title: Mild hypothermia protects against oxygen glucose deprivation/reoxygenation-induced apoptosis via the Wnt/β-catenin signaling pathway in hippocampal neurons.
abstract: Mild hypothermia is thought to be one of the most effective therapies for cerebral ischemia/reperfusion injuries. Our previous research revealed that mild hypothermia inhibits the activation of caspase-3 and protects against oxygen glucose deprivation/reoxygenation (OGD/R)-induced injury in hippocampal neurons. However, the mechanisms behind the activation of caspase-3 remain unclear. The aims of this study were to determine whether the protective effects of mild hypothermia were exerted through the Wnt/β-catenin signaling pathway. We found that, under OGD/R conditions, the pathway was down regulated, but mild hypothermia induced the reactivation of the Wnt/β-catenin signaling pathway, which had been suppressed by OGD/R injury. Mild hypothermia also caused the down regulation of the expression of apoptosis promoting proteins (Bax cleaved caspase-3), up-regulated the expression of apoptosis inhibiting proteins (Bcl-2), and ameliorated OGD/R injury-induced apoptosis. The protective effects of mild hypothermia were blocked by DKK1 (an antagonist of the canonical Wnt signaling pathway). Taken together, these results indicate that the Wnt/β-catenin signaling pathway mediates the protective effects of mild hypothermia against OGD/R-induced apoptosis. Our study provides evidence that mild hypothermia reactivates the Wnt/β-catenin signaling pathway, which is suppressed by OGD/R injury, in hippocampal neurons and protects neurons from OGD/R-induced apoptosis via the reactivation of the Wnt/β-catenin signaling pathway, ultimately suggesting that mild hypothermia could have therapeutic effects on OGD/R-induced apoptosis.
authors.affiliation: Department of Emergency, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Tianen
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Yanran
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Department of Emergency, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Longyuan
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Emergency, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.affiliation: Department of Emergency, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
authors.forename: Chaotao
authors.initials: C
authors.lastname: Zeng
authors.affiliation: Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. Electronic address: enxiangtao55@yeah.net.
authors.forename: Enxiang
authors.initials: E
authors.lastname: Tao
mesh_terms: D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000378:metabolism* / Q000517:prevention & control*; D002478:Cells, Cultured; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology; D007036:Hypothermia, Induced / Q000379:methods*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D016896:Treatment Outcome; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D051176:beta Catenin; D005947:Glucose; D010100:Oxygen
keywords: Apoptosis; Mild hypothermia; OGD/R; Wnt/β-catenin