Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders worldwide and a major public health concern that is associated with grave consequences. Systemic complexity and feedback processes among diverse drivers of the depression disorder contribute to the considerable variation in responses to the treatment of depression. Dysfunctional microRNA (miRNA) is involved in MDD. miR-124 is enriched in the brain and may be critical in neuronal differentiation. Previous studies have shown the value of miRNA-124 as a putative therapeutic target and a biomarker for major depression. However, the detailed mechanism of action of miR-124 in depression remains poorly understood. Here, we observed that miR-124 was downregulated in the hippocampus of mice with chronic unpredictable mild stress (CUMS). Restoration of miR-124 expression significantly attenuated depressive-like behavior and inhibited microglial activation induced by CUMS. Mechanistically, miR-124 directly targeted signal transducer and activator of transcription 3 (STAT3) in BV2 cells; in addition, upregulation of miR-124 inhibited the increase of inducible nitric oxide synthetase and proinflammatory cytokines, including IL-6, IL-1β, TNF-α, and MCP-1, in LPS-stimulated BV2 cells. The collective data suggest that dysfunction of miR-124 may be a foundation for the development of depression by promoting microglial activation.

中文翻译：

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miR-124通过靶向STAT3来调节小胶质细胞活化来改善抑郁症样行为。

重度抑郁症（MDD）是全世界最普遍的精神疾病之一，也是与严重后果相关的主要公共卫生问题。抑郁症疾病的多种驱动因素之间的系统复杂性和反馈过程导致了对抑郁症治疗反应的显着变化。功能异常的microRNA（miRNA）参与了MDD。miR-124在大脑中富集，可能在神经元分化中起关键作用。先前的研究表明，miRNA-124作为推定的治疗靶标和重度抑郁症的生物标志物的价值。但是，人们对miR-124在抑郁症中的详细作用机制仍知之甚少。在这里，我们观察到miR-124在患有慢性不可预测的轻度应激（CUMS）的小鼠海马中被下调。miR-124表达的恢复显着减弱了抑郁样行为并抑制了CUMS诱导的小胶质细胞活化。从机理上讲，miR-124直接靶向BV2细胞中的信号转导子和转录激活因子3（STAT3）；此外，miR-124的上调抑制了LPS刺激的BV2细胞中诱导型一氧化氮合成酶和促炎性细胞因子（包括IL-6，IL-1β，TNF-α和MCP-1）的增加。集体数据表明，miR-124的功能障碍可能是通过促进小胶质细胞活化而发展为抑郁症的基础。miR-124的上调抑制了LPS刺激的BV2细胞中诱导型一氧化氮合成酶和促炎性细胞因子（包括IL-6，IL-1β，TNF-α和MCP-1）的增加。集体数据表明，miR-124的功能障碍可能是通过促进小胶质细胞活化而发展为抑郁症的基础。miR-124的上调抑制了LPS刺激的BV2细胞中诱导型一氧化氮合成酶和促炎性细胞因子（包括IL-6，IL-1β，TNF-α和MCP-1）的增加。集体数据表明，miR-124的功能障碍可能是通过促进小胶质细胞活化而发展为抑郁症的基础。