miR-98-5p plays a critical role in depression and antidepressant effect of ketamine
Chao Huang, Yuanyuan Wang, Zifeng Wu, Jiali Xu, Ling Zhou, Di Wang, Ling Yang, Bin Zhu, Guiquan Chen, Cunming Liu, Chun Yang
Translational Psychiatry September 3, 2021 DOI: 10.1038/s41398-021-01588-0 via Semantic Scholar
Summary
Ketamine acts as a rapid and long-lasting antidepressant, but its molecular mechanisms are unclear. In mice subjected to chronic social stress, microRNA miR-98-5p was downregulated in the prefrontal cortex and hippocampus. Overexpressing miR-98-5p with an agonist alleviated depression-like behaviors. Ketamine administration upregulated miR-98-5p, and inhibiting it with an antagonist blocked ketamine's antidepressant effect. This suggests a novel molecular mechanism for ketamine's action and that targeting miR-98-5p could be beneficial for depression treatment.
Study at a glance
| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Mice subjected to chronic social stress |
| Keywords | Medicine Psychology |
| Citations | 29 |
| Key finding | miR-98-5p is downregulated in the prefrontal cortex and hippocampus of stressed mice, and ketamine's antidepressant effect requires upregulation of miR-98-5p. |
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.