鸢尾素通过抑制小胶质细胞NLRP3炎性体通路改善脂多糖诱导的神经炎症小鼠模型的认知障碍

IF 4.6 2区 医学 Q1 NEUROSCIENCES
Da-Qi Zhang , Ge Li , Zong-Dong Fu , Yu-Sheng Huang , Xiao-Li Feng , Li-Jun Chen , Rong Wang , Wen-Jie Zhao , Qifu Li
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引用次数: 0

摘要

神经炎症与神经退行性疾病的发生有关。鸢尾素最初被确定为一种运动诱导的骨骼肌分泌的糖基化蛋白。鸢尾素的主要生理功能最初被认为包括促进血管生成;改善氧化代谢;调节葡萄糖,脂质和线粒体代谢。然而,尽管鸢尾素在阿尔茨海默病中具有神经保护作用,但其在神经炎症,特别是脂多糖(LPS)诱导的认知障碍中的确切作用仍不清楚。本研究旨在探讨鸢尾素对lps诱导的炎性认知障碍的保护作用及其机制。我们使用LPS诱导小鼠认知功能损伤,并采用Morris水迷宫实验评估认知功能。此外,我们使用免疫荧光染色和流式细胞术来评估皮质和海马的小胶质细胞激活和极化,这两个大脑区域参与认知行为。Western blotting检测NLRP3信号通路相关蛋白水平。此外,我们使用小鼠酶联免疫吸附测定试剂盒检测BV2细胞中肿瘤坏死因子-α、白细胞介素(IL)-6、CCL2、IL-4和IL-10的水平,并使用流式细胞术表征M1和M2极化。鸢尾素改善了lps处理小鼠的学习和认知能力,但抑制了小胶质细胞的激活和M1极化。鸢尾素显著降低lps处理小鼠NLRP3炎性小体信号通路分子的表达。此外,鸢尾素抑制了BV2细胞中小胶质细胞的激活并减少了促炎细胞因子的产生。此外,鸢尾素可以保护PC12细胞免受lps激活的BV2小胶质细胞诱导的神经毒性,并抑制BV2条件培养基诱导的PC12细胞凋亡。鸢尾素通过抑制NLRP3信号通路减轻炎性认知功能障碍,抑制小胶质细胞活化和m1型极化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Irisin ameliorates cognitive impairment in a lipopolysaccharide-induced neuroinflammation mouse model by inhibiting the NLRP3 inflammasome pathway in microglia
Neuroinflammation is implicated in the development of neurodegenerative diseases. Irisin was first identified as an exercise-induced skeletal muscle-secreted glycosylated protein. The main physiological functions of irisin were initially thought to include the promotion of angiogenesis; improvement of oxidative metabolism; and regulation of glucose, lipid, and mitochondrial metabolism. However, despite its demonstrated neuroprotective effects in Alzheimer's disease, the precise role of irisin in neuroinflammation, particularly in lipopolysaccharide (LPS)-induced cognitive impairment, remains unclear. This study was performed to investigate the protective effects and mechanisms of irisin on LPS-induced inflammatory cognitive impairment both in vivo and in vitro. We induced cognitive impairment in mice using LPS and evaluated cognitive function by employing the Morris water maze test. Further, we used immunofluorescence staining and flow cytometry to assess microglial activation and polarization in the cortex and hippocampus, two brain regions involved in cognitive behaviors. Western blotting was used to detect the levels of proteins related to the NLRP3 signaling pathway. Furthermore, we measured tumor necrosis factor -α, interleukin (IL)-6, CCL2, IL-4 and IL-10 levels in BV2 cells using a mouse enzyme-linked immunosorbent assay kit and characterized M1 and M2 polarization using flow cytometry. Irisin administration improved learning and cognitive abilities but inhibited microglial activation and M1 polarization in LPS-treated mice. Irisin significantly decreased the expression of NLRP3 inflammasome signaling pathway molecules in LPS-treated mice. Further, irisin suppressed microglial activation and reduced the production of proinflammatory cytokines in BV2 cells. Moreover, irisin protected PC12 cells from LPS-activated BV2 microglia-induced neurotoxicity and inhibited apoptosis in PC12 cells induced by BV2 conditioned medium. Irisin mitigated inflammatory cognitive dysfunction and suppressed microglial activation and M1-type polarization by inhibiting the NLRP3 signaling pathway.
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来源期刊
Neuropharmacology
Neuropharmacology 医学-神经科学
CiteScore
10.00
自引率
4.30%
发文量
288
审稿时长
45 days
期刊介绍: Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).
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