Basic fibroblast growth factor modulates sensitivity of cultured hippocampal pyramidal neurons to glutamate cytotoxicity: interaction with ganglioside GM1.
Basic fibroblast growth factor (bFGF), a polypeptide originally identified as a mitogen for a variety of cells including astroglial cells, also exhibits neurotrophic (survival) effects on a number of neuronal populations, among the latter being hippocampal pyramidal cells. The present study investigated the effects of bFGF on the sensitivity of pyramidal neurons to the excitatory neurotransmitter, glutamate, and possible modulation by monosialoganglioside GM1. Cultures were generated from embryonic day 18 rat hippocampus, and first treated with bFGF at 4-5 days in vitro. Twenty-four hours later, cells were exposed to glutamate (100 microM-1 mM) for a further 24 h in the continued presence of bFGF. The cytotoxic action caused by 200-500 microM glutamate, which normally is present at this culture stage, was reduced by bFGF in a concentration- and time-dependent manner. GM1 (100 microM), given alone 2 h prior to glutamate, also limited this neuronal loss by 50-80%. At lower concentrations, neither bFGF (0.3 ng/ml) nor GM1 (1-10 microM) alone for 24 h was effective in altering neuronal sensitivity to glutamate. However, given together for 24 h these levels of bFGF and GM1 were almost as efficacious as bFGF alone at 3-10 ng/ml. Similar results were obtained with more mature (12 day) cultures. The ability of GM1 to modulate trophic factor actions towards excitatory amino acids makes gangliosides useful tools in the study of central nervous system plasticity and repair processes.
Skaper
S D
SD
Fidia Research Laboratories, Abano Terme, Italy.
Leon
A
A
Facci
L
L
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D006624:Hippocampus / Q000166:cytology*; D007700:Kinetics; D009410:Nerve Degeneration; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009498:Neurotoxins / Q000494:pharmacology*; D011712:Pyramidal Tracts / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D005971:Glutamates; D009498:Neurotoxins; D016222:Fibroblast Growth Factor 2; D005677:G(M1) Ganglioside; D018698:Glutamic Acid