MicroRNA‐204‐5p Deficiency within the vmPFC Region Contributes to Neuroinflammation and Behavioral Disorders via the JAK2/STAT3 Signaling Pathway in Rats
Abstract Major depressive disorder (MDD) is usually considered associate with immune inflammation and synaptic injury within specific brain regions. However, the molecular mechanisms underlying the neural deterioration resulting in depression remain unclear. Here, it is found that miR‐204‐5p is mark...
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Wiley
2025-03-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202403080 |
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| author | Xiao Chen Yeting Gan Kaiqi Zhang Yuhan Wu Ye Li Tian Lan Xianghua Zhuang Shihong Chen Shuyan Yu |
| author_facet | Xiao Chen Yeting Gan Kaiqi Zhang Yuhan Wu Ye Li Tian Lan Xianghua Zhuang Shihong Chen Shuyan Yu |
| author_sort | Xiao Chen |
| collection | DOAJ |
| description | Abstract Major depressive disorder (MDD) is usually considered associate with immune inflammation and synaptic injury within specific brain regions. However, the molecular mechanisms underlying the neural deterioration resulting in depression remain unclear. Here, it is found that miR‐204‐5p is markedly downregulated in the ventromedial prefrontal cortex (vmPFC) in a chronic unpredictable mild stress (CUMS) induce rat model of depression. Knockdown of miR‐204‐5p in the vmPFC of normal rats results in depression and anxiety‐like behaviors accompanied with the activation of microglia, elevated levels of pro‐inflammatory 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‐204‐5p induces abnormal excitability of pyramidal neurons. In contrast, upregulation of miR‐204‐5p 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‐like behaviors. Moreover, pharmacological blocking of the JAK2/STAT3 signaling pathway significantly ameliorates abnormal behaviors resulting from miR‐204‐5p deficiency within the vmPFC. Collectively, these results provide robust evidence that the miR‐204‐5p/JAK2/STAT3 pathway may critically involve in the pathogenesis of depression, which may serve as potentially critical therapeutic target in the treatment of MDD. |
| format | Article |
| id | doaj-art-62371cc771d040faa02accf8b189a6f3 |
| institution | DOAJ |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
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| series | Advanced Science |
| spelling | doaj-art-62371cc771d040faa02accf8b189a6f32025-08-20T03:10:53ZengWileyAdvanced Science2198-38442025-03-011210n/an/a10.1002/advs.202403080MicroRNA‐204‐5p Deficiency within the vmPFC Region Contributes to Neuroinflammation and Behavioral Disorders via the JAK2/STAT3 Signaling Pathway in RatsXiao Chen0Yeting Gan1Kaiqi Zhang2Yuhan Wu3Ye Li4Tian Lan5Xianghua Zhuang6Shihong Chen7Shuyan Yu8Key Laboratory of Mental Disorders The Second Hospital of Shandong University School of Basic Medical Sciences Shandong University Jinan Shandong 250012 ChinaKey Laboratory of Mental Disorders The Second Hospital of Shandong University School of Basic Medical Sciences Shandong University Jinan Shandong 250012 ChinaKey Laboratory of Mental Disorders The Second Hospital of Shandong University School of Basic Medical Sciences Shandong University Jinan Shandong 250012 ChinaKey Laboratory of Mental Disorders The Second Hospital of Shandong University School of Basic Medical Sciences Shandong University Jinan Shandong 250012 ChinaKey Laboratory of Mental Disorders The Second Hospital of Shandong University School of Basic Medical Sciences Shandong University Jinan Shandong 250012 ChinaKey Laboratory of Mental Disorders The Second Hospital of Shandong University School of Basic Medical Sciences Shandong University Jinan Shandong 250012 ChinaDepartment of Endocrinology and Metabolism The Second Hospital of Shandong University Jinan Shandong 250033 ChinaDepartment of Endocrinology and Metabolism The Second Hospital of Shandong University Jinan Shandong 250033 ChinaKey Laboratory of Mental Disorders The Second Hospital of Shandong University School of Basic Medical Sciences Shandong University Jinan Shandong 250012 ChinaAbstract Major depressive disorder (MDD) is usually considered associate with immune inflammation and synaptic injury within specific brain regions. However, the molecular mechanisms underlying the neural deterioration resulting in depression remain unclear. Here, it is found that miR‐204‐5p is markedly downregulated in the ventromedial prefrontal cortex (vmPFC) in a chronic unpredictable mild stress (CUMS) induce rat model of depression. Knockdown of miR‐204‐5p in the vmPFC of normal rats results in depression and anxiety‐like behaviors accompanied with the activation of microglia, elevated levels of pro‐inflammatory 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‐204‐5p induces abnormal excitability of pyramidal neurons. In contrast, upregulation of miR‐204‐5p 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‐like behaviors. Moreover, pharmacological blocking of the JAK2/STAT3 signaling pathway significantly ameliorates abnormal behaviors resulting from miR‐204‐5p deficiency within the vmPFC. Collectively, these results provide robust evidence that the miR‐204‐5p/JAK2/STAT3 pathway may critically involve in the pathogenesis of depression, which may serve as potentially critical therapeutic target in the treatment of MDD.https://doi.org/10.1002/advs.202403080JAK2/STAT3 signaling pathwayMDDmiR‐204‐5pneuroinflammationneuronal apoptosissynaptic plasticity |
| spellingShingle | Xiao Chen Yeting Gan Kaiqi Zhang Yuhan Wu Ye Li Tian Lan Xianghua Zhuang Shihong Chen Shuyan Yu MicroRNA‐204‐5p Deficiency within the vmPFC Region Contributes to Neuroinflammation and Behavioral Disorders via the JAK2/STAT3 Signaling Pathway in Rats Advanced Science JAK2/STAT3 signaling pathway MDD miR‐204‐5p neuroinflammation neuronal apoptosis synaptic plasticity |
| title | MicroRNA‐204‐5p Deficiency within the vmPFC Region Contributes to Neuroinflammation and Behavioral Disorders via the JAK2/STAT3 Signaling Pathway in Rats |
| title_full | MicroRNA‐204‐5p Deficiency within the vmPFC Region Contributes to Neuroinflammation and Behavioral Disorders via the JAK2/STAT3 Signaling Pathway in Rats |
| title_fullStr | MicroRNA‐204‐5p Deficiency within the vmPFC Region Contributes to Neuroinflammation and Behavioral Disorders via the JAK2/STAT3 Signaling Pathway in Rats |
| title_full_unstemmed | MicroRNA‐204‐5p Deficiency within the vmPFC Region Contributes to Neuroinflammation and Behavioral Disorders via the JAK2/STAT3 Signaling Pathway in Rats |
| title_short | MicroRNA‐204‐5p Deficiency within the vmPFC Region Contributes to Neuroinflammation and Behavioral Disorders via the JAK2/STAT3 Signaling Pathway in Rats |
| title_sort | microrna 204 5p deficiency within the vmpfc region contributes to neuroinflammation and behavioral disorders via the jak2 stat3 signaling pathway in rats |
| topic | JAK2/STAT3 signaling pathway MDD miR‐204‐5p neuroinflammation neuronal apoptosis synaptic plasticity |
| url | https://doi.org/10.1002/advs.202403080 |
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