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

Journal of Neuroscience Research - Tập 70 Số 3 - Trang 462-473 - 2002
Vittorio Colangelo1, Jill R. Schurr2, Melvyn J. Ball3, Ricardo Palacios Peláez4, Nicolás G. Bazán5,1, Walter J. Lukiw5,1
1Neuroscience Center, Louisiana State University Health Sciences Center, New Orleans, Louisiana
2Department of Biometry, Louisiana State University Health Sciences Center, New Orleans, Louisiana
3Oregon Health and Science University, Portland, Oregon
4Diater Laboratories, San Martin de la Vega, Madrid, Spain
5Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, Louisiana

Tóm tắt

AbstractAlterations 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 (A260/280 ≥ 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 ≤ 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, cPLA2, CDP5, NF‐κBp52/p100, FAS, βAPP, 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. © 2002 Wiley‐Liss, Inc.

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Journal of Neuroscience Research

Tập 70 Số 3

462-473

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