Short-term Immobilization Stress Research Articles

A study on alpha-terpineol in Alzheimer’s disease with the use of rodent in vivo model, restraint stress effect and in vitro Amyloid beta fibrils

Alzheimer’s disease (AD) is a neurological disorder in which the neuronal degeneration is associated with inflammatory processes and oxidative stress. Since alpha-terpineol was shown to possess antioxidant and anti-inflammatory effects, the administration of this compound was studied on a rat model of AD. To create this model, Aβ1-42 was injected into the hippocampus of male Wistar rats. Generated AD models were divided into simple AD models and AD models in which short-term immobilization stress was added. Preventive and therapeutic (post-AD induction) effects of alpha-terpineol consumption (100 mg/Kg) were subsequently investigated in AD models, which were compared with control groups. Biochemical factors (superoxide dismutase and malondialdehyde), histological manifestations (amyloid plaques and neuron counts) and possible memory impairment (shuttle-box experiment) were investigated in all groups. For the in vitro experiment, alpha-terpineol effect was checked on Aβ1-42 fibril formation. In preventive and therapeutic modes, alpha-terpineol consumption could improve neurogenesis and long-term memory while reducing amyloid plaque counts and ameliorating biochemical factors (higher levels of superoxide dismutase and malondialdehyde and reduced levels of MDA). In vitro, shorter fibrillar structures were formed in the presence of alpha-terpineol, which indicates an anti-amyloid effect for this compound. In conclusion, alpha-terpineol significantly counteracted AD consequences.

ENDOGENOUS OPIOID SYSTEM AS A MEDIATOR OF ACUTE AND LONG-TERM ADAPTATION TO STRESS. PROSPECTS FOR CLINICAL USE OF OPIOID PEPTIDES

It has been well established that opioid peptides (OPs) affect various hormonal systems. Opioids exhibit stress-limiting and gastro-protective effects in stressed animals, acting via mu- and delta-opioid receptors (OR). Peripheral mu-OR stimulation by endogenous and exogenous opioids increases cardiac tolerance to pathological consequences of stress. Enhancement ofprostacyclin synthesis, decrease of thromboxane production as well as suppression of lipid peroxidation can be directly responsible for cardioprotective effects of OPs in stressed animals. Adaptive responses are accompanied by increased OP levels in blood and tissues. Reduction of ventricular arrhythmias induced by repeated short-term immobilization stress is mediated via mu-OR stimulation by endogenous opioids, while delta-OR account for an antiarrhythmic effect of adaptation to chronic intermittent hypobaric hypoxia. The mechanism of infarct size-limiting effect of continuous normobaric hypoxia involves both mu- and delta-OR stimulation. Peptide OR agonists can be considered in future clinical practice for treatment of withdrawal syndrome, stress-related cardiac disease or myocardial injury caused by ischemia-reperfusion insult.

Subsequent stress increases gene expression of catecholamine synthetic enzymes in cardiac ventricles of chronic-stressed rats

Since previous experience of stressful situation profoundly affects response to a subsequent novel stressor, we examined changes in gene expression and protein levels of catecholamine biosynthetic enzymes in cardiac ventricles after exposure of chronic psychosocially isolated adult Wistar male rats to short-term immobilization stress. Chronic social isolation did not affect gene expression of tyrosine hydroxylase (TH) in either right or left ventricle. Subsequent immobilization of these animals produced an elevation of TH mRNA level in right and left ventricles. The levels of dopamine-β-hydroxylase (DBH) mRNA were detectable only after immobilization both in right and left ventricles of control and chronically isolated rats. Chronic isolation stress increased phenylethanolamine N-methyltransferase (PNMT) mRNA levels in the right ventricle. Immobilization led to an elevated PNMT mRNA level in right and left ventricles of both control and chronically stressed animals. Protein levels of TH, DBH, and PNMT in right and left ventricles of socially isolated rats were increased after subsequent immobilization. Taking into consideration the role of cardiac catecholamines in physiological and pathophysiological processes, it could be hypothesized that increased catecholamine synthesis in the ventricles after novel immobilization stress could point to the susceptibility of the heart to subsequent stress.

One of the Pathways of Transmission of Afferent Activity to the Locus Coeruleus Under Conditions of Immobilization Stress

An electrophysiological proof has been obtained for the morphological data on the existence of afferent inputs from the medullary nucl. praepositus hypoglossi (NPH) to the brainstem locus coeruleus. The crucial role of the NPH in the formation of background spike activity of neurons of the locus coeruleus under conditions of short-term immobilization stress has been demonstrated.

Serum protein peroxidation in rats selected by the rate of active avoidance conditioning under normal conditions and during stress.

Serum protein peroxidation was studied in rats with different strategy of adaptive behavior at rest and during short-term immobilization stress. Oxidative destruction of serum proteins was less intensive in KLA rats compared to that in KHA rats. Stress stimulated peroxidation of serum proteins in KHA rats.

Opiatergic mechanisms of cardioprotective and antiarrhythmic effects of adaptation

Adaptation to hypoxia and short-term immobilization stress, as well as preconditioning with Rhodiolae rosea extract produces pronounced antiarrhythmic and cardioprotective effects in the model of adrenergic damage to the heart. Preliminary blockade of opioid receptor significantly decreases the protective effect of adaptation. Using selective opiate receptor antagonists (naltrindole, ICI 174,864, and norbinaltorphimine) we show that the antiarrhythmic effect of adaptation is mediated predominantly via activation ofk-receptors, and to a lesser extent μ-and σ-receptors.

Adrenalectomy Causes Oxidative Damage and Monoamine Increase in the Brain of Rats and Enhances Immobilization Stress-Induced Oxidative Damage and Neurotransmitter Changes

The paradox that increased levels of glucocorticoids can either enhance or suppress the organism's defense against stress, has been an obstacle to formulating a unified picture of glucocorticoid function. To clarify the glucocorticoid paradox, we examined male Sprague-Dawley rats exposed to immobilization stress and/or bilateral adrenalectomy (ADX), and measured oxidative damage to lipid, protein, and DNA, as well as monoamine neurotransmitter turnover. ADX, which is similar to stress, induces an increase in lipid peroxidation and protein oxidation, accompanied by increased monoamine neurotransmitter turnover in several regions of the brain of rats. The effect of ADX is greater than that induced by short-term immobilization stress. In addition, ADX enhances stress-induced oxidative damage and increase of monoamine neurotransmitter turnover. These results, together with our previous finding that long-term stress causes oxidative damage to the brain, suggest that stress levels of glucocorticoids, or levels lower than basal, cause oxidative damage. However, basal levels of glucocorticoids appear to buffer against oxidative damage. These findings provide possible mechanisms to understand the glucocorticoid paradox, and support the stress-oxidative hypothesis of aging acceleration.

A neurotensin antagonist, SR 48692, inhibits colonic responses to immobilization stress in rats.

We previously reported that short-term immobilization stress of rats causes increased colonic mucin release, goblet cell depletion, prostaglandin E2 secretion, and colonic mast cell activation, as well as increased colonic motility. The purpose of this study was to investigate whether neurotensin (NT), a peptide expressed in both brain and digestive tract, participates in these responses. Rats were pretreated with SR 48692 (1 mg/kg, i.p.), an NT antagonist, 15 min before immobilization (30 min). The administration of the antagonist significantly inhibited stress-mediated secretion of colonic mucin, prostaglandin E2, and a product of rat mast cells, rat mast cell protease II (P < 0.05), but did not alter the increase in fecal pellet output caused by immobilization stress. Immobilization stress also resulted in a quantifiable decrease in the abundance of NT receptor mRNA in rat colon compared with that in colonic tissues from nonimmobilized rats as measured by densitometric analysis of in situ hybridization studies (P < 0.03). We conclude that the peptide NT is involved in colonic goblet cell release and mucosal mast cell activation after immobilization stress.

Acute stress in rats produces a rapid and sustained increase in prostacyclin production in aortic tissue: Dependence on corticosterone

Immobilization stress in rats is accompanied by a fast and transient increase in plasma catecholamines (CA) and a slow but more sustained increase in plasma corticosterone (CORT) levels. CA are reported to increase prostacyclin (PGI 2) secretion in endothelial cells in culture and in isolated vascular tissue. The present study was undertaken to determine a) whether short term immobilization stress in rats affects PGI 2 synthesis in aortic tissue and b) whether such effects are dependent on the maintenance of an intact hypothalamic-pituitary-adrenal axis. Male Sprague Dawley rats were immobilized for 5, 15 and 30 min., killed by a blow to the head and aortic rings immediately prepared and incubated in oxygenated Krebs-Ringer buffer at 37 °C. Secretion of PGI 2 was assessed by measuring the amount of 6-keto-PGF 1α, the stable hydrolysis product of PGI 2, formed in the incubation medium during 90 min. Rats immobilized for 15 min demonstrated a six to seven times increase in plasma ACTH and a more than ten times increase in plasma CORT levels. Aortic rings from stressed rats also demonstrated a significant and sustained (2 hours) increase in PGI 2 secretion when compared with tissue from unstressed rats (68 pg 6-keto-PGF 1α/mg tissue per min vs 35 pg 6-keto-PGF 1α/mg tissue per min during the first hour). Shorter (5 min) or longer (30 min) periods of stress gave comparable results. Adrenalectomy (ADX) carried out 7 days prior to immobilization, did not affect the baseline secretion of the eicosanoid, but completely prevented the increase in PGI 2 by immobilization stress. Administration of 2 μg/kg and 200 μg/kg i.a. of CORT to ADX-rats produced plasma levels of the hormone (36 ± 12 ng/ml and 934 ± 366 ng/ml respectively) comparable to those seen in unstressed and stressed rats. However only the higher dose of CORT when administered immediately prior to stress, restored the effect of immobilization stress on PGI 2 synthesis in aortic tissue of ADX-rats. Administration of the protein synthesis inhibitor cycloheximide (1 mg/kg) prior to stress did not affect the increase in PGI 2 secretion. In contrast to restraint stress, co-administration of ACTH and NE which also raised plasma levels of ACTH, CORT and NE to peak stress levels, did not increase prostacyclin production in aortic tissue. In conclusion, our findings demonstrate that short periods of immobilization stress produce a rapid and sustained increase in PGI 2 synthesis in the rat aorta, provided plasma levels of CORT are elevated. Since this permissive effect of CORT on stress induced prostacylin synthesis is rapid in onset, and insensitive to cycloheximide, it is probably mediated by a non-genomic mechanism. Although NE is known to activate PGI 2 synthesis in arterial tissue in vitro, the increase in aortic eicosanoid synthesis by stress does however not appear to be caused by a rise in plasma concentrations of NE.

Increased generation of nitric oxide in tissues of rats following their adaptation to short-term stress (An EPR study)

Adaptation of rats to short-term immobilization stress increases the ability of their isolated organs to generate nitric oxide (NO): its spontaneous release by the liver, gut, heart, and kidney tissues rises 2- to 4-fold and its carbachol-stimulated release by these tissues rises 4- to 5-fold. It is suggested that such adaptation leads to rapid NO generation in the adapted animal in response to exogenous or endogenous stimuli and thus increases the efficacy of defense reactions.

Significance of hormonal feedback regulation for hypothalamic nonapeptidergic center response to short-term immobilization stress

Significance of hormonal feedback regulation for hypothalamic nonapeptidergic center response to short-term immobilization stress

Effect of eicosapentaenoic acid and the calcium antagonist isradipin on lipid metabolism and erythrocytes in cholesterol-fed rabbits

Adaptation to intermittent short-term immobilization stress exposure increases the resistance of rats to hypoxic hypoxia. This was evidenced by the fact that in acute experiments in respiration with gas-mixture containing 6% of oxygen, the mortality of control rats was 65% compared with 10% of that of adapted rats. It has been estimated that this protective cross-effect of adaptation to stress is due to more stable and efficient mobilization of external respiration in adapted animals, and to a greater extent, to the fact that adapted rats tissues have gained a capacity of extracting more oxygen from hypoxemic blood compared to control animals. The role of previously stated phenomenon of adaptive stabilization of structures in superresistance to hypoxic hypoxia is discussed.

Effect of continuous vasopressin infusion on circadian rhythms of food and water intake, diuresis, and electrolyte excretion in brattleboro rats

In the experiments on rats a significant decrease of resistance to the contracture and arrhythmogenic effect of increased Ca2+ on the isolated hearts of animals after short term immobilization stress has been shown. After a long term stress (6 hours) the changes of the studied physiological parameters of the isolated hearts were not observed. Transport in the homogenates of the rat hearts was measured by the Ca--selective electrode on the ionometer ORION EA 940. After a 1-hour stress the rate of Ca--transport in sarcoplasmic reticulum (SR) substantially decreased as compared with the control (3.5 fold at 20 mcM), but at the higher concentration the Ca-transport was inhibited. The long term stress lead to a slower damage of functional Ca-transport system of SR--at 20 mcM the rate decreased by 25% as compared with control and at the higher concentration of Ca2+ depression of transport was not observed.

Disturbance of vascular permeability and the microcirculation during short-term immobilization stress

Immobilization of rats for 1 or 3 h leads to an increase in vascular permeability for ink particles and disturbances of the microcirculation in the mesenteric microvessels (formation of aggregates, appearance of “plasmatic vessels,” closure of arteriolar-venular shunts). An important role in the pathogeneis of these changes is played by histamine liberated from the mast cells without their undergoing degranulation. Liberation of histamine may be the trigger mechanism in the development of disturbances of vascular permeability during prolonged immobilization stress.