ABSTRACT
The hypothalamus-pituitary-adrenal (HPA) axis directly controls the stress response. Dysregulation of this neuroendocrine system is a common feature among psychiatric disorders. Steroid hormone receptors, like glucocorticoid receptor (GR), function as transcription factors of a diverse set of genes upon activation. This activity is regulated by molecular chaperone heterocomplexes. Much is known about the structure and function of these GR/heterocomplexes. There is strong evidence suggesting altered regulation of steroid receptor hormones by chaperones, particularly the 51 kDa FK506-binding protein (FKBP51), may work with environmental factors to increase susceptibility to various psychiatric illnesses including post-traumatic stress disorder (PTSD), major depressive disorder (MDD), and anxiety. This review highlights the regulation of steroid receptor dynamics by the 90kDa heat shock protein (Hsp90)/cochaperone heterocomplexes with an in depth look at how the structural regulation and imbalances in cochaperones can cause functional effects on GR activity. Links between the stress response and circadian systems and the development of novel chaperone-targeting therapeutics are also discussed.
Subject(s)
Depressive Disorder, Major/pathology , HSP90 Heat-Shock Proteins/metabolism , Receptors, Steroid/metabolism , Circadian Rhythm , Cyclophilins/metabolism , Depressive Disorder, Major/metabolism , Glycoproteins/metabolism , Humans , Signal Transduction , Tacrolimus Binding Proteins/metabolismABSTRACT
Based on the autonomic nervous system (ANS) study by klein Selle, Verschuere, Kindt, Meijer, & Ben Shakhar (2016), 15 participants pretended to perform a crime shown on a video, which 16 other participants pretended to witness. Both groups then experienced a P300-based Concealed Information Test (CIT) protocol called the complex trial protocol. Both groups showed CIT effects, with a larger probe than irrelevant P300s at Pz. However, this effect was significantly larger in the suspect group. In contrast, only the suspect group showed delayed N200/N300 responses at F3-putative inhibitory signs. This supports the klein Selle et al. (2016) ANS study in that the suspect versus witness role-playing manipulation differentially affected inhibitory (vs. orienting) aspects of the CIT situation. Our results are also consistent with Ambach, Stark, Peper, & Vaitl (2008), who saw the same autonomic response fractionation as klein Selle et al., but using Furedy's differentiation of deception method (Furedy, Davis, & Gurevich, 1988). These similarities are discussed.
