Acute Immobilization Stress Research Articles

Effects of Chronic Psychosocial Stress on Reduction of Basal Glucocorticoid Levels and Suppression of Glucocorticoid Levels Following Dexamethasone Administration in Animal Model of PTSD

Aim: To further examine the neurobiological mechanisms and their outcomes responsible for the PTSD sequelae induced by laboratory animal model and to explore the effects of chronic psychosocial paradigm. We tested the hypothesis that our animal model of PTSD would display abnormalities in glucocorticoid levels that are manifest in people with PTSD and that psychosocially stressed rats exhibit a significantly greater suppression of corticosterone levels than control rats following the administration of dexamethasone.Methods: Animals were divided into two groups. The experimental group was scheduled to exposure to two types of stressors: double exposure to acute immobilization stress, and combined predator-threat stress and daily social stress. There was also administration of dexamethasone in combination with stress exposure.Results: There was a statistical difference between masses of thymus in the stress group and stress group with dexamethasone appliance (p=0.024). We found statistical significance between baseline cortisol and stress induced levels of cortisol and between stress induced group and return to baseline group.Conclusion: Significant changes in HPA activity, reductions in basal glucocorticoid levels and enhanced dexamethasone induced inhibition of glucocorticoid levels have been manifested. All of this is manifested in PTSD patients also as many other stress induces changes.

Effects of Chronic Psychosocial Stress on Reduction of Basal Glucocorticoid Levels and Suppression of Glucocorticoid Levels Following Dexamethasone Administration in Animal Model of PTSD

Aim: To further examine the neurobiological mechanisms and their outcomes responsible for the PTSD sequelae induced by laboratory animal model and to explore the effects of chronic psychosocial paradigm. We tested the hypothesis that our animal model of PTSD would display abnormalities in glucocorticoid levels that are manifest in people with PTSD and that psychosocially stressed rats exhibit a significantly greater suppression of corticosterone levels than control rats following the administration of dexamethasone.Methods: Animals were divided into two groups. The experimental group was scheduled to exposure to two types of stressors: double exposure to acute immobilization stress, and combined predator-threat stress and daily social stress. There was also administration of dexamethasone in combination with stress exposure.Results: There was a statistical difference between masses of thymus in the stress group and stress group with dexamethasone appliance (p=0.024). We found statistical significance between baseline cortisol and stress induced levels of cortisol and between stress induced group and return to baseline group.Conclusion: Significant changes in HPA activity, reductions in basal glucocorticoid levels and enhanced dexamethasone induced inhibition of glucocorticoid levels have been manifested. All of this is manifested in PTSD patients also as many other stress induces changes.

Deafferentation of the hypothalamic paraventricular nucleus (PVN) exaggerates the sympathoadrenal system activity in stressed rats.

The hypothalamic paraventricular nucleus is a key structure in the regulation of the autonomic and neuroendocrine systems response to acute and chronic stress challenges. In this study, we examined the effect of a mechanical posterolateral deafferentation of the PVN on the activity of sympathoadrenal system (SAS) and hypothalamo-pituitary-adrenal (HPA) axis by measuring plasma concentrations of epinephrine (EPI), norepinephrine (NE), and corticosterone (CORT) in rats exposed to acute immobilization (IMO) stress. The surgical posterolateral deafferentation of the PVN (PVN-deaf) was performed by Halasz knife, in brain of the adult male Sprague Dawley rats, according to coordinates of a stereotaxic atlas. Sham-operated (SHAM) animals underwent a craniotomy only. The animals were allowed to recover 14 days. Thereafter, the tail artery was cannulated and the animals exposed to acute IMO for 2 h. The blood samples were collected via cannula at the time points of 0, 5, 30, 60, and 120 min of the IMO. Concentrations of plasma EPI, NE, and CORT were determined by radioimmunoassay. The IMO-induced elevation of plasma EPI concentrations in the PVN-deaf rats reached statistical significance at 60 min of the IMO, when compared to SHAM rats. Similarly, the stress-induced elevation of the NE plasma levels in the PVN-deaf rats was significantly exaggerated at all time intervals of IMO in comparison with SHAM rats, whereas plasma CORT levels were significantly reduced. In contrast to the traditional view of excitatory role of the PVN in response to stress, our data indicate that some projections from the PVN to caudally localized hypothalamic structures, the brainstem or the spinal cord, exert inhibitory effect on the SAS system activity during acute IMO stress. The data indicate that stress-induced activation of the HPA axis is partially dependent on inputs from the brainstem to the PVN.

The nitrogen oxide synthase effect in endothelium reaction and change in peripheral perfusion under THz radiation of nitrogen oxide occurrence exposure

Introduction Progressing and severity of the cardiovascular system disease significantly determine microcirculatory dynamics and peripheral perfusion of tissues as well [1]. Changes in regional, coronary, cerebral, renal blood flows and circulatory dynamics, also blood circulation failure, are connected with microcirculation defects [2]. Experimental research had shown an

MORPHOLOGICAL CHANGES OF TESTIS TISSUES IN INBRED MALE WHITE RATS UNDER THE EFFECT OF ACUTE IMMOBILIZATION STRESS

The present work showed negative effect of acute immobilization stress on the morphology of the rats` testis. The study was conducted in 22 sexually mature male albino rats (per 11 animals in the experimental and control groups). The rats of the experimental group were subjected to three-hour acute immobilization stress. The animals of the experimental group had degenerative changes in the epithelium of the seminiferous tubules until the development of focal necrosis. Also, the rats, exposed to stress, revealed a statistically significant reduction in the diameter of the seminiferous tubules and germinal layer thickness.

Treadmill exercise does not change gene expression of adrenal catecholamine biosynthetic enzymes in chronically stressed rats

Chronic isolation of adult animals represents a form of psychological stress that produces sympatho-adrenomedullar activation. Exercise training acts as an important modulator of sympatho-adrenomedullary system. This study aimed to investigate physical exercise-related changes in gene expression of catecholamine biosynthetic enzymes (tyrosine hydroxylase, dopamine-ß-hydroxylase and phenylethanolamine N-methyltransferase) and cyclic adenosine monophosphate response element-binding (CREB) in the adrenal medulla, concentrations of catecholamines and corticosterone (CORT) in the plasma and the weight of adrenal glands of chronically psychosocially stressed adult rats exposed daily to 20 min treadmill running for 12 weeks. Also, we examined how additional acute immobilization stress changes the mentioned parameters. Treadmill running did not result in modulation of gene expression of catecholamine synthesizing enzymes and it decreased the level of CREB mRNA in the adrenal medulla of chronically psychosocially stressed adult rats. The potentially negative physiological adaptations after treadmill running were recorded as increased concentrations of catecholamines and decreased morning CORT concentration in the plasma, as well as the adrenal gland hypertrophy of chronically psychosocially stressed rats. The additional acute immobilization stress increases gene expression of catecholamine biosynthetic enzymes in the adrenal medulla, as well as catecholamines and CORT levels in the plasma. Treadmill exercise does not change the activity of sympatho-adrenomedullary system of chronically psychosocially stressed rats.

Protective effect of Hsp70i against chronic social isolation stress in the rat hippocampus

Stress-related glucocorticoids and glutamate release has been implicated in depression. Glutamate neurotoxicity is mediated, in part, by the production of nitric oxide via nitric oxide synthase (NOS) isoforms and mitochondrial damage. We previously reported that chronic social isolation stress triggers proapoptotic signaling in the rat prefrontal cortex, but not in the hippocampus. Given that the hippocampus is highly sensitive to stress, we examined signaling cascades underlying the hippocampal cellular protection through the NOS pathway, antioxidant capacity and heat shock protein (Hsp) expression. We investigated neuronal (nNOS) and inducible (iNOS) protein levels, subcellular protein distributions of nuclear factor-κB (NF-κB), CuZnSOD and MnSOD activity, reduced glutathione (GSH), stress-inducible Hsp70 (Hsp70i) protein expression and serum corticosterone (CORT) levels of rats exposed to 21 days of chronic social isolation, an animal model of depression, alone or in combination with 2 h of acute immobilization or cold stress (combined stress). Both acute stressors elevated CORT, with lesser magnitude increase in chronically isolated rats exposed to novel acute stress as compared to acute stressors alone, indicating compromised HPA axis activity. Acute cold decreased nuclear CuZnSOD activity and stimulated NF-κB nuclear translocation. Chronic social isolation resulted in no activation of NF-κB, but led to decreased GSH, iNOS and increased nNOS and Hsp70i levels, alterations that remained following combined stressors. Decreased mitochondrial MnSOD activity after combined stressors suggests compromised detoxifying capacity. These data indicate that Hsp70i upregulation may provide hippocampal cellular protection against chronic social isolation stress mediated by downregulation of iNOS protein expression through suppression of NF-κB activation.

Age-Related Changes in the Reliability of Antioxidant Enzyme Defense in Monkeys with Different Types of Adaptive Behavior

We have investigated age-related changes in the reliability of glutathione-related antioxidant enzyme defense in monkeys that differ in adaptive behavior. Activities of gluthatione reductase (GR), glutathione peroxidase (GSH-Px), and gluthatione-S-transferase (GST) and also lipid peroxidation products (TBARS) under basal conditions and under acute psycho-emotional stress were evaluated in erythrocytes of young (6-8 years) and old (20-27 years) female rhesus monkeys with depression-like and standard (control) behavior. We have found that young animals with depression-like behavior, in comparison with young monkeys of standard behavior, demonstrated higher activity of GR in basal conditions and no significant changes in response to acute immobilization stress. With aging the activity of GR increased in monkeys with standard behavior in basal conditions but retained the ability to increase under acute stress. At the same time during aging in monkeys with depression-like behavior GR activity did not undergo significant changes in basal conditions and did not change in response to acute stress. Moreover, old animals with depression-like behavior demonstrated reduced activity of GSH-Px. More pronounced disturbances in GR and GSH-Px activities in animals with depression-like behavior evidence a more marked decrease in the reliability of antioxidant enzyme defense of cells and lead to activation of lipid peroxidation that may be considered as an important factor of aging. Thus, age-related dysfunctions of the antioxidant enzyme system correlate with the type of adaptive behavior characteristic of animals.

Chronic social isolation induces NF-κB activation and upregulation of iNOS protein expression in rat prefrontal cortex

Exposure of an organism to stress, results in oxidative stress and increased nitric oxide (NO) production in the brain. The role of the processes caused by chronic stress in the prefrontal cortex has not been fully investigated. Considering that chronic stress increases NO production by the enzyme nitric oxide synthase (NOS), we examined the cytosolic neuronal (nNOS) or inducible (iNOS) protein levels in the prefrontal cortex of rats exposed to 21d of chronic social isolation stress, an animal model of depression, alone or in combination with 2h of acute immobilization or cold (4°C) stress (combined stress). Antioxidative status via cytosolic CuZnSOD and mitochondrial MnSOD activity, cytosolic redox status via reduced glutathione (GSH) concentration were determined. Furthermore, cytosolic inducible heat shock protein 70 (Hsp70i), cytosolic/nuclear distributions of NF-κB and serum corticosterone (CORT) were also investigated to elucidate the possible mechanism involved in the cellular NOS pathway. Our results showed that both acute stressors led to increases of CORT and nNOS protein while iNOS protein expression was unaffected. In contrast to the acute stress, chronic social isolation compromised hypothalamic–pituitary-adrenal axis functioning such that the normal stress response was impaired following subsequent acute stressors. Downregulated redox GSH status as well as decreased activity of CuZnSOD and MnSOD suggests the existence of oxidative stress which remained as such following combined stressors. Changes in redox-status associated with decreased Hsp70i protein expression enabled NF-κB translocation into the nucleus, causing increased cytosolic nNOS and iNOS protein expression. Results suggest that NOS signaling pathway plays a differential role between acute and chronic stress whereby state of oxidative/nitrosative stress after chronic social isolation is caused, at least in part, by NF-κB activation and increased iNOS protein expression.

The influences of reproductive status and acute stress on the levels of phosphorylated delta opioid receptor immunoreactivity in rat hippocampus

In the hippocampus, ovarian hormones and sex can alter the trafficking of delta opioid receptors (DORs) and the proportion of DORs that colocalize with the stress hormone, corticotropin releasing factor. Here, we assessed the effects of acute immobilization stress (AIS) and sex on the phosphorylation of DORs in the rat hippocampus. We first localized an antibody to phosphorylated DOR (pDOR) at the SER363 carboxy-terminal residue, and demonstrated its response to an opioid agonist. By light microscopy, pDOR-immunoreactivity (ir) was located predominantly in CA2/CA3a pyramidal cell apical dendrites and in interneurons in CA1-3 stratum oriens and the dentate hilus. By electron microscopy, pDOR-ir primarily was located in somata and dendrites, associated with endomembranes, or in dendritic spines. pDOR-ir was less frequently found in mossy fibers terminals. Quantitative light microscopy revealed a significant increase in pDOR-ir in the CA2/CA3a region of male rats 1h following an injection of the opioid agonist morphine (20mg/kg, I.P). To look at the effects of stress on pDOR, we compared pDOR-ir in males and cycling females after AIS. The level of pDOR-ir in stratum radiatum of CA2/CA3a was increased in control estrus (elevated estrogen and progesterone) females compared to proestrus and diestrus females and males. However, immediately following 30min of AIS, no significant differences in pDOR levels were seen across estrous cycle phase or sex. These findings suggest that hippocampal levels of phosphorylated DORs vary with estrous cycle phase and that acute stress may dampen the differential effects of hormones on DOR activation in females.

Correction of disorders in tissue perfusion, blood coagulation and fibrinolysis with Orbita apparatus on terahertz waves of cell metabolites

This article contains information on principle of operation, technical parameters and possible application of Orbita {transliteration from Russian} apparatus for hemodynamic, fibrinolytic and peripheral perfusion disorders treatment. A single exposure to terahertz waves emitted by Orbita apparatus, corresponding to frequencies of molecular absorption and emission spectra of atmospheric oxygen (129.0 GHz), completely cures coagulant and fibrinolytic disorders of animals with acute immobilization stress. A course of treatment with electromagnetic waves corresponding to frequencies of molecular absorption and emission spectra of nitrogen oxide (150.176 – 150.664) leads to normalization of disrupted peripheral tissue perfusion parameters of animal undergoing treatment and stimulates basal and induced output of nitrogen oxide. This leads to decrease in peripheral vascular resistance to microcirculation and increase in blood flow to microvasculature. Experimental data provided in this article serves as a proof of viability of Orbita apparatus for treatment of coagulant, fibrinolytic and tissue perfusion disorders.

Up-regulation of immunoglobulin G gene expression in the hippocampus of rats subjected to acute immobilization stress

Immunoglobulin G (IgG) is thought to be produced by matured B lymphocytes, however, it was recently found to be synthesized in neurons of the brain, especially showing higher expression level in the hippocampus. To study the possible effects of IgG in the hippocampus, we examined IgG protein and mRNA expressions in rat hippocampal neurons with immunohistochemistry, immunofluorescence, in situ hybridization and laser microdissection-assisted RT-PCR. Increased IgG expressions at both protein and mRNA levels were detected in the hippocampus of an acute immobilization stress model of rat. No change was observed in the cortex or the thalamus. Furthermore, the microtubule-associated protein 2 (MAP2) and β III tubulin proteins did not show significant changes. Based on these findings, we hypothesize that hippocampal IgG may play a key role in adverse circumstances such as stress. The finding of increased IgG expression in the hippocampus following stress may also provide possibilities for developing antidepressant medication.

Effect of acute immobilization stress with or without a heme oxygenase inducer on testicular structure and function in male albino rats

Stress disturbs homeostasis and may induce various disorders. Immobilization stress (IS) induced due to reduced area provided for mobility results in the imbalance of oxidant and antioxidant status. Stress leads to male reproductive dysfunction in many species, including rodents and humans. Induction of heme oxygenase-1 (HO-1), the rate limiting enzyme in heme degradation, increases host antioxidant defenses. We elucidated the protective role of induction of HO-1 by hemin on testicular damage induced by acute IS. Male albino rats were immobilized for a period of 6 h. Hemin was given for 3 consecutive days (40 μmol/kg/day, s.c.), before subjecting the animals to acute IS. Upregulation of HO-1 following hemin administration was evidenced in our study by increasing carboxyhemoglobin (COHb) level. Histopathological evaluation confirmed that acute IS caused significant testicular tissue injury, which improves in groups pretreated with hemin. Acute IS also caused significant increases in serum catecholamines and corticosterone levels; however, it produced a significant decrease in testosterone level with non-significant changes in luteinizing hormone (LH) level. In addition, it was found that IS significantly increased testicular malondialdehyde (MDA) and decreased catalase activities. The HO-1 inducer (i.e., hemin) significantly decreased catecholamines and corticosterone levels, and increased testosterone and LH levels. Hemin also decreased testicular MDA and increased catalase activities significantly. Induction of HO-1 protects the testes through its antioxidant and anti-inflammatory effects. Thus, it represents a potential therapeutic option to protect testicular tissue from detrimental effects of IS.

Correction of Disorders in Tissue Perfusion, Blood Coagulation and Fibrinolysis with Orbita Apparatus on Terahertz Waves of Cell Metabolites

This article contains information on principle of operation, technical parameters and possible application of Orbita apparatus for hemodynamic, fibrinolytic and peripheral perfusion disorders treatment. A single exposure to terahertz waves emitted by Orbita apparatus, corresponding to frequencies of molecular absorption and emission spectra of atmospheric oxygen (129.0 GHz), completely cures coagulant and fibrinolytic disorders of animals with acute immobilization stress. A course of treatment with electromagnetic waves corresponding to frequencies of molecular absorption and emission spectra of nitrogen oxide (150.176 - 150.664) leads to normalization of disrupted peripheral tissue perfusion parameters of animal undergoing treatment and stimulates basal and induced output of nitrogen oxide. This leads to decrease in peripheral vascular resistance to microcirculation and increase in blood flow to microvasculature. Experimental data provided in this article serves as a proof of viability of Orbita apparatus for treatment of coagulant, fibrinolytic and tissue perfusion disorders.

Hemodynamic Changes Caused by Exposure of Animals with Acute Immobilization Stress to Continuous Terahertz Radiation

Experimental simulation of hemodynamic disorders during acute immobilization stress has shown that expo-sure to continuous terahertz radiation with frequencies equal to absorption and emission frequencies of nitrogen oxide (150.176-150.664 GHz) and atmospheric oxygen (129.0 ± 0.75 GHz) for 5, 15 and 30 minutes allows to revert post-stress hemodynamic changes in great vessels. This allows using terahertz electromagnetic radiation with frequencies equal to absorption and emission frequencies of nitrogen oxide (150.176-150.664 GHz) and atmospheric oxygen (129.0 ± 0.75 GHz) to treat hemodynamic disorders accompanying some of pathologic diseases.

Effects of acute stress on gene expression of splenic catecholamine biosynthetic enzymes in chronically stressed rats

The aim of this study was to examine how acute immobilization stress affects the concentrations of catecholamines in the plasma and the expression of the splenic catecholamine biosynthetic enzymes tyrosine hydroxylase (TH), dopamine-?-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in chronically socially isolated rats. We found that acute immobilization increases the plasma catecholamine levels and splenic PNMT protein levels in chronically socially isolated rats. These results show that acute stress of chronically stressed animals activates the sympatho-adrenomedullary system and increases synthesis of splenic PNMT by 37%, both of which can modulate the immune function.

Changes in Activity of Stress-Realizing Body Systems as a Result of Terahertz Irradiation at Nitric Oxide Frequencies in Albino Rats under Conditions of Acute Stress

We studied the effects of irradiation with teraherz electromagnetic waves at frequencies corresponding to nitric oxide emission and absorption molecular spectrum (150,176-150,664 GHz) on activity of the sympathoadrenal and pituitary-adrenal axes of the stress response in albino male rats under conditions of acute immobilization stress. It was shown that terahertz waves exert stress-limiting effect and are capable of reducing the levels of catecholamines, corticotropin, and corticosterone in male rats exposed to acute stress.

Hemodynamic changes caused by exposure of animals with acute immobilization stress to continuous terahertz radiation with frequencies equal to absorption and emission frequencies of nitrogen oxide and atmospheric oxygen

The aim was to study the effects of exposure of albino rats to continuous terahertz radiation with frequencies equal to absorption and emission frequencies of nitrogen oxide (150.176-150.664 GHz) and atmospheric oxygen (129.0 ± 0.75 GHz) during their immobilization stress on their blood flow rate. Methods – The group of 120 male non-pedigree albino rats with average weight of 180-220 g was chosen as a test subject. Simulation of hemodynamic disorders was achieved by incurring active immobilization stress. All rats were exposed to electromagnetic terahertz radiation equal to absorption and emission frequencies of nitrogen oxide (150.176-150.664 GHz) and atmospheric oxygen (129.0 ± 0.75 GHz) for 5, 15 and 30 minutes. Results – Experimental simulation of hemodynamic disorders during acute immobilization stress has shown that exposure to continuous terahertz radiation with frequencies equal to absorption and emission frequencies of nitrogen oxide (150.176-150.664 GHz) and atmospheric oxygen (129.0 ± 0.75 GHz) for 5, 15 and 30 minutes allows to revert post-stress hemodynamic changes in great vessels. Conclusion – This allows using terahertz electromagnetic radiation with frequencies equal to absorption and emission frequencies of nitrogen oxide (150.176-150.664 GHz) and atmospheric oxygen (129.0 ± 0.75 GHz) to treat hemodynamic disorders accompanying some of pathologic diseases.

Distribution of the Vasotocin Subtype Four Receptor (VT4R) in the Anterior Pituitary Gland of the Chicken, Gallus gallus, and its Possible Role in the Avian Stress Response

The neurohormone arginine vasotocin (AVT) in non mammalian vertebrates is homologous to arginine vasopressin (AVP) in mammals. Its actions are mediated via G protein-coupled receptors that belong to the vasotocin/mesotocin family. Because of the known regulatory effects of nonapeptide hormones on anterior pituitary functions, receptor subtypes in that family have been proposed to be located in anterior pituitary cells. Recently, an avian vasotocin receptor subtype designated VT4R has been cloned, which shares 69% sequence homology with a human vasopressin receptor, the V1aR. In the present study, a polyclonal antibody to the VT4R was developed and validated to confirm its specificity to the VT4R. The antibody was used to test the hypothesis that the VT4R is present in the avian anterior pituitary and is specifically associated with certain cell types, where its expression is modulated by acute stress. Western blotting of membrane protein extracts from pituitary tissue, the use of HeLa cells transfected with the VT4R and peptide competition assays all confirmed the specificity of the antibody to the VT4R. Dual-labelling immunofluorescence microscopy was utilised to identify pituitary cell types that contained immunoreactive VT4R. The receptor was found to be widely distributed throughout the cephalic lobe but not in the caudal lobe of the anterior pituitary. Immunoreactive VT4R was associated with corticotrophs. Approximately 89% of immunolabelled corticotrophs were shown to contain the VT4R. The immunoreactive VT4R was not found in gonadotrophs, somatotrophs or lactotrophs. To determine a possible functional role of the VT4R and previously characterised VT2R, gene expression levels in the anterior pituitary were determined after acute immobilisation stress by quantitative reverse transcriptase-polymerase chain reaction. The results showed a significant increase in plasma corticosterone levels (three- to four-fold), a significant reduction of VT4R mRNA and an increase of VT2R mRNA (P < 0.05) in acutely immobilised chicks compared to controls. The data suggest a role of the VT4R in the avian stress response.

Role of TrkB expression in rat adrenal gland during acute immobilization stress

Expression of tyrosine receptor kinase B (TrkB), a receptor for brain-derived neurotrophic factor (BDNF), is markedly elevated in the adrenal medulla during immobilization stress. Catecholamine release was confirmed in vitro by stimulating chromaffin cells with recombinant BDNF. We investigated the role of TrkB and the localization of BDNF in the adrenal gland during immobilization stress for 60 min. Blood catecholamine levels increased after stimulation with TrkB expressed in the adrenal medulla during 60-min stress; however, blood catecholamine levels did not increase in adrenalectomized rats. Furthermore, expression of BDNF mRNA and protein was detected in the adrenal medulla during 60-min stress. Similarly, in rats undergoing sympathetic nerve block with propranolol, BDNF mRNA and protein were detected in the adrenal medulla during 60-min stress. These results suggest that signal transduction of TrkB in the adrenal medulla evokes catecholamine release. In addition, catecholamine release was evoked by both the hypothalamic–pituitary–adrenal axis and autocrine signaling by BDNF in the adrenal gland. BDNF–TrkB interaction may play a role in a positive feedback loop in the adrenal medulla during immobilization stress.