Early spread of scrapie from the gastrointestinal tract to the central nervous system involves autonomic fibers of the splanchnic and vagus nerves

Although the ultimate target of infection is the central nervous system (CN S), there is evidence that the enteric nervous system (ENS) and the periphe ral nervous system (PNS) are involved in the pathogenesis of orally communi cated transmissible spongiform encephalopathies. In several peripherally ch allenged rodent models of scrapie, spread of infectious agent to the brain and spinal cord shows a pattern consistent with propagation along nerves su pplying the viscera. We used immunocytochemistry (ICC) and paraffin-embedde d tissue (PET) blotting to identify the location and temporal sequence of p athological accumulation of a host protein, PrP, in the CNS, PNS, and ENS o f hamsters orally infected with the 263K scrapie strain. Enteric ganglia an d components of splanchnic and vagus nerve circuitry were examined along wi th the brain and spinal cord. Bioassays were carried out with selected PNS constituents. Deposition of pathological PrP detected by ICC was consistent with immunostaining of a partially protease-resistant form of PrP (PrPSc) in PET blots. PrPSc could be observed from approximately one-third of the w ay through the incubation period in enteric ganglia and autonomic ganglia o f splanchnic or vagus circuitry prior to sensory ganglia. PrPSc accumulated , in a defined temporal sequence, in sites that accurately reflected known autonomic and sensory relays. Scrapie agent infectivity was present in the PNS at low or moderate levels. The data suggest that, in this scrapie model , the infectious agent primarily uses synaptically linked autonomic ganglia and efferent fibers of the vagus and splanchnic nerves to invade initial t arget sites in the brain and spinal cord.