Mayfield R Dayne, Lewohl Joanne M, Dodd Peter R, Herlihy Amy, Liu Jianwen, Harris R Adron
Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA.
J Neurochem. 2002 May;81(4):802-13. doi: 10.1046/j.1471-4159.2002.00860.x.
Alcoholism is a major health problem in Western countries, yet relatively little is known about the mechanisms by which chronic alcohol abuse causes the pathologic changes associated with the disease. It is likely that chronic alcoholism affects a number of signaling cascades and transcription factors, which in turn result in distinct gene expression patterns. These patterns are difficult to detect by traditional experiments measuring a few mRNAs at a time, but are well suited to microarray analyses. We used cDNA microarrays to analyze expression of approximately 10 000 genes in the frontal and motor cortices of three groups of chronic alcoholic and matched control cases. A functional hierarchy was devised for classification of brain genes and the resulting groups were compared based on differential expression. Comparison of gene expression patterns in these brain regions revealed a selective reprogramming of gene expression in distinct functional groups. The most pronounced differences were found in myelin-related genes and genes involved in protein trafficking. Significant changes in the expression of known alcohol-responsive genes, and genes involved in calcium, cAMP, and thyroid signaling pathways were also identified. These results suggest that multiple pathways may be important for neuropathology and altered neuronal function observed in alcoholism.
酒精中毒是西方国家的一个主要健康问题，但对于慢性酒精滥用导致与该疾病相关的病理变化的机制，人们了解得相对较少。慢性酒精中毒可能会影响多个信号级联反应和转录因子，进而导致不同的基因表达模式。这些模式很难通过一次测量少数几种mRNA的传统实验来检测，但非常适合微阵列分析。我们使用cDNA微阵列分析了三组慢性酒精中毒患者和匹配的对照病例的额叶和运动皮质中约10000个基因的表达。设计了一个功能层次结构来对脑基因进行分类，并根据差异表达对所得组进行比较。这些脑区基因表达模式的比较揭示了不同功能组中基因表达的选择性重编程。在髓鞘相关基因和参与蛋白质运输的基因中发现了最显著的差异。还确定了已知酒精反应性基因以及参与钙、环磷酸腺苷（cAMP）和甲状腺信号通路的基因表达的显著变化。这些结果表明，多种途径可能对酒精中毒中观察到的神经病理学和神经元功能改变很重要。
