Disease-associated PrP in the enteric nervous system of scrapie-affected Suffolk sheep

• Published in: Journal of general virology 2003-05, Vol.84 (5), p.1327-1338
• Main Authors: Heggebo, Ragna, Gonzalez, Lorenzo, Press, Charles McL, Gunnes, Gjermund, Espenes, Arild, Jeffrey, Martin
• Format: Article
• Language: English
• Subjects: Animals; Enteric Nervous System - metabolism; Enteric Nervous System - pathology; Immunohistochemistry; Microscopy, Electron; Peyer's Patches - metabolism; Peyer's Patches - ultrastructure; Prions - metabolism; Prions - pathogenicity; Scrapie - metabolism; Scrapie - pathology; Scrapie - physiopathology; Sheep
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/vir.0.18874-0

1 Department of Morphology, Genetics and Aquatic Biology, Norwegian School of Veterinary Science, PO Box 8146 Dep., N-0033 Oslo, Norway 2 Lasswade Veterinary Laboratory, Pentlands Science Park, Bush Loan, Penicuik, Midlothian EH26 0PZ, UK Correspondence Charles Press Charles.Press{at}veths.no Disease-associated prion protein (PrP d ) in the enteric nervous system (ENS) of 20- to 24-month-old Suffolk sheep in the late subclinical and early clinical phase of scrapie was studied. Sites in the alimentary tract extending from the forestomachs and abomasum to the colon from scrapie-affected sheep (PrP ARQ/ARQ ) and scrapie-resistant sheep (PrP ARR/ARQ and PrP ARR/ARR ) were examined. PrP d was found only in scrapie-affected sheep and was most prominent in the ENS when abundant deposits of PrP d were also present in adjacent lymphoid nodules. Immunolabelling with the nerve fibre markers PgP 9.5 and neuron-specific enolase and the satellite cell marker glial fibrillary acidic protein revealed the extensive ganglionated networks of the myenteric and submucosal plexi. Fewer nerve fibres were present in the lamina propria, T-cell dominated interfollicular areas and dome regions of Peyer's patches. A substantial network of nerve fibres was detected in many lymphoid nodules of both the scrapie-affected and scrapie-resistant sheep. Nerve fibres were also detected within the capsule of lymphoid nodules. Electron microscopy revealed the presence of nerves in the lymphoid nodules, showing a close association with follicular dendritic cells, lymphocytes and tingible body macrophages. In demonstrating that lymphoid nodules in the Peyer's patches of scrapie-affected sheep possess a substantial network of nerve fibres, the present study shows that nodules provide close contact between nerve fibres and cell populations known to contain abundant PrP d , including follicular dendritic cells and tingible body macrophages, and that gut-associated lymphoid nodules in sheep may represent an important site for neuroinvasion. Published ahead of print on 10 February 2003 as DOI 10.1099/vir.0.18874-0.