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

[ Vol. 17 , Issue. 2 ]

Author(s):

Wei Yang, Min Liu, Qianwei Zhang , Jiahua Zhang , Jun Chen , Qiaoyun Chen and Lixia Suo *   Pages 196 - 203 ( 8 )

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.

Affiliation:

Department of Endocrinology, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, Department of Endocrinology, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, Department of Endocrinology, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, Department of Endocrinology, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, Department of Endocrinology, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, Department of Endocrinology, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, Department of Endocrinology, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai



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