Genes and gene expression in human alcoholic brain

Dodd, Peter R., Buckley, S. Tracey, Foley, Philomena F., Eckert, Alison L. and Innes, David J. (2006). Genes and gene expression in human alcoholic brain. In: Alcoholism: Clinical and Experimental Research. 29th Annual Meeting of the Research Society on Alcoholism, Baltimore, USA, (218A-218A). 23-29 June, 2006. doi:10.1111/j.1530-0277.2006.00150.x


Author Dodd, Peter R.
Buckley, S. Tracey
Foley, Philomena F.
Eckert, Alison L.
Innes, David J.
Title of paper Genes and gene expression in human alcoholic brain
Conference name 29th Annual Meeting of the Research Society on Alcoholism
Conference location Baltimore, USA
Conference dates 23-29 June, 2006
Proceedings title Alcoholism: Clinical and Experimental Research   Check publisher's open access policy
Journal name Alcoholism-Clinical and Experimental Research   Check publisher's open access policy
Place of Publication Maryland, USA
Publisher Blackwell
Publication Year 2006
Sub-type Published abstract
DOI 10.1111/j.1530-0277.2006.00150.x
ISSN 0145-6008
Volume 30
Issue Supp 1
Start page 218A
End page 218A
Total pages 1
Language eng
Abstract/Summary Chronic alcoholism leads to localized brain damage, which is prominent in superior frontal cortex but mild in motor cortex. The likelihood of developing alcohol dependence is associated with genetic markers. GABA-A receptor expression differs between alcoholics and controls, whereas glutamate receptor differences are muted. We determined whether genotype differentiated the localized expression of glutamate N-methyl-D-aspartate (NMDA) and GABA-A receptors to influence the severity of alcohol-induced brain damage. Cerebral cortex tissue was obtained at autopsy from alcoholics without disease comorbid with alcoholics, alcoholics with cirrhosis, and matched controls. DRD2A, DRD2B, GABRB2, SLC1A2, and 5HTT genotypes did not divide alcoholic cases and controls on NMDA receptor parameters. In contrast, a specific alcohol dehydrogenase (ADHIC) genotype interacted significantly with NMDA efficacy and affinity in a region-specific manner SLC1A2 (glutamate transporter-2) genotype interacted significantly with local GABAA receptor b subunit mRNA expression, and ADHIC, DRD2B, SLC1A2, and APOE genotypes with b subunit isoform protein expression. In the latter instance, possession of the alcoholism- associated allele altered b isoform protein expression patterns toward a less-efficacious form of the GABA-A receptor in the pathologically vulnerable region. GABRB2 and GRIN2B (NMDA receptor 2B subunit} Genotypes were associated with significant regional difference in the pattern of b subunit protein isoform expression, but this was not influenced by alcoholism status. Genotype may modulate amino acid transmission locally so as to mediate neuronal vulnerability. This has implications for the effectiveness of pharmacological interventions aimed at ameliorating brain damage and, possibly, dependence.
Subjects EX
780105 Biological sciences
060405 Gene Expression (incl. Microarray and other genome-wide approaches)
1101 Medical Biochemistry and Metabolomics
1109 Neurosciences
Keyword Alcoholism
GABA-A
Glutamate
Q-Index Code EX
Additional Notes DOI is for all abstracts published between Pp. 7A-234A

 
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Created: Thu, 23 Aug 2007, 21:45:04 EST