Microglial dystrophy in the aged and Alzheimer's disease brain is associated with ferritin immunoreactivity
Microglial dystrophy in the aged and Alzheimer's disease brain is associated with ferritin immunoreactivity
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DOI：
10.1002/glia.20678
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发表时间：
2008-08-01
期刊：
影响因子：
6.2
通讯作者：
Streit, Wolfgang J.
中科院分区：
文献类型：
--
作者：
Lopes, Kryslaine O.;Sparks, D. Larry;Streit, Wolfgang J.
小胶质细胞的变性对于理解与衰老相关的神经变性和神经退行性疾病的发病机制可能很重要。在本研究中，我们使用铁蛋白免疫组化分析了非痴呆和阿尔茨海默病 (AD) 人脑中小胶质细胞的形态特征。中心假设是，铁储存蛋白铁蛋白的表达增加了小胶质细胞退化的易感性，特别是在衰老的大脑中，因为衰老的小胶质细胞在维持铁稳态方面可能变得不太有效，而游离铁可以促进氧化损伤。在 24 名受试者（年龄范围 34-97 岁）的主要检查中，发现对铁蛋白具有免疫反应的小胶质细胞构成了用 HLA-DR 抗原抗体标记的较大小胶质细胞库的一个亚群。这些铁蛋白阳性小胶质细胞中的大多数在老年人中尤其是 AD 大脑中表现出异常的形态（营养不良）变化。 AD 组织中铁蛋白阳性营养不良型小胶质细胞与老年斑之间没有发现空间相关性。对第二组具有广泛死后间隔（PMI，平均 10.94 +/- 5.69 小时）的人类死后脑组织的分析表明，小胶质细胞营养不良的发生与 PMI 无关，因此不是组织自溶的产物。总的来说，这些结果表明，小胶质细胞参与铁储存和代谢，可能通过增加细胞暴露于氧化应激而导致其退化。我们的结论是，铁蛋白免疫组织化学可能是检测人脑中退化小胶质细胞的有用方法。 (c) 2008 年 Wiley-Liss, Inc.
Degeneration of microglial cells may be important for understanding the pathogenesis of aging-related neurodegeneration and neurodegenerative diseases. In this study, we analyzed the morphological characteristics of microglial cells in the nondemented and Alzheimer's disease (AD) human brain using ferritin immunohistocbemistry. The central hypothesis was that expression of the iron storage protein ferritin increases the susceptibility of microglia to degeneration, particularly in the aged brain since senescent microglia might become less efficient in maintaining iron homeostasis and free iron can promote oxidative damage. In a primary set of 24 subjects (age range 34-97 years) examined, microglial cells immunoreactive for ferritin were found to constitute a subpopulation of the larger microglial pool labeled with an antibody for HLA-DR antigens. The majority of these ferritin-positive microglia exhibited aberrant morphological (dystrophic) changes in the aged and particularly in the AD brain. No spatial correlation was found between ferritin-positive dystrophic microglia and senile plaques in AD tissues. Analysis of a secondary set of human postmortem brain tissues with a wide range of postmortem intervals (PMI, average 10.94 +/- 5.69 h) showed that the occurrence of microglial dystrophy was independent of PMI and consequently not a product of tissue autolysis. Collectively, these results suggest that microglial involvement in iron storage and metabolism contributes to their degeneration, possibly through increased exposure of the cells to oxidative stress. We conclude that ferritin immunohistochemistry may be a useful method for detecting degenerating microglia in the human brain. (c) 2008 Wiley-Liss, Inc.