Hippocampal miR-124 Participates in the Pathogenesis of Depression via Regulating the Expression of BDNF in a Chronic Social Defeat Stress Model of Depression.

Abstract

As one of the most prevalent psychiatric disorders, the exact pathogenesis of depression remains elusive. Therefore, there is an urgent need to identify novel antidepressants for effective treatment. MicroRNA-124 (miR-124), the most abundant miRNA in brain tissue, plays a key effect on adult neurogenesis and neuronal differentiation. However, the mechanism of miR-124 in depression has not been clarified so far. The aim of this study is to provide broad insight into the mechanisms underlying depression. In the study, we used the forced swim test (FST), the tail suspension test (TST), and a Chronic Social Defeat Stress (CSDS) mice model of depression. Quantitative real-time reverse transcription PCR (qRT-PCR), western blotting, immunofluorescence and virus-mediated gene transfer were used together. The level of plasma corticosterone in mice was analyzed by Enzyme Linked Immunosorbent Assay (ELISA). It was found that CSDS robustly increased the level of miR-124 in the hippocampus. Genetic knockdown of hippocampal miR-124 produced significant antidepressant-like effects in the CSDS model of depression. Furthermore, AAV-siR-124-EGFP treatment increased the level of plasma corticosterone in CSDS-induced mice. Moreover, it was found that the antidepressant-like effects induced by miR-124 inhibition required the hippocampal BDNF-TrkB system. Hippocampal miR-124 participated in the pathogenesis of depression by regulating BDNF biosynthesis and was a feasible antidepressant target.