Effects Of Mild Stress Research Articles

Effects of Corticosterone on Beta-Amyloid-Induced Cell Death in SH-SY5Y Cells.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by neuronal cell death and memory impairment. Corticosterone (CORT) is a glucocorticoid hormone produced by the hypothalamic-pituitary-adrenal axis in response to a stressful condition. Excessive stress and high CORT levels are known to cause neurotoxicity and aggravate various diseases, whereas mild stress and low CORT levels exert beneficial actions under pathophysiological conditions. However, the effects of mild stress on AD have not been clearly elucidated yet. In this study, the effects of low (3 and 30 nM) CORT concentration on Aβ25-35-induced neurotoxicity in SH-SY5Y cells and underlying molecular mechanisms have been investigated. Cytotoxicity caused by Aβ25-35 was significantly inhibited by the low concentration of CORT treatment in the cells. Furthermore, CORT pretreatment significantly reduced Aβ25-35-mediated pro-apoptotic signals, such as increased Bim/Bcl-2 ratio and caspase-3 cleavage. Moreover, low concentration of CORT treatment inhibited the Aβ25-35-induced cyclooxygenase-2 and pro-inflammatory cytokine expressions, including tumor necrosis factor-α and interleukin-1β. Aβ25-35 resulted in intracellular accumulation of reactive oxygen species and lipid peroxidation, which were effectively reduced by the low CORT concentration. As a molecular mechanism, low CORT concentration activated the nuclear factor-erythroid 2-related factor 2, a redox-sensitive transcription factor mediating cellular defense and upregulating the expression of antioxidant enzymes, such as NAD(P)H:quinone oxidoreductase, glutamylcysteine synthetase, and manganese superoxide dismutase. These findings suggest that low CORT concentration exerts protective actions against Aβ25-35-induced neurotoxicity and might be used to treat and/or prevent AD.

Mild stress induces brain region-specific alterations of selective ER stress markers’ mRNA expression in Wfs1-deficient mice

In this work, the effect of mild stress (elevated plus maze test, EPM) on the expression of endoplasmic reticulum (ER) stress markers in different brain areas of wild type (WT) and Wfs1-deficient (Wfs1KO) mice was investigated. The following ER stress markers were studied: activating transcription factor 6α (Atf6α), protein kinase-like ER kinase (Perk), X-box binding protein 1 (Xbp1) and its spliced form (Xbp1s), 78-kilodalton glucose regulated protein (Grp78), 94-kilodalton glucose regulated protein (Grp94), C/EBP homologous protein (Chop). Wfs1KO and WT mice, not exposed to EPM, had similar patterns of ER stress markers in the studied brain areas. The exploratory activity of Wfs1KO mice in the EPM was inhibited compared to WT mice, probably reflecting increased anxiety in genetically modified mice. In response to the EPM, activation of inositol-requiring transmembrane kinase and endonuclease 1α (Ire1α) ER stress pathway was seen in both genotypes, but in different brain areas. Such a brain region-specific Ire1α activation was linked with dominant behavioural trends in these mice as more anxious, neophobic Wfs1KO mice had increased ER stress markers expression in the temporal lobe, the brain region related to anxiety, and more curious WT mice had ER stress markers increased in the ventral striatum which is related to the exploratory drive. The molecular mechanism triggering respective changes in ER stress markers in these brain regions is likely related to altered levels of monoamine neurotransmitters (serotonin, dopamine) in Wfs1KO mice.

La modulation du vieillissement par le stress modéré

Hormesis is the phenomenon by which adaptive responses to low doses of otherwise harmful conditions improve the functional ability of organisms. Some mild stresses have beneficial effects on longevity, aging and resistance to strong stresses (heat or cold shocks, infection) in Drosophila flies. Studies on rodents are indeed scarce but mild stress seems to be effective in humans because, for instance, patients suffering from angina have a higher survival when confronted with a heart attack. A few studies, in less tragic situations however, suggest that mild stress could have positive effects in elderly people. Performing more experiments on the effects of mild stress in humans would help to know whether it could be used in therapy or to improve healthspan of elderly.

Mild stress facilitates learning and exercise improves retention in aged mice

While chronic or severe stress generally has negative consequences in the brain, moderate stress has been shown to facilitate learning in young animals. It is unknown if stress facilitates or impairs learning in an aged animal. In this study, the effect of mild stress on learning and task retention (1 week later) was assessed in young and aged mice. In addition, because exercise can counteract negative effects of stress and facilitate learning, the effect of 1 week of voluntary exercise on task retention was assessed. Regulation of the learning/memory related genes BDNF exon VI, synapsin, MAPK, and CRFR1 were also examined in the hippocampus using real-time PCR. Results of this study demonstrate that mild stress 24 h prior to the learning test improved performance in aged, but not young animals. However, exercise for 1 week between tests improved the performance of both groups of animals in the retention task. In aged, but not young animals, all four genes increased significantly after exercise. Thus, in aged animals mild stress facilitates learning and the retention of this task is improved by voluntary exercise.

It is Time to Thoroughly Study the Effects of Mild Stress in Rodents, but also in Human Beings

Many experiments on the effect of mild stress on aging have been done in invertebrates, but not in mammals. Using mild stress to improve healthspan seems to be possible, because the few studies on humans which have been published appear to be promising. Particularly, one may wonder whether heat shocks could be of some use in therapy or as an integrated part of daily life of elderly people. However, the top priority is probably to study more thoroughly the effects of mild stress in rodents, and not only in invertebrates.

Contribution of Glucocorticoids to Protective Influence of Preconditioning Mild Stress against Stress‐induced Gastric Erosions

It is known that preconditioning stress may attenuate stress-induced gastric injury and that this effect is mediated by prostaglandins. In the present study we investigated the contribution of glucocorticoids to the gastroprotective effect of preconditioning stress. The effects of mild stress on gastric erosion caused by severe stress were compared in rats with normal and deficient corticosterone response to preconditioning mild stress. Mild stress decreased the gastric ulceration caused by severe stress, and this effect was prevented by glucocorticoid deficiency during mild stress. The results suggest that glucocorticoids released during preconditioning mild stress contribute to the gastroprotective effect of this stress.

Abstracts

Abstracts

Mice overexpressing CRH show reduced responsiveness in plasma corticosterone after a5-HT1A receptor challenge.

Corticotropin-releasing hormone (CRH) overproduction and serotonergic dysfunction have both been implicated in a range of psychiatric disorders, such as anxiety and depression, and several studies have shown interactions between these two neurotransmitter systems. In this study, we investigated the effects of CRH challenge on hypothalamo-pituitary-adrenal (HPA) axis activity in female transgenic mice overproducing CRH. Furthermore, the effects of mild stress on HPA axis activity and body temperature were investigated in these mice. Pre- and post-synaptic 5-HT1A receptor function were studied by monitoring body temperature and plasma corticosterone levels after challenge with the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propyl-amino)-tetralin (8-OH-DPAT). Hypothermia in response to 8-OH-DPAT treatment did not differ between transgenic and wild type mice, indicating unaltered somatodendritic 5-HT1A autoreceptor function in mice overproducing CRH. In wild type mice 8-OH-DPAT increased plasma corticosterone levels, but not in transgenic animals. CRH injection, however, increased corticosterone levels in both groups. These data suggest desensitization of post-synaptic, but not pre-synaptic, 5-HT1A receptors in mice overproducing CRH. These findings resemble those seen in depressed patients following 5-HT1A challenge, which is in accord with the hypothesized role of CRH in the pathogenesis of depression.

Influence of Stress on Faecal Carriage ofClostridium perfringens

A drastic change in a human’s way of life is known to lead to dramatic modifications in intestinal microbial balance. The effects of mild stress of everyda y life have, however , been poorly investigated. In this study, we have attempted to assess whether final written examination stress modifies the faecal microbiota in healthy young adults. Diet was standardised and faecal samples collected during two periods of 48 h each, the first 6 weeks before and the second during the final written examination. Faecal hydration as well as count s in total aerobes, anaerobes, enterobacteria, enterococci, Clostridium perfringens and bifidobacteria were determined. Bifidobacteria, enterococci and enterobacteria did not show any significant variation. A significant rise in C. perfringens counts was observed throughout this examination period. It preceded the increase in faecal hydration only observed after a change in diet. Since psychological stress is known to increase intestinal mucin release, C. perfringens overgrowth might reflect a better adaptation to substrates provided by the stressed host. Keywords: Clostridium perfringens , stress, clinical trial.

Corticosterone responses in 5-HT1B receptor knockout mice to stress or 5-HT1A receptor activation are normal.

Previous research found no adaptations in presynaptic 5-HT1A receptors in mice lacking 5-HT1B receptors (5-HT1B KO). Stress and 5-HT1A receptor agonists induce corticosterone release in mice via hypothalamus-pituitary-adrenal (HPA) axis activation. 5-HT1B KO mice are hyperreactive to mild stressors and this might be reflected in altered postsynaptic 5-HT1A receptor sensitivity. Our aim was to determine whether the activity of the HPA axis was increased in 5-HT1B KO mice in response to mild stress and pharmacological activation of 5-HT1A receptors as an indication of putative adaptive changes in postsynaptic 5-HT1A receptor function. The effect of mild stress [i.e., the stress-induced hyperthermia (SIH) paradigm], induced by rectal temperature measurement, was determined on temperature and corticosterone over time (0, 5, 10, 20, 30, 60, and 90 min) in 5-HT1B KO and wildtype mice. In addition, corticosterone was measured 60 min after 5-HT1A receptor activation by flesinoxan (0, 0.03, 0.1, 0.3, 1, and 3 mg/kg s.c.). Blood was collected and plasma corticosterone levels were determined by radioimmunoassay. Both genotypes showed comparable time-dependent SIH responses, whereas basal temperature was higher in 5-HT1B KO mice. The effect of SIH on temperature was mirrored by mild increases in plasma corticosterone. Activation of 5-HT1A receptors caused a strong dose-dependent release of corticosterone in both genotypes. Neither response observed showed differences between both genotypes. Although 5-HT1B KO mice are hyperreactive to mild stress, this reactivity is not reflected by stronger corticosterone responses in the SIH paradigm. The lack of shift in dose-response curves for flesinoxan suggests that postsynaptic 5-HT1A receptor function is unaffected in 5-HT1B KO mice.

Effects of mild stress on the immune response against pseudorabies virus in mice

Stress is a recognised problem in intensive pig husbandry, which might lead to changes in immune reactivity. To study the effect of stress on the development of an anti-viral immune response, we used a murine model in which mice were immunized with an attenuated strain of pseudorabies virus (PRV). The effect of two stress treatments, both relevant to intensive pig husbandry, on the development of the specific immune response against PRV was investigated. The stress treatments consisted of restraint, social isolation, and transport and they differed in predictability. The specific immune response against PRV, which developed in the draining lymph nodes, was measured by a lymphocyte proliferation assay and cytokine production assays. Our results showed that the unpredictable stress treatment had no effect on the development of the immune response against PRV in mice, whereas the predictable stress treatment actually hastened the immune response.

Heat Stress-induced Abortion of Buds and Flowers in Pea: Is Sensitivity Linked to Organ Age or to Relations between Reproductive Organs?

Abstract A short period of heat stress can cause a significant increase in abortion frequency of floral buds and flowers in pea, but a large variability in sensitivity exists among reproductive organs (ROs) within a plant or between plants. We have analysed spatial distribution of abortion frequency in plants subjected or not subjected to heat stress in: (1) four controlled environment experiments in which apex temperature was increased to 31 °C for 6 h per day for 4 d (moderate stress); (2) one field experiment with a similar level of stress; and (3) one experiment with 2 d with 33/30 °C day/night (severe stress) in addition to treatment (1). Influence of neighbouring organs on sensitivity to heat stress was analysed by partial flower removal. Severe heat stress caused rapid interruption of RO development followed by abscission while, in moderate stress, at leat 4 d elapsed between cessation of stress and first symptoms of abortion. In both moderate stress and control treatments, abortion frequency followed a consistent pattern along the stem with no abortion on the lowest reproductive phytomeres, a temperature-dependent abortion frequency on intermediate phytomeres and 100% abortion on apical phytomeres. Regardless of temperature, this pattern was shifted by four positions if ROs were removed on the lowest four reproductive phytomeres, and no abortion was observed if young pods were sequentially removed. Moderate heat stress increased the effect of developing ROs on abortion frequency of younger ROs located above them. We suggest that the effect of mild stress should be viewed as the acceleration of a programme linked to the normal termination of phytomere production during the plant cycle, rather than as an abrupt event linked to stress.

Physiological stimulation increases nonoxidative glucose metabolism in the brain of the freely moving rat.

The effects of mild stress on nonoxidative glucose metabolism were studied in the brain of the freely moving rat. Extracellular lactate levels in the hippocampus and striatum were monitored at 2.5-min intervals with microdialysis coupled with an enzyme-based flow injection analysis system. Ten minutes of restraint stress led to a 235% increase in extracellular lactate levels in the striatum. A 5-min tail pinch caused an increase of 193% in the striatum and 170% in the hippocampus. Local application of tetrodotoxin in the striatum blocked the rise in lactate following tail pinch and inhibited the subsequent clearance of lactate from the extracellular fluid. Local application of the noncompetitive N-methyl-D-aspartate receptor antagonist MK-801 had no effect on the tail pinch-stimulated increase in lactate in the striatum. These results show that mild physiological stimulation can lead to a rapid increase in nonoxidative glucose metabolism in the brain.

The effect of mild stress during pregnancy on birthweight and neuromotor maturation in rhesus monkey infants ( Macaca mulatta)

This prospective study investigated whether mild maternal stress during pregnancy could influence performance on a variety of developmental measures in rhesus monkey infants ( Macaca mulatta ). Twenty-four infants were tested during the first month of life for interactive, neuromotor, and temperamental characteristics and capabilities using instruments adapted directly from human neonatal assessments. Twelve infants were derived from mothers exposed during pregnancy to a mild stressor in the form of a daily 10-min removal from home cage and exposure to three unpredictable noise stimuli. Twelve infants were derived from mothers undisturbed during pregnancy. Prenatally stressed infants had lower birthweights, were delayed in self-feeding, were more distractible, and had lower scores on a Motor Maturity composite score when compared to offspring from undisturbed pregnancies. Close inspection of the Motor Maturity score revealed that low muscle tonus, poor coordination, and slow response speed characterized the prenatally stressed offspring.

Contrasting effects of stress on medial and sulcal prefrontal cortex self-stimulation

Male Wistar rats were subjected to either 25 controllable or uncontrollable footshocks and then tested for changes in fixed-interval 5-second (FI-5) self-stimulation of the medial prefrontal cortex (MPC), sulcal prefrontal cortex (SPC) or nucleus accumbens (NAS). Controllable footshock caused a moderate facilitation of MPC self-stimulation (30% above baseline rates) but inhibited SPC self-stimulation (32% below baseline rates). Uncontrollable footshock had no effect on MPC self-stimulation but inhibited SPC self-stimulation (52% below baseline rates). An inhibition of SPC self-stimulation was also evident 24 hours following controllable or uncontrollable footshock. NAS self-stimulation was unaffected by footshock. Changes in locomotor activity were not consistently related to changes in self-stimulation following footshock. These results are discussed in terms of the different effects of mild stress on the release of reward-relevant neurotransmitters in the MPC, SPC and NAS. The possible role of stress-induced hypoalgesia in determining the stress-induced facilitation of MPC self-stimulation is also discussed.

Effects of mild stress on adrenal and heart catecholamines in male and female rats

The present study was undertaken with the aim of evaluating the sensitivity and convenience of a stress model reflecting sympatho-adrenal activation. Rats of both sexes were subjected to mild stress, consisting of four body temperature recordings, and investigated with regard to adrenal and heart catecholamine levels. Adrenal dopamine (DA) levels were considered to reflect medullary synthesis activity and heart adrenaline (A) concentrations were presumed to reflect A released from the adrenals. Expressed in relation to heart weight, adrenal catecholamine levels were about 50% higher in female rats. Following stress, adrenal DA levels were enhanced in both male and female rats; the magnitude of the stress response appeared similar in the two sexes. Concentrations of A in the hearts of unstressed animals were about 85% higher in females than in males but rose to a similar extent in male and female rats following stress. On the other hand, the stress-induced alterations in heart DA and NA concentrations, reflecting sympathetic activity, were gender-dependent. The advantages of the present model in relation to other techniques for measuring sympatho-adrenal activation in response to mild stress are discussed.

Effect of stress and sampling site on metabolite concentration in rat plasma.

The effect of mild stress on various plasma metabolites in the rat has been studied. Mild stress resulted in significant decreases in liver size and glycogen content, as well as in an increase of blood glucose. In addition, plasma lactate, insulin, glycerol and urea, as well as a number of amino acids were altered by stress. These data indicate that minimal stress can have major effects upon the composition of blood, and suggest the need for strict precautions on the handling of animals during blood sampling. The site of blood extraction--tail tip vs. neck--was also found to have a significant effect on plasma lactate, glucose and urea concentrations. In stressed animals the differences between tail- and neck blood composition were increased.

A method for studying acute insulin secretion and glucose tolerance in unanesthetized and unrestrained rats. The effect of mild stress on carbohydrate metabolism

A method for studying acute insulin secretion and glucose tolerance in unanesthetized and unrestrained rats. The effect of mild stress on carbohydrate metabolism