CB1R regulates CDK5 signaling and epigenetically controls Rac1 expression contributing to neurobehavioral abnormalities in mice postnatally exposed to ethanol.

ABSTRACT: Fetal alcohol spectrum disorders (FASD) represent a wide array of defects that arise from ethanol exposure during development. However, the underlying molecular mechanisms are limited. In the current report, we aimed to further evaluate the cannabinoid receptor type 1 (CB1R)-mediated mechanisms in a postnatal ethanol-exposed animal model. We report that the exposure of postnatal day 7 (P7) mice to ethanol generates p25, a CDK5-activating peptide, in a time- and CB1R-dependent manner in the hippocampus and neocortex brain regions. Pharmacological inhibition of CDK5 activity before ethanol exposure prevented accumulation of cleaved caspase-3 (CC3) and hyperphosphorylated tau (PHF1) (a marker for neurodegeneration) in neonatal mice and reversed cAMP response element-binding protein (CREB) act

SUBMITTER: Joshi V 

PROVIDER: S-EPMC6333777 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature