In vivo toxicity of prion protein in murine scrapie: Ultrastructural and immunogold studies
In vivo toxicity of prion protein in murine scrapie: Ultrastructural and immunogold studies
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DOI：
10.1111/j.1365-2990.1997.tb01191.x
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发表时间：
1997-04-01
影响因子：
5
通讯作者：
Fraser, JR
中科院分区：
文献类型：
--
作者：
Jeffrey, M;Goodsir, CM;Fraser, JR
朊蛋白（PrP）是一种细胞表面、宿主编码的唾液糖蛋白，在痒病、克雅氏病、牛海绵状脑病和其他传染性海绵状脑病中积累过量。小鼠感染87 V或ME7痒病菌株后，会出现独特且非常不同的光镜下空泡化模式和疾病特异性PrP积累。在这两种痒病菌株中，用免疫金电镜定位PrP在神经元质膜上的位置，PrP从质膜释放到神经细胞中。在缺乏淀粉样原纤维的神经元周围和早期斑块中，最初的PrP积累通常与释放PrP的神经元或树突的形态学改变或相邻神经元中过量PrP积累的形态学改变无关。然而，某些脑区淀粉样蛋白前PrP的积累与树突棘和轴突末端的特异性变性有关。初始PrP聚集成原纤维与ME7和87 V斑块和弥漫性积聚的组织损伤有关。与纤维形成相关的组织损伤是局部的，预计不会有临床意义。我们得出结论，淀粉样蛋白前PrP的释放和积累并不总是有毒的，无论是对释放PrP的神经元还是对被释放的神经细胞。然而，一些神经解剖区域的轴突终末变性和树突状脊柱丢失可能是特异性PrP毒性的指示，可能是小鼠痒病神经功能障碍的主要原因。
Prion protein (PrP) is a cell surface, host coded, sialoglycoprotein which accumulates in excess in scrapie, Cruetzfeldt-Jakob disease, bovine spongiform encephalopathy and other transmissible spongiform encephalopathies. Infection of mice with the 87 V or ME7 scrapie strains results in distinctive and very different light microscopical patterns of vacuolation and disease specific PrP accumulation. In both of these scrapie strains immunogold electron microscopy was used to locate PrP to the plasmalemma of neurons from where it was released into the neuropil. Initial PrP accumulation around neurons and in early plaques lacking amyloid fibrils was generally not associated with morphological changes either of the neuron or dendrite releasing the PrP or in the adjacent neuropil in which excess PrP accumulated. However, accumulation of pre-amyloid PrP in some brain areas was associated with specific degeneration of dendritic spines and axon terminals. Initial PrP aggregation into fibrils was associated with tissue damage with both ME7 and 87 V plaques and diffuse accumulations. Tissue damage associated with fibrillogenesis was localized and would not be expected to have clinical significance. We conclude that pre-amyloid PrP release and accumulation is not invariably toxic, either to the neuron releasing PrP or to the neuropil into which it is released . However, axon terminal degeneration and dendritic spine loss in some neuroanatomical areas may be indicative of specific PrP toxicity and may be the main cause of neurological dysfunction in murine scrapie.