Ammonia downregulates GLAST mRNA glutamate transporter in rat astrocyte cultures

Abnormalities in glutamate metabolism and glutamatergic neurotransmission a ppear to play an important role in the pathogenesis of hyperammonemia and h epatic encephalopathy. Previous studies from our laboratory have shown that treatment of cultured astrocytes with NH4Cl result in decreased glutamate uptake. To extend these observations, we performed a Northern blot analysis of the astroglial glutamate transporter GLAST (EAAT1) in NH4Cl-treated pri mary rat astrocyte cultures. Following treatment with 2, 5, 10 mM NH4Cl for 3 days, cortical astrocytes showed a 22, 29, 36% decrease: in GLAST mRNA, respectively. Striatal astrocytes showed 25, 51, 50% reduction, while cereb ellar cultures showed decrements of 18, 37, 38%. Similar decreases in GLAST mRNA were also observed after 1 day of ammonia treatment. These findings, together with recent reports on the reduction of the GLT-1 glutamate transp orter in in vivo models of acute liver failure and hyperammonemia, strongly suggest that an abnormality in astroglial glutamate uptake constitutes a c ritical aspect in the pathogenesis of hepatic encephalopathy and other hype rammonemic conditions. (C) 1999 Published by Elsevier Science Ireland Ltd. All rights reserved.