ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2005
Regulation of NMDA receptors by neuregulin signaling in prefrontal cortex.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers.
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Who cites it
104 citing papers in PubMed, 216 citations in OpenAlex.
- Chronic Overexpression of Neuronal NRG1-III in Mice Causes Long-Term Detrimental Changes in Lower Motor Neurons, Neuromuscular Synapses and Motor Behaviour.International journal of molecular sciences · 2025Article
- Advances in the Treatment of Cognitive Impairment in Schizophrenia: Targeting NMDA Receptor Pathways.International journal of molecular sciences · 2024Review
- CorticalProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Role of the NRG1/ErbB4 and PI3K/AKT/mTOR signaling pathways in the anti-psychotic effects of aripiprazole and sertindole in ketamine-induced schizophrenia-like behaviors in rats.Inflammopharmacology · 2022Article
- Plasma neuregulin 1 as a synaptic biomarker in Alzheimer's disease: a discovery cohort study.Alzheimer's research & therapy · 2022Article
- UPF2 leads to degradation of dendritically targeted mRNAs to regulate synaptic plasticity and cognitive function.Molecular psychiatry · 2020Article
- Protopanaxadiol ginsenoside Rd protects against NMDA receptor-mediated excitotoxicity by attenuating calcineurin-regulated DAPK1 activity.Scientific reports · 2020Article
- The impact of D-cycloserine and sarcosine on in vivo frontal neural activity in a schizophrenia-like model.BMC psychiatry · 2019Article
- NMDAR Hypofunction Animal Models of Schizophrenia.Frontiers in molecular neuroscience · 2019Review
- The Complex Work of Proteases and Secretases in Wallerian Degeneration: Beyond Neuregulin-1.Frontiers in cellular neuroscience · 2019Review
- Neuroketotherapeutics: A modern review of a century-old therapy.Neurochemistry international · 2018Review
- Hippocampal protein kinase D1 is necessary for DHPG-induced learning and memory impairments in rats.PloS one · 2018Article
- mGluR1-Dependent Long Term Depression in Rodent Midbrain Dopamine Neurons Is Regulated by Neuregulin 1/ErbB Signaling.Frontiers in molecular neuroscience · 2018Article
- Variation at NRG1 genotype related to modulation of small-world properties of the functional cortical network.European archives of psychiatry and clinical neuroscience · 2017Article
- BACE1-Dependent Neuregulin-1 Signaling: An Implication for Schizophrenia.Frontiers in molecular neuroscience · 2017Review
- Synaptic Actin Dysregulation, a Convergent Mechanism of Mental Disorders?The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Review
- Neurological dysfunctions associated with altered BACE1-dependent Neuregulin-1 signaling.Journal of neurochemistry · 2016Review
- Modulation of schizophrenia-related genes in the forebrain of adolescent and adult rats exposed to maternal immune activation.Schizophrenia research · 2015Article
- Neuregulin 1 Controls Glutamate Uptake by Up-regulating Excitatory Amino Acid Carrier 1 (EAAC1).The Journal of biological chemistry · 2015Article
- Scaffolding protein Homer1a protects against NMDA-induced neuronal injury.Cell death & disease · 2015Article
44 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Recent linkage studies have identified a significant association of the neuregulin gene with schizophrenia, but how neuregulin is involved in schizophrenia is primarily unknown. Aberrant NMDA receptor functions have been implicated in the pathophysiology of schizophrenia. Therefore, we hypothesize that neuregulin, which is present in glutamatergic synaptic vesicles, may affect NMDA receptor functions via actions on its ErbB receptors enriched in postsynaptic densities, hence participating in emotional regulation and cognitive processes that are impaired in schizophrenia. To test this, we examined the regulation of NMDA receptor currents by neuregulin signaling pathways in prefrontal cortex (PFC), a prominent area affected in schizophrenia. We found that bath perfusion of neuregulin significantly reduced whole-cell NMDA receptor currents in acutely isolated and cultured PFC pyramidal neurons and decreased NMDA receptor-mediated EPSCs in PFC slices. The effect of neuregulin was mainly blocked by application of the ErbB receptor tyrosine kinase inhibitor, phospholipase C (PLC) inhibitor, IP3 receptor (IP3R) antagonist, or Ca2+ chelators. The neuregulin regulation of NMDA receptor currents was also markedly attenuated in cultured neurons transfected with mutant forms of Ras or a dominant-negative form of MEK1 (mitogen-activated protein kinase kinase 1). Moreover, the neuregulin effect was prevented by agents that stabilize or disrupt actin polymerization but not by agents that interfere with microtubule assembly. Furthermore, neuregulin treatment increased the abundance of internalized NMDA receptors in cultured PFC neurons, which was also sensitive to agents affecting actin cytoskeleton. Together, our study suggests that both PLC/IP3R/Ca2+ and Ras/MEK/ERK (extracellular signal-regulated kinase) signaling pathways are involved in the neuregulin-induced reduction of NMDA receptor currents, which is likely through enhancing NR1 internalization via an actin-dependent mechanism.
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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.