| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Kazuo Kitasato Univ., School of Medicine, Assistant Professor, 医学部, 講師 (40189030)
KIJIMA Hisako Kitasato Univ., School of Medicine, Associate Professor, 医学部, 助教授 (90118810)
SASAHARA Takeshi Kitasato Univ., School of Medicine, Assistant Professor, 医学部, 講師 (10154014)
TAKI Tatsuo Kitasato Univ., School of Allied Health Sciences, Associate Professor, 医療衛生学部, 助教授 (70049097)
TAGUCHI Fumiaki Kitasato Univ., School of Allied Health Sciences, Professor, 医療衛生学部, 教授 (40050455)
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| Research Abstract |
1. It has been suspected that cytokines such as TNFα and IL1α participate in various neuropathological processes including spongy degeneration in transmissible spongiform encephalopathy. To explore this hypothesis, we inoculated Creutzfeld-Jakob disease (CJD) agent into brains of TNFα gene-deficient mice, and examined the expression of mRNAs of TNFα, IL1α, and glial fibrillary acidic protein (GFAP) by RT-PCR. The brains were also histologically and immuohistochemically examined. Both TNFα (+/+) and (-/-) mice showed clinical symptomes on 140 days after the inoculation. Overexpression of GFAP-mRNA was observed in all inoculated mice. Vacuolation of the brain tissues was observed at various levels diffusely in cereberum and cerebellum of TNFα (+/+) and (-/-) mice, in association with astologliaosis. There were no differences in neuropathological findings between TNFα (+/+) and (-/-) mice. Accumulation of PrPSc was detected particularly in the areas where vacuolation is prominent. Based o
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n the results obtained, it was concluded that TNFα is not an essential requirement for pathogenesis of CJD.
2. We found heightened expression of inducible nitric oxide synthase (iNOS)-mRNA in the brain of mice inoculated with CJD agent. To elucidate the de of iNOS in pathogenesis of CJD, CJD agent was inoculated into iNOS gene-deficient mice. Incubation periods, clinical symptomes, accumulation of PrPSc, and histopathological findings showing spongy degeneration in brain were not different between iNOS gene (+/+) and (-/-) mice. Like the findings observed in the experiment with TNFα gene-deficient mice, it was found that iNOS is not n essential requirement for pathogenesis of CJD.
3. Neuronal cell loss and spongiform degeneration are prominent histopathological features in CJD. Previously, histopathological observation showed that neuronal loss in CJD occurs through a process of programmed cell loss, apoptosis. However, apoptotic processes have not been examined biochemically in CJD brain so far. In this study, we evidenced that apoptosis occurs in the brain of CJD mice, showing DM.X fragmentation. Less
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