Purpose: The imbalance between tau protein kinase and phosphatase leads to tauopathy in Alzheimer’s Disease (AD) and estrogens may exert their neuroprotective effects by reestablishing the balance between tau protein kinase and phosphatase.
Methods: Ovariectomized female rats were used to produce an AD model by microinfusion of Okadaic acid (OA) into the dorsal hippocampus unilaterally. Also, SH-SY5Y cells were used to test the neuroprotective potency and mechanisms of estrogen effects on tau phosphorylation.
Results: Our previous data showed that infusion of OA into the dorsal hippocampus can induce cognitive deficiency in rats. The present data showed that OA can induce tau phosphorylation (T205) in cortex and hippocampus with minor change of non-phospho-tau protein. Our results also showed that high dose OA can induce an increase of certain tau protein kinases, including cdk5 and GSK3ß, in both hippocampus and cortex. These results were consistent with our in vitro data that OA induces tau phosphorylation and increase of cdk5 and GSK3ß in a SH-SY5Y cell line. We also observed that 17ß-estrodial inhibits tau phosphorylation (T205) and increase of cdk5 and GSK3ß in vitro.
Conclusions: We conclude that the inhibition of phosphatase leads to tauopathy and estrogen exerts its neuroprotective effects by reestablishing the balance between tau protein kinases and phosphatase.