Ersdal C, Goodsir C M, Simmons M M, McGovern G, Jeffrey M
Department of Basic Sciences and Aquatic Medicine, Oslo, Norway.
Neuropathol Appl Neurobiol. 2009 Jun;35(3):259-71. doi: 10.1111/j.1365-2990.2008.00988.x. Epub 2008 Sep 18.
Transmissible spongiform encephalopathies (TSEs) or prion diseases are fatal neurodegenerative diseases of man and animals characterized by vacuolation and gliosis of neuropil and the accumulation of abnormal isoforms of a host protein known as prion protein (PrP). It is widely assumed that the abnormal isoforms of PrP (PrP(d), disease-specific form of PrP) are the proximate cause of neurodegeneration.
To determine the nature of subcellular changes and their association with PrP(d) we perfusion-fixed brains of eight bovine spongiform encephalopathy (BSE)-affected cows and three control cattle for immunogold electron microscopy at two different neuroanatomical sites.
All affected cattle presented plasma membrane alterations of dendrites and astrocytes that were labelled for PrP(d). PrP(d) on membranes of dendrites and occasionally of neuronal perikarya was associated with abnormal endocytotic events, including bizarre coated pits and invagination of the plasma membrane. BSE-affected cattle also presented excess and abnormal multivesicular bodies, sometimes associated to the plasma membrane perturbations. In contrast, two TSE-specific lesions, vacuolation and rare tubulovesicular bodies, were not labelled for PrP(d) as were a number of other nonspecific lesions, such as autophagy and dystrophic neurites. At least two different morphological pathways to vacuoles were recognized.
When compared with other TSEs, these changes are common to those of sheep and rodent scrapie and shows that there are consistent membrane toxicity properties of PrP(d). This toxicity involves an aberration of endocytosis. However, it is by no means clear that the lesions are of sufficient severity to result in clinical deficits.
传染性海绵状脑病（TSEs）或朊病毒病是人和动物的致命性神经退行性疾病，其特征为神经毡空泡化和胶质细胞增生，以及一种称为朊病毒蛋白（PrP）的宿主蛋白异常异构体的积累。人们普遍认为，PrP的异常异构体（PrP(d)，疾病特异性PrP形式）是神经退行性变的直接原因。
为了确定亚细胞变化的性质及其与PrP(d)的关联，我们对8头患牛海绵状脑病（BSE）的奶牛和3头对照牛的大脑进行灌注固定，用于在两个不同神经解剖部位进行免疫金电子显微镜检查。
所有患病牛的树突和星形胶质细胞的质膜均出现改变，并被标记为PrP(d)。树突膜上以及偶尔神经元胞体上的PrP(d)与异常的内吞事件有关，包括奇异的被膜小窝和质膜内陷。受BSE影响的牛还出现了过多且异常的多囊泡体，有时与质膜扰动有关。相比之下，两个TSE特异性病变，即空泡化和罕见的小管状囊泡体，以及许多其他非特异性病变，如自噬和营养不良性神经突，均未被PrP(d)标记。至少识别出两种通向空泡的不同形态学途径。
与其他TSEs相比，这些变化与绵羊和啮齿动物瘙痒病的变化相同，表明PrP(d)具有一致的膜毒性特性。这种毒性涉及内吞作用的异常。然而，目前尚不清楚这些病变的严重程度是否足以导致临床缺陷。
