Alcohol-responsive genes in the frontal cortex and nucleus accumbens of human alcoholics
Alcohol-responsive genes in the frontal cortex and nucleus accumbens of human alcoholics
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DOI：
10.1111/j.1471-4159.2004.03021.x
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发表时间：
2005-04-01
影响因子：
4.7
通讯作者：
Wilce, PA
中科院分区：
文献类型：
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作者：
Flatscher-Bader, T;van der Brug, M;Wilce, PA
酒精依赖的分子过程尚未完全了解。许多特征性行为是中皮质边缘系统神经适应的结果。此外，酒精中毒与一种独特的神经病理学有关。为了阐明这些功能的分子基础，我们比较了使用cDNA微阵列匹配的个体酒精和对照病例的人脑前额叶皮质和脑髓核的RNA表达谱。大约6%的具有明显酒精反应的基因在两个大脑区域中是共同的。酒精反应基因被分为11个功能类别。前额叶皮层中主要的酒精反应基因是那些编码DNA结合蛋白的基因，包括转录因子和修复蛋白。编码线粒体蛋白的基因也下调，这可能导致线粒体功能和能量产生中断，从而导致氧化应激。前额叶皮层中的其他酒精反应基因与神经保护/细胞凋亡相关。相比之下，在神经核中，酒精反应基因与囊泡的形成和细胞结构的调节有关，这表明在突触结构和功能水平上对慢性酒精暴露的神经适应。我们的数据与先前报道的酒精中毒相关的病理特征的前额叶皮层，但建议持续减少神经传递和可塑性的变化，在核的酒精。
The molecular processes underlying alcohol dependence are not fully understood. Many characteristic behaviours result from neuroadaptations in the mesocorticolimbic system. In addition, alcoholism is associated with a distinct neuropathology. To elucidate the molecular basis of these features, we compared the RNA expression profile of the nucleus accumbens and prefrontal cortex of human brain from matched individual alcoholic and control cases using cDNA microarrays. Approximately 6% of genes with a marked alcohol response were common to the two brain regions. Alcohol-responsive genes were grouped into 11 functional categories. Predominant alcohol-responsive genes in the prefrontal cortex were those encoding DNA-binding proteins including transcription factors and repair proteins. There was also a down-regulation of genes encoding mitochondrial proteins, which could result in disrupted mitochondrial function and energy production leading to oxidative stress. Other alcohol-responsive genes in the prefrontal cortex were associated with neuroprotection/apoptosis. In contrast, in the nucleus accumbens, alcohol-responsive genes were associated with vesicle formation and regulation of cell architecture, which suggests a neuroadaptation to chronic alcohol exposure at the level of synaptic structure and function. Our data are in keeping with the previously reported alcoholism-related pathology characteristic of the prefrontal cortex, but suggest a persistent decrease in neurotransmission and changes in plasticity in the nucleus accumbens of the alcoholic.