KUDA Takashi Osaka University, Assistant, 医学部, 助手 (10273632)
TANIGUCHI Norio Osaka University, Assistant, 医学部, 助手 (30263255)
武田 雅俊 大阪大学, 医学部, 講師 (00179649)
播口 之朗 大阪大学, 医学部, 助教授 (10028459)
|Budget Amount *help
¥7,500,000 (Direct Cost : ¥7,500,000)
Fiscal Year 1995 : ¥1,400,000 (Direct Cost : ¥1,400,000)
Fiscal Year 1994 : ¥6,100,000 (Direct Cost : ¥6,100,000)
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.