摘要
rRNA和 rDNA表达的改变与细胞和机体衰老有关,并且与AD的病机紧密相关。我们研究了AD患者和老年对照组不同的尸检脑组织区(嗅、听觉皮层和海马)中核糖体基因(28S/18S) 和前体β-淀粉样蛋白(APP)的mRNA的表达,并讨论了其在年轻人、健康人、老年人和AD患者外周血液中的表达程度,以此来确定这些人是否经历了衰老的影响。利用通过实时聚合酶链反应和聚合酶链反应-限制性片段长度多态性(PCR-RFLP) 的比较阈循环法分别分析基因表达与载脂蛋白E(APOE))基因型。当大脑区域进行分析时发现,与健康老年人相比,我们观察到AD患者APP 表达的显著下降, 18S 和28SmRNA表达水平显著上升。此外,AD患者内嗅皮质和海马中28SrRNA表达水平明显上升,而听觉皮质中没有变化。另外,对血液样本的检测表明AD患者28S rRNA 表达降低。这些结果说明AD患者rRNA改变是组织特异性,并且它独立发生在每个不同的组织中。然而,下一个挑战找明导致健康的老年人和老年痴呆症患者血液和大脑中基因表达差异的机制,以及这些基因对AD病理的影响。
关键词: 阿尔茨海默病,脑,血液,核糖体基因,18S, 28S。
Current Alzheimer Research
Title:Differential Expression of Ribosomal Genes in Brain and Blood of Alzheimer’s Disease Patients
Volume: 12 Issue: 10
Author(s): Lucas Rasmussen, Roger W. de Labio, Gustavo A. Viani, Elizabeth Chen, Joao Villares, Paulo-Henrique Bertolucci and Thais S. Minett, Gustavo Turecki, Danielle Cecyre, Sandra A. Drigo, Marilia C. Smith and Spencer L.M. Payao
Affiliation:
关键词: 阿尔茨海默病,脑,血液,核糖体基因,18S, 28S。
摘要: Changes in rRNA and rDNA expression have been associated with cellular and organism aging and have been linked to Alzheimer’s disease (AD) pathogenesis. In this study, we investigated the mRNA expression of ribosomal genes (28S/18S) and β-amyloid precursor protein (APP) in different post mortem brain tissue regions (the entorhinal and auditory cortices and the hippocampus) of AD patients and elderly control subjects and also evaluated the extent of expression in peripheral blood from young, healthy, elderly, and Alzheimer’s disease patients in order to investigate whether these individuals experienced the effects of aging. The comparative threshold cycle (CT) method via Real Time Polymerase Chain Reaction and the Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) were used to analyze gene expression and the Apolipoprotein E (APOE) genotype, respectively. When the brain areas were analyzed collectively, we observed a significant decrease in APP expression and a significant increase in levels of mRNA of 18S and 28S in Alzheimer’s disease patients compared to healthy elderly individuals. Furthermore, there was a significant upregulation of 28SrRNA in the entorhinal cortex and hippocampus, but not in the auditory cortex of patients with AD. On the other hand, tests of blood samples verified a decreased expression of 28S rRNA in patients with AD. These results support the hypothesis that changes in rRNA are present in AD patients, are tissue-specific, and seem to occur independently and differently in each tissue. However, the next challenge is to discover the mechanisms responsible for the differences in expression observed in the blood and the brain in both healthy elderly individuals and Alzheimer’s disease patients, as well as the impact of these genes on AD pathogenesis.
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Lucas Rasmussen, Roger W. de Labio, Gustavo A. Viani, Elizabeth Chen, Joao Villares, Paulo-Henrique Bertolucci and Thais S. Minett, Gustavo Turecki, Danielle Cecyre, Sandra A. Drigo, Marilia C. Smith and Spencer L.M. Payao , Differential Expression of Ribosomal Genes in Brain and Blood of Alzheimer’s Disease Patients, Current Alzheimer Research 2015; 12 (10) . https://dx.doi.org/10.2174/1567205012666151027124017
DOI https://dx.doi.org/10.2174/1567205012666151027124017 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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