Methylmercury-induced neurotoxicity in cerebral neuron culture is blocked by antioxidants and NMDA receptor antagonists.
The neurotoxic effects of methylmercury on cerebral neuron cultures derived from neonatal mouse were studied. Exposure of cerebral neurons to methylmercury chloride resulted in significant cell damage and death in a time-dependent manner in cerebral neuron cultures. The methylmercury neurotoxicity was blocked by oxygen radical scavengers such as glutathione, catalase, selenium, and cysteine. Antagonists of the N-methyl-D-aspartate (NMDA) receptor, including MK-801 (a non-competitive NMDA antagonist), D-2-amino-5-phosphonovaleric acid (APV) (a competitive NMDA antagonist), and 7-chlorokynurenic acid (an antagonist at the glycine site associated with the NMDA receptor), similarly blocked methylmercury-induced neurotoxicity in cerebral neuron cultures. These results indicate that both oxygen radicals and excitotixic amino acids are involved in the methylmercury-induced neurotoxicity of cerebral neuron cultures.
Park
S T
ST
Department of Medicine, University of British Columbia, Vancouver.
Lim
K T
KT
Chung
Y T
YT
Kim
S U
SU
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000975:Antioxidants; D018691:Excitatory Amino Acid Antagonists; D008767:Methylmercury Compounds; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D002374:Catalase; D005978:Glutathione; D007736:Kynurenic Acid; C004925:methylmercuric chloride; C057013:7-chlorokynurenic acid