Silencing of long noncoding RNA X-inactive specific transcript alleviates Aß1-42-induced microglia-mediated neurotoxicity by shifting microglial M1/M2 polarization.
Int J Immunopathol Pharmacol
; 37: 3946320231184988, 2023.
Article
em En
| MEDLINE
| ID: mdl-37400958
ABSTRACT
OBJECTIVES:
This 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).METHODS:
The 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.RESULTS:
The 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 Aß1-42-treated BV-2 cells. XIST knockdown reduced Aß1-42-induced microglia-mediated apoptosis and enhanced cell viability in HT22 cells. XIST silencing down-regulated miR-107 level and attenuated Aß1-42-caused suppression of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling. Those effects of XIST silencing were attenuated by miR-107 inhibitor or LY294002.CONCLUSION:
Downregulation of XIST lessened Aß1-42-induced microglia-mediated neurotoxicity by modulating microglial M1/M2 polarization, which may be mediated by the miR-107/PI3K/Akt pathway.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
MicroRNAs
/
Doença de Alzheimer
/
RNA Longo não Codificante
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article