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Δ 9 ‐Tetrahydrocannabinol promotes functional remyelination in the mouse brain
Author(s) -
Aguado Tania,
HuergaGómez Alba,
Sánchezde la Torre Aníbal,
Resel Eva,
Chara Juan Carlos,
Matute Carlos,
Mato Susana,
GalveRoperh Ismael,
Guzman Manuel,
Palazuelos Javier
Publication year - 2021
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/bph.15608
Subject(s) - remyelination , oligodendrocyte , neuroscience , cannabinoid , neuroprotection , myelin , biology , regeneration (biology) , central nervous system , microbiology and biotechnology , receptor , biochemistry
Background and purpose Research on demyelinating disorders aims to find novel molecules that are able to induce oligodendrocyte precursor cell differentiation to promote central nervous system remyelination and functional recovery. Δ 9 ‐Tetrahydrocannabinol (THC), the most prominent active constituent of the hemp plant Cannabis sativa , confers neuroprotection in animal models of demyelination. However, the possible effect of THC on myelin repair has never been studied. Experimental approach By using oligodendroglia‐specific reporter mouse lines in combination with two models of toxin‐induced demyelination, we analysed the effect of THC on the processes of oligodendrocyte regeneration and functional remyelination. Key results We show that THC administration enhanced oligodendrocyte regeneration, white matter remyelination and motor function recovery. THC also promoted axonal remyelination in organotypic cerebellar cultures. THC remyelinating action relied on the induction of oligodendrocyte precursor differentiation upon cell cycle exit and via CB 1 cannabinoid receptor activation. Conclusions and implications Overall, our study identifies THC administration as a promising pharmacological strategy aimed to promote functional CNS remyelination in demyelinating disorders.