A comparison between acute exposures to ethanol and acetaldehyde on neurotoxicity, nitric oxide production and NMDA-induced excitotoxicity in primary cultures of cortical neurons.
Chronic exposure of primary neuronal cultures to ethanol has been shown to potentiate N-methyl-D-aspartate (NMDA) receptor-mediated processes, such as nitric oxide (NO) formation and excitotoxicity. In the present study, we compared the effects of acute ethanol and acetaldehyde on NMDA receptor-mediated excitotoxicity and NO production in primary cultures of rat cortical neurons. The delayed cell death induced by NMDA (300 mM, 25 min) was evaluated by morphological examination and by measuring the release of the cytotoxic indicator, lactate dehydrogenase, in the culture media 24 hours after the NMDA exposure. The accumulation of nitrite, as an index of NO production, was also measured 24 hours after NMDA treatment. NMDA caused a dose-dependent cell death and nitrite accumulation, both effects were blocked by pretreatment of MK-801 (100 microM). Acute exposure to ethanol (1-1000 mM) or acetaldehyde (0.1-1 mM) for 35 minutes did not affect neuronal viability in the following 24-hr period. However, acute exposure to acetaldehyde (> or =10 mM) was neurotoxic. Neither ethanol nor acetaldehyde changed basal nitrite levels in the culture media. Acute ethanol (50-400 mM, 10 min) given before the NMDA treatment (25 min) resulted in a concentration-dependent suppression of the delayed cell death. The NMDA-induced NO production was, however, not affected by ethanol. Neither the NMDA excitotoxicity nor NO production was affected by acute ethanol given after NMDA treatment. Acute acetaldehyde (0.01-0.5 mM, 10 min) given before or after NMDA treatment had no effect on delayed NMDA neurotoxicity and NO production. Our data suggest that acute exposure to ethanol is not neurotoxic and is even protective against delayed NMDA-excitotoxicity when given before but not after NMDA treatment. Neither NO nor metabolism of ethanol to acetaldehyde is required for ethanol-mediated suppression of NMDA excititoxicity. Acetaldehyde, on the other hand, is toxic by itself at low concentrations (> or =10 mM). Furthermore, acute exposure to non-toxic concentrations of acetaldehyde could not protect cortical neurons against NMDA-induced excitotoxicity.
Wan
J Y
JY
Graduate Institute of Life Sciences Department of Physiology, National Defense Medical Center, Taipei, Taiwan, ROC.
Wang
J Y
JY
Wang
Y
Y
Wang
J Y
JY
D000079:Acetaldehyde / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000633:toxicity*; D002540:Cerebral Cortex / Q000166:cytology; D000431:Ethanol / Q000633:toxicity*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D002492:Central Nervous System Depressants; D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D000431:Ethanol; D016202:N-Methylaspartate; D000079:Acetaldehyde