Knockdown of miR-124 Reduces Depression-like Behavior by Targeting CREB1 and BDNF

Author(s): Wei Yang, Min Liu, Qianwei Zhang, Jiahua Zhang, Jun Chen, Qiaoyun Chen, Lixia Suo*

Journal Name: Current Neurovascular Research

Volume 17 , Issue 2 , 2020


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Abstract:

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.

Keywords: miR-124, chronic unpredictable mild stress, depression, cyclic AMP-responsive element binding protein1, brainderived neurotrophic factor.

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Article Details

VOLUME: 17
ISSUE: 2
Year: 2020
Published on: 04 August, 2020
Page: [196 - 203]
Pages: 8
DOI: 10.2174/1567202617666200319141755

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