ArticleJournal of neuroendocrinology2012
Maternal deprivation in rats is associated with corticotrophin-releasing hormone (CRH) promoter hypomethylation and enhances CRH transcriptional responses to stress in adulthood.
Article in Journal of neuroendocrinology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 199 citations in OpenAlex.
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- Sex-specific and developmental effects of early life adversity on stress reactivity are rescued by postnatal knockdown of 5-HTNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Prenatal maternal life adversity impacts on learning and memory in offspring: implication to transgenerational epigenetic inheritance.Frontiers in neuroscience · 2025Article
- Enduring Neurobiological Consequences of Early-Life Stress: Insights from Rodent Behavioral Paradigms.Biomedicines · 2024Review
- The role of epigenetic mechanisms in the long-term effects of early-life adversity and mother-infant relationship on physiology and behavior of offspring in laboratory rats and mice.Developmental psychobiology · 2024Review
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- Global research trends on maternal separation paradigms as an early life stress model: A bibliometric analysis.Heliyon · 2023Article
- Exposure to Juvenile Stress Induces Epigenetic Alterations in the GABAergic System in Rats.Genes · 2023Article
- The impact of early-life environment on absence epilepsy and neuropsychiatric comorbidities.IBRO neuroscience reports · 2022Review
- Corticotropin releasing factor neurons in the visual cortex mediate long-term changes in visual function induced by early adversity.Neurobiology of stress · 2022Article
- Cell-type-specific epigenetic effects of early life stress on the brain.Translational psychiatry · 2022Review
- Epigenetic Mechanism of Early Life Stress-Induced Depression: Focus on the Neurotransmitter Systems.Frontiers in cell and developmental biology · 2022Review
- Marine algae as emerging therapeutic alternatives for depression: A review.Iranian journal of basic medical sciences · 2021Review
- Effect of early life social adversity on drug abuse vulnerability: Focus on corticotropin-releasing factor and oxytocin.Neuropharmacology · 2021Review
- Maternal exposure to childhood traumatic events, but not multi-domain psychosocial stressors, predict placental corticotrophin releasing hormone across pregnancy.Social science & medicine (1982) · 2020Article
- The influence of psychological stress in early life on sexual maturation and sexual behavior in male and female rats.Reproductive medicine and biology · 2020Article
- Intrarenal Renin Angiotensin System Imbalance During Postnatal Life Is Associated With Increased Microvascular Density in the Mature Kidney.Frontiers in physiology · 2020Article
- Effect of Early Life Stress on the Epigenetic Profiles in Depression.Frontiers in cell and developmental biology · 2020Review
- The biological embedding of neonatal stress exposure: A conceptual model describing the mechanisms of stress-induced neurodevelopmental impairment in preterm infants.Research in nursing & health · 2019Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Exposure to stress during early development causes long-lasting alterations in behaviour and hypothalamic pituitary adrenal (HPA) axis activity, including increased expression of corticotrophin-releasing hormone (CRH). To determine whether early-life stress causes epigenetic changes in the CRH promoter leading to increased CRH transcription, 8-week old female and male rats, subjected to maternal deprivation (MD) between days 2 and 13 post-birth, were studied for HPA axis responses to stress and CRH promoter methylation in the hypothalamic paraventricular nucleus (PVN) and central nucleus of the amygdala (CeA). Plasma corticosterone and PVN CRH heteronuclear (hn)RNA responses to acute restraint stress were higher in MD rats of both sexes. DNA methylation analysis of the CRH promoter revealed a significantly lower percentage of methylation in two CpGs preceding (CpG1) and inside (CpG2) the cyclic AMP-response element (CRE) at -230 bp in the CRH promoter in the PVN but not the CeA of MD rats. Gel-shift assays, using nuclear proteins from forskolin-treated hypothalamic 4B cells and CRH promoter CRE oligonucleotides, unmethylated or methylated at CpG1, revealed a strong band that was supershifted by phospho-cAMP response element-binding antibody. This band was 50% weaker using oligonucleotides methylated at CpG2 (intra-CRE), or methylated at both CpG1 and CpG2. These findings demonstrate that HPA axis hypersensitivity caused by neonatal stress causes long-lasting enhanced CRH transcriptional activity in the PVN of both sexes. Hypomethylation of the CRH promoter CRE, a region critical for CRH transcriptional activation, could serve as a mechanism for the increased transcriptional responses to stress observed in MD rats.
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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.