Trillium tschonoskii Maxim improves cognitive dysfunction in Alzheimer’s disease induced by okadaic acid in rats and its possible mechanism / 中国药理学通报

ABSTRACT

Aim To assess the effects of Trillium Tschonoskii Maxim ( TTM) decoction on learning and memory dysfunction in Alzheimer’ s disease ( AD ) model rats which induced by okadaic acid( OA) and its possible mechanism. Methods The SD rats were di-vided into ten groups,namely,d DMSO control group, OA group, TTM high-dose ( 0. 5 g·kg-1·d-1) group,TTM medium-dose ( 1 g·kg-1·d-1) group, TTM lower-dose (2 g·kg-1·d-1) group,and these groups were divided into one week and two weeks of gavage. Treatment groups were gavaged with TTM de-coction twice a day. After 5 days of Morris water maze training,treatment groups and AD model groups were injected with OA (0.392 mmol·L-1,1. 5 μL) in bi-lateral hippocampal of the rats. The DMSO groups were injected with 10% DMSO. The spatial memory reten- tion wereas detected by water maze at 24 h after injec-tion. After the test, we prepared sample for Western blot and Nissl’s staining. The Western blotting test was used to detect the PP2A activity and the phospho-rylation of Tau protein in the hippocampus. Nissl’'s staining was used to observe the changes of the number of Nissl’s bodies in the hippocampal CA1 and CA3 re-gions. Results The Morris water maze test showed that after injection of OA, the latency of TTM groups wereas shorter than that of OA groups. Western blot showed that the high dose TTM could increase the ac-tivity of PP2A and decrease the level of Tau phospho-rylation at PS-Tau396,,PT-Tau404. The Nissl’s stai-ning results showed that the number of Nissl’s bodies in the hippocampal CA1 and CA3 regions of OA groups wereas significantly attenuated compared with that of 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 morewas larger than that of OA group. Conclusion The results show that TTM can improve the learning and memory dysfunction in AD model rats which induced by OA. The mecha- nism wasis probably that TTM can increase PP2A ac-tivity and then down-regulate the level of Tau phospho-rylation and improve neural development.