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.

氯胺酮已被证明是一种快速起效和长效的抗抑郁药，但其潜在的分子机制仍不清楚。最近的研究表明，microRNAs 是抑郁症治疗的重要调节剂。在这项研究中，我们报告了 miR-98-5p 在遭受慢性社会压力的小鼠的前额叶皮层和海马体中下调，而通过其激动剂过度表达可以缓解抑郁样行为。更重要的是，我们证明 miR-98-5p 被氯胺酮给药上调，而其拮抗剂对其的抑制阻断了氯胺酮的抗抑郁作用。我们的数据暗示了氯胺酮抗抑郁作用的新分子机制，靶向 miR-98-5p 的治疗策略可能对抑郁症治疗产生有益作用。