ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
G-protein-coupled receptor 30 mediates rapid neuroprotective effects of estrogen via depression of NR2B-containing NMDA receptors.
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 81 papers.
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Who cites it
81 citing papers in PubMed, 162 citations in OpenAlex.
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- Histological features of the Purkinje neurons of the Albino rat (Anatomy & cell biology · 2025Article
- Triolein alleviates ischemic stroke brain injury by regulating autophagy and inflammation through the AKT/mTOR signaling pathway.Molecular medicine (Cambridge, Mass.) · 2024Article
- Effects of Sarcosine (N-methylglycine) on NMDA (N-methyl-D-aspartate) Receptor Hypofunction Induced by MK801: In Vivo Calcium Imaging in the CA1 Region of the Dorsal Hippocampus.Brain sciences · 2024Article
- Gentiopicroside Attenuates Lithium/Pilocarpine-Induced Epilepsy Seizures by Down-Regulating NR2B/CaMKII/CREB and TLR4/NF-κB Signaling Pathways in the Hippocampus of Mice.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Antidepressant- and Anxiolytic-like Effects of Pomegranate: Is It Acting by Common or Well-Known Mechanisms of Action?Plants (Basel, Switzerland) · 2024Review
- Effect of astrocyte GPER on the optic nerve inflammatory response following optic nerve injury in mice.Heliyon · 2024Article
- PJA1 mediates the effects of astrocytic GPR30 on learning and memory in female mice.The Journal of clinical investigation · 2023Article
- Involvement of the G-Protein-Coupled Estrogen Receptor-1 (GPER) Signaling Pathway in Neurodegenerative Disorders: A Review.Cellular and molecular neurobiology · 2023Review
- Sex and the Estrous-Cycle Phase Influence the Expression of G Protein-Coupled Estrogen Receptor 1 (GPER) in Schizophrenia: Translational Evidence for a New Target.Molecular neurobiology · 2023Article
- Deciphering the Influence of Estradiol and Estrogen Receptors on Cognitive Function: A Bibliometric Analysis and Emerging Research Trends.Medical science monitor : international medical journal of experimental and clinical research · 2023Article
- Non-genomic Effect of Estradiol on the Neurovascular Unit and Possible Involvement in the Cerebral Vascular Accident.Molecular neurobiology · 2023Review
- Ablation of Death-Associated Protein Kinase 1 Changes the Transcriptomic Profile and Alters Neural-Related Pathways in the Brain.International journal of molecular sciences · 2023Article
- Localisation of oestrogen receptors in stem cells and in stem cell-derived neurons of the mouse.Journal of neuroendocrinology · 2023Article
- G-protein coupled estrogen receptor (GPER1) activation promotes synaptic insertion of AMPA receptors and induction of chemical LTP at hippocampal temporoammonic-CA1 synapses.Molecular brain · 2023Article
- Article
- Association of the ADORA2A receptor and CD73 polymorphisms with epilepsy.Frontiers in pharmacology · 2023Article
- Neuroprotection of Kaji-Ichigoside F1 via the BDNF/Akt/mTOR Signaling Pathways against NMDA-Induced Neurotoxicity.International journal of molecular sciences · 2022Article
21 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
15 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
17-β-estradiol (E2) is a steroid hormone involved in neuroprotection against excitotoxicity and other forms of brain injury. Through genomic and nongenomic mechanisms, E2 modulates neuronal excitability and signal transmission by regulating NMDA and non-NMDA receptors. However, the mechanisms and identity of the receptors involved remain unclear, even though studies have suggested that estrogen G-protein-coupled receptor 30 (GPR30) is linked to protection against ischemic injury. In the culture cortical neurons, treatment with E2 and the GPR30 agonist G1 for 45 min attenuated the excitotoxicity induced by NMDA exposure. The acute neuroprotection mediated by GPR30 is dependent on G-protein-coupled signals and ERK1/2 activation, but independent on transcription or translation. Knockdown of GPR30 using short hairpin RNAs (shRNAs) significantly reduced the E2-induced rapid neuroprotection. Patch-clamp recordings revealed that GPR30 activation depressed exogenous NMDA-elicited currents. Short-term GPR30 activation did not affect the expression of either NR2A- or NR2B-containing NMDARs; however, it depressed NR2B subunit phosphorylation at Ser-1303 by inhibiting the dephosphorylation of death-associated protein kinase 1 (DAPK1). DAPK1 knockdown using shRNAs significantly blocked NR2B subunit phosphorylation at Ser-1303 and abolished the GPR30-mediated depression of exogenous NMDA-elicited currents. Lateral ventricle injection of the GPR30 agonist G1 (0.2 μg) provided significant neuroprotection in the ovariectomized female mice subjected to middle cerebral artery occlusion. These findings provide direct evidence that fast neuroprotection by estradiol is partially mediated by GPR30 and the subsequent downregulation of NR2B-containing NMDARs. The modulation of DAPK1 activity by GPR30 may be an important mediator of estradiol-dependent neuroprotection.
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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.