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Résultat de la recherche
3 recherche sur le mot-clé 'postsynaptic density'




Effects of sex and DTNBP1 (dysbindin) null gene mutation on the developmental GluN2B-GluN2A switch in the mouse cortex and hippocampus / D. SINCLAIR in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)
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[article]
Titre : Effects of sex and DTNBP1 (dysbindin) null gene mutation on the developmental GluN2B-GluN2A switch in the mouse cortex and hippocampus Type de document : Texte imprimé et/ou numérique Auteurs : D. SINCLAIR, Auteur ; J. CESARE, Auteur ; M. MCMULLEN, Auteur ; G. C. CARLSON, Auteur ; C. G. HAHN, Auteur ; K. E. BORGMANN-WINTER, Auteur Article en page(s) : p.14 Langues : Anglais (eng) Mots-clés : Cortex Dtnbp1 Development Dysbindin GluN2B Hippocampus Nmda Phosphorylation Postsynaptic density Sex difference Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders such as autism spectrum disorders and schizophrenia differentially impact males and females and are highly heritable. The ways in which sex and genetic vulnerability influence the pathogenesis of these disorders are not clearly understood. The n-methyl-d-aspartate (NMDA) receptor pathway has been implicated in schizophrenia and autism spectrum disorders and changes dramatically across postnatal development at the level of the GluN2B-GluN2A subunit "switch" (a shift from reliance on GluN2B-containing receptors to reliance on GluN2A-containing receptors). We investigated whether sex and genetic vulnerability (specifically, null mutation of DTNBP1 [dysbindin; a possible susceptibility gene for schizophrenia]) influence the developmental GluN2B-GluN2A switch. METHODS: Subcellular fractionation to enrich for postsynaptic density (PSD), together with Western blotting and kinase assay, were used to investigate the GluN2B-GluN2A switch in the cortex and hippocampus of male and female DTNBP1 null mutant mice and their wild-type littermates. Main effects of sex and DTNBP1 genotype, and interactions with age, were assessed using factorial ANOVA. RESULTS: Sex differences in the GluN2B-GluN2A switch emerged across development at the frontal cortical synapse, in parameters related to GluN2B. Males across genotypes displayed higher GluN2B:GluN2A and GluN2B:GluN1 ratios (p < 0.05 and p < 0.01, respectively), higher GluN2B phosphorylation at Y1472 (p < 0.01), and greater abundance of PLCgamma (p < 0.01) and Fyn (p = 0.055) relative to females. In contrast, effects of DTNBP1 were evident exclusively in the hippocampus. The developmental trajectory of GluN2B was disrupted in DTNBP1 null mice (genotype x age interaction p < 0.05), which also displayed an increased synaptic GluN2A:GluN1 ratio (p < 0.05) and decreased PLCgamma (p < 0.05) and Fyn (only in females; p < 0.0005) compared to wild-types. CONCLUSIONS: Sex and DTNBP1 mutation influence the GluN2B-GluN2A switch at the synapse in a brain-region-specific fashion involving pY1472-GluN2B, Fyn, and PLCgamma. This highlights the possible mechanisms through which risk factors may mediate their effects on vulnerability to disorders of NMDA receptor dysfunction. En ligne : http://dx.doi.org/10.1186/s11689-016-9148-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348
in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.14[article] Effects of sex and DTNBP1 (dysbindin) null gene mutation on the developmental GluN2B-GluN2A switch in the mouse cortex and hippocampus [Texte imprimé et/ou numérique] / D. SINCLAIR, Auteur ; J. CESARE, Auteur ; M. MCMULLEN, Auteur ; G. C. CARLSON, Auteur ; C. G. HAHN, Auteur ; K. E. BORGMANN-WINTER, Auteur . - p.14.
Langues : Anglais (eng)
in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.14
Mots-clés : Cortex Dtnbp1 Development Dysbindin GluN2B Hippocampus Nmda Phosphorylation Postsynaptic density Sex difference Index. décimale : PER Périodiques Résumé : BACKGROUND: Neurodevelopmental disorders such as autism spectrum disorders and schizophrenia differentially impact males and females and are highly heritable. The ways in which sex and genetic vulnerability influence the pathogenesis of these disorders are not clearly understood. The n-methyl-d-aspartate (NMDA) receptor pathway has been implicated in schizophrenia and autism spectrum disorders and changes dramatically across postnatal development at the level of the GluN2B-GluN2A subunit "switch" (a shift from reliance on GluN2B-containing receptors to reliance on GluN2A-containing receptors). We investigated whether sex and genetic vulnerability (specifically, null mutation of DTNBP1 [dysbindin; a possible susceptibility gene for schizophrenia]) influence the developmental GluN2B-GluN2A switch. METHODS: Subcellular fractionation to enrich for postsynaptic density (PSD), together with Western blotting and kinase assay, were used to investigate the GluN2B-GluN2A switch in the cortex and hippocampus of male and female DTNBP1 null mutant mice and their wild-type littermates. Main effects of sex and DTNBP1 genotype, and interactions with age, were assessed using factorial ANOVA. RESULTS: Sex differences in the GluN2B-GluN2A switch emerged across development at the frontal cortical synapse, in parameters related to GluN2B. Males across genotypes displayed higher GluN2B:GluN2A and GluN2B:GluN1 ratios (p < 0.05 and p < 0.01, respectively), higher GluN2B phosphorylation at Y1472 (p < 0.01), and greater abundance of PLCgamma (p < 0.01) and Fyn (p = 0.055) relative to females. In contrast, effects of DTNBP1 were evident exclusively in the hippocampus. The developmental trajectory of GluN2B was disrupted in DTNBP1 null mice (genotype x age interaction p < 0.05), which also displayed an increased synaptic GluN2A:GluN1 ratio (p < 0.05) and decreased PLCgamma (p < 0.05) and Fyn (only in females; p < 0.0005) compared to wild-types. CONCLUSIONS: Sex and DTNBP1 mutation influence the GluN2B-GluN2A switch at the synapse in a brain-region-specific fashion involving pY1472-GluN2B, Fyn, and PLCgamma. This highlights the possible mechanisms through which risk factors may mediate their effects on vulnerability to disorders of NMDA receptor dysfunction. En ligne : http://dx.doi.org/10.1186/s11689-016-9148-7 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348
in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA
Titre : Mutations in Synaptic Adhesion Molecules Type de document : Texte imprimé et/ou numérique Auteurs : Jaewon KO, Auteur ; Caterina MONTANI, Auteur ; Eunjoon KIM, Auteur ; Carlo SALA, Auteur Année de publication : 2016 Importance : p.161-175 Langues : Anglais (eng) Mots-clés : Excitatory synapse Inhibitory synapse Neurodevelopmental diseases Postsynaptic density Presynapse Synapse formation Index. décimale : SCI-D SCI-D - Neurosciences Résumé : Synaptic connections are established between neurons during development of the nervous system after axon path finding and dendrite development. Synapse development is mediated by specific synaptic cell adhesion molecules (SCAMs) that accumulate at pre- and postsynaptic sites and trigger synaptic differentiation through interactions with intra- and extracellular proteins. These interactions are essential to align pre- and postsynaptic specializations and to couple the sites of cell-to-cell adhesion to the cytoskeletal and signaling complexes required to recruit and recycle presynaptic vesicles, components of exo- and endocytic zones, and postsynaptic receptors. Not surprisingly, it has been demonstrated that in humans, deletions or mutations in some of the SCAM genes are associated with several neurodevelopmental disorders, including autism spectrum disorders, intellectual disability, and schizophrenia, although the exact connection between genetic background and biochemical mechanisms by which these mutations contribute to the diseases has been only partially revealed. This chapter describes the multiple functions and associated synaptic alterations of the SCAM genes found mutated in neurodevelopmental diseases. En ligne : http://dx.doi.org/10.1016/B978-0-12-800109-7.00011-X Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301 Mutations in Synaptic Adhesion Molecules [Texte imprimé et/ou numérique] / Jaewon KO, Auteur ; Caterina MONTANI, Auteur ; Eunjoon KIM, Auteur ; Carlo SALA, Auteur . - 2016 . - p.161-175.
in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA
Langues : Anglais (eng)
Mots-clés : Excitatory synapse Inhibitory synapse Neurodevelopmental diseases Postsynaptic density Presynapse Synapse formation Index. décimale : SCI-D SCI-D - Neurosciences Résumé : Synaptic connections are established between neurons during development of the nervous system after axon path finding and dendrite development. Synapse development is mediated by specific synaptic cell adhesion molecules (SCAMs) that accumulate at pre- and postsynaptic sites and trigger synaptic differentiation through interactions with intra- and extracellular proteins. These interactions are essential to align pre- and postsynaptic specializations and to couple the sites of cell-to-cell adhesion to the cytoskeletal and signaling complexes required to recruit and recycle presynaptic vesicles, components of exo- and endocytic zones, and postsynaptic receptors. Not surprisingly, it has been demonstrated that in humans, deletions or mutations in some of the SCAM genes are associated with several neurodevelopmental disorders, including autism spectrum disorders, intellectual disability, and schizophrenia, although the exact connection between genetic background and biochemical mechanisms by which these mutations contribute to the diseases has been only partially revealed. This chapter describes the multiple functions and associated synaptic alterations of the SCAM genes found mutated in neurodevelopmental diseases. En ligne : http://dx.doi.org/10.1016/B978-0-12-800109-7.00011-X Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301 Exemplaires
Code-barres Cote Support Localisation Section Disponibilité aucun exemplaire Early communication deficits in the Shank1 knockout mouse model for autism spectrum disorder: Developmental aspects and effects of social context / A. Özge SUNGUR in Autism Research, 9-6 (June 2016)
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[article]
Titre : Early communication deficits in the Shank1 knockout mouse model for autism spectrum disorder: Developmental aspects and effects of social context Type de document : Texte imprimé et/ou numérique Auteurs : A. Özge SUNGUR, Auteur ; Rainer K. W. SCHWARTING, Auteur ; Markus WÖHR, Auteur Article en page(s) : p.696-709 Langues : Anglais (eng) Mots-clés : animal model postsynaptic density neurodevelopmental disorders autism communication ultrasonic vocalization social context Index. décimale : PER Périodiques Résumé : Alterations in SHANK genes were repeatedly reported in autism spectrum disorder (ASD). ASD is a group of neurodevelopmental disorders diagnosed by persistent deficits in social communication/interaction across multiple contexts, with restricted/repetitive patterns of behavior. To date, diagnostic criteria for ASD are purely behaviorally defined and reliable biomarkers have still not been identified. The validity of mouse models for ASD therefore strongly relies on their behavioral phenotype. Here, we studied communication by means of isolation-induced pup ultrasonic vocalizations (USV) in the Shank1 mouse model for ASD by comparing Shank1?/? null mutant, Shank1+/? heterozygous, and Shank1+/+ wildtype littermate controls. The first aim of the present study was to evaluate the effects of Shank1 deletions on developmental aspects of communication in order to see whether ASD-related communication deficits are due to general impairment or delay in development. Second, we focused on social context effects on USV production. We show that Shank1?/? pups vocalized less and displayed a delay in the typical inverted U-shaped developmental USV emission pattern with USV rates peaking on postnatal day (PND) 9, resulting in a prominent genotype difference on PND6. Moreover, testing under social conditions revealed even more prominently genotype-dependent deficits regardless of the familiarity of the social context. As communication by definition serves a social function, introducing a social component to the typically nonsocial test environment could therefore help to reveal communication deficits in mouse models for ASD. Together, these results indicate that SHANK1 is involved in acoustic communication across species, with genetic alterations in SHANK1 resulting in social communication/interaction deficits. Autism Res 2016, 9: 696–709. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1564 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=290
in Autism Research > 9-6 (June 2016) . - p.696-709[article] Early communication deficits in the Shank1 knockout mouse model for autism spectrum disorder: Developmental aspects and effects of social context [Texte imprimé et/ou numérique] / A. Özge SUNGUR, Auteur ; Rainer K. W. SCHWARTING, Auteur ; Markus WÖHR, Auteur . - p.696-709.
Langues : Anglais (eng)
in Autism Research > 9-6 (June 2016) . - p.696-709
Mots-clés : animal model postsynaptic density neurodevelopmental disorders autism communication ultrasonic vocalization social context Index. décimale : PER Périodiques Résumé : Alterations in SHANK genes were repeatedly reported in autism spectrum disorder (ASD). ASD is a group of neurodevelopmental disorders diagnosed by persistent deficits in social communication/interaction across multiple contexts, with restricted/repetitive patterns of behavior. To date, diagnostic criteria for ASD are purely behaviorally defined and reliable biomarkers have still not been identified. The validity of mouse models for ASD therefore strongly relies on their behavioral phenotype. Here, we studied communication by means of isolation-induced pup ultrasonic vocalizations (USV) in the Shank1 mouse model for ASD by comparing Shank1?/? null mutant, Shank1+/? heterozygous, and Shank1+/+ wildtype littermate controls. The first aim of the present study was to evaluate the effects of Shank1 deletions on developmental aspects of communication in order to see whether ASD-related communication deficits are due to general impairment or delay in development. Second, we focused on social context effects on USV production. We show that Shank1?/? pups vocalized less and displayed a delay in the typical inverted U-shaped developmental USV emission pattern with USV rates peaking on postnatal day (PND) 9, resulting in a prominent genotype difference on PND6. Moreover, testing under social conditions revealed even more prominently genotype-dependent deficits regardless of the familiarity of the social context. As communication by definition serves a social function, introducing a social component to the typically nonsocial test environment could therefore help to reveal communication deficits in mouse models for ASD. Together, these results indicate that SHANK1 is involved in acoustic communication across species, with genetic alterations in SHANK1 resulting in social communication/interaction deficits. Autism Res 2016, 9: 696–709. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1564 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=290