Abstract
Chronic stress exposure during development can have lasting behavioral consequences that differ in males and females. More specifically, increased depressive behaviors in females, but not males, are observed in both humans and rodent models of chronic stress. Despite these known stress-induced outcomes, the molecular consequences of chronic adolescent stress in the adult brain are less clear. The stress hormone corticosterone activates the glucocorticoid receptor, and activity of the receptor is regulated through interactions with co-chaperones—such as the immunophilin FK506 binding proteins 5 (FKBP5). Previously, it has been reported that the adult stress response is modified by a history of chronic stress; therefore, the current study assessed the impact of chronic adolescent stress on the interactions of the glucocorticoid receptor (GR) with its regulatory co-chaperone FKBP5 in response to acute stress in adulthood. Although protein presence for FKBP5 did not differ by group, assessment of GR-FKBP5 interactions demonstrated that adult females with a history of chronic adolescent stress had elevated GR-FKBP5 interactions in the hippocampus following an acute stress challenge which could potentially contribute to a reduced translocation pattern given previous literature describing the impact of FKBP5 on GR activity. Interestingly, the altered co-chaperone interactions of the GR in the stressed female hippocampus were not coupled to an observable difference in transcription of GR-regulated genes. Together, these studies show that chronic adolescent stress causes lasting changes to co-chaperone interactions with the glucocorticoid receptor following stress exposure in adulthood and highlight the potential role that FKBP5 plays in these modifications. Understanding the long-term implications of adolescent stress exposure will provide a mechanistic framework to guide the development of interventions for adult disorders related to early life stress exposures.
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No potential conflict of interest was reported by the author(s).
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Notes on contributors
Sydney Rowson
Sydney Rowson, Phd is a Associate Laboratory Project Set-Up Manager with expertise in both translational animal models and clinical research
Mandakh Bekhbat
Mandakh Bekhbat, Phd is a postdoctoral fellow with expertise in the study of immune and endocrine mechanisms underlying psychiatric illnesses.
Sean Kelly
Sean Kelly, is a Senior Research Specialist with expertise in animal models of developmental stress and neuroimmune methods.
Molly M. Hyer
Molly M. Hyer, Phd is Director of Research Development and Innovation for the VCU Institute of Women’s Health and an experienced researcher in psychoneuroendocrinology.
Samya Dyer
Samya Dyer, MPH professional experience performing laboratory research involving continuous data collection, analysis, and interpretation in team settings.
David Weinshenker
David Weinshenker, Phd is a Professor of Human Genetics at Emory University and Scientific Director of the Emory School of Medicine Rodent Behavioral Core.
Gretchen Neigh
Gretchen Neigh, PhD, MBA is a Professor of Anatomy & Neurobiology. Dr. Neigh is director of Translational Research for the VCU Institute of Women’s Health, co-director of research for BIRCWH, and co-director for the Clinical and Translational Sciences PhD Program at Virginia Commonwealth University.