Chronic Psychosocial Stress and Negative Feedback Inhibition: Enhanced Hippocampal Glucocorticoid Signaling despite Lower Cytoplasmic GR Expression

• Published in: PloS one Vol. 11; no. 4; p. e0153164
• Main Authors: Füchsl, Andrea M, Reber, Stefan O
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08-04-2016; Public Library of Science (PLoS)
• Subjects: Adrenocorticotropic hormone; Adrenocorticotropic Hormone - blood; Alzheimer's disease; Alzheimers disease; Animals; Biology and Life Sciences; Cell Count; Cell Nucleus - metabolism; Corticosterone; Corticosterone - blood; Corticosterone - pharmacology; Cytoplasm - metabolism; Endocrinology; Feedback inhibition; Feedback, Physiological; Gene expression; Glucocorticoids; Hippocampus; Hippocampus (Brain); Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Homeostasis; Housing; In Vitro Techniques; Laboratories; Ligands; Male; Medicine and Health Sciences; Metabolism; Mice; Mice, Inbred C57BL; Negative feedback; Nervous system; Neurobiology; Neurosciences; Organ Size; Period Circadian Proteins - genetics; Protein expression; Proteins; Psychosomatic disorders; Psychosomatic medicine; Psychotherapy; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - metabolism; Receptors, Mineralocorticoid - genetics; Receptors, Mineralocorticoid - metabolism; Research and Analysis Methods; Risk factors; RNA, Messenger - genetics; RNA, Messenger - metabolism; Shc protein; Signal Transduction; Signaling; Social interactions; Social Sciences; Stress; Stress, Psychological - genetics; Stress, Psychological - metabolism; Stress, Psychological - pathology; Stresses; Tacrolimus; Tacrolimus Binding Proteins - genetics; Tacrolimus Binding Proteins - metabolism; Tacrolimus-binding protein; Transcription; Transcription factors; Translocation; Trends; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0153164

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.