Gene expression profiling of individual cases reveals consistent transcriptional changes in alcoholic human brain.
Chronic alcohol exposure induces lasting behavioral changes, tolerance, and dependence. This results, at least partially, from neural adaptations at a cellular level. Previous genome-wide gene expression studies using pooled human brain samples showed that alcohol abuse causes widespread changes in the pattern of gene expression in the frontal and motor cortices of human brain. Because these studies used pooled samples, they could not determine variability between different individuals. In the present study, we profiled gene expression levels of 14 postmortem human brains (seven controls and seven alcoholic cases) using cDNA microarrays (46,448 clones per array). Both frontal cortex and motor cortex brain regions were studied. The list of genes differentially expressed confirms and extends previous studies of alcohol responsive genes. Genes identified as differentially expressed in two brain regions fell generally into similar functional groups, including metabolism, immune response, cell survival, cell communication, signal transduction and energy production. Importantly, hierarchical clustering of differentially expressed genes accurately distinguished between control and alcoholic cases, particularly in the frontal cortex.
Liu
Jianwen
J
Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, Texas 78712, USA. liujw@mail.utexas.edu
Lewohl
Joanne M
JM
Dodd
Peter R
PR
Randall
Patrick K
PK
Harris
R Adron
RA
Mayfield
R Dayne
RD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000437:Alcoholism / Q000235:genetics / Q000378:metabolism*; D001499:Bayes Theorem; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014158:Transcription, Genetic / Q000187:drug effects*
D002492:Central Nervous System Depressants; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000431:Ethanol