环磷酸腺苷效应元件结合蛋白/脑源性神经营养因子信号通路在调心方改善APP/PS1小鼠学习记忆中的作用

doi:10.3969/j.issn.1006-9771.2018.01.003

《中国康复理论与实践》 ›› 2018, Vol. 24 ›› Issue (1): 11-16.doi: 10.3969/j.issn.1006-9771.2018.01.003

• 专题阿尔茨海默病的干预机制 • 上一篇下一篇

环磷酸腺苷效应元件结合蛋白/脑源性神经营养因子信号通路在调心方改善APP/PS1小鼠学习记忆中的作用

王晓雯, 邓海燕, 王健, 徐颖

1.上海中医药大学,a.康复医学院;b.生理教研室,上海市 201203

收稿日期:2017-10-23 修回日期:2017-12-05 出版日期:2018-01-25 发布日期:2018-01-31
通讯作者: 王健,男,博士,副研究员,硕士研究生导师,主要研究方向：老年认知障碍的中西医结合康复。徐颖,女,博士,教授,硕士研究生导师,主要研究方向：中药及有效成分对神经系统疾病的作用机制。E-mail:wangjiantcm@126.com(王健);ying6122003@aliyun.com(徐颖)
作者简介:王晓雯(1992-),女,汉族,上海市人,硕士研究生,主要研究方向：老年认知障碍的中西医结合康复。
基金资助:
上海市自然科学基金项目(No.13ZR1439700)

Role of cAMP Response Element Binding Protein/Brain-derived Neurotrophic Factor Signaling Pathway in Tiaoxin Formula Improving Learning and Memory of APP/PS1 Mice

WANG Xiao-wen, DENG Hai-yan, WANG Jian, XU Ying

1. a. School of Rehabilitation Science b. Department of Physiology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China

Received:2017-10-23 Revised:2017-12-05 Published:2018-01-25 Online:2018-01-31
Contact: WANG Jian, XU Ying.E-mail:wangjiantcm@126.com (WANG Jian);ying6122003@aliyun.com (XU Ying)
Supported by:
Shanghai Municipal Natural Science Foundation (No. 13ZR1439700)

摘要/Abstract

摘要： 目的通过观察APP/PS1双转基因阿尔茨海默病(AD)小鼠海马环磷酸腺苷效应元件结合蛋白(CREB)/脑源性神经营养因子(BDNF)信号通路的变化,探讨调心方对APP/PS1双转基因AD小鼠学习记忆的影响机制。方法将3月龄APP/PS1雄性小鼠54只随机分为模型组(n=18)、多奈哌齐组(n=18)和调心方组(n=18);另设同月龄同品系的C57/BL6雄性小鼠18只为对照组。各给药组给予相应药物。给药12周后,每组采用Morris水迷宫进行行为学测试,采用实时荧光定量聚合酶链反应(RT-qPCR)法检测海马CREB mRNA和BDNF mRNA表达的变化,Western blotting法检测海马磷酸化CREB (p-CREB)、BDNF蛋白表达的变化。结果与模型组比较,调心方组逃避潜伏期显著缩短(P<0.001),在原平台所在象限停留的时间百分比增加(P<0.05),海马CREB mRNA、BDNF mRNA表达较模型组均增加(P<0.05),海马p-CREB、BDNF蛋白表达较模型组明显增加(P<0.01)。结论调心方可有效改善APP/PS1双转基因AD小鼠的空间学习记忆,可能与上调CREB/BDNF信号通路有关。

关键词: 阿尔茨海默病, 调心方, Morris水迷宫, 学习记忆, 环磷酸腺苷效应元件结合蛋白, 脑源性神经营养因子, 信号通路, 小鼠

Abstract: Objective To observe the changes of cAMP response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway in the hippocampus of APP/PS1 double transgenic Alzheimer's disease mice, and investigate the effects of Tiaoxin formula on learning and memory.Methods Totally, 54 three-month-old APP/PS1 transgenic mice were randomly divided into model group (n=18), positive control (donepezil) group (n=18) and Tiaoxin formula group (n=18). Another 18 three-month-old C57/BL6 wild mice were chosen as normal group with same strain and same age. All administration groups received relevant medicine. Twelve weeks later, Morris water maze test was used to test the behavior. The real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of CREB mRNA and BDNF mRNA in hippocampus. Western blotting was used to detect the expression of phosphorylated CREB (p-CREB) and BDNF in hippocampus.Results Compared with the model group, the escape latency significantly shortened (P<0.01), the percentage of staying time in the quadrant of original platform significantly increased (P<0.05), the expression of CREB mRNA and BDNF mRNA in hippocampus significantly increased (P<0.05), and the expression of p-CREB and BDNF protein in hippocampus significantly increased (P<0.01) in Tiaoxin formula group.Conclusion Tiaoxin formula could improve the spatial learning and memory of APP/PS1 double transgenic mice with AD, which might be related to the up-regulation of CREB/BDNF signaling pathway.

Key words: Alzheimer's disease, Tiaoxin formula, Morris water maze, learning and memory, cAMP response element binding protein, brain-derived neurotrophic factor, signaling pathway, mice

中图分类号:

R749.1

王晓雯, 邓海燕, 王健, 徐颖. 环磷酸腺苷效应元件结合蛋白/脑源性神经营养因子信号通路在调心方改善APP/PS1小鼠学习记忆中的作用[J]. 《中国康复理论与实践》, 2018, 24(1): 11-16.

WANG Xiao-wen, DENG Hai-yan, WANG Jian, XU Ying. Role of cAMP Response Element Binding Protein/Brain-derived Neurotrophic Factor Signaling Pathway in Tiaoxin Formula Improving Learning and Memory of APP/PS1 Mice[J]. 《Chinese Journal of Rehabilitation Theory and Practice》, 2018, 24(1): 11-16.

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环磷酸腺苷效应元件结合蛋白/脑源性神经营养因子信号通路在调心方改善APP/PS1小鼠学习记忆中的作用

Role of cAMP Response Element Binding Protein/Brain-derived Neurotrophic Factor Signaling Pathway in Tiaoxin Formula Improving Learning and Memory of APP/PS1 Mice

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