ArticleNature neuroscience2021
Long-term behavioral and cell-type-specific molecular effects of early life stress are mediated by H3K79me2 dynamics in medium spiny neurons.
Article in Nature neuroscience, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 63 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
63 citing papers in PubMed, 112 citations in OpenAlex.
- Relationship of immune-inflammatory pathway and stress-induced depression with neural regeneration.Neural regeneration research · 2026Article
- Early life experiences, the neural epigenome and affective disorder risk.Nature reviews. Neuroscience · 2026Review
- Multilevel sex-influenced neurobiological signatures of early life adversity.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Altered Postnatal Chromatin Development in the Nucleus Accumbens Primes Enduring Stress Sensitivity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Epigenetic dysregulation in depression: molecular mechanisms, clinical biomarkers, and therapeutic opportunities.Journal of translational medicine · 2026Review
- Article
- From epigenetic scripts to kinase signals: linking DOT1L and RIPK1 in the neurobiology of degeneration.Molecular biology reports · 2026Review
- Neurobiology of resilience to early life stress.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Epigenetic regulation of brain development, plasticity, and response to early-life stress.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Chemical strategies for brain delivery of genomic therapy.Nature reviews. Chemistry · 2025Review
- Altered postnatal chromatin development in the nucleus accumbens primes lifelong stress sensitivity.bioRxiv : the preprint server for biology · 2025Article
- Optic disc morphometrics as a potential ocular biomarker for depression: evidence from two cross-sectional cohort studies.Translational psychiatry · 2025Article
- Prelimbic cortex to ventral tegmental area projection regulates early social isolation stress-potentiated heroin seeking in mice.Nature communications · 2025Article
- Dysfunction of the paraventricular thalamus-prelimbic cortex circuit underlies maternal separation-induced deficits in contagious pain.Science advances · 2025Article
- Design and validation of novel brain-penetrant HCN channel inhibitors to ameliorate social stress-induced susceptible phenotype.Molecular psychiatry · 2025Article
- How dopamine guides our social world.Pharmacological reviews · 2025Review
- Article
- Elucidating neuroepigenetic mechanisms to inform targeted therapeutics for brain disorders.iScience · 2025Review
- Early-life stress sensitizes response to future stress: Evidence and mechanisms.Neurobiology of stress · 2025Review
- Editorial: Community series in early life stress and depression, Volume II.Frontiers in psychiatry · 2025Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
Animals susceptible to chronic social defeat stress (CSDS) exhibit depression-related behaviors, with aberrant transcription across several limbic brain regions, most notably in the nucleus accumbens (NAc). Early life stress (ELS) promotes susceptibility to CSDS in adulthood, but associated enduring changes in transcriptional control mechanisms in the NAc have not yet been investigated. In this study, we examined long-lasting changes to histone modifications in the NAc of male and female mice exposed to ELS. Dimethylation of lysine 79 of histone H3 (H3K79me2) and the enzymes (DOT1L and KDM2B) that control this modification are enriched in D2-type medium spiny neurons and are shown to be crucial for the expression of ELS-induced stress susceptibility. We mapped the site-specific regulation of this histone mark genome wide to reveal the transcriptional networks it modulates. Finally, systemic delivery of a small molecule inhibitor of DOT1L reversed ELS-induced behavioral deficits, indicating the clinical relevance of this epigenetic mechanism.
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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.