Wharton Stephen B, Williams Gareth H, Stoeber Kai, Gelsthorpe Catherine H, Baxter Lynne, Johnson Anthony L, Ince Paul G
Academic Unit of Pathology, University of Sheffield, Medical School, UK.
Neurosci Lett. 2005;383(1-2):33-8. doi: 10.1016/j.neulet.2005.04.019. Epub 2005 Apr 26.
Cell-cycle mechanisms may be aberrantly reactivated in the ageing brain and associated with the development of pathology, including Alzheimer's disease. Activation of cell-cycle mechanisms in glia has, however, been little studied. Our aim was to determine whether expression of a marker for chromosomal replication licensing, Mcm2, occurs in glia of the ageing hippocampus, and to compare its expression to that of Ki67 and PCNA. Blocks of hippocampus were obtained from 19 elderly brains derived from the MRC-CFAS neuropathology cohort, which included a spectrum of Alzheimer-type pathology, semi-quantified using the Braak scoring system for neurofibrillary tangles. Mcm2, PCNA and Ki67 were detected immunohistochemically. Expression of Mcm2, Ki67 and PCNA was observed in glial cells and neurons, with a trend to increased expression in association with higher burdens of Alzheimer-type pathology. Mcm2 expression in glial cells showed a significant linear trend across Braak stages (P = 0.043). This study demonstrates that grey and white matter glial cells show expression of cell-cycle markers in the ageing brain and that re-licensing for chromosomal replication is a component of the mechanisms activated. A quantitative relationship to the burden of Alzheimer-type pathology suggests that cell-cycle re-entry in glial cells may be important in the pathogenesis of age-related neurodegeneration.
细胞周期机制可能在衰老大脑中异常重新激活，并与包括阿尔茨海默病在内的病理发展相关。然而，胶质细胞中细胞周期机制的激活研究较少。我们的目的是确定染色体复制许可标记物Mcm2在衰老海马体的胶质细胞中是否表达，并将其表达与Ki67和PCNA的表达进行比较。从MRC-CFAS神经病理学队列的19个老年大脑中获取海马体组织块，该队列包括一系列阿尔茨海默病类型的病理学情况，使用用于神经原纤维缠结的Braak评分系统进行半定量分析。通过免疫组织化学检测Mcm2、PCNA和Ki67。在胶质细胞和神经元中观察到Mcm2、Ki67和PCNA的表达，并且随着阿尔茨海默病类型病理学负担的增加有表达增加的趋势。胶质细胞中Mcm2的表达在Braak分期中呈现出显著的线性趋势（P = 0.043）。这项研究表明，在衰老大脑中，灰质和白质胶质细胞均显示出细胞周期标记物的表达，并且染色体复制的重新许可化是激活机制的一个组成部分。与阿尔茨海默病类型病理学负担的定量关系表明，胶质细胞中细胞周期的重新进入可能在与年龄相关的神经退行性变的发病机制中起重要作用。
