microRNA-124 targets glucocorticoid receptor and is involved in depression-like behaviors

•miR-124 antagomir produced antidepressant in corticosterone-induced depression.•GR and BDNF up-regulation engaged during the antidepressant of miR-124 antagomir.•miR-124 can directly target GR.

Dysregulation of microRNA (miRNA) has been shown to be involved in early observations of depression. MicroRNA-124-3p (miR-124) is the most abundant microRNA in the brain. Previous studies have shown that miR-124 plays a major role in depression. Here we showed that miR-124 directly targeted glucocorticoid receptor (GR) in HEK 293 cells. In addition, inhibition of miR-124 by its antagomir (2 nmol/every two days) could reverse the decrease of sucrose preference and the increase of immobility time in mice exposed to chronic corticosterone (CORT, 40 mg/kg) injection. Moreover, these effects on behavioral improvement were coupled to the activation of brain-derived neurotrophic factor (BDNF), TrkB, ERK, and CREB, as well as the induction of synaptogenesis and neuronal proliferation. Altogether, our study suggests that miR-124 can be served as a biomarker for depression and a novel target for drug development, and demonstrates that inhibition of miR-124 may be a strategy for treating depression by activating BDNF-TrkB signaling pathway in the hippocampus.