Glucose deprivation neuronal injury in vitro is modified by withdrawal of extracellular glutamine.
Cultured cortical neurons deprived of glucose in a defined solution containing 2 mM glutamine became acutely swollen and went on to degenerate over the next day; this neuronal loss could be substantially attenuated by an N-methyl-D-aspartate (NMDA) antagonist. Removal of extracellular glutamine produced two effects: an increase in overall neuronal injury and a decrease in the protective effect of an NMDA antagonist. Both effects of glutamine removal were glutamine concentration dependent (EC50 for both approximately 300 microM) and not reversed by substitution of equimolar concentrations of alanine or arginine. These observations suggest that glucose deprivation neuronal injury may be tonically regulated by the presence of extracellular glutamine. We speculate that glutamine may reduce overall injury by serving as an energy substrate in the absence of glucose, but may increase NMDA receptor-mediated injury by serving as a precursor for transmitter excitatory amino acids.
Department of Neurology, Stanford University School of Medicine, California 94305.
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D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D016202:N-Methylaspartate; D009474:Neurons / Q000378:metabolism* / Q000473:pathology
D005973:Glutamine; D001224:Aspartic Acid; D016202:N-Methylaspartate; D005947:Glucose