ArticleThe European journal of neuroscience2016
Neonatal maternal separation stress elicits lasting DNA methylation changes in the hippocampus of stress-reactive Wistar Kyoto rats.
Article in The European journal of neuroscience, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- Early-Life Adversity-Induced Epigenetic Reprogramming of Prefrontal Cortex in Rats Subjected to Maternal Separation.Biological psychiatry global open science · 2025Article
- Depression-associated gut microbes, metabolites and clinical trials.Frontiers in microbiology · 2024Review
- Overexpression of ATF4 Inhibits Ferroptosis to Alleviate Anxiety Disorders by Activating the TGF-β Signaling Pathway.Neuropsychiatric disease and treatment · 2024Article
- Methyl Donors, Epigenetic Alterations, and Brain Health: Understanding the Connection.International journal of molecular sciences · 2023Review
- Influence of gut microbiota on resilience and its possible mechanisms.International journal of biological sciences · 2023Review
- The impact of early-life environment on absence epilepsy and neuropsychiatric comorbidities.IBRO neuroscience reports · 2022Review
- DNA Methylation in Depression and Depressive-Like Phenotype: Biomarker or Target of Pharmacological Intervention?Current neuropharmacology · 2022Review
- Holistic Rehabilitation: Biological Embedding of Social Adversity and Its Health Implications.Physical therapy · 2022Article
- Reviewing the role of gut microbiota in the pathogenesis of depression and exploring new therapeutic options.Frontiers in neuroscience · 2022Review
- Perinatal SSRI Exposure Disrupts G Protein-coupled Receptor BAI3 in Developing Dentate Gyrus and Adult Emotional Behavior: Relevance to Psychiatric Disorders.Neuroscience · 2021Article
- Exposure to different early-life stress experiences results in differentially altered DNA methylation in the brain and immune system.Neurobiology of stress · 2020Article
- The effects of maternal separation stress experienced by parents on male reproductive potential in the next generation.Heliyon · 2020Article
- Sex differences in the epigenetic regulation of chronic visceral pain following unpredictable early life stress.Neurogastroenterology and motility · 2020Article
- The Way to a Human's Brain Goes Through Their Stomach: Dietary Factors in Major Depressive Disorder.Frontiers in neuroscience · 2020Review
- The microbiota-gut-brain axis: An emerging role for the epigenome.Experimental biology and medicine (Maywood, N.J.) · 2020Review
- Alteration of the brain methylation landscape following postnatal inflammatory injury in rat pups.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Effect of Early Life Stress on the Epigenetic Profiles in Depression.Frontiers in cell and developmental biology · 2020Review
- Early-Life Stress Alters Synaptic Plasticity and mTOR Signaling: Correlation With Anxiety-Like and Cognition-Related Behavior.Frontiers in genetics · 2020Article
- Gut microbial metabolites in depression: understanding the biochemical mechanisms.Microbial cell (Graz, Austria) · 2019Review
- Effect of early maternal separation stress on attention, spatial learning and social interaction behaviour.Experimental brain research · 2019Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Early-life stress (ELS) can alter neurodevelopment in variable ways, ranging from producing deleterious outcomes to stress resilience. While most ELS studies focus on its harmful effects, recent work by our laboratory and others shows that ELS elicits positive effects in certain individuals. We exposed Wistar Kyoto (WKY) rats, known for a stress reactive, anxiety/depression-like phenotype, to maternal separation (MS), a model of ELS. MS exposure elicited anxiolytic and antidepressant behavioral effects as well as improved cardiovascular function in adult WKY offspring. This study interrogates an epigenetic mechanism (DNA methylation) that may confer the adaptive effects of MS in WKY offspring. We quantified global genome methylation levels in limbic brain regions of adult WKYs exposed to daily 180-min MS or neonatal handling from postnatal day 1-14. MS exposure triggered dramatic DNA hypermethylation specifically in the hippocampus. Next-generation sequencing methylome profiling revealed reduced methylation at intragenic sites within two key nodes of insulin signaling pathways: the insulin receptor and one of its major downstream targets, mitogen-activated protein kinase kinase kinase 5 (Map3k5). We then tested the hypothesis that enhancing DNA methylation in WKY rats would elicit adaptive changes akin to the effects of MS. Dietary methyl donor supplementation improved WKY rats' anxiety/depression-like behaviors and also improved cardiovascular measures, similar to previous observations following MS. Overall, these data suggest a potential molecular mechanism that mediates a predicted adaptive response, whereby ELS induces DNA methylation changes in the brain that may contribute to successful stress coping and adaptive physiological changes in adulthood.
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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.