Chronic wasting disease prion trafficking via the autonomic nervous system.
Chronic wasting disease prion trafficking via the autonomic nervous system.
复制标题
慢性消耗性疾病朊病毒通过自主神经系统贩运。
DOI：
10.1016/j.ajpath.2011.05.057
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Hoover,EdwardA
中科院分区：
文献类型：
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作者：
Seelig,DavisM;Mason,GaryL;Telling,GlennC;Hoover,EdwardA
慢性消耗性疾病(CWD)是一种致命的海绵状脑病，在鹿科哺乳动物成员中有效传播，包括鹿、麋鹿和驼鹿。CWD是一种典型的普恩病毒病，其特征是天然的对蛋白酶敏感的蛋白PrPC转化为一种抗蛋白酶的亚型，称为PrPRES。在本地物种中，疾病的传播可能是由于摄入了含有普里昂的排泄物，包括尿液、唾液或粪便。尽管表达Cervid Prion蛋白的转基因[TG(CerPrP)]小鼠已被证明是天然CWD的有效替代品，但CWD Prion在体内运输的机制仍然不确定，包括CWD Prion从胃肠道运输到中枢神经系统的方式。我们使用三种不同接种途径感染的表达麋鹿Prion蛋白的转基因[TG(CerPrP-E)]小鼠和基于组织的IHC来阐明向心性和离心性CWD Prion转运途径涉及自主神经系统的细胞和纤维，包括肠道神经系统和中枢自主神经网络。此外，我们还发现CWD PrPRES与CWD感染的TG(CerPrP-E)小鼠肠神经系统内肠神经胶质细胞的胞体和突起有关。本研究结果证实了外周和中枢自主神经网络在CWD神经侵袭和神经发病机制中的重要性，并提示肠上皮细胞可能促进Pron通过肠道的脱落。
Chronic wasting disease (CWD) is a fatal spongiform encephalopathy that is efficiently transmitted among members of the mammalian family Cervidae, including deer, elk, and moose. Typical of prion diseases, CWD is characterized by the conversion of the native protease-sensitive protein PrPCto a protease-resistant isoform, denoted PrPRES. In native species, spread of the disease likely results from the ingestion of prion-containing excreta, including urine, saliva, or feces. Although cervid prion protein-expressing transgenic [Tg(CerPrP)] mice have been shown to be effective surrogates of natural CWD, uncertainties remain regarding the mechanisms by which CWD prions trafficin vivo, including the manner by which CWD prions traffic from the gastrointestinal tract to the central nervous system. We used elk prion protein-expressing transgenic [Tg(CerPrP-E)] mice, infected by three different routes of inoculation, and tissue-based IHC to elucidate that centripetal and centrifugal CWD prion transit pathways involve cells and fibers of the autonomic nervous systems, including the enteric nervous system and central autonomic network. Moreover, we identified CWD PrPRESassociated with the cell bodies and processes of enteric glial cells within the enteric nervous system of CWD-infected Tg(CerPrP-E) mice. The present findings demonstrate the importance of the peripheral and central autonomic networks in CWD neuroinvasion and neuropathogenesis and suggest that enteroglial cells may facilitate the shedding of prions via the intestinal tract.