Cerebral GABA-ergic and glutamatergic function in hepatic encephalopathy.
Measurement of amino acids in brain tissue obtained at autopsy from cirrhotic patients dying in hepatic coma revealed a threefold increase in glutamine and a concomitant decrease in brain glutamate. The GABA levels were found to be unaltered. Studies using an animal model of portal-systemic encephalopathy gave similar results. Glutamic acid decarboxylase (GAD) activities were within normal limits, both in the brains of cirrhotic patients and portocaval-shunted rats. A previous study reported normal [3H]GABA binding to synaptic membrane preparations from cerebral cortex in these animals. Taken together, these findings suggest that cerebral GABA function is not impaired in hepatic encephalopathy associated with chronic liver disease and portal-systemic shunting. On the other hand, there is evidence to suggest that the releasable pool of glutamate may be depleted in brain in hepatic encephalopathy. Data consistent with this hypothesis include: Reduction in the evoked release of endogenous glutamate by superfusion of hippocampal slices with pathophysiological levels of ammonia; ammonia-induced reduction of glutamatergic neurotransmission; and an increase in the number of [3H]glutamate binding sites in synaptic membrane preparations from hyperammonemia rats and from rats with portocaval shunts. Such neurochemical changes may be of pathophysiological significance in hepatic encephalopathy.
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D005973:Glutamine / Q000378:metabolism*; D006501:Hepatic Encephalopathy / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D008297:Male; D011167:Portacaval Shunt, Surgical; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D005971:Glutamates; D005973:Glutamine; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase