title: Glycogen Synthase Kinase 3β Influences Injury Following Cerebral Ischemia/Reperfusion in Rats.
abstract: Abnormal activation of GSK-3β is associated with psychiatric and neurodegenerative disorders. However, no study has examined the effect of GSK-3β on cerebral ischemia/reperfusion injury. We used oxygen-glucose deprivation/reoxygenation (OGD/R) and middle cerebral artery occlusion (MCAO) as models of ischemia/reperfusion in rats in vitro and in vivo. Our study showed that knockdown of GSK-3β with a GSK-3β siRNA virus improved injury and increased viability of neurons subjected to OGD/R. Levels of total Nrf2, nuclear Nrf2, and Nrf2 downstream proteins sulfiredoxin (Srx1) and thioredoxin (Trx1) increased after transfection with the GSK-3β siRNA virus. GSK-3β siRNA increased SOD activity and decreased MDA levels. Overexpression of GSK-3β with a pcDNA-GSK-3β virus showed opposite results. We also demonstrated that intracerebroventricular injection of GSK-3β siRNA in rats ameliorated neurological deficits, reduced brain infarct volume and water content, and reduced damage to cerebral cortical neurons after MCAO. Changes in total Nrf2, nuclear Nrf2, Srx1, Trx1, SOD, and MDA were similar to those observed in vitro. Our results show for the first time that GSK-3β can influence cerebral ischemia/reperfusion injury. The effects may be due to regulating the Nrf2/ARE pathway and decreasing oxidative stress. These results suggest a potential new drug target for clinical treatment of stroke.
authors.affiliation: ; ;
authors.forename: Yixin
authors.initials: Y
authors.lastname: Li
authors.affiliation: ; ;
authors.forename: Jin
authors.initials: J
authors.lastname: Zhu
authors.affiliation: ; ;
authors.forename: Yuanling
authors.initials: Y
authors.lastname: Liu
authors.affiliation: ; ;
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Shipeng
authors.initials: S
authors.lastname: Lei
authors.affiliation: ; ;
authors.forename: Lingyu
authors.initials: L
authors.lastname: Li
authors.affiliation: ; ;
authors.forename: Beibei
authors.initials: B
authors.lastname: Jiang
authors.affiliation: ; ;
authors.forename: Li
authors.initials: L
authors.lastname: Tan
authors.affiliation: ; ;
authors.forename: Shanshan
authors.initials: S
authors.lastname: Yu
authors.affiliation: ; ;
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000201:enzymology* / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009474:Neurons; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology* / Q000378:metabolism* / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D000071679:Glycogen Synthase Kinase 3 beta
keywords: NF-E2-related factor 2.; cerebral ischemia/reperfusion injury; glycogen synthase kinase-3β