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Fasudil treatment in adult reverses behavioural changes and brain ventricular enlargement in Oligophrenin-1 mouse model of intellectual disability

hal.structure.identifierInstitut de génétique et biologie moléculaire et cellulaire [IGBMC]
dc.contributor.authorMEZIANE, Hamid
hal.structure.identifierInstitut Cochin [UMR_S567 / UMR 8104]
dc.contributor.authorKHELFAOUI, Malik
dc.contributor.authorMORELLO, Noemi
hal.structure.identifierCentre de Recherche et d'Application en Traitement de l'Image et du Signal [CREATIS]
dc.contributor.authorHIBA, Bassem
dc.contributor.authorCALCAGNO, Eleonora
dc.contributor.authorREIBEL-FOISSET, Sophie
hal.structure.identifierInstitut Clinique de la Souris [ICS]
dc.contributor.authorSELLOUM, Mohammed
hal.structure.identifierInstitut de Génétique et de Biologie Moléculaire et Cellulaire [IGBMC]
dc.contributor.authorCHELLY, Jamel
dc.contributor.authorHUMEAU, Yann
hal.structure.identifierInstitut de Génétique et de Biologie Moléculaire et Cellulaire [IGBMC]
dc.contributor.authorRIET, Fabrice
hal.structure.identifierMedical Genetics and Pediatric Cardiology
dc.contributor.authorZANNI, Ginevra
hal.structure.identifierImmunologie et Embryologie Moléculaires [IEM]
dc.contributor.authorHÉRAULT, Yann
hal.structure.identifierService de biochimie et de génétique moléculaire [CHU Cochin]
dc.contributor.authorBIENVENU, Thierry
hal.structure.identifierDipartimento di Neuroscienza
dc.contributor.authorGIUSTETTO, Maurizio
hal.structure.identifierInstitut Cochin [UMR_S567 / UMR 8104]
dc.contributor.authorBILLUART, Pierre
dc.date.accessioned2021-10-07T16:29:26Z
dc.date.available2021-10-07T16:29:26Z
dc.date.issued2016-10-24
dc.identifier.issn0964-6906
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/112651
dc.description.abstractEnLoss of function mutations in human Oligophrenin1 (OPHN1) gene are responsible for syndromic intellectual disability (ID) associated with cerebellar hypoplasia and cerebral ventricles enlargement. Functional studies in rodent models suggest that OPHN1 linked ID is a consequence of abnormal synaptic transmission and shares common pathophysiological mechanisms with other cognitive disorders. Variants of this gene have been also identified in autism spectrum disorder and schizophrenia. The advanced understanding of the mechanisms underlying OPHN1-related ID, allowed us to develop a therapeutic approach targeting the Ras homolog gene family, member A (RHOA) signalling pathway and repurpose Fasudil-a well-tolerated Rho Kinase (ROCK) and Protein Kinase A (PKA) inhibitor-as a treatment of ID. We have previously shown ex-vivo its beneficial effect on synaptic transmission and plasticity in a mouse model of the OPHN1 loss of function. Here, we report that chronic treatment in adult mouse with Fasudil, is able to counteract vertical and horizontal hyperactivities, restores recognition memory and limits the brain ventricular dilatation observed in Ophn1 À/y. However, deficits in working and spatial memories are partially or not rescued by the treatment. These results highlight the potential of Fasudil treatment in synaptopathies and also the need for multiple therapeutic approaches especially in adult where brain plasticity is reduced. †
dc.language.isoen
dc.publisherOxford University Press (OUP)
dc.title.enFasudil treatment in adult reverses behavioural changes and brain ventricular enlargement in Oligophrenin-1 mouse model of intellectual disability
dc.typeArticle de revue
dc.identifier.doi10.1093/hmg/ddw102
dc.subject.halSciences du Vivant [q-bio]
bordeaux.journalHuman Molecular Genetics
bordeaux.page2314-2323
bordeaux.volume25
bordeaux.hal.laboratoriesCentre de Résonance Magnétique des Systèmes Biologiques (CRMSB) - UMR 5536*
bordeaux.issue11
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionCNRS
bordeaux.peerReviewedoui
hal.identifierhal-02404671
hal.version1
hal.origin.linkhttps://hal.archives-ouvertes.fr//hal-02404671v1
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