Development of the animal model for Alzhcimer disease

本文以流行病学因素、金属中毒、感染、头部创伤为基础，建立了阿尔茨海默病（Alzheimer disease，AD）动物模型，并探讨了其意义。在注射AD血沉棕黄层的脑中，在脑干核中观察到抗磷酸化神经丝H（NFH）和抗tau抗体免疫阳性的纤维聚集。第三代实验，即接种仓鼠脑匀浆，也发现去磷酸化的NFH在脑内积聚。反复轻度撞击，如果单次打击，其影响很小，在一些神经元细胞中引起抗MAP 2和抗pNFH的高免疫反应性。在撞击部位，有神经元丢失，胶质细胞酸性蛋白积聚。一个月后，即使对侧也出现神经元丢失，并伴有p-NFH的蓄积。在特别是中毒脑干中观察到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的蓄积过程中，去磷酸化NFH在早期聚集，但磷酸化NFH逐渐增多，而非去磷酸化NFH。这表明，轴突运输障碍是最常见的事件，通过三个模型。

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.