ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Activation of neuronal NMDA receptors induces superoxide-mediated oxidative stress in neighboring neurons and astrocytes.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 116 citations in OpenAlex.
- Caveolin-1 Attenuates Excitotoxic Signaling by Regulating NMDA, AMPA, and Kainate Receptor-Mediated Calcium Influx in Hippocampal Neuronal Cultures.International journal of molecular sciences · 2026Article
- Pathological Roles of Astrocytes in Traumatic Brain Injury.CNS neuroscience & therapeutics · 2026Review
- Mitochondrial CaBiomolecules · 2026Review
- The interaction between oxidative stress and Schwann cells.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- Neuron-Glia Crosstalk in the Regulation of Astrocytic Antioxidative Mechanisms Following CNS Injury.Antioxidants (Basel, Switzerland) · 2025Review
- The development but not the maintenance of phrenic and sympathetic long-term facilitation after acute intermittent hypoxia requires nucleus tractus solitarii HExperimental neurology · 2025Article
- The Pathobiological Underpinnings of Psychosis: From the Stress-Related Hypothesis to a Multisystemic Approach.NeuroSci · 2025Review
- Excitotoxic neuronal death requires superoxide entry into neurons through volume-regulated anion channels.Science advances · 2025Article
- The protective role of melatonin and agomelatine against oxidative stress following laparoscopic ovariectomy in dogs.BMC veterinary research · 2025Article
- Misprogramming of glucose metabolism impairs recovery of hippocampal slices from neuronal GLT-1 knockout mice and contributes to excitotoxic injury through mitochondrial superoxide production.Journal of neurochemistry · 2025Article
- NMDA receptors antagonists alleviated the acute phase of traumatic brain injury.Iranian journal of basic medical sciences · 2025Article
- Protective effects of fermentedMolecular medicine reports · 2024Article
- Dual Effect of Carnosine on ROS Formation in Rat Cultured Cortical Astrocytes.Molecular neurobiology · 2024Article
- Alzheimer's Disease: A Review of Pathology, Current Treatments, and the Potential Therapeutic Effect of Decreasing Oxidative Stress by Combined Vitamin D and l-Cysteine Supplementation.Antioxidants & redox signaling · 2024Review
- Mitochondrial Dysfunction as the Major Basis of Brain Aging.Biomolecules · 2024Review
- Investigation of the Effects of a Novel NOX2 Inhibitor, GLX7013170, against Glutamate Excitotoxicity and Diabetes Insults in the Retina.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Review
- Evidence that Alzheimer's Disease Is a Disease of Competitive Synaptic Plasticity Gone Awry.Journal of Alzheimer's disease : JAD · 2024Review
- A Narrative Review of the Reciprocal Relationship Between Sleep Deprivation and Chronic Pain: The Role of Oxidative Stress.Journal of pain research · 2024Review
- Astrocytes derived from neural progenitor cells are susceptible to Zika virus infection.PloS one · 2023Article
12 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Excitotoxic neuronal death is mediated in part by NMDA receptor-induced activation of NOX2, an enzyme that produces superoxide and resultant oxidative stress. It is not known, however, whether the superoxide is generated in the intracellular space, producing oxidative stress in the neurons responding to NMDA receptor activation, or in the extracellular space, producing oxidative stress in neighboring cells. We evaluated these alternatives by preparing cortical neuron cultures from p47(phox-/-) mice, which are unable to form a functional NOX2 complex, and transfecting the cultures at low density with GFP-tagged p47(phox) to reconstitute NOX2 activity in widely scattered neurons. NMDA exposure did not induce oxidative stress or cell death in the nontransfected, p47-phox(-/-) cultures, but did produce oxidative stress and neuronal death in neurons surrounding the transfected, NOX2-competent neurons. This cell-to-cell spread of NMDA-induced oxidative injury was blocked by coincubation with either superoxide dismutase or the anion channel blocker 4'-diisothiocyanostilbene-2,2'-disulphonate, confirming superoxide anion as the mediating oxidant. In neurons plated on a preexisting astrocyte layer, NMDA induced oxidative stress in both the neurons and the astrocytes, and this was also prevented by superoxide dismutase. These findings show that activation of NMDA receptors on one neuron can lead to oxidative stress and cell death in neighboring neurons and astrocytes by a process involving the extracellular release of superoxide by NOX2.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.