Anesthesia induces phosphorylation of tau.
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.
Run
Xiaoqin
X
Department of Neurochemistry, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314-6399, USA.
Liang
Zhihou
Z
Zhang
Lan
L
Iqbal
Khalid
K
Grundke-Iqbal
Inge
I
Gong
Cheng-Xin
CX
D000759:Adjuvants, Anesthesia / Q000009:adverse effects; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000378:metabolism*; D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D003072:Cognition Disorders / Q000453:epidemiology / Q000378:metabolism; D004986:Ether / Q000009:adverse effects*; D005260:Female; D007036:Hypothermia, Induced / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010424:Pentobarbital / Q000009:adverse effects; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism; D012307:Risk Factors; D016875:tau Proteins / Q000378:metabolism*
D000759:Adjuvants, Anesthesia; D018685:Anesthetics, Inhalation; D016875:tau Proteins; D004986:Ether; D011494:Protein Kinases; D010424:Pentobarbital