Connection failure: Genotype-phenotype interactions at the alcoholic synapse

Dodd, P. R. (2010). Connection failure: Genotype-phenotype interactions at the alcoholic synapse. In: Special Issue: Abstracts from the International Society for Biomedical Research on Alcoholism World Congress. World Congress on International-Society-for-Biomedical-Research-on-Alcoholism, Paris, France, (30A-30A). 13-16 September 2010. doi:10.1111/j.1530-0277.2010.01292_3.x


Author Dodd, P. R.
Title of paper Connection failure: Genotype-phenotype interactions at the alcoholic synapse
Conference name World Congress on International-Society-for-Biomedical-Research-on-Alcoholism
Conference location Paris, France
Conference dates 13-16 September 2010
Proceedings title Special Issue: Abstracts from the International Society for Biomedical Research on Alcoholism World Congress   Check publisher's open access policy
Journal name Alcoholism: Clinical and Experimental Research   Check publisher's open access policy
Place of Publication Hoboken, NJ, United States
Publisher Wiley-Blackwell Publishing
Publication Year 2010
Sub-type Published abstract
DOI 10.1111/j.1530-0277.2010.01292_3.x
ISSN 0145-6008
1530-0277
Volume 34
Issue s3
Start page 30A
End page 30A
Total pages 1
Language eng
Abstract/Summary To understand the effects of chronic alcohol misuse on synaptic signalling, we compare vulnerable and relatively spared cortical areas in brains taken at autopsy from alcoholics and matched controls. Cases with and without common comorbid diseases add important insights: cirrhosis, for example, has major sequelæ for brain function because the failing liver cannot remove a range of toxins, especially ammonia. Male-female comparisons form another dimension, since there are well-known sex differences in susceptibility. We have developed a series of molecular techniques to study transcript and protein expression human autopsy brain, and are exploring interactions with markers brought to light by genetic studies. Using synaptosomal and synaptic membrane preparations from well-characterized cases and controls we can quantify receptor binding as well as the expression of isoform subunit transcripts and proteins. We find, in general, that alcoholics without comorbid disease show more marked differences from controls in GABA receptor parameters, whereas NMDA sites are more prominently affected in cirrhotic alcoholics. However, both genotype and gender can modify these outcomes. For example, the A1 allele in the ANKK1 gene, downstream of DRD2, modulates NMDA subunit expression differentially in males and females. As well as hypothesis-driven approaches we have applied discoverybased techniques and were the first to use microarray analysis with human brain. These approaches provide new, sometimes unexpected, leads. Proteomic studies have portrayed selective post-translational changes in the synaptosomal proteins that suggest that epigenetic processes can alter key components of the synaptic machinery. These alterations will have consequences for the efficacy of trans-synaptic signalling in damaged areas of the brain of the alcoholic.
Q-Index Code CX
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Speaker abstracts - S057

Document type: Conference Paper
Collection: School of Chemistry and Molecular Biosciences
 
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