BDNF prevents NO mediated glutamate cytotoxicity in cultured cortical neurons.
The effects of brain-derived neurotrophic factor (BDNF) on glutamate-induced cytotoxicity were examined using primary cultures of rat cortical neurons. BDNF induced TrkB tyrosine phosphorylation in rat cultured cortical neurons. The cell viability was significantly reduced when cultures were briefly exposed to glutamate and incubated with normal medium for 24 h. Glutamate cytotoxicity was prevented by MK-801, which is a non-competitive blocker of N-methyl-D-aspartate and N(omega)-nitro-L-arginine, which is a blocker of nitric oxide synthetase. Delayed neurotoxicity was also induced by ionomycin, a calcium ionophore, and nitric oxide (NO) donors such as S-nitrosocysteine (SNOC) and 3-morpholinosydnonimine (SIN-1). Incubating cultures with BDNF for 10 min to 24 h protected cortical neurons against glutamate neurotoxicity. The protective effects of BDNF against glutamate cytotoxicity were dependent on both its concentrations and incubation time. BDNF also prevented the ionomycin-, SNOC-, and SIN-1 induced cytotoxicity. These results indicate that BDNF protects cultured cortical neurons from NMDA receptor-mediated glutamate neurotoxicity by reducing cytotoxic action of NO.
Kume
T
T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Kouchiyama
H
H
Kaneko
S
S
Maeda
T
T
Kaneko
S
S
Akaike
A
A
Shimohama
S
S
Kihara
T
T
Kimura
J
J
Wada
K
K
Koizumi
S
S
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D018698:Glutamic Acid / Q000506:poisoning*; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats / Q000196:embryology; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism
D019208:Brain-Derived Neurotrophic Factor; D007476:Ionophores; D018696:Neuroprotective Agents; D020801:Receptor, Ciliary Neurotrophic Factor; D017475:Receptors, Nerve Growth Factor; D009569:Nitric Oxide; D018698:Glutamic Acid; D015759:Ionomycin; D002118:Calcium