THE GLIAL GLUTAMATE TRANSPORTER IN HYPERAMMONEMIA AND HEPATIC-ENCEPHALOPATHY - RELATION TO ENERGY-METABOLISM AND GLUTAMATERGIC NEUROTRANSMISSION

Abnormalities in glutamate metabolism and glutamatergic neurotransmiss ion appear to play a major role in the pathogenesis of hyperammonemia and hepatic encephalopathy. Astrocytes may be involved in these derang ements as ammonia has been shown to impair the ability of these cells to take up glutamate. This study presents a northern blot analysis of the GLT-1 glutamate transporter in hyperammonemic rats, and in rats wi th thioacetamide-induced acute liver failure. Our findings demonstrate a downregulation of GLT-1 mRNA in both conditions. This article exami nes the potential impact of deficits in glutamate uptake on energy met abolism and glutamatergic neurotransmission in the context of abnormal ities in glial-neuronal interactions. We propose that an ammonia-induc ed abnormality in astroglial glutamate uptake constitutes a critical a spect in the pathogenesis of hepatic encephalopathy and other hyperamm onemic conditions. (C) 1997 Wiley-Liss, Inc.