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Published on: October 24, 2018
microRNA-124 targets glucocorticoid receptor and is involved in depression-like behaviors
Shuang-Shuang Wang1, Rong-Hao Mu1, Cheng-Fu Li2
1Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, PR China; Institute of Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, PR China.
Abstract:
Dysregulation of microRNA (miRNA) has been shown to be involved in early observations of depression. MicroRNA-124-3p (miR-124) is the most abundant microRNA in the brain. Previous studies have shown that miR-124 plays a major role in depression. Here we showed that miR-124 directly targeted glucocorticoid receptor (GR) in HEK 293 cells. In addition, inhibition of miR-124 by its antagomir (2nmol/every two days) could reverse the decrease of sucrose preference and the increase of immobility time in mice exposed to chronic corticosterone (CORT, 40mg/kg) injection. Moreover, these effects on behavioral improvement were coupled to the activation of brain-derived neurotrophic factor (BDNF), TrkB, ERK, and CREB, as well as the induction of synaptogenesis and neuronal proliferation. Altogether, our study suggests that miR-124 can be served as a biomarker for depression and a novel target for drug development, and demonstrates that inhibition of miR-124 may be a strategy for treating depression by activating BDNF-TrkB signaling pathway in the hippocampus.
Insights
MicroRNA-124-3p (miR-124) inhibition reverses depression-like behaviors in mice by targeting the glucocorticoid receptor and activating the BDNF pathway. This suggests miR-124 as a potential biomarker and therapeutic target for depression.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- MicroRNA (miRNA) dysregulation is implicated in depression.
- MicroRNA-124-3p (miR-124) is highly abundant in the brain and plays a role in depression.
Purpose of the Study:
- To investigate the role of miR-124 in depression.
- To explore miR-124 as a potential biomarker and therapeutic target for depression.
Main Methods:
- Investigated miR-124 targeting of the glucocorticoid receptor (GR) in HEK 293 cells.
- Administered miR-124 antagomir to mice exposed to chronic corticosterone (CORT) injection.
- Assessed behavioral changes (sucrose preference, immobility time) and molecular markers (BDNF, TrkB, ERK, CREB, synaptogenesis, neuronal proliferation).
Main Results:
- miR-124 directly targets GR.
- Inhibition of miR-124 reversed depression-like behaviors in mice.
- Behavioral improvements were associated with activation of the BDNF-TrkB signaling pathway, synaptogenesis, and neuronal proliferation.
Conclusions:
- miR-124 may serve as a biomarker for depression.
- Inhibiting miR-124 is a potential therapeutic strategy for depression by activating the hippocampal BDNF-TrkB signaling pathway.
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