دورية أكاديمية
Cannabinoid signaling modulation through JZL184 restores key phenotypes of a mouse model for Williams-Beuren syndrome
| العنوان: | Cannabinoid signaling modulation through JZL184 restores key phenotypes of a mouse model for Williams-Beuren syndrome |
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| المؤلفون: | Navarro Romero, Alba, Galera López, Lorena, Ortíz Romero, Paula, Llorente Ovejero, Alberto, de los Reyes Ramírez, Lucía, Bengoetxea de Tena, Iker, García Elías, Anna, Mas-Stachurska, Aleksandra, Reixachs Solé, Marina, Pastor, Antoni, De la Torre, Rafael, Maldonado, Rafael, Benito, Begoña, Eyras, Eduardo, Rodríguez Puertas, Rafael, Campuzano, Victoria, Ozaita, Andres |
| بيانات النشر: | eLife Sciences |
| سنة النشر: | 2022 |
| المجموعة: | ADDI: Repositorio Institucional de la Universidad del País Vasco / Euskal Herriko Unibertsitatea (UPV/EHU - Basque Country University) |
| مصطلحات موضوعية: | Williams-Beuren syndrome, intellectual disability, endocannabinoid system, cannabinoid type-1 receptor, mouse |
| الوصف: | 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. ; 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2050-084X |
| العلاقة: | info:eu-repo/grantAgreement/MICINN/BES-2016-077950; info:eu-repo/grantAgreement/MICIU/RTI2018-099282-B-I00; info:eu-repo/grantAgreement/MINECO/SAF2017-84060-R; info:eu-repo/grantAgreement/MICINN/SAF2016-78508-R; info:eu-repo/grantAgreement/MINECO/MDM-2014-0370; info:eu-repo/grantAgreement/MICINN/PRE2019-087644; https://elifesciences.org/articles/72560Test; eLife 11 : (2022) // Article ID e72560; http://hdl.handle.net/10810/58850Test |
| DOI: | 10.7554/eLife.72560 |
| الإتاحة: | https://doi.org/10.7554/eLife.72560Test http://hdl.handle.net/10810/58850Test |
| حقوق: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/3.0/esTest/ ; 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. ; Atribución 3.0 España |
| رقم الانضمام: | edsbas.4E7AE424 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.72560 |