Hippocampal protein kinase C signaling mediates the short-term memory impairment induced by delta9-tetrahydrocannabinol

Mostra el registre complet Registre parcial de l'ítem

• dc.contributor.author Busquets Garcia, Arnau, 1985-ca
• dc.contributor.author Gomis González, Maria, 1988-ca
• dc.contributor.author Salgado Mendialdúa, Victòriaca
• dc.contributor.author Galera López, Lorena, 1993-ca
• dc.contributor.author Puighermanal Puigvert, Emma, 1983-ca
• dc.contributor.author Martín García, Elena, 1975-ca
• dc.contributor.author Maldonado, Rafael, 1961-ca
• dc.contributor.author Ozaita Mintegui, Andrés, 1969-ca
• dc.date.accessioned 2017-09-07T08:20:50Z
• dc.date.issued 2017
• dc.description.abstract Cannabis affects cognitive performance through the activation of the endocannabinoid system, and the molecular mechanisms involved in this process are poorly understood. Using the novel object-recognition memory test in mice, we found that the main psychoactive component of cannabis, delta9-tetrahydrocannabinol (THC), alters short-term object-recognition memory specifically involving protein kinase C (PKC)-dependent signaling. Indeed, the systemic or intra-hippocampal pre-treatment with the PKC inhibitors, prevented the short-term, but not the long-term, memory impairment induced by THC. In contrast, systemic pre-treatment with mammalian target of rapamycin complex 1 (mTORC1) inhibitors, known to block the amnesic-like effects of THC on long-term memory, did not modify such a short-term cognitive deficit. Immunoblot analysis revealed a transient increase in PKC signaling activity in the hippocampus after THC treatment. Thus, THC administration induced the phosphorylation of a specific Ser residue in the hydrophobic-motif at the C-terminal tail of several PKC isoforms. This significant immunoreactive band that paralleled cognitive performance did not match in size with the major PKC isoforms expressed in the hippocampus except for PKCθ. Moreover, THC transiently enhanced the phosphorylation of the postsynaptic calmodulin-binding protein neurogranin in a PKC dependent manner. These data demonstrate that THC alters short-term object-recognition memory through hippocampal PKC/neurogranin signaling.
• dc.description.sponsorship Predoctoral fellowship from the Spanish Ministry of Education (A. B-G. and E.P.). Partial support by FP7-PEOPLE-2013-IEF-623638 (A.B-G). Partial support by FRAXA Research Foundation (M.G-G.). Predoctoral fellowship by FPI (MINEICO/FEDER, EU) (V.S-M. and L.G-L). Research supported by BFU2015-68568P (A.O.), (MINECO/FEDER, UE); Redes temáticas de investigación cooperativa en salud (RETICS) del Instituto de Salud Carlos III (#RD16/0017/0020)-Red de trastornos adictivos (RTA) (R.M.); Generalitat de Catalunya, AGAUR (#2014-SGR-1547) (R.M.); ICREA (Institució Catalana de Recerca i Estudis Avançats) Acadèmia (R.M. and A.O.)
• dc.format.mimetype application/pdfca
• dc.identifier.citation Busquets-Garcia A, Gomis-González M, Salgado-Mendialdúa V, Galera-López L, Puighermanal E, Martín-García E et al. Hippocampal protein kinase C signaling mediates the short-term memory impairment induced by delta9-tetrahydrocannabinol. Neuropsychopharmacology. 2018 Apr;43(5):1021-31. DOI: 10.1038/npp.2017.175
• dc.identifier.doi http://dx.doi.org/10.1038/npp.2017.175
• dc.identifier.issn 0893-133X
• dc.identifier.uri http://hdl.handle.net/10230/32757
• dc.language.iso eng
• dc.publisher Nature Publishing Groupca
• dc.relation.ispartof Neuropsychopharmacology. 2018 Apr;43(5):1021-31
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/623638
• dc.rights © Nature Publishing Group. http://dx.doi.org/10.1038/npp.2017.175
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.other Cànnabis
• dc.subject.other Sistema endocannabinoid
• dc.subject.other Proteïnes quinases
• dc.subject.other Memòria
• dc.title Hippocampal protein kinase C signaling mediates the short-term memory impairment induced by delta9-tetrahydrocannabinolca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion