Glutamate is the main excitatory and γ-aminobutyric acid (GABA) is the main inhibitory transmitter in the human brain. Drugs that affect the glutamatergic or the GABAergic signaling systems will alter the normal balance regulating neuronal excitability. The brain is one of the main targets of alcohol. Ethanol, the active molecule in alcoholic beverages, targets both glutamate and GABA-gated ion channels. We have examined the expression of glutamate channel subunit mRNAs in human post-mortem hippocampal dentate gyrus (HP-DG), orbitofrontal (OFC), and dorsolateral prefrontal cortex (DL-PFC) of individuals suffering from alcohol dependence and have compared the results to brain samples from individuals without alcohol dependence. HP-DC, OFC and DL-PFC samples from 21 controls and 19 individuals with chronic alcohol dependence were included in the study. Total RNA was isolated and assayed using the method of quantitative RT-PCR as described (Jin et al., 2011). Statistical analysis was carried out using SigmaPlot and SigmaStat analysis software. Shapiro-Wilk normality test was used to examine the normality of data distribution. The differences between the control and alcoholic groups were analysed by one-way ANOVA with Bonferroni post hoc test for normally distributed data and by non-parametric Kruskal-Wallis ANOVA on ranks with Dunn’s post hoc test for not normally distributed data. A significant level was set to p < 0.05. Out of the 16 glutamate receptor subunits, mRNAs encoding two AMPA (2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid) receptor subunits: GluA2, GluA3; three kainate receptor subunit : GluK1, GluK2, GluK5 and six NMDA (N-Methyl-D-aspartate) receptor subunits: GluN1, GluN2A, GluN2B, GluN2C, GluN2D, GluN3A in the HP-DG region were significantly increased. In the OFC, mRNA encoding the NMDA subunit GluN3A was increased. In the DL-PFC no changes in mRNA levels were detected between controls and alcoholics. Alcohol consumption clearly alters the expression of genes encoding the glutamate channels in a brain area-specific manner. Our laboratory has shown previously that genes encoding GABA-A receptors are altered in the HP-DG and the OFC from alcoholics (Jin et al, 2011). Whether changes in one neurotransmitter system drives changes in the other or if they change independently remains to be resolved.
37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCD129
Poster Communications: Selective changes of AMPA, NMDA and Kainate receptor subunit mRNAs in the hippocampus and orbitofrontal cortex but not in prefrontal cortex of human alcoholics
A. K. Bhandage1, Z. Jin1, I. Bazov2, O. Kononenko2, E. R. Korpi3, G. Bakalkin2, B. Birnir1
1. Neuroscience (Molecular Physiology), Biomedical Center, Uppsala University, Uppsala, Sweden. 2. Pharmaceutical Bioscience (Biological Research on Drug Dependence), Biomedical Center, Uppsala University, Uppsala, Sweden. 3. Pharmacology, Institute of Biomedicine, University of Helsinki, Helsinki, Finland.
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Where applicable, experiments conform with Society ethical requirements.