MicroRNA expression profile and functional analysis reveal that miR-206 is a critical novel gene for the expression of BDNF induced by ketamine.

Depression is a major social and health concern, and ketamine exerts a quick, remarkable and persistent anti-depressive effect. microRNAs (miRNAs) show remarkable potential in the treatment of clinical depression. Here, we determined the expression profile of miRNAs in the hippocampus of rats treated with ketamine (15 mg/kg). The results suggest that multiple miRNAs were aberrantly expressed in rat hippocampus after ketamine injection (18 miRNAs were significantly reduced, while 22 miRNAs were significantly increased). Among them, miR-206 was down-regulated in ketamine-treated rats. In both cultured neuronal cells in vitro and hippocampus in vivo, we identified that the brain-derived neurotrophic factor (BDNF) was a direct target gene of miR-206. Via this target gene, miR-206 strongly modulated the expression of BDNF. Moreover, overexpression of miR-206 significantly attenuated ketamine-induced up-regulation of BDNF. The results indicated that miRNA-206 was involved in novel therapeutic targets for the anti-depressive effect of ketamine.