The Effects And Mechanisms Of Evodamine On AD In The APP^swe/PS?E9 Transgenic Mouse

Backgroud Alzheimer's disease is one of the main threats to human health in an aging society. Although drugs can temporarily improve cognitive abilities of Alzheimer patients. At present there are no treatments that can totally stop or reverse neurodegenerative process of Alzheimer. The management of Alzheimer's disease (AD) has been a long-standing challenge and area of interest. In recent years, Chinese medicine in the treatment of Alzheimer's research, great progress has been made to become a force to be reckoned. Here, using the APPswe/PSAE9 transgenic mouse model of AD, evodamine was screening out from 12 kinds of compounds from Chinese herbs which showed beneficial effect on central nervous system, as the potential drugs for improvement ability of learning and memory in AD. We further studied the effects and the possible underlying mechanisms of evodamine on learning and memory improvement of AD in APPswe/PS?E9 transgenic mouse.Methods APPswe/PS?E9 transgenic and SAMP8 mice in 5 months were used,and 20 wild type mice and R1 mice matched with sex, weight were selected. We divided AD model mice into 4 groups:model group, aricept treatment group(2 mg/kg/d), evodamine treatment group(50 mg/kg/d) and evodamine treatment group(100 mg/kg/d). While model group and wild group mice were given routine and standard rat food, aricept treatment group and evodamine treatment group were given an appropriate dose of the drug added to the standard rat food. The daily food intake of rats as the following Weight 20g per mouse, daily food intake of rats for the 3g. The drug was administered for 28 days. After administration the water maze test were performed, PET was used to observe glucose uptake, immunohistochemical was used to detect senile plaques, the expression of brain cytokines IL-1?,IL-6, TNF-a was detected by ELISA and brain cox-2, inos, p-tau, A?oligomers was by western blot.Results The water maze test results showed that evodamine administration significantly improved learning and memory deficits presenting in APPswe/PSAE9 transgenic mice and senescence-accelerated mice(SAMP8). The most effective dose of the drug ameliorating learning and memory ability was 100mg/kg/d. Glucose uptake detected by PET observed that evodamine may enhance disturbance of brain energy metabolism in APPswe/PSAE9 transgenic mice remarkably. Evodamine administration may reduce overexpression of cytokines IL-1?,IL-6, TNF-a and obviously inhibit production of COX-2 in APPswe/PSAE9 transgenic mice.Conclusion Our study showed that evodamine could be the potential drugs for AD therapy. These findings revealed that evodamine could improve cognitive functions of AD in APPswe/PSAE9 transgenic mice, partly through regulating cytokines expression and depressing the COX-2 expression, thereby inhibiting inflammatory damage in Alzheimer's disease brain tissue. Background To study the locomotor activity changes of APPswe/PS?E9 double-transgenic mice and to investigate the possibility that the locomotor activity test could be used as behaviour evaluation in Alzheimer Disease. And study the changes in inflammation from the cellular, molecular level.Methods At 4.6,8 months, Morris water maze and open field trials were performed in transgenic mice and wildtype mice. All collected data were analyzed by SPSS software. The astrocyte activation in 6 months old mouse brain was detected by immunohistochemistry. And the expression of cox-2 was Detected by Western blotting.Results 4-and 6- months old APPswe/PS?E9 double-transgenic mice showed decrease in ability of learning and memory, but increase in excitement and in locomotor activity. There was statistically significant difference in the behaviour changes compared with wild type mice, and these features were similar to symptoms of AD patients. The GFAP and cytokines secretion were obviously enhanced, which showed the astrocyte was activated significantly. In addition, the expression of Cox-2 was significantly increased.Conclusions By the locomotor activity test, the behaviors like dysthesia, increased excitement and increased locomotor activity were observed in the Alzheimer Disease transgenic mice, which are the behavior phenotypes of human Alzheimer Disease. The transgenic mice show obvious inflammatory reaction in molecular and cellular level.It suggested that locomotor activity test could be an useful tool for evaluation of the Alzheimer Disease animal model.