摘要
目的探讨睡眠剥夺对β淀粉样前体蛋白(amyloid precursor protein,APP)/早老素1(PS1)双转基因小鼠学习记忆及海马组织自噬相关蛋白表达的影响。方法选择APP/PS1双转基因小鼠24只,随机分为睡眠剥夺组12只和对照组12只。建立急性睡眠剥夺模型,Morris水迷宫检测小鼠行为学改变;免疫组织化学法检测颞叶内侧皮质及海马组织β淀粉样蛋白42(Aβ42)及自噬相关蛋白LC3表达;Western blot法测海马组织LC3-Ⅱ表达。结果与对照组比较,睡眠剥夺组小鼠逃避潜伏期明显延长,穿越平台次数明显减少;Aβ42阳性反应物表达明显增多,差异有统计学意义(P<0.05);海马组织LC3-Ⅱ相对表达量明显上调(0.27±0.15 vs 0.16±0.04,t=-2.61,P<0.05)。结论睡眠剥夺可促进APP/PS1双转基因小鼠认知功能障碍加重;海马组织自噬活性增强,可能是其介导阿尔茨海默病发病及进展的机制。
Objective To study the effect of sleep deprivation(SD)on learning and memory in APP/PS1 double transgenic mice and the expression of autophagy-related proteins in their hippocampus.Methods Twenty-four APP/PS1 double transgenic mice were randomly divided into SD group(n=12)and control group(n=12).An acute SD model was established.Changes in behaviors of the animals were recorded in Morris water maze.Expression of Aβ42 in temporal cortex and hippocampus and that of LC3 protein in hippocampus were detected with immunohistochemical staining.Expression of LC3-Ⅱ protein in hippocampus was detected by Western blot.ResultsThe escape latency time was significantly longer,the number of crossing platform times was significantly less,the expression level of Aβ42-positive reactant was significantly higher in SD group than in control group(P<0.05).The expression level of LC3-Ⅱin hippocampus was significantly higher in SD group than in control group(0.27±0.15 vs 0.16±0.04,t=-2.61,P<0.05).Conclusion SD can exacerbate the cognitive impairment and increase the autophagy activity in APP/PS1 double transgenic mice by mediating the onset and progression of AD.
作者
范倩倩
劳基通
贾丹丹
陈永敏
刘力源
刘晓斌
李其富
廖小平
马琳
Fan Qianqian;Lao Jitong;Jia Dandan;Chen Yongmin;Liu Liyuan;Liu Xiaobin;Li Qifu;Liao Xiaoping;Ma Lin(Department of Neurology,First Affiliated Hospital of Hainan Medical College,Haikou 570100,Hainan Province,China)
出处
《中华老年心脑血管病杂志》
CAS
北大核心
2018年第11期1202-1206,共5页
Chinese Journal of Geriatric Heart,Brain and Vessel Diseases
基金
海南省自然科学基金(20168300)
关键词
睡眠剥夺
淀粉样Β蛋白前体
早老素1
小鼠
转基因
自噬
阿尔茨海默病
记忆障碍
sleep deprivation
amyloid beta-protein precursor
presenilin-1
mice,transgenic
autophagy
Alzheimer disease
memory disorders
