Methylation analysis of SST and SSTR4 promoters in the neocortex of Alzheimer's disease patients
Methylation analysis of SST and SSTR4 promoters in the neocortex of Alzheimer's disease patients
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DOI：
10.1016/j.neulet.2014.02.046
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发表时间：
2014-04-30
影响因子：
2.5
通讯作者：
van de Nes, Johannes
中科院分区：
文献类型：
--
作者：
Grosser, Christian;Neumann, Lisa;van de Nes, Johannes
一些观察结果已经指出生长抑素耗尽在淀粉样蛋白积累方面的主要致病作用，淀粉样蛋白积累通常被认为是导致阿尔茨海默病（AD）的级联反应中的关键事件。由于CpG岛甲基化在基因沉默中起重要作用，我们研究了生长抑素（SST）及其在大脑皮层中的受体亚型SSTR 4启动子中CpG岛的甲基化状态，在颞叶中部的组织样本中（Brodmann 22区）和上级额回（Brodmann区域9）的5名严重受累的AD患者（年龄72-94岁（Braak阶段V-C或VI-C））和5名非痴呆对照（年龄50-92岁）。皮质灰质和皮质下白色物质DNA的亚硫酸氢盐测序显示，在分析的任何区域中，AD和对照样品之间SST和SSTR 4启动子处的DNA甲基化状态没有显著差异。我们使用SST启动子的PCR产物的深亚硫酸氢盐测序证实了这些结果，SST启动子是从所有AD患者和非痴呆对照的上级额回皮质灰质的DNA扩增的。我们观察到DNA甲基化随着年龄的增长而增加的趋势。总之，AD皮质中生长抑素信号的失调不能用SST或SSTR 4启动子CpG岛的高甲基化来解释。(C)2014爱思唯尔爱尔兰有限公司版权所有。
Several observations have pointed to a major pathogenic role of somatostatin depletion with respect to amyloid accumulation, which is often thought to be the crucial event in a cascade leading to Alzheimer's disease (AD). As methylation of CpG islands plays an important role in gene silencing, we studied the methylation status of the CpG islands in the promoters of somatostatin (SST) and in that of its receptor subtype in the cerebral cortex, SSTR4, in tissue samples from the middle temporal (Brodmann area 22) and superior frontal gyrus (Brodmann area 9) of 5 severely affected AD patients aged 72-94 years (Braak stages V-C or VI-C) and 5 non-demented controls aged 50-92 years. Bisulfite sequencing of DNA from cortical gray and infracortical white matter showed that the DNA methylation status at the promoters of SST and SSTR4 did not significantly differ between AD and control samples in any of the regions analyzed. We confirmed these results using deep bisulfite sequencing of PCR products from the SST promoter amplified from DNA from the cortical gray of the superior frontal gyrus of all AD patients and non-demented controls. We observed a trend toward increased DNA methylation with increasing age. In conclusion, deregulated somatostatin signaling in the AD cortices studied cannot be explained by hypermethylation of the SST or SSTR4 promoter CpG islands. (C) 2014 Elsevier Ireland Ltd. All rights reserved.