APP/PS1年轻小鼠的早期学习记忆缺陷及血清注射治疗效果分析

Serum Injection Rescues Learning and Memory Deficits in APP/PS1 Young Mice

目的:明确经典阿尔兹海默症(Alzheimer's Disease,AD)小鼠模型APP/PS1的年轻小鼠是否存在学习记忆障碍,并探讨尾静脉注射同龄小鼠的血清是否可以改善年老AD小鼠的认知能力。方法:根据转基因小鼠的基因型,将同龄小鼠分为wildtype(WT)和APP/PS1两组,首先用物体辨别实验(Novel object recognition,NOR)检测2个月龄小鼠的认知能力(90min retention:WT n=6,APP/PS1 n=8; 24hours retention:WT n=7, APP/PS1=8),同时用Morris水迷宫实验(Morris water maze,MWM)检测2个月龄小鼠的空间学习记忆能力(WT n=6, APP/PS1 n=5);采用内眦取血法从8月龄小鼠中获取全血,高速离心获得血清。将8月龄APP/PS1小鼠分为两组:对照组注射PBS(n=7),实验组注射血清(n=6),每周注射两次,100μL/只/次,连续注射3周。注射结束后,用NOR法检测对照组和实验组小鼠的认知能力。结果:NOR实验结果显示APP/PS1小鼠的辨别指数(Discrimination index(%))显著低于WT小鼠(P<0.05);MWM实验结果显示APP/PS1小鼠到达平台的时间明显长于WT小鼠,同时在测试阶段中,APP/PS1小鼠在目的象限的探索时间及穿越次数显著低于WT小鼠(P<0.05);治疗实验中,与对照组APP/PS1小鼠的辨别指数相比较,实验组APP/PS1小鼠在注射同龄小鼠的血清后,其物体辨别指数显著升高(P<0.05),小鼠脑中的Aβ沉淀明显减少。结论:APP/PS1小鼠在2个月左右就会表现出明显的学习记忆障碍;注射正常同龄鼠的血清可以明显改善APP/PS1小鼠的学习记忆能力同时阻碍Aβ沉淀的形成。

Objective:To investigate the learning and memory ability in young Alzheimer’s disease(AD)APP/PS1 mouse model,and identify whether serum injection can rescue these defects.Methods:According to the genotype,the same age male mice were divided into two groups,the wildtype(WT)and APP/PS1 groups.Firstly,we performed novel object recognition(NOR)to evaluate the recognition ability of two-months old male mice(90 min retention:WT n=6,APP/PS1 n=8;24 hours retention:WT n=7,APP/PS1=8),and carried out Morris water maze(MWM)to test the spatial learning and memory in two-months old mice(WT n=6,APP/PS1 n=5);Blood was collected from the inner canthus of 8-months old mice,and the serum was obtained by super-centrifugation.8-months old APP/PS1 mice were divided into two groups,the control group which was injected by PBS buffer(APP/PS1 n=7),and the experimental group was injected with serum(APP/PS1 n=6),injection was performed twice a week,100μL/mice/time,for 3 weeks.After injection,NOR was performed to evaluate the therapeutic effect.Results:Compared with the WT mice,the discrimination index of APP/PS1 mice is significantly decreased in NOR(P<0.05).The latency of APP/PS1 mice is obviously longer than that of WT mice(P<0.05).Moreover,compared with those of WT mice,the time spent and crossing number of APP/PS1 in target quadrant are significantly reduced during the testing stage(P<0.05).About the rescue experiment,we find that the group which injected with serum obtained higher discrimination index and less Aβplaque than those in PBS injected group(P<0.05).Conclusions:Obvious learning and memory deficits occurred in APP/PS1 young mice at about 2-months old,and the same-age serum injection could rescue recognition defects and reduce Aβformation in APP/PS1 mice.