title: Hippocampal gene expression induced by cold swim stress depends on sex and handling.
abstract: Stress-related disorders such as PTSD and depression are more prevalent in women than men. One reason for such discordance may be that brain regions involved in stress responses are more sensitive to stress in females. Here, we compared the effects of acute stress on gene transcription in the hippocampus of female and male mice, and also examined the involvement of two key stress-related hormones, corticosterone and corticotropin releasing hormone (Crh). Using quantitative reverse transcription polymerase chain reaction (RT-qPCR), we measured gene expression of Fos, Per1 and Sgk1 45 min after exposure to brief cold swim stress. Stress induced a stronger increase in Fos and Per1 expression in females than males. The handling control procedure increased Fos in both sexes, but occluded the effects of stress in males. Further, handling increased Per1 only in males. Sgk1 was insensitive to handling, and increased in response to stress similarly in males and females. The transcriptional changes observed after swim stress were not mimicked by corticosterone injections, and the stress-induced increase in Fos, Per1 and Sgk1 could neither be prevented by pharmacologically blocking glucocorticoid receptor (GR) nor by blocking Crh receptor 1 (Crhr1) before stress exposure. Finally, we demonstrate that the effects are stressor-specific, as the expression of target genes could not be increased by brief restraint stress in either sex. In summary, we find strong effects of acute swim stress on hippocampal gene expression, complex interactions between handling and sex, and a remarkably unique response pattern for each gene. Overall, females respond to a cold swim challenge with stronger hippocampal gene transcription than males, independent of two classic mediators of the stress response, corticosterone and Crh. These findings may have important implications for understanding the higher vulnerability of women to certain stress-related neuropsychiatric diseases.
authors.affiliation: Brain Research Institute, Neuroscience Center Zürich, University of Zurich/ETH Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Electronic address: bohacek@hifo.uzh.ch.
authors.forename: Johannes
authors.initials: J
authors.lastname: Bohacek
authors.affiliation: Brain Research Institute, Neuroscience Center Zürich, University of Zurich/ETH Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Francesca
authors.initials: F
authors.lastname: Manuella
authors.affiliation: Brain Research Institute, Neuroscience Center Zürich, University of Zurich/ETH Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Roszkowski
authors.affiliation: Brain Research Institute, Neuroscience Center Zürich, University of Zurich/ETH Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
authors.forename: Isabelle M
authors.initials: IM
authors.lastname: Mansuy
mesh_terms: D000818:Animals; D003080:Cold Temperature; D003345:Corticosterone / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism*; D017874:Immediate-Early Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D056950:Period Circadian Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012737:Sex Factors; D013315:Stress, Psychological / Q000209:etiology / Q000378:metabolism*; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D003345:Corticosterone; D003346:Corticotropin-Releasing Hormone; D017874:Immediate-Early Proteins; D056950:Period Circadian Proteins; D017346:Protein Serine-Threonine Kinases; D016760:Proto-Oncogene Proteins c-fos; D000099184:Serum-Glucocorticoid Regulated Kinases; C539023:Per1 protein, mouse
keywords: Corticosterone; Hippocampus; Per1; Sex; Sgk1; Stress