Polymorphisms in the FK506 binding protein 5 (FKBP5) gene have been shown to influence glucocorticoid receptor sensitivity, stress response regulation, and depression risk in traumatized subjects, with most consistent findings reported for the functional variant rs1360780.
The glucocorticoid receptor (GR) gene (NR3C1) has been found to be susceptible to epigenetic modification, specifically DNA methylation, in the context of environmental stress such as early life trauma, which is an established risk for depression later in life.
Glucocorticoid receptor dysfunction orchestrates inflammasome effects on chronic obstructive pulmonary disease-induced depression: A potential mechanism underlying the cross talk between lung and brain.
Network modeling and animal experiments suggest that these genetic differences in GR-induced transcriptional activation may mediate the risk for depression and other psychiatric disorders by altering a network of functionally related stress-sensitive genes in blood and brain.
The present study shows that depression attenuates the mechanical allodynia and thermal hyperalgesia of neuropathic pain and suggests that altered spinal GR-BDNF-TrkB signaling may be one of the reasons for depression-induced hypoalgesia.
We investigated PTSD and depression severity, plasma cortisol, GR and mineralocorticoid receptor (MR) levels, and methylation status of NR3C1 and NR3C2 promoter regions in 25 women exposed to the Tutsi genocide during pregnancy and their children, and 25 women from the same ethnicity, pregnant during the same period but not exposed to the genocide, and their children.
Studies investigating Glucocorticoid Receptor (GR/NR3C1) in the brain have primarily focused on the forebrain, however in recent years, the hindbrain has become a region of interest for research into the development of anxiety and depression, though the role of GR signalling in the hindbrain remains poorly characterised.
FKBP5 is a glucocorticoid receptor-regulating co-chaperone of hsp-90 and, therefore, is suggested to play a role in the regulation of the hypothalamic-pituitary-adrenocortical system and the pathophysiology of depression.
The hypo‑level of adrenocorticotropic hormone, noradrenaline and glucocorticoid receptor in serum and hypothalamus of depression‑like rats was enhanced by PHC.
Using high throughput technologies for the identification of genes regulated by glucocorticoid receptor (GR) and MR in brain areas responsible for specific symptoms of stress-related disorders will yield potential new drug targets for the treatment of depression and anxiety.
Given the role of GR-mediated negative feedback in mediating response to stress, and the clear link between stress and depression, it is plausible that polymorphisms in the GR gene (NR3C1) act to increase susceptibility.
[Effects of ginsenosides on hypothalamic-pituitary-adrenal function and brain-derived neurotrophic factor in rats exposed to chronic unpredictable mild stress].
Recent research suggests an important role of FKBP5, a glucocorticoid receptor regulating co-chaperone, in the development of stress-related diseases such as depression and anxiety disorders.
Combining both models resulted in 22 new and confirmed HSP90-independent NR3C1 inhibitors, providing two scaffolds (i.e., pyrimidine and pyrazolo-pyrimidine), which could potentially be of interest in the treatment of depression (i.e., inhibiting the glucocorticoid receptor (i.e., NR3C1), while leaving its chaperone, HSP90, unaffected).
Altered DNA methylation (DNAm) levels of hypothalamic-pituitary-adrenal (HPA) axis genes has been associated with exposure to childhood maltreatment (CM) and depression; however, it is unknown whether CM and depression have joint and potentially interacting effects on the glucocorticoid receptor (NR3C1) DNAm.