title: Alpha-lipoic acid upregulates SIRT1-dependent PGC-1α expression and protects mouse brain against focal ischemia.
abstract: OBJECTIVE
  Silent mating type information regulation 2 homolog 1 (SIRT1) is a class III histone deacetylase and activates peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) which attenuates oxidative damage. Alpha-lipoic acid (ALA) has been proven to protect the rat brain against cerebral ischemia injury by reducing oxidative stress. However, the underlying mechanisms are poorly understood. In this study, we investigated the potential neuroprotection and the possible role of ALA in SIRT1 pathway.
  
  
  METHODS
  Male CD-1 mice were randomly assigned to three groups: Sham, permanent middle cerebral artery occlusion (pMCAO) and ALA group (ALA, 50mg/kg). ALA was administered intraperitoneally 30min prior to ischemia in the ALA group. Neurological deficit, infarct volume, and brain edema were detected at 24h after cerebral ischemia. Immunohistochemistry, western blot and quantitative reverse transcription polymerase chain reaction (RT-qPCR) were used to detect the expression of SIRT1 and PGC-1α. Activities of superoxide dismutase (SOD) were measured by assay kits.
  
  
  RESULTS
  Compared with the pMCAO group, the ALA group significantly ameliorated neurological deficit, lessened infarct volume and brain edema, increased the expression of SIRT1, PGC-1α and activities of SOD (P<0.05).
  
  
  CONCLUSIONS
  ALA protected the mouse brain against ischemic damage, and this protection may be through up-regulating SIRT1-dependent PGC-1α expression.
authors.affiliation: Department of Geriatrics, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: B
authors.initials: B
authors.lastname: Fu
authors.affiliation: Department of Geriatrics, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China; Hebei Key Laboratory for Neurology, Shijiazhuang, Hebei 050000, PR China. Electronic address: zhang6xj@heinfo.net.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: C
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: T
authors.initials: T
authors.lastname: He
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: P
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Geriatrics, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Geriatrics, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease, Shijiazhuang, Hebei 050000, PR China. Electronic address: wangxl2014@yahoo.com.
authors.forename: X
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology*; D002545:Brain Ischemia / Q000517:prevention & control*; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D008297:Male; D051379:Mice; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism*; D056564:Sirtuin 1 / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*; D008063:Thioctic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D008063:Thioctic Acid; D013482:Superoxide Dismutase; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1
keywords: alpha-lipoic acid; ischemic stroke; oxidative stress; peroxisome proliferator-activated receptor-γ co-activator-1α; silent mating-type information regulation 2 homolog 1