Department of Clinical Psychology, Hebei General Hospital, Shijiazhuang City, Hebei Province, 050059951, China.
Department of Neurology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, 201399, China.
J Chem Neuroanat. 2020 Dec;110:101872. doi: 10.1016/j.jchemneu.2020.101872. Epub 2020 Oct 15.
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.
抑郁症是全球范围内一种重要的普遍精神障碍。miR-497 被认为是癌症的诊断生物标志物和有前途的治疗靶点。然而，miR-497 在抑郁症中的作用尚不清楚。在这项研究中，我们证明 CUS 诱导了大鼠的抑郁样行为和 miR-497 的过表达。有趣的是，miR-497 的敲低改善了 CUS 诱导的大鼠的抑郁样行为。此外，miR-497 的敲低抑制了 CUS 诱导的大鼠中小胶质细胞的激活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。在挽救实验中，FGF2 的过表达抑制了 miR-497 诱导的促炎细胞因子和 iNOS 表达。这些结果表明，miR-497 通过靶向 FGF2 加重了 CUS 诱导的抑郁大鼠海马小胶质细胞的激活，为抑郁症的治疗提供了一个新的潜在靶点。
