Expression and localization of lactotransferrin messenger RNA in the cortex of Alzheimer's disease.

Expression and localization of lactotransferrin messenger RNA in the cortex of Alzheimer's disease.
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DOI:
10.1016/j.neulet.2009.01.071
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发表时间:
2009-03-20
影响因子:
2.5
通讯作者:
Tooyama I
Tooyama I
中科院分区:
医学4区
文献类型:
--
作者:
An L;Sato H;Konishi Y;Walker DG;Beach TG;Rogers J;Tooyama I

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我们和其他人以前曾报道,乳转铁蛋白(LF),作为一种铁结合蛋白和炎症调节剂,在阿尔茨海默病(AD)患者的大脑中大大上调。然而,AD大脑中哪种类型的细胞表达LF仍不清楚。因此,在这项研究中,我们研究了LF信使RNA(mRNA)的表达和定位在大脑皮层的AD和控制情况下,使用实时聚合酶链反应(PCR)和原位杂交组织化学。Real-time PCR结果显示,AD患者大脑皮层LF mRNA表达明显高于对照组。LF mRNA阳性颗粒在大脑皮质原位杂交组织化学观察,阳性颗粒的数量增加,AD患者与对照组相比。LF mRNA原位杂交和D相关人类白细胞抗原(HLA-DR)免疫组化双重染色技术显示,阳性颗粒定位于HLA-DR阳性反应性小胶质细胞亚群。此外,在HLA-DR阴性的细胞中也可观察到LF mRNA阳性颗粒,这些细胞也是CD 4和CD 8阴性,但白细胞共同抗原(CD 45 RB)阳性,提示它们是单核/巨噬细胞。这些结果表明,大脑皮质中的反应性小胶质细胞和从循环中浸润的单核/巨噬细胞可能是AD脑中合成LF的原因。
We and others have previously reported that lactotransferrin (LF), acting both as an iron-binding protein and inflammatory modulator, is greatly up-regulated in the brain of patients with Alzheimer’s disease (AD). However, it remains unknown which type of cells express LF in the brain of AD. In this study, therefore, we investigated the expression and localization of LF messenger RNA (mRNA) in the cerebral cortex of AD and control cases using real-time polymerase chain reaction (PCR) and in situ hybridization histochemistry. Real-time PCR demonstrated that LF mRNA expression in the cortex of AD cases was significantly greater than that in control cases. LF mRNA-positive granules were observed in the cortex by in situ hybridization histochemistry, and the number of positive granules was increased in AD cases compared to controls. The double staining technique of LF mRNA in situ hybridization and D-related human leukocyte antigen (HLA-DR) immunohistochemistry revealed that positive granules were localized in a subpopulation of HLA-DR-positive reactive microglia. In addition, LF mRNA-positive granules were observed in some cells that were negative for HLA-DR. These cells were also negative for CD4 and CD8 but positive for leukocyte common antigen (CD45RB), suggesting they were monocytes/macrophages. These results indicate that reactive microglia in the cerebral cortex and monocytes/macrophages infiltrating from the circulation might be responsible for synthesizing LF in AD brain.
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