Microglia and the Development of Spongiform Change in Creutzfeldt-Jakob Disease
Microglia and the Development of Spongiform Change in Creutzfeldt-Jakob Disease
复制标题
小胶质细胞和克雅氏病海绵状变的发展
DOI：
10.1097/00005072-199803000-00006
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发表时间：
1998
影响因子：
3.2
通讯作者：
M. Graeber
中科院分区：
文献类型：
--
作者：
U. Eitzen;R. Egensperger;S. Kösel;E. Grasbon;Y. Imai;K. Bise;S. Kohsaka;P. Mehraein;M. Graeber
最近的体外实验表明，朊病毒蛋白的神经毒性取决于小胶质细胞的存在。我们使用免疫细胞化学结合计算机图像分析研究了 11 例克雅氏病 (CJD)，以阐明海绵状变化与小胶质细胞激活之间的关系。 MHC II 类阳性小胶质细胞几乎完全局限于皮质灰质，这些细胞占据的神经毡面积是对照组的 350 倍以上。在具有海绵状变性双峰分布的皮质区域中，II类阳性小胶质细胞的存在与V层中空泡化的存在密切相关，但与II层和III层中海绵状变化的相关性显着较低。在海绵状变性影响整个皮质深度的区域，活化的小胶质细胞主要位于皮质的内侧一半或均匀分布在所有皮质层中。在这里，小胶质细胞表现出非典型、曲折的细胞过程，偶尔还有胞浆内空泡，表明小胶质细胞本身可能成为疾病靶标。综上所述，我们的结果提供了间接证据，证明小胶质细胞早期参与海绵状变化的发展。然而，在后期，患病的小胶质细胞可能会产生介导星形胶质细胞增生和神经元损伤的有害因子。
Recent in vitro experiments suggest that neurotoxicity of the prion protein is dependent on the presence of microglia. We have studied 11 cases of Creutzfeldt-Jakob disease (CJD) using immunocytochemistry in combination with computerized image analysis to clarify the relationship between spongiform change and microglial activation. MHC class II-positive microglia were almost exclusively confined to cortical gray matter where the neuropil area occupied by these cells exceeded that of controls more than 350-fold. In cortical regions with a bimodal distribution of spongiform degeneration, the presence of class II-positive microglia correlated well with the presence of vacuolation in layer V, but significantly less with spongiform change in layers II and III. In areas where spongiform degeneration affected the entire depth of the cortex, activated microglia were predominantly located in the inner one-half of the cortex or were evenly distributed throughout all cortical laminae. Here, microglia exhibited atypical, tortuous cell processes and occasionally intracytoplasmic vacuoles, suggesting that microglia themselves may become a disease target. Taken together, our results provide indirect evidence against an early causative involvement of microglia in the development of spongiform change. At later stages, however, diseased microglia could produce harmful factors which mediate both astrogliosis and neuronal injury.