title: Intranasal insulin prevents anesthesia-induced hyperphosphorylation of tau in 3xTg-AD mice.
abstract: BACKGROUND
  It is well documented that elderly individuals are at increased risk of cognitive decline after anesthesia. General anesthesia is believed to be a risk factor for Alzheimer's disease (AD). Recent studies suggest that anesthesia may increase the risk for cognitive decline and AD through promoting abnormal hyperphosphorylation of tau, which is crucial to neurodegeneration seen in AD.
  
  
  METHODS
  We treated 3xTg-AD mice, a commonly used transgenic mouse model of AD, with daily intranasal administration of insulin (1.75 U/day) for one week. The insulin- and control-treated mice were then anesthetized with single intraperitoneal injection of propofol (250 mg/kg body weight). Tau phosphorylation and tau protein kinases and phosphatases in the brains of mice 30 min and 2 h after propofol injection were then investigated by using Western blots and immunohistochemistry.
  
  
  RESULTS
  Propofol strongly promoted hyperphosphorylation of tau at several AD-related phosphorylation sites. Intranasal administration of insulin attenuated propofol-induced hyperphosphorylation of tau, promoted brain insulin signaling, and led to up-regulation of protein phosphatase 2A, a major tau phosphatase in the brain. Intranasal insulin also resulted in down-regulation of several tau protein kinases, including cyclin-dependent protein kinase 5, calcium/calmodulin-dependent protein kinase II, and c-Jun N-terminal kinase.
  
  
  CONCLUSIONS
  Our results demonstrate that pretreatment with intranasal insulin prevents AD-like tau hyperphosphorylation. These findings provide the first evidence supporting that intranasal insulin administration might be used for the prevention of anesthesia-induced cognitive decline and increased risk for AD and dementia.
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities Staten Island, NY, USA ; Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, China.
authors.forename: Yanxing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Run
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology Wuhan, Hubei, China.
authors.forename: Zhihou
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities Staten Island, NY, USA ; Department of Neurology, The First Hospital of Jilin University Changchun, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities Staten Island, NY, USA.
authors.forename: Chun-Ling
authors.initials: CL
authors.lastname: Dai
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities Staten Island, NY, USA.
authors.forename: Khalid
authors.initials: K
authors.lastname: Iqbal
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities Staten Island, NY, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities Staten Island, NY, USA.
authors.forename: Cheng-Xin
authors.initials: CX
authors.lastname: Gong
keywords: Alzheimer’s disease; anesthesia; brain insulin signaling; hyperphosphorylation of tau; intranasal insulin; propofol; protein phosphatase 2A; tau protein kinases