How is the enteric nervous system involved in experimentally scrapie-infected sheep?

Although scrapie is extensively investigated in laboratory rodents, it is not a spontaneous disease of these animals, so that much can be learned from sheep, its natural host. After oral scrapie challenge, one of the early infection targets is the enteric nervous system (ENS), which, along with GALT, is a neuroinvasion site. We analysed the neurochemical code [nitric oxide synthase (nNOS), calbindin (CB) and glial fibrillary acid protein (GFAP) immunoreactivity (IR)] of ileum myenteric plexuses from Sarda breed sheep carrying various PrP genotypes. We have recently described the detailed pattern of nNOS and CB expression of healthy sheep ileum ENS (Chiocchetti, Cell Tiss. Res., 318, 2004). In this respect, alteration of the normal patterns of expression of calcium binding proteins would be likely to have profound effects on neuronal cell physiology, thus preceding their death. The results indicate an impressive reduction of CB-IR in cells and fibres. In several animals we observed that CB-IR was localized only in neuronal nuclei. A dramatic reduction of nNOS-IR was observed only in two sheep. Furthermore, in some specimens there were restricted ganglionic areas showing GFAP-IR depletion, suggesting a possible role of enteric glia in the infection’s pathogenesis. The results let us speculate that the sheep ENS could be a site of neuronal degeneration, anticipating that occurring at the central nervous system level.