van Keulen L J, Schreuder B E, Vromans M E, Langeveld J P, Smits M A
Institute for Animal Science and Health, Lelystad, The Netherlands.
Arch Virol Suppl. 2000(16):57-71. doi: 10.1007/978-3-7091-6308-5_5.
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 PrP(Sc) in various tissues, collected during a natural scrapie infection from sheep with the PrP(VRQ)/PrP(VRQ) genotype which were purposely bred for their short incubation period for natural scrapie. PrP(Sc) was present in the lymphoid tissues of all animals from the age of 5 months onwards. At this age, PrP(Sc) 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, PrP(Sc) 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. PrP(Sc) 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 PrP(Sc), 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. PrP(Sc) 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.
尽管痒病作为绵羊和山羊的一种自然疾病已为人所知很久了，但其在自然宿主中的发病机制仍不清楚。为了研究自然痒病的发病机制，我们使用免疫组织化学方法监测PrP(Sc)在各种组织中的沉积情况，这些组织是在自然痒病感染期间从具有PrP(VRQ)/PrP(VRQ)基因型的绵羊身上采集的，这些绵羊因其自然痒病潜伏期短而特意培育。从5个月大开始，所有动物的淋巴组织中都存在PrP(Sc)。在这个年龄，仅在十二指肠和回肠水平的肠神经系统（ENS）的神经组织中检测到PrP(Sc)。在10个月大时，不仅在ENS中发现了PrP(Sc)，还在颅肠系膜神经节/腹腔神经节、迷走神经背运动核以及胸段T8 - T10的中间外侧柱中发现了PrP(Sc)。在17个月大时首次在孤束核和结节神经节中检测到PrP(Sc)，在21个月大时在三叉神经节和几个脊髓神经节中检测到PrP(Sc)。由于痒病病原体如果不是完全由PrP(Sc)组成，也是主要由其组成，这些结果表明ENS作为痒病病原体进入神经组织的门户，随后通过自主神经系统的交感和副交感传出纤维分别向脊髓和延髓进行向心和逆行传播。感觉神经节中的PrP(Sc)积累发生在中枢神经系统感染之后，因此可能是由于痒病病原体从中枢神经系统通过传入神经纤维进行离心和顺行传播所致。
