The expression of NMDA receptor subunit mRNA in human chronic alcoholics.
Ethanol is a modulator at the N-methyl-d-aspartate class of glutamate receptors in the brain. In animal studies the receptor adapts to sustained ethanol exposure through altered expression of the subunits that make up the receptor complex. We used real-time RT-PCR normalized to GAPDH to assay NR1, NR2A, and NR2B subunit mRNA in superior frontal and primary motor cortex tissue obtained at autopsy from chronic alcoholics with and without co-morbid cirrhosis of the liver, and from matched controls. The expression of all three subunits was significantly lower in both areas of cirrhotic alcoholics than in the corresponding areas in both controls and alcoholics without co-morbid disease, who did not differ significantly from each other. The decrease was area-dependent when cases were partitioned by the 5-HTTLPR allele. Thus, polymorphisms in one gene can have a significant effect on the expression of a second, unrelated, gene. The expression of the N-methyl-d-aspartate glutamate receptor complex is under multifactorial control.
Ridge
Justin P
JP
SMMS, University of Queensland, Brisbane, Queensland, Australia.
Ho
Ada M-C
AM
Innes
David J
DJ
Dodd
Peter R
PR
D000437:Alcoholism / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D011110:Polymorphism, Genetic; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D012044:Regression Analysis; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism
C409466:NR1 NMDA receptor; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D021122:Protein Subunits; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D000431:Ethanol