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dc.contributor.authorGomis González, María
dc.contributor.authorBusquets García, Arnau
dc.contributor.authorMatute Almau, Carlos José
dc.contributor.authorMaldonado, Rafael
dc.contributor.authorMato Santos, Susana ORCID
dc.contributor.authorOzaita, Andres
dc.date.accessioned2018-05-07T17:54:30Z
dc.date.available2018-05-07T17:54:30Z
dc.date.issued2016-08
dc.identifier.citationGenes 7(9) : (2016) // Article ID 56es_ES
dc.identifier.issn2073-4425
dc.identifier.urihttp://hdl.handle.net/10810/26716
dc.description.abstractFragile X syndrome (FXS) is the most common monogenetic cause of intellectual disability. The cognitive deficits in the mouse model for this disorder, the Fragile X Mental Retardation 1 (Fmr1) knockout (KO) mouse, have been restored by different pharmacological approaches, among those the blockade of cannabinoid type 1 (CB1) receptor. In this regard, our previous study showed that the CB1 receptor antagonist/inverse agonist rimonabant normalized a number of core features in the Fmr1 knockout mouse. Rimonabant was commercialized at high doses for its anti-obesity properties, and withdrawn from the market on the bases of mood-related adverse effects. In this study we show, by using electrophysiological approaches, that low dosages of rimonabant (0.1 mg/kg) manage to normalize metabotropic glutamate receptor dependent long-term depression (mGluR-LTD). In addition, low doses of rimonabant (from 0.01 mg/kg) equally normalized the cognitive deficit in the mouse model of FXS. These doses of rimonabant were from 30 to 300 times lower than those required to reduce body weight in rodents and to presumably produce adverse effects in humans. Furthermore, NESS0327, a CB1 receptor neutral antagonist, was also effective in preventing the novel object-recognition memory deficit in Fmr1 KO mice. These data further support targeting CB1 receptors as a relevant therapy for FXS.es_ES
dc.description.sponsorshipWe thank Dulce Real and Francisco Porron for expert technical assistance and the Laboratory of Neuropharmacology for helpful comments. M.G.-G. was partially supported by FRAXA Research Foundation. A. B.-G. was recipient of a predoctoral fellowship (Ministerio de Educacion y Ciencia). S.M. is recipient of a Ramon y Cajal contract (Ministerio de Educacion y Ciencia). This study was supported by grants from FRAXA Research Foundation (A.O. and S.M.), Grants from the Ministerio de Ciencia e Innovacion (#BFU2015-68568-P to A.O., #SAF2014-59648-P to R.M. and SAF2013-45084-R to C.M., MINECO/FEDER, UE); Instituto de Salud Carlos III (RD06/0001/0001 to R.M. and CIBERNED PRY-15-404 to C.M.); Generalitat de Catalunya (SGR-2014-1547 to R.M.); ICREA (Institucio Catalana de Recerca i Estudis Avancats) Academia to R.M.es_ES
dc.language.isoenges_ES
dc.publisherMDPIes_ES
dc.relationinfo:eu-repo/grantAgreement/MINECO/BFU2015-68568-Pes_ES
dc.relationinfo:eu-repo/grantAgreement/MINECO/SAF2014-59648-Pes_ES
dc.relationinfo:eu-repo/grantAgreement/MINECO/AF2013-45084-Res_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/es/*
dc.subjectfragile X syndromees_ES
dc.subjectsynaptic plasticityes_ES
dc.subjectlong-term depressiones_ES
dc.subjectmemoryes_ES
dc.subjecttreatmentes_ES
dc.subjectcannabinoid receptores_ES
dc.subjectCB1es_ES
dc.subjectendocannabinoid systemes_ES
dc.titlePossible therapeutic doses of cannabinoid type 1 receptor antagonist reverses key alterations in fragile X syndrome mouse modeles_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.rights.holder© 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).es_ES
dc.rights.holderAtribución 3.0 España*
dc.relation.publisherversionhttp://www.mdpi.com/2073-4425/7/9/56es_ES
dc.identifier.doi10.3390/genes7090056
dc.departamentoesNeurocienciases_ES
dc.departamentoeuNeurozientziakes_ES


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© 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
Except where otherwise noted, this item's license is described as © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).