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GABA A , Receptor α 1 , α 4 , and β 3 Subunit mRNA and Protein Expression in the Frontal Cortex of Human Alcoholics
Author(s) -
Mitsuyama Hiroki,
Little Karley Y.,
Sieghart Werner,
Devaud Leslie L.,
Morrow A. Leslie
Publication year - 1998
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1998.tb03873.x
Subject(s) - protein subunit , receptor , endocrinology , medicine , messenger rna , biology , human brain , gene expression , alcohol dependence , alcohol , gene , biochemistry , neuroscience
Animal studies have shown that chronic ethanol consumption produces physical dependence upon ethanol and alters γ‐aminobutyric acid‐A (GABA A ) receptor subunit gene expression in brain. Although extensive investigation has been conducted in animal models, relatively little work has been performed directly on human alcoholic brain tissue to determine if there are alterations in GABA A , receptor gene expression. In this study, GABA A , receptor α 1 , α 4 , and β 3 subunit mRNA and peptide expression in postmortem frontal cortex from human alcoholics ( n = 15) and age‐ and sex‐matched controls ( n = 13) were measured by quantitative, competitive reverse transcription polymerase chain reaction and Western blot analysis. GABA A , receptor β 3 subunit mRNA expression was 35% greater ( p < 0.05) in alcoholics, compared with nonalcoholic controls. We found no significant difference in α 1 , and α 4 , subunit mRNA levels between groups. However, there was a trend toward greater (21%) α 1 subunit mRNA expression. There was no difference in α 1 , α 4 , or β 2/3 subunit peptide levels in frontal cortex between controls and alcoholics. Neither the age of the subjects nor the postmortem interval correlated with mRNA or peptide levels. Blood ethanol content also did not correlate with mRNA or peptide expression in alcoholic samples. These data suggest that GABA A , receptor adaptations, resulting from prolonged alcohol consumption in human alcoholics, may differ from animal models of alcohol dependence. These differences may be related to the longevity of alcohol exposure in human alcoholics, as well as variability in the dependence/withdrawal state of the human subjects. Therefore, further studies in human postmortem brain tissue are warranted.