Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: Transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling
Gene expression profiling of 12633 genes in Alzheimer hippocampal CA1: Transcription and neurotrophic factor down-regulation and up-regulation of apoptotic and pro-inflammatory signaling
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DOI：
10.1002/jnr.10351
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发表时间：
2002-11-01
影响因子：
4.2
通讯作者：
Lukiw, WJ
中科院分区：
文献类型：
--
作者：
Colangelo, V;Schurr, J;Lukiw, WJ
转录、RNA编辑、翻译、蛋白质加工和清除的改变是阿尔茨海默病（AD）大脑的一致特征。为了扩展我们最初的研究（Alzheimer Reports[2000] 3:161-167），我们使用DNA微阵列（HG-U95Av2 Genechips; Affymetrix, Santa Clara， CA）分析了从对照和AD海马cornu amonis 1 （CA1）中分离的RNA样本12633基因和表达序列标签（EST）的表达水平。海马CA1组织从国内外脑库获得的数百个潜在标本中精心挑选。为了尽量减少基因表达个体差异的影响，从6名对照或6名AD受试者的CA1中收集了高光谱质量（A（260/280）大于或等于1.9）的RNA。结果作为一组进行比较；个体基因表达模式的最大变化的RNA信息水平也被描绘。两脑组在年龄、死后间隔（平均小于或等于2.1小时）和组织pH值（范围6.6-6.9）方面均无显著差异。AD组织来源于临床分类为CDR 2-3 （CERAD/NIA）的受试者。使用genesspring （Silicon Genetics, Redwood City， CA）和Microarray data Mining Tool （Affymetrix）软件分析表达数据。与对照组和354个背景/比对标记相比，阿尔茨海默病脑显示出脑基因转录的普遍抑制，包括RNA编码转录因子（tf）、神经营养因子、突触素、金属硫蛋白III和金属调节因子-1等突触可塑性信号元件的减少。编码DAXX、cPLA(2)、CDP5、NF-kappaBp52/p100、FAS、betaAPP、DPP1、NFIL6、IL前体、B94、HB15、COX-2和CEX-1信号的rna显著增加3倍或更多。这些数据支持了在中度影响的AD海马CA1中广泛的转录改变、参与金属离子稳态的rna的错误调节、TF信号缺陷、神经营养支持减少以及激活的凋亡和神经炎症信号的假设。(C) 2002 Wiley-Liss, Inc。
Alterations in transcription, RNA editing, translation, protein processing, and clearance are a consistent feature of Alzheimer's disease (AD) brain. To extend our initial study (Alzheimer Reports [2000] 3:161-167), RNA samples isolated from control and AD hippocampal cornu ammonis 1 (CA1) were analyzed for 12633 gene and expressed sequence tag (EST) expression levels using DNA microarrays (HG-U95Av2 Genechips; Affymetrix, Santa Clara, CA). Hippocampal CA1 tissues were carefully selected from several hundred potential specimens obtained from domestic and international brain banks. To minimize the effects of individual differences in gene expression, RNA of high spectral quality (A(260/280) greater than or equal to 1.9) was pooled from CA1 of six control or six AD subjects. Results were compared as a group; individual gene expression patterns for the most-changed RNA message levels were also profiled. There were no significant differences in age, postmortem interval (mean less than or equal to 2.1 hr) nor tissue pH (range 6.6-6.9) between the two brain groups. AD tissues were derived from subjects clinically classified as CDR 2-3 (CERAD/NIA). Expression data were analyzed using GeneSpring (Silicon Genetics, Redwood City, CA) and Microarray Data Mining Tool (Affymetrix) software. Compared to controls and 354 background/alignment markers, AD brain showed a generalized depression in brain gene transcription, including decreases in RNA encoding transcription factors (TFs), neurotrophic factors, signaling elements involved in synaptic plasticity such as synaptophysin, metallothionein III, and metal regulatory factor-1. Three- or morefold increases in RNAs encoding DAXX, cPLA(2), CDP5, NF-kappaBp52/p100, FAS, betaAPP, DPP1, NFIL6, IL precursor, B94, HB15, COX-2, and CEX-1 signals were strikingly apparent. These data support the hypothesis of widespread transcriptional alterations, misregulation of RNAs involved in metal ion homeostasis, TF signaling deficits, decreases in neurotrophic support and activated apoptotic and neuroinflammatory signaling in moderately affected AD hippocampal CA1. (C) 2002 Wiley-Liss, Inc.