NR AWRJ
AU Jeffrey,M.J.; McGovern,G.; Goodsir,C.M.; Gonzalez,L.; Martin,S.; Siso,S.
TI Different scrapie strains direct alterations in abnormal PrP processing pathways
QU European Society of Veterinary Pathology, 24th Meeting, Edinburgh, Scotland, 30.8.-2.9.2006, Poster 64: 172
IA http://www.esvp.eu/ESVP_meetings/Proceedings_2006.pdf
PT Konferenz-Poster
AB Using electron microscopy, we have studied the cellular changes and their relationship toPrPd accumulation in the brains of sheep infected with scrapie and compared these with the findings in conventional and transgenic mice infected with ME7, 263K, CWD and 87V. Scrapie-associated cellular changes included vacuolation, abnormal coated pits, membrane proliferation, increased lysosomes, and fibril formation. Fibrils were only seen in experimental rodent infections. Abnormally elongated and branched coated pits, sometimes connected directly to endosomes gave positive immunolabelling for both ubiquitin and PrPd. They were abundant in some sheep and rodent infections but were not found in others. They occurred on neuronal plasmalemma and along dendrites but not on axons, and were associated with increased cytoplasmic volume of endosomes and immature lysosomes. These changes suggest that a fraction of PrPd is not recycled but abnormally endocytosed. Membrane proliferation were found in astrocyte processes and in dendrites. These changes were directly and proportionally associated with PrPd localisation on cell membranes suggesting a causal relationship. Some PrPd was seen on cell processes adjacent to these areas suggesting PrPd release from infected cells to adjacent cell membranes. The proportions of each of these changes varied according to neuroanatomic site, cell type infected and source or strain. We suggest that different scrapie strains may be defined by distinct processing pathways of abnormal PrP. There are no consistent associations between PrPd accumulation and vacuolation or other non-specific degenerative features such as axon terminal degeneration or apoptosis.
AD Martin J. Jeffrey (m.jeffrey@vla.maff.gov.uk), Gillian McGovern, Caroline M. Goodsir, Lorenzo González, Stuart Martin, Sílvia Sisó (s.siso@vla.defra.gsi.gov.uk), VLA Lasswade Veterinary Laboratory, Pentlands Science Park, Bush Loan, Penicuik, Edinburgh EH26 OPZ, Scotland, UK
SP englisch
PO UK