Cannabinoid signaling modulation through JZL184 restores key phenotypes of a mouse model for Williams-Beuren syndrome
dc.contributor.author | Navarro Romero, Alba | |
dc.contributor.author | Galera López, Lorena | |
dc.contributor.author | Ortíz Romero, Paula | |
dc.contributor.author | Llorente Ovejero, Alberto | |
dc.contributor.author | de los Reyes Ramírez, Lucía | |
dc.contributor.author | Bengoetxea de Tena, Iker | |
dc.contributor.author | García Elías, Anna | |
dc.contributor.author | Mas-Stachurska, Aleksandra | |
dc.contributor.author | Reixachs Solé, Marina | |
dc.contributor.author | Pastor, Antoni | |
dc.contributor.author | De la Torre, Rafael | |
dc.contributor.author | Maldonado, Rafael | |
dc.contributor.author | Benito, Begoña | |
dc.contributor.author | Eyras, Eduardo | |
dc.contributor.author | Rodríguez Puertas, Rafael | |
dc.contributor.author | Campuzano, Victoria | |
dc.contributor.author | Ozaita, Andres | |
dc.date.accessioned | 2022-12-16T16:45:16Z | |
dc.date.available | 2022-12-16T16:45:16Z | |
dc.date.issued | 2022-10 | |
dc.identifier.citation | eLife 11 : (2022) // Article ID e72560 | es_ES |
dc.identifier.issn | 2050-084X | |
dc.identifier.uri | http://hdl.handle.net/10810/58850 | |
dc.description.abstract | Williams-Beuren syndrome (WBS) is a rare genetic multisystemic disorder characterized by mild-to-moderate intellectual disability and hypersocial phenotype, while the most life-threatening features are cardiovascular abnormalities. Nowadays, there are no pharmacological treatments to directly ameliorate the main traits of WBS. The endocannabinoid system (ECS), given its relevance for both cognitive and cardiovascular function, could be a potential druggable target in this syndrome. We analyzed the components of the ECS in the complete deletion (CD) mouse model of WBS and assessed the impact of its pharmacological modulation in key phenotypes relevant for WBS. CD mice showed the characteristic hypersociable phenotype with no preference for social novelty and poor short-term object-recognition performance. Brain cannabinoid type-1 receptor (CB1R) in CD male mice showed alterations in density and coupling with no detectable change in main endocannabinoids. Endocannabinoid signaling modulation with subchronic (10 days) JZL184, a selective inhibitor of monoacylglycerol lipase, specifically normalized the social and cognitive phenotype of CD mice. Notably, JZL184 treatment improved cardiovascular function and restored gene expression patterns in cardiac tissue. These results reveal the modulation of the ECS as a promising novel therapeutic approach to improve key phenotypic alterations in WBS. | es_ES |
dc.description.sponsorship | Ministerio de Ciencia, Innovacion y Universidades FPU13/01867 Alba Navarro-Romero Ministerio de Ciencia e Innovacion BES-2016-077950 Lorena Galera-Lopez Ministerio de Ciencia e Innovacion RTI2018-099282-B-I00 Andres Ozaita Ministerio de Ciencia e Innovacion SAF2017-84060-R Rafael Maldonado Generalitat de Catalunya 2017SGR-669 Rafael Maldonado Ministerio de Ciencia e Innovacion SAF2016-78508-R Victoria Campuzano Basque Country Government IT1454-22 Rafael Rodriguez-Puertas Instituto de Salud Carlos III PI20/00153, co-funded by the European Union (ERDF "A way to make Europe") Rafael Rodriguez-Puertas Institucio Catalana de Recerca i Estudis Avancats Rafael Maldonado Ministerio de Economia y Competitividad #MDM-2014-0370 Alba Navarro-Romero Ministerio de Economia y Competitividad #MDM-2014-0370 Eduardo Eyras Ministerio de Ciencia e Innovacion PRE2019-087644 Lucia de los Reyes-Ramirez Ministerio de Ciencia e Innovacion AEI/MINEICO/FEDER Andres Ozaita Ministerio de Ciencia e Innovacion AEI/MINEICO/FEDER Rafael Maldonado Ministerio de Ciencia e Innovacion AEI/MINEICO/FEDER Victoria Campuzano Ministerio de Economia y Competitividad FEDER Alba Navarro-Romero Ministerio de Economia y Competitividad FEDER Eduardo Eyras Ministerio de Economia y Competitividad IPEP MdM-2017 Eduardo Eyras Ministerio de Ciencia e Innovacion UE Andres Ozaita Ministerio de Ciencia e Innovacion UE Rafael Maldonado Ministerio de Economia y Competitividad UE Alba Navarro-Romero Ministerio de Ciencia e Innovacion UE Victoria Campuzano Ministerio de Economia y Competitividad EU Eduardo Eyras FRAXA Research Foundation Lorena Galera-Lopez The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | eLife Sciences | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/BES-2016-077950 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICIU/RTI2018-099282-B-I00 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2017-84060-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/SAF2016-78508-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/MDM-2014-0370 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PRE2019-087644 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | Williams-Beuren syndrome | es_ES |
dc.subject | intellectual disability | es_ES |
dc.subject | endocannabinoid system | es_ES |
dc.subject | cannabinoid type-1 receptor | es_ES |
dc.subject | mouse | es_ES |
dc.title | Cannabinoid signaling modulation through JZL184 restores key phenotypes of a mouse model for Williams-Beuren syndrome | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | Copyright Navarro-Romero, Galera- López et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://elifesciences.org/articles/72560 | es_ES |
dc.identifier.doi | 10.7554/eLife.72560 | |
dc.departamentoes | Farmacología | es_ES |
dc.departamentoeu | Farmakologia | es_ES |
Files in this item
This item appears in the following Collection(s)
Except where otherwise noted, this item's license is described as Copyright Navarro-Romero,
Galera- López et al. This article
is distributed under the terms
of the Creative Commons
Attribution License, which
permits unrestricted use and
redistribution provided that the
original author and source are
credited.