NR AOVE
AU Krüger,D.; Lenz,G.; Thomzig,A.; Beekes,M.
TI Monitoring the Gut Wall of Hamsters Fed with Scrapie
QU International Conference - Prion diseases: from basic research to intervention concepts - TSE-Forum, 08.10.-10.10.2003, Gasteig, München - Poster session - PG-10
PT Konferenz-Poster
AB
Background: To further elucidate the intestinal pathogenesis of perorally acquired transmissible spongiform encephalopathies (TSEs) we investigated the small intestine of hamsters for the initial sites and spread of PrPsc deposition after oral uptake of infectivity. Also, the rectum was examined for the occurence of PrPsc in order to assess whether rectal biopsies could be used for the pre-clinical diagnosis of TSEs.
Methods: Hamsters were orally challenged with 263K scrapie. The rectum and small intestine were removed at various times after infection and the latter was dissected into 20 segments. PrPsc was extracted from samples and visualized by Western blotting.
Results: At 14 days post infection (dpi) no PrPsc could be detected in the small intestine. However, at 30 dpi, up to three speparate PrPsc-foci were observed in 3/6 animals in distal parts of the jejunum. At 60 dpi up to seven gut segments showing PrPsc deposition, predominantly in the distal part of the small intestine, were present in 4/6 animals. At this time, previously isolated PrPsc-foci started to show increasing confluence. In terminally ill hamsters (~170 dpi) the entire small intestine was positive for PrPsc. In contrast, rectal deposition of PrPsc could not be demonstrated at 70, 100 and 130 dpi but only at the clinical stage of scrapie.
Implications: Following ingestion of scrapie agent, initial infection of the intestinal wall may occur in separated foci at various and multiple sites. These sites need to be further scrutinized for the involvement of the gut-associated lymphoid tissue and enteric nervous system in gut-mediated neuroinvasion and must be differentiated from intestinal regions of PrPsc accumulation which have been invaded by secondary spread of agent within the intestinal wall. Rectal biopsy does not appear to allow a preclinical diagnosis of infection. However, when orally acquired human TSE is suspected, it might possibly provide a useful tool for differential diagnosis.
AD Dominique Krüger, Gudrun Lenz, Achim Thomzig, Michael Beekes, Robert Koch-Institut, Berlin, Germany
SP englisch
PO Deutschland