Low glucocorticoids in stress-related disorders: the role of inflammation

Sarapultsev, Alexey; Sarapultsev, Petr; Dremencov, Eliyahu; Komelkova, Maria; Tseilikman, Olga; Tseĭlikman, Vadim

doi:10.1080/10253890.2020.1766020

Cited by 29 publications

(19 citation statements)

References 123 publications

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“…It is in agreement with our previous suggestion that increased metabolism of glucocorticoids contributes to decreased glucocorticoid signaling in stress-related psychopathologies [23,36].…”

Section: Discussionsupporting

confidence: 93%

Effect of Repeated Predator Scent Exposure on Excitability of Serotonin Neurons and Stress Markers in Rats

Dremencov¹,

Grinchii²,

Buzgoova³

et al. 2021

Preprint

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Exposure to predator scent (PS) has been used aa a model of stress associated with danger to life and body integrity. We tested the hypothesis that repeated PS exposure alters the excitability of 5-HT neurons of the dorsal raphe nucleus. To study the mechanisms involved, we approached serum and adrenal corticosterone and aldosterone concentrations, as well as cortical brain-derived neurotrophic factor (BDNF) expression. Adult male Sprague-Dawleys rats were exposed to PS for ten minutes daily for ten consecutive days. Two weeks after the last exposure, the selected electrophysiological and biochemical assessments were performed. Measurements by in vivo electrophysiology showed increased spontaneous firing activity of 5-HT neurons in rats exposed to repeated PS. Repeated PS exposure resulted in reduced serum corticosterone and aldosterone concentrations. Concentrations of both corticosteroids in the adrenal glands, as well as the relative weight of the adrenals, were unaffected. The gene expression of hippocampal BDNF of rats exposed to PS remained unaltered. In conclusion, repeated exposure of rats to PS leads to enhanced firing activity of 5HT neurons accompanied by reduced serum, but not adrenal aldosterone and corticosterone concentrations. Reduced corticosteroid concentrations in the blood appear to be the result of increased metabolism and/or tissue uptake. The decrease in circulating corticosterone in rats experienced repeated PS may represent part of the mechanisms leading to increased excitability of 5-HT neurons. The increase in 5-HT neuronal firing activity might be an important compensatory mechanism designated to diminish the harmful effects of the repeated PS exposure on the brain.

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“…It is in agreement with our previous suggestion that increased metabolism of glucocorticoids contributes to decreased glucocorticoid signaling in stress-related psychopathologies [23,36].…”

Section: Discussionsupporting

confidence: 93%

Effect of Repeated Predator Scent Exposure on Excitability of Serotonin Neurons and Stress Markers in Rats

Dremencov¹,

Grinchii²,

Buzgoova³

et al. 2021

Preprint

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“…These results indicate that genes were shown to be regulated by MR pathway activation in RPE cells [37], following the same regulations in the RPE/choroid of dexamethasone treated rats. nt.…”

Section: Regulation Of Mr-induced Genes In the Retina And Rpe/choroidsupporting

confidence: 54%

“…In our experiments, Nr3c2 was also downregulated in the neural retina of rats treated with saline, in which corticosterone levels are reduced in the ocular media and in the serum but in which no dexamethasone could influence Nr3c2 or Nr3c1 expression. Other mechanisms such as chronic stress and potential associated inflammation could explain these regulations [37].…”

Section: Discussionmentioning

confidence: 99%

Chronic Systemic Dexamethasone Regulates the Mineralocorticoid/Glucocorticoid Pathways Balance in Rat Ocular Tissues

Zola

Mejlachowicz

Arribada

et al. 2022

IJMS

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Central serous chorioretinopathy (CSCR) is a retinal disease affecting the retinal pigment epithelium (RPE) and the choroid. This is a recognized side-effect of glucocorticoids (GCs), administered through nasal, articular, oral and dermal routes. However, CSCR does not occur after intraocular GCs administration, suggesting that a hypothalamic-pituitary-adrenal axis (HPA) brake could play a role in the mechanistic link between CSCR and GS. The aim of this study was to explore this hypothesis. To induce HPA brake, Lewis rats received a systemic injection of dexamethasone daily for five days. Control rats received saline injections. Baseline levels of corticosterone were measured by Elisa at baseline and at 5 days in the serum and the ocular media and dexamethasone levels were measured at 5 days in the serum and ocular media. The expression of genes encoding glucocorticoid receptor (GR), mineralocorticoid receptors (MR), and the 11 beta hydroxysteroid dehydrogenase (HSD) enzymes 1 and 2 were quantified in the neural retina and in RPE/ choroid. The expression of MR target genes was quantified in the retina (Scnn1A (encoding ENac-α, Kir4.1 and Aqp4) and in the RPE/choroid (Shroom 2, Ngal, Mmp9 and Omg, Ptx3, Plaur and Fosl-1). Only 10% of the corticosterone serum concentration was measured in the ocular media. Corticosterone levels in the serum and in the ocular media dropped after 5 days of dexamethasone systemic treatment, reflecting HPA axis brake. Whilst both GR and MR were downregulated in the retina without MR/GR imbalance, in the RPE/choroid, both MR/GR and 11β-hsd2/11β-hsd1 ratio increased, indicating MR pathway activation. MR-target genes were upregulated in the RPE/ choroid but not in the retina. The psychological stress induced by the repeated injection of saline also induced HPA axis brake with a trend towards MR pathway activation in RPE/ choroid. HPA axis brake causes an imbalance of corticoid receptors expression in the RPE/choroid towards overactivation of MR pathway, which could favor the occurrence of CSCR.

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“…It is possible that elevated levels of 6βCort in stressed SM rats were associated with that previously detected decrease in the level of cerebral serotonin. Moreover, a more pronounced decrease in corticosterone levels in stressed SM rats could enhance the effects of pro-inflammatory cytokines up to neuroinflammation [ 20 ], and thus could contribute to the higher anxiety in those rats.…”

Section: Discussionmentioning

confidence: 99%

Hexobarbital Sleep Test for Predicting the Susceptibility or Resistance to Experimental Posttraumatic Stress Disorder

Komelkova

Манухина

Downey

et al. 2020

IJMS

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Hexobarbital sleep test (HST) was performed in male Wistar rats (hexobarbital 60 mg/kg, i.p.) 30 days prior to stress exposure. Based on the duration of hexobarbital-induced sleep, rats were divided into two groups, animals with high intensity (fast metabolizers (FM), sleep duration <15 min) or low intensity of hexobarbital metabolism (slow metabolizers (SM), sleep duration ≥15 min). The SM and FM groups were then divided into two subgroups: unstressed and stressed groups. The stressed subgroups were exposed to predator scent stress for 10 days followed by 15 days of rest. SM and FM rats from the unstressed group exhibited different behavioral and endocrinological patterns. SM showed greater anxiety and higher corticosterone levels. In stressed animals, anxiety-like posttraumatic stress disorder (PTSD) behavior was aggravated only in SM. Corticosterone levels in the stressed FM, PTSD-resistant rats, were lower than in unstressed SM. Thus, HST was able to predict the susceptibility or resistance to experimental PTSD, which was consistent with the changes in glucocorticoid metabolism.

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Low glucocorticoids in stress-related disorders: the role of inflammation

Cited by 29 publications

References 123 publications

Effect of Repeated Predator Scent Exposure on Excitability of Serotonin Neurons and Stress Markers in Rats

Effect of Repeated Predator Scent Exposure on Excitability of Serotonin Neurons and Stress Markers in Rats

Chronic Systemic Dexamethasone Regulates the Mineralocorticoid/Glucocorticoid Pathways Balance in Rat Ocular Tissues

Hexobarbital Sleep Test for Predicting the Susceptibility or Resistance to Experimental Posttraumatic Stress Disorder

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