Depression is one of important prevalent psychiatric disorders worldwide. MiR-497 is considered as a diagnostic biomarker and a promising therapeutic target in cancers. However, the role of miR-497 in depression remains unknown. In this study, we demonstrated that CUS induced depression-like behaviors and overexpression of miR-497 in rats. Interestingly, knockdown miR-497 ameliorated CUS-induced depressive-like behavior in rats. Moreover, knockdown of miR-497 inhibited the activation of microglia and the production of proinflammatory cytokines including IL-6, IL-1β, MCP-1 and TNF-α in CUS-induced rats. Luciferase activity assay proved that Fibroblast Growth Factor-2 (FGF2) was a direct target of miR-497 and modulated by miR-497 in microglia. In rescue experiments, overexpression of FGF2 inhibited miR-497-induced proinflammatory cytokines and iNOS expression. These results showed that miR-497 aggravated hippocampal microglial activation in CUS-induced depression in rat via targeting FGF2, providing a novel potential target for treatment of depression.

中文翻译：

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MiR-497 通过靶向 FGF2 促进慢性不可预测的压力诱导的抑郁症中小胶质细胞的激活和促炎细胞因子的产生

抑郁症是世界范围内重要的普遍精神疾病之一。MiR-497 被认为是癌症的诊断生物标志物和有前景的治疗靶点。然而，miR-497在抑郁症中的作用仍然未知。在这项研究中，我们证明了 CUS 在大鼠中诱导了抑郁样行为和 miR-497 的过度表达。有趣的是，敲低 miR-497 改善了 CUS 诱导的大鼠抑郁样行为。此外，在 CUS 诱导的大鼠中，miR-497 的敲低抑制了小胶质细胞的活化和促炎细胞因子的产生，包括 IL-6、IL-1β、MCP-1 和 TNF-α。荧光素酶活性测定证明成纤维细胞生长因子-2 (FGF2) 是 miR-497 的直接靶标，并在小胶质细胞中受 miR-497 调节。在救援实验中，FGF2 的过表达抑制了 miR-497 诱导的促炎细胞因子和 iNOS 的表达。这些结果表明 miR-497 通过靶向 FGF2 加剧了 CUS 诱导的大鼠抑郁症海马小胶质细胞的活化，为治疗抑郁症提供了一个新的潜在靶点。