DNA microarray analysis of the contused spinal cord: Effect of NMDA receptor inhibition
DNA microarray analysis of the contused spinal cord: Effect of NMDA receptor inhibition
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DOI：
10.1002/jnr.10171
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发表时间：
2002-05-15
影响因子：
4.2
通讯作者：
Perez-Polo, JR
中科院分区：
文献类型：
--
作者：
Nesic, O;Svrakic, NM;Perez-Polo, JR
脊髓损伤(SCI)引起的神经退行性变导致不可逆转的破坏性运动和感觉功能障碍。创伤后的结局由脊髓损伤后24小时内发生的事件决定。细胞外谷氨酸浓度升高到神经毒性水平是脊髓损伤后最早的事件之一。我们使用Affymetrix DNA寡核苷酸芯片(带有1,322个DNA探针)分析基因表达，以验证脊髓损伤诱导的N-甲基-D-天冬氨酸(NMDA)受体激活触发损伤后显著转录变化的假设。在这里，我们报道了脊髓损伤后1小时，引起165个基因和表达序列标签(EST)的mRNA水平的变化。脊髓损伤影响了那些主要调控转录因子、炎症、细胞存活和膜兴奋性的基因的mRNA水平。我们还报道了NMDA受体抑制(用-(+)-5-甲基-10，11-二氢-5H-二苯并[a，d]-环庚烯-5，10-亚胺氢马来酸[MK-801])逆转了脊髓损伤后约50%受脊髓损伤影响的mRNAs的作用。特别有趣的是，NMDA受体的激活参与了炎症因子的上调。因此，脊髓损伤诱导的NMDA受体激活是创伤后主要的早期信号之一，导致与恢复过程相关的一些基因的mRNA水平的变化。本文报道的MK-801对脊髓损伤诱导的信使核糖核酸变化的影响大多是新的。此外，我们还发现，MK-801治疗还改变了168个基因和EST的mRNA水平，这些基因和EST没有单独受到脊髓损伤的影响，它们的一些基因产物可能对脊髓损伤的结局产生不利影响。(C)2002年Wiley-Liss，Inc.
Spinal cord injury (SCI)-induced neurodegeneration leads to irreversible and devastating motor and sensory dysfunction. Post-traumatic outcomes are determined by events occurring during the first 24 hours after SCI. An increase in extracellular glutamate concentration to neurotoxic levels is one of the earliest events after SCI. We used Affymetrix DNA oligonucleotide microarrays (with 1,322 DNA probes) analysis to measure gene expression in order to test the hypothesis that SCI-induced N-methyl-D-aspartate (NMDA) receptor activation triggers significant postinjury transcriptional changes. Here we report that SCI, 1 hour after trauma, induced change in mRNA levels of 165 genes and expression sequence tags (ESTs). SCI affected mRNA levels of those genes that regulate predominantly transcription factors, inflammation, cell survival, and membrane excitability. We also report that NMDA receptor inhibition (with -(+)-5-methyl-10,11 -dihydro-5H-dibenzo[a,d]-cyclohepten-5, 10-imine hydrogen maleate [MK-801]) reversed the effect of SCI on about 50% of the SCI-affected mRNAs. Especially interesting is the finding that NMDA receptor activation participates in the up-regulation of inflammatory factors. Therefore, SCI-induced NMDA receptor activation is one of the dominant, early signals after trauma that leads to changes in mRNA levels of a number of genes relevant to recovery processes. The majority of MK-801 effects on the SCI-induced mRNA changes reported here are novel. Additionally, we found that the MK-801 treatment also changed the mRNA levels of 168 genes and ESTs that had not been affected by SCI alone, and that some of their gene products could have harmful effects on SCI outcome. (C) 2002 Wiley-Liss, Inc.