title: [Regulation of neuronal death by endogenous protective factors].
abstract: Glutamate is postulated to play an important role in the pathogenesis of the neuronal cell loss that is associated with neurological disorders in the CNS. Nitric oxide (NO) mediates glutamate neurotoxicity observed in the primary culture derived from the cerebral cortex, substantia nigra and retina. In search of endogenous protective factors that inhibit the neurotoxic action of glutamate and NO, we found that certain neurotransmitters such as nicotinic acetylcholine, dopamine and cholecystokinin prevent glutamate neurotoxicity by suppressing the activity of NO synthase. Neurotrophins such as brain-derived neurotrophic factor (BDNF) also prevented glutamate neurotoxicity via TrkB neurotrophin receptors although prolonged pretreatment was necessary to induce marked neuroprotection. BDNF prevented the neurotoxic actions of NO donors. This evidence indicates that BDNF protects neurons against glutamate cytotoxicity by reducing the radical chain reaction triggered by NO. We also found that the conditioned medium of the striatal cultures reduced glutamate neurotoxicity. Moreover, ether extract of fetal calf serum (FCS), contained in the conditioned medium, also reduced glutamate neurotoxicity. Concomitant application of ether extract of FCS with S-nitrosocysteine (SNOC), a NO donor, markedly reduced SNOC-induced neurotoxicity. These substances may have roles as neuroprotective factors that promote neuron survival under neurological disease states in the CNS.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Akaike
authors.forename: T
authors.initials: T
authors.lastname: Kume
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000502:physiology; D016923:Cell Death / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009569:Nitric Oxide; D018698:Glutamic Acid