ArticlePsychopharmacology2021
H3K9me2 regulation of BDNF expression in the hippocampus and medial prefrontal cortex is involved in the depressive-like phenotype induced by maternal separation in male rats.
Article in Psychopharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- Epigenetic mechanisms affected by stress during adolescence and the increased risk for depression later in life: a systematic review.Molecular psychiatry · 2026Pooled it
- "The wrong tools for the right job": a critical meta-analysis of traditional tests to assess behavioural impacts of maternal separation.Psychopharmacology · 2023Pooled it
- Effects of Serotonin Transporter Genotype and (Un)Predictable Maternal Separation on Affective, Cognitive, and Social Behaviors in Female Rats.Genes, brain, and behavior · 2026Article
- Neurodevelopmental effects of early life stress: PFC and cognition.Neuroscience and biobehavioral reviews · 2026Review
- Addictive drug abuse and depression-a focus on epigenetics.Communications biology · 2026Review
- Modifications on histone tails in psychiatric disorders.EC psychology and psychiatry · 2026Article
- Lifelong Impact of Prenatal Stress: Exacerbated Memory Impairments and Gene Expression Changes Under Adult Chronic Stress.Brain and behavior · 2025Article
- Early maternal separation potentiates the impact of later social isolation in inducing depressive-like behavior via oxidative stress in adult rats.Psychopharmacology · 2025Article
- Targeting Histone H3K9 Methyltransferase G9a as a Potential Therapeutic Strategy for Neuropsychiatric Disorders.Medicinal research reviews · 2025Review
- Role of Repressive Histone Lysine Demethylases and Methylases in Susceptibility to Depression Using a Novel Progressive Social Defeat Stress Mouse Model.Cellular and molecular neurobiology · 2025Article
- Progress in Molecular Mechanisms of Depression Induced by Mother-Infant Separation and Intervention of Traditional Chinese Medicine.Alpha psychiatry · 2025Review
- G9a an Epigenetic Therapeutic Strategy for Neurodegenerative Conditions: From Target Discovery to Clinical Trials.Medicinal research reviews · 2025Review
- [Effects of Vitamin BSichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- Development of the rodent prefrontal cortex: circuit formation, plasticity, and impacts of early life stress.Frontiers in neural circuits · 2025Review
- [Neuronal plasticity changes in the central amygdala and prelimbic cortex network in mice with chronic unpredictable mild stress-induced depression].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Epigenetic Modifications and Neuroplasticity in the Pathogenesis of Depression: A Focus on Early Life Stress.Behavioral sciences (Basel, Switzerland) · 2024Review
- Salt-inducible kinase 1-CREB-regulated transcription coactivator 1 signalling in the paraventricular nucleus of the hypothalamus plays a role in depression by regulating the hypothalamic-pituitary-adrenal axis.Molecular psychiatry · 2024Article
- Epigenetic regulation in major depression and other stress-related disorders: molecular mechanisms, clinical relevance and therapeutic potential.Signal transduction and targeted therapy · 2023Review
- A Novel Early Life Stress Model Affects Brain Development and Behavior in Mice.International journal of molecular sciences · 2023Article
- Resveratrol ameliorates maternal separation-induced anxiety- and depression-like behaviors and reduces Sirt1-NF-kB signaling-mediated neuroinflammation.Frontiers in behavioral neuroscience · 2023Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEarly life stress (ELS) induces a depressive-like phenotype and increases the risk of depression. Brain-derived neurotrophic factor (BDNF) has been confirmed to be involved in the pathophysiology of depression. However, the mechanism by which ELS alters the epigenetic regulation of BDNF and changes susceptibility to depression has not been fully clarified.
methodsThe present study used maternal separation (MS) and chronic unpredicted mild stress (CUMS) to establish an MS animal model and a depressive animal model. We assessed depressive-like behaviours, including anhedonia, locomotor activity, anxiety-like behaviour, and spatial memory, using the sucrose preference test, the open field test, the elevated plus maze test, and the Morris water maze test. We also investigated BDNF and H3K9me2 expression in the hippocampus and medial prefrontal cortex (mPFC) by immunohistochemistry, western blotting, and qPCR analysis. Additionally, we used Unc0642, a small molecule inhibitor of histone methyltransferase (G9a), as an intervention.
resultsThe results showed that CUMS induced depressive-like behaviours in rats and resulted in increased H3K9me2 expression and decreased BDNF expression in the hippocampus and mPFC. More importantly, adult MS rats experiencing CUMS had more severe depressive behaviours, had higher expression of H3K9me2 in the hippocampus and mPFC, and had lower expression of BDNF in the hippocampus and mPFC. In addition, administration of the G9a inhibitor reversed most of the changes.
conclusionsOur study suggests that ELS changed BDNF and H3K9me2 expression in the rat brain, resulting in a depressive-like phenotype.
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