Cited by 149Stress Responses and CortisolEpigenetics and DNA MethylationNeurotransmitter Receptor Influence on Behavior

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Chronic Stress Induces Sex-Specific Alterations in Methylation and Expression of Corticotropin-Releasing Factor Gene in the Rat

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Sterrenburg, Linda, Gaszner, Balázs, Boerrigter, Jeroen, Santbergen, Lennart, Bramini, Mattia, Elliott, Evan, Chen, Alon, Peeters, Bernard W. M. M., Roubos, Eric W., Kozicz, Tamás·2011·PLoS ONE

DOI 10.1371/journal.pone.0028128PMC PMC3223222

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Abstract

BACKGROUND: Although the higher prevalence of depression in women than in men is well known, the neuronal basis of this sex difference is largely elusive. METHODS: Male and female rats were exposed to chronic variable mild stress (CVMS) after which immediate early gene products, corticotropin-releasing factor (CRF) mRNA and peptide, various epigenetic-associated enzymes and DNA methylation of the Crf gene were determined in the hypothalamic paraventricular nucleus (PVN), oval (BSTov) and fusiform (BSTfu) parts of the bed nucleus of the stria terminalis, and central amygdala (CeA). RESULTS: CVMS induced site-specific changes in Crf gene methylation in all brain centers studied in female rats and in the male BST and CeA, whereas the histone acetyltransferase, CREB-binding protein was increased in the female BST and the histone-deacetylase-5 decreased in the male CeA. These changes were accompanied by an increased amount of c-Fos in the PVN, BSTfu and CeA in males, and of FosB in the PVN of both sexes and in the male BSTov and BSTfu. In the PVN, CVMS increased CRF mRNA in males and CRF peptide decreased in females. CONCLUSIONS: The data confirm our hypothesis that chronic stress affects gene expression and CRF transcriptional, translational and secretory activities in the PVN, BSTov, BSTfu and CeA, in a brain center-specific and sex-specific manner. Brain region-specific and sex-specific changes in epigenetic activity and neuronal activation may play, too, an important role in the sex specificity of the stress response and the susceptibility to depression.

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The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585
An analysis of variance test for normality (complete samples)
SHAPIRO, S. S., & WILK, M. B. (1965) · Biometrika · doi:10.1093/biomet/52.3-4.591 · Cited by 23,480
Statistical Methods -6th ed.-
Snedecor, G. W., & Cochran, W. G. (1967) · Cited by 6,573
Research confuses me: what is the difference between case-control and cohort studies in quantitative research?
Higgins, S. M. F., Macken, A. P., Cullen, W., Saunders, J., Dunne, C. P., & O’Gorman, C. S. (2013) · PubMed · doi:10.34961/9953 · Cited by 4,807
Stress and the brain: from adaptation to disease
de Kloet, E. R., Joëls, M., & Holsboer, F. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1683 · Cited by 4,621
AChE-stained horizontal sections of the rat brain in stereotaxic coordinates
Paxinos, G., WATSON, C. R. R., & Emson, P. C. (1980) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(80)90021-7 · Cited by 4,501
Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study
Murray, C. J., & Lopez, A. D. (1997) · The Lancet · doi:10.1016/s0140-6736(96)07495-8 · Cited by 4,492 · cited 1×
“Chronic exposure to stressors can result in psychopathologies, of which depression is ranked second in the global burden of disease [1–7].”
Background
Characterization of a 41-Residue Ovine Hypothalamic Peptide That Stimulates Secretion of Corticotropin and β-Endorphin
Vale, W., Spiess, J., Rivier, C., & Rivier, J. (1981) · Science · doi:10.1126/science.6267699 · Cited by 3,965
Characterization of a 41-Residue Ovine Hypothalamic Peptide that Stimulates Secretion of Corticotropin and β-Endorphin
Vale, W., Spiess, J., RIVIER, C. L., & Rivier, J. (1982) · Obstetrical & Gynecological Survey · doi:10.1097/00006254-198205000-00013 · Cited by 3,904
The Corticosteroid Receptor Hypothesis of Depression
Holsboer, F. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00159-7 · Cited by 2,181

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EJ Nestler, 1999, DeltaFosB: a molecular mediator of long-term neural and behavioral plasticity., Brain Res, 835, 10

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Authors: Sterrenburg, L., Gaszner, B., Boerrigter, J., Santbergen, L., Bramini, M., Elliott, E., Chen, A., Peeters, B. W. M. M., Roubos, E. W., & Kozicz, T.
Affiliations: Radboud University Nijmegen (NL)
University of Pecs (HU)
Bar-Ilan University (IL)
Weizmann Institute of Science (IL)
Corresponding author: Kozicz, Tamás
ORCID: Gaszner, Balázs
Bramini, Mattia
Elliott, Evan
Chen, Alon
Kozicz, Tamás
Venue: PLoS ONE
Publisher: Public Library of Science (PLoS)
Published: 2011-11-23
Volume: 6
Issue: 11
Pages: e28128
ISSN: 1932-6203 (ISSN-L)
DOI: 10.1371/journal.pone.0028128
PMC: PMC3223222
OpenAlex: W2159916106
Cited by: 149
References: 80
Citations by year: 2026: 4 · 2025: 3 · 2024: 1 · 2023: 8 · 2022: 11 · 2021: 12 · 2020: 17 · 2019: 10 · 2018: 10 · 2017: 9 · 2016: 16 · 2015: 9 · 2014: 15 · 2013: 13 · 2012: 10
FWCI: 4.90
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (unspecified)
Locations: PLoS ONE (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Institutional Repository of the University of Granada (University of Granada) (submittedVersion, cc-by-nc-nd)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Figshare (submittedVersion, cc-by)
Radboud Repository (Radboud University) (submittedVersion)
Radboud Repository (Radboud University) (submittedVersion, other-oa)
Funders: Nederlandse Organisatie voor Wetenschappelijk Onderzoek (864.05.008)
Magyar Tudományos Akadémia
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords: corticotropin-releasing factor, DNA methylation, sex differences, depression, hypothalamic paraventricular nucleus, bed nucleus of the stria terminalis, central amygdala, CREB-binding protein, HDAC5, c-fos, FosB, immediate early genes, epigenetic regulation, stress response
MeSH terms: Animals, Body Weight, Chronic Disease, Corticosterone, Corticotropin-Releasing Hormone, Female, Gene Expression Regulation, Immunohistochemistry, Male, Models, Biological, Paraventricular Hypothalamic Nucleus, Septal Nuclei, Sex Characteristics, Stress, Psychological, Rats, Wistar, In Situ Hybridization, DNA Methylation, Epigenesis, Genetic, Rats

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Chronic Stress Induces Sex-Specific Alterations in Methylation and Expression of Corticotropin-Releasing Factor Gene in the Rat

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