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邢敏,毛敬洁,陈文列,李钻芳.APP / PS1 双转基因 AD 模型小鼠海马区磁共振波谱和超微结构分析[J].中国实验动物学报,2020,28(2):0.
APP / PS1 双转基因 AD 模型小鼠海马区磁共振波谱和超微结构分析
Analyses of magnetic resonance spectroscopy and ultrastructure changes in the hippocampus of APP/ PS1 double transgenic AD model mice
投稿时间:2019-11-07  
DOI:10. 3969 / j.issn.1005-4847. 2020. 02. 013
中文关键词:  阿尔茨海默病  APP / PS1 转基因鼠  磁共振波谱  透射电镜  超微结构
英文关键词:Alzheimer’s disease, APP / PS1 transgenic mice, magnetic resonance spectroscopy, transmission electron microscope, ultrastructure
基金项目:
作者单位E-mail
邢敏 福建中医药大学中西医结合研究院,福州 350122 yiyaaha@ 163.com 
毛敬洁 1.福建中医药大学中西医结合研究院,福州 350122
2. 福建省中西医结合老年性疾病重点实验室,福州 350122 
maojingjie@ fjtcm.edu.cn 
陈文列 1.福建中医药大学中西医结合研究院,福州 350122
2. 福建省中西医结合老年性疾病重点实验室,福州 350122 
 
李钻芳 1.福建中医药大学中西医结合研究院,福州 350122
2. 福建省中西医结合老年性疾病重点实验室,福州 350122 
 
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中文摘要:
      目的 观察 APP / PS1 转基因鼠海马区中代谢物的变化与超微病理改变之间的联系,使该基因鼠更好地应用于阿尔茨海默病(AD)的实验研究。 方法 通过新物体识别实验比较 APP / PS1 转基因鼠和同龄、同背景野生鼠的学习记忆能力;通过氢质子磁共振波谱(1HMRS) 检测比较两组海马区 N-乙酰天冬氨酸(NAA)、肌醇 (mI)、胆碱(Cho)和谷氨酸(Glu)等代谢物的含量;通过透射电镜观察神经细胞和星形胶质细胞的超微结构。 结果 与野生鼠相比,转基因鼠学习记忆能力下降,两组间差异有统计学意义(P < 0. 05);海马区 NAA 与肌酸(Cr)比 值明显减少(P < 0. 05),mI/ Cr 和 Cho / Cr 增加(P < 0. 05);神经细胞和星形胶质细胞线粒体变性、固缩,次级溶酶 体数量增加,星形胶质细胞过度活化、吞噬营养障碍性突触。 结论 APP / PS1 转基因小鼠海马区 NAA、mI、Cho 等 代谢物的变化可以反映 AD 病变过程中 β-淀粉样蛋白诱发的异常炎症反应和突触结构的破坏等病理特征,为 APP / PS1 基因鼠更好地应用于 AD 研究提供实验依据。
英文摘要:
      Objective To investigate the connection between metabolic features and ultrastructure changes in hippocampus of APP / PS1 double transgenic mice, and to confirm whether this model is appropriate for Alzheimer’s disease (AD) research. Methods A novel object recognition test was conducted to compare learning and memory in APP / PS1 mice with age- and background-matched wild type mice. Metabolic features such as N-acetylaspartate (NAA), myo-Inositol (mI), choline (Cho), and glutamate (Glu) levels in the hippocampus were assessed using proton magnetic resonance spectroscopy. Cellular ultrastructures were observed using a transmission electron microscope. Results Compared with wild type mice, APP / PS1 mice exhibited significantly decreased learning and memory ability ( P < 0. 05), a significantly reduced NAA to creatine ( Cr) ratio ( P < 0. 05), and increased mI/ Cr and Cho / Cr (P < 0. 05 ) ratios in the hippocampus. Compared with wild type mice, APP / PS1 mice had the following features: mitochondria in neurons and astrocytes were irregularly shaped and condensed, there were more secondary lysosomes, astrocytes were over-active, and there were phagocytosed dystrophic neurites. Conclusions Pathological changes in NAA, mI, and Cho in the hippocampus of APP / PS1 mice could reflect abnormal inflammation and aberrant neurites evoked by beta amyloid in AD. Thus, APP / PS1 transgenic mice may represent a beneficial model for AD research.
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