Patterns of gene expression are altered in the frontal and motor cortices of human alcoholics.
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.
Mayfield
R Dayne
RD
Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA. dayne.mayfield@mail.utexas.edu
Lewohl
Joanne M
JM
Dodd
Peter R
PR
Herlihy
Amy
A
Liu
Jianwen
J
Harris
R Adron
RA
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D000437:Alcoholism / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002908:Chronic Disease; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D009044:Motor Cortex / Q000378:metabolism* / Q000473:pathology; D009186:Myelin Sheath / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D021381:Protein Transport / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D015398:Signal Transduction / Q000235:genetics
D012333:RNA, Messenger