Stimulation of the N-methyl-D-aspartate receptor has a trophic effect on differentiating cerebellar granule cells.
N-methyl-D-aspartate (NMDA) supplementation of cerebellar cultures enriched in granule neurones (about 90%) prevented the extensive cell loss which occurs when cultivation takes place, in serum containing media, in the presence of 'low' K+ (5-15 mM). Estimation of tetanus toxin receptors and N-CAM contents indicated that NMDA rescued primarily nerve cells. The influence of NMDA in promoting cell survival was blocked by the receptor antagonist, 2-amino-5-phosphonovalerate. The effect depended both on the concentration of NMDA and on the degree of depolarization of cells, the affinity in the presence of 15 mM K+ being similar to that of NMDA receptor binding. The results attest a new role for excitatory amino acid transmitters by showing that they can exert a stage-dependent trophic action on developing nerve cells.
Balázs
R
R
MRC Developmental Neurobiology Unit, London, U.K.
Hack
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N
Jørgensen
O S
OS
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D015815:Cell Adhesion Molecules; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016202:N-Methylaspartate; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D013744:Tetanus Toxin / Q000378:metabolism
D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D013744:Tetanus Toxin; D001224:Aspartic Acid; D016202:N-Methylaspartate