To Study On The Prevention And Treatment Of AD Model Rats Induced By OA And Its Possible Mechanism

Objective: To explore whether the Trillium Tschonoskii Maxim(TTM)preventive and therapeutic effect on AD rats induced by okadaic acid(OA)and its possible mechanism.Methods: The SD rats were divided into ten groups,named DMSO control group,OA model group,TTM high-dose group,TTM medium-dose group,TTM lower-dose group,and these TTM groups were divided into one week and two weeks.Treatment groups were gavaged with TTM decoction while other groups were gavaged with drinking water.After 5 days training,treatment groups and AD model groups were injected with OA in hippocampal of the rats.The DMSO groups were injected with10% DMSO.The spatial memory retention was detected by water maze 24 hours after injection.Then,changes in the spatial learning memory of rats were observed.The level of Tau phosphorylation in SD rat hippocampus and the expression and activity changes of PP2 A and the expression of synapse-associated proteins were detected by Western blot.The changes of Nissl bodies in SD rat hippocampus were observed by Nissl's staining;The number and morphological changes of synaptic development and dendritic spines were detected by Golgi staining;The Detection of synaptic plasticity were detected by LTP.Results:The Morris water maze test showed that after injection of OA,the latency of OA groups were significantly longer than DMSO groups,while the TTM groups were shorter than OA groups.Western blot show that the high dose TTM could increase the activity of PP2 A and decrease the level of Tau phosphorylation and increase the expression of synapse-associated proteins with a dose dependence.Compared with DMSO groups,the level of Tau phosphorylation was increased in OA groups.Nissl's staining results show that OA groups were significantly attenuate the number of Nissl's bodies in the hippocampal CA1 and CA3 regions than DMSO groups.The number of Nissl's bodies in high groups were more than OA group.The density of dendritic spine of hippocampal neurons in AD rats were improved in TTM groups.LTP of PP-DG pathway was enhanced in TTM groups.Conclusions:The results show that TTM can improve the learning and memory dysfunction in AD model rats which induced by OA.The mechanism was probably that TTM can increase PP2 A activity and then down-regulate the level of Tau phosphorylation while promoting neuronal development and synaptic plasticity.