Alcohol and Alcoholism Advance Access originally published online on September 7, 2009
Alcohol and Alcoholism 2009 44(6):594-601; doi:10.1093/alcalc/agp052
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Sex Differences in NMDA Receptor Expression in Human Alcoholics
School of Chemistry and Molecular Biosciences, The University of Queensland, Australia
* Corresponding author: Molecular Biosciences, Building no. 76, SCMB, University of Queensland St Lucia, Brisbane 4072, Australia. Tel: +61-7-3365-3364; Fax: +61-7-3365-4699; E-mail: p.dodd{at}uq.edu.au
Received 9 January 2009; first review notified 3 March 2009; in revised form 31 March 2009; accepted 6 May 2009; advance access publication 7 September 2009
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Abstract |
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Aim: The aim of this study was to assess whether chronic alcohol misuse affects N-methyl-D-aspartate (NMDA) receptor subunit concentrations in human cases, and whether male and female subjects respond differently. Methods: Real-time RT-PCR normalized to GAPDH was used to assay NR1, NR2A and NR2B subunit mRNA in superior frontal (SFC) and primary motor (PMC) cortex tissue obtained at autopsy from chronic alcoholics with and without comorbid cirrhosis of the liver, and from matched controls. Results: The expression of all three subunits was significantly lower in both areas of cirrhotic alcoholics than in either controls or alcoholics without comorbid disease, who did not differ significantly. Values were also influenced by the subject's sex and genotype. The µ-opiate receptor C1031G polymorphism selectively modulated NMDA transcript expression in cirrhotic-alcoholic SFC, an effect that was more marked for NR1 and NR2A than for NR2B subunit transcripts. Contrasting 5HT1B genotypes affected NMDA mRNA expression differently in male and female SFC, but not PMC, in cirrhotic alcoholics. Conclusion: NMDA receptor subunit expression may differentially influence male and female cirrhotic alcoholics’ susceptibility to brain damage.