Sánchez De La Torre, AníbalEzquerro Herce, SaraHuerga Gómez, AlbaSánchez Martín, EsterChara, Juan CarlosMatute, CarlosMonory, KrisztinaMato, SusanaLutz, BeatGuzmán Pastor, ManuelAguado Sánchez, TaniaPalazuelos Diego, JavierElsevier2024-11-192024-11-192024Sánchez De La Torre A, Ezquerro-Herce S, Huerga-Gómez A, Sánchez-Martín E, Chara JC, Matute C, Monory K, Mato S, Lutz B, Guzmán M, Aguado T, Palazuelos J. CB1 receptors in NG2 cells mediate cannabinoid-evoked functional myelin regeneration. Progress in Neurobiology 2024;243:102683. https://doi.org/10.1016/j.pneurobio.2024.102683.10.1016/j.pneurobio.2024.102683https://hdl.handle.net/20.500.14352/110814This work was supported by the MINECO grants PID2020-112640RB-I00 and CNS2022-135321, and the Comunidad de Madrid grant 2020–5A/BMD-19728, Atracción del Talento Investigador Program, to J.P. A.S.T was supported by Fundación Tatiana Pérez de Guzmán el Bueno. Support was also provided by MINECO (grants PID2021–125118OB-I00 to MG. and SAF2016–75292-R to C.M.), CIBERNED (grants CB06/05/0005 to M.G. and CB06/0005/0076 to C.M.), FEDER and ISCIII (AES 2021 grant PI21/00629 to S.M.), Basque Government (grants IT1203–19 to C.M., IT1473–22 to S.M. and PIBA_2023_1_0046 to S.M.), and ARSEP Foundation (grant ARSEP-1310 to S.M.).Defects in myelin homeostasis have been reported in many neuropathological conditions. Cannabinoid compounds have been shown to efficiently promote myelin regeneration in animal models of demyelination. However, it is still unknown whether this action relies mostly on a cell autonomous effect on oligodendroglial-lineage-NG2 cells. By using conditional genetic mouse models, here we found that cannabinoid CB1 receptors located on NG2 cells are required for oligodendroglial differentiation and myelin regeneration after demyelination. Selective CB1 receptor gene depletion in NG2 cells following toxin-induced demyelination disrupted oligodendrocyte regeneration and functional remyelination and exacerbated axonal damage. These deficits were rescued by pharmacological blockade of the RhoA/ROCK/Cofilin pathway. Conversely, tetrahydrocannabinol administration promoted oligodendrocyte regeneration and functional remyelination in wild-type but not Ng2-CB1-deficient mice. Overall, this study identifies CB1 receptors as essential modulators of remyelination and support the therapeutic potential of cannabinoids for promoting remyelination in neurological disorders.engjournal articlehttps://doi.org/10.1016/j.pneurobio.2024.102683https://www.sciencedirect.com/science/article/pii/S0301008224001199restricted access577.1576.3612.82CannabinoidCB1 receptorNG2 cellDemyelinationRemyelinationBioquímica (Biología)Biología celular (Biología)Neurociencias (Medicina)2403 Bioquímica2407 Biología Celular2490.01 Neurofisiología