STUDY ON THE NERVE-IMMUNE SYSTEMS AND CELLULAR FACTORS INFLUENCE TO THE PATHOGENICTTY AND DISTRIBUTION OF PRP^<Sc>IN ANIMAL PRION DISEASES

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The pathogenesis of animal prion diseases is influenced by prion strain, genetic factors, natural immunology and several cellular factors in the affected hosts. In this study, genetic factors, nerve-immune system and uptake of PrP^<Sc> by macrophages were mainly studied. The following results were obtained.1. Polymorpbisms of PrP gene: Polymorphisms of the 863 cattle, 118 caprine and 136 sika dear (Cervus Nippon) PrP genes in Japan were examined. Several single-nucleotide polymorphisms (SNPs) were found in cattle and sika dear, but not find any amino acid substitutions. Two polymorphisms associated with the resistance to scrapie were found in 118 caprine.2. Bovine and sheep nerve systems: To determine the location, namber and segmental distribution of sympathetic, parasympathetic and sensory neurons innervating the ileum in cattle and sheep, tracer experiments with horseradish peroxidase were conducted. The labeled neurons were detected in the celiac and cranial mesenteric ganglion complex in both cattle and sheep. Only a few labeled neurons existed in the caudal mesenteric ganglion and the paravertebral ganglia.3. Uptake PrP^<Sc> by immune cells: To clarify the uptake the PrP^<Sc> by immune cells, the involvement of bovine macrophage in the early stage of prion infection was studied. Brain homogenates of scrapie and BSE were degraded sequentially in bovine macrophage and bovine peripheral immune cells.A part of this research has been published in the papers, the other parts are now prepared in the papers.