Anesthesia Induces Phosphorylation of Tau

Article type: Research Article

Authors: Run, Xiaoqin^{a; b; 1} | Liang, Zhihou^{a; c; 1} | Zhang, Lan^d | Iqbal, Khalid^a | Grundke-Iqbal, Inge^a | Gong, Cheng-Xin^{a; *}

Affiliations: [a] Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA | [b] Department of General Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China | [c] Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China | [d] Department of Pharmacology, Xuan-Wu Hospital of the Capital Medical University, Beijing, China

Correspondence: [*] Corresponding author: Cheng-Xin Gong, Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, 1050 Forest Hill Road, Staten Island, NY, 10314-6399, USA. Tel.: +1 718 494 5248; Fax: +1 718 494 1080; E-mail: cxgong@mail.csi.cuny.edu.

Note: [1] These authors contributed equally to this study.

Note: [] Communicated by Xiongwei Zhu

Abstract: Abnormal hyperphosphorylation and aggregation of microtubule-associated protein tau play a crucial role in neurodegeneration of Alzheimer's disease (AD). Anesthesia has been associated with cognitive impairment and the risk for AD. Here we investigated the effects of anesthesia on site-specific tau phosphorylation and the possible mechanisms. We found that anesthesia for short periods (30 sec to 5 min) induced tau phosphorylation at Thr181, Ser199, Thr205, Thr212, Ser262, and Ser404 to small, but significant, extents, which appeared to result from anesthesia-induced activation of stress-activated protein kinases. Anesthesia for a longer time (1 h) induced much more dramatic phosphorylation of tau at the above sites, and the further phosphorylation may be associated with hypothermia induced by anesthesia. Anesthesia-induced tau phosphorylation appears to be specific because the increased phosphorylation was only seen at half of the tau phosphorylation sites studied and was not observed in global brain proteins. These studies clarified the dynamic changes of tau phosphorylation at various sites and, thus, served as a fundamental guide for future studies on tau phosphorylation by using brains of anesthetized experimental animals. Our findings also provide a possible mechanism by which anesthesia may cause postoperative cognitive impairment and increase the risk for AD.

Keywords: Alzheimer's disease, anesthesia, phosphorylation, tau, tau kinases, tau phosphatases

DOI: 10.3233/JAD-2009-1003

Journal: Journal of Alzheimer's Disease, vol. 16, no. 3, pp. 619-626, 2009