ArticleScientific reports2018
Loss of MeCP2 in adult 5-HT neurons induces 5-HT1A autoreceptors, with opposite sex-dependent anxiety and depression phenotypes.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- A Meta-Analysis of Brain DNA Methylation Across Sex, Age, and Alzheimer's Disease Points for Accelerated Epigenetic Aging in Neurodegeneration.Frontiers in aging neuroscience · 2021Pooled it
- Molecular Mechanisms of Depression: The Interplay Between Genes and Receptors.International journal of molecular sciences · 2025Review
- The C/C Genotype of the C-1019G (rs6295) Polymorphism of the 5-HT1A Receptor Gene Is Associated with Lower Susceptibility to Depressive Symptoms in a Rural Population in Mexico.Neurology international · 2025Article
- Conserved transcription factors coordinate synaptic gene expression through repression.bioRxiv : the preprint server for biology · 2025Article
- Article
- Models for depression recognition and efficacy assessment based on clinical and sequencing data.Heliyon · 2024Article
- Chronic Desipramine Reverses Deficits in Cell Activity, Norepinephrine Innervation, and Anxiety-Depression Phenotypes in Fluoxetine-Resistant cF1ko Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Transcriptional Regulation of the Human 5-HT1A Receptor Gene by Lithium: Role of Deaf1 and GSK3β.International journal of molecular sciences · 2023Article
- Vitamin D modulates cortical transcriptome and behavioral phenotypes in an Mecp2 heterozygous Rett syndrome mouse model.Neurobiology of disease · 2022Article
- Mechanisms underlying anxiety in Rett Syndrome: Translational insights from preclinical findings.Neuroscience applied · 2022Review
- DNA methylation and behavioral dysfunction in males with 47,XXY and 49,XXXXY: a pilot study.Clinical epigenetics · 2021Article
- Astroglial Serotonin Receptors as the Central Target of Classic Antidepressants.Advances in neurobiology · 2021Article
- Schisandrin B exerts hypnotic effects in PCPA-treated rats by increasing hypothalamic 5-HT and γ-aminobutyric acid levels.Experimental and therapeutic medicine · 2020Article
- Sex differences in Mecp2-mutant Rett syndrome model mice and the impact of cellular mosaicism in phenotype development.Brain research · 2020Review
- Functional Interrogation of a Depression-Related Serotonergic Single Nucleotide Polymorphism, rs6295, Using a Humanized Mouse Model.ACS chemical neuroscience · 2019Article
- Genetic, epigenetic and posttranscriptional mechanisms for treatment of major depression: the 5-HT1A receptor gene as a paradigmJournal of psychiatry & neuroscience : JPN · 2019Review
- Loss of Adult 5-HT1A Autoreceptors Results in a Paradoxical Anxiogenic Response to Antidepressant Treatment.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Overcoming Resistance to Selective Serotonin Reuptake Inhibitors: Targeting Serotonin, Serotonin-1A Receptors and Adult Neuroplasticity.Frontiers in neuroscience · 2019Review
- Somato-Dendritic Regulation of Raphe Serotonin Neurons; A Key to Antidepressant Action.Frontiers in neuroscience · 2018Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
The 5-HT1A autoreceptor mediates feedback inhibition of serotonin (5-HT) neurons, and is implicated in major depression. The human 5-HT1A gene (HTR1A) rs6295 risk allele prevents Deaf1 binding to HTR1A, resulting in increased 5-HT1A autoreceptor transcription. Since chronic stress alters HTR1A methylation and expression, we addressed whether recruitment of methyl-binding protein MeCP2 may alter Deaf1 regulation at the HTR1A locus. We show that MeCP2 enhances Deaf1 binding to its HTR1A site and co-immunoprecipitates with Deaf1 in cells and brain tissue. Chromatin immunoprecipitation assays showed Deaf1-dependent recruitment of MeCP2 to the mouse HTR1A promoter, and MeCP2 modulated human and mouse HTR1A gene transcription in a Deaf1-dependent fashion, enhancing Deaf1-induced repression at the Deaf1 site. To address the role of MeCP2 in HTR1A regulation in vivo, mice with conditional knockout of MeCP2 in adult 5-HT neurons (MeCP2 cKO) were generated. These mice exhibited increased 5-HT1A autoreceptor levels and function, consistent with MeCP2 enhancement of Deaf1 repression in 5-HT neurons. Interestingly, female MeCP2-cKO mice displayed reduced anxiety, while males showed increased anxiety and reduced depression-like behaviors. These data uncover a novel role for MeCP2 in 5-HT neurons to repress HTR1A expression and drive adult anxiety- and depression-like behaviors in a sex-specific manner.
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Registered trials
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