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

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.