title: Effect of Continuous Propofol Infusion in Rat on Tau Phosphorylation with or without Temperature Control.
abstract: Several studies suggest a relationship between anesthesia-induced tau hyperphosphorylation and the development of postoperative cognitive dysfunction. This study further characterized the effects of continuous propofol infusion on tau protein phosphorylation in rats, with or without temperature control. Propofol was administered intravenously to 8-10-week-old male Sprague-Dawley rats and infused to the loss of the righting reflex for 2 h continuously. Proteins from cortex and hippocampus were examined by western blot and immunohistochemistry. Rectal temperature was significantly decreased during propofol infusion. Propofol with hypothermia significantly increased phosphorylation of tau at AT8, AT180, Thr205, and Ser199 in cortex and hippocampus except Ser396. With temperature maintenance, propofol still induced significant elevation of AT8, Thr205, and Ser199 in cortex and hippocampus; however, increase of AT180 and Ser396 was only found in hippocampus and cortex, respectively. Differential effects of propofol with or without hypothermia on multiple tau related kinases, such as Akt/GSK3β, MAPK pathways, or phosphatase (PP2A), were demonstrated in region-specific manner. These findings indicated that propofol increased tau phosphorylation under both normothermic and hypothermic conditions, and temperature control could partially attenuate the hyperphosphorylation of tau. Further studies are warranted to determine the long-term impact of propofol on the tau pathology and cognitive functions.
authors.affiliation: Department of Anaesthesiology, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.|Laboratory of Neurodegenerative Diseases, School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Chunxia
authors.initials: C
authors.lastname: Huang
authors.affiliation: Laboratory of Neurodegenerative Diseases, School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.|State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Olivia Tsz-Wa
authors.initials: OT
authors.lastname: Ng
authors.affiliation: School of Nursing, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China.
authors.forename: Yuen-Shan
authors.initials: YS
authors.lastname: Ho
authors.affiliation: Department of Anaesthesiology, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.|Research Centre of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Michael Garnet
authors.initials: MG
authors.lastname: Irwin
authors.affiliation: Laboratory of Neurodegenerative Diseases, School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.|Research Centre of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.|State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, China.
authors.forename: Raymond Chuen-Chung
authors.initials: RC
authors.lastname: Chang
authors.affiliation: Department of Anaesthesiology, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.|Research Centre of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Gordon Tin-Chun
authors.initials: GT
authors.lastname: Wong
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism; D000704:Analysis of Variance; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D018686:Anesthetics, Intravenous; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D000071679:Glycogen Synthase Kinase 3 beta; D015742:Propofol
keywords: Hypothermia; propofol; protein kinases; tau phosphorylation