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Title: | Cannabinoid signaling modulation through JZL184 restores key phenotypes of a mouse model for Williams-Beuren syndrome |
Author: | Navarro Romero, Alba Galera López, Lorena Ortiz Romero, Paula Llorente Ovejero, Alberto de Los Reyes Ramírez, Lucía Bengoetxea de Tena, Iker Garcia Elias, Anna Mas Stachurska, Aleksandra Reixachs Solé, Marina Pastor, Antoni de la Torre, Rafael Maldonado, Rafael, 1961- Benito, Begoña Eyras, Eduardo Rodríguez Puertas, Rafael Campuzano Uceda, María Victoria Ozaita, Andres |
Keywords: | Cànnabis Síndrome de Williams Persones amb discapacitat mental Ratolins Cannabis Williams syndrome People with mental disabilities Mice |
Issue Date: | 11-Oct-2022 |
Publisher: | eLife Sciences |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.7554/eLife.72560 |
It is part of: | eLife, 2022, vol. 11, p. e72560 |
URI: | http://hdl.handle.net/2445/189977 |
Related resource: | https://doi.org/10.7554/eLife.72560 |
ISSN: | 2050-084X |
Appears in Collections: | Articles publicats en revistes (Biomedicina) |
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