Enhanced release of synaptic glutamate underlies the potentiation of oxygen-glucose deprivation-induced neuronal injury after induction of NOS-2
| Autor: | Aniruddha S. Vidwans, Sandra J. Hewett |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Excitotoxicity
Glutamic Acid Nitric Oxide Synthase Type II Pharmacology medicine.disease_cause Mice Developmental Neuroscience Tetanus Toxin medicine Animals Channel blocker Cells Cultured Neurons Aspartic Acid Riluzole biology Cell Death Dose-Response Relationship Drug Glutamate receptor Long-term potentiation Cell Hypoxia Nitric oxide synthase Glucose Neuroprotective Agents Neurology Biochemistry Metabotropic glutamate receptor Enzyme Induction Nitrobenzoates Hypoxia-Ischemia Brain Synapses biology.protein NMDA receptor Nitric Oxide Synthase Extracellular Space medicine.drug |
| Zdroj: | Experimental neurology. 190(1) |
| ISSN: | 0014-4886 |
| Popis: | Reactive nitrogen oxide species (RNOS) may contribute to the progression/enhancement of ischemic injury by augmentation of glutamate release, reduction of glutamate uptake, or a combination of both. Consistent with this, induction of nitric oxide synthase (NOS-2) in murine neocortical cell cultures potentiated neuronal cell death caused by combined oxygen–glucose deprivation in association with a net increase in extracellular glutamate accumulation. However, uptake of glutamate via high affinity, sodium-dependent glutamate transporters was unimpaired by induction of NOS-2 under either aerobic or anaerobic conditions. Further, blocking possible routes of extra-synaptic glutamate release with NPPB [5-nitro-2-(3-phenylpropylamino)-benzoic acid], a volume-sensitive organic anion channel blocker, or TBOA ( d , l -threo-β-benzyloxyaspartate), an inhibitor of glutamate transport, exacerbated rather than ameliorated injury. Finally, treatment with riluzole or tetanus toxin attenuated the enhancement in both glutamate accumulation and oxygen–glucose deprivation-induced neuronal injury supporting the idea that increased synaptic release of glutamate underlies, at least in part, the potentiation of neuronal injury by RNOS after NOS-2 induction. |
| Databáze: | OpenAIRE |
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