Gene expression in human alcoholism: Microarray analysis of frontal cortex

Background: Changes in brain gene expression are thought to be responsible for the tolerance, dependence, and neurotoxicity produced by chronic alcoho l abuse, but there has been no large scale study of gene expression in huma n alcoholism. Methods: RNA was extracted from postmortem samples of superior frontal cort ex of alcoholics and nonalcoholics. Relative levels of RNA were determined by array techniques. We used both cDNA and oligonucleotide microarrays to p rovide coverage of a large number of genes and to allow cross-validation fo r those genes represented on both types of arrays. Results: Expression levels were determined for over 4000 genes and 163 of t hese were found to differ by 40% or more between alcoholics and nonalcoholi cs. Analysis of these changes revealed a selective reprogramming of gene ex pression 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 lea d to the neurotoxic actions of ethanol.