Imbalance Of Protein Kinase And Protein Phosphatase Induces Alzheimer-like Phosphorylation Of Tau And Abnormal Behavior In Rat

Objective Bradykinin (BK) is a calcium/ calmodulin dependent protein kinase Ⅱ (CaMK-Ⅱ) specific activator, and cyclosporin A is reported to suppress protein phosphatase (PP)-2B activity. In vitro studies have shown that CaMK-Ⅱ and PP-2B play an important role in Alzheimer-like phosphorylation of microtube-associated protein Tau.Methods To reconstitute an animal model based on the imbalance of protein kinase(s) and protein phosphatase(s) seen in Alzheimer brain, we have injected BK and CSA into hippocampus, observed their behaviors by electronic attack-jump experiment and phosphorylation of Tau by immunostaining assay.Result The results from behavioural study showed that an obvious disturbance in learning and memory was seen with BK and CSA injected rats. The results obtained by immunostaining assay indicated that the staining for 12E8 was stronger, and for Tau-1 or PHF-1 were weaker in BK and CSA injected rats compared with control group. The BK and CSA injected rats showed obvious deficits in behavior (Mistakes made by model and control rats during electronic attack-jump experiment: 9.85±0.27and 6.28±1.10(P<0.01) Response to electronic attack: 82.27±10.92 and 46.97±12.03 (P<0.01) .Conclusions BK and CSA can Induce both Alzheimer-like Tau phosphorylation and behavioural disturbance.