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

Glucocorticoids potentiate hippocampal damage induced by various noxious insults in vivo and in vitro and are implicated in age-related loss of neurons in the hippocampus of various species. The cholinergic innervation of the hippocampus appears to be especially prone to the endangering effect of glucocorticoids, since corticosterone, like acute stress or ACTH, induces a rapid activation of the cholinergic septo-hippocampal pathway. We now report the influence of glucocorticoids on the degeneration of this pathway induced by the cholinergic neurotoxin ethylcholine aziridinium (AF64A). The toxic effect of a submaximal dose of AF64A on cholinergic neurons was evaluated in rats during exposure to glucocorticoids or vehicle as well as in adrenalectomized or sham-operated rats. Daily treatment with either corticosterone or dexamethasone, starting 7 d before the bilateral intracerebroventricular injection of AF64A (1 nmol/ventricle), significantly increased the AF64A-induced loss of ChAT activity in the whole hippocampus, whereas bilateral adrenalectomy 7 d prior to AF64A-injection attenuated the effect of AF64A. Short-term exposure to corticosterone starting 24 hr before AF64A was as effective as the 7 d pretreatment. Dexamethasone exacerbated the AF64A-induced cholinergic lesion in the hippocampal subregions CA1, CA3, and dentate gyrus, and adrenalectomy protected all subregions against the action of AF64A. Along the longitudinal axis of the hippocampus a comparable influence was seen in the dorsal and ventral parts. The subregional pattern in the response to glucocorticoid suggests the involvement of mineralocorticoid type I receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of glucocorticoids in the cholinergic degeneration in rat hippocampus induced by ethylcholine aziridinium (AF64A). 768 81

Glucocorticoids and stress have deleterious effects on hippocampal cell morphology and survival. It has been hypothesized that these effects are mediated via an excitatory amino acid mechanism. The present study was designed to evaluate the effects of acute stress on the extracellular levels of glutamate in the hippocampus and to determine if adrenalectomy modifies this response. Rats were adrenalectomized or sham-adrenalectomized and implanted with microdialysis probes in the CA3 region of the hippocampus. Three days later rats were subjected to an acute 1-h period of immobilization stress. Stress significantly increased extracellular glutamate levels in the sham-operated rats, which peaked at 20 min following the initiation of stress. Extracellular glutamate levels also increased immediately following the termination of stress. In the adrenalectomized rats there was a 30% decrease in basal extracellular concentrations of glutamate and a marked attenuation (-70%) of the stress-induced increase in extracellular glutamate levels. Extracellular concentrations of taurine were not modified by adrenalectomy and did not change in response to stress. These results suggest that glucocorticoid-induced elevations in extracellular glutamate concentrations may contribute to the deleterious effects of stress on hippocampal neurons.
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PMID:Adrenalectomy attenuates stress-induced elevations in extracellular glutamate concentrations in the hippocampus. 790 39

We studied messenger RNA (mRNA) expressions of receptors for glucocorticoid (GR), thyroid hormone (TR), androgen (AR), and estrogen (ER) and their changes with age in the hippocampal subregions in postmortem human brain. In situ hybridization was done with biotin-labeled antisense synthetic oligonucleotide probes. About 80% or more of the pyramidal neurons in the hippocampal subregions expressed mRNAs for individual receptors in the brains of subjects younger than 65. The ratio of mRNA-containing neuron density to total neuron density significantly decreased with age for GR in CA1 and CA3, and for AR in CA1. Non-significant trends in the reduction with age in the ratio of ER mRNA-containing neurons in CA1 and the ratio of GR mRNA-containing neurons in the hilus also were found. Age-related reductions in nuclear receptor protein mRNA expression in neurons in the hippocampal subfields may be important in the impairments of cognition, emotion, and responses to acute stress in the aged.
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PMID:Effects of age on messenger RNA expression of glucocorticoid, thyroid hormone, androgen, and estrogen receptors in postmortem human hippocampus. 862 17

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.
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PMID:Defense of adrenocorticosteroid receptor expression in rat hippocampus: effects of stress and strain. 1046 67

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.
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PMID:Stress regulation of adrenocorticosteroid receptor gene transcription and mRNA expression in rat hippocampus: time-course analysis. 1103 47

The hippocampus is an important structure for declarative, spatial, and contextual memory and is implicated in the perception of chronic pain. The hippocampal formation is vulnerable to damage from seizures, ischemia, and head trauma and is particularly sensitive to the effects of adrenal glucocorticoids secreted during the diurnal rhythm and chronic stress. Adrenal steroids typically have adaptive effects in the short run, but promote pathophysiology when there is either repeated stress or dysregulation of the HPA axis. The damaging actions of glucocorticoids under such conditions have been termed "allostatic load", referring to the cost to the body of adaptation to adverse conditions. Adrenal steroids display both protective and damaging effects in the hippocampus. They biphasically modulate excitability of hippocampal neurons, and high glucocorticoid levels and severe acute stress impair declarative memory in a reversible manner. The hippocampus also displays structural plasticity, involving ongoing neurogenesis of the dentate gyrus, synaptogenesis under control of estrogens in the CA1 region, and dendritic remodeling caused by repeated stress or elevated levels of exogenous glucocorticoids in the CA3 region. In all three forms of structural plasticity, excitatory amino acids participate along with circulating steroid hormones. Glucocorticoids and stressors suppress neurogenesis in the dentate gyrus. They also potentiate the damage produced by ischemia and seizures. Moreover, the aging rat hippocampus displays elevated and prolonged levels of excitatory amino acids released during acute stress. Our working hypothesis is that structural plasticity in response to repeated stress starts out as an adaptive and protective response, but ends up as damage if the imbalance in the regulation of the key mediators is not resolved. It is likely that morphological rearrangements in the hippocampus brought on by various types of allostatic load alter the manner in which the hippocampus participates in memory functions and it is conceivable that these may also have a role in chronic pain perception.
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PMID:Plasticity of the hippocampus: adaptation to chronic stress and allostatic load. 1200 27

Chronic stress causes atrophy of the apical dendrites of CA3 pyramidal neurons and deficits in spatial memory. We investigated the effects of chronic stress on hippocampal physiology and long-term potentiation (LTP) in the CA3 and dentate gyrus (DG). Rats were subjected to chronic (21 days, 6 h/day) restraint stress and tested for LTP 48 h following the last stress episode. Control animals were briefly handled each day, similar to the experimental group but without restraint. To eliminate acute stress effects, a second control group of rats was subjected to a single acute (6 h) restraint stress and tested for LTP 48 h later. Field potential recordings were made, under chloropent anesthesia, from the stratum lucidum of CA3, with stimulation of either the mossy fiber or commissural/associational pathways, or in the DG granule-cell layer, with stimulation of the medial perforant pathway. Chronic stress produced a suppression of LTP at 48 h compared to controls in a site-specific manner, namely, significantly lower LTP in the medial perforant input to the DG and also in the commissural/associational input to the CA3, but not in the mossy fiber input to CA3. The animals subjected to acute stress and tested 48 h later did not show a suppression in LTP. High-frequency stimulation (HFS) of the commissural/associational and mossy fiber inputs to CA3 produced epileptic afterdischarges in 56% of acutely stressed animals and in 29% of chronically stressed animals, whereas HFS caused afterdischarges in only 9% of nonstressed controls. No afterdischarges were seen in the medial perforant path input to DG. In order to explore the basis for these changes, we performed paired-pulse inhibition/facilitation (PPI/F) and current-source-density (CSD) analysis in stressed and control animals. For PPI/F, acute stress caused an overall significant enhancement of excitation in the commissural/associational input to CA3 and medial perforant path input to DG. In contrast, chronic stress did not produce significant changes in PPI/F. The CSD analysis revealed significant chronic stress-induced shifts in the current sources and sinks in the apical dendrites and pyramidal cell layers of the CA3 field but not in the DG. These results are consistent with the morphological findings for stress effects upon dendrites of CA3 neurons. Furthermore, they suggest that chronic stress produces changes in the input-output relationship in the hippocampal trisynaptic circuit which could affect information flow through this structure.
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PMID:Effects of chronic stress on hippocampal long-term potentiation. 1200 Jan 21

The mRNAs encoding the flip and flop isoforms of the glutamate receptor subunits GluR1 and 2 were detected and quantified by in situ hybridization in the hippocampal formation of rats following acute (6h) or chronic (6h daily for 21 days) restraint stress. The GluR1 flip mRNA was slightly reduced in CA1 after chronic stress and the GluR2 flip mRNA was increased in the dentate gyrus (DG), CA4, and CA3 after acute stress. There were no changes in the mRNA encoding the flop isoforms of either GluR1 or 2 in the hippocampus. In entorhinal cortex, the GluR1 flip mRNA was significantly increased after both acute and chronic stress, while the flop isoform increased only after chronic stress. The GluR2 flip mRNA was slightly increased after acute and chronic stress. However, no changes were found for the flop isoform of GluR2. These results suggest that different assembly of AMPA receptors subunits and isoforms may underlie, in a different way, the neuronal plastic changes induced by specific type and intensity of stressful stimuli.
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PMID:Effects of single or repeated restraint stress on GluR1 and GluR2 flip and flop mRNA expression in the hippocampal formation. 1237 42

The purpose of this investigation was to assess the ability of the hippocampus to withstand a metabolic challenge following chronic stress. An N-methyl-d-aspartate receptor excitotoxin (ibotenic acid, IBO) was infused into the CA3 region of the hippocampus following a period of restraint for 6 h/day/21 days. Following the end of restraint when CA3 dendritic retraction persists (3 to 4 days), rats were infused with IBO (or vehicle) into the CA3 region of the hippocampus. Stressed male rats showed significantly more CA3 damage after IBO infusion relative to controls and the saline-infused side. Moreover, IBO-exacerbation of damage in males was not observed in the CA3 region 3 to 4 days after acute stress (6 h restraint), nor in the CA1 region after chronic stress. Females were also examined and chronic stress did not exacerbate IBO damage in the CA3 region. Overall, these results demonstrate that chronic stress compromises the ability of the hippocampus to withstand a metabolic challenge days after the chronic stress regimen has subsided in male rats. Whether the conditions surrounding CA3 dendritic retraction in females represents vulnerability is less clear and warrants further investigation.
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PMID:Chronic stress enhances ibotenic acid-induced damage selectively within the hippocampal CA3 region of male, but not female rats. 1509 89

Animal studies on the effects of chronic variable stress during the peripubertal-juvenile period on hippocampal structure and function are lacking. Twenty-eight-day-old Sprague-Dawley rats were subjected to random, variable physical or social stress regimens for 4 weeks. Hippocampal volume was found to continue to grow in all lamina examined during the transition into young adulthood. Our variable physical stress paradigm led to inhibition of this growth in the CA1 pyramidal cell layer (PCL) and in the dentate gyrus-granular cell layer (DG-GCL), which reached full arrest in the CA3-PCL. Volume deficits were first observed after chronic stress exposure when 3 weeks, but not 24 h, of recovery had elapsed. Moreover, these volume deficits were associated with impairments in the Morris water-maze navigation, sustained down-regulation in the basal hippocampal glucocorticoid receptor gene expression, and deficits in the shutdown of acute stress-induced corticosterone secretion. Volume changes both due to normal maturation and after chronic stress exposure were independent of neuron number. Thus, a peripubertal-juvenile chronic stress paradigm that leads to significant alterations in the limbic-hypothalamic-pituitary-adrenal axis can produce robust effects in hippocampal structure and cognitive ability, lasting into adulthood.
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PMID:Delayed effects of chronic variable stress during peripubertal-juvenile period on hippocampal morphology and on cognitive and stress axis functions in rats. 1530 40


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