GeneChip® analysis shows altered mRNA expression of transcripts of neurotransmitter and signal transduction pathways in the cerebral cortex of portacaval shunted rats

Identifying the gene expression changes induced by hepatic encephalopathy (HE) leads to a better understanding of the molecular mechanisms of HE-induced neurological dysfunction. Using GeneChip(R) and real-time PCR, the present study evaluated the gene expression profile of rat cerebral cortex at 4 weeks after portacaval shunting. Among 1,263 transcripts represented on the chip, mRNA levels of 31 transcripts were altered (greater than twofold; 16 increased and 15 decreased) in the portacaval shunted (PCS) rat compared to sham control. Changes observed by GeneChip(R) analysis were confirmed for 20 transcripts (8 increased, 7 decreased, and 5 unchanged in PCS rat brain) by real-time PCR. Neurotransmitter receptors, transporters, and members of the second messenger signal transduction are the major groups of genes altered in PCS rat brain. Of importance was that the increased heme oxygenase-1 and decreased Cu,Zn-superoxide dismutase expression observed raise the possibility of oxidative stress playing a pathogenic role in chronic HE. (C) 2002 Wiley-Liss, Inc.