Title |
Genes and Gene Expression in the Brains of Human Alcoholics
|
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Published in |
Annals of the New York Academy of Sciences, September 2006
|
DOI | 10.1196/annals.1369.010 |
Pubmed ID | |
Authors |
PETER R. DODD, S. TRACEY BUCKLEY, ALLISON L. ECKERT, PHILOMENA F. FOLEY, DAVID J. INNES |
Abstract |
Chronic alcohol misuse by human subjects leads to neuronal loss in regions such as the superior frontal cortex (SFC). Propensity to alcoholism is associated with several genes. gamma-Aminobutyric acid (GABA)(A) receptor expression differs between alcoholics and controls, whereas glutamate receptor differences are muted. We determined whether genotype differentiated the regional presentation of GABA(A) and glutamate-NMDA (N-methyl-d-aspartate) receptors in SFC. Autopsy tissue was obtained from alcoholics without comorbid disease, alcoholics with liver cirrhosis, and matched controls. ADH1C, DRD2B, EAAT2, and APOE genotypes modulated GABA(A)-beta subunit protein expression in SFC toward a less-effective form of the receptor. Most genotypes did not divide alcoholics and controls on glutamate-NMDA receptor pharmacology, although gender and cirrhosis did. Genotype may affect amino acid transmission locally to influence neuronal vulnerability. |
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