NR AOQG

AU Beekes,M.; Thomzig,A.; Kratzel,C.; Lenz,G.; Mai,J.; Krüger,D.; Schulz-Schaeffer,W.J.; McBride,P.A.

TI Pathophysiology of peripheral PrPsc-routing in hamsters fed with scrapie

QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Oral sessions OS-25

PT Konferenz-Vortrag

AB Background: Hamsters fed with scrapie provide an animal model that during the past few years has revealed key pathogenetic features of the spread of infection through the body in orally acquired transmissible spongiform encephalopathies (TSEs).
Methods: Using PrPsc as a biochemical marker for infectious TSE agent, and immunohistochemistry, Western- and paraffin-embedded tissue (PET) blotting for its detection, it was possible to map the temporal-spatial spread of infection from the alimentary tract to the central nervous system.
Results: This revealed early infection of the gut-associated lymphoid tissue and the enteric nervous system following ingestion of infectivity. Subsequently, the agent invades initial target sites in the brain and spinal cord in a defined temporal sequence via synaptically linked autonomic ganglia and efferent fibres of the vagus and splanchnic nerves, respectively. Furthermore, at the terminal stage of the disease, skeletal muscles of hamsters orally infected with scrapie show substantial accumulations of PrPsc.
Implications: As similar pathogenetic mechanisms may also operate in naturally occurring scrapie of sheep and goats, field cases of bovine spongiform encephalopathy (BSE) in cattle, and orally transmitted or naturally occurring Chronic Wasting Disease (CWD) of elk and deer, the findings in our animal model highlight the necessity to investigate thoroughly the TSE risk in the autonomic nervous system and muscles of these species.

AD M. Beekes, A. Thomzig, C. Kratzel, G. Lenz, J. Mai, D. Krüger, Robert Koch-Institut (P26), Nordufer 20, 13353 Berlin, Germany; W.J. Schulz-Schaeffer, Georg-August-Universität Göttingen, Institut für Neuropathologie, Robert-Koch-Str. 40, 37075 Göttingen, Germany; Patricia A. McBride (tricia.mcbride@bbsrc.ac.uk), Institute for Animal Health, BBSRC and MRC, Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH9 3JF, Scotland, UK

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