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Current Neurovascular Research

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ISSN (Print): 1567-2026
ISSN (Online): 1875-5739

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Research Article

Hippocampal miR-124 Participates in the Pathogenesis of Depression via Regulating the Expression of BDNF in a Chronic Social Defeat Stress Model of Depression

Author(s): Lin-Sheng Shi*, Chun-Hui Ji, Wen-Qian Tang, Yue Liu, Wei Zhang and Wei Guan

Volume 19, Issue 2, 2022

Published on: 22 July, 2022

Page: [210 - 218] Pages: 9

DOI: 10.2174/1567202619666220713105306

Price: $65

Abstract

Objective: As one of the most prevalent psychiatric disorders, the exact pathogenesis of depression remains elusive. Therefore, there is an urgent need to identify novel antidepressants for effective treatment. MicroRNA-124 (miR-124), the most abundant miRNA in brain tissue, plays a key effect on adult neurogenesis and neuronal differentiation. However, the mechanism of miR-124 in depression has not been clarified so far. The aim of this study is to provide broad insight into the mechanisms underlying depression.

Methods: In the study, we used the forced swim test (FST), the tail suspension test (TST), and a Chronic Social Defeat Stress (CSDS) mice model of depression. Quantitative real-time reverse transcription PCR (qRT-PCR), western blotting, immunofluorescence and virus-mediated gene transfer were used together. The level of plasma corticosterone in mice was analyzed by Enzyme Linked Immunosorbent Assay (ELISA).

Results: It was found that CSDS robustly increased the level of miR-124 in the hippocampus. Genetic knockdown of hippocampal miR-124 produced significant antidepressant-like effects in the CSDS model of depression. Furthermore, AAV-siR-124-EGFP treatment increased the level of plasma corticosterone in CSDS-induced mice. Moreover, it was found that the antidepressant-like effects induced by miR-124 inhibition required the hippocampal BDNF-TrkB system.

Conclusion: Hippocampal miR-124 participated in the pathogenesis of depression by regulating BDNF biosynthesis and was a feasible antidepressant target.

Keywords: Antidepressant, brain-derived neurotrophic factor, chronic social defeat stress, depression, hippocampal neurogenesis, miR-124.

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