Checks and balances: The glucocorticoid receptor and NF kappa B in good times and bad

• Type of Material: Article
• Authors: Mandakh Bekhbat, Emory University; Sydney A. Rowson, Emory University; Gretchen Neigh, Emory University
• Language: English
• Date: 2017-07-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.yfrne.2017.05.001
• Title of Journal or Parent Work: Frontiers in Neuroendocrinology
• ISSN: 0091-3022
• Volume: 46
• Start Page: 15
• End Page: 31
• Grant/Funding Information: The authors receive funding from NIH: NR014886 and MH110364. SAR was supported by NIH training grant T32-GM008602.
• Keywords: Depression; ACTIVATED PROTEIN-KINASE; Nuclear factor kappa-light-chain-enhancer of activated B cells; PITUITARY-ADRENAL AXIS; Inflammation; HEAT-SHOCK-PROTEIN; MAJOR DEPRESSIVE DISORDER; FKBP5; Endocrinology & Metabolism; PTSD; Anxiety; OXIDE SYNTHASE EXPRESSION; BLOOD MONONUCLEAR-CELLS; Science & Technology; HIPPOCAMPAL HT22 CELLS; Glucocorticoid receptor; SEX-DEPENDENT MANNER; PEPTIDYLPROLYL ISOMERASE DOMAIN; Stress; Neurosciences & Neurology; STEROID-BINDING CONFORMATION; Neurosciences; Life Sciences & Biomedicine; Glucocorticoid resistance
• Research Categories: Biology, Neuroscience; Biology, Anatomy

Abstract

Mutual regulation and balance between the endocrine and immune systems facilitate an organism's stress response and are impaired following chronic stress or prolonged immune activation. Concurrent alterations in stress physiology and immunity are increasingly recognized as contributing factors to several stress-linked neuropsychiatric disorders including depression, anxiety, and post-traumatic stress disorder. Accumulating evidence suggests that impaired balance and crosstalk between the glucocorticoid receptor (GR) and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) – effectors of the stress and immune axes, respectively – may play a key role in mediating the harmful effects of chronic stress on mood and behavior. Here, we first review the molecular mechanisms of GR and NFκB interactions in health, then describe potential shifts in the GR-NFκB dynamics in chronic stress conditions within the context of brain circuitry relevant to neuropsychiatric diseases. Furthermore, we discuss developmental influences and sex differences in the regulation of these two transcription factors.