An emerging idea is that long-term alcohol abuse results in changes in gene
expression in the brain and that these changes are responsible at least pa
rtly for alcohol tolerance, dependence and neurotoxicity, The overall goal
of our research is to identify genes which are differentia[ly expressed in
the brains of well-characterized human alcoholics as compared with non-alco
holics. This should identify as-yet-unknown alcohol-responsive genes, and m
ay well confirm changes in the expression of genes which have been delineat
ed in animal models of alcohol abuse. Cases were carefully selected and sam
ples pooled on the basis of relevant criteria; differential expression was
monitored by microarray hybridization. The inherent diversity of human alco
holics can be exploited to identify genes associated with specific patholog
ical processes, as well as to assess the effects of concomitant disease, se
verity of brain damage, drinking behavior, and factors such as gender and s
moking history. initial results show selective changes in gene expression i
n alcoholics; of particular importance is a coordinated reduction in genes
coding for myelin components, Copyright (C) 2001 National Science Council,
ROC and S. Karger AG, Basel.