PMID- 36562806 OWN - NLM STAT- MEDLINE DCOM- 20230206 LR - 20230206 IS - 1432-1106 (Electronic) IS - 0014-4819 (Linking) VI - 241 IP - 2 DP - 2023 Feb TI - Up-regulation of lncRNA NEAT1 in cerebral ischemic stroke promotes activation of astrocytes by modulation of miR-488-3p/RAC1. PG - 395-406 LID - 10.1007/s00221-022-06519-z [doi] AB - We aim to research the molecular mechanism of lncRNA NEAT1 in the activation of astrocytes in a cerebral ischemia-reperfusion injury model. Mouse model of cerebral ischemia-reperfusion injury was constructed, and shNEAT1 was transfected. The infarct area, brain water content, and neurological deficiency were detected. Immunofluorescence detection and fluorescence in situ hybridization (FISH) assay were processed to detect glial fibrillary acidic protein (GFAP) expression. Astrocyte cells were cultured for oxygen-glucose deprivation/re-oxygenation (OGD)/re-oxygenation model construction. After treatment by shNEAT1, miR-488-3p mimic, miR-488-3p inhibitor, Q-PCR assay, western blot and ELISA were undertaken to detect the expressions of NEAT1, miR-488-3p, RAC1, inflammatory cytokines, RAC1 and GFAP. Dual luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) assay were used to verify the binding of NEAT1, miR-488-3p and RAC1. The expression of NEAT1 in brain tissue was significantly higher than that in Sham operation group. Knockdown of NEAT1 inhibited the brain damage caused by middle cerebral artery occlusion (MCAO) treatment, reduced the inflammatory response, and suppressed the activation of astrocytes. By constructing an in vitro OGD/R cell model, it was found that NEAT1 knockdown also inhibited the activation of astrocytes caused by OGD/R. Knockdown of NEAT1 caused the up-regulation of miR-488-3p and the down-regulation of RAC1. Knockdown of miR-488-3p or over-expression of RAC1 reversed the inhibitory effect of shNEAT1 on OGD/R-induced astrocyte activation. Over-expression of NEAT1 in cerebral ischemic stroke promotes activation of astrocytes by modulation miR-488-3p/RAC1, which is proved in vitro. Our study may provide a new idea for the diagnosis and treatment of MCAO. CI - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Zheng, Haijian AU - Zheng H AD - Department of General Medicine, The First Affiliated Hospital of Soochow University, NO. 899 Pinghai Road, Suzhou, 215006, People's Republic of China. FAU - Zhang, Gai AU - Zhang G AD - Department of General Medicine, The First Affiliated Hospital of Soochow University, NO. 899 Pinghai Road, Suzhou, 215006, People's Republic of China. FAU - Liu, Guanglan AU - Liu G AD - Department of General Surgery, The First Affiliated Hospital of Soochow University, NO. 899 Pinghai Road, Suzhou, 215006, People's Republic of China. languangliu0022@163.com. AD - Department of General surgery, Ganyu District People's Hospital, No.88 Haicheng road, Lianyungang, 222100, People's Republic of China. languangliu0022@163.com. FAU - Wang, Ling AU - Wang L AUID- ORCID: 0000-0002-4993-3165 AD - Department of General Medicine, The First Affiliated Hospital of Soochow University, NO. 899 Pinghai Road, Suzhou, 215006, People's Republic of China. sudawangling1111@163.com. LA - eng PT - Journal Article DEP - 20221223 PL - Germany TA - Exp Brain Res JT - Experimental brain research JID - 0043312 RN - 0 (RNA, Long Noncoding) RN - 0 (MicroRNAs) SB - IM MH - Mice MH - Animals MH - Up-Regulation MH - *RNA, Long Noncoding/genetics/metabolism MH - Astrocytes/metabolism MH - *Ischemic Stroke MH - In Situ Hybridization, Fluorescence MH - *MicroRNAs/genetics/metabolism MH - *Stroke/genetics MH - *Brain Ischemia/genetics MH - *Reperfusion Injury MH - Infarction, Middle Cerebral Artery MH - Apoptosis/genetics OTO - NOTNLM OT - Activation of astrocytes OT - Cerebral ischemic stroke OT - NEAT1 OT - RAC1 OT - miR-488-3p EDAT- 2022/12/24 06:00 MHDA- 2023/02/07 06:00 CRDT- 2022/12/23 11:13 PHST- 2022/07/18 00:00 [received] PHST- 2022/12/01 00:00 [accepted] PHST- 2022/12/24 06:00 [pubmed] PHST- 2023/02/07 06:00 [medline] PHST- 2022/12/23 11:13 [entrez] AID - 10.1007/s00221-022-06519-z [pii] AID - 10.1007/s00221-022-06519-z [doi] PST - ppublish SO - Exp Brain Res. 2023 Feb;241(2):395-406. doi: 10.1007/s00221-022-06519-z. Epub 2022 Dec 23.