Gene expression in human alcoholism: Microarray analysis of frontal cortex
Gene expression in human alcoholism: Microarray analysis of frontal cortex
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DOI：
10.1111/j.1530-0277.2000.tb01993.x
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发表时间：
2000-12-01
影响因子：
3.2
通讯作者：
Harris, RA
中科院分区：
文献类型：
--
作者：
Lewohl, JM;Wang, L;Harris, RA
背景资料：大脑基因表达的变化被认为是负责的耐受性，依赖性，和神经毒性产生的慢性酒精滥用，但一直没有大规模的研究人类alcoholis.Methods：RNA的基因表达提取自死后样本的上级额叶皮质的酗酒者和nonalcoholics。通过阵列技术测定RNA的相对水平。我们使用了cDNA和寡核苷酸微阵列，以提供大量的基因覆盖率，并允许交叉验证的这些基因上代表的两种类型的arrais.Results：表达水平被确定为超过4000个基因，其中163个被发现不同的酗酒者和nonalcoholics之间的40%或更多。对这些变化的分析揭示了该大脑区域基因表达的选择性重编程，特别是在酒精样本中下调的髓鞘相关基因。此外，细胞周期基因和几个神经元基因的表达发生了变化。结论：这些基因表达的变化表明，在酗酒者的大脑白色物质的损失，以及可能导致乙醇的神经毒性作用的改变的机制。
Background: Changes in brain gene expression are thought to be responsible for the tolerance, dependence, and neurotoxicity produced by chronic alcohol abuse, but there has been no large scale study of gene expression in human alcoholism.Methods: RNA was extracted from postmortem samples of superior frontal cortex of alcoholics and nonalcoholics. Relative levels of RNA were determined by array techniques. We used both cDNA and oligonucleotide microarrays to provide coverage of a large number of genes and to allow cross-validation for those genes represented on both types of arrays.Results: Expression levels were determined for over 4000 genes and 163 of these were found to differ by 40% or more between alcoholics and nonalcoholics. Analysis of these changes revealed a selective reprogramming of gene expression in this brain region, particularly for myelin-related genes which were downregulated in the alcoholic samples. In addition, cell cycle genes and several neuronal genes were changed in expression.Conclusions: These gene expression changes suggest a mechanism for the loss of cerebral white matter in alcoholics as well as alterations that may lead to the neurotoxic actions of ethanol.