ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2013
Glucocorticoid receptor and FKBP5 expression is altered following exposure to chronic stress: modulation by antidepressant treatment.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
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Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 194 citations in OpenAlex.
- Human Dermal Fibroblast: A Promising Cellular Model to Study Biological Mechanisms of Major Depression and Antidepressant Drug Response.Current neuropharmacology · 2020Pooled it
- Role for the kinase SGK1 in stress, depression, and glucocorticoid effects on hippocampal neurogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2013Trial
- Chronic Stress and the Brain-Kidney Axis in Renal Injury: From Neuroendocrine Dysregulation to Kidney Damage.International journal of molecular sciences · 2026Review
- Antidepressant effects of Gardeniae Fructus on chronic unpredictable mild stress model mice: involvement of DNMT3B-mediated epigenetic regulation of GR in the prefrontal cortex.Journal of natural medicines · 2026Article
- A Vortioxetine-Glycyrrhizic Acid Supramolecular Complex: Synthesis and Cellular Effects on Microglial and Blood Cells Under Inflammatory and Glucocorticoid Challenge.Biomedicines · 2026Article
- Glucocorticoid Receptor Signaling: Multilevel Organization, Roles in Fetal Development, and Postnatal Outcomes.International journal of molecular sciences · 2026Review
- Diabetes: A comprehensive review of the Indian landscape in contrast with global trends.World journal of diabetes · 2026Review
- Prenatal stress shapes discrete responses during early recovery from repeated adult stress.Frontiers in cellular neuroscience · 2026Article
- Disruption of a GalR2-mitochondrial axis in the ventral hippocampus contributes to depression-like phenotypes after prenatal stress.Frontiers in psychiatry · 2026Article
- α-synuclein in Parkinson's disease: a central point of convergence with depression.NPJ Parkinson's disease · 2025Review
- Toward Understanding and Halting Legacies of Trauma.Biological psychiatry · 2025Review
- Ventral hippocampal autophagy and mitophagy dynamics shape behavioral responses to chronic mild stress in adult male rats.Neurobiology of stress · 2025Article
- A depression-associated protein FKBP5 functions in autophagy initiation through scaffolding the VPS34 complex.Molecular neurobiology · 2025Article
- Transcriptomics insight into occupational exposure to engineered nanoparticles.Nanomedicine (London, England) · 2025Article
- The Role of the Glucocorticoid Receptor and Its Phosphorylation in Neurological Disorders.International journal of molecular sciences · 2025Review
- Lithium Treatment Increases FKBP5 Protein but Not mRNA Expression in the Pituitary Gland of Depressive-like Rats.Brain sciences · 2025Article
- Deep phenotyping reveals CRH and FKBP51-dependent behavioral profiles following chronic social stress exposure in male mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025Article
- Effects of prenatal iron deficiency on neurological development and related disorders in offspring.Frontiers in nutrition · 2025Review
- Sex-specific fear acquisition following early life stress is linked to amygdala and hippocampal purine and glutamate metabolism.Communications biology · 2024Article
- Targeting glucocorticoid receptor signaling pathway for treatment of stress-related brain disorders.Pharmacological reports : PR · 2024Review
33 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Major depression is thought to originate from the interaction between susceptibility genes and adverse environmental events, in particular stress. The hypothalamus-pituitary-adrenal (HPA) axis is the major system involved in stress response and its dysregulation is an important element in the pathogenesis of depression. The stress response is therefore finely tuned through a series of mechanisms that control the trafficking of glucocorticoid receptors (GRs) to the nucleus, including binding to the chaperone protein FKBP5 and receptor phosphorylation, suggesting that these elements may also be affected under pathologic conditions. On these bases, we investigated FKBP5 and GR expression and phosphorylation in the hippocampus (ventral and dorsal) and in the prefrontal cortex of rats exposed to chronic mild stress (CMS) and we analyzed the effect of a concomitant antidepressant treatment. We found that animals exposed to CMS show increased expression of FKBP5 as well as enhanced cytoplasmic levels of GR, primarily in ventral hippocampus and prefrontal cortex. Chronic treatment with the antidepressant duloxetine is able to normalize such alterations, mainly in the prefrontal cortex. Moreover, we demonstrate that CMS-induced alterations of GR trafficking and transcription may be sustained by changes in receptor phosphorylation, which are also modulated by pharmacological intervention. In summary, while GR-related changes after CMS might be relevant for the depressive phenotype, the ability of antidepressant treatment to correct some of these alterations may contribute to the normalization of HPA axis dysfunctions associated with stress-related disorders.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.