MicroRNA-202-3p Targets Brain-Derived Neurotrophic Factor and Is Involved in Depression-Like Behaviors

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, Peo...

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Autores principales: Xin C, Xia J, Liu Y, Zhang Y
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Publicado: Dove Medical Press 2020
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spelling oai:doaj.org-article:20812a110b1145b3954d2d55a62658f82021-12-02T09:36:27ZMicroRNA-202-3p Targets Brain-Derived Neurotrophic Factor and Is Involved in Depression-Like Behaviors1178-2021https://doaj.org/article/20812a110b1145b3954d2d55a62658f82020-04-01T00:00:00Zhttps://www.dovepress.com/microrna-202-3p-targets-brain-derived-neurotrophic-factor-and-is-invol-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Cuiyu 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 ChinaCorrespondence: Yongdong ZhangDepartment of Psychosis Ⅳ, Qingdao Mental Health Center, No. 299, Nanjing Road, Qingdao City, Shandong Province 266034, People’s Republic of ChinaTel +86-532-85621584Email mg2577@163.comBackground: 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, hippocampusXin CXia JLiu YZhang YDove Medical Pressarticlemir-202-3pbdnfcreb1depressionhippocampusNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 16, Pp 1073-1083 (2020)
institution DOAJ
collection DOAJ
language EN
topic mir-202-3p
bdnf
creb1
depression
hippocampus
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
spellingShingle mir-202-3p
bdnf
creb1
depression
hippocampus
Neurosciences. Biological psychiatry. Neuropsychiatry
RC321-571
Neurology. Diseases of the nervous system
RC346-429
Xin C
Xia J
Liu Y
Zhang Y
MicroRNA-202-3p Targets Brain-Derived Neurotrophic Factor and Is Involved in Depression-Like Behaviors
description 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 ChinaCorrespondence: Yongdong ZhangDepartment of Psychosis Ⅳ, Qingdao Mental Health Center, No. 299, Nanjing Road, Qingdao City, Shandong Province 266034, People’s Republic of ChinaTel +86-532-85621584Email mg2577@163.comBackground: 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
format article
author Xin C
Xia J
Liu Y
Zhang Y
author_facet Xin C
Xia J
Liu Y
Zhang Y
author_sort Xin C
title MicroRNA-202-3p Targets Brain-Derived Neurotrophic Factor and Is Involved in Depression-Like Behaviors
title_short MicroRNA-202-3p Targets Brain-Derived Neurotrophic Factor and Is Involved in Depression-Like Behaviors
title_full MicroRNA-202-3p Targets Brain-Derived Neurotrophic Factor and Is Involved in Depression-Like Behaviors
title_fullStr MicroRNA-202-3p Targets Brain-Derived Neurotrophic Factor and Is Involved in Depression-Like Behaviors
title_full_unstemmed MicroRNA-202-3p Targets Brain-Derived Neurotrophic Factor and Is Involved in Depression-Like Behaviors
title_sort microrna-202-3p targets brain-derived neurotrophic factor and is involved in depression-like behaviors
publisher Dove Medical Press
publishDate 2020
url https://doaj.org/article/20812a110b1145b3954d2d55a62658f8
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