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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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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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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437882 | PMC |
http://dx.doi.org/10.1038/npp.2016.253 | DOI Listing |
Mol Metab
December 2024
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Section of Integrative Physiology, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. Electronic address:
Objectives: Environmental factors such as physical activity induce epigenetic modification, with exercise-responsive DNA methylation changes occurring in skeletal muscle. To determine the skeletal muscle DNA methylation signature to endurance swim training we used whole-genome methylated DNA immunoprecipitation (MeDIP) sequencing.
Results: Gene set expression analysis (GSEA) of differentially methylated promoter regions (DMRs) an enrichment of four gene sets, including those annotated to lipid metabolic process, with differentially hypermethylated or hypomethylated promoter regions in skeletal muscle of exercise-trained rats.
Development
November 2024
Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London EC1M 6BQ, UK.
Hematopoietic stem cells (HSCs) sustain life-long hematopoiesis and emerge during mid-gestation from hemogenic endothelial progenitors via an endothelial-to-hematopoietic transition (EHT). The full scope of molecular mechanisms governing this process remains unclear. The NR4A subfamily of orphan nuclear receptors act as tumor suppressors in myeloid leukemogenesis and have never been implicated in HSC specification.
View Article and Find Full Text PDFBr J Pharmacol
November 2024
Goethe University Frankfurt, Institute for Cardiovascular Physiology, Frankfurt, Germany.
Background And Purpose: Endocannabinoids are lipid mediators, which elicit complex biological effects that extend beyond the central nervous system. Tissue concentrations of endocannabinoids increase in atherosclerosis, and for the endocannabinoid N-arachidonoyl-ethanolamine (anandamide, AEA), this has been linked to an anti-inflammatory function. In this study, we set out to determine the anti-inflammatory mechanism of action of AEA, specifically focusing on vascular smooth muscle cells.
View Article and Find Full Text PDFBMC Genomics
November 2024
Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture & National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University, Beijing, 100193, China.
Cell Commun Signal
September 2024
Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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