Pathogenesis of natural scrapie in sheep
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.
KeywordsGanglion Trigeminale Bovine Spongiform Encephalopathy Medulla Oblongata Vestibular Nucleus Enteric Nervous System
Unable to display preview. Download preview PDF.
- 7.Farquhar CF, Somerville RA, Dornan J, Armstrong D, Birkett CR, Hope J (1993) A review of the detection of PrPSc. In: Transmissible Spongiform Enceph-alopathies. A consultation on BSE with the Scientific Veterinary Committee of the Commission of the European Communities held in Brussels, 14–15 September 1993, Brussels, pp 301–313Google Scholar
- 10.Hadlow WJ (1990) To a better understanding of scrapie. In: Bradley R, Savey M, Marchant B (eds) Current topics in veterinary medicine and animal science, vol. 55: Sub- Acute Spongiform Encephalopathies, proceedings of a seminar in the CEC Agricultural Research programme held in Brussels, 12–14 November 1990. Kluwer Academic Publishers, Dordrecht, pp 117–130Google Scholar
- 33.Yates BJ, Grelot L, Kerman IA, Balaban CD, Jakus J, Miller AD (1994) Organization of vestibular inputs to nucleus tractus solitarius and adjacent structures in cat brain stem. Am J Physiol 267: 974–983Google Scholar