Knockdown of miR-124 reduces depression-like behavior in rats by targeting CREB1 and BDNF.

AIMS: To explore the role of miR-124 in depression and its potential targets. BACKGROUND: Depression is one of the most common mental illnesses, and symptoms include depression, decreased interest, and severe cases with suicidal tendencies. OBJECTIVE: As a brain-specific microRNA, the mechanism of miR-124 in depression has not been clarified. The present study aimed to explore the role of miR-124 in depression and its potential targets. METHODS: The depression model was first replicated by the chronic unpredictable mild stress (CUMS) method. miR-124 antagomir was injected into the hippocampus of CUMS rats. Sucrose preference test (SPT), open-field test (OFT), elevated-plus maze (EPM), and forced swimming test (FST) were used to analyze the depression-like behavior. The content of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in hypothalamus was analyzed by ELISA. qRT-PCR and western blot assay were used to functional analysis. RESULTS: miR-124 expression was up-regulated in the hippocampus of CUMS -induced depression model rats, while CREB1 and BDNF were down-regulated. Administration of miR-124 antagomir in hippocampus inhibited miR-124 expression in hippocampus of CUMS rats. Additionally, SPT, OFT, EPM, and FST also showed that miR-124 antagomir can reduce the depression-like behavior of CUMS rats. Furthermore, miR-124 antagomir injection increased the levels of NE, DA and 5-HT in the hypothalamus of CUMS rats. Moreover, miR-124 antagomir injection increased the expression of cyclic AMP-responsive element binding protein1 (CREB1) and brain-derived neurotrophic factor (BDNF) in hippocampus. Using a dual luciferase reporter assay, it was confirmed that miR-124 directly targets the 3'UTR of CREB1 and BDNF genes. CONCLUSION: Knockdown of miR-124 can improve depression-like behavior in CUMS-induced depressive rats, which may be related at least in part to the up-regulation of CREB1 and BDNF expression in the hippocampus.