NR AWNU
AU Siso,S.; Jeffrey,M.J.; Baird,H.; Martin,S.; Bellworthy,S.J.; Chianini,F.; Gonzalez,L.
TI The topographical distribution of prion protein in the brains of sheep challenges the current hypothesis of neuroinvasion
QU International Conference - Prion 2006: Strategies, advances and trends towards protection of society - 3.10.-6.10.2006, Torino, Italy, Lingotto Conference Centre - Poster sessions PA-52
PT Konferenz-Poster
AB Clinical signs in sheep scrapie usually appear after widespread accumulation of the disease-associated isoform of the prion protein (PrPd) in the brain. It is generally believed that, after oral exposure -often followed by lymphoid tissue replication-, neuroinvasion occurs via the autonomic nervous system and, as a result, the dorsal nucleus of the vagus nerve (DMNV) is the initial point of PrPd accumulation in the brain. Nevertheless, the topographical and temporal spread of PrPd to other brain areas during the preclinical period in relation to the route of exposure and other factors is not properly documented. We examined by immunohistochemistry the brains of 35 sheep either exposed to natural infection (Shetland and Suffolk sheep from two flocks) or to experimental challenge; these last included scrapie by the oral, subcutaneous and intravenous routes in Cheviot and Suffolk sheep, and BSE in Suffolk, Cheviot and Romney sheep by the oral or intracerebral routes. All animals were studied at preclinical stage of scrapie either because they died from intercurrent conditions, were part of a sequential killing strategy or were culled after confirmation of infection by biopsy. We found that initial PrPd accumulation occurred in most cases in the DMNV and in the hypothalamus, regardless of the breed of sheep, PrP genotype, TSE source and, more surprisingly, route of infection. Moreover, the topographical distribution and magnitude of PrPd deposition, with consistent involvement of the periventricular organs, suggest that the pathways of entry of the TSE agents in the brain might be different from those arising from the autonomic nervous system. Also, the pattern of PrPd spread within the brain seemed to be TSE strain-dependent. These findings, and the apparently route-related susceptibility to TSE infection in sheep of some genotypes, argue for a review of the current hypothesis of TSE neuroinvasion route.
AD Sílvia Sisó (s.siso@vla.defra.gsi.gov.uk), Martin J. Jeffrey, H. Baird, Stuart Martin, Lorenzo González, Veterinary Laboratories Agency - Lasswade, Pentlands Science Park, Bush Loan, Midlothian EH26 0PZ, UK; S. Bellworthy, VLA-Weybridge, Addlestone, Surrey KT15 3NB, UK; Francesca Chianini, Moredun Institute, Pentlands Science Park, Bush Loan, Midlothian EH26 0PZ, UK
SP englisch
PO Italien