白桦脂醇对APP/PS1双转基因痴呆模型小鼠认知及海马突触功能相关蛋白表达的影响

Effect of betulin on cognitive function and the expression of hippocampal synaptic function-related proteins in an APP/PS1 double transgenic mouse model of Alzheimer's disease

摘要:

目的 探讨白桦脂醇对阿尔茨海默病（AD）小鼠的学习记忆功能的干预作用及海马突触功能相关蛋白表达的影响，为探索治疗AD提供新的可能。方法 采用白桦脂醇干预APP/PS1双转基因痴呆模型小鼠，将小鼠随机分为模型组、药物高剂量组和低剂量组，C57BL/6J健康小鼠为对照组。通过行为学观察学习记忆能力、在体电生理记录海马神经元的生物电、TUNEL法检测神经元凋亡、Realtime PCR法检测PSD-95和Synapsin-I水平。结果 水迷宫检测结果发现白桦脂醇能改善模型小鼠认知功能障碍；电生理检测AD模型组长时程增强（LTP）幅值低于对照组，经过白桦脂醇干预治疗后，白桦脂醇各组LTP幅值较AD模型组升高；AD模型组神经元凋亡率显著高于对照组，经过白桦脂醇干预治疗后凋亡率下降；AD小鼠模型海马区PSD-95和Synapsin-I表达下降，但经白桦脂醇干预后其表达上升。结论 白桦脂醇通过使海马PSD-95和Synapsin-I的表达增加，发挥对APP/PS1双转基因痴呆模型小鼠认知功能的保护，使海马长时程增强。

Abstract:

Objective To investigate the interventional effect of betulin on the learning and memory functions and the expression of hippocampal synaptic function-related proteins in Alzheimer's disease (AD) mice, and to provide new insights into the treatment of AD.Methods APP/PS1 double transgenic mice were randomly divided into model group, high-dose betulin group, and low-dose betulin group. Healthy C57BL/6J mice were used as controls. The learning and memory abilities of the mice were determined by behavioral observation, and the bioelectricity of hippocampal neurons was measured by electrophysiological recording. In addition, neuronal apoptosis was measured by TUNEL staining, and postsynaptic density-95 (PSD-95) and synapsin-I expression was measured by real-time PCR.Results The water maze test showed that betulin improved the cognitive impairment of model mice. The amplitude of long-time potentiation (LTP) was lower in the AD model group than in the control group, but was higher in the betulin groups than in the AD model group. Compared with the control mice, the neuronal apoptosis rate was increased in the model mice but was reduced in the model mice treated with betulin. Furthermore, hippocampal expression of PSD-95 and synapsin-I was decreased in AD mice but was increased following betulin intervention.Conclusions Betulin can protect the cognitive function of APP/PS1 double transgenic mice with Alzheimer's disease by increasing the expression of PSD-95 and synapsin-I and enhancing the LTP of the hippocampus.