摘要
目的探讨慢性情感应激如社交挫败应激(Social defeat stress,SDS)对阿尔茨海默病(Alzheimer's disease,AD)发病的影响及SDS促进AD发病的可能机制。方法随机挑选8~10周龄的三重转基因(Triple-transgenic,3xTg)AD模型小鼠,性别不限;实验组小鼠给予持续4 d的SDS,未经历SDS的小鼠作为对照;SDS处理后利用Morris水迷宫和场景恐惧实验观察小鼠是否有认知功能障碍的加重;蛋白质免疫印迹和实时定量逆转录-聚合酶链反应分析其海马中转录因子CCAAT增强子结合蛋白β(CCAAT-enhancer binding proteinβ,C/EBPβ)水平变化以及C/EBPβ的水平变化与认知功能障碍的相关性;最后,为了理解慢性情感应激加重AD认知功能障碍的分子机制,使用C/EBPβ杂合敲除的3xTg(3xTg/C/EBPβ+/-)小鼠观察SDS对认知功能的损伤是否得到改善。结果SDS可以明显加重AD模型小鼠的认知功能障碍,这种作用可能是通过转录因子C/EBPβ介导的。结论SDS通过上调转录因子C/EBPβ表达来加重AD认知功能障碍,这可能是情感障碍或者是慢性情感应激促进AD发病的重要分子机制之一。
Objective To explore the impact of chronic emotional stress,such as social defeat stress(SDS),on the pathogenesis of Alzheimer's disease(AD)and the possible mechanism by which SDS promotes the pathogenesis of AD.Methods 3xTg AD model mice aged 2-3 months were randomly selected,regardless of gender.SDS-treated mice were given SDS for 4 days,and mice that did not undergo SDS served as controls.After SDS treatment,we used the Morris water maze and fear conditioning to observe whether the mice had cognitive impairment.Western blotting and real-time quantitative PCR were used to analyze the changes in the transcription factor C/EBPβin the hippocampus and the correlation between the changes in C/EBPβand cognitive impairment.Finally,to understand the molecular mechanism by which chronic emotional stress aggravates cognitive impairment in AD,3xTg/C/EBPβ+/-mice were used to observe whether the impairment of cognitive function caused by SDS was improved.Results SDS can significantly aggravate cognitive impairment in AD mice,which is mediated by upregulation of the transcription factor C/EBPβ.Conclusion SDS aggravates cognitive impairment in AD by upregulating the transcription factor C/EBPβ,which may be one of the important molecular mechanisms by which affective disorder or chronic emotional stress promotes the pathogenesis of AD.
作者
李芳
秦冬冬
李易易
高锋
余杭
王舰浩
王嘉贝
陈洪玉
刘松燕
张茜
李翔
王雅梅
张兆辉
王志昊
Li Fang;Qin Dongdong;Li Yiyi(Department of Neurology,Center for Neurodegenerative Disease Research,Renmin Hospital of Wuhan University,Wuhan 430060)
出处
《卒中与神经疾病》
2023年第5期433-439,共7页
Stroke and Nervous Diseases
基金
国家自然科学基金青年科学基金项目(82101479)
国家重点研究计划项目(2021YFA1302400)
湖北省实验动物研究领域项目(2022DFE021)
武汉大学人民医院交叉创新人才项目(JCRCZN-2022-002)。
