ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Phosphorylation of MeCP2 at Ser421 contributes to chronic antidepressant action.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 52 citations in OpenAlex.
- Genetic Mechanisms of Experience-Dependent Neuronal Plasticity.Annual review of genetics · 2025Review
- Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review.International journal of molecular sciences · 2024Review
- Ketamine and rapid antidepressant action: new treatments and novel synaptic signaling mechanisms.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Bridging rapid and sustained antidepressant effects of ketamine.Trends in molecular medicine · 2023Review
- BDNF exon IV promoter methylation and antidepressant action: a complex interplay.Clinical epigenetics · 2022Article
- Low levels of Methyl-CpG binding protein 2 are accompanied by an increased vulnerability to the negative outcomes of stress exposure during childhood in healthy women.Translational psychiatry · 2022Article
- BDNF as a Mediator of Antidepressant Response: Recent Advances and Lifestyle Interactions.International journal of molecular sciences · 2022Review
- Transgenerational Susceptibility to Food Addiction-Like Behavior in Rats Associates to a Decrease of the Anti-Inflammatory IL-10 in Plasma.Neurochemical research · 2022Article
- Novel drug developmental strategies for treatment-resistant depression.British journal of pharmacology · 2022Review
- The Role of MeCP2 in Regulating Synaptic Plasticity in the Context of Stress and Depression.Cells · 2022Review
- Circulating microRNA associated with future relapse status in major depressive disorder.Frontiers in psychiatry · 2022Article
- Excitation and Inhibition Imbalance in Rett Syndrome.Frontiers in neuroscience · 2022Review
- Sustained effects of rapidly acting antidepressants require BDNF-dependent MeCP2 phosphorylation.Nature neuroscience · 2021Article
- Escitalopram Targets Oxidative Stress, Caspase-3, BDNF and MeCP2 in the Hippocampus and Frontal Cortex of a Rat Model of Depression Induced by Chronic Unpredictable Mild Stress.International journal of molecular sciences · 2021Article
- Article
- Regulation of neural differentiation, synaptic scaling and animal behavior by MeCP2 phophorylation.Neurobiology of learning and memory · 2019Article
- Epigenetic Regulations in Neuropsychiatric Disorders.Frontiers in genetics · 2019Review
- Epigenetic regulation of Fgf1 transcription by CRTC1 and memory enhancement.Brain research bulletin · 2018Review
- Synaptically Localized Transcriptional Regulators in Memory Formation.Neuroscience · 2018Review
- BDNF Plasma Levels and BDNF Exon IV Promoter Methylation as Predictors for Antidepressant Treatment Response.Frontiers in psychiatry · 2018Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Although tricyclic antidepressants rapidly activate monoaminergic neurotransmission, these drugs must be administered chronically to alleviate symptoms of depression. This observation suggests that molecular mechanisms downstream of monoamine receptor activation, which include the induction of gene transcription, underlie chronic antidepressant-induced changes in behavior. Here we show that methyl-CpG-binding protein 2 (MeCP2) regulates behavioral responses to chronic antidepressant treatment. Imipramine administration induces phosphorylation of MeCP2 at Ser421 (pMeCP2) selectively in the nucleus accumbens and the lateral habenula, two brain regions important for depressive-like behaviors. To test the role of pMeCP2 in depressive-like behaviors, we used male mice that bear a germ-line mutation knocked into the X-linked Mecp2 locus that changes Ser421 to a nonphosphorylatable Ala residue (S421A). MeCP2 S421A knock-in (KI) mice showed increased immobility in forced-swim and tail-suspension tests compared with their wild-type (WT) littermates. However, immobility of both MeCP2 WT and KI mice in forced swim was reduced by acute administration of imipramine, demonstrating that loss of pMeCP2 does not impair acute pharmacological sensitivity to this drug. After chronic social defeat stress, chronic administration of imipramine significantly improved social interaction in the MeCP2 WT mice. In contrast, the MeCP2 KI mice did not respond to chronic imipramine administration. These data suggest novel roles for pMeCP2 in the sensitivity to stressful stimuli and demonstrate that pMeCP2 is required for the effects of chronic imipramine on depressive-like behaviors induced by chronic social defeat stress.
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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.