ArticleNeuropharmacology2017
Valproate increases dopamine transporter expression through histone acetylation and enhanced promoter binding of Nurr1.
Article in Neuropharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 34 citations in OpenAlex.
- Article
- CUDC-907, a dual PI3K/histone deacetylase inhibitor, increases meta-iodobenzylguanidine uptake (Journal of translational medicine · 2023Article
- Effects of DDT on Amyloid Precursor Protein Levels and Amyloid Beta Pathology: Mechanistic Links to Alzheimer's Disease Risk.Environmental health perspectives · 2022Article
- The Prospective Application of Melatonin in Treating Epigenetic Dysfunctional Diseases.Frontiers in pharmacology · 2022Review
- Gut microbiota dysbiosis: The potential mechanisms by which alcohol disrupts gut and brain functions.Frontiers in microbiology · 2022Review
- Epigenetic histone acetylation modulating prenatal Poly I:C induced neuroinflammation in the prefrontal cortex of rats: a study in a maternal immune activation model.Frontiers in cellular neuroscience · 2022Article
- Valproate-Induced Epigenetic Upregulation of Hypothalamic Fto Expression Potentially Linked with Weight Gain.Cellular and molecular neurobiology · 2021Article
- Chronic antipsychotic treatment exerts limited effects on the mania-like behavior of dopamine transporter knockdown mice.Behavioural brain research · 2021Article
- Changes in striatal dopamine transporters in bipolar disorder and valproate treatment.European psychiatry : the journal of the Association of European Psychiatrists · 2021Article
- Regulation of Social Stress and Neural Degeneration by Activity-Regulated Genes and Epigenetic Mechanisms in Dopaminergic Neurons.Molecular neurobiology · 2020Review
- Contribution of neuronal calcium sensor 1 (Ncs-1) to anxiolytic-like and social behavior mediated by valproate and Gsk3 inhibition.Scientific reports · 2020Article
- Epigenetic Effects Mediated by Antiepileptic Drugs and their Potential Application.Current neuropharmacology · 2020Review
- Activation of Peroxisome Proliferator-Activated Receptor-α Increases the Expression of Nuclear Receptor Related 1 Protein (Nurr1) in Dopaminergic Neurons.Molecular neurobiology · 2019Article
- Epigenetic Regulation of the Ontogenic Expression of the Dopamine Transporter.Frontiers in genetics · 2019Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The dopamine transporter (DAT) is the key regulator of dopaminergic transmission and is a target of several xenobiotics, including pesticides and pharmacological agents. Previously, we identified a prominent role for histone deacetylases in the regulation of DAT expression. Here, we utilized a rat dopaminergic cell line (N27) to probe the responsiveness of DAT mRNA expression to inhibitors of histone acetylation. Inhibition of histone deacetylases (HDACs) by valproate, butyrate and Trichostatin A led to a 3-10-fold increase in DAT mRNA expression, a 50% increase in protein levels, which were accompanied by increased H3 acetylation levels. To confirm the mechanism of valproate-mediated increase in DAT mRNA, chromatin immunoprecipitation (ChIP) assays were used and demonstrated a significant increase in enrichment of acetylation of histone 3 on lysines 9 and 14 (H3K9/K14ac) in the DAT promoter. Expression of Nurr1 and Pitx3, key regulators of DAT expression, were increased following valproate treatment and Nurr1 binding was enriched in the DAT promoter. Together, these results indicate that histone acetylation and subsequent enhancement of transcription factor binding are plausible mechanisms for DAT regulation by valproate and, perhaps, by other xenobiotics.
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