Ether stress-induced Alzheimer-like tau phosphorylation in the normal mouse brain

Tau is reversibly hyperphosphorylated in the mouse brain by starvation or cold water swimming. Here, we report tau phosphorylation in the hippocampus of normal mouse after ether anesthesia, known to trigger typical stress reactions. Robust phosphorylation of tau was observed immediately and 10 min after ether vapor exposure at Ser202/Thr205 and Thr231/Ser235, sites typically phosphorylated in Alzheimer brains. The phosphorylation levels returned to baseline by 1 h. The most conspicuous and consistent change in the protein kinases studied was the inactivating phosphorylation of Ser9 of TPKI/GSK3β in close correspondence with tau phosphorylation. These findings show that tau phosphorylation is a rapid physiological process integral to stress response system, and suggest involvement therein of TPKI/GSK3β.