ArticleMolecular psychiatry2018
NRSF-dependent epigenetic mechanisms contribute to programming of stress-sensitive neurons by neonatal experience, promoting resilience.
Article in Molecular psychiatry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 117 citations in OpenAlex.
- Phosphorylation by CaMKIV regulates the transcriptional repressor activity and half-life of REST/NRSF.Science advances · 2026Article
- Peptide signaling in the paraventricular thalamus contributes to disrupted adult reward behaviors after early-life adversity.bioRxiv : the preprint server for biology · 2026Article
- The adrenal is doing what it's supposed to do, you just don't understand it.Neurobiology of stress · 2026Article
- Neurobiology of resilience to early life stress.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Maternal separation disrupts noradrenergic control of adult coping behaviors.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- The evolving neurobiology of early-life stress.Neuron · 2025Review
- Prenatal maternal life adversity impacts on learning and memory in offspring: implication to transgenerational epigenetic inheritance.Frontiers in neuroscience · 2025Article
- Molecular and functional mapping of the neuroendocrine hypothalamus: a new era begins.Journal of endocrinological investigation · 2024Review
- Enduring memory consequences of early-life stress / adversity: Structural, synaptic, molecular and epigenetic mechanisms.Neurobiology of stress · 2024Review
- Microglia: The Drunken Gardeners of Early Adversity.Biomolecules · 2024Review
- Neurobiological basis of stress resilience.Neuron · 2024Review
- Paraventricular Thalamus Neuronal Ensembles Encode Early-life Adversity and Mediate the Consequent Sex-dependent Disruptions of Adult Reward Behaviors.bioRxiv : the preprint server for biology · 2024Article
- Leveraging the developmental neuroscience of caregiving to promote resilience among youth exposed to adversity.Development and psychopathology · 2023Article
- REST Is Not Resting: REST/NRSF in Health and Disease.Biomolecules · 2023Review
- Possible Involvement of Perineuronal Nets in Anti-Depressant Effects of Electroacupuncture in Chronic-Stress-Induced Depression in Rats.Neurochemical research · 2023Article
- Increases in maternal depressive symptoms during pregnancy and infant cortisol reactivity: Mediation by placental corticotropin-releasing hormone.Development and psychopathology · 2023Article
- Methyl-CpG binding protein 2 expression is associated with symptom severity in patients with PTSD in a sex-dependent manner.Translational psychiatry · 2023Article
- Brief and long maternal separation in C57Bl6J mice: behavioral consequences for the dam and the offspring.Frontiers in behavioral neuroscience · 2023Article
- Single-Cell Transcriptional Changes in Hypothalamic Corticotropin-Releasing Factor-Expressing Neurons After Early-Life Adversity Inform Enduring Alterations in Vulnerabilities to Stress.Biological psychiatry global open science · 2023Article
- The impact of early-life environment on absence epilepsy and neuropsychiatric comorbidities.IBRO neuroscience reports · 2022Review
6 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Resilience to stress-related emotional disorders is governed in part by early-life experiences. Here we demonstrate experience-dependent re-programming of stress-sensitive hypothalamic neurons, which takes place through modification of neuronal gene expression via epigenetic mechanisms. Specifically, we found that augmented maternal care reduced glutamatergic synapses onto stress-sensitive hypothalamic neurons and repressed expression of the stress-responsive gene, Crh. In hypothalamus in vitro, reduced glutamatergic neurotransmission recapitulated the repressive effects of augmented maternal care on Crh, and this required recruitment of the transcriptional repressor repressor element-1 silencing transcription factor/neuron restrictive silencing factor (NRSF). Increased NRSF binding to chromatin was accompanied by sequential repressive epigenetic changes which outlasted NRSF binding. chromatin immunoprecipitation-seq analyses of NRSF targets identified gene networks that, in addition to Crh, likely contributed to the augmented care-induced phenotype, including diminished depression-like and anxiety-like behaviors. Together, we believe these findings provide the first causal link between enriched neonatal experience, synaptic refinement and induction of epigenetic processes within specific neurons. They uncover a novel mechanistic pathway from neonatal environment to emotional resilience.
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