MicroRNA-129-5p in the mPFC is involved in the chronic mild stress-induced depression-like behaviors in rats

Current treatments for depression have focused on improving the dysregulated monoamine neurotransmitter systems in the brain. However, the conventional antidepressants based on the monoamine hypothesis usually exert side effects and unsatisfactory responses. MicroRNAs (miRNAs) are smaller noncoding RNA which are highly expressed in the brain and play important roles in the development of neurological disorders. In this study we investigated the role of miRNAs in the occurrence of depression. A rat depression model was established by exposure to chronic mild stress (CMS) over 4 weeks. In the next week, the sucrose preference test (SPT), the forced swimming test (FST), and the open field test (OFT) were used to evaluate the depression-like behaviors. Then the rats were euthanized and total RNA was isolated from rat mPFC. We showed that the level of microRNA-129-5p (miR-129-5p) was significantly increased in the mPFC of CMS rats. Overexpression of miR-129-5p in the mPFC by bilateral microinjection of lenti-miR-129-5p virus (OE-miR-129-5p) induced the depression-like behaviors in control rats, accompanied with the impairment in neuronal structures and a decrease in synaptic plasticity. In contrast, knockdown of miR-129-5p in the mPFC by bilateral microinjection of lenti-miR-129-5p sponge virus (KD-miR-129-5p) ameliorated the depression-like behaviors in CMS rats, along with the improvement in neuronal structures and an increase in synaptic plasticity. Furthermore, we demonstrated that miR-129-5p targeted to the brain-derived neurotrophic factor (BDNF) in the mPFC to contribute to the development of depression. This study suggests that miR-129-5p in the mPFC impairs the neuronal structures and reduces the synaptic plasticity after the exposure to CMS, which underlies the development of CMS-induced depression-like behaviors in rats.