MicroRNA-202-3p Targets Brain-Derived Neurotrophic Factor and Is Involved in Depression-Like Behaviors
Authors Xin C, Xia J, Liu Y, Zhang Y
Received 4 December 2019
Accepted for publication 17 March 2020
Published 23 April 2020 Volume 2020:16 Pages 1073—1083
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Prof. Dr. Yuping Ning
Cuiyu Xin,1 Jiejing Xia,2 Yulan Liu,3 Yongdong Zhang4
1Department of Geriatric Psychiatry, Qingdao Mental Health Center, Qingdao City, Shandong Province 266034, People’s Republic of China; 2Department of Psychosis Ⅶ, Qingdao Mental Health Center, Qingdao City, Shandong Province 266034, People’s Republic of China; 3Department of Psychosis Ⅴ, Qingdao Mental Health Center, Qingdao City, Shandong Province 266034, People’s Republic of China; 4Department of Psychosis Ⅳ, Qingdao Mental Health Center, Qingdao City, Shandong Province 266034, People’s Republic of China
Correspondence: Yongdong Zhang
Department of Psychosis Ⅳ, Qingdao Mental Health Center, No. 299, Nanjing Road, Qingdao City, Shandong Province 266034, People’s Republic of China
Background: Brain-derived neurotrophic factor (BDNF) and microRNA (miRNA) play crucial roles in the etiology of depression. However, the molecular mechanisms underlying this disease are not fully understood. The primary objective of this study was to investigate the relationship between miR-202-3p and BDNF in a chronic unpredictable mild stress (CUMS) model.
Methods: Depression model was established with chronic mild unpredictable mild stimulation (CUMS) combined with solitary feeding. The expression levels of miR-202-3p and BDNF in rat hippocampus were measured by qRT-PCR. The novelty inhibition feeding test (NSFT), sucrose preference test (SPT), and forced swimming test (FST) were used to evaluate the functions of miR-202-3p and BDNF. Target gene prediction and screening and luciferase reporter assay were used to verify the target of miR-202-3p. The expression levels of BNDF, CREB1 and p-CREB1 were detected by Western blot.
Results: Upregulation of miR-202-3p was associated with decreased expression of BDNF in the hippocampus of the CUMS model. Antidepressant was observed when LV-BDNF or LV-si-miR-202-3p was injected into the hippocampus. In addition, in the rat hippocampus and cultured nerve cells, the expression levels of BDNF and cyclic AMP response element binding protein 1 (CREB1), which is a target gene of BDNF, were reduced after LV-miR-202-3p injection. Overexpression of miR-202-3p aggravated depressive behavior and decreased the expression levels of BDNF. Luciferase reporter assay also confirmed that BDNF was a target of miR-202-3p.
Conclusion: Silencing miR-202-3p can reduce the damage to hippocampal nerve in CUMS rats; the mechanism may be related to the upregulation of BNDF expression. miR-202-3p may be an effective target for the treatment of depression.
Keywords: miR-202-3p, BDNF, CREB1, depression, hippocampus
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