Silencing of long noncoding RNA X-inactive specific transcript alleviates Aβ1-42-induced microglia-mediated neurotoxicity by shifting microglial M1/M2 polarization

被引:2
|
作者
Zhao, Kun-Peng [1 ,3 ]
Wang, Xin-Yu [2 ]
Shao, Mei-Qi [2 ]
He, Chen-Yang [1 ]
Yuan, Fu-Qiang [1 ]
机构
[1] Xinxiang Med Univ, Henan Mental Hosp, Affiliated Hosp 2, Dept Geriatr Psychiat, Xinxiang, Peoples R China
[2] Xinxiang Med Univ, Henan Mental Hosp, Affiliated Hosp 2, Dept Psychiat, Xinxiang, Peoples R China
[3] Xinxiang Med Univ, Henan Mental Hosp, Affiliated Hosp 2, Dept Geriatr Psychiat, 207 Qianjin Rd, Xinxiang 453002, Henan, Peoples R China
关键词
Alzheimer's disease; long noncoding RNA X-inactive specific transcript; microglial polarization; neurotoxicity; ALZHEIMERS-DISEASE PATHOGENESIS; APOPTOSIS; NETWORKS; TOXICITY; PATHWAYS; STRESS;
D O I
10.1177/03946320231184988
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
ObjectivesThis experimental study aims to investigate the role of long noncoding RNA X-inactive specific transcript (lncRNA XIST) in the microglial polarization and microglia-mediated neurotoxicity in Alzheimer's disease (AD).MethodsThe levels of XIST and microRNA-107 (miR-107) were detected by quantitative real-time polymerase chain reaction. The spatial learning and memory capability of APPswe/PS1dE9 (APP/PS1) mice were evaluated by the Morris water maze test. The morphology of mouse hippocampus cells was evaluated by hematoxylin and eosin staining. The Iba1-positive microglia were labeled by immunohistochemistry staining. The protein levels were determined by western blot and enzyme-linked immunosorbent assay. Neurotoxicity was evaluated by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, caspase-3 activity, and Cell Counting Kit-8 assay. The XIST, miR-107, and AD targets were predicted by bioinformatics analysis.ResultsThe level of XIST was increased in APP/PS1 mice, and XIST silencing ameliorated AD progression. XIST silencing suppressed microglia activation, microglial M1 polarization, and proinflammatory factor levels, but promoted microglial M2 polarization in APP/PS1 mice and A & beta;1-42-treated BV-2 cells. XIST knockdown reduced A & beta;1-42-induced microglia-mediated apoptosis and enhanced cell viability in HT22 cells. XIST silencing down-regulated miR-107 level and attenuated A & beta;(1-42)-caused suppression of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Those effects of XIST silencing were attenuated by miR-107 inhibitor or LY294002.ConclusionDownregulation of XIST lessened A & beta;1-42-induced microglia-mediated neurotoxicity by modulating microglial M1/M2 polarization, which may be mediated by the miR-107/PI3K/Akt pathway.
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页数:15
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