NR AOWM
AU McBride,P.A.; Donaldson,M.I.; Oxley,J.; Bruce,M.E.; Farquhar,C.F.
TI The Pathways of Scrapie Neuroinvasion Differ between Neurotropic and Lymphotropic Models of Oral TSE Infection
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - PG-20
PT Konferenz-Poster
AB The oral route is relevant for natural transmission of Transmissible Spongiform Encephalopathies (TSEs) but the mechanisms involved require elucidation. The peripheral nervous system (PNS) and lymphoreticular system (LRS) are known to have a role in peripheral infection. Previous studies using hamsters orally-challenged with 263K scrapie showed that the infectious agent spread from the gastrointestinal tract to the CNS via the splanchnic and vagus nerves. Autonomic and enteric ganglia were early reservoirs of infection but there was little LRS involvement. For ME7 scrapie agent in mice an initial LRS phase is required before neuroinvasion after intraperitoneal inoculation. We aimed to determine the details of neuroinvasion in ME7 orally-challenged mice. Immunocytochemistry and PET blotting were used to detect PrPsc in potentially relevant tissues removed throughout the incubation period. Results showed no evidence that ME7 reached the CNS primarily via vagus or splanchnic nerves and that other nerves/routes have a greater involvement in dissemination of agent in this model. PrPsc was first detected in the lateral hypothalamus and substantia gelatinosa of brain and spinal cord, respectively. While PrPsc was seen in the CNS nuclei connected with the vagus and splanchnic nerves (dorsal motor vagal nucleus and intermediolateral cell column) these were not early targets. PrPsc was undetected in autonomic or enteric ganglia until very late in the incubation but was seen in gut associated lymphoid tissue at early stages of disease. These data indicate that the interaction and relative contribution of the PNS and LRS in establishing oral infection differs between TSE models and that TSE agents can access the CNS by different routes from the GI tract. This may impact on the design of potential intervention strategies.
AD Patricia A. McBride (tricia.mcbride@bbsrc.ac.uk), Moira E. Bruce (moira.bruce@bbsrc.ac.uk), Christine F. Farquhar (christine.farquhar@bbsrc.ac.uk), Institute for Animal Health, BBSRC and MRC, Neuropathogenesis Unit, Ogston Building, West Mains Road, Edinburgh EH9 3JF, Scotland, UK
SP englisch
PO Deutschland