REGION-SELECTIVE REDUCTIONS IN ACTIVITIES OF GLUTAMINE-SYNTHETASE IN RAT-BRAIN FOLLOWING PORTACAVAL ANASTOMOSIS

Portacaval anastomosis in the rat results in liver atrophy, sustained hyperammonemia and mild encephalopathy. Previous studies have demonstr ated region-selective alterations of glutamine and other ammonia-relat ed amino acids in brain following portacaval anastomosis. Ammonia remo val by brain relies on glutamine synthesis and the enzyme responsible, glutamine synthetase, has an almost exclusively astrocytic localizati on. Glutamine synthetase activities were measured using a radioenzymat ic assay in homogenates of seven brain regions of rats four weeks afte r end-to-side portacaval anastomosis. Enzyme activities were significa ntly reduced in hippocampus (by 25%, p<0.01), in cerebellum (by 29%, p <0.01) and in cerebral cortex (by 14%, p<0.05). Enzyme activities in o ther brain regions were within normal limits. Region-selective reducti ons of glutamine synthetase following portacaval anastomosis could res ult in disruption of neuron-glial metabolic interactions and in a defi cit of glutamatergic synaptic regulation. Similar mechanisms could be implicated in the pathogenesis of hepatic encephalopathy accompanying chronic liver disease in humans.