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

来源：

INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY | 2023年 / 37卷

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.

引用

页数：15