Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Upregulation of miR-195a inhibits brain-derived neurotrophic factor in mouse hippocampus and may contribute to depression-like behaviors induced by chronic social stress

Xuping Wen¹, Mingshuan Lin²

¹Department of Student Affairs, Huzhou University Qiuzhen College, Huzhou, Zhejiang Province 313000; ²Department of Clinical Psychological Psychiatry, Affiliated Haikou Hospital of Xiangya Medical College, Central South University, Haikou City, Hainan Province 570208, China.

For correspondence:- Mingshuan Lin Email: shuanlm666@163.com Tel:+8689866151001

Accepted: 22 November 2020 Published: 30 December 2020

Citation: Wen X, Lin M. Upregulation of miR-195a inhibits brain-derived neurotrophic factor in mouse hippocampus and may contribute to depression-like behaviors induced by chronic social stress. Trop J Pharm Res 2020; 19(12):2537-2543 doi: 10.4314/tjpr.v19i12.8

© 2020 The authors.
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Abstract

Purpose: To explore the effect of miR-195a on nerve cells in the hippocampal region of depression-model mice.

Methods: A chronic social defeat stress (CSDS) model was used as a depressed mouse model. In vivo, C57BL/6J mice received CSDS treatment or miR-195a antagomir. Depression-like behaviors were evaluated. In vitro, the target relationship between miR-195a and brain-derived neurotrophic factor (BDNF) was validated by luciferase reporter assays in HEK-293 cells. In primary cortical neurons, expression levels of miR-195a and BDNF mRNA were evaluated using quantitative polymerase chain reaction (qPCR). BDNF protein expression was determined by western blotting.

Results: The sucrose preference ratio and social contact of the CSDS group were significantly decreased, whereas the immobility time was significantly increased, compared with the control group (p < 0.05). Interestingly, the expression of miR-195a was upregulated in the CSDS group compared with control group (p < 0.05). Bioinformatics prediction and luciferase reporter assay data indicate that miR-195a bound the BDNF 3’ untranslated region. BDNF protein expression levels were significantly reduced by miR-195a mimic but increased by miR-195a inhibitor, compared with the negative control mimic group (p < 0.05). In vivo, miR-195a antagomir alleviated depression-like behaviors compared with CSDS group. In addition, miR-195a antagomir restored the expression of BDNF in mouse hippocampus in the CSDS group (p < 0.05).

Conclusion: MiR-195a inhibitor ameliorates depression-like behaviors of depressed mice by downregulation of BDNF, whereas upregulation of miR-195a inhibits BDNF expression in mouse hippocampus and may contribute to depression.

Keywords: Chronic social defeat stress, Depression, MiR-195, brain-derived neurotrophic factor, BDNF