ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2010
Valproate and amitriptyline exert common and divergent influences on global and gene promoter-specific chromatin modifications in rat primary astrocytes.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.
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Who cites it
49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 135 citations in OpenAlex.
- Dissecting the Epigenetic Changes Induced by Non-Antipsychotic Mood Stabilizers on Schizophrenia and Affective Disorders: A Systematic Review.Frontiers in pharmacology · 2020Pooled it
- DNA Methylation as a Biomarker of Treatment Response Variability in Serious Mental Illnesses: A Systematic Review Focused on Bipolar Disorder, Schizophrenia, and Major Depressive Disorder.International journal of molecular sciences · 2018Pooled it
- Excitatory Amino Acid Transporters as Therapeutic Targets in the Treatment of Neurological Disorders: Their Roles and Therapeutic Prospects.Neurochemical research · 2025Review
- Genomics in Treatment Development.Advances in neurobiology · 2023Article
- Tricyclic antidepressants target FKBP51 SUMOylation to restore glucocorticoid receptor activity.Molecular psychiatry · 2022Article
- A history of childhood maltreatment is associated with altered DNA methylation levels of DNA methyltransferase 1 in maternal but not neonatal mononuclear immune cells.Frontiers in psychiatry · 2022Article
- Differential and paradoxical roles of new-generation antidepressants in primary astrocytic inflammation.Journal of neuroinflammation · 2021Article
- Epigenetic Neuropharmacology: Drugs Affecting the Epigenome in the Brain.Annual review of pharmacology and toxicology · 2021Review
- Neurobiology, Functions, and Relevance of Excitatory Amino Acid Transporters (EAATs) to Treatment of Refractory Epilepsy.CNS drugs · 2020Review
- The Effect of Chronic Mild Stress and Venlafaxine on the Expression and Methylation Levels of Genes Involved in the Tryptophan Catabolites Pathway in the Blood and Brain Structures of Rats.Journal of molecular neuroscience : MN · 2020Article
- Astrocytic histone deacetylase 2 facilitates delayed depression and memory impairment after subarachnoid hemorrhage by negatively regulating glutamate transporter-1.Annals of translational medicine · 2020Article
- Moving pharmacoepigenetics tools for depression toward clinical use.Journal of affective disorders · 2019Review
- Epigenetic Regulation of Excitatory Amino Acid Transporter 2 in Neurological Disorders.Frontiers in pharmacology · 2019Review
- FKBP5 DNA methylation does not mediate the association between childhood maltreatment and depression symptom severity in the Detroit Neighborhood Health Study.Journal of psychiatric research · 2018Article
- Glutamate Transport: A New Bench to Bedside Mechanism for Treating Drug Abuse.The international journal of neuropsychopharmacology · 2017Review
- Valproate increases dopamine transporter expression through histone acetylation and enhanced promoter binding of Nurr1.Neuropharmacology · 2017Article
- Drugging the pain epigenome.Nature reviews. Neurology · 2017Review
- Caregiver maltreatment causes altered neuronal DNA methylation in female rodents.Development and psychopathology · 2017Article
- Manganese Control of Glutamate Transporters' Gene Expression.Advances in neurobiology · 2017Review
- Chronic Treatment with Fluoxetine Induces Sex-Dependent Analgesic Effects and Modulates HDAC2 and mGlu2 Expression in Female Mice.Frontiers in pharmacology · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant biochemical processes in the brain frequently go along with subtle shifts of the cellular epigenetic profile that might support the pathogenic progression of psychiatric disorders. Although recent reports have implied the ability of certain antidepressants and mood stabilizers to modulate epigenetic parameters, studies comparing the actions of these compounds under the same conditions are lacking. In this study, we screened amitriptyline (AMI), venlafaxine, citalopram, as well as valproic acid (VPA), carbamazepine, and lamotrigine for their potential actions on global and local epigenetic modifications in rat primary astrocytes. Among all drugs, VPA exposure evoked the strongest global chromatin modifications, including histone H3/H4 hyperacetylation, 2MeH3K9 hypomethylation, and DNA demethylation, as determined by western blot and luminometric methylation analysis, respectively. CpG demethylation occurred independently of DNA methyltransferase (DNMT) suppression. Strikingly, AMI also induced slight cytosine demethylation, paralleled by the reduction in DNMT enzymatic activity, without affecting the global histone acetylation status. Locally, VPA-induced chromatin modifications were reflected at the glutamate transporter (GLT-1) promoter as shown by bisulfite sequencing and acetylated histone H4 chromatin immunoprecipitation analysis. Distinct CpG sites in the distal part of the GLT-1 promoter were demethylated and enriched in acetylated histone H4 in response to VPA. For the first time, we could show that these changes were associated with an enhanced transcription of this astrocyte-specific gene. In contrast, AMI failed to stimulate GLT-1 transcription and to alter promoter methylation levels. In conclusion, VPA and AMI globally exerted chromatin-modulating activities using different mechanisms that divergently precipitated at an astroglial gene locus.
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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.