Mutations in Synaptic Adhesion Molecules / Jaewon KO  

Public ISBD 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 in Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA 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. 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

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Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability / Carlo SALA

Public ISBD Titre : Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability Type de document : Texte imprimé et/ou numérique Auteurs : Carlo SALA, Directeur de publication ; Chiara VERPELLI, Directeur de publication Editeur : Issy les Moulineaux [France] : Academic Press Année de publication : 2016 Importance : 379 p. Présentation : ill. Format : 22cm x 28cm x 2,5cm ISBN/ISSN/EAN : 978-0-12-800109-7 Note générale : Bibliogr., Index Langues : Anglais (eng) Index. décimale : SCI-D SCI-D - Neurosciences Résumé : Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability provides the latest information on Autism spectrum disorders (ASDs), the lifelong neurodevelopmental disorders that present in early childhood and affect how individuals communicate and relate to others and their surroundings. In addition, three quarters of ASD patients also manifest severe intellectual disability. Though certain genes have been implicated, ASDs remain largely a mystery, and research looking into causes and cellular deficits are crucial for better understanding of neurodevelopmental disorders. Despite the prevalence and insidious nature of this disorder, this book remains to be an extensive resource of information and background on the state of current research in the field. The book serves as a reference for this purpose, and discusses the crucial role synaptic activity plays in proper brain function. In addition, the volume discusses the neurodevelopmental synaptopathies and serves as a resource for scientists and clinicians in all biomedical science specialties. This research has been crucial for recent studies that have provided a rationale for the development of pharmacological agents able to counteract functional synaptic anomalies and potentially ameliorate some ASD symptoms. - Introduces the genetic and non-genetic causes of autism and associated intellectual disabilities - Describes the genes implicated in autistic spectrum disorders and their function - Considers major individual genetic causes of autism, Rett syndrome, Fragile X syndrome, and other autism spectrum disorders, as well as their classification as synaptopathies - Presents a thorough discussion of the clinical aspects of multiple neurodevelopmental disorders and the experimental models that exist to study their pathophysiology in vitro and in vivo, including animal models and patient-derived stem cell culture. [Résumé d'Auteur/Editeur] Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301 Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability [Texte imprimé et/ou numérique] / Carlo SALA, Directeur de publication ; Chiara VERPELLI, Directeur de publication . - Issy les Moulineaux [France] : Academic Press, 2016 . - 379 p. : ill. ; 22cm x 28cm x 2,5cm. ISBN : 978-0-12-800109-7 Bibliogr., Index Langues : Anglais (eng) Index. décimale : SCI-D SCI-D - Neurosciences Résumé : Neuronal and Synaptic Dysfunction in Autism Spectrum Disorder and Intellectual Disability provides the latest information on Autism spectrum disorders (ASDs), the lifelong neurodevelopmental disorders that present in early childhood and affect how individuals communicate and relate to others and their surroundings. In addition, three quarters of ASD patients also manifest severe intellectual disability. Though certain genes have been implicated, ASDs remain largely a mystery, and research looking into causes and cellular deficits are crucial for better understanding of neurodevelopmental disorders. Despite the prevalence and insidious nature of this disorder, this book remains to be an extensive resource of information and background on the state of current research in the field. The book serves as a reference for this purpose, and discusses the crucial role synaptic activity plays in proper brain function. In addition, the volume discusses the neurodevelopmental synaptopathies and serves as a resource for scientists and clinicians in all biomedical science specialties. This research has been crucial for recent studies that have provided a rationale for the development of pharmacological agents able to counteract functional synaptic anomalies and potentially ameliorate some ASD symptoms. - Introduces the genetic and non-genetic causes of autism and associated intellectual disabilities - Describes the genes implicated in autistic spectrum disorders and their function - Considers major individual genetic causes of autism, Rett syndrome, Fragile X syndrome, and other autism spectrum disorders, as well as their classification as synaptopathies - Presents a thorough discussion of the clinical aspects of multiple neurodevelopmental disorders and the experimental models that exist to study their pathophysiology in vitro and in vivo, including animal models and patient-derived stem cell culture. [Résumé d'Auteur/Editeur] Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=301

Contenu

• Experimental Tools for the Identification of Specific Genes in Autism Spectrum Disorders and Intellectual Disability / Yiping SHEN  
• Genetic Causes of Autism Spectrum Disorders / Guillaume HUGUET  
• Genetics of X-Linked Intellectual Disability / Charles E. SCHWARTZ  
• Genetic Causes of Intellectual Disability: The Genes Controlling Cortical Development / Yoann SAILLOUR  
• Immune Dysfunction in Autism Spectrum Disorder / Natalia V. MALKOVA  
• Synapse Proteomes and Disease: The MASC Paradigm / Àlex BAYES  
• The Function of MeCP2 and Its Causality in Rett Syndrome / Janine M. LAMONICA  
• FMRP and the Pathophysiology of Fragile X Syndrome / Stephanie A. BARNES  
• X-Linked ASDs and ID Gene Mutations / Edoardo MORETTO  
• SHANK Mutations in Intellectual Disability and Autism Spectrum Disorder / Michael J. SCHMEISSER  
• Mutations in Synaptic Adhesion Molecules / Jaewon KO  
• CNTNAP2 Mutations in Autism / Olga PENAGARIKANO  
• Planar Cell Polarity Gene Mutations in Autism Spectrum Disorder, Intellectual Disabilities, and Related Deletion/Duplication Syndromes / Nathalie SANS  
• Protocadherin Mutations in Neurodevelopmental Disorders / Duyen PHAM  
• Mutations of Voltage-Gated Sodium Channel Genes SCN1A and SCN2A in Epilepsy, Intellectual Disability, and Autism / Kazuhiro YAMAKAWA  
• The iPSC Technology to Study Neurodevelopmental Disorders / Alysson Renato MUOTRI  
• Oxytocin in the Developing Brain: Relevance as Disease-Modifying Treatment in Autism Spectrum Disorders / Bice CHINI  
• Mouse Behavior and Models for Autism Spectrum Disorders / Laura RICCERI  
• Rett Syndrome: Clinical Aspects / Daniel C. TARQUINIO  
• Fragile X Syndrome / Anne HOFFMANN  

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DOC0004045	SCI-D SAL	Livre	Centre d'Information et de Documentation du CRA Rhône-Alpes	SCI - Disciplines Scientifiques	Disponible

Shank3 deletion in PV neurons is associated with abnormal behaviors and neuronal functions that are rescued by increasing GABAergic signaling / Silvia LANDI ; Alessia STEFANONI ; Gabriele NARDI ; Marica ALBANESI ; Helen F. BAUER ; Enrico PRACUCCI ; Michael SCHÖN ; Gian Michele RATTO ; Tobias M. BOECKERS ; Carlo SALA ; Chiara VERPELLI in Molecular Autism, 14 (2023)  

Public ISBD [article]  inMolecular Autism > 14 (2023) . - 28 p. Titre : Shank3 deletion in PV neurons is associated with abnormal behaviors and neuronal functions that are rescued by increasing GABAergic signaling Type de document : Texte imprimé et/ou numérique Auteurs : Silvia LANDI, Auteur ; Alessia STEFANONI, Auteur ; Gabriele NARDI, Auteur ; Marica ALBANESI, Auteur ; Helen F. BAUER, Auteur ; Enrico PRACUCCI, Auteur ; Michael SCHÖN, Auteur ; Gian Michele RATTO, Auteur ; Tobias M. BOECKERS, Auteur ; Carlo SALA, Auteur ; Chiara VERPELLI, Auteur Article en page(s) : 28 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder characterized by developmental delay, intellectual disability, and autistic-like behaviors and is primarily caused by haploinsufficiency of SHANK3 gene. Currently, there is no specific treatment for PMS, highlighting the need for a better understanding of SHANK3 functions and the underlying pathophysiological mechanisms in the brain. We hypothesize that SHANK3 haploinsufficiency may lead to alterations in the inhibitory system, which could be linked to the excitatory/inhibitory imbalance observed in models of autism spectrum disorder (ASD). Investigation of these neuropathological features may shed light on the pathogenesis of PMS and potential therapeutic interventions. METHODS: We recorded local field potentials and visual evoked responses in the visual cortex of Shank3?11(-/-) mice. Then, to understand the impact of Shank3 in inhibitory neurons, we generated Pv-cre(+/-) Shank3(Fl/Wt) conditional mice, in which Shank3 was deleted in parvalbumin-positive neurons. We characterized the phenotype of this murine model and we compared this phenotype before and after ganaxolone administration. RESULTS: We found, in the primary visual cortex, an alteration of the gain control of Shank3 KO compared with Wt mice, indicating a deficit of inhibition on pyramidal neurons. This alteration was rescued after the potentiation of GABA(A) receptor activity by Midazolam. Behavioral analysis showed an impairment in grooming, memory, and motor coordination of Pv-cre(+/-) Shank3(Fl/Wt) compared with Pv-cre(+/-) Shank3(Wt/Wt) mice. These deficits were rescued with ganaxolone, a positive modulator of GABA(A) receptors. Furthermore, we demonstrated that treatment with ganaxolone also ameliorated evocative memory deficits and repetitive behavior of Shank3 KO mice. LIMITATIONS: Despite the significant findings of our study, some limitations remain. Firstly, the neurobiological mechanisms underlying the link between Shank3 deletion in PV neurons and behavioral alterations need further investigation. Additionally, the impact of Shank3 on other classes of inhibitory neurons requires further exploration. Finally, the pharmacological activity of ganaxolone needs further characterization to improve our understanding of its potential therapeutic effects. CONCLUSIONS: Our study provides evidence that Shank3 deletion leads to an alteration in inhibitory feedback on cortical pyramidal neurons, resulting in cortical hyperexcitability and ASD-like behavioral problems. Specifically, cell type-specific deletion of Shank3 in PV neurons was associated with these behavioral deficits. Our findings suggest that ganaxolone may be a potential pharmacological approach for treating PMS, as it was able to rescue the behavioral deficits in Shank3 KO mice. Overall, our study highlights the importance of investigating the role of inhibitory neurons and potential therapeutic interventions in neurodevelopmental disorders such as PMS. En ligne : http://dx.doi.org/10.1186/s13229-023-00557-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513 [article] Shank3 deletion in PV neurons is associated with abnormal behaviors and neuronal functions that are rescued by increasing GABAergic signaling [Texte imprimé et/ou numérique] / Silvia LANDI, Auteur ; Alessia STEFANONI, Auteur ; Gabriele NARDI, Auteur ; Marica ALBANESI, Auteur ; Helen F. BAUER, Auteur ; Enrico PRACUCCI, Auteur ; Michael SCHÖN, Auteur ; Gian Michele RATTO, Auteur ; Tobias M. BOECKERS, Auteur ; Carlo SALA, Auteur ; Chiara VERPELLI, Auteur . - 28 p. Langues : Anglais (eng) in Molecular Autism > 14 (2023) . - 28 p. Index. décimale : PER Périodiques Résumé : BACKGROUND: Phelan-McDermid syndrome (PMS) is a neurodevelopmental disorder characterized by developmental delay, intellectual disability, and autistic-like behaviors and is primarily caused by haploinsufficiency of SHANK3 gene. Currently, there is no specific treatment for PMS, highlighting the need for a better understanding of SHANK3 functions and the underlying pathophysiological mechanisms in the brain. We hypothesize that SHANK3 haploinsufficiency may lead to alterations in the inhibitory system, which could be linked to the excitatory/inhibitory imbalance observed in models of autism spectrum disorder (ASD). Investigation of these neuropathological features may shed light on the pathogenesis of PMS and potential therapeutic interventions. METHODS: We recorded local field potentials and visual evoked responses in the visual cortex of Shank3?11(-/-) mice. Then, to understand the impact of Shank3 in inhibitory neurons, we generated Pv-cre(+/-) Shank3(Fl/Wt) conditional mice, in which Shank3 was deleted in parvalbumin-positive neurons. We characterized the phenotype of this murine model and we compared this phenotype before and after ganaxolone administration. RESULTS: We found, in the primary visual cortex, an alteration of the gain control of Shank3 KO compared with Wt mice, indicating a deficit of inhibition on pyramidal neurons. This alteration was rescued after the potentiation of GABA(A) receptor activity by Midazolam. Behavioral analysis showed an impairment in grooming, memory, and motor coordination of Pv-cre(+/-) Shank3(Fl/Wt) compared with Pv-cre(+/-) Shank3(Wt/Wt) mice. These deficits were rescued with ganaxolone, a positive modulator of GABA(A) receptors. Furthermore, we demonstrated that treatment with ganaxolone also ameliorated evocative memory deficits and repetitive behavior of Shank3 KO mice. LIMITATIONS: Despite the significant findings of our study, some limitations remain. Firstly, the neurobiological mechanisms underlying the link between Shank3 deletion in PV neurons and behavioral alterations need further investigation. Additionally, the impact of Shank3 on other classes of inhibitory neurons requires further exploration. Finally, the pharmacological activity of ganaxolone needs further characterization to improve our understanding of its potential therapeutic effects. CONCLUSIONS: Our study provides evidence that Shank3 deletion leads to an alteration in inhibitory feedback on cortical pyramidal neurons, resulting in cortical hyperexcitability and ASD-like behavioral problems. Specifically, cell type-specific deletion of Shank3 in PV neurons was associated with these behavioral deficits. Our findings suggest that ganaxolone may be a potential pharmacological approach for treating PMS, as it was able to rescue the behavioral deficits in Shank3 KO mice. Overall, our study highlights the importance of investigating the role of inhibitory neurons and potential therapeutic interventions in neurodevelopmental disorders such as PMS. En ligne : http://dx.doi.org/10.1186/s13229-023-00557-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=513

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