Death of cultured hippocampal pyramidal neurons induced by pathological activation of N-methyl-D-aspartate receptors is reduced by monosialogangliosides.
Glutamate-induced delayed neurotoxicity has been proposed to account for the selective loss of hippocampal pyramidal neurons after an ischemic period. We have studied the effects of exogenous glutamate and combined oxygen-glucose deprivation on the survival of hippocampal pyramidal neurons cultured from rat fetuses. Acute glutamate neurotoxicity (20 min, 23-25 degrees C) occurred in a concentration-dependent manner (LD50: 50 microM), destroying virtually all neurons 24 hr later. Such injury was prevented by N-methyl-D-aspartate (NMDA), but not non-NMDA, antagonists. Hippocampal cell death induced by removal of oxygen and glucose showed a similar pharmacological profile, indicating a role for NMDA receptor activation in neuronal loss associated with this energy crisis situation. Monosialogangliosides such as GM1 were effective in protecting against neurodegeneration induced by either direct glutamate exposure or oxygen and glucose deprivation. The selective action of gangliosides in disrupting the pathological consequences of glutamate receptor activation may provide a new therapeutic tool for excitatory amino acid-related brain injury processes.
Skaper
S D
SD
Fidia Research Laboratories, Abano Terme, Italy.
Leon
A
A
Facci
L
L
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists; D005732:Gangliosides / Q000494:pharmacology*; D005971:Glutamates / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D005732:Gangliosides; D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate