title: Glutamate-induced neurotoxicity is increased in cerebellar granule cells exposed chronically to ethanol.
abstract: Chronic exposure of primary cultures of cerebellar granule cells to ethanol has previously been shown to result in an enhanced response of the cells to N-methyl-D-aspartate (NMDA). To determine if this increase in NMDA receptor function alters glutamate-induced cytotoxicity, cells were incubated in the presence or absence of 100 mM ethanol for 3 days, the ethanol was removed, the cells were treated with glutamate, and cell survival was assessed with fluorescein diacetate fluorescence. The ethanol-treated cells showed a significantly increased cytotoxic response to glutamate. Treatment with receptor-selective antagonists demonstrated that the cytotoxicity was mediated by NMDA receptors. The increased vulnerability to glutamate-induced cytotoxicity in ethanol-exposed cells may underlie the neuronal degeneration observed in animals and humans after chronic ethanol intake and withdrawal.
authors.affiliation: Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
authors.forename: K R
authors.initials: KR
authors.lastname: Iorio
authors.forename: B
authors.initials: B
authors.lastname: Tabakoff
authors.forename: P L
authors.initials: PL
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005971:Glutamates / Q000633:toxicity*; D018698:Glutamic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D013050:Spectrometry, Fluorescence
chemical_list: D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D018698:Glutamic Acid; D002118:Calcium