miR-98-5p plays a critical role in depression and antidepressant effect of ketamine
Chaoli Huang, Yuan Yuan Wang, Zifeng Wu, Jiali Xu, Ling Zhou, Di Wang, Ling Yang, Bin Zhu, Guiquan Chen, Cunming Liu, Chun Yang
Abstract
Ketamine has been demonstrated to be a rapid-onset and long-lasting antidepressant, but its underlying molecular mechanisms remain unclear. Recent studies have emerged microRNAs as important modulators for depression treatment. In this study, we report that miR-98-5p is downregulated in the prefrontal cortex and hippocampus of mice subjected to chronic social stress, while overexpressing it by its agonist alleviates depression-like behaviors. More importantly, we demonstrate that miR-98-5p is upregulated by ketamine administration, while inhibition of it by its antagonist blocks the antidepressant effect of ketamine. Our data implicate a novel molecular mechanism underlying the antidepressant effect of ketamine, and that therapeutic strategies targeting miR-98-5p could exert beneficial effects for depression treatment.