MicroRNA-135b-5p Downregulation Causes Antidepressant Effects by Regulating SIRT1 Expression.


Journal

Biochemical genetics
ISSN: 1573-4927
Titre abrégé: Biochem Genet
Pays: United States
ID NLM: 0126611

Informations de publication

Date de publication:
Dec 2021
Historique:
received: 15 01 2021
accepted: 29 04 2021
pubmed: 18 5 2021
medline: 14 1 2022
entrez: 17 5 2021
Statut: ppublish

Résumé

Depression is a serious and potentially life-threatening mental illness. Recently, the role of sirtuin 1 (SIRT1) in chronic unpredictable mild stress (CUMS) management has been examined. The present study explored and clarified whether microRNA (miR)-135b-5p could play a role in depression by regulating the expression of SIRT1. SIRT1 was identified as the target gene of miR-135b-5p using TargetScan and the dual luciferase reporter assay. In addition, the expression levels of SIRT1 were significantly reduced in mouse peripheral blood and hippocampal tissue samples, while the expression of miR-135b-5p exhibited the opposite effects. Subsequently, the effects of miR-135b-5p inhibition were investigated in mice with depression. The results indicated that the miR-135b-5p inhibitor significantly increased the weight loss induced by CUMS compared with the model group, while reducing the expression levels of miR-135b-5p and further alleviating the depression-like behavior induced by CUMS. Concomitantly, the results indicated that the miR-135b-5p inhibitor inhibited CUMS-induced hippocampal cell apoptosis and significantly reduced the expression levels of cleaved caspase-3 and the ratio of cleaved caspase-3/caspase-3. Moreover, the miR-135b-5p inhibitor significantly reduced the CUMS-induced increase of the inflammatory factors IL-1β, IL-6 and TNF-α in the hippocampal mouse samples, while significantly increasing the expression levels of SIRT1. Finally, the results demonstrated that all the effects of the miR-135b-5p inhibitor on CUMS-induced mice were significantly reversed by SIRT1 silencing. In conclusion, the present study indicated that the miR-135b-5p/SIRT1 pathway was a key mediator of antidepressant effects induced in depressed mice. Therefore, it could be considered a potential therapeutic target for the treatment of CUMS-induced depression.

Identifiants

pubmed: 33999341
doi: 10.1007/s10528-021-10076-5
pii: 10.1007/s10528-021-10076-5
doi:

Substances chimiques

Antidepressive Agents 0
MIRN135 microRNA, human 0
MicroRNAs 0
Sirt1 protein, mouse EC 3.5.1.-
Sirtuin 1 EC 3.5.1.-

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1582-1598

Subventions

Organisme : Scientific research project of Hangzhou Science and Technology Bureau, Zhejiang Province, China 
ID : 20171226Y19
Organisme : Scientific research project of Hangzhou Science and Technology Bureau, Zhejiang Province, China 
ID : A20200609

Informations de copyright

© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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Auteurs

Yunhai Tao (Y)

Department of Psychiatry, The Seventh Hospital of Hangzhou, 305 Tianmushan Road, Hangzhou, 310013, P.R. China. tyh150021@163.com.

Kerun Gao (K)

Department of Psychiatry, The Seventh Hospital of Hangzhou, 305 Tianmushan Road, Hangzhou, 310013, P.R. China.

Bianhong Shen (B)

Department of Psychiatry, The Seventh Hospital of Hangzhou, 305 Tianmushan Road, Hangzhou, 310013, P.R. China.

Kaiyuan Zhang (K)

Department of Psychiatry, The Seventh Hospital of Hangzhou, 305 Tianmushan Road, Hangzhou, 310013, P.R. China.

Zhiwen Zhang (Z)

Department of Psychiatry, The Seventh Hospital of Hangzhou, 305 Tianmushan Road, Hangzhou, 310013, P.R. China.

Chengpeng Wang (C)

Department of Psychiatry, The Seventh Hospital of Hangzhou, 305 Tianmushan Road, Hangzhou, 310013, P.R. China.

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