Title:miR-204-5p Plays a Critical Role in the Pathogenesis of Depression
and Anti-depression Action of Venlafaxine in the Hippocampus of
Mice
Volume: 31
Issue: 22
Author(s): Wei Guan*, Xin-Yuan Wu, Xiang Jin, Xiao-Ming Sheng and Yan Fan
Affiliation:
- Department of Pharmacology, Pharmacy College, Nantong University, Nantong 226001, Jiangsu, China
Keywords:
Venlafaxine, miR-204-5p, depression, chronic social defeat stress, brain-derived neurotrophic factor, hippocampal neurogenesis.
Abstract:
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.
