Effects Of Xanthoceraside On Learning And Memory Impairment In Mice Induced By I.c.v. Aβ_1-42

One of the main pathologic hallmarks of Alzheimer's disease is senile plaques that are composed ofβ-Amyloid peptide (Aβ). A number of studies suggest that Aβfibrils exert a variety of toxicity to neurons. Hence, we investigated the improvement of Xanthoceraside on learning and memory impairment in mice induced by intraventricular injection of Aβ_1-42 (i.c.v. Aβ_1-42) and the possible mechanism of protection against AD.The improving effects of Xanthoceraside on learning and memory impairment in mice were inspected by Y-maze, water-maze, novel object recognition, step-down and step-through tests; Biochemical analysis was used to detect the activity of AchE, ChAT, CAT, T-AOC, ATPase and the content of GSH and MDA; the central cholinergic system and antioxidant defense were studied to investigate the protection of Xanthoceraside against the dementia induced by Aβ_1-42. The results showed that Xanthoceraside( 0.08～0.32mg/kg ) could significantly increase the alternation behaviour in Y-maze test, increase the total time of the novel object exploration and preferential index, increase the latency and decrease the number of errors and the total time of shock in the step-down test or step-through test. The results of biochemical determination showed that Xanthoceraside markedly inhibited the decrease of the activity of AchE and ChAT and increased the activity of CAT, T-AOC and ATPase, at the same time, decreased the content of MDA and increased the content of GSH and the ratio of GSH/GSSG.It can be concluded that Xanthoceraside can improve learning and memory impairment in mice induced by i.c.v. Aβ_1-42 significantly. The mechanism may be associated with the protection of cholinergic system; the protection against damage induced by free radicals; the inhibition of lipid peroxidation; the improvement of metabolism of brain and the modulation of calcium homeostasis.