Abstract: Objective: The pathological characteristics of AD are both extracellular A? senile plaques and intracellular hyperphosphorylated tau neurofibrillary tangles formed. Increasing evidences indicate that hyperphosphorylated Tau plays a key role in the pathogenic events that occur in AD. We set out to assess whether ketamine can induce Tau hyperphosphorylation by increasing activity of glycogen synthase kinase-3? (GSK-3?) in A?25-35 induced PC12 cells. Methods: We performed these studies in cultured rat pheochromocytoma cells(PC12) and randomly allocated PC12 cells into four groups: control group(C); 10μmol/LA?25-35 (A); 1mmol/L ketamine (K); A?25-35 and ketamine (AK), above all groups were incubated for 6 hours. The cell viability was determined by MTT assay. Western blotting was performed to observe the protein expression of Tau phosphorylation of different sites, GSK-3? and p-GSK-3?ser9. In addition, Lithium Chloride, inhibitor of GSK-3?, was administered to all above grounps to investgate the changes of protein expression. Results: The cell survival rate was significantly decreased in AK group compared with the others groups. The level of Tau phosphorylation in the sites of Ser396、Ser404 and Thr231 increased after intubation with ketamine and A?25-35. And these increases were accompanied by up-regulation of activity of GSK-3?. Lithium Chloride attenuates these changes above all. Conclusion: Ketamine increases Tau hyperphosphorylation by up-regulating activity of GSK-3? in A?25-35 induced PC12 cells.

Key words: ketamine, Tau protein, PC12 cell, Beta-amyloid peptide 25-35, GSK-3β