Cannabinoid CB₁ receptor gene inactivation in oligodendrocyte precursors disrupts oligodendrogenesis and myelination in mice.

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, pharmacologic

SUBMITTER: Sanchez-de la Torre A 

PROVIDER: S-EPMC9263142 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature