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Development of the animal model for Alzhcimer disease

阿尔茨海默病动物模型的开发

基本信息

批准号：
06454331
负责人：
TAKEDA Masatoshi
金额：
$ 4.8万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

项目摘要

The animal models for Alzheimer disease (AD) based on epidemiological factor, metal intoxication, infection, head trauma, were developed and their significance were investigated.As for infectious factor, we inoculated buffy coat from patients to hamster brains. In the brain injected with buffy coat from AD,accumulations of the fibers immunopositive with anti-phosphorylated neurofilament H (NFH) and anti-tau antibodies were observed in nuclei of brain stem. The third passage experiment, i.e.the inoculatoin of the homogenate from the suffered hamster brain, showed that dephosphorylated NFH was also accumulated.As a model for head trauma, we beat rats on the heads by fluid percussion. The repetition of mild impact, which effects little damage if single blow, cause high immunoreactivities with anti-MAP2 and anti-pNFH in some neuronal cells. In the impact site, there was neuronal loss with the accumulation of glial fibrillary acidic protein. One month later, even contralateral site showed neuronal loss with the accumulation of p-NFH.We made aluminum intoxication in rabbit brain as a model of metal intoxication. Time-dependent dissociation between NFH and NFL level was observed in especially intoxicated brain stems. Besides the distribution of these proteins was uneven in altered neurons. The level of mRNA of NFH increased in time-dependent manner in brain stem, but only this phenomenon could not account for the increase of NFH protein. In the process of the NFH accumulations, dephosphorylated forms gathered in early stage, but phosphorylated forms increased gradually instead of dephosporylated NFH.It is interesting that fibrous accumulations were observed in the brains of three different model. It is suggested that impairment of axonal transport is most common event through the three models.

建立了基于流行病学因素、金属中毒、感染、头部创伤的阿尔茨海默病(AD)动物模型，并探讨其意义。对于感染因素，我们将患者的血沉棕黄层接种到仓鼠大脑中。在注射AD血沉棕黄层的大脑中，在脑干细胞核中观察到抗磷酸化神经丝H（NFH）和抗tau抗体免疫阳性纤维的积累。第三次传代实验，即接种受害仓鼠脑组织匀浆，结果显示去磷酸化NFH也有积累。作为头部创伤模型，我们用流体冲击击打大鼠头部。重复轻微撞击（单次撞击造成的损伤很小）会在某些神经元细胞中引起抗 MAP2 和抗 pNFH 的高免疫反应性。在撞击部位，随着神经胶质原纤维酸性蛋白的积累，神经元损失。一个月后，随着p-NFH的积累，对侧部位也出现神经元损失。我们以兔脑铝中毒作为金属中毒模型。在特别中毒的脑干中观察到 NFH 和 NFL 水平之间的时间依赖性分离。此外，这些蛋白质在改变的神经元中的分布不均匀。脑干中NFH mRNA水平呈时间依赖性增加，但仅此现象并不能解释NFH蛋白的增加。在NFH积累的过程中，去磷酸化的NFH在早期聚集，但磷酸化的NFH逐渐增多，而不是去磷酸化的NFH。有趣的是，在三种不同模型的大脑中都观察到了纤维状的积累。这表明轴突运输受损是这三种模型中最常见的事件。