活体观察不同月龄阿尔茨海默病模型小鼠视网膜Aβ斑

Observation of β-amyloid plaques in retinas from live Alzheimer's model mice in different months

摘要:

目的：观察不同月龄阿尔茨海默病(AD)模型小鼠视网膜Aβ斑阳性率与AD病程的相关性。

方法：6、12月龄APP/PS1模型小鼠各6只，同月龄同背景非转基因C57小鼠各6只为正常对照。各组小鼠均进行水迷宫实验，检测空间学习记忆能力。姜黄素溶液连续灌胃3d，对24只48眼小鼠行眼底自发荧光照相检查，观察视网膜Aβ斑。

结果：水迷宫试验：与6月龄对照组(C6)相比，6月龄AD模型小鼠(AD6)游行时间显著增加(P<0.05)，游行路径长度及穿越站台次数也显著增加(P>0.05)； 与12月龄对照组(C12)相比，12月龄AD模型小鼠(AD12)游行持续时间、路径长度均显著增加(P<0.05)，穿越站台次数也显著增加(P>0.05)； 12月龄AD小鼠(AD12)与6月龄AD模型(AD6)小鼠相比，12月龄AD小鼠(AD12)游行持续时间、路径长度及穿越站台次数均显著增加(P<0.05)。姜黄素标记联合眼底自发荧光照相结果：AD6、AD12的视网膜后极部检测到了Aβ斑：6月龄AD模型小鼠中有2只小鼠出现了视网膜Aβ斑，视网膜Aβ斑阳性率为33%； 12月龄AD模型小鼠中有6只小鼠出现了视网膜Aβ斑，视网膜Aβ斑阳性率为100%； C6、C12均未检测出视网膜Aβ斑； 12月龄AD模型小鼠眼底Aβ斑阳性率明显高于6月龄AD模型小鼠(P<0.05)。

结论：6月龄AD模型小鼠已有认知功能障碍，且随着病程的延长病情逐渐加重，视网膜Aβ斑的阳性率也逐渐增加。

Abstract:

AIM: To study the correlation of β-amyloid(Aβ)plaques in retinas from Alzheimer's model mice in different months and progression of disease.

METHODS: Six-month(n=6)and twelve-month(n=6)old Alzheimer's model mice, together with six-month(n=6)and twelve-month(n=6)old C57 mice were in this experiment. Morris water maze test was to assess the spatial memory. After intragastrical administration of curcumin for consecutive three days, the Aβ plaques in retinas(n=48)from all mice(n=24)were detected by noninvasive in vivo optical imaging.

RESULTS: Morris water maze test: compared with the six-month control group(C6), six-month model mice(AD6)swam longer(P<0.05); and AD6 swam longer distance and experienced more crossing times than C6(P>0.05); compared with the twelve-month control group(C12), twelve-month model mice(AD12)swam longer, swam longer distance(P<0.05)and experienced more crossing times(P>0.05); compared with the six-month model mice(AD6), twelve-month model mice(AD12)swam longer, swam longer distance and experienced more crossing times(P<0.05). Moreover, the result of retinal Aβ plaques: We identified retinal Aβ plaques in postmortem from AD6 and AD12. Two six-month model mice had been detected retinal Aβ plaques, thus the positive rate of retinal Aβ plaques in six-month model mice was 33%; And six twelve-month model mice had been detected retinal Aβ plaques, thus the positive rate of retinal Aβ plaques in twelve-month model mice was 100%; Plaques were undetectable in age-matched non-AD individuals neither in six-month or in twelve-month; the positive rate of retinal Aβ plaques in AD12 was higher than AD6(P<0.05).

CONCLUSION: Six-month model mice(AD6)had already a decline of cognition; and the illness gradually increased with the extension of the disease, and the positive rate of retinal Aβ plaques is increasing with progression of Alzheimer's disease.