Sánchez de la Torre A, Ezquerro S, Huerga A, Sánchez 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
Prog Neurobiol. 2024
"CB1 receptors expression in oligodendrocyte precursor is essential for achieving functional remyelination". - Dr Javier Palazuelos & Dr Tania Aguado -
Summary:
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.
Why do you highlight this publication?
We establish CB1 receptors as critical regulators of NG2 cell differentiation and functional CNS myelination, underscoring their potential as therapeutic targets for the treatment of neurological disorders.
Publication commented by:
Dr. Javier Palazuelos Diego and Dr. Tania Aguado Sánchez
Department of Biochemistry and Molecular Biology at Complutense University of Madrid
NEURODEGENERATIVE DISEASES: PATHOGENIC MECHANISMS Group-IRYCIS
