Ethanol and glucose-deprivation neurotoxicity in cortical cell cultures.
The toxic effects of ethanol on rat cortical cell cultures were compared with neuronal damage induced by glucose deprivation. Exposure to decreased glucose concentrations produced dose-dependent neuronal injury, as indicated by the release of lactate dehydrogenase (LDH) into the culture medium. Complete glucose deprivation resulted in mean LDH release that was more than 60% greater than that from sister cultures incubated in the presence of 5.5 mmol/L glucose. Exposure to ethanol (25, 50, or 100 mmol/L) similarly resulted in dose-related LDH release. The degree of injury resulting from complete glucose deprivation or 100 mmol/L ethanol approximated that produced by exposure to 100 mmol/L glutamic acid. Ethanol did not significantly alter LDH release from cultures consisting of only astrocytes. Both effects were inhibited by the N-methyl-D-aspartate (NMDA) receptor antagonist, D,L-2-amino-5-phosphonovaleric acid (APV). Glutamate levels were increased in the culture medium to 191% +/- 8% of the control value after glucose deprivation (P < .001) and to 186% +/- 16% after exposure to 100 mmol/L ethanol (P < .01). 3H-glutamate uptake by cultured astrocytes was reduced by glucose deprivation and by ethanol. This range of ethanol concentrations has previously been shown to inhibit hexose uptake by cultured astrocytes. The present results suggest that decreased glucose uptake by astrocytes in the presence of ethanol impairs their uptake of glutamate, which contributes to excitotoxic neuronal injury.
Singh
S P
SP
Medical Research Service, Veterans Affairs Medical Center, North Chicago, IL 60064.
Ehmann
S
S
Snyder
A K
AK
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D016923:Cell Death; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000431:Ethanol / Q000494:pharmacology*; D005947:Glucose / Q000172:deficiency*; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D009498:Neurotoxins / Q000494:pharmacology*; D009994:Osmolar Concentration; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D005971:Glutamates; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D018698:Glutamic Acid; D015763:2-Amino-5-phosphonovalerate; D005947:Glucose