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Sample records for adult drosophila brain

  1. Neuropeptide Mapping of Dimmed Cells of Adult Drosophila Brain

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    Diesner, Max; Predel, Reinhard; Neupert, Susanne

    2018-05-01

    Neuropeptides are structurally highly diverse messenger molecules that act as regulators of many physiological processes such as development, metabolism, reproduction or behavior in general. Differentiation of neuropeptidergic cells often corresponds with the presence of the transcription factor DIMMED. In the central nervous system of the fruit fly Drosophila melanogaster, DIMMED commonly occurs in neuroendocrine neurons that release peptides as neurohormones but also in interneurons with complex branching patterns. Fly strains with green fluorescence protein (GFP)-expressing dimmed cells make it possible to systematically analyze the processed neuropeptides in these cells. In this study, we mapped individual GFP-expressing neurons of adult D. melanogaster from the dimmed ( c929)>GFP line. Using single cell mass spectrometry, we analyzed 10 types of dimmed neurons from the brain/gnathal ganglion. These cells included neuroendocrine cells with projection into the retrocerebral complex but also a number of large interneurons. Resulting mass spectra not only provided comprehensive data regarding mature products from 13 neuropeptide precursors but also evidence for the cellular co-localization of neuropeptides from different neuropeptide genes. The results can be implemented in a neuroanatomical map of the D. melanogaster brain. [Figure not available: see fulltext.

  2. Neuropeptide Mapping of Dimmed Cells of Adult Drosophila Brain

    Science.gov (United States)

    Diesner, Max; Predel, Reinhard; Neupert, Susanne

    2018-01-01

    Neuropeptides are structurally highly diverse messenger molecules that act as regulators of many physiological processes such as development, metabolism, reproduction or behavior in general. Differentiation of neuropeptidergic cells often corresponds with the presence of the transcription factor DIMMED. In the central nervous system of the fruit fly Drosophila melanogaster, DIMMED commonly occurs in neuroendocrine neurons that release peptides as neurohormones but also in interneurons with complex branching patterns. Fly strains with green fluorescence protein (GFP)-expressing dimmed cells make it possible to systematically analyze the processed neuropeptides in these cells. In this study, we mapped individual GFP-expressing neurons of adult D. melanogaster from the dimmed (c929)>GFP line. Using single cell mass spectrometry, we analyzed 10 types of dimmed neurons from the brain/gnathal ganglion. These cells included neuroendocrine cells with projection into the retrocerebral complex but also a number of large interneurons. Resulting mass spectra not only provided comprehensive data regarding mature products from 13 neuropeptide precursors but also evidence for the cellular co-localization of neuropeptides from different neuropeptide genes. The results can be implemented in a neuroanatomical map of the D. melanogaster brain. [Figure not available: see fulltext.

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

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    Brand Andrea H

    2009-03-01

    Full Text Available 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 Drosophila adult brain. The majority of clones cluster on the ventrolateral side of the antennal lobes, as do the BrdU-positive cells. Of the BrdU-labelled cells, 86% express the glial gene reversed polarity (repo, and 14% are repo negative. Conclusion We have observed cell proliferation in the Drosophila adult brain. The dividing cells may be adult stem cells, generating glial and/or non-glial cell types.

  4. A Statistically Representative Atlas for Mapping Neuronal Circuits in the Drosophila Adult Brain.

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    Arganda-Carreras, Ignacio; Manoliu, Tudor; Mazuras, Nicolas; Schulze, Florian; Iglesias, Juan E; Bühler, Katja; Jenett, Arnim; Rouyer, François; Andrey, Philippe

    2018-01-01

    Imaging the expression patterns of reporter constructs is a powerful tool to dissect the neuronal circuits of perception and behavior in the adult brain of Drosophila , one of the major models for studying brain functions. To date, several Drosophila brain templates and digital atlases have been built to automatically analyze and compare collections of expression pattern images. However, there has been no systematic comparison of performances between alternative atlasing strategies and registration algorithms. Here, we objectively evaluated the performance of different strategies for building adult Drosophila brain templates and atlases. In addition, we used state-of-the-art registration algorithms to generate a new group-wise inter-sex atlas. Our results highlight the benefit of statistical atlases over individual ones and show that the newly proposed inter-sex atlas outperformed existing solutions for automated registration and annotation of expression patterns. Over 3,000 images from the Janelia Farm FlyLight collection were registered using the proposed strategy. These registered expression patterns can be searched and compared with a new version of the BrainBaseWeb system and BrainGazer software. We illustrate the validity of our methodology and brain atlas with registration-based predictions of expression patterns in a subset of clock neurons. The described registration framework should benefit to brain studies in Drosophila and other insect species.

  5. A Statistically Representative Atlas for Mapping Neuronal Circuits in the Drosophila Adult Brain

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    Ignacio Arganda-Carreras

    2018-03-01

    Full Text Available Imaging the expression patterns of reporter constructs is a powerful tool to dissect the neuronal circuits of perception and behavior in the adult brain of Drosophila, one of the major models for studying brain functions. To date, several Drosophila brain templates and digital atlases have been built to automatically analyze and compare collections of expression pattern images. However, there has been no systematic comparison of performances between alternative atlasing strategies and registration algorithms. Here, we objectively evaluated the performance of different strategies for building adult Drosophila brain templates and atlases. In addition, we used state-of-the-art registration algorithms to generate a new group-wise inter-sex atlas. Our results highlight the benefit of statistical atlases over individual ones and show that the newly proposed inter-sex atlas outperformed existing solutions for automated registration and annotation of expression patterns. Over 3,000 images from the Janelia Farm FlyLight collection were registered using the proposed strategy. These registered expression patterns can be searched and compared with a new version of the BrainBaseWeb system and BrainGazer software. We illustrate the validity of our methodology and brain atlas with registration-based predictions of expression patterns in a subset of clock neurons. The described registration framework should benefit to brain studies in Drosophila and other insect species.

  6. Failure of the PTEN/aPKC/Lgl Axis Primes Formation of Adult Brain Tumours in Drosophila

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    Simona Paglia

    2017-01-01

    Full Text Available Different regions in the mammalian adult brain contain immature precursors, reinforcing the concept that brain cancers, such as glioblastoma multiforme (GBM, may originate from cells endowed with stem-like properties. Alterations of the tumour suppressor gene PTEN are very common in primary GBMs. Very recently, PTEN loss was shown to undermine a specific molecular axis, whose failure is associated with the maintenance of the GBM stem cells in mammals. This axis is composed of PTEN, aPKC, and the polarity determinant Lethal giant larvae (Lgl: PTEN loss promotes aPKC activation through the PI3K pathway, which in turn leads to Lgl inhibition, ultimately preventing stem cell differentiation. To find the neural precursors responding to perturbations of this molecular axis, we targeted different neurogenic regions of the Drosophila brain. Here we show that PTEN mutation impacts aPKC and Lgl protein levels also in Drosophila. Moreover, we demonstrate that PI3K activation is not sufficient to trigger tumourigenesis, while aPKC promotes hyperplastic growth of the neuroepithelium and a noticeable expansion of the type II neuroblasts. Finally, we show that these neuroblasts form invasive tumours that persist and keep growing in the adult, leading the affected animals to untimely death, thus displaying frankly malignant behaviours.

  7. The dopaminergic system in the aging brain of Drosophila

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    Katherine E White

    2010-12-01

    Full Text Available Drosophila models of Parkinson’s disease are characterised by two principal phenotypes: the specific loss of dopaminergic neurons in the aging brain and defects in motor behavior. However, an age-related analysis of these baseline parameters in wildtype Drosophila is lacking. Here we analysed the dopaminergic system and motor behavior in aging Drosophila. Dopaminergic neurons in the adult brain can be grouped into bilateral symmetric clusters, each comprising a stereotypical number of cells. Analysis of TH>mCD8::GFP and cell type-specific MARCM clones revealed that dopaminergic neurons show cluster-specific, stereotypical projection patterns with terminal arborization in target regions that represent distinct functional areas of the adult brain. Target areas include the mushroom bodies, involved in memory formation and motivation, and the central complex, involved in the control of motor behavior, indicating that similar to the mammalian brain, dopaminergic neurons in the fly brain are involved in the regulation of specific behaviors. Behavioral analysis revealed that Drosophila show an age-related decline in startle-induced locomotion and negative geotaxis. Motion tracking however, revealed that walking activity and exploration behavior, but not centrophobism increase at late stages of life. Analysis of TH>Dcr2, mCD8::GFP revealed a specific effect of Dcr2 expression on walking activity but not on exploratory or centrophobic behavior, indicating that the siRNA pathway may modulate distinct dopaminergic behaviors in Drosophila. Moreover, dopaminergic neurons were maintained between early- and late life, as quantified by TH>mCD8::GFP and anti-TH labelling, indicating that adult onset, age-related degeneration of dopaminergic neurons does not occur in the aging brain of Drosophila. Taken together, our data establish baseline parameters in Drosophila for the study of Parkinson’s disease as well as other disorders affecting dopaminergic neurons

  8. Odd-skipped labels a group of distinct neurons associated with the mushroom body and optic lobe in the adult Drosophila brain

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    Levy, Peter; Larsen, Camilla

    2013-01-01

    Olfactory processing has been intensively studied in Drosophila melanogaster. However, we still know little about the descending neural pathways from the higher order processing centers and how these connect with other neural circuits. Here we describe, in detail, the adult projections patterns that arise from a cluster of 78 neurons, defined by the expression of the Odd-skipped transcription factor. We term these neurons Odd neurons. By using expression of genetically encoded axonal and dendritic markers, we show that a subset of the Odd neurons projects dendrites into the calyx of the mushroom body (MB) and axons into the inferior protocerebrum. We exclude the possibility that the Odd neurons are part of the well-known Kenyon cells whose projections form the MB and conclude that the Odd neurons belong to a previously not described class of extrinsic MB neurons. In addition, three of the Odd neurons project into the lobula plate of the optic lobe, and two of these cells extend axons ipsi- and contralaterally in the brain. Anatomically, these cells do not resemble any previously described lobula plate tangential cells (LPTCs) in Drosophila. We show that the Odd neurons are predominantly cholinergic but also include a small number of γ-aminobutyric acid (GABA)ergic neurons. Finally, we provide evidence that the Odd neurons are a hemilineage, suggesting they are born from a defined set of neuroblasts. Our anatomical analysis hints at the possibility that subgroups of Odd neurons could be involved in olfactory and visual processing. PMID:23749685

  9. Ecdysteroid receptors in Drosophila melanogaster adult females

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    Ecdysteroid receptors were identified and partially characterized from total cell extracts of whole animals and dissected tissues from Drosophila melanogaster adult females. Binding studies indicated the presence of two ecdysteroid binding components having high affinity and specificity consistent w...

  10. 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, ...

  11. Drosophila type II neuroblast lineages keep Prospero levels low to generate large clones that contribute to the adult brain central complex

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    Drummond Michael L

    2010-10-01

    Full Text Available Abstract Tissue homeostasis depends on the ability of stem cells to properly regulate self-renewal versus differentiation. Drosophila neural stem cells (neuroblasts are a model system to study self-renewal and differentiation. Recent work has identified two types of larval neuroblasts that have different self-renewal/differentiation properties. Type I neuroblasts bud off a series of small basal daughter cells (ganglion mother cells that each generate two neurons. Type II neuroblasts bud off small basal daughter cells called intermediate progenitors (INPs, with each INP generating 6 to 12 neurons. Type I neuroblasts and INPs have nuclear Asense and cytoplasmic Prospero, whereas type II neuroblasts lack both these transcription factors. Here we test whether Prospero distinguishes type I/II neuroblast identity or proliferation profile, using several newly characterized Gal4 lines. We misexpress prospero using the 19H09-Gal4 line (expressed in type II neuroblasts but no adjacent type I neuroblasts or 9D11-Gal4 line (expressed in INPs but not type II neuroblasts. We find that differential prospero expression does not distinguish type I and type II neuroblast identities, but Prospero regulates proliferation in both type I and type II neuroblast lineages. In addition, we use 9D11 lineage tracing to show that type II lineages generate both small-field and large-field neurons within the adult central complex, a brain region required for locomotion, flight, and visual pattern memory.

  12. A novel role for ecdysone in Drosophila conditioned behavior: linking GPCR-mediated non-canonical steroid action to cAMP signaling in the adult brain.

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    Ishimoto, Hiroshi; Wang, Zhe; Rao, Yi; Wu, Chun-Fang; Kitamoto, Toshihiro

    2013-01-01

    The biological actions of steroid hormones are mediated primarily by their cognate nuclear receptors, which serve as steroid-dependent transcription factors. However, steroids can also execute their functions by modulating intracellular signaling cascades rapidly and independently of transcriptional regulation. Despite the potential significance of such "non-genomic" steroid actions, their biological roles and the underlying molecular mechanisms are not well understood, particularly with regard to their effects on behavioral regulation. The major steroid hormone in the fruit fly Drosophila is 20-hydroxy-ecdysone (20E), which plays a variety of pivotal roles during development via the nuclear ecdysone receptors. Here we report that DopEcR, a G-protein coupled receptor for ecdysteroids, is involved in activity- and experience-dependent plasticity of the adult central nervous system. Remarkably, a courtship memory defect in rutabaga (Ca²⁺/calmodulin-responsive adenylate cyclase) mutants was rescued by DopEcR overexpression or acute 20E feeding, whereas a memory defect in dunce (cAMP-specific phosphodiestrase) mutants was counteracted when a loss-of-function DopEcR mutation was introduced. A memory defect caused by suppressing dopamine synthesis was also restored through enhanced DopEcR-mediated ecdysone signaling, and rescue and phenocopy experiments revealed that the mushroom body (MB)--a brain region central to learning and memory in Drosophila--is critical for the DopEcR-dependent processing of courtship memory. Consistent with this finding, acute 20E feeding induced a rapid, DopEcR-dependent increase in cAMP levels in the MB. Our multidisciplinary approach demonstrates that DopEcR mediates the non-canonical actions of 20E and rapidly modulates adult conditioned behavior through cAMP signaling, which is universally important for neural plasticity. This study provides novel insights into non-genomic actions of steroids, and opens a new avenue for genetic

  13. A novel role for ecdysone in Drosophila conditioned behavior: linking GPCR-mediated non-canonical steroid action to cAMP signaling in the adult brain.

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    Hiroshi Ishimoto

    Full Text Available The biological actions of steroid hormones are mediated primarily by their cognate nuclear receptors, which serve as steroid-dependent transcription factors. However, steroids can also execute their functions by modulating intracellular signaling cascades rapidly and independently of transcriptional regulation. Despite the potential significance of such "non-genomic" steroid actions, their biological roles and the underlying molecular mechanisms are not well understood, particularly with regard to their effects on behavioral regulation. The major steroid hormone in the fruit fly Drosophila is 20-hydroxy-ecdysone (20E, which plays a variety of pivotal roles during development via the nuclear ecdysone receptors. Here we report that DopEcR, a G-protein coupled receptor for ecdysteroids, is involved in activity- and experience-dependent plasticity of the adult central nervous system. Remarkably, a courtship memory defect in rutabaga (Ca²⁺/calmodulin-responsive adenylate cyclase mutants was rescued by DopEcR overexpression or acute 20E feeding, whereas a memory defect in dunce (cAMP-specific phosphodiestrase mutants was counteracted when a loss-of-function DopEcR mutation was introduced. A memory defect caused by suppressing dopamine synthesis was also restored through enhanced DopEcR-mediated ecdysone signaling, and rescue and phenocopy experiments revealed that the mushroom body (MB--a brain region central to learning and memory in Drosophila--is critical for the DopEcR-dependent processing of courtship memory. Consistent with this finding, acute 20E feeding induced a rapid, DopEcR-dependent increase in cAMP levels in the MB. Our multidisciplinary approach demonstrates that DopEcR mediates the non-canonical actions of 20E and rapidly modulates adult conditioned behavior through cAMP signaling, which is universally important for neural plasticity. This study provides novel insights into non-genomic actions of steroids, and opens a new avenue for

  14. Drosophila Vps13 Is Required for Protein Homeostasis in the Brain.

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    Jan J Vonk

    Full Text Available Chorea-Acanthocytosis is a rare, neurodegenerative disorder characterized by progressive loss of locomotor and cognitive function. It is caused by loss of function mutations in the Vacuolar Protein Sorting 13A (VPS13A gene, which is conserved from yeast to human. The consequences of VPS13A dysfunction in the nervous system are still largely unspecified. In order to study the consequences of VPS13A protein dysfunction in the ageing central nervous system we characterized a Drosophila melanogaster Vps13 mutant line. The Drosophila Vps13 gene encoded a protein of similar size as human VPS13A. Our data suggest that Vps13 is a peripheral membrane protein located to endosomal membranes and enriched in the fly head. Vps13 mutant flies showed a shortened life span and age associated neurodegeneration. Vps13 mutant flies were sensitive to proteotoxic stress and accumulated ubiquitylated proteins. Levels of Ref(2P, the Drosophila orthologue of p62, were increased and protein aggregates accumulated in the central nervous system. Overexpression of the human Vps13A protein in the mutant flies partly rescued apparent phenotypes. This suggests a functional conservation of human VPS13A and Drosophila Vps13. Our results demonstrate that Vps13 is essential to maintain protein homeostasis in the larval and adult Drosophila brain. Drosophila Vps13 mutants are suitable to investigate the function of Vps13 in the brain, to identify genetic enhancers and suppressors and to screen for potential therapeutic targets for Chorea-Acanthocytosis.

  15. A map of octopaminergic neurons in the Drosophila brain.

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    Busch, Sebastian; Selcho, Mareike; Ito, Kei; Tanimoto, Hiromu

    2009-04-20

    The biogenic amine octopamine modulates diverse behaviors in invertebrates. At the single neuron level, the mode of action is well understood in the peripheral nervous system owing to its simple structure and accessibility. For elucidating the role of individual octopaminergic neurons in the modulation of complex behaviors, a detailed analysis of the connectivity in the central nervous system is required. Here we present a comprehensive anatomical map of candidate octopaminergic neurons in the adult Drosophila brain: including the supra- and subesophageal ganglia. Application of the Flp-out technique enabled visualization of 27 types of individual octopaminergic neurons. Based on their morphology and distribution of genetic markers, we found that most octopaminergic neurons project to multiple brain structures with a clear separation of dendritic and presynaptic regions. Whereas their major dendrites are confined to specific brain regions, each cell type targets different, yet defined, neuropils distributed throughout the central nervous system. This would allow them to constitute combinatorial modules assigned to the modulation of distinct neuronal processes. The map may provide an anatomical framework for the functional constitution of the octopaminergic system. It also serves as a model for the single-cell organization of a particular neurotransmitter in the brain. 2009 Wiley-Liss, Inc.

  16. Intestinal stem cells in the adult Drosophila midgut

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    Jiang, Huaqi; Edgar, Bruce A.

    2011-01-01

    Drosophila has long been an excellent model organism for studying stem cell biology. Notably, studies of Drosophila's germline stem cells have been instrumental in developing the stem cell niche concept. The recent discovery of somatic stem cells in adult Drosophila, particularly the intestinal stem cells (ISCs) of the midgut, has established Drosophila as an exciting model to study stem cell-mediated adult tissue homeostasis and regeneration. Here, we review the major signaling pathways that regulate the self-renewal, proliferation and differentiation of Drosophila ISCs, discussing how this regulation maintains midgut homeostasis and mediates regeneration of the intestinal epithelium after injury. -- Highlights: ► The homeostasis and regeneration of adult fly midguts are mediated by ISCs. ► Damaged enterocytes induce the proliferation of intestinal stem cells (ISC). ► EGFR and Jak/Stat signalings mediate compensatory ISC proliferation. ► Notch signaling regulates ISC self-renewal and differentiation.

  17. The Drosophila surface glia transcriptome: evolutionary conserved blood-brain barrier processes.

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    Michael K DeSalvo

    2014-11-01

    Full Text Available AbstractCentral nervous system (CNS function is dependent on the stringent regulation of metabolites, drugs, cells, and pathogens exposed to the CNS space. Cellular blood-brain barrier (BBB structures are highly specific checkpoints governing entry and exit of all small molecules to and from the brain interstitial space, but the precise mechanisms that regulate the BBB are not well understood. In addition, the BBB has long been a challenging obstacle to the pharmacologic treatment of CNS diseases; thus model systems that can parse the functions of the BBB are highly desirable. In this study, we sought to define the transcriptome of the adult Drosophila melanogaster BBB by isolating the BBB surface glia with FACS and profiling their gene expression with microarrays. By comparing the transcriptome of these surface glia to that of all brain glia, brain neurons, and whole brains, we present a catalog of transcripts that are selectively enriched at the Drosophila BBB. We found that the fly surface glia show high expression of many ABC and SLC transporters, cell adhesion molecules, metabolic enzymes, signaling molecules, and components of xenobiotic metabolism pathways. Using gene sequence-based alignments, we compare the Drosophila and Murine BBB transcriptomes and discover many shared chemoprotective and small molecule control pathways, thus affirming the relevance of invertebrate models for studying evolutionary conserved BBB properties. The Drosophila BBB transcriptome is valuable to vertebrate and insect biologists alike as a resource for studying proteins underlying diffusion barrier development and maintenance, glial biology, and regulation of drug transport at tissue barriers.

  18. The Drosophila surface glia transcriptome: evolutionary conserved blood-brain barrier processes.

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    DeSalvo, Michael K; Hindle, Samantha J; Rusan, Zeid M; Orng, Souvinh; Eddison, Mark; Halliwill, Kyle; Bainton, Roland J

    2014-01-01

    Central nervous system (CNS) function is dependent on the stringent regulation of metabolites, drugs, cells, and pathogens exposed to the CNS space. Cellular blood-brain barrier (BBB) structures are highly specific checkpoints governing entry and exit of all small molecules to and from the brain interstitial space, but the precise mechanisms that regulate the BBB are not well understood. In addition, the BBB has long been a challenging obstacle to the pharmacologic treatment of CNS diseases; thus model systems that can parse the functions of the BBB are highly desirable. In this study, we sought to define the transcriptome of the adult Drosophila melanogaster BBB by isolating the BBB surface glia with fluorescence activated cell sorting (FACS) and profiling their gene expression with microarrays. By comparing the transcriptome of these surface glia to that of all brain glia, brain neurons, and whole brains, we present a catalog of transcripts that are selectively enriched at the Drosophila BBB. We found that the fly surface glia show high expression of many ATP-binding cassette (ABC) and solute carrier (SLC) transporters, cell adhesion molecules, metabolic enzymes, signaling molecules, and components of xenobiotic metabolism pathways. Using gene sequence-based alignments, we compare the Drosophila and Murine BBB transcriptomes and discover many shared chemoprotective and small molecule control pathways, thus affirming the relevance of invertebrate models for studying evolutionary conserved BBB properties. The Drosophila BBB transcriptome is valuable to vertebrate and insect biologists alike as a resource for studying proteins underlying diffusion barrier development and maintenance, glial biology, and regulation of drug transport at tissue barriers.

  19. Quiescent gastric stem cells maintain the adult Drosophila stomach.

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    Strand, Marie; Micchelli, Craig A

    2011-10-25

    The adult Drosophila copper cell region or "stomach" is a highly acidic compartment of the midgut with pH stem cells (GSSCs) produces the acid-secreting copper cells, interstitial cells, and enteroendocrine cells of the stomach. Our assays demonstrate that GSSCs are largely quiescent but can be induced to regenerate the gastric epithelium in response to environmental challenge. Finally, genetic analysis reveals that adult GSSC maintenance depends on Wnt signaling. Characterization of the GSSC lineage in Drosophila, with striking similarities to mammals, will advance the study of both homeostatic and pathogenic processes in the stomach.

  20. Intestinal stem cells in the adult Drosophila midgut

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    Jiang, Huaqi, E-mail: Huaqi.Jiang@UTSouthwestern.edu [Department of Developmental Biology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX, 75235 (United States); Edgar, Bruce A., E-mail: b.edgar@dkfz.de [ZMBH-DKFZ Alliance, Im Neuenheimer Feld 282, D-69120 Heidelberg (Germany); Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109 (United States)

    2011-11-15

    Drosophila has long been an excellent model organism for studying stem cell biology. Notably, studies of Drosophila's germline stem cells have been instrumental in developing the stem cell niche concept. The recent discovery of somatic stem cells in adult Drosophila, particularly the intestinal stem cells (ISCs) of the midgut, has established Drosophila as an exciting model to study stem cell-mediated adult tissue homeostasis and regeneration. Here, we review the major signaling pathways that regulate the self-renewal, proliferation and differentiation of Drosophila ISCs, discussing how this regulation maintains midgut homeostasis and mediates regeneration of the intestinal epithelium after injury. -- Highlights: Black-Right-Pointing-Pointer The homeostasis and regeneration of adult fly midguts are mediated by ISCs. Black-Right-Pointing-Pointer Damaged enterocytes induce the proliferation of intestinal stem cells (ISC). Black-Right-Pointing-Pointer EGFR and Jak/Stat signalings mediate compensatory ISC proliferation. Black-Right-Pointing-Pointer Notch signaling regulates ISC self-renewal and differentiation.

  1. Shared visual attention and memory systems in the Drosophila brain.

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    Bruno van Swinderen

    Full Text Available BACKGROUND: Selective attention and memory seem to be related in human experience. This appears to be the case as well in simple model organisms such as the fly Drosophila melanogaster. Mutations affecting olfactory and visual memory formation in Drosophila, such as in dunce and rutabaga, also affect short-term visual processes relevant to selective attention. In particular, increased optomotor responsiveness appears to be predictive of visual attention defects in these mutants. METHODOLOGY/PRINCIPAL FINDINGS: To further explore the possible overlap between memory and visual attention systems in the fly brain, we screened a panel of 36 olfactory long term memory (LTM mutants for visual attention-like defects using an optomotor maze paradigm. Three of these mutants yielded high dunce-like optomotor responsiveness. We characterized these three strains by examining their visual distraction in the maze, their visual learning capabilities, and their brain activity responses to visual novelty. We found that one of these mutants, D0067, was almost completely identical to dunce(1 for all measures, while another, D0264, was more like wild type. Exploiting the fact that the LTM mutants are also Gal4 enhancer traps, we explored the sufficiency for the cells subserved by these elements to rescue dunce attention defects and found overlap at the level of the mushroom bodies. Finally, we demonstrate that control of synaptic function in these Gal4 expressing cells specifically modulates a 20-30 Hz local field potential associated with attention-like effects in the fly brain. CONCLUSIONS/SIGNIFICANCE: Our study uncovers genetic and neuroanatomical systems in the fly brain affecting both visual attention and odor memory phenotypes. A common component to these systems appears to be the mushroom bodies, brain structures which have been traditionally associated with odor learning but which we propose might be also involved in generating oscillatory brain activity

  2. Nanoliter hemolymph sampling and analysis of individual adult Drosophila melanogaster.

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    Piyankarage, Sujeewa C; Featherstone, David E; Shippy, Scott A

    2012-05-15

    The fruit fly (Drosophila melanogaster) is an extensively used and powerful, genetic model organism. However, chemical studies using individual flies have been limited by the animal's small size. Introduced here is a method to sample nanoliter hemolymph volumes from individual adult fruit-flies for chemical analysis. The technique results in an ability to distinguish hemolymph chemical variations with developmental stage, fly sex, and sampling conditions. Also presented is the means for two-point monitoring of hemolymph composition for individual flies.

  3. A signaling network for patterning of neuronal connectivity in the Drosophila brain.

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    Mohammed Srahna

    2006-10-01

    Full Text Available The precise number and pattern of axonal connections generated during brain development regulates animal behavior. Therefore, understanding how developmental signals interact to regulate axonal extension and retraction to achieve precise neuronal connectivity is a fundamental goal of neurobiology. We investigated this question in the developing adult brain of Drosophila and find that it is regulated by crosstalk between Wnt, fibroblast growth factor (FGF receptor, and Jun N-terminal kinase (JNK signaling, but independent of neuronal activity. The Rac1 GTPase integrates a Wnt-Frizzled-Disheveled axon-stabilizing signal and a Branchless (FGF-Breathless (FGF receptor axon-retracting signal to modulate JNK activity. JNK activity is necessary and sufficient for axon extension, whereas the antagonistic Wnt and FGF signals act to balance the extension and retraction required for the generation of the precise wiring pattern.

  4. An Evolutionarily Conserved Role of Presenilin in Neuronal Protection in the Aging Drosophila Brain.

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    Kang, Jongkyun; Shin, Sarah; Perrimon, Norbert; Shen, Jie

    2017-07-01

    Mutations in the Presenilin genes are the major genetic cause of Alzheimer's disease. Presenilin and Nicastrin are essential components of γ-secretase, a multi-subunit protease that cleaves Type I transmembrane proteins. Genetic studies in mice previously demonstrated that conditional inactivation of Presenilin or Nicastrin in excitatory neurons of the postnatal forebrain results in memory deficits, synaptic impairment, and age-dependent neurodegeneration. The roles of Drosophila Presenilin ( Psn ) and Nicastrin ( Nct ) in the adult fly brain, however, are unknown. To knockdown (KD) Psn or Nct selectively in neurons of the adult brain, we generated multiple shRNA lines. Using a ubiquitous driver, these shRNA lines resulted in 80-90% reduction of mRNA and pupal lethality-a phenotype that is shared with Psn and Nct mutants carrying nonsense mutations. Furthermore, expression of these shRNAs in the wing disc caused notching wing phenotypes, which are also shared with Psn and Nct mutants. Similar to Nct , neuron-specific Psn KD using two independent shRNA lines led to early mortality and rough eye phenotypes, which were rescued by a fly Psn transgene. Interestingly, conditional KD (cKD) of Psn or Nct in adult neurons using the elav-Gal4 and tubulin-Gal80 ts system caused shortened lifespan, climbing defects, increases in apoptosis, and age-dependent neurodegeneration. Together, these findings demonstrate that, similar to their mammalian counterparts, Drosophila Psn and Nct are required for neuronal survival during aging and normal lifespan, highlighting an evolutionarily conserved role of Presenilin in neuronal protection in the aging brain. Copyright © 2017 by the Genetics Society of America.

  5. Population and sex differences in Drosophila melanogaster brain gene expression

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    Catalán Ana

    2012-11-01

    Full Text Available Abstract Background Changes in gene regulation are thought to be crucial for the adaptation of organisms to their environment. Transcriptome analyses can be used to identify candidate genes for ecological adaptation, but can be complicated by variation in gene expression between tissues, sexes, or individuals. Here we use high-throughput RNA sequencing of a single Drosophila melanogaster tissue to detect brain-specific differences in gene expression between the sexes and between two populations, one from the ancestral species range in sub-Saharan Africa and one from the recently colonized species range in Europe. Results Relatively few genes (Cyp6g1 and CHKov1. Conclusions Analysis of the brain transcriptome revealed many genes differing in expression between populations that were not detected in previous studies using whole flies. There was little evidence for sex-specific regulatory adaptation in the brain, as most expression differences between populations were observed in both males and females. The enrichment of genes with sexually dimorphic expression on the X chromosome is consistent with dosage compensation mechanisms affecting sex-biased expression in somatic tissues.

  6. Dietary glucose regulates yeast consumption in adult Drosophila males

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    Sebastien eLebreton

    2014-12-01

    Full Text Available The adjustment of feeding behavior in response to hunger and satiety contributes to homeostatic regulation in animals. The fruit fly Drosophila melanogaster feeds on yeasts growing on overripe fruit, providing nutrients required for adult survival, reproduction and larval growth. Here, we present data on how the nutritional value of food affects subsequent yeast consumption in Drosophila adult males. After a period of starvation, flies showed intensive yeast consumption. In comparison, flies stopped feeding after having access to a nutritive cornmeal diet. Interestingly, dietary glucose was equally efficient as the complex cornmeal diet. In contrast, flies fed with sucralose, a non-metabolizable sweetener, behaved as if they were starved. The adipokinetic hormone and insulin-like peptides regulate metabolic processes in insects. We did not find any effect of the adipokinetic hormone pathway on this modulation. Instead, the insulin pathway was involved in these changes. Flies lacking the insulin receptor did not respond to nutrient deprivation by increasing yeast consumption. Together these results show the importance of insulin in the regulation of yeast consumption in response to starvation in adult D. melanogaster males.

  7. Dietary glucose regulates yeast consumption in adult Drosophila males.

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    Lebreton, Sébastien; Witzgall, Peter; Olsson, Marie; Becher, Paul G

    2014-01-01

    The adjustment of feeding behavior in response to hunger and satiety contributes to homeostatic regulation in animals. The fruit fly Drosophila melanogaster feeds on yeasts growing on overripe fruit, providing nutrients required for adult survival, reproduction and larval growth. Here, we present data on how the nutritional value of food affects subsequent yeast consumption in Drosophila adult males. After a period of starvation, flies showed intensive yeast consumption. In comparison, flies stopped feeding after having access to a nutritive cornmeal diet. Interestingly, dietary glucose was equally efficient as the complex cornmeal diet. In contrast, flies fed with sucralose, a non-metabolizable sweetener, behaved as if they were starved. The adipokinetic hormone and insulin-like peptides regulate metabolic processes in insects. We did not find any effect of the adipokinetic hormone pathway on this modulation. Instead, the insulin pathway was involved in these changes. Flies lacking the insulin receptor (InR) did not respond to nutrient deprivation by increasing yeast consumption. Together these results show the importance of insulin in the regulation of yeast consumption in response to starvation in adult D. melanogaster males.

  8. Rapid mounting of adult Drosophila structures in Hoyer's medium.

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    Stern, David L; Sucena, Elio

    2012-01-01

    The Drosophila cuticle carries a rich array of morphological details. Thus, cuticle examination has had a central role in the history of genetics. This protocol describes a procedure for mounting adult cuticles in Hoyer's medium, a useful mountant for both larval and adult cuticles. The medium digests soft tissues rapidly, leaving the cuticle cleared for observation. In addition, samples can be transferred directly from water to Hoyer's medium. However, specimens mounted in Hoyer's medium degrade over time. For example, the fine denticles on the larval dorsum are best observed soon after mounting; they begin to fade after 1 week, and can disappear completely after several months. More robust features, such as the ventral denticle belts, will persist for a longer period of time. Because adults cannot profitably be mounted whole in Hoyer's medium, some dissection is necessary.

  9. Brain development in the yellow fever mosquito Aedes aegypti: a comparative immunocytochemical analysis using cross-reacting antibodies from Drosophila melanogaster.

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    Mysore, Keshava; Flister, Susanne; Müller, Pie; Rodrigues, Veronica; Reichert, Heinrich

    2011-12-01

    Considerable effort has been directed towards understanding the organization and function of peripheral and central nervous system of disease vector mosquitoes such as Aedes aegypti. To date, all of these investigations have been carried out on adults but none of the studies addressed the development of the nervous system during the larval and pupal stages in mosquitoes. Here, we first screen a set of 30 antibodies, which have been used to study brain development in Drosophila, and identify 13 of them cross-reacting and labeling epitopes in the developing brain of Aedes. We then use the identified antibodies in immunolabeling studies to characterize general neuroanatomical features of the developing brain and compare them with the well-studied model system, Drosophila melanogaster, in larval, pupal, and adult stages. Furthermore, we use immunolabeling to document the development of specific components of the Aedes brain, namely the optic lobes, the subesophageal neuropil, and serotonergic system of the subesophageal neuropil in more detail. Our study reveals prominent differences in the developing brain in the larval stage as compared to the pupal (and adult) stage of Aedes. The results also uncover interesting similarities and marked differences in brain development of Aedes as compared to Drosophila. Taken together, this investigation forms the basis for future cellular and molecular investigations of brain development in this important disease vector. © Springer-Verlag 2011

  10. p53 is required for brain growth but is dispensable for resistance to nutrient restriction during Drosophila larval development.

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    Contreras, Esteban G; Sierralta, Jimena; Glavic, Alvaro

    2018-01-01

    Animal growth is influenced by the genetic background and the environmental circumstances. How genes promote growth and coordinate adaptation to nutrient availability is still an open question. p53 is a transcription factor that commands the cellular response to different types of stresses. In adult Drosophila melanogaster, p53 regulates the metabolic adaptation to nutrient restriction that supports fly viability. Furthermore, the larval brain is protected from nutrient restriction in a phenomenon called 'brain sparing'. Therefore, we hypothesised that p53 may regulate brain growth and show a protective role over brain development under nutrient restriction. Here, we studied the function of p53 during brain growth in normal conditions and in animals subjected to developmental nutrient restriction. We showed that p53 loss of function reduced animal growth and larval brain size. Endogenous p53 was expressed in larval neural stem cells, but its levels and activity were not affected by nutritional stress. Interestingly, p53 knockdown only in neural stem cells was sufficient to decrease larval brain growth. Finally, we showed that in p53 mutant larvae under nutrient restriction, the energy storage levels were not altered, and these larvae generated adults with brains of similar size than wild-type animals. Using genetic approaches, we demonstrate that p53 is required for proper growth of the larval brain. This developmental role of p53 does not have an impact on animal resistance to nutritional stress since brain growth in p53 mutants under nutrient restriction is similar to control animals.

  11. Identification of a novel Drosophila gene, beltless, using injectable embryonic and adult RNA interference (RNAi

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    Manev Hari

    2003-08-01

    Full Text Available Abstract Background RNA interference (RNAi is a process triggered by a double-stranded RNA that leads to targeted down-regulation/silencing of gene expression and can be used for functional genomics; i.e. loss-of-function studies. Here we report on the use of RNAi in the identification of a developmentally important novel Drosophila (fruit fly gene (corresponding to a putative gene CG5652/GM06434, that we named beltless based on an embryonic loss-of-function phenotype. Results Beltless mRNA is expressed in all developmental stages except in 0–6 h embryos. In situ RT-PCR localized beltless mRNA in the ventral cord and brain of late stage embryos and in the nervous system, ovaries, and the accessory glands of adult flies. RNAi was induced by injection of short (22 bp beltless double-stranded RNAs into embryos or into adult flies. Embryonic RNAi altered cuticular phenotypes ranging from partially-formed to missing denticle belts (thus beltless of the abdominal segments A2–A4. Embryonic beltless RNAi was lethal. Adult RNAi resulted in the shrinkage of the ovaries by half and reduced the number of eggs laid. We also examined Df(1RK4 flies in which deletion removes 16 genes, including beltless. In some embryos, we observed cuticular abnormalities similar to our findings with beltless RNAi. After differentiating Df(1RK4 embryos into those with visible denticle belts and those missing denticle belts, we assayed the presence of beltless mRNA; no beltless mRNA was detectable in embryos with missing denticle belts. Conclusions We have identified a developmentally important novel Drosophila gene, beltless, which has been characterized in loss-of-function studies using RNA interference. The putative beltless protein shares homologies with the C. elegans nose resistant to fluoxetine (NRF NRF-6 gene, as well as with several uncharacterized C. elegans and Drosophila melanogaster genes, some with prominent acyltransferase domains. Future studies should

  12. Inhibiting the Mitochondrial Calcium Uniporter during Development Impairs Memory in Adult Drosophila

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    Ilaria Drago

    2016-09-01

    Full Text Available The uptake of cytoplasmic calcium into mitochondria is critical for a variety of physiological processes, including calcium buffering, metabolism, and cell survival. Here, we demonstrate that inhibiting the mitochondrial calcium uniporter in the Drosophila mushroom body neurons (MBn—a brain region critical for olfactory memory formation—causes memory impairment without altering the capacity to learn. Inhibiting uniporter activity only during pupation impaired adult memory, whereas the same inhibition during adulthood was without effect. The behavioral impairment was associated with structural defects in MBn, including a decrease in synaptic vesicles and an increased length in the axons of the αβ MBn. Our results reveal an in vivo developmental role for the mitochondrial uniporter complex in establishing the necessary structural and functional neuronal substrates for normal memory formation in the adult organism.

  13. Inhibiting the Mitochondrial Calcium Uniporter during Development Impairs Memory in Adult Drosophila.

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    Drago, Ilaria; Davis, Ronald L

    2016-09-06

    The uptake of cytoplasmic calcium into mitochondria is critical for a variety of physiological processes, including calcium buffering, metabolism, and cell survival. Here, we demonstrate that inhibiting the mitochondrial calcium uniporter in the Drosophila mushroom body neurons (MBn)-a brain region critical for olfactory memory formation-causes memory impairment without altering the capacity to learn. Inhibiting uniporter activity only during pupation impaired adult memory, whereas the same inhibition during adulthood was without effect. The behavioral impairment was associated with structural defects in MBn, including a decrease in synaptic vesicles and an increased length in the axons of the αβ MBn. Our results reveal an in vivo developmental role for the mitochondrial uniporter complex in establishing the necessary structural and functional neuronal substrates for normal memory formation in the adult organism. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  14. Functional Maps of Mechanosensory Features in the Drosophila Brain.

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    Patella, Paola; Wilson, Rachel I

    2018-04-09

    Johnston's organ is the largest mechanosensory organ in Drosophila. It contributes to hearing, touch, vestibular sensing, proprioception, and wind sensing. In this study, we used in vivo 2-photon calcium imaging and unsupervised image segmentation to map the tuning properties of Johnston's organ neurons (JONs) at the site where their axons enter the brain. We then applied the same methodology to study two key brain regions that process signals from JONs: the antennal mechanosensory and motor center (AMMC) and the wedge, which is downstream of the AMMC. First, we identified a diversity of JON response types that tile frequency space and form a rough tonotopic map. Some JON response types are direction selective; others are specialized to encode amplitude modulations over a specific range (dynamic range fractionation). Next, we discovered that both the AMMC and the wedge contain a tonotopic map, with a significant increase in tonotopy-and a narrowing of frequency tuning-at the level of the wedge. Whereas the AMMC tonotopic map is unilateral, the wedge tonotopic map is bilateral. Finally, we identified a subregion of the AMMC/wedge that responds preferentially to the coherent rotation of the two mechanical organs in the same angular direction, indicative of oriented steady air flow (directional wind). Together, these maps reveal the broad organization of the primary and secondary mechanosensory regions of the brain. They provide a framework for future efforts to identify the specific cell types and mechanisms that underlie the hierarchical re-mapping of mechanosensory information in this system. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Metabolic stress responses in Drosophila are modulated by brain neurosecretory cells that produce multiple neuropeptides.

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    Lily Kahsai

    Full Text Available In Drosophila, neurosecretory cells that release peptide hormones play a prominent role in the regulation of development, growth, metabolism, and reproduction. Several types of peptidergic neurosecretory cells have been identified in the brain of Drosophila with release sites in the corpora cardiaca and anterior aorta. We show here that in adult flies the products of three neuropeptide precursors are colocalized in five pairs of large protocerebral neurosecretory cells in two clusters (designated ipc-1 and ipc-2a: Drosophila tachykinin (DTK, short neuropeptide F (sNPF and ion transport peptide (ITP. These peptides were detected by immunocytochemistry in combination with GFP expression driven by the enhancer trap Gal4 lines c929 and Kurs-6, both of which are expressed in ipc-1 and 2a cells. This mix of colocalized peptides with seemingly unrelated functions is intriguing and prompted us to initiate analysis of the function of the ten neurosecretory cells. We investigated the role of peptide signaling from large ipc-1 and 2a cells in stress responses by monitoring the effect of starvation and desiccation in flies with levels of DTK or sNPF diminished by RNA interference. Using the Gal4-UAS system we targeted the peptide knockdown specifically to ipc-1 and 2a cells with the c929 and Kurs-6 drivers. Flies with reduced DTK or sNPF levels in these cells displayed decreased survival time at desiccation and starvation, as well as increased water loss at desiccation. Our data suggest that homeostasis during metabolic stress requires intact peptide signaling by ipc-1 and 2a neurosecretory cells.

  16. Sex-specific signaling in the blood-brain barrier is required for male courtship in Drosophila.

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    Valbona Hoxha

    Full Text Available Soluble circulating proteins play an important role in the regulation of mating behavior in Drosophila melanogaster. However, how these factors signal through the blood-brain barrier (bbb to interact with the sex-specific brain circuits that control courtship is unknown. Here we show that male identity of the blood-brain barrier is necessary and that male-specific factors in the bbb are physiologically required for normal male courtship behavior. Feminization of the bbb of adult males significantly reduces male courtship. We show that the bbb-specific G-protein coupled receptor moody and bbb-specific Go signaling in adult males are necessary for normal courtship. These data identify sex-specific factors and signaling processes in the bbb as important regulators of male mating behavior.

  17. Detection of transgenerational spermatogenic inheritance of adult male acquired CNS gene expression characteristics using a Drosophila systems model.

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    Abhay Sharma

    Full Text Available Available instances of inheritance of epigenetic transgenerational phenotype are limited to environmental exposures during embryonic and adult gonadal development. Adult exposures can also affect gametogenesis and thereby potentially result in reprogramming of the germline. Although examples of epigenetic effects on gametogenesis exist, it is notable that transgenerational inheritance of environment-induced adult phenotype has not yet been reported. Epigenetic codes are considered to be critical in neural plasticity. A Drosophila systems model of pentylenetetrazole (PTZ induced long-term brain plasticity has recently been described. In this model, chronic PTZ treatment of adult males causes alterations in CNS transcriptome. Here, we describe our search for transgenerational spermatogenic inheritance of PTZ induced gene expression phenotype acquired by adult Drosophila males. We generated CNS transcriptomic profiles of F(1 adults after treating F(0 adult males with PTZ and of F(2 adults resulting from a cross between F(1 males and normal females. Surprisingly, microarray clustering showed F(1 male profile as closest to F(1 female and F(0 male profile closest to F(2 male. Differentially expressed genes in F(1 males, F(1 females and F(2 males showed significant overlap with those caused by PTZ. Interestingly, microarray evidence also led to the identification of upregulated rRNA in F(2 males. Next, we generated microarray expression profiles of adult testis from F(0 and F(1 males. Further surprising, clustering of CNS and testis profiles and matching of differentially expressed genes in them provided evidence of a spermatogenic mechanism in the transgenerational effect observed. To our knowledge, we report for the first time detection of transgenerational spermatogenic inheritance of adult acquired somatic gene expression characteristic. The Drosophila systems model offers an excellent opportunity to understand the epigenetic mechanisms underlying

  18. Detection of transgenerational spermatogenic inheritance of adult male acquired CNS gene expression characteristics using a Drosophila systems model.

    Science.gov (United States)

    Sharma, Abhay; Singh, Priyanka

    2009-06-02

    Available instances of inheritance of epigenetic transgenerational phenotype are limited to environmental exposures during embryonic and adult gonadal development. Adult exposures can also affect gametogenesis and thereby potentially result in reprogramming of the germline. Although examples of epigenetic effects on gametogenesis exist, it is notable that transgenerational inheritance of environment-induced adult phenotype has not yet been reported. Epigenetic codes are considered to be critical in neural plasticity. A Drosophila systems model of pentylenetetrazole (PTZ) induced long-term brain plasticity has recently been described. In this model, chronic PTZ treatment of adult males causes alterations in CNS transcriptome. Here, we describe our search for transgenerational spermatogenic inheritance of PTZ induced gene expression phenotype acquired by adult Drosophila males. We generated CNS transcriptomic profiles of F(1) adults after treating F(0) adult males with PTZ and of F(2) adults resulting from a cross between F(1) males and normal females. Surprisingly, microarray clustering showed F(1) male profile as closest to F(1) female and F(0) male profile closest to F(2) male. Differentially expressed genes in F(1) males, F(1) females and F(2) males showed significant overlap with those caused by PTZ. Interestingly, microarray evidence also led to the identification of upregulated rRNA in F(2) males. Next, we generated microarray expression profiles of adult testis from F(0) and F(1) males. Further surprising, clustering of CNS and testis profiles and matching of differentially expressed genes in them provided evidence of a spermatogenic mechanism in the transgenerational effect observed. To our knowledge, we report for the first time detection of transgenerational spermatogenic inheritance of adult acquired somatic gene expression characteristic. The Drosophila systems model offers an excellent opportunity to understand the epigenetic mechanisms underlying the

  19. Imaging Live Drosophila Brain with Two-Photon Fluorescence Microscopy

    Science.gov (United States)

    Ahmed, Syeed Ehsan

    Two-photon fluorescence microscopy is an imaging technique which delivers distinct benefits for in vivo cellular and molecular imaging. Cyclic adenosine monophosphate (cAMP), a second messenger molecule, is responsible for triggering many physiological changes in neural system. However, the mechanism by which this molecule regulates responses in neuron cells is not yet clearly understood. When cAMP binds to a target protein, it changes the structure of that protein. Therefore, studying this molecular structure change with fluorescence resonance energy transfer (FRET) imaging can shed light on the cAMP functioning mechanism. FRET is a non-radiative dipole-dipole coupling which is sensitive to small distance change in nanometer scale. In this study we have investigated the effect of dopamine in cAMP dynamics in vivo. In our study two-photon fluorescence microscope was used for imaging mushroom bodies inside live Drosophila melanogaster brain and we developed a method for studying the change in cyclic AMP level.

  20. Preparation and mounting of adult Drosophila structures in Canada balsam.

    Science.gov (United States)

    Stern, David L; Sucena, Elio

    2012-03-01

    The Drosophila cuticle carries a rich array of morphological details. Thus, cuticle examination has had a central role in the history of genetics. To prepare fine "museum-quality," permanent slides, it is best to mount specimens in Canada Balsam. It is difficult to give precise recipes for Canada Balsam, because every user seems to prefer a slightly different viscosity. Dilute solutions spread easily and do not dry too rapidly while mounting specimens. The disadvantage is that there is actually less Balsam in a "drop" of the solution, and when dried, it can contract from the sides of the coverslip, sometimes disturbing the specimen. Unfortunately, there is no substitute for experience when using Canada Balsam. This protocol describes a procedure for mounting adult cuticles in Canada Balsam.

  1. A Subset of Serotonergic Neurons Evokes Hunger in Adult Drosophila.

    Science.gov (United States)

    Albin, Stephanie D; Kaun, Karla R; Knapp, Jon-Michael; Chung, Phuong; Heberlein, Ulrike; Simpson, Julie H

    2015-09-21

    Hunger is a complex motivational state that drives multiple behaviors. The sensation of hunger is caused by an imbalance between energy intake and expenditure. One immediate response to hunger is increased food consumption. Hunger also modulates behaviors related to food seeking such as increased locomotion and enhanced sensory sensitivity in both insects and vertebrates. In addition, hunger can promote the expression of food-associated memory. Although progress is being made, how hunger is represented in the brain and how it coordinates these behavioral responses is not fully understood in any system. Here, we use Drosophila melanogaster to identify neurons encoding hunger. We found a small group of neurons that, when activated, induced a fed fly to eat as though it were starved, suggesting that these neurons are downstream of the metabolic regulation of hunger. Artificially activating these neurons also promotes appetitive memory performance in sated flies, indicating that these neurons are not simply feeding command neurons but likely play a more general role in encoding hunger. We determined that the neurons relevant for the feeding effect are serotonergic and project broadly within the brain, suggesting a possible mechanism for how various responses to hunger are coordinated. These findings extend our understanding of the neural circuitry that drives feeding and enable future exploration of how state influences neural activity within this circuit. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Amplification of neural stem cell proliferation by intermediate progenitor cells in Drosophila brain development

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    Bello Bruno C

    2008-02-01

    Full Text Available Abstract Background In the mammalian brain, neural stem cells divide asymmetrically and often amplify the number of progeny they generate via symmetrically dividing intermediate progenitors. Here we investigate whether specific neural stem cell-like neuroblasts in the brain of Drosophila might also amplify neuronal proliferation by generating symmetrically dividing intermediate progenitors. Results Cell lineage-tracing and genetic marker analysis show that remarkably large neuroblast lineages exist in the dorsomedial larval brain of Drosophila. These lineages are generated by brain neuroblasts that divide asymmetrically to self renew but, unlike other brain neuroblasts, do not segregate the differentiating cell fate determinant Prospero to their smaller daughter cells. These daughter cells continue to express neuroblast-specific molecular markers and divide repeatedly to produce neural progeny, demonstrating that they are proliferating intermediate progenitors. The proliferative divisions of these intermediate progenitors have novel cellular and molecular features; they are morphologically symmetrical, but molecularly asymmetrical in that key differentiating cell fate determinants are segregated into only one of the two daughter cells. Conclusion Our findings provide cellular and molecular evidence for a new mode of neurogenesis in the larval brain of Drosophila that involves the amplification of neuroblast proliferation through intermediate progenitors. This type of neurogenesis bears remarkable similarities to neurogenesis in the mammalian brain, where neural stem cells as primary progenitors amplify the number of progeny they generate through generation of secondary progenitors. This suggests that key aspects of neural stem cell biology might be conserved in brain development of insects and mammals.

  3. A role for the adult fat body in Drosophila male courtship behavior.

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    Anna A Lazareva

    2007-01-01

    Full Text Available Mating behavior in Drosophila depends critically on the sexual identity of specific regions in the brain, but several studies have identified courtship genes that express products only outside the nervous system. Although these genes are each active in a variety of non-neuronal cell types, they are all prominently expressed in the adult fat body, suggesting an important role for this tissue in behavior. To test its role in male courtship, fat body was feminized using the highly specific Larval serum protein promoter. We report here that the specific feminization of this tissue strongly reduces the competence of males to perform courtship. This effect is limited to the fat body of sexually mature adults as the feminization of larval fat body that normally persists in young adults does not affect mating. We propose that feminization of fat body affects the synthesis of male-specific secreted circulating proteins that influence the central nervous system. In support of this idea, we demonstrate that Takeout, a protein known to influence mating, is present in the hemolymph of adult males but not females and acts as a secreted protein.

  4. EGFR Signaling in the Brain Is Necessary for Olfactory Learning in "Drosophila" Larvae

    Science.gov (United States)

    Rahn, Tasja; Leippe, Matthias; Roeder, Thomas; Fedders, Henning

    2013-01-01

    Signaling via the epidermal growth factor receptor (EGFR) pathway has emerged as one of the key mechanisms in the development of the central nervous system in "Drosophila melanogaster." By contrast, little is known about the functions of EGFR signaling in the differentiated larval brain. Here, promoter-reporter lines of EGFR and its most prominent…

  5. Left Brain/Right Brain Learning for Adult Education.

    Science.gov (United States)

    Garvin, Barbara

    1986-01-01

    Contrasts and compares the theory and practice of adult education as it relates to the issue of right brain/left brain learning. The author stresses the need for a whole-brain approach to teaching and suggests that adult educators, given their philosophical directions, are the perfect potential users of this integrated system. (Editor/CT)

  6. Starvation-Induced Dietary Behaviour in Drosophila melanogaster Larvae and Adults.

    Science.gov (United States)

    Ahmad, Muhammad; Chaudhary, Safee Ullah; Afzal, Ahmed Jawaad; Tariq, Muhammad

    2015-09-24

    Drosophila melanogaster larvae are classified as herbivores and known to feed on non-carnivorous diet under normal conditions. However, when nutritionally challenged these larvae exhibit cannibalistic behaviour by consuming a diet composed of larger conspecifics. Herein, we report that cannibalism in Drosophila larvae is confined not only to scavenging on conspecifics that are larger in size, but also on their eggs. Moreover, such cannibalistic larvae develop as normally as those grown on standard cornmeal medium. When stressed, Drosophila melanogaster larvae can also consume a carnivorous diet derived from carcasses of organisms belonging to diverse taxonomic groups, including Musca domestica, Apis mellifera, and Lycosidae sp. While adults are ill-equipped to devour conspecific carcasses, they selectively oviposit on them and also consume damaged cadavers of conspecifics. Thus, our results suggest that nutritionally stressed Drosophila show distinct as well as unusual feeding behaviours that can be classified as detritivorous, cannibalistic and/or carnivorous.

  7. Raf-mediated cardiac hypertrophy in adult Drosophila

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    Lin Yu

    2013-07-01

    In response to stress and extracellular signals, the heart undergoes a process called cardiac hypertrophy during which cardiomyocytes increase in size. If untreated, cardiac hypertrophy can progress to overt heart failure that causes significant morbidity and mortality. The identification of molecular signals that cause or modify cardiomyopathies is necessary to understand how the normal heart progresses to cardiac hypertrophy and heart failure. Receptor tyrosine kinase (RTK signaling is essential for normal human cardiac function, and the inhibition of RTKs can cause dilated cardiomyopathies. However, neither investigations of activated RTK signaling pathways nor the characterization of hypertrophic cardiomyopathy in the adult fly heart has been previously described. Therefore, we developed strategies using Drosophila as a model to circumvent some of the complexities associated with mammalian models of cardiovascular disease. Transgenes encoding activated EGFRA887T, Ras85DV12 and Ras85DV12S35, which preferentially signal to Raf, or constitutively active human or fly Raf caused hypertrophic cardiomyopathy as determined by decreased end diastolic lumen dimensions, abnormal cardiomyocyte fiber morphology and increased heart wall thicknesses. There were no changes in cardiomyocyte cell numbers. Additionally, activated Raf also induced an increase in cardiomyocyte ploidy compared with control hearts. However, preventing increases in cardiomyocyte ploidy using fizzy-related (Fzr RNAi did not rescue Raf-mediated cardiac hypertrophy, suggesting that Raf-mediated polyploidization is not required for cardiac hypertrophy. Similar to mammals, the cardiac-specific expression of RNAi directed against MEK or ERK rescued Raf-mediated cardiac hypertrophy. However, the cardiac-specific expression of activated ERKD334N, which promotes hyperplasia in non-cardiac tissues, did not cause myocyte hypertrophy. These results suggest that ERK is necessary, but not sufficient, for Raf

  8. Regulation of Drosophila Brain Wiring by Neuropil Interactions via a Slit-Robo-RPTP Signaling Complex.

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    Oliva, Carlos; Soldano, Alessia; Mora, Natalia; De Geest, Natalie; Claeys, Annelies; Erfurth, Maria-Luise; Sierralta, Jimena; Ramaekers, Ariane; Dascenco, Dan; Ejsmont, Radoslaw K; Schmucker, Dietmar; Sanchez-Soriano, Natalia; Hassan, Bassem A

    2016-10-24

    The axonal wiring molecule Slit and its Round-About (Robo) receptors are conserved regulators of nerve cord patterning. Robo receptors also contribute to wiring brain circuits. Whether molecular mechanisms regulating these signals are modified to fit more complex brain wiring processes is unclear. We investigated the role of Slit and Robo receptors in wiring Drosophila higher-order brain circuits and identified differences in the cellular and molecular mechanisms of Robo/Slit function. First, we find that signaling by Robo receptors in the brain is regulated by the Receptor Protein Tyrosine Phosphatase RPTP69d. RPTP69d increases membrane availability of Robo3 without affecting its phosphorylation state. Second, we detect no midline localization of Slit during brain development. Instead, Slit is enriched in the mushroom body, a neuronal structure covering large areas of the brain. Thus, a divergent molecular mechanism regulates neuronal circuit wiring in the Drosophila brain, partly in response to signals from the mushroom body. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. Aging and Intermittent Fasting Impact on Transcriptional Regulation and Physiological Responses of Adult Drosophila Neuronal and Muscle Tissues.

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    Zhang, Sharon; Ratliff, Eric P; Molina, Brandon; El-Mecharrafie, Nadja; Mastroianni, Jessica; Kotzebue, Roxanne W; Achal, Madhulika; Mauntz, Ruth E; Gonzalez, Arysa; Barekat, Ayeh; Bray, William A; Macias, Andrew M; Daugherty, Daniel; Harris, Greg L; Edwards, Robert A; Finley, Kim D

    2018-04-10

    The progressive decline of the nervous system, including protein aggregate formation, reflects the subtle dysregulation of multiple functional pathways. Our previous work has shown intermittent fasting (IF) enhances longevity, maintains adult behaviors and reduces aggregates, in part, by promoting autophagic function in the aging Drosophila brain. To clarify the impact that IF-treatment has upon aging, we used high throughput RNA-sequencing technology to examine the changing transcriptome in adult Drosophila tissues. Principle component analysis (PCA) and other analyses showed ~1200 age-related transcriptional differences in head and muscle tissues, with few genes having matching expression patterns. Pathway components showing age-dependent expression differences were involved with stress response, metabolic, neural and chromatin remodeling functions. Middle-aged tissues also showed a significant increase in transcriptional drift-variance (TD), which in the CNS included multiple proteolytic pathway components. Overall, IF-treatment had a demonstrably positive impact on aged transcriptomes, partly ameliorating both fold and variance changes. Consistent with these findings, aged IF-treated flies displayed more youthful metabolic, behavioral and basal proteolytic profiles that closely correlated with transcriptional alterations to key components. These results indicate that even modest dietary changes can have therapeutic consequences, slowing the progressive decline of multiple cellular systems, including proteostasis in the aging nervous system.

  10. Aging and Intermittent Fasting Impact on Transcriptional Regulation and Physiological Responses of Adult Drosophila Neuronal and Muscle Tissues

    Directory of Open Access Journals (Sweden)

    Sharon Zhang

    2018-04-01

    Full Text Available The progressive decline of the nervous system, including protein aggregate formation, reflects the subtle dysregulation of multiple functional pathways. Our previous work has shown intermittent fasting (IF enhances longevity, maintains adult behaviors and reduces aggregates, in part, by promoting autophagic function in the aging Drosophila brain. To clarify the impact that IF-treatment has upon aging, we used high throughput RNA-sequencing technology to examine the changing transcriptome in adult Drosophila tissues. Principle component analysis (PCA and other analyses showed ~1200 age-related transcriptional differences in head and muscle tissues, with few genes having matching expression patterns. Pathway components showing age-dependent expression differences were involved with stress response, metabolic, neural and chromatin remodeling functions. Middle-aged tissues also showed a significant increase in transcriptional drift-variance (TD, which in the CNS included multiple proteolytic pathway components. Overall, IF-treatment had a demonstrably positive impact on aged transcriptomes, partly ameliorating both fold and variance changes. Consistent with these findings, aged IF-treated flies displayed more youthful metabolic, behavioral and basal proteolytic profiles that closely correlated with transcriptional alterations to key components. These results indicate that even modest dietary changes can have therapeutic consequences, slowing the progressive decline of multiple cellular systems, including proteostasis in the aging nervous system.

  11. The Drosophila blood-brain barrier: Development and function of a glial endothelium

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    Stefanie eLimmer

    2014-11-01

    Full Text Available The efficacy of neuronal function requires a well-balanced extracellular ion homeostasis and a steady supply with nutrients and metabolites. Therefore, all organisms equipped with a complex nervous system developed a so-called blood-brain barrier, protecting it from an uncontrolled entry of solutes, metabolites or pathogens. In higher vertebrates, this diffusion barrier is established by polarized endothelial cells that form extensive tight junctions, whereas in lower vertebrates and invertebrates the blood-brain barrier is exclusively formed by glial cells. Here, we review the development and function of the glial blood-brain barrier of Drosophila melanogaster. In the Drosophila nervous system, at least seven morphologically distinct glial cell classes can be distinguished. Two of these glial classes form the blood-brain barrier. Perineurial glial cells participate in nutrient uptake and establish a first diffusion barrier. The subperineurial glial cells form septate junctions, which block paracellular diffusion and thus seal the nervous system from the hemolymph. We summarize the molecular basis of septate junction formation and address the different transport systems expressed by the blood-brain barrier forming glial cells.

  12. The Drosophila blood-brain barrier: development and function of a glial endothelium.

    Science.gov (United States)

    Limmer, Stefanie; Weiler, Astrid; Volkenhoff, Anne; Babatz, Felix; Klämbt, Christian

    2014-01-01

    The efficacy of neuronal function requires a well-balanced extracellular ion homeostasis and a steady supply with nutrients and metabolites. Therefore, all organisms equipped with a complex nervous system developed a so-called blood-brain barrier, protecting it from an uncontrolled entry of solutes, metabolites or pathogens. In higher vertebrates, this diffusion barrier is established by polarized endothelial cells that form extensive tight junctions, whereas in lower vertebrates and invertebrates the blood-brain barrier is exclusively formed by glial cells. Here, we review the development and function of the glial blood-brain barrier of Drosophila melanogaster. In the Drosophila nervous system, at least seven morphologically distinct glial cell classes can be distinguished. Two of these glial classes form the blood-brain barrier. Perineurial glial cells participate in nutrient uptake and establish a first diffusion barrier. The subperineurial glial (SPG) cells form septate junctions, which block paracellular diffusion and thus seal the nervous system from the hemolymph. We summarize the molecular basis of septate junction formation and address the different transport systems expressed by the blood-brain barrier forming glial cells.

  13. Barrier mechanisms in the Drosophila blood-brain barrier

    Directory of Open Access Journals (Sweden)

    Samantha Jane Hindle

    2014-12-01

    Full Text Available The invertebrate blood-brain barrier field is growing at a rapid pace and, in recent years, studies have shown a physiologic and molecular complexity that has begun to rival its vertebrate counterpart. Novel mechanisms of paracellular barrier maintenance through GPCR signaling were the first demonstrations of the complex adaptive mechanisms of barrier physiology. Building upon this work, the integrity of the invertebrate blood-brain barrier has recently been shown to require coordinated function of all layers of the compound barrier structure, analogous to signaling between the layers of the vertebrate neurovascular unit. These findings strengthen the notion that many blood-brain barrier mechanisms are conserved between vertebrates and invertebrates, and suggest that novel findings in invertebrate model organisms will have a significant impact on the understanding of vertebrate BBB functions. In this vein, important roles in coordinating localized and systemic signaling to dictate organism development and growth are beginning to show how the blood-brain barrier can govern whole animal physiologies. This includes novel functions of blood-brain barrier gap junctions in orchestrating synchronized neuroblast proliferation, and of blood-brain barrier secreted antagonists of insulin receptor signaling. These advancements and others are pushing the field forward in exciting new directions. In this review, we provide a synopsis of invertebrate blood-brain barrier anatomy and physiology, with a focus on insights from the past 5 years, and highlight important areas for future study.

  14. [Influence of tissue-specific superoxide dismutase genes expression in brain cells on Drosophila melanogaster sensitivity to oxidative stress and viability].

    Science.gov (United States)

    Vitushynska, M V; Matiytsiv, N P; Chernyk, Y

    2015-01-01

    The study has shown that both functional gene knockout Sodl and Sod2 and their overexpression in neurons and glial tissue increase the sensitivity of Drosophila melanogaster to oxidative stress (OS) conditions. The lowest survival rate was only 20.5% in insects with Sod2 knockout in neurons. Comparative analysis of the survival curves showed that adults with altered tissue-specific expression of the studied genes had reduced average and maximum life span. Under OS conditions induced by 5% hydrogen peroxide the life spans of wild type Oregon R and transgenic insects were significantly reduced. Altered Sod gene expression in glial tissue leads to degenerative changes in Drosophila brain at the young age. During the aging of insects and the action of pro-oxidants increasing of neurodegenerative phenotype is observed.

  15. Super resolution imaging of genetically labelled synapses in Drosophila brain tissue

    Directory of Open Access Journals (Sweden)

    Isabelle Ayumi Spühler

    2016-05-01

    Full Text Available Understanding synaptic connectivity and plasticity within brain circuits and their relationship to learning and behavior is a fundamental quest in neuroscience. Visualizing the fine details of synapses using optical microscopy remains however a major technical challenge. Super resolution microscopy opens the possibility to reveal molecular features of synapses beyond the diffraction limit. With direct stochastic optical reconstruction microscopy, dSTORM, we image synaptic proteins in the brain tissue of the fruit fly, Drosophila melanogaster. Super resolution imaging of brain tissue harbors difficulties due to light scattering and the density of signals. In order to reduce out of focus signal, we take advantage of the genetic tools available in the Drosophila and have fluorescently tagged synaptic proteins expressed in only a small number of neurons. These neurons form synapses within the calyx of the mushroom body, a distinct brain region involved in associative memory formation. Our results show that super resolution microscopy, in combination with genetically labelled synaptic proteins, is a powerful tool to investigate synapses in a quantitative fashion providing an entry point for studies on synaptic plasticity during learning and memory formation

  16. Super Resolution Imaging of Genetically Labeled Synapses in Drosophila Brain Tissue.

    Science.gov (United States)

    Spühler, Isabelle A; Conley, Gaurasundar M; Scheffold, Frank; Sprecher, Simon G

    2016-01-01

    Understanding synaptic connectivity and plasticity within brain circuits and their relationship to learning and behavior is a fundamental quest in neuroscience. Visualizing the fine details of synapses using optical microscopy remains however a major technical challenge. Super resolution microscopy opens the possibility to reveal molecular features of synapses beyond the diffraction limit. With direct stochastic optical reconstruction microscopy, dSTORM, we image synaptic proteins in the brain tissue of the fruit fly, Drosophila melanogaster. Super resolution imaging of brain tissue harbors difficulties due to light scattering and the density of signals. In order to reduce out of focus signal, we take advantage of the genetic tools available in the Drosophila and have fluorescently tagged synaptic proteins expressed in only a small number of neurons. These neurons form synapses within the calyx of the mushroom body, a distinct brain region involved in associative memory formation. Our results show that super resolution microscopy, in combination with genetically labeled synaptic proteins, is a powerful tool to investigate synapses in a quantitative fashion providing an entry point for studies on synaptic plasticity during learning and memory formation.

  17. Adaptation to new nutritional environments: larval performance, foraging decisions, and adult oviposition choices in Drosophila suzukii.

    Science.gov (United States)

    Silva-Soares, Nuno F; Nogueira-Alves, A; Beldade, P; Mirth, Christen Kerry

    2017-06-07

    Understanding how species adapt to new niches is a central issue in evolutionary ecology. Nutrition is vital for the survival of all organisms and impacts species fitness and distribution. While most Drosophila species exploit rotting plant parts, some species have diversified to use ripe fruit, allowing earlier colonization. The decomposition of plant material is facilitated by yeast colonization and proliferation. These yeasts serve as the main protein source for Drosophila larvae. This dynamic rotting process entails changes in the nutritional composition of the food and other properties, and animals feeding on material at different stages of decay are expected to have behavioural and nutritional adaptations. We compared larval performance, feeding behaviour and adult oviposition site choice between the ripe fruit colonizer and invasive pest Drosophila suzukii, and a closely-related rotting fruit colonizer, Drosophila biarmipes. Through the manipulation of protein:carbohydrate ratios in artificial diets, we found that D. suzukii larvae perform better at lower protein concentrations and consume less protein rich diets relative to D. biarmipes. For adult oviposition, these species differed in preference for substrate hardness, but not for the substrate nutritional composition. Our findings highlight that rather than being an exclusive specialist on ripe fruit, D. suzukii's adaptation to use ripening fruit allow it to colonize a wider range of food substrates than D. biarmipes, which is limited to soft foods with higher protein concentrations. Our results underscore the importance of nutritional performance and feeding behaviours in the colonization of new food niches.

  18. Conserved mechanisms of tumorigenesis in the Drosophila adult midgut.

    Directory of Open Access Journals (Sweden)

    Òscar Martorell

    Full Text Available Whereas the series of genetic events leading to colorectal cancer (CRC have been well established, the precise functions that these alterations play in tumor progression and how they disrupt intestinal homeostasis remain poorly characterized. Activation of the Wnt/Wg signaling pathway by a mutation in the gene APC is the most common trigger for CRC, inducing benign lesions that progress to carcinomas due to the accumulation of other genetic alterations. Among those, Ras mutations drive tumour progression in CRC, as well as in most epithelial cancers. As mammalian and Drosophila's intestines share many similarities, we decided to explore the alterations induced in the Drosophila midgut by the combined activation of the Wnt signaling pathway with gain of function of Ras signaling in the intestinal stem cells. Here we show that compound Apc-Ras clones, but not clones bearing the individual mutations, expand as aggressive intestinal tumor-like outgrowths. These lesions reproduce many of the human CRC hallmarks such as increased proliferation, blockade of cell differentiation and cell polarity and disrupted organ architecture. This process is followed by expression of tumoral markers present in human lesions. Finally, a metabolic behavioral assay shows that these flies suffer a progressive deterioration in intestinal homeostasis, providing a simple readout that could be used in screens for tumor modifiers or therapeutic compounds. Taken together, our results illustrate the conservation of the mechanisms of CRC tumorigenesis in Drosophila, providing an excellent model system to unravel the events that, upon mutation in Apc and Ras, lead to CRC initiation and progression.

  19. Conserved mechanisms of tumorigenesis in the Drosophila adult midgut.

    Science.gov (United States)

    Martorell, Òscar; Merlos-Suárez, Anna; Campbell, Kyra; Barriga, Francisco M; Christov, Christo P; Miguel-Aliaga, Irene; Batlle, Eduard; Casanova, Jordi; Casali, Andreu

    2014-01-01

    Whereas the series of genetic events leading to colorectal cancer (CRC) have been well established, the precise functions that these alterations play in tumor progression and how they disrupt intestinal homeostasis remain poorly characterized. Activation of the Wnt/Wg signaling pathway by a mutation in the gene APC is the most common trigger for CRC, inducing benign lesions that progress to carcinomas due to the accumulation of other genetic alterations. Among those, Ras mutations drive tumour progression in CRC, as well as in most epithelial cancers. As mammalian and Drosophila's intestines share many similarities, we decided to explore the alterations induced in the Drosophila midgut by the combined activation of the Wnt signaling pathway with gain of function of Ras signaling in the intestinal stem cells. Here we show that compound Apc-Ras clones, but not clones bearing the individual mutations, expand as aggressive intestinal tumor-like outgrowths. These lesions reproduce many of the human CRC hallmarks such as increased proliferation, blockade of cell differentiation and cell polarity and disrupted organ architecture. This process is followed by expression of tumoral markers present in human lesions. Finally, a metabolic behavioral assay shows that these flies suffer a progressive deterioration in intestinal homeostasis, providing a simple readout that could be used in screens for tumor modifiers or therapeutic compounds. Taken together, our results illustrate the conservation of the mechanisms of CRC tumorigenesis in Drosophila, providing an excellent model system to unravel the events that, upon mutation in Apc and Ras, lead to CRC initiation and progression.

  20. A mighty small heart: the cardiac proteome of adult Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Anthony Cammarato

    2011-04-01

    Full Text Available Drosophila melanogaster is emerging as a powerful model system for the study of cardiac disease. Establishing peptide and protein maps of the Drosophila heart is central to implementation of protein network studies that will allow us to assess the hallmarks of Drosophila heart pathogenesis and gauge the degree of conservation with human disease mechanisms on a systems level. Using a gel-LC-MS/MS approach, we identified 1228 protein clusters from 145 dissected adult fly hearts. Contractile, cytostructural and mitochondrial proteins were most abundant consistent with electron micrographs of the Drosophila cardiac tube. Functional/Ontological enrichment analysis further showed that proteins involved in glycolysis, Ca(2+-binding, redox, and G-protein signaling, among other processes, are also over-represented. Comparison with a mouse heart proteome revealed conservation at the level of molecular function, biological processes and cellular components. The subsisting peptidome encompassed 5169 distinct heart-associated peptides, of which 1293 (25% had not been identified in a recent Drosophila peptide compendium. PeptideClassifier analysis was further used to map peptides to specific gene-models. 1872 peptides provide valuable information about protein isoform groups whereas a further 3112 uniquely identify specific protein isoforms and may be used as a heart-associated peptide resource for quantitative proteomic approaches based on multiple-reaction monitoring. In summary, identification of excitation-contraction protein landmarks, orthologues of proteins associated with cardiovascular defects, and conservation of protein ontologies, provides testimony to the heart-like character of the Drosophila cardiac tube and to the utility of proteomics as a complement to the power of genetics in this growing model of human heart disease.

  1. Delivery of circulating lipoproteins to specific neurons in the Drosophila brain regulates systemic insulin signaling.

    Science.gov (United States)

    Brankatschk, Marko; Dunst, Sebastian; Nemetschke, Linda; Eaton, Suzanne

    2014-10-02

    The Insulin signaling pathway couples growth, development and lifespan to nutritional conditions. Here, we demonstrate a function for the Drosophila lipoprotein LTP in conveying information about dietary lipid composition to the brain to regulate Insulin signaling. When yeast lipids are present in the diet, free calcium levels rise in Blood Brain Barrier glial cells. This induces transport of LTP across the Blood Brain Barrier by two LDL receptor-related proteins: LRP1 and Megalin. LTP accumulates on specific neurons that connect to cells that produce Insulin-like peptides, and induces their release into the circulation. This increases systemic Insulin signaling and the rate of larval development on yeast-containing food compared with a plant-based food of similar nutritional content.

  2. Mass Spectrometry Imaging Shows Cocaine and Methylphenidate Have Opposite Effects on Major Lipids in Drosophila Brain.

    Science.gov (United States)

    Philipsen, Mai H; Phan, Nhu T N; Fletcher, John S; Malmberg, Per; Ewing, Andrew G

    2018-03-20

    Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to study the effects of cocaine versus methylphenidate administration on both the localization and abundance of lipids in Drosophila melanogaster brain. A J105 ToF-SIMS with a 40 keV gas cluster primary ion source enabled us to probe molecular ions of biomolecules on the fly with a spatial resolution of ∼3 μm, giving us unique insights into the effect of these drugs on molecular lipids in the nervous system. Significant changes in phospholipid composition were observed in the central brain for both. Principal components image analysis revealed that changes occurred mainly for phosphatidylcholines, phosphatidylethanolamines, and phosphatidylinositols. When the lipid changes caused by cocaine were compared with those induced by methylphenidate, it was shown that these drugs exert opposite effects on the brain lipid structure. We speculate that this might relate to the molecular mechanism of cognition and memory.

  3. A subset of neurons controls the permeability of the peritrophic matrix and midgut structure in Drosophila adults.

    Science.gov (United States)

    Kenmoku, Hiroyuki; Ishikawa, Hiroki; Ote, Manabu; Kuraishi, Takayuki; Kurata, Shoichiro

    2016-08-01

    The metazoan gut performs multiple physiological functions, including digestion and absorption of nutrients, and also serves as a physical and chemical barrier against ingested pathogens and abrasive particles. Maintenance of these functions and structures is partly controlled by the nervous system, yet the precise roles and mechanisms of the neural control of gut integrity remain to be clarified in Drosophila Here, we screened for GAL4 enhancer-trap strains and labeled a specific subsets of neurons, using Kir2.1 to inhibit their activity. We identified an NP3253 line that is susceptible to oral infection by Gram-negative bacteria. The subset of neurons driven by the NP3253 line includes some of the enteric neurons innervating the anterior midgut, and these flies have a disorganized proventricular structure with high permeability of the peritrophic matrix and epithelial barrier. The findings of the present study indicate that neural control is crucial for maintaining the barrier function of the gut, and provide a route for genetic dissection of the complex brain-gut axis in adults of the model organism Drosophila. © 2016. Published by The Company of Biologists Ltd.

  4. Olfactory map formation in the Drosophila brain: genetic specificity and neuronal variability.

    Science.gov (United States)

    Brochtrup, Anna; Hummel, Thomas

    2011-02-01

    The development of the Drosophila olfactory system is a striking example of how genetic programs specify a large number of different neuron types and assemble them into functional circuits. To ensure precise odorant perception, each sensory neuron has to not only select a single olfactory receptor (OR) type out of a large genomic repertoire but also segregate its synaptic connections in the brain according to the OR class identity. Specification and patterning of second-order interneurons in the olfactory brain center occur largely independent of sensory input, followed by a precise point-to-point matching of sensory and relay neurons. Here we describe recent progress in the understanding of how cell-intrinsic differentiation programs and context-dependent cellular interactions generate a stereotyped sensory map in the Drosophila brain. Recent findings revealed an astonishing morphological diversity among members of the same interneuron class, suggesting an unexpected variability in local microcircuits involved in insect sensory processing. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Control of Drosophila Type I and Type II central brain neuroblast proliferation by bantam microRNA

    DEFF Research Database (Denmark)

    Weng, Ruifen; Cohen, Stephen M

    2015-01-01

    Post-transcriptional regulation of stem cell self-renewal by microRNAs is emerging as an important mechanism controlling tissue homeostasis. Here, we provide evidence that bantam microRNA controls neuroblast number and proliferation in the Drosophila central brain. Bantam also supports proliferat......Post-transcriptional regulation of stem cell self-renewal by microRNAs is emerging as an important mechanism controlling tissue homeostasis. Here, we provide evidence that bantam microRNA controls neuroblast number and proliferation in the Drosophila central brain. Bantam also supports...

  6. Affecting Rhomboid-3 function causes a dilated heart in adult Drosophila.

    Directory of Open Access Journals (Sweden)

    Lin Yu

    2010-05-01

    Full Text Available Drosophila is a well recognized model of several human diseases, and recent investigations have demonstrated that Drosophila can be used as a model of human heart failure. Previously, we described that optical coherence tomography (OCT can be used to rapidly examine the cardiac function in adult, awake flies. This technique provides images that are similar to echocardiography in humans, and therefore we postulated that this approach could be combined with the vast resources that are available in the fly community to identify new mutants that have abnormal heart function, a hallmark of certain cardiovascular diseases. Using OCT to examine the cardiac function in adult Drosophila from a set of molecularly-defined genomic deficiencies from the DrosDel and Exelixis collections, we identified an abnormally enlarged cardiac chamber in a series of deficiency mutants spanning the rhomboid 3 locus. Rhomboid 3 is a member of a highly conserved family of intramembrane serine proteases and processes Spitz, an epidermal growth factor (EGF-like ligand. Using multiple approaches based on the examination of deficiency stocks, a series of mutants in the rhomboid-Spitz-EGF receptor pathway, and cardiac-specific transgenic rescue or dominant-negative repression of EGFR, we demonstrate that rhomboid 3 mediated activation of the EGF receptor pathway is necessary for proper adult cardiac function. The importance of EGF receptor signaling in the adult Drosophila heart underscores the concept that evolutionarily conserved signaling mechanisms are required to maintain normal myocardial function. Interestingly, prior work showing the inhibition of ErbB2, a member of the EGF receptor family, in transgenic knock-out mice or individuals that received herceptin chemotherapy is associated with the development of dilated cardiomyopathy. Our results, in conjunction with the demonstration that altered ErbB2 signaling underlies certain forms of mammalian cardiomyopathy, suggest

  7. Dexterous robotic manipulation of alert adult Drosophila for high-content experimentation.

    Science.gov (United States)

    Savall, Joan; Ho, Eric Tatt Wei; Huang, Cheng; Maxey, Jessica R; Schnitzer, Mark J

    2015-07-01

    We present a robot that enables high-content studies of alert adult Drosophila by combining operations including gentle picking; translations and rotations; characterizations of fly phenotypes and behaviors; microdissection; or release. To illustrate, we assessed fly morphology, tracked odor-evoked locomotion, sorted flies by sex, and dissected the cuticle to image neural activity. The robot's tireless capacity for precise manipulations enables a scalable platform for screening flies' complex attributes and behavioral patterns.

  8. Larval Population Density Alters Adult Sleep in Wild-Type Drosophila melanogaster but Not in Amnesiac Mutant Flies

    Directory of Open Access Journals (Sweden)

    Michael W. Chi

    2014-08-01

    Full Text Available Sleep has many important biological functions, but how sleep is regulated remains poorly understood. In humans, social isolation and other stressors early in life can disrupt adult sleep. In fruit flies housed at different population densities during early adulthood, social enrichment was shown to increase subsequent sleep, but it is unknown if population density during early development can also influence adult sleep. To answer this question, we maintained Drosophila larvae at a range of population densities throughout larval development, kept them isolated during early adulthood, and then tested their sleep patterns. Our findings reveal that flies that had been isolated as larvae had more fragmented sleep than those that had been raised at higher population densities. This effect was more prominent in females than in males. Larval population density did not affect sleep in female flies that were mutant for amnesiac, which has been shown to be required for normal memory consolidation, adult sleep regulation, and brain development. In contrast, larval population density effects on sleep persisted in female flies lacking the olfactory receptor or83b, suggesting that olfactory signals are not required for the effects of larval population density on adult sleep. These findings show that population density during early development can alter sleep behavior in adulthood, suggesting that genetic and/or structural changes are induced by this developmental manipulation that persist through metamorphosis.

  9. Barrier mechanisms in the Drosophila blood-brain barrier.

    Science.gov (United States)

    Hindle, Samantha J; Bainton, Roland J

    2014-01-01

    The invertebrate blood-brain barrier (BBB) field is growing at a rapid pace and, in recent years, studies have shown a physiologic and molecular complexity that has begun to rival its vertebrate counterpart. Novel mechanisms of paracellular barrier maintenance through G-protein coupled receptor signaling were the first demonstrations of the complex adaptive mechanisms of barrier physiology. Building upon this work, the integrity of the invertebrate BBB has recently been shown to require coordinated function of all layers of the compound barrier structure, analogous to signaling between the layers of the vertebrate neurovascular unit. These findings strengthen the notion that many BBB mechanisms are conserved between vertebrates and invertebrates, and suggest that novel findings in invertebrate model organisms will have a significant impact on the understanding of vertebrate BBB functions. In this vein, important roles in coordinating localized and systemic signaling to dictate organism development and growth are beginning to show how the BBB can govern whole animal physiologies. This includes novel functions of BBB gap junctions in orchestrating synchronized neuroblast proliferation, and of BBB secreted antagonists of insulin receptor signaling. These advancements and others are pushing the field forward in exciting new directions. In this review, we provide a synopsis of invertebrate BBB anatomy and physiology, with a focus on insights from the past 5 years, and highlight important areas for future study.

  10. Notch is required in adult Drosophila sensory neurons for morphological and functional plasticity of the olfactory circuit.

    Directory of Open Access Journals (Sweden)

    Simon Kidd

    2015-05-01

    Full Text Available Olfactory receptor neurons (ORNs convey odor information to the central brain, but like other sensory neurons were thought to play a passive role in memory formation and storage. Here we show that Notch, part of an evolutionarily conserved intercellular signaling pathway, is required in adult Drosophila ORNs for the structural and functional plasticity of olfactory glomeruli that is induced by chronic odor exposure. Specifically, we show that Notch activity in ORNs is necessary for the odor specific increase in the volume of glomeruli that occurs as a consequence of prolonged odor exposure. Calcium imaging experiments indicate that Notch in ORNs is also required for the chronic odor induced changes in the physiology of ORNs and the ensuing changes in the physiological response of their second order projection neurons (PNs. We further show that Notch in ORNs acts by both canonical cleavage-dependent and non-canonical cleavage-independent pathways. The Notch ligand Delta (Dl in PNs switches the balance between the pathways. These data define a circuit whereby, in conjunction with odor, N activity in the periphery regulates the activity of neurons in the central brain and Dl in the central brain regulates N activity in the periphery. Our work highlights the importance of experience dependent plasticity at the first olfactory synapse.

  11. Wiring economy and volume exclusion determine neuronal placement in the Drosophila brain.

    Science.gov (United States)

    Rivera-Alba, Marta; Vitaladevuni, Shiv N; Mishchenko, Yuriy; Mischenko, Yuriy; Lu, Zhiyuan; Takemura, Shin-Ya; Scheffer, Lou; Meinertzhagen, Ian A; Chklovskii, Dmitri B; de Polavieja, Gonzalo G

    2011-12-06

    Wiring economy has successfully explained the individual placement of neurons in simple nervous systems like that of Caenorhabditis elegans [1-3] and the locations of coarser structures like cortical areas in complex vertebrate brains [4]. However, it remains unclear whether wiring economy can explain the placement of individual neurons in brains larger than that of C. elegans. Indeed, given the greater number of neuronal interconnections in larger brains, simply minimizing the length of connections results in unrealistic configurations, with multiple neurons occupying the same position in space. Avoiding such configurations, or volume exclusion, repels neurons from each other, thus counteracting wiring economy. Here we test whether wiring economy together with volume exclusion can explain the placement of neurons in a module of the Drosophila melanogaster brain known as lamina cartridge [5-13]. We used newly developed techniques for semiautomated reconstruction from serial electron microscopy (EM) [14] to obtain the shapes of neurons, the location of synapses, and the resultant synaptic connectivity. We show that wiring length minimization and volume exclusion together can explain the structure of the lamina microcircuit. Therefore, even in brains larger than that of C. elegans, at least for some circuits, optimization can play an important role in individual neuron placement. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Adult Heat Tolerance Variation in Drosophila melanogaster is Not Related to Hsp70 Expression

    DEFF Research Database (Denmark)

    Jensen, Louise Toft; Cockerell, Fiona Elizabeth; Kristensen, Torsten Nygaard

    2010-01-01

    in Drosophila larvae Hsp70 expression may be a key determinant of heat tolerance, the evidence for this in adults is equivocal. We therefore examined heat-induced Hsp70 expression and several measurements of adult heat tolerance in three independent collections of D. melanogaster, measured in three laboratories...

  13. Death following traumatic brain injury in Drosophila is associated with intestinal barrier dysfunction

    Science.gov (United States)

    Katzenberger, Rebeccah J; Chtarbanova, Stanislava; Rimkus, Stacey A; Fischer, Julie A; Kaur, Gulpreet; Seppala, Jocelyn M; Swanson, Laura C; Zajac, Jocelyn E; Ganetzky, Barry; Wassarman, David A

    2015-01-01

    Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Unfavorable TBI outcomes result from primary mechanical injuries to the brain and ensuing secondary non-mechanical injuries that are not limited to the brain. Our genome-wide association study of Drosophila melanogaster revealed that the probability of death following TBI is associated with single nucleotide polymorphisms in genes involved in tissue barrier function and glucose homeostasis. We found that TBI causes intestinal and blood–brain barrier dysfunction and that intestinal barrier dysfunction is highly correlated with the probability of death. Furthermore, we found that ingestion of glucose after a primary injury increases the probability of death through a secondary injury mechanism that exacerbates intestinal barrier dysfunction. Our results indicate that natural variation in the probability of death following TBI is due in part to genetic differences that affect intestinal barrier dysfunction. DOI: http://dx.doi.org/10.7554/eLife.04790.001 PMID:25742603

  14. Drosophila insulin release is triggered by adipose Stunted ligand to brain Methuselah receptor.

    Science.gov (United States)

    Delanoue, Renald; Meschi, Eleonora; Agrawal, Neha; Mauri, Alessandra; Tsatskis, Yonit; McNeill, Helen; Léopold, Pierre

    2016-09-30

    Animals adapt their growth rate and body size to available nutrients by a general modulation of insulin-insulin-like growth factor signaling. In Drosophila, dietary amino acids promote the release in the hemolymph of brain insulin-like peptides (Dilps), which in turn activate systemic organ growth. Dilp secretion by insulin-producing cells involves a relay through unknown cytokines produced by fat cells. Here, we identify Methuselah (Mth) as a secretin-incretin receptor subfamily member required in the insulin-producing cells for proper nutrient coupling. We further show, using genetic and ex vivo organ culture experiments, that the Mth ligand Stunted (Sun) is a circulating insulinotropic peptide produced by fat cells. Therefore, Sun and Mth define a new cross-organ circuitry that modulates physiological insulin levels in response to nutrients. Copyright © 2016, American Association for the Advancement of Science.

  15. larvalign: Aligning Gene Expression Patterns from the Larval Brain of Drosophila melanogaster.

    Science.gov (United States)

    Muenzing, Sascha E A; Strauch, Martin; Truman, James W; Bühler, Katja; Thum, Andreas S; Merhof, Dorit

    2018-01-01

    The larval brain of the fruit fly Drosophila melanogaster is a small, tractable model system for neuroscience. Genes for fluorescent marker proteins can be expressed in defined, spatially restricted neuron populations. Here, we introduce the methods for 1) generating a standard template of the larval central nervous system (CNS), 2) spatial mapping of expression patterns from different larvae into a reference space defined by the standard template. We provide a manually annotated gold standard that serves for evaluation of the registration framework involved in template generation and mapping. A method for registration quality assessment enables the automatic detection of registration errors, and a semi-automatic registration method allows one to correct registrations, which is a prerequisite for a high-quality, curated database of expression patterns. All computational methods are available within the larvalign software package: https://github.com/larvalign/larvalign/releases/tag/v1.0.

  16. Ultrastructural findings in the brain of fruit flies (Drosophila melanogaster) and mice exposed to high-energy particle radiation

    International Nuclear Information System (INIS)

    D'Amelio, F.; Kraft, L.M.; D'Antoni-D'Amelio, E.; Benton, E.V.; Miquel, J.

    1984-01-01

    Effects of high energy, heavy particle (HZE) radiation were studied in the brain of the fruit fly (Drosophila melanogaster) exposed to argon (40Ar) or krypton (84Kr) ions. In the flies exposed to argon the fluence ranged from 6 X 10(4) to 8 X 10(7) particles/cm2. The insects were killed 35 days after exposure. Extensive tissue fragmentation was observed at the higher fluence employed. At fluences ranging from 5 X 10(6) (one hit/two cell bodies) to 9 X 10(4) (one hit/90 cell bodies) particles/cm2, swelling of the neuronal cytoplasm and focally fragmented membranes was observed. Marked increase of glial lamellae around nerve cell processes was seen at fluences ranging from one hit/six to one hit/135 cell bodies. In the flies irradiated with krypton, the fluences employed were 5.8 X 10(3) and 2.2 X 10(6) particles/cm2. Acute and late effects were evaluated. In the flies killed 36 hours after exposure (acute effects) to either fluence, glycogen particles were found in the neuroglial compartment. The granules were no longer present in flies killed 35 days later (late effects). From these studies it appears that the Drosophila brain is a useful model to investigate radiation damage to mature neurons, neuroglia, and therefore, to the glio-neuronal metabolic unit. In a separate study, the synaptic profiles of the neuropil in layers II-III of the frontal cerebral cortex of anesthesized adult LAFl mice were quantitatively appraised after exposure to argon (40Ar) particles. The absorbed dose ranged from 0.05 to 5 gray (Gy) plateau. It was determined that the sodium pentobarbital anesthesia per se results in a significant decrease in synaptic profile length one day after anesthetization, with return to normal values after 2-28 days. Irradiation with 0.05-5 Gy argon particles significantly inhibited the synaptic shortening effect of anesthesia at one day after exposure

  17. Signalling pathways involved in adult heart formation revealed by gene expression profiling in Drosophila.

    Directory of Open Access Journals (Sweden)

    Bruno Zeitouni

    2007-10-01

    Full Text Available Drosophila provides a powerful system for defining the complex genetic programs that drive organogenesis. Under control of the steroid hormone ecdysone, the adult heart in Drosophila forms during metamorphosis by a remodelling of the larval cardiac organ. Here, we evaluated the extent to which transcriptional signatures revealed by genomic approaches can provide new insights into the molecular pathways that underlie heart organogenesis. Whole-genome expression profiling at eight successive time-points covering adult heart formation revealed a highly dynamic temporal map of gene expression through 13 transcript clusters with distinct expression kinetics. A functional atlas of the transcriptome profile strikingly points to the genomic transcriptional response of the ecdysone cascade, and a sharp regulation of key components belonging to a few evolutionarily conserved signalling pathways. A reverse genetic analysis provided evidence that these specific signalling pathways are involved in discrete steps of adult heart formation. In particular, the Wnt signalling pathway is shown to participate in inflow tract and cardiomyocyte differentiation, while activation of the PDGF-VEGF pathway is required for cardiac valve formation. Thus, a detailed temporal map of gene expression can reveal signalling pathways responsible for specific developmental programs and provides here substantial grasp into heart formation.

  18. Fatigue in adults with traumatic brain injury

    DEFF Research Database (Denmark)

    Mollayeva, Tatyana; Kendzerska, Tetyana; Mollayeva, Shirin

    2013-01-01

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

  19. Identified peptidergic neurons in the Drosophila brain regulate insulin-producing cells, stress responses and metabolism by coexpressed short neuropeptide F and corazonin.

    Science.gov (United States)

    Kapan, Neval; Lushchak, Oleh V; Luo, Jiangnan; Nässel, Dick R

    2012-12-01

    Insulin/IGF-like signaling regulates the development, growth, fecundity, metabolic homeostasis, stress resistance and lifespan in worms, flies and mammals. Eight insulin-like peptides (DILP1-8) are found in Drosophila. Three of these (DILP2, 3 and 5) are produced by a set of median neurosecretory cells (insulin-producing cells, IPCs) in the brain. Activity in the IPCs of adult flies is regulated by glucose and several neurotransmitters and neuropeptides. One of these, short neuropeptide F (sNPF), regulates food intake, growth and Dilp transcript levels in IPCs via the sNPF receptor (sNPFR1) expressed on IPCs. Here we identify a set of brain neurons that utilizes sNPF to activate the IPCs. These sNPF-expressing neurons (dorsal lateral peptidergic neurons, DLPs) also produce the neuropeptide corazonin (CRZ) and have axon terminations impinging on IPCs. Knockdown of either sNPF or CRZ in DLPs extends survival in flies exposed to starvation and alters carbohydrate and lipid metabolism. Expression of sNPF in DLPs in the sNPF mutant background is sufficient to rescue wild-type metabolism and response to starvation. Since CRZ receptor RNAi in IPCs affects starvation resistance and metabolism, similar to peptide knockdown in DLPs, it is likely that also CRZ targets the IPCs. Knockdown of sNPF, but not CRZ in DLPs decreases transcription of Dilp2 and 5 in the brain, suggesting different mechanisms of action on IPCs of the two co-released peptides. Our findings indicate that sNPF and CRZ co-released from a small set of neurons regulate IPCs, stress resistance and metabolism in adult Drosophila.

  20. Age-related Decline of Abiotic Stress Tolerance in Young Drosophila melanogaster Adults.

    Science.gov (United States)

    Colinet, Hervé; Chertemps, Thomas; Boulogne, Isabelle; Siaussat, David

    2016-12-01

    Stress tolerance generally declines with age as a result of functional senescence. Age-dependent alteration of stress tolerance can also occur in early adult life. In Drosophila melanogaster, evidence of such a decline in young adults has only been reported for thermotolerance. It is not known whether early adult life entails a general stress tolerance reduction and whether the response is peculiar to thermal traits. The present work was designed to investigate whether newly eclosed D melanogaster adults present a high tolerance to a range of biotic and abiotic insults. We found that tolerance to most of the abiotic stressors tested (desiccation, paraquat, hydrogen peroxide, deltamethrin, and malathion) was high in newly eclosed adults before dramatically declining over the next days of adult life. No clear age-related pattern was found for resistance to biotic stress (septic or fungal infection) and starvation. These results suggest that newly eclosed adults present a culminating level of tolerance to extrinsic stress which is likely unrelated to immune process. We argue that stress tolerance variation at very young age is likely a residual attribute from the previous life stage (ontogenetic carryover) or a feature related to the posteclosion development. © The Author 2015. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Polyploidization and cell fusion contribute to wound healing in the adult Drosophila epithelium.

    Science.gov (United States)

    Losick, Vicki P; Fox, Donald T; Spradling, Allan C

    2013-11-18

    Reestablishing epithelial integrity and biosynthetic capacity is critically important following tissue damage. The adult Drosophila abdominal epithelium provides an attractive new system to address how postmitotic diploid cells contribute to repair. Puncture wounds to the adult Drosophila epidermis close initially by forming a melanized scab. We found that epithelial cells near the wound site fuse to form a giant syncytium, which sends lamellae under the scab to re-epithelialize the damaged site. Other large cells arise more peripherally by initiating endocycles and becoming polyploid, or by cell fusion. Rac GTPase activity is needed for syncytium formation, while the Hippo signaling effector Yorkie modulates both polyploidization and cell fusion. Large cell formation is functionally important because when both polyploidization and fusion are blocked, wounds do not re-epithelialize. Our observations indicate that cell mass lost upon wounding can be replaced by polyploidization instead of mitotic proliferation. We propose that large cells generated by polyploidization or cell fusion are essential because they are better able than diploid cells to mechanically stabilize wounds, especially those containing permanent acellular structures, such as scar tissue. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. The influence of Adh function on ethanol preference and tolerance in adult Drosophila melanogaster.

    Science.gov (United States)

    Ogueta, Maite; Cibik, Osman; Eltrop, Rouven; Schneider, Andrea; Scholz, Henrike

    2010-11-01

    Preference determines behavioral choices such as choosing among food sources and mates. One preference-affecting chemical is ethanol, which guides insects to fermenting fruits or leaves. Here, we show that adult Drosophila melanogaster prefer food containing up to 5% ethanol over food without ethanol and avoid food with high levels (23%) of ethanol. Although female and male flies behaved differently at ethanol-containing food sources, there was no sexual dimorphism in the preference for food containing modest ethanol levels. We also investigated whether Drosophila preference, sensitivity and tolerance to ethanol was related to the activity of alcohol dehydrogenase (Adh), the primary ethanol-metabolizing enzyme in D. melanogaster. Impaired Adh function reduced ethanol preference in both D. melanogaster and a related species, D. sechellia. Adh-impaired flies also displayed reduced aversion to high ethanol concentrations, increased sensitivity to the effects of ethanol on postural control, and negative tolerance/sensitization (i.e., a reduction of the increased resistance to ethanol's effects that normally occurs upon repeated exposure). These data strongly indicate a linkage between ethanol-induced behavior and ethanol metabolism in adult fruit flies: Adh deficiency resulted in reduced preference to low ethanol concentrations and reduced aversion to high ones, despite recovery from ethanol being strongly impaired.

  3. Requirement of matrix metalloproteinase-1 for intestinal homeostasis in the adult Drosophila midgut

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Shin-Hae; Park, Joung-Sun [Department of Molecular Biology, College of Natural Science, Pusan National University, Busan 609-735 (Korea, Republic of); Kim, Young-Shin [Research Institute of Genetic Engineering, Pusan National University, Busan 609-735 (Korea, Republic of); Chung, Hae-Young [Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan 609-735 (Korea, Republic of); Yoo, Mi-Ae, E-mail: mayoo@pusan.ac.kr [Department of Molecular Biology, College of Natural Science, Pusan National University, Busan 609-735 (Korea, Republic of)

    2012-03-10

    Stem cells are tightly regulated by both intrinsic and extrinsic signals as well as the extracellular matrix (ECM) for tissue homeostasis and regenerative capacity. Matrix metalloproteinases (MMPs), proteolytic enzymes, modulate the turnover of numerous substrates, including cytokine precursors, growth factors, and ECM molecules. However, the roles of MMPs in the regulation of adult stem cells are poorly understood. In the present study, we utilize the Drosophila midgut, which is an excellent model system for studying stem cell biology, to show that Mmp1 is involved in the regulation of intestinal stem cells (ISCs). The results showed that Mmp1 is expressed in the adult midgut and that its expression increases with age and with exposure to oxidative stress. Mmp1 knockdown or Timp-overexpressing flies and flies heterozygous for a viable, hypomorphic Mmp1 allele increased ISC proliferation in the gut, as shown by staining with an anti-phospho-histone H3 antibody and BrdU incorporation assays. Reduced Mmp1 levels induced intestinal hyperplasia, and the Mmp1depletion-induced ISC proliferation was rescued by the suppression of the EGFR signaling pathway, suggesting that Mmp1 regulates ISC proliferation through the EGFR signaling pathway. Furthermore, adult gut-specific knockdown and whole-animal heterozygotes of Mmp1 increased additively sensitivity to paraquat-induced oxidative stress and shortened lifespan. Our data suggest that Drosophila Mmp1 is involved in the regulation of ISC proliferation for maintenance of gut homeostasis. -- Highlights: Black-Right-Pointing-Pointer Mmp1 is expressed in the adult midgut. Black-Right-Pointing-Pointer Mmp1 is involved in the regulation of ISC proliferation activity. Black-Right-Pointing-Pointer Mmp1-related ISC proliferation is associated with EGFR signaling. Black-Right-Pointing-Pointer Mmp1 in the gut is required for the intestinal homeostasis and longevity.

  4. Requirement of matrix metalloproteinase-1 for intestinal homeostasis in the adult Drosophila midgut

    International Nuclear Information System (INIS)

    Lee, Shin-Hae; Park, Joung-Sun; Kim, Young-Shin; Chung, Hae-Young; Yoo, Mi-Ae

    2012-01-01

    Stem cells are tightly regulated by both intrinsic and extrinsic signals as well as the extracellular matrix (ECM) for tissue homeostasis and regenerative capacity. Matrix metalloproteinases (MMPs), proteolytic enzymes, modulate the turnover of numerous substrates, including cytokine precursors, growth factors, and ECM molecules. However, the roles of MMPs in the regulation of adult stem cells are poorly understood. In the present study, we utilize the Drosophila midgut, which is an excellent model system for studying stem cell biology, to show that Mmp1 is involved in the regulation of intestinal stem cells (ISCs). The results showed that Mmp1 is expressed in the adult midgut and that its expression increases with age and with exposure to oxidative stress. Mmp1 knockdown or Timp-overexpressing flies and flies heterozygous for a viable, hypomorphic Mmp1 allele increased ISC proliferation in the gut, as shown by staining with an anti-phospho-histone H3 antibody and BrdU incorporation assays. Reduced Mmp1 levels induced intestinal hyperplasia, and the Mmp1depletion-induced ISC proliferation was rescued by the suppression of the EGFR signaling pathway, suggesting that Mmp1 regulates ISC proliferation through the EGFR signaling pathway. Furthermore, adult gut-specific knockdown and whole-animal heterozygotes of Mmp1 increased additively sensitivity to paraquat-induced oxidative stress and shortened lifespan. Our data suggest that Drosophila Mmp1 is involved in the regulation of ISC proliferation for maintenance of gut homeostasis. -- Highlights: ► Mmp1 is expressed in the adult midgut. ► Mmp1 is involved in the regulation of ISC proliferation activity. ► Mmp1-related ISC proliferation is associated with EGFR signaling. ► Mmp1 in the gut is required for the intestinal homeostasis and longevity.

  5. The Drosophila melanogaster Muc68E Mucin Gene Influences Adult Size, Starvation Tolerance, and Cold Recovery.

    Science.gov (United States)

    Reis, Micael; Silva, Ana C; Vieira, Cristina P; Vieira, Jorge

    2016-07-07

    Mucins have been implicated in many different biological processes, such as protection from mechanical damage, microorganisms, and toxic molecules, as well as providing a luminal scaffold during development. Nevertheless, it is conceivable that mucins have the potential to modulate food absorption as well, and thus contribute to the definition of several important phenotypic traits. Here we show that the Drosophila melanogaster Muc68E gene is 40- to 60-million-yr old, and is present in Drosophila species of the subgenus Sophophora only. The central repeat region of this gene is fast evolving, and shows evidence for repeated expansions/contractions. This and/or frequent gene conversion events lead to the homogenization of its repeats. The amino acid pattern P[ED][ED][ST][ST][ST] is found in the repeat region of Muc68E proteins from all Drosophila species studied, and can occur multiple times within a single conserved repeat block, and thus may have functional significance. Muc68E is a nonessential gene under laboratory conditions, but Muc68E mutant flies are smaller and lighter than controls at birth. However, at 4 d of age, Muc68E mutants are heavier, recover faster from chill-coma, and are more resistant to starvation than control flies, although they have the same percentage of lipids as controls. Mutant flies have enlarged abdominal size 1 d after chill-coma recovery, which is associated with higher lipid content. These results suggest that Muc68E has a role in metabolism modulation, food absorption, and/or feeding patterns in larvae and adults, and under normal and stress conditions. Such biological function is novel for mucin genes. Copyright © 2016 Reis et al.

  6. 454-Pyrosequencing survey of microbiota in adult Spotted Wing Drosophila (SWD) corroborates a core microbiome and additional symbiotic and entomopathogenic bacterial associates

    Science.gov (United States)

    Complete surveys of insect endosymbionts including species of economic importance have until recently been hampered by a lack of high-throughput genetic assays. We used 454-pyrosequencing of the 16S rRNA gene amplicon of adult spotted wing Drosophila (SWD) Drosophila suzukii (Matsumura) from souther...

  7. Evolution of increased adult longevity in Drosophila melanogaster populations selected for adaptation to larval crowding.

    Science.gov (United States)

    Shenoi, V N; Ali, S Z; Prasad, N G

    2016-02-01

    In holometabolous animals such as Drosophila melanogaster, larval crowding can affect a wide range of larval and adult traits. Adults emerging from high larval density cultures have smaller body size and increased mean life span compared to flies emerging from low larval density cultures. Therefore, adaptation to larval crowding could potentially affect adult longevity as a correlated response. We addressed this issue by studying a set of large, outbred populations of D. melanogaster, experimentally evolved for adaptation to larval crowding for 83 generations. We assayed longevity of adult flies from both selected (MCUs) and control populations (MBs) after growing them at different larval densities. We found that MCUs have evolved increased mean longevity compared to MBs at all larval densities. The interaction between selection regime and larval density was not significant, indicating that the density dependence of mean longevity had not evolved in the MCU populations. The increase in longevity in MCUs can be partially attributed to their lower rates of ageing. It is also noteworthy that reaction norm of dry body weight, a trait probably under direct selection in our populations, has indeed evolved in MCU populations. To the best of our knowledge, this is the first report of the evolution of adult longevity as a correlated response of adaptation to larval crowding. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

  8. Functional genomics identifies regulators of the phototransduction machinery in the Drosophila larval eye and adult ocelli.

    Science.gov (United States)

    Mishra, Abhishek Kumar; Bargmann, Bastiaan O R; Tsachaki, Maria; Fritsch, Cornelia; Sprecher, Simon G

    2016-02-15

    Sensory perception of light is mediated by specialized Photoreceptor neurons (PRs) in the eye. During development all PRs are genetically determined to express a specific Rhodopsin (Rh) gene and genes mediating a functional phototransduction pathway. While the genetic and molecular mechanisms of PR development is well described in the adult compound eye, it remains unclear how the expression of Rhodopsins and the phototransduction cascade is regulated in other visual organs in Drosophila, such as the larval eye and adult ocelli. Using transcriptome analysis of larval PR-subtypes and ocellar PRs we identify and study new regulators required during PR differentiation or necessary for the expression of specific signaling molecules of the functional phototransduction pathway. We found that the transcription factor Krüppel (Kr) is enriched in the larval eye and controls PR differentiation by promoting Rh5 and Rh6 expression. We also identified Camta, Lola, Dve and Hazy as key genes acting during ocellar PR differentiation. Further we show that these transcriptional regulators control gene expression of the phototransduction cascade in both larval eye and adult ocelli. Our results show that PR cell type-specific transcriptome profiling is a powerful tool to identify key transcriptional regulators involved during several aspects of PR development and differentiation. Our findings greatly contribute to the understanding of how combinatorial action of key transcriptional regulators control PR development and the regulation of a functional phototransduction pathway in both larval eye and adult ocelli. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Sex-switching of the Drosophila brain by two antagonistic chromatin factors

    Science.gov (United States)

    Ito, Hiroki; Sato, Kosei; Yamamoto, Daisuke

    2013-01-01

    In Drosophila melanogaster, the fruitless (fru) gene encoding BTB-Zn-finger transcription factors organizes male sexual behavior by controlling the development of sexually dimorphic neuronal circuitry. However, the molecular mechanism by which fru controls the sexual fate of neurons has been unknown. Our recent study represents a first step toward clarification of this mechanism. We have shown that: (1) Fru forms a complex with the transcriptional cofactor Bonus (Bon), which recruits either of two chromatin regulators, Histone deacetylase 1 (HDAC1) or Heterochromatin protein 1a (HP1a), to Fru-target sites; (2) the Fru-Bon complex has a masculinizing effect on single sexually-dimorphic neurons when it recruits HDAC1, whereas it has a demasculinizing effect when it recruits HP1a; (3) HDAC1 or HP1a thus recruited to Fru-target sites determines the sexual fate of single neurons in an all-or-none manner, as manipulations of HDAC1 or HP1a expression levels affect the proportion of male-typical neurons and female-typical neurons without producing neurons of intersexual characteristics. Here, we hypothesize that chromatin landscape changes induced by ecdysone surges direct the HDAC1- or HP1a-containing Fru complex to distinct targets, thereby allowing them to switch the neuronal sexual fate in the brain. PMID:23519136

  10. Dynamic, mating-induced gene expression changes in female head and brain tissues of Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Stirling Emma J

    2010-10-01

    Full Text Available Abstract Background Drosophila melanogaster females show changes in behavior and physiology after mating that are thought to maximize the number of progeny resulting from the most recent copulation. Sperm and seminal fluid proteins induce post-mating changes in females, however, very little is known about the resulting gene expression changes in female head and central nervous system tissues that contribute to the post-mating response. Results We determined the temporal gene expression changes in female head tissues 0-2, 24, 48 and 72 hours after mating. Females from each time point had a unique post-mating gene expression response, with 72 hours post-mating having the largest number of genes with significant changes in expression. At most time points, genes expressed in the head fat body that encode products involved in metabolism showed a marked change in expression. Additional analysis of gene expression changes in dissected brain tissues 24 hours post-mating revealed changes in transcript abundance of many genes, notably, the reduced transcript abundance of genes that encode ion channels. Conclusions Substantial changes occur in the regulation of many genes in female head tissues after mating, which might underlie aspects of the female post-mating response. These results provide new insights into the physiological and metabolic changes that accompany changes in female behaviors.

  11. Alternative NF-κB Isoforms in the Drosophila Neuromuscular Junction and Brain.

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    Bo Zhou

    Full Text Available The Drosophila NF-κB protein Dorsal is expressed at the larval neuromuscular junction, where its expression appears unrelated to known Dorsal functions in embryonic patterning and innate immunity. Using confocal microscopy with domain-specific antisera, we demonstrate that larval muscle expresses only the B isoform of Dorsal, which arises by intron retention. We find that Dorsal B interacts with and stabilizes Cactus at the neuromuscular junction, but exhibits Cactus independent localization and an absence of detectable nuclear translocation. We further find that the Dorsal-related immune factor Dif encodes a B isoform, reflecting a conservation of B domains across a range of insect NF-κB proteins. Carrying out mutagenesis of the Dif locus via a site-specific recombineering approach, we demonstrate that Dif B is the major, if not sole, Dif isoform in the mushroom bodies of the larval brain. The Dorsal and Dif B isoforms thus share a specific association with nervous system tissues as well as an alternative protein structure.

  12. Drosophila ovipositor extension in mating behavior and egg deposition involves distinct sets of brain interneurons.

    Directory of Open Access Journals (Sweden)

    Ken-ichi Kimura

    Full Text Available Oviposition is a female-specific behavior that directly affects fecundity, and therefore fitness. If a fertilized female encounters another male that she has evaluated to be of better quality than her previous mate, it would be beneficial for her to remate with this male rather than depositing her eggs. Females who decided not to remate exhibited rejection behavior toward a courting male and engaged in oviposition. Although recent studies of Drosophila melanogaster identified sensory neurons and putative second-order ascending interneurons that mediate uterine afferents affecting female reproductive behavior, little is known about the brain circuitry that selectively activates rejection versus oviposition behaviors. We identified the sexually dimorphic pC2l and female-specific pMN2 neurons, two distinct classes of doublesex (dsx-expressing neurons that can initiate ovipositor extension associated with rejection and oviposition behavior, respectively. pC2l interneurons, which induce ovipositor extrusion for rejection in females, have homologues that control courtship behavior in males. Activation of these two classes of neurons appears to be mutually exclusive and each governs hierarchical control of the motor program in the VNC either for rejection or oviposition, contributing centrally to the switching on or off of the alternative motor programs.

  13. Lipid metabolic perturbation is an early-onset phenotype in adult spinster mutants: a Drosophila model for lysosomal storage disorders.

    Science.gov (United States)

    Hebbar, Sarita; Khandelwal, Avinash; Jayashree, R; Hindle, Samantha J; Chiang, Yin Ning; Yew, Joanne Y; Sweeney, Sean T; Schwudke, Dominik

    2017-12-15

    Intracellular accumulation of lipids and swollen dysfunctional lysosomes are linked to several neurodegenerative diseases, including lysosomal storage disorders (LSD). Detailed characterization of lipid metabolic changes in relation to the onset and progression of neurodegeneration is currently missing. We systematically analyzed lipid perturbations in spinster (spin) mutants, a Drosophila model of LSD-like neurodegeneration. Our results highlight an imbalance in brain ceramide and sphingosine in the early stages of neurodegeneration, preceding the accumulation of endomembranous structures, manifestation of altered behavior, and buildup of lipofuscin. Manipulating levels of ceramidase and altering these lipids in spin mutants allowed us to conclude that ceramide homeostasis is the driving force in disease progression and is integral to spin function in the adult nervous system. We identified 29 novel physical interaction partners of Spin and focused on the lipid carrier protein, Lipophorin (Lpp). A subset of Lpp and Spin colocalize in the brain and within organs specialized for lipid metabolism (fat bodies and oenocytes). Reduced Lpp protein was observed in spin mutant tissues. Finally, increased levels of lipid metabolites produced by oenocytes in spin mutants allude to a functional interaction between Spin and Lpp, underscoring the systemic nature of lipid perturbation in LSD. © 2017 Hebbar et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  14. The IGFBP7 homolog Imp-L2 promotes insulin signaling in distinct neurons of the Drosophila brain.

    Science.gov (United States)

    Bader, R; Sarraf-Zadeh, L; Peters, M; Moderau, N; Stocker, H; Köhler, K; Pankratz, M J; Hafen, E

    2013-06-15

    In Drosophila, Insulin-like peptide 2 (Dilp-2) is expressed by insulin-producing cells in the brain, and is secreted into the hemolymph to activate insulin signaling systemically. Within the brain, however, a more local activation of insulin signaling may be required to couple behavioral and physiological traits to nutritional inputs. We show that a small subset of neurons in the larval brain has high Dilp-2-mediated insulin signaling activity. This local insulin signaling activation is accompanied by selective Dilp-2 uptake and depends on the expression of the Imaginal morphogenesis protein-late 2 (Imp-L2) in the target neurons. We suggest that Imp-L2 acts as a licensing factor for neuronal IIS activation through Dilp-2 to further increase the precision of insulin activity in the brain.

  15. Muscle organizers in Drosophila: the role of persistent larval fibers in adult flight muscle development

    Science.gov (United States)

    Farrell, E. R.; Fernandes, J.; Keshishian, H.

    1996-01-01

    In many organisms muscle formation depends on specialized cells that prefigure the pattern of the musculature and serve as templates for myoblast organization and fusion. These include muscle pioneers in insects and muscle organizing cells in leech. In Drosophila, muscle founder cells have been proposed to play a similar role in organizing larval muscle development during embryogenesis. During metamorphosis in Drosophila, following histolysis of most of the larval musculature, there is a second round of myogenesis that gives rise to the adult muscles. It is not known whether muscle founder cells organize the development of these muscles. However, in the thorax specific larval muscle fibers do not histolyze at the onset of metamorphosis, but instead serve as templates for the formation of a subset of adult muscles, the dorsal longitudinal flight muscles (DLMs). Because these persistent larval muscle fibers appear to be functioning in many respects like muscle founder cells, we investigated whether they were necessary for DLM development by using a microbeam laser to ablate them singly and in combination. We found that, in the absence of the larval muscle fibers, DLMs nonetheless develop. Our results show that the persistent larval muscle fibers are not required to initiate myoblast fusion, to determine DLM identity, to locate the DLMs in the thorax, or to specify the total DLM fiber volume. However, they are required to regulate the number of DLM fibers generated. Thus, while the persistent larval muscle fibers are not obligatory for DLM fiber formation and differentiation, they are necessary to ensure the development of the correct number of fibers.

  16. Multichannel brain recordings in behaving Drosophila reveal oscillatory activity and local coherence in response to sensory stimulation and circuit activation.

    Science.gov (United States)

    Paulk, Angelique C; Zhou, Yanqiong; Stratton, Peter; Liu, Li; van Swinderen, Bruno

    2013-10-01

    Neural networks in vertebrates exhibit endogenous oscillations that have been associated with functions ranging from sensory processing to locomotion. It remains unclear whether oscillations may play a similar role in the insect brain. We describe a novel "whole brain" readout for Drosophila melanogaster using a simple multichannel recording preparation to study electrical activity across the brain of flies exposed to different sensory stimuli. We recorded local field potential (LFP) activity from >2,000 registered recording sites across the fly brain in >200 wild-type and transgenic animals to uncover specific LFP frequency bands that correlate with: 1) brain region; 2) sensory modality (olfactory, visual, or mechanosensory); and 3) activity in specific neural circuits. We found endogenous and stimulus-specific oscillations throughout the fly brain. Central (higher-order) brain regions exhibited sensory modality-specific increases in power within narrow frequency bands. Conversely, in sensory brain regions such as the optic or antennal lobes, LFP coherence, rather than power, best defined sensory responses across modalities. By transiently activating specific circuits via expression of TrpA1, we found that several circuits in the fly brain modulate LFP power and coherence across brain regions and frequency domains. However, activation of a neuromodulatory octopaminergic circuit specifically increased neuronal coherence in the optic lobes during visual stimulation while decreasing coherence in central brain regions. Our multichannel recording and brain registration approach provides an effective way to track activity simultaneously across the fly brain in vivo, allowing investigation of functional roles for oscillations in processing sensory stimuli and modulating behavior.

  17. The Ly6 protein coiled is required for septate junction and blood brain barrier organisation in Drosophila.

    Directory of Open Access Journals (Sweden)

    Assia Hijazi

    Full Text Available BACKGROUND: Genetic analysis of the Drosophila septate junctions has greatly contributed to our understanding of the mechanisms controlling the assembly of these adhesion structures, which bear strong similarities with the vertebrate tight junctions and the paranodal septate junctions. These adhesion complexes share conserved molecular components and have a common function: the formation of paracellular barriers restraining the diffusion of solutes through epithelial and glial envelopes. METHODOLOGY/PRINCIPAL FINDINGS: In this work we characterise the function of the Drosophila cold gene, that codes for a protein belonging to the Ly6 superfamily of extracellular ligands. Analysis of cold mutants shows that this gene is specifically required for the organisation of the septate junctions in epithelial tissues and in the nervous system, where its contribution is essential for the maintenance of the blood-brain barrier. We show that cold acts in a cell autonomous way, and we present evidence indicating that this protein could act as a septate junction component. CONCLUSION/SIGNIFICANCE: We discuss the specific roles of cold and three other Drosophila members of the Ly6 superfamily that have been shown to participate in a non-redundant way in the process of septate junction assembly. We propose that vertebrate Ly6 proteins could fulfill analogous roles in tight junctions and/or paranodal septate junctions.

  18. The Ly6 protein coiled is required for septate junction and blood brain barrier organisation in Drosophila.

    Science.gov (United States)

    Hijazi, Assia; Haenlin, Marc; Waltzer, Lucas; Roch, Fernando

    2011-03-15

    Genetic analysis of the Drosophila septate junctions has greatly contributed to our understanding of the mechanisms controlling the assembly of these adhesion structures, which bear strong similarities with the vertebrate tight junctions and the paranodal septate junctions. These adhesion complexes share conserved molecular components and have a common function: the formation of paracellular barriers restraining the diffusion of solutes through epithelial and glial envelopes. In this work we characterise the function of the Drosophila cold gene, that codes for a protein belonging to the Ly6 superfamily of extracellular ligands. Analysis of cold mutants shows that this gene is specifically required for the organisation of the septate junctions in epithelial tissues and in the nervous system, where its contribution is essential for the maintenance of the blood-brain barrier. We show that cold acts in a cell autonomous way, and we present evidence indicating that this protein could act as a septate junction component. We discuss the specific roles of cold and three other Drosophila members of the Ly6 superfamily that have been shown to participate in a non-redundant way in the process of septate junction assembly. We propose that vertebrate Ly6 proteins could fulfill analogous roles in tight junctions and/or paranodal septate junctions.

  19. Multichannel brain recordings in behaving Drosophila reveal oscillatory activity and local coherence in response to sensory stimulation and circuit activation

    Science.gov (United States)

    Paulk, Angelique C.; Zhou, Yanqiong; Stratton, Peter; Liu, Li

    2013-01-01

    Neural networks in vertebrates exhibit endogenous oscillations that have been associated with functions ranging from sensory processing to locomotion. It remains unclear whether oscillations may play a similar role in the insect brain. We describe a novel “whole brain” readout for Drosophila melanogaster using a simple multichannel recording preparation to study electrical activity across the brain of flies exposed to different sensory stimuli. We recorded local field potential (LFP) activity from >2,000 registered recording sites across the fly brain in >200 wild-type and transgenic animals to uncover specific LFP frequency bands that correlate with: 1) brain region; 2) sensory modality (olfactory, visual, or mechanosensory); and 3) activity in specific neural circuits. We found endogenous and stimulus-specific oscillations throughout the fly brain. Central (higher-order) brain regions exhibited sensory modality-specific increases in power within narrow frequency bands. Conversely, in sensory brain regions such as the optic or antennal lobes, LFP coherence, rather than power, best defined sensory responses across modalities. By transiently activating specific circuits via expression of TrpA1, we found that several circuits in the fly brain modulate LFP power and coherence across brain regions and frequency domains. However, activation of a neuromodulatory octopaminergic circuit specifically increased neuronal coherence in the optic lobes during visual stimulation while decreasing coherence in central brain regions. Our multichannel recording and brain registration approach provides an effective way to track activity simultaneously across the fly brain in vivo, allowing investigation of functional roles for oscillations in processing sensory stimuli and modulating behavior. PMID:23864378

  20. Cold hardiness of winter-acclimated Drosophila suzukii (Diptera: Drosophilidae) adults

    Science.gov (United States)

    A.R. Stephens; M.K. Asplen; W.D. Hutchison; Robert C. Venette

    2015-01-01

    Drosophila suzukii Matsumura, often called spotted wing drosophila, is an exotic vinegar fly that is native to Southeast Asia and was first detected in the continental United States in 2008. Previous modeling studies have suggested that D. suzukii might not survive in portions of the northern United States or southern Canada...

  1. Chronic exposure to dim artificial light at night decreases fecundity and adult survival in Drosophila melanogaster.

    Science.gov (United States)

    McLay, L K; Green, M P; Jones, T M

    2017-07-01

    The presence of artificial light at night is expanding in geographical range and increasing in intensity to such an extent that species living in urban environments may never experience natural darkness. The negative ecological consequences of artificial night lighting have been identified in several key life history traits across multiple taxa (albeit with a strong vertebrate focus); comparable data for invertebrates is lacking. In this study, we explored the effect of chronic exposure to different night-time lighting intensities on growth, reproduction and survival in Drosophila melanogaster. We reared three generations of flies under identical daytime light conditions (2600lx) and one of four ecologically relevant ALAN treatments (0, 1, 10 or 100lx), then explored variation in oviposition, number of eggs produced, juvenile growth and survival and adult survival. We found that, in the presence of light at night (1, 10 and 100lx treatments), the probability of a female commencing oviposition and the number of eggs laid was significantly reduced. This did not translate into differences at the juvenile phase: juvenile development times and the probability of eclosing as an adult were comparable across all treatments. However, we demonstrate for the first time a direct link between chronic exposure to light at night (greater than 1lx) and adult survival. Our data highlight that ALAN has the capacity to cause dramatic shifts in multiple life history traits at both the individual and population level. Such shifts are likely to be species-specific, however a more in depth understanding of the broad-scale impact of ALAN and the relevant mechanisms driving biological change is urgently required as we move into an increasing brightly lit future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. The Drosophila BTB domain protein Jim Lovell has roles in multiple larval and adult behaviors.

    Directory of Open Access Journals (Sweden)

    Sonia M Bjorum

    Full Text Available Innate behaviors have their origins in the specification of neural fates during development. Within Drosophila, BTB (Bric-a-brac,Tramtrack, Broad domain proteins such as Fruitless are known to play key roles in the neural differentiation underlying such responses. We previously identified a gene, which we have termed jim lovell (lov, encoding a BTB protein with a role in gravity responses. To understand more fully the behavioral roles of this gene we have investigated its function through several approaches. Transcript and protein expression patterns have been examined and behavioral phenotypes of new lov mutations have been characterized. Lov is a nuclear protein, suggesting a role as a transcriptional regulator, as for other BTB proteins. In late embryogenesis, Lov is expressed in many CNS and PNS neurons. An examination of the PNS expression indicates that lov functions in the late specification of several classes of sensory neurons. In particular, only two of the five abdominal lateral chordotonal neurons express Lov, predicting functional variation within this highly similar group. Surprisingly, Lov is also expressed very early in embryogenesis in ways that suggests roles in morphogenetic movements, amnioserosa function and head neurogenesis. The phenotypes of two new lov mutations that delete adjacent non-coding DNA regions are strikingly different suggesting removal of different regulatory elements. In lov(47 , Lov expression is lost in many embryonic neurons including the two lateral chordotonal neurons. lov(47 mutant larvae show feeding and locomotor defects including spontaneous backward movement. Adult lov(47 males perform aberrant courtship behavior distinguished by courtship displays that are not directed at the female. lov(47 adults also show more defective negative gravitaxis than the previously isolated lov(91Y mutant. In contrast, lov(66 produces largely normal behavior but severe female sterility associated with ectopic lov

  3. Genetic Architecture of Natural Variation Underlying Adult Foraging Behavior That Is Essential for Survival of Drosophila melanogaster.

    Science.gov (United States)

    Lee, Yuh Chwen G; Yang, Qian; Chi, Wanhao; Turkson, Susie A; Du, Wei A; Kemkemer, Claus; Zeng, Zhao-Bang; Long, Manyuan; Zhuang, Xiaoxi

    2017-05-01

    Foraging behavior is critical for the fitness of individuals. However, the genetic basis of variation in foraging behavior and the evolutionary forces underlying such natural variation have rarely been investigated. We developed a systematic approach to assay the variation in survival rate in a foraging environment for adult flies derived from a wild Drosophila melanogaster population. Despite being such an essential trait, there is substantial variation of foraging behavior among D. melanogaster strains. Importantly, we provided the first evaluation of the potential caveats of using inbred Drosophila strains to perform genome-wide association studies on life-history traits, and concluded that inbreeding depression is unlikely a major contributor for the observed large variation in adult foraging behavior. We found that adult foraging behavior has a strong genetic component and, unlike larval foraging behavior, depends on multiple loci. Identified candidate genes are enriched in those with high expression in adult heads and, demonstrated by expression knock down assay, are involved in maintaining normal functions of the nervous system. Our study not only identified candidate genes for foraging behavior that is relevant to individual fitness, but also shed light on the initial stage underlying the evolution of the behavior. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  4. Drosophila Clock Is Required in Brain Pacemaker Neurons to Prevent Premature Locomotor Aging Independently of Its Circadian Function.

    Directory of Open Access Journals (Sweden)

    Alexandra Vaccaro

    2017-01-01

    Full Text Available Circadian clocks control many self-sustained rhythms in physiology and behavior with approximately 24-hour periodicity. In many organisms, oxidative stress and aging negatively impact the circadian system and sleep. Conversely, loss of the clock decreases resistance to oxidative stress, and may reduce lifespan and speed up brain aging and neurodegeneration. Here we examined the effects of clock disruptions on locomotor aging and longevity in Drosophila. We found that lifespan was similarly reduced in three arrhythmic mutants (ClkAR, cyc0 and tim0 and in wild-type flies under constant light, which stops the clock. In contrast, ClkAR mutants showed significantly faster age-related locomotor deficits (as monitored by startle-induced climbing than cyc0 and tim0, or than control flies under constant light. Reactive oxygen species accumulated more with age in ClkAR mutant brains, but this did not appear to contribute to the accelerated locomotor decline of the mutant. Clk, but not Cyc, inactivation by RNA interference in the pigment-dispersing factor (PDF-expressing central pacemaker neurons led to similar loss of climbing performance as ClkAR. Conversely, restoring Clk function in these cells was sufficient to rescue the ClkAR locomotor phenotype, independently of behavioral rhythmicity. Accelerated locomotor decline of the ClkAR mutant required expression of the PDF receptor and correlated to an apparent loss of dopaminergic neurons in the posterior protocerebral lateral 1 (PPL1 clusters. This neuronal loss was rescued when the ClkAR mutation was placed in an apoptosis-deficient background. Impairing dopamine synthesis in a single pair of PPL1 neurons that innervate the mushroom bodies accelerated locomotor decline in otherwise wild-type flies. Our results therefore reveal a novel circadian-independent requirement for Clk in brain circadian neurons to maintain a subset of dopaminergic cells and avoid premature locomotor aging in Drosophila.

  5. TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in behavior and plasticity of L2 interneurons in the brain of Drosophila melanogaster.

    Science.gov (United States)

    Kijak, Ewelina; Pyza, Elżbieta

    2017-01-01

    Drosophila melanogaster is a common model used to study circadian rhythms in behavior and circadian clocks. However, numerous circadian rhythms have also been detected in non-clock neurons, especially in the first optic neuropil (lamina) of the fly's visual system. Such rhythms have been observed in the number of synapses and in the structure of interneurons, which exhibit changes in size and shape in a circadian manner. Although the patterns of these changes are known, the mechanism remains unclear. In the present study, we investigated the role of the TOR signaling pathway and autophagy in regulating circadian rhythms based on the behavior and structural plasticity of the lamina L2 monopolar cell dendritic trees. In addition, we examined the cyclic expression of the TOR signaling pathway (Tor, Pi3K class 1, Akt1) and autophagy (Atg5 and Atg7) genes in the fly's brain. We observed that Tor, Atg5 and Atg7 exhibit rhythmic expressions in the brain of wild-type flies in day/night conditions (LD 12:12) that are abolished in per01 clock mutants. The silencing of Tor in per expressing cells shortens a period of the locomotor activity rhythm of flies. In addition, silencing of the Tor and Atg5 genes in L2 cells disrupts the circadian plasticity of the L2 cell dendritic trees measured in the distal lamina. In turn, silencing of the Atg7 gene in L2 cells changes the pattern of this rhythm. Our results indicate that the TOR signaling pathway and autophagy are involved in the regulation of circadian rhythms in the behavior and plasticity of neurons in the brain of adult flies.

  6. Developmentally regulated expression of reporter gene in adult ...

    Indian Academy of Sciences (India)

    pression of reporter gene in adult brain specific GAL4 enhancer traps of. Drosophila ... genes based on their expression pattern, thus enabling us to overcome the ... order association and storage centres of olfactory learning and memory, and ...

  7. Remodeling of peripheral nerve ensheathment during the larval-to-adult transition in Drosophila.

    Science.gov (United States)

    Subramanian, Aswati; Siefert, Matthew; Banerjee, Soumya; Vishal, Kumar; Bergmann, Kayla A; Curts, Clay C M; Dorr, Meredith; Molina, Camillo; Fernandes, Joyce

    2017-10-01

    Over the course of a 4-day period of metamorphosis, the Drosophila larval nervous system is remodeled to prepare for adult-specific behaviors. One example is the reorganization of peripheral nerves in the abdomen, where five pairs of abdominal nerves (A4-A8) fuse to form the terminal nerve trunk. This reorganization is associated with selective remodeling of four layers that ensheath each peripheral nerve. The neural lamella (NL), is the first to dismantle; its breakdown is initiated by 6 hours after puparium formation, and is completely removed by the end of the first day. This layer begins to re-appear on the third day of metamorphosis. Perineurial glial (PG) cells situated just underneath the NL, undergo significant proliferation on the first day of metamorphosis, and at that stage contribute to 95% of the glial cell population. Cells of the two inner layers, Sub-Perineurial Glia (SPG) and Wrapping Glia (WG) increase in number on the second half of metamorphosis. Induction of cell death in perineurial glia via the cell death gene reaper and the Diptheria toxin (DT-1) gene, results in abnormal bundling of the peripheral nerves, suggesting that perineurial glial cells play a role in the process. A significant number of animals fail to eclose in both reaper and DT-1 targeted animals, suggesting that disruption of PG also impacts eclosion behavior. The studies will help to establish the groundwork for further work on cellular and molecular processes that underlie the co-ordinated remodeling of glia and the peripheral nerves they ensheath. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1144-1160, 2017. © 2017 Wiley Periodicals, Inc.

  8. Desiccation resistance: effect of cuticular hydrocarbons and water content in Drosophila melanogaster adults

    Directory of Open Access Journals (Sweden)

    Jean-Francois Ferveur

    2018-02-01

    Full Text Available Background The insect cuticle covers the whole body and all appendages and has bi-directionnal selective permeability: it protects against environmental stress and pathogen infection and also helps to reduce water loss. The adult cuticle is often associated with a superficial layer of fatty acid-derived molecules such as waxes and long chain hydrocarbons that prevent rapid dehydration. The waterproofing properties of cuticular hydrocarbons (CHs depend on their chain length and desaturation number. Drosophila CH biosynthesis involves an enzymatic pathway including several elongase and desaturase enzymes. Methods The link between desiccation resistance and CH profile remains unclear, so we tested (1 experimentally selected desiccation-resistant lines, (2 transgenic flies with altered desaturase expression and (3 natural and laboratory-induced CH variants. We also explored the possible relationship between desiccation resistance, relative water content and fecundity in females. Results We found that increased desiccation resistance is linked with the increased proportion of desaturated CHs, but not with their total amount. Experimentally-induced desiccation resistance and CH variation both remained stable after many generations without selection. Conversely, flies with a higher water content and a lower proportion of desaturated CHs showed reduced desiccation resistance. This was also the case in flies with defective desaturase expression in the fat body. Discussion We conclude that rapidly acquired desiccation resistance, depending on both CH profile and water content, can remain stable without selection in a humid environment. These three phenotypes, which might be expected to show a simple relationship, turn out to have complex physiological and genetic links.

  9. CT brain demonstration of basal ganglion calcification in adult HIV ...

    African Journals Online (AJOL)

    brain barrier has been postulated. Calcification of the basal ganglia in encephalopathic HIV/AIDS children has been relatively well documented. Only two adult HIV cases with basal ganglion calcification (BGC) have been reported in the literature.

  10. Guidelines for Better Communication with Brain Impaired Adults

    Science.gov (United States)

    ... FCA - A A + A You are here Home Guidelines for Better Communication with Brain-Impaired Adults Printer- ... there are no easy solutions, following some basic guidelines should ease communication, and lower levels of stress ...

  11. Unc-51/ATG1 controls axonal and dendritic development via kinesin-mediated vesicle transport in the Drosophila brain.

    Directory of Open Access Journals (Sweden)

    Hiroaki Mochizuki

    2011-05-01

    Full Text Available Members of the evolutionary conserved Ser/Thr kinase Unc-51 family are key regulatory proteins that control neural development in both vertebrates and invertebrates. Previous studies have suggested diverse functions for the Unc-51 protein, including axonal elongation, growth cone guidance, and synaptic vesicle transport.In this work, we have investigated the functional significance of Unc-51-mediated vesicle transport in the development of complex brain structures in Drosophila. We show that Unc-51 preferentially accumulates in newly elongating axons of the mushroom body, a center of olfactory learning in flies. Mutations in unc-51 cause disintegration of the core of the developing mushroom body, with mislocalization of Fasciclin II (Fas II, an IgG-family cell adhesion molecule important for axonal guidance and fasciculation. In unc-51 mutants, Fas II accumulates in the cell bodies, calyx, and the proximal peduncle. Furthermore, we show that mutations in unc-51 cause aberrant overshooting of dendrites in the mushroom body and the antennal lobe. Loss of unc-51 function leads to marked accumulation of Rab5 and Golgi components, whereas the localization of dendrite-specific proteins, such as Down syndrome cell adhesion molecule (DSCAM and No distributive disjunction (Nod, remains unaltered. Genetic analyses of kinesin light chain (Klc and unc-51 double heterozygotes suggest the importance of kinesin-mediated membrane transport for axonal and dendritic development. Moreover, our data demonstrate that loss of Klc activity causes similar axonal and dendritic defects in mushroom body neurons, recapitulating the salient feature of the developmental abnormalities caused by unc-51 mutations.Unc-51 plays pivotal roles in the axonal and dendritic development of the Drosophila brain. Unc-51-mediated membrane vesicle transport is important in targeted localization of guidance molecules and organelles that regulate elongation and compartmentalization of

  12. Expression of a truncated receptor protein tyrosine phosphatase kappa in the brain of an adult transgenic mouse

    DEFF Research Database (Denmark)

    Shen, P; Canoll, P D; Sap, J

    1999-01-01

    processes such as axonal growth and target recognition, as has been demonstrated for certain Drosophila RPTPs. The brain distribution of RPTP-kappa-expressing cells has not been determined, however. In a gene-trap mouse model with a beta-gal+neo (beta-geo) insertion in the endogenous RPTP-kappa gene......-6596]. Nevertheless, since the transgene's expression is driven by the endogenous RPTP-kappa promoter, distribution of the truncated RPTP-kappa/beta-geo fusion protein should reflect the regional and cellular expression of wild-type RPTP-kappa, and thus may identify sites where RPTP-kappa is important. Towards...... that goal, we have used this mouse model to map the distribution of the truncated RPTP-kappa/beta-geo fusion protein in the adult mouse brain using beta-galactosidase as a marker enzyme. Visualization of the beta-galactosidase activity revealed a non-random pattern of expression, and identified cells...

  13. Multidendritic sensory neurons in the adult Drosophila abdomen: origins, dendritic morphology, and segment- and age-dependent programmed cell death

    Directory of Open Access Journals (Sweden)

    Sugimura Kaoru

    2009-10-01

    Full Text Available Abstract Background For the establishment of functional neural circuits that support a wide range of animal behaviors, initial circuits formed in early development have to be reorganized. One way to achieve this is local remodeling of the circuitry hardwiring. To genetically investigate the underlying mechanisms of this remodeling, one model system employs a major group of Drosophila multidendritic sensory neurons - the dendritic arborization (da neurons - which exhibit dramatic dendritic pruning and subsequent growth during metamorphosis. The 15 da neurons are identified in each larval abdominal hemisegment and are classified into four categories - classes I to IV - in order of increasing size of their receptive fields and/or arbor complexity at the mature larval stage. Our knowledge regarding the anatomy and developmental basis of adult da neurons is still fragmentary. Results We identified multidendritic neurons in the adult Drosophila abdomen, visualized the dendritic arbors of the individual neurons, and traced the origins of those cells back to the larval stage. There were six da neurons in abdominal hemisegment 3 or 4 (A3/4 of the pharate adult and the adult just after eclosion, five of which were persistent larval da neurons. We quantitatively analyzed dendritic arbors of three of the six adult neurons and examined expression in the pharate adult of key transcription factors that result in the larval class-selective dendritic morphologies. The 'baseline design' of A3/4 in the adult was further modified in a segment-dependent and age-dependent manner. One of our notable findings is that a larval class I neuron, ddaE, completed dendritic remodeling in A2 to A4 and then underwent caspase-dependent cell death within 1 week after eclosion, while homologous neurons in A5 and in more posterior segments degenerated at pupal stages. Another finding is that the dendritic arbor of a class IV neuron, v'ada, was immediately reshaped during post

  14. Protein and carbohydrate composition of larval food affects tolerance tothermal stress and desiccation in adult Drosophila melanogaster

    DEFF Research Database (Denmark)

    Andersen, Laila H; Kristensen, Torsten N; Loeschcke, Volker

    2010-01-01

    stress compared to males. Egg production was highest in females that had developed on the protein-enriched medium. However, there was a sex-specific effect of nutrition on egg-to-adult viability, with higher viability for males developing on the sucrose-enriched medium, while female survival was highest......Larval nutrition may affect a range of different life history traits as well as responses to environmental stress in adult insects. Here we test whether raising larvae of fruit flies, Drosophila melanogaster, on two different nutritional regimes affects resistance to cold, heat and desiccation....... In contrast, flies developed on the carbohydrate-enriched growth medium recovered faster from chill coma stress compared to flies developed on a protein-enriched medium. We also found gender differences in stress tolerance, with female flies being more tolerant to chill coma, heat knockdown and desiccation...

  15. The adult Drosophila malphigian tubules are maintained by multipotent stem cells | Center for Cancer Research

    Science.gov (United States)

    All animals must excrete the waste products of metabolism. Excretion is performed by the kidney in vertebrates and by the Malpighian tubules in Drosophila. The mammalian kidney has an inherent ability for recovery and regeneration after ischemic injury. Stem cells and progenitor cells have been proposed to be responsible for repair and regeneration of injured renal tissue.

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

    Science.gov (United States)

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

    2011-12-05

    A role for vitamin D in brain development and function has been gaining support over the last decade. Multiple lines of evidence suggest that this vitamin is actually a neuroactive steroid that acts on brain development, leading to alterations in brain neurochemistry and adult brain function. Early deficiencies have been linked with neuropsychiatric disorders, such as schizophrenia, and adult deficiencies have been associated with a host of adverse brain outcomes, including Parkinson's disease, Alzheimer's disease, depression and cognitive decline. This review summarises the current state of research on the actions of vitamin D in the brain and the consequences of deficiencies in this vitamin. Furthermore, we discuss specific implications of vitamin D status on the neurotransmitter, dopamine. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Protein expression profiling of the drosophila fragile X mutant brain reveals up-regulation of monoamine synthesis.

    Science.gov (United States)

    Zhang, Yong Q; Friedman, David B; Wang, Zhe; Woodruff, Elvin; Pan, Luyuan; O'donnell, Janis; Broadie, Kendal

    2005-03-01

    Fragile X syndrome is the most common form of inherited mental retardation, associated with both cognitive and behavioral anomalies. The disease is caused by silencing of the fragile X mental retardation 1 (fmr1) gene, which encodes the mRNA-binding, translational regulator FMRP. Previously we established a disease model through mutation of Drosophila fmr1 (dfmr1) and showed that loss of dFMRP causes defects in neuronal structure, function, and behavioral output similar to the human disease state. To uncover molecular targets of dFMRP in the brain, we use here a proteomic approach involving two-dimensional difference gel electrophoresis analyses followed by mass spectrometry identification of proteins with significantly altered expression in dfmr1 null mutants. We then focus on two misregulated enzymes, phenylalanine hydroxylase (Henna) and GTP cyclohydrolase (Punch), both of which mediate in concert the synthetic pathways of two key monoamine neuromodulators, dopamine and serotonin. Brain enzymatic assays show a nearly 2-fold elevation of Punch activity in dfmr1 null mutants. Consistently brain neurochemical assays show that both dopamine and serotonin are significantly increased in dfmr1 null mutants. At a cellular level, dfmr1 null mutant neurons display a highly significant elevation of the dense core vesicles that package these monoamine neuromodulators for secretion. Taken together, these data indicate that dFMRP normally down-regulates the monoamine pathway, which is consequently up-regulated in the mutant condition. Elevated brain levels of dopamine and serotonin provide a plausible mechanistic explanation for aspects of cognitive and behavioral deficits in human patients.

  18. Effects of high-LET particles (40A) on the brain of Drosophila melanogaster

    International Nuclear Information System (INIS)

    Miquel, J.; Herman, M.M.; Benton, E.V.; Welch, G.

    1976-01-01

    To investigate the effects of galactic heavy particles on nervous tissue, Drosophila melanogaster flies were exposed to 40 A from the Super-HILAC accelerator at the Lawrence Berkeley Laboratory. The energy of the particles reaching the Drosophila neurons was 4.8 MeV/nucleon, and the fluence ranged from 6 x 10 4 to 8 x 10 7 particles/cm 2 . Thirty-five days after irradiation at the higher fluences, extensive tissue fragmentation and cysts were found. At fluences as low as one hit/two cell bodies (about 5 x 10 6 ) and one hit/90 cell bodies (about 9 x 10 4 particles/cm 2 or 21 rad average dose) swelling of neuronal cytoplasm and focally fragmented membranes were noted; at fluences ranging from one hit/six to one hit/135 cell bodies, there was frequently a marked increase in glial lamellae around nerve-cell processes, which often had degenerative features. These findings support the view that single hits by heavy particles may injure nervous tissue. (author)

  19. Optical Dissection of Experience-Dependent Pre- and Postsynaptic Plasticity in the Drosophila Brain

    Directory of Open Access Journals (Sweden)

    Ulrike Pech

    2015-03-01

    Full Text Available Drosophila represents a key model organism for dissecting neuronal circuits that underlie innate and adaptive behavior. However, this task is limited by a lack of tools to monitor physiological parameters of spatially distributed, central synapses in identified neurons. We generated transgenic fly strains that express functional fluorescent reporters targeted to either pre- or postsynaptic compartments. Presynaptic Ca2+ dynamics are monitored using synaptophysin-coupled GCaMP3, synaptic transmission is monitored using red fluorescent synaptophysin-pHTomato, and postsynaptic Ca2+ dynamics are visualized using GCaMP3 fused with the postsynaptic matrix protein, dHomer. Using two-photon in vivo imaging of olfactory projection neurons, odor-evoked activity across populations of synapses is visualized in the antennal lobe and the mushroom body calyx. Prolonged odor exposure causes odor-specific and differential experience-dependent changes in pre- and postsynaptic activity at both levels of olfactory processing. The approach advances the physiological analysis of synaptic connections across defined groups of neurons in intact Drosophila.

  20. Effects of high-LET particles /A-40/ on the brain of Drosophila melanogaster

    Science.gov (United States)

    Miquel, J.; Herman, M. M.; Benton, E. V.; Welch, G.

    1976-01-01

    To investigate the effects of galactic heavy particles on nervous tissue, Drosophila melanogaster flies were exposed to A-40 from the Super-HILAC accelerator at the Lawrence Berkeley Laboratory. The energy of the particles reaching the Drosophila neurons was 4.8 MeV/nucleon, and the fluence ranged from 60,000 to 80 million particles/sq cm. Thirty-five days after irradiation at the higher fluences, extensive tissue fragmentation and cysts were found. At fluences as low as one hit/two cell bodies (about 5 million) and one hit/90 cell bodies (about 90,000 particles/sq cm or 21 rad average dose) swelling of neuronal cytoplasm and focally fragmented membranes were noted; at fluences ranging from one hit/six to one hit/135 cell bodies, there was frequently a marked increase in glial lamellae around nerve-cell processes, which often had degenerative features. These findings support the view that single hits by heavy particles may injure nervous tissue.

  1. Three-dimensional imaging of Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Leeanne McGurk

    2007-09-01

    Full Text Available The major hindrance to imaging the intact adult Drosophila is that the dark exoskeleton makes it impossible to image through the cuticle. We have overcome this obstacle and describe a method whereby the internal organs of adult Drosophila can be imaged in 3D by bleaching and clearing the adult and then imaging using a technique called optical projection tomography (OPT. The data is displayed as 2D optical sections and also in 3D to provide detail on the shape and structure of the adult anatomy.We have used OPT to visualize in 2D and 3D the detailed internal anatomy of the intact adult Drosophila. In addition this clearing method used for OPT was tested for imaging with confocal microscopy. Using OPT we have visualized the size and shape of neurodegenerative vacuoles from within the head capsule of flies that suffer from age-related neurodegeneration due to a lack of ADAR mediated RNA-editing. In addition we have visualized tau-lacZ expression in 2D and 3D. This shows that the wholemount adult can be stained without any manipulation and that this stain penetrates well as we have mapped the localization pattern with respect to the internal anatomy.We show for the first time that the intact adult Drosophila can be imaged in 3D using OPT, also we show that this method of clearing is also suitable for confocal microscopy to image the brain from within the intact head. The major advantage of this is that organs can be represented in 3D in their natural surroundings. Furthermore optical sections are generated in each of the three planes and are not prone to the technical limitations that are associated with manual sectioning. OPT can be used to dissect mutant phenotypes and to globally map gene expression in both 2D and 3D.

  2. Partial ablation of adult Drosophila insulin-producing neurons modulates glucose homeostasis and extends life span without insulin resistance.

    Science.gov (United States)

    Haselton, Aaron; Sharmin, Effat; Schrader, Janel; Sah, Megha; Poon, Peter; Fridell, Yih-Woei C

    2010-08-01

    In Drosophila melanogaster (D. melanogaster), neurosecretory insulin-like peptide-producing cells (IPCs), analogous to mammalian pancreatic beta cells are involved in glucose homeostasis. Extending those findings, we have developed in the adult fly an oral glucose tolerance test and demonstrated that IPCs indeed are responsible for executing an acute glucose clearance response. To further develop D. melanogaster as a relevant system for studying age-associated metabolic disorders, we set out to determine the impact of adult-specific partial ablation of IPCs (IPC knockdown) on insulin-like peptide (ILP) action, metabolic outcomes and longevity. Interestingly, while IPC knockdown flies are hyperglycemic and glucose intolerant, these flies remain insulin sensitive as measured by peripheral glucose disposal upon insulin injection and serine phosphorylation of a key insulin-signaling molecule, Akt. Significant increases in stored glycogen and triglyceride levels as well as an elevated level of circulating lipid measured in adult IPC knockdown flies suggest profound modulation in energy metabolism. Additional physiological outcomes measured in those flies include increased resistance to starvation and impaired female fecundity. Finally, increased life span and decreased mortality rates measured in IPC knockdown flies demonstrate that it is possible to modulate ILP action in adult flies to achieve life span extension without insulin resistance. Taken together, we have established and validated an invertebrate genetic system to further investigate insulin action, metabolic homeostasis and regulation of aging regulated by adult IPCs.

  3. Evolutionary conservation of vertebrate blood-brain barrier chemoprotective mechanisms in Drosophila

    OpenAIRE

    Mayer, Fahima; Mayer, Nasima; Chinn, Leslie; Pinsonneault, Robert L.; Kroetz, Deanna; Bainton, Roland J.

    2009-01-01

    Pharmacologic remedy of many brain diseases is difficult because of the powerful drug exclusion properties of the blood-brain barrier (BBB). Chemical isolation of the vertebrate brain is achieved through the highly integrated, anatomically compact and functionally overlapping chemical isolation processes of the BBB. These include functions that need to be coordinated between tight diffusion junctions and unidirectionally-acting xenobiotic transporters. Understanding of many of these processes...

  4. A high-resolution whole-genome map of key chromatin modifications in the adult Drosophila melanogaster.

    Science.gov (United States)

    Yin, Hang; Sweeney, Sarah; Raha, Debasish; Snyder, Michael; Lin, Haifan

    2011-12-01

    Epigenetic research has been focused on cell-type-specific regulation; less is known about common features of epigenetic programming shared by diverse cell types within an organism. Here, we report a modified method for chromatin immunoprecipitation and deep sequencing (ChIP-Seq) and its use to construct a high-resolution map of the Drosophila melanogaster key histone marks, heterochromatin protein 1a (HP1a) and RNA polymerase II (polII). These factors are mapped at 50-bp resolution genome-wide and at 5-bp resolution for regulatory sequences of genes, which reveals fundamental features of chromatin modification landscape shared by major adult Drosophila cell types: the enrichment of both heterochromatic and euchromatic marks in transposons and repetitive sequences, the accumulation of HP1a at transcription start sites with stalled polII, the signatures of histone code and polII level/position around the transcriptional start sites that predict both the mRNA level and functionality of genes, and the enrichment of elongating polII within exons at splicing junctions. These features, likely conserved among diverse epigenomes, reveal general strategies for chromatin modifications.

  5. CCHamide-2 is an orexigenic brain-gut peptide in Drosophila

    DEFF Research Database (Denmark)

    Ren, Guilin Robin; Hauser, Frank; Rewitz, Kim Furbo

    2015-01-01

    with a focus on ccha-2 mutants. We found that both larval and adult ccha2 mutants showed a significantly reduced food intake as measured in adult flies by the Capillary Feeding (CAFE) assay (up to 72% reduced food intake compared to wild-type). Locomotion tests in adult flies showed that ccha2 mutants had...

  6. Molecular and Cellular Organization of Taste Neurons in Adult Drosophila Pharynx

    OpenAIRE

    Yu-Chieh David Chen; Anupama Dahanukar

    2017-01-01

    Summary: The Drosophila pharyngeal taste organs are poorly characterized despite their location at important sites for monitoring food quality. Functional analysis of pharyngeal neurons has been hindered by the paucity of molecular tools to manipulate them, as well as their relative inaccessibility for neurophysiological investigations. Here, we generate receptor-to-neuron maps of all three pharyngeal taste organs by performing a comprehensive chemoreceptor-GAL4/LexA expression analysis. The ...

  7. Dichoptic training enables the adult amblyopic brain to learn.

    Science.gov (United States)

    Li, Jinrong; Thompson, Benjamin; Deng, Daming; Chan, Lily Y L; Yu, Minbin; Hess, Robert F

    2013-04-22

    Adults with amblyopia, a common visual cortex disorder caused primarily by binocular disruption during an early critical period, do not respond to conventional therapy involving occlusion of one eye. But it is now clear that the adult human visual cortex has a significant degree of plasticity, suggesting that something must be actively preventing the adult brain from learning to see through the amblyopic eye. One possibility is an inhibitory signal from the contralateral eye that suppresses cortical inputs from the amblyopic eye. Such a gating mechanism could explain the apparent lack of plasticity within the adult amblyopic visual cortex. Here we provide direct evidence that alleviating suppression of the amblyopic eye through dichoptic stimulus presentation induces greater levels of plasticity than forced use of the amblyopic eye alone. This indicates that suppression is a key gating mechanism that prevents the amblyopic brain from learning to see. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Parallel neural pathways in higher visual centers of the Drosophila brain that mediate wavelength-specific behavior

    Directory of Open Access Journals (Sweden)

    Hideo eOtsuna

    2014-02-01

    Full Text Available Compared with connections between the retinae and primary visual centers, relatively less is known in both mammals and insects about the functional segregation of neural pathways connecting primary and higher centers of the visual processing cascade. Here, using the Drosophila visual system as a model, we demonstrate two levels of parallel computation in the pathways that connect primary visual centers of the optic lobe to computational circuits embedded within deeper centers in the central brain. We show that a seemingly simple achromatic behavior, namely phototaxis, is under the control of several independent pathways, each of which is responsible for navigation towards unique wavelengths. Silencing just one pathway is enough to disturb phototaxis towards one characteristic monochromatic source, whereas phototactic behavior towards white light is not affected. The response spectrum of each demonstrable pathway is different from that of individual photoreceptors, suggesting subtractive computations. A choice assay between two colors showed that these pathways are responsible for navigation towards, but not for the detection itself of, the monochromatic light. The present study provides novel insights about how visual information is separated and processed in parallel to achieve robust control of an innate behavior.

  9. Drosophila Pumilio protein contains multiple autonomous repression domains that regulate mRNAs independently of Nanos and brain tumor.

    Science.gov (United States)

    Weidmann, Chase A; Goldstrohm, Aaron C

    2012-01-01

    Drosophila melanogaster Pumilio is an RNA-binding protein that potently represses specific mRNAs. In developing embryos, Pumilio regulates a key morphogen, Hunchback, in collaboration with the cofactor Nanos. To investigate repression by Pumilio and Nanos, we created cell-based assays and found that Pumilio inhibits translation and enhances mRNA decay independent of Nanos. Nanos robustly stimulates repression through interactions with the Pumilio RNA-binding domain. We programmed Pumilio to recognize a new binding site, which garners repression of new target mRNAs. We show that cofactors Brain Tumor and eIF4E Homologous Protein are not obligatory for Pumilio and Nanos activity. The conserved RNA-binding domain of Pumilio was thought to be sufficient for its function. Instead, we demonstrate that three unique domains in the N terminus of Pumilio possess the major repressive activity and can function autonomously. The N termini of insect and vertebrate Pumilio and Fem-3 binding factors (PUFs) are related, and we show that corresponding regions of human PUM1 and PUM2 have repressive activity. Other PUF proteins lack these repression domains. Our findings suggest that PUF proteins have evolved new regulatory functions through protein sequences appended to their conserved PUF repeat RNA-binding domains.

  10. The Drosophila surface glia transcriptome: evolutionary conserved blood-brain barrier processes

    OpenAIRE

    DeSalvo, Michael K.; Hindle, Samantha J.; Rusan, Zeid M.; Orng, Souvinh; Eddison, Mark; Halliwill, Kyle; Bainton, Roland J.

    2014-01-01

    Central nervous system (CNS) function is dependent on the stringent regulation of metabolites, drugs, cells, and pathogens exposed to the CNS space. Cellular blood-brain barrier (BBB) structures are highly specific checkpoints governing entry and exit of all small molecules to and from the brain interstitial space, but the precise mechanisms that regulate the BBB are not well understood. In addition, the BBB has long been a challenging obstacle to the pharmacologic treatment of CNS diseases; ...

  11. Pattern of brain computed tomography findings of adult patients with ...

    African Journals Online (AJOL)

    two adult head injured patients referred to the Radiology department for brain CT over a 3-year period was done. The patients were scanned using Toshiba Aquilion 64 slice spiral CT scan machine, data was collected using a proforma and ...

  12. Whole mount preparation of the adult Drosophila ventral nerve cord for giant fiber dye injection.

    Science.gov (United States)

    Boerner, Jana; Godenschwege, Tanja A

    2011-06-04

    To analyze the axonal and dendritic morphology of neurons, it is essential to obtain accurate labeling of neuronal structures. Preparing well labeled samples with little to no tissue damage enables us to analyze cell morphology and to compare individual samples to each other, hence allowing the identification of mutant anomalies. In the demonstrated dissection method the nervous system remains mostly inside the adult fly. Through a dorsal incision, the abdomen and thorax are opened and most of the internal organs are removed. Only the dorsal side of the ventral nerve cord (VNC) and the cervical connective (CvC) containing the big axons of the giant fibers (GFs) are exposed, while the brain containing the GF cell body and dendrites remains in the intact head. In this preparation most nerves of the VNC should remain attached to their muscles. Following the dissection, the intracellular filling of the giant fiber (GF) with a fluorescent dye is demonstrated. In the CvC the GF axons are located at the dorsal surface and thus can be easily visualized under a microscope with differential interference contrast (DIC) optics. This allows the injection of the GF axons with dye at this site to label the entire GF including the axons and their terminals in the VNC. This method results in reliable and strong staining of the GFs allowing the neurons to be imaged immediately after filling with an epifluorescent microscope. Alternatively, the fluorescent signal can be enhanced using standard immunohistochemistry procedures suitable for high resolution confocal microscopy.

  13. A Sox Transcription Factor Is a Critical Regulator of Adult Stem Cell Proliferation in the Drosophila Intestine

    Directory of Open Access Journals (Sweden)

    Fanju W. Meng

    2015-11-01

    Full Text Available Adult organs and their resident stem cells are constantly facing the challenge of adapting cell proliferation to tissue demand, particularly in response to environmental stresses. Whereas most stress-signaling pathways are conserved between progenitors and differentiated cells, stem cells have the specific ability to respond by increasing their proliferative rate, using largely unknown mechanisms. Here, we show that a member of the Sox family of transcription factors in Drosophila, Sox21a, is expressed in intestinal stem cells (ISCs in the adult gut. Sox21a is essential for the proliferation of these cells during both normal epithelium turnover and repair. Its expression is induced in response to tissue damage, downstream of the Jun N-terminal kinase (JNK and extracellular signal-regulated kinase (ERK pathways, to promote ISC proliferation. Although short-lived, Sox21a mutant flies show no developmental defects, supporting the notion that this factor is a specific regulator of adult stem cell proliferation.

  14. Pedophilic brain potential responses to adult erotic stimuli.

    Science.gov (United States)

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

    2016-02-01

    Cognitive mechanisms associated with the relative lack of sexual interest in adults by pedophiles are poorly understood and may benefit from investigations examining how the brain processes adult erotic stimuli. The current study used event-related brain potentials (ERP) to investigate the time course of the explicit processing of erotic, emotional, and neutral pictures in 22 pedophilic patients and 22 healthy controls. Consistent with previous studies, early latency anterior ERP components were highly selective for erotic pictures. Although the ERPs elicited by emotional stimuli were similar in patients and controls, an early frontal positive (P2) component starting as early as 185 ms was significantly attenuated and slow to onset in pedophilia, and correlated with a clinical measure of cognitive distortions. Failure of rapid attentional capture by erotic stimuli suggests a relative reduction in early processing in pedophilic patients which may be associated with relatively diminished sexual interest in adults. Copyright © 2016. Published by Elsevier B.V.

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

    International Nuclear Information System (INIS)

    Rakic, P.

    1985-01-01

    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 [ 3 H] thymidine at ages ranging from 6 postnatal months to 17 years

  16. The Nutrient-Responsive Hormone CCHamide-2 Controls Growth by Regulating Insulin-like Peptides in the Brain of Drosophila melanogaster.

    Science.gov (United States)

    Sano, Hiroko; Nakamura, Akira; Texada, Michael J; Truman, James W; Ishimoto, Hiroshi; Kamikouchi, Azusa; Nibu, Yutaka; Kume, Kazuhiko; Ida, Takanori; Kojima, Masayasu

    2015-05-01

    The coordination of growth with nutritional status is essential for proper development and physiology. Nutritional information is mostly perceived by peripheral organs before being relayed to the brain, which modulates physiological responses. Hormonal signaling ensures this organ-to-organ communication, and the failure of endocrine regulation in humans can cause diseases including obesity and diabetes. In Drosophila melanogaster, the fat body (adipose tissue) has been suggested to play an important role in coupling growth with nutritional status. Here, we show that the peripheral tissue-derived peptide hormone CCHamide-2 (CCHa2) acts as a nutrient-dependent regulator of Drosophila insulin-like peptides (Dilps). A BAC-based transgenic reporter revealed strong expression of CCHa2 receptor (CCHa2-R) in insulin-producing cells (IPCs) in the brain. Calcium imaging of brain explants and IPC-specific CCHa2-R knockdown demonstrated that peripheral-tissue derived CCHa2 directly activates IPCs. Interestingly, genetic disruption of either CCHa2 or CCHa2-R caused almost identical defects in larval growth and developmental timing. Consistent with these phenotypes, the expression of dilp5, and the release of both Dilp2 and Dilp5, were severely reduced. Furthermore, transcription of CCHa2 is altered in response to nutritional levels, particularly of glucose. These findings demonstrate that CCHa2 and CCHa2-R form a direct link between peripheral tissues and the brain, and that this pathway is essential for the coordination of systemic growth with nutritional availability. A mammalian homologue of CCHa2-R, Bombesin receptor subtype-3 (Brs3), is an orphan receptor that is expressed in the islet β-cells; however, the role of Brs3 in insulin regulation remains elusive. Our genetic approach in Drosophila melanogaster provides the first evidence, to our knowledge, that bombesin receptor signaling with its endogenous ligand promotes insulin production.

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

    Science.gov (United States)

    2013-01-01

    Surrogate or 'proxy' measures of brain temperature are used in the routine management of patients with brain damage. The prevailing view is that the brain is 'hotter' than the body. The polarity and magnitude of temperature differences between brain and body, however, remains unclear after severe traumatic brain injury (TBI). The focus of this systematic review is on the adult patient admitted to intensive/neurocritical care with a diagnosis of severe TBI (Glasgow Coma Scale score of less than 8). The review considered studies that measured brain temperature and core body temperature. Articles published in English from the years 1980 to 2012 were searched in databases, CINAHL, PubMed, Scopus, Web of Science, Science Direct, Ovid SP, Mednar and ProQuest Dissertations & Theses Database. For the review, publications of randomised controlled trials, non-randomised controlled trials, before and after studies, cohort studies, case-control studies and descriptive studies were considered for inclusion. Of 2,391 records identified via the search strategies, 37 were retrieved for detailed examination (including two via hand searching). Fifteen were reviewed and assessed for methodological quality. Eleven studies were included in the systematic review providing 15 brain-core body temperature comparisons. The direction of mean brain-body temperature differences was positive (brain higher than body temperature) and negative (brain lower than body temperature). Hypothermia is associated with large brain-body temperature differences. Brain temperature cannot be predicted reliably from core body temperature. Concurrent monitoring of brain and body temperature is recommended in patients where risk of temperature-related neuronal damage is a cause for clinical concern and when deliberate induction of below-normal body temperature is instituted. PMID:23680353

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

    International Nuclear Information System (INIS)

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

    1996-01-01

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

  19. Molecular and Cellular Organization of Taste Neurons in Adult Drosophila Pharynx

    Directory of Open Access Journals (Sweden)

    Yu-Chieh David Chen

    2017-12-01

    Full Text Available Summary: The Drosophila pharyngeal taste organs are poorly characterized despite their location at important sites for monitoring food quality. Functional analysis of pharyngeal neurons has been hindered by the paucity of molecular tools to manipulate them, as well as their relative inaccessibility for neurophysiological investigations. Here, we generate receptor-to-neuron maps of all three pharyngeal taste organs by performing a comprehensive chemoreceptor-GAL4/LexA expression analysis. The organization of pharyngeal neurons reveals similarities and distinctions in receptor repertoires and neuronal groupings compared to external taste neurons. We validate the mapping results by pinpointing a single pharyngeal neuron required for feeding avoidance of L-canavanine. Inducible activation of pharyngeal taste neurons reveals functional differences between external and internal taste neurons and functional subdivision within pharyngeal sweet neurons. Our results provide roadmaps of pharyngeal taste organs in an insect model system for probing the role of these understudied neurons in controlling feeding behaviors. : Chen and Dahanukar carry out a large-scale, systematic analysis to understand the molecular organization of pharyngeal taste neurons. Taking advantage of the molecular genetic toolkit that arises from this map, they use genetic dissection strategies to probe the functional roles of selected pharyngeal neurons in food choice. Keywords: Drosophila, taste, pharynx, chemosensory receptors, gustatory receptors, ionotropic receptors, feeding

  20. File list: DNS.Neu.05.AllAg.Adult_brains [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: ALL.Neu.20.AllAg.Adult_brains [Chip-atlas[Archive

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  14. File list: ALL.Neu.05.AllAg.Adult_brains [Chip-atlas[Archive

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

    Science.gov (United States)

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

    2014-01-01

    Adult survivors of childhood brain tumors experience multiple, significant, lifelong deficits as a consequence of their malignancy and therapy. Current survivorship literature documents the substantial impact such impairments have on survivors' physical health and quality of life. Psychosocial reports detail educational, cognitive, and emotional limitations characterizing survivors as especially fragile, often incompetent, and unreliable in evaluating their circumstances. Anecdotal data suggest some survivors report life experiences similar to those of healthy controls. The aim of our investigation was to determine whether life satisfaction in adult survivors of childhood brain tumors differs from that of healthy controls and to identify potential predictors of life satisfaction in survivors. This cross-sectional study compared 78 brain tumor survivors with population-based matched controls. Chi-square tests, t tests, and linear regression models were used to investigate patterns of life satisfaction and identify potential correlates. Results indicated that life satisfaction of adult survivors of childhood brain tumors was similar to that of healthy controls. Survivors' general health expectations emerged as the primary correlate of life satisfaction. Understanding life satisfaction as an important variable will optimize the design of strategies to enhance participation in follow-up care, reduce suffering, and optimize quality of life in this vulnerable population. © 2014 by Association of Pediatric Hematology/Oncology Nurses.

  16. Open source tracking and analysis of adult Drosophila locomotion in Buridan's paradigm with and without visual targets.

    Directory of Open Access Journals (Sweden)

    Julien Colomb

    Full Text Available BACKGROUND: Insects have been among the most widely used model systems for studying the control of locomotion by nervous systems. In Drosophila, we implemented a simple test for locomotion: in Buridan's paradigm, flies walk back and forth between two inaccessible visual targets [1]. Until today, the lack of easily accessible tools for tracking the fly position and analyzing its trajectory has probably contributed to the slow acceptance of Buridan's paradigm. METHODOLOGY/PRINCIPAL FINDINGS: We present here a package of open source software designed to track a single animal walking in a homogenous environment (Buritrack and to analyze its trajectory. The Centroid Trajectory Analysis (CeTrAn software is coded in the open source statistics project R. It extracts eleven metrics and includes correlation analyses and a Principal Components Analysis (PCA. It was designed to be easily customized to personal requirements. In combination with inexpensive hardware, these tools can readily be used for teaching and research purposes. We demonstrate the capabilities of our package by measuring the locomotor behavior of adult Drosophila melanogaster (whose wings were clipped, either in the presence or in the absence of visual targets, and comparing the latter to different computer-generated data. The analysis of the trajectories confirms that flies are centrophobic and shows that inaccessible visual targets can alter the orientation of the flies without changing their overall patterns of activity. CONCLUSIONS/SIGNIFICANCE: Using computer generated data, the analysis software was tested, and chance values for some metrics (as well as chance value for their correlation were set. Our results prompt the hypothesis that fixation behavior is observed only if negative phototaxis can overcome the propensity of the flies to avoid the center of the platform. Together with our companion paper, we provide new tools to promote Open Science as well as the collection and

  17. Wingless, decapentaplegic and EGF receptor signaling pathways interact to specify dorso-ventral pattern in the adult abdomen of Drosophila.

    Science.gov (United States)

    Kopp, A; Blackman, R K; Duncan, I

    1999-08-01

    Adult abdominal segments of Drosophila are subdivided along the dorso-ventral axis into a dorsal tergite, a ventral sternite and ventro-lateral pleural cuticle. We report that this pattern is largely specified during the pupal stage by Wingless (Wg), Decapentaplegic (Dpp) and Drosophila EGF Receptor (DER) signaling. Expression of wg and dpp is activated at the posterior edge of the anterior compartment by Hedgehog signaling. Within this region, wg and dpp are expressed in domains that are mutually exclusive along the dorso-ventral axis: wg is expressed in the sternite and medio-lateral tergite, whereas dpp expression is confined to the pleura and the dorsal midline. Neither gene is expressed in the lateral tergite. Shirras and Couso (1996, Dev. Biol. 175, 24-36) have shown that tergite and sternite cell fates are specified by Wg signaling. We find that DER acts synergistically with Wg to promote tergite and sternite identities, and that Wg and DER activities are opposed by Dpp signaling, which promotes pleural identity. Wg and Dpp interact antagonistically at two levels. First, their expression is confined to complementary domains by mutual transcriptional repression. Second, Wg and Dpp compete directly with one another by exerting opposite effects on cell fate. DER signaling does not affect the expression of wg or dpp, indicating that it interacts with Wg and Dpp at the level of cell fate determination. Within the tergite, the requirements for Wg and DER function are roughly complementary: Wg is required mainly in the medial region, whereas DER is most important laterally. Finally, we show that Dpp signaling at the dorsal midline controls dorso-ventral patterning within the tergite by promoting pigmentation in the medial region.

  18. The genetic basis of natural variation in mushroom body size in Drosophila melanogaster.

    Science.gov (United States)

    Zwarts, Liesbeth; Vanden Broeck, Lies; Cappuyns, Elisa; Ayroles, Julien F; Magwire, Michael M; Vulsteke, Veerle; Clements, Jason; Mackay, Trudy F C; Callaerts, Patrick

    2015-12-11

    Genetic variation in brain size may provide the basis for the evolution of the brain and complex behaviours. The genetic substrate and the selective pressures acting on brain size are poorly understood. Here we use the Drosophila Genetic Reference Panel to map polymorphic variants affecting natural variation in mushroom body morphology. We identify 139 genes and 39 transcription factors and confirm effects on development and adult plasticity. We show correlations between morphology and aggression, sleep and lifespan. We propose that natural variation in adult brain size is controlled by interaction of the environment with gene networks controlling development and plasticity.

  19. Plasticity in the Drosophila larval visual System

    Directory of Open Access Journals (Sweden)

    Abud J Farca-Luna

    2013-07-01

    Full Text Available The remarkable ability of the nervous system to modify its structure and function is mostly experience and activity modulated. The molecular basis of neuronal plasticity has been studied in higher behavioral processes, such as learning and memory formation. However, neuronal plasticity is not restricted to higher brain functions, but may provide a basic feature of adaptation of all neural circuits. The fruit fly Drosophila melanogaster provides a powerful genetic model to gain insight into the molecular basis of nervous system development and function. The nervous system of the larvae is again a magnitude simpler than its adult counter part, allowing the genetic assessment of a number of individual genetically identifiable neurons. We review here recent progress on the genetic basis of neuronal plasticity in developing and functioning neural circuits focusing on the simple visual system of the Drosophila larva.

  20. Speaker gaze increases information coupling between infant and adult brains.

    Science.gov (United States)

    Leong, Victoria; Byrne, Elizabeth; Clackson, Kaili; Georgieva, Stanimira; Lam, Sarah; Wass, Sam

    2017-12-12

    When infants and adults communicate, they exchange social signals of availability and communicative intention such as eye gaze. Previous research indicates that when communication is successful, close temporal dependencies arise between adult speakers' and listeners' neural activity. However, it is not known whether similar neural contingencies exist within adult-infant dyads. Here, we used dual-electroencephalography to assess whether direct gaze increases neural coupling between adults and infants during screen-based and live interactions. In experiment 1 ( n = 17), infants viewed videos of an adult who was singing nursery rhymes with ( i ) direct gaze (looking forward), ( ii ) indirect gaze (head and eyes averted by 20°), or ( iii ) direct-oblique gaze (head averted but eyes orientated forward). In experiment 2 ( n = 19), infants viewed the same adult in a live context, singing with direct or indirect gaze. Gaze-related changes in adult-infant neural network connectivity were measured using partial directed coherence. Across both experiments, the adult had a significant (Granger) causal influence on infants' neural activity, which was stronger during direct and direct-oblique gaze relative to indirect gaze. During live interactions, infants also influenced the adult more during direct than indirect gaze. Further, infants vocalized more frequently during live direct gaze, and individual infants who vocalized longer also elicited stronger synchronization from the adult. These results demonstrate that direct gaze strengthens bidirectional adult-infant neural connectivity during communication. Thus, ostensive social signals could act to bring brains into mutual temporal alignment, creating a joint-networked state that is structured to facilitate information transfer during early communication and learning. Copyright © 2017 the Author(s). Published by PNAS.

  1. Maintenance of the adult Drosophila intestine: all roads lead to homeostasis.

    Science.gov (United States)

    Guo, Zheng; Lucchetta, Elena; Rafel, Neus; Ohlstein, Benjamin

    2016-10-01

    Maintenance of tissue homeostasis is critical in tissues with high turnover such as the intestinal epithelium. The intestinal epithelium is under constant cellular assault due to its digestive functions and its function as a barrier to chemical and bacterial insults. The resulting high rate of cellular turnover necessitates highly controlled mechanisms of regeneration to maintain the integrity of the tissue over the lifetime of the organism. Transient increase in stem cell proliferation is a commonly used and elaborate mechanism to ensure fast and efficient repair of the gut. However, tissue repair is not limited to regulating ISC proliferation, as emerging evidence demonstrates that the Drosophila intestine uses multiple strategies to ensure proper tissue homeostasis that may also extend to other tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Molecular and cellular organization of taste neurons in adult Drosophila pharynx

    Science.gov (United States)

    Chen, Yu-Chieh (David); Dahanukar, Anupama

    2017-01-01

    SUMMARY The Drosophila pharyngeal taste organs are poorly characterized despite their location at important sites for monitoring food quality. Functional analysis of pharyngeal neurons has been hindered by the paucity of molecular tools to manipulate them, as well as their relative inaccessibility for neurophysiological investigations. Here, we generate receptor-to-neuron maps of all three pharyngeal taste organs by performing a comprehensive chemoreceptor-GAL4/LexA expression analysis. The organization of pharyngeal neurons reveals similarities and distinctions in receptor repertoires and neuronal groupings compared to external taste neurons. We validate the mapping results by pinpointing a single pharyngeal neuron required for feeding avoidance of L-canavanine. Inducible activation of pharyngeal taste neurons reveals functional differences between external and internal taste neurons and functional subdivision within pharyngeal sweet neurons. Our results provide road maps of pharyngeal taste organs in an insect model system for probing the role of these understudied neurons in controlling feeding behaviors. PMID:29212040

  3. Aging and Autophagic Function Influences the Progressive Decline of Adult Drosophila Behaviors.

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    Eric P Ratliff

    Full Text Available Multiple neurological disorders are characterized by the abnormal accumulation of protein aggregates and the progressive impairment of complex behaviors. Our Drosophila studies demonstrate that middle-aged wild-type flies (WT, ~4-weeks exhibit a marked accumulation of neural aggregates that is commensurate with the decline of the autophagy pathway. However, enhancing autophagy via neuronal over-expression of Atg8a (Atg8a-OE reduces the age-dependent accumulation of aggregates. Here we assess basal locomotor activity profiles for single- and group-housed male and female WT flies and observed that only modest behavioral changes occurred by 4-weeks of age, with the noted exception of group-housed male flies. Male flies in same-sex social groups exhibit a progressive increase in nighttime activity. Infrared videos show aged group-housed males (4-weeks are engaged in extensive bouts of courtship during periods of darkness, which is partly repressed during lighted conditions. Together, these nighttime courtship behaviors were nearly absent in young WT flies and aged Atg8a-OE flies. Previous studies have indicated a regulatory role for olfaction in male courtship partner choice. Coincidently, the mRNA expression profiles of several olfactory genes decline with age in WT flies; however, they are maintained in age-matched Atg8a-OE flies. Together, these results suggest that middle-aged male flies develop impairments in olfaction, which could contribute to the dysregulation of courtship behaviors during dark time periods. Combined, our results demonstrate that as Drosophila age, they develop early behavior defects that are coordinate with protein aggregate accumulation in the nervous system. In addition, the nighttime activity behavior is preserved when neuronal autophagy is maintained (Atg8a-OE flies. Thus, environmental or genetic factors that modify autophagic capacity could have a positive impact on neuronal aging and complex behaviors.

  4. Inhibition of GSK-3 ameliorates Abeta pathology in an adult-onset Drosophila model of Alzheimer's disease.

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    Oyinkan Sofola

    2010-09-01

    Full Text Available Abeta peptide accumulation is thought to be the primary event in the pathogenesis of Alzheimer's disease (AD, with downstream neurotoxic effects including the hyperphosphorylation of tau protein. Glycogen synthase kinase-3 (GSK-3 is increasingly implicated as playing a pivotal role in this amyloid cascade. We have developed an adult-onset Drosophila model of AD, using an inducible gene expression system to express Arctic mutant Abeta42 specifically in adult neurons, to avoid developmental effects. Abeta42 accumulated with age in these flies and they displayed increased mortality together with progressive neuronal dysfunction, but in the apparent absence of neuronal loss. This fly model can thus be used to examine the role of events during adulthood and early AD aetiology. Expression of Abeta42 in adult neurons increased GSK-3 activity, and inhibition of GSK-3 (either genetically or pharmacologically by lithium treatment rescued Abeta42 toxicity. Abeta42 pathogenesis was also reduced by removal of endogenous fly tau; but, within the limits of detection of available methods, tau phosphorylation did not appear to be altered in flies expressing Abeta42. The GSK-3-mediated effects on Abeta42 toxicity appear to be at least in part mediated by tau-independent mechanisms, because the protective effect of lithium alone was greater than that of the removal of tau alone. Finally, Abeta42 levels were reduced upon GSK-3 inhibition, pointing to a direct role of GSK-3 in the regulation of Abeta42 peptide level, in the absence of APP processing. Our study points to the need both to identify the mechanisms by which GSK-3 modulates Abeta42 levels in the fly and to determine if similar mechanisms are present in mammals, and it supports the potential therapeutic use of GSK-3 inhibitors in AD.

  5. Glial-Specific Functions of Microcephaly Protein WDR62 and Interaction with the Mitotic Kinase AURKA Are Essential for Drosophila Brain Growth.

    Science.gov (United States)

    Lim, Nicholas R; Shohayeb, Belal; Zaytseva, Olga; Mitchell, Naomi; Millard, S Sean; Ng, Dominic C H; Quinn, Leonie M

    2017-07-11

    The second most commonly mutated gene in primary microcephaly (MCPH) patients is wd40-repeat protein 62 (wdr62), but the relative contribution of WDR62 function to the growth of major brain lineages is unknown. Here, we use Drosophila models to dissect lineage-specific WDR62 function(s). Interestingly, although neural stem cell (neuroblast)-specific depletion of WDR62 significantly decreased neuroblast number, brain size was unchanged. In contrast, glial lineage-specific WDR62 depletion significantly decreased brain volume. Moreover, loss of function in glia not only decreased the glial population but also non-autonomously caused neuroblast loss. We further demonstrated that WDR62 controls brain growth through lineage-specific interactions with master mitotic signaling kinase, AURKA. Depletion of AURKA in neuroblasts drives brain overgrowth, which was suppressed by WDR62 co-depletion. In contrast, glial-specific depletion of AURKA significantly decreased brain volume, which was further decreased by WDR62 co-depletion. Thus, dissecting relative contributions of MCPH factors to individual neural lineages will be critical for understanding complex diseases such as microcephaly. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  6. Hormonal Signaling Cascade during an Early-Adult Critical Period Required for Courtship Memory Retention in Drosophila.

    Science.gov (United States)

    Lee, Sang Soo; Ding, Yike; Karapetians, Natalie; Rivera-Perez, Crisalejandra; Noriega, Fernando Gabriel; Adams, Michael E

    2017-09-25

    Formation and expression of memories are critical for context-dependent decision making. In Drosophila, a courting male rejected by a mated female subsequently courts less avidly when paired with a virgin female, a behavioral modification attributed to "courtship memory." Here we show the critical role of hormonal state for maintenance of courtship memory. Ecdysis-triggering hormone (ETH) is essential for courtship memory through regulation of juvenile hormone (JH) levels in adult males. Reduction of JH levels via silencing of ETH signaling genes impairs short-term courtship memory, a phenotype rescuable by the JH analog methoprene. JH-deficit-induced memory impairment involves rapid decay rather than failure of memory acquisition. A critical period governs memory performance during the first 3 days of adulthood. Using sex-peptide-expressing "pseudo-mated" trainers, we find that robust courtship memory elicited in the absence of aversive chemical mating cues also is dependent on ETH-JH signaling. Finally, we find that JH acts through dopaminergic neurons and conclude that an ETH-JH-dopamine signaling cascade is required during a critical period for promotion of social-context-dependent memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Preimaginal exposure to azadirachtin affects food selection and digestive enzymes in adults of Drosophila melanogaster (Diptera: Drosophilidae).

    Science.gov (United States)

    Kilani-Morakchi, Samira; Bezzar-Bendjazia, Radia; Ferdenache, Maroua; Aribi, Nadia

    2017-08-01

    Among the plant derived product, azadirachtin, a neem-based insecticide, is exceptional in having a broad range of bioactivity including toxicity, growth, development and reproduction effects, repellency and antifeedancy. If considerable progress on the physiological and biological activities and agricultural application of azadirachtin has been achieved, its exact mechanism of action remains uncertain. In this study, we aimed at assessing the lethal and sublethal behavioral and physiological effects of azadirachtin on Drosophila melanogaster Meigen, 1830 (Diptera: Drosophilidae) as biological model. Azadirachtin was applied topically at two doses LD 25 (0.28μg) and LD 50 (0.67μg) on early third instar larvae. Results showed that flies preferentially ingested control medium rather than azadirachtin-treated medium. Pre-imaginal exposure (L3) to azadirachtin increased aversion to this substance suggesting a memorability of the learned avoidance. In addition, all tested flies revealed a clear preference for solvent odour rather than azadirachtin odour. Moreover, azadirachtin treatment decreased significantly the amount of food intake in the adults of both sexes. Finally, azadirachtin was found to affect digestive enzyme activities in the midgut of flies. Indeed, an inhibition of α-amylase, chitinase, and protease activities and an increase of lipasic activity were noted. These results may reflect interference of azadirachtin with regulation of feeding and metabolism, and provide some evidence of a long term antifeedancy and delayed effects through developmental stage which may reinforce the insecticidal activity of this bioinsecticide. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Assessing Basal and Acute Autophagic Responses in the Adult Drosophila Nervous System: The Impact of Gender, Genetics and Diet on Endogenous Pathway Profiles.

    Directory of Open Access Journals (Sweden)

    Eric P Ratliff

    Full Text Available The autophagy pathway is critical for the long-term homeostasis of cells and adult organisms and is often activated during periods of stress. Reduced pathway efficacy plays a central role in several progressive neurological disorders that are associated with the accumulation of cytotoxic peptides and protein aggregates. Previous studies have shown that genetic and transgenic alterations to the autophagy pathway impacts longevity and neural aggregate profiles of adult Drosophila. In this study, we have identified methods to measure the acute in vivo induction of the autophagy pathway in the adult fly CNS. Our findings indicate that the genotype, age, and gender of adult flies can influence pathway responses. Further, we demonstrate that middle-aged male flies exposed to intermittent fasting (IF had improved neuronal autophagic profiles. IF-treated flies also had lower neural aggregate profiles, maintained more youthful behaviors and longer lifespans, when compared to ad libitum controls. In summary, we present methodology to detect dynamic in vivo changes that occur to the autophagic profiles in the adult Drosophila CNS and that a novel IF-treatment protocol improves pathway response in the aging nervous system.

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

    Directory of Open Access Journals (Sweden)

    Yu-Kai Chang

    2014-03-01

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

  10. 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.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  12. 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.

  13. Brain aging and Aβ₁₋₄₂ neurotoxicity converge via deterioration in autophagy-lysosomal system: a conditional Drosophila model linking Alzheimer's neurodegeneration with aging.

    Science.gov (United States)

    Ling, Daijun; Salvaterra, Paul M

    2011-02-01

    Aging is known to be the most prominent risk factor for Alzheimer's disease (AD); however, the underlying mechanism linking brain aging with AD pathogenesis remains unknown. The expression of human amyloid beta 42 peptide (Aβ₁₋₄₂), but not Aβ₁₋₄₀ in Drosophila brain induces an early onset and progressive autophagy-lysosomal neuropathology. Here we show that the natural process of brain aging also accompanies a chronic and late-onset deterioration of neuronal autophagy-lysosomal system. This process is characterized by accumulation of dysfunctional autophagy-lysosomal vesicles, a compromise of these vesicles leading to damage of intracellular membranes and organelles, necrotic-like intraneuronal destruction and neurodegeneration. In addition, conditional activation of neuronal autophagy in young animals is protective while late activation is deleterious for survival. Intriguingly, conditional Aβ₁₋₄₂ expression limited to young animals exacerbates the aging process to a greater extent than Aβ₁₋₄₂ expression in old animals. These data suggest that the neuronal autophagy-lysosomal system may shift from a functional and protective state to a pathological and deleterious state either during brain aging or via Aβ₁₋₄₂ neurotoxicity. A chronic deterioration of the neuronal autophagy-lysosomal system is likely to be a key event in transitioning from normal brain aging to pathological aging leading to Alzheimer's neurodegeneration.

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

    Science.gov (United States)

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

    2015-03-01

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

  15. Glycogen distribution in adult and geriatric mice brains

    KAUST Repository

    Alrabeh, Rana

    2017-05-01

    Astrocytes, the most abundant glial cell type in the brain, undergo a number of roles in brain physiology; among them, the energetic support of neurons is the best characterized. Contained within astrocytes is the brain’s obligate energy store, glycogen. Through glycogenolysis, glycogen, a storage form of glucose, is converted to pyruvate that is further reduced to lactate and transferred to neurons as an energy source via MCTs. Glycogen is a multi-branched polysaccharide synthesized from the glucose uptaken in astrocytes. It has been shown that glycogen accumulates with age and contributes to the physiological ageing process in the brain. In this study, we compared glycogen distribution between young adults and geriatric mice to understand the energy consumption of synaptic terminals during ageing using computational tools. We segmented and densely reconstructed neuropil and glycogen granules within six (three 4 month old old and three 24 month old) volumes of Layer 1 somatosensory cortex mice brains from FIB-SEM stacks, using a combination of semi-automated and manual tools, ilastik and TrakEM2. Finally, the 3D visualization software, Blender, was used to analyze the dataset using the DBSCAN and KDTree Nearest neighbor algorithms to study the distribution of glycogen granules compared to synapses, using a plugin that was developed for this purpose. The Nearest Neighbors and clustering results of 6 datasets show that glycogen clusters around excitatory synapses more than inhibitory synapses and that, in general, glycogen is found around axonal boutons more than dendritic spines. There was no significant accumulation of glycogen with ageing within our admittedly small dataset. However, there was a homogenization of glycogen distribution with age and that is consistent with published literature. We conclude that glycogen distribution in the brain is not a random process but follows a function distribution.

  16. Asymmetry of the structural brain connectome in healthy older adults.

    Directory of Open Access Journals (Sweden)

    Leonardo eBonilha

    2014-01-01

    Full Text Available 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.Methods: We obtained high-resolution structural magnetic resonance images (MRI from 17 healthy older adults. For each subject, the brain connectome was reconstructed by parcelating the probabilistic map of gray matter into anatomically defined regions of interested (ROIs. White matter fiber tractography was reconstructed from diffusion tensor imaging and streamlines connecting gray matter ROIs were computed. Asymmetry indices were calculated regarding ROI connectivity (representing the sum of connectivity weight of each cortical ROI and for regional white matter links. All asymmetry measures were compared to a normal distribution with mean=0 through one sample t-tests.Results: Leftward cortical ROI asymmetry was observed in medial temporal, dorsolateral frontal and occipital regions. Rightward cortical ROI asymmetry was observed in middle temporal and orbito-frontal regions. Link-wise asymmetry revealed stronger connections in the left hemisphere between the medial temporal, anterior and posterior peri-Sylvian and occipito-temporal regions. Rightward link asymmetry was observed in lateral temporal, parietal and dorsolateral frontal connections.Conclusions: We postulate that asymmetry of specific connections may be related to functional hemispheric organization. This study may provide reference for future studies evaluating the architecture of the connectome in health and disease processes in senior individuals.

  17. Brain natriuretic peptide and insulin resistance in older adults.

    Science.gov (United States)

    Kim, F; Biggs, M L; Kizer, J R; Brutsaert, E F; de Filippi, C; Newman, A B; Kronmal, R A; Tracy, R P; Gottdiener, J S; Djoussé, L; de Boer, I H; Psaty, B M; Siscovick, D S; Mukamal, K J

    2017-02-01

    Higher levels of brain natriuretic peptide (BNP) have been associated with a decreased risk of diabetes in adults, but whether BNP is related to insulin resistance in older adults has not been established. N-terminal of the pro hormone brain natriuretic peptide (NT-pro BNP) was measured among Cardiovascular Health Study participants at the 1989-1990, 1992-1993 and 1996-1997 examinations. We calculated measures of insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Gutt index, Matsuda index] from fasting and 2-h concentrations of glucose and insulin among 3318 individuals with at least one measure of NT-proBNP and free of heart failure, coronary heart disease and chronic kidney disease, and not taking diabetes medication. We used generalized estimating equations to assess the cross-sectional association of NT-proBNP with measures of insulin resistance. Instrumental variable analysis with an allele score derived from nine genetic variants (single nucleotide polymorphisms) within or near the NPPA and NPPB loci was used to estimate an un-confounded association of NT-proBNP levels on insulin resistance. Lower NT-proBNP levels were associated with higher insulin resistance even after adjustment for BMI, waist circumference and other risk factors (P insulin resistance (P = 0.38; P = 0.01 for comparison with the association of measured levels of NT-proBNP). In older adults, lower NT-proBNP is associated with higher insulin resistance, even after adjustment for traditional risk factors. Because related genetic variants were not associated with insulin resistance, the causal nature of this association will require future study. © 2016 Diabetes UK.

  18. Resting-state brain activity in adult males who stutter.

    Directory of Open Access Journals (Sweden)

    Yun Xuan

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

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

    Science.gov (United States)

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

    2012-01-01

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

  20. Tools for neuroanatomy and neurogenetics in Drosophila

    Energy Technology Data Exchange (ETDEWEB)

    Pfeiffer, Barret D.; Jenett, Arnim; Hammonds, Ann S.; Ngo, Teri-T B.; Misra, Sima; Murphy, Christine; Scully, Audra; Carlson, Joseph W.; Wan, Kenneth H.; Laverty, Todd R.; Mungall, Chris; Svirskas, Rob; Kadonaga, James T.; Doe, Chris Q.; Eisen, Michael B.; Celniker, Susan E.; Rubin, Gerald M.

    2008-08-11

    We demonstrate the feasibility of generating thousands of transgenic Drosophila melanogaster lines in which the expression of an exogenous gene is reproducibly directed to distinct small subsets of cells in the adult brain. We expect the expression patterns produced by the collection of 5,000 lines that we are currently generating to encompass all neurons in the brain in a variety of intersecting patterns. Overlapping 3-kb DNA fragments from the flanking noncoding and intronic regions of genes thought to have patterned expression in the adult brain were inserted into a defined genomic location by site-specific recombination. These fragments were then assayed for their ability to function as transcriptional enhancers in conjunction with a synthetic core promoter designed to work with a wide variety of enhancer types. An analysis of 44 fragments from four genes found that >80% drive expression patterns in the brain; the observed patterns were, on average, comprised of <100 cells. Our results suggest that the D. melanogaster genome contains >50,000 enhancers and that multiple enhancers drive distinct subsets of expression of a gene in each tissue and developmental stage. We expect that these lines will be valuable tools for neuroanatomy as well as for the elucidation of neuronal circuits and information flow in the fly brain.

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

    International Nuclear Information System (INIS)

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

    1987-01-01

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

  2. Magnetic Resonance Fingerprinting of Adult Brain Tumors: Initial Experience

    Science.gov (United States)

    Badve, Chaitra; Yu, Alice; Dastmalchian, Sara; Rogers, Matthew; Ma, Dan; Jiang, Yun; Margevicius, Seunghee; Pahwa, Shivani; Lu, Ziang; Schluchter, Mark; Sunshine, Jeffrey; Griswold, Mark; Sloan, Andrew; Gulani, Vikas

    2016-01-01

    Background Magnetic resonance fingerprinting (MRF) allows rapid simultaneous quantification of T1 and T2 relaxation times. This study assesses the utility of MRF in differentiating between common types of adult intra-axial brain tumors. Methods MRF acquisition was performed in 31 patients with untreated intra-axial brain tumors: 17 glioblastomas, 6 WHO grade II lower-grade gliomas and 8 metastases. T1, T2 of the solid tumor (ST), immediate peritumoral white matter (PW), and contralateral white matter (CW) were summarized within each region of interest. Statistical comparisons on mean, standard deviation, skewness and kurtosis were performed using univariate Wilcoxon rank sum test across various tumor types. Bonferroni correction was used to correct for multiple comparisons testing. Multivariable logistic regression analysis was performed for discrimination between glioblastomas and metastases and area under the receiver operator curve (AUC) was calculated. Results Mean T2 values could differentiate solid tumor regions of lower-grade gliomas from metastases (mean±sd: 172±53ms and 105±27ms respectively, p =0.004, significant after Bonferroni correction). Mean T1 of PW surrounding lower-grade gliomas differed from PW around glioblastomas (mean±sd: 1066±218ms and 1578±331ms respectively, p=0.004, significant after Bonferroni correction). Logistic regression analysis revealed that mean T2 of ST offered best separation between glioblastomas and metastases with AUC of 0.86 (95% CI 0.69–1.00, p<0.0001). Conclusion MRF allows rapid simultaneous T1, T2 measurement in brain tumors and surrounding tissues. MRF based relaxometry can identify quantitative differences between solid-tumor regions of lower grade gliomas and metastases and between peritumoral regions of glioblastomas and lower grade gliomas. PMID:28034994

  3. Analysis of Neurotransmitter Tissue Content of Drosophila melanogaster in Different Life Stages

    Science.gov (United States)

    2015-01-01

    Drosophila melanogaster is a widely used model organism for studying neurological diseases with similar neurotransmission to mammals. While both larva and adult Drosophila have central nervous systems, not much is known about how neurotransmitter tissue content changes through development. In this study, we quantified tyramine, serotonin, octopamine, and dopamine in larval, pupal, and adult fly brains using capillary electrophoresis coupled to fast-scan cyclic voltammetry. Tyramine and octopamine content varied between life stages, with almost no octopamine being present in the pupa, while tyramine levels in the pupa were very high. Adult females had significantly higher dopamine content than males, but no other neurotransmitters were dependent on sex in the adult. Understanding the tissue content of different life stages will be beneficial for future work comparing the effects of diseases on tissue content throughout development. PMID:25437353

  4. Central Artery Stiffness, Baroreflex Sensitivity, and Brain White Matter Neuronal Fiber Integrity in Older Adults

    OpenAIRE

    Tarumi, Takashi; de Jong, Daan L.K.; Zhu, David C.; Tseng, Benjamin Y.; Liu, Jie; Hill, Candace; Riley, Jonathan; Womack, Kyle B.; Kerwin, Diana R.; Lu, Hanzhang; Cullum, C. Munro; Zhang, Rong

    2015-01-01

    Cerebral hypoperfusion elevates the risk of brain white matter (WM) lesions and cognitive impairment. Central artery stiffness impairs baroreflex, which controls systemic arterial perfusion, and may deteriorate neuronal fiber integrity of brain WM. The purpose of this study was to examine the associations among brain WM neuronal fiber integrity, baroreflex sensitivity (BRS), and central artery stiffness in older adults. Fifty-four adults (65±6 years) with normal cognitive function or mild cog...

  5. The Visual Orientation Memory of "Drosophila" Requires Foraging (PKG) Upstream of Ignorant (RSK2) in Ring Neurons of the Central Complex

    Science.gov (United States)

    Kuntz, Sara; Poeck, Burkhard; Sokolowski, Marla B.; Strauss, Roland

    2012-01-01

    Orientation and navigation in a complex environment requires path planning and recall to exert goal-driven behavior. Walking "Drosophila" flies possess a visual orientation memory for attractive targets which is localized in the central complex of the adult brain. Here we show that this type of working memory requires the cGMP-dependent protein…

  6. INTERACTION BETWEEN THE ADH AND ALPHA-GPDH LOCI IN DROSOPHILA-MELANOGASTER - ADULT SURVIVAL AT HIGH-TEMPERATURE

    NARCIS (Netherlands)

    OUDMAN, L; VANDELDEN, W; KAMPING, A; BIJLSMA, R

    The role of high temperature resistance in the world-wide cline of Adh and alpha-Gpdh allele frequencies of Drosophila melanogaster was investigated. Experimental strains were used with different combinations of Adh and alpha-Gpdh alleles but with similar genetic background. The survival time of

  7. dp53 Restrains ectopic neural stem cell formation in the Drosophila brain in a non-apoptotic mechanism involving Archipelago and cyclin E.

    Directory of Open Access Journals (Sweden)

    Yingshi Ouyang

    Full Text Available Accumulating evidence suggests that tumor-initiating stem cells or cancer stem cells (CSCs possibly originating from normal stem cells may be the root cause of certain malignancies. How stem cell homeostasis is impaired in tumor tissues is not well understood, although certain tumor suppressors have been implicated. In this study, we use the Drosophila neural stem cells (NSCs called neuroblasts as a model to study this process. Loss-of-function of Numb, a key cell fate determinant with well-conserved mammalian counterparts, leads to the formation of ectopic neuroblasts and a tumor phenotype in the larval brain. Overexpression of the Drosophila tumor suppressor p53 (dp53 was able to suppress ectopic neuroblast formation caused by numb loss-of-function. This occurred in a non-apoptotic manner and was independent of Dacapo, the fly counterpart of the well-characterized mammalian p53 target p21 involved in cellular senescence. The observation that dp53 affected Edu incorporation into neuroblasts led us to test the hypothesis that dp53 acts through regulation of factors involved in cell cycle progression. Our results show that the inhibitory effect of dp53 on ectopic neuroblast formation was mediated largely through its regulation of Cyclin E (Cyc E. Overexpression of Cyc E was able to abrogate dp53's ability to rescue numb loss-of-function phenotypes. Increasing Cyc E levels by attenuating Archipelago (Ago, a recently identified transcriptional target of dp53 and a negative regulator of Cyc E, had similar effects. Conversely, reducing Cyc E activity by overexpressing Ago blocked ectopic neuroblast formation in numb mutant. Our results reveal an intimate connection between cell cycle progression and NSC self-renewal vs. differentiation control, and indicate that p53-mediated regulation of ectopic NSC self-renewal through the Ago/Cyc E axis becomes particularly important when NSC homeostasis is perturbed as in numb loss-of-function condition. This has

  8. Adult Neurogenesis in the Mammalian Brain: Significant Answers and Significant Questions

    Science.gov (United States)

    Ming, Guo-li; Song, Hongjun

    2011-01-01

    Summary Adult neurogenesis, a process of generating functional neurons from adult neural precursors, occurs throughout life in restricted brain regions in mammals. The past decade has witnessed tremendous progress in addressing questions related to almost every aspect of adult neurogenesis in the mammalian brain. Here we review major advances in our understanding of adult mammalian neurogenesis in the dentate gyrus of the hippocampus and from the subventricular zone of the lateral ventricle, the rostral migratory stream to the olfactory bulb. We highlight emerging principles that have significant implications for stem cell biology, developmental neurobiology, neural plasticity, and disease mechanisms. We also discuss remaining questions related to adult neural stem cells and their niches, underlying regulatory mechanisms and potential functions of newborn neurons in the adult brain. Building upon the recent progress and aided by new technologies, the adult neurogenesis field is poised to leap forward in the next decade. PMID:21609825

  9. It takes two to tango, a dance between the cells of origin and cancer stem cells in the Drosophila larval brain.

    Science.gov (United States)

    Janssens, Derek H; Lee, Cheng-Yu

    2014-04-01

    During malignant transformation the cells of origin give rise to cancer stem cells which possess the capacity to undergo limitless rounds of self-renewing division, regenerating themselves while producing more tumor cells. Within normal tissues, a limitless self-renewal capacity is unique to the stem cells, which divide asymmetrically to produce more restricted progenitors. Accumulating evidence suggests that misregulation of the self-renewal machinery in stem cell progeny can lead to tumorigenesis, but how it influences the properties of the resulting tumors remains unclear. Studies of the type II neural stem cell (neuroblast) lineages in the Drosophila larval brain have identified a regulatory cascade that promotes commitment to a progenitor cell identity by restricting their response to the self-renewal machinery. Brain tumor (Brat) and Numb initiate this cascade by asymmetrically extinguishing the activity of the self-renewal factors. Subsequently, Earmuff (Erm) and the SWI/SNF complex stably restrict the competence of the progenitor cell to respond to reactivation of self-renewal mechanisms. Together, this cascade programs the progenitor cell to undergo limited rounds of division, generating exclusive differentiated progeny. Here we review how defects in this cascade lead to tumor initiation and how inhibiting the self-renewal mechanisms may be an effective strategy to block CSC expansion. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Adding insult to brain injury: young adults' experiences of residing in nursing homes following acquired brain injury.

    Science.gov (United States)

    Dwyer, Aoife; Heary, Caroline; Ward, Marcia; MacNeela, Pádraig

    2017-08-28

    There is general consensus that adults under age 65 with acquired brain injury residing in nursing homes is inappropriate, however there is a limited evidence base on the issue. Previous research has relied heavily on third-party informants and qualitative studies have been of questionable methodological quality, with no known study adopting a phenomenological approach. This study explored the lived experiences of young adults with brain injury residing in aged care facilities. Interpretative phenomenological analysis was employed to collect and analyze data from six semi-structured interviews with participants regarding their experiences of living in nursing homes. Two themes were identified, including "Corporeal prison of acquired brain injury: broken selves" and "Existential prison of the nursing home: stagnated lives". Results illustrated that young adults with acquired brain injury can experience aged care as an existential prison in which their lives feel at a standstill. This experience was characterized by feelings of not belonging in a terminal environment, confinement, disempowerment, emptiness and hope for greater autonomy through rehabilitation. It is hoped that this study will provide relevant professionals, services and policy-makers with insight into the challenges and needs of young adults with brain injury facing these circumstances. Implications for rehabilitation This study supports the contention that more home-like and age-appropriate residential rehabilitation services for young adults with acquired brain injury are needed. As development of alternative accommodation is a lengthy process, the study findings suggest that the interim implementation of rehabilitative care in nursing homes should be considered. Taken together with existing research, it is proposed that nursing home staff may require training to deliver evidence-based rehabilitative interventions to those with brain injury. The present findings add support to the call for systemic

  11. Epigenetic control of vasopressin expression is maintained by steroid hormones in the adult male rat brain

    Science.gov (United States)

    Auger, Catherine J.; Coss, Dylan; Auger, Anthony P.; Forbes-Lorman, Robin M.

    2011-01-01

    Although some DNA methylation patterns are altered by steroid hormone exposure in the developing brain, less is known about how changes in steroid hormone levels influence DNA methylation patterns in the adult brain. Steroid hormones act in the adult brain to regulate gene expression. Specifically, the expression of the socially relevant peptide vasopressin (AVP) within the bed nucleus of the stria terminalis (BST) of adult brain is dependent upon testosterone exposure. Castration dramatically reduces and testosterone replacement restores AVP expression within the BST. As decreases in mRNA expression are associated with increases in DNA promoter methylation, we explored the hypothesis that AVP expression in the adult brain is maintained through sustained epigenetic modifications of the AVP gene promoter. We find that castration of adult male rats resulted in decreased AVP mRNA expression and increased methylation of specific CpG sites within the AVP promoter in the BST. Similarly, castration significantly increased estrogen receptor α (ERα) mRNA expression and decreased ERα promoter methylation within the BST. These changes were prevented by testosterone replacement. This suggests that the DNA promoter methylation status of some steroid responsive genes in the adult brain is actively maintained by the presence of circulating steroid hormones. The maintenance of methylated or demethylated states of some genes in the adult brain by the presence of steroid hormones may play a role in the homeostatic regulation of behaviorally relevant systems. PMID:21368111

  12. Drosophila mutants of the autism candidate gene neurobeachin (rugose) exhibit neuro-developmental disorders, aberrant synaptic properties, altered locomotion, and impaired adult social behavior and activity patterns.

    Science.gov (United States)

    Wise, Alexandria; Tenezaca, Luis; Fernandez, Robert W; Schatoff, Emma; Flores, Julian; Ueda, Atsushi; Zhong, Xiaotian; Wu, Chun-Fang; Simon, Anne F; Venkatesh, Tadmiri

    2015-01-01

    Autism spectrum disorder (ASD) is a neurodevelopmental disorder in humans characterized by complex behavioral deficits, including intellectual disability, impaired social interactions, and hyperactivity. ASD exhibits a strong genetic component with underlying multigene interactions. Candidate gene studies have shown that the neurobeachin (NBEA) gene is disrupted in human patients with idiopathic autism ( Castermans et al., 2003 ). The NBEA gene spans the common fragile site FRA 13A and encodes a signal scaffold protein ( Savelyeva et al., 2006 ). In mice, NBEA has been shown to be involved in the trafficking and function of a specific subset of synaptic vesicles. ( Medrihan et al., 2009 ; Savelyeva et al., 2006 ). Rugose (rg) is the Drosophila homolog of the mammalian and human NBEA. Our previous genetic and molecular analyses have shown that rg encodes an A kinase anchor protein (DAKAP 550), which interacts with components of the epidermal growth factor receptor or EGFR and Notch-mediated signaling pathways, facilitating cross talk between these and other pathways ( Shamloula et al., 2002 ). We now present functional data from studies on the larval neuromuscular junction that reveal abnormal synaptic architecture and physiology. In addition, adult rg loss-of-function mutants exhibit defective social interactions, impaired habituation, aberrant locomotion, and hyperactivity. These results demonstrate that Drosophila NBEA (rg) mutants exhibit phenotypic characteristics reminiscent of human ASD and thus could serve as a genetic model for studying ASDs.

  13. Community integration after severe traumatic brain injury in adults.

    Science.gov (United States)

    Truelle, Jean-Luc; Fayol, Patrick; Montreuil, Michèle; Chevignard, Mathilde

    2010-12-01

    Despite being the main cause of death and disability in young adults, traumatic brain injury (TBI) is a rather neglected epidemic. Community integration of persons with TBI was, until recently, insufficiently informed by clinical research. To bridge the gap between rehabilitation and community re-entry, the first task is to assess the person, using TBI-specific outcome measures. The second task is to provide re-entry programs, the effectiveness of which is assessed by those measures, using well designed studies. There are very few such studies. However, there are some effective comprehensive programs and others which are specifically targeted dealing mainly with return to work, behavior, and family issues. The complex psychological and environmental components of the disability require individualized and often long-term care. For persons with severe TBI trying to achieve the best possible community integration a new semiology is required, not just limited to medical care, but also involving social and psychological care that is tailored to the needs of each individual and family, living within his/her environment. Currently, only a minority benefit from well validated programs.

  14. 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.

  15. Glycogen distribution in adult and geriatric mice brains

    KAUST Repository

    Alrabeh, Rana

    2017-01-01

    Astrocytes, the most abundant glial cell type in the brain, undergo a number of roles in brain physiology; among them, the energetic support of neurons is the best characterized. Contained within astrocytes is the brain’s obligate energy store

  16. dHb9 expressing larval motor neurons persist through metamorphosis to innervate adult-specific muscle targets and function in Drosophila eclosion.

    Science.gov (United States)

    Banerjee, Soumya; Toral, Marcus; Siefert, Matthew; Conway, David; Dorr, Meredith; Fernandes, Joyce

    2016-12-01

    The Drosophila larval nervous system is radically restructured during metamorphosis to produce adult specific neural circuits and behaviors. Genesis of new neurons, death of larval neurons and remodeling of those neurons that persistent collectively act to shape the adult nervous system. Here, we examine the fate of a subset of larval motor neurons during this restructuring process. We used a dHb9 reporter, in combination with the FLP/FRT system to individually identify abdominal motor neurons in the larval to adult transition using a combination of relative cell body location, axonal position, and muscle targets. We found that segment specific cell death of some dHb9 expressing motor neurons occurs throughout the metamorphosis period and continues into the post-eclosion period. Many dHb9 > GFP expressing neurons however persist in the two anterior hemisegments, A1 and A2, which have segment specific muscles required for eclosion while a smaller proportion also persist in A2-A5. Consistent with a functional requirement for these neurons, ablating them during the pupal period produces defects in adult eclosion. In adults, subsequent to the execution of eclosion behaviors, the NMJs of some of these neurons were found to be dismantled and their muscle targets degenerate. Our studies demonstrate a critical continuity of some larval motor neurons into adults and reveal that multiple aspects of motor neuron remodeling and plasticity that are essential for adult motor behaviors. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 76: 1387-1416, 2016. © 2016 Wiley Periodicals, Inc.

  17. Changes in brain-behavior relationships following a 3-month pilot cognitive intervention program for adults with traumatic brain injury.

    Science.gov (United States)

    Porter, S; Torres, I J; Panenka, W; Rajwani, Z; Fawcett, D; Hyder, A; Virji-Babul, N

    2017-08-01

    Facilitating functional recovery following brain injury is a key goal of neurorehabilitation. Direct, objective measures of changes in the brain are critical to understanding how and when meaningful changes occur, however, assessing neuroplasticity using brain based results remains a significant challenge. Little is known about the underlying changes in functional brain networks that correlate with cognitive outcomes in traumatic brain injury (TBI). The purpose of this pilot study was to assess the feasibility of an intensive three month cognitive intervention program in individuals with chronic TBI and to evaluate the effects of this intervention on brain-behavioral relationships. We used tools from graph theory to evaluate changes in global and local brain network features prior to and following cognitive intervention. Network metrics were calculated from resting state electroencephalographic (EEG) recordings from 10 adult participants with mild to severe brain injury and 11 age and gender matched healthy controls. Local graph metrics showed hyper-connectivity in the right inferior frontal gyrus and hypo-connectivity in the left inferior frontal gyrus in the TBI group at baseline in comparison with the control group. Following the intervention, there was a statistically significant increase in the composite cognitive score in the TBI participants and a statistically significant decrease in functional connectivity in the right inferior frontal gyrus. In addition, there was evidence of changes in the brain-behavior relationships following intervention. The results from this pilot study provide preliminary evidence for functional network reorganization that parallels cognitive improvements after cognitive rehabilitation in individuals with chronic TBI.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Experimental studies suggest that changes in brain ventricle size are key events in bacterial meningitis. This study investigated the relationship between ventricle size, clinical condition and risk of poor outcome in patients with bacterial meningitis. METHODS: Adult patients diagnos...

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

    Directory of Open Access Journals (Sweden)

    He Liu

    2016-01-01

    Full Text Available 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.

  20. Drosophila melanogaster gene expression changes after spaceflight.

    Data.gov (United States)

    National Aeronautics and Space Administration — Gene expression levels were determined in 3rd instar and adult Drosophila melanogaster reared during spaceflight to elucidate the genetic and molecular mechanisms...

  1. 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...... 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...

  2. Doublecortin-like knockdown in the adult mouse brain : implications for neurogenesis, neuroplasticity and behaviour

    NARCIS (Netherlands)

    Saaltink, Dirk-Jan

    2014-01-01

    The results in this thesis showed for the first time doublecortin-like (DCL)-specific expression in the adult mouse brain. Besides the expected regions with the capacity to generate new neurons (hippocampus and olfactory forebrain), DCL expression was found in three novel brain areas namely

  3. Hippotherapy in Adult Patients with Chronic Brain Disorders: A Pilot Study

    OpenAIRE

    Sunwoo, Hyuk; Chang, Won Hyuk; Kwon, Jeong-Yi; Kim, Tae-Won; Lee, Ji-Young; Kim, Yun-Hee

    2012-01-01

    Objective To investigate the effects of hippotherapy for adult patients with brain disorders. Method Eight chronic brain disorder patients (7 males, mean age 42.4?16.6 years) were recruited. The mean duration from injury was 7.9?7.7 years. The diagnoses were stroke (n=5), traumatic brain disorder (n=2), and cerebral palsy (n=1). Hippotherapy sessions were conducted twice a week for eight consecutive weeks in an indoor riding arena. Each hippotherapy session lasted 30 minutes. All participants...

  4. Infectious diseases of brain parenchyma in adults: imaging and differential diagnosis

    International Nuclear Information System (INIS)

    Haehnel, S.; Kress, B.; Stippich, C.; Sartor, K.; Seitz, A.; Storch-Hagenlocher, B.; Forsting, M.; Jansen, O.

    2005-01-01

    Infectious diseases of the central nervous system have often to be considered in differential diagnosis, particularly in immunocompromised persons. Neuroimaging, specifically advanced techniques such as diffusion-weighted MRI and perfusion MRI contribute much to the differentiation of various brain infections and to delineation of brain infections from other, for instance, neoplastic diseases. In this review we present the imaging criteria for the most important brain infections in adults and discuss in detail differential diagnostic aspects. (orig.)

  5. Scalloped a member of the Hippo tumor suppressor pathway controls mushroom body size in Drosophila brain by non-canonical regulation of neuroblast proliferation.

    Science.gov (United States)

    Rohith, Basavanahalli Nanjundaiah; Shyamala, Baragur Venkatanarayanasetty

    2017-12-15

    Cell proliferation, growth and survival are three different basic processes which converge at determining a fundamental property -the size of an organism. Scalloped (Sd) is the first characterised transcriptional partner to Yorkie (Yki), the downstream effector of the Hippo pathway which is a highly potential and evolutionarily conserved regulator of organ size. Here we have studied the hypomorphic effect of sd on the development of Mushroom Bodies (MBs) in Drosophila brain. We show that, sd non-function results in an increase in the size of MBs. We demonstrate that, sd regulation on MB size operates through multiple routes. Sd expressed in the differentiated MB neurons, imposes non-cell autonomous repression on the proliferation of MB precursor cells, and Sd expression in the MB neuroblasts (NB) cell autonomously represses mushroom body neuroblast (MBNB) proliferation. Further Sd in Kenyon cells (KCs) imparts a cell autonomous restriction on their growth. Our findings are distinctive because, while the classical sd loss of function phenotypes in eye, wing and lymph gland are reported as loss of tissue or reduced organ size, the present study shows that, Sd inactivation in the developing MB, promotes precursor cell proliferation and results in an increase in the organ size. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Splicing Regulatory Elements and mRNA-abundance of dlg1 and capt, Genetically Interacting with dFMRP in Drosophila Brain

    Directory of Open Access Journals (Sweden)

    Maria Petrova

    2014-09-01

    Full Text Available To further understand the molecular and cellular mechanisms underlying the disease, we used the Drososphila FraX model and investigated a not well studied role of Drosophila Fragile X Mental Retardation Protein (dFMRP in alternative splicing of neuronal mRNAs to which it binds via a G-quartet sequence. By means of qRT-PCR we established the relative abundance of some isoforms of the gene dlg1, resulting from alternative exon skipping nearby a G-quartet and an exonic ESE-sequence, both acting as exonic splicing enhancers. We also investigated the relative mRNA-abundance of all capt-isoforms and the pre-mRNAs of both genes. We proposed a possible involvement of dFMRP in alternative splicing of genes, interacting with dfmr1. In the absence of dFMRP in larval and pupal brains, we found a change in the mRNA-level of one of the studied isoforms of dlg1 and of its pre-mRNA.We also established previously reported splicing regulatory elements and predicted computationally novel hexamere sequences in the exonic/intronic ends of both genes with p upative regulatory roles in alternative splicing.

  7. 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.

  8. Genetic human prion disease modelled in PrP transgenic Drosophila.

    Science.gov (United States)

    Thackray, Alana M; Cardova, Alzbeta; Wolf, Hanna; Pradl, Lydia; Vorberg, Ina; Jackson, Walker S; Bujdoso, Raymond

    2017-09-20

    Inherited human prion diseases, such as fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD), are associated with autosomal dominant mutations in the human prion protein gene PRNP and accumulation of PrP Sc , an abnormal isomer of the normal host protein PrP C , in the brain of affected individuals. PrP Sc is the principal component of the transmissible neurotoxic prion agent. It is important to identify molecular pathways and cellular processes that regulate prion formation and prion-induced neurotoxicity. This will allow identification of possible therapeutic interventions for individuals with, or at risk from, genetic human prion disease. Increasingly, Drosophila has been used to model human neurodegenerative disease. An important unanswered question is whether genetic prion disease with concomitant spontaneous prion formation can be modelled in Drosophila We have used pUAST/PhiC31-mediated site-directed mutagenesis to generate Drosophila transgenic for murine or hamster PrP (prion protein) that carry single-codon mutations associated with genetic human prion disease. Mouse or hamster PrP harbouring an FFI (D178N) or fCJD (E200K) mutation showed mild Proteinase K resistance when expressed in Drosophila Adult Drosophila transgenic for FFI or fCJD variants of mouse or hamster PrP displayed a spontaneous decline in locomotor ability that increased in severity as the flies aged. Significantly, this mutant PrP-mediated neurotoxic fly phenotype was transferable to recipient Drosophila that expressed the wild-type form of the transgene. Collectively, our novel data are indicative of the spontaneous formation of a PrP-dependent neurotoxic phenotype in FFI- or CJD-PrP transgenic Drosophila and show that inherited human prion disease can be modelled in this invertebrate host. © 2017 The Author(s).

  9. As tears go by : Baby tears trigger more brain activity than adult tears in nulliparous women

    NARCIS (Netherlands)

    Hendricx-Riem, M.M.E.; De Carli, P.; van IJzendoorn, M.H.; Vingerhoets, A.J.J.M.; Bakermans-Kranenburg, M.J.

    2017-01-01

    The current functional magnetic resonance imaging study examines brain activity during the perception of infant and adult tears. Infant tears evoke stronger responses in the visual cortex than adult tears, indicating that infant tears are highly salient. In addition, our study shows that infant

  10. Factors affecting mortality in severe traumatic brain injury in adults at ...

    African Journals Online (AJOL)

    Objective: To assess factors contributing to mortality of adult patients admitted to intensive care units for severe traumatic brain injury (TBI). Patients and methods: This is a retrospective, descriptive and analytical study. Included in the study were all adults patients admitted for severe TBI. From the hospital records, ...

  11. 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

  12. Distinct types of glial cells populate the Drosophila antenna

    Directory of Open Access Journals (Sweden)

    Jhaveri Dhanisha

    2005-11-01

    Full Text Available Abstract Background The development of nervous systems involves reciprocal interactions between neurons and glia. In the Drosophila olfactory system, peripheral glial cells arise from sensory lineages specified by the basic helix-loop-helix transcription factor, Atonal. These glia wrap around the developing olfactory axons early during development and pattern the three distinct fascicles as they exit the antenna. In the moth Manduca sexta, an additional set of central glia migrate to the base of the antennal nerve where axons sort to their glomerular targets. In this work, we have investigated whether similar types of cells exist in the Drosophila antenna. Results We have used different P(Gal4 lines to drive Green Fluorescent Protein (GFP in distinct populations of cells within the Drosophila antenna. Mz317::GFP, a marker for cell body and perineural glia, labels the majority of peripheral glia. An additional ~30 glial cells detected by GH146::GFP do not derive from any of the sensory lineages and appear to migrate into the antenna from the brain. Their appearance in the third antennal segment is regulated by normal function of the Epidermal Growth Factor receptor and small GTPases. We denote these distinct populations of cells as Mz317-glia and GH146-glia respectively. In the adult, processes of GH146-glial cells ensheath the olfactory receptor neurons directly, while those of the Mz317-glia form a peripheral layer. Ablation of GH146-glia does not result in any significant effects on the patterning of the olfactory receptor axons. Conclusion We have demonstrated the presence of at least two distinct populations of glial cells within the Drosophila antenna. GH146-glial cells originate in the brain and migrate to the antenna along the newly formed olfactory axons. The number of cells populating the third segment of the antenna is regulated by signaling through the Epidermal Growth Factor receptor. These glia share several features of the sorting

  13. Cognitive deficits in adult patients with brain tumours.

    NARCIS (Netherlands)

    Taphoorn, M.J.B.; Klein, M.

    2004-01-01

    Cognitive function, with survival and response on brain imaging, is increasingly regarded as an important outcome measure in patients with brain tumours. This measure provides us with information on a patient's clinical situation and adverse treatment effects. Radiotherapy has been regarded as the

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

    Science.gov (United States)

    Kizil, Caghan; Brand, Michael

    2011-01-01

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

  15. Hypergravity-induced altered behavior in Drosophila

    Science.gov (United States)

    Hosamani, Ravikumar; Wan, Judy; Marcu, Oana; Bhattacharya, Sharmila

    2012-07-01

    Microgravity and mechanical stress are important factors of the spaceflight environment, and affect astronaut health and behavior. Structural, functional, and behavioral mechanisms of all cells and organisms are adapted to Earth's gravitational force, 1G, while altered gravity can pose challenges to their adaptability to this new environment. On ground, hypergravity paradigms have been used to predict and complement studies on microgravity. Even small changes that take place at a molecular and genetic level during altered gravity may result in changes in phenotypic behavior. Drosophila provides a robust and simple, yet very reliable model system to understand the complexity of hypergravity-induced altered behavior, due to availability of a plethora of genetic tools. Locomotor behavior is a sensitive parameter that reflects the array of molecular adaptive mechanisms recruited during exposure to altered gravity. Thus, understanding the genetic basis of this behavior in a hypergravity environment could potentially extend our understanding of mechanisms of adaptation in microgravity. In our laboratory we are trying to dissect out the cellular and molecular mechanisms underlying hypergravity-induced oxidative stress, and its potential consequences on behavioral alterations by using Drosophila as a model system. In the present study, we employed pan-neuronal and mushroom body specific knock-down adult flies by using Gal4/UAS system to express inverted repeat transgenes (RNAi) to monitor and quantify the hypergravity-induced behavior in Drosophila. We established that acute hypergravity (3G for 60 min) causes a significant and robust decrease in the locomotor behavior in adult Drosophila, and that this change is dependent on genes related to Parkinson's disease, such as DJ-1α , DJ-1β , and parkin. In addition, we also showed that anatomically the control of this behavior is significantly processed in the mushroom body region of the fly brain. This work links a molecular

  16. Mood stabilizing drugs regulate transcription of immune, neuronal and metabolic pathway genes in Drosophila.

    Science.gov (United States)

    Herteleer, L; Zwarts, L; Hens, K; Forero, D; Del-Favero, J; Callaerts, P

    2016-05-01

    Lithium and valproate (VPA) are drugs used in the management of bipolar disorder. Even though they reportedly act on various pathways, the transcriptional targets relevant for disease mechanism and therapeutic effect remain unclear. Furthermore, multiple studies used lymphoblasts of bipolar patients as a cellular proxy, but it remains unclear whether peripheral cells provide a good readout for the effects of these drugs in the brain. We used Drosophila culture cells and adult flies to analyze the transcriptional effects of lithium and VPA and define mechanistic pathways. Transcriptional profiles were determined for Drosophila S2-cells and adult fly heads following lithium or VPA treatment. Gene ontology categories were identified using the DAVID functional annotation tool with a cut-off of p neuronal development, neuronal function, and metabolism. (i) Transcriptional effects of lithium and VPA in Drosophila S2 cells and heads show significant overlap. (ii) The overlap between transcriptional alterations in peripheral versus neuronal cells at the single gene level is negligible, but at the gene ontology and pathway level considerable overlap can be found. (iii) Lithium and VPA act on evolutionarily conserved pathways in Drosophila and mammalian models.

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

    Science.gov (United States)

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

    2014-06-01

    Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P brain stimulation. Our finding of decreased metabolism in vermis and hippocampus of asymptomatic relatives suggests that heterozygocity influences the function of these brain regions. Published by Oxford University Press on behalf of the Guarantors of Brain 2014. This work is written by US Government employees and is in the public domain in the US.

  18. A major QTL affects temperature sensitive adult lethality and inbreeding depression in life span in Drosophila melanogaster.

    DEFF Research Database (Denmark)

    Vermeulen, Corneel J.; Bijlsma, R.; Loeschcke, Volker

    2008-01-01

    of inbreeding effects in specific traits, such as age-specific mortality and life span, provide a good starting point, as a limited set of genes is expected to be involved. Results Here we report on a QTL mapping study on inbreeding related and temperature sensitive lethality in male Drosophila melanogaster...... and the molecular properties of genes that give rise to or modulate its deleterious effects is lacking. These questions warrant the detailed study of genetic loci giving rise to inbreeding depression. However, the complex and polygenic nature of general inbreeding depression makes this a daunting task. Study...... simple, being due mainly to a single recessive QTL on the left arm of chromosome 2. This locus colocalised with a QTL that conditioned variation in female life span, acting as an overdominant locus for this trait. Male life span was additionally affected by variation at the X-chromosome. Conclusion...

  19. White matter sexual dimorphism of the adult human brain

    Directory of Open Access Journals (Sweden)

    Bourisly Ali K.

    2017-05-01

    Full Text Available Sex-biased psychophysiology, behavior, brain function, and conditions are extensive, yet underlying structural brain mechanisms remain unclear. There is contradicting evidence regarding sexual dimorphism when it comes to brain structure, and there is still no consensus on whether or not there exists such a dimorphism for brain white matter. Therefore, we conducted a voxel-based morphometry (VBM analysis along with global volume analysis for white matter across sex. We analyzed 384 T1-weighted MRI brain images (192 male, 192 female to investigate any differences in white matter (WM between males and females. In the VBM analysis, we found males to have larger WM, compared to females, in occipital, temporal, insular, parietal, and frontal brain regions. In contrast, females showed only one WM region to be significantly larger than males: the right postcentral gyrus in the parietal lobe region. Although, on average, males showed larger global WM volume, we did not find any significant difference in global WM volume between males and females.

  20. Changes in brain-behavior relationships following a 3-month pilot cognitive intervention program for adults with traumatic brain injury

    Directory of Open Access Journals (Sweden)

    S. Porter

    2017-08-01

    Full Text Available Facilitating functional recovery following brain injury is a key goal of neurorehabilitation. Direct, objective measures of changes in the brain are critical to understanding how and when meaningful changes occur, however, assessing neuroplasticity using brain based results remains a significant challenge. Little is known about the underlying changes in functional brain networks that correlate with cognitive outcomes in traumatic brain injury (TBI. The purpose of this pilot study was to assess the feasibility of an intensive three month cognitive intervention program in individuals with chronic TBI and to evaluate the effects of this intervention on brain-behavioral relationships. We used tools from graph theory to evaluate changes in global and local brain network features prior to and following cognitive intervention. Network metrics were calculated from resting state electroencephalographic (EEG recordings from 10 adult participants with mild to severe brain injury and 11 age and gender matched healthy controls. Local graph metrics showed hyper-connectivity in the right inferior frontal gyrus and hypo-connectivity in the left inferior frontal gyrus in the TBI group at baseline in comparison with the control group. Following the intervention, there was a statistically significant increase in the composite cognitive score in the TBI participants and a statistically significant decrease in functional connectivity in the right inferior frontal gyrus. In addition, there was evidence of changes in the brain-behavior relationships following intervention. The results from this pilot study provide preliminary evidence for functional network reorganization that parallels cognitive improvements after cognitive rehabilitation in individuals with chronic TBI.

  1. 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.

  2. 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

    .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 cancer......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...

  3. Altered Gravity Induces Oxidative Stress in Drosophila Melanogaster

    Science.gov (United States)

    Bhattacharya, Sharmila; Hosamani, Ravikumar

    2015-01-01

    Altered gravity environments can induce increased oxidative stress in biological systems. Microarray data from our previous spaceflight experiment (FIT experiment on STS-121) indicated significant changes in the expression of oxidative stress genes in adult fruit flies after spaceflight. Currently, our lab is focused on elucidating the role of hypergravity-induced oxidative stress and its impact on the nervous system in Drosophila melanogaster. Biochemical, molecular, and genetic approaches were combined to study this effect on the ground. Adult flies (2-3 days old) exposed to acute hypergravity (3g, for 1 hour and 2 hours) showed significantly elevated levels of Reactive Oxygen Species (ROS) in fly brains compared to control samples. This data was supported by significant changes in mRNA expression of specific oxidative stress and antioxidant defense related genes. As anticipated, a stress-resistant mutant line, Indy302, was less vulnerable to hypergravity-induced oxidative stress compared to wild-type flies. Survival curves were generated to study the combined effect of hypergravity and pro-oxidant treatment. Interestingly, many of the oxidative stress changes that were measured in flies showed sex specific differences. Collectively, our data demonstrate that altered gravity significantly induces oxidative stress in Drosophila, and that one of the organs where this effect is evident is the brain.

  4. Electrophysiological Recordings from Lobula Plate Tangential Cells in Drosophila.

    Science.gov (United States)

    Mauss, Alex S; Borst, Alexander

    2016-01-01

    Drosophila has emerged as an important model organism for the study of the neural basis of behavior. Its main asset is the experimental accessibility of identified neurons by genetic manipulation and physiological recordings. Drosophila therefore offers the opportunity to reach an integrative understanding of the development and neural underpinnings of behavior at all processing stages, from sensing to motor control, in a single species. Here, we will provide an account of the procedures involved in recording the electrical potential of individual neurons in the visual system of adult Drosophila using the whole-cell patch-clamp method. To this end, animals are fixed to a holder and mounted below a recording chamber. The head capsule is cut open and the glial sheath covering the brain is ruptured by a combination of shearing and enzymatic digest. Neuronal somata are thus exposed and targeted by low-resistance patch electrodes. After formation of a high resistance seal, electrical access to the cell is gained by small current pulses and suction. Stable recordings of large neurons are feasible for >1 h and can be combined with controlled visual stimulation as well as genetic and pharmacological manipulation of upstream circuit elements to infer circuit function in great detail.

  5. Dynamic genome wide expression profiling of Drosophila head development reveals a novel role of Hunchback in retinal glia cell development and blood-brain barrier integrity.

    Directory of Open Access Journals (Sweden)

    Montserrat Torres-Oliva

    2018-01-01

    Full Text Available Drosophila melanogaster head development represents a valuable process to study the developmental control of various organs, such as the antennae, the dorsal ocelli and the compound eyes from a common precursor, the eye-antennal imaginal disc. While the gene regulatory network underlying compound eye development has been extensively studied, the key transcription factors regulating the formation of other head structures from the same imaginal disc are largely unknown. We obtained the developmental transcriptome of the eye-antennal discs covering late patterning processes at the late 2nd larval instar stage to the onset and progression of differentiation at the end of larval development. We revealed the expression profiles of all genes expressed during eye-antennal disc development and we determined temporally co-expressed genes by hierarchical clustering. Since co-expressed genes may be regulated by common transcriptional regulators, we combined our transcriptome dataset with publicly available ChIP-seq data to identify central transcription factors that co-regulate genes during head development. Besides the identification of already known and well-described transcription factors, we show that the transcription factor Hunchback (Hb regulates a significant number of genes that are expressed during late differentiation stages. We confirm that hb is expressed in two polyploid subperineurial glia cells (carpet cells and a thorough functional analysis shows that loss of Hb function results in a loss of carpet cells in the eye-antennal disc. Additionally, we provide for the first time functional data indicating that carpet cells are an integral part of the blood-brain barrier. Eventually, we combined our expression data with a de novo Hb motif search to reveal stage specific putative target genes of which we find a significant number indeed expressed in carpet cells.

  6. Dynamic genome wide expression profiling of Drosophila head development reveals a novel role of Hunchback in retinal glia cell development and blood-brain barrier integrity

    Science.gov (United States)

    Torres-Oliva, Montserrat; Schneider, Julia; Wiegleb, Gordon

    2018-01-01

    Drosophila melanogaster head development represents a valuable process to study the developmental control of various organs, such as the antennae, the dorsal ocelli and the compound eyes from a common precursor, the eye-antennal imaginal disc. While the gene regulatory network underlying compound eye development has been extensively studied, the key transcription factors regulating the formation of other head structures from the same imaginal disc are largely unknown. We obtained the developmental transcriptome of the eye-antennal discs covering late patterning processes at the late 2nd larval instar stage to the onset and progression of differentiation at the end of larval development. We revealed the expression profiles of all genes expressed during eye-antennal disc development and we determined temporally co-expressed genes by hierarchical clustering. Since co-expressed genes may be regulated by common transcriptional regulators, we combined our transcriptome dataset with publicly available ChIP-seq data to identify central transcription factors that co-regulate genes during head development. Besides the identification of already known and well-described transcription factors, we show that the transcription factor Hunchback (Hb) regulates a significant number of genes that are expressed during late differentiation stages. We confirm that hb is expressed in two polyploid subperineurial glia cells (carpet cells) and a thorough functional analysis shows that loss of Hb function results in a loss of carpet cells in the eye-antennal disc. Additionally, we provide for the first time functional data indicating that carpet cells are an integral part of the blood-brain barrier. Eventually, we combined our expression data with a de novo Hb motif search to reveal stage specific putative target genes of which we find a significant number indeed expressed in carpet cells. PMID:29360820

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

    Science.gov (United States)

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

    2015-07-01

    Docosahexaenoic acid (DHA) is important for brain function, and can be obtained directly from the diet or synthesized in the body from α-linolenic acid (ALA). Debate exists as to whether DHA synthesized from ALA can provide sufficient DHA for the adult brain, as measures of DHA synthesis from ingested ALA are typically <1% of the oral ALA dose. However, the primary fate of orally administered ALA is β-oxidation and long-term storage in adipose tissue, suggesting that DHA synthesis measures involving oral ALA tracer ingestion may underestimate total DHA synthesis. There is also evidence that DHA synthesized from ALA can meet brain DHA requirements, as animals fed ALA-only diets have brain DHA concentrations similar to DHA-fed animals, and the brain DHA requirement is estimated to be only 2.4-3.8 mg/day in humans. This review summarizes evidence that DHA synthesis from ALA can provide sufficient DHA for the adult brain by examining work in humans and animals involving estimates of DHA synthesis and brain DHA requirements. Also, an update on methods to measure DHA synthesis in humans is presented highlighting a novel approach involving steady-state infusion of stable isotope-labeled ALA that bypasses several limitations of oral tracer ingestion. It is shown that this method produces estimates of DHA synthesis that are at least 3-fold higher than brain uptake rates in rats. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2010-01-01

    sensitive to plastic changes, such as nucleus higher vocal center (HVC) and area X, recruited similar numbers of new neurons as their surrounding brain tissues, employing no specific directional mechanisms. The distribution pattern in and around HVC could best be described by a random displacement model......Neuron recruitment has been implicated in morphological and functional plasticity in the adult brain. Whereas mammals restrict neuron recruitment specifically to two regions of known plasticity, the hippocampus and olfactory bulb, newborn neurons are found throughout the forebrain of adult...... songbirds. In order to study the area-specificity of the widespread proliferation and recruitment in the songbird brain, six adult male canaries received repetitive intraperitoneal injections of the mitotic marker BrdU (5-bromo-2-deoxyuridine) and were sacrificed after 24 hours to study proliferation...

  9. Neutral genetic variation in adult Chinook salmon (Oncorhynchus tshawytscha) affects brain-to-body trade-off and brain laterality

    Science.gov (United States)

    Heath, Daniel D.; Higgs, Dennis M.

    2017-01-01

    Low levels of heterozygosity can have detrimental effects on life history and growth characteristics of organisms but more subtle effects such as those on trade-offs of expensive tissues and morphological laterality, especially of the brain, have not been explicitly tested. The objective of the current study was to investigate how estimated differences in heterozygosity may potentially affect brain-to-body trade-offs and to explore how these heterozygosity differences may affect differential brain growth, focusing on directional asymmetry in adult Chinook salmon (Oncorhynchus tshawytscha) using the laterality and absolute laterality indices. Level of inbreeding was estimated as mean microsatellite heterozygosity resulting in four ‘inbreeding level groups’ (Very High, High, Medium, Low). A higher inbreeding level corresponded with a decreased brain-to-body ratio, thus a decrease in investment in brain tissue, and also showed a decrease in the laterality index for the cerebellum, where the left hemisphere was larger than the right across all groups. These results begin to show the role that differences in heterozygosity may play in differential tissue investment and in morphological laterality, and may be useful in two ways. Firstly, the results may be valuable for restocking programmes that wish to emphasize brain or body growth when crossing adults to generate individuals for release, as we show that genetic variation does affect these trade-offs. Secondly, this study is one of the first examinations to test the hypothesized relationship between genetic variation and laterality, finding that in Chinook salmon there is potential for an effect of inbreeding on lateralized morphology, but not in the expected direction. PMID:29308240

  10. Modelling glioblastoma tumour-host cell interactions using adult brain organotypic slice co-culture

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    Maria Angeles Marques-Torrejon

    2018-02-01

    Full Text Available Glioblastoma multiforme (GBM is an aggressive incurable brain cancer. The cells that fuel the growth of tumours resemble neural stem cells found in the developing and adult mammalian forebrain. These are referred to as glioma stem cells (GSCs. Similar to neural stem cells, GSCs exhibit a variety of phenotypic states: dormant, quiescent, proliferative and differentiating. How environmental cues within the brain influence these distinct states is not well understood. Laboratory models of GBM can be generated using either genetically engineered mouse models, or via intracranial transplantation of cultured tumour initiating cells (mouse or human. Unfortunately, these approaches are expensive, time-consuming, low-throughput and ill-suited for monitoring live cell behaviours. Here, we explored whole adult brain coronal organotypic slices as an alternative model. Mouse adult brain slices remain viable in a serum-free basal medium for several weeks. GSCs can be easily microinjected into specific anatomical sites ex vivo, and we demonstrate distinct responses of engrafted GSCs to diverse microenvironments in the brain tissue. Within the subependymal zone – one of the adult neural stem cell niches – injected tumour cells could effectively engraft and respond to endothelial niche signals. Tumour-transplanted slices were treated with the antimitotic drug temozolomide as proof of principle of the utility in modelling responses to existing treatments. Engraftment of mouse or human GSCs onto whole brain coronal organotypic brain slices therefore provides a simplified, yet flexible, experimental model. This will help to increase the precision and throughput of modelling GSC-host brain interactions and complements ongoing in vivo studies. This article has an associated First Person interview with the first author of the paper.

  11. Identification of four Drosophila allatostatins as the cognate ligands for the Drosophila orphan receptor DAR-2

    DEFF Research Database (Denmark)

    Lenz, C; Williamson, M; Hansen, G N

    2001-01-01

    The allatostatins are generally inhibitory insect neuropeptides. The Drosophila orphan receptor DAR-2 is a G-protein-coupled receptor, having 47% amino acid residue identity with another Drosophila receptor, DAR-1 (which is also called dros. GPCR, or DGR) that was previously shown...... to be the receptor for an intrinsic Drosophila A-type (cockroach-type) allatostatin. Here, we have permanently expressed DAR-2 in CHO cells and found that it is the cognate receptor for four Drosophila A-type allatostatins, the drostatins-A1 to -A4. Of all the drostatins, drostatin-A4 (Thr...... weakly in the brain. The Drosophila larval gut also contains about 20-30 endocrine cells, expressing the gene for the drostatins-A1 to -A4. We suggest, therefore, that DAR-2 mediates an allatostatin (drostatin)-induced inhibition of gut motility. This is the first report on the permanent and functional...

  12. Birth of projection neurons in adult avian brain may be related to perceptual or motor learning

    International Nuclear Information System (INIS)

    Alvarez-Buylla, A.; Kirn, J.R.; Nottebohm, F.

    1990-01-01

    Projection neurons that form part of the motor pathway for song control continue to be produced and to replace older projection neurons in adult canaries and zebra finches. This is shown by combining [3H]thymidine, a cell birth marker, and fluorogold, a retrogradely transported tracer of neuronal connectivity. Species and seasonal comparisons suggest that this process is related to the acquisition of perceptual or motor memories. The ability of an adult brain to produce and replace projection neurons should influence our thinking on brain repair

  13. MRI visualization of endogenous neural progenitor cell migration along the RMS in the adult mouse brain

    DEFF Research Database (Denmark)

    Vreys, Ruth; Vande Velde, Greetje; Krylychkina, Olga

    2010-01-01

    The adult rodent brain contains neural progenitor cells (NPCs), generated in the subventricular zone (SVZ), which migrate along the rostral migratory stream (RMS) towards the olfactory bulb (OB) where they differentiate into neurons. The aim of this study was to visualize endogenous NPC migration...... by a longitudinal MRI study and validated with histology. Here, we visualized endogenous NPC migration in the mouse brain by in vivo MRI and demonstrated accumulation of MPIO-labeled NPCs in the OB over time with ex vivo MRI. Furthermore, we investigated the influence of in situ injection of MPIOs on adult...

  14. The effect of developmental nutrition on life span and fecundity depends on the adult reproductive environment in Drosophila melanogaster

    NARCIS (Netherlands)

    May, C.M.; Doroszuk, A.; Zwaan, B.J.

    2015-01-01

    Both developmental nutrition and adult nutrition affect life-history traits; however, little is known about whether the effect of developmental nutrition depends on the adult environment experienced. We used the fruit fly to determine whether life-history traits, particularly life span and

  15. Brain glucose and acetoacetate metabolism: a comparison of young and older adults.

    Science.gov (United States)

    Nugent, Scott; Tremblay, Sebastien; Chen, Kewei W; Ayutyanont, Napatkamon; Roontiva, Auttawut; Castellano, Christian-Alexandre; Fortier, Melanie; Roy, Maggie; Courchesne-Loyer, Alexandre; Bocti, Christian; Lepage, Martin; Turcotte, Eric; Fulop, Tamas; Reiman, Eric M; Cunnane, Stephen C

    2014-06-01

    The extent to which the age-related decline in regional brain glucose uptake also applies to other important brain fuels is presently unknown. Ketones are the brain's major alternative fuel to glucose, so we developed a dual tracer positron emission tomography protocol to quantify and compare regional cerebral metabolic rates for glucose and the ketone, acetoacetate. Twenty healthy young adults (mean age, 26 years) and 24 healthy older adults (mean age, 74 years) were studied. In comparison with younger adults, older adults had 8 ± 6% (mean ± SD) lower cerebral metabolic rates for glucose in gray matter as a whole (p = 0.035), specifically in several frontal, temporal, and subcortical regions, as well as in the cingulate and insula (p ≤ 0.01, false discovery rate correction). The effect of age on cerebral metabolic rates for acetoacetate in gray matter did not reach significance (p = 0.11). Rate constants (min(-1)) of glucose (Kg) and acetoacetate (Ka) were significantly lower (-11 ± 6%; [p = 0.005], and -19 ± 5%; [p = 0.006], respectively) in older adults compared with younger adults. There were differential effects of age on Kg and Ka as seen by significant interaction effects in the caudate (p = 0.030) and post-central gyrus (p = 0.023). The acetoacetate index, which expresses the scaled residuals of the voxel-wise linear regression of glucose on ketone uptake, identifies regions taking up higher or lower amounts of acetoacetate relative to glucose. The acetoacetate index was higher in the caudate of young adults when compared with older adults (p ≤ 0.05 false discovery rate correction). This study provides new information about glucose and ketone metabolism in the human brain and a comparison of the extent to which their regional use changes during normal aging. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. 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)

  17. Differences between child and adult large-scale functional brain networks for reading tasks.

    Science.gov (United States)

    Liu, Xin; Gao, Yue; Di, Qiqi; Hu, Jiali; Lu, Chunming; Nan, Yun; Booth, James R; Liu, Li

    2018-02-01

    Reading is an important high-level cognitive function of the human brain, requiring interaction among multiple brain regions. Revealing differences between children's large-scale functional brain networks for reading tasks and those of adults helps us to understand how the functional network changes over reading development. Here we used functional magnetic resonance imaging data of 17 adults (19-28 years old) and 16 children (11-13 years old), and graph theoretical analyses to investigate age-related changes in large-scale functional networks during rhyming and meaning judgment tasks on pairs of visually presented Chinese characters. We found that: (1) adults had stronger inter-regional connectivity and nodal degree in occipital regions, while children had stronger inter-regional connectivity in temporal regions, suggesting that adults rely more on visual orthographic processing whereas children rely more on auditory phonological processing during reading. (2) Only adults showed between-task differences in inter-regional connectivity and nodal degree, whereas children showed no task differences, suggesting the topological organization of adults' reading network is more specialized. (3) Children showed greater inter-regional connectivity and nodal degree than adults in multiple subcortical regions; the hubs in children were more distributed in subcortical regions while the hubs in adults were more distributed in cortical regions. These findings suggest that reading development is manifested by a shift from reliance on subcortical to cortical regions. Taken together, our study suggests that Chinese reading development is supported by developmental changes in brain connectivity properties, and some of these changes may be domain-general while others may be specific to the reading domain. © 2017 Wiley Periodicals, Inc.

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

    Science.gov (United States)

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

    2013-08-01

    Comparison of brain function between children and adults with autism provides an understanding of the effects of the disorder and associated maturational differences on language processing. Functional imaging (functional magnetic resonance imaging) was used to examine brain activation and cortical synchronization during the processing of literal and ironic texts in 15 children with autism, 14 children with typical development, 13 adults with autism, and 12 adult controls. Both the children and adults with autism had lower functional connectivity (synchronization of brain activity among activated areas) than their age and ability comparison group in the left hemisphere language network during irony processing, and neither autism group had an increase in functional connectivity in response to increased task demands. Activation differences for the literal and irony conditions occurred in key language-processing regions (left middle temporal, left pars triangularis, left pars opercularis, left medial frontal, and right middle temporal). The children and adults with autism differed from each other in the use of some brain regions during the irony task, with the adults with autism having activation levels similar to those of the control groups. Overall, the children and adults with autism differed from the adult and child controls in (a) the degree of network coordination, (b) the distribution of the workload among member nodes, and (3) the dynamic recruitment of regions in response to text content. Moreover, the differences between the two autism age groups may be indicative of positive changes in the neural function related to language processing associated with maturation and/or educational experience. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

  19. Sonic Hedgehog (SHH) pathway in the adult brain: key signaling for astrocyte reactivation and brain repair

    OpenAIRE

    Bermúdez-Muñoz, Olga M

    2016-01-01

    While neurons play a key role in neurotransmission in the nervous central system (CNS) of animals, glial cells are crucial for neuron support and brain maintenance. Recent studies reveal that glial cells regulate the release and reuptake of neurotransmitters, pyruvate and glutathione metabolism, ion buffering, the organization of blood brain barrier and ensures the production of myelin and cerebrospinal fluid. The activity of glial cells is coordinated by the communication between neurons and...

  20. 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.

  1. The calcineurin inhibitor Sarah (Nebula) exacerbates Aβ42 phenotypes in a Drosophila model of Alzheimer's disease.

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    Lee, Soojin; Bang, Se Min; Hong, Yoon Ki; Lee, Jang Ho; Jeong, Haemin; Park, Seung Hwan; Liu, Quan Feng; Lee, Im-Soon; Cho, Kyoung Sang

    2016-03-01

    Expression of the Down syndrome critical region 1 (DSCR1) protein, an inhibitor of the Ca(2+)-dependent phosphatase calcineurin, is elevated in the brains of individuals with Down syndrome (DS) or Alzheimer's disease (AD). Although increased levels of DSCR1 were often observed to be deleterious to neuronal health, its beneficial effects against AD neuropathology have also been reported, and the roles of DSCR1 on the pathogenesis of AD remain controversial. Here, we investigated the role of sarah (sra; also known as nebula), a Drosophila DSCR1 ortholog, in amyloid-β42 (Aβ42)-induced neurological phenotypes in Drosophila. We detected sra expression in the mushroom bodies of the fly brain, which are a center for learning and memory in flies. Moreover, similar to humans with AD, Aβ42-expressing flies showed increased Sra levels in the brain, demonstrating that the expression pattern of DSCR1 with regard to AD pathogenesis is conserved in Drosophila. Interestingly, overexpression of sra using the UAS-GAL4 system exacerbated the rough-eye phenotype, decreased survival rates and increased neuronal cell death in Aβ42-expressing flies, without modulating Aβ42 expression. Moreover, neuronal overexpression of sra in combination with Aβ42 dramatically reduced both locomotor activity and the adult lifespan of flies, whereas flies with overexpression of sra alone showed normal climbing ability, albeit with a slightly reduced lifespan. Similarly, treatment with chemical inhibitors of calcineurin, such as FK506 and cyclosporin A, or knockdown of calcineurin expression by RNA interference (RNAi), exacerbated the Aβ42-induced rough-eye phenotype. Furthermore, sra-overexpressing flies displayed significantly decreased mitochondrial DNA and ATP levels, as well as increased susceptibility to oxidative stress compared to that of control flies. Taken together, our results demonstrating that sra overexpression augments Aβ42 cytotoxicity in Drosophila suggest that DSCR1

  2. The calcineurin inhibitor Sarah (Nebula exacerbates Aβ42 phenotypes in a Drosophila model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Soojin Lee

    2016-03-01

    Full Text Available Expression of the Down syndrome critical region 1 (DSCR1 protein, an inhibitor of the Ca2+-dependent phosphatase calcineurin, is elevated in the brains of individuals with Down syndrome (DS or Alzheimer's disease (AD. Although increased levels of DSCR1 were often observed to be deleterious to neuronal health, its beneficial effects against AD neuropathology have also been reported, and the roles of DSCR1 on the pathogenesis of AD remain controversial. Here, we investigated the role of sarah (sra; also known as nebula, a Drosophila DSCR1 ortholog, in amyloid-β42 (Aβ42-induced neurological phenotypes in Drosophila. We detected sra expression in the mushroom bodies of the fly brain, which are a center for learning and memory in flies. Moreover, similar to humans with AD, Aβ42-expressing flies showed increased Sra levels in the brain, demonstrating that the expression pattern of DSCR1 with regard to AD pathogenesis is conserved in Drosophila. Interestingly, overexpression of sra using the UAS-GAL4 system exacerbated the rough-eye phenotype, decreased survival rates and increased neuronal cell death in Aβ42-expressing flies, without modulating Aβ42 expression. Moreover, neuronal overexpression of sra in combination with Aβ42 dramatically reduced both locomotor activity and the adult lifespan of flies, whereas flies with overexpression of sra alone showed normal climbing ability, albeit with a slightly reduced lifespan. Similarly, treatment with chemical inhibitors of calcineurin, such as FK506 and cyclosporin A, or knockdown of calcineurin expression by RNA interference (RNAi, exacerbated the Aβ42-induced rough-eye phenotype. Furthermore, sra-overexpressing flies displayed significantly decreased mitochondrial DNA and ATP levels, as well as increased susceptibility to oxidative stress compared to that of control flies. Taken together, our results demonstrating that sra overexpression augments Aβ42 cytotoxicity in Drosophila suggest that DSCR1

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

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    Garrett, Douglas D; Nagel, Irene E; Preuschhof, Claudia; Burzynska, Agnieszka Z; Marchner, Janina; Wiegert, Steffen; Jungehülsing, Gerhard J; Nyberg, Lars; Villringer, Arno; Li, Shu-Chen; Heekeren, Hauke R; Bäckman, Lars; Lindenberger, Ulman

    2015-06-16

    Better-performing younger adults typically express greater brain signal variability relative to older, poorer performers. Mechanisms for age and performance-graded differences in brain dynamics have, however, not yet been uncovered. Given the age-related decline of the dopamine (DA) system in normal cognitive aging, DA neuromodulation is one plausible mechanism. Hence, agents that boost systemic DA [such as d-amphetamine (AMPH)] may help to restore deficient signal variability levels. Furthermore, despite the standard practice of counterbalancing drug session order (AMPH first vs. placebo first), it remains understudied how AMPH may interact with practice effects, possibly influencing whether DA up-regulation is functional. We examined the effects of AMPH on functional-MRI-based blood oxygen level-dependent (BOLD) signal variability (SD(BOLD)) in younger and older adults during a working memory task (letter n-back). Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult SD(BOLD) levels in the presence of AMPH. Drug session order greatly moderated change-change relations between AMPH-driven SD(BOLD) and reaction time means (RT(mean)) and SDs (RT(SD)). Older adults who received AMPH in the first session tended to improve in RT(mean) and RT(SD) when SD(BOLD) was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SD(BOLD) decreased (for RT(mean)) or no effect at all (for RT(SD)). The present findings support the hypothesis that age differences in brain signal variability reflect aging-induced changes in dopaminergic neuromodulation. The observed interactions among AMPH, age, and session order highlight the state- and practice-dependent neurochemical basis of human brain dynamics.

  4. 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.

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

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    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…

  6. Financial Exploitation Is Associated With Structural and Functional Brain Differences in Healthy Older Adults.

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    Spreng, R Nathan; Cassidy, Benjamin N; Darboh, Bri S; DuPre, Elizabeth; Lockrow, Amber W; Setton, Roni; Turner, Gary R

    2017-10-01

    Age-related brain changes leading to altered socioemotional functioning may increase vulnerability to financial exploitation. If confirmed, this would suggest a novel mechanism leading to heightened financial exploitation risk in older adults. Development of predictive neural markers could facilitate increased vigilance and prevention. In this preliminary study, we sought to identify structural and functional brain differences associated with financial exploitation in older adults. Financially exploited older adults (n = 13, 7 female) and a matched cohort of older adults who had been exposed to, but avoided, a potentially exploitative situation (n = 13, 7 female) were evaluated. Using magnetic resonance imaging, we examined cortical thickness and resting state functional connectivity. Behavioral data were collected using standardized cognitive assessments, self-report measures of mood and social functioning. The exploited group showed cortical thinning in anterior insula and posterior superior temporal cortices, regions associated with processing affective and social information, respectively. Functional connectivity encompassing these regions, within default and salience networks, was reduced, while between network connectivity was increased. Self-reported anger and hostility was higher for the exploited group. We observed financial exploitation associated with brain differences in regions involved in socioemotional functioning. These exploratory and preliminary findings suggest that alterations in brain regions implicated in socioemotional functioning may be a marker of financial exploitation risk. Large-scale, prospective studies are necessary to validate this neural mechanism, and develop predictive markers for use in clinical practice. © The Author 2017. Published by Oxford University Press on behalf of The Gerontological Society of America.

  7. Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults

    DEFF Research Database (Denmark)

    Hoogman, Martine; Bralten, Janita; Hibar, Derrek P

    2017-01-01

    BACKGROUND: Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies...... and adults for the pallidum (p=0·79) or thalamus (p=0·89). Case-control differences in adults were non-significant (all p>0·03). Psychostimulant medication use (all p>0·15) or symptom scores (all p>0·02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0...

  8. Quantitative expression profile of distinct functional regions in the adult mouse brain.

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    Takeya Kasukawa

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

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

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

    2015-09-01

    Associative memory involves binding two or more items into a coherent memory episode. Relative to memory for single items, associative memory declines greatly in aging. However, older individuals vary substantially in their ability to memorize associative information. Although functional studies link associative memory to the medial temporal lobe (MTL) and prefrontal cortex (PFC), little is known about how volumetric differences in MTL and PFC might contribute to individual differences in associative memory. We investigated regional gray-matter volumes related to individual differences in associative memory in a sample of healthy older adults (n=54; age=60years). To differentiate item from associative memory, participants intentionally learned face-scene picture pairs before performing a recognition task that included single faces, scenes, and face-scene pairs. Gray-matter volumes were analyzed using voxel-based morphometry region-of-interest (ROI) analyses. To examine volumetric differences specifically for associative memory, item memory was controlled for in the analyses. Behavioral results revealed large variability in associative memory that mainly originated from differences in false-alarm rates. Moreover, associative memory was independent of individuals' ability to remember single items. Older adults with better associative memory showed larger gray-matter volumes primarily in regions of the left and right lateral PFC. These findings provide evidence for the importance of PFC in intentional learning of associations, likely because of its involvement in organizational and strategic processes that distinguish older adults with good from those with poor associative memory. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Advances in Brain Tumor Surgery for Glioblastoma in Adults

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    Montserrat Lara-Velazquez

    2017-12-01

    Full Text Available Glioblastoma (GBM is the most common primary intracranial neoplasia, and is characterized by its extremely poor prognosis. Despite maximum surgery, chemotherapy, and radiation, the histological heterogeneity of GBM makes total eradication impossible, due to residual cancer cells invading the parenchyma, which is not otherwise seen in radiographic images. Even with gross total resection, the heterogeneity and the dormant nature of brain tumor initiating cells allow for therapeutic evasion, contributing to its recurrence and malignant progression, and severely impacting survival. Visual delimitation of the tumor’s margins with common surgical techniques is a challenge faced by many surgeons. In an attempt to achieve optimal safe resection, advances in approaches allowing intraoperative analysis of cancer and non-cancer tissue have been developed and applied in humans resulting in improved outcomes. In addition, functional paradigms based on stimulation techniques to map the brain’s electrical activity have optimized glioma resection in eloquent areas such as the Broca’s, Wernike’s and perirolandic areas. In this review, we will elaborate on the current standard therapy for newly diagnosed and recurrent glioblastoma with a focus on surgical approaches. We will describe current technologies used for glioma resection, such as awake craniotomy, fluorescence guided surgery, laser interstitial thermal therapy and intraoperative mass spectrometry. Additionally, we will describe a newly developed tool that has shown promising results in preclinical experiments for brain cancer: optical coherence tomography.

  11. Regulation of neurogenesis: factors affecting of new neurons formation in adult mammals brain

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    Michalina Respondek

    2015-12-01

    Full Text Available 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.

  12. Pupil diameter for confirmation of brain death in adult organ donors in Japan.

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    Sagishima, Katsuyuki; Kinoshita, Yoshihiro

    2017-01-01

    The criteria for brain death in Japan include a bilateral pupil diameter of ≥4 mm. We evaluated the appropriateness of a 4-mm pupil diameter in adult brain-dead donors in Japan. We retrospectively reviewed the records of 148 consecutive adult brain-dead donors with an average age of 46 years. All records were anonymously registered to the Japanese Ministry of Health, Labour and Welfare (the Japanese Ministry of Health and Welfare before 2001) from the various designated emergency institutes that performed organ donation under brain death from 1999 to 2012 in Japan. All donors had a Glasgow Coma Scale score of 3, absence of all seven brain stem reflexes, an isoelectric electroencephalogram for >30 min, and apnea as tested by the standard method. All of these examinations were repeated approximately 6 h later for confirmation. The pupil diameter (average ± standard deviation) was 6.1 ± 1.1 mm at the first assessment and 6.4 ± 1.1 mm approximately 6 h later. The 95% probability distribution as calculated by statistical analysis was 3.93-8.30 mm in the left eye and 3.88-8.28 mm in the right eye in the first assessment, and 4.25-8.58 mm in the left eye and 4.32-8.43 mm in the right eye approximately 6 h later. Despite the various original causes of brain death, we conclude that a pupil diameter of ≥4 mm is a reasonable criterion for brain death in adults.

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

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    Cecilie Jonsgar Sandberg

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

  14. Drosophila suzukii population response to environment and management strategies

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    Spotted wing drosophila, Drosophila suzukii, quickly emerged as a devastating invasive pest of small and stone fruits in the Americas and Europe. To better understand the population dynamics of D. suzukii, we reviewed recent work on juvenile development, adult reproduction, and seasonal variation in...

  15. A sleep state in Drosophila larvae required for neural stem cell proliferation

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    Szuperak, Milan; Churgin, Matthew A; Borja, Austin J; Raizen, David M; Fang-Yen, Christopher

    2018-01-01

    Sleep during development is involved in refining brain circuitry, but a role for sleep in the earliest periods of nervous system elaboration, when neurons are first being born, has not been explored. Here we identify a sleep state in Drosophila larvae that coincides with a major wave of neurogenesis. Mechanisms controlling larval sleep are partially distinct from adult sleep: octopamine, the Drosophila analog of mammalian norepinephrine, is the major arousal neuromodulator in larvae, but dopamine is not required. Using real-time behavioral monitoring in a closed-loop sleep deprivation system, we find that sleep loss in larvae impairs cell division of neural progenitors. This work establishes a system uniquely suited for studying sleep during nascent periods, and demonstrates that sleep in early life regulates neural stem cell proliferation. PMID:29424688

  16. Functional Characterization of CCHamide and Muscarinic Acetylcholine Receptor Signalling in Drosophila melanogaster

    DEFF Research Database (Denmark)

    Ren, Guilin Robin

    G-protein coupled receptors (GPCRs) constitute a large and ancient superfamily of membraneproteins responsible for the transduction of extracellular signals to the inside of the cells. In thisPh.D. thesis, Drosophila melanogaster (Dm) was used as a model organism to investigate a numberof topics...... is a newly discovered insect peptide hormone. The function of this novel peptide hasnot been well characterised. In this Ph.D. thesis, I identified CCHamide-2 peptides in endocrinecells of the gut and neurones of the brain of larvae and endocrine cells of the gut of adultDrosophila. Behavioural assays...... little is known about muscarinic acetylcholine receptorsignalling in insects. In this study, I found that two types of mAChRs occur in D. melanogaster, onecoupling to Gq (A-type) and the other to Gi (B-type). Both A- and B-type Dm-mAChRs can beactivated by acetylcholine (ACh), but the classical...

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

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    Wylie, Korey P; Rojas, Donald C; Ross, Randal G; Hunter, Sharon K; Maharajh, Keeran; Cornier, Marc-Andre; Tregellas, Jason R

    2014-01-01

    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. 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. 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. 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.

  18. 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

  19. Reproducibility assessment of brain responses to visual food stimuli in adults with overweight and obesity.

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    Drew Sayer, R; Tamer, Gregory G; Chen, Ningning; Tregellas, Jason R; Cornier, Marc-Andre; Kareken, David A; Talavage, Thomas M; McCrory, Megan A; Campbell, Wayne W

    2016-10-01

    The brain's reward system influences ingestive behavior and subsequently obesity risk. Functional magnetic resonance imaging (fMRI) is a common method for investigating brain reward function. This study sought to assess the reproducibility of fasting-state brain responses to visual food stimuli using BOLD fMRI. A priori brain regions of interest included bilateral insula, amygdala, orbitofrontal cortex, caudate, and putamen. Fasting-state fMRI and appetite assessments were completed by 28 women (n = 16) and men (n = 12) with overweight or obesity on 2 days. Reproducibility was assessed by comparing mean fasting-state brain responses and measuring test-retest reliability of these responses on the two testing days. Mean fasting-state brain responses on day 2 were reduced compared with day 1 in the left insula and right amygdala, but mean day 1 and day 2 responses were not different in the other regions of interest. With the exception of the left orbitofrontal cortex response (fair reliability), test-retest reliabilities of brain responses were poor or unreliable. fMRI-measured responses to visual food cues in adults with overweight or obesity show relatively good mean-level reproducibility but considerable within-subject variability. Poor test-retest reliability reduces the likelihood of observing true correlations and increases the necessary sample sizes for studies. © 2016 The Obesity Society.

  20. Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications.

    Science.gov (United States)

    Abou-Antoun, Tamara J; Hale, James S; Lathia, Justin D; Dombrowski, Stephen M

    2017-04-01

    Brain tumors represent some of the most malignant cancers in both children and adults. Current treatment options target the majority of tumor cells but do not adequately target self-renewing cancer stem cells (CSCs). CSCs have been reported to resist the most aggressive radiation and chemotherapies, and give rise to recurrent, treatment-resistant secondary malignancies. With advancing technologies, we now have a better understanding of the genetic, epigenetic and molecular signatures and microenvironmental influences which are useful in distinguishing between distinctly different tumor subtypes. As a result, efforts are now underway to identify and target CSCs within various tumor subtypes based on this foundation. This review discusses progress in CSC biology as it relates to targeted therapies which may be uniquely different between pediatric and adult brain tumors. Studies to date suggest that pediatric brain tumors may benefit more from genetic and epigenetic targeted therapies, while combination treatments aimed specifically at multiple molecular pathways may be more effective in treating adult brain tumors which seem to have a greater propensity towards microenvironmental interactions. Ultimately, CSC targeting approaches in combination with current clinical therapies have the potential to be more effective owing to their ability to compromise CSCs maintenance and the mechanisms which underlie their highly aggressive and deadly nature.

  1. Gap43 transcription modulation in the adult brain depends on sensory activity and synaptic cooperation.

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    Nicole Rosskothen-Kuhl

    Full Text Available Brain development and learning is accompanied by morphological and molecular changes in neurons. The growth associated protein 43 (Gap43, indicator of neurite elongation and synapse formation, is highly expressed during early stages of development. Upon maturation of the brain, Gap43 is down-regulated by most neurons with the exception of subdivisions such as the CA3 region of hippocampus, the lateral superior olive (LSO and the central inferior colliculus (CIC. Little is known about the regulation of this mRNA in adult brains. We found that the expression of Gap43 mRNA in specific neurons can be modulated by changing sensory activity of the adult brain. Using the central auditory system of rats as a model, Gap43 protein and mRNA levels were determined in LSO and CIC of hearing-experienced rats unilaterally or bilaterally deafened or unilaterally stimulated by a cochlear implant (CI. Our data indicate that Gap43 is a marker useful beyond monitoring neuronal growth and synaptogenesis, reflecting also specific patterns of synaptic activities on specific neurons. Thus, unilateral loss of input to an adult auditory system directly causes asymmetrical expression of Gap43 mRNA between LSOs or CICs on both sides of the brainstem. This consequence can be prevented by simple-patterned stimulation of a dysfunctional ear by way of a CI. We suggest that as a function of input balance and activity pattern, Gap43 mRNA expression changes as cells associate converging afferent signals.

  2. Patterning Muscles Using Organizers: Larval Muscle Templates and Adult Myoblasts Actively Interact to Pattern the Dorsal Longitudinal Flight Muscles of Drosophila

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    Roy, Sudipto; VijayRaghavan, K.

    1998-01-01

    Pattern formation in muscle development is often mediated by special cells called muscle organizers. During metamorphosis in Drosophila, a set of larval muscles function as organizers and provide scaffolding for the development of the dorsal longitudinal flight muscles. These organizers undergo defined morphological changes and dramatically split into templates as adult fibers differentiate during pupation. We have investigated the cellular mechanisms involved in the use of larval fibers as templates. Using molecular markers that label myoblasts and the larval muscles themselves, we show that splitting of the larval muscles is concomitant with invasion by imaginal myoblasts and the onset of differentiation. We show that the Erect wing protein, an early marker of muscle differentiation, is not only expressed in myoblasts just before and after fusion, but also in remnant larval nuclei during muscle differentiation. We also show that interaction between imaginal myoblasts and larval muscles is necessary for transformation of the larval fibers. In the absence of imaginal myoblasts, the earliest steps in metamorphosis, such as the escape of larval muscles from histolysis and changes in their innervation, are normal. However, subsequent events, such as the splitting of these muscles, fail to progress. Finally, we show that in a mutant combination, null for Erect wing function in the mesoderm, the splitting of the larval muscles is aborted. These studies provide a genetic and molecular handle for the understanding of mechanisms underlying the use of muscle organizers in muscle patterning. Since the use of such organizers is a common theme in myogenesis in several organisms, it is likely that many of the processes that we describe are conserved. PMID:9606206

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

    Science.gov (United States)

    2017-04-27

    Acoustic Schwannoma; Adult Anaplastic Astrocytoma; Adult Anaplastic Ependymoma; Adult Anaplastic Meningioma; Adult Anaplastic Oligodendroglioma; Adult Brain Stem Glioma; Adult Choroid Plexus Tumor; Adult Craniopharyngioma; Adult Diffuse Astrocytoma; Adult Ependymoblastoma; Adult Ependymoma; Adult Giant Cell Glioblastoma; Adult Glioblastoma; Adult Gliosarcoma; Adult Grade I Meningioma; Adult Grade II Meningioma; Adult Medulloblastoma; Adult Meningeal Hemangiopericytoma; Adult Mixed Glioma; Adult Myxopapillary Ependymoma; Adult Oligodendroglioma; Adult Papillary Meningioma; Adult Pilocytic Astrocytoma; Adult Pineal Gland Astrocytoma; Adult Pineoblastoma; Adult Pineocytoma; Adult Subependymal Giant Cell Astrocytoma; Adult Subependymoma; Adult Supratentorial Primitive Neuroectodermal Tumor (PNET); Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebellar Astrocytoma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebellar Astrocytoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Medulloepithelioma; Childhood Supratentorial Ependymoma; Meningeal Melanocytoma; Newly Diagnosed Childhood Ependymoma; Recurrent Adult Brain Tumor; Recurrent Childhood Anaplastic Astrocytoma; Recurrent Childhood Anaplastic Oligoastrocytoma; Recurrent Childhood Anaplastic Oligodendroglioma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Diffuse Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Fibrillary Astrocytoma; Recurrent Childhood Gemistocytic Astrocytoma; Recurrent Childhood Giant Cell Glioblastoma; Recurrent Childhood Glioblastoma; Recurrent Childhood Gliomatosis Cerebri; Recurrent Childhood Gliosarcoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood

  4. Organotypic hippocampal slice culture from the adult mouse brain: a versatile tool for translational neuropsychopharmacology.

    Science.gov (United States)

    Kim, Hyunjeong; Kim, Eosu; Park, Minsun; Lee, Eun; Namkoong, Kee

    2013-03-05

    One of the most significant barriers towards translational neuropsychiatry would be an unavailability of living brain tissues. Although organotypic brain tissue culture could be a useful alternative enabling observation of temporal changes induced by various drugs in living brain tissues, a proper method to establish a stable organotypic brain slice culture system using adult (rather than neonatal) hippocampus has been still elusive. In this study, we evaluated our simple method using the serum-free culture medium for successful adult organotypic hippocampal slice culture. Several tens of hippocampal slices from a single adult mouse (3-5 months old) were cultured in serum-free versus serum-containing conventional culture medium for 30 days and underwent various experiments to validate the effects of the existence of serum in the culture medium. Neither the excessive regression of neuronal viability nor metabolic deficiency was observed in the serum-free medium culture in contrast to the serum-containing medium culture. Despite such viability, newly generated immature neurons were scarcely detected in the serum-free culture, suggesting that the original neurons in the brain slice persist rather than being replaced by neurogenesis. Key structural features of in vivo neural tissue constituting astrocytes, neural processes, and pre- and post-synapses were also well preserved in the serum-free culture. In conclusion, using the serum-free culture medium, the adult hippocampal slice culture system will serve as a promising ex vivo tool for various fields of neuroscience, especially for studies on aging-related neuropsychiatric disorders or for high throughput screening of potential agents working against such disorders. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Adult and embryonic GAD transcripts are spatiotemporally regulated during postnatal development in the rat brain.

    Directory of Open Access Journals (Sweden)

    Anke Popp

    Full Text Available BACKGROUND: GABA (gamma-aminobutyric acid, the main inhibitory neurotransmitter in the brain, is synthesized by glutamic acid decarboxylase (GAD. GAD exists in two adult isoforms, GAD65 and GAD67. During embryonic brain development at least two additional transcripts exist, I-80 and I-86, which are distinguished by insertions of 80 or 86 bp into GAD67 mRNA, respectively. Though it was described that embryonic GAD67 transcripts are not detectable during adulthood there are evidences suggesting re-expression under certain pathological conditions in the adult brain. In the present study we systematically analyzed for the first time the spatiotemporal distribution of different GADs with emphasis on embryonic GAD67 mRNAs in the postnatal brain using highly sensitive methods. METHODOLOGY/PRINCIPAL FINDINGS: QPCR was used to precisely investigate the postnatal expression level of GAD related mRNAs in cortex, hippocampus, cerebellum, and olfactory bulb of rats from P1 throughout adulthood. Within the first three postnatal weeks the expression of both GAD65 and GAD67 mRNAs reached adult levels in hippocampus, cortex, and cerebellum. The olfactory bulb showed by far the highest expression of GAD65 as well as GAD67 transcripts. Embryonic GAD67 splice variants were still detectable at birth. They continuously declined to barely detectable levels during postnatal development in all investigated regions with exception of a comparatively high expression in the olfactory bulb. Radioactive in situ hybridizations confirmed the occurrence of embryonic GAD67 transcripts in the olfactory bulb and furthermore detected their localization mainly in the subventricular zone and the rostral migratory stream. CONCLUSIONS/SIGNIFICANCE: Embryonic GAD67 transcripts can hardly be detected in the adult brain, except for specific regions associated with neurogenesis and high synaptic plasticity. Therefore a functional role in processes like proliferation, migration or

  6. Neurotrophin-4 in the brain of adult Nothobranchius furzeri.

    Science.gov (United States)

    D'Angelo, L; Avallone, L; Cellerino, A; de Girolamo, P; Paolucci, M; Varricchio, E; Lucini, C

    2016-09-01

    Neurotrophin-4 (NT-4) is a member of the well-known family of neurotrophins that regulate the development of neuronal networks by participating in neuronal survival and differentiation, the growth of neuronal processes, synaptic development and plasticity, as well as myelination. NT-4 interacts with two distinct receptors: TrkB, high affinity receptor and p75 low-affinity neurotrophin receptor (p75(NTR)). In the present survey, we identified the gene encoding NT-4 in the teleost Nothobranchius furzeri, a model species for aging research. The identified gene shows a similarity of about 72% with medaka, the closest related species. The neuroanatomical localization of NT-4 mRNA is obtained by using an LNA probe. NT-4 mRNA expression is observed in neurons and glial cells of the forebrain and hindbrain, with very low signal found in the midbrain. This survey confirms that NT-4 is expressed in the brain of N. furzeri during adulthood, suggesting that it could also be implicated in the maintenance and regulation of neuronal functions. Copyright © 2016 Elsevier GmbH. All rights reserved.

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

    International Nuclear Information System (INIS)

    Lee, Myoung Hoon; Yoon, Seok Nam; Joh, Chul Woo; Lee, Dong Soo; Lee, Jae Sung

    2002-01-01

    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

  8. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. An exploration of the experiences of young adults who acquired a brain injury

    OpenAIRE

    Schrover, Isabella

    2015-01-01

    In the United Kingdom at least 15,600 young adults are admitted to hospital following an acquired brain injury each year. For those who survive, the brain injury-related consequences to their psychological well-being (e.g. feelings of anxiety and low mood, low self-esteem) and social environment (e.g. very limited social support, loss of relationships and friendships) are understood to be the ones that have the most effect on a young person’s life in the long term. The social environment, suc...

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

    International Nuclear Information System (INIS)

    Shahbazian, F.M.

    1985-01-01

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

  12. The association between adverse childhood experiences and adult traumatic brain injury/concussion: a scoping review.

    Science.gov (United States)

    Ma, Zechen; Bayley, Mark T; Perrier, Laure; Dhir, Priya; Dépatie, Lana; Comper, Paul; Ruttan, Lesley; Lay, Christine; Munce, Sarah E P

    2018-01-12

    Adverse childhood experiences are significant risk factors for physical and mental illnesses in adulthood. Traumatic brain injury/concussion is a challenging condition where pre-injury factors may affect recovery. The association between childhood adversity and traumatic brain injury/concussion has not been previously reviewed. The research question addressed is: What is known from the existing literature about the association between adverse childhood experiences and traumatic brain injury/concussion in adults? All original studies of any type published in English since 2007 on adverse childhood experiences and traumatic brain injury/concussion outcomes were included. The literature search was conducted in multiple electronic databases. Arksey and O'Malley and Levac et al.'s scoping review frameworks were used. Two reviewers independently completed screening and data abstraction. The review yielded six observational studies. Included studies were limited to incarcerated or homeless samples, and individuals at high-risk of or with mental illnesses. Across studies, methods for childhood adversity and traumatic brain injury/concussion assessment were heterogeneous. A positive association between adverse childhood experiences and traumatic brain injury occurrence was identified. The review highlights the importance of screening and treatment of adverse childhood experiences. Future research should extend to the general population and implications on injury recovery. Implications for rehabilitation Exposure to adverse childhood experiences is associated with increased risk of traumatic brain injury. Specific types of adverse childhood experiences associated with risk of traumatic brain injury include childhood physical abuse, psychological abuse, household member incarceration, and household member drug abuse. Clinicians and researchers should inquire about adverse childhood experiences in all people with traumatic brain injury as pre-injury health conditions can

  13. The influences of silent cerebral infarction and hypertension on brain atrophy in normal adults

    International Nuclear Information System (INIS)

    Zhefeng, Quan; Bokura, Hirokazu; Iijima, Kenichi; Oguro, Hiroaki; Yamaguchi, Shuhei

    2008-01-01

    We studied the influences of silent brain infarction (SBI) and hypertension on brain atrophy and its longitudinal progression in healthy adults. MRI scans were performed on 109 neurologically normal adults (mean age, 58.6±5.8 years), with follow-up at an average of 4.9 years later. Patient histories of hypertension, smoking habits, and alcohol consumption were examined. We evaluated brain atrophy using the brain atrophy index (BAI; the ratio of the brain area to the intracranial area) and the ventricular atrophy index (VAI; the ratio of the ventricular area to the brain area) on MRI T1-weighted images at the levels of the basal ganglia and lateral ventricle in horizontal sections. There were no differences in age, sex, dyslipidemia, body mass index (BMI), smoking habit, and alcohol consumption between the normal group and the SBI or hypertension group. The BAI was significantly lower at entry for the SBI (+) group than for the SBI (-) group at both the basal ganglia and lateral ventricle levels (basal ganglia level, p=0.02; and lateral ventricle level, p=0.05). Moreover, the VAI was significantly higher at entry for the SBI (+) group than for the SBI (-) group at the lateral ventricle level (p=0.03). Furthermore, the BAI was significantly lower at entry for the hypertensive group than for the non-hypertensive group at the basal ganglia level (p=0.007). There were no significant differences in the annual variations of the BAI and VAI between the normal group and the SBI (+) or hypertensive group. The present results suggest that the SBI and hypertension are accelerating factors for brain atrophy and ventricular dilatation. (author)

  14. The influences of silent cerebral infarction and hypertension on brain atrophy in normal adults

    Energy Technology Data Exchange (ETDEWEB)

    Zhefeng, Quan; Bokura, Hirokazu; Iijima, Kenichi; Oguro, Hiroaki; Yamaguchi, Shuhei [Shimane Univ., Faculty of Medicine, Izumo, Shimane (Japan)

    2008-03-15

    We studied the influences of silent brain infarction (SBI) and hypertension on brain atrophy and its longitudinal progression in healthy adults. MRI scans were performed on 109 neurologically normal adults (mean age, 58.6{+-}5.8 years), with follow-up at an average of 4.9 years later. Patient histories of hypertension, smoking habits, and alcohol consumption were examined. We evaluated brain atrophy using the brain atrophy index (BAI; the ratio of the brain area to the intracranial area) and the ventricular atrophy index (VAI; the ratio of the ventricular area to the brain area) on MRI T1-weighted images at the levels of the basal ganglia and lateral ventricle in horizontal sections. There were no differences in age, sex, dyslipidemia, body mass index (BMI), smoking habit, and alcohol consumption between the normal group and the SBI or hypertension group. The BAI was significantly lower at entry for the SBI (+) group than for the SBI (-) group at both the basal ganglia and lateral ventricle levels (basal ganglia level, p=0.02; and lateral ventricle level, p=0.05). Moreover, the VAI was significantly higher at entry for the SBI (+) group than for the SBI (-) group at the lateral ventricle level (p=0.03). Furthermore, the BAI was significantly lower at entry for the hypertensive group than for the non-hypertensive group at the basal ganglia level (p=0.007). There were no significant differences in the annual variations of the BAI and VAI between the normal group and the SBI (+) or hypertensive group. The present results suggest that the SBI and hypertension are accelerating factors for brain atrophy and ventricular dilatation. (author)

  15. Brain metabolism and memory in age differentiated healthy adults

    International Nuclear Information System (INIS)

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

    1984-01-01

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

  16. Limited taste discrimination in Drosophila.

    Science.gov (United States)

    Masek, Pavel; Scott, Kristin

    2010-08-17

    In the gustatory systems of mammals and flies, different populations of sensory cells recognize different taste modalities, such that there are cells that respond selectively to sugars and others to bitter compounds. This organization readily allows animals to distinguish compounds of different modalities but may limit the ability to distinguish compounds within one taste modality. Here, we developed a behavioral paradigm in Drosophila melanogaster to evaluate directly the tastes that a fly distinguishes. These studies reveal that flies do not discriminate among different sugars, or among different bitter compounds, based on chemical identity. Instead, flies show a limited ability to distinguish compounds within a modality based on intensity or palatability. Taste associative learning, similar to olfactory learning, requires the mushroom bodies, suggesting fundamental similarities in brain mechanisms underlying behavioral plasticity. Overall, these studies provide insight into the discriminative capacity of the Drosophila gustatory system and the modulation of taste behavior.

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

    Science.gov (United States)

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

    2013-01-01

    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. 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). 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. 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. UMIN Clinical Trial Registry 000005618.

  18. 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

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

    International Nuclear Information System (INIS)

    Zhao Jinhua; Lin Xiangtong; Jiang Kaida; Ang Qiuqing; Shi Shenxun; Xue Fangping

    2000-01-01

    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 99 Tc m -ECD SPECT were performed on 25 of the 39 adult patients with depression and 17 normal adult controls. Baseline 99 Tc m -ECD SPECT only was performed on the remaining 14 patients with depression. Baseline and cognitively activated 99 Tc m -ECD SPECT were performed on 12 of the 18 elderly patients with depression and 18 of the 21 normal elderly controls. Baseline 99 Tc m -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

  20. 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 because its exogenous administration to rodents enhanced astrogliosis after adult or neonatal insults. A lack of requirement for endogenous IFN-gamma was demonstrated by three lines of evidence. First, no increase in IFN-gamma transcripts could be found at injury. Second, the administration...

  1. Competition among oxidizable substrates in brains of young and adult rats. Dissociated cells.

    OpenAIRE

    Roeder, L M; Tildon, J T; Holman, D C

    1984-01-01

    The rates of conversion of D-(-)-3-hydroxy[3-14C]butyrate, [3-14C]acetoacetate, [6-14C]glucose and [U-14C]glutamine into 14CO2 were measured in the presence and absence of alternative oxidizable substrates in intact dissociated cells from the brains of young and adult rats. When unlabelled glutamine was added to [6-14C]glucose or unlabelled glucose was added to [U-14C]glutamine, the rate of 14CO2 production was decreased in both young and adult rats. The rate of oxidation of 3-hydroxy[3-14C]b...

  2. Genetic Dissection of Aversive Associative Olfactory Learning and Memory in Drosophila Larvae.

    Science.gov (United States)

    Widmann, Annekathrin; Artinger, Marc; Biesinger, Lukas; Boepple, Kathrin; Peters, Christina; Schlechter, Jana; Selcho, Mareike; Thum, Andreas S

    2016-10-01

    Memory formation is a highly complex and dynamic process. It consists of different phases, which depend on various neuronal and molecular mechanisms. In adult Drosophila it was shown that memory formation after aversive Pavlovian conditioning includes-besides other forms-a labile short-term component that consolidates within hours to a longer-lasting memory. Accordingly, memory formation requires the timely controlled action of different neuronal circuits, neurotransmitters, neuromodulators and molecules that were initially identified by classical forward genetic approaches. Compared to adult Drosophila, memory formation was only sporadically analyzed at its larval stage. Here we deconstruct the larval mnemonic organization after aversive olfactory conditioning. We show that after odor-high salt conditioning larvae form two parallel memory phases; a short lasting component that depends on cyclic adenosine 3'5'-monophosphate (cAMP) signaling and synapsin gene function. In addition, we show for the first time for Drosophila larvae an anesthesia resistant component, which relies on radish and bruchpilot gene function, protein kinase C activity, requires presynaptic output of mushroom body Kenyon cells and dopamine function. Given the numerical simplicity of the larval nervous system this work offers a unique prospect for studying memory formation of defined specifications, at full-brain scope with single-cell, and single-synapse resolution.

  3. Genetic Dissection of Aversive Associative Olfactory Learning and Memory in Drosophila Larvae

    Science.gov (United States)

    Widmann, Annekathrin; Artinger, Marc; Biesinger, Lukas; Boepple, Kathrin; Schlechter, Jana; Selcho, Mareike; Thum, Andreas S.

    2016-01-01

    Memory formation is a highly complex and dynamic process. It consists of different phases, which depend on various neuronal and molecular mechanisms. In adult Drosophila it was shown that memory formation after aversive Pavlovian conditioning includes—besides other forms—a labile short-term component that consolidates within hours to a longer-lasting memory. Accordingly, memory formation requires the timely controlled action of different neuronal circuits, neurotransmitters, neuromodulators and molecules that were initially identified by classical forward genetic approaches. Compared to adult Drosophila, memory formation was only sporadically analyzed at its larval stage. Here we deconstruct the larval mnemonic organization after aversive olfactory conditioning. We show that after odor-high salt conditioning larvae form two parallel memory phases; a short lasting component that depends on cyclic adenosine 3’5’-monophosphate (cAMP) signaling and synapsin gene function. In addition, we show for the first time for Drosophila larvae an anesthesia resistant component, which relies on radish and bruchpilot gene function, protein kinase C activity, requires presynaptic output of mushroom body Kenyon cells and dopamine function. Given the numerical simplicity of the larval nervous system this work offers a unique prospect for studying memory formation of defined specifications, at full-brain scope with single-cell, and single-synapse resolution. PMID:27768692

  4. Genetic Dissection of Aversive Associative Olfactory Learning and Memory in Drosophila Larvae.

    Directory of Open Access Journals (Sweden)

    Annekathrin Widmann

    2016-10-01

    Full Text Available Memory formation is a highly complex and dynamic process. It consists of different phases, which depend on various neuronal and molecular mechanisms. In adult Drosophila it was shown that memory formation after aversive Pavlovian conditioning includes-besides other forms-a labile short-term component that consolidates within hours to a longer-lasting memory. Accordingly, memory formation requires the timely controlled action of different neuronal circuits, neurotransmitters, neuromodulators and molecules that were initially identified by classical forward genetic approaches. Compared to adult Drosophila, memory formation was only sporadically analyzed at its larval stage. Here we deconstruct the larval mnemonic organization after aversive olfactory conditioning. We show that after odor-high salt conditioning larvae form two parallel memory phases; a short lasting component that depends on cyclic adenosine 3'5'-monophosphate (cAMP signaling and synapsin gene function. In addition, we show for the first time for Drosophila larvae an anesthesia resistant component, which relies on radish and bruchpilot gene function, protein kinase C activity, requires presynaptic output of mushroom body Kenyon cells and dopamine function. Given the numerical simplicity of the larval nervous system this work offers a unique prospect for studying memory formation of defined specifications, at full-brain scope with single-cell, and single-synapse resolution.

  5. Central Artery Stiffness, Baroreflex Sensitivity, and Brain White Matter Neuronal Fiber Integrity in Older Adults

    Science.gov (United States)

    Tarumi, Takashi; de Jong, Daan L.K.; Zhu, David C.; Tseng, Benjamin Y.; Liu, Jie; Hill, Candace; Riley, Jonathan; Womack, Kyle B.; Kerwin, Diana R.; Lu, Hanzhang; Cullum, C. Munro; Zhang, Rong

    2015-01-01

    Cerebral hypoperfusion elevates the risk of brain white matter (WM) lesions and cognitive impairment. Central artery stiffness impairs baroreflex, which controls systemic arterial perfusion, and may deteriorate neuronal fiber integrity of brain WM. The purpose of this study was to examine the associations among brain WM neuronal fiber integrity, baroreflex sensitivity (BRS), and central artery stiffness in older adults. Fifty-four adults (65±6 years) with normal cognitive function or mild cognitive impairment (MCI) were tested. The neuronal fiber integrity of brain WM was assessed from diffusion metrics acquired by diffusion tensor imaging. BRS was measured in response to acute changes in blood pressure induced by bolus injections of vasoactive drugs. Central artery stiffness was measured by carotid-femoral pulse wave velocity (cfPWV). The WM diffusion metrics including fractional anisotropy (FA) and radial (RD) and axial (AD) diffusivities, BRS, and cfPWV were not different between the control and MCI groups. Thus, the data from both groups were combined for subsequent analyses. Across WM, fiber tracts with decreased FA and increased RD were associated with lower BRS and higher cfPWV, with many of the areas presenting spatial overlap. In particular, the BRS assessed during hypotension was strongly correlated with FA and RD when compared with hypertension. Executive function performance was associated with FA and RD in the areas that correlated with cfPWV and BRS. These findings suggest that baroreflex-mediated control of systemic arterial perfusion, especially during hypotension, may play a crucial role in maintaining neuronal fiber integrity of brain WM in older adults. PMID:25623500

  6. Spatio-temporal neural stem cell behavior that leads to both perfect and imperfect structural brain regeneration in adult newts.

    Science.gov (United States)

    Urata, Yuko; Yamashita, Wataru; Inoue, Takeshi; Agata, Kiyokazu

    2018-06-14

    Adult newts can regenerate large parts of their brain from adult neural stem cells (NSCs), but how adult NSCs reorganize brain structures during regeneration remains unclear. In development, elaborate brain structures are produced under broadly coordinated regulations of embryonic NSCs in the neural tube, whereas brain regeneration entails exquisite control of the reestablishment of certain brain parts, suggesting a yet-unknown mechanism directs NSCs upon partial brain excision. Here we report that upon one-quarter excision of the adult newt ( Pleurodeles waltl ) mesencephalon, active participation of local NSCs around specific brain subregions' boundaries leads to some imperfect and some perfect brain regeneration along an individual's rostrocaudal axis. Regeneration phenotypes depend on how the wound closing occurs using local NSCs, and perfect regeneration replicates development-like processes but takes more than one year. Our findings indicate that newt brain regeneration is supported by modularity of boundary-domain NSCs with self-organizing ability in neighboring fields. © 2018. Published by The Company of Biologists Ltd.

  7. Dynamic regulation of NMDAR function in the adult brain by the stress hormone corticosterone

    Directory of Open Access Journals (Sweden)

    Yiu Chung eTse

    2012-03-01

    Full Text Available Stress and corticosteroids dynamically modulate the expression of synaptic plasticity at glutamatergic synapses in the developed brain. Together with alpha-amino-3-hydroxy-methyl-4-isoxazole propionic acid receptors (AMPAR, N-methyl-D-aspartate receptors (NMDAR are critical mediators of synaptic function and are essential for the induction of many forms of synaptic plasticity. Regulation of NMDAR function by cortisol/corticosterone (CORT may be fundamental to the effects of stress on synaptic plasticity. Recent reports of the efficacy of NMDAR antagonists in treating certain stress-associated psychopathologies further highlight the importance of understanding the regulation of NMDAR function by CORT. Knowledge of how corticosteroids regulate NMDAR function within the adult brain is relatively sparse, perhaps due to a common belief that NMDAR function is relatively stable in the adult brain. We review recent results from our laboratory and others demonstrating dynamic regulation of NMDAR function by CORT in the adult brain. In addition, we consider the issue of how differences in the early life environment may program differential sensitivity to modulation of NMDAR function by CORT and how this may influence synaptic function during stress. Findings from these studies demonstrate that NMDAR function in the adult hippocampus remains sensitive to even brief exposures to CORT and that the capacity for modulation of NMDAR may be programmed, in part, by the early life environment. Modulation of NMDAR function may contribute to dynamic regulation of synaptic plasticity and adaptation in the face of stress, however enhanced NMDAR function may be implicated in mechanisms of stress related psychopathologies including depression.

  8. Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats.

    Science.gov (United States)

    Pong, Alice C; Jugé, Lauriane; Bilston, Lynne E; Cheng, Shaokoon

    2017-01-01

    Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus.

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

    International Nuclear Information System (INIS)

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

    2012-01-01

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

  10. Hippotherapy in adult patients with chronic brain disorders: a pilot study.

    Science.gov (United States)

    Sunwoo, Hyuk; Chang, Won Hyuk; Kwon, Jeong-Yi; Kim, Tae-Won; Lee, Ji-Young; Kim, Yun-Hee

    2012-12-01

    To investigate the effects of hippotherapy for adult patients with brain disorders. Eight chronic brain disorder patients (7 males, mean age 42.4±16.6 years) were recruited. The mean duration from injury was 7.9±7.7 years. The diagnoses were stroke (n=5), traumatic brain disorder (n=2), and cerebral palsy (n=1). Hippotherapy sessions were conducted twice a week for eight consecutive weeks in an indoor riding arena. Each hippotherapy session lasted 30 minutes. All participants were evaluated by the Berg balance scale, Tinetti Performance-Oriented Mobility Assessment, 10 Meter Walking Test, Functional Ambulatory Category, Korean Beck Depression Inventory, and Hamilton Depression Rating Scale. We performed baseline assessments twice just before starting hippotherapy. We also assessed the participants immediately after hippotherapy and at eight weeks after hippotherapy. All participants showed no difference in balance, gait function, and emotion between the two baseline assessments before hippotherapy. During the eight-week hippotherapy program, all participants showed neither adverse effects nor any accidents; all had good compliance. After hippotherapy, there were significant improvements in balance and gait speed in comparison with the baseline assessment (phippotherapy. However, there was no significant difference in emotion after hippotherapy. We could observe hippotherapy to be a safe and effective alternative therapy for adult patients with brain disorders in improving balance and gait function. Further future studies are warranted to delineate the benefits of hippotherapy on chronic stroke patients.

  11. Dynamic Remodeling of Pericytes In Vivo Maintains Capillary Coverage in the Adult Mouse Brain

    Directory of Open Access Journals (Sweden)

    Andrée-Anne Berthiaume

    2018-01-01

    Full Text Available Summary: Direct contact and communication between pericytes and endothelial cells is critical for maintenance of cerebrovascular stability and blood-brain barrier function. Capillary pericytes have thin processes that reach hundreds of micrometers along the capillary bed. The processes of adjacent pericytes come in close proximity but do not overlap, yielding a cellular chain with discrete territories occupied by individual pericytes. Little is known about whether this pericyte chain is structurally dynamic in the adult brain. Using in vivo two-photon imaging in adult mouse cortex, we show that while pericyte somata were immobile, the tips of their processes underwent extensions and/or retractions over days. The selective ablation of single pericytes provoked exuberant extension of processes from neighboring pericytes to contact uncovered regions of the endothelium. Uncovered capillary regions had normal barrier function but were dilated until pericyte contact was regained. Pericyte structural plasticity may be critical for cerebrovascular health and warrants detailed investigation. : Pericyte-endothelial contact is important for many aspects of cerebrovascular health. Berthiaume et al. use longitudinal two-photon imaging to show that the processes of brain capillary pericytes are structurally plastic in vivo. Their processes can grow hundreds of micrometers to ensure contact with exposed endothelium following ablation of a single pericyte. Keywords: capillary, pericyte, endothelium, blood-brain barrier, blood flow, plasticity, two-photon imaging, Alzheimer’s disease, dementia, stroke

  12. Midsagittal brain variation and MRI shape analysis of the precuneus in adult individuals

    Science.gov (United States)

    Bruner, Emiliano; Rangel de Lázaro, Gizéh; de la Cuétara, José Manuel; Martín-Loeches, Manuel; Colom, Roberto; Jacobs, Heidi I L

    2014-01-01

    Recent analyses indicate that the precuneus is one of the main centres of integration in terms of functional and structural processes within the human brain. This neuroanatomical element is formed by different subregions, involved in visuo-spatial integration, memory and self-awareness. We analysed the midsagittal brain shape in a sample of adult humans (n = 90) to evidence the patterns of variability and geometrical organization of this area. Interestingly, the major brain covariance pattern within adult humans is strictly associated with the relative proportions of the precuneus. Its morphology displays a marked individual variation, both in terms of geometry (mostly in its longitudinal dimensions) and anatomy (patterns of convolution). No patent differences are evident between males and females, and the allometric effect of size is minimal. However, in terms of morphology, the precuneus does not represent an individual module, being influenced by different neighbouring structures. Taking into consideration the apparent involvement of the precuneus in higher-order human brain functions and evolution, its wide variation further stresses the important role of these deep parietal areas in modern neuroanatomical organization. PMID:24397462

  13. Increased frontal functional networks in adult survivors of childhood brain tumors

    Directory of Open Access Journals (Sweden)

    Hongbo Chen

    2016-01-01

    Full Text Available Childhood brain tumors and associated treatment have been shown to affect brain development and cognitive outcomes. Understanding the functional connectivity of brain many years after diagnosis and treatment may inform the development of interventions to improve the long-term outcomes of adult survivors of childhood brain tumors. This work investigated the frontal region functional connectivity of 16 adult survivors of childhood cerebellar tumors after an average of 14.9 years from diagnosis and 16 demographically-matched controls using resting state functional MRI (rs-fMRI. Independent component analysis (ICA was applied to identify the resting state activity from rs-fMRI data and to select the specific regions associated with executive functions, followed by the secondary analysis of the functional networks connecting these regions. It was found that survivors exhibited differences in the functional connectivity in executive control network (ECN, default mode network (DMN and salience network (SN compared to demographically-matched controls. More specifically, the number of functional connectivity observed in the survivors is higher than that in the controls, and with increased strength, or stronger correlation coefficient between paired seeds, in survivors compared to the controls. Observed hyperconnectivity in the selected frontal functional network thus is consistent with findings in patients with other neurological injuries and diseases.

  14. Neurogenetics of female reproductive behaviors in Drosophila melanogaster

    NARCIS (Netherlands)

    Laturney, Meghan; Billeter, Jean-Christophe; Friedmann, T; Dunlap, JC; Goodwin, SF

    2014-01-01

    We follow an adult Drosophila melanogaster female through the major reproductive decisions she makes during her lifetime, including habitat selection, precopulatory mate choice, postcopulatory physiological changes, polyandry, and egg-laying site selection. In the process, we review the molecular

  15. Regulation by commensal bacteria of neurogenesis in the subventricular zone of adult mouse brain.

    Science.gov (United States)

    Sawada, Naoki; Kotani, Takenori; Konno, Tasuku; Setiawan, Jajar; Nishigaito, Yuka; Saito, Yasuyuki; Murata, Yoji; Nibu, Ken-Ichi; Matozaki, Takashi

    2018-04-15

    In the mouse olfactory bulb (OB), interneurons such as granule cells and periglomerular cells are continuously replaced by adult-born neurons, which are generated in the subventricular zone (SVZ) of the brain. We have now investigated the role of commensal bacteria in regulation of such neuronal cell turnover in the adult mouse brain. Administration of mixture of antibiotics to specific pathogen-free (SPF) mice markedly attenuated the incorporation of bromodeoxyuridine (BrdU) into the SVZ cells. The treatment with antibiotics also reduced newly generated BrdU-positive neurons in the mouse OB. In addition, the incorporation of BrdU into the SVZ cells of germ-free (GF) mice was markedly reduced compared to that apparent for SPF mice. In contrast, the reduced incorporation of BrdU into the SVZ cells of GF mice was recovered by their co-housing with SPF mice, suggesting that commensal bacteria promote the incorporation of BrdU into the SVZ cells. Finally, we found that administration of ampicillin markedly attenuated the incorporation of BrdU into the SVZ cells of SPF mice. Our results thus suggest that ampicillin-sensitive commensal bacteria regulate the neurogenesis in the SVZ of adult mouse brain. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-06-28

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

  17. Embryonic expression of shuttle craft, a Drosophila gene involved in neuron development, is associated with adult lifespan.

    Science.gov (United States)

    Roshina, Natalia V; Symonenko, Alexander V; Krementsova, Anna V; Trostnikov, Mikhail V; Pasyukova, Elena G

    2014-12-01

    Despite the progress in aging research that highlights the role of the nervous system in longevity, whether genes that control development and consequently structure of the nervous system affect lifespan is unclear. We demonstrated that a mutation inshuttle craft, a gene involved in the nervous system development, increased the lifespan of unmated females and decreased the lifespan of mated females, without affecting males. Precise reversions of the mutation lead to the restoration of the lifespan specific to control females. In mutant unmated females, increased lifespan was associated with elevated locomotion at older ages, indicating slowed aging. In mutant mated females, reproduction was decreased compared to controls, indicating a lack of tradeoff between this trait and lifespan. No differences in shuttle craft transcription were observed between whole bodies, ovaries, and brains of mutant and control females of different ages, either unmated or mated. The amount of shuttle craft transcript appeared to be substantially decreased in mutant embryos. Our results demonstrated that a gene that regulates development of the nervous system might also influence longevity, and thus expanded the spectrum of genes involved in lifespan control. We hypothesize that this "carry-over" effect might be the result of transcription regulation in embryos.

  18. 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.

  19. 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.

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

    Science.gov (United States)

    Acosta-Cabronero, Julio; Betts, Matthew J; Cardenas-Blanco, Arturo; Yang, Shan; Nestor, Peter J

    2016-01-13

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

  1. Low fetal hemoglobin percentage is associated with silent brain lesions in adults with homozygous sickle cell disease

    OpenAIRE

    Calvet, David; Tuilier, Titien; Mélé, Nicolas; Turc, Guillaume; Habibi, Anoosha; Abdallah, Nassim Ait; Majhadi, Loubna; Hemery, François; Edjlali, Myriam; Galacteros, Frédéric; Bartolucci, Pablo

    2017-01-01

    Low %HbF is independently associated with silent WMCs on brain imaging in adults with SCD.Our results highlight the potential use of therapeutic strategies inducing HbF expression in SCD patients with silent white matter changes.

  2. Recent Advances on the Role of Neurogenesis in the Adult Brain: Therapeutic Potential in Parkinson's and Alzheimer's Diseases.

    Science.gov (United States)

    Radad, Khaled; Moldzio, Rudolf; Al-Shraim, Mubarak; Kranner, Barbara; Krewenka, Christopher; Rausch, Wolf-Dieter

    2017-01-01

    Generation of nascent functional neurons from neural stem cells in the adult brain has recently become largely accepted by the neuroscience community. In adult mammals including humans, the process of neurogenesis has been well documented in two brain regions; the subventricular zone of the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus. Some evidence has indicated neurogenesis in other regions of the adult mammalian brain such as the neocortex, cerebellum, striatum, amygdala and hypothalamus. These discoveries question a long standing dogma on nervous system regeneration and provide medical science with potential new strategies to harness the process of neurogenesis for treating neurological disabilities and neurodegenerative diseases. In this current review, we address the most recent advances on the role of neurogenesis in the adult brain and therapeutic potential in the two most common neurodegenerative disorders, Parkinson's and Alzheimer's diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. From Blood to Brain: Adult-Born Neurons in the Crayfish Brain Are the Progeny of Cells Generated by the Immune System

    Directory of Open Access Journals (Sweden)

    Barbara S. Beltz

    2017-12-01

    Full Text Available New neurons continue to be born and integrated into the brains of adult decapod crustaceans. Evidence in crayfish indicates that the 1st-generation neural precursors that generate these adult-born neurons originate in the immune system and travel to the neurogenic niche via the circulatory system. These precursors are attracted to the niche, become integrated amongst niche cells, and undergo mitosis within a few days; both daughters of this division migrate away from the niche toward the brain clusters where they will divide again and differentiate into neurons. In the crustacean brain, the rate of neuronal production is highly sensitive to serotonin (5-hydroxytryptamine, 5-HT levels. These effects are lineage-dependent, as serotonin's influence is limited to late 2nd-generation neural precursors and their progeny. Experiments indicate that serotonin regulates adult neurogenesis in the crustacean brain by multiple mechanisms: via direct effects of serotonin released from brain neurons into the hemolymph or by local release onto target cells, or by indirect influences via a serotonin-mediated release of agents from other regions, such as hormones from the sinus gland and cytokines from hematopoietic tissues. Evidence in crayfish also indicates that serotonin mediates the attraction of neural precursors generated by the immune system to the neurogenic niche. Thus, studies in the crustacean brain have revealed multiple roles for this monoamine in adult neurogenesis, and identified several pathways by which serotonin influences the generation of new neurons.

  4. Defining Optimal Brain Health in Adults: A Presidential Advisory From the American Heart Association/American Stroke Association.

    Science.gov (United States)

    Gorelick, Philip B; Furie, Karen L; Iadecola, Costantino; Smith, Eric E; Waddy, Salina P; Lloyd-Jones, Donald M; Bae, Hee-Joon; Bauman, Mary Ann; Dichgans, Martin; Duncan, Pamela W; Girgus, Meighan; Howard, Virginia J; Lazar, Ronald M; Seshadri, Sudha; Testai, Fernando D; van Gaal, Stephen; Yaffe, Kristine; Wasiak, Hank; Zerna, Charlotte

    2017-10-01

    Cognitive function is an important component of aging and predicts quality of life, functional independence, and risk of institutionalization. Advances in our understanding of the role of cardiovascular risks have shown them to be closely associated with cognitive impairment and dementia. Because many cardiovascular risks are modifiable, it may be possible to maintain brain health and to prevent dementia in later life. The purpose of this American Heart Association (AHA)/American Stroke Association presidential advisory is to provide an initial definition of optimal brain health in adults and guidance on how to maintain brain health. We identify metrics to define optimal brain health in adults based on inclusion of factors that could be measured, monitored, and modified. From these practical considerations, we identified 7 metrics to define optimal brain health in adults that originated from AHA's Life's Simple 7: 4 ideal health behaviors (nonsmoking, physical activity at goal levels, healthy diet consistent with current guideline levels, and body mass index brain health but recognize that the truly ideal circumstance may be uncommon because there is a continuum of brain health as demonstrated by AHA's Life's Simple 7. Therefore, there is opportunity to improve brain health through primordial prevention and other interventions. Furthermore, although cardiovascular risks align well with brain health, we acknowledge that other factors differing from those related to cardiovascular health may drive cognitive health. Defining optimal brain health in adults and its maintenance is consistent with the AHA's Strategic Impact Goal to improve cardiovascular health of all Americans by 20% and to reduce deaths resulting from cardiovascular disease and stroke by 20% by the year 2020. This work in defining optimal brain health in adults serves to provide the AHA/American Stroke Association with a foundation for a new strategic direction going forward in cardiovascular health

  5. The whole-brain N-acetylaspartate correlates with education in normal adults.

    Science.gov (United States)

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

    2012-10-30

    N-acetylaspartate (NAA) is an index of neuronal integrity. We hypothesized that in healthy subjects its whole brain concentration (WBNAA) may be related to formal educational attainment, a common proxy for cognitive reserve. To test this hypothesis, 97 middle aged to elderly subjects (51-89 years old, 38% women) underwent brain magnetic resonance imaging and non-localizing proton spectroscopy. Their WBNAA was obtained by dividing their whole-head NAA amount by the brain volume. Intracranial volume and fractional brain volume, a metric of brain atrophy, were also determined. Each subject's educational attainment was the sum of his/her years of formal education. In the entire group higher education was associated with larger intracranial volume. The relationship between WBNAA and education was observed only in younger (51-70 years old) participants. In this group, education explained 21% of the variance in WBNAA. More WBNAA was related to more years of formal education in adults and younger elders. Prospective studies can determine whether this relationship reflects a true advantage from years of training versus innate characteristics predisposing a subject to higher achievements later in life. We propose that late-life WBNAA may be more affected by other factors acting at midlife and later. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

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

    Science.gov (United States)

    Pialoux, Vincent; Corbett, Dale; Drogos, Lauren; Erickson, Kirk I.; Eskes, Gail A.

    2016-01-01

    Abstract 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

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

    Science.gov (United States)

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

    2013-12-30

    In patients with attention deficit hyperactivity disorder (ADHD), quantitative neuroimaging techniques have revealed abnormalities in various brain regions, including the frontal cortex, striatum, cerebellum, and occipital cortex. Nonlinear signal processing techniques such as sample entropy have been used to probe the regularity of brain magnetoencephalography signals in patients with ADHD. In the present study, we extend this technique to analyse the complex output patterns of the 4 dimensional resting state functional magnetic resonance imaging signals in adult patients with ADHD. After adjusting for the effect of age, we found whole brain entropy differences (P=0.002) between groups and negative correlation (r=-0.45) between symptom scores and mean whole brain entropy values, indicating lower complexity in patients. In the regional analysis, patients showed reduced entropy in frontal and occipital regions bilaterally and a significant negative correlation between the symptom scores and the entropy maps at a family-wise error corrected cluster level of Pentropy is a useful tool in revealing abnormalities in the brain dynamics of patients with psychiatric disorders. © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. MicroRNAs show mutually exclusive expression patterns in the brain of adult male rats

    DEFF Research Database (Denmark)

    Olsen, Line; Klausen, Mikkel; Helboe, Lone

    2009-01-01

    BACKGROUND: The brain is a major site of microRNA (miRNA) gene expression, but the spatial expression patterns of miRNAs within the brain have not yet been fully covered. METHODOLOGY/PRINCIPAL FINDINGS: We have characterized the regional expression profiles of miRNAs in five distinct regions...... of the adult rat brain: amygdala, cerebellum, hippocampus, hypothalamus and substantia nigra. Microarray profiling uncovered 48 miRNAs displaying more than three-fold enrichment between two or more brain regions. Notably, we found reciprocal expression profiles for a subset of the miRNAs predominantly found...... (> ten times) in either the cerebellum (miR-206 and miR-497) or the forebrain regions (miR-132, miR-212, miR-221 and miR-222). CONCLUSIONS/SIGNIFICANCE: The results indicate that some miRNAs could be important for area-specific functions in the brain. Our data, combined with previous studies in mice...

  9. 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

  10. CRMP5 regulates generation and survival of newborn neurons in olfactory and hippocampal neurogenic areas of the adult mouse brain.

    Directory of Open Access Journals (Sweden)

    Alexandra Veyrac

    Full Text Available The Collapsin Response Mediator Proteins (CRMPS are highly expressed in the developing brain, and in adult brain areas that retain neurogenesis, ie: the olfactory bulb (OB and the dentate gyrus (DG. During brain development, CRMPs are essentially involved in signaling of axon guidance and neurite outgrowth, but their functions in the adult brain remain largely unknown. CRMP5 has been initially identified as the target of auto-antibodies involved in paraneoplasic neurological diseases and further implicated in a neurite outgrowth inhibition mediated by tubulin binding. Interestingly, CRMP5 is also highly expressed in adult brain neurogenic areas where its functions have not yet been elucidated. Here we observed in both neurogenic areas of the adult mouse brain that CRMP5 was present in proliferating and post-mitotic neuroblasts, while they migrate and differentiate into mature neurons. In CRMP5(-/- mice, the lack of CRMP5 resulted in a significant increase of proliferation and neurogenesis, but also in an excess of apoptotic death of granule cells in the OB and DG. These findings provide the first evidence that CRMP5 is involved in the generation and survival of newly generated neurons in areas of the adult brain with a high level of activity-dependent neuronal plasticity.

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

    Science.gov (United States)

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

    2014-01-01

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

  12. Autistic traits and brain activation during face-to-face conversations in typically developed adults.

    Science.gov (United States)

    Suda, Masashi; Takei, Yuichi; Aoyama, Yoshiyuki; Narita, Kosuke; Sakurai, Noriko; Fukuda, Masato; Mikuni, Masahiko

    2011-01-01

    Autism spectrum disorders (ASD) are characterized by impaired social interaction and communication, restricted interests, and repetitive behaviours. The severity of these characteristics is posited to lie on a continuum that extends into the general population. Brain substrates underlying ASD have been investigated through functional neuroimaging studies using functional magnetic resonance imaging (fMRI). However, fMRI has methodological constraints for studying brain mechanisms during social interactions (for example, noise, lying on a gantry during the procedure, etc.). In this study, we investigated whether variations in autism spectrum traits are associated with changes in patterns of brain activation in typically developed adults. We used near-infrared spectroscopy (NIRS), a recently developed functional neuroimaging technique that uses near-infrared light, to monitor brain activation in a natural setting that is suitable for studying brain functions during social interactions. We monitored regional cerebral blood volume changes using a 52-channel NIRS apparatus over the prefrontal cortex (PFC) and superior temporal sulcus (STS), 2 areas implicated in social cognition and the pathology of ASD, in 28 typically developed participants (14 male and 14 female) during face-to-face conversations. This task was designed to resemble a realistic social situation. We examined the correlations of these changes with autistic traits assessed using the Autism-Spectrum Quotient (AQ). Both the PFC and STS were significantly activated during face-to-face conversations. AQ scores were negatively correlated with regional cerebral blood volume increases in the left STS during face-to-face conversations, especially in males. Our results demonstrate successful monitoring of brain function during realistic social interactions by NIRS as well as lesser brain activation in the left STS during face-to-face conversations in typically developed participants with higher levels of autistic

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

    Directory of Open Access Journals (Sweden)

    Yu Sun

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

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

    Science.gov (United States)

    Sun, Yu; Lee, Renick; Chen, Yu; Collinson, Simon; Thakor, Nitish; Bezerianos, Anastasios; Sim, Kang

    2015-01-01

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

  15. Dietary docosahexaenoic acid (DHA) as lysophosphatidylcholine, but not as free acid, enriches brain DHA and improves memory in adult mice

    OpenAIRE

    Sugasini, Dhavamani; Thomas, Riya; Yalagala, Poorna C. R.; Tai, Leon M.; Subbaiah, Papasani V.

    2017-01-01

    Docosahexaenoic acid (DHA) is uniquely concentrated in the brain, and is essential for its function, but must be mostly acquired from diet. Most of the current supplements of DHA, including fish oil and krill oil, do not significantly increase brain DHA, because they are hydrolyzed to free DHA and are absorbed as triacylglycerol, whereas the transporter at blood brain barrier is specific for phospholipid form of DHA. Here we show that oral administration of DHA to normal adult mice as lysopho...

  16. 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 < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  17. Region-specific reduction in brain volume in young adults with perinatal hypoxic-ischaemic encephalopathy.

    Science.gov (United States)

    Bregant, Tina; Rados, Milan; Vasung, Lana; Derganc, Metka; Evans, Alan C; Neubauer, David; Kostovic, Ivica

    2013-11-01

    A severe form of perinatal hypoxic-ischaemic encephalopathy (HIE) carries a high risk of perinatal death and severe neurological sequelae while in mild HIE only discrete cognitive disorders may occur. To compare total brain volumes and region-specific cortical measurements between young adults with mild-moderate perinatal HIE and a healthy control group of the same age. MR imaging was performed in a cohort of 14 young adults (9 males, 5 females) with a history of mild or moderate perinatal HIE. The control group consisted of healthy participants, matched with HIE group by age and gender. Volumetric analysis was done after the processing of MR images using a fully automated CIVET pipeline. We measured gyrification indexes, total brain volume, volume of grey and white matter, and of cerebrospinal fluid. We also measured volume, thickness and area of the cerebral cortex in the parietal, occipital, frontal, and temporal lobe, and of the isthmus cinguli, parahippocampal and cingulated gyrus, and insula. The HIE patient group showed smaller absolute volumetric data. Statistically significant (p right hemisphere, of cortical areas in the right temporal lobe and parahippocampal gyrus, of cortical volumes in the right temporal lobe and of cortical thickness in the right isthmus of the cingulate gyrus were found. Comparison between the healthy group and the HIE group of the same gender showed statistically significant changes in the male HIE patients, where a significant reduction was found in whole brain volume; left parietal, bilateral temporal, and right parahippocampal gyrus cortical areas; and bilateral temporal lobe cortical volume. Our analysis of total brain volumes and region-specific corticometric parameters suggests that mild-moderate forms of perinatal HIE lead to reductions in whole brain volumes. In the study reductions were most pronounced in temporal lobe and parahippocampal gyrus. Copyright © 2013 European Paediatric Neurology Society. All rights reserved.

  18. 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.)

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    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.)

  20. Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

    International Nuclear Information System (INIS)

    Schindler, Matthew K.; Forbes, M. Elizabeth; Robbins, Mike E.; Riddle, David R.

    2008-01-01

    Purpose: To assess the impact of aging on the radiation response in the adult rat brain. Methods and Materials: Male rats 8, 18, or 28 months of age received a single 10-Gy dose of whole-brain irradiation (WBI). The hippocampal dentate gyrus was analyzed 1 and 10 weeks later for sensitive neurobiologic markers associated with radiation-induced damage: changes in density of proliferating cells, immature neurons, total microglia, and activated microglia. Results: A significant decrease in basal levels of proliferating cells and immature neurons and increased microglial activation occurred with normal aging. The WBI induced a transient increase in proliferation that was greater in older animals. This proliferation response did not increase the number of immature neurons, which decreased after WBI in young rats, but not in old rats. Total microglial numbers decreased after WBI at all ages, but microglial activation increased markedly, particularly in older animals. Conclusions: Age is an important factor to consider when investigating the radiation response of the brain. In contrast to young adults, older rats show no sustained decrease in number of immature neurons after WBI, but have a greater inflammatory response. The latter may have an enhanced role in the development of radiation-induced cognitive dysfunction in older individuals

  1. Longitudinal Whole-Brain N-acetylaspartate Concentration in Healthy Adults

    Science.gov (United States)

    Rigotti, Daniel J.; Kirov, Ivan I.; Djavadi, Bejan; Perry, Nissa N.; Babb, James S.; Gonen, Oded

    2011-01-01

    BACKGROUND AND PURPOSE Though N-acetylaspartate (NAA) is often used as a marker of neural integrity and health in different neurological disorders, the temporal behavior of its whole-brain concentration (WBNAA) is not well characterized. Our goal, therefore, was to establish its normal variations in a cohort of healthy adults over typical clinical trial periods. METHODS Baseline amount of brain NAA, QNAA, was obtained with non-localizing proton MR spectroscopy from 9 subjects (7 women, 2 men) 31.2±5.6 years old. QNAA was converted into absolute millimole amount using phantom-replacement. The WBNAA concentration was derived by dividing QNAA with the brain parenchyma volume, VB, segmented from MRI. Temporal variations were determined with four annual scans of each participant. RESULTS The distribution of WBNAA levels was not different among time points with respect to the mean, 12.1±1.5 mM (p 0.6) nor was its intra-subject change (CV = 8.6%) significant between any two scans (p 0.5). There was a small (0.2 mL), but significant (p=0.05) annual VB decline. CONCLUSION WBNAA is stable over a three year period in healthy adults. It qualifies therefore, as a biomarker for global neuronal loss and dysfunction in diffuse neurological disorders that may be well worth considering as a secondary outcome measure candidate for clinical trials. PMID:21511862

  2. Inference Generation during Text Comprehension by Adults with Right Hemisphere Brain Damage: Activation Failure Versus Multiple Activation.

    Science.gov (United States)

    Tompkins, Connie A.; Fassbinder, Wiltrud; Blake, Margaret Lehman; Baumgaertner, Annette; Jayaram, Nandini

    2004-01-01

    ourse comprehensionEvidence conflicts as to whether adults with right hemisphere brain damage (RHD) generate inferences during text comprehension. M. Beeman (1993) reported that adults with RHD fail to activate the lexical-semantic bases of routine bridging inferences, which are necessary for comprehension. But other evidence indicates that adults…

  3. Regional Brain Responses Are Biased Toward Infant Facial Expressions Compared to Adult Facial Expressions in Nulliparous Women.

    Science.gov (United States)

    Li, Bingbing; Cheng, Gang; Zhang, Dajun; Wei, Dongtao; Qiao, Lei; Wang, Xiangpeng; Che, Xianwei

    2016-01-01

    Recent neuroimaging studies suggest that neutral infant faces compared to neutral adult faces elicit greater activity in brain areas associated with face processing, attention, empathic response, reward, and movement. However, whether infant facial expressions evoke larger brain responses than adult facial expressions remains unclear. Here, we performed event-related functional magnetic resonance imaging in nulliparous women while they were presented with images of matched unfamiliar infant and adult facial expressions (happy, neutral, and uncomfortable/sad) in a pseudo-randomized order. We found that the bilateral fusiform and right lingual gyrus were overall more activated during the presentation of infant facial expressions compared to adult facial expressions. Uncomfortable infant faces compared to sad adult faces evoked greater activation in the bilateral fusiform gyrus, precentral gyrus, postcentral gyrus, posterior cingulate cortex-thalamus, and precuneus. Neutral infant faces activated larger brain responses in the left fusiform gyrus compared to neutral adult faces. Happy infant faces compared to happy adult faces elicited larger responses in areas of the brain associated with emotion and reward processing using a more liberal threshold of p facial expressions compared to adult facial expressions among nulliparous women, and this bias may be modulated by individual differences in Interest-In-Infants and perspective taking ability.

  4. Methylphenidate increases glucose uptake in the brain of young and adult rats.

    Science.gov (United States)

    Réus, Gislaine Z; Scaini, Giselli; Titus, Stephanie E; Furlanetto, Camila B; Wessler, Leticia B; Ferreira, Gabriela K; Gonçalves, Cinara L; Jeremias, Gabriela C; Quevedo, João; Streck, Emilio L

    2015-10-01

    Methylphenidate (MPH) is the drug of choice for pharmacological treatment of attention deficit hyperactivity disorder. Studies have pointed to the role of glucose and lactate as well as in the action mechanisms of drugs used to treat these neuropsychiatric diseases. Thus, this study aims to evaluate the effects of MPH administration on lactate release and glucose uptake in the brains of young and adult rats. MPH (1.0, 2.0 and 10.0mg/kg) or saline was injected in young and adult Wistar male rats either acutely (once) or chronically (once daily for 28 days). Then, the levels of lactate release and glucose uptake were assessed in the prefrontal cortex, hippocampus, striatum, cerebellum and cerebral cortex. Chronic MPH treatment increased glucose uptake at the dose of 10.0mg/kg in the prefrontal cortex and striatum, and at the dose of 2.0mg/kg in the cerebral cortex of young rats. In adult rats, an increase in glucose uptake was observed after acute administration of MPH at the dose of 10.0mg/kg in the prefrontal cortex. After chronic treatment, there was an increase in glucose uptake with MPH doses of 2.0 and 10.0mg/kg in the prefrontal cortex, and at an MPH dose of 2.0mg/kg in the striatum of adult rats. The lactate release did not change with either acute or chronic treatments in young or adult rats. These findings indicate that MPH increases glucose consumption in the brain, and that these changes are dependent on age and posology. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  5. Lifetime History of Traumatic Brain Injury and Current Disability Among Ohio Adults.

    Science.gov (United States)

    Yi, Honggang; Corrigan, John D; Singichetti, Bhavna; Bogner, Jennifer A; Manchester, Kara; Guo, Jinhong; Yang, Jingzhen

    2017-10-27

    To examine the associations between lifetime history of traumatic brain injury (TBI) with loss of consciousness (LOC) and several types of current disability among adult, noninstitutionalized residents of Ohio. 2014 Ohio Behavioral Risk Factors Surveillance System participants (n = 6998). Statewide population-based survey. Lifetime history of TBI with LOC (number and severity of injury, age of first injury), and number and type of disability (vision, cognition, mobility, self-care, and/or independent living). Of the 6998 participants, 1325 reported lifetime history of TBI with LOC, and 1959 reported currently having one or more disabilities. When weighted, these represented 21.7% and 23.7% of Ohio's noninstitutionalized adult population, respectively. Adults with a history of TBI with LOC showed greater odds of any disability compared with adults with no history (odds ratio = 2.49; 95% confidence interval = 1.97-3.15). The likelihood of having any and each type of disability increased as the number of TBIs or the severity of worst TBI increased, regardless of sustaining first TBI before or after the age of 15 years. Lifetime history of TBI with LOC is significantly associated with disability among Ohio adults. Further research on the natural course of the relation and preventive strategies is warranted.

  6. Stuttering treatment and brain research in adults: A still unfolding relationship.

    Science.gov (United States)

    Ingham, Roger J; Ingham, Janis C; Euler, Harald A; Neumann, Katrin

    2018-03-01

    Brain imaging and brain stimulation procedures have now been used for more than two decades to investigate the neural systems that contribute to the occurrence of stuttering in adults, and to identify processes that might enhance recovery from stuttering. The purpose of this paper is to review the extent to which these dual lines of research with adults who stutter have intersected and whether they are contributing towards the alleviation of this impairment. Several areas of research are reviewed in order to determine whether research on the neurology of stuttering is showing any potential for advancing the treatment of this communication disorder: (a) attempts to discover the neurology of stuttering, (b) neural changes associated with treated recovery, and (c) direct neural intervention. Although much has been learned about the neural underpinnings of stuttering, little research in any of the reviewed areas has thus far contributed to the advancement of stuttering treatment. Much of the research on the neurology of stuttering that does have therapy potential has been largely driven by a speech-motor model that is designed to account for the efficacy of fluency-inducing strategies and strategies that have been shown to yield therapy benefits. Investigations on methods that will induce neuroplasticity are overdue. Strategies profitable with other disorders have only occasionally been employed. However, there are signs that investigations on the neurology of adults who have recovered from stuttering are slowly being recognized for their potential in this regard. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Multimodal mapping of the brain's functional connectivity and the adult outcome of attention deficit hyperactivity disorder.

    Science.gov (United States)

    Sudre, Gustavo; Szekely, Eszter; Sharp, Wendy; Kasparek, Steven; Shaw, Philip

    2017-10-31

    We have a limited understanding of why many children with attention deficit hyperactivity disorder do not outgrow the disorder by adulthood. Around 20-30% retain the full syndrome as young adults, and about 50% show partial, rather than complete, remission. Here, to delineate the neurobiology of this variable outcome, we ask if the persistence of childhood symptoms into adulthood impacts on the brain's functional connectivity. We studied 205 participants followed clinically since childhood. In early adulthood, participants underwent magnetoencephalography (MEG) to measure neuronal activity directly and functional MRI (fMRI) to measure hemodynamic activity during a task-free period (the "resting state"). We found that symptoms of inattention persisting into adulthood were associated with disrupted patterns of typical functional connectivity in both MEG and fMRI. Specifically, those with persistent inattention lost the typical balance of connections within the default mode network (DMN; prominent during introspective thought) and connections between this network and those supporting attention and cognitive control. By contrast, adults whose childhood inattentive symptoms had resolved did not differ significantly from their never-affected peers, both hemodynamically and electrophysiologically. The anomalies in functional connectivity tied to clinically significant inattention centered on midline regions of the DMN in both MEG and fMRI, boosting confidence in a possible pathophysiological role. The findings suggest that the clinical course of this common childhood onset disorder impacts the functional connectivity of the adult brain. Published under the PNAS license.

  8. Mice with ablated adult brain neurogenesis are not impaired in antidepressant response to chronic fluoxetine.

    Science.gov (United States)

    Jedynak, Paulina; Kos, Tomasz; Sandi, Carmen; Kaczmarek, Leszek; Filipkowski, Robert K

    2014-09-01

    The neurogenesis hypothesis of major depression has two main facets. One states that the illness results from decreased neurogenesis while the other claims that the very functioning of antidepressants depends on increased neurogenesis. In order to verify the latter, we have used cyclin D2 knockout mice (cD2 KO mice), known to have virtually no adult brain neurogenesis, and we demonstrate that these mice successfully respond to chronic fluoxetine. After unpredictable chronic mild stress, mutant mice showed depression-like behavior in forced swim test, which was eliminated with chronic fluoxetine treatment, despite its lack of impact on adult hippocampal neurogenesis in cD2 KO mice. Our results suggest that new neurons are not indispensable for the action of antidepressants such as fluoxetine. Using forced swim test and tail suspension test, we also did not observe depression-like behavior in control cD2 KO mice, which argues against the link between decreased adult brain neurogenesis and major depression. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Adult sex ratio effects on male survivorship of Drosophila melanogaster Meigen (Diptera, Drosophilidae Efeito da razão sexual de adultos na curva de sobrevivência de machos de Drosophila melanogaster Meigen (Diptera, Drosophilidae

    Directory of Open Access Journals (Sweden)

    Marcelo Costa

    2010-01-01

    Full Text Available The behavioral biology has a central role in evolutionary biology mainly because the antagonistic relations that occur in the sexual reproduction. One involves the effect of reproduction on the future life expectation. In this scenario, changes in male operational sex ratio could lead to an increase in mortality due to costs associated with excessive courtship and mating displays. Thus, this work experimentally altered the male sex ratio of Drosophila melanogaster Meigen, 1830, to determine its impact on mortality. The results indicated that mortality increases as the sex ratio changes, including modifications in the survivorship curve type and in the curve concavity, measured by entropy.A biologia comportamental tem um papel central na biologia evolutiva principalmente pelas relações antagônicas que ocorrem na reprodução sexuada. Uma destas relações envolve o efeito da reprodução sobre a expectativa de vida futura. Neste cenário, alterações na razão sexual operacional de machos podem levar a um aumento na mortalidade por causa dos custos associados com o excesso de displays de corte e cópulas. Neste sentido este trabalho alterou experimentalmente a razão sexual em machos de Drosophila melanogaster Meigen, 1830, para determinar os efeitos em termos de mortalidade. Os resultados indicam que a mortalidade aumenta a medida que a razão sexual se enviesa incluindo alterações no tipo de curva de sobrevivência e da concavidade da curva, medida pela entropia.

  10. Detecting novel low-abundant transcripts in Drosophila

    DEFF Research Database (Denmark)

    Lee, Sanggyu; Bao, Jingyue; Zhou, Guolin

    2005-01-01

    Increasing evidence suggests that low-abundant transcripts may play fundamental roles in biological processes. In an attempt to estimate the prevalence of low-abundant transcripts in eukaryotic genomes, we performed a transcriptome analysis in Drosophila using the SAGE technique. We collected 244......,313 SAGE tags from transcripts expressed in Drosophila embryonic, larval, pupae, adult, and testicular tissue. From these SAGE tags, we identified 40,823 unique SAGE tags. Our analysis showed that 55% of the 40,823 unique SAGE tags are novel without matches in currently known Drosophila transcripts...... in the Drosophila genome. Our study reveals the presence of a significant number of novel low-abundant transcripts in Drosophila, and highlights the need to isolate these novel low-abundant transcripts for further biological studies. Udgivelsesdato: 2005-Jun...

  11. Methylmercury Induced Neurotoxicity and the Influence of Selenium in the Brains of Adult Zebrafish (Danio rerio

    Directory of Open Access Journals (Sweden)

    Josef Daniel Rasinger

    2017-03-01

    Full Text Available The neurotoxicity of methylmercury (MeHg is well characterised, and the ameliorating effects of selenium have been described. However, little is known about the molecular mechanisms behind this contaminant-nutrient interaction. We investigated the influence of selenium (as selenomethionine, SeMet and MeHg on mercury accumulation and protein expression in the brain of adult zebrafish (Danio rerio. Fish were fed diets containing elevated levels of MeHg and/or SeMet in a 2 × 2 full factorial design for eight weeks. Mercury concentrations were highest in the brain tissue of MeHg-exposed fish compared to the controls, whereas lower levels of mercury were found in the brain of zebrafish fed both MeHg and SeMet compared with the fish fed MeHg alone. The expression levels of proteins associated with gap junction signalling, oxidative phosphorylation, and mitochondrial dysfunction were significantly (p < 0.05 altered in the brain of zebrafish after exposure to MeHg and SeMet alone or in combination. Analysis of upstream regulators indicated that these changes were linked to the mammalian target of rapamycin (mTOR pathways, which were activated by MeHg and inhibited by SeMet, possibly through a reactive oxygen species mediated differential activation of RICTOR, the rapamycin-insensitive binding partner of mTOR.

  12. 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.

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

    Science.gov (United States)

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

    2016-09-01

    Aging is associated with decreased resting-state functional connectivity (RSFC) within the default mode network (DMN), but most functional imaging studies have restricted the analysis to specific brain regions or networks, a strategy not appropriate to describe system-wide changes. Moreover, few investigations have employed operational psychiatric interviewing procedures to select participants; this is an important limitation since mental disorders are prevalent and underdiagnosed and can be associated with RSFC abnormalities. In this study, resting-state fMRI was acquired from 59 adults free of cognitive and psychiatric disorders according to standardized criteria and based on extensive neuropsychological and clinical assessments. We tested for associations between age and whole-brain RSFC using Partial Least Squares, a multivariate technique. We found that normal aging is not only characterized by decreased RSFC within the DMN but also by ubiquitous increases in internetwork positive correlations and focal internetwork losses of anticorrelations (involving mainly connections between the DMN and the attentional networks). Our results reinforce the notion that the aging brain undergoes a dedifferentiation processes with loss of functional diversity. These findings advance the characterization of healthy aging effects on RSFC and highlight the importance of adopting a broad, system-wide perspective to analyze brain connectivity. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. The predictive nature of transcript expression levels on protein expression in adult human brain.

    Science.gov (United States)

    Bauernfeind, Amy L; Babbitt, Courtney C

    2017-04-24

    Next generation sequencing methods are the gold standard for evaluating expression of the transcriptome. When determining the biological implications of such studies, the assumption is often made that transcript expression levels correspond to protein levels in a meaningful way. However, the strength of the overall correlation between transcript and protein expression is inconsistent, particularly in brain samples. Following high-throughput transcriptomic (RNA-Seq) and proteomic (liquid chromatography coupled with tandem mass spectrometry) analyses of adult human brain samples, we compared the correlation in the expression of transcripts and proteins that support various biological processes, molecular functions, and that are located in different areas of the cell. Although most categories of transcripts have extremely weak predictive value for the expression of their associated proteins (R 2 values of < 10%), transcripts coding for protein kinases and membrane-associated proteins, including those that are part of receptors or ion transporters, are among those that are most predictive of downstream protein expression levels. The predictive value of transcript expression for corresponding proteins is variable in human brain samples, reflecting the complex regulation of protein expression. However, we found that transcriptomic analyses are appropriate for assessing the expression levels of certain classes of proteins, including those that modify proteins, such as kinases and phosphatases, regulate metabolic and synaptic activity, or are associated with a cellular membrane. These findings can be used to guide the interpretation of gene expression results from primate brain samples.

  15. 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

  16. Optogenetic pacing in Drosophila melanogaster

    Science.gov (United States)

    Alex, Aneesh; Li, Airong; Tanzi, Rudolph E.; Zhou, Chao

    2015-01-01

    Electrical stimulation is currently the gold standard for cardiac pacing. However, it is invasive and nonspecific for cardiac tissues. We recently developed a noninvasive cardiac pacing technique using optogenetic tools, which are widely used in neuroscience. Optogenetic pacing of the heart provides high spatial and temporal precisions, is specific for cardiac tissues, avoids artifacts associated with electrical stimulation, and therefore promises to be a powerful tool in basic cardiac research. We demonstrated optogenetic control of heart rhythm in a well-established model organism, Drosophila melanogaster. We developed transgenic flies expressing a light-gated cation channel, channelrhodopsin-2 (ChR2), specifically in their hearts and demonstrated successful optogenetic pacing of ChR2-expressing Drosophila at different developmental stages, including the larva, pupa, and adult stages. A high-speed and ultrahigh-resolution optical coherence microscopy imaging system that is capable of providing images at a rate of 130 frames/s with axial and transverse resolutions of 1.5 and 3.9 μm, respectively, was used to noninvasively monitor Drosophila cardiac function and its response to pacing stimulation. The development of a noninvasive integrated optical pacing and imaging system provides a novel platform for performing research studies in developmental cardiology. PMID:26601299

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

    Directory of Open Access Journals (Sweden)

    Kuan Zhang

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

  18. Experience with adults shapes multisensory representation of social familiarity in the brain of a songbird.

    Directory of Open Access Journals (Sweden)

    Isabelle George

    Full Text Available Social animals learn to perceive their social environment, and their social skills and preferences are thought to emerge from greater exposure to and hence familiarity with some social signals rather than others. Familiarity appears to be tightly linked to multisensory integration. The ability to differentiate and categorize familiar and unfamiliar individuals and to build a multisensory representation of known individuals emerges from successive social interactions, in particular with adult, experienced models. In different species, adults have been shown to shape the social behavior of young by promoting selective attention to multisensory cues. The question of what representation of known conspecifics adult-deprived animals may build therefore arises. Here we show that starlings raised with no experience with adults fail to develop a multisensory representation of familiar and unfamiliar starlings. Electrophysiological recordings of neuronal activity throughout the primary auditory area of these birds, while they were exposed to audio-only or audiovisual familiar and unfamiliar cues, showed that visual stimuli did, as in wild-caught starlings, modulate auditory responses but that, unlike what was observed in wild-caught birds, this modulation was not influenced by familiarity. Thus, adult-deprived starlings seem to fail to discriminate between familiar and unfamiliar individuals. This suggests that adults may shape multisensory representation of known individuals in the brain, possibly by focusing the young's attention on relevant, multisensory cues. Multisensory stimulation by experienced, adult models may thus be ubiquitously important for the development of social skills (and of the neural properties underlying such skills in a variety of species.

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

    Science.gov (United States)

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

    2011-04-01

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

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

    Science.gov (United States)

    Hallahan, Brian P; Craig, Michael C; Toal, Fiona; Daly, Eileen M; Moore, Caroline J; Ambikapathy, Anita; Robertson, Dene; Murphy, Kieran C; Murphy, Declan G M

    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. Copyright © 2010 Elsevier Inc. All rights reserved.

  1. 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.

  2. Characterization of TLX expression in neural stem cells and progenitor cells in adult brains.

    Directory of Open Access Journals (Sweden)

    Shengxiu Li

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

  3. Characterization of TLX expression in neural stem cells and progenitor cells in adult brains.

    Science.gov (United States)

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

    2012-01-01

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

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

    International Nuclear Information System (INIS)

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

    1990-01-01

    Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors. One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered safe treatment for benign brain tumors. 163 refs

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1990-10-01

    Radiation therapy plays an integral part in managing intracranial tumors. While the risk:benefit ratio is considered acceptable for treating malignant tumors, risks of long-term complications of radiotherapy need thorough assessment in adults treated for benign tumors. Many previously reported delayed complications of radiotherapy can be attributed to inappropriate treatment or to the sensitivity of a developing child's brain to radiation. Medical records, radiological studies, autopsy findings, and follow-up information were reviewed for 58 adult patients (31 men and 27 women) treated between 1958 and 1987 with radiotherapy for benign intracranial tumors. Patient ages at the time of irradiation ranged from 21 to 87 years (mean 47.7 years). The pathology included 46 pituitary adenomas, five meningiomas, four glomus jugulare tumors, two pineal area tumors, and one craniopharyngioma. Average radiation dosage was 4984 cGy (range 3100 to 7012 cGy), given in an average of 27.2 fractions (range 15 to 45 fractions), over a period averaging 46.6 days. The follow-up period ranged from 3 to 31 years (mean 8.1 years). Findings related to tumor recurrence or surgery were excluded. Twenty-two patients had complications considered to be delayed side effects of radiotherapy. Two patients had visual deterioration developing 3 and 6 years after treatment; six had pituitary dysfunction; and 17 had varying degrees of parenchymal changes of the brain, occurring mostly in the temporal lobes and relating to the frequent presentation of pituitary tumors. One clival tumor with the radiographic appearance of a meningioma, developed 30 years post-irradiation for acromegaly. This study unveils considerable delayed sequelae of radiotherapy in a series of adult patients receiving what is considered safe treatment for benign brain tumors. 163 refs.

  6. Molecular and Functional Properties of Regional Astrocytes in the Adult Brain.

    Science.gov (United States)

    Morel, Lydie; Chiang, Ming Sum R; Higashimori, Haruki; Shoneye, Temitope; Iyer, Lakshmanan K; Yelick, Julia; Tai, Albert; Yang, Yongjie

    2017-09-06

    The molecular signature and functional properties of astroglial subtypes in the adult CNS remain largely undefined. By using translational ribosome affinity purification followed by RNA-Seq, we profiled astroglial ribosome-associated (presumably translating) mRNAs in major cortical and subcortical brain regions (cortex, hippocampus, caudate-putamen, nucleus accumbens, thalamus, and hypothalamus) of BAC aldh1l1 -translational ribosome affinity purification (TRAP) mice (both sexes). We found that the expression of astroglial translating mRNAs closely follows the dorsoventral axis, especially from cortex/hippocampus to thalamus/hypothalamus posteriorly. This region-specific expression pattern of genes, such as synaptogenic modulator sparc and transcriptional factors ( emx2 , lhx2 , and hopx ), was validated by qRT-PCR and immunostaining in brain sections. Interestingly, cortical or subcortical astrocytes selectively promote neurite growth and synaptic activity of neurons only from the same region in mismatched cocultures, exhibiting region-matched astrocyte to neuron communication. Overall, these results generated new molecular signature of astrocyte types in the adult CNS, providing insights into their origin and functional diversity. SIGNIFICANCE STATEMENT We investigated the in vivo molecular and functional heterogeneity of astrocytes inter-regionally from adult brain. Our results showed that the expression pattern of ribosome-associated mRNA profiles in astrocytes closely follows the dorsoventral axis, especially posteriorly from cortex/hippocampus to thalamus/hypothalamus. In line with this, our functional results further demonstrated region-selective roles of cortical and subcortical astrocytes in regulating cortical or subcortical neuronal synaptogenesis and maturation. These in vivo studies provide a previously uncharacterized and important molecular atlas for exploring region-specific astroglial functions. Copyright © 2017 the authors 0270-6474/17/378706-12$15.00/0.

  7. Changes in brain-behavior relationships following a 3-month pilot cognitive intervention program for adults with traumatic brain injury

    OpenAIRE

    S. Porter; I.J. Torres; W. Panenka; Z. Rajwani; D. Fawcett; A. Hyder; N. Virji-Babul

    2017-01-01

    Facilitating functional recovery following brain injury is a key goal of neurorehabilitation. Direct, objective measures of changes in the brain are critical to understanding how and when meaningful changes occur, however, assessing neuroplasticity using brain based results remains a significant challenge. Little is known about the underlying changes in functional brain networks that correlate with cognitive outcomes in traumatic brain injury (TBI). The purpose of this pilot study was to asse...

  8. Modeling glial contributions to seizures and epileptogenesis: cation-chloride cotransporters in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Zeid M Rusan

    Full Text Available Flies carrying a kcc loss-of-function mutation are more seizure-susceptible than wild-type flies. The kcc gene is the highly conserved Drosophila melanogaster ortholog of K+/Cl- cotransporter genes thought to be expressed in all animal cell types. Here, we examined the spatial and temporal requirements for kcc loss-of-function to modify seizure-susceptibility in flies. Targeted RNA interference (RNAi of kcc in various sets of neurons was sufficient to induce severe seizure-sensitivity. Interestingly, kcc RNAi in glia was particularly effective in causing seizure-sensitivity. Knockdown of kcc in glia or neurons during development caused a reduction in seizure induction threshold, cell swelling, and brain volume increase in 24-48 hour old adult flies. Third instar larval peripheral nerves were enlarged when kcc RNAi was expressed in neurons or glia. Results suggest that a threshold of K+/Cl- cotransport dysfunction in the nervous system during development is an important determinant of seizure-susceptibility in Drosophila. The findings presented are the first attributing a causative role for glial cation-chloride cotransporters in seizures and epileptogenesis. The importance of elucidating glial cell contributions to seizure disorders and the utility of Drosophila models is discussed.

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

    International Nuclear Information System (INIS)

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

    1986-01-01

    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 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

  10. Magnetic resonance imaging of the brain in epileptic adult patients: experience in Ramathibodi Hospital.

    Science.gov (United States)

    Solosrungruang, Anusorn; Laothamatas, Jiraporn; Chinwarun, Yotin

    2007-04-01

    The purpose of the present study was to classify the imaging structural abnormalities of epileptic adult patients referred for magnetic resonance imaging (MR imaging) of the brain at Ramathibodi Hospital and to correlate with the clinical data and EEG. MR imaging of 91 adult epileptic patients (age ranging from 15-85 years old with an average of 36.90 years old) were retrospectively reviewed and classified into eight groups according to etiologies. Then clinical data and EEG correlations were analyzed using the Kappa analysis. All of the MR imaging of the brain were performed at Ramathibodi Hospital from January 2001 to December 2002. Secondary generalized tonic clonic seizure was the most common clinical presenting seizure type. Extra temporal lobe epilepsy was the most common clinical diagnosis. Of the thirty-three patients who underwent EEG before performing MR imaging, 17 had normal EEG From MR imaging, temporal lobe lesion was the main affected location and mesial temporal sclerosis (MTS) was the most common cause of the epilepsy in patients. For age group classification, young adult (15-34 years old) and adult (35-64 years old) age groups, MTS was the most common etiology of epilepsy with cortical dysplasia being the second most common cause for the first group and vascular disease for the latter group. For the older age group (> 64 years old), vascular disease and idiopathic cause were equally common etiologies. MRI, EEG findings, and clinical data were all concordant with statistical significance. MRI is the non-invasive modality of choice for evaluation of the epileptic patients. The result is concordant with the clinical and EEG findings. It can detect and localize the structural abnormality accurately and is useful in the treatment planning.

  11. 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.

  12. New aspects of fenestrated vasculature and tissue dynamics in the sensory circumventricular organs of adult brains

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    Seiji eMiyata

    2015-10-01

    Full Text Available The blood–brain barrier (BBB generally consists of endothelial tight junction barriers that prevent the free entry of blood-derived substances, thereby maintaining the extracellular environment of the brain. However, the circumventricular organs (CVOs, which are located along the midlines of the brain ventricles, lack these endothelial barriers and have fenestrated capillaries; therefore, they have a number of essential functions, including the transduction of information between the blood circulation and brain. Previous studies have demonstrated the extensive contribution of the CVOs to body fluid and thermal homeostasis, energy balance, the chemoreception of blood-derived substances, and neuroinflammation. In this review, recent advances have been discussed in fenestrated capillary characterization and dynamic tissue reconstruction accompanied by angiogenesis and neurogliogenesis in the sensory CVOs of adult brains. The sensory CVOs, including the organum vasculosum of the lamina terminalis (OVLT, subfornical organ (SFO, and area postrema (AP, have size-selective and heterogeneous vascular permeabilities. Astrocyte-/tanycyte-like neural stem cells (NSCs sense blood- and cerebrospinal fluid-derived information through the transient receptor potential vanilloid 1, a mechanical/osmotic receptor, Toll-like receptor 4, a lipopolysaccharide receptor, and Nax, a Na-sensing Na channel. They also express tight junction proteins and densely and tightly surround mature neurons to protect them from blood-derived neurotoxic substances, indicating that the NSCs of the CVOs perform BBB functions while maintaining the capacity to differentiate into new neurons and glial cells. In addition to neurogliogenesis, the density of fenestrated capillaries is regulated by angiogenesis, which is accompanied by the active proliferation and sprouting of endothelial cells. Vascular endothelial growth factor (VEGF signaling may be involved in angiogenesis and

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

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    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.

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

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

    2012-12-01

    Chemotherapy, especially if prolonged, disrupts attention, working memory and speed of processing in humans. Most cancer drugs that cross the blood-brain barrier also decrease adult neurogenesis. Because new neurons are generated in the hippocampus, this decrease may contribute to the deficits in working memory and related thought processes. The neurophysiological mechanisms that underlie these deficits are generally unknown. A possible mediator is hippocampal oscillatory activity within the theta range (3-12 Hz). Theta activity predicts and promotes efficient learning in healthy animals and humans. Here, we hypothesised that chemotherapy disrupts learning via decreases in hippocampal adult neurogenesis and theta activity. Temozolomide was administered to adult male Sprague-Dawley rats in a cyclic manner for several weeks. Treatment was followed by training with different types of eyeblink classical conditioning, a form of associative learning. Chemotherapy reduced both neurogenesis and endogenous theta activity, as well as disrupted learning and related theta-band responses to the conditioned stimulus. The detrimental effects of temozolomide only occurred after several weeks of treatment, and only on a task that requires the association of events across a temporal gap and not during training with temporally overlapping stimuli. Chemotherapy did not disrupt the memory for previously learned associations, a memory independent of (new neurons in) the hippocampus. In conclusion, prolonged systemic chemotherapy is associated with a decrease in hippocampal adult neurogenesis and theta activity that may explain the selective deficits in processes of learning that describe the 'chemobrain'. © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  15. Correspondence Between Aberrant Intrinsic Network Connectivity and Gray-Matter Volume in the Ventral Brain of Preterm Born Adults.

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    Bäuml, Josef G; Daamen, Marcel; Meng, Chun; Neitzel, Julia; Scheef, Lukas; Jaekel, Julia; Busch, Barbara; Baumann, Nicole; Bartmann, Peter; Wolke, Dieter; Boecker, Henning; Wohlschläger, Afra M; Sorg, Christian

    2015-11-01

    Widespread brain changes are present in preterm born infants, adolescents, and even adults. While neurobiological models of prematurity facilitate powerful explanations for the adverse effects of preterm birth on the developing brain at microscale, convincing linking principles at large-scale level to explain the widespread nature of brain changes are still missing. We investigated effects of preterm birth on the brain's large-scale intrinsic networks and their relation to brain structure in preterm born adults. In 95 preterm and 83 full-term born adults, structural and functional magnetic resonance imaging at-rest was used to analyze both voxel-based morphometry and spatial patterns of functional connectivity in ongoing blood oxygenation level-dependent activity. Differences in intrinsic functional connectivity (iFC) were found in cortical and subcortical networks. Structural differences were located in subcortical, temporal, and cingulate areas. Critically, for preterm born adults, iFC-network differences were overlapping and correlating with aberrant regional gray-matter (GM) volume specifically in subcortical and temporal areas. Overlapping changes were predicted by prematurity and in particular by neonatal medical complications. These results provide evidence that preterm birth has long-lasting effects on functional connectivity of intrinsic networks, and these changes are specifically related to structural alterations in ventral brain GM. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Differential Roles of the Fan-Shaped Body and the Ellipsoid Body in "Drosophila" Visual Pattern Memory

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    Pan, Yufeng; Zhou, Yanqiong; Guo, Chao; Gong, Haiyun; Gong, Zhefeng; Liu, Li

    2009-01-01

    The central complex is a prominent structure in the "Drosophila" brain. Visual learning experiments in the flight simulator, with flies with genetically altered brains, revealed that two groups of horizontal neurons in one of its substructures, the fan-shaped body, were required for "Drosophila" visual pattern memory. However,…

  17. Gustatory Processing in Drosophila melanogaster.

    Science.gov (United States)

    Scott, Kristin

    2018-01-07

    The ability to identify nutrient-rich food and avoid toxic substances is essential for an animal's survival. Although olfaction and vision contribute to food detection, the gustatory system acts as a final checkpoint control for food acceptance or rejection. The vinegar fly Drosophila melanogaster tastes many of the same stimuli as mammals and provides an excellent model system for comparative studies of taste detection. The relative simplicity of the fly brain and behaviors, along with the molecular genetic and functional approaches available in this system, allow the examination of gustatory neural circuits from sensory input to motor output. This review discusses the molecules and cells that detect taste compounds in the periphery and the circuits that process taste information in the brain. These studies are providing insight into how the detection of taste compounds regulates feeding decisions.

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

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    Qing-quan Li

    2015-01-01

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

  19. Wechsler Adult Intelligence Scale-Revised Block Design broken configuration errors in nonpenetrating traumatic brain injury.

    Science.gov (United States)

    Wilde, M C; Boake, C; Sherer, M

    2000-01-01

    Final broken configuration errors on the Wechsler Adult Intelligence Scale-Revised (WAIS-R; Wechsler, 1981) Block Design subtest were examined in 50 moderate and severe nonpenetrating traumatically brain injured adults. Patients were divided into left (n = 15) and right hemisphere (n = 19) groups based on a history of unilateral craniotomy for treatment of an intracranial lesion and were compared to a group with diffuse or negative brain CT scan findings and no history of neurosurgery (n = 16). The percentage of final broken configuration errors was related to injury severity, Benton Visual Form Discrimination Test (VFD; Benton, Hamsher, Varney, & Spreen, 1983) total score and the number of VFD rotation and peripheral errors. The percentage of final broken configuration errors was higher in the patients with right craniotomies than in the left or no craniotomy groups, which did not differ. Broken configuration errors did not occur more frequently on designs without an embedded grid pattern. Right craniotomy patients did not show a greater percentage of broken configuration errors on nongrid designs as compared to grid designs.

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

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    Tetsuya Kimura

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

  1. Effects of multicomponent training of cognitive control on cognitive function and brain activation in older adults.

    Science.gov (United States)

    Kim, Hoyoung; Chey, Jeanyung; Lee, Sanghun

    2017-11-01

    The aim of this study was to investigate the changes in cognitive functions and brain activation after multicomponent training of cognitive control in non-demented older adults, utilizing neuropsychological tests and fMRI. We developed and implemented a computerized Multicomponent Training of Cognitive Control (MTCC), characterized by task variability and adaptive procedures, in order to maximize training effects in cognitive control and transfer to other cognitive domains. Twenty-seven community-dwelling adults, aged 64-77 years, without any history of neurological or psychiatric problems, participated in this study (14 in the training group and 13 in the control group). The MTCC was administered to the participants assigned to the training group for 8 weeks, while those in the control group received no training. Neuropsychological tests and fMRI were administered prior to and after the training. Trained participants showed improvements in cognitive control, recognition memory and general cognitive functioning. Furthermore, the MTCC led to an increased brain activation of the regions adjacent to the baseline cognitive control-related areas in the frontoparietal network. Future studies are necessary to confirm our hypothesis that MTCC improves cognitive functioning of healthy elderly individuals by expanding their frontoparietal network that is involved in cognitive control. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Mapping of brain lipid binding protein (Blbp) in the brain of adult zebrafish, co-expression with aromatase B and links with proliferation.

    Science.gov (United States)

    Diotel, Nicolas; Vaillant, Colette; Kah, Olivier; Pellegrini, Elisabeth

    2016-01-01

    Adult fish exhibit a strong neurogenic capacity due to the persistence of radial glial cells. In zebrafish, radial glial cells display well-established markers such as the estrogen-synthesizing enzyme (AroB) and the brain lipid binding protein (Blbp), which is known to strongly bind omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA). While Blpb is mainly described in the telencephalon of adult zebrafish, its expression in the remaining regions of the brain is poorly documented. The present study was designed to further investigate Blbp expression in the brain, its co-expression with AroB, and its link with radial glial cells proliferation in zebrafish. We generated a complete and detailed mapping of Blbp expression in the whole brain and show its complete co-expression with AroB, except in some tectal and hypothalamic regions. By performing PCNA and Blbp immunohistochemistry on cyp19a1b-GFP (AroB-GFP) fish, we also demonstrated preferential Blbp expression in proliferative radial glial cells in almost all regions studied. To our knowledge, this is the first complete and detailed mapping of Blbp-expressing cells showing strong association between Blbp and radial glial cell proliferation in the adult brain of fish. Given that zebrafish is now recognized models for studying neurogenesis and brain repair, our data provide detailed characterization of Blbp in the entire brain and open up a broad field of research investigating the role of omega-3 polyunsaturated fatty acids in neural stem cell activity in fish. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Interplay between TETs and microRNAs in the adult brain for memory formation.

    Science.gov (United States)

    Kremer, Eloïse A; Gaur, Niharika; Lee, Melissa A; Engmann, Olivia; Bohacek, Johannes; Mansuy, Isabelle M

    2018-01-26

    5-hydroxymethylation (5-hmC) is an epigenetic modification on DNA that results from the conversion of 5-methylcytosine by Ten-Eleven Translocation (TET) proteins. 5-hmC is widely present in the brain and is subjected to dynamic regulation during development and upon neuronal activity. It was recently shown to be involved in memory processes but currently, little is known about how it is controlled in the brain during memory formation. Here, we show that Tet3 is selectively up-regulated by activity in hippocampal neurons in vitro, and after formation of fear memory in the hippocampus. This is accompanied by a decrease in miR-29b expression that, through complementary sequences, regulates the level of Tet3 by preferential binding to its 3'UTR. We newly reveal that SAM68, a nuclear RNA-binding protein known to regulate splicing, acts upstream of miR-29 by modulating its biogenesis. Together, these findings identify novel players in the adult brain necessary for the regulation of 5-hmC during memory formation.

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

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    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.

  5. Brain Network Modularity Predicts Exercise-Related Executive Function Gains in Older Adults.

    Science.gov (United States)

    Baniqued, Pauline L; Gallen, Courtney L; Voss, Michelle W; Burzynska, Agnieszka Z; Wong, Chelsea N; Cooke, Gillian E; Duffy, Kristin; Fanning, Jason; Ehlers, Diane K; Salerno, Elizabeth A; Aguiñaga, Susan; McAuley, Edward; Kramer, Arthur F; D'Esposito, Mark

    2017-01-01

    Recent work suggests that the brain can be conceptualized as a network comprised of groups of sub-networks or modules. The extent of segregation between modules can be quantified with a modularity metric, where networks with high modularity have dense connections within modules and sparser connections between modules. Previous work has shown that higher modularity predicts greater improvements after cognitive training in patients with traumatic brain injury and in healthy older and young adults. It is not known, however, whether modularity can also predict cognitive gains after a physical exercise intervention. Here, we quantified modularity in older adults ( N = 128, mean age = 64.74) who underwent one of the following interventions for 6 months (NCT01472744 on ClinicalTrials.gov): (1) aerobic exercise in the form of brisk walking (Walk), (2) aerobic exercise in the form of brisk walking plus nutritional supplement (Walk+), (3) stretching, strengthening and stability (SSS), or (4) dance instruction. After the intervention, the Walk, Walk+ and SSS groups showed gains in cardiorespiratory fitness (CRF), with larger effects in both walking groups compared to the SSS and Dance groups. The Walk, Walk+ and SSS groups also improved in executive function (EF) as measured by reasoning, working memory, and task-switching tests. In the Walk, Walk+, and SSS groups that improved in EF, higher baseline modularity was positively related to EF gains, even after controlling for age, in-scanner motion and baseline EF. No relationship between modularity and EF gains was observed in the Dance group, which did not show training-related gains in CRF or EF control. These results are consistent with previous studies demonstrating that individuals with a more modular brain network organization are more responsive to cognitive training. These findings suggest that the predictive power of modularity may be generalizable across interventions aimed to enhance aspects of cognition and that

  6. Revisited: A Systematic Review of Therapeutic Hypothermia for Adult Patients Following Traumatic Brain Injury.

    Science.gov (United States)

    Watson, Hannah I; Shepherd, Andrew A; Rhodes, Jonathan K J; Andrews, Peter J D

    2018-06-01

    Therapeutic hypothermia has been of topical interest for many years and with the publication of two international, multicenter randomized controlled trials, the evidence base now needs updating. The aim of this systematic review of randomized controlled trials is to assess the efficacy of therapeutic hypothermia in adult traumatic brain injury focusing on mortality, poor outcomes, and new pneumonia. The following databases were searched from January 1, 2011, to January 26, 2018: Cochrane Central Register of Controlled Trial, MEDLINE, PubMed, and EMBASE. Only foreign articles published in the English language were included. Only articles that were randomized controlled trials investigating adult traumatic brain injury sustained following an acute, closed head injury were included. Two authors independently assessed at each stage. Quality was assessed using the Cochrane Collaboration's tool for assessing the risk of bias. All extracted data were combined using the Mantel-Haenszel estimator for pooled risk ratio with 95% CIs. p value of less than 0.05 was considered statistically significant. All statistical analyses were conducted using RevMan 5 (Cochrane Collaboration, Version 5.3, Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014). Twenty-two studies with 2,346 patients are included. Randomized controlled trials with a low risk of bias show significantly more mortality in the therapeutic hypothermia group (risk ratio, 1.37; 95% CI, 1.04-1.79; p = 0.02), whereas randomized controlled trials with a high risk of bias show the opposite with a higher mortality in the control group (risk ratio, 0.70; 95% CI, 0.60-0.82; p < 0.00001). Overall, this review is in-keeping with the conclusions published by the most recent randomized controlled trials. High-quality studies show no significant difference in mortality, poor outcomes, or new pneumonia. In addition, this review shows a place for fever control in the management of traumatic brain injury.

  7. Brain Network Modularity Predicts Exercise-Related Executive Function Gains in Older Adults

    Directory of Open Access Journals (Sweden)

    Pauline L. Baniqued

    2018-01-01

    Full Text Available Recent work suggests that the brain can be conceptualized as a network comprised of groups of sub-networks or modules. The extent of segregation between modules can be quantified with a modularity metric, where networks with high modularity have dense connections within modules and sparser connections between modules. Previous work has shown that higher modularity predicts greater improvements after cognitive training in patients with traumatic brain injury and in healthy older and young adults. It is not known, however, whether modularity can also predict cognitive gains after a physical exercise intervention. Here, we quantified modularity in older adults (N = 128, mean age = 64.74 who underwent one of the following interventions for 6 months (NCT01472744 on ClinicalTrials.gov: (1 aerobic exercise in the form of brisk walking (Walk, (2 aerobic exercise in the form of brisk walking plus nutritional supplement (Walk+, (3 stretching, strengthening and stability (SSS, or (4 dance instruction. After the intervention, the Walk, Walk+ and SSS groups showed gains in cardiorespiratory fitness (CRF, with larger effects in both walking groups compared to the SSS and Dance groups. The Walk, Walk+ and SSS groups also improved in executive function (EF as measured by reasoning, working memory, and task-switching tests. In the Walk, Walk+, and SSS groups that improved in EF, higher baseline modularity was positively related to EF gains, even after controlling for age, in-scanner motion and baseline EF. No relationship between modularity and EF gains was observed in the Dance group, which did not show training-related gains in CRF or EF control. These results are consistent with previous studies demonstrating that individuals with a more modular brain network organization are more responsive to cognitive training. These findings suggest that the predictive power of modularity may be generalizable across interventions aimed to enhance aspects of cognition and

  8. Intrinsic gray-matter connectivity of the brain in adults with autism spectrum disorder.

    Science.gov (United States)

    Ecker, Christine; Ronan, Lisa; Feng, Yue; Daly, Eileen; Murphy, Clodagh; Ginestet, Cedric E; Brammer, Michael; Fletcher, Paul C; Bullmore, Edward T; Suckling, John; Baron-Cohen, Simon; Williams, Steve; Loth, Eva; Murphy, Declan G M

    2013-08-06

    Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions that are accompanied by atypical brain connectivity. So far, in vivo evidence for atypical structural brain connectivity in ASD has mainly been based on neuroimaging studies of cortical white matter. However, genetic studies suggest that abnormal connectivity in ASD may also affect neural connections within the cortical gray matter. Such intrinsic gray-matter connections are inherently more difficult to describe in vivo but may be inferred from a variety of surface-based geometric features that can be measured using magnetic resonance imaging. Here, we present a neuroimaging study that examines the intrinsic cortico-cortical connectivity of the brain in ASD using measures of "cortical separation distances" to assess the global and local intrinsic "wiring costs" of the cortex (i.e., estimated length of horizontal connections required to wire the cortex within the cortical sheet). In a sample of 68 adults with ASD and matched controls, we observed significantly reduced intrinsic wiring costs of cortex in ASD, both globally and locally. Differences in global and local wiring cost were predominantly observed in fronto-temporal regions and also significantly predicted the severity of social and repetitive symptoms (respectively). Our study confirms that atypical cortico-cortical "connectivity" in ASD is not restricted to the development of white-matter connections but may also affect the intrinsic gray-matter architecture (and connectivity) within the cortical sheet. Thus, the atypical connectivity of the brain in ASD is complex, affecting both gray and white matter, and forms part of the core neural substrates underlying autistic symptoms.

  9. Endothelial β-Catenin Signaling Is Required for Maintaining Adult Blood-Brain Barrier Integrity and Central Nervous System Homeostasis.

    Science.gov (United States)

    Tran, Khiem A; Zhang, Xianming; Predescu, Dan; Huang, Xiaojia; Machado, Roberto F; Göthert, Joachim R; Malik, Asrar B; Valyi-Nagy, Tibor; Zhao, You-Yang

    2016-01-12

    The blood-brain barrier (BBB) formed by brain endothelial cells interconnected by tight junctions is essential for the homeostasis of the central nervous system. Although studies have shown the importance of various signaling molecules in BBB formation during development, little is known about the molecular basis regulating the integrity of the adult BBB. Using a mouse model with tamoxifen-inducible endothelial cell-restricted disruption of ctnnb1 (iCKO), we show here that endothelial β-catenin signaling is essential for maintaining BBB integrity and central nervous system homeostasis in adult mice. The iCKO mice developed severe seizures accompanied by neuronal injury, multiple brain petechial hemorrhages, and central nervous system inflammation, and all had postictal death. Disruption of endothelial β-catenin induced BBB breakdown and downregulation of the specific tight junction proteins claudin-1 and -3 in adult brain endothelial cells. The clinical relevance of the data is indicated by the observation of decreased expression of claudin-1 and nuclear β-catenin in brain endothelial cells of hemorrhagic lesions of hemorrhagic stroke patients. These results demonstrate the prerequisite role of endothelial β-catenin in maintaining the integrity of adult BBB. The results suggest that BBB dysfunction secondary to defective β-catenin transcription activity is a key pathogenic factor in hemorrhagic stroke, seizure activity, and central nervous system inflammation. © 2015 American Heart Association, Inc.

  10. Intrinsic spontaneous brain activity predicts individual variability in associative memory in older adults.

    Science.gov (United States)

    Zheng, Zhiwei; Li, Rui; Xiao, Fengqiu; He, Rongqiao; Zhang, Shouzi; Li, Juan

    2018-04-19

    Older adults demonstrate notable individual differences in associative memory. Here, resting-state functional magnetic resonance imaging (rsfMRI) was used to investigate whether intrinsic brain activity at rest could predict individual differences in associative memory among cognitively healthy older adults. Regional amplitude of low-frequency fluctuations (ALFF) analysis and a correlation-based resting-state functional connectivity (RSFC) approach were used to analyze data acquired from 102 cognitively normal elderly who completed the paired-associative learning test (PALT) and underwent fMRI scans. Participants were divided into two groups based on the retrospective self-reports on whether or not they utilized encoding strategies during the PALT. The behavioral results revealed better associative memory performance in the participants who reported utilizing memory strategies compared with participants who reported not doing so. The fMRI results showed that higher associative memory performance was associated with greater functional connectivity between the right superior frontal gyrus and the right posterior cerebellum lobe in the strategy group. The regional ALFF values in the right superior frontal gyrus were linked to associative memory performance in the no-strategy group. These findings suggest that the regional spontaneous fluctuations and functional connectivity during rest may subserve the individual differences in the associative memory in older adults, and that this is modulated by self-initiated memory strategy use. © 2018 The Institute of Psychology, Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

  11. 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

  12. Biologic variability of N-terminal pro-brain natriuretic peptide in adult healthy cats.

    Science.gov (United States)

    Harris, Autumn N; Estrada, Amara H; Gallagher, Alexander E; Winter, Brandy; Lamb, Kenneth E; Bohannon, Mary; Hanscom, Jancy; Mainville, Celine A

    2017-02-01

    Objectives The biologic variability of N-terminal pro-brain natriuretic peptide (NT-proBNP) and its impact on diagnostic utility is unknown in healthy cats and those with cardiac disease. The purpose of this study was to determine the biologic variation of NT-proBNP within-day and week-to-week in healthy adult cats. Methods Adult cats were prospectively evaluated by complete blood count (CBC), biochemistry, total thyroxine, echocardiography, electrocardiography and blood pressure, to exclude underlying systemic or cardiac disease. Adult healthy cats were enrolled and blood samples were obtained at 11 time points over a 6 week period (0, 2 h, 4 h, 6 h, 8 h, 10 h and at weeks 2, 3, 4, 5 and 6). The intra-individual (coefficient of variation [CV I ]) biologic variation along with index of individuality and reference change values (RCVs) were calculated. Univariate models were analyzed and included comparison of the six different time points for both daily and weekly samples. This was followed by a Tukey's post-hoc adjustment, with a P value of cats. Further research is warranted to evaluate NT-proBNP variability, particularly how serial measurements of NT-proBNP may be used in the diagnosis and management of cats with cardiac disease.

  13. 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.

  14. 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.

  15. An evaluation of reading comprehension of expository text in adults with traumatic brain injury.

    Science.gov (United States)

    Sohlberg, McKay Moore; Griffiths, Gina G; Fickas, Stephen

    2014-05-01

    This project was conducted to obtain information about reading problems of adults with traumatic brain injury (TBI) with mild-to-moderate cognitive impairments and to investigate how these readers respond to reading comprehension strategy prompts integrated into digital versions of text. Participants from 2 groups, adults with TBI (n = 15) and matched controls (n = 15), read 4 different 500-word expository science passages linked to either a strategy prompt condition or a no-strategy prompt condition. The participants' reading comprehension was evaluated using sentence verification and free recall tasks. The TBI and control groups exhibited significant differences on 2 of the 5 reading comprehension measures: paraphrase statements on a sentence verification task and communication units on a free recall task. Unexpected group differences were noted on the participants' prerequisite reading skills. For the within-group comparison, participants showed significantly higher reading comprehension scores on 2 free recall measures: words per communication unit and type-token ratio. There were no significant interactions. The results help to elucidate the nature of reading comprehension in adults with TBI with mild-to-moderate cognitive impairments and endorse further evaluation of reading comprehension strategies as a potential intervention option for these individuals. Future research is needed to better understand how individual differences influence a person's reading and response to intervention.

  16. Biological effects of radon in Drosophila

    International Nuclear Information System (INIS)

    Pimentel P, A.E.; Tavera D, L.; Cruces M, M.P.; Arceo M, C.; Rosa D, M.E. de la

    1992-04-01

    The main objective of this investigation, is to study the biological effects of the Radon-222 at low dose in 'Drosophila melanogaster'. It is necessary to mention that these effects will analyze from the genetic point of view for: 1) To evaluate in which form the Radon-222 to low dose it influences in some genetic components of the adaptation in Drosophila, such as: fecundity, viability egg-adult and sex proportion. 2) To evaluate which is the genetic effect that induces the Radon to low dose by means of the SMART technique in Drosophila melanogaster, and this way to try of to identify which is the possible mechanism that causes the genetic damage to somatic level. The carried out investigation was divided in three stages: 1. Tests to the vacuum resistance. 2. Test of somatic mutation, and 3. Determination of the presence of radon daughters on the adult of Drosophila. It is necessary to point out that all the experiments were made by triplicate and in each one of them was placed detectors in preset places. Those obtained results are presented inside the 4 charts included in the present work. (Author)

  17. The brain anatomy of attention-deficit/hyperactivity disorder in young adults - a magnetic resonance imaging study.

    Science.gov (United States)

    Gehricke, Jean-G; Kruggel, Frithjof; Thampipop, Tanyaporn; Alejo, Sharina Dyan; Tatos, Erik; Fallon, James; Muftuler, L Tugan

    2017-01-01

    This is one of the first studies to examine the structural brain anatomy and connectivity associated with an ADHD diagnosis and child as well as adult ADHD symptoms in young adults. It was hypothesized that an adult ADHD diagnosis and in particular childhood symptoms, are associated with widespread changes in the brain macro- and microstructure, which can be used to develop a morphometric biomarker for ADHD. Voxel-wise linear regression models were used to examine structural and diffusion-weighted MRI data in 72 participants (31 young adults with ADHD and 41 controls without ADHD) in relation to diagnosis and the number of self-reported child and adult symptoms. Findings revealed significant associations between ADHD diagnosis and widespread changes to the maturation of white matter fiber bundles and gray matter density in the brain, such as structural shape changes (incomplete maturation) of the middle and superior temporal gyrus, and fronto-basal portions of both frontal lobes. ADHD symptoms in childhood showed the strongest association with brain macro- and microstructural abnormalities. At the brain circuitry level, the superior longitudinal fasciculus (SLF) and cortico-limbic areas are dysfunctional in individuals with ADHD. The morphometric findings predicted an ADHD diagnosis correctly up to 83% of all cases. An adult ADHD diagnosis and in particular childhood symptoms are associated with widespread micro- and macrostructural changes. The SLF and cortico-limbic findings suggest complex audio-visual, motivational, and emotional dysfunctions associated with ADHD in young adults. The sensitivity of the morphometric findings in predicting an ADHD diagnosis was sufficient, which indicates that MRI-based assessments are a promising strategy for the development of a biomarker.

  18. The brain anatomy of attention-deficit/hyperactivity disorder in young adults - a magnetic resonance imaging study.

    Directory of Open Access Journals (Sweden)

    Jean-G Gehricke

    Full Text Available This is one of the first studies to examine the structural brain anatomy and connectivity associated with an ADHD diagnosis and child as well as adult ADHD symptoms in young adults. It was hypothesized that an adult ADHD diagnosis and in particular childhood symptoms, are associated with widespread changes in the brain macro- and microstructure, which can be used to develop a morphometric biomarker for ADHD.Voxel-wise linear regression models were used to examine structural and diffusion-weighted MRI data in 72 participants (31 young adults with ADHD and 41 controls without ADHD in relation to diagnosis and the number of self-reported child and adult symptoms.Findings revealed significant associations between ADHD diagnosis and widespread changes to the maturation of white matter fiber bundles and gray matter density in the brain, such as structural shape changes (incomplete maturation of the middle and superior temporal gyrus, and fronto-basal portions of both frontal lobes. ADHD symptoms in childhood showed the strongest association with brain macro- and microstructural abnormalities. At the brain circuitry level, the superior longitudinal fasciculus (SLF and cortico-limbic areas are dysfunctional in individuals with ADHD. The morphometric findings predicted an ADHD diagnosis correctly up to 83% of all cases.An adult ADHD diagnosis and in particular childhood symptoms are associated with widespread micro- and macrostructural changes. The SLF and cortico-limbic findings suggest complex audio-visual, motivational, and emotional dysfunctions associated with ADHD in young adults. The sensitivity of the morphometric findings in predicting an ADHD diagnosis was sufficient, which indicates that MRI-based assessments are a promising strategy for the development of a biomarker.

  19. Pattern of chondroitin sulfate proteoglycan expression after ablation of the sensorimotor cortex of the neonatal and adult rat brain

    Directory of Open Access Journals (Sweden)

    Dacić Sanja

    2008-01-01

    Full Text Available The central nervous system has a limited capacity for self-repair after damage. However, the neonatal brain has agreater capacity for recovery than the adult brain. These differences in the regenerative capability depend on local environmental factors and the maturational stage of growing axons. Among molecules which have both growth-promoting and growth-inhibiting activities is the heterogeneous class of chondroitin sulfate proteoglycans (CSPGs. In this paper, we investigated the chondroitin-4 and chondroitin-6 sulfate proteoglycan expression profile after left sensorimotor cortex ablation of the neonatal and adult rat brain. Immunohistochemical analysis revealed that compared to the normal uninjured cortex, lesion provoked up regulation of CSPGs showing a different pattern of expression in the neonatal vs. the adult brain. Punctuate and membrane-bound labeling was predominate after neonatal lesion, where as heavy deposition of staining in the extracellular matrix was observed after adult lesion. Heavy deposition of CSPG immunoreactivity around the lesionsite in adult rats, in contrast to a less CSPG-rich environment in neonatal rats, indicated that enhancement of the recovery process after neonatal injury is due to amore permissive environment.

  20. Isolation of a novel protein, P12-from adult Drosophila melanogaster that inhibits deoxyribonucleoside and protein kinase activities and activates 3'-5'-exonuclease activity

    DEFF Research Database (Denmark)

    Christiansen, Louise Slot; Zanten, Gabriella van; Berenstein, Dvora

    2016-01-01

    We have previously found that Drosophila melanogaster only has one deoxyribonucleoside kinase, Dm-dNK, however, capable to phosphorylate all four natural deoxyribonucleosides. Dm-dNK was originally isolated from an embryonic cell line. We wanted to study the expression of Dm-dNK during development......-dNK, also inhibited the two protein kinases to the same degree. Furthermore, testing P12 in a DNA polymerase based assay we found that the 3'-5'-exonuclease part of the DNA polymerase (Klenow polymerase) was activated....

  1. Current self-reported symptoms of attention deficit/hyperactivity disorder are associated with total brain volume in healthy adults.

    Directory of Open Access Journals (Sweden)

    Martine Hoogman

    Full Text Available BACKGROUND: Reduced total brain volume is a consistent finding in children with Attention Deficit/Hyperactivity Disorder (ADHD. In order to get a better understanding of the neurobiology of ADHD, we take the first step in studying the dimensionality of current self-reported adult ADHD symptoms, by looking at its relation with total brain volume. METHODOLOGY/PRINCIPAL FINDINGS: In a sample of 652 highly educated adults, the association between total brain volume, assessed with magnetic resonance imaging, and current number of self-reported ADHD symptoms was studied. The results showed an association between these self-reported ADHD symptoms and total brain volume. Post-hoc analysis revealed that the symptom domain of inattention had the strongest association with total brain volume. In addition, the threshold for impairment coincides with the threshold for brain volume reduction. CONCLUSIONS/SIGNIFICANCE: This finding improves our understanding of the biological substrates of self-reported ADHD symptoms, and suggests total brain volume as a target intermediate phenotype for future gene-finding in ADHD.

  2. Thyroid Hormone Regulates the Expression of the Sonic Hedgehog Signaling Pathway in the Embryonic and Adult Mammalian Brain

    OpenAIRE

    Desouza, Lynette A.; Sathanoori, Malini; Kapoor, Richa; Rajadhyaksha, Neha; Gonzalez, Luis E.; Kottmann, Andreas H.; Tole, Shubha; Vaidya, Vidita A.

    2011-01-01

    Thyroid hormone is important for development and plasticity in the immature and adult mammalian brain. Several thyroid hormone-responsive genes are regulated during specific developmental time windows, with relatively few influenced across the lifespan. We provide novel evidence that thyroid hormone regulates expression of the key developmental morphogen sonic hedgehog (Shh), and its coreceptors patched (Ptc) and smoothened (Smo), in the early embryonic and adult forebrain. Maternal hypo- and...

  3. Organotypic brain slice cultures of adult transgenic P301S mice--a model for tauopathy studies.

    Directory of Open Access Journals (Sweden)

    Agneta Mewes

    Full Text Available BACKGROUND: Organotypic brain slice cultures represent an excellent compromise between single cell cultures and complete animal studies, in this way replacing and reducing the number of animal experiments. Organotypic brain slices are widely applied to model neuronal development and regeneration as well as neuronal pathology concerning stroke, epilepsy and Alzheimer's disease (AD. AD is characterized by two protein alterations, namely tau hyperphosphorylation and excessive amyloid β deposition, both causing microglia and astrocyte activation. Deposits of hyperphosphorylated tau, called neurofibrillary tangles (NFTs, surrounded by activated glia are modeled in transgenic mice, e.g. the tauopathy model P301S. METHODOLOGY/PRINCIPAL FINDINGS: In this study we explore the benefits and limitations of organotypic brain slice cultures made of mature adult transgenic mice as a potential model system for the multifactorial phenotype of AD. First, neonatal (P1 and adult organotypic brain slice cultures from 7- to 10-month-old transgenic P301S mice have been compared with regard to vitality, which was monitored with the lactate dehydrogenase (LDH- and the MTT (3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assays over 15 days. Neonatal slices displayed a constant high vitality level, while the vitality of adult slice cultures decreased significantly upon cultivation. Various preparation and cultivation conditions were tested to augment the vitality of adult slices and improvements were achieved with a reduced slice thickness, a mild hypothermic cultivation temperature and a cultivation CO(2 concentration of 5%. Furthermore, we present a substantial immunohistochemical characterization analyzing the morphology of neurons, astrocytes and microglia in comparison to neonatal tissue. CONCLUSION/SIGNIFICANCE: Until now only adolescent animals with a maximum age of two months have been used to prepare organotypic brain slices. The current study

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

    Science.gov (United States)

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

    2016-04-01

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

  5. Metabolomic Studies in Drosophila.

    Science.gov (United States)

    Cox, James E; Thummel, Carl S; Tennessen, Jason M

    2017-07-01

    Metabolomic analysis provides a powerful new tool for studies of Drosophila physiology. This approach allows investigators to detect thousands of chemical compounds in a single sample, representing the combined contributions of gene expression, enzyme activity, and environmental context. Metabolomics has been used for a wide range of studies in Drosophila , often providing new insights into gene function and metabolic state that could not be obtained using any other approach. In this review, we survey the uses of metabolomic analysis since its entry into the field. We also cover the major methods used for metabolomic studies in Drosophila and highlight new directions for future research. Copyright © 2017 by the Genetics Society of America.

  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. Systematic review of self-reported prognosis in adults after mild traumatic brain injury

    DEFF Research Database (Denmark)

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

    2014-01-01

    accepted and form our evidence base of prognostic studies. Of these, 23 addressed self-reported outcomes in adults, including 2 of the 3 original ICoMP research studies. These studies show that common postconcussion symptoms are not specific to MTBI/concussion and occur after other injuries as well. Poor...... recovery after MTBI is associated with poorer premorbid mental and physical health status and with more injury-related stress. Most recover over 1 year, but persistent symptoms are more likely in those with more acute symptoms and more emotional stress. CONCLUSIONS: Common subjective symptoms after MTBI......OBJECTIVE: To update the mild traumatic brain injury (MTBI) prognosis review published by the World Health Organization Task Force in 2004. DATA SOURCES: MEDLINE, PsycINFO, Embase, CINAHL, and SPORTDiscus were searched from 2001 to 2012. We included published, peer-reviewed studies with more than...

  8. Clinical utility of the Wechsler Adult Intelligence Scale-Fourth Edition after traumatic brain injury.

    Science.gov (United States)

    Donders, Jacobus; Strong, Carrie-Ann H

    2015-02-01

    The performance of 100 patients with traumatic brain injury (TBI) on the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV) was compared with that of 100 demographically matched neurologically healthy controls. Processing Speed was the only WAIS-IV factor index that was able to discriminate between persons with moderate-severe TBI on the one hand and persons with either less severe TBI or neurologically healthy controls on the other hand. The Processing Speed index also had acceptable sensitivity and specificity when differentiating between patients with TBI who either did or did not have scores in the clinically significant range on the Trail Making Test. It is concluded that WAIS-IV Processing Speed has acceptable clinical utility in the evaluation of patients with moderate-severe TBI but that it should be supplemented with other measures to assure sufficient accuracy in the diagnostic process. © The Author(s) 2014.

  9. 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.

  10. Increased Brain Glucose Uptake After 12 Weeks of Aerobic High-Intensity Interval Training in Young and Older Adults.

    Science.gov (United States)

    Robinson, Matthew M; Lowe, Val J; Nair, K Sreekumaran

    2018-01-01

    Aerobic exercise training can increase brain volume and blood flow, but the impact on brain metabolism is less known. We determined whether high-intensity interval training (HIIT) increases brain metabolism by measuring brain glucose uptake in younger and older adults. Brain glucose uptake was measured before and after HIIT or a sedentary (SED) control period within a larger exercise study. Study procedures were performed at the Mayo Clinic in Rochester, MN. Participants were younger (18 to 30 years) or older (65 to 80 years) SED adults who were free of major medical conditions. Group sizes were 15 for HIIT (nine younger and six older) and 12 for SED (six younger and six older). Participants completed 12 weeks of HIIT or SED. HIIT was 3 days per week of 4 × 4 minute intervals at over 90% of peak aerobic capacity (VO2peak) with 2 days per week of treadmill walking at 70% VO2peak. Resting brain glucose uptake was measured using 18F-fluorodeoxyglucose positron emission tomography scans at baseline and at week 12. Scans were performed at 96 hours after exercise. VO2peak was measured by indirect calorimetry. Glucose uptake increased significantly in the parietal-temporal and caudate regions after HIIT compared with SED. The gains with HIIT were not observed in all brain regions. VO2peak was increased for all participants after HIIT and did not change with SED. We demonstrate that brain glucose metabolism increased after 12 weeks of HIIT in adults in regions where it is reduced in Alzheimer's disease. Copyright © 2017 Endocrine Society

  11. 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'. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

    Kim, Ung Jin; Chang, Kee Hyun; Han, Man Chung

    1981-01-01

    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

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

    International Nuclear Information System (INIS)

    Kim, Ung Jin; Chang, Kee Hyun; Han, Man Chung

    1981-01-01

    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

  14. Effects of hypoglycaemia on neuronal metabolism in the adult brain: role of alternative substrates to glucose.

    Science.gov (United States)

    Amaral, Ana I

    2013-07-01

    Hypoglycaemia is characterized by decreased blood glucose levels and is associated with different pathologies (e.g. diabetes, inborn errors of metabolism). Depending on its severity, it might affect cognitive functions, including impaired judgment and decreased memory capacity, which have been linked to alterations of brain energy metabolism. Glucose is the major cerebral energy substrate in the adult brain and supports the complex metabolic interactions between neurons and astrocytes, which are essential for synaptic activity. Therefore, hypoglycaemia disturbs cerebral metabolism and, consequently, neuronal function. Despite the high vulnerability of neurons to hypoglycaemia, important neurochemical changes enabling these cells to prolong their resistance to hypoglycaemia have been described. This review aims at providing an overview over the main metabolic effects of hypoglycaemia on neurons, covering in vitro and in vivo findings. Recent studies provided evidence that non-glucose substrates including pyruvate, glycogen, ketone bodies, glutamate, glutamine, and aspartate, are metabolized by neurons in the absence of glucose and contribute to prolong neuronal function and delay ATP depletion during hypoglycaemia. One of the pathways likely implicated in the process is the pyruvate recycling pathway, which allows for the full oxidation of glutamate and glutamine. The operation of this pathway in neurons, particularly after hypoglycaemia, has been re-confirmed recently using metabolic modelling tools (i.e. Metabolic Flux Analysis), which allow for a detailed investigation of cellular metabolism in cultured cells. Overall, the knowledge summarized herein might be used for the development of potential therapies targeting neuronal protection in patients vulnerable to hypoglycaemic episodes.

  15. Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain

    Directory of Open Access Journals (Sweden)

    Katharine Askew

    2017-01-01

    Full Text Available Summary: Microglia play key roles in brain development, homeostasis, and function, and it is widely assumed that the adult population is long lived and maintained by self-renewal. However, the precise temporal and spatial dynamics of the microglial population are unknown. We show in mice and humans that the turnover of microglia is remarkably fast, allowing the whole population to be renewed several times during a lifetime. The number of microglial cells remains steady from late postnatal stages until aging and is maintained by the spatial and temporal coupling of proliferation and apoptosis, as shown by pulse-chase studies, chronic in vivo imaging of microglia, and the use of mouse models of dysregulated apoptosis. Our results reveal that the microglial population is constantly and rapidly remodeled, expanding our understanding of its role in the maintenance of brain homeostasis. : The mechanism or mechanisms underlying microglial homeostasis are unknown. Askew et al. show that microglia self-renewal is maintained by coupled proliferation and apoptosis, resulting in a stable microglia number over a mouse or human lifetime. Keywords: self-renewal, BrdU, CSF1R, CX3CR1, Macgreen, Vav-Bcl2, RNA-seq

  16. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

    Qasmi, S.A.; Ghaffar, A.; Akram, M.

    2015-01-01

    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)

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

    Science.gov (United States)

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

    2013-12-15

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

  19. Selective insulin resistance in homeostatic and cognitive control brain areas in overweight and obese adults.

    Science.gov (United States)

    Kullmann, Stephanie; Heni, Martin; Veit, Ralf; Scheffler, Klaus; Machann, Jürgen; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

    2015-06-01

    Impaired brain insulin action has been linked to obesity, type 2 diabetes, and neurodegenerative diseases. To date, the central nervous effects of insulin in obese humans still remain ill defined, and no study thus far has evaluated the specific brain areas affected by insulin resistance. In 25 healthy lean and 23 overweight/obese participants, we performed magnetic resonance imaging to measure cerebral blood flow (CBF) before and 15 and 30 min after application of intranasal insulin or placebo. Additionally, participants explicitly rated pictures of high-caloric savory and sweet food 60 min after the spray for wanting and liking. In response to insulin compared with placebo, we found a significant CBF decrease in the hypothalamus in both lean and overweight/obese participants. The magnitude of this response correlated with visceral adipose tissue independent of other fat compartments. Furthermore, we observed a differential response in the lean compared with the overweight/obese group in the prefrontal cortex, resulting in an insulin-induced CBF reduction in lean participants only. This prefrontal cortex response significantly correlated with peripheral insulin sensitivity and eating behavior measures such as disinhibition and food craving. Behaviorally, we were able to observe a significant reduction for the wanting of sweet foods after insulin application in lean men only. Brain insulin action was selectively impaired in the prefrontal cortex in overweight and obese adults and in the hypothalamus in participants with high visceral adipose tissue, potentially promoting an altered homeostatic set point and reduced inhibitory control contributing to overeating behavior. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  20. Brain serotonin and dopamine transporter bindings in adults with high-functioning autism.

    Science.gov (United States)

    Nakamura, Kazuhiko; Sekine, Yoshimoto; Ouchi, Yasuomi; Tsujii, Masatsugu; Yoshikawa, Etsuji; Futatsubashi, Masami; Tsuchiya, Kenji J; Sugihara, Genichi; Iwata, Yasuhide; Suzuki, Katsuaki; Matsuzaki, Hideo; Suda, Shiro; Sugiyama, Toshiro; Takei, Nori; Mori, Norio

    2010-01-01

    Autism is a neurodevelopmental disorder that is characterized by repetitive and/or obsessive interests and behavior and by deficits in sociability and communication. Although its neurobiological underpinnings are postulated to lie in abnormalities of the serotoninergic and dopaminergic systems, the details remain unknown. To determine the occurrence of changes in the binding of serotonin and dopamine transporters, which are highly selective markers for their respective neuronal systems. Using positron emission tomography, we measured the binding of brain serotonin and dopamine transporters in each individual with the radioligands carbon 11 ((11)C)-labeled trans-1,2,3,5,6,10-beta-hexahydro-6-[4-(methylthio)phenyl]pyrrolo-[2,1-a]isoquinoline ([(11)C](+)McN-5652) and 2beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane ([(11)C]WIN-35,428), respectively. Statistical parametric mapping was used for between-subject analysis and within-subject correlation analysis with respect to clinical variables. Participants recruited from the community. Twenty men (age range, 18-26 years; mean [SD] IQ, 99.3 [18.1]) with autism and 20 age- and IQ-matched control subjects. Serotonin transporter binding was significantly lower throughout the brain in autistic individuals compared with controls (P dopamine transporter binding was significantly higher in the orbitofrontal cortex of the autistic group (P dopamine transporter binding was significantly inversely correlated with serotonin transporter binding (r = -0.61; P = .004). The brains of autistic individuals have abnormalities in both serotonin transporter and dopamine transporter binding. The present findings indicate that the gross abnormalities in these neurotransmitter systems may underpin the neurophysiologic mechanism of autism. Our sample was not characteristic or representative of a typical sample of adults with autism in the community.

  1. 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.

  2. Malnutrition and Risk of Structural Brain Changes Seen on Magnetic Resonance Imaging in Older Adults.

    Science.gov (United States)

    de van der Schueren, Marian A E; Lonterman-Monasch, Sabine; van der Flier, Wiesje M; Kramer, Mark H; Maier, Andrea B; Muller, Majon

    2016-12-01

    To study the associations between protein energy malnutrition, micronutrient malnutrition, brain atrophy, and cerebrovascular lesions. Cross-sectional. Geriatric outpatient clinic. Older adults (N = 475; mean age 80 ± 7). Nutritional status was assessed using the Mini Nutritional Assessment (MNA) and according to serum micronutrient levels (vitamins B1, B6, B12, D; folic acid). White matter hyperintensities (WMHs), global cortical brain atrophy, and medial temporal lobe atrophy on magnetic resonance imaging (MRI) were rated using visual rating scales. Logistic regression analyses were performed to assess associations between the three MNA categories (malnutrition (MNA = 17-23.5). Participants at risk of malnutrition (odds ratio (OR) = 1.93, 95% confidence interval (CI) = 1.01-3.71) or who were malnourished (OR = 2.80, 95% CI = 1.19-6.60) had a greater probability of having severe WMHs independent of age and sex than those with adequate nutritional status. Results remained significant after further adjustments for cognitive function, depressive symptoms, cardiovascular risk factors, history of cardiovascular disease, smoking and alcohol use, and micronutrient levels. Lower vitamin B1 (OR = 1.51, 95% CI = 1.11-2.08) and B12 (OR = 1.45, 95% CI = 1.02-2.04) levels were also related to greater risk of severe WMHs, independent of age and sex. Results remained significant after additional adjustments. MNA and vitamin levels were not associated with measures of brain atrophy. Malnutrition and lower vitamin B1 and B12 levels were independently associated with greater risk of WMHs. Underlying mechanisms need to be further clarified, and whether nutritional interventions can modify these findings also needs to be studied. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

  3. 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)

    Chen, Z.G.; Hindmarsh, T.; Li, T.Q.

    2001-01-01

    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

  4. The Reliability, Validity, and Feasibility of Physical Activity Measurement in Adults With Traumatic Brain Injury: An Observational Study

    NARCIS (Netherlands)

    Hassett, L.; Moseley, A.; Harmer, A.; van der Ploeg, H.P.

    2015-01-01

    Objective: To determine the reliability and validity of the Physical Activity Scale for Individuals with a Physical Disability (PASIPD) in adults with severe traumatic brain injury (TBI) and estimate the proportion of the sample participants who fail to meet the World Health Organization guidelines

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

    Science.gov (United States)

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

    2011-04-01

    Dietary restriction (DR) has recognized health benefits that may extend to brain. We examined how DR affects bioenergetics-relevant enzymes and signaling pathways in the brains of C57BL/6 mice. Five-month-old male mice were placed in ad libitum or one of two repeated fasting and refeeding (RFR) groups, an alternate day (intermittent fed; IF) or alternate day plus antioxidants (blueberry, pomegranate, and green tea extracts) (IF + AO) fed group. During the 24-h fast blood glucose levels initially fell but stabilized within 6 h of starting the fast, thus avoiding frank hypoglycemia. DR in general appeared to enhance insulin sensitivity. After six weeks brain AKT and glycogen synthase kinase 3 beta phosphorylation were lower in the RFR mice, suggesting RFR reduced brain insulin-signaling pathway activity. Pathways that mediate mitochondrial biogenesis were not activated; AMP kinase phosphorylation, silent information regulator 2 phosphorylation, peroxisomal proliferator-activated receptor-gamma coactivator 1 alpha levels, and cytochrome oxidase subunit 4 levels did not change. ATP levels also did not decline, which suggests the RFR protocols did not directly impact brain bioenergetics. Antioxidant supplementation did not affect the brain parameters we evaluated. Our data indicate in young adult male C57BL/6 mice, RFR primarily affects brain energy metabolism by reducing brain insulin signaling, which potentially results indirectly as a consequence of reduced peripheral insulin production. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  6. Caspase inhibition in select olfactory neurons restores innate attraction behavior in aged Drosophila.

    Directory of Open Access Journals (Sweden)

    Takahiro Chihara

    2014-06-01

    Full Text Available Sensory and cognitive performance decline with age. Neural dysfunction caused by nerve death in senile dementia and neurodegenerative disease has been intensively studied; however, functional changes in neural circuits during the normal aging process are not well understood. Caspases are key regulators of cell death, a hallmark of age-related neurodegeneration. Using a genetic probe for caspase-3-like activity (DEVDase activity, we have mapped age-dependent neuronal changes in the adult brain throughout the lifespan of Drosophila. Spatio-temporally restricted caspase activation was observed in the antennal lobe and ellipsoid body, brain structures required for olfaction and visual place memory, respectively. We also found that caspase was activated in an age-dependent manner in specific subsets of Drosophila olfactory receptor neurons (ORNs, Or42b and Or92a neurons. These neurons are essential for mediating innate attraction to food-related odors. Furthermore, age-induced impairments of neural transmission and attraction behavior could be reversed by specific inhibition of caspase in these ORNs, indicating that caspase activation in Or42b and Or92a neurons is responsible for altering animal behavior during normal aging.

  7. Caspase inhibition in select olfactory neurons restores innate attraction behavior in aged Drosophila.

    Science.gov (United States)

    Chihara, Takahiro; Kitabayashi, Aki; Morimoto, Michie; Takeuchi, Ken-ichi; Masuyama, Kaoru; Tonoki, Ayako; Davis, Ronald L; Wang, Jing W; Miura, Masayuki

    2014-06-01

    Sensory and cognitive performance decline with age. Neural dysfunction caused by nerve death in senile dementia and neurodegenerative disease has been intensively studied; however, functional changes in neural circuits during the normal aging process are not well understood. Caspases are key regulators of cell death, a hallmark of age-related neurodegeneration. Using a genetic probe for caspase-3-like activity (DEVDase activity), we have mapped age-dependent neuronal changes in the adult brain throughout the lifespan of Drosophila. Spatio-temporally restricted caspase activation was observed in the antennal lobe and ellipsoid body, brain structures required for olfaction and visual place memory, respectively. We also found that caspase was activated in an age-dependent manner in specific subsets of Drosophila olfactory receptor neurons (ORNs), Or42b and Or92a neurons. These neurons are essential for mediating innate attraction to food-related odors. Furthermore, age-induced impairments of neural transmission and attraction behavior could be reversed by specific inhibition of caspase in these ORNs, indicating that caspase activation in Or42b and Or92a neurons is responsible for altering animal behavior during normal aging.

  8. Drosophila Regulate Yeast Density and Increase Yeast Community Similarity in a Natural Substrate

    OpenAIRE

    Stamps, Judy A.; Yang, Louie H.; Morales, Vanessa M.; Boundy-Mills, Kyria L.

    2012-01-01

    Drosophila melanogaster adults and larvae, but especially larvae, had profound effects on the densities and community structure of yeasts that developed in banana fruits. Pieces of fruit exposed to adult female flies previously fed fly-conditioned bananas developed higher yeast densities than pieces of the same fruits that were not exposed to flies, supporting previous suggestions that adult Drosophila vector yeasts to new substrates. However, larvae alone had dramatic effects on yeast densit...

  9. Research progress on Drosophila visual cognition in China

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Visual cognition,as one of the fundamental aspects of cognitive neuroscience,is generally associated with high-order brain functions in animals and human.Drosophila,as a model organism,shares certain features of visual cognition in common with mammals at the genetic,molecular,cellular,and even higher behavioral levels.From learning and memory to decision making,Drosophila covers a broad spectrum of higher cognitive behaviors beyond what we had expected.Armed with powerful tools of genetic manipulation in Drosophila,an increasing number of studies have been conducted in order to elucidate the neural circuit mechanisms underlying these cognitive behaviors from a genes-brain-behavior perspective.The goal of this review is to integrate the most important studies on visual cognition in Drosophila carried out in mainland China during the last decade into a body of knowledge encompassing both the basic neural operations and circuitry of higher brain function in Drosophila.Here,we consider a series of the higher cognitive behaviors beyond learning and memory,such as visual pattern recognition,feature and context generalization,different feature memory traces,salience-based decision,attention-like behavior,and cross-modal leaning and memory.We discuss the possible general gain-gating mechanism implementing by dopamine-mushroom body circuit in fly’s visual cognition.We hope that our brief review on this aspect will inspire further study on visual cognition in flies,or even beyond.

  10. Research progress on Drosophila visual cognition in China.

    Science.gov (United States)

    Guo, AiKe; Zhang, Ke; Peng, YueQin; Xi, Wang

    2010-03-01

    Visual cognition, as one of the fundamental aspects of cognitive neuroscience, is generally associated with high-order brain functions in animals and human. Drosophila, as a model organism, shares certain features of visual cognition in common with mammals at the genetic, molecular, cellular, and even higher behavioral levels. From learning and memory to decision making, Drosophila covers a broad spectrum of higher cognitive behaviors beyond what we had expected. Armed with powerful tools of genetic manipulation in Drosophila, an increasing number of studies have been conducted in order to elucidate the neural circuit mechanisms underlying these cognitive behaviors from a genes-brain-behavior perspective. The goal of this review is to integrate the most important studies on visual cognition in Drosophila carried out in mainland China during the last decade into a body of knowledge encompassing both the basic neural operations and circuitry of higher brain function in Drosophila. Here, we consider a series of the higher cognitive behaviors beyond learning and memory, such as visual pattern recognition, feature and context generalization, different feature memory traces, salience-based decision, attention-like behavior, and cross-modal leaning and memory. We discuss the possible general gain-gating mechanism implementing by dopamine - mushroom body circuit in fly's visual cognition. We hope that our brief review on this aspect will inspire further study on visual cognition in flies, or even beyond.

  11. 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-na?ve adult SAD patients and 19 healthy controls. Voxels wer...

  12. Biotic and abiotic factors impacting development, behavior, phenology, and reproductive biology of Drosophila suzukii

    Science.gov (United States)

    Spotted wing drosophila, Drosophila suzukii, quickly emerged as a devastating invasive pest of small and stone fruits in the Americas and Europe. To better understand the population dynamics of D. suzukii, we reviewed recent work on juvenile development, adult reproduction, and seasonal variation in...

  13. Evidence for transgenerational metabolic programming in Drosophila

    Directory of Open Access Journals (Sweden)

    Jessica L. Buescher

    2013-09-01

    Worldwide epidemiologic studies have repeatedly demonstrated an association between prenatal nutritional environment, birth weight and susceptibility to adult diseases including obesity, cardiovascular disease and type 2 diabetes. Despite advances in mammalian model systems, the molecular mechanisms underlying this phenomenon are unclear, but might involve programming mechanisms such as epigenetics. Here we describe a new system for evaluating metabolic programming mechanisms using a simple, genetically tractable Drosophila model. We examined the effect of maternal caloric excess on offspring and found that a high-sugar maternal diet alters body composition of larval offspring for at least two generations, augments an obese-like phenotype under suboptimal (high-calorie feeding conditions in adult offspring, and modifies expression of metabolic genes. Our data indicate that nutritional programming mechanisms could be highly conserved and support the use of Drosophila as a model for evaluating the underlying genetic and epigenetic contributions to this phenomenon.

  14. Is performance on the Wechsler test of adult reading affected by traumatic brain injury?

    Science.gov (United States)

    Mathias, J L; Bowden, S C; Bigler, E D; Rosenfeld, J V

    2007-11-01

    The validity of the National Adult Reading Test (NART) as a predictor of premorbid IQ when used with patients who have sustained a traumatic brain injury (TBI) has been questioned in recent years. This study examined whether performance on the Wechsler Test of Adult Reading (WTAR) is similarly affected by TBI in the first year after an injury. The WTAR scores of participants who had sustained a mild TBI (N=82), moderate TBI (N=73), severe TBI (N=61) or an orthopaedic injury (N=95) were compared (cross-sectional study). A subset of 21 mild TBI, 31 moderate TBI, 26 severe TBI and 21 control group participants were additionally reassessed 6 months later to assess the impact of recovery on WTAR scores (longitudinal study). The severe TBI group had significantly lower scores on the WTAR than the mild TBI, moderate TBI and control groups in the cross-sectional study, despite being matched demographically. The findings from the longitudinal study revealed a significant group difference and a small improvement in performance over time but the interaction between group and time was not significant, suggesting that the improvements in WTAR performance over time were not restricted to more severely injured individuals whose performance was temporarily suppressed. These findings suggest that reading performance may be affected by severe TBI and that the WTAR may underestimate premorbid IQ when used in this context, which may cause clinicians to underestimate the cognitive deficits experienced by these patients.

  15. Tai Chi Chuan and Baduanjin Increase Grey Matter Volume in Older Adults: A Brain Imaging Study.

    Science.gov (United States)

    Tao, Jing; Liu, Jiao; Liu, Weilin; Huang, Jia; Xue, Xiehua; Chen, Xiangli; Wu, Jinsong; Zheng, Guohua; Chen, Bai; Li, Ming; Sun, Sharon; Jorgenson, Kristen; Lang, Courtney; Hu, Kun; Chen, Shanjia; Chen, Lidian; Kong, Jian

    2017-01-01

    The aim of this study is to investigate and compare how 12-weeks of Tai Chi Chuan and Baduanjin exercise can modulate brain structure and memory function in older adults. Magnetic resonance imaging and memory function measurements (Wechsler Memory Scale-Chinese revised, WMS-CR) were applied at both the beginning and end of the study. Results showed that both Tai Chi Chuan and Baduanjin could significantly increase grey matter volume (GMV) in the insula, medial temporal lobe, and putamen after 12-weeks of exercise. No significant differences were observed in GMV between the Tai Chi Chuan and Baduanjin groups. We also found that compared to healthy controls, Tai Chi Chuan and Baduanjin significantly improved visual reproduction subscores on the WMS-CR. Baduanjin also improved mental control, recognition, touch, and comprehension memory subscores of the WMS-CR compared to the control group. Memory quotient and visual reproduction subscores were both associated with GMV increases in the putamen and hippocampus. Our results demonstrate the potential of Tai Chi Chuan and Baduanjin exercise for the prevention of memory deficits in older adults.

  16. 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.

  17. Effects of adult attachment and emotional distractors on brain mechanisms of cognitive control.

    Science.gov (United States)

    Warren, Stacie L; Bost, Kelly K; Roisman, Glenn I; Silton, Rebecca Levin; Spielberg, Jeffrey M; Engels, Anna S; Choi, Eunsil; Sutton, Bradley P; Miller, Gregory A; Heller, Wendy

    2010-12-01

    Using data from 34 participants who completed an emotion-word Stroop task during functional magnetic resonance imaging, we examined the effects of adult attachment on neural activity associated with top-down cognitive control in the presence of emotional distractors. Individuals with lower levels of secure-base-script knowledge--reflected in an adult's inability to generate narratives in which attachment-related threats are recognized, competent help is provided, and the problem is resolved--demonstrated more activity in prefrontal cortical regions associated with emotion regulation (e.g., right orbitofrontal cortex) and with top-down cognitive control (left dorsolateral prefrontal cortex, anterior cingulate cortex, and superior frontal gyrus). Less efficient performance and related increases in brain activity suggest that insecure attachment involves a vulnerability to distraction by attachment-relevant emotional information and that greater cognitive control is required to attend to task-relevant, nonemotional information. These results contribute to the understanding of mechanisms through which attachment-related experiences may influence developmental adaptation.

  18. Examination of validity in spoken language evaluations: Adult onset stuttering following mild traumatic brain injury.

    Science.gov (United States)

    Roth, Carole R; Cornis-Pop, Micaela; Beach, Woodford A

    2015-01-01

    Reports of increased incidence of adult onset stuttering in veterans and service members with mild traumatic brain injury (mTBI) from combat operations in Iraq and Afghanistan lead to a reexamination of the neurogenic vs. psychogenic etiology of stuttering. This article proposes to examine the merit of the dichotomy between neurogenic and psychogenic bases of stuttering, including symptom exaggeration, for the evaluation and treatment of the disorder. Two case studies of adult onset stuttering in service members with mTBI from improvised explosive device blasts are presented in detail. Speech fluency was disrupted by abnormal pauses and speech hesitations, brief blocks, rapid repetitions, and occasional prolongations. There was also wide variability in the frequency of stuttering across topics and conversational situations. Treatment focused on reducing the frequency and severity of dysfluencies and included educational, psychological, environmental, and behavioral interventions. Stuttering characteristics as well as the absence of objective neurological findings ruled out neurogenic basis of stuttering in these two cases and pointed to psychogenic causes. However, the differential diagnosis had only limited value for developing the plan of care. The successful outcomes of the treatment serve to illustrate the complex interaction of neurological, psychological, emotional, and environmental factors of post-concussive symptoms and to underscore the notion that there are many facets to symptom presentation in post-combat health.

  19. Prevalence of traumatic brain injury in the general adult population: a meta-analysis.

    Science.gov (United States)

    Frost, R Brock; Farrer, Thomas J; Primosch, Mark; Hedges, Dawson W

    2013-01-01

    Traumatic brain injury (TBI) is a significant public-health concern. To understand the extent of TBI, it is important to assess the prevalence of TBI in the general population. However, the prevalence of TBI in the general population can be difficult to measure because of differing definitions of TBI, differing TBI severity levels, and underreporting of sport-related TBI. Additionally, prevalence reports vary from study to study. In this present study, we used meta-analytic methods to estimate the prevalence of TBI in the adult general population. Across 15 studies, all originating from developed countries, which included 25,134 adults, 12% had a history of TBI. Men had more than twice the odds of having had a TBI than did women, suggesting that male gender is a risk factor for TBI. The adverse behavioral, cognitive and psychiatric effects associated with TBI coupled with the high prevalence of TBI identified in this study indicate that TBI is a considerable public and personal-health problem. Copyright © 2012 S. Karger AG, Basel.

  20. Frontal brain asymmetry in adult attention-deficit/hyperactivity disorder (ADHD): extending the motivational dysfunction hypothesis.

    Science.gov (United States)

    Keune, Philipp M; Wiedemann, Eva; Schneidt, Alexander; Schönenberg, Michael

    2015-04-01

    Attention-deficit/hyperactivity disorder (ADHD) involves motivational dysfunction, characterized by excessive behavioral approach tendencies. Frontal brain asymmetry in the alpha band (8-13 Hz) in resting-state electroencephalogram (EEG) represents a neural correlate of global motivational tendencies, and abnormal asymmetry, indicating elevated approach motivation, was observed in pediatric and adult patients. To date, the relation between ADHD symptoms, depression and alpha asymmetry, its temporal metric properties and putative gender-specificity remain to be explored. Adult ADHD patients (n=52) participated in two resting-state EEG recordings, two weeks apart. Asymmetry measures were aggregated across recordings to increase trait specificity. Putative region-specific associations between asymmetry, ADHD symptoms and depression, its gender-specificity and test-retest reliability were examined. ADHD symptoms were associated with approach-related asymmetry (stronger relative right-frontal alpha power). Approach-related asymmetry was pronounced in females, and also associated with depression. The latter association was mediated by ADHD symptoms. Test-retest reliability was sufficient. The association between reliably assessable alpha asymmetry and ADHD symptoms supports the motivational dysfunction hypothesis. ADHD symptoms mediating an atypical association between asymmetry and depression may be attributed to depression arising secondary to ADHD. Gender-specific findings require replication. Frontal alpha asymmetry may represent a new reliable marker of ADHD symptoms. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  1. Proton Chemical Shift Imaging of the Brain in Pediatric and Adult Developmental Stuttering.

    Science.gov (United States)

    O'Neill, Joseph; Dong, Zhengchao; Bansal, Ravi; Ivanov, Iliyan; Hao, Xuejun; Desai, Jay; Pozzi, Elena; Peterson, Bradley S

    2017-01-01

    Developmental stuttering is a neuropsychiatric condition of incompletely understood brain origin. Our recent functional magnetic resonance imaging study indicates a possible partial basis of stuttering in circuits enacting self-regulation of motor activity, attention, and emotion. To further characterize the neurophysiology of stuttering through in vivo assay of neurometabolites in suspect brain regions. Proton chemical shift imaging of the brain was performed in a case-control study of children and adults with and without stuttering. Recruitment, assessment, and magnetic resonance imaging were performed in an academic research setting. Ratios of N-acetyl-aspartate plus N-acetyl-aspartyl-glutamate (NAA) to creatine (Cr) and choline compounds (Cho) to Cr in widespread cerebral cortical, white matter, and subcortical regions were analyzed using region of interest and data-driven voxel-based approaches. Forty-seven children and adolescents aged 5 to 17 years (22 with stuttering and 25 without) and 47 adults aged 21 to 51 years (20 with stuttering and 27 without) were recruited between June 2008 and March 2013. The mean (SD) ages of those in the stuttering and control groups were 12.2 (4.2) years and 13.4 (3.2) years, respectively, for the pediatric cohort and 31.4 (7.5) years and 30.5 (9.9) years, respectively, for the adult cohort. Region of interest-based findings included lower group mean NAA:Cr ratio in stuttering than nonstuttering participants in the right inferior frontal cortex (-7.3%; P = .02), inferior frontal white matter (-11.4%; P < .001), and caudate (-10.6%; P = .04), while the Cho:Cr ratio was higher in the bilateral superior temporal cortex (left: +10.0%; P = .03 and right: +10.8%; P = .01), superior temporal white matter (left: +14.6%; P = .003 and right: +9.5%; P = .02), and thalamus (left: +11.6%; P = .002 and right: +11.1%; P = .001). False discovery rate-corrected voxel-based findings were highly consistent

  2. Persistent short-term memory defects following sleep deprivation in a drosophila model of Parkinson disease.

    Science.gov (United States)

    Seugnet, Laurent; Galvin, James E; Suzuki, Yasuko; Gottschalk, Laura; Shaw, Paul J

    2009-08-01

    Parkinson disease (PD) is the second most common neurodegenerative disorder in the United States. It is associated with motor deficits, sleep disturbances, and cognitive impairment. The pathology associated with PD and the effects of sleep deprivation impinge, in part, upon common molecular pathways suggesting that sleep loss may be particularly deleterious to the degenerating brain. Thus we investigated the long-term consequences of sleep deprivation on shortterm memory using a Drosophila model of Parkinson disease. Transgenic strains of Drosophila melanogaster. Using the GAL4-UAS system, human alpha-synuclein was expressed throughout the nervous system of adult flies. Alpha-synuclein expressing flies (alpha S flies) and the corresponding genetic background controls were sleep deprived for 12 h at age 16 days and allowed to recover undisturbed for at least 3 days. Short-term memory was evaluated using aversive phototaxis suppression. Dopaminergic systems were assessed using mRNA profiling and immunohistochemistry. MEASURMENTS AND RESULTS: When sleep deprived at an intermediate stage of the pathology, alpha S flies showed persistent short-term memory deficits that lasted > or = 3 days. Cognitive deficits were not observed in younger alpha S flies nor in genetic background controls. Long-term impairments were not associated with accelerated loss of dopaminergic neurons. However mRNA expression of the dopamine receptors dDA1 and DAMB were significantly increased in sleep deprived alpha S flies. Blocking D1-like receptors during sleep deprivation prevented persistent shortterm memory deficits. Importantly, feeding flies the polyphenolic compound curcumin blocked long-term learning deficits. These data emphasize the importance of sleep in a degenerating/reorganizing brain and shows that pathological processes induced by sleep deprivation can be dissected at the molecular and cellular level using Drosophila genetics.

  3. Mediators of a long-term movement abnormality in a Drosophila melanogaster model of classic galactosemia

    Directory of Open Access Journals (Sweden)

    Emily L. Ryan

    2012-11-01

    Despite neonatal diagnosis and life-long dietary restriction of galactose, many patients with classic galactosemia grow to experience significant long-term complications. Among the more common are speech, cognitive, behavioral, ovarian and neurological/movement difficulties. Despite decades of research, the pathophysiology of these long-term complications remains obscure, hindering prognosis and attempts at improved intervention. As a first step to overcome this roadblock we have begun to explore long-term outcomes in our previously reported GALT-null Drosophila melanogaster model of classic galactosemia. Here we describe the first of these studies. Using a countercurrent device, a simple climbing assay, and a startle response test to characterize and quantify an apparent movement abnormality, we explored the impact of cryptic GALT expression on phenotype, tested the role of sublethal galactose exposure and galactose-1-phosphate (gal-1P accumulation, tested the impact of age, and searched for potential anatomical defects in brain and muscle. We found that about 2.5% residual GALT activity was sufficient to reduce outcome severity. Surprisingly, sublethal galactose exposure and gal-1P accumulation during development showed no effect on the adult phenotype. Finally, despite the apparent neurological or neuromuscular nature of the complication we found no clear morphological differences between mutants and controls in brain or muscle, suggesting that the defect is subtle and/or is physiologic rather than structural. Combined, our results confirm that, like human patients, GALT-null Drosophila experience significant long-term complications that occur independently of galactose exposure, and serve as a proof of principle demonstrating utility of the GALT-null Drosophila model as a tool for exploring genetic and environmental modifiers of long-term outcome in GALT deficiency.

  4. dyschronic, a Drosophila homolog of a deaf-blindness gene, regulates circadian output and Slowpoke channels.

    Directory of Open Access Journals (Sweden)

    James E C Jepson

    Full Text Available Many aspects of behavior and physiology are under circadian control. In Drosophila, the molecular clock that regulates rhythmic patterns of behavior has been extensively characterized. In contrast, genetic loci involved in linking the clock to alterations in motor activity have remained elusive. In a forward-genetic screen, we uncovered a new component of the circadian output pathway, which we have termed dyschronic (dysc. dysc mutants exhibit arrhythmic locomotor behavior, yet their eclosion rhythms are normal and clock protein cycling remains intact. Intriguingly, dysc is the closest Drosophila homolog of whirlin, a gene linked to type II Usher syndrome, the leading cause of deaf-blindness in humans. Whirlin and other Usher proteins are expressed in the mammalian central nervous system, yet their function in the CNS has not been investigated. We show that DYSC is expressed in major neuronal tracts and regulates expression of the calcium-activated potassium channel SLOWPOKE (SLO, an ion channel also required in the circadian output pathway. SLO and DYSC are co-localized in the brain and control each other's expression post-transcriptionally. Co-immunoprecipitation experiments demonstrate they form a complex, suggesting they regulate each other through protein-protein interaction. Furthermore, electrophysiological recordings of neurons in the adult brain show that SLO-dependent currents are greatly reduced in dysc mutants. Our work identifies a Drosophila homolog of a deaf-blindness gene as a new component of the circadian output pathway and an important regulator of ion channel expression, and suggests novel roles for Usher proteins in the mammalian nervous system.

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

    Directory of Open Access Journals (Sweden)

    Jiaxing Zhang

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

  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. 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.

  8. Shared neurocircuitry underlying feeding and drugs of abuse in Drosophila.

    Science.gov (United States)

    Landayan, Dan; Wolf, Fred W

    2015-12-01

    The neural circuitry and molecules that control the rewarding properties of food and drugs of abuse appear to partially overlap in the mammalian brain. This has raised questions about the extent of the overlap and the precise role of specific circuit elements in reward and in other behaviors associated with feeding regulation and drug responses. The much simpler brain of invertebrates including the fruit fly Drosophila, offers an opportunity to make high-resolution maps of the circuits and molecules that govern behavior. Recent progress in Drosophila has revealed not only some common substrates for the actions of drugs of abuse and for the regulation of feeding, but also a remarkable level of conservation with vertebrates for key neuromodulatory transmitters. We speculate that Drosophila may serve as a model for distinguishing the neural mechanisms underlying normal and pathological motivational states that will be applicable to mammals. Copyright © 2016 Chang Gung University. Published by Elsevier B.V. All rights reserved.

  9. Shared neurocircuitry underlying feeding and drugs of abuse in Drosophila

    Directory of Open Access Journals (Sweden)

    Dan Landayan

    2015-12-01

    Full Text Available The neural circuitry and molecules that control the rewarding properties of food and drugs of abuse appear to partially overlap in the mammalian brain. This has raised questions about the extent of the overlap and the precise role of specific circuit elements in reward and in other behaviors associated with feeding regulation and drug responses. The much simpler brain of invertebrates including the fruit fly Drosophila, offers an opportunity to make high-resolution maps of the circuits and molecules that govern behavior. Recent progress in Drosophila has revealed not only some common substrates for the actions of drugs of abuse and for the regulation of feeding, but also a remarkable level of conservation with vertebrates for key neuromodulatory transmitters. We speculate that Drosophila may serve as a model for distinguishing the neural mechanisms underlying normal and pathological motivational states that will be applicable to mammals.

  10. Multi-disciplinary rehabilitation for acquired brain injury in adults of working age.

    Science.gov (United States)

    Turner-Stokes, Lynne; Pick, Anton; Nair, Ajoy; Disler, Peter B; Wade, Derick T

    2015-12-22

    Evidence from systematic reviews demonstrates that multi-disciplinary rehabilitation is effective in the stroke population, in which older adults predominate. However, the evidence base for the effectiveness of rehabilitation following acquired brain injury (ABI) in younger adults has not been established, perhaps because this scenario presents different methodological challenges in research. To assess the effects of multi-disciplinary rehabilitation following ABI in adults 16 to 65 years of age. We ran the most recent search on 14 September 2015. We searched the Cochrane Injuries Group Specialised Register, The Cochrane Library, Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R), Embase Classic+Embase (OvidSP), Web of Science (ISI WOS) databases, clinical trials registers, and we screened reference lists. Randomised controlled trials (RCTs) comparing multi-disciplinary rehabilitation versus routinely available local services or lower levels of intervention; or trials comparing an intervention in different settings, of different intensities or of different timing of onset. Controlled clinical trials were included, provided they met pre-defined methodological criteria. Three review authors independently selected trials and rated their methodological quality. A fourth review author would have arbitrated if consensus could not be reached by discussion, but in fact, this did not occur. As in previous versions of this review, we used the method described by Van Tulder 1997 to rate the quality of trials and to perform a 'best evidence' synthesis by attributing levels of evidence on the basis of methodological quality. Risk of bias assessments were performed in parallel using standard Cochrane methodology. However, the Van Tulder system provided a more discriminative evaluation of rehabilitation trials, so we have continued to use it for our primary synthesis of evidence. We subdivided trials in terms of

  11. Socioeconomic status moderates age-related differences in the brain's functional network organization and anatomy across the adult lifespan.

    Science.gov (United States)

    Chan, Micaela Y; Na, Jinkyung; Agres, Phillip F; Savalia, Neil K; Park, Denise C; Wig, Gagan S

    2018-05-14

    An individual's environmental surroundings interact with the development and maturation of their brain. An important aspect of an individual's environment is his or her socioeconomic status (SES), which estimates access to material resources and social prestige. Previous characterizations of the relation between SES and the brain have primarily focused on earlier or later epochs of the lifespan (i.e., childhood, older age). We broaden this work to examine the relationship between SES and the brain across a wide range of human adulthood (20-89 years), including individuals from the less studied middle-age range. SES, defined by education attainment and occupational socioeconomic characteristics, moderates previously reported age-related differences in the brain's functional network organization and whole-brain cortical structure. Across middle age (35-64 years), lower SES is associated with reduced resting-state system segregation (a measure of effective functional network organization). A similar but less robust relationship exists between SES and age with respect to brain anatomy: Lower SES is associated with reduced cortical gray matter thickness in middle age. Conversely, younger and older adulthood do not exhibit consistent SES-related difference in the brain measures. The SES-brain relationships persist after controlling for measures of physical and mental health, cognitive ability, and participant demographics. Critically, an individual's childhood SES cannot account for the relationship between their current SES and functional network organization. These findings provide evidence that SES relates to the brain's functional network organization and anatomy across adult middle age, and that higher SES may be a protective factor against age-related brain decline. Copyright © 2018 the Author(s). Published by PNAS.

  12. 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.

  13. 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.

  14. 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

  15. Biological effects of radon in Drosophila; Efectos biologicos del radon en Drosophila

    Energy Technology Data Exchange (ETDEWEB)

    Pimentel P, A E; Tavera D, L; Cruces M, M P; Arceo M, C; Rosa D, M.E. de la

    1992-04-15

    The main objective of this investigation, is to study the biological effects of the Radon-222 at low dose in 'Drosophila melanogaster'. It is necessary to mention that these effects will analyze from the genetic point of view for: 1) To evaluate in which form the Radon-222 to low dose it influences in some genetic components of the adaptation in Drosophila, such as: fecundity, viability egg-adult and sex proportion. 2) To evaluate which is the genetic effect that induces the Radon to low dose by means of the SMART technique in Drosophila melanogaster, and this way to try of to identify which is the possible mechanism that causes the genetic damage to somatic level. The carried out investigation was divided in three stages: 1. Tests to the vacuum resistance. 2. Test of somatic mutation, and 3. Determination of the presence of radon daughters on the adult of Drosophila. It is necessary to point out that all the experiments were made by triplicate and in each one of them was placed detectors in preset places. Those obtained results are presented inside the 4 charts included in the present work. (Author)

  16. Biological effects of radon in Drosophila; Efectos biologicos del radon en Drosophila

    Energy Technology Data Exchange (ETDEWEB)

    Pimentel P, A.E.; Tavera D, L.; Cruces M, M.P.; Arceo M, C.; Rosa D, M.E. de la

    1992-04-15

    The main objective of this investigation, is to study the biological effects of the Radon-222 at low dose in 'Drosophila melanogaster'. It is necessary to mention that these effects will analyze from the genetic point of view for: 1) To evaluate in which form the Radon-222 to low dose it influences in some genetic components of the adaptation in Drosophila, such as: fecundity, viability egg-adult and sex proportion. 2) To evaluate which is the genetic effect that induces the Radon to low dose by means of the SMART technique in Drosophila melanogaster, and this way to try of to identify which is the possible mechanism that causes the genetic damage to somatic level. The carried out investigation was divided in three stages: 1. Tests to the vacuum resistance. 2. Test of somatic mutation, and 3. Determination of the presence of radon daughters on the adult of Drosophila. It is necessary to point out that all the experiments were made by triplicate and in each one of them was placed detectors in preset places. Those obtained results are presented inside the 4 charts included in the present work. (Author)

  17. Can older "at risk" adults benefit from psychoeducation targeting healthy brain aging?

    Science.gov (United States)

    Norrie, Louisa M; Diamond, Keri; Hickie, Ian B; Rogers, Naomi L; Fearns, Samantha; Naismith, Sharon L

    2011-04-01

    Multifactorial strategies that prevent or delay the onset or progress of cognitive decline and dementia are needed, and should include education regarding recognized risk factors. The current study sought to investigate whether older adults "at risk" of cognitive decline benefit from psychoeducation targeting healthy brain aging. 65 participants (mean age 64.8 years, SD 9.6) with a lifetime history of major depression; vascular risk as evidenced by at least one vascular risk factor; and/or subjective or objective memory impairment were allocated to weekly psychoeducation sessions or a waitlist control group. The small group sessions were conducted over ten weeks by a team of medical and allied health professionals with expertise in late-life depression and cognition. Sessions focused on modifiable risk factors for cognitive decline including vascular risk, diet, exercise, depression, anxiety and sleep disturbance, as well as providing practical strategies for memory and cognition. Both the psychoeducation and waitlist group completed a 20-item knowledge test at baseline and follow-up. Participants in the psychoeducation group were asked to complete follow-up self-report satisfaction questionnaires. Repeated measures ANOVA showed a significant interaction effect depicting improvements in knowledge associated with psychoeducation, corresponding to an improvement of 15% from baseline. Satisfaction data additionally showed that 92.3% of participants rated the program as "good" to "excellent", and over 90% suggested they would recommend it to others. A group-based psychoeducation program targeting healthy brain aging is effective in improving knowledge. Additionally, it is acceptable and rated highly by participants.

  18. Brain volumes in healthy adults aged 40 years and over: a voxel-based morphometry study.

    Science.gov (United States)

    Riello, Roberta; Sabattoli, Francesca; Beltramello, Alberto; Bonetti, Matteo; Bono, Giorgio; Falini, Andrea; Magnani, Giuseppe; Minonzio, Giorgio; Piovan, Enrico; Alaimo, Giuseppina; Ettori, Monica; Galluzzi, Samantha; Locatelli, Enrico; Noiszewska, Malgorzata; Testa, Cristina; Frisoni, Giovanni B

    2005-08-01

    Gender and age effect on brain morphology have been extensively investigated. However, the great variety in methods applied to morphology partly explain the conflicting results of linear patterns of tissue changes and lateral asymmetry in men and women. The aim of the present study was to assess the effect of age, gender and laterality on the volumes of gray matter (GM) and white matter (WM) in a large group of healthy adults by means of voxel-based morphometry. This technique, based on observer-independent algorithms, automatically segments the 3 types of tissue and computes the amount of tissue in each single voxel. Subjects were 229 healthy subjects of 40 years of age or older, who underwent magnetic resonance (MR) for reasons other than cognitive impairment. MR images were reoriented following the AC-PC line and, after removing the voxels below the cerebellum, were processed by Statistical Parametric Mapping (SPM99). GM and WM volumes were normalized for intracranial volume. Women had more fractional GM and WM volumes than men. Age was negatively correlated with both fractional GM and WM, and a gender x age interaction effect was found for WM, men having greater WM loss with advancing age. Pairwise differences between left and right GM were negative (greater GM in right hemisphere) in men, and positive (greater GM in left hemisphere) in women (-0.56+/-4.2 vs 0.99+/-4.8; p=0.019). These results support side-specific accelerated WM loss in men, and may help our better understanding of changes in regional brain structures associated with pathological aging.

  19. Effects of exercise on brain activity during walking in older adults: a randomized controlled trial.

    Science.gov (United States)

    Shimada, Hiroyuki; Ishii, Kenji; Makizako, Hyuma; Ishiwata, Kiichi; Oda, Keiichi; Suzukawa, Megumi

    2017-05-30

    Physical activity may preserve neuronal plasticity, increase synapse formation, and cause the release of hormonal factors that promote neurogenesis and neuronal function. Previous studies have reported enhanced neurocognitive function following exercise training. However, the specific cortical regions activated during exercise training remain largely undefined. In this study, we quantitatively and objectively evaluated the effects of exercise on brain activity during walking in healthy older adults. A total of 24 elderly women (75-83 years old) were randomly allocated to either an intervention group or a control group. Those in the intervention group attended 3 months of biweekly 90-min sessions focused on aerobic exercise, strength training, and physical therapy. We monitored changes in regional cerebral glucose metabolism during walking in both groups using positron emission tomography (PET) and [ 18 F]fluorodeoxyglucose (FDG). All subjects completed the 3-month experiment and the adherence to the exercise program was 100%. Compared with the control group, the intervention group showed a significantly greater step length in the right foot after 3 months of physical activity. The FDG-PET assessment revealed a significant post-intervention increase in regional glucose metabolism in the left posterior entorhinal cortex, left superior temporal gyrus, and right superior temporopolar area in the intervention group. Interestingly, the control group showed a relative increase in regional glucose metabolism in the left premotor and supplemental motor areas, left and right somatosensory association cortex, and right primary visual cortex after the 3-month period. We found no significant differences in FDG uptake between the intervention and control groups before vs. after the intervention. Exercise training increased activity in specific brain regions, such as the precuneus and entorhinal cortices, which play an important role in episodic and spatial memory. Further

  20. Chronic Δ⁸-THC Exposure Differently Affects Histone Modifications in the Adolescent and Adult Rat Brain.

    Science.gov (United States)

    Prini, Pamela; Penna, Federica; Sciuccati, Emanuele; Alberio, Tiziana; Rubino, Tiziana

    2017-10-04

    Adolescence represents a vulnerable period for the psychiatric consequences of delta9-tetrahydrocannabinol (Δ⁸-THC) exposure, however, the molecular underpinnings of this vulnerability remain to be established. Histone modifications are emerging as important epigenetic mechanisms involved in the etiopathogenesis of psychiatric diseases, thus, we investigated the impact of chronic Δ⁸-THC exposure on histone modifications in different brain areas of female rats. We checked histone modifications associated to both transcriptional repression (H3K9 di- and tri-methylation, H3K27 tri-methylation) and activation (H3K9 and H3K14 acetylation) after adolescent and adult chronic Δ⁸-THC exposure in the hippocampus, nucleus accumbens, and amygdala. Chronic exposure to increasing doses of Δ⁸-THC for 11 days affected histone modifications in a region- and age-specific manner. The primary effect in the adolescent brain was represented by changes leading to transcriptional repression, whereas the one observed after adult treatment led to transcriptional activation. Moreover, only in the adolescent brain, the primary effect was followed by a homeostatic response to counterbalance the Δ⁸-THC-induced repressive effect, except in the amygdala. The presence of a more complex response in the adolescent brain may be part of the mechanisms that make the adolescent brain vulnerable to Δ⁸-THC adverse effects.

  1. Enhanced task-related brain activation and resting perfusion in healthy older adults after chronic blueberry supplementation.

    Science.gov (United States)

    Bowtell, Joanna L; Aboo-Bakkar, Zainie; Conway, Myra E; Adlam, Anna-Lynne R; Fulford, Jonathan

    2017-07-01

    Blueberries are rich in flavonoids, which possess antioxidant and anti-inflammatory properties. High flavonoid intakes attenuate age-related cognitive decline, but data from human intervention studies are sparse. We investigated whether 12 weeks of blueberry concentrate supplementation improved brain perfusion, task-related activation, and cognitive function in healthy older adults. Participants were randomised to consume either 30 mL blueberry concentrate providing 387 mg anthocyanidins (5 female, 7 male; age 67.5 ± 3.0 y; body mass index, 25.9 ± 3.3 kg·m -2 ) or isoenergetic placebo (8 female, 6 male; age 69.0 ± 3.3 y; body mass index, 27.1 ± 4.0 kg·m -2 ). Pre- and postsupplementation, participants undertook a battery of cognitive function tests and a numerical Stroop test within a 1.5T magnetic resonance imaging scanner while functional magnetic resonance images were continuously acquired. Quantitative resting brain perfusion was determined using an arterial spin labelling technique, and blood biomarkers of inflammation and oxidative stress were measured. Significant increases in brain activity were observed in response to blueberry supplementation relative to the placebo group within Brodmann areas 4/6/10/21/40/44/45, precuneus, anterior cingulate, and insula/thalamus (p blueberry versus placebo supplementation (p = 0.05). Supplementation with an anthocyanin-rich blueberry concentrate improved brain perfusion and activation in brain areas associated with cognitive function in healthy older adults.

  2. 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.

  3. A comparison of Frost expression among species and life stages of Drosophila.

    Science.gov (United States)

    Bing, X; Zhang, J; Sinclair, Brent J

    2012-02-01

    Frost (Fst) is a gene associated with cold exposure in Drosophila melanogaster. We used real-time PCR to assess whether cold exposure induces expression of Fst in 10 different life stages of D. melanogaster, and adults of seven other Drosophila species. We exposed groups of individuals to 0 °C (2 h), followed by 1 h recovery (22 °C). Frost was significantly upregulated in response to cold in eggs, third instar larvae, and 2- and 5-day-old male and female adults in D. melanogaster. Life stages in which cold did not upregulate Fst had high constitutive expression. Frost is located on the opposite strand of an intron of Diuretic hormone (DH), but cold exposure did not upregulate DH. Frost orthologues were identified in six other species within the Melanogaster group (Drosophila sechellia, Drosophila simulans, Drosophila yakuba, Drosophila erecta, Drosophila ananassae and Drosophila mauritiana). Frost orthologues were upregulated in response to cold exposure in both sexes in adults of all of these species. The predicted structure of a putative Frost consensus protein shows highly conserved tandem repeats of motifs involved in cell signalling (PEST and TRAF2), suggesting that Fst might encode an adaptor protein involved in acute stress or apoptosis signalling in vivo. © 2011 The Authors. Insect Molecular Biology © 2011 The Royal Entomological Society.

  4. Cell Proliferation, Migration, and Neurogenesis in the Adult Brain of the Pulse Type Weakly Electric Fish, Gymnotus omarorum

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    Valentina Olivera-Pasilio

    2017-08-01

    Full Text Available Adult neurogenesis, an essential mechanism of brain plasticity, enables brain development along postnatal life, constant addition of new neurons, neuronal turnover, and/or regeneration. It is amply distributed but negatively modulated during development and along evolution. Widespread cell proliferation, high neurogenic, and regenerative capacities are considered characteristics of teleost brains during adulthood. These anamniotes are promising models to depict factors that modulate cell proliferation, migration, and neurogenesis, and might be intervened to promote brain plasticity in mammals. Nevertheless, the migration path of derived cells to their final destination was not studied in various teleosts, including most weakly electric fish. In this group adult brain morphology is attributed to sensory specialization, involving the concerted evolution of peripheral electroreceptors and electric organs, encompassed by the evolution of neural networks involved in electrosensory information processing. In wave type gymnotids adult brain morphology is proposed to result from lifelong region specific cell proliferation and neurogenesis. Consistently, pulse type weakly electric gymnotids and mormyrids show widespread distribution of proliferation zones that persists in adulthood, but their neurogenic potential is still unknown. Here we studied the migration process and differentiation of newborn cells into the neuronal phenotype in the pulse type gymnotid Gymnotus omarorum. Pulse labeling of S-phase cells with 5-Chloro-2′-deoxyuridine thymidine followed by 1 to 180 day survivals evidenced long distance migration of newborn cells from the rostralmost telencephalic ventricle to the olfactory bulb, and between layers of all cerebellar divisions. Shorter migration appeared in the tectum opticum and torus semicircularis. In many brain regions, derived cells expressed early neuronal markers doublecortin (chase: 1–30 days and HuC/HuD (chase: 7–180 days

  5. Shifting brain inhibitory balance and connectivity of the prefrontal cortex of adults with autism spectrum disorder.

    Science.gov (United States)

    Ajram, L A; Horder, J; Mendez, M A; Galanopoulos, A; Brennan, L P; Wichers, R H; Robertson, D M; Murphy, C M; Zinkstok, J; Ivin, G; Heasman, M; Meek, D; Tricklebank, M D; Barker, G J; Lythgoe, D J; Edden, R A E; Williams, S C; Murphy, D G M; McAlonan, G M

    2017-05-23

    Currently, there are no effective pharmacologic treatments for the core symptoms of autism spectrum disorder (ASD). There is, nevertheless, potential for progress. For example, recent evidence suggests that the excitatory (E) glutamate and inhibitory (I) GABA systems may be altered in ASD. However, no prior studies of ASD have examined the 'responsivity' of the E-I system to pharmacologic challenge; or whether E-I modulation alters abnormalities in functional connectivity of brain regions implicated in the disorder. Therefore, we used magnetic resonance spectroscopy ([1H]MRS) to measure prefrontal E-I flux in response to the glutamate and GABA acting drug riluzole in adult men with and without ASD. We compared the change in prefrontal 'Inhibitory Index'-the GABA fraction within the pool of glutamate plus GABA metabolites-post riluzole challenge; and the impact of riluzole on differences in resting-state functional connectivity. Despite no baseline differences in E-I balance, there was a significant group difference in response to pharmacologic challenge. Riluzole increased the prefrontal cortex inhibitory index in ASD but decreased it in controls. There was also a significant group difference in prefrontal functional connectivity at baseline, which was abolished by riluzole within the ASD group. Our results also show, for we believe the first time in ASD, that E-I flux can be 'shifted' with a pharmacologic challenge, but that responsivity is significantly different from controls. Further, our initial evidence suggests that abnormalities in functional connectivity can be 'normalised' by targeting E-I, even in adults.

  6. Brain abscesses associated with right-to-left shunts in adults.

    Science.gov (United States)

    Memon, Kashif A; Cleveland, Kerry O; Gelfand, Michael S

    2012-04-01

    Although brain abscesses are frequently cryptogenic in origin, bacteria must reach the brain either by direct or hematogenous spread. Right-to-left shunts, caused either by intrapulmonary vascular malformations or congenital heart defects, may allow microorganisms to evade the normal host defenses in the lungs and lead to development of brain abscesses. Two patients recently presented with brain abscesses and were found to have conditions associated with right-to-left shunts. The diagnosis of brain abscess should prompt the clinician to consider right-to-left shunts as a possible predisposing condition for brain abscess.

  7. Endocrine morbidity in adults treated with cerebral irradiation for brain tumours during childhood

    International Nuclear Information System (INIS)

    Shalet, S.M.; Beardwell, C.G.; MacFarlane, I.A.; Morris Jones, P.H.; Pearson, D.

    1977-01-01

    Hypothalamic-pituitary function was assessed in 20 adult subjects who were treated with cerebral irradiation for brain tumours during childhood between 8 and 32 years earlier. Nine patients showed impaired growth hormone (GH) responses to hypoglycaemia, of whom, 7 are below the third centile for standing height. All GH deficient subjects recieved more than 2950 rads to the hypothalamic-pituitary axis with a maximum dose of approximately 5000 rads being used in one case. Three subjects have an elevated basal serum thyroid stimulating hormone (TSH) level and 2 of these show an exaggerated TSH response to thyrotrophin releasing hormone (TRH) but no patient was clinically or biochemically hypothyroid. The rest of hypothalamic-pituitary function was essentially normal. This study shows that multiple pituitary hormone deficiencies do not develop with time when the radiation dose is below a critical level. Thus it appears that there is a gradation of radiation damage to the hypothalamic-pituitary axis which is dependent primarily on the dose received rather than the time interval after radiotherapy. (auth.)

  8. Severity and Co-occurrence of Oral and Verbal Apraxias in Left Brain Damaged Adults

    Directory of Open Access Journals (Sweden)

    Fariba Yadegari

    2012-04-01

    Full Text Available Objective: Oral and verbal apraxias represent motor programming deficits of nonverbal and verbal movements respectively. Studying their properties may shed light on speech motor control processes. This study was focused on identifying cases with oral or verbal apraxia, their co–occurrences and severities. Materials & Methods: In this non-experimental study, 55 left adult subjects with left brain lesion including 22 women and 33 men with age range of 23 to 84 years, were examined and videotaped using oral apraxia and verbal apraxia tasks. Three speech and language pathologists independently scored apraxia severities. Data were analyzed by independent t test, Pearson, Phi and Contingency coefficients using SPSS 12. Results: Mean score of oral and verbal apraxias in patients with and without oral and verbal apraxias were significantly different (P<0.001. Forty- two patients had simultaneous oral and verbal apraxias, with significant correlation between their oral and verbal apraxia scores (r=0.75, P<0.001. Six patients showed no oral or verbal apraxia and 7 had just one type of apraxia. Comparison of co-occurrence of two disorders (Phi=0.59 and different oral and verbal intensities (C=0.68 were relatively high (P<0.001. Conclusion: The present research revealed co-occurrence of oral and verbal apraxias to a great extent. It appears that speech motor control is influenced by a more general verbal and nonverbal motor control.

  9. Identifying endogenous neural stem cells in the adult brain in vitro and in vivo: novel approaches.

    Science.gov (United States)

    Rueger, Maria Adele; Androutsellis-Theotokis, Andreas

    2013-01-01

    In the 1960s, Joseph Altman reported that the adult mammalian brain is capable of generating new neurons. Today it is understood that some of these neurons are derived from uncommitted cells in the subventricular zone lining the lateral ventricles, and the dentate gyrus of the hippocampus. The first area generates new neuroblasts which migrate to the olfactory bulb, whereas hippocampal neurogenesis seems to play roles in particular types of learning and memory. A part of these uncommitted (immature) cells is able to divide and their progeny can generate all three major cell types of the nervous system: neurons, astrocytes, and oligodendrocytes; these properties define such cells as neural stem cells. Although the roles of these cells are not yet clear, it is accepted that they affect functions including olfaction and learning/memory. Experiments with insults to the central nervous system also show that neural stem cells are quickly mobilized due to injury and in various disorders by proliferating, and migrating to injury sites. This suggests a role of endogenous neural stem cells in disease. New pools of stem cells are being discovered, suggesting an even more important role for these cells. To understand these cells and to coax them to contribute to tissue repair it would be very useful to be able to image them in the living organism. Here we discuss advances in imaging approaches as well as new concepts that emerge from stem cell biology with emphasis on the interface between imaging and stem cells.

  10. Effect of Message Type on the Visual Attention of Adults With Traumatic Brain Injury.

    Science.gov (United States)

    Thiessen, Amber; Brown, Jessica; Beukelman, David; Hux, Karen; Myers, Angela

    2017-05-17

    The purpose of this investigation was to measure the effect of message type (i.e., action, naming) on the visual attention patterns of individuals with and without traumatic brain injury (TBI) when viewing grids composed of 3 types of images (i.e., icons, decontextualized photographs, and contextualized photographs). Fourteen adults with TBI and 14 without TBI-assigned either to an action or naming message condition-viewed grids composed of 3 different image types. Participants' task was to select/sustain visual fixation on the image they felt best represented a stated message (i.e., action or naming). With final fixation location serving as a proxy for selection, participants in the naming message condition selected decontextualized photographs significantly more often than the other 2 image types. Participants in the action message condition selected contextualized photographs significantly more frequently than the other 2 image types. Minimal differences were noted between participant groups. This investigation provides preliminary evidence of the relationship between image and message type. Clinicians involved in the selection of images used for message representation should consider the message being represented when designing supports for people with TBI. Further research is necessary to fully understand the relationship between images and message type.

  11. Effects of neurofeedback training on the brain wave of adults with forward head posture

    Science.gov (United States)

    Oh, Hyun-Ju; Song, Gui-Bin

    2016-01-01

    [Purpose] The purpose of the present study was to examine the effects of neurofeedback training on electroencephalogram changes in the cervical spine in adults with forward head posture through x-ray. [Subjects and Methods] The subjects of the study were 40 college students with forward head posture, randomly divided into a neurofeedback training group (NFTG, n=20) and a control group (CG, n=20). The neurofeedback training group performed six sessions of pottery and archery games, each for two minutes, three times per week for four weeks, while using the neurofeedback system. [Results] There were significant effects within and between groups in terms of the Delta wave, the Theta wave, the Alpha wave, the Beta wave, or the sensory motor rhythm. Especially, the Delta wave, Beta wave, and the sensory motor rhythm were showed significant effects between the groups. [Conclusion] It is thought that neurofeedback training, a training approach to self-regulate brain waves, enhances concentration and relaxation without stress, as well as an increase in attention, memory, and verbal cognitive performance. Therefore an effective intervention method to improve neck pain and daily activities. PMID:27821966

  12. The Wechsler Test of Adult Reading as a Measure of Premorbid Intelligence Following Traumatic Brain Injury.

    Science.gov (United States)

    Steward, Kayla A; Novack, Thomas A; Kennedy, Richard; Crowe, Michael; Marson, Daniel C; Triebel, Kristen L

    2017-02-01

    The current study sought to determine whether the Wechsler Test of Adult Reading (WTAR) provides a stable estimate of premorbid intellectual ability in acutely injured patients recovering from traumatic brain injury (TBI). A total of 135 participants (43 mild TBI [mTBI], 40 moderate/severe TBI [msevTBI], 52 healthy controls) were administered the WTAR at 1 and 12 months post-injury. Despite similar demographic profiles, participants with msevTBI performed significantly worse than controls on the WTAR at both time points. Moreover, the msevTBI group had a significant improvement in WTAR performance over the 1-year period. In contrast, those participants with mTBI did not significantly differ from healthy controls and both the mTBI and control groups demonstrated stability on the WTAR over time. Results indicate that word-reading tests may underestimate premorbid intelligence during the immediate recovery period for patients with msevTBI. Clinicians should consider alternative estimation measures in this TBI subpopulation. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Weighted wrist cuffs for tremor reduction during eating in adults with static brain lesions.

    Science.gov (United States)

    McGruder, Juli; Cors, Denise; Tiernan, Anne M; Tomlin, George

    2003-01-01

    This study examined whether weighting the forearm during feeding decreased tremors and increased functional feeding in adults with intention tremor caused by static brain lesions. Five individuals with various diagnoses, ages 30-81, were videotaped during 8 or 16 meal sessions, alternating treatment and control conditions within each meal. In this single-case design, treatment consisted of application of a weighted fabric wrist cuff and the baseline (control) condition employed an identical cuff with the weights removed. Dependent variables studied were time to acquire and deliver a bite, grams of food eaten, number of times food was spilled, number of times a compensatory technique was used, participant self-rating, and investigator rating of the severity of the tremor. All five participants demonstrated improvement during treatment in one or more of the dependent variables. t Tests of the means of baseline and treatment half-sessions incorporating conservative control of Type I error revealed the following statistically significant improvements under the weighted condition: Participants 3, 4, and 5 took less time to acquire a bite; Participants 4 and 5 made fewer spills; Participants 3 and 5 showed a diminished tremor. There were no statistically significant decreases in function on any variable for any participants during the weighted condition. The application of weight to the wrist of a person with upper-extremity tremor is accompanied by some functional improvement in self-feeding for some individuals. The size of benefit seems to be sensitive to the amount of weight used.

  14. Abnormal serotonin transporter availability in the brains of adults with conduct disorder.

    Science.gov (United States)

    Chang, Chieh; Gau, Susan Shur-Fen; Huang, Wen-Sheng; Shiue, Chyng-Yann; Yeh, Chin-Bin

    2017-06-01

    The aims of the current study were to determine whether patients with conduct disorder (CD) showed an abnormal availability of serotonin reuptake transporter (SERT), and if their hyperkinetic symptoms, impulsivity, and quality of life were correlated with the availability of SERT. We recruited 14 drug-naïve patients with CD and eight age-matched healthy controls (HCs). The adult attention-deficit/hyperactivity disorder (ADHD) self-report scale (ASRS), Barrett impulsivity scale (BIS), and the World Health Organization quality of life-brief version (WHOQOL-BREF) scale were administered. Positron emission tomography (PET) of the brain with 4-[ 18 F]-ADAM was arranged for SERT imaging. SERT availability was significantly reduced in the striatum and midbrain of patients with CD. Quality of life and inattention symptoms were also significantly correlated with the availability of SERT in the prefrontal cortex. The study suggested that a reduction in the availability of SERT might be associated with CD and could potentially predict poor quality of life or symptoms of inattention for these patients. The implications of our results might be limited to individuals with CD; a future study with a larger sample to validate our preliminary results is warranted. Copyright © 2016. Published by Elsevier B.V.

  15. Effects of 60Co γ-radiation on brain hippocampal tissue of adult mice

    International Nuclear Information System (INIS)

    Liu Yongbao; Rao Yongqing; Xu Luxi

    2000-01-01

    Objective: To study neuro-pathological changes of hippocampus tissue in adult mice following a series of irradiation with 60 Co γ-rays. Methods: Male mice of Kunming strain in experimental group (n = 8) were exposed total-bodily to 60 Co γ-rays at 2.0 Gy once every two days. A histopathological imaging analysis of the mouse brain tissue was carried out after paraffin embedding and a series of sections were made and stained with Nissl and Weil staining methods. Results: In the irradiation group (the cumulative dose = 26 Gy) loss of pyramidal cells in hippocampus was significant when compared with the control group. Neuro-pathological changes were characterised by reduced neuron size, nuclear pyknosis and karyolysis. The neurofibrillar density of the pyramidal layer in the irradiation group was much lower than that of the control group (P CA2>CA3>CA4 in the hippocampus. Conclusion: The neuronal damage in hippocampus after 60 Co irradiation could form a pathological basis in reduction of memorial and learning ability

  16. Diffusion tensor spectroscopic imaging of the human brain in children and adults.

    Science.gov (United States)

    Fotso, Kevin; Dager, Stephen R; Landow, Alec; Ackley, Elena; Myers, Orrin; Dixon, Mindy; Shaw, Dennis; Corrigan, Neva M; Posse, Stefan

    2017-10-01

    We developed diffusion tensor spectroscopic imaging (DTSI), based on proton-echo-planar-spectroscopic imaging (PEPSI), and evaluated the feasibility of mapping brain metabolite diffusion in adults and children. PRESS prelocalized DTSI at 3 Tesla (T) was performed using navigator-based correction of movement-related phase errors and cardiac gating with compensation for repetition time (TR) related variability in T 1 saturation. Mean diffusivity (MD) and fractional anisotropy (FA) of total N-acetyl-aspartate (tNAA), total creatine (tCr), and total choline (tCho) were measured in eight adults (17-60 years) and 10 children (3-24 months) using b max  = 1734 s/mm 2 , 1 cc and 4.5 cc voxel sizes, with nominal scan times of 17 min and 8:24 min. Residual movement-related phase encoding ghosting (PEG) was used as a regressor across scans to correct overestimation of MD. After correction for PEG, metabolite slice-averaged MD estimated at 20% PEG were lower (P < 0.042) for adults (0.17/0.20/0.18 × 10 -3 mm 2 /s) than for children (0.26/0.27/0.24 × 10 -3 mm 2 /s). Extrapolated to 0% PEG, the MD estimates decreased further (0.09/0.11/0.11 × 10 -3 mm 2 /s versus 0.15/0.16/0.15 × 10 -3 mm 2 /s). Slice-averaged FA of tNAA (P = 0.049), tCr (P = 0.067), and tCho (P = 0.003) were higher in children. This high-speed DTSI approach with PEG regression allows for estimation of metabolite MD and FA with improved tolerance to movement. Our preliminary data suggesting age-related changes support DTSI as a sensitive technique for investigating intracellular markers of biological processes. Magn Reson Med 78:1246-1256, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  17. Rapid establishment of a regular distribution of adult tropical Drosophila parasitoids in a multi-patch environment by patch defence behaviour.

    Science.gov (United States)

    de Jong, Peter W; Hemerik, Lia; Gort, Gerrit; van Alphen, Jacques J M

    2011-01-01

    Females of the larval parasitoid of Drosophila, Asobara citri, from sub-Saharan Africa, defend patches with hosts by fighting and chasing conspecific females upon encounter. Females of the closely related, palearctic species Asobara tabida do not defend patches and often search simultaneously in the same patch. The effect of patch defence by A. citri females on their distribution in a multi-patch environment was investigated, and their distributions were compared with those of A. tabida. For both species 20 females were released from two release-points in replicate experiments. Females of A. citri quickly reached a regular distribution across 16 patches, with a small variance/mean ratio per patch. Conversely, A. tabida females initially showed a clumped distribution, and after gradual dispersion, a more Poisson-like distribution across patches resulted (variance/mean ratio was closer to 1 and higher than for A. citri). The dispersion of A. tabida was most probably an effect of exploitation: these parasitoids increasingly made shorter visits to already exploited patches. We briefly discuss hypotheses on the adaptive significance of patch defence behaviour or its absence in the light of differences in the natural history of both parasitoid species, notably the spatial distribution of their hosts.

  18. The bacterial communities of Drosophila suzukii collected from undamaged cherries

    Directory of Open Access Journals (Sweden)

    James Angus Chandler

    2014-07-01

    Full Text Available Drosophila suzukii is an introduced pest insect that feeds on undamaged, attached fruit. This diet is distinct from the fallen, discomposing fruits utilized by most other species of Drosophila. Since the bacterial microbiota of Drosophila, and of many other animals, is affected by diet, we hypothesized that the bacteria associated with D. suzukii are distinct from that of other Drosophila. Using 16S rDNA PCR and Illumina sequencing, we characterized the bacterial communities of larval and adult D. suzukii collected from undamaged, attached cherries in California, USA. We find that the bacterial communities associated with these samples of D. suzukii contain a high frequency of Tatumella. Gluconobacter and Acetobacter, two taxa with known associations with Drosophila, were also found, although at lower frequency than Tatumella in four of the five samples examined. Sampling D. suzukii from different locations and/or while feeding on different fruits is needed to determine the generality of the results determined by these samples. Nevertheless this is, to our knowledge, the first study characterizing the bacterial communities of this ecologically unique and economically important species of Drosophila.

  19. Hearing regulates Drosophila aggression.

    Science.gov (United States)

    Versteven, Marijke; Vanden Broeck, Lies; Geurten, Bart; Zwarts, Liesbeth; Decraecker, Lisse; Beelen, Melissa; Göpfert, Martin C; Heinrich, Ralf; Callaerts, Patrick

    2017-02-21

    Aggression is a universal social behavior important for the acquisition of food, mates, territory, and social status. Aggression in Drosophila is context-dependent and can thus be expected to involve inputs from multiple sensory modalities. Here, we use mechanical disruption and genetic approaches in Drosophila melanogaster to identify hearing as an important sensory modality in the context of intermale aggressive behavior. We demonstrate that neuronal silencing and targeted knockdown of hearing genes in the fly's auditory organ elicit abnormal aggression. Further, we show that exposure to courtship or aggression song has opposite effects on aggression. Our data define the importance of hearing in the control of Drosophila intermale aggression and open perspectives to decipher how hearing and other sensory modalities are integrated at the neural circuit level.

  20. That's Using Your Brain!

    Science.gov (United States)

    Visser, Dana R.

    1996-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

    Radiation therapy has proven efficacy for treating brain tumors and metastases. Higher doses and larger treatment fields increase the probability of eliminating neoplasms and preventing reoccurrence, but dose and field are limited by damage to normal tissues. Normal tissue injury is greatest during development and in populations of prolif