多靶点分子显像活体检测转基因阿尔兹海默病鼠脑神经病理变化  

Neuropathological changes in Alzheimer’s disease mice model based on multi-target molecular imaging

作　　者：魏枫 郭沈睿 程维维[1] 马玉飞 王辉[1] 尹雅芙 WEI Feng;GUO Shen-rui;CHENG Wei-wei;MA Yu-fei;WANG Hui;YIN Ya-fu(Department of Nuclear Medicine,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China)

机构地区：[1]上海交通大学医学院附属新华医院核医学科,上海200092

出　　处：《中国临床医学影像杂志》2023年第6期381-389,共9页Journal of China Clinic Medical Imaging

基　　金：国家自然科学基金面上项目(81974270)。

摘　　要：目的:通过多靶点分子影像技术及分子生物学技术检测三转基因阿尔茨海默病(3xTg-AD)小鼠的神经病理进展变化。方法:对不同月龄的3xTg-AD小鼠及杂交野生型对照小鼠进行多靶点分子显像。通过^(18)F-AV45、^(18)F-PBR06、^(18)F-FDG mi-cro PET/CT检测小鼠脑内的淀粉样斑块(Aβ)沉积、神经炎症、小胶质细胞激活及神经元功能情况;动物行为学实验检测小鼠认知功能的变化;免疫组织化学染色法检测小鼠脑内Aβ沉积情况及小胶质细胞激活情况。结果:动物行为学结果显示3xTg-AD小鼠6月龄时出现明显认知障碍。Micro PET/CT半定量分析显示,6月龄起3xTg-AD小鼠脑内^(18)F-FDG摄取较杂交野生型小鼠下降明显;6月龄、9月龄、12月龄组3xTg-AD小鼠大脑皮层及海马^(18)F-AV45摄取均较杂交野生型小鼠升高;3xTg-AD小鼠大脑皮层^(18)F-PBR06摄取随月龄增加而增加,但杂交野生型小鼠随月龄增加变化不明显。免疫荧光染色结果显示,6月龄3xTg-AD小鼠大脑皮层中出现Aβ沉积及小胶质细胞增生,并随月龄增加Aβ沉积增多、小胶质细胞增生明显。结论:3xTg-AD小鼠的认知功能呈进行性下降,神经病理随月龄增加进展明显。分子影像技术^(18)F-FDG、^(18)F-AV45、^(18)F-PBR06 micro PET/CT显像可活体检测3xTg-AD小鼠的神经病理进展。Objective:To investigate the neuropathologic changes of 3xTg-AD mice model of Alzheimer’s disease(AD)by multi-target molecular imaging and molecular biology techniques.Methods:^(18)F-AV45,^(18)F-PBR06,and^(18)F-FDG micro PET/CT were used to detect the deposition of amyloid beta(Aβ),neuroinflammation,microglia activation,and neuronal function in the brain of 3xTg-AD mice and wild type mice at different months of age.Behavioral experiments were applied to detect the changes in cognitive function.The deposition of Aβand the activation of microglia in the brain was detected by immunohisto-chemical staining.Results:The behavioral results showed that the 3xTg-AD mice had obvious cognitive impairment at the age of 6 months.Micro PET/CT semi-quantitative analysis showed that the^(18)F-FDG uptake in the cerebral cortex of 3xTg-AD mice was significantly lower than that of wild type mice since 6 months of age.The^(18)F-AV45 uptake in the cerebral cortex and hippocampus of 3xTg-AD mice was higher than that of wild type mice at the age of 6 months,9 months and 12 months.The uptake of^(18)F-PBR06 in the cerebral cortex of 3xTg-AD mice increased with age,while there was no significant increase in wild type mice.Immunofluorescent staining results showed that there were Aβdeposition and microglia proliferation in the cerebral cortex of 3xTg-AD mice at the age of 6 months.The Aβdeposition increased significantly with age.Conclusion:The cognitive function of 3xTg-AD mice declined progressively.The neuropathological changes progressed significantly with aging.Micro PET/CT can detect the neuropathological progresses of 3xTg-AD mice in vivo.

关 键 词：阿尔茨海默病 正电子发射断层显像计算机体层摄影术 

分 类 号：R749.16[医药卫生—神经病学与精神病学] R817.4[医药卫生—临床医学]