dc.creator | Mejías Estévez, Rebeca María | es |
dc.creator | Chiu, Shu-Ling | es |
dc.creator | Rose, Rebecca | es |
dc.creator | Gil Infante, Ana | es |
dc.creator | Zhao, Yifan | es |
dc.creator | Wang, Tao | es |
dc.creator | Huganir, Richard L | es |
dc.date.accessioned | 2020-03-09T11:46:11Z | |
dc.date.available | 2020-03-09T11:46:11Z | |
dc.date.issued | 2019 | |
dc.identifier.citation | Mejías Estévez, R.M., Chiu, S., Rose, R., Gil Infante, A., Zhao, Y., Wang, T. y Huganir, R.L. (2019). Purkinje cell-specific Grip1/2 knockout mice show increased repetitive self-grooming and enhanced mGluR5 signaling in cerebellum. Neurobiology of Disease, 132, 1-10. | |
dc.identifier.issn | 1095-953X | es |
dc.identifier.uri | https://hdl.handle.net/11441/94035 | |
dc.description.abstract | Cerebellar Purkinje cell (PC) loss is a consistent pathological finding in autism. However, neural mechanisms of PC-dysfunction in autism remain poorly characterized. Glutamate receptor interacting proteins 1/2 (Grip1/2) regulate AMPA receptor (AMPAR) trafficking and synaptic strength. To evaluate role of PC-AMPAR signaling in autism, we produced PC-specific Grip1/2 knockout mice by crossing Grip2 conventional and Grip1 conditional KO with L7-Cre driver mice. PCs in the mutant mice showed normal morphology and number, and a lack of Grip1/2 expression. Rodent behavioral testing identified normal ambulation, anxiety, social interaction, and an increase in repetitive self-grooming. Electrophysiology studies revealed normal mEPSCs but an impaired mGluR-LTD at the Parallel Fiber-PC synapses. Immunoblots showed increased expression of mGluR5 and Arc, and enhanced phosphorylation of P38 and AKT in cerebellum of PC-specific Grip1/2 knockout mice. Results indicate that loss of Grip1/2 in PCs contributes to increased repetitive self-grooming, a core autism behavior in mice. Results support a role of AMPAR trafficking defects in PCs and disturbances of mGluR5 signaling in cerebellum in the pathogenesis of repetitive behaviors. | es |
dc.description.sponsorship | University of Seville (V PPIT-US) | es |
dc.description.sponsorship | Spain and an National Institute of Health (NIH) (NS085358) | es |
dc.format | application/pdf | es |
dc.format.extent | 10 p. | es |
dc.language.iso | eng | es |
dc.publisher | Elsevier | es |
dc.relation.ispartof | Neurobiology of Disease, 132, 1-10. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | AMPA receptors | es |
dc.subject | Autism | es |
dc.subject | Cerebellum | es |
dc.subject | Glutamate signaling | es |
dc.subject | Grip1/2 | es |
dc.subject | Grooming | es |
dc.subject | LTD | es |
dc.subject | Purkinje cells | es |
dc.subject | mGluR receptors | es |
dc.title | Purkinje cell-specific Grip1/2 knockout mice show increased repetitive self-grooming and enhanced mGluR5 signaling in cerebellum | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Fisiología | es |
dc.relation.projectID | (V PPIT-US) | es |
dc.relation.projectID | NS085358 | es |
dc.relation.publisherversion | http://dx.doi.org/10.1016/j.nbd.2019.104602 | es |
dc.identifier.doi | 10.1016/j.nbd.2019.104602 | es |
dc.journaltitle | Neurobiology of Disease | es |
dc.publication.volumen | 132 | es |
dc.publication.initialPage | 1 | es |
dc.publication.endPage | 10 | es |
dc.contributor.funder | Universidad de Sevilla | es |
dc.contributor.funder | NIH | es |