Abstract: Abstract Objective To investigate the effect of S3 on learning and memory in model rats induced by hypercholesterolemic with i.c.v. injection of Aβ25-35. Method 70 female Wistar rats were divided into 7 groups. Except the normal group, other 60 rats were fed with hypercholemic chow for six weeks, and then received an intracerebroventricular injection for once. The E2 and S3-treatment groups’ rats were treated with E2 or S3 for another 7 days. Behavioral changes were evaluated by Morris water maze and step-down test. The activities of choline acetyl transferase (ChAT) and acetylcholine esterase (Ach E) were analyzed by spectrophotometric method, and the content of acetylcholine was by ELISA. Result The data shown that S3 dose-dependently decreased serum total and LDL-C levels (P<0.01) in model rats with hypercholesterolemic plus i.v.c. injection of Aβ25-35. The highest dose of S3 shortened the escape latency significantly. The step-down latency of S3 treated groups was restored to near that of the control group and the number of errors was reduced markedly. Meanwhile, S3 reversed the decreased activity of ChAT as well as the increased activity of Ach E in hippocampus. Conclusion These findings suggest that S3 improved the model rats learning and memory by decreased the serum cholesterol, increased the concentration of Ach in hippocampus through changes of ChAT and Ach E activities.

Key words: Key Words: tran-2,4-dimethoxystibene (S3), hypercholesterolemic rat, learning and memory, cholinergic, Aβ25-35