Articles: glucocorticoid-receptors.
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Corticosteroid signaling plays a critical role in modulating the neural systems underlying reward and addiction, but the specific contributions of glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) in the medial prefrontal cortex (mPFC) to opioid reward and dopaminergic plasticity remain unclear. Here, we investigated the effects of intra-mPFC injection of corticosteroid receptor ligand (corticosterone; CORT), glucocorticoid receptor antagonist (RU38486; RU), and mineralocorticoid receptor antagonist (spironolactone; SP) on morphine-induced conditioned place preference (CPP) and dopamine transporter (DAT) expression in the mPFC. Adult male Wistar rats received intra-mPFC injections of CORT, RU, SP, or their respective vehicles prior to morphine CPP conditioning. ⋯ These findings demonstrate that corticosteroid receptor signaling within the mPFC modulates the rewarding properties of morphine and morphine-induced dopaminergic plasticity. This preclinical study suggests that targeting GRs and MRs in the mPFC could be a possible therapeutic approach for treating opioid addiction. By targeting these receptors, it may be possible to reduce opioid reward and counteract the neuroadaptations in dopamine systems associated with addiction.
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Eur. J. Clin. Invest. · Dec 2024
Synovial expression of glucocorticoid receptor parallels fibroblast activation in patients with rheumatoid arthritis.
Hypocortisolemia is associated with increased expression of NR3C1 (glucocorticoid receptor, GR) in blood cells. As endogenous cortisol production is decreased in some RA patients, we tested the hypothesis that GR may be aberrantly expressed in rheumatoid synovium. ⋯ GR is overexpressed in the synovium of some RA patients in association with proinflammatory gene expression and activated sublining fibroblast status. Further studies should examine whether GR overexpression may act as a compensatory mechanism sensitizing synovial tissue to glucocorticoid action in RA.
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Stress, a risk factor for major depressive disorder and Alzheimer disease, leads to the release of high-mobility group box-1 (HMGB1) protein, which in turn causes neuroinflammation. The mechanism underlying stress-induced HMGB1 release is unknown, but stress-associated glucocorticoids could be involved. Primary cultured rat cortical microglia and neurons were treated with corticosterone, a stress-associated glucocorticoid, and HMGB1 release was measured by ELISA and western blotting to test this hypothesis. ⋯ Immunocytochemistry showed that HMGB1 translocated from the nucleus to the cytoplasm following dexamethasone or dexamethasone-BSA treatment through glucocorticoid receptors. The present findings suggest that glucocorticoids stimulate microglial membrane glucocorticoid receptors and trigger cytoplasmic translocation and extracellular release of nuclear HMGB1. Thus, under stress conditions, glucocorticoids induce microglial HMGB1 release, leading to a neuroinflammatory state that could mediate neurological disorders.
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We aim to investigate the methylation of NR3C1 gene promotor and NR3C1 BclI polymorphism in schizophrenia (SCZ) patients with attempted suicide or non-suicidal self-injury (NSSI). A sample of 112 patients with SCZ was included in the study. Structured Clinical Interview for Diagnostic and Statistical Manual-Fourth Edition Axis I Disorders was used to confirm the diagnosis according to The Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria. ⋯ SCZ patients carrying the CC genotype had a lower risk of attempted suicide (Odds Ratio [OR]: 0.421; 95% Confidence Interval [CI]: 0.183-0.970; p = 0.040), while having the GG genotype in SCZ patients was associated with a higher risk of attempted suicide (OR: 3.785; 95% Cl: 1.107-12.945; p = 0.042). Additionally, due to NSSI in SCZ patients, there were no significant differences in NR3C1 gene methylation and NR3C1 genotype distribution among the groups. We propose that the NR3C1 BclI polymorphism may be associated with attempted suicide in Turkish patients diagnosed with SCZ.
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This study aimed to investigate the anti-depressant effect of traditional pediatric massage (TPM) in adolescent rats and its possible mechanism. The adolescent depression model in rats was established by using chronic unpredictable mild stress (CUMS). All rats were randomly divided into five groups (seven per group), including the groups of control (CON), CUMS, CUMS with TPM, CUMS with back stroking massage (BSM) and CUMS with fluoxetine (FLX). ⋯ TPM could effectively prevent depression-related behaviors in CUMS-exposed adolescent rats, manifested as increasing weight gain, sucrose consumption, ratio of open-arm entry, times of crossing the specific quadrant and shortening escape latency. TPM also decreased CORT level in plasma, together with enhancing expressions of GR, IGF-1 and BDNF in the hippocampus. These results may support the clinical application of TPM to prevent and treat adolescent depression.