Effect of Continuous Propofol Infusion in Rat on Tau Phosphorylation with or without Temperature Control

Article type: Research Article

Authors: Huang, Chunxia^{a; b} | Ng, Olivia Tsz-Wa^{b; d} | Ho, Yuen-Shan^e | Irwin, Michael Garnet^{a; c} | Chang, Raymond Chuen-Chung^{b; c; d; *} | Wong, Gordon Tin-Chun^{a; c; *}

Affiliations: [a] Department of Anaesthesiology, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China | [b] Laboratory of Neurodegenerative Diseases, School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China | [c] Research Centre of Heart, Brain, Hormone and Healthy Aging, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China | [d] State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, China | [e] School of Nursing, Faculty of Health and Social Sciences, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong SAR, China

Correspondence: [*] Correspondence to: Dr. Raymond Chuen-Chung Chang, Rm. L1-49, Laboratory Block, School of Biomedical Sciences, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam, Hong Kong. Tel.: +852 3917 9127; Fax: +852 2817 0857; E-mail: [email protected].

Correspondence: [*] Correspondence to: Dr. Gordon T.-C. Wong, MD, Department of Anaesthesiology, The University of Hong Kong, Room K424, Queen Mary Hospital, Pokfulam, Hong Kong. Tel.: +852 2255 3303; Fax: +852 2255 1654; E-mail: [email protected].

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.

Keywords: Hypothermia, propofol, protein kinases, tau phosphorylation

DOI: 10.3233/JAD-150645

Journal: Journal of Alzheimer's Disease, vol. 51, no. 1, pp. 213-226, 2016