Scrapie-associated prion protein in the gastrointestinal tract of sheep with natural scrapie.

The scrapie-associated prion protein (PrPSc), which is closely associated with scrapie infectivity, accumulates in the brain and lymphoid tissues of sheep with natural scrapie. The most probable portal of entry of the scrapie agent in sheep is the alimentary tract; little attention, however, has been paid to the gastro-intestinal tract in scrapie research. In this study, we examined the presence and distribution of PrPSc within the gastro-intestinal tract of sheep with natural scrapie and scrapie-negative sheep. It was found that PrPSc accumulated in the enteric nervous system (ENS) of all scrapie-infected sheep but not in scrapie-negative sheep. The distribution of PrPSc within the ENS was then studied along the entire gastro-intestinal tract in seven scrapie-infected sheep carrying various PrP genotypes. In sheep with the highest genetically determined susceptibility to scrapie, PrPSc was detected in the ENS from the oesophagus to the rectum. In sheep with a lower genetic susceptibility to scrapie, PrPSc was present in the ENS of the forestomachs, small intestine and large intestine but not in the oesophagus. In a scrapie-negative sheep with a PrP genotype associated with scrapie resistance, no PrPSc was seen in the ENS at any site along the gastro-intestinal tract. The presence of PrPSc within the ENS of scrapie-infected sheep indicates a possible role of the ENS in the pathogenesis of natural scrapie as a portal of entry to the central nervous system.