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人脑海马星形胶质细胞中的DJ-1免疫反应性取决于梗死灶的存在和梗死灶的年龄。

DJ-1 immunoreactivity in human brain astrocytes is dependent on infarct presence and infarct age.

作者信息

Mullett Steven J, Hamilton Ronald L, Hinkle David A

机构信息

Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.

出版信息

Neuropathology. 2009 Apr;29(2):125-31. doi: 10.1111/j.1440-1789.2008.00955.x. Epub 2008 Jul 20.

Abstract

DJ-1 is a protein with anti-oxidative stress and anti-apoptotic properties that is abundantly expressed in reactive CNS astrocytes in chronic neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and Pick's disease. Genetic mutations which eliminate DJ-1 expression in humans are sufficient to produce an early-onset form of familial PD, PARK7, suggesting that DJ-1 is a critical component of the neuroprotective arsenal of the brain. Previous studies in parkinsonism/dementia brain tissues have revealed that reactive astrocytes within and surrounding incidentally identified infarcts were often robustly immunoreactive for DJ-1, especially if the infarcts showed histological features consistent with older age. Given this, we sought to evaluate astrocytic DJ-1 expression in human stroke more extensively, and with a particular emphasis on determining whether immunohistochemical DJ-1 expression in astrocytes correlates with histological infarct age. The studies presented here show that DJ-1 is abundantly expressed in reactive infarct region astrocytes in both gray and white matter, that subacute and chronic infarct region astrocytes are much more robustly DJ-1+ than are acute infarct and non-infarct region astrocytes, and that DJ-1 staining intensity in astrocytes generally correlates with that of the reactive astrocyte marker GFAP. Confocal imaging of DJ-1 and GFAP dual-labelled human brain sections were used to confirm the localization to and expression of DJ-1 in astrocytes. Neuronal DJ-1 staining was minimal under all infarct and non-infarct conditions. Our data support the conclusion that the major cellular DJ-1 response to stroke in the human brain is astrocytic, and that there is a temporal correlation between DJ-1 expression in these cells and advanced infarct age.

摘要

DJ-1是一种具有抗氧化应激和抗凋亡特性的蛋白质,在帕金森病(PD)、阿尔茨海默病(AD)和皮克病等慢性神经退行性疾病的反应性中枢神经系统星形胶质细胞中大量表达。消除人类DJ-1表达的基因突变足以产生早发性家族性PD(PARK7),这表明DJ-1是大脑神经保护武器库的关键组成部分。先前对帕金森病/痴呆脑组织的研究表明,偶然发现的梗死灶内部和周围的反应性星形胶质细胞通常对DJ-1有强烈的免疫反应,特别是如果梗死灶表现出与老年一致的组织学特征。鉴于此,我们试图更广泛地评估人类中风中星形胶质细胞DJ-1的表达,并特别强调确定星形胶质细胞中免疫组化DJ-1的表达是否与梗死灶的组织学年龄相关。本文的研究表明,DJ-1在灰质和白质的反应性梗死灶区域星形胶质细胞中大量表达,亚急性和慢性梗死灶区域的星形胶质细胞比急性梗死灶和非梗死灶区域的星形胶质细胞DJ-1阳性表达更强,并且星形胶质细胞中DJ-1染色强度通常与反应性星形胶质细胞标志物GFAP的染色强度相关。对DJ-1和GFAP双标记的人脑切片进行共聚焦成像,以确认DJ-1在星形胶质细胞中的定位和表达。在所有梗死和非梗死条件下,神经元DJ-1染色均极少。我们的数据支持以下结论:人类大脑中对中风的主要细胞DJ-1反应是星形胶质细胞的反应,并且这些细胞中DJ-1的表达与晚期梗死灶年龄之间存在时间相关性。

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