scholarly journals Common genes associated with antidepressant response in mouse and man identify key role of glucocorticoid receptor sensitivity

PLoS Biology ◽  
2017 ◽  
Vol 15 (12) ◽  
pp. e2002690 ◽  
Author(s):  
Tania Carrillo-Roa ◽  
Christiana Labermaier ◽  
Peter Weber ◽  
David P. Herzog ◽  
Caleb Lareau ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Antidepressant Response ◽  
Receptor Sensitivity

scholarly journals Mechanistic insights on metabolic dysfunction in PTSD: Role of glucocorticoid receptor sensitivity and energy deficit

2018 ◽  
Author(s):  
Pramod R. Somvanshi ◽  
Synthia H. Mellon ◽  
Janine D. Flory ◽  
Duna Abu-Amara ◽  
Owen M. Wolkowitz ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Hpa Axis ◽  
Metabolic Control Analysis ◽  
Energy Deficit ◽  
Control Analysis ◽  
Metabolic Dysfunction ◽  
Receptor Sensitivity ◽  
Regulatory Effects ◽  
Metabolic Comorbidities

AbstractPTSD is associated with metabolic comorbidities; however it is not clear how the neuroendocrine disturbances affect metabolism. To analyze this we employed a systems biological approach using an integrated mathematical model of metabolism, HPA axis and inflammation. We combined the metabolomics, neuroendocrine, clinical lab and cytokine data from combat-exposed veterans with and without PTSD, to characterize the differences in regulatory effects. We used the pattern of fold change in metabolites representing pathway level differences as reference for metabolic control analysis (MCA) using the model. MCA revealed parameters constituting the HPA axis, inflammation and GPCR pathway that yielded metabolic dysfunction consistent with PTSD. To support this, we performed causal analysis between regulatory components and the significantly different metabolites in our sample. Causal inference revealed that the changes in glucocorticoid receptor sensitivity were mechanistically associated with metabolic dysfunction and the effects were jointly mediated by insulin resistance, inflammation, oxidative stress and energy deficit.

scholarly journals Glucocorticoid receptor wields chromatin interactions to tune transcription for cytoskeleton stabilization in podocytes

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Hong Wang ◽  
Aiping Duan ◽  
Jing Zhang ◽  
Qi Wang ◽  
Yuexian Xing ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Glucocorticoid Receptor ◽  
Protective Effect ◽  
Histone Modification ◽  
Regulatory Networks ◽  
Target Gene ◽  
Regulatory Elements ◽  
Chromatin Interactions ◽  
Super Enhancer

AbstractElucidating transcription mediated by the glucocorticoid receptor (GR) is crucial for understanding the role of glucocorticoids (GCs) in the treatment of diseases. Podocyte is a useful model for studying GR regulation because GCs are the primary medication for podocytopathy. In this study, we integrated data from transcriptome, transcription factor binding, histone modification, and genome topology. Our data reveals that the GR binds and activates selective regulatory elements in podocyte. The 3D interactome captured by HiChIP facilitates the identification of remote targets of GR. We found that GR in podocyte is enriched at transcriptional interaction hubs and super-enhancers. We further demonstrate that the target gene of the top GR-associated super-enhancer is indispensable to the effective functioning of GC in podocyte. Our findings provided insights into the mechanisms underlying the protective effect of GCs on podocyte, and demonstrate the importance of considering transcriptional interactions in order to fine-map regulatory networks of GR.

scholarly journals Sexual dimorphic role of the glucocorticoid receptor in chronic muscle pain produced by early-life stress

2021 ◽  
Vol 17 ◽  
pp. 174480692110113
Author(s):  
Paul G Green ◽  
Pedro Alvarez ◽  
Jon D Levine
Keyword(s):  
Glucocorticoid Receptor ◽  
Adult Male ◽  
Life Stress ◽  
Early Life ◽  
Glucocorticoid Receptors ◽  
Early Life Stress ◽  
Nociceptive Threshold ◽  
Male And Female ◽  
Mechanical Nociceptive Threshold

Fibromyalgia and other chronic musculoskeletal pain syndromes are associated with stressful early life events, which can produce a persistent dysregulation in the hypothalamic-pituitary adrenal (HPA) stress axis function, associated with elevated plasm levels of corticosterone in adults. To determine the contribution of the HPA axis to persistent muscle hyperalgesia in adult rats that had experienced neonatal limited bedding (NLB), a form of early-life stress, we evaluated the role of glucocorticoid receptors on muscle nociceptors in adult NLB rats. In adult male and female NLB rats, mechanical nociceptive threshold in skeletal muscle was significantly lower than in adult control (neonatal standard bedding) rats. Furthermore, adult males and females that received exogenous corticosterone (via dams’ milk) during postnatal days 2–9, displayed a similar lowered mechanical nociceptive threshold. To test the hypothesis that persistent glucocorticoid receptor signaling in the adult contributes to muscle hyperalgesia in NLB rats, nociceptor expression of glucocorticoid receptor (GR) was attenuated by spinal intrathecal administration of an oligodeoxynucleotide (ODN) antisense to GR mRNA. In adult NLB rats, GR antisense markedly attenuated muscle hyperalgesia in males, but not in females. These findings indicate that increased corticosterone levels during a critical developmental period (postnatal days 2–9) produced by NLB stress induces chronic mechanical hyperalgesia in male and female rats that persists in adulthood, and that this chronic muscle hyperalgesia is mediated, at least in part, by persistent stimulation of glucocorticoid receptors on sensory neurons, in the adult male, but not female rat.

scholarly journals Role of TATA-element in transcription from glucocorticoid receptor-responsive model promoters

1990 ◽  
Vol 18 (17) ◽  
pp. 5113-5118 ◽  
Author(s):  
Stefan Wieland ◽  
Michael D. Schatt ◽  
Sandro Rusconi
Keyword(s):  
Glucocorticoid Receptor ◽  
Tata Element

S.12.07 Role of 5-HT1A/5-HT2A receptors interaction in the severity of depression and antidepressant response

2013 ◽  
Vol 23 ◽  
pp. S131
Author(s):  
G. Quesseveur ◽  
A.C. Petit ◽  
F. Gressier ◽  
R. Colle ◽  
D.J. David ◽  
...  
Keyword(s):  
Antidepressant Response ◽  
Severity Of Depression

New insights into the role of cortisol and the glucocorticoid receptor in severe depression

2002 ◽  
Vol 52 (5) ◽  
pp. 381-385 ◽  
Author(s):  
Philip W Gold ◽  
Wayne C Drevets ◽  
Dennis S Charney ◽  
Wayne C Drevets
Keyword(s):  
Glucocorticoid Receptor ◽  
Severe Depression
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