Patterns of gene expression are altered in the frontal and motor cortices of human alcoholics

TLDR

Alcoholism is a major health problem, yet the mechanisms by which chronic alcohol abuse alters brain function remain poorly understood, likely involving disrupted signaling cascades and transcription factors that produce distinct gene expression patterns detectable only by microarray analyses. The authors profiled ~10,000 genes in frontal and motor cortices of chronic alcoholics and controls using cDNA microarrays, then classified genes into functional hierarchies to compare differential expression across groups. They found selective reprogramming of gene expression, with the greatest changes in myelin‑related and protein‑trafficking genes, and significant alterations in alcohol‑responsive, calcium, cAMP, and thyroid signaling pathways, indicating multiple pathways contribute to alcoholism neuropathology.

Abstract

Abstract 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.