Original Article

Neuropsychopharmacology (2016) 41, 2749–2758; doi:10.1038/npp.2016.87; published online 6 July 2016

Potential of Environmental Enrichment to Prevent Transgenerational Effects of Paternal Trauma

Katharina Gapp1,3, Johannes Bohacek1, Jonas Grossmann2, Andrea M Brunner1,4, Francesca Manuella1, Paolo Nanni2 and Isabelle M Mansuy1

  1. 1Laboratory of Neuroepigenetics, University of Zurich and ETH Zurich, Brain Research Institute, Neuroscience Center Zürich, Zurich, Switzerland
  2. 2Functional Genomics Center Zurich (FGCZ), University Zurich/ETH Zurich, Zurich Switzerland

Correspondence: Professor IM Mansuy, Brain Research Institute, University Zurich/Swiss Federal Institute of Technology, Winterthurerstrasse 190, Zurich 8057, Switzerland, Tel: +41 44 635 33 60, Fax: +41 44 635 33 03, E-mail: mansuy@hifo.uzh.ch

3Current address: Gurdon Institute, University of Cambridge, Tennis Court Road, Cambridge CB2 1QN, UK.

4Current address: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Padualaan 8, 3584CH Utrecht, The Netherlands.

Received 15 February 2016; Revised 9 May 2016; Accepted 28 May 2016
Accepted article preview online 9 June 2016; Advance online publication 6 July 2016



Adverse experiences in early life are risk factors for the development of behavioral and physiological symptoms that can lead to psychiatric and cognitive disorders later in life. Some of these symptoms can be transmitted to the offspring, in some cases by non-genomic mechanisms involving germ cells. Using a mouse model of unpredictable maternal separation and maternal stress, we show that postnatal trauma alters coping behaviors in adverse conditions in exposed males when adult and in their adult male progeny. The behavioral changes are accompanied by increased glucocorticoid receptor (GR) expression and decreased DNA methylation of the GR promoter in the hippocampus. DNA methylation is also decreased in sperm cells of exposed males when adult. Transgenerational transmission of behavioral symptoms is prevented by paternal environmental enrichment, an effect associated with the reversal of alterations in GR gene expression and DNA methylation in the hippocampus of the male offspring. These findings highlight the influence of both negative and positive environmental factors on behavior across generations and the plasticity of the epigenome across life.

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