Summary
Although scrapie has been known for a long time as a natural disease of sheep and goats, the pathogenesis in its natural host still remains unclear. To study the pathogenesis of natural scrapie, we used immunohistochemistry to monitor the deposition of PrPSc in various tissues, collected during a natural scrapie infection from sheep with the PrPVRQ/PrPVRQ genotype which were purposely bred for their short incubation period for natural scrapie. PrPSc was present in the lymphoid tissues of all animals from the age of 5 months 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. At 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 in-termediolateral column of the thoracic segments T8–T10. PrPSc 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 several spinal ganglia at 21 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 parasympathetic efferent fibers of the autonomic nervous system to the spinal cord and medulla 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 nerve fibers.
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van Keulen, L.J.M., Schreuder, B.E.C., Vromans, M.E.W., Langeveld, J.P.M., Smits, M.A. (2000). Pathogenesis of natural scrapie in sheep. In: Groschup, M.H., Kretzschmar, H.A. (eds) Prion Diseases. Archives of Virology. Supplementa, vol 16. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6308-5_5
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DOI: https://doi.org/10.1007/978-3-7091-6308-5_5
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