ArticleJournal of neurochemistry2017
Epigenetic mechanisms underlying NMDA receptor hypofunction in the prefrontal cortex of juvenile animals in the MAM model for schizophrenia.
Article in Journal of neurochemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 56 citations in OpenAlex.
- Prefrontal Cortex Dysfunction as a Precipitating Factor for Schizophrenia and Depression.Journal of neurochemistry · 2026Review
- Metabolic Mechanisms in Electroconvulsive Therapy for Schizophrenia: Role, Potential and Future Directions.International journal of molecular sciences · 2026Review
- Elucidating the Complex Etiology of Schizophrenia: Comprehensive Insights into the Therapeutic Roles of Natural Compounds and Pharmacological Interventions.Current pharmaceutical design · 2026Review
- NMDA receptor kinetics drive distinct routes to chaotic firing in pyramidal neurons.Frontiers in computational neuroscience · 2026Article
- The Dynamic Roles of Repressor Element 1-Silencing Transcription Factor (REST): A Double-Edged Sword in Neural Health and Disease.Molecular neurobiology · 2025Review
- Construction and Brain Validation of circRNAs-miRNAs-mRNAs Regulatory Axis in Early-Onset Schizophrenia.Neuropsychiatric disease and treatment · 2025Article
- Transcriptomic analysis of rat prefrontal cortex following chronic stress induced by social isolation - Relevance to psychiatric and neurodevelopmental illness, and implications for treatment.Neurobiology of stress · 2024Article
- Upregulation of KDM6B in the anterior cingulate cortex contributes to neonatal maternal deprivation-induced chronic visceral pain in mice.Molecular pain · 2024Article
- DNA methylation and the opposing NMDAR dysfunction in schizophrenia and major depression disorders: a converging model for the therapeutic effects of psychedelic compounds in the treatment of psychiatric illness.Molecular psychiatry · 2023Review
- REST Is Not Resting: REST/NRSF in Health and Disease.Biomolecules · 2023Review
- Epigenetic Targets in Schizophrenia Development and Therapy.Brain sciences · 2023Review
- Methylation pattern and mRNA expression of synapse-relevant genes in the MAM model of schizophrenia in the time-course of adolescence.Schizophrenia (Heidelberg, Germany) · 2022Article
- Dopaminergic dysfunction and excitatory/inhibitory imbalance in treatment-resistant schizophrenia and novel neuromodulatory treatment.Molecular psychiatry · 2022Review
- LY395756 promotes NR2B expression via activation of AKT/CREB signaling in the juvenile methylazoxymethanol mice model of schizophrenia.Brain and behavior · 2022Article
- Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia.Biomolecules · 2022Article
- Sexual Dimorphism in the Effect of Neonatal Inflammatory Pain on Stress Reactivity of Hormonal Response and Cognitive Functions in Adult Rats.Journal of evolutionary biochemistry and physiology · 2022Article
- Using animal models for the studies of schizophrenia and depression: The value of translational models for treatment and prevention.Frontiers in behavioral neuroscience · 2022Review
- Review
- Mechanisms of synaptic transmission dysregulation in the prefrontal cortex: pathophysiological implications.Molecular psychiatry · 2022Review
- EZH2-Mediated H3K27me3 Targets Transcriptional Circuits of Neuronal Differentiation.Frontiers in neuroscience · 2022Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Schizophrenia (SCZ) is characterized not only by psychosis, but also by working memory and executive functioning deficiencies, processes that rely on the prefrontal cortex (PFC). Because these cognitive impairments emerge prior to psychosis onset, we investigated synaptic function during development in the neurodevelopmental methylazoxymethanol (MAM) model for SCZ. Specifically, we hypothesize that N-methyl-D-aspartate receptor (NMDAR) hypofunction is attributable to reductions in the NR2B subunit through aberrant epigenetic regulation of gene expression, resulting in deficient synaptic physiology and PFC-dependent cognitive dysfunction, a hallmark of SCZ. Using western blot and whole-cell patch-clamp electrophysiology, we found that the levels of synaptic NR2B protein are significantly decreased in juvenile MAM animals, and the function of NMDARs is substantially compromised. Both NMDA-mEPSCs and synaptic NMDA-eEPSCs are significantly reduced in prelimbic PFC (plPFC). This protein loss during the juvenile period is correlated with an aberrant increase in enrichment of the epigenetic transcriptional repressor RE1-silencing transcription factor (REST) and the repressive histone marker H3K27me3 at the Grin2b promoter, as assayed by ChIP-quantitative polymerase chain reaction. Glutamate hypofunction has been a prominent hypothesis in the understanding of SCZ pathology; however, little attention has been given to the NMDAR system in the developing PFC in models for SCZ. Our work is the first to confirm that NMDAR hypofunction is a feature of early postnatal development, with epigenetic hyper-repression of the Grin2b promoter being a contributing factor. The selective loss of NR2B protein and subsequent synaptic dysfunction weakens plPFC function during development and may underlie early cognitive impairments in SCZ models and patients. Read the Editorial Highlight for this article on page 264.
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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.