[Protective effect of neurotrophin against glutamate neurotoxicity in cortical cultures].
This study was performed to investigate the effects of neurotrophins on glutamate cytotoxicity by using cultured cortical neurons. Primary cultures obtained from the cerebral cortex of fetal rats (17-19 days gestation) were used for experiments. NGF did not elicit tyrosine phosphorylation of Trks whereas BDNF induced Trk tyrosine phosphorylation within 10 min, followed by time-dependent decrease. Brief glutamate exposure to the cell induced delayed cytotoxicity. Similar cytotoxicity was observed with the brief application of a calcium ionophore, ionomycin, and nitric oxide (NO) generating agents, S-nitrosocysteine (SNOC) and SIN-1. Exposure of the cultures to NGF and BDNF for 1 or 24 hr prior to glutamate exposure reduced glutamate-induced cytotoxicity. In contrast, simultaneous addition of NGF and BDNF with glutamate did not affect glutamate-induced cytotoxicity. Ionomycin-induced cytotoxicity was prevented by exposing cultures to NGF and BDNF for 24-hr. Moreover, NGF and BDNF ameliorated cytotoxicity induced by SNOC and SIN-1. These results suggest that neurotrophins prevent NO mediated glutamate cytotoxicity.
Kume
T
T
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Katsuki
H
H
Kaneko
S
S
Akaike
A
A
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D003545:Cysteine / Q000031:analogs & derivatives / Q000633:toxicity; D018698:Glutamic Acid / Q000633:toxicity*; D015759:Ionomycin / Q000633:toxicity; D007476:Ionophores / Q000633:toxicity; D009414:Nerve Growth Factors / Q000502:physiology*; D009474:Neurons / Q000187:drug effects*; D009603:Nitroso Compounds / Q000633:toxicity; D051381:Rats; D026403:S-Nitrosothiols
D019208:Brain-Derived Neurotrophic Factor; D007476:Ionophores; D009414:Nerve Growth Factors; D009603:Nitroso Compounds; D026403:S-Nitrosothiols; D018698:Glutamic Acid; D015759:Ionomycin; C021315:S-nitrosocysteine; D003545:Cysteine