ArticleThe Journal of biological chemistry2013
Involvement of the GluN2A and GluN2B subunits in synaptic and extrasynaptic N-methyl-D-aspartate receptor function and neuronal excitotoxicity.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 148 citations in OpenAlex.
- Hyperfunction of PSD-95 leads to hyperexcitability and cognitive abnormalities in MEF2C haploinsufficiency.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- State-specific inhibition of NMDA receptors by memantine provides insight into NMDAR channel blocker tolerability.Science advances · 2026Article
- Emerging Roles of GluN3B NMDA Receptor Subunit in the Central Nervous System.Neuroscience bulletin · 2026Review
- Negr1 deficiency alters glutamate signalling and kynurenine pathway in a mouse model of psychiatric disorders.Scientific reports · 2026Article
- New advances in small molecule drugs targeting NMDA receptors.Acta pharmacologica Sinica · 2026Review
- Huntingtin reduction results in altered nuclear structure and heterochromatic instability.Human molecular genetics · 2025Article
- Bridging Inflammation and Repair: The Promise of MFG-E8 in Ischemic Stroke Therapy.International journal of molecular sciences · 2025Review
- Phospho-CREB Regulation on NMDA Glutamate Receptor 2B and Mitochondrial Calcium Uniporter in the Ventrolateral Periaqueductal Gray Controls Chronic Morphine Withdrawal in Male Rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Advances in the Structural Basis of GluN2A-Selective Negative Allosteric Modulators.ACS medicinal chemistry letters · 2025Article
- Curcumin Improves Hippocampal Cell Bioenergetics, Redox and Inflammatory Markers, and Synaptic Proteins, Regulating Mitochondrial Calcium Homeostasis.Neurotoxicity research · 2025Article
- Agmatine inhibits NMDA receptor-mediated calcium transients in mouse spinal cord dorsal horn via intact PSD95-nNOS signaling.The Journal of pharmacology and experimental therapeutics · 2024Article
- NMDARs in Alzheimer's Disease: Between Synaptic and Extrasynaptic Membranes.International journal of molecular sciences · 2024Review
- The underlying mechanism of calcium toxicity-induced autophagic cell death and lysosomal degradation in early stage of cerebral ischemia.Anatomy & cell biology · 2024Review
- Astrocyte β-Adrenergic Receptor Activity Regulates NMDA Receptor Signaling of Medial Prefrontal Cortex Pyramidal Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Exploring the Neuroprotective Effects of Lithium in Ischemic Stroke: A literature review.International journal of medical sciences · 2024Review
- Adolescent intermittent ethanol exposure alters adult exploratory and affective behaviors, and cerebellar Grin2b expression in C57BL/6J mice.Drug and alcohol dependence · 2023Article
- The GluN2B-Containing NMDA Receptor Alleviates Neuronal Apoptosis in Neonatal Hypoxic-Ischemic Encephalopathy by Activating PI3K-Akt-CREB Signaling Pathwa.Physiological research · 2023Article
- The Disruption of NMDAR/TRPM4 Death Signaling with TwinF Interface Inhibitors: A New Pharmacological Principle for Neuroprotection.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Intensive exercise ameliorates motor and cognitive symptoms in experimental Parkinson's disease restoring striatal synaptic plasticity.Science advances · 2023Article
- Extrasynaptic NMDA receptors in acute and chronic excitotoxicity: implications for preventive treatments of ischemic stroke and late-onset Alzheimer's disease.Molecular neurodegeneration · 2023Review
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 3 countries.
Funding
Abstract
GluN2A and GluN2B are the major subunits of functional NMDA receptors (NMDAR). Previous studies have suggested that GluN2A and GluN2B may differentially mediate NMDAR function at synaptic and extrasynaptic locations and play opposing roles in excitotoxicity, such as neurodegeneration triggered by ischemic stroke and brain injury. By using pharmacological and molecular approaches to suppress or enhance the function of GluN2A and GluN2B in cultured cortical neurons, we examined NMDAR-mediated, bidirectional regulation of prosurvival signaling (i.e. the cAMP response element-binding protein (CREB)-Bdnf cascade) and cell death. Inhibition of GluN2A or GluN2B attenuated the up-regulation of prosurvival signaling triggered by the activation of either synaptic or extrasynaptic NMDAR. Inhibition of GluN2A or GluN2B also attenuated the down-regulation of prosurvival signaling triggered by the coactivation of synaptic and extrasynaptic receptors. The effects of GluN2B on CREB-Bdnf signaling were larger than those of GluN2A. Consistently, compared with suppression of GluN2A, suppression of GluN2B resulted in more reduction of NMDA- and oxygen glucose deprivation-induced excitotoxicity as well as NMDAR-mediated elevation of intracellular calcium. Moreover, excitotoxicity and down-regulation of CREB were exaggerated in neurons overexpressing GluN2A or GluN2B. Together, we found that GluN2A and GluN2B are involved in the function of both synaptic and extrasynaptic NMDAR, demonstrating that they play similar rather than opposing roles in NMDAR-mediated bidirectional regulation of prosurvival signaling and neuronal death.
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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.