Study on the Effect and Mechanism of Early Intervention with Compound Danshen Tablet on Learning and Memory in APP/PS1 Transgenic Mice

Abstract

Abstract: Objective: To investigate effect of compound danshan tablet (CDST) on learning and memory in APP/PS1 transgenic mice and the underlying mechanism. Methods: APP/PS1 transgenic mice at the age of 4 months were orally administered with vehicle or CDST or donepezil for 8 weeks, then the behavioral performance of mice was tested using novel object recognition and step-down passive avoidance. Aβ40 and Aβ42 level in the hippocampus of wild-type mice and APP/PS1 mice were determined by ELISA assay. Real time PCR and Western blot were used to examine mRNA and protein expression of insulin degrading enzyme (IDE) and neprilysin (NEP) respectively. Results: Result of novel object recognition test showed that CDST (720 mg·kg-1) significantly increased the recognition index for the novel object in APP/PS1 mice. Step-down passive avoidance suggested that CDST (720，360mg·kg-1)-treated APP/PS1 mice significantly decreased the latency to stay on the platform. In addition, APP/PS1 mice treated by CDST (720 mg·kg-1) significantly increased retention on the platform. ELISA analysis showed that CDST (720，360mg·kg-1) decreased the level of Aβ40 and Aβ42 in the hippocampus of APP/PS1 mice. In Real time PCR, CDST (720mg·kg-1) statistically increased the mRNA expression of IDE and NEP in the hippocampus of APP/PS1 mice. Western blot analysis indicated that CDST (720mg·kg-1) significantly increased IDE expression in APP/PS1 mice. Conclusion: Improvement of learning and memory by CDST in APP/PS1 mice may be associated with the decreased of Aβ and increased of IDE expression.

Key words: Alzheimer&, rsquo, s disease (AD), APP/PS1 transgenic mice, Compound danshen tablet (CDST), &, beta, -amyloid (A&, beta, ), Insulin degrading enzyme (IDE), Neprilysin (NEP)

CLC Number:

R965

Liu Min, Guo Hai-biao, Li Chu-yuan, Wang De-qin, Xu Jiang-ping, Qin Ren-an. Study on the Effect and Mechanism of Early Intervention with Compound Danshen Tablet on Learning and Memory in APP/PS1 Transgenic Mice[J]. Acta Neuropharmacologica, 2014, 4(5): 1-7.

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