title: Chronic Psychosocial Stress and Negative Feedback Inhibition: Enhanced Hippocampal Glucocorticoid Signaling despite Lower Cytoplasmic GR Expression.
abstract: Chronic subordinate colony housing (CSC), a pre-clinically validated mouse model for chronic psychosocial stress, results in increased basal and acute stress-induced plasma adrenocorticotropic hormone (ACTH) levels. We assessed CSC effects on hippocampal glucocorticoid (GC) receptor (GR), mineralocorticoid receptor (MR), and FK506 binding protein (FKBP51) expression, acute heterotypic stressor-induced GR translocation, as well as GC effects on gene expression and cell viability in isolated hippocampal cells. CSC mice showed decreased GR mRNA and cytoplasmic protein levels compared with single-housed control (SHC) mice. Basal and acute stress-induced nuclear GR protein expression were comparable between CSC and SHC mice, as were MR and FKBP51 mRNA and/or cytoplasmic protein levels. In vitro the effect of corticosterone (CORT) on hippocampal cell viability and gene transcription was more pronounced in CSC versus SHC mice. In summary, CSC mice show an, if at all, increased hippocampal GC signaling capacity despite lower cytoplasmic GR protein expression, making negative feedback deficits in the hippocampus unlikely to contribute to the increased ACTH drive following CSC.
authors.affiliation: Department of Behavioural and Molecular Neurobiology, University of Regensburg, 93053, Regensburg, Germany.
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Füchsl
authors.affiliation: Department of Behavioural and Molecular Neurobiology, University of Regensburg, 93053, Regensburg, Germany.
authors.forename: Stefan O
authors.initials: SO
authors.lastname: Reber
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D002452:Cell Count; D002467:Cell Nucleus / Q000378:metabolism; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D025461:Feedback, Physiological; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D056950:Period Circadian Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013315:Stress, Psychological / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism; D000099159:Tacrolimus Binding Protein 5
chemical_list: D000324:Adrenocorticotropic Hormone; D003345:Corticosterone; D056950:Period Circadian Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5; C539023:Per1 protein, mouse