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 Sánchez, Tania | |
dc.contributor.author | Huerga-Gómez, Alba | |
dc.contributor.author | Santamaría, Silvia | |
dc.contributor.author | Gentile, Antonietta | |
dc.contributor.author | Chara, Juan Carlos | |
dc.contributor.author | Matute, Carlos | |
dc.contributor.author | Monory, Krisztina | |
dc.contributor.author | Mato, Susana | |
dc.contributor.author | Guzmán Pastor, Manuel | |
dc.contributor.author | Lutz, Beat | |
dc.contributor.author | Galve Roperh, Ismael | |
dc.contributor.author | Palazuelos Diego, Javier | |
dc.date.accessioned | 2023-11-23T12:27:02Z | |
dc.date.available | 2023-11-23T12:27:02Z | |
dc.date.issued | 2022 | |
dc.description.abstract | 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 receptordeficient 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 cellautonomous 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. | |
dc.description.department | Depto. de Bioquímica y Biología Molecular | |
dc.description.faculty | Fac. de Ciencias Biológicas | |
dc.description.refereed | TRUE | |
dc.description.sponsorship | Ministerio Economía y Transformación Digital (España) | |
dc.description.sponsorship | Comunidad de Madrid | |
dc.description.sponsorship | Institituto de Salud Carlos III | |
dc.description.sponsorship | Eusko Jaurlaritza | |
dc.description.sponsorship | European Commission | |
dc.description.sponsorship | Multiple Sclerosis Research Foundation (France) | |
dc.description.status | pub | |
dc.identifier.citation | Sánchez-de la Torre, A., Aguado, T., Huerga-Gómez, A. et al. Cannabinoid CB1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice. Cell Death Dis 13, 585 (2022). https://doi.org/10.1038/s41419-022-05032-z | |
dc.identifier.doi | 10.1038/s41419-022-05032-z | |
dc.identifier.issn | 2041-4889 | |
dc.identifier.officialurl | https://doi.org/10.1038/s41419-022-05032-z | |
dc.identifier.uri | https://hdl.handle.net/20.500.14352/88941 | |
dc.issue.number | 585 | |
dc.journal.title | Cell Death and Disease | |
dc.language.iso | eng | |
dc.page.final | 13 | |
dc.page.initial | 1 | |
dc.publisher | Springer Nature | |
dc.relation.projectID | (SAF2017–83516 and PID2020–112640RB-I00) (grants RTI2018–095311-B-I00 and SAF2016–75292-R) | |
dc.relation.projectID | ( grants 2016-T1/BMD-1060 and 2020–5 A/BMD-19728) ( contract PEJD-2017- PRE/BMD-3703) | |
dc.relation.projectID | (AES 2018 grants PI18–00941 and PI18/00513) | |
dc.relation.projectID | (grants IT1203–19 and PIBA19–0059) | |
dc.rights | Attribution 4.0 International | en |
dc.rights.accessRights | open access | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject.cdu | 615.9 | |
dc.subject.cdu | 591.18 | |
dc.subject.cdu | 612.8 | |
dc.subject.keyword | Cannabinoid CB1 receptor | |
dc.subject.keyword | Oligodendrogenesis | |
dc.subject.keyword | Myelination | |
dc.subject.ucm | Bioquímica (Biología) | |
dc.subject.ucm | Biología molecular (Biología) | |
dc.subject.ucm | Neurociencias (Biológicas) | |
dc.subject.unesco | 2403 Bioquímica | |
dc.subject.unesco | 2407 Biología Celular | |
dc.subject.unesco | 2490 Neurociencias | |
dc.title | Cannabinoid CB1 receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice | |
dc.type | journal article | |
dc.type.hasVersion | VoR | |
dc.volume.number | 13 | |
dspace.entity.type | Publication | |
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relation.isAuthorOfPublication | 40a55557-1c65-4708-bb50-9ddff8f0bf25 | |
relation.isAuthorOfPublication.latestForDiscovery | d9ea208a-0dd5-43a8-93f2-9c1dd8c20c4d |
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