Pathogenesis of natural scrapie in sheep

Although scrapie has been known for a long time as a natural disease of she ep and goats, the pathogenesis in its natural host still remains unclear. T o study the pathogenesis of natural scrapie, we used immunohistochemistry t o monitor the deposition of PrPSc in various tissues, collected during a na tural scrapie infection from sheep with the PrPVRQ/PrPVRQ genotype which we re purposely bred for their short incubation period for natural scrapie. Pr PSc was present in the lymphoid tissues of all animals from the age of 5 mo nths onwards. At this age, PrPSc was detected in the neural tissues only in the enteric nervous system (ENS) at the level of the duodenum and ileum. A t the age of 10 months, PrPSc was not only found in the ENS but also in the ganglion mesentericum cranialis/coeliacum, the dorsal motor nucleus of the vagus, and the intermediolateral column of the thoracic segments T8-T10. P rPSc was detected for the first time in the nucleus tractus solitarius and ganglion nodosus at 17 months of age and in the ganglion trigeminale and se veral spinal ganglia at 31 months of age. Since the scrapie agent consists largely, if not entirely of PrPSc, these results indicate that the ENS acts as a portal of entry to the neural tissues for the scrapie agent followed by centripetal and retrograde spread through sympathetic and parasympatheti c efferent fibers of the autonomic nervous system to the spinal cord and me dulla oblongata respectively. PrPSc accumulation in sensory ganglia occurs after infection of the CNS and is therefore probably due to centrifugal and anterograde spread of the scrapie agent from the CNS through afferent nerv e fibers.