Johnson S a, Young-Chan C S, Laping N J, Finch C E
Neurogerontology Division, Andrus Gerontology Center, University of Southern California, Los Angeles, 90089-0191, USA.
Exp Neurol. 1996 Apr;138(2):198-205. doi: 10.1006/exnr.1996.0058.
The presence of complement system proteins in amyloid plaques and the up-regulation of several complement mRNAs in neurons and glial cells in affected brain regions during Alzheimer disease (AD) provided a basis for further examination of complement protein expression in a rodent lesion model of AD. Perforant path transection in rats was used as a model for the degeneration of entorhinal cortex (EC) layer II neurons and the consequent deafferentation of the hippocampus that occurs during AD. Immunostaining for C9, a key terminal component of the complement cascade membrane attack complex (MAC), showed extracellular C9 deposition in parenchyma around the EC wound and in hippocampus as early as 1 day, and disappeared by 14 days postlesion. Apoptosis of EC layer II neurons was seen and was presumably due to severing of their axonal projections to the hippocampus by the transection lesion. However, apoptotic EC layer II neurons were not immunostained by anti-rat C9 antibody, suggesting complement was not involved in inducing apoptosis. In the deafferented hippocampus, extracellular C9 immunostaining was localized to the dentate gyrus middle molecular layer, a region of synaptic loss, dendritic degeneration, and early synaptogenesis. In addition, intracellular C9 immunostaining was seen only in select hippocampal interneurons. Dentate gyrus granule neurons and pyramidal neurons were not C9 immunostained. Clusterin (SGP-2), a soluble inhibitor of the MAC that is up-regulated in AD, was also detected in the wound area (extracellular), the dentate gyrus middle molecular layer (extracellular), and intracellularly in scattered hippocampal interneurons. The data support the hypothesis that the complement system generally participates in responses to brain injury, as well as in AD.
在阿尔茨海默病（AD）期间，淀粉样斑块中存在补体系统蛋白，且受影响脑区的神经元和胶质细胞中几种补体mRNA上调，这为进一步研究AD啮齿动物损伤模型中的补体蛋白表达提供了基础。大鼠的穿通路径横断被用作AD期间内嗅皮质（EC）II层神经元变性以及随之而来的海马去传入的模型。对补体级联膜攻击复合物（MAC）的关键终末成分C9进行免疫染色，结果显示早在损伤后1天，EC伤口周围实质和海马中就有细胞外C9沉积，损伤后14天消失。可见EC II层神经元发生凋亡，推测是由于横断损伤切断了它们至海马的轴突投射。然而，凋亡的EC II层神经元未被抗大鼠C9抗体免疫染色，提示补体不参与诱导凋亡。在去传入的海马中，细胞外C9免疫染色定位于齿状回中分子层，该区域存在突触丧失、树突退变和早期突触形成。此外，仅在特定的海马中间神经元中可见细胞内C9免疫染色。齿状回颗粒神经元和锥体细胞未被C9免疫染色。在AD中上调的MAC可溶性抑制剂聚集素（SGP - 2），也在伤口区域（细胞外）、齿状回中分子层（细胞外）以及散在的海马中间神经元的细胞内被检测到。这些数据支持以下假说：补体系统一般参与对脑损伤的反应以及AD的发病过程。
