Development of the animal model for Alzhcimer disease

建立了基于流行病学因素、金属中毒、感染、头部外伤的阿尔茨海默病（AD）动物模型，并探讨了其意义。至于感染因子，我们将患者的灰褐色皮毛接种到仓鼠脑内。在脑内注射了AD的灰白色涂层后，脑干核内可见抗磷酸化神经丝H （NFH）和抗tau抗体免疫阳性纤维的积累。第三次传代实验，即接种鼠脑匀浆，发现也积累了去磷酸化的NFH。作为头部创伤的模型，我们用液体击打老鼠的头部。轻击的重复，单次损伤小，可引起部分神经细胞抗map2和抗pnfh的高免疫反应。撞击部位出现神经元丢失，胶质原纤维酸性蛋白积聚。1个月后，甚至对侧部位也出现神经元丢失，p-NFH积累。我们用兔脑铝中毒作为金属中毒模型。特别是在醉酒的脑干中，NFH和NFL水平存在时间依赖性分离。此外，这些蛋白质在改变的神经元中分布不均匀。脑干中NFH mRNA水平呈时间依赖性升高，但仅这一现象不能解释NFH蛋白的升高。在NFH积累过程中，早期有去磷酸化的形式聚集，但磷酸化形式逐渐增加，而非去磷酸化的NFH。有趣的是，在三种不同模型的大脑中观察到纤维堆积。这三种模型表明，轴突运输损伤是最常见的事件。

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.