隔离应激加速SAMP8小鼠记忆功能减退(英文)  

Isolation stress exacerbates memory- related behavioral deficits in SAMP8 mice

作　　者：董红心[1,2] 曾俊伟[2] 陈倩[1] 李菲[2] Susan A.Farr William A.Banks John E.Morley 

机构地区：[1]西北大学芬伯格医学院精神病学和行为科学教研室 [2]遵义医学院生理和药理教研室 [3]圣路易斯大学VA医学中心 [4]圣路易斯大学医学院老年病研究部,内科教研室

出　　处：《遵义医学院学报》2014年第1期26-33,38,共9页Journal of Zunyi Medical University

基　　金：美国国立卫生研究院科研基金资助项目(NO:[RO1]:AG 025824)

摘　　要：目的采用非转基因的早老小鼠(senescence-accelerated prone mice,SAMP8)模型以观察隔离应激是否影响该模型小鼠脑内Amyloid-β(Aβ)水平及记忆功能。方法将SAMP8小鼠从断奶开始单独隔离饲养至6个月,空白对照组每3只一笼不给予隔离处理。于实验第3个月和6个月,采用条件恐惧实验、空间逆向学习法测定小鼠的学习记忆能力。行为学检测结束后,检测血浆皮质酮水平、测定海马体积、脑组织Aβ含量、观察Aβ斑块及蛋白羰基水平。结果 3个月时,应激小鼠关联和暗示记忆能力严重受损;6个月时,应激小鼠空间逆向学习能力下降明显。与空白对照组小鼠相比,血浆皮质酮水平在应激小鼠组明显升高,海马体积显著缩小。然而,隔离应激6个月后并不能明显增加脑组织内可溶性Aβ水平,也无Aβ斑块沉积,但脑组织蛋白羰基水平显著提高。结论隔离应激可加速SAMP8小鼠记忆功能减退,可能与脑内氧化应激损伤相关。Objective To investigate whether isolation stress could influence Amyloid - 13 （AI3） -levels and im- pair memory function in a non - transgenic animal model of Alzheimer＇ s disease （AD） using senescence - accel- erated prone mice （SAMP8）. Methods SAMP8 mice performed from weaning for 6 months, while control mice that were not isolated were housed in groups of 3 in a standard - sized cage. After 3 and 6 months of isolation stress, all of the mice were accepted the tests of fear conditioning and spatial reversal learning. Following com- pletion of behavioral testing, plasma was collected for corticosterone measurement, hippocampal volume, tissueAβ levels, amyloid plaque deposition and protein carbonyl levels were assessed. Results The isolated mice showed significant contextual and cued memory deficits after 3 months, and spatial reversal learning deficits after 6 months. Compared to control mice, the corticosterone levels were higher in the stressed mice, the hippocampal volume was significantly smaller. However, isolation stress did not significantly increase soluble A[3 levels, and no amyloid plaques were detected after 6 months. But the protein carbonyl levels in isolated mice were signifi- cantly increased. Conclusion Isolation stress could exacerbate memory - related behavioral deficits in SAMP8 mice, the possible mechanism may be the injury produced by oxidative stress in brain.

关 键 词：隔离应激 条件性恐惧 空间逆向学习 海马体积 SAMP8小鼠 

分 类 号：R778[医药卫生—眼科]