Phosphorylation of tau protein over time in rats subjected to transient brain ischemia
摘要
Transient brain ischemia has been shown to induce hyperphosphorylation of the microtubule-associated protein tau.To further determine the mechanisms underlying these processes,we investigated the interaction between tau,glycogen synthase kinase(GSK)-3βand protein phosphatase 2A.The results confirmed that tau protein was dephosphorylated during brain ischemia;in addition,the activity of GSK-3βwas increased and the activity of protein phosphatase2A was decreased.After reperfusion,tau protein was hyperphosphorylated,the activity of GSK-3βwas decreased and the activity of protein phosphatase 2A remained low.Importantly,the interaction of tau with GSK-3βand protein phosphatase 2A was altered during ischemia and reperfusion Lithium chloride could affect tau phosphorylation by regulating the interaction of tau with GSK-3βand protein phosphatase 2A,and improve learning and memory ability of rats after transient brain ischemia.The present study demonstrated that it was the interaction of tau with GSK-3βand protein phosphatase 2A,rather than their individual activities,that dominates the phosphorylation of tau in transient brain ischemia.Hyperphosphorylated tau protein may play an important role in the evolution of brain injury in ischemic stroke.The neuroprotective effects of lithium chloride partly depend on the inhibition of tau phosphorylation during transient brain ischemia.