Cannabinoid CB1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice
dc.contributor.author | Sánchez de la Torre, Aníbal | |
dc.contributor.author | Aguado, Tania | |
dc.contributor.author | Huerga Gómez, Alba | |
dc.contributor.author | Santamaría, Silvia | |
dc.contributor.author | Gentile, Antonietta | |
dc.contributor.author | Chara Ventura, Juan Carlos | |
dc.contributor.author | Matute Almau, Carlos José | |
dc.contributor.author | Monory, Krisztina | |
dc.contributor.author | Mato Santos, Susana | |
dc.contributor.author | Guzmán, Manuel | |
dc.contributor.author | Lutz, Beat | |
dc.contributor.author | Galve-Roperh, Ismael | |
dc.contributor.author | Palazuelos, Javier | |
dc.date.accessioned | 2022-09-09T12:03:38Z | |
dc.date.available | 2022-09-09T12:03:38Z | |
dc.date.issued | 2022 | |
dc.identifier.citation | Cell Death & Disease 13 : (2022) // Article ID 585 | es_ES |
dc.identifier.issn | 2041-4889 | |
dc.identifier.uri | http://hdl.handle.net/10810/57678 | |
dc.description.abstract | [EN] Cannabinoids are known to modulate oligodendrogenesis and developmental CNS myelination. However, the cell-autonomous action of these compounds on oligodendroglial cells in vivo, and the molecular mechanisms underlying these effects have not yet been studied. Here, by using oligodendroglial precursor cell (OPC)-targeted genetic mouse models, we show that cannabinoid CB1 receptors exert an essential role in modulating OPC differentiation at the critical periods of postnatal myelination. We found that selective genetic inactivation of CB1 receptors in OPCs in vivo perturbs oligodendrogenesis and postnatal myelination by altering the RhoA/ROCK signaling pathway, leading to hypomyelination, and motor and cognitive alterations in young adult mice. Conversely, pharmacological CB1 receptor activation, by inducing E3 ubiquitin ligase-dependent RhoA proteasomal degradation, promotes oligodendrocyte development and CNS myelination in OPCs, an effect that was not evident in OPC-specific CB1 receptor-deficient mice. Moreover, pharmacological inactivation of ROCK in vivo overcomes the defects in oligodendrogenesis and CNS myelination, and behavioral alterations found in OPC-specific CB1 receptor-deficient mice. Overall, this study supports a cell-autonomous role for CB1 receptors in modulating oligodendrogenesis in vivo, which may have a profound impact on the scientific knowledge and therapeutic manipulation of CNS myelination by cannabinoids. | es_ES |
dc.description.sponsorship | This work was supported by the MINECO grants SAF2017-83516 and PID2020-112640RB-I00, and the Comunidad de Madrid grants 2016-T1/BMD-1060 and 2020-5 A/BMD-19728, Atraccion del Talento Investigador Program, to JP. AHG and TA. AHG was also supported by the Comunidad de Madrid contract PEJD-2017PRE/BMD-3703, and A.S.T by Fundacion Tatiana Perez de Guzman el Bueno. Support was also provided by MINECO (grants RTI2018-095311-B-I00 to MG. and SAF2016-75292-R to CM), CIBERNED (grants CB06/05/0005 to M.G. and CB06/0005/0076 to C.M.), FEDER and ISCIII (AES 2018 grants PI18-00941 to IG-R and PI18/00513 to SM), Basque Government (grants IT1203-19 to C.M. and PIBA19-0059 to SM), and ARSEP Foundation (grant to SM). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | SpringerNature | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2016-75292-R | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO/SAF2017-83516 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICIU/RTI2018-095311-B-I00 | es_ES |
dc.relation | info:eu-repo/grantAgreement/MICINN/PID2020-112640RB-I00 | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | endocannabinoid system | es_ES |
dc.subject | differentiation | es_ES |
dc.subject | rhoa | es_ES |
dc.subject | exposure | es_ES |
dc.subject | degradation | es_ES |
dc.subject | cells | es_ES |
dc.subject | ubiquitination | es_ES |
dc.subject | remyelination | es_ES |
dc.subject | consequences | es_ES |
dc.subject | modulation | es_ES |
dc.title | Cannabinoid CB1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http:// creativecommons.org/licenses/by/4.0/. | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www.nature.com/articles/s41419-022-05032-z | es_ES |
dc.identifier.doi | 10.1038/s41419-022-05032-z | |
dc.departamentoes | Neurociencias | es_ES |
dc.departamentoeu | Neurozientziak | es_ES |
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