Strain specific and common pathogenic events in murine models of scrapie and bovine spongiform encephalopathy.
Strain specific and common pathogenic events in murine models of scrapie and bovine spongiform encephalopathy.
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痒病和牛海绵状脑病小鼠模型中菌株特异性和常见的致病事件。
DOI：
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发表时间：
1996
影响因子：
3.8
通讯作者：
D. Dormont
中科院分区：
文献类型：
--
作者：
C. Lasmézas;J. Deslys;R. Demaimay;K. Adjou;J. Hauw;D. Dormont
实验模型中传染性海绵状脑病的发生取决于两个主要因素：PrP (PrPres) 的异常、蛋白酶抗性异构体在脑内积聚，PrP 是一种主要在神经元中表达的宿主蛋白；以及不同菌株的存在。为了区分取决于宿主源性 PrPres 积累和菌株特异性效应的致病机制，我们量化并比较了分子 [PrPres 和胶质纤维酸性蛋白 (GFAP) 积累] 的序列以及在两种不同菌株感染过程中同系小鼠大脑中的病理事件。牛海绵状脑病 (BSE) 制剂表现出不同于任何已知瘙痒病来源的特性，并且已与经典瘙痒病菌株进行了比较研究。两个模型中的趋同动力学数据证实了PrPres与病理变化之间的因果关系，并表明PrPres积累直接负责体内星形胶质细胞的激活。此外，我们观察到 PrPres 对星形胶质细胞产生这种影响的阈值水平。然而，尽管传染性滴度相似，BSE 模型产生的 PrPres 比痒病少，而且神经胶质增生的相对重要性更高。脑内或腹膜内接种后分子和病理特征的比较也揭示了模型之间的差异。因此，导致分子事件的靶向和精细调节的机制似乎独立于宿主 PrP 并依赖于药剂。必须考虑调节分子可能参与解释这些特异性。
The development of transmissible spongiform encephalopathies in experimental models depends on two major factors: the intracerebral accumulation of an abnormal, protease-resistant isoform of PrP (PrPres), which is a host protein mainly expressed in neurons; and the existence of different strains of agent. In order to make a distinction between pathogenic mechanisms depending upon the accumulation of host-derived PrPres and the strain-specific effects, we quantified and compared the sequence of molecular [PrPres and glial fibrillary acidic protein (GFAP) accumulation] and pathological events in the brains of syngeneic mice throughout the course of infection with two different strains of agent. The bovine spongiform encephalopathy (BSE) agent exhibits properties different from any known scrapie source and has been studied in comparison with a classical scrapie strain. Convergent kinetic data in both models confirmed the cause-effect relationship between PrPres and pathological changes and showed that PrPres accumulation is directly responsible for astrocyte activation in vivo. Moreover, we observed a threshold level of PrPres for this effect on astroglial cells. However, despite similar infectivity titres, the BSE model produced less PrPres than scrapie, and the relative importance of gliosis was higher. The comparison of the molecular and pathological features after intracerebral or intraperitoneal inoculation also revealed differences between the models. Therefore, the mechanisms leading to the targeting and the fine regulation of the molecular events seem to be independent of the host PrP and to depend upon the agent. The possible involvement of a regulatory molecule accounting for these specificities has to be considered.
影响因子：
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作者：
Lawrence F. Eng;Albert C.H. Yu;Yuen‐Ling Lee
通讯作者：
Lawrence F. Eng;Albert C.H. Yu;Yuen‐Ling Lee
影响因子：
56.9
作者：
BOLTON, DC;MCKINLEY, MP;PRUSINER, SB
通讯作者：
PRUSINER, SB
感染痒病的仓鼠大脑中的 PrPSc 在空间和时间上与组织病理学和感染滴度相关。
DOI：
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发表时间：
1989
期刊：
Progress in clinical and biological research
影响因子：
--
作者：
DeArmond,SJ;Gonzales,M;Mobley,WC;Kon,AA;Stern,A;Prusiner,H;Prusiner,SB
通讯作者：
Prusiner,SB