Increased expression of mitochondrial genes in human alcoholic brain revealed by differential display

Polymerase chain reaction (PCR)-based differential display was used to scre en for alterations in gene expression in the mesolimbic system of the human alcoholic brain. Total RNA was extracted from the nucleus accumbens of fiv e alcoholic and five control brains. A selected subpopulation of mRNA was r everse-transcribed to cDNA and amplified by PCR. A differentially expressed cDNA fragment was recovered, cloned, and sequenced. Full sequence analysis of this 467 bp fragment revealed 98.2% homology with the human mitochondri al 12S rRNA gene. Dot-blot analysis showed increased expression of this gem in nucleus accumbens and hippocampus, but not in the superior frontal cort ex, primary motor cortex, caudate, and pallidus/putamen In a total of eight human alcoholic brains, compared with seven control brains. A similar incr eased expression was observed by dot-blot analysis, using RNA from the cere bral cortex of rats chronically treated with alcohol vapor. Hybridization o f a 16S rRNA oligonucleotide probe indicated that the expression of both rR NAs genes was significantly increased in nucleus accumbens. These results i ndicate that chronic alcohol consumption induces alteration in expression o f mitochondrial genes in selected brain regions. The altered gene expressio n may reflect mitochondrial dysfunction In the alcohol-affected brain.