Original Article

Molecular Psychiatry (2015) 20, 621–631; doi:10.1038/mp.2014.80; published online 5 August 2014

Pathological brain plasticity and cognition in the offspring of males subjected to postnatal traumatic stress

J Bohacek1, M Farinelli1, O Mirante1, G Steiner2, K Gapp1, G Coiret1, M Ebeling2, G Durán-Pacheco2, A L Iniguez3, F Manuella1, J-L Moreau2 and I M Mansuy1

  1. 1Brain Research Institute, Neuroscience Center Zürich, University of Zurich/ETH Zurich, Zurich, Switzerland
  2. 2Pharma Division, Hoffmann-La Roche, Basel, Switzerland
  3. 3Roche NimbleGen, Inc., Madison, WI, USA

Correspondence: Professor Dr I Mansuy, Brain Research Institute, University Zurich/Swiss Federal Institute of Technology, Winterthurerstrasse 190, Zurich 8057, Switzerland. E-mail: mansuy@hifo.uzh.ch

Received 3 February 2014; Revised 8 May 2014; Accepted 18 June 2014
Advance online publication 5 August 2014

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Abstract

Traumatic stress in early-life increases the risk for cognitive and neuropsychiatric disorders later in life. Such early stress can also impact the progeny even if not directly exposed, likely through epigenetic mechanisms. Here, we report in mice that the offspring of males subjected to postnatal traumatic stress have decreased gene expression in molecular pathways necessary for neuronal signaling, and altered synaptic plasticity when adult. Long-term potentiation is abolished and long-term depression is enhanced in the hippocampus, and these defects are associated with impaired long-term memory in both the exposed fathers and their offspring. The brain-specific gamma isoform of protein kinase C (Prkcc) is one of the affected signaling components in the hippocampus. Its expression is reduced in the offspring, and DNA methylation at its promoter is altered both in the hippocampus of the offspring and the sperm of fathers. These results suggest that postnatal traumatic stress in males can affect brain plasticity and cognitive functions in the adult progeny, possibly through epigenetic alterations in the male germline.