MiR-182-5p: a novel biomarker in the treatment of depression in CSDS-induced mice
Ya-Bin Zheng, Xiao-Ming Sheng, Xiang Jin, Wei Guan- Pharmacology (medical)
- Psychiatry and Mental health
- Pharmacology
Abstract
Background
Depression is a neuropsychiatric disease with high disability rate and mainly caused by the chronic stresses or genetic factors. There is increasing evidences that miRNAs play a critical role in the pathogenesis of depression. However, the underlying molecular mechanism for the pathophysiology of depression of miRNA remains entirely unclear so far.
Methods
We first established a Chronic Social Defeat Stress (CSDS) mice model of depression, and depression-like behaviors of mice were evaluated by a series of behavioral tests. Next, we detected several abundantly expressive miRNAs that had been suggested to be involved in depression in previous reports and found miR-182-5p was selected as a candidate for analysis in the hippocampus, then western blotting and immunofluorescence were used together to examine whether AAV-siR-182-5p treatment alleviated chronic stress-induced decrease in hippocampal Akt/GSK3β/CREB signaling pathway and increase in neurogenesis impairment and neuroinflammation. Furthermore, cAMP-response element binding protein (CREB) inhibitor was adopted to examine if blockade of Akt/GSK3β/CREB signaling pathway abolished the antidepressant actions of AAV-siR-182-5p in mice.
Results
Knock-down of miR-182-5p alleviated depression-like behaviors and impaired neurogenesis of CSDS-induced mice. Intriguingly, the usage of agomiR-182-5p, produced significant increases in immobility times and aggravated neuronal neurogenesis damage of mice. More importantly, it suggested that the 666-15 blocked the reversal effects of AAV-siR-182-5p on the CSDS-induced depressive-like behaviors in the behavioral testing and the neuronal neurogenesis within hippocampus of mice.
Conclusions
These findings indicated that hippocampal miR-182-5p/Akt/GSK3β/CREB signaling pathway participated in the pathogenesis of depression, itmight be given more opportunities for new drug developments based on the miRNA target in the clinic.