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Epigenetic Transmission of the Impact of Early Stress Across Generations

  • Tamara B. Franklin
    Affiliations
    Brain Research Institute, Medical Faculty of the University of Zürich, Zürich, Switzerland

    Department of Biology, Swiss Federal Institute of Technology, Zürich, Switzerland
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  • Holger Russig
    Affiliations
    Brain Research Institute, Medical Faculty of the University of Zürich, Zürich, Switzerland

    Department of Biology, Swiss Federal Institute of Technology, Zürich, Switzerland
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  • Isabelle C. Weiss
    Affiliations
    Brain Research Institute, Medical Faculty of the University of Zürich, Zürich, Switzerland

    Department of Biology, Swiss Federal Institute of Technology, Zürich, Switzerland
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  • Johannes Gräff
    Affiliations
    Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, Massachusetts
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  • Natacha Linder
    Affiliations
    Brain Research Institute, Medical Faculty of the University of Zürich, Zürich, Switzerland

    Department of Biology, Swiss Federal Institute of Technology, Zürich, Switzerland
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  • Aubin Michalon
    Affiliations
    Preclinical CNS Research, Hoffmann Laroche, Basel, Switzerland
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  • Sandor Vizi
    Affiliations
    Brain Research Institute, Medical Faculty of the University of Zürich, Zürich, Switzerland

    Department of Biology, Swiss Federal Institute of Technology, Zürich, Switzerland
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  • Isabelle M. Mansuy
    Correspondence
    Address correspondence to Isabelle M. Mansuy, Ph.D., Brain Research Institute, Medical Faculty of the University of Zurich, and Department of Biology, Swiss Federal Institute of Technology, Winterthurerstrasse 190, 8057 Zurich Switzerland
    Affiliations
    Brain Research Institute, Medical Faculty of the University of Zürich, Zürich, Switzerland

    Department of Biology, Swiss Federal Institute of Technology, Zürich, Switzerland
    Search for articles by this author

      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.

      Key Words

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