ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2017
Pharmacological Activators of the NR4A Nuclear Receptors Enhance LTP in a CREB/CBP-Dependent Manner.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 56 citations in OpenAlex.
- Epigenetic Control of Stress-Induced Depression: Emerging Roles of HDAC3 and HDAC6.International journal of molecular sciences · 2026Review
- Nurr1 Orchestrates Claustrum Development and Functionality.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting Nurr1 With Amodiaquine Preserves Dendritic Spines and Cognitive Function After Chronic Cerebral Hypoperfusion.Neural plasticity · 2026Article
- Review
- HDAC3 as an Emerging Therapeutic Target for Alzheimer's Disease and other Neurological Disorders.Molecular neurobiology · 2025Review
- Controversy and multiple roles of the solitary nucleus receptor Nur77 in disease and physiology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- 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
- GSK3: A potential target and pending issues for treatment of Alzheimer's disease.CNS neuroscience & therapeutics · 2024Review
- Progressive reduction of nuclear receptor Nr4a1 mediates age-dependent cognitive decline.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Mapping the spatial transcriptomic signature of the hippocampus during memory consolidation.Nature communications · 2023Article
- Chronic N-Acetyl-Cysteine Treatment Enhances the Expression of the Immediate Early GeneInternational journal of molecular sciences · 2023Article
- Cracking the Code of Neuronal Cell Fate.Cells · 2023Review
- Convergent abnormalities in striatal gene networks in human cocaine use disorder and mouse cocaine administration models.Science advances · 2023Article
- Mapping the spatial transcriptomic signature of the hippocampus during memory consolidation.bioRxiv : the preprint server for biology · 2023Article
- Molecular pathways underlying sympathetic autonomic overshooting leading to fear and traumatic memories: looking for alternative therapeutic options for post-traumatic stress disorder.Frontiers in molecular neuroscience · 2023Review
- Excess BAFF Alters NR4As Expression Levels and Breg Function of Human Precursor-like Marginal Zone B-Cells in the Context of HIV-1 Infection.International journal of molecular sciences · 2022Article
- Cocaine regulation of Nr4a1 chromatin bivalency and mRNA in male and female mice.Scientific reports · 2022Article
- ADRAM is an experience-dependent long noncoding RNA that drives fear extinction through a direct interaction with the chaperone protein 14-3-3.Cell reports · 2022Article
- Marginal Zone B-Cell Populations and Their Regulatory Potential in the Context of HIV and Other Chronic Inflammatory Conditions.International journal of molecular sciences · 2022Review
- Comprehensive insights into the function and molecular and pharmacological regulation of neuron-derived orphan receptor 1, an orphan receptor.Frontiers in pharmacology · 2022Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Nr4a nuclear receptors contribute to long-term memory formation and are required for long-term memory enhancement by a class of broad-acting drugs known as histone deacetylase (HDAC) inhibitors. Understanding the molecular mechanisms that regulate these genes and identifying ways to increase their activity may provide novel therapeutic approaches for ameliorating cognitive dysfunction. In the present study, we find that Nr4a gene expression after learning requires the cAMP-response element binding (CREB) interaction domain of the histone acetyltransferase CREB-binding protein (CBP). These gene expression deficits emerge at a time after learning marked by promoter histone acetylation in wild-type mice. Further, mutation of the CREB-CBP interaction domain reduces Nr4a promoter acetylation after learning. As memory enhancement by HDAC inhibitors requires CREB-CBP interaction and Nr4a gene function, these data support the notion that the balance of histone acetylation at the Nr4a promoters is critical for memory formation. NR4A ligands have recently been described, but the effect of these drugs on synaptic plasticity or memory has not been investigated. We find that the 'C-DIM' NR4A ligands, para-phenyl substituted di-indolylmethane compounds, enhance long-term contextual fear memory and increase the duration of long-term potentiation (LTP), a form of hippocampal synaptic plasticity. LTP enhancement by these drugs is eliminated in mice expressing a dominant negative form of NR4A and attenuated in mice with mutation of the CREB-CBP interaction domain. These data define the molecular connection between histone acetylation and Nr4a gene expression after learning. In addition, they suggest that NR4A-activating C-DIM compounds may serve as a potent and selective means to enhance memory and synaptic plasticity.
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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.