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MicroRNA-129-5p inhibits the development of autoimmune encephalomyelitis-related epilepsy by targeting HMGB1 through the TLR4/NF-kappa B signaling pathway

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机构: [1]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China
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关键词: MicroRNA-129-5p HMGB1 TLR4/NF-kappa B signaling pathway Autoimmune encephalomyelitis-related epilepsy Neuronal injury Microglial cell

摘要:
The study aimed to explore the effects of microRNA-129-5p (miR-129-5p) on the development of autoimmune encephalomyelitis (AE)-related epilepsy by targeting HMGB1 through the TLR4/NF-kB signaling pathway in a rat model. AE -related epilepsy models were established. Sprague-Dawley (SD) rats were randomly divided into control, model, miR-129-5p mimics, miR-129-5p inhibitor, HMGB1 shRNA, TLR4/NF-kB (TLR4/NF-kB signaling pathway was inhibited) and miR-129-5p mimics + HMGB1 shRNA groups respectively. Latency to a first epilepsy seizure attack was recorded. Neuronal injuries in the hippocampus regions were detected using HE, Nissl and FJB staining methods 24 h following model establishment. Microglial cells were detected by OX-42 immunohistochemistry. Expressions of miR-129-5p, HMGB1 and TLR4/NF-kB signaling pathway-related proteins were detected by qRT-PCR. Protein expressions of HMGB1 and TLR4/NF-kB signaling pathway -related proteins were detected by Western blotting. Dual luciferase reporter gene assay showed that miR-129-5p was negatively targeting HMGB1. Neurons of hippocampal tissues in rats were heavily injured by an injection of lithium chloride. Compared with the model and control groups, neuronal injury of the hippocampus and AE -related epilepsy decreased and microglial cells increased in the miR-129-5p mimics, HMGB1 shRNA and TLR4/NF-kB groups; however, in the miR-129-5p inhibitor group, miR-129-5p expression decreased, HMGB1 expression increased, TLR4/NF-kB signaling pathway was activated, latency to a first epilepsy seizure attack was shortened, and neuronal injury increased. This study provides evidence that miR-129-5p inhibits the development of AE-related epilepsy by suppressing HMGB1 expression and inhibiting TLR4/NF-kB signaling pathway.

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出版当年[2016]版:
大类 | 3 区 医学
小类 | 4 区 神经科学
最新[2023]版:
大类 | 3 区 医学
小类 | 3 区 神经科学
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出版当年[2015]版:
Q3 NEUROSCIENCES
最新[2023]版:
Q2 NEUROSCIENCES

影响因子: 最新[2023版] 最新五年平均 出版当年[2015版] 出版当年五年平均 出版前一年[2014版] 出版后一年[2016版]

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第一作者机构: [1]Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China
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通讯机构: [*1]Department of Neurology, Xuanwu Hospital, Capital Medical University, No. 45, Changchun Street, Xicheng Distrcit, Beijing 100053, PR China
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