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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

    Directory of Open Access Journals (Sweden)

    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

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    ... 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. Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of Parkinson's disease.

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    Bertilsson, Göran; Patrone, Cesare; Zachrisson, Olof; Andersson, Annica; Dannaeus, Karin; Heidrich, Jessica; Kortesmaa, Jarkko; Mercer, Alex; Nielsen, Elisabet; Rönnholm, Harriet; Wikström, Lilian

    2008-02-01

    We investigated the effects of exendin-4 on neural stem/progenitor cells in the subventricular zone of the adult rodent brain and its functional effects in an animal model of Parkinson's disease. Our results showed expression of GLP-1 receptor mRNA or protein in the subventricular zone and cultured neural stem/progenitor cells isolated from this region. In vitro, exendin-4 increased the number of neural stem/progenitor cells, and the number of cells expressing the neuronal markers microtubule-associated protein 2, beta-III-tubulin, and neuron-specific enolase. When exendin-4 was given intraperitoneally to naïve rodents together with bromodeoxyuridine, a marker for DNA synthesis, both the number of bromodeoxyuridine-positive cells and the number of neuronal precursor cells expressing doublecortin were increased. Exendin-4 was tested in the 6-hydroxydopamine model of Parkinson's disease to investigate its possible functional effects in an animal model with neuronal loss. After unilateral lesion and a 5-week stabilization period, the rats were treated for 3 weeks with exendin-4. We found a reduction of amphetamine-induced rotations in animals receiving exendin-4 that persisted for several weeks after drug administration had been terminated. Histological analysis showed that exendin-4 significantly increased the number of both tyrosine hydroxylase- and vesicular monoamine transporter 2-positive neurons in the substantia nigra. In conclusion, our results show that exendin-4 is able to promote adult neurogenesis in vitro and in vivo, normalize dopamine imbalance, and increase the number of cells positive for markers of dopaminergic neurons in the substantia nigra in a model of Parkinson's disease. PMID:17803225

  5. Cellular scaling rules for rodent brains

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    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...

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

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

    2008-06-10

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

  7. Brain tumor - primary - adults

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    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... wireless devices Head injuries Smoking Hormone therapy SPECIFIC TUMOR TYPES Brain tumors are classified depending on: Location of the ...

  8. 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.

  9. 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) ...

  10. 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

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    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

  11. 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…

  12. Low Level Primary Blast Injury in Rodent Brain

    OpenAIRE

    Pun, Pamela B. L.; Kan, Enci Mary; Salim, Agus; Li, Zhaohui; Ng, Kian Chye; Moochhala, Shabbir M; Ling, Eng-Ang; Tan, Mui Hong; Lu, Jia

    2011-01-01

    The incidence of blast attacks and resulting traumatic brain injuries has been on the rise in recent years. Primary blast is one of the mechanisms in which the blast wave can cause injury to the brain. The aim of this study was to investigate the effects of a single sub-lethal blast over pressure (BOP) exposure of either 48.9 kPa (7.1 psi) or 77.3 kPa (11.3 psi) to rodents in an open-field setting. Brain tissue from these rats was harvested for microarray and histopathological analyses. Gross...

  13. Low level primary blast injury in rodent brain

    OpenAIRE

    Enci MaryKan; AgusSalim; Zhao HuiLi; Eng-AngLing

    2011-01-01

    The incidence of blast attacks and resulting traumatic brain injuries has been on the rise in recent years. Primary blast is one of the mechanisms in which the blast wave can cause injury to the brain. The aim of this study was to investigate the effects of a single sub-lethal blast over pressure exposure of either 48.9 kPa (7.1 psi) or 77.3 kPa (11.3 psi) to rodents in an open-field setting. Brain tissue from these rats was harvested for microarray and histopathological analyses. Gross histo...

  14. Active training for amblyopia in adult rodents

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    Nicoletta Berardi

    2015-10-01

    Full Text Available Amblyopia is the most diffused form of visual function impairment affecting one eye, with a prevalence of 1-5% in the total world population. Amblyopia is usually caused by an early functional imbalance between the two eyes, deriving from anisometropia, strabismus, or congenital cataract, leading to severe deficits in visual acuity, contrast sensitivity and stereopsis. While amblyopia can be efficiently treated in children, it becomes irreversible in adults, as result of a dramatic decline in visual cortex plasticity which occurs at the end of the critical period in the primary visual cortex. Notwithstanding this widely accepted dogma, recent evidence in animal models and in human patients have started to challenge this view, revealing a previously unsuspected possibility to enhance plasticity in the adult visual system and to achieve substantial visual function recovery. Among the new proposed intervention strategies, non invasive procedures based on environmental enrichment, physical exercise or visual perceptual learning appear particularly promising in terms of future applicability in the clinical setting. In this survey, we will review recent literature concerning the application of these behavioral intervention strategies to the treatment of amblyopia, with a focus on possible underlying molecular and cellular mechanisms.

  15. Active training for amblyopia in adult rodents.

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    Sale, Alessandro; Berardi, Nicoletta

    2015-01-01

    Amblyopia is the most diffused form of visual function impairment affecting one eye, with a prevalence of 1-5% in the total world population. Amblyopia is usually caused by an early functional imbalance between the two eyes, deriving from anisometropia, strabismus, or congenital cataract, leading to severe deficits in visual acuity, contrast sensitivity and stereopsis. While amblyopia can be efficiently treated in children, it becomes irreversible in adults, as a result of a dramatic decline in visual cortex plasticity which occurs at the end of the critical period (CP) in the primary visual cortex. Notwithstanding this widely accepted dogma, recent evidence in animal models and in human patients have started to challenge this view, revealing a previously unsuspected possibility to enhance plasticity in the adult visual system and to achieve substantial visual function recovery. Among the new proposed intervention strategies, non invasive procedures based on environmental enrichment, physical exercise or visual perceptual learning (vPL) appear particularly promising in terms of future applicability in the clinical setting. In this survey, we will review recent literature concerning the application of these behavioral intervention strategies to the treatment of amblyopia, with a focus on possible underlying molecular and cellular mechanisms. PMID:26578911

  16. 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...

  17. Acute Blast Injury Reduces Brain Abeta in Two Rodent Species

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    GregoryAElder

    2012-12-01

    Full Text Available Blast-induced traumatic brain injury (TBI has been a major cause of morbidity and mortality in the conflicts in Iraq and Afghanistan. How the primary blast wave affects the brain is not well understood. In particular, it is unclear whether blast injures the brain through mechanisms similar to those found in non-blast closed impact injuries (nbTBI. The β-amyloid (Aβ peptide associated with the development of Alzheimer’s disease (AD is elevated acutely following TBI in humans as well as in experimental animal models of nbTBI. We examined levels of brain Aβ following experimental blast injury using enzyme-linked immunosorbent assays for Aβ 40 and 42. In both rat and mouse models of blast injury, rather than being increased, endogenous rodent brain Aβ levels were decreased acutely following injury. Levels of the amyloid precursor protein (APP were increased following blast exposure although there was no evidence of axonal pathology based on APP immunohistochemical staining. Unlike the findings in nbTBI animal models, levels of the β-secretase, BACE-1, and the γ-secretase component presenilin-1 were unchanged following blast exposure. These studies have implications for understanding the nature of blast injury to the brain. They also suggest that strategies aimed at lowering Aβ production may not be effective for treating acute blast injury to the brain.

  18. 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

  19. 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 wide variety of benign and malignant brain neoplasms and how contemporary radiotherapy affects survival. In each case the intent of radiation therapy is to destroy the neoplasm without affecting normal tissues. However, 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. Successful outcome after radiation therapy of brain tumors usually requires that (1) there is no tumor extension beyond the target volume, (2) adequate dose is delivered to the target volume, and (3) normal tissue tolerance doses are not exceeded. For some tumors it may be impossible to satisfy all three criteria. Three-dimensional treatment planning based on MRI or CT makes it possible to guarantee delivery of the full dose of radiation 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 and are usually preferable to opposed lateral fields. Examples of planning solutions for a variety of tumor types, sizes, and anatomic location will be given. For some tumors, protocols involving substantial dose escalation require a large number of non-coplanar x-ray beams or particle therapy. Several concepts and techniques which relate to the treatment of brain tumors will be discussed, including conformal radiotherapy, brachytherapy, radiosurgery, fractionated stereotactic radiotherapy, altered fractionation, inverse treatment planning, re-irradiation and biologically effective dose (BED)

  20. 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

  1. 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

  2. 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 ...

  3. 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.

  4. 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.

  5. Low level primary blast injury in rodent brain

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    Enci MaryKan

    2011-04-01

    Full Text Available The incidence of blast attacks and resulting traumatic brain injuries has been on the rise in recent years. Primary blast is one of the mechanisms in which the blast wave can cause injury to the brain. The aim of this study was to investigate the effects of a single sub-lethal blast over pressure exposure of either 48.9 kPa (7.1 psi or 77.3 kPa (11.3 psi to rodents in an open-field setting. Brain tissue from these rats was harvested for microarray and histopathological analyses. Gross histopathology of the brains showed that cortical neurons were ‘darkened’ and shrunken with narrowed vasculature in the cerebral cortex day 1 after blast with signs of recovery at day 4 and day 7 after blast. TUNEL-positive cells were predominant in the white matter of the brain at day 1 after blast and double-labeling of brain tissue showed that these DNA-damaged cells were both oligodendrocytes and astrocytes but were mainly not apoptotic due to the low caspase-3 immunopositivity. There was also an increase in amyloid precursor protein immunoreactive cells in the white matter which suggests acute axonal damage. In contrast, Iba-1 staining for macrophages or microglia was not different from control post-blast. Blast exposure altered the expression of over 5786 genes in the brain which occurred mostly at day 1 and day 4 post-blast. These genes were narrowed down to 10 overlapping genes after time-course evaluation and functional analyses. These genes pointed towards signs of repair at day 4 and 7 post-blast. Our findings suggest that the blast over pressure levels in the study resulted in mild cellular injury to the brain as evidenced by acute neuronal, cerebrovascular and white matter perturbations that showed signs of resolution. It is unclear whether these perturbations exist at a milder level or normalize completely and will need more investigation. Specific changes in gene expression may be further evaluated to understand the mechanism of blast

  6. 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.

  7. 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...

  8. Tool use specific adult neurogenesis and synaptogenesis in rodent (Octodon degus hippocampus.

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    Noriko Kumazawa-Manita

    Full Text Available We previously demonstrated that degus (Octodon degus, which are a species of small caviomorph rodents, could be trained to use a T-shaped rake as a hand tool to expand accessible spaces. To elucidate the neurobiological underpinnings of this higher brain function, we compared this tool use learning task with a simple spatial (radial maze memory task and investigated the changes that were induced in the hippocampal neural circuits known to subserve spatial perception and learning. With the exposure to an enriched environment in home cage, adult neurogenesis in the dentate gyrus of the hippocampus was augmented by tool use learning, but not radial maze learning, when compared to control conditions. Furthermore, the proportion of new synapses formed in the CA3 region of the hippocampus, the target area for projections of mossy fiber axons emanating from newborn neurons, was specifically increased by tool use learning. Thus, active tool use behavior by rodents, learned through multiple training sessions, requires the hippocampus to generate more novel neurons and synapses than spatial information processing in radial maze learning.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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

  11. 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...

  12. 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.

  13. Acute Blast Injury Reduces Brain Abeta in Two Rodent Species

    OpenAIRE

    GregoryAElder; MiguelA.Gama Sosa; RitaDe Gasperi; MichaelCShaughness; StevenTDeKosky; SamGandy; MadhusoodanaPNambiar; JohnWSteele

    2012-01-01

    Blast-induced traumatic brain injury (TBI) has been a major cause of morbidity and mortality in the conflicts in Iraq and Afghanistan. How the primary blast wave affects the brain is not well understood. In particular, it is unclear whether blast injures the brain through mechanisms similar to those found in non-blast closed impact injuries (nbTBI). The β-amyloid (Aβ) peptide associated with the development of Alzheimer’s disease (AD) is elevated acutely following TBI in humans as well as in ...

  14. Acute Blast Injury Reduces Brain Abeta in Two Rodent Species

    OpenAIRE

    De Gasperi, Rita; Gama Sosa, Miguel A; Kim, Soong Ho; Steele, John W.; Shaughness, Michael C; Maudlin-Jeronimo, Eric; Hall, Aaron A.; DeKosky, Steven T.; McCarron, Richard M; Nambiar, Madhusoodana P.; Gandy, Sam; Ahlers, Stephen T.; Elder, Gregory A.

    2012-01-01

    Blast-induced traumatic brain injury (TBI) has been a major cause of morbidity and mortality in the conflicts in Iraq and Afghanistan. How the primary blast wave affects the brain is not well understood. In particular, it is unclear whether blast injures the brain through mechanisms similar to those found in non-blast closed impact injuries (nbTBI). The β-amyloid (Aβ) peptide associated with the development of Alzheimer’s disease is elevated acutely following TBI in humans as well as in exper...

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

    Science.gov (United States)

    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

  16. Cytochrome p450 mRNA expression in the rodent brain: species-, sex-, and region-dependent differences.

    Science.gov (United States)

    Stamou, Marianna; Wu, Xianai; Kania-Korwel, Izabela; Lehmler, Hans-Joachim; Lein, Pamela J

    2014-02-01

    Cytochrome P450 (P450) enzymes play a critical role in the activation and detoxication of many neurotoxic chemicals. Although research has largely focused on P450-mediated metabolism in the liver, emerging evidence suggests that brain P450s influence neurotoxicity by modulating local metabolite levels. As a first step toward better understanding the relative role of brain P450s in determining neurotoxic outcome, we characterized mRNA expression of specific P450 isoforms in the rodent brain. Adult mice (male and female) and rats (male) were treated with vehicle, phenobarbital, or dexamethasone. Transcripts for CYP2B, CYP3A, CYP1A2, and the orphan CYP4X1 and CYP2S1 were quantified in the liver, hippocampus, cortex, and cerebellum by quantitative (real-time) polymerase chain reaction. These P450s were all detected in the liver with the exception of CYP4X1, which was detected in rat but not mouse liver. P450 expression profiles in the brain varied regionally. With the exception of the hippocampus, there were no sex differences in regional brain P450 expression profiles in mice; however, there were marked species differences. In the liver, phenobarbital induced CYP2B expression in both species. Dexamethasone induced hepatic CYP2B and CYP3A in mice but not rats. In contrast, brain P450s did not respond to these classic hepatic P450 inducers. Our findings demonstrate that P450 mRNA expression in the brain varies by region, regional brain P450 profiles vary between species, and their induction varies from that of hepatic P450s. These novel data will be useful for designing mechanistic studies to examine the relative role of P450-mediated brain metabolism in neurotoxicity. PMID:24255117

  17. 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.

  18. Differentiation and Death of Premyelinating Oligodendrocytes in Developing Rodent Brain

    OpenAIRE

    Trapp, Bruce D.; Nishiyama, Akiko; Cheng, David; Macklin, Wendy

    1997-01-01

    Previous studies have indicated that newly formed oligodendrocytes are dynamic cells whose production, survival, and differentiation depend upon axonal influences. This study has characterized the appearance and fate of newly formed oligodendrocytes in developing rat brain. Oligodendrocytes appear in predictable locations and radially extend DM-20–positive processes that cover 80-μm domains in the cortex and 40-μm domains in the corpus callosum. These premyelinating oligodendrocytes have one ...

  19. 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

  20. Determination of endogenous corticosterone in rodent's blood, brain and hair with LC-APCI-MS/MS.

    Science.gov (United States)

    Yu, Tian; Xu, Hang; Wang, Weiwen; Li, Shifei; Chen, Zheng; Deng, Huihua

    2015-10-01

    Endogenous corticosterone in rodent's hair would be a potential biomarker to assess the response of the hypothalamus-pituitary-adrenal axis to chronic stress. However, currently unknown is whether hair corticosterone is associated with endogenous corticosterone in blood and brain. The present study aimed to develop an enhanced assay for determination of endogenous corticosterone in blood, brain and hair, and to examine associations of hair corticosterone with blood and brain corticosterone under basal condition and association with blood corticosterone under chronic stressful condition. Hair at the back and blood samples were collected from non-stressed and stressed rodents, and prefrontal lobe and thalamus from non-stressed rodents. Chronic stress exerted on mice was 30-day repeated social defeat. The analyses were done using high performance liquid chromatography tandem mass spectrometry with atmospheric pressure chemical ionization in positive mode. Limits of detection and quantification were 0.2 and 0.5ng/ml for rat's blood, and 0.5 and 1.0pg/mg for rat's hair and brain, and 1.25 and 2.50ng/ml (or pg/mg) for mouse's blood (or hair). Recovery ranged from 84.2 to 108.0%. The intra- and inter-day coefficients of variation were less than 10%. Additionally, correlation of hair corticosterone with blood corticosterone was significant in both mice and rats, but correlations with corticosterone in prefrontal lobe and thalamus were not significant in rats. Both hair and blood corticosterone were significantly higher in stressed mice compared with controls. PMID:26343018

  1. Recommended Methods for Brain Processing and Quantitative Analysis in Rodent Developmental Neurotoxicity Studies.

    Science.gov (United States)

    Garman, Robert H; Li, Abby A; Kaufmann, Wolfgang; Auer, Roland N; Bolon, Brad

    2016-01-01

    Neuropathology methods in rodent developmental neurotoxicity (DNT) studies have evolved with experience and changing regulatory guidance. This article emphasizes principles and methods to promote more standardized DNT neuropathology evaluation, particularly procurement of highly homologous brain sections and collection of the most reproducible morphometric measurements. To minimize bias, brains from all animals at all dose levels should be processed from brain weighing through paraffin embedding at one time using a counterbalanced design. Morphometric measurements should be anchored by distinct neuroanatomic landmarks that can be identified reliably on the faced block or in unstained sections and which address the region-specific circuitry of the measured area. Common test article-related qualitative changes in the developing brain include abnormal cell numbers (yielding altered regional size), displaced cells (ectopia and heterotopia), and/or aberrant differentiation (indicated by defective myelination or synaptogenesis), but rarely glial or inflammatory reactions. Inclusion of digital images in the DNT pathology raw data provides confidence that the quantitative analysis was done on anatomically matched (i.e., highly homologous) sections. Interpreting DNT neuropathology data and their presumptive correlation with neurobehavioral data requires an integrative weight-of-evidence approach including consideration of maternal toxicity, body weight, brain weight, and the pattern of findings across brain regions, doses, sexes, and ages. PMID:26296631

  2. 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

  3. Simplified methods for in vivo measurement of acetylcholinesterase activity in rodent brain

    International Nuclear Information System (INIS)

    Simplified methods for in vivo studies of acetylcholinesterase (AChE) activity in rodent brain were evaluated using N-[11C]methylpiperidinyl propionate ([11C]PMP) as an enzyme substrate. Regional mouse brain distributions were determined at 1 min (representing initial brain uptake) and 30 min (representing trapped product) after intravenous [11C]PMP administration. Single time point tissue concentrations (percent injected dose/gram at 30 min), tissue concentration ratios (striatum/cerebellum and striatum/cortex ratios at 30 min), and regional tissue retention fractions (defined as percent injected dose 30 min/percent injected dose 1 min) were evaluated as measures of AChE enzymatic activity in mouse brain. Studies were carried out in control animals and after dosing with phenserine, a selective centrally active AChE inhibitor; neostigmine, a peripheral cholinesterase inhibitor; and a combination of the two drugs. In control and phenserine-treated animals, absolute tissue concentrations and regional retention fractions provide good measures of dose-dependent inhibition of brain AChE; tissue concentration ratios, however, provide erroneous conclusions. Peripheral inhibition of cholinesterases, which changes the blood pharmacokinetics of the radiotracer, diminishes the sensitivity of all measures to detect changes in central inhibition of the enzyme. We conclude that certain simple measures of AChE hydrolysis rates for [11C]PMP are suitable for studies where alterations of the peripheral blood metabolism of the tracer are kept to a minimum

  4. 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

  5. Stress-induced alterations in large-scale functional networks of the rodent brain.

    Science.gov (United States)

    Henckens, Marloes J A G; van der Marel, Kajo; van der Toorn, Annette; Pillai, Anup G; Fernández, Guillén; Dijkhuizen, Rick M; Joëls, Marian

    2015-01-15

    Stress-related psychopathology is associated with altered functioning of large-scale brain networks. Animal research into chronic stress, one of the most prominent environmental risk factors for development of psychopathology, has revealed molecular and cellular mechanisms potentially contributing to human mental disease. However, so far, these studies have not addressed the system-level changes in extended brain networks, thought to critically contribute to mental disorders. We here tested the effects of chronic stress exposure (10 days immobilization) on the structural integrity and functional connectivity patterns in the brain, using high-resolution structural MRI, diffusion kurtosis imaging, and resting-state functional MRI, while confirming the expected changes in neuronal dendritic morphology using Golgi-staining. Stress effectiveness was confirmed by a significantly lower body weight and increased adrenal weight. In line with previous research, stressed animals displayed neuronal dendritic hypertrophy in the amygdala and hypotrophy in the hippocampal and medial prefrontal cortex. Using independent component analysis of resting-state fMRI data, we identified ten functional connectivity networks in the rodent brain. Chronic stress appeared to increase connectivity within the somatosensory, visual, and default mode networks. Moreover, chronic stress exposure was associated with an increased volume and diffusivity of the lateral ventricles, whereas no other volumetric changes were observed. This study shows that chronic stress exposure in rodents induces alterations in functional network connectivity strength which partly resemble those observed in stress-related psychopathology. Moreover, these functional consequences of stress seem to be more prominent than the effects on gross volumetric change, indicating their significance for future research. PMID:25462693

  6. 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

  7. 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.

  8. 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

  9. Assessment of variability in cerebral vasculature for neuro-anatomical surgery planning in rodent brain

    Science.gov (United States)

    Rangarajan, J. R.; Van Kuyck, K.; Himmelreich, U.; Nuttin, B.; Maes, F.; Suetens, P.

    2011-03-01

    Clinical and pre-clinical studies show that deep brain stimulation (DBS) of targeted brain regions by neurosurgical techniques ameliorate psychiatric disorder such as anorexia nervosa. Neurosurgical interventions in preclinical rodent brain are mostly accomplished manually with a 2D atlas. Considering both the large number of animals subjected to stereotactic surgical experiments and the associated imaging cost, feasibility of sophisticated pre-operative imaging based surgical path planning and/or robotic guidance is limited. Here, we spatially normalize vasculature information and assess the intra-strain variability in cerebral vasculature for a neurosurgery planning. By co-registering and subsequently building a probabilistic vasculature template in a standard space, we evaluate the risk of a user defined electrode trajectory damaging a blood vessel on its path. The use of such a method may not only be confined to DBS therapy in small animals, but also could be readily applicable to a wide range of stereotactic small animal surgeries like targeted injection of contrast agents and cell labeling applications.

  10. Frequency-domain measurements of changes of optical pathlength during spreading depression in a rodent brain model

    Science.gov (United States)

    Maris, Michael B.; Mayevsky, Avraham; Sevick, Eva M.; Chance, Britton

    1991-05-01

    Previously, we have shown that time-resolved spectroscopy can monitor changes in the distribution of photon migration pathlengths which are reflective of the changes in the tissue absorption due primarily to oxygenated or deoxygenated hemoglobin. In this study, we have monitored mean photon migration pathlengths in the frequency domain in the rodent brain insulted by hypoxia, ischemia and spreading depression (SD) using phase modulated spectroscopy (PMS). This technique consisted of monitoring light which emerged from the exposed rodent skull at 8 mm form an incident light source of 754 nm and 816 nm whose intensity was modulated at 220 MHz. The changes in phase-shift, (theta), of the emergent light with respect to the incident light are reflective of the photon pathlengths and hemoglobin absorbance. A multiprobe assembly holding PMS source fiber, nicotinamide dinucleotide (NADH) fluorometric probe, electrocortigraph (ECoG) electrodes, and doppler blood flow probe was placed on the rodent brain to simultaneously monitor brain metabolism, electrical cortical activity (ECoG) and blood flow. The PMS detector fiber was placed 8 mm posterior to the multiprobe assembly. Correlations between changes in intracellular deoxygenation (NADH) and hemoglobin deoxygenation as measured by PMS changes at 754 nm and 816 nm during hypoxia, and ischemia were found. The depolarization phase of spreading depression resulted in a similar increase at both 754 nm and 816 nm. We attribute this result to vasoconstriction and/or the decrease of extracellular space due to water shift in the rodent brain.

  11. 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

  12. 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...

  13. 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...

  14. 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

  15. Quantification of anandamide, oleoylethanolamide and palmitoylethanolamide in rodent brain tissue using high performance liquid chromatography–electrospray mass spectroscopy

    OpenAIRE

    Liput, Daniel J.; Eleftheria Tsakalozou; Hammell, Dana C.; Paudel, Kalpana S.; Kimberly Nixon; Stinchcomb, Audra L.

    2014-01-01

    Reported concentrations for endocannabinoids and related lipids in biological tissues can vary greatly; therefore, methods used to quantify these compounds need to be validated. This report describes a method to quantify anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) from rodent brain tissue. Analytes were extracted using acetonitrile without further sample clean up, resolved on a C18 reverse-phase column using a gradient mobile phase and detected using electrospra...

  16. Metagonimus yokogawai: metacercariae survey in fishes and its development to adult worms in various rodents.

    Science.gov (United States)

    Li, Ming-Hsien; Huang, Hai-I; Chen, Pei-Lain; Huang, Chiung-Hua; Chen, Yu-Hsuan; Ooi, Hong-Kean

    2013-04-01

    A parasitological survey for Metagonimus yokogawai metacercariae was carried out by examining a total of 321 freshwater fish comprising of 7 species. Of the 321 fish samples examined, 182 (56.7%) were found to be infected with M. yokogawai metacercariae. The prevalence of M. yokogawai metacercariae in Opsariichthys pachycephalus was 93.4% (86/92), Zacco platypus 75.0% (30/40), Distoechodon turmirostris 61.3% (38/62), Varicorhinus barbatulus 56.5% (13/23), Hemibarbus labeo 33.3% (1/3), Acrossocheilus formosanus 15.9% (14/88), and 0% in Sinibrama macrops (0/13), respectively. This is the first record of M. yokogawai infection in Z. platypus, D. turmirostris, V. barbatulus, and H. labeo in Taiwan. The major site of predilection of the metacercariae in the fishes was in the scale, but some metacercariae were also observed in the flesh and fins. The M. yokogawai metacercariae were orally inoculated into mice, rat, gerbil, and golden hamster to study their infectivity and also to obtain the adult worms for taxonomic study. Worm recovery in hamsters was 75.3%, in mice was 70.0%, in rats was 23.3%, and in gerbils was 6.0%, respectively. Moreover, larger worms were recovered from the golden hamster. Golden hamster was thus found to be the most susceptible experimental rodent host for the infectivity study of Metagonimus. Besides M. yokogawai, metacercariae of Centrocestus formosanus was also observed in the fishes examined. PMID:23388732

  17. 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

    RATIONALE: Dividing cells can be detected in the live brain by positron emission tomography or optical imaging. Here we apply proton magnetic resonance spectroscopy (1HMRS) and a widely used spectral fitting algorithm to characterize the effect of increased neurogenesis after electroconvulsive...... 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...

  18. 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...

  19. [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

  20. Mild traumatic brain injuries in adults

    Directory of Open Access Journals (Sweden)

    Dhaval Shukla

    2010-01-01

    Full Text Available Mild traumatic brain injury (mTBI is the commonest form of TBI. Though the name implies, it may not be mild in certain cases. There is a lot of heterogeneity in nomenclature, classification, evaluation and outcome of mTBI. We have reviewed the relevant articles on mTBI in adults, particularly its definition, evaluation and outcome, published in the last decade. The aspects of mTBI like pediatric age group, sports concussion, and postconcussion syndrome were not reviewed. There is general agreement that Glasgow coma score (GCS of 13 should not be considered as mTBI as the risk of intracranial lesion is higher than in patients with GCS 14-15. All patients with GCS of <15 should be evaluated with a computed tomography (CT scan. Patients with GCS 15 and risk factors or neurological symptoms should also be evaluated with CT scan. The outcome of mTBI depends on the combination of preinjury, injury and postinjury factors. Overall outcome of mTBI is good with mortality around 0.1% and disability around 10%.

  1. Fully automated rodent brain MR image processing pipeline on a Midas server: from acquired images to region-based statistics.

    Science.gov (United States)

    Budin, Francois; Hoogstoel, Marion; Reynolds, Patrick; Grauer, Michael; O'Leary-Moore, Shonagh K; Oguz, Ipek

    2013-01-01

    Magnetic resonance imaging (MRI) of rodent brains enables study of the development and the integrity of the brain under certain conditions (alcohol, drugs etc.). However, these images are difficult to analyze for biomedical researchers with limited image processing experience. In this paper we present an image processing pipeline running on a Midas server, a web-based data storage system. It is composed of the following steps: rigid registration, skull-stripping, average computation, average parcellation, parcellation propagation to individual subjects, and computation of region-based statistics on each image. The pipeline is easy to configure and requires very little image processing knowledge. We present results obtained by processing a data set using this pipeline and demonstrate how this pipeline can be used to find differences between populations. PMID:23964234

  2. Fully automated rodent brain MR image processing pipeline on a Midas server: from acquired images to region-based statistics

    Directory of Open Access Journals (Sweden)

    Francois Budin

    2013-08-01

    Full Text Available Magnetic Resonance Imaging (MRI of rodent brains enables study of the development and the integrity of the brain under certain conditions (alcohol, drugs etc.. However, these images are difficult to analyze for biomedical researchers with limited image processing experience. In this paper we present an image processing pipeline running on a Midas server, a web-based data storage system. It is composed of the following steps: rigid registration, skull-stripping, average computation, average segmentation, segmentation propagation to individual subjects and computation of region-based statistics on each image. The pipeline is easy to configure and requires very little image processing knowledge. We present results obtained by processing a data set using this pipeline and demonstrate how this pipeline can be used to find differences between populations.

  3. Regulation and function of neurogenesis in the adult vertebrate brain

    Directory of Open Access Journals (Sweden)

    Mendez-Otero R.

    2005-01-01

    Full Text Available Most adult tissues retain a reservoir of self-renewing, multipotent stem cells that can generate differentiated tissue components. Until recently, the brain was thought to be an exception to this rule and for many years the pervasive dogma of neurobiology relegated neurogenesis to the embryonic and earlier postnatal stages of development. The discovery of constant neuronal replacement in the adult brain has changed the way we think about neurological diseases and about the exploration of new strategies for brain repair. In this review we will explore the potential of adult neural stem cells and we will present some of our own work on this subject. We will also discuss the possibility that adult neurogenesis and neuronal replacement may also play a role in therapies aimed at restoring impaired brain function. A better understanding of the various aspects of spontaneous neuronal replacement may also be used to increase the success of procedures with cell therapies.

  4. Transcriptional signature of an adult brain tumor in Drosophila

    Directory of Open Access Journals (Sweden)

    Loop Thomas

    2004-04-01

    Full Text Available Abstract Background Mutations and gene expression alterations in brain tumors have been extensively investigated, however the causes of brain tumorigenesis are largely unknown. Animal models are necessary to correlate altered transcriptional activity and tumor phenotype and to better understand how these alterations cause malignant growth. In order to gain insights into the in vivo transcriptional activity associated with a brain tumor, we carried out genome-wide microarray expression analyses of an adult brain tumor in Drosophila caused by homozygous mutation in the tumor suppressor gene brain tumor (brat. Results Two independent genome-wide gene expression studies using two different oligonucleotide microarray platforms were used to compare the transcriptome of adult wildtype flies with mutants displaying the adult bratk06028 mutant brain tumor. Cross-validation and stringent statistical criteria identified a core transcriptional signature of bratk06028 neoplastic tissue. We find significant expression level changes for 321 annotated genes associated with the adult neoplastic bratk06028 tissue indicating elevated and aberrant metabolic and cell cycle activity, upregulation of the basal transcriptional machinery, as well as elevated and aberrant activity of ribosome synthesis and translation control. One fifth of these genes show homology to known mammalian genes involved in cancer formation. Conclusion Our results identify for the first time the genome-wide transcriptional alterations associated with an adult brain tumor in Drosophila and reveal insights into the possible mechanisms of tumor formation caused by homozygous mutation of the translational repressor brat.

  5. 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

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

    Science.gov (United States)

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

    2016-06-01

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

  7. Diversity of Neural Precursors in the Adult Mammalian Brain.

    Science.gov (United States)

    Bonaguidi, Michael A; Stadel, Ryan P; Berg, Daniel A; Sun, Jiaqi; Ming, Guo-Li; Song, Hongjun

    2016-01-01

    Aided by advances in technology, recent studies of neural precursor identity and regulation have revealed various cell types as contributors to ongoing cell genesis in the adult mammalian brain. Here, we use stem-cell biology as a framework to highlight the diversity of adult neural precursor populations and emphasize their hierarchy, organization, and plasticity under physiological and pathological conditions. PMID:26988967

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

    Science.gov (United States)

    Hecox, K.; Galambos, R.

    1974-01-01

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

  9. Oral noribogaine shows high brain uptake and anti-withdrawal effects not associated with place preference in rodents.

    Science.gov (United States)

    Mash, Deborah C; Ameer, Barbara; Prou, Delphine; Howes, John F; Maillet, Emeline L

    2016-07-01

    This study investigated the effects of noribogaine, the principal metabolite of the drug ibogaine, on substance-related disorders. In the first experiment, mice chronically treated with morphine were subjected to naloxone-precipitated withdrawal two hours after oral administration of noribogaine. Oral noribogaine dose dependently decreased the global opiate withdrawal score by up to 88% of vehicle control with an ED50 of 13 mg/kg. In the second experiment, blood and brain levels of noribogaine showed a high brain penetration and a brain/blood ratio of 7±1 across all doses tested. In a third experiment, rats given oral noribogaine up to 100 mg/kg were tested for abuse liability using a standard biased conditioned place paradigm. Noribogaine-treated rats did not display place preference, suggesting that noribogaine is not perceived as a hedonic stimulus in rodents. Retrospective review of published studies assessing the efficacy of ibogaine on morphine withdrawal shows that the most likely cause of the discrepancies in the literature is the different routes of administration and time of testing following ibogaine administration. These results suggest that the metabolite noribogaine rather than the parent compound mediates the effects of ibogaine on blocking naloxone-precipitated withdrawal. Noribogaine may hold promise as a non-addicting alternative to standard opiate replacement therapies to transition patients to opiate abstinence. PMID:27044509

  10. Tooth pulp inflammation increases brain-derived neurotrophic factor expression in rodent trigeminal ganglion neurons.

    Science.gov (United States)

    Tarsa, L; Bałkowiec-Iskra, E; Kratochvil, F J; Jenkins, V K; McLean, A; Brown, A L; Smith, J A; Baumgartner, J C; Balkowiec, A

    2010-06-01

    Nociceptive pathways with first-order neurons located in the trigeminal ganglion (TG) provide sensory innervation to the head, and are responsible for a number of common chronic pain conditions, including migraines, temporomandibular disorders and trigeminal neuralgias. Many of those conditions are associated with inflammation. Yet, the mechanisms of chronic inflammatory pain remain poorly understood. Our previous studies show that the neurotrophin brain-derived neurotrophic factor (BDNF) is expressed by adult rat TG neurons, and released from cultured newborn rat TG neurons by electrical stimulation and calcitonin gene-related peptide (CGRP), a well-established mediator of trigeminal inflammatory pain. These data suggest that BDNF plays a role in activity-dependent plasticity at first-order trigeminal synapses, including functional changes that take place in trigeminal nociceptive pathways during chronic inflammation. The present study was designed to determine the effects of peripheral inflammation, using tooth pulp inflammation as a model, on regulation of BDNF expression in TG neurons of juvenile rats and mice. Cavities were prepared in right-side maxillary first and second molars of 4-week-old animals, and left open to oral microflora. BDNF expression in right TG was compared with contralateral TG of the same animal, and with right TG of sham-operated controls, 7 and 28 days after cavity preparation. Our ELISA data indicate that exposing the tooth pulp for 28 days, with confirmed inflammation, leads to a significant upregulation of BDNF in the TG ipsilateral to the affected teeth. Double-immunohistochemistry with antibodies against BDNF combined with one of nociceptor markers, CGRP or transient receptor potential vanilloid type 1 (TRPV1), revealed that BDNF is significantly upregulated in TRPV1-immunoreactive (IR) neurons in both rats and mice, and CGRP-IR neurons in mice, but not rats. Overall, the inflammation-induced upregulation of BDNF is stronger in mice

  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 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 host hippocampal neuron survival in hNSC transplanted animals and demonstrate that a correlation exists between hippocampal neuron survival and cognitive performance. Together, these findings support the use of immunodeficient rodents in models of TBI that involve the transplantation of human cells, and suggest that hNSC transplantation may be a viable, long-term therapy to restore cognition after brain injury. PMID:27079998

  12. Selective Brain Uptake and Behavioral Effects of the Cyanobacterial Toxin BMAA (β-N-Methylamino-L-alanine) following Neonatal Administration to Rodents

    OpenAIRE

    Karlsson, Oskar; Lindquist, Nils Gunnar; Brittebo, Eva B.; Roman, Erika

    2009-01-01

    Cyanobacteria are extensively distributed in terrestrial and aquatic environments all over the world. Most cyanobacteria can produce the neurotoxin ss-N-methylamino-L-alanine (BMAA), which has been detected in several water systems and could accumulate in food chains. The aim of the study was to investigate the transfer of BMAA to fetal and neonatal brains and the effects of BMAA on the development of behavioral characteristics during the brain growth spurt (BGS) in rodents Pregnant and neona...

  13. 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

  14. 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.

  15. 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 ...

  16. 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...

  17. Metabolic clues to salubrious longevity in the brain of the longest-lived rodent: the naked mole-rat.

    Science.gov (United States)

    Triplett, Judy C; Swomley, Aaron; Kirk, Jessime; Lewis, Katilyn; Orr, Miranda; Rodriguez, Karl; Cai, Jian; Klein, Jon B; Buffenstein, Rochelle; Butterfield, D Allan

    2015-08-01

    Naked mole-rats (NMRs) are the oldest-living rodent species. Living underground in a thermally stable ecological niche, NMRs have evolved certain exceptional traits, resulting in sustained health spans, negligible cognitive decline, and a pronounced resistance to age-related disease. Uncovering insights into mechanisms underlying these extraordinary traits involved in successful aging may conceivably provide crucial clues to extend the human life span and health span. One of the most fundamental processes inside the cell is the production of ATP, which is an essential fuel in driving all other energy-requiring cellular activities. Not surprisingly, a prominent hallmark in age-related diseases, such as neurodegeneration and cancer, is the impairment and dysregulation of metabolic pathways. Using a two-dimensional polyacrylamide gel electrophoresis proteomics approach, alterations in expression and phosphorylation levels of metabolic proteins in the brains of NMRs, aged 2-24 years, were evaluated in an age-dependent manner. We identified 13 proteins with altered levels and/or phosphorylation states that play key roles in various metabolic pathways including glycolysis, β-oxidation, the malate-aspartate shuttle, the Tricarboxylic Acid Cycle (TCA) cycle, the electron transport chain, NADPH production, as well as the production of glutamate. New insights into potential pathways involved in metabolic aspects of successful aging have been obtained by the identification of key proteins through which the NMR brain responds and adapts to the aging process and how the NMR brain adapted to resist age-related degeneration. This study examines the changes in the proteome and phosphoproteome in the brain of the naked mole-rat aged 2-24 years. We identified 13 proteins (labeled in red) with altered expression and/or phosphorylation levels that are conceivably associated with sustained metabolic functions in the oldest NMRs that may promote a sustained health span and life span

  18. Asymmetry of the Structural Brain Connectome in Healthy Older Adults

    OpenAIRE

    Bonilha, Leonardo; Nesland, Travis; Rorden, Chris; Fridriksson, Julius

    2014-01-01

    Background: It is now possible to map neural connections in vivo across the whole brain (i.e., the brain connectome). This is a promising development in neuroscience since many health and disease processes are believed to arise from the architecture of neural networks. Objective: To describe the normal range of hemispheric asymmetry in structural connectivity in healthy older adults. Materials and Methods: We obtained high-resolution structural magnetic resonance images (MRI) from 17 he...

  19. 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...

  20. Neuronal regeneration in a zebrafish model of adult brain injury

    Directory of Open Access Journals (Sweden)

    Norihito Kishimoto

    2012-03-01

    Neural stem cells in the subventricular zone (SVZ of the adult mammalian forebrain are a potential source of neurons for neural tissue repair after brain insults such as ischemic stroke and traumatic brain injury (TBI. Recent studies show that neurogenesis in the ventricular zone (VZ of the adult zebrafish telencephalon has features in common with neurogenesis in the adult mammalian SVZ. Here, we established a zebrafish model to study injury-induced neurogenesis in the adult brain. We show that the adult zebrafish brain possesses a remarkable capacity for neuronal regeneration. Telencephalon injury prompted the proliferation of neuronal precursor cells (NPCs in the VZ of the injured hemisphere, compared with in the contralateral hemisphere. The distribution of NPCs, viewed by BrdU labeling and ngn1-promoter-driven GFP, suggested that they migrated laterally and reached the injury site via the subpallium and pallium. The number of NPCs reaching the injury site significantly decreased when the fish were treated with an inhibitor of γ-secretase, a component of the Notch signaling pathway, suggesting that injury-induced neurogenesis mechanisms are at least partly conserved between fish and mammals. The injury-induced NPCs differentiated into mature neurons in the regions surrounding the injury site within a week after the injury. Most of these cells expressed T-box brain protein (Tbr1, suggesting they had adopted the normal neuronal fate in this region. These results suggest that the telencephalic VZ contributes to neural tissue recovery following telencephalic injury in the adult zebrafish, and that the adult zebrafish is a useful model for regenerative medicine.

  1. 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.

  2. Quantification of anandamide, oleoylethanolamide and palmitoylethanolamide in rodent brain tissue using high performance liquid chromatography–electrospray mass spectroscopy

    Directory of Open Access Journals (Sweden)

    Daniel J. Liput

    2014-08-01

    Full Text Available Reported concentrations for endocannabinoids and related lipids in biological tissues can vary greatly; therefore, methods used to quantify these compounds need to be validated. This report describes a method to quantify anandamide (AEA, oleoylethanolamide (OEA and palmitoylethanolamide (PEA from rodent brain tissue. Analytes were extracted using acetonitrile without further sample clean up, resolved on a C18 reverse-phase column using a gradient mobile phase and detected using electrospray ionization in positive selected ion monitoring mode on a single quadrupole mass spectrometer. The method produced high recovery rates for AEA, OEA and PEA, ranging from 98.1% to 106.2%, 98.5% to 102.2% and 85.4% to 89.5%, respectively. The method resulted in adequate sensitivity with a lower limit of quantification for AEA, OEA and PEA of 1.4 ng/mL, 0.6 ng/mL and 0.5 ng/mL, respectively. The method was reproducible as intraday and interday accuracies and precisions were under 15%. This method was suitable for quantifying AEA, OEA and PEA from rat brain following pharmacological inhibition of fatty acid amide hydrolase.

  3. Expression of galanin and its receptors are perturbed in a rodent model of mild, blast-induced traumatic brain injury.

    Science.gov (United States)

    Kawa, Lizan; Barde, Swapnali; Arborelius, Ulf P; Theodorsson, Elvar; Agoston, Denes; Risling, Mårten; Hökfelt, Tomas

    2016-05-01

    The symptomatology, mood and cognitive disturbances seen in post-traumatic stress disorder (PTSD) and mild blast-induced traumatic brain injury (mbTBI) overlap considerably. However the pathological mechanisms underlying the two conditions are currently unknown. The neuropeptide galanin has been suggested to play a role in the development of stress and mood disorders. Here we applied bio- and histochemical methods with the aim to elucidate the nature of any changes in the expression of galanin and its receptors in a rodent model of mbTBI. In situ hybridization and quantitative polymerase chain reaction studies revealed significant, injury-induced changes, in some cases lasting at least for one week, in the mRNA levels of galanin and/or its three receptors, galanin receptor 1-3 (GalR1-3). Such changes were seen in several forebrain regions, and the locus coeruleus. In the ventral periaqueductal gray GalR1 mRNA levels were increased, while GalR2 were decreased. Analysis of galanin peptide levels using radioimmunoassay demonstrated an increase in several brain regions including the locus coeruleus, dorsal hippocampal formation and amygdala. These findings suggest a role for the galanin system in the endogenous response to mbTBI, and that pharmacological studies of the effects of activation or inhibition of different galanin receptors in combination with functional assays of behavioral recovery may reveal promising targets for new therapeutic strategies in mbTBI. PMID:26928087

  4. 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...

  5. Toxicogenomic profiling in maternal and fetal rodent brains following gestational exposure to chlorpyrifos

    International Nuclear Information System (INIS)

    Considering the wide variety of effects that have been reported to occur in the developmental neurotoxicity of chlorpyrifos (CP) and the lack of consensus on their dependence of brain acetylcholinesterase (AChE) activity inhibition, we applied microarray technology to explore dose-dependent alterations in transcriptional response in the fetal and maternal C57BL/6 mouse brain after daily gestational exposure (days 6 to 17) to CP (2, 4, 10, 12 or 15 mg/kg, sc). We identified significantly altered genes across doses and assessed for overrepresentation of Gene Ontology (GO) biological processes and KEGG pathways. We further clustered genes based on their expression profiles across doses and repeated the GO/pathways analysis for each cluster. The dose-effect relationship of CP on gene expression, both at the gene and pathway levels was non-monotonic and not necessarily related to brain AChE inhibition. The largest impact was observed in the 10 mg/kg dose group which was also the LOAEL for brain AChE inhibition. In the maternal brain, lower doses (4 mg/kg) influenced GO categories and pathways such as cell adhesion, behavior, lipid metabolism, long-term potentiation, nervous system development, neurogenesis, synaptic transmission. In the fetal brain, lower doses (2 and/or 4 mg/kg) significantly altered cell division, translation, transmission of nerve impulse, chromatin modification, long-term potentiation. In addition, some genes involved in nervous system development and signaling were shown to be specifically influenced by these lower CP doses. Our approach was sensitive and reflected the diversity of responses known to be disrupted by CP and highlighted possible additional consequences of CP neurotoxicity, such as disturbance of the ubiquitin proteasome system.

  6. 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.

  7. Inflammation is detrimental for neurogenesis in adult brain

    Science.gov (United States)

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

    2003-11-01

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

  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. 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

  10. 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...... quality appraisal. Randomized control trial data will be treated as a cohort. The quality will be assessed using the criteria defined by Hayden and colleagues. The review will be conducted and reported in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines...

  11. 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 ...

  12. [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

  13. Systemic Administration of Glibenclamide Fails to Achieve Therapeutic Levels in the Brain and Cerebrospinal Fluid of Rodents.

    Directory of Open Access Journals (Sweden)

    Carolina Lahmann

    Full Text Available Activating mutations in the Kir6.2 (KCNJ11 subunit of the ATP-sensitive potassium channel cause neonatal diabetes (ND. Patients with severe mutations also suffer from neurological complications. Glibenclamide blocks the open KATP channels and is the treatment of choice for ND. However, although glibenclamide successfully restores normoglycaemia, it has a far more limited effect on the neurological problems. To assess the extent to which glibenclamide crosses the blood-brain barrier (BBB in vivo, we quantified glibenclamide concentrations in plasma, cerebrospinal fluid (CSF, and brain tissue of rats, control mice, and mice expressing a human neonatal diabetes mutation (Kir6.2-V59M selectively in neurones (nV59M mice. As only small sample volumes can be obtained from rodents, we developed a highly sensitive method of analysis, using liquid chromatography tandem mass spectrometry acquisition with pseudo-selected reaction monitoring, achieving a quantification limit of 10ng/ml (20nM glibenclamide in a 30μl sample. Glibenclamide was not detectable in the CSF or brain of rats after implantation with subcutaneous glibenclamide pellets, despite high plasma concentrations. Further, one hour after a suprapharmacological glibenclamide dose was administered directly into the lateral ventricle of the brain, the plasma concentration was twice that of the CSF. This suggests the drug is rapidly exported from the CSF. Elacridar, an inhibitor of P-glycoprotein and breast cancer resistance protein (major multidrug resistance transporters at the BBB, did not affect glibenclamide levels in CSF and brain tissue. We also identified a reduced sensitivity to volatile anaesthetics in nV59M mice and showed this was not reversed by systemic delivery of glibenclamide. Our results therefore suggest that little glibenclamide reaches the central nervous system when given systemically, that glibenclamide is rapidly removed across the BBB when given intracranioventricularly

  14. 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...

  15. 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 ...

  16. Ethanol reduces the phase locking of neural activity in human and rodent brain

    OpenAIRE

    Ehlers, Cindy L.; Wills, Derek N.; Havstad, James

    2012-01-01

    How the neuromolecular actions of ethanol translate to its observed intoxicating effects remains poorly understood. 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 ethanol’s effects. Using a similar auditory event-related potential paradigm in both rats and humans we investigated the phase vari...

  17. 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.

  18. 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

  19. 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

  20. Effects of Habitat and Social Complexity on Brain Size, Brain Asymmetry and Dentate Gyrus Morphology in Two Octodontid Rodents.

    Science.gov (United States)

    Sobrero, Raúl; Fernández-Aburto, Pedro; Ly-Prieto, Álvaro; Delgado, Scarlett E; Mpodozis, Jorge; Ebensperger, Luis A

    2016-01-01

    Navigational and social challenges due to habitat conditions and sociality are known to influence dentate gyrus (DG) morphology, yet the relative importance of these factors remains unclear. Thus, we studied three natural populations of O. lunatus (Los Molles) and Octodon degus (El Salitre and Rinconada), two caviomorph species that differ in the extent of sociality and with contrasting vegetation cover of habitat used. The brains and DG of male and female breeding degus with simultaneous information on their physical and social environments were examined. The extent of sociality was quantified from total group size and range area overlap. O. degus at El Salitre was more social than at Rinconada and than O. lunatus from Los Molles. The use of transects to quantify cover of vegetation (and other physical objects in the habitat) and measures of the spatial behavior of animals indicated animal navigation based on unique cues or global landmarks is more cognitively challenging to O. lunatus. During lactation, female O. lunatus had larger brains than males. Relative DG volume was similar across sexes and populations. The right hemisphere of male and female O. lunatus had more cells than the left hemisphere, with DG directional asymmetry not found in O. degus. Degu population differences in brain size and DG cell number seemed more responsive to differences in habitat than to differences in sociality. Yet, large-sized O. degus (but not O. lunatus) that ranged over larger areas and were members of larger social groups had more DG cells per hemisphere. Thus, within-population variation in DG cell number by hemisphere was consistent with a joint influence of habitat and sociality in O. degus at El Salitre. PMID:27045373

  1. 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

  2. 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.

  3. 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

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  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. Resting state functional connectivity data supports detection of cognition in the rodent brain.

    Science.gov (United States)

    Nasrallah, Fatima A; To, Xuan Vinh; Chen, Der-Yow; Routtenberg, Aryeh; Chuang, Kai-Hsiang

    2016-06-01

    Learning is a process which induces plastic changes in the synapses and connections across different regions of the brain. It is hypothesized that these new connections can be tracked with resting state functional connectivity MRI. While most of the evidence of learning-induced plasticity arises from previous human data, data from sedated rats that had undergone training for either 1 day or 5 days in a Morris Watermaze is presented. Seed points were taken from the somatosensory and visual cortices, and the hippocampal CA3 to detect connectivity changes. The data demonstrates that 5-day trained rats showed increased correlations between the hippocampal CA3 and thalamus, septum and cingulate cortex, compared to swim control or naïve animals. Seven days after the training, persistent but reorganized networks toward the cortex were observed. Data from the 1-day trained rats, on the contrary, showed connectivity similar to the swim control and less persistent. The connectivity in several regions was highly correlated with the behavioral performance in these animals. The data demonstrates that longitudinal changes following learning-induced plasticity can be detected and tracked with resting state connectivity. PMID:27115031

  20. 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

  1. Homeobox Genes in the Rodent Pineal Gland

    DEFF Research Database (Denmark)

    Rath, Martin Fredensborg; Rohde, Kristian; Klein, David C;

    2013-01-01

    The pineal gland is a neuroendocrine gland responsible for nocturnal synthesis of melatonin. During early development of the rodent pineal gland from the roof of the diencephalon, homeobox genes of the orthodenticle homeobox (Otx)- and paired box (Pax)-families are expressed and are essential for...... normal pineal development consistent with the well-established role that homeobox genes play in developmental processes. However, the pineal gland appears to be unusual because strong homeobox gene expression persists in the pineal gland of the adult brain. Accordingly, in addition to developmental...... functions, homeobox genes appear to be key regulators in postnatal phenotype maintenance in this tissue. In this paper, we review ontogenetic and phylogenetic aspects of pineal development and recent progress in understanding the involvement of homebox genes in rodent pineal development and adult function...

  2. 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 ...

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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.

  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. 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.

  11. 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...

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

    Science.gov (United States)

    Galvan, Veronica; Bredesen, Dale E

    2007-10-01

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

  14. 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

  15. 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

  16. 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.

  17. 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)

  18. 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

  19. 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

  20. Gender and age related expression of Oct-6--a POU III domain transcription factor, in the adult mouse brain.

    Science.gov (United States)

    Ilia, Maria; Sugiyama, Yuka; Price, Jack

    2003-06-26

    Oct-6 is a POU III domain transcription factor whose primary role is thought to be developmental. It is expressed in embryonic stem cells, Schwann cells, and in neuronal subpopulations during telencephalic development. Its best characterised role is in Schwann cells where it is thought to regulate myelin specific gene expression. Expression of Oct-6 was recently discovered in neurons in post-mortem human schizophrenic specimens while being undetectable in matched controls. This study of human tissue contrasted in a number of regards with earlier studies of rodent brain, and questioned what we can consider to be normal adult expression of this gene. In this study, we have investigated Oct-6 expression via in situ hybridisation and Western blot analysis in normal adult female mice of different ages. We show that both RNA and protein levels of Oct-6 expression are highly sustained in the adult and aging cerebellum, whereas they are attenuated in the telencephalon by PW30 (postnatal week 30). These observations suggest that Oct-6 expression takes place in a sex and age dependent way. PMID:12782346

  1. Reduction of protein kinase MARK4 in the brains of experimental scrapie rodents and human prion disease correlates with deposits of PrP(Sc).

    Science.gov (United States)

    Gong, Han-Shi; Guo, Yan; Tian, Chan; Xie, Wu-Ling; Shi, Qi; Zhang, Jin; Xu, Yin; Wang, Shao-Bin; Zhang, Bao-Yun; Chen, Cao; Liu, Yong; Dong, Xiao-Ping

    2012-09-01

    Microtubule affinity-regulating kinase 4 (MARK4) belongs to a family of kinases that are able to actively phosphorylate the neuronal microtubule-associate proteins (MAPs), such as tau, MAP2 and the ubiquitous MAP4. Abnormal changes in tubulin and the profiles of tau have been previously reported in the human brain and animal transmissible spongiform encephalopathies (TSEs), which may be associated with abnormal alterations of various cellular kinases. To elucidate the possible role of MARK4 in TSE pathogenesis, the MARK4 levels in the brain tissues of scrapie-infected rodents and human prion diseases were evaluated using western blotting and immunohistochemical assays. The results revealed that at terminal stages of the diseases, MARK4 levels in the brain tissues of the scrapie 263K-infected hamsters, 139A-infected mice and a case of Creutzfeldt-Jakob disease (CJD, G114V gCJD) correlated with amounts of PrP(Sc) deposits that were almost undetectable. On the other hand MARK4 signals were noticeable in the brain tissues of a fatal familial insomnia (FFI) patient without PrP(Sc). The reduction of MARK4 was closely related to the prolonged incubation times. These results could be reproduced in SK-N-SH and PC12 cell lines after being exposed to the synthetic peptide PrP106-126. Accordingly, the levels of phosphorylated tau at Ser262 (p-tau262) in cultured cells exposed to PrP106-126, or the ratios of p-tau262/total tau in the brain tissues of 263K-infected hamsters were also significantly decreased. According to our data there is a correlation between a TSE pathological-associated decline of MARK4 in the brain tissues with the deposits of PrP(Sc). Reduction of MARK4 will result in abnormalities of tau phosphorylation, and possibly induce further detachment of microtubules and hinder microtubule transportation. PMID:22692785

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

    Science.gov (United States)

    Richmond, Erick; Rogol, Alan D

    2014-02-01

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

  3. Effect of cyclosporin A administration on the biodistribution and multipinhole {mu}SPECT imaging of [{sup 123}I]R91150 in rodent brain

    Energy Technology Data Exchange (ETDEWEB)

    Blanckaert, P.; Burvenich, I.; Bruyne, S. de; Moerman, L.; Wyffels, L.; Vos, F. de [Faculty of Pharmaceutical Sciences, Ghent University, Laboratory for Radiopharmacy, Gent (Belgium); Staelens, S. [Ghent University - IBBT, MEDISIP, Faculty of Engineering, Gent (Belgium)

    2009-03-15

    P-glycoprotein (Pgp) is an efflux protein found amongst other locations in the blood-brain barrier. It is important to investigate the effect of Pgp modulation on clinically used brain tracers, because brain uptake of the tracer can be altered by blocking of the Pgp efflux transporter. The function of Pgp can be blocked with cyclosporin A. We investigated the effect of cyclosporin A administration on the biodistribution of [{sup 123}I]R91150 in rodents, and the effect of Pgp blocking on the quality of multipinhole {mu}SPECT imaging with [{sup 123}I]R91150. The influence of increasing doses of cyclosporin A on the brain uptake of [{sup 123}I]R91150 was investigated in NMRI mice. A biodistribution study with [{sup 123}I]R91150 was performed in male Sprague-Dawley rats pretreated with cyclosporin A and not pretreated. Brain uptake of [{sup 123}I]R91150 after cyclosporin A injection was compared to the brain uptake in untreated animals, and a displacement study with ketanserin was performed in both groups. A multipinhole {mu}SPECT brain imaging study was also performed using a Milabs U-SPECT-II camera in male Sprague-Dawley rats. To exclude the effect of possible metabolites, a metabolite study was also performed. At the highest cyclosporin A dose (50 mg/kg), a sevenfold increase in brain radioactivity concentration was observed in NMRI mice. Also, a dose-response relationship was established between the dose of cyclosporin A and the brain uptake of [{sup 123}I]R91150 in mice. Compared to the control group, a five-fold increase in [{sup 123}I]R91150 radioactivity concentration was observed in the brain of Sprague-Dawley rats after cyclosporin A treatment (50 mg/kg). Radioactivity concentration in the frontal cortex increased from 0.24{+-}0.0092 to 1.58{+-}0.097% injected dose per gram of tissue after treatment with cyclosporin A (at the 1-h time-point). Blood radioactivity concentrations did not increase to the same extent. The cortical activity was displaced by

  4. Effect of cyclosporin A administration on the biodistribution and multipinhole μSPECT imaging of [123I]R91150 in rodent brain

    International Nuclear Information System (INIS)

    P-glycoprotein (Pgp) is an efflux protein found amongst other locations in the blood-brain barrier. It is important to investigate the effect of Pgp modulation on clinically used brain tracers, because brain uptake of the tracer can be altered by blocking of the Pgp efflux transporter. The function of Pgp can be blocked with cyclosporin A. We investigated the effect of cyclosporin A administration on the biodistribution of [123I]R91150 in rodents, and the effect of Pgp blocking on the quality of multipinhole μSPECT imaging with [123I]R91150. The influence of increasing doses of cyclosporin A on the brain uptake of [123I]R91150 was investigated in NMRI mice. A biodistribution study with [123I]R91150 was performed in male Sprague-Dawley rats pretreated with cyclosporin A and not pretreated. Brain uptake of [123I]R91150 after cyclosporin A injection was compared to the brain uptake in untreated animals, and a displacement study with ketanserin was performed in both groups. A multipinhole μSPECT brain imaging study was also performed using a Milabs U-SPECT-II camera in male Sprague-Dawley rats. To exclude the effect of possible metabolites, a metabolite study was also performed. At the highest cyclosporin A dose (50 mg/kg), a sevenfold increase in brain radioactivity concentration was observed in NMRI mice. Also, a dose-response relationship was established between the dose of cyclosporin A and the brain uptake of [123I]R91150 in mice. Compared to the control group, a five-fold increase in [123I]R91150 radioactivity concentration was observed in the brain of Sprague-Dawley rats after cyclosporin A treatment (50 mg/kg). Radioactivity concentration in the frontal cortex increased from 0.24±0.0092 to 1.58±0.097% injected dose per gram of tissue after treatment with cyclosporin A (at the 1-h time-point). Blood radioactivity concentrations did not increase to the same extent. The cortical activity was displaced by administration of ketanserin. A metabolite study

  5. 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...

  6. 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.

  7. Preparation of Developing and Adult Drosophila Brains and Retinae for Live Imaging

    OpenAIRE

    Williamson, W. Ryan; Hiesinger, P. Robin

    2010-01-01

    The Drosophila brain and visual system are widely utilized model systems to study neuronal development, function and degeneration. Here we show three preparations of the brain and visual system that cover the range from the developing eye disc-brain complex in the developing pupae to individual eye and brain dissection from adult flies. All protocols are optimized for the live culture of the preparations. However, we also present the conditions for fixed tissue immunohistochemistry where appl...

  8. Pre-treatment effects of peripheral tumors on brain and behavior: neuroinflammatory mechanisms in humans and rodents.

    Science.gov (United States)

    Schrepf, Andrew; Lutgendorf, Susan K; Pyter, Leah M

    2015-10-01

    Cancer patients suffer high levels of affective and cognitive disturbances, which have been attributed to diagnosis-related distress, impairment of quality of life, and side effects of primary treatment. An inflammatory microenvironment is also a feature of the vast majority of solid tumors. However, the ability of tumor-associated biological processes to affect the central nervous system (CNS) has only recently been explored in the context of symptoms of depression and cognitive disturbances. In this review, we summarize the burgeoning evidence from rodent cancer models that solid tumors alter neurobiological pathways and subsequent behavioral processes with relevance to affective and cognitive disturbances reported in human cancer populations. We consider, in parallel, the evidence from human clinical cancer research demonstrating that affective and cognitive disturbances are common in some malignancies prior to diagnosis and treatment. We further consider the underlying neurobiological pathways, including altered neuroinflammation, tryptophan metabolism, prostaglandin synthesis and associated neuroanatomical changes, that are most strongly implicated in the rodent literature and supported by analogous evidence from human cancer populations. We focus on the implications of these findings for behavioral researchers and clinicians, with particular emphasis on methodological issues and areas of future research. PMID:25958011

  9. 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.

  10. 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...

  11. Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer β-amyloid peptide in rodent

    OpenAIRE

    Greig, Nigel H.; Utsuki, Tadanobu; Ingram, Donald K.; Wang, Yue; Pepeu, Giancarlo; Scali, Carla; Yu, Qian-sheng; Mamczarz, Jacek; Holloway, Harold W.; Giordano, Tony; Chen, DeMao; Furukawa, Katsutoshi; Sambamurti, Kumar; Brossi, Arnold; Lahiri, Debomoy K.

    2005-01-01

    Like acetylcholinesterase, butyrylcholinesterase (BChE) inactivates the neurotransmitter acetylcholine (ACh) and is hence a viable therapeutic target in Alzheimer's disease, which is characterized by a cholinergic deficit. Potent, reversible, and brain-targeted BChE inhibitors (cymserine analogs) were developed based on binding domain structures to help elucidate the role of this enzyme in the central nervous system. In rats, cymserine analogs caused long-term inhibition of brain BChE and ele...

  12. 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

  13. 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

  14. 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.)

  15. 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

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

    DEFF Research Database (Denmark)

    Sporrborn, Janni L; Baunbæk-Knudsen, Gertrud Louise; Sølling, Mette; Seierøe, Karina; Farre, Annette; Lindhardt, Bjarne Ø; Benfield, Thomas; Brandt, Christian T

    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...

  17. 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

  18. 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; Nordestgaard, Børge G

    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 are at...... increased risk of developing thyroid cancer, brain cancer, and NHL. We included the entire adult Danish population (14 years of age or older), in a 28-year follow-up period from 1980 through 2007, composed of 6 542 639 persons; during this period, 18 834 developed adult leukemia, 4561 developed thyroid...... cancer, 13 362 developed brain cancer, and 15 967 developed NHL. In nested studies using Cox regression models on individual participant data, we found that, after adult leukemia, the multivariate adjusted hazard ratios were 4.9 (95% confidence interval [CI], 2.8-8.5) for thyroid cancer, 1.9 (95% CI, 1...

  19. 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.

  20. 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…

  1. 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

  2. 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…

  3. 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

  4. 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

  5. Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer’s disease

    OpenAIRE

    Nagahara, Alan H.; Merrill, David A.; Coppola, Giovanni; Tsukada, Shingo; Schroeder, Brock E; Shaked, Gideon M.; Wang, Ling; Blesch, Armin; Kim, Albert; Conner, James M; Rockenstein, Edward; Chao, Moses V.; Koo, Edward H.; Geschwind, Daniel; Masliah, Eliezer

    2009-01-01

    Profound neuronal dysfunction in the entorhinal cortex contributes to early loss of short-term memory in Alzheimer’s disease1–3. Here we show broad neuroprotective effects of entorhinal brain-derived neurotrophic factor (BDNF) administration in several animal models of Alzheimer’s disease, with extension of therapeutic benefits into the degenerating hippocampus. In amyloid-transgenic mice, BDNF gene delivery, when administered after disease onset, reverses synapse loss, partially normalizes a...

  6. 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

  7. Seizure Suppression Efficacy of Closed-Loop Versus Open-Loop Deep Brain Stimulation in a Rodent Model of Epilepsy.

    Science.gov (United States)

    Salam, M Tariqus; Perez Velazquez, Jose Luis; Genov, Roman

    2016-06-01

    We assess and compare the effects of both closed-loop and open-loop neurostimulation of the rat hippocampus by means of a custom low-power programmable therapeutic neurostimulation device on the suppression of spontaneous seizures in a rodent model of epilepsy. Chronic seizures were induced by intraperitoneal kainic acid injection. Two bipolar electrodes were implanted into the CA1 regions of both hippocampi. The electrodes were connected to the custom-built programmable therapeutic neurostimulation device that can trigger an electrical stimulation either in a periodic manner or upon detection of the intracerebral electroencephalographic (icEEE) seizure onset. This device includes a microchip consisting of a 256-channel icEEG recording system and a 64-channel stimulator, and a programmable seizure detector implemented in a field-programmable gate array (FPGA). The neurostimulator was used to evaluate seizure suppression efficacy in ten epileptic rats for a total of 240 subject-days (5760 subject-hours). For this purpose, all rats were randomly divided into two groups: the no-stimulation group and the stimulation group. The no-stimulation group did not receive stimulation. The stimulation group received, first, closed-loop stimulation and, next, open-loop stimulation. The no-stimulation and stimulation groups had a similar seizure frequency baseline, averaging five seizures per day. Closed-loop stimulation reduced seizure frequency by 90% and open-loop stimulation reduced seizure frequency by 17%, both in the stimulation group as compared to the no-stimulation group. PMID:26571534

  8. 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.

  9. 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...

  10. 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...

  11. 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 ...

  12. 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...

  13. 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...

  14. 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...

  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 are at...... increased risk of developing thyroid cancer, brain cancer, and NHL. We included the entire adult Danish population (14 years of age or older), in a 28-year follow-up period from 1980 through 2007, composed of 6 542 639 persons; during this period, 18 834 developed adult leukemia, 4561 developed thyroid.......2-3.1) for brain cancer, and 3.3 (95% CI, 2.5-4.4) for NHL. Corresponding hazard ratios after childhood leukemia were 10.4 (95% CI, 0.4-223) for thyroid cancer, 7.2 (95% CI, 2.0-26) for brain cancer, and 6.5 (95% CI, 0.4-110) for NHL. Patients with adult leukemia have excess risk of thyroid cancer, brain...

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

    OpenAIRE

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

    2008-01-01

    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 ambu...

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

    Science.gov (United States)

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

    2015-04-15

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

  18. 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...

  19. 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...

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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...

  5. 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, ...

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

    International Nuclear Information System (INIS)

    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. (author)

  7. 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.

  8. Brain Swelling and Mannitol Therapy in Adult Cerebral Malaria: A Randomized Trial

    OpenAIRE

    Mohanty, Sanjib; Mishra, Saroj Kanti; Patnaik, Rajyabardhan; Dutt, Anil Kumar; Pradhan, Sudhir; Das, Bhabanisankar; Patnaik, Jayakrushna; Mohanty, Akshaya Kumar; Lee, Sue J.; Dondorp, Arjen M.

    2011-01-01

    Background.  Coma is a frequent presentation of severe malaria in adults and an important cause of death. The role of cerebral swelling in its pathogenesis, and the possible benefit of intravenous mannitol therapy to treat this, is uncertain. Methods.  A computed tomographic (CT) scan of the cerebrum and lumbar puncture with measurement of cerebrospinal fluid (CSF) pressure were performed on admission for 126 consecutive adult Indian patients with cerebral malaria. Patients with brain swellin...

  9. 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...

  10. 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...

  11. 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)

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

    International Nuclear Information System (INIS)

    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)

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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…

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Silencing relaxin-3 in nucleus incertus of adult rodents: a viral vector-based approach to investigate neuropeptide function.

    Directory of Open Access Journals (Sweden)

    Gabrielle E Callander

    Full Text Available Relaxin-3, the most recently identified member of the relaxin peptide family, is produced by GABAergic projection neurons in the nucleus incertus (NI, in the pontine periventricular gray. Previous studies suggest relaxin-3 is a modulator of stress responses, metabolism, arousal and behavioural activation. Knockout mice and peptide infusions in vivo have significantly contributed to understanding the function of this conserved neuropeptide. Yet, a definitive role remains elusive due to discrepancies between models and a propensity to investigate pharmacological effects over endogenous function. To investigate the endogenous function of relaxin-3, we generated a recombinant adeno-associated viral (rAAV vector expressing microRNA against relaxin-3 and validated its use to knock down relaxin-3 in adult rats. Bilateral stereotaxic infusion of rAAV1/2 EmGFP miR499 into the NI resulted in significant reductions in relaxin-3 expression as demonstrated by ablation of relaxin-3-like immunoreactivity at 3, 6 and 9 weeks and by qRT-PCR at 12 weeks. Neuronal health was unaffected as transduced neurons in all groups retained expression of NeuN and stained for Nissl bodies. Importantly, qRT-PCR confirmed that relaxin-3 receptor expression levels were not altered to compensate for reduced relaxin-3. Behavioural experiments confirmed no detrimental effects on general health or well-being and therefore several behavioural modalities previously associated with relaxin-3 function were investigated. The validation of this viral vector-based model provides a valuable alternative to existing in vivo approaches and promotes a shift towards more physiologically relevant investigations of endogenous neuropeptide function.

  20. Cell attachment to frozen sections of injured adult mouse brain: effects of tenascin antibody and lectin perturbation of wound-related extracellular matrix molecules.

    Science.gov (United States)

    Laywell, E D; Friedman, P; Harrington, K; Robertson, J T; Steindler, D A

    1996-06-01

    Previous studies describing the use of cryoculture methods have focused on the efficacy of the method for studying neuron attachment and neurite outgrowth on intact sections of nerve, and rodent and even human brain. The cryoculture method has shown promise for determining the presence of cell attachment- and neurite-growth-inhibiting molecules in such specimens, and some studies have also attempted to neutralize such molecules with antibodies to myelin inhibitory proteins, nerve growth factor, or factors present in conditioned media that may counteract the repulsiveness of some of these molecules preserved in sections of, for example, myelinated nerves or adult brain white matter. The present study describes the novel use of lesioned central nervous system cryocultures as substrates for investigating the attachment of embryonic neurons and PC12 cells. In addition to demonstrating the use of this novel scar substrate to extend previous 'scar-in-a-dish' models (David et al. (1990) Neuron, 5:463-469; Rudge and Silver (1990) J. Neurosci., 10: 3594-3603; Rudge et al. (1989) Exp. Neurol., 103: 1-16), the present study also describes antibody and lectin perturbations of putative inhibitory molecules that result in an enhanced attachment of cells to cryosection cultures of brain and spinal cord wounds. PMID:8835793

  1. 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

  2. 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

  3. Proliferation zones in the brain of adult fish Austrolebias (Cyprinodontiform: Rivulidae): a comparative study.

    Science.gov (United States)

    Fernández, A S; Rosillo, J C; Casanova, G; Olivera-Bravo, S

    2011-08-25

    In contrast with mammals, adult fish brains exhibit an enormous potential to produce new cells. Proliferation zones, however, have been described in only a few species, hindering comparisons among genuses and orders. Here we analyzed brain cell proliferation in annual teleostean fishes Austrolebias (Cyprinodontiform: Rivulidae). Immunocytochemistry against 5-bromo-2'-deoxyuridine (BrdU) was quantitated and mapped 24 h after injection in three species with different phylogenetic positions or habitats. All species had similar brain anatomy and total volume, but olfactory bulbs, torus longitudinalis and cerebellum were of different sizes in different species. Cell proliferation was found throughout the brain. Three-D reconstructions provided evidence for contiguity along the rostro-caudal axis and concentration in the vicinity of the ventricles. Brain regions analyzed exhibited high mitotic activity, and the torus longitudinalis had the highest volume-normalized proliferation index. A. affinis exhibited the highest normalized proliferation indexes in visual regions but the lowest in olfactory bulb. A. reicherti showed an inverse pattern, suggesting that these species have a different hierarchy of sensorial modalities that could be related to phylogeny or habitat. Double immunostaining against BrdU and cell-type specific markers was performed to determine the fate of proliferating cells. A widespread gliogenesis was evidenced. Few cells positive for both BrdU and the neuronal marker HuC/D were found in the brain of the three species, demonstrating neurogenesis in the adult Austrolebias brain. Summarizing, adult members of the three species showed similar brain anatomy and cell proliferation patterns. Among species, volume-normalized proliferation indexes varied in regions involved in different sensory modalities. To our knowledge, this is the first report showing proliferating cells with neuronal markers as earlier as 24 h after BrdU injection. PMID:21664435

  4. 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.

  5. 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

  6. Humor, Rapport, and Uncomfortable Moments in Interactions with Adults with Traumatic Brain Injury

    Science.gov (United States)

    Kovarsky, Dana; Schiemer, Christine; Murray, Allison

    2011-01-01

    We examined uncomfortable moments that damaged rapport during group interactions between college students in training to become speech-language pathologists and adults with traumatic brain injury. The students worked as staff in a community-based program affiliated with a university training program that functioned as a recreational gathering…

  7. 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.

  8. 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...

  9. [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

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

    Science.gov (United States)

    2016-06-17

    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

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

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    Petra eSántha

    2016-01-01

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

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

    International Nuclear Information System (INIS)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. 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.

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

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    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.

  16. 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

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

    Science.gov (United States)

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

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. PMID:26890892

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

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    AmandaSierra

    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.

  19. 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

  20. 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

  1. 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

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

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    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.

  3. Adult-Onset Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and Normal Lactate: Case Report

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    Özdem Ertürk

    2010-06-01

    Full Text Available Leukoencephalopathy with brain stem and spinal cord involvement and high lactate (LBSL is a recently described leukoencephalopathy with a genetically proven underlying defect. Clinical features are slowly progressive pyramidal, cerebellar and dorsal column dysfunction with childhood or rarely adult onset. The genetic basis of the disease was recently identified, which concerned mutations in the DARS2 gene encoding mitochondrial aspartly-tRNA synthetase. The disease has distinct magnetic resonance imaging findings including inhomogeneous cerebral white matter abnormalities and selective brain stem and spinal cord tract involvement. Additionally, there are usually increased lactate levels on magnetic resonance spectroscopy (MRS of the abnormal white matter. In this case report, we describe the clinical and radiological features of a patient with genetically proven adult-onset LBSL and normal lactate levels on MRS.

  4. 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.

  5. 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

  6. 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

  7. 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

  8. 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...

  9. 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 ...

  10. Daily Marijuana Use Is Not Associated with Brain Morphometric Measures in Adolescents or Adults

    OpenAIRE

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

    2015-01-01

    Recent research has suggested that marijuana use is associated with volumetric and shape differences in subcortical structures, including the nucleus accumbens and amygdala, in a dose-dependent fashion. Replication of such results in well controlled studies is essential to clarify the effects of marijuana. To that end, this retrospective study examined brain morphology in a sample of adult daily marijuana users (n = 29) versus nonusers (n = 29) and a sample of adolescent daily users (n = 50) ...

  11. 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

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Daniel A Peterson

    2014-09-01

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

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. Comparative study of delayed brain damage in pubescent and adult rhesus monkeys from radiation within the therapeutic range

    International Nuclear Information System (INIS)

    The whole brains of pubescent and fully adult rhesus monkeys were subjected to 6,000 rads of fractionated supervoltage X-irradiation, and the difference of these two age groups in clinical and neuropathological changes after the irradiation was studied. The pubescent monkey was more vulnerable to irradiation than the fully adult monkey, and showed more clinical signs and more focal lesions of delayed brain damage from radiation. (author)

  1. 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 ...

  2. 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...

  3. 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

  4. 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

  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. 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...

  8. 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....

  9. A Factor Analysis of Global GABAergic Gene Expression in Human Brain Identifies Specificity in Response to Chronic Alcohol and Cocaine Exposure

    OpenAIRE

    Enoch, Mary-Anne; Baghal, Basel; Yuan, Qiaoping; Goldman, David

    2013-01-01

    Although expression patterns of GABAergic genes in rodent brain have largely been elucidated, no comprehensive studies have been performed in human brain. The purpose of this study was to identify global patterns of GABAergic gene expression in healthy adults, including trans and cis effects in the GABAA gene clusters, before determining the effects of chronic alcohol and cocaine exposure on gene expression in the hippocampus. RNA-Seq data from ‘BrainSpan’ was obtained across 16 brain regions...

  10. Oligodendrogenesis after Cerebral Ischaemia and Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

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

    Science.gov (United States)

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

    2011-06-01

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

  12. 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.

  13. The effects of radiotherapy on psychosocial and cognitive functioning in adults with a primary brain tumor: a prospective evaluation†

    OpenAIRE

    Kangas, Maria; Tate, Robyn L.; Williams, Janet R.; Smee, Robert I.

    2012-01-01

    A paucity of studies have evaluated the biopsychosocial factors contributing to quality of life (QoL) in adults with a primary brain tumor (BT). Our objective was to investigate (i) the effects of radiotherapy on the psychosocial (ie, posttraumatic stress symptoms [PTSS]) and cognitive functioning of adults with a primary BT, assessed preradiotherapy [T1] and postradiotherapy [T2], and (ii) predictors of PTSS and QoL postradiotherapy. Seventy adults with a BT were assessed at T1, and 67 patie...

  14. 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.)

  15. 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.)

  16. Rodent Research-1 Validation of Rodent Hardware

    Science.gov (United States)

    Globus, Ruth; Beegle, Janet

    2013-01-01

    To achieve novel science objectives, validation of a rodent habitat on ISS will enable - In-flight analyses during long duration spaceflight- Use of genetically altered animals- Application of modern analytical techniques (e.g. genomics, proteomics, and metabolomics)

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

    Directory of Open Access Journals (Sweden)

    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

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. Dopamine from the brain promotes spinal motor neuron generation during development and adult regeneration.

    Science.gov (United States)

    Reimer, Michell M; Norris, Anneliese; Ohnmacht, Jochen; Patani, Rickie; Zhong, Zhen; Dias, Tatyana B; Kuscha, Veronika; Scott, Angela L; Chen, Yu-Chia; Rozov, Stanislav; Frazer, Sarah L; Wyatt, Cameron; Higashijima, Shin-ichi; Patton, E Elizabeth; Panula, Pertti; Chandran, Siddharthan; Becker, Thomas; Becker, Catherina G

    2013-06-10

    Coordinated development of brain stem and spinal target neurons is pivotal for the emergence of a precisely functioning locomotor system. Signals that match the development of these far-apart regions of the central nervous system may be redeployed during spinal cord regeneration. Here we show that descending dopaminergic projections from the brain promote motor neuron generation at the expense of V2 interneurons in the developing zebrafish spinal cord by activating the D4a receptor, which acts on the hedgehog pathway. Inhibiting this essential signal during early neurogenesis leads to a long-lasting reduction of motor neuron numbers and impaired motor responses of free-swimming larvae. Importantly, during successful spinal cord regeneration in adult zebrafish, endogenous dopamine promotes generation of spinal motor neurons, and dopamine agonists augment this process. Hence, we describe a supraspinal control mechanism for the development and regeneration of specific spinal cell types that uses dopamine as a signal. PMID:23707737

  4. 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. PMID:27156560

  5. 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

  6. 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.

  7. 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.

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

    DEFF Research Database (Denmark)

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

    1997-01-01

    inflammatory cytokines in injury systems in which the presence or absence of astrogliosis could be produced selectively. A stab injury to the adult mouse brain using a piece of nitrocellulose (NC) membrane elicited a prompt and marked increase in levels of transcripts for interleukin (IL)-1alpha, IL-1beta, and...... greater extent by an NC-implant injury, which produced astrogliosis, than after an NC-stab, with minimal astrogliosis. We determined whether endogenous interferon (IFN)-gamma could be responsible for the observed increases in IL-1 and TNF-alpha, because IFN-gamma is a potent microglia/macrophage activator...

  9. 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. PMID:24811179

  10. 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.

  11. Primary Neuronal Precursors in Adult Crayfish Brain: Replenishment from a Non-neuronal Source

    Directory of Open Access Journals (Sweden)

    Sandeman David C

    2011-06-01

    Full Text Available Abstract Background Adult neurogenesis, the production and integration of new neurons into circuits in the brains of adult animals, is a common feature of a variety of organisms, ranging from insects and crustaceans to birds and mammals. In the mammalian brain the 1st-generation neuronal precursors, the astrocytic stem cells, reside in neurogenic niches and are reported to undergo self-renewing divisions, thereby providing a source of new neurons throughout an animal's life. In contrast, our work shows that the 1st-generation neuronal precursors in the crayfish (Procambarus clarkii brain, which also have glial properties and lie in a neurogenic niche resembling that of vertebrates, undergo geometrically symmetrical divisions and both daughters appear to migrate away from the niche. However, in spite of this continuous efflux of cells, the number of neuronal precursors in the crayfish niche continues to expand as the animals grow and age. Based on these observations we have hypothesized that (1 the neuronal stem cells in the crayfish brain are not self-renewing, and (2 a source external to the neurogenic niche must provide cells that replenish the stem cell pool. Results In the present study, we tested the first hypothesis using sequential double nucleoside labeling to track the fate of 1st- and 2nd-generation neuronal precursors, as well as testing the size of the labeled stem cell pool following increasing incubation times in 5-bromo-2'-deoxyuridine (BrdU. Our results indicate that the 1st-generation precursor cells in the crayfish brain, which are functionally analogous to neural stem cells in vertebrates, are not a self-renewing population. In addition, these studies establish the cycle time of these cells. In vitro studies examining the second hypothesis show that Cell Tracker™ Green-labeled cells extracted from the hemolymph, but not other tissues, are attracted to and incorporated into the neurogenic niche, a phenomenon that appears to

  12. 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...

  13. 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, ...

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

    International Nuclear Information System (INIS)

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1986-03-01

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

  16. Object Recognition Memory and the Rodent Hippocampus

    Science.gov (United States)

    Broadbent, Nicola J.; Gaskin, Stephane; Squire, Larry R.; Clark, Robert E.

    2010-01-01

    In rodents, the novel object recognition task (NOR) has become a benchmark task for assessing recognition memory. Yet, despite its widespread use, a consensus has not developed about which brain structures are important for task performance. We assessed both the anterograde and retrograde effects of hippocampal lesions on performance in the NOR…

  17. 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.

  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. 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.

  20. 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.

  1. 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 ...

  2. 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

  3. [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

  4. 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

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    Jonathan List

    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.

  7. Expression of Npas4 mRNA in telencephalic areas of adult and postnatal mouse brain

    Directory of Open Access Journals (Sweden)

    Ursula H Winzer-Serhan

    2015-11-01

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

  8. 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

  9. 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.

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

    OpenAIRE

    Laura Ponce de León; John Waterworth

    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-hr non-action video game training sessions with games selected from a commercially available package (Lumosity) on a series of age-declined cogn...

  11. Radionuclide gamma-topography of the brain in the diagnosis of inflammatory process in adults and children

    International Nuclear Information System (INIS)

    Gamma-topography of the brain as a differential diagnostic method permits the recognition of an inflammatory process and specification of its localization. Altogether 61 patients were investigated: abscesses of the brain (36 patients, of them 16 children); focal arachnoencephalitides (14 patients, of them 5 children); arachnoiditides (11 patients). Due to its simplicity, small radiation exposure and noninvasive character of the method gamma-topography can be recommended in outpatient clinics and hospitals both for children and adults

  12. 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...

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

    Science.gov (United States)

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

    2009-06-01

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

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

    Science.gov (United States)

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

    2005-03-01

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

  15. 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)

  16. 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 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 home. CONCLUSIONS Age, hypotension on ED admission, severity of head and extracranial injuries

  17. 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.)

  18. 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.

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

    International Nuclear Information System (INIS)

    We have developed 18F-fluoxetine as a radiotracer analog of the antidepressant drug fluoxetine (Prozac). In vitro saturation experiments of 18F-fluoxetine were carried out on rat midbrain tissue and citalopram was used for measuring nonspecific binding. A saturation curve for the binding of 18F-fluoxetine was not obtained. Even when fluoxetine (10 μM) 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 18F-fluoxetine. Ex vivo autoradiographic experiments with 18F-fluoxetine did not reveal any specific uptake in various brain regions. In vivo administration of 18F-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 18F-fluoxetine indicated significant amounts of binding in mitochondria and synaptosomes. In summary, in vitro experiments with 18F-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 18F-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. 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…

  1. 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

  2. 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.

  3. 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'. PMID:26644026

  4. A study on brain ventricle measurement of normal Korean adults using computed tomography

    International Nuclear Information System (INIS)

    The study was undertaken to assess the ventricular system of the brain in normal Korean adults on the base of computed tomography. The computerized tomographic examinations of 334 Korean adults between ages of 15 to 50 years, performed at Seoul National University Hospital, were evaluated. The cerebro- or cerebello-ventricular ratio, between ventricular size and brain parenchyme width, has been known to be a reliable indicator of the ventricular size. This ratio was measured at the level of the lateral, third and fourth ventricles respectively. The shape of the quardigeminal and suprasellar cistern was analyzed. The results are as follows: 1. The cerebroventricular ratios of the lateral ventricle at the level of the widest bifrontal and bicaudate diameters were 0.30 ± 0.04 and 0.14 ± 0.02, respectively. The lateral ventricle was asymmetric in 12.6%, of which the left side was usually larger than the right. 2. There was correlation between the cerebroventricular ratio and age, i.e., with increase of age, the C-V ratio increased slightly. 3. The cerebroventricular ratio of the third ventricle was 0.03 ± 0.01. 4. The cerebroventricular ratio of the fourth ventricle in width and height was 0.14± 0.02 and 0.10 ± 0.03, respectively. The anteroposterior position index of the fourth ventricle was 0.42 ± 0.04. 5. The quadrigeminal cistern showed W-shape in 76.6% and U-shape in 23.4%. 6. The suprasellar cistern showed pentagonal shape in 61.1%, round in 28.4% and hexagonal in 10.5%. 7. There was no significant difference between male and female according to the above results

  5. A study on brain ventricle measurements of normal Korean adults using computed tomography

    International Nuclear Information System (INIS)

    The study was undertaken to assess the ventricular system of the brain in normal Korean adults on the base of computed tomography. The computerized tomographic examinations of 334 Korean adults between ages of 15 to 50 years, performed at Seoul National University Hospital, were evaluated. The cerebro- or cerebello-ventricular ratio, between ventricular size and brain parenchyme width, has been known to be reliable indicator of the ventricular size. This ratio was measured at the level of the lateral, third and fourth ventricles respectively. The shape of the quardigeminal and suprasellar cistern was analyzed. The results are as follows: 1. The cerebroventricular ratios of the lateral ventricle at the level of the widest bifrontal and bicaudate diameters were 0.30 ± 0.04 and 0.14 ± 0.02, respectively. The lateral ventricle was asymmetric in 12.6%, of which the left side was usually larger than the right. 2. There was correlation between the cerebroventricular ratio and age, i.e., with increase of age, the C-V ratio increased slightly. 3. The cerebrocventricular ratio of the third ventricle was 0.03 ± 0.01. 4. The cerebroventricular ratio of the fourth ventricle in width and height was 0.14 ± 0.02 and 0.10 ± 0.03, respectively. The anteroposterior position index of the fourth ventricle was 0.42 ± 0.04. 5. The quadrigeminal cistern showed W-shape in 76.6% and U-shaped in 23.4%. 6. The suprasellar cistern showed pentagonal shape in 61.1%, round in 28.4% and hexagonal in 10.5%. 7. There was no significant difference between male and female according to the above results

  6. 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

  7. 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

  8. Outcome of decompressive craniectomy (DC) for severe traumatic brain injury (stbi) in adults

    International Nuclear Information System (INIS)

    To evaluate the outcomes of decompressive craniectomy (DC) in adults with severe traumatic brain injury (STBI). Study Design: Observational cross-sectional. Place and Duration of Study: Neurosurgical unit CMH Rawalpindi from July, 2011 to June 2014. Material and Methods: Total of 39 patients who underwent DC for STBI were included in the study. Patients of both sexes and of age range 20 - 48 (32.03 +- 8.01) years were included in the study. The DC was performed within 24 and after 24 hours. Parameters recorded were mortality, neurological outcome / complications like brain herniation, wound dehiscence, cerebrospinal fluid (CSF) leak, contusion expansion, sinking flap syndrome, subdural hygromas and hydrocephalus. Data was analyzed by using SPSS version 17 and descriptive statistics, frequency, rate and percentage was computed for presentation of qualitative outcomes. Results: Favourable neurological outcome was seen in 21 patients (53.85%) where as 6 patients (15.38%) had moderate to severe disability and 3 patients (7.69%) were vegetative respectively. Patients operated within 24 hours and with Glasgow coma scale (GCS) range 6-8 had better outcome. Overall 9 patients (23.08%) did not survive the injury and procedure. Conclusion: As high mortality is associated with STBI, DC is an effective option to lower down the refractory intracranial hypertension with an acceptable surgical outcome. (author)

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

    Science.gov (United States)

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

    2010-06-01

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

  10. 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

  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. 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)…

  13. 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...

  14. Remarkable Reduction of MAP2 in the Brains of Scrapie-Infected Rodents and Human Prion Disease Possibly Correlated with the Increase of Calpain

    OpenAIRE

    Guo, Yan; Gong, Han-Shi; Zhang, Jin; Xie, Wu-Ling; Tian, Chan; Chen, Cao; Shi, Qi; Wang, Shao-Bin; Xu, Yin; Zhang, Bao-Yun; Dong, Xiao-Ping

    2012-01-01

    Microtubule-associated protein 2 (MAP2) belongs to the family of heat stable MAPs, which takes part in neuronal morphogenesis, maintenance of cellular architecture and internal organization, cell division and cellular processes. To obtain insight into the possible alteration and the role of MAP2 in transmissible spongiform encephalopathies (TSEs), the MAP2 levels in the brain tissues of agent 263K-infected hamsters and human prion diseases were evaluated. Western blots and IHC revealed that a...

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Remarkable reduction of MAP2 in the brains of scrapie-infected rodents and human prion disease possibly correlated with the increase of calpain.

    Science.gov (United States)

    Guo, Yan; Gong, Han-Shi; Zhang, Jin; Xie, Wu-Ling; Tian, Chan; Chen, Cao; Shi, Qi; Wang, Shao-Bin; Xu, Yin; Zhang, Bao-Yun; Dong, Xiao-Ping

    2012-01-01

    Microtubule-associated protein 2 (MAP2) belongs to the family of heat stable MAPs, which takes part in neuronal morphogenesis, maintenance of cellular architecture and internal organization, cell division and cellular processes. To obtain insight into the possible alteration and the role of MAP2 in transmissible spongiform encephalopathies (TSEs), the MAP2 levels in the brain tissues of agent 263K-infected hamsters and human prion diseases were evaluated. Western blots and IHC revealed that at the terminal stages of the diseases, MAP2 levels in the brain tissues of scrapie infected hamsters, a patient with genetic Creutzfeldt-Jakob disease (G114V gCJD) and a patient with fatal familial insomnia (FFI) were almost undetectable. The decline of MAP2 was closely related with prolonged incubation time. Exposure of SK-N-SH neuroblastoma cell line to cytotoxic PrP106-126 peptide significantly down-regulated the cellular MAP2 level and remarkably disrupted the microtubule structure, but did not alter the level of tubulin. Moreover, the levels of calpain, which mediated the degradation of a broad of cytoskeletal proteins, were significantly increased in both PrP106-126 treated SK-N-SH cells and brain tissues of 263K prion-infected hamsters. Our data indicate that the decline of MAP2 is a common phenomenon in TSEs, which seems to occur at an early stage of incubation period. Markedly increased calpain level might contribute to the reduction of MAP2. PMID:22272295

  18. The enteric bacterial metabolite propionic acid alters brain and plasma phospholipid molecular species: further development of a rodent model of autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Thomas Raymond H

    2012-07-01

    Full Text Available Abstract Gastrointestinal symptoms and altered blood phospholipid profiles have been reported in patients with autism spectrum disorders (ASD. Most of the phospholipid analyses have been conducted on the fatty acid composition of isolated phospholipid classes following hydrolysis. A paucity of information exists on how the intact phospholipid molecular species are altered in ASD. We applied ESI/MS to determine how brain and blood intact phospholipid species were altered during the induction of ASD-like behaviors in rats following intraventricular infusions with the enteric bacterial metabolite propionic acid. Animals were infused daily for 8 days, locomotor activity assessed, and animals killed during the induced behaviors. Propionic acid infusions increased locomotor activity. Lipid analysis revealed treatment altered 21 brain and 30 blood phospholipid molecular species. Notable alterations were observed in the composition of brain SM, diacyl mono and polyunsaturated PC, PI, PS, PE, and plasmalogen PC and PE molecular species. These alterations suggest that the propionic acid rat model is a useful tool to study aberrations in lipid metabolism known to affect membrane fluidity, peroxisomal function, gap junction coupling capacity, signaling, and neuroinflammation, all of which may be associated with the pathogenesis of ASD.

  19. 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

  20. 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.

  1. 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

  2. Analysis of Altered Baseline Brain Activity in Drug-Naive Adult Patients with Social Anxiety Disorder Using Resting-State Functional MRI

    OpenAIRE

    Qiu, Changjian; Feng, Yuan; Meng, Yajing; Liao, Wei; Huang, Xiaoqi; Lui, Su; Zhu, Chunyan; Chen, Huafu; Gong, Qiyong; ZHANG Wei

    2015-01-01

    Objective We hypothesize that the amplitude of low-frequency fluctuations (ALFF) is involved in the altered regional baseline brain function in social anxiety disorder (SAD). The aim of the study was to analyze the altered baseline brain activity in drug-naive adult patients with SAD. Methods We investigated spontaneous and baseline brain activities by obtaining the resting-state functional magnetic resonance imaging data of 20 drug-naïve adult SAD patients and 19 healthy controls. Voxels wer...

  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. Expression of the Otx2 homeobox gene in the developing mammalian brain: embryonic and adult expression in the pineal gland

    DEFF Research Database (Denmark)

    Rath, Martin F; Muñoz, Estela; Ganguly, Surajit;

    2006-01-01

    Otx2 is a vertebrate homeobox gene, which has been found to be essential for the development of rostral brain regions and appears to play a role in the development of retinal photoreceptor cells and pinealocytes. In this study, the temporal expression pattern of Otx2 was revealed in the rat brain......, with special emphasis on the pineal gland throughout late embryonic and postnatal stages. Widespread high expression of Otx2 in the embryonic brain becomes progressively restricted in the adult to the pineal gland. Crx (cone-rod homeobox), a downstream target gene of Otx2, showed a pineal expression...... the level of Otx2 mRNA appears to be independent of the photoneural input to the gland. Our results are consistent with the view that pineal expression of Otx2 is required for development and we hypothesize that it plays a role in the adult in controlling the expression of the cluster of genes...

  5. 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 ...

  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. 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

  8. Diffusion tensor trace mapping in normal adult brain using single-shot EPI technique: A methodological study of the aging brain

    International Nuclear Information System (INIS)

    Purpose: To quantify age-related changes of the average diffusion coefficient value in normal adult brain using orientation-independent diffusion tensor trace mapping and to address the methodological influences on diffusion quantification. Material and Methods: Fifty-four normal subjects (aged 20-79 years) were studied on a 1.5-T whole-body MR medical unit using a diffusion-weighted single-shot echo-planar imaging technique. Orientation-independent diffusion tensor trace maps were constructed for each subject using diffusion-weighted MR measurements in four different directions using a tetrahedral gradient combination pattern. The global average (including cerebral spinal fluid) and the tissue average of diffusion coefficients in adult brains were determined by analyzing the diffusion coefficient distribution histogram for the entire brain. Methodological influences on the measured diffusion coefficient were also investigated by comparing the results obtained using different experimental settings. Results: Both global and tissue averages of the diffusion coefficient are significantly correlated with age (p<0.03). The global average of the diffusion coefficient increases 3% per decade after the age of 40, whereas the increase in the tissue average of diffusion coefficient is about 1% per decade. Experimental settings for self-diffusion measurements, such as data acquisition methods and number of b-values, can slightly influence the statistical distribution histogram of the diffusion tensor trace and its average value. Conclusion: Increased average diffusion coefficient in adult brains with aging are consistent with findings regarding structural changes in the brain that have been associated with aging. The study also demonstrates that it is desirable to use the same experimental parameters for diffusion coefficient quantification when comparing between different subjects and groups of interest

  9. 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

  10. In vitro and ex vivo autoradiographic studies of nicotinic acetylcholine receptors using [18F]fluoronorchloroepibatidine in rodent and human brain

    International Nuclear Information System (INIS)

    A fluorine-18-labeled analog of the potent nicotinic agonist epibatidine is a candidate radioligand for positron emission tomographic (PET) studies of nicotinic acetylcholine receptors (nAcChR). Following intravenous administration of [18F]exo-2-(2'-fluoro-5'-pyridinyl)-7-azabicyclo[2.2.1]heptane (NFEP), high uptake in thalamus was visualized in sections of mouse and rat brain by autoradiography using a phosphor imaging device. Binding of [18F]NFEP to rat thalamic homogenate was consistent with a single class of binding site with a Kd value of 71 pM. In vitro autoradiography of thaw-mounted sections of human thalamus revealed a heterogeneous pattern of binding; Bmax values for ventrolateral nucleus, insular cortex and dorsomedial nucleus, and internal capsule were 20, 8, and 3 pmol/cc of tissue, respectively. However, similar Kd values close to 50 pM were calculated for all regions. These studies support the suitability of [18F]NFEP as a radioligand for PET studies of nAcChR in the living human brain

  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. 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...

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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.

  2. Cell culture: Progenitor cells from human brain after death

    Science.gov (United States)

    Palmer, Theo D.; Schwartz, Philip H.; Taupin, Philippe; Kaspar, Brian; Stein, Stuart A.; Gage, Fred H.

    2001-05-01

    Culturing neural progenitor cells from the adult rodent brain has become routine and is also possible from human fetal tissue, but expansion of these cells from postnatal and adult human tissue, although preferred for ethical reasons, has encountered problems. Here we describe the isolation and successful propagation of neural progenitor cells from human postmortem tissues and surgical specimens. Although the relative therapeutic merits of adult and fetal progenitor cells still need to be assessed, our results may extend the application of these progenitor cells in the treatment of neurodegenerative diseases.

  3. Correlation of Nr4a2 expression with the neuron progenitors in adult zebrafish brain.

    Science.gov (United States)

    Chen, Sheng; Luo, Guang Rui; Li, Ting; Liu, Ting Xi; Le, Weidong

    2013-11-01

    Our previous study showed that although Nr4a2b transcripts have little co-localization with tyrosine hydroxylase (TH) in the posterior tuberculum area, knockdown of Nr4a2 caused a decrease in the number of TH-positive (TH(+)) neurons in the posterior tuberculum area. It suggests that Nr4a2 expression in the progenitors may play an important role in regulating differentiation rather than survival of TH(+) progenitors in the posterior tuberculum area during early zebrafish embryogenesis. In this study, we determined the correlation between TH and Nr4a2 in adult zebrafish brain and found that Nr4a2b was co-localized with the spindle-shaped TH(+) cells in the posterior tuberculum area and some small round TH(+) cells in the pretectum area, but not with large pear-shaped TH(+) cells in adult zebrafish diencephalon. In the pretectum area, Nr4a2(+) cells were localized next to the dorsal side of TH(+) cells. Furthermore, we demonstrated that Nr4a2 was co-expressed with nestin in the progenitors of pretectum area and caudal periventricular hypothalamic zones with a lateral symmetry pattern beside the diencephalic ventricle. Co-expression of Nr4a2 and nestin in these areas was remarkably declined with aging. These findings indicate that Nr4a2 is expressed in the neuronal progenitors and plays a crucial role in the differentiation process of dopamine neuron from the stem cell. The change in Nr4a2 expression with aging suggests its possible association with neurodegenerative diseases. PMID:23842887

  4. 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 ...

  5. 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...

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

    OpenAIRE

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

    2012-01-01

    Ethanol treatment on postnatal day seven (P7) causes robust brain cell death and is a model of late gestational alcohol exposure (Ikonomidou et al., 2000). To investigate the long-term effects of P7 ethanol treatment on adult brain, mice received either two doses of saline or ethanol on P7 (2.5g/kg, s.c., 2 hours apart) and were assessed as adults (P82) for brain volume (using postmortem MRI) and cellular architecture (using immunohistochemistry). Adult mice that received P7 ethanol had reduc...

  7. Yoga Therapy in Treating Patients With Malignant Brain Tumors

    Science.gov (United States)

    2015-07-27

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

  8. 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

  9. 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

  10. 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)

  11. Estrogen and Hippocampal Plasticity in Rodent Models

    OpenAIRE

    Foy, Michael R.; Baudry, Michel; Brinton, Roberta Diaz; Thompson, Richard F.

    2008-01-01

    Accumulating evidence indicates that ovarian hormones regulate a wide variety of non-reproductive functions in the central nervous system by interacting with several molecular and cellular processes. A growing animal literature using both adult and aged rodent models indicates that 17β-estradiol, the most potent of the biologically relevant estrogens, facilitates some forms of learning and memory, in particular those that involve hippocampal-dependent tasks. A recently developed triple-transg...

  12. 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.

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

    Science.gov (United States)

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

    2015-08-01

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

  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. Gene expression analysis of neuronal precursors from adult mouse brain and differential screen for neural stem cell markers

    OpenAIRE

    Pennartz, Sandra

    2004-01-01

    In the adult mouse brain, neuronal precursor cells continuously emanate from neural stem cells (NSC) in the subventricular zone (SVZ) and migrate into the olfactory bulb (OB) where they differentiate to serve as replenishment for GABAergic interneurons. During the migration process, PSA-NCAM (Polysialic acid-Neural cell adhesion molecule) specifically marks the neuronal precursors (PSA+ cells). This phenomenon was exploited in the framework of this doctoral thesis to isolate a homogeneous cel...

  17. Brain lateralization and self-reported symptoms of ADHD in non-clinical adults: A dimensional approach

    OpenAIRE

    Saleh M. H. Mohamed; Borger, Norbertus; Geuze, Reint; van der Meere, Jacob

    2015-01-01

    Many clinical studies reported a compromised Brain Lateralization (BL) in patients with Attention-Deficit/Hyperactivity Disorder (ADHD). However, the question remains whether the deficit is in the left or right hemisphere. It is well-recognized that research on patients is vulnerable to comorbidities involved in clinical ADHD and medical history variability. Therefore, the present study applied the dimensional approach to test the relationship between BL in a non-clinical healthy adults and s...

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

    Science.gov (United States)

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

    2016-03-01

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

  19. 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.

  20. Contribution of non-genetic factors to dopamine and serotonin receptor availability in the adult human brain

    DEFF Research Database (Denmark)

    Borg, J; Cervenka, S; Kuja-Halkola, R; Matheson, G J; Jönsson, E G; Lichtenstein, P; Henningsson, S; Ichimiya, T; Larsson, H; Stenkrona, P; Halldin, C; Farde, L

    2016-01-01

    and environmental factors, respectively, on dopaminergic and serotonergic markers in the living human brain. Eleven monozygotic and 10 dizygotic healthy male twin pairs were examined with PET and [(11)C]raclopride binding to the D2- and D3-dopamine receptor and [(11)C]WAY100635 binding to the......The dopamine (DA) and serotonin (5-HT) neurotransmission systems are of fundamental importance for normal brain function and serve as targets for treatment of major neuropsychiatric disorders. Despite central interest for these neurotransmission systems in psychiatry research, little is known about...... binding and a major contribution of environmental factors (pairwise shared and unique individual; 0.70-0.75) on neocortical 5-HT1A receptor binding. Our findings indicate that individual variation in neuroreceptor availability in the adult brain is the end point of a nature-nurture interplay, and call for...

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

    International Nuclear Information System (INIS)

    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)

  2. 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)

  3. 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.

  4. 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 ...

  5. 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

  6. 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

  7. 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.

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

    Science.gov (United States)

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

    2016-08-01

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

  9. Time course of hypothalamic-pituitary deficiency in adults receiving cranial radiotherapy for primary extrasellar brain tumors

    International Nuclear Information System (INIS)

    Background: No longitudinal data on hypothalamic-pituitary (HP) function are available in patients who had received cranial radiation therapy (CRT) for primary extrasellar brain tumors (PBT). Purpose: To investigate the effects of CRT on HP function in adults with PBT. Patients and methods: Twenty-six adults irradiated for PBT and six CRT naive controls were studied. CRT was delivered with 6 MV X-ray by a linear accelerator (2 Gy fraction schedule). Gross Tumor Volume (GTV) excluded the HP region that was contoured on the planning CT. Median dose to the HP region was 41.8 Gy (IQR: 30.7-49.8). Results: All controls maintained normal HP function. Hypopituitarism developed in 38% of CRT patients (GH deficiency 29%, ACTH 22%, TSH 14%, gonadotropin 4%, no abnormal prolactin level or diabetes insipidus). All HP failures occurred within 32 months after CRT. Conclusions: Adults undergoing CRT for PBT are at increased risk for HP dysfunction within 3 years from CRT. Endocrine surveillance is recommended also in adults patients exposed to CRT for primary brain tumors distant from HP region.

  10. 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.

  11. 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 ...

  12. 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.

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

    Science.gov (United States)

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

    2016-05-01

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

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

    Science.gov (United States)

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

    2016-03-01

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

  15. Neuron-enriched gene expression patterns are regionally anti-correlated with oligodendrocyte-enriched patterns in the adult mouse and human brain

    Directory of Open Access Journals (Sweden)

    Powell PatrickChengTan

    2013-02-01

    Full Text Available An important goal in neuroscience is to understand gene expression patterns in the brain. The recent availability of comprehensive and detailed expression atlases for mouse and human creates opportunities to discover global patterns and perform cross-species comparisons. Recently we reported that the major source of variation in gene transcript expression in the adult normal mouse brain can be parsimoniously explained as reflecting regional variation in glia-to-neuron ratios, and is correlated with degree of connectivity and location in the brain along the anterior-posterior axis. Here we extend this investigation to two gene expression assays of adult normal human brains that consisted of over 300 brain region samples, and perform comparative analyses of brain-wide expression patterns to the mouse. We performed principal components analysis (PCA on the regional gene expression of the adult human brain to identify the expression pattern that has the largest variance. As in the mouse, we observed that the first principal component is composed of two anti-correlated patterns enriched in oligodendrocyte and neuron markers respectively. However, we also observed interesting discordant patterns between the two species. For example, a few mouse neuron markers show expression patterns that are more correlated with the human oligodendrocyte-enriched pattern and vice-versa. In conclusion, our work provides insights into human brain function and evolution by probing global relationships between regional cell type marker expression patterns in the human and mouse brain.

  16. 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.

  17. Rodent Carcinogenicity Dataset

    OpenAIRE

    Fjodorova, Natalja; Novič, Marjana

    2013-01-01

    The rodent carcinogenicity dataset was compiled from the Carcinogenic Potency Database (CPDBAS) and was applied for the classification of quantitative structure-activity relationship (QSAR) models for the prediction of carcinogenicity based on the counter-propagation artificial neural network (CP ANN) algorithm. The models were developed within EU-funded project CAESAR for regulatory use. The dataset contains the following information: common information about chemicals (ID, chemical name, an...

  18. 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.

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

    Science.gov (United States)

    Zhang, Ning

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

  20. 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...

  1. 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 ...

  2. 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.

  3. 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. PMID:25352805

  4. 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

  5. Transient activation of dopaminergic neurons during development modulates visual responsiveness, locomotion and brain activity in a dopamine ontogeny model of schizophrenia

    OpenAIRE

    Calcagno, B; Eyles, D; Alphen, B. van; van Swinderen, B

    2013-01-01

    It has been observed that certain developmental environmental risk factors for schizophrenia when modeled in rodents alter the trajectory of dopaminergic development, leading to persistent behavioural changes in adults. This has recently been articulated as the “dopamine ontogeny hypothesis of schizophrenia”. To test one aspect of this hypothesis, namely that transient dopaminergic effects during development modulate attention-like behavior and arousal in adults, we turned to a small-brain mo...

  6. 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

  7. 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.

  8. 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…

  9. 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)....

  10. 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 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

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

    Science.gov (United States)

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

    2016-01-01

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

  12. 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.

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

    Science.gov (United States)

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

    2013-01-01

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

  14. Screening for Psychological Distress in Adult Primary Brain Tumor Patients and Caregivers: Considerations for Cancer Care Coordination

    OpenAIRE

    Trad, Wafa; Koh, Eng-Siew; Daher, Maysaa; Bailey, Alanah; Kastelan, Marina; Legge, Dianne; Fleet, Marcia; Simpson, Grahame K.; Hovey, Elizabeth

    2015-01-01

    Introduction This study aimed to assess psychological distress (PD) as scored by the Distress Thermometer (DT) in adult primary brain tumor patients and caregivers (CGs) in a clinic setting and ascertain if any high-risk subgroups for PD exist. Material and methods From May 2012 to August 2013, n = 96 patients and n = 32 CG underwent DT screening at diagnosis, and a differing cohort of n = 12 patients and n = 14 CGs at first recurrence. Groups were described by diagnosis (high grad...

  15. 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

  16. 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. PMID:25712402

  17. 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.

  18. 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...

  19. 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...

  20. Metabolism of plasma-derived B-methyl-heptadecanoic acid in adult, awake rat brain

    International Nuclear Information System (INIS)

    The authors have determined the utilization of [1-14C]-3-methyl-heptadecanoic acid (BHM), a beta-methyl fatty acid analog considered unable to undergo beta-oxidation, by brain in awake, 3 month-old Fischer-344 rats. BMH purity, structure, and mass were verified by TLC, NMR, and EI-MS. The distribution of radioactivity between CO2, water-soluble metabolites, lipids, and proteins was measured in plasma and brain after an intravenous bolus administration. Plasma radioactivity decreased rapidly within 20 min after injection, whereas the proportion of plasma 14CO2 increased to represent 20% of plasma radioactivity from 10-20 min, 6% at 1 h, and less thereafter. Total brain radioactivity peaked at 45 min, and decreased by 50% at 4 h and by 70% at 48 h. The proportion of label in the lipid fraction initially declined very rapidly, representing only 15% of total brain radioactivity at 1 h with 70 and 15% in the water-soluble and protein fractions. However, by 4 h, the lipid, protein, and aqueous compartments contained 30, 25, and 45% of the brain label, respectively, and 50, 35, and 15% at 48 h. Amino acids comprised most of the water-soluble radioactivity, with the combined glutamate and glutamine pools containing 60-70% of the aqueous label from 5 min to 6 h. Therefore, in addition to being incorporated into brain lipids, significant oxidation of BMH occurred, labelling brain amino acids and proteins, such that the decrease in brain radioactivity primarily represents decreasing water-soluble radioactivity

  1. 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...

  2. 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. ...

  3. Intrinsic Brain Connectivity Related to Age in Young and Middle Aged Adults

    OpenAIRE

    Hampson, Michelle; Tokoglu, Fuyuze; Shen, Xilin; Scheinost, Dustin; Papademetris, Xenophon; Constable, R. Todd

    2012-01-01

    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 re...

  4. Conservation and diversity of Foxp2 expression in muroid rodents: functional implications.

    Science.gov (United States)

    Campbell, Polly; Reep, Roger L; Stoll, Margaret L; Ophir, Alexander G; Phelps, Steven M

    2009-01-01

    FOXP2, the first gene causally linked to a human language disorder, is implicated in song acquisition, production, and perception in oscine songbirds, the evolution of speech and language in hominids, and the evolution of echolocation in bats. Despite the evident relevance of Foxp2 to vertebrate acoustic communication, a comprehensive description of neural expression patterns is currently lacking in mammals. Here we use immunocytochemistry to systematically describe the neural distribution of Foxp2 protein in four species of muroid rodents: Scotinomys teguina and S. xerampelinus ("singing mice"), the deer mouse, Peromyscus maniculatus, and the lab mouse, Mus musculus. While expression patterns were generally highly conserved across brain regions, we identified subtle but consistent interspecific differences in Foxp2 distribution, most notably in the medial amygdala and nucleus accumbens, and in layer V cortex throughout the brain. Throughout the brain, Foxp2 was highly enriched in areas involved in modulation of fine motor output (striatum, mesolimbic dopamine circuit, olivocerebellar system) and in multimodal sensory processing and sensorimotor integration (thalamus, cortex). We propose a generalized model for Foxp2-modulated pathways in the adult brain including, but not limited to, fine motor production and auditory perception. PMID:18972576

  5. Differential expression of three gap junction proteins in developing and mature brain tissues.

    OpenAIRE

    Dermietzel, R; Traub, O; Hwang, T K; Beyer, E.; Bennett, M V; Spray, D C; Willecke, K.

    1989-01-01

    By using antibodies directed against gap junction proteins of liver (connexins 26 and 32) and heart (connexin 43), we have localized immunoreactivity to specific cell types in frozen sections of adult rodent brains. Connexin 32 reactivity was found in oligodendrocytes and also in a few neurons, whereas reactivity to connexins 26 and 43 was localized to leptomeningeal cells, ependymal cells, and pineal gland. Immunoreactivity with antibodies to connexin 43 also occurred in astrocytes. Furtherm...

  6. 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

  7. 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

  8. 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

  9. Management and survival of pineoblastoma. An analysis of 34 adults from the brain tumor registry of Japan

    International Nuclear Information System (INIS)

    Pineoblastoma is a rare tumor in adults, and factors influencing survival are poorly understood. Data from the Brain Tumor Registry of Japan (BTRJ) was analyzed to examine patient, tumor, and treatment characteristics associated with increased survival in adults with pineoblastomas. All pineoblastoma cases in adults aged 16 years or older were identified in the BTRJ. Data were extracted on demographics, presentation, tumor characteristics, treatments, and outcomes. Kaplan-Meier plots, the log rank method, and p value <0.15 was used to screen variables for inclusion in a multivariate Cox regression estimating survival. In the final Cox multivariate model, all variables with p values <0.05 were considered significant predictors of survival, and all variables with p values 0.05-0.099 were considered trends. The BTRJ contained 34 adults with pineoblastomas diagnosed from 1969-1998. The patients were predominantly male (22 patients), with a median age of 35 years (range 16-66 years). Median survival from diagnosis was 25.7 months, with a median follow up of 20.5 months. Median surgical resection was 75-94%, and five of the 34 patients had gross total resection. Twenty-nine of the 34 patients received cranial irradiation therapy with a median dose of 50 Gy (range 30-70 Gy). In the final multivariate model, cranial irradiation≥40 Gy (p=0.014) and gross total resection (p=0.034) were associated with improved survival. There was a trend towards improved survival for women (p=0.099). Adult pineoblastoma patients have poor survival prognosis. Cranial irradiation therapy using at least 40 Gy and complete surgical resection are associated with improved survival. (author)

  10. 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.

  11. The cell birth marker BrdU does not affect recruitment of subsequent cell divisions in the adult avian brain.

    Science.gov (United States)

    Cattan, Anat; Ayali, Amir; Barnea, Anat

    2015-01-01

    BrdU is commonly used to quantify neurogenesis but also causes mutation and has mitogenic, transcriptional, and translational effects. In mammalian studies, attention had been given to its dosage, but in birds such examination was not conducted. Our previous study suggested that BrdU might affect subsequent cell divisions and neuronal recruitment in the brain. Furthermore, this effect seemed to increase with time from treatment. Accordingly, we examined whether BrdU might alter neurogenesis in the adult avian brain. We compared recruitment of [(3)H]-thymidine(+) neurons in brains of zebra finches (Taeniopygia guttata) when no BrdU was involved and when BrdU was given 1 or 3 months prior to [(3)H]-thymidine. In nidopallium caudale, HVC, and hippocampus, no differences were found between groups in densities and percentages of [(3)H]-thymidine(+) neurons. The number of silver grains per [(3)H]-thymidine(+) neuronal nucleus and their distribution were similar across groups. Additionally, time did not affect the results. The results indicate that the commonly used dosage of BrdU in birds has no long-term effects on subsequent cell divisions and neuronal recruitment. This conclusion is also important in neuronal replacement experiments, where BrdU and another cell birth marker are given, with relatively long intervals between them. PMID:25759813

  12. 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.

  13. 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

  14. 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

  15. 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...

  16. 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...

  17. Thyroid Hormone Homeostasis in Adult Mammalian Brain: A Novel Mechanism for Functional Preservation of Cerebral T3 Content During Initial Peripheral Hypothyroidism

    Directory of Open Access Journals (Sweden)

    Samita Kundu

    2010-01-01

    Full Text Available brain is well known. But the action of THs in the adult brain was not widely a focus of study by endocrinologists based on lack of increased energy metabolism and oxygen consumption with changing thyroid status and thus not widely acknowledged. Extensive research has, however, revealed interesting findings like sequestration of T3, possible release of T3 as a neurotransmitter in nerve terminals, identification of specific membrane binding sites of T3 in the synaptosomal fraction of adult rat brain and many non-genomic neurotransmitter-like actions of TH in the adult mammalian brain. Most importantly, thyroid dysfunction is associated with significant disruption of psychobehavioural system in the adult, which can however be reversed with therapeutic hormonal intervention. A complex regulatory network involving transfer of TH through the brain barriers, interactions between neurons and glial cells, and deiodinase expression works synchronously to deliver the appropriate amount of T3 to the neurons. Despite peripheral hypo- or hyper-thyroidism, brain can maintain a normal level of TH up to certain duration. Thus, presence of a novel homeostatic mechanism in the adult mammalian brain (‘central homeostasis for thyroid hormone’ to defend the adverse neuropsychological manifestations commonly associated with peripheral hypothyroidism has been known for a long time. Unfortunately, the exact time course and the mechanism of such central homeostasis were not determined, till we made a pioneering attempt to evaluate the same. The entire phenomenon appeared to be coupled with nuclear mediated genomic processes like mRNA and protein synthesis. Moreover, the effects of THs on some key enzymes and ions related to neurotransmission during the start and end days of this central homeostatic phenomenon point towards a dependency of the enzymes on TH and an involvement of TH in the neurobiochemical events

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. Preoperative mapping of cortical language areas in adult brain tumour patients using PET and individual non-normalised SPM analyses

    International Nuclear Information System (INIS)

    In patients scheduled for the resection of perisylvian brain tumours, knowledge of the cortical topography of language functions is crucial in order to avoid neurological deficits. We investigated the applicability of statistical parametric mapping (SPM) without stereotactic normalisation for individual preoperative language function brain mapping using positron emission tomography (PET). Seven right-handed adult patients with left-sided brain tumours (six frontal and one temporal) underwent 12 oxygen-15 labelled water PET scans during overt verb generation and rest. Individual activation maps were calculated for P<0.005 and P<0.001 without anatomical normalisation and overlaid onto the individuals' magnetic resonance images for preoperative planning. Activations corresponding to Broca's and Wernicke's areas were found in five and six cases, respectively, for P<0.005 and in three and six cases, respectively, for P<0.001. One patient with a glioma located in the classical Broca's area without aphasic symptoms presented an activation of the adjacent inferior frontal cortex and of a right-sided area homologous to Broca's area. Four additional patients with left frontal tumours also presented activations of the right-sided Broca's homologue; two of these showed aphasic symptoms and two only a weak or no activation of Broca's area. Other frequently observed activations included bilaterally the superior temporal gyri, prefrontal cortices, anterior insulae, motor areas and the cerebellum. The middle and inferior temporal gyri were activated predominantly on the left. An SPM group analysis (P<0.05, corrected) in patients with left frontal tumours confirmed the activation pattern shown by the individual analyses. We conclude that SPM analyses without stereotactic normalisation offer a promising alternative for analysing individual preoperative language function brain mapping studies. The observed right frontal activations agree with proposed reorganisation processes, but

  3. 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

  4. 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.

  5. 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...

  6. 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...

  7. Child, Adolescent, and Young Adult Community Integration after a Traumatic Brain Injury

    Science.gov (United States)

    Barton, Barbara; Brouwers, Lynn; Ruoff, Janis; Trudel, Tina M.; Valnes, Betsy; Elias, Eileen; Pines, Hayley

    2010-01-01

    "Rehabilitation," as a term in and of itself, implies a goal of bringing something back to its original state of being. However, for many people living with traumatic brain injury (TBI), rehabilitation means learning to live all over again. Through means of education and employment, this article explores the quest for inclusive community…

  8. 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.

  9. Chronic social isolation affects thigmotaxis and whole-brain serotonin levels in adult zebrafish.

    Science.gov (United States)

    Shams, Soaleha; Chatterjee, Diptendu; Gerlai, Robert

    2015-10-01

    The popularity of the zebrafish has been growing in behavioral brain research. Previously utilized mainly in developmental biology and genetics, the zebrafish has turned out to possess a complex behavioral repertoire. For example, it is a highly social species, and individuals form tight groups, a behavior called shoaling. Social isolation induced changes in brain function and behavior have been demonstrated in a variety of laboratory organisms. However, despite its highly social nature, the zebrafish has rarely been utilized in this research area. Here, we investigate the effects of chronic social isolation (lasting 90 days) on locomotor activity and anxiety-related behaviors in an open tank. We also examine the effect of chronic social isolation on levels of whole-brain serotonin and dopamine and their metabolites. We found that long-term social deprivation surprisingly decreased anxiety-related behavious during open-tank testing but had no effect on locomotor activity. We also found that serotonin levels, decreased significantly in socially isolated fish, but levels of dopamine and metabolites of these neurotransmitters 5HIAA and DOPAC, respectively, remained unchanged. Our results imply that the standard high density housing employed in most zebrafish laboratories may not be the optimal way to keep these fish, and open a new avenue towards the analysis of the biological mechanisms of social behavior and of social deprivation induced changes in brain function using this simple vertebrate model organism. PMID:26119237

  10. 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…

  11. 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…

  12. Reduced N400 Semantic Priming Effects in Adult Survivors of Paediatric and Adolescent Traumatic Brain Injury

    Science.gov (United States)

    Knuepffer, C.; Murdoch, B. E.; Lloyd, D.; Lewis, F. M.; Hinchliffe, F. J.

    2012-01-01

    The immediate and long-term neural correlates of linguistic processing deficits reported following paediatric and adolescent traumatic brain injury (TBI) are poorly understood. Therefore, the current research investigated event-related potentials (ERPs) elicited during a semantic picture-word priming experiment in two groups of highly functioning…

  13. 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.

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

    DEFF Research Database (Denmark)

    Dramsdahl, Margaretha; Ersland, Lars; Plessen, Kerstin J; Haavik, Jan; Hugdahl, Kenneth; Specht, Karsten

    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...

  15. Prognostic and predictive biomarkers in adult and paediatric gliomas: towards personalised brain tumour treatment

    Directory of Open Access Journals (Sweden)

    KathreenaMaryKurian

    2014-03-01

    Full Text Available It is increasingly clear that both adult and paediatric glial tumour entities represent collections of neoplastic lesions, each with individual pathological molecular events and treatment responses. In this review we discuss the current prognostic biomarkers validated for clinical use or with future clinical validity for gliomas. Accurate prognostication is crucial for managing patients as treatments may be associated with high morbidity and the benefits of high risk interventions must be judged by the treating clinicians. We also review biomarkers with predictive validity which may become clinically relevant with the development of targeted therapies for adult and paediatric gliomas.

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

    DEFF Research Database (Denmark)

    Dramsdahl, Margaretha; Ersland, Lars; Plessen, Kerstin J; Haavik, Jan; Hugdahl, Kenneth; Specht, Karsten

    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...... 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...

  17. 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...

  18. 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

  19. 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...

  20. 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...

  1. Tai Chi Chuan Optimizes the Functional Organization of the Intrinsic Human Brain Architecture in Older Adults

    OpenAIRE

    Jing Luo; Xi-Nian Zuo

    2014-01-01

    Whether Tai Chi Chuan (TCC) can influence the intrinsic functional architecture of the human brain remains unclear. To examine TCC-associated changes in functional connectomes, resting-state functional magnetic resonance images were acquired from 40 older individuals including 22 experienced TCC practitioners (experts) and 18 demographically matched TCC-naïve healthy controls, and their local functional homogeneities across the cortical mantle were compared. Compared to the controls, the TCC ...

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

    OpenAIRE

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

    2014-01-01

    Whether Tai Chi Chuan (TCC) can influence the intrinsic functional architecture of the human brain remains unclear. To examine TCC-associated changes in functional connectomes, resting-state functional magnetic resonance images were acquired from 40 older individuals including 22 experienced TCC practitioners (experts) and 18 demographically matched TCC-naïve healthy controls, and their local functional homogeneities across the cortical mantle were compared. Compared to the controls, the TCC ...

  3. Adults with PKU and brain damage : Composition and management of a protein restricted diet

    OpenAIRE

    2007-01-01

    Summary Phenylketonuria (PKU) is an inborn error of metabolism, due to a defective liver enzyme the conversion of the amino acid phenylalanine (phe) to tyrosine is not functioning. PKU was first described in 1934 by the Norwegian doctor and scientist Asbjørn Følling. Without treatment persons with PKU suffer permanent neurological damage and mental retardation. Today newborn screening programmes result in early diagnosis. Dietary treatment is started shortly after birth to prevent brain da...

  4. Additional Brain Functional Network in Adults with Attention-Deficit/Hyperactivity Disorder: A Phase Synchrony Analysis

    OpenAIRE

    Yu, Dongchuan

    2013-01-01

    We develop a method to construct a new type of functional networks by the usage of phase synchrony degree that is different from the widely used Pearson's correlation approach. By a series of very strict statistical tests, we found that there is an additional network in attention-deficit/hyperactivity disorder (ADHD) subjects, superimposing the original (normal) brain functional network corresponding to healthy controls. The additional network leads to the increase in clustering coefficient, ...

  5. Additional brain functional network in adults with attention-deficit/hyperactivity disorder: a phase synchrony analysis.

    Directory of Open Access Journals (Sweden)

    Dongchuan Yu

    Full Text Available We develop a method to construct a new type of functional networks by the usage of phase synchrony degree that is different from the widely used Pearson's correlation approach. By a series of very strict statistical tests, we found that there is an additional network in attention-deficit/hyperactivity disorder (ADHD subjects, superimposing the original (normal brain functional network corresponding to healthy controls. The additional network leads to the increase in clustering coefficient, cost, local efficiency, and global efficiency. Our findings are inconsistent with many previous researches (using the Pearson's correlation approach revealing both increased and decreased functional connections between brain regions and many reports revealing that the brain functional networks of ADHD patients have slow information flow and low global efficiency. We also confirm that the additional network in ADHD subjects contains 6 communities, and three of them are associated with emotional control, sensory information integration, and motor control, respectively. Furthermore, we find that there is a pathway connecting the left insula and left anterior cingular gyrus via the frontal gyrus and putamen in the additional network in ADHD subjects. This implies that due to the pathway connecting brain regions in the salience network, the ADHD patients are more sensitive to external stimuli or internal thoughts and are easier to switch to the executive network and hence harder to inhibit. For clinical diagnostic purposes, we apply the k-means clustering method to distinguish ADHD patients with healthy controls at the individual subject level, and obtain a meaningful diagnostic result. More interestingly, we find that the suggested technique using phase synchrony degree to construct functional networks may obtain higher classification accuracy than the method using the Pearson's correlation coefficient.

  6. Acute Stress Differentially Affects Aromatase Activity in Specific Brain Nuclei of Adult Male and Female Quail

    OpenAIRE

    Dickens, Molly J; Cornil, Charlotte; Balthazart, Jacques

    2011-01-01

    The rapid and temporary suppression of reproductive behavior is often assumed to be an important feature of the adaptive acute stress response. However, how this suppression operates at the mechanistic level is poorly understood. The enzyme aromatase converts testosterone to estradiol in the brain to activate reproductive behavior in male Japanese quail (Coturnix japonica). The discovery of rapid and reversible modification of aromatase activity (AA) provides a potential mechanism for fast, s...

  7. Proton spectroscopic imaging of brain metabolites in basal ganglia of healthy older adults

    OpenAIRE

    Parikh, Jehill; Thrippleton, Michael J.; Murray, Catherine; Armitage, Paul A.; Harris, Bridget A.; Andrews, Peter J D; Wardlaw, Joanna M.; Starr, John M.; Deary, Ian J.; Marshall, Ian

    2014-01-01

    Object We sought to measure brain metabolite levels in healthy older people. Materials and methods Spectroscopic imaging at the level of the basal ganglia was applied in 40 participants aged 73–74 years. Levels of the metabolites N-acetyl aspartate (NAA), choline, and creatine were determined in "institutional units" (IU) corrected for T1 and T2 relaxation effects. Structural imaging enabled determination of grey matter (GM), white matter (WM), and cerebrospinal fluid content. ANOVA analysis ...

  8. 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...

  9. Expression of activity-dependent neuroprotective protein in the brain of adult rats

    OpenAIRE

    Gennet, N.; Herden, C.; Bubb, V J; Quinn, J P; Kipar, A.

    2008-01-01

    Activity-dependent neuroprotective protein (ADNP) is a VIP-regulated gene, which is essential for brain development. A synthetic peptide (NAP) derived from the ADNP sequence is highly neuroprotective, therefore it has been hypothesised that ADNP has a similar role. ADNP contains classical transcription factor motifs and nuclear localisation domains, but it has also been reported to be secreted and to co-localise with microtubules, indicating that ADNP may have multiple...

  10. Self-awareness of prospective memory failure in adults with traumatic brain injury.

    Science.gov (United States)

    Roche, Nadine L; Fleming, Jennifer M; Shum, David H K

    2002-11-01

    The frequency of prospective memory failure in individuals with severe traumatic brain injury (TBI) was investigated by comparison with a non-brain-injured control group. Self-awareness of prospective memory function was also assessed by comparing self-ratings with ratings by significant others. Study participants included 33 individuals with severe TBI and 29 non-brain-injured persons. Each participant nominated a close friend or relative who completed the informant's version of the questionnaire. Participants and their significant others both rated the participants' frequency of prospective memory lapses using the Comprehensive Assessment of Prospective Memory (CAPM). An independent groups design was adopted to compare the TBI and control groups. No significant difference was found between the TBI and control participants' self-ratings of frequency of prospective memory failure, but ratings by significant others were significantly different. The TBI group demonstrated less self-awareness (i.e. underestimated the frequency of prospective memory failure compared to significant others) than the control group. PMID:12443545

  11. 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.

  12. Expression of activity-dependent neuroprotective protein in the brain of adult rats.

    Science.gov (United States)

    Gennet, N; Herden, C; Bubb, V J; Quinn, J P; Kipar, A

    2008-03-01

    Activity-dependent neuroprotective protein (ADNP) is a VIP-regulated gene, which is essential for brain development. A synthetic peptide (NAP) derived from the ADNP sequence is highly neuroprotective, therefore it has been hypothesised that ADNP has a similar role. ADNP contains classical transcription factor motifs and nuclear localisation domains, but it has also been reported to be secreted and to co-localise with microtubules, indicating that ADNP may have multiple functions. We investigated the pattern of ADNP expression by immunohistology in normal rat brain, in order to generate a framework for future studies examining changes in ADNP expression in response to noxious stimuli or in models of disease. We found widespread ADNP-like immunoreactivity in neurons throughout the rat brain, with the highest expression in the cerebellum, and strong expression in the thalamus, mesencephalon, pons and medulla oblongata. ADNP-like immunoreactivity was mainly observed in the cytoplasm of neurons, and fibre tracts were often strongly positive as well. In addition, positive neuronal nuclei were occasionally observed. ADNP-like immunoreactivity was lost in degenerating "dark" neurons, whereas it appeared to locate to the nucleus in some of the morphologically unaltered adjacent cells. Occasional astrocyte and microglial cells were also positive. We suggest that the widespread expression of ADNP may correlate with the wide-ranging protective effects of NAP, and that the cytoplasmic and axonal localisation of ADNP-like immunoreactivity suggests additional, non-transcriptional functions of ADNP. PMID:18072088

  13. 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

  14. 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.

  15. International Case-Control Study of Adult Brain, Head and Neck Tumours: Results of the Feasibility Study (invited paper)

    International Nuclear Information System (INIS)

    The objectives of the feasibility study were to collect and analyse the information necessary to assess the feasibility of a multi-centric study of adult head and neck tumours (including brain tumours) and mobile telephones. Information was obtained on the availability and accessibility of records from companies, the prevalence of mobile telephone use over time and the expected number of tumour cases in the proposed study regions. The conclusion is that it is feasible to develop a study of the relation between mobile telephone use and brain cancer risk. The feasibility of a study of the relation between radiofrequency exposure and cancer risk is, however, unclear at present. It is unknown whether a sufficiently accurate and precise RF exposure gradient can be derived to classify adequately each subject in the proposed study. A study of the relation between mobile telephone use and risk of salivary gland tumours and acoustic neurinomas is probably feasible, but more information is required about the logistic difficulties of ascertaining these cases in the study regions. Two subcommittees have been formed to develop the exposure measurement and epidemiological aspect of the study. (author)

  16. 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.

  17. 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…

  18. 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

  19. The incidence of critical-illness-related-corticosteroid-insufficiency is associated with severity of traumatic brain injury in adult rats.

    Science.gov (United States)

    Chen, Xin; Zhao, Zilong; Chai, Yan; Luo, Lanlan; Jiang, Rongcai; Zhang, Jianning

    2014-07-15

    Traumatic brain injury (TBI) causes deleterious critical-illness-related-corticosteroid-insufficiency (CIRCI), leading to high mortality and morbidity. However, the incidence of CIRCI following different TBI severities is not fully defined. This study was designed to investigate mechanistically the effects of injury severity on corticosteroid response and the development of CIRCI in a rat model of experimentally controlled TBI. Adult male Wistar rats were randomly assigned to sham, mild injury, moderate injury or severe injury groups. TBI was induced using a fluid percussion device at magnitudes of 1.2-1.4 atm (mild injury), 2.0-2.2 atm (moderate injury), and 3.2-3.5 atm (severe injury). We first assessed the effects of injury severity on the mortality and CIRCI occurrence using electrical stimulation test to assess corticosteroid response. We also investigated a series of pathological changes in the hypothalamus, especially in the paraventricular nuclei (PVN), among different injury group including: apoptosis detected by a TUNEL assay, blood-brain-barrier (BBB) permeability assessed by brain water content and Evans Blue extravasation into the cerebral parenchyma, and BBB integrity evaluated by CD31 and Claudin-5 expression and transmission electron microscopy. We made the following observations. First, 6.7% of mild-injured, 13.3% of moderate-injured, and 68.8% of severe-injured rats developed CIRCI, with a peak incidence on post-injury day 7. Second, TBI-induced CIRCI is closely correlated with injury severity. As the injury severity rises both the incidence of CIRCI and mortality surge; Third, increased level of injury severity reduces the expression of endothelial tight junction protein, aggravate BBB permeability and exacerbate the ensuing neural apoptosis in the PVN of hypothalamus. These findings indicate that increased severity of TBI aggravate the incidence of CIRCI by causing damage to tight junctions of vascular endothelial cells and increasing neuronal

  20. The pattern of amyloid accumulation in the brains of adults with Down syndrome

    Science.gov (United States)

    Annus, Tiina; Wilson, Liam R.; Hong, Young T.; Acosta–Cabronero, Julio; Fryer, Tim D.; Cardenas–Blanco, Arturo; Smith, Robert; Boros, Istvan; Coles, Jonathan P.; Aigbirhio, Franklin I.; Menon, David K.; Zaman, Shahid H.; Nestor, Peter J.; Holland, Anthony J.

    2016-01-01

    Introduction Adults with Down syndrome (DS) invariably develop Alzheimer's disease (AD) neuropathology. Understanding amyloid deposition in DS can yield crucial information about disease pathogenesis. Methods Forty-nine adults with DS aged 25–65 underwent positron emission tomography with Pittsburgh compound–B (PIB). Regional PIB binding was assessed with respect to age, clinical, and cognitive status. Results Abnormal PIB binding became evident from 39 years, first in striatum followed by rostral prefrontal-cingulo-parietal regions, then caudal frontal, rostral temporal, primary sensorimotor and occipital, and finally parahippocampal cortex, thalamus, and amygdala. PIB binding was related to age, diagnostic status, and cognitive function. Discussion PIB binding in DS, first appearing in striatum, began around age 40 and was strongly associated with dementia and cognitive decline. The absence of a substantial time lag between amyloid accumulation and cognitive decline contrasts to sporadic/familial AD and suggests this population's suitability for an amyloid primary prevention trial. PMID:26362596

  1. TAM receptors affect adult brain neurogenesis by negative regulation of microglial cell activation1

    OpenAIRE

    Ji, Rui; Tian, Shifu; Lu, Helen J.; LU, QINGJUN; Yan ZHENG; Wang, Xiaomin; Ding, Jixiang; Li, Qiutang; Lu, Qingxian

    2013-01-01

    TAM tyrosine kinases play multiple functional roles including regulation of the target genes important in homeostatic regulation of cytokine receptors or Toll-like receptor-mediated signal transduction pathways. Here, we show that TAM receptors affect adult hippocampal neurogenesis and loss of TAM receptors impair hippocampal neurogenesis, largely attributed to exaggerated inflammatory responses by microglia characterized by increased MAP kinase and NF-κB activation and elevated production of...

  2. 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. PMID:25642951

  3. 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

  4. 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

  5. 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

  6. 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...

  7. Invasive rodent eradication on islands.

    Science.gov (United States)

    Howald, Gregg; Donlan, C Josh; Galván, Juan Pablo; Russell, James C; Parkes, John; Samaniego, Araceli; Wang, Yiwei; Veitch, Dick; Genovesi, Piero; Pascal, Michel; Saunders, Alan; Tershy, Bernie

    2007-10-01

    Invasive mammals are the greatest threat to island biodiversity and invasive rodents are likely responsible for the greatest number of extinctions and ecosystem changes. Techniques for eradicating rodents from islands were developed over 2 decades ago. Since that time there has been a significant development and application of this conservation tool. We reviewed the literature on invasive rodent eradications to assess its current state and identify actions to make it more effective. Worldwide, 332 successful rodent eradications have been undertaken; we identified 35 failed eradications and 20 campaigns of unknown result. Invasive rodents have been eradicated from 284 islands (47,628 ha). With the exception of two small islands, rodenticides were used in all eradication campaigns. Brodifacoum was used in 71% of campaigns and 91% of the total area treated. The most frequent rodenticide distribution methods (from most to least) are bait stations, hand broadcasting, and aerial broadcasting. Nevertheless, campaigns using aerial broadcast made up 76% of the total area treated. Mortality of native vertebrates due to nontarget poisoning has been documented, but affected species quickly recover to pre-eradication population levels or higher. A variety of methods have been developed to mitigate nontarget impacts, and applied research can further aid in minimizing impacts. Land managers should routinely remove invasive rodents from islands <100 ha that lack vertebrates susceptible to nontarget poisoning. For larger islands and those that require nontarget mitigation, expert consultation and greater planning effort are needed. With the exception of house mice (Mus musculus), island size may no longer be the limiting factor for rodent eradications; rather, social acceptance and funding may be the main challenges. To be successful, large-scale rodent campaigns should be integrated with programs to improve the livelihoods of residents, island biosecurity, and reinvasion response

  8. Resistin in Rodents and Humans

    OpenAIRE

    Hyeong Kyu Park; Ahima, Rexford S.

    2013-01-01

    Obesity is characterized by excess accumulation of lipids in adipose tissue and other organs, and chronic inflammation associated with insulin resistance and an increased risk of type 2 diabetes. Obesity, type 2 diabetes, and cardiovascular diseases are major health concerns. Resistin was first discovered as an adipose-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents. Adipocyte-derived resistin is increased in obese rodents and strongly related to insulin resis...

  9. 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

  10. 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

  11. Attentional deficit Syndrome in adults: Correlation of clinical findings of imaging using brain SPECT technique

    International Nuclear Information System (INIS)

    The Attention Deficit Syndrome (ADS) in the adult is a clinical entity of difficult diagnosis and with a rewarding improvement of quality of life when this entity is diagnosed and treated successfully. There is an absence of diagnostic tests and therefore there is full justification for research applications for Functional NeuroIMaging techniques in ADS. Objectives We report functional imaging findings by means of HMPAO NeuroSPECT in a group of 23 adult SDA patients. These findings submit diagnostic Neuroimaging functional patterns that are characteristic of adult SDA. Method We report results in a group of 23 adult patients (17 males and 6 females) with clinical diagnosis of SDA. Patients were subjected to NeuroSPECT imaging and 58 Brodmann areas ROIS were analyzed including cortex and subcortical structures. Results Analysis of MAXIMAL perfusion within the Brodmann Area (2.5% higher pixel counts, expressed as % of higher pixel in cortex or cerebellum, whichever was smaller) demonstrates bilateral focal hyperperfusion in areas 9,10, 17,18,22,23,24 and 31 of Brodmann. In the analysis of MINIMAL values (2.5% minimal values within the Brodmann area) there is bilateral focal hypoperfusion in areas 4,11,12,18,19, and 36 and area 20 left. MEAN uptake in these Broadmann areas was diminished in area 24 left and bilateral areas 25. In the subcortical structures there is bilateral thalamic hyperperfusion. Conclusions Our results support the concept of the role of structures outside of the cerebral frontal cortex in the pathogenic of SDA. We refer to areas in the intersection of temporo-occipital lobes and also the parietal lobes. We analyzed the clinical weight of medial frontal hyperperfusion as part of the default mode, and the explanation that this model might have in the variance of neuropsychological performances observed in these patients. Furthermore our findings support also the significance of subcortical structures in the bottom-up regulation. This current report

  12. 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

  13. 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.

  14. 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 ...

  15. The relationship between cognition and functional independence in adults with traumatic brain injury.

    Science.gov (United States)

    Kaplan, C P; Corrigan, J D

    1994-06-01

    This study investigates the relationship between cognitive impairment, as measured by Orientation Group Monitoring System (OGMS) scores, and disability as measured by Functional Independence Measure (FIM) scores in a sample of 122 persons with traumatic brain injury admitted to an inpatient rehabilitation unit. The relationships between Aggregate OGMS and FIM Total, FIM Motor, and FIM Cognitive scores were significant (rho = .49, p OGMS score contributed 24%, and time to rehabilitation 5% unique variance to FIM Total score. These results support previous findings of distinct cognitive and motor subscales of the FIM, and suggest the importance of cognitive impairment to both. PMID:8002762

  16. Brain regions associated with Anhedonia in healthy adults: a PET correlation study

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. Mindfulness Based Cognitive Therapy and the Adult ADHD Brain –A Neuropsychotherapeutic Perspective

    Directory of Open Access Journals (Sweden)

    Katharina Bachmann

    2016-06-01

    Full Text Available 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.

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. Associative memory and underlying brain correlates in older adults with mild cognitive impairment.

    Science.gov (United States)

    Chen, Pei-Ching; Chang, Yu-Ling

    2016-05-01

    This study investigated associative recognition memory by using unique features of the Chinese language and the underlying neuroanatomical correlates. The study participants were 22 Chinese speakers with mild cognitive impairment (MCI) and 25 cognitively normal (CN) Chinese speakers. The results revealed that the MCI group demonstrated impaired associative memory performance, despite exhibiting item memory performance comparable with that of the CN group, and that associative memory performance in older adults was associated with gray matter integrity in the medial temporal regions as well as executive function. An abnormal elevation was also observed in false-positive errors related to features unique to Chinese characters, namely orthographical errors, in addition to rearranged and semantic errors in the MCI group relative to the CN group, and the three error subtypes were differentially associated with gray matter integrity in the hippocampus or lateral prefrontal regions. Overall, these results demonstrate the value of evaluating associative memory in people with prodromal Alzheimer's disease (AD), and further elucidate the underlying neural substrates related to associative recognition memory in older adults. PMID:27033742

  3. [Does the brain have a gender? A literature review in younger and older adults].

    Science.gov (United States)

    Compère, Laurie; Piolino, Pascale

    2014-12-01

    There are no longer doubts about the existence of gender's differences in cognition, only their origin is still controversial. The literature provides evidence of differences in cognitive performance and brain activation patterns and links these differences in men and women with biological, social and psychological measures. To date, the favored hypothesis explaining these differences is the cognitive style hypothesis according to which women and men would favor different strategies while resolving some tasks. Some of these tasks are autobiographical memory tasks, which are also the most sensitive to the effects of age but very few studies had explored the impact of aging on the differences in cognition between men and women. We discuss the importance of such studies about the gender's differences in aging. A better understanding of gender differences in cognition in pathological aging as in health would provide the opportunity to offer a more personalized care. PMID:25515905

  4. In vivo 3D digital atlas database of the adult C57BL/6J mouse brain by magnetic resonance microscopy

    Directory of Open Access Journals (Sweden)

    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.

  5. Increased Intraregional Synchronized Neural Activity in Adult Brain After Prolonged Adaptation to High-Altitude Hypoxia: A Resting-State fMRI Study.

    Science.gov (United States)

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

    2016-03-01

    Chen, Ji, Cunxiu Fan, Jinqiang Li, Qiaoqing Han, Jianzhong Lin, Tianhe Yang, and Jiaxing Zhang. Increased intraregional, synchronized neural activity in adult brain after prolonged adaptation to high-altitude hypoxia: a resting-state fMRI study. High Alt Med Biol. 17:16-24, 2016-The human brain is intrinsically plastic such that its functional architecture can be reorganized in response to environmental pressures and physiological changes. However, it remains unclear whether a compensatory modification of spontaneous neural activity occurs in adult brain during prolonged high-altitude (HA) adaptation. In this study, we obtained resting-state functional magnetic resonance (MR) images in 16 adults who have immigrated to Qinghai-Tibet Plateau (2300-4400 m) for 2 years and in 16 age-matched sea level (SL) controls. A validated regional homogeneity (Reho) method was employed to investigate the local synchronization of resting-state functional magnetic resonance imaging (fMRI) signals. Seed connectivity analysis was carried out subsequently. Cognitive and physiological assessments were made and correlated with the image metrics. Compared with SL controls, global mean Reho was significantly increased in HA immigrants as well as a regional increase in the right inferolateral sensorimotor cortex. Furthermore, mean z-Reho value extracted within the inferolateral sensorimotor area showed trend-level significant inverse correlation with memory search reaction time in HA immigrants. These observations, for the first time, provide evidence of adult brain resilience of spontaneous neural activity after long-term HA exposure without inherited and developmental effects. Resting-state fMRI could yield valuable information for central mechanisms underlying respiratory and cognitive compensations in adults during prolonged environmentally hypoxic adaptation, paving the way for future HA-adaptive training. PMID:26906285

  6. The Relieving Effects of BrainPower Advanced, a Dietary Supplement, in Older Adults with Subjective Memory Complaints: A Randomized, Double-Blind, Placebo-Controlled Trial

    Science.gov (United States)

    Zhu, Jingfen; Shi, Rong; Chen, Su; Dai, Lihua; Shen, Tian; Feng, Yi; Gu, Pingping; Shariff, Mina; Nguyen, Tuong; Ye, Yeats; Rao, Jianyu; Xing, Guoqiang

    2016-01-01

    Subjective memory complaints (SMCs) are common in older adults that can often predict further cognitive impairment. No proven effective agents are available for SMCs. The effect of BrainPower Advanced, a dietary supplement consisting of herbal extracts, nutrients, and vitamins, was evaluated in 98 volunteers with SMCs, averaging 67 years of age (47–88), in a randomized, double-blind, placebo-controlled trial. Subjective hypomnesis/memory loss (SML) and attention/concentration deficits (SAD) were evaluated before and after 12-week supplementation of BrainPower Advanced capsules (n = 47) or placebo (n = 51), using a 5-point memory questionnaire (1 = no/slight, 5 = severe). Objective memory function was evaluated using 3 subtests of visual/audio memory, abstraction, and memory recall that gave a combined total score. The BrainPower Advanced group had more cases of severe SML (severity ⩾ 3) (44/47) and severe SAD (43/47) than the placebo group (39/51 and 37/51, < 0.05, < 0.05, resp.) before the treatment. BrainPower Advanced intervention, however, improved a greater proportion of the severe SML (29.5%)(13/44) (P < 0.01) and SAD (34.9%)(15/43)(P < 0.01) than placebo (5.1% (2/39) and 13.5% (5/37), resp.). Thus, 3-month BrainPower Advanced supplementation appears to be beneficial to older adults with SMCs.

  7. 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

  8. 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

  9. 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.

  10. Perceived importance of prospective memory failures in adults with traumatic brain injury.

    Science.gov (United States)

    Huang, Jia; Fleming, Jennifer; Pomery, Nadine L; O'Gorman, John G; Chan, Raymond C K; Shum, David H K

    2014-01-01

    Prospective memory (PM) is the ability to carry out an intended action in the future. Failures in PM are often observed as more frequent in individuals with traumatic brain injury (TBI) than controls. However, it remains unknown how individuals with TBI and their significant others perceive the importance of these PM problems. In the current study, four groups (38 TBI, 34 TBI-other, 34 controls, 31 control-other) were recruited to report on the perceived importance of PM failures using Part B of the Comprehensive Assessments of Prospective Memory (CAPM). Individuals with TBI perceived PM failures as being more important than did their significant others. Controls' ratings did not differ from their significant others. There were no statistically significant differences in rated importance for PM problems involving the basic activities of daily living (BADL) component and those involving the instrumental activities of daily living (IADL) component. Implications of the results are discussed in terms of the motivation of people with TBI. PMID:24171841

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. Neural processing of reward in adolescent rodents

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    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.

  18. 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.

  19. Screening for psychological distress in adult primary brain tumor patients and caregivers: considerations for cancer care coordination

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    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.

  20. Regrowing the adult brain: NF-κB controls functional circuit formation and tissue homeostasis in the dentate gyrus.

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    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.