral low-grade gliomas after radiotherapy. None of them had shown mental deterioration before radiotherapy nor tumor recurrence after radiotherapy. Radiation was given at a dose of 48 to 78 Gy (mean: 54.2 Gy). Patients were assigned for mental functional levels according to Karnofsky performance scale (KPS) after radiotherapy. Ten patients (40%) were normal. Seven patients (28%) showed moderate disabilities and 8 (32%) severe disabilities. The median interval time from radiotherapy to the onset of mental deterioration was 2.5 years in the moderate group and 1.6 years in the severe group. CT findings in severe group demonstrated severe brain atrophy and diffuse low density in the white matter after radiotherapy. The risk factors responsible for progressive mental deterioration after radiotherapy may be radiation site and size (whole frontal lobe), total dose (over 60 Gy) and patient age at the time of radiotherapy (over 60 yrs). (author)

  13. Uus Multiphonic Rodent

    Index Scriptorium Estoniae

    2009-01-01

    Tartus tegutsenud eksperimentaal-rock-duo Opium Flirt Eestisse jäänud liige Erki Hõbe (paarimees Ervin Trofimov tegutseb Ungaris) annab välja oma teise sooloalbumi nime all Multiphonic Rodent, heliplaadi "Astral Dance" esitluskontsert toimub 5. veebruaril Tallinnas baaris Juuksur

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Kun Hua

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

  18. 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.

    Directory of Open Access Journals (Sweden)

    Sandra A Acosta

    Full Text Available 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.

  19. Study Design for a Case Control Investigation of Cellular Telephones and Other Risk Factors for Brain Tumors in Adults

    Energy Technology Data Exchange (ETDEWEB)

    Inskip, P.D.; Hatch, E.E.; Stewart, P.A.; Heineman, E.F.; Ziegler, R.G.; Dosemeci, M.; Parry, D.; Rothman, N.; Boice, J.D. Jr.; Wilcosky, T.C.; Watson, D.J.; Shapiro, W.R.; Selker, R.G.; Fine, H.A.; Black, P. McL.; Loeffler, J.S.; Linet, M.S

    1999-07-01

    The aetiology of brain tumours is poorly understood. Due, in part, to public concern about a postulated relationship between the use of cellular telephones or other increasingly prevalent environmental exposures and the incidence of brain cancer in adults, the National Cancer Institute is collaborating with three US hospitals in a comprehensive case control study of malignant and benign brain tumours. Factors under consideration include use of cellular phones and other wireless communication devices, workplace exposures to chemical agents and electromagnetic fields, dietary factors, family history of tumours, genetic determinants of susceptibility, home appliance use, reproductive history and hormonal exposures, viruses, medical and dental exposure to ionising radiation, and other aspects of medical history. Approximately 800 newly diagnosed brain tumour cases and 800 controls were enrolled at hospitals in Boston, Phoenix and Pittsburgh from 1994 to 1998. Cases include all adults (age {>=} 18 y) newly diagnosed with a histologically confirmed intracranial glioma, histologically confirmed intracranial meningioma or acoustic neuroma. Controls are patients admitted to the same hospitals as the cases, and treated for any of a variety of non-malignant conditions. Key features of the study include its large size, the emphasis on rapid ascertainment of incident cases and interview of study subjects rather than surrogate respondents, the use of detailed, job-specific questions developed by industrial hygienists to ascertain occupational exposures, and the storage of blood samples for future evaluation of inherited susceptibility, biomarkers of exposure and gene environment interactions. (author)

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

    Directory of Open Access Journals (Sweden)

    Ryan Anderson

    Full Text Available 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.

  1. The generation of C-3α epimer of 25-hydroxyvitamin D and its biological effects on bone mineral density in adult rodents.

    Science.gov (United States)

    Bianchini, Christina; Lavery, Paula; Agellon, Sherry; Weiler, Hope A

    2015-05-01

    The source and function of C-3α epimer of 25(OH)D (C-3 epimer) is unknown. The objectives were to (1) establish if increasing doses of vitamin D (VD) results in a proportionate dose-response in C-3 epimer; and (2) determine the biological response of bone to C-3 epimer treatment. Sprague Dawley rats (12 weeks, n = 36 female, n = 36 male) were randomized to control AIN93-M diet (1 IU VD3/g diet) or an experimental diet for 8 weeks containing VD3 at 2 or 4 IU/g diet, C-3 epimer at 0.5 or 1 IU/g diet or 25(OH)D (0.5 IU/g diet). BW and food consumption were measured weekly. Blood was sampled at week 0, 4, and 8 for assessment of VD metabolites and bone metabolism biomarkers. DXA (week 0, 4, and 8) and in vivo micro CT (μCT) (week 0 and 8) were performed in vivo plus ex vivo μCT imaging and bone biomechanics. Dietary intake and anthropometry did not differ among diet groups. The dose-response of VD generated significantly elevated C-3 epimer only in females with concentrations of 4 IU VD diet group [mean 84.6 (62.5) nmol/L] exceeding control [mean 21.4 (18.5) nmol/L, p = 0.005]. Both sexes in the 25(OH)D group did not show significant increases in C-3 epimer, whereas 0.5 and 1 IU epimer groups exceeded 100 nmol/L of C-3 epimer by 8 weeks. These data suggest C-3 epimer is endogenously generated with higher intakes of VD. Endogenous and exogenous C-3 epimer accumulates in serum without impact upon bone health outcomes in a healthy young adult model over 8 weeks.

  2. Disruption of White Matter Integrity in Adult Survivors of Childhood Brain Tumors: Correlates with Long-Term Intellectual Outcomes.

    Directory of Open Access Journals (Sweden)

    Tricia Z King

    Full Text Available 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.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.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.Lower long-term intellectual outcomes of childhood brain tumor survivors are associated with lower white

  3. Expression and regulation of the Fkbp5 gene in the adult mouse brain.

    Directory of Open Access Journals (Sweden)

    Sebastian H Scharf

    Full Text Available 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.

  4. Association of Seafood Consumption, Brain Mercury Level, and APOEε4 Status With Brain Neuropathology in OlderAdults

    NARCIS (Netherlands)

    Morris, Martha Clare; Brockman, John; Schneider, J.; Wang, Yamin; Bennett, D.; Tangney, Christy; Nieuwerth-van de Rest, O.

    2016-01-01

    Importance Seafood consumption is promoted for its many health benefits even though its contamination by mercury, a known neurotoxin, is a growing concern.

    Objective To determine whether seafood consumption is correlated with increased brain mercury levels and also whether seafood consumpti

  5. Adolescent, but not adult, binge ethanol exposure leads to persistent global reductions of choline acetyltransferase expressing neurons in brain.

    Directory of Open Access Journals (Sweden)

    Ryan P Vetreno

    Full Text Available 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.

  6. Cellular scaling rules for primate brains

    OpenAIRE

    Herculano-Houzel, Suzana; Collins, Christine E.; Wong, Peiyan; Kaas, Jon H.

    2007-01-01

    Primates are usually found to have richer behavioral repertoires and better cognitive abilities than rodents of similar brain size. This finding raises the possibility that primate brains differ from rodent brains in their cellular composition. Here we examine the cellular scaling rules for primate brains and show that brain size increases approximately isometrically as a function of cell numbers, such that an 11× larger brain is built with 10× more neurons and ≈12× more nonneuronal cells of ...

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

    Directory of Open Access Journals (Sweden)

    Katja eFranke

    2013-12-01

    Full Text Available 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 MRIs. The Brain Age Gap Estimation (i.e., 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 3T, 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 (TNFα levels, lower verbal fluency scores and more severe depression. 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.

  8. Rodents of the Caribbean

    DEFF Research Database (Denmark)

    Fabre, Pierre-Henri; Mouatt, Julia Thidamarth Vilstrup; Raghavan, Maanasa;

    2014-01-01

    The Capromyidae (hutias) are endemic rodents of the Caribbean and represent a model of dispersal for non-flying mammals in the Greater Antilles. This family has experienced severe extinctions during the Holocene and its phylogenetic affinities with respect to other caviomorph relatives are still ...... (Bahamas, Cuba, Jamaica) hutias. Recent divergences among these western hutias suggest Plio-Pleistocene dispersal waves associated with glacial cycles....

  9. Susceptibility of juvenile and adult blood–brain barrier to endothelin-1: regulation of P-glycoprotein and breast cancer resistance protein expression and transport activity

    Directory of Open Access Journals (Sweden)

    Harati Rania

    2012-12-01

    Full Text Available Abstract Background P-glycoprotein (P-gp and breast cancer resistance protein (BCRP play a critical role in keeping neurotoxic substances from entering the brain. We and others have previously reported an impact of inflammation on the regulation of adult blood–brain barrier (BBB efflux transporters. However, studies in children have not been done. From the pediatric clinical perspective, it is important to understand how the central nervous system (CNS and BBB drug efflux transporters differ in childhood from those of adults under normal and inflammatory conditions. Therefore, we examined and compared the regulation of P-gp and BCRP expression and transport activity in young and adult BBB and investigated the molecular mechanisms underlying inflammatory responses. Methods Rats at postnatal day (P P21 and P84, corresponding to the juvenile and adult stages of human brain maturation, respectively, were treated with endothelin-1 (ET-1 given by the intracerebroventricular (icv route. Twenty-four hours later, we measured P-gp and BCRP protein expression in isolated brain capillary by immunoblotting as well as by transport activity in vivo by measuring the unbound drug partitioning coefficient of the brain (Kp,uu,brain of known efflux transporter substrates administered intravenously. Glial activation was measured by immunohistochemistry. The release of cytokines/chemokines (interleukins-1α, 1-β (IL-1β, -6 (IL-6, -10 (IL-10, monocyte chemoattractant protein (MCP-1/CCL2, fractalkine and tissue inhibitor of metalloproteinases-1 (TIMP-1 were simultaneously measured in brain and serum samples using the Agilent Technology cytokine microarray. Results We found that juvenile and adult BBBs exhibited similar P-gp and BCRP transport activities in the normal physiological conditions. However, long-term exposure of the juvenile brain to low-dose of ET-1 did not change BBB P-gp transport activity but tended to decrease BCRP transport activity in the juvenile

  10. Array tomography: rodent brain fixation and embedding.

    Science.gov (United States)

    Micheva, Kristina D; O'Rourke, Nancy; Busse, Brad; Smith, Stephen J

    2010-11-01

    Array tomography is a volumetric microscopy method based on physical serial sectioning. Ultrathin sections of a plastic-embedded tissue are cut using an ultramicrotome, bonded in an ordered array to a glass coverslip, stained as desired, and imaged. The resulting two-dimensional image tiles can then be reconstructed computationally into three-dimensional volume images for visualization and quantitative analysis. The minimal thickness of individual sections permits high-quality rapid staining and imaging, whereas the array format allows reliable and convenient section handling, staining, and automated imaging. Also, the physical stability of the arrays permits images to be acquired and registered from repeated cycles of staining, imaging, and stain elution, as well as from imaging using multiple modalities (e.g., fluorescence and electron microscopy). Array tomography makes it possible to visualize and quantify previously inaccessible features of tissue structure and molecular architecture. However, careful preparation of the tissue is essential for successful array tomography; these steps can be time-consuming and require some practice to perfect. This protocol describes the fixation and processing required to prepare tissues for immunofluorescence array tomography. PMID:21041396

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

    Brain-derived neurotrophic factor (BDNF) plays an important role in neurodevelopment, synaptic plas-ticity, 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 circuitsin 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 ma-jority of studies on synaptic plasticity, learning and memory were performed in acute brain slices orin 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 ifndings into the context of existing literature and discuss how they impact our understanding of how BDNF can reshape the brain.

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

    Directory of Open Access Journals (Sweden)

    Heather Bowling

    2016-01-01

    Full Text Available 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.

  13. Childhood brain tumours : Health and function in adult survivors and parental fears

    OpenAIRE

    Anclair, Malin

    2009-01-01

    The general aim of the present research was to investigate health and functional ability of patients treated for childhood brain tumour and systematically examine parental fears after a child s brain tumour. The aims were realised through two part-studies. Childhood cancer once regarded as an acute fatal illness has become a life threatening disease. Previous studies of the long-term sequelae in survivors of children treated for a brain tumour reflect the fact that most ...

  14. Exploration and visualization of gene expression with neuroanatomy in the adult mouse brain

    OpenAIRE

    Pathak Sayan; Thompson Carol; Ng Lydia; Lau Christopher; Kuan Leonard; Jones Allan; Hawrylycz Mike

    2008-01-01

    Abstract Background Spatially mapped large scale gene expression databases enable quantitative comparison of data measurements across genes, anatomy, and phenotype. In most ongoing efforts to study gene expression in the mammalian brain, significant resources are applied to the mapping and visualization of data. This paper describes the implementation and utility of Brain Explorer, a 3D visualization tool for studying in situ hybridization-based (ISH) expression patterns in the Allen Brain At...

  15. Whole-brain structural topology in adult attention-deficit/hyperactivity disorder: Preserved global – disturbed local network organization

    Directory of Open Access Journals (Sweden)

    Justina Sidlauskaite

    2015-01-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  17. Susceptibility of laboratory rodents to Trichinella papuae.

    Science.gov (United States)

    Sadaow, Lakkhana; Intapan, Pewpan M; Boonmars, Thidarut; Morakote, Nimit; Maleewong, Wanchai

    2013-12-01

    Members of the genus Trichinella are small nematodes that can infect a wide range of animal hosts. However, their infectivity varies depending on the parasite and host species combination. In this study, we examined the susceptibility of 4 species of laboratory rodents, i.e., mice, rats, hamsters, and gerbils to Trichinella papuae, an emerging non-encapsulated Trichinella species. Trichinella spiralis and Trichinella pseudospiralis were also included in this study for comparison. Fifteen animals of each rodent species were infected orally with 100 muscle larvae of each Trichinella species. Intestinal worm burden was determined at day 6 and 10 post-inoculation (PI). The numbers of muscle larvae were examined at day 45 PI. The reproductive capacity index (RCI) of the 3 Trichinella species in different rodent hosts was determined. By day 6 PI, 33.2-69.6% of the inoculated larvae of the 3 Trichinella species became adult worms in the small intestines of the host animals. However, in rats, more than 96% of adult worms of all 3 Trichinella species were expelled from the gut by day 10 PI. In gerbils, only 4.8-18.1% of adult worms were expelled by day 10 PI. In accordance with the intestinal worm burden and the persistence of adults, the RCI was the highest in gerbils with values of 241.5±41.0 for T. papuae, 432.6±48 for T. pseudospiralis, and 528.6±20.6 for T. spiralis. Hamsters ranked second and mice ranked third in susceptibility in terms of the RCI, Rats yielded the lowest parasite RCI for all 3 Trichinella species. Gerbils may be an alternative laboratory animal for isolation and maintenance of Trichinella spp. PMID:24516265

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

    Science.gov (United States)

    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.

  19. Rodent neurotoxicity bioassays for screening contaminated Great Lakes fish

    Energy Technology Data Exchange (ETDEWEB)

    Beattie, M.K.; Hoffman, R. [Univ. of Minnesota, Duluth, MN (United States); Gerstenberger, S. [Univ. of Illinois, Urbana, IL (United States). Dept. of Veterinary Biosciences; Dellinger, J.A. [Medical Coll. of Wisconsin, Milwaukee, MI (United States). Dept. of Preventive Medicine

    1996-03-01

    Standard laboratory rat neurotoxicity protocols were used to study the consequences resulting from the consumption of walleye (Stizostedion vitreum), whitefish (Coregonus clupeaformis), and lake trout (Salvelinus namaycush) from Lake Superior (LS) and the consumption of carp (Cyprinus carpio) from Little Lake Butte des Morte (LLBM) near Oshkosh, Wisconsin, USA. Two 90-d subchronic studies are described, including a 45-d exposure to fish diets using male Sprague-Dawley hooded rats, and a 90-d exposure to fish diets using female rats of the same species. Behavioral alterations were tested using a battery of behavioral tests. In addition, pharmacologic challenges using apomorphine and D-amphetamine were administered to the rats to reveal latent neurotoxic effects. Cumulative fish consumption data were recorded daily, weight gain recorded weekly, and behavior data collected prior to exposure, and on days 7, 14, 55 {+-} 2, 85 {+-} 2. Motor activity data were collected on days 30 {+-} 2, 60 {+-} 2, and 90 {+-} 2 of the feeding protocols. Brain tissue from rodents fed these fish were subsequently analyzed for either mercury (Hg) or polychlorinated biphenyls (PCB). Mercury concentrations were increased in the brains of the walleye-fed rats, and PCB concentrations ranged from 0.5 nl/L to 10 nl/L in the brains of rats fed carp from LLBM, a Lake Michigan tributary. Adult male rats fed LLBM carp for 45 d exhibited the greatest behavior responses to the dopaminergic agonist apomorphine on the accelerating rotarod, although these differences were not significant. The 90-d exposure of LS walleye or Hg-spiked LS walleye resulted in behavior alterations on tactile startle response and second footsplay. D-Amphetamine challenge caused changes in tactile startle response, second footsplay, and accelerating rotarod performance after consuming walleye diets. Rats fed LLBM carp had altered behavioral responses to apomorphine on the accelerating rotarod.

  20. Alcohol-induced One-carbon Metabolism Impairment Promotes Dysfunction of DNA Base Excision Repair in Adult Brain*

    Science.gov (United States)

    Fowler, Anna-Kate; Hewetson, Aveline; Agrawal, Rajiv G.; Dagda, Marisela; Dagda, Raul; Moaddel, Ruin; Balbo, Silvia; Sanghvi, Mitesh; Chen, Yukun; Hogue, Ryan J.; Bergeson, Susan E.; Henderson, George I.; Kruman, Inna I.

    2012-01-01

    The brain is one of the major targets of chronic alcohol abuse. Yet the fundamental mechanisms underlying alcohol-mediated brain damage remain unclear. The products of alcohol metabolism cause DNA damage, which in conditions of DNA repair dysfunction leads to genomic instability and neural death. We propose that one-carbon metabolism (OCM) impairment associated with long term chronic ethanol intake is a key factor in ethanol-induced neurotoxicity, because OCM provides cells with DNA precursors for DNA repair and methyl groups for DNA methylation, both critical for genomic stability. Using histological (immunohistochemistry and stereological counting) and biochemical assays, we show that 3-week chronic exposure of adult mice to 5% ethanol (Lieber-Decarli diet) results in increased DNA damage, reduced DNA repair, and neuronal death in the brain. These were concomitant with compromised OCM, as evidenced by elevated homocysteine, a marker of OCM dysfunction. We conclude that OCM dysfunction plays a causal role in alcohol-induced genomic instability in the brain because OCM status determines the alcohol effect on DNA damage/repair and genomic stability. Short ethanol exposure, which did not disturb OCM, also did not affect the response to DNA damage, whereas additional OCM disturbance induced by deficiency in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR) in Mthfr+/− mice, exaggerated the ethanol effect on DNA repair. Thus, the impact of long term ethanol exposure on DNA repair and genomic stability in the brain results from OCM dysfunction, and MTHFR mutations such as Mthfr 677C→T, common in human population, may exaggerate the adverse effects of ethanol on the brain. PMID:23118224

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

    Science.gov (United States)

    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…

  2. Hydrocephalus following severe traumatic brain injury in adults. Incidence, timing, and clinical predictors during rehabilitation

    DEFF Research Database (Denmark)

    Kammersgaard, Lars Peter; Linnemann, Mia; Tibæk, Maiken

    2013-01-01

    To investigate timing and clinical predictors that might predict hydrocephalus emerging during rehabilitation until 1 year following severe traumatic brain injury (TBI).......To investigate timing and clinical predictors that might predict hydrocephalus emerging during rehabilitation until 1 year following severe traumatic brain injury (TBI)....

  3. Matrix metalloproteinases in the adult brain physiology: a link between c-Fos, AP-1 and remodeling of neuronal connections?

    Science.gov (United States)

    Kaczmarek, Leszek; Lapinska-Dzwonek, Joanna; Szymczak, Sylwia

    2002-12-16

    Matrix metalloproteinases (MMPs), together with their endogenous inhibitors (TIMPs) form an enzymatic system that plays an important role in a variety of physiological and pathological conditions. These proteins are also expressed in the brain, especially under pathological conditions, in which glia as well as invading inflammatory cells provide the major source of the MMP activity. Surprisingly little is known about the MMP function(s) in adult neuronal physiology. This review describes available data on this topic, which is presented in a context of knowledge about the MMP/TIMP system in other organs as well as in brain disorders. An analysis of the MMP and TIMP expression patterns in the brain, along with a consideration of their regulatory mechanisms and substrates, leads to the proposal of possible roles of the MMP system in the brain. This analysis suggests that MMPs may play an important role in the neuronal physiology, especially in neuronal plasticity, including their direct participation in the remodeling of synaptic connections-a mechanism pivotal for learning and memory.

  4. Orthodenticle is necessary for survival of a cluster of clonally related dopaminergic neurons in the Drosophila larval and adult brain

    Directory of Open Access Journals (Sweden)

    Pandey Rahul

    2011-10-01

    Full Text Available Abstract Background The dopaminergic (DA neurons present in the central brain of the Drosophila larva are spatially arranged in stereotyped groups that define clusters of bilaterally symmetrical neurons. These clusters have been classified according to anatomical criteria (position of the cell bodies within the cortex and/or projection pattern of the axonal tracts. However, information pertaining to the developmental biology, such as lineage relationship of clustered DA neurons and differential cell subtype-specific molecular markers and mechanisms of differentiation and/or survival, is currently not available. Results Using MARCM and twin-spot MARCM techniques together with anti-tyrosine hydroxylase immunoreactivity, we have analyzed the larval central brain DA neurons from a developmental point of view and determined their time of birth, their maturation into a DA neurotransmitter phenotype as well as their lineage relationships. In addition, we have found that the homeodomain containing transcription factor Orthodenticle (Otd is present in a cluster of clonally related DA neurons in both the larval and adult brain. Taking advantage of the otd hypomorphic mutation ocelliless (oc and the oc2-Gal4 reporter line, we have studied the involvement of orthodenticle (otd in the survival and/or cell fate specification of these post-mitotic neurons. Conclusions Our findings provide evidence of the presence of seven neuroblast lineages responsible for the generation of the larval central brain DA neurons during embryogenesis. otd is expressed in a defined group of clonally related DA neurons from first instar larvae to adulthood, making it possible to establish an identity relationship between the larval DL2a and the adult PPL2 DA clusters. This poses otd as a lineage-specific and differential marker of a subset of clonally related DA neurons. Finally, we show that otd is required in those DA neurons for their survival.

  5. Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

    OpenAIRE

    Kathrin Hemmer; Mingyue Zhang; Thea van Wüllen; Marna Sakalem; Natalia Tapia; Aidos Baumuratov; Christian Kaltschmidt; Barbara Kaltschmidt; Hans R. Schöler; Weiqi Zhang; Jens C. Schwamborn

    2014-01-01

    Summary Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear ...

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

    Science.gov (United States)

    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

  7. Elevated adult neurogenesis in brain subventricular zone following in vivo manganese exposure: roles of copper and DMT1.

    Science.gov (United States)

    Fu, Sherleen; O'Neal, Stefanie; Hong, Lan; Jiang, Wendy; Zheng, Wei

    2015-02-01

    The brain subventricular zone (SVZ) is a source of neural precursor cells; these cells travel along the rostral migratory stream (RMS) to destination areas in the process of adult neurogenesis. Recent x-ray fluorescence (XRF) studies reveal an extensive accumulation of copper (Cu) in the SVZ. Earlier human and animal studies also suggest an altered Cu homeostasis after manganese (Mn) exposure. This study was designed to test the hypothesis that Mn exposure by acting on the divalent metal transporter-1 (DMT1) altered Cu levels in SVZ and RMS, thereby affecting adult neurogenesis. Adult rats received intraperitoneal (i.p.) injections of 6 mg Mn/kg as MnCl2 once daily for 4 weeks with concomitant injections of bromodeoxyuridine (BrdU) for 5 days in the last week. In control rats, Cu levels were significantly higher in the SVZ than other brain regions examined. Mn exposure significantly reduced Cu concentrations in the SVZ (P exposure significantly increased numbers of BrdU(+) cells, which were accompanied with increased GFAP(+) astrocytic stem cells and DCX(+) neuroblasts in SVZ and RMS. Quantitative RT-PCR and Western blot confirmed the increased expression of DMT1 in SVZ following in vivo Mn exposure, which contributed to Mn accumulation in the neurogenesis pathway. Taken together, these results indicate a clear disruptive effect of Mn on adult neurogenesis; the effect appears due partly to Mn induction of DMT1 and its interference with cellular Cu regulation in SVZ and RMS. The future research directions based on these observations are also discussed. PMID:25575534

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

    Science.gov (United States)

    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.

  9. Disentangling Brain Networks in Adult ADHD: Studies with fMRI and TMS

    NARCIS (Netherlands)

    M.K.F-F. Schneider (Marc )

    2012-01-01

    textabstractAttention Deficit/ Hyperactivity Disorder (ADHD) is not only limited to young patients. It is increasingly diagnosed in adults. Although the estimated prevalence in Europe ranges between 2 and 3% (48), the knowledge about adult ADHD pathophysiology and its neurobiological basis developed

  10. Chronic treatment with fibrates elevates superoxide dismutase in adult mouse brain microvessels

    OpenAIRE

    Wang, Guangming; Liu, Xiaowei; Guo, Qingmin; Namura, Shobu

    2010-01-01

    Fibrates are activators of peroxisome proliferator-activated receptor (PPAR) α. Pretreatment with fibrates has been shown to protect brain against ischemia in mice. We hypothesized that fibrates elevate superoxide dismutase (SOD) levels in the brain microvessels (BMV). BMV were isolated from male C57BL/6 and PPARα null mice that had been treated with fenofibrate or gemfibrozil for 7 days. To examine the effect of discontinuation of fenofibrate, another animal group treated with fenofibrate wa...

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

    OpenAIRE

    Petra eSántha; Szilvia eVeszelka; Zsófia eHoyk; Mária eMészáros; Walter, Fruzsina R.; Andrea E Tóth; Lóránd eKiss; András eKincses; Zita eOláh; György eSeprényi; Gabor eRakhely; András eDér; Magdolna ePákáski; Janos eKalman; Ágnes eKittel

    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 th...

  12. Sonic hedgehog controls stem cell behavior in the postnatal and adult brain

    OpenAIRE

    Palma, Veronica; Lim, D A; Dahmane, Nadia; Sanchez, Pilar; Brionne, T. C.; Herzberg, C. D.; Gitton, Yorick; Carleton, Alan; Alvarez-Buylla, Arturo; Ruiz Altaba, Ariel

    2005-01-01

    Sonic hedgehog (Shh) signaling controls many aspects of ontogeny, orchestrating congruent growth and patterning. During brain development, Shh regulates early ventral patterning while later on it is critical for the regulation of precursor proliferation in the dorsal brain, namely in the neocortex, tectum and cerebellum. We have recently shown that Shh also controls the behavior of cells with stem cell properties in the mouse embryonic neocortex, and additional studies have implicated it in t...

  13. Sex differences in the effects of adolescent stress on adult brain inflammatory markers in rats

    OpenAIRE

    Pyter, Leah M.; Kelly, Sean D.; Harrell, Constance S; Neigh, Gretchen N.

    2013-01-01

    Both basic and clinical research indicates that females are more susceptible to stress-related affective disorders than males. One of the mechanisms by which stress induces depression is via inflammatory signaling in the brain. Stress during adolescence, in particular, can also disrupt the activation and continued development of both the hypothalamic–pituitary–adrenal (HPA) and –gonadal (HPG) axes, both of which modulate inflammatory pathways and brain regions involved in affective behavior. ...

  14. Distribution and densitometry mapping of L1-CAM Immunoreactivity in the adult mouse brain – light microscopic observation

    Directory of Open Access Journals (Sweden)

    Yamasaki Hironobu

    2003-04-01

    Full Text Available Abstract Background The importance of L1 expression in the matured brain is suggested by physiological and behavioral studies showing that L1 is related to hippocampal plasticity and fear conditioning. The distribution of L1 in mouse brain might provide a basis for understanding its role in the brain. Results We examined the overall distribution of L1 in the adult mouse brain by immunohistochemistry using two polyclonal antibodies against different epitopes for L1. Immunoreactive L1 was widely but unevenly distributed from the olfactory bulb to the upper cervical cord. The accumulation of immunoreactive L1 was greatest in a non-neuronal element of the major fibre bundles, i.e. the lateral olfactory tract, olfactory and temporal limb of the anterior commissure, corpus callosum, stria terminalis, globus pallidus, fornix, mammillothalamic tract, solitary tract, and spinal tract of the trigeminal nerve. High to highest levels of non-neuronal and neuronal L1 were found in the grey matter; i.e. the piriform and entorhinal cortices, hypothalamus, reticular part of the substantia nigra, periaqueductal grey, trigeminal spinal nucleus etc. High to moderate density of neuronal L1 was found in the olfactory bulb, layer V of the cerebral cortex, amygdala, pontine grey, superior colliculi, cerebellar cortex, solitary tract nucleus etc. Only low to lowest levels of neuronal L1 were found in the hippocampus, grey matter in the caudate-putamen, thalamus, cerebellar nuclei etc. Conclusion L1 is widely and unevenly distributed in the matured mouse brain, where immunoreactivity was present not only in neuronal elements; axons, synapses and cell soma, but also in non-neuronal elements.

  15. Cognitive dysfunction and histological findings in adult rats one year after whole brain irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Akiyama, Katsuhiko; Tanaka, Ryuichi; Sato, Mitsuya; Takeda, Norio [Niigata Univ. (Japan). Brain Research Inst.

    2001-12-01

    Cognitive dysfunction and histological changes in the brain were investigated following irradiation in 20 Fischer 344 rats aged 6 months treated with whole brain irradiation (WBR) (25 Gy/single dose), and compared with the same number of sham-irradiated rats as controls. Performance of the Morris water maze task and the passive avoidance task were examined one year after WBR. Finally, histological and immunohistochemical examinations using antibodies to myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and neurofilament (NF) were performed of the rat brains. The irradiated rats continued to gain weight 7 months after WBR whereas the control rats stopped gaining weight. Cognitive functions in both the water maze task and the passive avoidance task were lower in the irradiated rats than in the control rats. Brain damage consisting of demyelination only or with necrosis was found mainly in the body of the corpus callosum and the parietal white matter near the corpus callosum in the irradiated rats. Immunohistochemical examination of the brains without necrosis found MBP-positive fibers were markedly decreased in the affected areas by irradiation; NF-positive fibers were moderately decreased and irregularly dispersed in various shapes in the affected areas; and GFAP-positive fibers were increased, with gliosis in those areas. These findings are similar to those in clinically accelerated brain aging in conditions such as Alzheimer's disease, Binswanger's disease, and multiple sclerosis. (author)

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

    Science.gov (United States)

    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

  17. Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Gondi, Vinai [Department of Human Oncology, University of Wisconsin, Madison, WI (United States); Hermann, Bruce P. [Department of Neurology, University of Wisconsin, Madison, WI (United States); Mehta, Minesh P. [Department of Radiation Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL (United States); Tome, Wolfgang A., E-mail: tome@humonc.wisc.edu [Department of Human Oncology, University of Wisconsin, Madison, WI (United States); Department of Medical Physics, University of Wisconsin, Madison, WI (United States); Department of Biomedical Engineering, University of Wisconsin, Madison, WI (United States)

    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

  18. Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

    International Nuclear Information System (INIS)

    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 (EQD2) assuming an α/β 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 EQD2 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 EQD2 to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). Conclusion: EQD2 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 should be enrolled in

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

    Energy Technology Data Exchange (ETDEWEB)

    Goodarzi, Samereh, E-mail: samere.g@gmail.com [Department of Nuclear Engineering, Science and Research Branch, Islamic Azad University, PO Box 19395-1943, Tehran (Iran, Islamic Republic of); Pazirandeh, Ali, E-mail: paziran@yahoo.com [Department of Nuclear Engineering, Science and Research Branch, Islamic Azad University, PO Box 19395-1943, Tehran (Iran, Islamic Republic of); Jameie, Seyed Behnamedin, E-mail: behnamjameie@tums.ac.ir [Basic Science Department, Faculty of Allied Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Department of Anatomy, Faculty of Medicine, Tehran University of Medical Sciences, Tehran (Iran, Islamic Republic of); Baghban Khojasteh, Nasrin, E-mail: khojasteh_n@yahoo.com [Department of Nuclear Engineering, Science and Research Branch, Islamic Azad University, PO Box 19395-1943, Tehran (Iran, Islamic Republic of)

    2012-06-15

    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. - Highlights: Black-Right-Pointing-Pointer Boron distribution in male and female rats' normal brain was studied in this research. Black-Right-Pointing-Pointer Coronal sections of animal tissue samples were irradiated with thermal neutrons. Black-Right-Pointing-Pointer Alpha and Lithium tracks were counted using alpha autoradiography. Black-Right-Pointing-Pointer Different boron concentration was seen in brain sections of male and female rats. Black-Right-Pointing-Pointer The highest boron concentration was seen in 4 h after boron compound injection.

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

    Science.gov (United States)

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

    2007-09-01

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

  1. Effects of aluminum sulfate on delta-aminolevulinate dehydratase from kidney, brain, and liver of adult mice

    Directory of Open Access Journals (Sweden)

    Schetinger M.R.C.

    1999-01-01

    Full Text Available The purpose of the present study was to investigate the in vitro and in vivo effects of aluminum sulfate on delta-aminolevulinic acid dehydratase (ALA-D activity from the brain, liver and kidney of adult mice (Swiss albine. In vitro experiments showed that the aluminum sulfate concentration needed to inhibit the enzyme activity was 1.0-5.0 mM (N = 3 in brain, 4.0-5.0 mM (N = 3 in liver and 0.0-5.0 mM (N = 3 in kidney. The in vivo experiments were performed on three groups for one month: 1 control animals (N = 8; 2 animals treated with 1 g% (34 mM sodium citrate (N = 8 and 3 animals treated with 1 g% (34 mM sodium citrate plus 3.3 g% (49.5 mM aluminum sulfate (N = 8. Exposure to aluminum sulfate in drinking water inhibited ALA-D activity in kidney (23.3 ± 3.7%, mean ± SEM, P<0.05 compared to control, but enhanced it in liver (31.2 ± 15.0%, mean ± SEM, P<0.05. The concentrations of aluminum in the brain, liver and kidney of adult mice were determined by graphite furnace atomic absorption spectrometry. The aluminum concentrations increased significantly in the liver (527 ± 3.9%, mean ± SEM, P<0.05 and kidney (283 ± 1.7%, mean ± SEM, P<0.05 but did not change in the brain of aluminum-exposed mice. One of the most important and striking observations was the increase in hepatic aluminum concentration in the mice treated only with 1 g% sodium citrate (34 mM (217 ± 1.5%, mean ± SEM, P<0.05 compared to control. These results show that aluminum interferes with delta-aminolevulinate dehydratase activity in vitro and in vivo. The accumulation of this element was in the order: liver > kidney > brain. Furthermore, aluminum had only inhibitory properties in vitro, while in vivo it inhibited or stimulated the enzyme depending on the organ studied.

  2. Concise review: Preclinical studies on human cell-based therapy in rodent ischemic stroke models: where are we now after a decade?

    Science.gov (United States)

    Leong, Wai Khay; Lewis, Martin D; Koblar, Simon A

    2013-06-01

    Stroke, a debilitating brain insult, afflicts millions of individuals globally each year. In the last decade, researchers have investigated cell-based therapy as an alternative strategy to improve neurological outcome following stroke. This concise review critically examines preclinical reports using human adult and fetal stem/progenitor cells in rodent models of ischemic stroke. As we enter the second decade of study, we should aim to optimize our collective likelihood to translational success for stroke victims worldwide. We advocate international consensus recommendations be developed for future preclinical research. PMID:23390084

  3. Effects of cerebrospinal fluid proteins on brain atrophy rates in cognitively healthy older adults.

    Science.gov (United States)

    Mattsson, Niklas; Insel, Philip; Nosheny, Rachel; Trojanowski, John Q; Shaw, Leslie M; Jack, Clifford R; Tosun, Duygu; Weiner, Michael

    2014-03-01

    Biomarkers associated with Alzheimer's disease (AD)-like brain atrophy in healthy individuals may identify mechanisms involved in early stage AD. Aside from cerebrospinal fluid (CSF) β-amyloid42 (Aβ42) and tau, no studies have tested associations between CSF proteins and AD-like brain atrophy. We studied 90 healthy elders, who underwent lumbar puncture at baseline, and serial magnetic resonance imaging scans for up to 4 years. We tested statistical effects of baseline CSF proteins (N = 70 proteins related to Aβ42-metabolism, microglial activity, and synaptic/neuronal function) on atrophy rates in 7 AD-related regions. Besides the effects of Aβ42 and phosphorylated tau (P-tau) that were seen in several regions, novel CSF proteins were found to have effects in inferior and middle temporal cortex (including apolipoprotein CIII, apolipoprotein D, and apolipoprotein H). Several proteins (including S100β and matrix metalloproteinase-3) had effects that depended on the presence of brain Aβ pathology, as measured by CSF Aβ42. Other proteins (including P-tau and apolipoprotein D) had effects even after adjusting for CSF Aβ42. The statistical effects in this exploratory study were mild and not significant after correction for multiple comparisons, but some of the identified proteins may be associated with brain atrophy in healthy persons. Proteins interacting with CSF Aβ42 may be related to Aβ brain pathology, whereas proteins associated with atrophy even after adjusting for CSF Aβ42 may be related to Aβ-independent mechanisms.

  4. Postmortem Adult Human Microglia Proliferate in Culture to High Passage and Maintain Their Response to Amyloid-β

    Science.gov (United States)

    Guo, Ling; Rezvanian, Aras; Kukreja, Lokesh; Hoveydai, Ramez; Bigio, Eileen H.; Mesulam, M.-Marsel; El Khoury, Joseph; Geula, Changiz

    2016-01-01

    Microglia are immune cells of the brain that display a range of functions. Most of our knowledge about microglia biology and function is based on cells from the rodent brain. Species variation in the complexity of the brain and differences in microglia response in the primate when compared with the rodent, require use of adult human microglia in studies of microglia biology. While methods exist for isolation of microglia from postmortem human brains, none allow culturing cells to high passage. Thus cells from the same case could not be used in parallel studies and multiple conditions. Here we report a method, which includes use of growth factors such as granulocyte macrophage colony stimulating factor, for successful culturing of adult human microglia from postmortem human brains up to 28 passages without significant loss of proliferation. Such cultures maintained their phenotype, including uptake of the scavenger receptor ligand acetylated low density lipoprotein and response to the amyloid-β peptide, and were used to extend in vivo studies in the primate brain demonstrating that inhibition of microglia activation protects neurons from amyloid-β toxicity. Significantly, microglia cultured from brains with pathologically confirmed Alzheimer’s disease displayed the same characteristics as microglia cultured from normal aged brains. The method described here provides the scientific community with a new and reliable tool for mechanistic studies of human microglia function in health from childhood to old age, and in disease, enhancing the relevance of the findings to the human brain and neurodegenerative conditions. PMID:27567845

  5. Methylphenidate treatment leads to abnormalities on krebs cycle enzymes in the brain of young and adult rats.

    Science.gov (United States)

    Réus, Gislaine Z; Scaini, Giselli; Furlanetto, Camila B; Morais, Meline O S; Jeremias, Isabela C; Mello-Santos, Lis Mairá; Freitas, Karolina V; Quevedo, João; Streck, Emilio L

    2013-08-01

    Studies have shown a relationship between energy metabolism and methylphenidate (MPH); however, there are no studies evaluating the effects of MPH in Krebs cycle. So, we investigated if MPH treatment could alter the activity of citrate synthase (CS), malate dehydrogenase (MD), and isocitrate dehydrogenase (ID) in the brain of young and adult Wistar rats. Our results showed that MPH (2 and 10 mg/kg) reduced CS in the striatum and prefrontal cortex (PF), with MPH at all doses in the cerebellum and hippocampus after chronic treatment in young rats. In adult rats the CS was reduced in the cerebellum after acute treatment with MPH at all doses, and after chronic treatment in the PF and cerebellum with MPH (10 mg/kg), and in the hippocampus with MPH (2 and 10 mg/kg). The ID decreased in the hippocampus and striatum with MPH (2 and 10 mg/kg), and in the cortex (10 mg/kg) after acute treatment in young rats. In adult rats acute treatment with MPH (2 and 10 mg/kg) reduced ID in the cerebellum, and with MPH (10 mg/kg) in the cortex; chronic treatment with MPH (10 mg/kg) decreased ID in the PF; with MPH (2 and 10 mg/kg) in the cerebellum, and with MPH at all doses in the hippocampus. The MD did not alter. In conclusion, our results suggest that MPH can alter enzymes of Krebs cycle in brain areas involved with circuits related with attention deficit hyperactivity disorder; however, such effects depend on age of animal and treatment regime.

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

    Directory of Open Access Journals (Sweden)

    Soledad eBallesteros

    2014-10-01

    Full Text Available 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-hr 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. Trial Registration: ClinicalTrials.gov identifier NCT02007616http://clinicaltrials.gov/show/NCT02007616

  7. Features of adult neurogenesis and neurochemical signaling in the Cherry salmon Oncorhynchus masou brain

    Institute of Scientific and Technical Information of China (English)

    Evgeniya V. Pushchina; Dmitry K. Оbukhov; Anatoly A. Varaksin

    2013-01-01

    We investigated the distribution of gamma aminobutyric acid, tyrosine hydroxylase and nitric oxide-producing elements in a cherry salmon Oncorhynchus masou brain at various stages of postnatal ontogenesis by immunohistochemical staining and histochemical staining. The periventricular region cells exhibited the morphology of neurons and glia including radial glia-like cells and contained several neurochemical substances. Heterogeneous populations of tyrosine dinucleotide phosphate diaphorase-positive cells were observed in proliferating cell nuclear antigen-immunoreactive proliferative zones in periventricular area of diencephalon, central grey layer of dorsomedial tegmentum, medulla and spinal cord. Immunolocalization of Pax6 in the cherry salmon brain revealed a neuromeric construction of the brain at various stages of postnatal ontogenesis, and this was confirmed by tyrosine hydroxylase and gamma aminobutyric acid labeling.

  8. Intrinsic brain connectivity related to age in young and middle aged adults.

    Directory of Open Access Journals (Sweden)

    Michelle Hampson

    Full Text Available Age-related variations in resting state connectivity of the human brain were examined from young adulthood through middle age. A voxel-based network measure, degree, was used to assess age-related differences in tissue connectivity throughout the brain. Increases in connectivity with age were found in paralimbic cortical and subcortical regions. Decreases in connectivity were found in cortical regions, including visual areas and the default mode network. These findings differ from those of recent developmental studies examining earlier growth trajectories, and are consistent with known changes in cognitive function and emotional processing during mature aging. The results support and extend previous findings that relied on a priori definitions of regions of interest for their analyses. This approach of applying a voxel-based measure to examine the functional connectivity of individual tissue elements over time, without the need for a priori region of interest definitions, provides an important new tool in brain science.

  9. Feeling present in arousing virtual reality worlds: prefrontal brain regions differentially orchestrate presence experience in adults and children

    Directory of Open Access Journals (Sweden)

    2008-08-01

    Full Text Available 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.

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

    Science.gov (United States)

    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

  11. Effects of Neonatal Antiepileptic Drug Exposure on Cognitive, Emotional, and Motor Function in Adult Rats

    OpenAIRE

    Patrick A Forcelli; Kozlowski, Ryan; Snyder, Charles; Kondratyev, Alexei; Gale, Karen

    2012-01-01

    Despite the potent proapoptotic effect of several antiepileptic drugs (AEDs) in developmental rodent models, little is known about the long-term impact of exposure during brain development. Clinically, this is of growing concern. To determine the behavioral consequences of such exposure, we examined phenobarbital, phenytoin, and lamotrigine for their effects on adult behaviors after administration to neonatal rats throughout the second postnatal week. AED treatment from postnatal days 7 to 13...

  12. Sex Differences and Laterality in Astrocyte Number and Complexity in the Adult Rat Medial Amygdala

    OpenAIRE

    JOHNSON, RYAN T.; Breedlove, S. Marc; Jordan, Cynthia L.

    2008-01-01

    The posterodorsal portion of the medial amygdala (MePD) is sexually dimorphic in several rodent species. In several other brain nuclei, astrocytes change morphology in response to steroid hormones. We visualized MePD astrocytes using glial-fibrillary acidic protein (GFAP) immunocytochemistry. We compared the number and process complexity of MePD astrocytes in adult wildtype male and female rats and testicular feminized mutant (TFM) male rats that lack functional androgen receptors (ARs) to de...

  13. Exergame and Balance Training modulate Prefrontal Brain Activity during Walking and enhance Executive Function in Older Adults

    Directory of Open Access Journals (Sweden)

    Patrick eEggenberger

    2016-04-01

    Full Text Available 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 minutes 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 < .05 or trend, r = .25 to .36, while DANCE showed a larger reduction at the end of the 30-second walking task compared to BALANCE in the left PFC (F(1, 31 = 3.54, p = .035, r = .32. These exercise training induced modulations in PFC oxygenation correlated with improved executive functions (p < .05 or trend, r = .31 to .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.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Timothy C. Durazzo

    2015-07-01

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

  16. Adult Professional Development: Can Brain-Based Teaching Strategies Increase Learning Effectiveness?

    Science.gov (United States)

    Tilton, Wendy

    2011-01-01

    Brain-based teaching strategies, compared to facilitative student-centered teaching strategies, were employed with 62 real estate professionals in a quasi-mixed-methods study. Participants attended a 2-day proprietary real estate continuing education course. Both the experimental and control groups received the same facilitative instruction, as…

  17. Gene × Smoking Interactions on Human Brain Gene Expression: Finding Common Mechanisms in Adolescents and Adults

    Science.gov (United States)

    Wolock, Samuel L.; Yates, Andrew; Petrill, Stephen A.; Bohland, Jason W.; Blair, Clancy; Li, Ning; Machiraju, Raghu; Huang, Kun; Bartlett, Christopher W.

    2013-01-01

    Background: Numerous studies have examined gene × environment interactions (G × E) in cognitive and behavioral domains. However, these studies have been limited in that they have not been able to directly assess differential patterns of gene expression in the human brain. Here, we assessed G × E interactions using two publically available datasets…

  18. MTR variations in normal adult brain structures using balanced steady-state free precession

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, Meritxell; Wetzel, Stephan G.; Radue, Ernst-Wilhelm [University of Basel Hospital, Department of Neuroradiology, Institute of Radiology, Basel (Switzerland); Gloor, Monika; Bieri, Oliver; Scheffler, Klaus [University of Basel Hospital, Division of Radiological Physics, Institute of Radiology, Basel (Switzerland)

    2011-03-15

    Magnetization transfer (MT) is sensitive to the macromolecular environment of water protons and thereby provides information not obtainable from conventional magnetic resonance imaging (MRI). Compared to standard methods, MT-sensitized balanced steady-state free precession (bSSFP) offers high-resolution images with significantly reduced acquisition times. In this study, high-resolution magnetization transfer ratio (MTR) images from normal appearing brain structures were acquired with bSSFP. Twelve subjects were studied on a 1.5 T scanner. MTR values were calculated from MT images acquired in 3D with 1.3 mm isotropic resolution. The complete MT data set was acquired within less than 3.5 min. Forty-one brain structures of the white matter (WM) and gray matter (GM) were identified for each subject. MTR values were higher for WM than GM. In general, MTR values of the WM and GM structures were in good accordance with the literature. However, MTR values showed more homogenous values within WM and GM structures than previous studies. MT-sensitized bSSFP provides isotropic high-resolution MTR images and hereby allows assessment of reliable MTR data in also very small brain structures in clinically feasible acquisition times and is thus a promising sequence for being widely used in the clinical routine. The present normative data can serve as a reference for the future characterization of brain pathologies. (orig.)

  19. A simple assessment model to quantifying the dynamic hippocampal neurogenic process in the adult mammalian brain.

    Science.gov (United States)

    Choi, Minee L; Begeti, Faye; Barker, Roger A; Kim, Namho

    2016-04-01

    Adult hippocampal neurogenesis is a highly dynamic process in which new cells are born, but only some of which survive. Of late it has become clear that these surviving newborn neurons have functional roles, most notably in certain forms of memory. Conventional methods to look at adult neurogenesis are based on the quantification of the number of newly born neurons using a simple cell counting methodology. However, this type of approach fails to capture the dynamic aspects of the neurogenic process, where neural proliferation, death and differentiation take place continuously and simultaneously. In this paper, we propose a simple mathematical approach to better understand the adult neurogenic process in the hippocampus which in turn will allow for a better analysis of this process in disease states and following drug therapies. PMID:26443687

  20. Adults with attention-deficit/hyperactivity disorder – a brain magnetic resonance spectroscopy study

    Directory of Open Access Journals (Sweden)

    Margaretha eDramsdahl

    2011-11-01

    Full Text Available BackgroundImpaired cognitive control in individuals with Attention-Deficit/Hyperactivity Disorder (ADHD may be related to a prefrontal cortical glutamatergic deficit. We assessed the glutamate level in the left and the right midfrontal region including the anterior cingulate cortex (ACC in adults with ADHD and healthy controls. MethodsTwenty-nine adults with ADHD and 38 healthy controls were included. We used Proton Magnetic Resonance Imaging with single-voxel point-resolved spectroscopy to measure the ratio of glutamate to creatine (Glu/Cre in the left and the right midfrontal region in the two groups. ResultsThe ADHD group showed a significant reduction of Glu/Cre in the left midfrontal region compared to the controls. ConclusionsThe reduction of Glu/Cre in the left midfrontal region in the ADHD group may reflect a glutamatergic deficit in prefrontal neuronal circuitry in adults with ADHD, resulting in problems with cognitive control.

  1. Adults with attention-deficit/hyperactivity disorder - a brain magnetic resonance spectroscopy study

    DEFF Research Database (Denmark)

    Dramsdahl, Margaretha; Ersland, Lars; Plessen, Kerstin J;

    2011-01-01

    Background: Impaired cognitive control in individuals with attention-deficit/hyperactivity disorder (ADHD) may be related to a prefrontal cortical glutamatergic deficit. We assessed the glutamate level in the left and the right midfrontal region including the anterior cingulate cortex in adults...... with ADHD and healthy controls. Methods: Twenty-nine adults with ADHD and 38 healthy controls were included. We used Proton Magnetic Resonance Imaging with single voxel point-resolved spectroscopy to measure the ratio of glutamate to creatine (Glu/Cre) in the left and the right midfrontal region in the two...... groups. Results: The ADHD group showed a significant reduction of Glu/Cre in the left midfrontal region compared to the controls. Conclusion: The reduction of Glu/Cre in the left midfrontal region in the ADHD group may reflect a glutamatergic deficit in prefrontal neuronal circuitry in adults with ADHD...

  2. The Effects of Exercise on Cognitive Recovery after Acquired Brain Injury in Animal Models: A Systematic Review

    OpenAIRE

    Elise Wogensen; Hana Malá; Jesper Mogensen

    2015-01-01

    The objective of the present paper is to review the current status of exercise as a tool to promote cognitive rehabilitation after acquired brain injury (ABI) in animal model-based research. Searches were conducted on the PubMed, Scopus, and psycINFO databases in February 2014. Search strings used were: exercise (and) animal model (or) rodent (or) rat (and) traumatic brain injury (or) cerebral ischemia (or) brain irradiation. Studies were selected if they were (1) in English, (2) used adult a...

  3. Memory and Memories: an exploratory mixed method case series study with brain injured adults and their families, using PhotoFrame Therapy and wireless digital photo frame technology

    OpenAIRE

    Harding, Abigail

    2012-01-01

    Introduction Existing research and treatment for brain injured adults uses cognitive rehabilitation to address memory deficits including compensatory and remedial techniques. Electronic devices such as the Neuropage and palm top computers are effective in compensating for memory deficits. However, these require the user to be trained and proficient in their use. This exploratory study investigates the effectiveness of pre-programmed wireless digital photo frame as a memory aid for adults with...

  4. Organs at risk in the brain and their dose-constraints in adults and in children: A radiation oncologist’s guide for delineation in everyday practice

    International Nuclear Information System (INIS)

    Purpose: Accurate organs at risk definition is essential for radiation treatment of brain tumors. The aim of this study is to provide a stepwise and simplified contouring guide to delineate the OARs in the brain as it would be done in the everyday practice of planning radiotherapy for brain cancer treatment. Methods: Anatomical descriptions and neuroimaging atlases of the brain were studied. The dosimetric constraints used in literature were reviewed. Results: A Computed Tomography and Magnetic Resonance Imaging based detailed atlas was developed jointly by radiation oncologists, a neuroradiologist and a neurosurgeon. For each organ brief anatomical notion, main radiological reference points and useful considerations are provided. Recommended dose-constraints both for adult and pediatric patients were also provided. Conclusions: This report provides guidelines for OARs delineation and their dose-constraints for the treatment planning of patients with brain tumors

  5. Suppression and Narrative Time Shifts in Adults with Right-Hemisphere Brain Damage

    Science.gov (United States)

    Scharp, Victoria L.; Tompkins, Connie A.

    2013-01-01

    Purpose: This study examined the functioning of a central comprehension mechanism, suppression, in adults with right-hemisphere damage (RHD) while they processed narratives that cued a shift in time frame. In normal language comprehension, mental activation of concepts from a prior time frame is suppressed. The (re)activation of information…

  6. Influx mechanisms in the embryonic and adult rat choroid plexus

    DEFF Research Database (Denmark)

    Saunders, Norman R; Dziegielewska, Katarzyna M; Møllgård, Kjeld;

    2015-01-01

    The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analyzed by functional groups of influx transporters, particularly solute carrier (SLC) transporters. RNA-Seq was performed at embryonic day (E) 15 and a...... studies suggests that the choroid plexus in embryonic brain plays a major role in supplying the developing brain with essential nutrients.......The transcriptome of embryonic and adult rat lateral ventricular choroid plexus, using a combination of RNA-Sequencing and microarray data, was analyzed by functional groups of influx transporters, particularly solute carrier (SLC) transporters. RNA-Seq was performed at embryonic day (E) 15 and...... in the adult plexus were expressed at higher levels than in embryos. These results are compared with earlier published physiological studies of amino acid and monocarboxylate transport in developing rodents. This comparison shows correlation of high expression of some transporters in the developing...

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

    OpenAIRE

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

    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. prefro...

  8. Systemic Effects of Fractionated, Whole-Brain Irradiation in Young Adult and Aging Rats

    OpenAIRE

    Forbes, M. E.; Paitsel, M.; Bourland, J. D.; Riddle, D. R.

    2013-01-01

    Cranial irradiation is a critical and effective treatment for primary brain tumors and metastases. Unfortunately, most patients who are treated and survive for more than a few months develop neural and cognitive problems as the result of radiation-induced normal tissue injury. The neurobiological mechanisms underlying these cognitive deficits remain largely unknown and there are no validated treatments to prevent or ameliorate them; thus, there is a significant and continuing need for preclin...

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

    OpenAIRE

    Hansson, Magnus; Morota, Saori; Li CHEN; Matsuyama, Nagahisa; SUZUKI, YOSHIAKI; Nakajima, Satoshi; Tanoue, Tadashi; Omi, Akibumi; Shibasaki, Futoshi; Shimazu, Motohide; IKEDA, Yukio; Uchino, Hiroyuki; Elmér, Eskil

    2011-01-01

    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 tar...

  10. Wechsler Adult Intelligence Scale-Third Edition profiles and their relationship to self-reported outcome following traumatic brain injury.

    Science.gov (United States)

    Harman-Smith, Yasmin E; Mathias, Jane L; Bowden, Stephen C; Rosenfeld, Jeffrey V; Bigler, Erin D

    2013-01-01

    Neuropsychological assessments of outcome after traumatic brain injury (TBI) are often unrelated to self-reported problems after TBI. The current study cluster-analyzed the Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) subtest scores from mild, moderate, and severe TBI (n=220) and orthopedic injury control (n=95) groups, to determine whether specific cognitive profiles are related to people's perceived outcomes after TBI. A two-stage cluster analysis produced 4- and 6-cluster solutions, with the 6-cluster solution better capturing subtle variations in cognitive functioning. The 6 clusters differed in the levels and profiles of cognitive performance, self-reported recovery, and education and injury severity. The findings suggest that subtle cognitive impairments after TBI should be interpreted in conjunction with patient's self-reported problems.

  11. Epidermal growth factor treatment of the adult brain subventricular zone leads to focal microglia/macrophage accumulation and angiogenesis.

    Science.gov (United States)

    Lindberg, Olle R; Brederlau, Anke; Kuhn, H Georg

    2014-04-01

    One of the major components of the subventricular zone (SVZ) neurogenic niche is the specialized vasculature. The SVZ vasculature is thought to be important in regulating progenitor cell proliferation and migration. Epidermal growth factor (EGF) is a mitogen with a wide range of effects. When stem and progenitor cells in the rat SVZ are treated with EGF, using intracerebroventricular infusion, dysplastic polyps are formed. Upon extended infusion, blood vessels are recruited into the polyps. In the current study we demonstrate how polyps develop through distinct stages leading up to angiogenesis. As polyps progress, microglia/macrophages accumulate in the polyp core concurrent with increasing cell death. Both microglia/macrophage accumulation and cell death peak during angiogenesis and subsequently decline following polyp vascularization. This model of inducible angiogenesis in the SVZ neurogenic niche suggests involvement of microglia/macrophages in acquired angiogenesis and can be used in detail to study angiogenesis in the adult brain.

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

    Science.gov (United States)

    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

  13. Ex-vivo HRMAS of adult brain tumours: metabolite quantification and assignment of tumour biomarkers

    Directory of Open Access Journals (Sweden)

    Wilson M

    2010-03-01

    Full Text Available Abstract Background High-resolution magic angle spinning (HRMAS NMR spectroscopy allows detailed metabolic analysis of whole biopsy samples for investigating tumour biology and tumour classification. Accurate biochemical assignment of small molecule metabolites that are "NMR visible" will improve our interpretation of HRMAS data and the translation of NMR tumour biomarkers to in-vivo studies. Results 1D and 2D 1H HRMAS NMR was used to determine that 29 small molecule metabolites, along with 8 macromolecule signals, account for the majority of the HRMAS spectrum of the main types of brain tumour (astrocytoma grade II, grade III gliomas, glioblastomas, metastases, meningiomas and also lymphomas. Differences in concentration of 20 of these metabolites were statistically significant between these brain tumour types. During the course of an extended 2D data acquisition the HRMAS technique itself affects sample analysis: glycine, glutathione and glycerophosphocholine all showed small concentration changes; analysis of the sample after HRMAS indicated structural damage that may affect subsequent histopathological analysis. Conclusions A number of small molecule metabolites have been identified as potential biomarkers of tumour type that may enable development of more selective in-vivo 1H NMR acquisition methods for diagnosis and prognosis of brain tumours.

  14. The ethics of rodent control

    OpenAIRE

    Meerburg, Dr Bastiaan G; Brom, Prof Frans W A; Kijlstra, Prof. Aize

    2008-01-01

    Because western societies generally see animals as objects of moral concern, demands have been made on the way they are treated, e.g. during animal experimentation. In the case of rodent pests, however, inhumane control methods are often applied. This inconsistency in the human-animal relationship requires clarification. This paper analyses the criteria that must be met when judging the use of animals during experiments, and investigates whether these can be applied in rodent control. This is...

  15. Repeated BOLD-fMRI imaging of deep brain stimulation responses in rats.

    Science.gov (United States)

    Chao, Tzu-Hao Harry; Chen, Jyh-Horng; Yen, Chen-Tung

    2014-01-01

    Functional magnetic resonance imaging (fMRI) provides a picture of the global spatial activation pattern of the brain. Interest is growing regarding the application of fMRI to rodent models to investigate adult brain plasticity. To date, most rodent studies used an electrical forepaw stimulation model to acquire fMRI data, with α-chloralose as the anesthetic. However, α-chloralose is harmful to animals, and not suitable for longitudinal studies. Moreover, peripheral stimulation models enable only a limited number of brain regions to be studied. Processing between peripheral regions and the brain is multisynaptic, and renders interpretation difficult and uncertain. In the present study, we combined the medetomidine-based fMRI protocol (a noninvasive rodent fMRI protocol) with chronic implantation of an MRI-compatible stimulation electrode in the ventroposterior (VP) thalamus to repetitively sample thalamocortical responses in the rat brain. Using this model, we scanned the forebrain responses evoked by the VP stimulation repeatedly of individual rats over 1 week. Cortical BOLD responses were compared between the 2 profiles obtained at day1 and day8. We discovered reproducible frequency- and amplitude-dependent BOLD responses in the ipsilateral somatosensory cortex (S1). The S1 BOLD responses during the 2 sessions were conserved in maximal response amplitude, area size (size ratio from 0.88 to 0.91), and location (overlap ratio from 0.61 to 0.67). The present study provides a long-term chronic brain stimulation protocol for studying the plasticity of specific neural circuits in the rodent brain by BOLD-fMRI. PMID:24825464

  16. Repeated BOLD-fMRI imaging of deep brain stimulation responses in rats.

    Directory of Open Access Journals (Sweden)

    Tzu-Hao Harry Chao

    Full Text Available Functional magnetic resonance imaging (fMRI provides a picture of the global spatial activation pattern of the brain. Interest is growing regarding the application of fMRI to rodent models to investigate adult brain plasticity. To date, most rodent studies used an electrical forepaw stimulation model to acquire fMRI data, with α-chloralose as the anesthetic. However, α-chloralose is harmful to animals, and not suitable for longitudinal studies. Moreover, peripheral stimulation models enable only a limited number of brain regions to be studied. Processing between peripheral regions and the brain is multisynaptic, and renders interpretation difficult and uncertain. In the present study, we combined the medetomidine-based fMRI protocol (a noninvasive rodent fMRI protocol with chronic implantation of an MRI-compatible stimulation electrode in the ventroposterior (VP thalamus to repetitively sample thalamocortical responses in the rat brain. Using this model, we scanned the forebrain responses evoked by the VP stimulation repeatedly of individual rats over 1 week. Cortical BOLD responses were compared between the 2 profiles obtained at day1 and day8. We discovered reproducible frequency- and amplitude-dependent BOLD responses in the ipsilateral somatosensory cortex (S1. The S1 BOLD responses during the 2 sessions were conserved in maximal response amplitude, area size (size ratio from 0.88 to 0.91, and location (overlap ratio from 0.61 to 0.67. The present study provides a long-term chronic brain stimulation protocol for studying the plasticity of specific neural circuits in the rodent brain by BOLD-fMRI.

  17. Saccadic eye movement characteristics in adult Niemann-Pick Type C disease: relationships with disease severity and brain structural measures.

    Directory of Open Access Journals (Sweden)

    Larry A Abel

    Full Text Available Niemann-Pick Type C disease (NPC is a rare genetic disorder of lipid metabolism. A parameter related to horizontal saccadic peak velocity was one of the primary outcome measures in the clinical trial assessing miglustat as a treatment for NPC. Neuropathology is widespread in NPC, however, and could be expected to affect other saccadic parameters. We compared horizontal saccadic velocity, latency, gain, antisaccade error percentage and self-paced saccade generation in 9 adult NPC patients to data from 10 age-matched controls. These saccadic measures were correlated with appropriate MRI-derived brain structural measures (e.g., dorsolateral prefrontal cortex, frontal eye fields, supplemental eye fields, parietal eye fields, pons, midbrain and cerebellar vermis and with measures of disease severity and duration. The best discriminators between groups were reflexive saccade gain and the two volitional saccade measures. Gain was also the strongest correlate with disease severity and duration. Most of the saccadic measures showed strongly significant correlations with neurophysiologically appropriate brain regions. While our patient sample is small, the apparent specificity of these relationships suggests that as new diagnostic methods and treatments become available for NPC, a broader range of saccadic measures may be useful tools for the assessment of disease progression and treatment efficacy.

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

    Directory of Open Access Journals (Sweden)

    Deepti Chugh

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

  19. Premitotic DNA synthesis in the brain of the adult frog (Rana esculenta L.): An autoradiographic 3H-thymidine study

    International Nuclear Information System (INIS)

    Replicative synthesis of DNA in the brain of the adult frog was studied by light microscope autoradiography. Animals collected during the active period (May-June) and in hibernation (January) were used. In active frogs, 3H-thymidine labelling occurred mainly in the ependymal cells which line the ventricles. The mean labelling index (LI%) was higher in the ependyma of the lateral and fourth ventricles than in the ependyma of the lateral diencephalon and tectal parts of the mesencephalon. In the recessus infundibularis and preopticus the number of labelled cells (LCs) was several times greater than in the lateral parts of the third ventricle. LCs were seen subependymally only occasionally. The incidence of LCs in the parenchyma of the brain was much lower in most regions than in the ventricular ependyma; LCs were mainly small and, from their nuclear morphology, they were glial cells. The LI% reached the highest value in the septum hippocampi and in the nucleus entopeduncularis. In these locations, LCs were larger and closer in size to the nerve cells of these regions. From comparison with data obtained earlier in the brain of mammals, it is evident that the distribution of proliferating cells in the olfactory and limbic system is phylogenetically conservative. The occurrence of pyknotic cells in the same areas which contain LCs, suggests that cell division reflects in part the process of cell renewal observed in mammals. However, proliferating cells could also be linked to the continuous growth observed in non-mammalian vertebrates. In hibernating frogs, LCs and pyknoses were not seen or were found occasionally, which further indicates the functional significance of both processes

  20. Phonetically Irregular Word Pronunciation and Cortical Thickness in the Adult Brain

    OpenAIRE

    Blackmon, Karen; Barr, William B; Kuzniecky, Ruben; DuBois, Jonathan; Carlson, Chad; Quinn, Brian T.; Blumberg, Mark; Halgren, Eric; Hagler, Donald J.; Mikhly, Mark; Devinsky, Orrin; McDonald, Carrie R.; Anders M Dale; Thesen, Thomas

    2010-01-01

    Accurate pronunciation of phonetically irregular words (exception words) requires prior exposure to unique relationships between orthographic and phonemic features. Whether such word knowledge is accompanied by structural variation in areas associated with orthographic-to-phonemic transformations has not been investigated. We used high resolution MRI to determine whether performance on a visual word-reading test composed of phonetically irregular words, the Wechsler Test of Adult Reading (WTA...

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

    Science.gov (United States)

    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…

  2. Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain.

    Science.gov (United States)

    Elmore, Monica R P; Najafi, Allison R; Koike, Maya A; Dagher, Nabil N; Spangenberg, Elizabeth E; Rice, Rachel A; Kitazawa, Masashi; Matusow, Bernice; Nguyen, Hoa; West, Brian L; Green, Kim N

    2014-04-16

    The colony-stimulating factor 1 receptor (CSF1R) is a key regulator of myeloid lineage cells. Genetic loss of the CSF1R blocks the normal population of resident microglia in the brain that originates from the yolk sac during early development. However, the role of CSF1R signaling in microglial homeostasis in the adult brain is largely unknown. To this end, we tested the effects of selective CSF1R inhibitors on microglia in adult mice. Surprisingly, extensive treatment results in elimination of ∼99% of all microglia brain-wide, showing that microglia in the adult brain are physiologically dependent upon CSF1R signaling. Mice depleted of microglia show no behavioral or cognitive abnormalities, revealing that microglia are not necessary for these tasks. Finally, we discovered that the microglia-depleted brain completely repopulates with new microglia within 1 week of inhibitor cessation. Microglial repopulation throughout the CNS occurs through proliferation of nestin-positive cells that then differentiate into microglia.

  3. Efficacy of Brain Gym Training on the Cognitive Performance and Fitness Level of Active Older Adults: A Preliminary Study.

    Science.gov (United States)

    Cancela, José M; Vila Suárez, Ma Helena; Vasconcelos, Jamine; Lima, Ana; Ayán, Carlos

    2015-10-01

    This study evaluates the impact of Brain Gym (BG) training in active older adults. Eighty-five participants were assigned to four training groups: BG (n = 18), BG plus water-based exercise (n = 18), land-based exercise (n = 30), and land plus water-based exercise (n = 19). The effects of the programs on the attention and memory functions were assessed by means of the symbol digit modality test. The two-min step and the eight-foot up-and-go tests were used to evaluate their impact on fitness level. No program had a significant influence on the participant's cognitive performance, while different effects on the sample' fitness levels were observed. These findings suggest that the effects of BG on the cognitive performance and fitness level of active older adults are similar to those obtained after the practice of a traditional exercise program. Whether BG is performed in isolation or combined with other exercise programs seems to have no influence on such effects.

  4. Acceptance and commitment therapy program for distressed adults with a primary brain tumor: a case series study.

    Science.gov (United States)

    Kangas, Maria; McDonald, Skye; Williams, Janet R; Smee, Robert I

    2015-10-01

    Research has indicated that adults diagnosed with a primary brain tumor (BT) are susceptible to experiencing anxiety and depressive problems post-diagnosis. However, there is a notable paucity of psychological interventions which have been tested with adult BT patients. An acceptance and commitment therapy (ACT)-based manualized program was developed for anxious and/or depressed BT patients. The preliminary efficacy of this program was initially tested using a proof-of-concept study design based on a case series of four clinically distressed BT patients. Three of the four participants no longer met criteria for anxiety and/or depressive disorders at post-therapy, and these effects were maintained at 3 months of follow-up. The fourth participant, who had a premorbid psychiatric history, experienced a stabilization of anxiety and depressive symptoms. Given the current dearth of studies which have tested psychological interventions for distressed BT survivors, these preliminary findings have promising clinical utility. However, the efficacy of psychological interventions tailored for clinically distressed BT patients needs to be further tested using larger-scale controlled trial designs.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    OpenAIRE

    Sussman, Dafna; Germann, Jurgen; Henkelman, Mark

    2014-01-01

    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 ...

  9. Special Issue on Occupational Therapy for Adults With Traumatic Brain Injury.

    Science.gov (United States)

    Powell, Janet M

    2016-01-01

    Awareness of the incidence and consequences of traumatic brain injury (TBI) has increased in recent years, along with interest in knowing how best to treat this complex condition. This editorial provides an overview of the various factors that contribute to the complexity of TBI and introduces the six systematic reviews and one qualitative study included in this special issue of the American Journal of Occupational Therapy focusing on interventions for TBI from an occupational therapy perspective. Issues with the generation and interpretation of research evidence are discussed, along with the importance of valuing clinician expertise and client perspectives along with research findings in implementing evidence-based and evidence-informed practice.

  10. Systematic review of self-reported prognosis in adults after mild traumatic brain injury

    DEFF Research Database (Denmark)

    Cassidy, John David; Cancelliere, Carol; Carroll, Linda J;

    2014-01-01

    OBJECTIVE: To update the mild traumatic brain injury (MTBI) prognosis review published by the World Health Organization Task Force in 2004. DATA SOURCES: MEDLINE, PsycINFO, Embase, CINAHL, and SPORTDiscus were searched from 2001 to 2012. We included published, peer-reviewed studies with more than...... quality. This includes 3 original International Collaboration on MTBI Prognosis (ICoMP) research studies. DATA EXTRACTION: Eligible studies were critically appraised using the Scottish Intercollegiate Guidelines Network criteria. Two reviewers independently reviewed each study and tabled data from...

  11. Global Integration of the Hot-State Brain Network of Appetite Predicts Short Term Weight Loss in Older Adult

    Directory of Open Access Journals (Sweden)

    Brielle M Paolini

    2015-05-01

    Full Text Available Obesity is a public health crisis in North America. While lifestyle interventions for weight loss (WL remain popular, the rate of success is highly variable. Clearly, self-regulation of eating behavior is a challenge and patterns of activity across the brain may be an important determinant of success. The current study prospectively examined whether integration across the Hot-State Brain Network of Appetite (HBN-A predicts WL after 6-months of treatment in older adults. Our metric for network integration was global efficiency (GE. The present work is a sub-study (n = 56 of an ongoing randomized clinical trial involving WL. Imaging involved a baseline food-cue visualization functional MRI (fMRI scan following an overnight fast. Using graph theory to build functional brain networks, we demonstrated that regions of the HBN-A (insula, anterior cingulate cortex (ACC, superior temporal pole, amygdala and the parahippocampal gyrus were highly integrated as evidenced by the results of a principal component analysis. After accounting for known correlates of WL (baseline weight, age, sex, and self-regulatory efficacy and treatment condition, which together contributed 36.9% of the variance in WL, greater GE in the HBN-A was associated with an additional 19% of the variance. The ACC of the HBN-A was the primary driver of this effect, accounting for 14.5% of the variance in WL when entered in a stepwise regression following the covariates, p = 0.0001. The HBN-A is comprised of limbic regions important in the processing of emotions and visceral sensations and the ACC is key for translating such processing into behavioral consequences. The improved integration of these regions may enhance awareness of body and emotional states leading to more successful self-regulation and to greater WL. This is the first study among older adults to prospectively demonstrate that, following an overnight fast, GE of the HBN-A during a food visualization task is predictive of

  12. Global integration of the hot-state brain network of appetite predicts short term weight loss in older adult.

    Science.gov (United States)

    Paolini, Brielle M; Laurienti, Paul J; Simpson, Sean L; Burdette, Jonathan H; Lyday, Robert G; Rejeski, W Jack

    2015-01-01

    Obesity is a public health crisis in North America. While lifestyle interventions for weight loss (WL) remain popular, the rate of success is highly variable. Clearly, self-regulation of eating behavior is a challenge and patterns of activity across the brain may be an important determinant of success. The current study prospectively examined whether integration across the Hot-State Brain Network of Appetite (HBN-A) predicts WL after 6-months of treatment in older adults. Our metric for network integration was global efficiency (GE). The present work is a sub-study (n = 56) of an ongoing randomized clinical trial involving WL. Imaging involved a baseline food-cue visualization functional MRI (fMRI) scan following an overnight fast. Using graph theory to build functional brain networks, we demonstrated that regions of the HBN-A (insula, anterior cingulate cortex (ACC), superior temporal pole (STP), amygdala and the parahippocampal gyrus) were highly integrated as evidenced by the results of a principal component analysis (PCA). After accounting for known correlates of WL (baseline weight, age, sex, and self-regulatory efficacy) and treatment condition, which together contributed 36.9% of the variance in WL, greater GE in the HBN-A was associated with an additional 19% of the variance. The ACC of the HBN-A was the primary driver of this effect, accounting for 14.5% of the variance in WL when entered in a stepwise regression following the covariates, p = 0.0001. The HBN-A is comprised of limbic regions important in the processing of emotions and visceral sensations and the ACC is key for translating such processing into behavioral consequences. The improved integration of these regions may enhance awareness of body and emotional states leading to more successful self-regulation and to greater WL. This is the first study among older adults to prospectively demonstrate that, following an overnight fast, GE of the HBN-A during a food visualization task is predictive of

  13. Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

    Science.gov (United States)

    Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy

    2016-01-01

    Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor.

  14. Prenatal Exposure to Autism-Specific Maternal Autoantibodies Alters Proliferation of Cortical Neural Precursor Cells, Enlarges Brain, and Increases Neuronal Size in Adult Animals.

    Science.gov (United States)

    Martínez-Cerdeño, Verónica; Camacho, Jasmin; Fox, Elizabeth; Miller, Elaine; Ariza, Jeanelle; Kienzle, Devon; Plank, Kaela; Noctor, Stephen C; Van de Water, Judy

    2016-01-01

    Autism spectrum disorders (ASDs) affect up to 1 in 68 children. Autism-specific autoantibodies directed against fetal brain proteins have been found exclusively in a subpopulation of mothers whose children were diagnosed with ASD or maternal autoantibody-related autism. We tested the impact of autoantibodies on brain development in mice by transferring human antigen-specific IgG directly into the cerebral ventricles of embryonic mice during cortical neurogenesis. We show that autoantibodies recognize radial glial cells during development. We also show that prenatal exposure to autism-specific maternal autoantibodies increased stem cell proliferation in the subventricular zone (SVZ) of the embryonic neocortex, increased adult brain size and weight, and increased the size of adult cortical neurons. We propose that prenatal exposure to autism-specific maternal autoantibodies directly affects radial glial cell development and presents a viable pathologic mechanism for the maternal autoantibody-related prenatal ASD risk factor. PMID:25535268

  15. Increased brain temserotoneric transporter availability in adult migraineurs: ([18F]FP-CIT PET imaging pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eun Kyung [Dept. of Nuclear Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul (Korea, Republic of); Hwang, Yu Mi [Center for Research Information, Korea University, Seoul (Korea, Republic of); Chu, Min Kyung [Dept. of Neurology, Sacred Heart Hospital, Hallym University College of Medicine, Anyang (Korea, Republic of); Jung, Ki Young [Dept. of Neurology, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2016-03-15

    Recent studies have proposed central serotonergic dysfunction as a major pathophysiology of migraine. We investigated serotonin transporter (SERT) availability in migraineurs using F-18-N-(3-fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ([18F]FP-CIT) positron emission tomography (PET). Brain [18F]FP-CIT PET images were obtained in eight women with migraine during headache free phase and 12 healthy adult women, 120 min after injection of 185 MBq. Non-displaceable binding potential (BP ND) of [18F]FP-CIT, which is an estimate of SERT availability, was calculated at the brainstem and compared with clinical parameters. BP ND at the brainstem was significantly higher in adult migraineurs (n = 6, 1.15 ± 0.17) than healthy subjects (0.95 ± 0.14) (p = 0.04). Healthy subjects demonstrated negative correlation between brainstem BP ND and age (r = −0.64, p = 0.02), whereas this age-related decline pattern was not found in the migraineurs. Severity of migraine attack was significantly correlated with brainstem BP ND (r = 0.66, p = 0.02), when age and duration of illness were corrected. Increased SERT availability in the brainstem of adult migraineurs indicates low serotonin neurotransmission during headache-free phase. Patients who experience more painful headaches have lower serotonin neurotransmission. [18F]FP-CIT PET is a useful in vivo imaging technique for evaluating brainstem SERT availability in migraineurs.

  16. Emergency Department Visits for Traumatic Brain Injury in Older Adults in the United States: 2006-08

    Directory of Open Access Journals (Sweden)

    William S. Pearson

    2012-08-01

    Full Text Available Introduction: Traumatic brain injury (TBI can be complicated among older adults due to age-related frailty, a greater prevalence of chronic conditions and the use of anticoagulants. We conducted this study using the latest available, nationally-representative emergency department (ED data to characterize visits for TBI among older adults.Methods: We used the 2006-2008 National Hospital Ambulatory Medical Care – Emergency Department (NHAMCS-ED data to examine ED visits for TBI among older adults. Population-level estimates of triage immediacy, receipt of a head computed tomography (CT and/or head magnetic resonance imaging (MRI, and hospital admission by type were used to characterize 1,561 sample visits, stratified by age <65 and ≥65 years of age.Results: Of ED visits made by persons ≥65 years of age, 29.1% required attention from a physician within 15 minutes of arrival; 82.1% required a head CT, and 20.9% required hospitalization. Persons≥65 years of age were 3 times more likely to receive a head CT or MRI compared to younger patients presenting with TBI (adjusted odds ratio [aOR] 3.2; 95% confidence interval [CI], 1.8-5.8, and were 4 times more likely to be admitted to an intensive care unit, step-down unit, or surgery (aOR 4.1; 95% CI 2.1-8.0 compared to younger patients presenting with TBI, while controlling for sex and race.Conclusion: Results demonstrate increased emergent service delivery for older persons presenting with TBI. As the United States population ages and continues to grow, TBI will become an even more important public health issue that will place a greater demand on the healthcare system. [West J Emerg Med. 2012;13(3:289-293.

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

    Directory of Open Access Journals (Sweden)

    Yang eJiang

    2016-02-01

    Full Text Available ß-amyloid (Aß 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 patterns within the default-mode network (DMN, age, CSF biomarkers (Aß42 and pTau181 and cognitive status in older adults. Multiple measures of functional connectivity 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 Aß42 or pTau181 and cognitive scores or regional brain volumes. However, we observed several novel relationships between these biomarkers and measures of functional connectivity 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.

  18. Increased expression of neurotrophin 4 following focal cerebral ischemia in adult rat brain with treadmill exercise.

    Directory of Open Access Journals (Sweden)

    Jin-Young Chung

    Full Text Available Neurotrophin 4 (NT-4 belongs to the family of neurotrophic factors, and it interacts with the tyrosine kinase B (trkB receptor. NT-4 has neuroprotective effects following cerebral ischemia. Its role might be similar to brain-derived neurotrophic factor (BDNF, because both interact with trkB. Exercise also improves neural function by increasing neurotrophic factors. However, expression profiles of NT-4 in the brain during exercise are unknown. Here, we assessed the expressions of NT-4 and its receptor, trkB, following cerebral ischemia and hypothesized that exercise changes the expressions of NT-4 and trkB. Results showed that in a permanent middle cerebral artery occlusion rat model, ischemia decreased NT-4 and trkB expression. Immunohistochemistry showed their immunoreactivities around the region of the ischemic area. Treadmill exercise changed the expression of NT-4, which increased in the contralateral hemisphere in rats with ischemic injury. TrkB also showed similar patterns to its neurotophins. The change in NT-4 suggested that exercise might have primed NT4 production so that further injury causes slightly greater increases in NT4 compared with non-exercise controls.

  19. Plasticity of Adult Sensorimotor System in Severe Brain Infarcts: Challenges and Opportunities

    Directory of Open Access Journals (Sweden)

    Annette Sterr

    2012-01-01

    Full Text Available Functional reorganization forms the critical mechanism for the recovery of function after brain damage. These processes are driven by inherent changes within the central nervous system (CNS triggered by the insult and further depend on the neural input the recovering system is processing. Therefore these processes interact with not only the interventions a patient receives, but also the activities and behaviors a patient engages in. In recent years, a wide range of research programs has addressed the association between functional reorganization and the spontaneous and treatment-induced recovery. The bulk of this work has focused on upper-limb and hand function, and today there are new treatments available that capitalize on the neuroplasticity of the brain. However, this is only true for patients with mild to moderated impairments; for those with very limited hand function, the basic understanding is much poorer and directly translates into limited treatment opportunities for these patients. The present paper aims to highlight the knowledge gap on severe stroke with a brief summary of the literature followed by a discussion of the challenges involved in the study and treatment of severe stroke and poor long-term outcome.

  20. Mindfulness-Based Cognitive Therapy and the Adult ADHD Brain: A Neuropsychotherapeutic Perspective

    Science.gov (United States)

    Bachmann, Katharina; Lam, Alexandra P.; Philipsen, Alexandra

    2016-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a recognized serious mental disorder that often persists into adulthood. The symptoms and impairments associated with ADHD often cause significant mental suffering in affected individuals. ADHD has been associated with abnormal neuronal activity in various neuronal circuits, such as the dorsofrontostriatal, orbitofrontostriatal, and frontocerebellar circuits. Psychopharmacological treatment with methylphenidate hydrochloride is recommended as the first-line treatment for ADHD. It is assumed that medication ameliorates ADHD symptoms by improving the functioning of the brain areas affected in the condition. However, side effects, contraindications, or non-response can limit the effectiveness of a psychopharmacological treatment for ADHD. It is therefore necessary to develop non-pharmacological interventions that target neuronal mechanisms associated with the condition in the same way as pharmacological treatment. We think that mindfulness meditation employed as a neuropsychotherapeutic intervention could help patients with ADHD to regulate impaired brain functioning and thereby reduce ADHD symptoms. In this paper, we highlight the mechanisms of such mindfulness meditation, and thus provide a rationale for further research and treatment development from a neuropsychotherapeutic perspective. We conclude that mindfulness meditation employed as a neuropsychotherapeutic intervention in therapy is a promising treatment approach in ADHD. PMID:27445873

  1. The ABCs of TBI. Evidence-based guidelines for adult traumatic brain injury care.

    Science.gov (United States)

    Dewall, Jeremy

    2010-04-01

    The images of Olympic athlete Nodar Kumaritasvili flying off his luge and contacting a fixed steel beam at the recent Winter Olympics in Vancouver, British Columbia, were shocking. But the resultant injuries and death of the young athlete were not surprising to EMS personnel who witnessed the incident, because training and experience with similar mechanisms of injury intuitively teach us that these types of patients are susceptible to traumatic brain injury (TBI). Worldwide, TBI is the leading injury cause of death and permanent disability. In the U.S. alone, 1.4 million cases of TBI present to emergency services every year. Many more cases go unreported and untreated. These TBIs lead to 235,000 hospitalizations and, ultimately, 50,000 deaths.(1) For instance, blunt trauma alone kills 1% of those affected, but when a TBI is also involved, the mortality rate increases to 30%.(2) Some 50% of those who die from TBI do so within the first two hours of injury, making emergent prehospital intervention critical.(3) Preventing secondary injury by proper prehospital management can save brain function and lives. PMID:20399377

  2. Mindfulness-Based Cognitive Therapy and the Adult ADHD Brain: A Neuropsychotherapeutic Perspective.

    Science.gov (United States)

    Bachmann, Katharina; Lam, Alexandra P; Philipsen, Alexandra

    2016-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a recognized serious mental disorder that often persists into adulthood. The symptoms and impairments associated with ADHD often cause significant mental suffering in affected individuals. ADHD has been associated with abnormal neuronal activity in various neuronal circuits, such as the dorsofrontostriatal, orbitofrontostriatal, and frontocerebellar circuits. Psychopharmacological treatment with methylphenidate hydrochloride is recommended as the first-line treatment for ADHD. It is assumed that medication ameliorates ADHD symptoms by improving the functioning of the brain areas affected in the condition. However, side effects, contraindications, or non-response can limit the effectiveness of a psychopharmacological treatment for ADHD. It is therefore necessary to develop non-pharmacological interventions that target neuronal mechanisms associated with the condition in the same way as pharmacological treatment. We think that mindfulness meditation employed as a neuropsychotherapeutic intervention could help patients with ADHD to regulate impaired brain functioning and thereby reduce ADHD symptoms. In this paper, we highlight the mechanisms of such mindfulness meditation, and thus provide a rationale for further research and treatment development from a neuropsychotherapeutic perspective. We conclude that mindfulness meditation employed as a neuropsychotherapeutic intervention in therapy is a promising treatment approach in ADHD. PMID:27445873

  3. Mindfulness-Based Cognitive Therapy and the Adult ADHD Brain: A Neuropsychotherapeutic Perspective.

    Science.gov (United States)

    Bachmann, Katharina; Lam, Alexandra P; Philipsen, Alexandra

    2016-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a recognized serious mental disorder that often persists into adulthood. The symptoms and impairments associated with ADHD often cause significant mental suffering in affected individuals. ADHD has been associated with abnormal neuronal activity in various neuronal circuits, such as the dorsofrontostriatal, orbitofrontostriatal, and frontocerebellar circuits. Psychopharmacological treatment with methylphenidate hydrochloride is recommended as the first-line treatment for ADHD. It is assumed that medication ameliorates ADHD symptoms by improving the functioning of the brain areas affected in the condition. However, side effects, contraindications, or non-response can limit the effectiveness of a psychopharmacological treatment for ADHD. It is therefore necessary to develop non-pharmacological interventions that target neuronal mechanisms associated with the condition in the same way as pharmacological treatment. We think that mindfulness meditation employed as a neuropsychotherapeutic intervention could help patients with ADHD to regulate impaired brain functioning and thereby reduce ADHD symptoms. In this paper, we highlight the mechanisms of such mindfulness meditation, and thus provide a rationale for further research and treatment development from a neuropsychotherapeutic perspective. We conclude that mindfulness meditation employed as a neuropsychotherapeutic intervention in therapy is a promising treatment approach in ADHD.

  4. Brain regions associated with Anhedonia in healthy adults: a PET correlation study

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    Jung, Young Chul; Chun, Ji Won; Kim, Jae Jin; Park, Hae Jeong; Lee, Jong Doo [Yonsei University College of Medicine, Gwangju (Korea, Republic of); Seok, Jeong Ho [Hallym University Sacred Heart Hospital, Anyang (Korea, Republic of)

    2005-10-15

    Anhedonia has been proposed to be the result of a basic neurophysiologic dysfunction and a vulnerability marker that precede and contribute to the liability of developing schizophrenia. We hypothesized that anhedonia, as a construct reflecting the decreased capacity to experience pleasure, should be associated with decreased positive hedonic affect trait. This study examined the relationship between anhedonia and positive hedonic affect trait and searched for the brain regions which correlate with anhedonia in normal subjects. Using {sup 18}F-FDG PET scan, we investigated the brain activity of twenty one subjects during resting state. Questionnaires were administrated after the scan in order to assess the self-rated individual differences in physical/social anhedonia and positive/negative affect traits. Negative correlation between physical anhedonia score and positive affect trait score was significant (Pearson coefficient=-0.440, {rho} <0.05). The subjects' physical and social anhedonia scores showed positive correlation with metabolic rates in the cerebellum and negative correlation with metabolic rates in the inferior temporal gyrus and middle frontal gyrus. In addition, the positive affect trait score positively correlated with various areas, most prominent with the inferior temporal gyrus. These results suggest that neural substrates, such as the inferior temporal gyrus and prefrontal-cerebellar circuit, which dysfunction has been proposed to be involved with the cognitive deficits of schizophrenia, may also play a significant role in the liability of affective deficits like anhedonia.

  5. The role of rodents in the ecology of Ixodes ricinus and associated pathogens in Central and Eastern Europe

    Directory of Open Access Journals (Sweden)

    Andrei Daniel Mihalca

    2013-10-01

    Full Text Available Rodents comprise more species than any other mammal order. Most rodents are considered keystone species in their ecological communities, hence the survival of many other species in the ecosystem depend on them. From medical point of view, this is particularly important for rodent-dependent pathogens. In the particular case of tick-borne diseases, rodents are important as hosts for vector ticks and as reservoir hosts (Lyme borreliosis, human granulocytic anaplasmosis, Crimean-Congo hemorrhagic fever, Tick-borne relapsing fevers, tick-borne rickettsioses, babesiosis. Community and population ecology of rodents was shown to be correlated with disease ecology in the case of many tick-borne diseases. In Eastern Europe, several adult hard-tick species use rodents as their principal hosts: Ixodes apronophorus, I. crenulatus, I. laguri, I. redikorzevi, I. trianguliceps. However, the majority of ticks feeding on rodents are immature stages of ticks which as adults are parasitic on larger mammals. Larvae and nymphs of I. ricinus, the most abundant and medically important tick from Europe, are commonly found on rodents. This is particularly important, as many rodents are synanthropic and, together with other micromammals and birds are often the only available natural hosts for ticks in urban environments. This work reviews the correlated ecology of rodents and Ixodes ricinus.

  6. The role of rodents in the ecology of Ixodes ricinus and associated pathogens in Central and Eastern Europe.

    Science.gov (United States)

    Mihalca, Andrei D; Sándor, Attila D

    2013-01-01

    Rodents comprise more species than any other mammal order. Most rodents are considered keystone species in their ecological communities, hence the survival of many other species in the ecosystem depend on them. From medical point of view, this is particularly important for rodent-dependent pathogens. In the particular case of tick-borne diseases, rodents are important as hosts for vector ticks and as reservoir hosts (Lyme borreliosis, human granulocytic anaplasmosis, Crimean-Congo hemorrhagic fever, Tick-borne relapsing fevers, tick-borne rickettsioses, babesiosis). Community and population ecology of rodents was shown to be correlated with disease ecology in the case of many tick-borne diseases. In Eastern Europe, several adult hard-tick species use rodents as their principal hosts: Ixodes apronophorus, I. crenulatus, I. laguri, I. redikorzevi, I. trianguliceps. However, the majority of ticks feeding on rodents are immature stages of ticks which as adults are parasitic on larger mammals. Larvae and nymphs of Ixodes ricinus, the most abundant and medically important tick from Europe, are commonly found on rodents. This is particularly important, as many rodents are synanthropic and, together with other micromammals and birds are often the only available natural hosts for ticks in urban environments. This work reviews the correlated ecology of rodents and I. ricinus.

  7. Human fetal brain-derived neural stem/progenitor cells grafted into the adult epileptic brain restrain seizures in rat models of temporal lobe epilepsy.

    Directory of Open Access Journals (Sweden)

    Haejin Lee

    Full Text Available Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%, APC-CC1+ oligodendrocytes (∼28%, and GFAP+ astrocytes (∼8%. Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest

  8. An investigation of body part as object (BPO) responses in normal and brain-damaged adults.

    Science.gov (United States)

    Duffy, R J; Duffy, J R

    1989-07-01

    A test of simple pantomime was administered to three groups of adults and comparisons were made across groups of the incidence of subjects who exhibited body part as object (BPO) responses and of the mean frequency of occurrence of BPO in each group. The three groups were left-hemisphere-damaged aphasics (N = 28), right-hemisphere-damaged (N = 24), and normal controls (N = 28). The results indicated no significant differences among groups on the BPO measures. Also, to test the strength of association between the frequency of occurrence of BPO and measures of limb apraxia and severity of aphasia for the left-hemisphere-damaged aphasic group, correlation coefficients were obtained. The correlations were low and nonsignificant. The results of this investigation do not support the common clinical assumption that the occurrence of BPO during the performance of simple pantomimes is pathognomic for left-hemisphere pathology or associated with limb apraxia.

  9. Traffic-related air pollution and brain development

    Directory of Open Access Journals (Sweden)

    Nicholas Woodward

    2015-05-01

    Full Text Available Automotive traffic-related air pollution (TRP imposes an increasing health burden with global urbanization. Gestational and early child exposure to urban TRP is associated with higher risk of autism spectrum disorders and schizophrenia, as well as low birth weight. While cardio-respiratory effects from exposure are well documented, cognitive effects are only recently becoming widely recognized. This review discusses effects of TRP on brain and cognition in human and animal studies. The mechanisms underlying these epidemiological associations are studied with rodent models of pre- and neonatal exposure to TRP, which show persisting inflammatory changes and altered adult behaviors and cognition. Some behavioral and inflammatory changes show male bias. Rodent models may identify dietary and other interventions for neuroprotection to TRP.

  10. In vivo 3D digital atlas database of the adult C57BL/6J mouse brain by magnetic resonance microscopy

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    Yu Ma

    2008-04-01

    Full Text Available In this study, a 3D digital atlas of the live mouse brain based on magnetic resonance microscopy (MRM is presented. C57BL/6J adult mouse brains were imaged in vivo on a 9.4 Tesla MR instrument at an isotropic spatial resolution of 100 μm. With sufficient signal-to-noise (SNR and contrast-to-noise ratio (CNR, 20 brain regions were identified. Several atlases were constructed including 12 individual brain atlases, an average atlas, a probabilistic atlas and average geometrical deformation maps. We also investigated the feasibility of using lower spatial resolution images to improve time efficiency for future morphological phenotyping. All of the new in vivo data were compared to previous published in vitro C57BL/6J mouse brain atlases and the morphological differences were characterized. Our analyses revealed significant volumetric as well as unexpected geometrical differences between the in vivo and in vitro brain groups which in some instances were predictable (e.g. collapsed and smaller ventricles in vitro but not in other instances. Based on these findings we conclude that although in vitro datasets, compared to in vivo images, offer higher spatial resolutions, superior SNR and CNR, leading to improved image segmentation, in vivo atlases are likely to be an overall better geometric match for in vivo studies, which are necessary for longitudinal examinations of the same animals and for functional brain activation studies. Thus the new in vivo mouse brain atlas dataset presented here is a valuable complement to the current mouse brain atlas collection and will be accessible to the neuroscience community on our public domain mouse brain atlas website.

  11. Commentary to Krishna et al. (2014): brain deposition and neurotoxicity of manganese in adult mice exposed via the drinking water.

    Science.gov (United States)

    Kumasaka, Mayuko Y; Yajima, Ichiro; Ohgami, Nobutaka; Naito, Hisao; Omata, Yasuhiro; Kato, Masashi

    2014-05-01

    Krishna et al. (Arch Toxicol 88(1):47-64, 2014) recently published the results of a study in which adult C57BL/6 mice were subchronically exposed to 400,000 μg/L manganese (Mn) using manganese chloride via drinking water for 8 weeks and examined the neurotoxic effects. After 5 weeks of Mn exposure, significant deposition of Mn in all of the brain regions examined by magnetic resonance imaging was detected. After 6 weeks of Mn exposure, neurobehavioral deficits in an open field test, a grip strength test, and a forced swim test were observed. Eight weeks of Mn exposure increased striatal 5-hydroxyindoleacetic acid (a serotonin metabolite) levels, but did not alter the levels of striatal dopamine, its metabolites and serotonin. Krishna et al. also reported significant increases in mRNA levels of GFAP (an astrocyte activation marker), HO-1 (an oxidative stress marker) and NOS2 (a nitrosative stress marker), and in protein expression level of GFAP in the substantia nigra pars reticulata after 8 weeks of Mn exposure. These results suggest that 400,000 μg/L Mn exposure via drinking water in mice induces neurobehavioral deficits, serotonergic imbalance, and glial activation accompanied by an increase in brain Mn deposition. The report by Krishna et al. is interesting because the studies on the neurobehavioral effect of Mn exposure by drinking water in mice are very limited. However, Mn concentrations previously reported in well drinking water (Agusa et al. in Vietnam Environ Pollut 139(1):95-106, 2006; Buschmann et al. in Environ Int 34(6):756-764, 2008; Hafeman et al. in Environ Health Perspect 115(7):1107-1112, 2007; Wasserman et al. in Bangladesh Environ Health Perspect 114(1):124-129, 2006) were lower than 400,000 μg/L.

  12. Multiple infections of rodents with zoonotic pathogens in Austria.

    Science.gov (United States)

    Schmidt, Sabrina; Essbauer, Sandra S; Mayer-Scholl, Anne; Poppert, Sven; Schmidt-Chanasit, Jonas; Klempa, Boris; Henning, Klaus; Schares, Gereon; Groschup, Martin H; Spitzenberger, Friederike; Richter, Dania; Heckel, Gerald; Ulrich, Rainer G

    2014-07-01

    Rodents are important reservoirs for a large number of zoonotic pathogens. We examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in Austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, Leptospira spp., Borrelia spp., Rickettsia spp., Bartonella spp., Coxiella burnetii, and Toxoplasma gondii. In 2008, 110 rodents of four species (40 Clethrionomys glareolus, 29 Apodemus flavicollis, 26 Apodemus sylvaticus, and 15 Microtus arvalis) were trapped at two rural sites in Lower Austria. Chest cavity fluid and samples of lung, spleen, kidney, liver, brain, and ear pinna skin were collected. We screened selected tissue samples for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, Leptospira, Borrelia, Rickettsia, Bartonella spp., C. burnetii, and T. gondii by RT-PCR/PCR and detected nucleic acids of Tula hantavirus, Leptospira spp., Borrelia afzelii, Rickettsia spp., and different Bartonella species. Serological investigations were performed for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, and Rickettsia spp. Here, Dobrava-Belgrade hantavirus-, Tula hantavirus-, lymphocytic choriomeningitis virus-, orthopox virus-, and rickettsia-specific antibodies were demonstrated. Puumala hantavirus, C. burnetii, and T. gondii were neither detected by RT-PCR/PCR nor by serological methods. In addition, multiple infections with up to three pathogens were shown in nine animals of three rodent species from different trapping sites. In conclusion, these results show that rodents in Austria may host multiple zoonotic pathogens. Our observation raises important questions regarding the interactions of different pathogens in the host, the countermeasures of the host's immune system, the impact of the host-pathogen interaction on the fitness of the host, and the spread of infectious agents among wild rodents and from those to other animals or humans.

  13. Multiple infections of rodents with zoonotic pathogens in Austria.

    Science.gov (United States)

    Schmidt, Sabrina; Essbauer, Sandra S; Mayer-Scholl, Anne; Poppert, Sven; Schmidt-Chanasit, Jonas; Klempa, Boris; Henning, Klaus; Schares, Gereon; Groschup, Martin H; Spitzenberger, Friederike; Richter, Dania; Heckel, Gerald; Ulrich, Rainer G

    2014-07-01

    Rodents are important reservoirs for a large number of zoonotic pathogens. We examined the occurrence of 11 viral, bacterial, and parasitic agents in rodent populations in Austria, including three different hantaviruses, lymphocytic choriomeningitis virus, orthopox virus, Leptospira spp., Borrelia spp., Rickettsia spp., Bartonella spp., Coxiella burnetii, and Toxoplasma gondii. In 2008, 110 rodents of four species (40 Clethrionomys glareolus, 29 Apodemus flavicollis, 26 Apodemus sylvaticus, and 15 Microtus arvalis) were trapped at two rural sites in Lower Austria. Chest cavity fluid and samples of lung, spleen, kidney, liver, brain, and ear pinna skin were collected. We screened selected tissue samples for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, Leptospira, Borrelia, Rickettsia, Bartonella spp., C. burnetii, and T. gondii by RT-PCR/PCR and detected nucleic acids of Tula hantavirus, Leptospira spp., Borrelia afzelii, Rickettsia spp., and different Bartonella species. Serological investigations were performed for hantaviruses, lymphocytic choriomeningitis virus, orthopox viruses, and Rickettsia spp. Here, Dobrava-Belgrade hantavirus-, Tula hantavirus-, lymphocytic choriomeningitis virus-, orthopox virus-, and rickettsia-specific antibodies were demonstrated. Puumala hantavirus, C. burnetii, and T. gondii were neither detected by RT-PCR/PCR nor by serological methods. In addition, multiple infections with up to three pathogens were shown in nine animals of three rodent species from different trapping sites. In conclusion, these results show that rodents in Austria may host multiple zoonotic pathogens. Our observation raises important questions regarding the interactions of different pathogens in the host, the countermeasures of the host's immune system, the impact of the host-pathogen interaction on the fitness of the host, and the spread of infectious agents among wild rodents and from those to other animals or humans. PMID:24915446

  14. Tai Chi Chuan Optimizes the Functional Organization of the Intrinsic Human Brain Architecture in Older Adults

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    Gao-Xia eWei

    2014-04-01

    Full Text Available 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 postcentral gyrus (PosCG and less functional homogeneity in the left anterior cingulate cortex (ACC and the right dorsal lateral prefrontal cortex (DLPFC. 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.

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

    Science.gov (United States)

    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

  16. Golli myelin basic proteins stimulate oligodendrocyte progenitor cell proliferation and differentiation in remyelinating adult mouse brain.

    Science.gov (United States)

    Paez, Pablo M; Cheli, Veronica T; Ghiani, Cristina A; Spreuer, Vilma; Handley, Vance W; Campagnoni, Anthony T

    2012-07-01

    Golli myelin basic proteins are necessary for normal myelination, acting via voltage and store-dependent Ca(2+) entry at multiple steps during oligodendrocyte progenitor cell (OPC) development. To date nothing is known regarding the role of golli proteins in demyelination or remyelination events. Here the effects of golli ablation and overexpression in myelin loss and recovery were examined using the cuprizone (CPZ) model of demyelination/remyelination. We found severe demyelination in the corpus callosum (CC) of golli-overexpressing mice (JOE) during the CPZ treatment, which was accompanied by an increased number of reactive astrocytes and activation of microglia/macrophages. During demyelination of JOE brains, a significant increase in the number of proliferating OPCs was found in the CC as well as in the subventricular zone, and our data indicate that these progenitors matured and fully remyelinated the CC of JOE animals after CPZ withdrawal. In contrast, in the absence of golli (golli-KO mice) delayed myelin loss associated with a smaller immune response, and a lower number of OPCs was found in these mice during the CPZ treatment. Furthermore, incomplete remyelination was observed after CPZ removal in large areas of the CC of golli-KO mice, reflecting irregular recovery of the oligodendrocyte population and subsequent myelin sheath formation. Our findings demonstrate that golli proteins sensitize mature oligodendrocytes to CPZ-induced demyelination, while at the same time stimulate the proliferation/recruitment of OPCs during demyelination, resulting in accelerated remyelination.

  17. Prediction of individual differences in risky behaviour in young adults via variations in local brain structure

    Directory of Open Access Journals (Sweden)

    Zahra eNasiriavanaki

    2015-10-01

    Full Text Available In recent years the problem of how inter-individual differences play a role in risk-taking behaviour has become a much debated issue. We investigated this problem based on the well-known balloon analogue risk task (BART in which participants inflate a virtual balloon opting for a higher score in the face of a riskier chance of the balloon explosion. In this study, based on a structural Voxel Based Morphometry (VBM technique we demonstrate a significant positive correlation between BART score and size of the grey matter volume in the anterior insula in riskier subjects. Although the anterior insula is among the candidate brain areas that were involved in the risk taking behaviour in fMRI studies, here based on our structural data it is the sole area with a significant structural variation among different subjects. Also a seemingly conflicting finding is discussed where the anterior insula is shown to be more active in risk aversive subjects.

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

    Science.gov (United States)

    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.

  19. Behavioral disturbances in adult mice following neonatal virus infection or kynurenine treatment--role of brain kynurenic acid.

    Science.gov (United States)

    Liu, Xi-Cong; Holtze, Maria; Powell, Susan B; Terrando, Niccolò; Larsson, Markus K; Persson, Anna; Olsson, Sara K; Orhan, Funda; Kegel, Magdalena; Asp, Linnea; Goiny, Michel; Schwieler, Lilly; Engberg, Göran; Karlsson, Håkan; Erhardt, Sophie

    2014-02-01

    Exposure to infections in early life is considered a risk-factor for developing schizophrenia. Recently we reported that a neonatal CNS infection with influenza A virus in mice resulted in a transient induction of the brain kynurenine pathway, and subsequent behavioral disturbances in immune-deficient adult mice. The aim of the present study was to investigate a potential role in this regard of kynurenic acid (KYNA), an endogenous antagonist at the glycine site of the N-methyl-D-aspartic acid (NMDA) receptor and at the cholinergic α7 nicotinic receptor. C57BL/6 mice were injected i.p. with neurotropic influenza A/WSN/33 virus (2400 plaque-forming units) at postnatal day (P) 3 or with L-kynurenine (2×200 mg/kg/day) at P7-16. In mice neonatally treated with L-kynurenine prepulse inhibition of the acoustic startle, anxiety, and learning and memory were also assessed. Neonatally infected mice showed enhanced sensitivity to D-amphetamine-induced (5 mg/kg i.p.) increase in locomotor activity as adults. Neonatally L-kynurenine treated mice showed enhanced sensitivity to D-amphetamine-induced (5 mg/kg i.p.) increase in locomotor activity as well as mild impairments in prepulse inhibition and memory. Also, D-amphetamine tended to potentiate dopamine release in the striatum in kynurenine-treated mice. These long-lasting behavioral and neurochemical alterations suggest that the kynurenine pathway can link early-life infection with the development of neuropsychiatric disturbances in adulthood. PMID:24140727

  20. Early Exposure to Intermediate-Frequency Magnetic Fields Alters Brain Biomarkers without Histopathological Changes in Adult Mice

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    Tin-Tin Win-Shwe

    2015-04-01

    Full Text Available Recently we have reported that intermediate-frequency magnetic field (IF-MF exposure transiently altered the mRNA expression levels of memory function-related genes in the hippocampi of adult male mice. However, the effects of IF-MF exposure during brain development on neurological biomarkers have not yet been clarified. In the present study, we investigated the effect of IF-MF exposure during development on neurological and immunological markers in the mouse hippocampus in 3- and 7-week-old male mice. Pregnant C57BL/6J mice were exposed to IF-MF (21 kHz, 3.8 mT for one hour per day from organogenesis period day 7 to 17. At adolescence, some IF-MF-exposed mice were further divided into exposure, recovery, and sham-exposure groups. The adolescent-exposure groups were exposed again to IF-MF from postnatal day 27 to 48. The expression of mRNA in the hippocampi was examined using a real-time RT-PCR method, and microglia activation was examined by immunohistochemical analysis. The expression levels of NR1 and NR2B as well as transcription factors (CaMKIV, CREB1, inflammatory mediators (COX2, IL-1 b,TNF-α, and the oxidative stress marker heme-oxygenase (HO-1 were significantly increased in the IF-MF-exposed mice, compared with the control group, in the 7-week-old mice, but not in the 3-week-old mice. Microglia activation was not different between the control and other groups. This study provides the first evidence that early exposure to IF-MF reversibly affects the NMDA receptor, its related signaling pathways, and inflammatory mediators in the hippocampus of young adult mice; these changes are transient and recover after termination of exposure without histopathological changes.

  1. Menstrual cycle-dependent neural plasticity in the adult human brain is hormone, task, and region specific.

    NARCIS (Netherlands)

    Fernandez, G.S.E.; Weis, S.; Stoffel-Wagner, B.; Tendolkar, I.; Reuber, M.; Beyenburg, S.; Klaver, P.; Fell, J.; Greiff, A. de; Ruhlmann, J.; Reul, J.; Elger, C.E.

    2003-01-01

    In rodents, cyclically fluctuating levels of gonadal steroid hormones modulate neural plasticity by altering synaptic transmission and synaptogenesis. Alterations of mood and cognition observed during the menstrual cycle suggest that steroid-related plasticity also occurs in humans. Cycle phase-depe

  2. Neural processing of reward in adolescent rodents

    Directory of Open Access Journals (Sweden)

    Nicholas W. Simon

    2015-02-01

    Full Text Available Immaturities in adolescent reward processing are thought to contribute to poor decision making and increased susceptibility to develop addictive and psychiatric disorders. Very little is known; however, about how the adolescent brain processes reward. The current mechanistic theories of reward processing are derived from adult models. Here we review recent research focused on understanding of how the adolescent brain responds to rewards and reward-associated events. A critical aspect of this work is that age-related differences are evident in neuronal processing of reward-related events across multiple brain regions even when adolescent rats demonstrate behavior similar to adults. These include differences in reward processing between adolescent and adult rats in orbitofrontal cortex and dorsal striatum. Surprisingly, minimal age related differences are observed in ventral striatum, which has been a focal point of developmental studies. We go on to discuss the implications of these differences for behavioral traits affected in adolescence, such as impulsivity, risk-taking, and behavioral flexibility. Collectively, this work suggests that reward-evoked neural activity differs as a function of age and that regions such as the dorsal striatum that are not traditionally associated with affective processing in adults may be critical for reward processing and psychiatric vulnerability in adolescents.

  3. Cre-dependent selection yields AAV variants for widespread gene transfer to the adult brain.

    Science.gov (United States)

    Deverman, Benjamin E; Pravdo, Piers L; Simpson, Bryan P; Kumar, Sripriya Ravindra; Chan, Ken Y; Banerjee, Abhik; Wu, Wei-Li; Yang, Bin; Huber, Nina; Pasca, Sergiu P; Gradinaru, Viviana

    2016-02-01

    Recombinant adeno-associated viruses (rAAVs) are commonly used vehicles for in vivo gene transfer. However, the tropism repertoire of naturally occurring AAVs is limited, prompting a search for novel AAV capsids with desired characteristics. Here we describe a capsid selection method, called Cre recombination-based AAV targeted evolution (CREATE), that enables the development of AAV capsids that more efficiently transduce defined Cre-expressing cell populations in vivo. We use CREATE to generate AAV variants that efficiently and widely transduce the adult mouse central nervous system (CNS) after intravenous injection. One variant, AAV-PHP.B, transfers genes throughout the CNS with an efficiency that is at least 40-fold greater than that of the current standard, AAV9 (refs. 14,15,16,17), and transduces the majority of astrocytes and neurons across multiple CNS regions. In vitro, it transduces human neurons and astrocytes more efficiently than does AAV9, demonstrating the potential of CREATE to produce customized AAV vectors for biomedical applications. PMID:26829320

  4. Neurotoxic effects of ochratoxin A on the subventricular zone of adult mouse brain.

    Science.gov (United States)

    Paradells, Sara; Rocamonde, Brenda; Llinares, Cristina; Herranz-Pérez, Vicente; Jimenez, Misericordia; Garcia-Verdugo, Jose Manuel; Zipancic, Ivan; Soria, Jose Miguel; Garcia-Esparza, Ma Angeles

    2015-07-01

    Ochratoxin A (OTA), a mycotoxin that was discovered as a secondary metabolite of the fungal species Aspergillus and Penicillium, is a common contaminant in food and animal feed. This mycotoxin has been described as teratogenic, carcinogenic, genotoxic, immunotoxic and has been proven a potent neurotoxin. Other authors have previously reported the effects of OTA in different structures of the central nervous system as well as in some neurogenic regions. However, the impact of OTA exposure in the subventricular zone (SVZ) has not been assessed yet. To elucidate whether OTA affects neural precursors of the mouse SVZ we investigated, in vitro and in vivo, the effects of OTA exposure on the SVZ and on the neural precursors obtained from this neurogenic niche. In this work, we prove the cumulative effect of OTA exposure on proliferation, differentiation and depletion of neural stem cells cultured from the SVZ. In addition, we corroborated these results in vivo by immunohistochemistry and electron microscopy. As a result, we found a significant alteration in the proliferation process, which was evidenced by a decrease in the number of 5-bromo-2-deoxyuridine-positive cells and glial cells, as well as, a significant decrease in the number of neuroblasts in the SVZ. To summarize, in this study we demonstrate how OTA could be a threat to the developing and the adult SVZ through its impact in cell viability, proliferation and differentiation in a dose-dependent manner.

  5. Neurotoxic effects of ochratoxin A on the subventricular zone of adult mouse brain.

    Science.gov (United States)

    Paradells, Sara; Rocamonde, Brenda; Llinares, Cristina; Herranz-Pérez, Vicente; Jimenez, Misericordia; Garcia-Verdugo, Jose Manuel; Zipancic, Ivan; Soria, Jose Miguel; Garcia-Esparza, Ma Angeles

    2015-07-01

    Ochratoxin A (OTA), a mycotoxin that was discovered as a secondary metabolite of the fungal species Aspergillus and Penicillium, is a common contaminant in food and animal feed. This mycotoxin has been described as teratogenic, carcinogenic, genotoxic, immunotoxic and has been proven a potent neurotoxin. Other authors have previously reported the effects of OTA in different structures of the central nervous system as well as in some neurogenic regions. However, the impact of OTA exposure in the subventricular zone (SVZ) has not been assessed yet. To elucidate whether OTA affects neural precursors of the mouse SVZ we investigated, in vitro and in vivo, the effects of OTA exposure on the SVZ and on the neural precursors obtained from this neurogenic niche. In this work, we prove the cumulative effect of OTA exposure on proliferation, differentiation and depletion of neural stem cells cultured from the SVZ. In addition, we corroborated these results in vivo by immunohistochemistry and electron microscopy. As a result, we found a significant alteration in the proliferation process, which was evidenced by a decrease in the number of 5-bromo-2-deoxyuridine-positive cells and glial cells, as well as, a significant decrease in the number of neuroblasts in the SVZ. To summarize, in this study we demonstrate how OTA could be a threat to the developing and the adult SVZ through its impact in cell viability, proliferation and differentiation in a dose-dependent manner. PMID:25256750

  6. Brain imaging of language plasticity in adopted adults: can a second language replace the first?

    Science.gov (United States)

    Pallier, C; Dehaene, S; Poline, J-B; LeBihan, D; Argenti, A-M; Dupoux, E; Mehler, J

    2003-02-01

    Do the neural circuits that subserve language acquisition lose plasticity as they become tuned to the maternal language? We tested adult subjects born in Korea and adopted by French families in childhood; they have become fluent in their second language and report no conscious recollection of their native language. In behavioral tests assessing their memory for Korean, we found that they do not perform better than a control group of native French subjects who have never been exposed to Korean. We also used event-related functional magnetic resonance imaging to monitor cortical activations while the Korean adoptees and native French listened to sentences spoken in Korean, French and other, unknown, foreign languages. The adopted subjects did not show any specific activations to Korean stimuli relative to unknown languages. The areas activated more by French stimuli than by foreign stimuli were similar in the Korean adoptees and in the French native subjects, but with relatively larger extents of activation in the latter group. We discuss these data in light of the critical period hypothesis for language acquisition.

  7. Phonetically Irregular Word Pronunciation and Cortical Thickness in the Adult Brain

    Science.gov (United States)

    Blackmon, Karen; Barr, William B.; Kuzniecky, Ruben; DuBois, Jonathan; Carlson, Chad; Quinn, Brian T.; Blumberg, Mark; Halgren, Eric; Hagler, Donald J.; Mikhly, Mark; Devinsky, Orrin; McDonald, Carrie R.; Dale, Anders M.; Thesen, Thomas

    2010-01-01

    Accurate pronunciation of phonetically irregular words (exception words) requires prior exposure to unique relationships between orthographic and phonemic features. Whether such word knowledge is accompanied by structural variation in areas associated with orthographic-to-phonemic transformations has not been investigated. We used high resolution MRI to determine whether performance on a visual word-reading test composed of phonetically irregular words, the Wechsler Test of Adult Reading (WTAR), is associated with regional variations in cortical structure. A sample of 60 right-handed, neurologically intact individuals were administered the WTAR and underwent 3T volumetric MRI. Using quantitative, surface-based image analysis, cortical thickness was estimated at each vertex on the cortical mantle and correlated with WTAR scores while controlling for age. Higher scores on the WTAR were associated with thicker cortex in bilateral anterior superior temporal gyrus, bilateral angular gyrus/posterior superior temporal gyrus, and left hemisphere intraparietal sulcus. Higher scores were also associated with thinner cortex in left hemisphere posterior fusiform gyrus and central sulcus, bilateral inferior frontal gyrus, and right hemisphere lingual gyrus and supramarginal gyrus. These results suggest that the ability to correctly pronounce phonetically irregular words is associated with structural variations in cortical areas that are commonly activated in functional neuroimaging studies of word reading, including areas associated with grapheme-to–phonemic conversion. PMID:20302944

  8. The SRI24 multichannel atlas of normal adult human brain structure.

    Science.gov (United States)

    Rohlfing, Torsten; Zahr, Natalie M; Sullivan, Edith V; Pfefferbaum, Adolf

    2010-05-01

    This article describes the SRI24 atlas, a new standard reference system of normal human brain anatomy, that was created using template-free population registration of high-resolution magnetic resonance images acquired at 3T in a group of 24 normal control subjects. The atlas comprises anatomical channels (T1, T2, and proton density weighted), diffusion-related channels (fractional anisotropy, mean diffusivity, longitudinal diffusivity, mean diffusion-weighted image), tissue channels (CSF probability, gray matter probability, white matter probability, tissue labels), and two cortical parcellation maps. The SRI24 atlas enables multichannel atlas-to-subject image registration. It is uniquely versatile in that it is equally suited for the two fundamentally different atlas applications: label propagation and spatial normalization. Label propagation, herein demonstrated using diffusion tensor image fiber tracking, is enabled by the increased sharpness of the SRI24 atlas compared with other available atlases. Spatial normalization, herein demonstrated using data from a young-old group comparison study, is enabled by its unbiased average population shape property. For both propagation and normalization, we also report the results of quantitative comparisons with seven other published atlases: Colin27, MNI152, ICBM452 (warp5 and air12), and LPBA40 (SPM5, FLIRT, AIR). Our results suggest that the SRI24 atlas, although based on 3T MR data, allows equally accurate spatial normalization of data acquired at 1.5T as the comparison atlases, all of which are based on 1.5T data. Furthermore, the SRI24 atlas is as suitable for label propagation as the comparison atlases and detailed enough to allow delineation of anatomical structures for this purpose directly in the atlas. PMID:20017133

  9. The pattern and loci of training-induced brain changes in healthy older adults are predicted by the nature of the intervention.

    Directory of Open Access Journals (Sweden)

    Sylvie Belleville

    Full Text Available There is enormous interest in designing training methods for reducing cognitive decline in healthy older adults. Because it is impaired with aging, multitasking has often been targeted and has been shown to be malleable with appropriate training. Investigating the effects of cognitive training on functional brain activation might provide critical indication regarding the mechanisms that underlie those positive effects, as well as provide models for selecting appropriate training methods. The few studies that have looked at brain correlates of cognitive training indicate a variable pattern and location of brain changes--a result that might relate to differences in training formats. The goal of this study was to measure the neural substrates as a function of whether divided attentional training programs induced the use of alternative processes or whether it relied on repeated practice. Forty-eight older adults were randomly allocated to one of three training programs. In the single repeated training, participants practiced an alphanumeric equation and a visual detection task, each under focused attention. In the divided fixed training, participants practiced combining verification and detection by divided attention, with equal attention allocated to both tasks. In the divided variable training, participants completed the task by divided attention, but were taught to vary the attentional priority allocated to each task. Brain activation was measured with fMRI pre- and post-training while completing each task individually and the two tasks combined. The three training programs resulted in markedly different brain changes. Practice on individual tasks in the single repeated training resulted in reduced brain activation whereas divided variable training resulted in a larger recruitment of the right superior and middle frontal gyrus, a region that has been involved in multitasking. The type of training is a critical factor in determining the pattern of

  10. Promotion of Cortical Neurogenesis from the Neural Stem Cells in the Adult Mouse Subcallosal Zone.

    Science.gov (United States)

    Kim, Joo Yeon; Choi, Kyuhyun; Shaker, Mohammed R; Lee, Ju-Hyun; Lee, Boram; Lee, Eunsoo; Park, Jae-Yong; Lim, Mi-Sun; Park, Chang-Hwan; Shin, Ki Soon; Kim, Hyun; Geum, Dongho; Sun, Woong

    2016-04-01

    Neurogenesis occurs spontaneously in the subventricular zone (SVZ) of the lateral ventricle in adult rodent brain, but it has long been debated whether there is sufficient adult neurogenesis in human SVZ. Subcallosal zone (SCZ), a posterior continuum of SVZ closely associated with posterior regions of cortical white matter, has also been reported to contain adult neural stem cells (aNSCs) in both rodents and humans. However, little is known whether SCZ-derived aNSC (SCZ-aNSCs) can produce cortical neurons following brain injury. We found that SCZ-aNSCs exhibited limited neuronal differentiation potential in culture and after transplantation in mice. Neuroblasts derived from SCZ initially migrated toward injured cortex regions following brain injury, but later exhibited apoptosis. Overexpression of anti-apoptotic bcl-xL in the SCZ by retroviral infection rescued neuroblasts from cell death in the injured cortex, but neuronal maturation was still limited, resulting in atrophy. In combination with Bcl-xL, infusion of brain-derived neurotropic factor rescued atrophy, and importantly, a subset of such SCZ-aNSCs differentiated and attained morphological and physiological characteristics of mature, excitatory neurons. These results suggest that the combination of anti-apoptotic and neurotrophic factors might enable the use of aNSCs derived from the SCZ in cortical neurogenesis for neural replacement therapy. Stem Cells 2016;34:888-901. PMID:26701067

  11. Age-dependent actions of dexamethasone on the development of focal hypoxic-ischemic brain in new-born and adult rats

    International Nuclear Information System (INIS)

    Complete text of publication follows. The pharmacotherapy of hypoxic-ischemic (H-I) brain oedema is poorly characterized. Several clinical trials have shown that glucocorticoids exert a harmful effect in patients with cerebral ischemia, but others have described opposite results. The mechanism of H-I brain oedema and cell death is not fully elucidated yet. It is well-known that glucocorticoids have membrane stabilizing and antioxidants properties. These types of steroids may indirectly act on different enzymes playing role in H-I damage. The hypoxic brain oedema is associated with impaired water metabolism and brain water electrolyte contents change. The aim of the present study was to examine whether the neuroprotective effect of the dexamethasone on focal H-I cytotoxic and vasogenic brain oedema depends on its penetration into the brain tissue or is exerted by other mechanisms. We measured the effect of glucocorticoid dexamethasone, antiglucocorticoid mifepristone (RU 486) and their combination on focal H-I cytotoxic and vasogenic brain oedema in neonate and adult rats. We also studied different calcium-channel inhibitors influence on the survival of the H-I animals. Mifepristone alone had no effect however antagonized the inhibitory effect of dexamethasone in ipsilateral hemisphere of 1-week old rats. Our work demonstrates that dexamethasone can penetrate into both ipsilateral and contralateral hemispheres of the one and two-weeks-old rats but not in 4 or 12-weeks-old animals. Thus, the results suggest that the site of protective action of dexamethasone is in the brain tissue and the penetration of it depends on the total development of blood-brain barrier.

  12. Epidermal Growth Factor Treatment of the Adult Brain Subventricular Zone Leads to Focal Microglia/Macrophage Accumulation and Angiogenesis

    Directory of Open Access Journals (Sweden)

    Olle R. Lindberg

    2014-04-01

    Full Text Available One of the major components of the subventricular zone (SVZ neurogenic niche is the specialized vasculature. The SVZ vasculature is thought to be important in regulating progenitor cell proliferation and migration. Epidermal growth factor (EGF is a mitogen with a wide range of effects. When stem and progenitor cells in the rat SVZ are treated with EGF, using intracerebroventricular infusion, dysplastic polyps are formed. Upon extended infusion, blood vessels are recruited into the polyps. In the current study we demonstrate how polyps develop through distinct stages leading up to angiogenesis. As polyps progress, microglia/macrophages accumulate in the polyp core concurrent with increasing cell death. Both microglia/macrophage accumulation and cell death peak during angiogenesis and subsequently decline following polyp vascularization. This model of inducible angiogenesis in the SVZ neurogenic niche suggests involvement of microglia/macrophages in acquired angiogenesis and can be used in detail to study angiogenesis in the adult brain.

  13. Induced neural stem cells achieve long-term survival and functional integration in the adult mouse brain.

    Science.gov (United States)

    Hemmer, Kathrin; Zhang, Mingyue; van Wüllen, Thea; Sakalem, Marna; Tapia, Natalia; Baumuratov, Aidos; Kaltschmidt, Christian; Kaltschmidt, Barbara; Schöler, Hans R; Zhang, Weiqi; Schwamborn, Jens C

    2014-09-01

    Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]). iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC) technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications. PMID:25241741

  14. Induced Neural Stem Cells Achieve Long-Term Survival and Functional Integration in the Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    Kathrin Hemmer

    2014-09-01

    Full Text Available Differentiated cells can be converted directly into multipotent neural stem cells (i.e., induced neural stem cells [iNSCs]. iNSCs offer an attractive alternative to induced pluripotent stem cell (iPSC technology with regard to regenerative therapies. Here, we show an in vivo long-term analysis of transplanted iNSCs in the adult mouse brain. iNSCs showed sound in vivo long-term survival rates without graft overgrowths. The cells displayed a neural multilineage potential with a clear bias toward astrocytes and a permanent downregulation of progenitor and cell-cycle markers, indicating that iNSCs are not predisposed to tumor formation. Furthermore, the formation of synaptic connections as well as neuronal and glial electrophysiological properties demonstrated that differentiated iNSCs migrated, functionally integrated, and interacted with the existing neuronal circuitry. We conclude that iNSC long-term transplantation is a safe procedure; moreover, it might represent an interesting tool for future personalized regenerative applications.

  15. Acute high-intensity exercise-induced cognitive enhancement and brain-derived neurotrophic factor in young, healthy adults.

    Science.gov (United States)

    Hwang, Jungyun; Brothers, R Matthew; Castelli, Darla M; Glowacki, Elizabeth M; Chen, Yen T; Salinas, Mandy M; Kim, Jihoon; Jung, Yeonhak; Calvert, Hannah G

    2016-09-01

    Acute exercise can positively impact cognition. The present study examined the effect of acute high-intensity aerobic exercise on prefrontal-dependent cognitive performance and brain-derived neurotrophic factor (BDNF). Fifty-eight young adults were randomly assigned to one of two experimental groups: (a) an acute bout of high-intensity exercise (n=29) or (b) a non-exercise control (n=29). Participants in the exercise group improved performance on inhibitory control in Stroop interference and on cognitive flexibility in Trail Making Test (TMT) Part-B compared with participants in the control group and increased BDNF immediately after exercise. There was a significant relationship between BDNF and TMT Part-B on the pre-post change following exercise. These findings provide support for the association between improved prefrontal-dependent cognitive performance and increased BDNF in response to acute exercise. We conclude that the changes in BDNF concentration may be partially responsible for prefrontal-dependent cognitive functioning following an acute bout of exercise. PMID:27450438

  16. Regrowing the adult brain: NF-κB controls functional circuit formation and tissue homeostasis in the dentate gyrus.

    Directory of Open Access Journals (Sweden)

    Yvonne Imielski

    Full Text Available Cognitive decline during aging is correlated with a continuous loss of cells within the brain and especially within the hippocampus, which could be regenerated by adult neurogenesis. Here we show that genetic ablation of NF-κB resulted in severe defects in the neurogenic region (dentate gyrus of the hippocampus. Despite increased stem cell proliferation, axogenesis, synaptogenesis and neuroprotection were hampered, leading to disruption of the mossy fiber pathway and to atrophy of the dentate gyrus during aging. Here, NF-κB controls the transcription of FOXO1 and PKA, regulating axogenesis. Structural defects culminated in behavioral impairments in pattern separation. Re-activation of NF-κB resulted in integration of newborn neurons, finally to regeneration of the dentate gyrus, accompanied by a complete recovery of structural and behavioral defects. These data identify NF-κB as a crucial regulator of dentate gyrus tissue homeostasis suggesting NF-κB to be a therapeutic target for treating cognitive and mood disorders.

  17. Screening for psychological distress in adult primary brain tumor patients and caregivers: considerations for cancer care coordination

    Directory of Open Access Journals (Sweden)

    Wafa eTrad

    2015-09-01

    Full Text Available IntroductionThis study aimed to assess psychological distress (PD as scored by the Distress Thermometer (DT in adult primary brain tumor (PBT patients and caregivers in a clinic setting, and ascertain if any high risk sub-groups for PD exist. Material and MethodsFrom May 2012 to August 2013, n=96 patients and n=32 caregivers (CG underwent DT screening at diagnosis, and a differing cohort of n=12 patients and n=14 caregivers at first recurrence. Groups were described by diagnosis (high grade, low grade and benign, and English versus non-English speaking. Those with DT score≥4 met caseness criteria for referral to psycho-oncology services. One-way ANOVA tests were conducted to test for between group differences where appropriate.ResultsAt diagnosis and first recurrence, 37.5% and 75.0% (respectively of patients had DT scores above the cut-off for distress. At diagnosis, 78.1% of caregivers met caseness criteria for distress. All caregivers at recurrence met distress criterion. Patients with high grade glioma had significantly higher scores than those with a benign tumor. For patients at diagnosis, non-English speaking participants did not report significantly higher DT scores than English speaking participants.DiscussionPsychological distress is particularly elevated in caregivers, and in patients with high grade glioma at diagnosis. Effective PD screening, triage and referral by skilled care coordinators is vital to enable timely needs assessment, psychological support and effective intervention.

  18. fMRI brain activation during a delay discounting task in HIV-positive adults with and without cocaine dependence

    Science.gov (United States)

    Meade, Christina S.; Lowen, Steven B.; MacLean, Robert R.; Key, Mary D.; Lukas, Scott E.

    2011-01-01

    Cocaine use is associated with poorer HIV clinical outcomes and may contribute to neurobiological impairments associated with impulsive decision making. This study examined the effect of cocaine dependence on brain activation during a delay discounting task involving choices between smaller immediate rewards and larger delayed ones. Participants were 39 HIV-positive adults on antiretroviral therapy who had current cocaine dependence (“active,” n=15), past cocaine dependence (“recovered,” n=13), or no lifetime substance dependence (“naïve,” n=11). Based on responses on a traditional delay discounting task, three types of choices were individualized for presentation during fMRI scanning: hard (similarly valued), easy (disparately valued), and no (single option). Active participants had significantly smaller increases in activation than naïve participants during hard versus easy choices bilaterally in the precentral gyrus and anterior cingulate cortex and in the right frontal pole (including dorsolateral, ventrolateral, and orbitofrontal cortex). During hard and easy choices relative to no choices, active participants had smaller increases in activation compared to naïve participants in frontoparietal cortical regions. These deficits in the executive network during delay discounting choices may contribute to impulsive decision making among HIV-positive cocaine users, with implications for risk behaviors associated with disease transmission and progression. PMID:21546221

  19. Resurrecting Brinley Plots for a Novel Use: Meta-Analyses of Functional Brain Imaging Data in Older Adults

    Directory of Open Access Journals (Sweden)

    Ann M. Peiffer

    2008-01-01

    Full Text Available By plotting response times of young and older adults across a variety of tasks, Brinley spurred investigation and debate into the theory of general cognitive slowing. Though controversial, Brinley plots can assess between-task differences, the impact of increasing task demand, and the relationship between responses in two groups of subjects. Since a relationship exists between response times and the blood-oxygen level dependent (BOLD signal of functional MRI (fMRI, Brinley's plotting method could be applied as a meta-analysis tool in fMRI studies of aging. Here, fledgling “Peiffer plots” are discussed for their potential impact on understanding general cognitive brain activity in aging. Preliminary results suggest that general cognitive slowing may be localized at the sensorimotor transformation in the precentral gyrus. Although this meta-analysis method is naturally used with imaging studies of aging, theoretically it may be applied to other study pairs (e.g., schizophrenic versus normal or imaging datasets (e.g., PET.

  20. Forecasting rodent outbreaks in Africa

    DEFF Research Database (Denmark)

    Leirs, Herwig; Verhagen, Ron; Verheyen, Walter;

    1996-01-01

    1. Rainfall data were collated for years preceding historical outbreaks of Mastomys rats in East Africa in order to test the hypothesis that such outbreaks occur after long dry periods. 2. Rodent outbreaks were generally not preceded by long dry periods. 3. Population dynamics of Mastomys natalen...

  1. The Ethics of Rodent Control

    NARCIS (Netherlands)

    Meerburg, B.G.; Brom, F.W.A.; Kijlstra, A.

    2008-01-01

    Because western societies generally see animals as objects of moral concern, demands have been made on the way they are treated, e.g. during animal experimentation. In the case of rodent pests, however, inhumane control methods are often applied. This inconsistency in the human-animal relationship r

  2. 21 CFR 1250.96 - Rodent control.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Rodent control. 1250.96 Section 1250.96 Food and... SANITATION Sanitation Facilities and Conditions on Vessels § 1250.96 Rodent control. Vessels shall be... of rodent control....

  3. Adult human brain neural progenitor cells (NPCs and fibroblast-like cells have similar properties in vitro but only NPCs differentiate into neurons.

    Directory of Open Access Journals (Sweden)

    Thomas In-Hyeup Park

    Full Text Available The ability to culture neural progenitor cells from the adult human brain has provided an exciting opportunity to develop and test potential therapies on adult human brain cells. To achieve a reliable and reproducible adult human neural progenitor cell (AhNPC culture system for this purpose, this study fully characterized the cellular composition of the AhNPC cultures, as well as the possible changes to this in vitro system over prolonged culture periods. We isolated cells from the neurogenic subventricular zone/hippocampus (SVZ/HP of the adult human brain and found a heterogeneous culture population comprised of several types of post-mitotic brain cells (neurons, astrocytes, and microglia, and more importantly, two distinct mitotic cell populations; the AhNPCs, and the fibroblast-like cells (FbCs. These two populations can easily be mistaken for a single population of AhNPCs, as they both proliferate under AhNPC culture conditions, form spheres and express neural progenitor cell and early neuronal markers, all of which are characteristics of AhNPCs in vitro. However, despite these similarities under proliferating conditions, under neuronal differentiation conditions, only the AhNPCs differentiated into functional neurons and glia. Furthermore, AhNPCs showed limited proliferative capacity that resulted in their depletion from culture by 5-6 passages, while the FbCs, which appear to be from a neurovascular origin, displayed a greater proliferative capacity and dominated the long-term cultures. This gradual change in cellular composition resulted in a progressive decline in neurogenic potential without the apparent loss of self-renewal in our cultures. These results demonstrate that while AhNPCs and FbCs behave similarly under proliferative conditions, they are two different cell populations. This information is vital for the interpretation and reproducibility of AhNPC experiments and suggests an ideal time frame for conducting Ah

  4. Effect of voluntary alcohol consumption on Maoa expression in the mesocorticolimbic brain of adult male rats previously exposed to prolonged maternal separation. : Maoa,ELS and alcohol

    OpenAIRE

    Bendre, Megha; Comasco, Erika; Nylander, Ingrid; Nilsson, Kent W.

    2015-01-01

    Discordant associations between monoamine oxidase A (MAOA) genotype and high alcohol drinking have been reported in human and non-human primates. Environmental influences likely moderate genetic susceptibility. The biological basis for this interplay remains elusive, and inconsistencies call for translational studies in which conditions can be controlled and brain tissue is accessible. The present study investigated whether early life stress and subsequent adult episodic alcohol consumption a...

  5. Willingness to Favor Aggressive Care and Live with Disability Following Severe Traumatic Brain Injury: A Survey of Healthy Young Adults in Hawai‘i

    OpenAIRE

    Nakagawa, Kazuma; Obana, Kyle K

    2014-01-01

    Traumatic brain injury (TBI) is a major public health problem that significantly impacts young adults. Since severe TBI patients lack decision-making capacity, the providers and patient surrogates are often faced with the challenging task of deciding whether to continue with aggressive life-prolonging care or to transition to comfort-focused care with an expected outcome of natural death. The assumption is often made that aggressive care is appropriate for young patients who suffer severe TBI...

  6. Affective communication in rodents: ultrasonic vocalizations as a tool for research on emotion and motivation.

    Science.gov (United States)

    Wöhr, Markus; Schwarting, Rainer K W

    2013-10-01

    Mice and rats emit and perceive calls in the ultrasonic range, i.e., above the human hearing threshold of about 20 kHz: so-called ultrasonic vocalizations (USV). Juvenile and adult rats emit 22-kHz USV in aversive situations, such as predator exposure and fighting or during drug withdrawal, whereas 50-kHz USV occur in appetitive situations, such as rough-and-tumble play and mating or in response to drugs of abuse, e.g., amphetamine. Aversive 22-kHz USV and appetitive 50-kHz USV serve distinct communicative functions. Whereas 22-kHz USV induce freezing behavior in the receiver, 50-kHz USV lead to social approach behavior. These opposite behavioral responses are paralleled by distinct patterns of brain activation. Freezing behavior in response to 22-kHz USV is paralleled by increased neuronal activity in brain areas regulating fear and anxiety, such as the amygdala and periaqueductal gray, whereas social approach behavior elicited by 50-kHz USV is accompanied by reduced activity levels in the amygdala but enhanced activity in the nucleus accumbens, a brain area implicated in reward processing. These opposing behavioral responses, together with distinct patterns of brain activation, particularly the bidirectional tonic activation or deactivation of the amygdala elicited by 22-kHz and 50-kHz USV, respectively, concur with a wealth of behavioral and neuroimaging studies in humans involving emotionally salient stimuli, such as fearful and happy facial expressions. Affective ultrasonic communication therefore offers a translational tool for studying the neurobiology underlying socio-affective communication. This is particularly relevant for rodent models of neurodevelopmental disorders characterized by social and communication deficits, such as autism and schizophrenia.

  7. Fast gene transfer into the adult zebrafish brain by herpes simplex virus 1 (HSV-1 and electroporation: methods and optogenetic applications

    Directory of Open Access Journals (Sweden)

    Ming eZou

    2014-05-01

    Full Text Available The zebrafish has various advantages as a model organism to analyze the structure and function of neural circuits but efficient viruses or other tools for fast gene transfer are lacking. We show that transgenes can be introduced directly into the adult zebrafish brain by herpes simplex type I viruses (HSV-1 or electroporation. We developed a new procedure to target electroporation to defined brain areas and identified promoters that produced strong long-term expression. The fast workflow of electroporation was exploited to express multiple channelrhodopsin-2 variants and genetically encoded calcium indicators in telencephalic neurons for measurements of neuronal activity and synaptic connectivity. The results demonstrate that HSV-1 and targeted electroporation are efficient tools for gene delivery into the zebrafish brain, similar to adeno-associated viruses and lentiviruses in other species. These methods fill an important gap in the spectrum of molecular tools for zebrafish and are likely to have a wide range of applications.

  8. Intraperitoneal Exposure to Nano/Microparticles of Fullerene (C60) Increases Acetylcholinesterase Activity and Lipid Peroxidation in Adult Zebrafish (Danio rerio) Brain

    Science.gov (United States)

    Dal Forno, Gonzalo Ogliari; Kist, Luiza Wilges; de Azevedo, Mariana Barbieri; Fritsch, Rachel Seemann; Pereira, Talita Carneiro Brandão; Britto, Roberta Socoowski; Guterres, Sílvia Stanisçuaski; Külkamp-Guerreiro, Irene Clemes; Bonan, Carla Denise; Monserrat, José María; Bogo, Maurício Reis

    2013-01-01

    Even though technologies involving nano/microparticles have great potential, it is crucial to determine possible toxicity of these technological products before extensive use. Fullerenes C60 are nanomaterials with unique physicochemical and biological properties that are important for the development of many technological applications. The aim of this study was to evaluate the consequences of nonphotoexcited fullerene C60 exposure in brain acetylcholinesterase expression and activity, antioxidant responses, and oxidative damage using adult zebrafish as an animal model. None of the doses tested (7.5, 15, and 30 mg/kg) altered AChE activity, antioxidant responses, and oxidative damage when zebrafish were exposed to nonphotoexcited C60 nano/microparticles during 6 and 12 hours. However, adult zebrafish exposed to the 30 mg/kg dose for 24 hours have shown enhanced AChE activity and augmented lipid peroxidation (TBARS assays) in brain. In addition, the up-regulation of brain AChE activity was neither related to the transcriptional control (RT-qPCR analysis) nor to the direct action of nonphotoexcited C60 nano/microparticles on the protein (in vitro results) but probably involved a posttranscriptional or posttranslational modulation of this enzymatic activity. Taken together these findings provided further evidence of toxic effects on brain after C60 exposure. PMID:23865059

  9. In vivo imaging of neuro-inflammation in the rodent brain with [11C]SSR180575, a novel indoleacetamide radioligand of the translocator protein (18 kDa)

    International Nuclear Information System (INIS)

    Purpose Neuro-inflammation is involved in neurological disorders through the activation of micro-glial cells. Imaging of neuro-inflammation with radioligands for the translocator protein (18 kDa) (TSPO) could prove to be an attractive bio-marker for disease diagnosis and therapeutic evaluation. The indoleacetamide-derived 7-chloro-N, N, 5- trimethyl-4-oxo-3-phenyl-3, 5-dihydro-4H-pyridazino[4, 5-b] indole-1-acetamide, SSR180575, is a selective high-affinity TSPO ligand in human and rodents with neuro-protective effects. Methods Here we report the radiolabelling of SSR180575 with 11C and in vitro and in vivo imaging in an acute model of neuro-inflammation in rats. Results The image contrast and the binding of [11C] SSR180575 are higher than that obtained with the isoquinoline- based TSPO radioligand, [11C]PK11195. Competition studies demonstrate that [11C]SSR180575 has high specific binding for the TSPO. Conclusion [11C]SSR180575 is the first PET radioligand for the TSPO based on an indoleacetamide scaffold designed for imaging neuro-inflammation in animal models and in the clinic. (authors)

  10. Diffusion tensor imaging reveals adolescent binge ethanol-induced brain structural integrity alterations in adult rats that correlate with behavioral dysfunction.

    Science.gov (United States)

    Vetreno, Ryan P; Yaxley, Richard; Paniagua, Beatriz; Crews, Fulton T

    2016-07-01

    Adolescence is characterized by considerable brain maturation that coincides with the development of adult behavior. Binge drinking is common during adolescence and can have deleterious effects on brain maturation because of the heightened neuroplasticity of the adolescent brain. Using an animal model of adolescent intermittent ethanol [AIE; 5.0 g/kg, intragastric, 20 percent EtOH w/v; 2 days on/2 days off from postnatal day (P)25 to P55], we assessed the adult brain structural volumes and integrity on P80 and P220 using diffusion tensor imaging (DTI). While we did not observe a long-term effect of AIE on structural volumes, AIE did reduce axial diffusivity (AD) in the cerebellum, hippocampus and neocortex. Radial diffusivity (RD) was reduced in the hippocampus and neocortex of AIE-treated animals. Prior AIE treatment did not affect fractional anisotropy (FA), but did lead to long-term reductions of mean diffusivity (MD) in both the cerebellum and corpus callosum. AIE resulted in increased anxiety-like behavior and diminished object recognition memory, the latter of which was positively correlated with DTI measures. Across aging, whole brain volumes increased, as did volumes of the corpus callosum and neocortex. This was accompanied by age-associated AD reductions in the cerebellum and neocortex as well as RD and MD reductions in the cerebellum. Further, we found that FA increased in both the cerebellum and corpus callosum as rats aged from P80 to P220. Thus, both age and AIE treatment caused long-term changes to brain structural integrity that could contribute to cognitive dysfunction. PMID:25678360

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

    Directory of Open Access Journals (Sweden)

    Masaaki Kanai

    2010-07-01

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

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

    OpenAIRE

    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. Fort...

  13. Physical Exercise Habits Correlate with Gray Matter Volume of the Hippocampus in Healthy Adult Humans

    Science.gov (United States)

    Killgore, William D. S.; Olson, Elizabeth A.; Weber, Mareen

    2013-12-01

    Physical activity facilitates neurogenesis of dentate cells in the rodent hippocampus, a brain region critical for memory formation and spatial representation. Recent findings in humans also suggest that aerobic exercise can lead to increased hippocampal volume and enhanced cognitive functioning in children and elderly adults. However, the association between physical activity and hippocampal volume during the period from early adulthood through middle age has not been effectively explored. Here, we correlated the number of minutes of self-reported exercise per week with gray matter volume of the hippocampus using voxel-based morphometry (VBM) in 61 healthy adults ranging from 18 to 45 years of age. After controlling for age, gender, and total brain volume, total minutes of weekly exercise correlated significantly with volume of the right hippocampus. Findings highlight the relationship between regular physical exercise and brain structure during early to middle adulthood.

  14. Menstrual cycle-dependent neural plasticity in the adult human brain is hormone, task, and region specific.

    OpenAIRE

    Fernandez, G.S.E.; Weis, S.; Stoffel-Wagner, B.; Tendolkar, I.; Reuber, M; Beyenburg, S; Klaver, P.; Fell, J.; Greiff, A. de; Ruhlmann, J; Reul, J.; Elger, C E

    2003-01-01

    In rodents, cyclically fluctuating levels of gonadal steroid hormones modulate neural plasticity by altering synaptic transmission and synaptogenesis. Alterations of mood and cognition observed during the menstrual cycle suggest that steroid-related plasticity also occurs in humans. Cycle phase-dependent differences in cognitive performance have almost exclusively been found in tasks probing lateralized neuronal domains, i.e., cognitive domains such as language, which are predominantly execut...

  15. Associations between a History of Traumatic Brain Injuries and Current Cigarette Smoking, Substance Use, and Elevated Psychological Distress in a Population Sample of Canadian Adults.

    Science.gov (United States)

    Ilie, Gabriela; Adlaf, Edward M; Mann, Robert E; Ialomiteanu, Anca; Hamilton, Hayley; Rehm, Jürgen; Asbridge, Mark; Cusimano, Michael D

    2015-07-15

    This study describes the prevalence of reported history of traumatic brain injury (TBI) and its association with reports of current substance use, cigarette smoking, and psychological distress among Canadian adults in a population sample. A cross-sectional sample of 1999 Ontario adults 18-93 years of age were surveyed by telephone in 2011 as part of the Center for Addiction and Mental Health's ongoing representative survey of adult mental health and substance use in Ontario, Canada. Loss of consciousness for at least 5 min or at least one overnight hospitalization resulting from symptoms associated with the TBI injury represented minimum criteria for TBI. An estimated 16.8% (95% confidence interval, 14.8, 19.0) of adults reported a TBI in their lifetime. Men had higher prevalence of TBI than women. Adults who reported a history of TBI had higher odds of reported past-year daily smoking (adjusted odds ratio [AOR] = 2.15), using cannabis (AOR = 2.80) and nonmedical opioids (AOR = 2.90), as well as screened significantly for recent elevated psychological distress (AOR = 1.97) in the past few weeks, compared to adults without a history of TBI. Co-occurrence of a history of TBI with current elevated psychological distress and substance use warrants vigilance among medical practitioners to assess the possibility of a history of TBI during reviews of the history leading to the occurrence of these conditions.

  16. Associations between a History of Traumatic Brain Injuries and Current Cigarette Smoking, Substance Use, and Elevated Psychological Distress in a Population Sample of Canadian Adults.

    Science.gov (United States)

    Ilie, Gabriela; Adlaf, Edward M; Mann, Robert E; Ialomiteanu, Anca; Hamilton, Hayley; Rehm, Jürgen; Asbridge, Mark; Cusimano, Michael D

    2015-07-15

    This study describes the prevalence of reported history of traumatic brain injury (TBI) and its association with reports of current substance use, cigarette smoking, and psychological distress among Canadian adults in a population sample. A cross-sectional sample of 1999 Ontario adults 18-93 years of age were surveyed by telephone in 2011 as part of the Center for Addiction and Mental Health's ongoing representative survey of adult mental health and substance use in Ontario, Canada. Loss of consciousness for at least 5 min or at least one overnight hospitalization resulting from symptoms associated with the TBI injury represented minimum criteria for TBI. An estimated 16.8% (95% confidence interval, 14.8, 19.0) of adults reported a TBI in their lifetime. Men had higher prevalence of TBI than women. Adults who reported a history of TBI had higher odds of reported past-year daily smoking (adjusted odds ratio [AOR] = 2.15), using cannabis (AOR = 2.80) and nonmedical opioids (AOR = 2.90), as well as screened significantly for recent elevated psychological distress (AOR = 1.97) in the past few weeks, compared to adults without a history of TBI. Co-occurrence of a history of TBI with current elevated psychological distress and substance use warrants vigilance among medical practitioners to assess the possibility of a history of TBI during reviews of the history leading to the occurrence of these conditions. PMID:25496189

  17. NF-kappaB in long-term memory and structural plasticity in the adult mammalian brain

    Directory of Open Access Journals (Sweden)

    Barbara eKaltschmidt

    2015-11-01

    Full Text Available The transcription factor nuclear factor kappaB (NF-κB is a well known regulator of inflammation, stress and immune responses as well as cell survival. In the nervous system NF-κB is one of the crucial components in the molecular switch, that converts short- to long-term memory, a process requiring de novo gene expression. Here, we will review published research on NF-κB and downstream target genes in mammals, which are necessary for structural plasticity and long-term memory, both under normal and pathological conditions in the brain. Genetic evidence has revealed that NF-κB does regulate neuroprotection, neuronal transmission and long-term memory. Additionally, after genetic ablation of all NF-κB subunits, a severe defect in hippocampal adult neurogenesis was observed during aging. Proliferation of neural precursors is increased, however axon outgrowth, synaptogenesis and tissue homeostasis of the dentate gyrus is hampered. In this process, the NF-κB target gene PKAcat and other downstream target genes such as Igf2 are critically involved. Thus, NF-κB activity seems to be crucial in regulating structural plasticity and replenishment of granule cells within the hippocampus throughout life. In addition to the function of NF-κB in neurons we will discuss data on a neuro-inflammatory role of the transcription factor in glia. Finally a model for NF-κB homeostasis on the molecular level is presented, in order to explain seemingly contradictory the friend or foe role of NF-κB in the nervous system.

  18. Sex Differences in Mechanisms and Outcome of Neonatal Hypoxia-Ischemia in Rodent Models: Implications for Sex-Specific Neuroprotection in Clinical Neonatal Practice

    OpenAIRE

    Hill, Courtney A.; R. Holly Fitch

    2012-01-01

    Clinical findings show that male infants with