title: Paternal environmental enrichment transgenerationally alters affective behavioral and neuroendocrine phenotypes.
abstract: Recent studies have demonstrated that paternal stress in rodents can result in modification of offspring behavior. Environmental enrichment, which enhances cognitive stimulation and physical activity, modifies various behaviors and reduces stress responses in adult rodents. We investigated the transgenerational influence of paternal environmental enrichment on offspring behavior and physiological stress response. Adult C57BL/6J male mice (F0) were exposed to either environmental enrichment or standard housing for four weeks and then pair-mated with naïve females. The F2 generation was generated using F1 male offspring. Male and female F1 and F2 offspring were tested for anxiety using the elevated-plus maze and large open field at 8 weeks of age. Depression-related behavior was assessed using the forced-swim test. Hypothalamic-pituitary-adrenal (HPA) axis function was determined by quantification of serum corticosterone and adrenocorticotropic hormone (ACTH) levels at baseline and after forced-swim stress. Paternal environmental enrichment was associated with increased body weights of male F1 and F2 offspring. There was no significant effect on F1 offspring anxiety and depression-related behaviors. There were no changes in anxiety-related behaviors in the F2 offspring, however these mice displayed a reduced latency to immobility in the forced-swim test. Furthermore, F2 females had significantly higher serum corticosterone levels post-stress, but not ACTH. These results show that paternal environmental enrichment exerts a sex-specific transgenerational impact on the behavioral and physiological response to stress. Our findings have implications for the modelling of psychiatric disorders in rodents.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, VIC, 3010, Australia.
authors.forename: Shlomo
authors.initials: S
authors.lastname: Yeshurun
authors.affiliation: Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, VIC, 3010, Australia.
authors.forename: Annabel K
authors.initials: AK
authors.lastname: Short
authors.affiliation: Queensland Brain Institute, University of Queensland, Brisbane, QLD, 4072, Australia; Center for the Neurobiology of Learning and Memory and Department of Neurobiology and Behavior, University of California, Irvine, CA, 92617, USA.
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Bredy
authors.affiliation: Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, VIC, 3010, Australia; Department of Anatomy and Neuroscience, University of Melbourne, Parkville, VIC, 3010, Australia.
authors.forename: Terence Y
authors.initials: TY
authors.lastname: Pang
authors.affiliation: Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, VIC, 3010, Australia; Department of Anatomy and Neuroscience, University of Melbourne, Parkville, VIC, 3010, Australia. Electronic address: anthony.hannan@florey.edu.au.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hannan
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000097:blood / Q000503:physiopathology; D004777:Environment; D044127:Epigenesis, Genetic; D005260:Female; D006799:Housing, Animal; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000503:physiopathology*; D013312:Stress, Physiological / Q000502:physiology*; D013315:Stress, Psychological / Q000097:blood / Q000503:physiopathology*; D013550:Swimming
chemical_list: D000324:Adrenocorticotropic Hormone; D003345:Corticosterone
keywords: Corticosterone; Environmental enrichment; Epigenetic inheritance; HPA axis; Stress response; Transgenerational