miR-124 ameliorates depressive-like behavior by targeting STAT3 to regulate microglial activation

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.