Cited by 1,125Epigenetics and DNA MethylationStress Responses and CortisolMaternal Mental Health During Pregnancy and Postpartum

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Epigenetic Transmission of the Impact of Early Stress Across Generations

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Franklin, Tamara B., Russig, Holger, Weiss, Isabelle C., Gräff, Johannes, Linder, Natacha, Michalon, Aubin, Vizi, Sandor, Mansuy, Isabelle M.·2010·Biological Psychiatry

DOI 10.1016/j.biopsych.2010.05.036

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Abstract

Background Traumatic experiences in early life are risk factors for the development of behavioral and emotional disorders. Such disorders can persist through adulthood and have often been reported to be transmitted across generations.Methods To investigate the transgenerational effect of early stress, mice were exposed to chronic and unpredictable maternal separation from postnatal day 1 to 14.Results We show that chronic and unpredictable maternal separation induces depressive-like behaviors and alters the behavioral response to aversive environments in the separated animals when adult. Most of the behavioral alterations are further expressed by the offspring of males subjected to maternal separation, despite the fact that these males are reared normally. Chronic and unpredictable maternal separation also alters the profile of DNA methylation in the promoter of several candidate genes in the germline of the separated males. Comparable changes in DNA methylation are also present in the brain of the offspring and are associated with altered gene expression.Conclusions These findings highlight the negative impact of early stress on behavioral responses across generations and on the regulation of DNA methylation in the germline.

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PORSOLT, R. D., LE PICHON, M., & JALFRE, M. (1977) · Nature · doi:10.1038/266730a0 · Cited by 4,451
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Gardiner‐Garden, M., & Frommer, M. (1987) · Journal of Molecular Biology · doi:10.1016/0022-2836(87)90689-9 · Cited by 3,417
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Robertson, K. D. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1655 · Cited by 2,864
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Klose, R. J., & Bird, A. P. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2005.12.008 · Cited by 2,501
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Jirtle, R. L., & Skinner, M. K. (2007) · Nature Reviews Genetics · doi:10.1038/nrg2045 · Cited by 2,492
Distribution, silencing potential and evolutionary impact of promoter DNA methylation in the human genome
Weber, M., Hellmann, I., Stadler, M. B., Ramos, L., Pääbo, S., Rebhan, M., & Schübeler, D. (2007) · Nature Genetics · doi:10.1038/ng1990 · Cited by 2,297
The link between childhood trauma and depression: insights from HPA axis studies in humans
Heim, C., Newport, D. J., Mletzko, T., Miller, A. H., & Nemeroff, C. B. (2008) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2008.03.008 · Cited by 1,704

Show all 68 references

Research works printed but not linked: 1

Weaver, 2004, Epigenetic programming by maternal behavior, Nat Neurosci, 7, 847, 10.1038/nn1276 · DOI · Paper page

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“In contrast, a reduction of MeCP2 levels in male germ cells (Franklin et al. 2010) © 2013 Society for the Study of Addiction Addiction Biology, 20, 120–131 was described in maternal separation mice models.”
BackgroundInfluential
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Kubota, T., Hirasawa, T., & Miyake, K. (2012) · Pharmaceuticals · doi:10.3390/ph5040369 · Cited by 27
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Background
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“females were exposed to an unpredictable stressor during separation as previously described [16].”
BackgroundMethodInfluentialSelf-citation
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“Another study showed that male mice exposed to unpredictable maternal separation early on later developed anxiety and depressive-like behaviors, as well as impairment in social functioning; these phenotypes were later observed in their offspring, even in circumstances of adequate maternal care [37, 38].”
Background
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Background
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“…trauma may be passed through an epigenetic change in the gametes, change in cortisol levels during gestation, or through the relationship with the parent changing after vicariously experiencing trauma (Antonelli, 2012; Bowers & Yehuda, 2016; Franklin et al., 2010; Yehuda et al., 2005).”
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BackgroundInfluential
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“Another gene is corticotrophin-releasing factor receptor 2 (CRFR2), G protein-coupled receptor for corticotropin-releasing hormone (CRH) (Franklin et al., 2010; Pal et al., 2010).”
BackgroundResultInfluential
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“We aim to exploit unique preand postnatal rodent models of stress [27,33] to identify ELS-associated molecular pathways causally linked to multi-morbid symptoms in adult life.”
Self-citation
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Duque-Quintero, M., Hooijmans, C. R., Hurowitz, A., Ahmed, A., Barris, B., Homberg, J. R., Hen, R., Harris, A. Z., Balsam, P. D., & Atsak, P. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104849 · Cited by 26
Early adversity disrupts the adult use of aversive prediction errors to reduce fear in uncertainty
Wright, K. M., DiLeo, A., & McDannald, M. A. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00227 · Cited by 23
“…PTSD Introduction Early adversity increases anxiety in adult rodents (Avital and Richter-Levin, 2005; Pohl et al., 2007; Tsoory et al., 2007; Franklin et al., 2010) and primates (Sánchez et al., 2005; Sanchez, 2006), and also increases the risk for post-traumatic stress disorder (PTSD) in…”
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Authors: Franklin, T. B., Russig, H., Weiss, I. C., Gräff, J., Linder, N., Michalon, A., Vizi, S., & Mansuy, I. M.
Affiliations: University of Zurich (CH)
Massachusetts Institute of Technology (US)
F. Hoffmann-La Roche AG (CH)
Corresponding author: Mansuy, Isabelle M.
ORCID: Franklin, Tamara B.
Gräff, Johannes
Michalon, Aubin
Mansuy, Isabelle M.
Venue: Biological Psychiatry
Publisher: Elsevier BV
Published: 2010-09
Volume: 68
Issue: 5
Pages: 408-415
ISSN: 0006-3223 (ISSN-L)
DOI: 10.1016/j.biopsych.2010.05.036
OpenAlex: W2035616108
Cited by: 1,125
References: 68
Citations by year: 2026: 35 · 2025: 43 · 2024: 39 · 2023: 63 · 2022: 48 · 2021: 63 · 2020: 115 · 2019: 75 · 2018: 96 · 2017: 79 · 2016: 89 · 2015: 88 · 2014: 95 · 2013: 82 · 2012: 66
FWCI: 25.65
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biological Psychiatry (publishedVersion)
PubMed (publishedVersion)
Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
Funders: University of Zürich
Swiss Federal Institute of Technology
Swiss National Science Foundation
National Center for Competence in Research “Neural Plasticity and Repair,”
Human Frontier Science Program
Borderline Personality Disorder Research Foundation
Roche
European Molecular Biology Organization Young Investigator Program
Novartis Research Foundation
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
Keywords: transgenerational transmission, early life stress, maternal separation, chronic unpredictable mild stress, depression-like behavior, DNA methylation, offspring behavior, gene expression
MeSH terms: Age Factors, Animals, Behavior, Animal, Mental Disorders, Brain, Female, Humans, Male, Maternal Deprivation, Sex Factors, Stress, Psychological, Gene Expression, DNA Methylation, Models, Animal, Epigenesis, Genetic, Mice

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Epigenetic Transmission of the Impact of Early Stress Across Generations

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