In FY09 the neurodegenerative effect of expression of truncated prion protein (PrP) was blocked by expression of normal full-length PrP on neurons only or astrocytes only, indicating that there was not a specific cell type required for this rescue effect. In agreement with this conclusion, anchorless PrP secreted from cells could also mediate a partial but significant rescue effect. Furthermore, hamster PrP was as efficient as mouse PrP in mediating this rescue, so the species-specific PrP sequence differences between hamster and mouse, which are so important for prion disease species-barriers, are not important in the rescue from neurodegeneration mediated by truncated PrP. This result implies that these species-specific sequence differences might influence PrP misfolding in prion diseases, whereas they might not influence molecular interactions between normally folded PrP and other brain molecules involved in the truncated PrP neurodegenerative process. Work studying scrapie infection in C57BL/10 wild-type mice as well as in transgenic mice expressing anchorless PrP has shown high infectivity titers in brown and white fat tissues. Further experiments have demonstrated that fat tissues of deer with chronic wasting disease also have significant prion infectivity in fat. Therefore fat tissue should be considered in assessment of risk of prion disease spread among animal species. In other experiments the possible roles of cytokines and chemokines in the scrapie pathogenesis and the host response to scrapie-induced disease was studied. Protein levels of 24 cytokines and chemokines were analyzed by multiplex analysis in brain homogenates of scrapie-infected and uninfected C57BL/10 mice, PrPnull mice and transgenic mice expressing only anchorless PrP. Elevation of levels of 10 cytokines or chemokines were detected in infected brains. Cytokines were also studied in culture fluids of microglia and astroglia stimulated by scrapie-infected or uninfected brain homogenates. The results indicated that after stimulation by scrapie brain, microglia made only two cytokines, whereas astroglia made ten. These responses to scrapie infection or in vitro stimulation were more likely responses to the damage induced by scrapie rather than an essential parts of the scrapie pathogenic disease-inducing process.
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