慢性应激通过增加齿状回的促肾上腺皮质激素释放因子减轻阿尔茨海默病样大鼠空间学习记忆损伤  

Chronic stress attenuates spatial learning and memory impairment in a rat model of Alzheimer disease by increasing CRF expression in hippocampal dentate gyrus

作　　者：徐铭振 冯慧 李盛辉 卿培 吴喜悦 肖斌[1] XU Mingzhen;FENG Hui;LI Shenghui;QING Pei;WU Xiyue;XIAO Bin(College of Medicine,Yanbian University,Yanji 133002,China)

机构地区：[1]延边大学医学院,吉林延吉133002

出　　处：《中国病理生理杂志》2023年第7期1181-1187,共7页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.32160195);吉林省科技厅项目(No.YDZJ202201ZYTS255);延边大学大学生创新创业训练计划项目。

摘　　要：目的:观察慢性应激(CS)对阿尔茨海默病(AD)样学习记忆损伤模型大鼠海马齿状回(DG)的促肾上腺皮质激素释放因子(CRF)及其1型受体(CRFR1)的影响,并探讨CRFR1在CS引起的AD样模型大鼠空间学习和记忆能力改变中的作用。方法:雄性Wistar大鼠随机分为对照(CON)组、AD模型(AD)组和AD给予CS(AD+CS)组,每组7只。用侧脑室单次注射链脲佐菌素联合长期腹腔注射D-半乳糖(每天1次,共6周)的方法制备AD样学习记忆损伤模型大鼠;AD+CS组大鼠在D-半乳糖注射的后4周,每天随机给予一种应激原刺激。Morris水迷宫评估大鼠的空间学习和记忆能力;免疫组织化学染色观察海马Aβ_(1-42)的表达;ELISA检测DG区CRF的水平;Western blot法观察DG区CRFR1表达。之后,AD大鼠DG区注射CRFR1阻断剂R121919,观察其对CS条件下的AD样模型大鼠空间学习和记忆能力的影响。结果:与CON组比较,AD样模型大鼠的空间学习和记忆能力显著下降,且海马区Aβ_(1-42)沉积增多;而给予CS可缓解AD样模型大鼠的空间学习记忆障碍,减少海马Aβ_(1-42)沉积。与CON组比较,AD组大鼠DG区CRF水平和CRFR1表达均显著降低(P<0.05),而AD+CS大鼠DG区的CRF水平和CRFR1表达均显著高于AD组(P<0.05)。大鼠DG区微量注射R121919显著损伤CS条件下AD大鼠的空间学习和记忆能力(P<0.05)。结论:CS增加AD样模型大鼠DG区CRF水平,后者通过激活CRFR1减轻AD样模型大鼠的空间学习和记忆功能损伤。AIM:To observe the effects of chronic stress(CS)on corticotropin-releasing factor(CRF)and its receptor CRFR1 in the hippocampal dentate gyrus(DG)of Alzheimer disease(AD)model rats,and to explore the role of CRFR1 in the spatial learning and memory impairment of AD-like rats under CS conditions.METHODS:Male Wistar rats were randomly divided into control(CON),AD,and AD+CS groups(n=7 per group).The AD model was generated via a single intracerebroventricular injection of streptozotocin combined with a daily intraperitoneal injection of D-galactose for 6 consecutive weeks.The rats in AD+CS group were randomly given one of seven different stressors daily in the last 4 weeks.The spatial learning and memory abilities of the animals were evaluated using Morris water maze test.The expression level of Aβ1-42 in the hippocampus was measured by immunohistochemistry.The level of CRF in the DG was measured by ELISA.The expression of CRFR1 in the DG was determined by Western blot.The role of CRFR1 in spatial learning and memory of AD rats under CS was examined via microinjection of its antagonist(R121919)into the DG.RESULTS:Compared with CON rats,AD model animals displayed impaired spatial learning and memory capacity,as well as increased expression of Aβ1-42 in the hippocampus.However,these effects were significantly attenuated by exposure to CS.Additionally,compared with CON group,the levels of CRF and CRFR1 in the DG were significantly lower in AD group(P<0.05),but these changes were significantly mitigated in AD+CS group(P<0.05).Meanwhile,the microinjection of R121919 into the DG significantly impaired the spatial learning and memory abilities of AD+CS rats(P<0.05).CONCLUSION:Chronic stress attenuates spatial learning and memory impairment in AD model rats by increasing CRF level and CRFR1 expression in the DG.

关 键 词：慢性应激 阿尔茨海默病 促肾上腺皮质激素释放因子 海马齿状回 空间学习和记忆 

分 类 号：R338.6[医药卫生—人体生理学] R363[医药卫生—基础医学]