The brain to gut pathway: a possible route of prion transmission
The brain to gut pathway: a possible route of prion transmission
复制标题
大脑到肠道途径：朊病毒传播的可能途径
作者：
V. Lawson;J. Furness;Helen M J Klemm;L. Pontell;E. Chan;A. Hill;R. Chiocchetti
目的肠道在朊病毒病的传播中起着重要作用。这些疾病与正常细胞朊蛋白（PrPC）的病理亚型（PrPSc）有关，可以在个体之间传播或自发发生。脑作为朊病毒复制的主要场所，可向周围组织提供感染性朊病毒。在这里，我们研究大脑是否是肠道朊病毒积累的来源。方法采用免疫印迹和免疫组织化学方法，观察朊病毒感染BalbC小鼠后回肠中PrPSc的表达，以及肠神经胶质细胞（EGCs）和肠肌间神经丛及粘膜下神经丛中特异性神经元亚群的存活情况。结果13/13只脑内接种朊病毒小鼠回肠中检测到PrPSc，0/4只生理盐水接种小鼠回肠中检测到PrPSc。PrPSc在感染小鼠的派伊尔集合淋巴结中以可检测的水平定位。神经元亚群的研究显示，与盐水接种的小鼠（23± 5%，n=3）相比，神经丝反应性神经元（11± 8%，p<0.05，n=5）显著减少。神经元型一氧化氮合酶（nNOS）和酪氨酸羟化酶反应神经元减少，在一些（2 4和1 3，分别），但不是所有的朊病毒感染的小鼠，而钙视黄蛋白和血管活性肠肽反应神经元不受影响。EGCs在肌间神经丛的限制性神经节中高度扭曲。在神经胶质细胞紊乱的地区，神经元表现出不明确的轮廓和微弱的细胞质免疫反应性的泛神经元标记胡和nNOS反应性的损失。结论PrPSc可从脑内进入肠道。这导致肠神经胶质细胞和神经元的病理变化。我们的结论是，PrPSc的大脑起源发现一个基板中的天然存在的PrPC的EGCs和神经元。这导致PrPSc在肠道中的储存，这可能是通过外科手术和环境污染传播朊病毒疾病的来源。
Objective The intestine is recognised to play a key role in the transmission of prion diseases. These diseases are associated with pathological isoforms (PrPSc) of the normal cellular prion protein (PrPC) and can be transmitted between individuals or arise spontaneously. The brain, as the primary site of prion replication, could provide infectious prions to peripheral tissues. Here, we examine whether the brain is a source of intestinal prion accumulation. Methods Following intracerebral inoculation with human origin prions the ileums of BalbC mice with clinical prion disease were assessed by Western immunoblot and immunohistochemical analysis for the presence of PrPSc and the survival of enteric glial cells (EGCs) and specific neuronal subpopulations in the myenteric and submucosal plexus. Results PrPSc was detected in the ileum of 13/13 mice following intracerebral inoculation with prions and 0/4 saline-inoculated mice. PrPSc was localised at detectable levels in the Peyer's patches of infected mice. Investigation of neuronal subpopulations revealed a significant decrease in neurofilament reactive neurons (11±8%, p<0.05, n=5) compared with saline-inoculated mice (23±5%, n=3). Neuronal nitric oxide synthase (nNOS) and tyrosine hydroxylase reactive neurons were decreased in some (2 of 4 and 1 of 3, respectively) but not all prion-infected mice, whereas calretinin and vasoactive intestinal peptide reactive neurons were unaffected. EGCs were highly distorted in circumscribed ganglia of the myenteric plexus. In areas of glial derangement, the neurons showed undefined outlines and faint cytoplasmic immuoreactivity for the pan-neuronal marker Hu and loss of nNOS reactivity. Conclusions The present work shows that PrPSc can be transmitted from the brain to the intestine. This causes pathological changes in enteric glia and neurons. We conclude that PrPSc of brain origin finds a substrate in the naturally occurring PrPC of EGCs and neurons. This results in a reservoir of PrPSc in the intestine, which may represent a source of prion disease transmission through surgical procedures and environmental contamination.
鉴定与痒病朊病毒蛋白结合的细胞蛋白。
影响因子：
2.9
作者：
Oesch,B;Teplow,DB;Stahl,N;Serban,D;Hood,LE;Prusiner,SB
通讯作者：
Prusiner,SB
DOI：
10.1086/588193
发表时间：
2008-07-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Safar JG;Lessard P;Tamgüney G;Freyman Y;Deering C;Letessier F;Dearmond SJ;Prusiner SB
通讯作者：
Prusiner SB