The glial glutamate transporter in hyperammonemia and hepatic encephalopathy: relation to energy metabolism and glutamatergic neurotransmission.
Abnormalities in glutamate metabolism and glutamatergic neurotransmission appear to play a major role in the pathogenesis of hyperammonemia and hepatic encephalopathy. Astrocytes may be involved in these derangements 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 with thioacetamide-induced acute liver failure. Our findings demonstrate a downregulation of GLT-1 mRNA in both conditions. This article examines the potential impact of deficits in glutamate uptake on energy metabolism and glutamatergic neurotransmission in the context of abnormalities in glial-neuronal interactions. We propose that an ammonia-induced abnormality in astroglial glutamate uptake constitutes a critical aspect in the pathogenesis of hepatic encephalopathy and other hyperammonemic conditions.
Norenberg
M D
MD
Veterans Administration Medical Center and the Department of Pathology, University of Miami School of Medicine, Florida 33101, USA. mnorenbe@mednet.med.miami.edu
Huo
Z
Z
Neary
J T
JT
Roig-Cantesano
A
A
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG; D000641:Ammonia / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001692:Biological Transport; D001921:Brain / Q000378:metabolism* / Q000502:physiology / Q000503:physiopathology; D002952:Citric Acid Cycle; D004734:Energy Metabolism; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology*; D006501:Hepatic Encephalopathy / Q000139:chemically induced / Q000378:metabolism*; D008956:Models, Chemical; D009457:Neuroglia / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000378:metabolism* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission; D013853:Thioacetamide; D014158:Transcription, Genetic
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D012333:RNA, Messenger; D013853:Thioacetamide; D018698:Glutamic Acid; D000641:Ammonia