Identical Pathogenesis and Neuropathological Phenotype of Scrapie in Valine, Arginine, Glutamine/Valine, Arginine, Glutamine Sheet, Infected Experimentally by the Oral and Conjunctival Routes
Identical Pathogenesis and Neuropathological Phenotype of Scrapie in Valine, Arginine, Glutamine/Valine, Arginine, Glutamine Sheet, Infected Experimentally by the Oral and Conjunctival Routes
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DOI：
10.1016/j.jcpa.2013.06.006
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发表时间：
2014-01-01
影响因子：
0.8
通讯作者：
Jeffrey, M.
中科院分区：
文献类型：
--
作者：
Gonzalez, L.;Pitarch, J. L.;Jeffrey, M.
绵羊自然或经口接触传染原后患瘙痒病的发病机制通常涉及疾病相关朊病毒蛋白 (PrPd) 在淋巴网状系统 (LRS) 中的早期积累。此阶段之后是神经侵袭，假设有两种途径：上行神经侵袭和血行侵袭。本研究报告使用免疫组织化学来追踪通过口服或结膜途径施用的单一、高度痒病易感性 PrP 基因型的绵羊中 PrPd 沉积的组织进展。无论感染途径如何，最早检测到的 PrPd 是在肠道和咽部相关的 LRS 组织中。随后，大脑与其他 LRS 组织同时变为 PrPd 阳性，但先于脊髓和肠道、副交感神经和交感系统的周围神经组织。 PrPd 在大脑中最初积累的部位是迷走神经和下丘脑的背运动核及其相关的室周器官（分别为后区和正中隆起）。两种感染途径的这些都是相同的。在经口或结膜感染的绵羊中观察到疾病迅速进展为临床疾病，分别在感染后约 6 个月和 8 个月时记录到明显的痒病症状。通过结膜途径感染的绵羊的潜伏期较长，可能是因为它们接受的剂量低于经口感染的绵羊。无论感染途径如何，临床受影响的羊都表现出相同的病理表型（PrPd 谱）和 PrPd 在整个大脑中的分布。在两组绵羊中观察到的相同的外周和中枢发病机制表明感染原在血流中的早期传播和共同的神经侵袭途径。肠道和自主神经系统的晚期参与支持了脑部感染的血行途径。 Crown 版权所有 (C) 2013 由 Elsevier Ltd 出版。保留所有权利。
The pathogenesis of scrapie in sheep after natural or oral exposure to the infectious agent generally involves the early accumulation of disease-associated prion protein (PrPd) in the lymphoreticular system (LRS). This phase is followed by neuroinvasion, for which two routes, ascending neural and haematogenous, have been postulated. The present study reports the use of immunohistochemistry to track the tissue progression of PrPd deposition in sheep of a single, highly scrapie-susceptible PrP genotype administered by the oral or conjunctival routes. Regardless of the route of infection, the earliest detection of PrPd was in gut- and pharynx-associated LRS tissues. Subsequently, the brain became PrPd positive simultaneously with other LRS tissues, but before the spinal cord and peripheral nervous tissues of the enteric, parasympathetic and sympathetic systems. The sites of initial PrPd accumulation in the brain were the dorsal motor nucleus of the vagus and the hypothalamus and their related circumventricular organs (the area postrema and the median eminence, respectively). These were the same for both routes of infection. Rapid progression to clinical disease was observed in sheep infected orally or conjunctivally, with definite signs of scrapie recorded at around 6 and 8 months after infection, respectively. Longer incubation periods in sheep infected by the conjunctival route were probably due to them receiving a lower dose than those infected orally. Irrespective of the route of infection, clinically affected sheep showed the same pathological phenotype (PrPd profile) and PrPd distribution throughout the brain. The identical peripheral and central pathogenesis observed in sheep of both groups suggests early dissemination of the infectious agent in the bloodstream and a common neuroinvasion pathway. The late involvement of the enteric and autonomic nervous system supports a haematogenous route of infection to the brain. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.