Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0848237 (acute stress)
 4,619 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

These studies further evaluated the relative role of mineralocorticoid (type I) and glucocorticoid (type II) receptors in mediating corticosteroid feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Acute treatment of rats with the selective mineralocorticoid receptor antagonist, RU28318 (50 mg/kg sc), produced elevated basal corticosterone levels in the morning, but had no effect on basal corticosterone levels in the evening or on restraint stress corticosterone levels at either time of day. Acute treatment with the selective glucocorticoid receptor antagonist, RU40555 (30 mg/kg sc) had no effect on basal or restraint stress corticosterone levels at either time of day. However, combined treatment with RU28318 and RU40555 produced an elevation of evening basal corticosterone levels (and morning basal on one occasion) and produced an increase in corticosterone levels during and after stress at both times of day. In a separate experiment conducted in the morning, the combined RU28318 and RU40555 treatment also produced elevated ACTH responses during restraint stress. Based on available corticosteroid receptor measures, the RU28318 treatment was estimated to selectively occupy approximately 85% of mineralocorticoid receptors in rat brain, whereas the RU40555 treatment was estimated to selectively occupy approximately 50% of glucocorticoid receptors in rat brain. We conclude that mineralocorticoid receptor activation is necessary and sufficient to maintain low basal corticosterone levels during the circadian trough, whereas glucocorticoid receptor activation is necessary to constrain corticosterone secretion during the circadian peak or during acute stress. However, even during the circadian peak or acute stress, mineralocorticoid receptor activation plays an important role in facilitating the glucocorticoid receptor dependent regulation of HPA axis activity by corticosterone.
 ...
PMID:Evidence for mineralocorticoid receptor facilitation of glucocorticoid receptor-dependent regulation of hypothalamic-pituitary-adrenal axis activity. 960 77

Previous studies have shown that corticosteroids affect the changes in membrane potential evoked in CA1 hippocampal neurons by serotonin and the metabolically stable cholinergic analogue carbachol: Low corticosteroid levels induced by steroid administration to adrenalectomized rats or obtained in adrenally intact rats were associated with small transmitter responses. High corticosteroid levels induced by exogenous corticosteroid application or by an acute stress in adrenally intact rats generally evoked large transmitter responses. In the present study we investigated the consequences of this steroid modulation for the main stream of synaptic information in the CA1 hippocampal region, which is carried by amino acids. To this purpose the effect of serotonin and carbachol administration on both extracellularly and intracellularly recorded synaptic responses to Schaffer collateral stimulation were investigated. The data show that the effect of in vivo activation of corticosteroid receptors on the serotonin-induced hyperpolarization of the membrane responses is clearly reflected in the inhibitory effect of serotonin on synaptic responsiveness in the CA1 area. Low circulating levels of corticosterone or selective mineralocorticoid receptor activation reduced the serotonin mediated inhibition of synaptically evoked responses, whereas high corticosterone levels were associated with strong serotonin mediated suppression of synaptic responses. This steroid modulation seems to be specifically aimed at serotonin neurotransmission, as the cholinergic effects on excitatory synaptic transmission were not affected by the hormone treatment.
 ...
PMID:Serotonin and carbachol induced suppression of synaptic responses in rat CA1 hippocampal area: effects of corticosteroid receptor activation in vivo. 978 66

1. We have recently shown that neurones in the rostral region of the medial vestibular nucleus (MVN) develop a sustained increase in their intrinsic excitability within 4 h of a lesion of the vestibular receptors of the ipsilateral inner ear. This increased excitability may be important in the rapid recovery of resting activity in these neurones during 'vestibular compensation', the behavioural recovery that follows unilateral vestibular deafferentation. In this study we investigated the role of the acute stress that normally accompanies the symptoms of unilateral labyrinthectomy (UL), and in particular the role of glucocorticoid receptors (GRs), in the development of the increase in excitability in the rostral MVN cells after UL in the rat. 2. The compensatory increase in intrinsic excitability (CIE) of MVN neurones failed to occur in animals that were labyrinthectomized under urethane anaesthesia and kept at a stable level of anaesthesia for either 4 or 6 h after UL, so that they did not experience the stress normally associated with the vestibular deafferentation syndrome. In these animals, 'mimicking' the stress response by administration of the synthetic GR agonist dexamethasone at the time of UL, restored and somewhat potentiated CIE in the MVN cells. Administration of dexamethasone in itself had no effect on the intrinsic excitability of MVN cells in sham-operated animals. 3. In animals that awoke after labyrinthectomy, and which therefore experienced the full range of oculomotor and postural symptoms of UL, there was a high level of Fos-like immunoreactivity in the paraventricular nucleus of the hypothalamus over 1.5-3 h post-UL, indicating a strong activation of the stress axis. 4. The GR antagonist RU38486 administered at the time of UL abolished CIE in the rostral MVN cells, and significantly delayed behavioural recovery as indicated by the persistence of circular walking. The mineralocorticoid receptor (MR) antagonist spironolactone administered at the time of UL had no effect. 5. Vestibular compensation thus involves a novel form of 'metaplasticity' in the adult brain, in which the increase in intrinsic excitability of rostral MVN cells and the initial behavioural recovery are dependent both on the vestibular deafferentation and on the activation of glucocorticoid receptors, during the acute behavioural stress response that follows UL. These findings help elucidate the beneficial effects of neuroactive steroids on vestibular plasticity in various species including man, while the lack of such an effect in the guinea-pig may be due to the significant differences in the physiology of the stress axis in that species.
 ...
PMID:Lesion-induced plasticity in rat vestibular nucleus neurones dependent on glucocorticoid receptor activation. 1037 97

Neuronal mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) proteins are glucocorticoid-activated transcription factors that bind identical DNA response elements yet transduce distinct physiological/transcriptional actions. The present study assessed regulation of adrenocorticosteroid receptor RNA and protein following intermittent stress exposure, using Sprague Dawley (S-D) and stress-hyperresponsive Fischer 344 (F344) rat strains. The F344 (but not S-D) strain showed enhanced acute stress responsivity and enhanced corticosterone secretion following prolonged stress. F344 rats also showed reduced responsiveness to a novel stressor after prolonged stress exposure, suggestive of enhanced glucocorticoid negative feed-back. Upon prolonged stress, F344 rats down-regulated MR hnRNA in CA1, CA3, and dentate gyrus. Transcriptional changes were accompanied by decreased expression of the alpha 5' messenger RNA (mRNA) form, consistent with altered promoter utilization. In contrast, alpha 5' splice variant, full-length mRNA, and MR protein expression were not affected by stress in either strain, implying that transcriptional changes do not affect overall mRNA or protein expression. GR protein was increased in pyramidal and granule cell somata/nuclei of F344 rats despite lack of a change in mRNA expression. These data suggest that prolonged stress elicits restricted changes in MR and GR expression in the F344 strain only. Overall, stable expression of adrenocorticosteroid receptors is rigorously defended in hippocampal neurons, apparently through transcriptional and posttranscriptional mechanisms.
 ...
PMID:Defense of adrenocorticosteroid receptor expression in rat hippocampus: effects of stress and strain. 1046 67

Stressors produce rapid activation of the hypothalamic-pituitary-adrenal axis, which typically resolves within 60-90 min following termination of the stressor. In addition, some stressors such as inescapable tailshock (IS) also produce elevated basal levels of corticosterone (CORT), and reduced serum levels of corticosteroid binding globulin (CBG). The elevated basal levels of CORT produced by IS are only observed at the trough of the circadian rhythm of CORT secretion, and are sustained for 2-3 days following stressor termination. The goal of the following experiments was to determine the extent to which the elevated basal levels of CORT observed following IS exposure produced greater corticosteroid receptor occupancy in the brain and pituitary. To do so, rats (n=8-10 per group) received either sham or bilateral adrenalectomy (with CORT replacement in their drinking water; 25 microg/ml) and were given 3 days to recover. Rats were then exposed to 100 ISs (1.6 mA, 5 s each) administered on a 60 s variable intertrial interval, or remained in their home cages. As seen previously, IS produced an increase in basal CORT (5 microg/dl) and a decrease in CBG (30% decrease). Rats were sacrificed 24 h following IS for trunk blood samples and brain dissections. IS exposure had very little effect on corticosteroid receptor protein expression as determined by mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) binding levels in ADX rats. In addition, no changes in whole cell GR levels (as detected by Western blot) were observed in sham rats exposed to IS. On the other hand, IS exposure led to greater occupancy of MR (ranging from 25%-50%) in hippocampus, hypothalamus, pituitary, and posterior cortex. IS also produced greater occupancy of GR (approximately 20%) in hypothalamus and posterior cortex. These long-term changes in corticosteroid receptor activation, evident 24 h after IS exposure, may be responsible for some of the long-term neural, behavioral and immune changes observed following this acute stress procedure.
 ...
PMID:Long-term changes in mineralocorticoid and glucocorticoid receptor occupancy following exposure to an acute stressor. 1057 90

The two subtypes of corticosterone receptors in the rat brain play a pivotal role in the modulation of the stress response. Appropriate control of their gene expression is therefore critical for the maintenance of cellular and organism homeostasis. In this study, we investigated the contribution of gender and of the cellular environment of certain brain areas to the expression of both types of corticosteroid receptors, following restraint stress. Adult Wistar rats of both sexes were subjected to acute, chronic or to a combined chronic plus acute stress regimen, and the expression of glucocorticoid and mineralocorticoid receptors was evaluated in their hippocampus, hypothalamus, pituitary and frontal cortex, by using Northern blot analysis. Significant sex differences were observed in the first three brain areas examined as to the stress-induced expression of corticosteroid receptors. Among these, females showed a distinct mechanism of regulating glucocorticoid/mineralocorticoid receptor ratio in the hippocampus upon chronic stress, while the female hypothalamus was more prone than the male to changing corticosteroid receptor expression in response to restraint stress. In another set of experiments, we assessed the influence of ovarian steroids on stress-induced corticosteroid receptor expression in the above brain areas by analyzing ovariectomized rats exposed to short-term restraint. Our results showed that although ovarian steroids affect the stress-induced expression of receptor genes in a region-specific manner, their elimination does not appear to lead to the male pattern of expression. These findings provide further evidence for the existence of both regional and gender specificity in the regulation of brain and pituitary corticosteroid receptors following stress, and support the hypothesis of a distinct male and female neuroendocrine axis in response to stress.
 ...
PMID:Contribution of sex and cellular context in the regulation of brain corticosteroid receptors following restraint stress. 1087 96

Acute stress increases circulating ACTH and glucocorticoid levels. The hippocampus (HIP) is a target of such stress hormones as glucocorticoid and it also expresses receptors for growth hormone (GH), particularly in the dentate gyms (DG). In order to understand the interactions between glucocorticoids and functions of GH in HIP during acute stress, the mRNA levels for GH receptor (GHR), glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) were investigated in DG in rats exposed to restraint stress in the water (RSW). Using in situ hybridization histochemistry (ISHH), high level expressions of GHR mRNA were detected in DG. These were down-regulated by 14% after 0.5 h of RSW and then up-regulated by 38% over the initial level after 4 h of RSW. This biphasic enhancement of GHR mRNA expression in DG followed the elevation of plasma glucocorticoid levels and paralleled with biphasic expressions of mRNAs for GR and MR in DG. Although circulating GH levels did not show any correlation with the hippocampal GHR mRNA expression, adrenalectomy (ADX) decreased GHR mRNA expression in DG, and the dexamethasone treatment (DEX; 20 microg/100 microl, i.p.) of ADX rats rapidly increased the GHR mRNA expression in DG. These results have suggested that the GHR mRNA expression in the DG is regulated, at least in part, by glucocorticoids and that GH may be involved in responses of the DG to acute stress.
 ...
PMID:A biphasic regulation of receptor mRNA expressions for growth hormone, glucocorticoid and mineralocorticoid in the rat dentate gyrus during acute stress. 1096 Jun 3

Neuronal glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) proteins mediate the transcriptional effects of circulating glucocorticoids. These receptors bind the same DNA response element, yet mediate quite different cellular functions. The present study tests the hypothesis that acute and chronic stress, which cause increases in glucocorticoids sufficient to bind the GR, will regulate expression of the GR and MR genes in the hippocampal formation. Analysis of MR gene transcription using an intronic MR probe revealed a transient 50% decrease in MR hnRNA in CA1, CA3 and dentate gyrus at 60-120 min post-stress, consistent with glucocorticoid down-regulation of the MR gene. However, no changes were seen in full-length MR mRNA at any post-stress time point. In contrast, GR hnRNA was not affected by acute stress, but GR mRNA was decreased 120 min post stress in all hippocampal subregions. Chronic stress exposure down-regulated GR mRNA in CA3 only; effects were first evident 7 days post stress and persisted for the entire stress time-course (28 days). There was no evidence for down-regulation of GR hnRNA or MR hnRNA/mRNA at any point in the chronic stress regimen. The transient decrease in MR hnRNA in the absence of mRNA changes suggests increased MR mRNA stability. In contrast, acute stress decreases the availability of GR mRNA without demonstrably affecting transcription, suggesting reduced GR mRNA stability. The results suggest that acute stress alters GR mRNA expression by largely post-transcriptional mechanisms. However, elevations in basal corticosterone secretion seen following chronic stress are not sufficient to markedly down-regulate GR/MR expression in a long-term fashion.
 ...
PMID:Stress regulation of adrenocorticosteroid receptor gene transcription and mRNA expression in rat hippocampus: time-course analysis. 1103 47

Corticosteroid receptors are key mediators of the neuroendocrine response to stress. Previously, we have determined the effects of restraint stress on the regulation of corticosteroid receptor genes in the brain and pituitary of male and female rats. Significant gender- and regional-specific regulation of receptor mRNAs was observed. To further investigate the stressor specificity in the same context, we have determined glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) mRNAs following exposure to swimming stress paradigms applied alone, or in combination with restraint stress. Our data revealed stressor-specific alterations in GR or MR mRNA levels, which were more pronounced in males, the gender most affected by swimming stress. No alterations in GR or MR mRNA levels were detected in the female hippocampus and hypothalamus upon exposure to swimming paradigms, while in males the same stressors down-regulated GR mRNA in the hippocampus (chronic exposure) and up-regulated both genes in the hypothalamus (acute exposure). In the frontal cortex, acute swimming stress caused a reciprocal change in GR mRNA levels in the two sexes. The above difference is not due to circulating ovarian steroids, since ovariectomy did not change the female pattern of GR gene expression following acute stress. Our results further showed a hypothalamic-pituitary-adrenal axis facilitation to a novel superimposed stressor expressed at the level of limbic corticosteroid receptors: When chronically restrained rats of both sexes were exposed to acute swimming stress, a reduced GR/MR mRNA ratio, implying reduced feedback axis sensitivity, was detected in both the hippocampus and the hypothalamus. In conclusion, our work provides additional evidence on stressor, gender and region specificity in the regulation of brain corticosteroid receptors.
 ...
PMID:Forced swimming differentially affects male and female brain corticosteroid receptors. 1197 52

The aim of this study was to evaluate the efficacy of agomelatine (S 20098) to accelerate reversal of the neuroendocrinological, behavioural and cyclical changes seen in a transgenic mouse model of the neuroendocrine characteristics of depression. The effects of agomelatine were assessed in transgenic mice with low glucocorticoid receptor (GR) function, after acute stress or induced phase shift, and compared to desipramine and melatonin. Mice were injected 2 h before the onset of the dark period with agomelatine (10 mg/kg, i.p.), desipramine (10 mg/kg, i.p.), melatonin (10 mg/kg, i.p.) or vehicle (hydroxy-ethyl-cellulose (HEC) 1%) each day for 21 to 42 days. Agomelatine was effective in reversing the transgenic mouse behavioural changes noted in the Porsolt forced swim test as well as in the elevated plus maze. Both the number of open arm entries and the total time spent in open arms of the elevated plus maze is greatly increased in transgenic mice. The mean time spent in open arms is exquisitely sensitive to reversal by agomelatine and desipramine. Agomelatine also markedly accelerated readjustment of circadian cycles of temperature and activity following an induced phase shift. This action of agomelatine was superior to that of melatonin while desipramine was without effect. The accelerating effect of agomelatine was particularly notable if treatment was started 3 weeks prior to the induced phase shift. Agomelatine treatment did not cause any major change in corticosterone or adrenocorticotropic hormone (ACTH) concentrations nor in vasopressin (AVP), corticotropin-releasing hormone (CRH), GR and mineralocorticoid receptor (MR) mRNAs levels, which make it unlikely that the mechanism of agomelatine action is related to hypothalamic-pituitary-adrenocortical (HPA) axis changes. The present study shows that agomelatine displays some characteristics of antidepressant drug action in the transgenic mouse model, effects that could be partially related to its chronobiotic properties.
 ...
PMID:Antidepressant action of agomelatine (S 20098) in a transgenic mouse model. 1600 35


1 2 3 Next >>