ArticleCell death & disease2013
NMDA receptor-mediated excitotoxicity depends on the coactivation of synaptic and extrasynaptic receptors.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 205 citations in OpenAlex.
- Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics.Biomolecules · 2022Pooled it
- Memantine: updates from the past decade and implications for future novel therapeutic applications.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Morin Improves Cognitive Deficits in an in Vivo Model of Vascular Dementia by Modulating the N-methyl-D-aspartate Receptor Signaling Pathways.Neurochemical research · 2026Article
- Anandamide-Induced Neuroprotection of Cortical Neurons Relies on Metabolic/Redox Regulation and Mitochondrial Dynamics.Molecular neurobiology · 2025Article
- The Role of Magnesium in Depression, Migraine, Alzheimer's Disease, and Cognitive Health: A Comprehensive Review.Nutrients · 2025Review
- Distinct Regulation of Early Trafficking of the NMDA Receptors by the Ligand-Binding Domains of the GluN1 and GluN2A Subunits.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- The kinase RIPK3 promotes neuronal survival by suppressing excitatory neurotransmission during central nervous system viral infection.Immunity · 2025Article
- The diverse effects of ketamine, jack-of-all-trades: a narrative review.British journal of anaesthesia · 2025Review
- A Hypothesis: Metabolic Contributions to 16p11.2 Deletion Syndrome.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Neuronal activity drives PCDH9 cleavage and nuclear translocation to coordinate structural and functional remodeling.Frontiers in cellular neuroscience · 2025Article
- How is Excitotoxicity Being Modelled in iPSC-Derived Neurons?Neurotoxicity research · 2024Review
- Brief and Diverse Excitotoxic Insults Increase the Neuronal Nuclear Membrane Permeability in the Neonatal Brain, Resulting in Neuronal Dysfunction and Cell Death.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Review
- NMDA Receptors: Distribution, Role, and Insights into Neuropsychiatric Disorders.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Advancements in the Research of New Modulators of Nitric Oxide Synthases Activity.International journal of molecular sciences · 2024Review
- RIPK3 promotes neuronal survival by suppressing excitatory neurotransmission during CNS viral infection.bioRxiv : the preprint server for biology · 2024Article
- Seizure as the main presenting manifestation of three patients with acute glufosinate-ammonium poisoning.Journal of Zhejiang University. Science. B · 2024Article
- Physiological acetic acid concentrations from ethanol metabolism stimulate accumbens shell medium spiny neurons via NMDAR activation in a sex-dependent manner.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Plasticity in the Functional Properties of NMDA Receptors Improves Network Stability during Severe Energy Stress.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Parkinson's disease models and death signaling: what do we know until now?Frontiers in neuroanatomy · 2024Review
46 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
N-methyl-D-aspartate receptors (NMDAR) overactivation is linked to neurodegeneration. The current prevailing theory suggests that synaptic and extrasynaptic NMDAR (syn- and ex-NMDAR) impose counteracting effects on cell fate, and neuronal cell death is mainly mediated by the activation of ex-NMDAR. However, several lines of evidence implicate the limitation of this theory. Here, we demonstrate that activation of NMDAR bi-directionally regulated cell fate through stimulating pro-survival or pro-death signaling. While low-dose NMDA preferentially activated syn-NMDAR and stimulated the extracellular signal-regulated kinase ½-cAMP responsive element-binding protein-brain-derived neurotrophic factor pro-survival signaling, higher doses progressively activated increasing amount of ex-NMDAR along with syn-NMDAR and triggered cell death program. Interestingly, the activation of syn- or ex-NMDAR alone did not cause measurable cell death. Consistently, activation of syn- or ex-NMDAR alone stimulated pro-survival but not pro-death signaling. Next, we found that memantine, which was previously identified as an ex-NMDAR blocker, inhibited intracellular signaling mediated by syn- or ex-NMDAR. Simultaneous blockade of syn- and ex-NMDAR by memantine dose-dependently attenuated NMDAR-mediated death. Moreover, long- but not short-term treatment with high-dose NMDA or oxygen-glucose deprivation triggered cell death and suppressed pro-survival signaling. These data implicate that activation of syn- or ex-NMDAR alone is not neurotoxic. The degree of excitotoxicity depends on the magnitude and duration of syn- and ex-NMDAR coactivation. Finally, genome-wide examination demonstrated that the activation of syn- and ex-NMDAR lead to significant overlapping rather than counteracting transcriptional responses.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.