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、头部创伤的阿尔茨海默病(AD)动物模型，并对其意义进行了研究。在注射AD黄褐色大衣的大鼠脑内，可见抗磷酸化神经丝H(NFH)和抗tau抗体免疫阳性的纤维聚集在脑干的核团中。第三代实验，即接种病鼠脑组织匀浆，发现也积累了去磷酸化的NFH。作为头部创伤的模型，我们用液压冲击法敲打大鼠的头部。轻微撞击的重复，单次撞击几乎不会造成损伤，导致一些神经细胞中抗MAP2和抗pNFH的高免疫反应。撞击部位有神经元丢失，胶质纤维酸性蛋白积聚。1个月后，对侧脑组织也出现神经元丢失，p-NFH积聚。我们制作兔脑铝中毒模型。尤其是在中毒的脑干中，NFH和NFL水平之间存在着时间依赖性的解离。此外，这些蛋白在改变的神经元中的分布是不均匀的。脑干中NFH的mRNA水平呈时间依赖性增加，但仅此现象不能解释NFH蛋白的增加。在NFH的积聚过程中，早期有去磷酸化形式聚集，但磷酸化形式逐渐增加，而不是去磷孢子化NFH。有趣的是，在三种不同模型的脑中都观察到纤维堆积。这三种模型均提示轴突运输受损是最常见的事件。

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.