Title:Hippocampal miR-124 Participates in the Pathogenesis of Depression via
Regulating the Expression of BDNF in a Chronic Social Defeat Stress
Model of Depression
Volume: 19
Issue: 2
Author(s): Lin-Sheng Shi*, Chun-Hui Ji, Wen-Qian Tang, Yue Liu, Wei Zhang and Wei Guan
Affiliation:
- Department of Cardiology, Affiliated Hospital 2 of Nantong University, Nantong 226001, Jiangsu, China
Keywords:
Antidepressant, brain-derived neurotrophic factor, chronic social defeat stress, depression, hippocampal neurogenesis, miR-124.
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.