Objective: As a brain-specific microRNA, the mechanism of miR-124 in depression has
not been clarified so far. 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 the hypothalamus was analyzed by ELISA.
qRT-PCR and western blot assay were used for 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 the hippocampus inhibited miR-124 expression in the 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 the hippocampus. Using the dual-luciferase reporter assay, it was
confirmed that miR-124 directly targets 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.