title: Early life stress in fathers improves behavioural flexibility in their offspring.
abstract: Traumatic experiences in childhood can alter behavioural responses and increase the risk for psychopathologies across life, not only in the exposed individuals but also in their progeny. In some conditions, such experiences can however be beneficial and facilitate the appraisal of adverse environments later in life. Here we expose newborn mice to unpredictable maternal separation combined with unpredictable maternal stress (MSUS) for 2 weeks and assess the impact on behaviour in the offspring when adult. We show that MSUS in male mice favours goal-directed behaviours and behavioural flexibility in the adult offspring. This effect is accompanied by epigenetic changes involving histone post-translational modifications at the mineralocorticoid receptor (MR) gene and decreased MR expression in the hippocampus. Mimicking these changes pharmacologically in vivo reproduces the behavioural phenotype. These findings highlight the beneficial impact that early adverse experiences can have in adulthood, and the implication of epigenetic modes of gene regulation.
authors.affiliation: Brain Research Institute, Medical Faculty of the University of Zürich and Department of Health Sciences and Technology of the Swiss Federal Institute of Technology, Neuroscience Center Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Gapp
authors.affiliation: Brain Research Institute, Medical Faculty of the University of Zürich and Department of Health Sciences and Technology of the Swiss Federal Institute of Technology, Neuroscience Center Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Saray
authors.initials: S
authors.lastname: Soldado-Magraner
authors.affiliation: Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zürich, Winterthurerstrasse 260, CH-88057 Zurich, Switzerland.
authors.forename: María
authors.initials: M
authors.lastname: Alvarez-Sánchez
authors.affiliation: Brain Research Institute, Medical Faculty of the University of Zürich and Department of Health Sciences and Technology of the Swiss Federal Institute of Technology, Neuroscience Center Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Bohacek
authors.affiliation: Brain Research Institute, Medical Faculty of the University of Zürich and Department of Health Sciences and Technology of the Swiss Federal Institute of Technology, Neuroscience Center Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Gregoire
authors.initials: G
authors.lastname: Vernaz
authors.affiliation: Brain Research Institute, Medical Faculty of the University of Zürich and Department of Health Sciences and Technology of the Swiss Federal Institute of Technology, Neuroscience Center Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Huan
authors.initials: H
authors.lastname: Shu
authors.affiliation: EMBL Monterotondo, Via Ramarini 32, 00015 Rome, Italy.
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Franklin
authors.affiliation: Zurich Center for Integrative Human Physiology (ZIHP), Institute of Anatomy of the University of Zürich, and Institute for Human Movement Sciences of the Swiss Federal Institute of Technology Zürich, 8093 Zürich, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Wolfer
authors.affiliation: Brain Research Institute, Medical Faculty of the University of Zürich and Department of Health Sciences and Technology of the Swiss Federal Institute of Technology, Neuroscience Center Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
authors.forename: Isabelle M
authors.initials: IM
authors.lastname: Mansuy
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D005220:Fathers / Q000523:psychology*; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D008426:Maternal Deprivation; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010375:Pedigree; D011499:Protein Processing, Post-Translational; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological
chemical_list: D006657:Histones; D018161:Receptors, Mineralocorticoid