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However, the molecular mechanisms underlying the neural deterioration resulting in depression remain unclear. Here, it is found that miR\u2010204\u20105p is markedly downregulated in the ventromedial prefrontal cortex (vmPFC) in a chronic unpredictable mild stress (CUMS) induce rat model of depression. Knockdown of miR\u2010204\u20105p in the vmPFC of normal rats results in depression and anxiety\u2010like behaviors accompanied with the activation of microglia, elevated levels of pro\u2010inflammatory cytokines, and increased numbers of neural apoptotic cells, effects which appear to be mediated by activation of the JAK2\/STAT3 signaling pathway. Electrophysiological recordings further demonstrate that knockdown of miR\u2010204\u20105p induces abnormal excitability of pyramidal neurons. In contrast, upregulation of miR\u2010204\u20105p in the vmPFC of CUMS rats significantly causes inhibition of JAK2\/STAT3 signaling pathway, improvements in neuronal impairments, and an abolition of the depression and anxiety\u2010like behaviors. Moreover, pharmacological blocking of the JAK2\/STAT3 signaling pathway significantly ameliorates abnormal behaviors resulting from miR\u2010204\u20105p deficiency within the vmPFC. Collectively, these results provide robust evidence that the miR\u2010204\u20105p\/JAK2\/STAT3 pathway may critically involve in the pathogenesis of depression, which may serve as potentially critical therapeutic target in the treatment of MDD.<\/jats:p>","DOI":"10.1002\/advs.202403080","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T15:10:37Z","timestamp":1736521837000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["MicroRNA\u2010204\u20105p Deficiency within the vmPFC Region Contributes to Neuroinflammation and Behavioral Disorders via the JAK2\/STAT3 Signaling Pathway in Rats"],"prefix":"10.1002","volume":"12","author":[{"given":"Xiao","family":"Chen","sequence":"first","affiliation":[{"name":"Key Laboratory of Mental Disorders The Second Hospital of Shandong University School of Basic Medical Sciences Shandong University  Jinan Shandong 250012 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