Traute Flatscher-Bader and Marcel van der Brug contributed equally to this research.
Alcohol-responsive genes in the frontal cortex and nucleus accumbens of human alcoholics
Article first published online: 2 MAR 2005
Journal of Neurochemistry
Volume 93, Issue 2, pages 359–370, April 2005
How to Cite
Flatscher-Bader, T., van der Brug, M., Hwang, J. W., Gochee, P. A., Matsumoto, I., Niwa, S.-i. and Wilce, P. A. (2005), Alcohol-responsive genes in the frontal cortex and nucleus accumbens of human alcoholics. Journal of Neurochemistry, 93: 359–370. doi: 10.1111/j.1471-4159.2004.03021.x
- Issue published online: 2 MAR 2005
- Article first published online: 2 MAR 2005
- Received July 27, 2004; revised manuscript received November 30, 2004; accepted December 8, 2004.
- alcohol dependence;
- gene expression;
- mesolimbic system
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.