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Study of the establishment of animal model with Alzheimer's disease to control thepathological aging

建立阿尔茨海默病动物模型控制病理性衰老的研究

基本信息

批准号：
10670921
负责人：
TADOKORO Mamoru
金额：
$ 1.73万
依托单位：
St. Marianna University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670921/
关键词：
Pathological Aging Alzheimer's desease Animal Model Niemann-Pick disease

项目摘要

Neuropathological studies of patients with Niemann-Pick disease type C (NPC) have revealed neurofibrillary tangles (NFT) in cases showing slowly progressive chronic courses. However, no NFT have been noted in NPC patients younger that 20 years, and it is known that long-term perturbation of neuronal cellular metabolism for 10 years or more may result in NFT formatiion.Mice with NPC, which shows autosomal recessive inheritance, develop hepatosplenomegaly and neurological manifestations such as ataxia and tremor, and die at about 14 weeks of age. This is not comparable with the time scale of NFT positive NPC in humans. Here we examined murine NPC (spm/spm) neuropathologically, using LFB-Bodian staining , electron microscopy and immunohistochemistry with anti Alzheimer's neurofibrillary tangle (ANT, Ab39) antibody, in order to investigate Alzheimer's neurofibrillary changes.Neurofibrillary changes resembling NFT can be seen microscopically in neuranal cells of cerebral cortex, hippocampal gyrus and midbrain older at 11 and 13-week old spm/spm by LBF-Bodian staining and by immunostaining with commercially available anti-PHF-tau. However, only neuron from neocortex can be staind with anti ANT (Ab39) antibody. Equally, paired helical filaments only can be seen in the neuron of neocortex. The present findings of NFT-like structure in the neocortex of murine NPC may provide an animal model for elucidating the pathogenesis of Alzheimer's disease. We also tried to establish the neuronal cell culture from the brain of newborn spm, but have not been successful yet.

对C型尼曼-匹克病（NPC）患者的神经病理学研究显示，在慢性病程缓慢进展的病例中存在神经元缠结（NFT）。然而，在年龄小于20岁的NPC患者中没有发现NFT，并且已知神经元细胞代谢的长期扰动10年或更长时间可能导致NFT的形成。具有NPC的小鼠表现为常染色体隐性遗传，发展为肝脾肿大和神经系统表现如共济失调和震颤，并且在约14周龄时死亡。这与人类NFT阳性NPC的时间尺度不可比较。本文应用LFB-Bodian染色、电镜和抗Alzheimer神经元缠结免疫组化等方法对小鼠NPC（spm/spm）进行了神经病理学研究（ANT，Ab 39）抗体，以研究阿尔茨海默氏病的神经细胞学变化。在显微镜下可以在大脑皮层的神经元细胞中看到类似NFT的神经细胞学变化，通过LBF-Bodian染色和通过用可商购的抗PHF-tau进行免疫染色，在11和13周龄spm/spm的海马回和中脑老化。但抗ANT（Ab 39）抗体只能显示新皮层神经元。同样，成对的螺旋丝也仅见于新皮层神经元。小鼠鼻咽癌新皮层神经纤维瘤样结构的发现可能为阐明Alzheimer病的发病机制提供了一个动物模型。我们也尝试建立新生spm脑神经细胞培养，但尚未成功。