Changes in glutamate-cycle enzyme mRNA levels in a rat model of hepatic encephalopathy.

To detect possible changes in the regulation of glutamate/gamma-aminobutyric acid (GABA) enzymes at the level of gene expression in a thioacetamide-induced rat model of acute hepatic encephalopathy, we have examined changes in the mRNAs of four glutamate/GABA enzymes by quantitative RNA blot hybridization analysis. Such changes could reflect cell adaptation to excess ammonia or some other associated metabolic stress. The mRNA levels of glutamate dehydrogenase (GDH) decreased similarly in three different brain regions, whereas those of glutamine synthetase (GS) and glutaminase (GA) increased. The mRNA levels of glutamate decarboxylase (GAD) were unchanged. The results indicate that some effect of liver damage, presumably hyperammonemia, affected the expression of some, but not all, genes associated with ammonia and glutamate metabolism in the brain. This adaptation of gene expression to secondary effects of ammonia on brain amino acid neurotransmitter metabolism or brain energy metabolism could play a role in the physiological changes observed in hepatic encephalopathy.