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

Molecular Psychiatry volume 20, pages 621–631 (2015)Cite this article

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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.

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Acknowledgements

We thank Carl Kashuk for help with microarray data processing, Heidi Rosenbaum for help in microarray data acquisition, Bechara Saab for technical help, and Heiko Hörster, Gisep Bazzell and Yvonne Zipfel for animal care. The lab of IMM is supported by the University Zürich, the Swiss Federal Institute of Technology Zürich, the Swiss National Science Foundation, Roche, the National Center of Competence in Research Neural Plasticity and Repair. JB is supported by a postdoc ETHZ fellowship and a Roche fellowship. MF is supported by a Roche postdoc fellowship. KG is supported by a DOC-fFORTE Fellowship from the Austrian Academy of Science.

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  1. Brain Research Institute, Neuroscience Center Zürich, University of Zurich/ETH Zurich, Zurich, Switzerland

    J Bohacek, M Farinelli, O Mirante, K Gapp, G Coiret, F Manuella & I M Mansuy

  2. Pharma Division, Hoffmann-La Roche, Basel, Switzerland

    G Steiner, M Ebeling, G Durán-Pacheco & J-L Moreau

  3. Roche NimbleGen, Inc., Madison, WI, USA

    A L Iniguez

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  1. J Bohacek
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Bohacek, J., Farinelli, M., Mirante, O. et al. Pathological brain plasticity and cognition in the offspring of males subjected to postnatal traumatic stress. Mol Psychiatry 20, 621–631 (2015). https://doi.org/10.1038/mp.2014.80

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