Expression of glia maturation factor in neuropathological lesions of Alzheimer's disease.

Expression of glia maturation factor in neuropathological lesions of Alzheimer's disease.
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DOI:
10.1111/j.1365-2990.2011.01232.x
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发表时间:
2012-10
影响因子:
5
通讯作者:
Zaheer A
Zaheer A
中科院分区:
医学2区
文献类型:
--
作者:
Thangavel R;Stolmeier D;Yang X;Anantharam P;Zaheer A

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阿尔茨海默病(AD)的病理学特征在于淀粉样蛋白斑(AP)、神经元缠结(NFT)、变性神经元以及大量反应性星形胶质细胞和小胶质细胞的存在。我们的目的是研究胶质成熟因子(GMF)的表达,活化的星形胶质细胞/小胶质细胞,AP,和NFT在AD影响的大脑区域之间的关联。脑切片用硫磺素-S染色以研究AD病理学,并依次用抗GMF、胶质细胞酸性蛋白(GFAP,反应性星形胶质细胞的标志物)和离子化钙结合衔接分子1(Iba 1,活化小胶质细胞的标志物)的抗体免疫标记,然后用抗生物素蛋白-生物素过氧化物酶复合物可视化。我们的双重免疫荧光标记与细胞特异性标记证明了神经胶质细胞定位的GMF。免疫组织化学数据显示,与非AD对照相比,AP和NFT与AD脑反应性胶质细胞中GMF表达增加相关。这是第一份报告,表明GMF,CNS炎症的介质,在受影响的AD的大脑区域中表达,并且GMF主要定位于AP/NFT周围的反应性星形胶质细胞。在硫磺素-S染色的AP和NFT中及其周围的GMF免疫反应细胞的分布表明GMF通过反应性胶质细胞参与炎症反应,并且GMF在AD病理学中起作用。
The pathology of Alzheimers's disease (AD) is characterized by the presence of amyloid plaques (APs), neurofibrillary tangles (NFTs), degenerating neurons, and an abundance of reactive astrocytes and microglia. We aim to examine the association between glia maturation factor (GMF) expression, activated astrocytes/microglia, APs, and NFTs in AD affected brain regions. Brain sections were stained with Thioflavin-S to study AD pathology and sequentially immunolabeled with antibodies against GMF, glial fibrillary acidic protein (GFAP, marker for reactive astrocytes), and Ionized calcium binding adaptor molecule 1 (Iba1, marker for activated microglia) followed by visualization with avidin-biotin peroxidase complex. Our double immunofluorescence labeling with cell-specific markers demonstrated the glial localization of GMF. The immunohistochemical data showed that APs and NFTs are associated with increased expression of GMF in reactive glia of AD brains compared to non-AD controls. This is the first report that shows GMF, a mediator of CNS inflammation, is expressed in the brain regions affected in AD and that GMF is mainly localized in reactive astrocytes surrounding APs/NFTs. The distribution of GMF-immunoreactive cells in and around Thioflavin-S stained APs and NFTs suggests involvement of GMF in inflammatory responses through reactive glia and a role of GMF in AD pathology.
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