| Autor: |
Alba Navarro-Romero, Lorena Galera-López, Paula Ortiz-Romero, Alberto Llorente-Ovejero, Lucía de los Reyes-Ramírez, Iker Bengoetxea de Tena, Anna Garcia-Elias, Aleksandra Mas-Stachurska, Marina Reixachs-Solé, Antoni Pastor, Rafael de la Torre, Rafael Maldonado, Begoña Benito, Eduardo Eyras, Rafael Rodríguez-Puertas, Victoria Campuzano, Andres Ozaita |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
|
| Zdroj: |
eLife, Vol 11 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2050-084X |
| DOI: |
10.7554/eLife.72560 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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