miR-204-5p Plays a Critical Role in the Pathogenesis of Depression and Anti-depression Action of Venlafaxine in the Hippocampus of Mice

Background: Venlafaxine has been demonstrated to treat diseases such as social anxiety disorder and depression. Most of antidepressants including venlafaxine have a certain effect, but significant side effects. Therefore, it is necessary for us to research the development of novel antidepressants for effective treatment in practice. MicroRNA-204 (miR-204) is highly expressed in brain tissue, and plays a critical role in the synaptic plasticity of hippocampal neurons in rats. However, the underlying molecular mechanism of miR-204 remains unclear to date, this study aims to offer unique insights into depression and provide a theoretical basis for clinical physicians. Methods: A chronic social defeat stress (CSDS) was initially adopted for establishing a mice model of depression in this research and depression-like behaviors were evaluated by a series of behavioral experiments including the sucrose preference test (SPT), the tail suspension test (TST), the forced swim test (FST) and the social interaction test (SIT). Quantitative real-time reverse transcription PCR (qRT-PCR) was also conducted to test the expression levels of miR-204 and BDNF in the hippocampus of mice. Finally, gene interference of miR-204-5p was further adopted to test whether miR-204-5p played an effective role in the antidepressant effects of venlafaxine in mice. Results: Our data implicated that CSDS significantly increased the miR-204-5p but not miR-204-3p levels in the hippocampus of mice. The treatment of venlafaxine obviously relieved depression- like behaviors of CSDS-induced mice. The usage of venlafaxine abolished the increasing effects on the expression of miR-204-5p but up-regulated the BDNF expression level in CSDS-exposured mice. More importantly, we found that genetic overexpression of miR-204-5p decreased the reverse effects of venlafaxine on depressive-like behaviors and genetic knockdown of hippocampal miR-204-5p relieved the depressive-like behaviors and neurogenesis in CSDS-induced mice. Conclusion: miR-204-5p played an effective role in the antidepressant effects of venlafaxine in CSDS-induced mice.