ArticleNeurobiology of disease2015
Chronic mild stress and antidepressant treatment alter 5-HT1A receptor expression by modifying DNA methylation of a conserved Sp4 site.
Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 72 citations in OpenAlex.
- Pooled it
- Methylome-wide association study of antidepressant use in Generation Scotland and the Netherlands Twin Register implicates the innate immune system.Molecular psychiatry · 2022Pooled it
- Insights from a methylome-wide association study of antidepressant exposure.Nature communications · 2025Article
- Relationships between serotonin 1A receptor DNA methylation, self-reported history of childhood abuse and gray matter volume in major depression.Journal of affective disorders · 2024Article
- PRKCB methylation: a potential biomarker of MDD with childhood chronic stress, a cross-sectional study in drug-naive, first-episode adolescent MDD.Epigenetics · 2024Observational
- Models for depression recognition and efficacy assessment based on clinical and sequencing data.Heliyon · 2024Article
- Antidepressant Effect of Sodium Butyrate is Accompanied by Brain Epigenetic Modulation in Rats Subjected to Early or Late Life Stress.Current neurovascular research · 2024Article
- Article
- Brain serotonin 1A receptor binding: relationship to peripheral blood DNA methylation, recent life stress and childhood adversity in unmedicated major depression.The British journal of psychiatry : the journal of mental science · 2023Article
- Review
- The Role of Serotonergic Gene Methylation in Regulating Anxiety-Related Personality Traits in Chimpanzees.Biology · 2022Article
- DNA Methylation in Depression and Depressive-Like Phenotype: Biomarker or Target of Pharmacological Intervention?Current neuropharmacology · 2022Review
- Chronic stress induces NPD-like behavior in APPPS1 and WT mice with subtle differences in gene expression.Genes, brain, and behavior · 2021Article
- MicroRNA Regulates Early-Life Stress-Induced Depressive Behavior via Serotonin Signaling in a Sex-Dependent Manner in the Prefrontal Cortex of Rats.Biological psychiatry global open science · 2021Article
- The Importance of Epigenetics in Diagnostics and Treatment of Major Depressive Disorder.Journal of personalized medicine · 2021Review
- Modulation of DNA Methylation and Gene Expression in Rodent Cortical Neuroplasticity Pathways Exerts Rapid Antidepressant-Like Effects.Molecular neurobiology · 2021Article
- Epigenetic landscape of stress surfeit disorders: Key role for DNA methylation dynamics.International review of neurobiology · 2021Article
- [EJNMMI research · 2020Article
- Genetic and Epigenetic Consequence of Early-Life Social Stress on Depression: Role of Serotonin-Associated Genes.Frontiers in genetics · 2020Review
- Early Life Stress Induced DNA Methylation of Monoamine Oxidases Leads to Depressive-Like Behavior.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The serotonin 1A receptor (5-HT1A), a critical regulator of the brain serotonergic tone, is implicated in major depressive disorder (MDD) where it is often found to be dys-regulated. However, the extent to which stress and antidepressant treatment impact 5-HT1A expression in adults remains unclear. To address this issue, we subjected adult male BALB/c mice to unpredictable chronic mild stress (UCMS) to induce a depression-like phenotype that was reversed by chronic treatment with the antidepressant imipramine. In prefrontal cortex (PFC) and midbrain tissue, UCMS increased 5-HT1A RNA and protein levels, changes that are expected to decrease the brain serotonergic activity. The stress-induced increase in 5-HT1A expression was paralleled by a specific increase in DNA methylation of the conserved -681 CpG promoter site, located within a Sp1-like element. We show that the -681 CpG site is recognized and repressed by Sp4, the predominant neuronal Sp1-like factor and that Sp4-induced repression is attenuated by DNA methylation, despite a stress-induced increase in PFC Sp4 levels. These results indicate that adult life stress induces DNA methylation of a conserved promoter site, antagonizing Sp4 repression to increase 5-HT1A expression. Chronic imipramine treatment fully reversed the UCMS-induced increase in methylation of the -681 CpG site in the PFC but not midbrain of stressed animals and also increased 5-HT1A expression in the PFC of control animals. Incomplete reversal by imipramine of stress-induced changes in 5-HT1A methylation and expression indicates a persistence of stress vulnerability, and that sustained reversal of behavioral impairments may require additional pathways.
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