Cannabinoids reshape astrocyte glucose metabolism
Arnau Busquets Garcia
NeuroCentre Magendie, Bordeaux
Mitochondrial metabolism in astrocytes is a key determinant of brain functions, but its mechanistic roles in animal behavior were not explored. In this study, we show that specific activation of type-1 cannabinoid receptors located in astroglial mitochondria (mtCB1) impairs social behavior by altering brain glucose and lactate metabolism. By reducing the phosphorylation of the mitochondrial complex I subunit NDUFS4, activation of astroglial mtCB1 receptors inhibits stability and activity of complex I, decreases reactive oxygen species production and alters glucose metabolism, eventually reducing lactate production in astrocytes. Conditional deletion of astroglial CB1 receptors, genetic inhibition of cannabinoid effects on phosphorylation of NDUFS4 and brain lactate supplementation reversed the social interaction deficits produced by in vivo cannabinoid administration. These results unveil the importance of astroglial mitochondrial bioenergetic processes in complex behavioral functions and provide a mechanistic explanation for impairment of social interactions, one of the most deleterious effects of cannabis intoxication.
Host: Susana Mato