Greater Physiological and Behavioral Effects of Interrupted Stress Pattern Compared to Daily Restraint Stress in Rats

Repeated stress can trigger a range of psychiatric disorders, including anxiety. The propensity to develop abnormal behaviors after repeated stress is related to the severity, frequency and number of stressors. However, the pattern of stress exposure may contribute to the impact of stress. In addition, the anxiogenic nature of repeated stress exposure can be moderated by the degree of coping that occurs, and can be reflected in homotypic habituation to the repeated stress. However, expectations are not clear when a pattern of stress presentation is utilized that diminishes habituation. The purpose of these experiments is to test whether interrupted stress exposure decreases homotypic habituation and leads to greater effects on anxiety-like behavior in adult male rats. We found that repeated interrupted restraint stress resulted in less overall homotypic habituation compared to repeated daily restraint stress. This was demonstrated by greater production of fecal boli and greater corticosterone response to restraint. Furthermore, interrupted restraint stress resulted in a lower body weight and greater adrenal gland weight than daily restraint stress, and greater anxiety-like behavior in the elevated plus maze. Control experiments demonstrated that these effects of the interrupted pattern could not be explained by differences in the total number of stress exposures, differences in the total number of days that the stress periods encompased, nor could it be explained as a result of only the stress exposures after an interruption from stress. These experiments demonstrate that the pattern of stress exposure is a significant determinant of the effects of repeated stress, and that interrupted stress exposure that decreases habituation can have larger effects than a greater number of daily stress exposures. Differences in the pattern of stress exposure are therefore an important factor to consider when predicting the severity of the effects of repeated stress on psychiatric disorders.     

逆境胁迫下作物基因表达更替的研究进展

本文综述了高等植物在厌氧、热激,盐分胁迫,养分胁迫,紫外辐射等各种逆境条件下,基因表达更替的一系列过程,提出基因表达变化对作物适应逆境条件的意义,并对今后的研究作了展望。     

Conserved features of chronic stress across phyla: the effects of long-term stress on behavior and the concentration of the neurohormone octopamine in the cricket, Gryllus texensis

Many of the deleterious effects of chronic stress in vertebrates are caused by the long-term elevation of stress hormones. These negative effects are thought to be unavoidable by-products of sustained activation of the stress response, but the details remain unclear. A comparative perspective may help in understanding chronic stress. We exposed crickets (Gryllus texensis) to a mock predator. A single exposure to a mock predator induced a transient increase in the hemolymph (blood) concentration of the insect stress neurohormone, octopamine. Repeated exposure to the mock predator increased basal levels of octopamine, similar to the effects of chronic stress on the basal levels of vertebrate stress hormones. This study is the first to report an increase in the basal levels of an invertebrate stress hormone in response to repeated flight-or-fight stress. Chronic stress reduced weight gain, and decreased feeding and enhanced weight loss after food deprivation in adult female crickets. However, chronic stress also increased the tendency of crickets to produce sustained flight. Therefore, this study supports the hypothesis that increasing basal levels of stress hormones may be a phylogenetically common response to chronically stressful conditions. It also demonstrates that chronic stress has both positive and negative effects in insects.     

Intracellular distribution of heat-induced stress glycoproteins

Cellular heat stress results in elevated heat-shock protein (HSP) synthesis and in thermotolerance development. Recently, we demonstrated that protein glycosylation is also an integral part of the stress response with the identification of two major stress glycoproteins, GP50, associated with thermotolerance, and P-SG67, the “prompt” stress glycoprotein induced immediately during acute heat stress. In the present study, we characterized the subcellular location and redistribution of these proteins during the cellular injury and recovery phase. In unheated and heated CHO cells, both stress glycoproteins were present in each subcellular fraction isolated by differential centrifugation. However, the subcellular redistribution in the course of cellular recovery after heat stress was specific for each stress glycoprotein. GP50 was present in all subcellular fractions before heat stress, but showed relatively little redistribution after heat stress. By 24 h of recovery following stress, GP50 showed partial depletion from lysosomes and microsomes, and was mainly present in the mitochondria. Glycosylated P-SG67 was redistributed in a more complex fashion. It was seen predominantly in the lysosomes and microsomes immediately following heat-stress, but after 6 h of recovery following heat stress, it largely disappeared from the microsomes and was present mainly in the cytosol. By 24 h of recovery following heat stress, it was found predominantly in the nucleus-rich fraction and mitochondria. The localization of GP50 and P-SG67 by subcellular fractionation is consistent with immunolocalization studies and contrasts with the translocation of HSP70 after heat stress from cytosol to nuclei and nucleoli. These results reflect a characteristic distribution for each stress glycoprotein; their presence in virtually all subcellular fractions suggests multifunctional roles for the various stress glycoproteins in the cellular heat stress response. J. Cell. Biochem. 66:98–111, 1997. © 1997 Wiley-Liss, Inc.     

Contributions of individual σB-dependent general stress genes to oxidative stress resistance of Bacillus subtilis

The general stress regulon of Bacillus subtilis comprises approximately 200 genes and is under the control of the alternative sigma factor σ(B). The activation of σ(B) occurs in response to multiple physical stress stimuli as well as energy starvation conditions. The expression of the general stress proteins provides growing and stationary nonsporulating vegetative cells with nonspecific and broad stress resistance. A previous comprehensive phenotype screening analysis of 94 general stress gene mutants in response to severe growth-inhibiting stress stimuli, including ethanol, NaCl, heat, and cold, indicated that secondary oxidative stress may be a common component of severe physical stress. Here we tested the individual contributions of the same set of 94 mutants to the development of resistance against exposure to the superoxide-generating agent paraquat and hydrogen peroxide (H(2)O(2)). In fact, 62 mutants displayed significantly decreased survival rates in response to paraquat and/or H(2)O(2) stress compared to the wild type at a confidence level of an α value of ≤ 0.01. Thus, we were able to assign 47 general stress genes to survival against superoxide, 6 genes to protection from H(2)O(2) stress, and 9 genes to the survival against both. Furthermore, we show that a considerable overlap exists between the phenotype clusters previously assumed to be involved in oxidative stress management and the actual group of oxidative-stress-sensitive mutants. Our data provide information that many general stress proteins with still unknown functions are implicated in oxidative stress resistance and further support the notion that different severe physical stress stimuli elicit a common secondary oxidative stress.     

Psychophysiological characterization of persons with different resistance to stress

On the basis of behavioral characteristics while performing operator activity under the conditions of emotional stress, two types of subjects were identified with different neurophysiological reactions to emoional stress. In high stress resistant subjects, irrespective of the character of errors under stress, a decrease in the spectral power of theta-rhythm and an increase in the power in beta hand was observed. As compared to low stress resistant subjects, they were characterized by the predominance of activity of the right hemisphere. In low stress resistant subjects during the work under stress conditions the spectral power in beta-1 hand decreased. As compared to high stress resistant, they were characterized by the predominance of the left hemisphere.     

Tensile Tissue Stress Affects the Orientation of Cortical Microtubules in the Epidermis of Sunflower Hypocotyl

Abstract In turgid multicellular organs, it is convenient to differentiate between the two kinds of tensile forces acting in cell walls as a result of turgor pressure. The primary forces occur both in situ and in cells isolated from the organ, whereas the secondary forces occur only in situ. The latter are an unavoidable physical consequence of the variation in mechanical parameters of tissues forming layers or strands. The most rigid tissue is under maximal tensile force, whereas the least rigid is under maximal compressive force. These forces cause tissue stresses (that is, certain tissues are under tensile stress, whereas others are under compressive stress in the organ). The primary and secondary forces result in primary and secondary stress in cell walls, respectively. The anisotropy of the primary stress is a function of cell shape. For instance, in cylindric cells the anisotropy expressed as the ratio of longitudinal to transverse stresses is 0.5. The anisotropy of the secondary stress is a function of the compound structure of the organ. For example, in the epidermis of sunflower hypocotyl, the longitudinal secondary stress is much higher than the transverse stress. The primary and secondary stresses are superimposed, and, as a consequence, the stress anisotropy in the outer thick walls of epidermal cells is greater than 1. These outer epidermal walls transmit most of the tissue stress. When the epidermis is peeled but remains turgid, only primary stress remains, but loading of the peel can reestablish the original stress anisotropy. We studied the effect of stress anisotropy changes on the orientation of cortical microtubules (CMTs) in the sunflower hypocotyl epidermis. We showed that changes in stress anisotropy cause the CMT orientation to change in the direction of maximal wall stress. In situ, the relatively high tensile tissue stress in the epidermis causes maximal stress in the longitudinal direction and relatively steep CMT orientation. When the tissue stress is removed from the epidermis by peeling, the CMTs tend to reorient toward the transverse direction, which is the direction of maximal stress in the primary component. On application of external longitudinal stress, to substitute for tissue stress, CMTs tend to reorient in the longitudinal direction. However, a relatively high rate of plastic strain is caused by the stress applied to the peel in an acid medium. This produces a less steep orientation of CMTs. It appears that the change in stress anisotropy orients the CMT in the direction in which the stress is maximal after the change, but there is also some effect of the growth rate on the orientation. Received 4 January 2000; accepted 10 February, 2000     

Conserved features of chronic stress across phyla: The effects of long-term stress on behavior and the concentration of the neurohormone octopamine in the cricket,Gryllus texensis

Many of the deleterious effects of chronic stress in vertebrates are caused by the long-term elevation of stress hormones. These negative effects are thought to be unavoidable by-products of sustained activation of the stress response, but the details remain unclear. A comparative perspective may help in understanding chronic stress. We exposed crickets (Gryllus texensis) to a mock predator. A single exposure to a mock predator induced a transient increase in the hemolymph (blood) concentration of the insect stress neurohormone, octopamine. Repeated exposure to the mock predator increased basal levels of octopamine, similar to the effects of chronic stress on the basal levels of vertebrate stress hormones. This study is the first to report an increase in the basal levels of an invertebrate stress hormone in response to repeated flight-or-fight stress. Chronic stress reduced weight gain, and decreased feeding and enhanced weight loss after food deprivation in adult female crickets. However, chronic stress also increased the tendency of crickets to produce sustained flight. Therefore, this study supports the hypothesis that increasing basal levels of stress hormones may be a phylogenetically common response to chronically stressful conditions. It also demonstrates that chronic stress has both positive and negative effects in insects.     

Inter-individual variations in wall shear stress and mechanical stress distributions at the carotid artery bifurcation of healthy humans

Fluid shear stress and mechanical wall stress may play a role in the formation of early atherosclerotic lesions, but these quantities are difficult to measure in vivo. Our objective was to quantify these parameters in normal subjects in a clinical setting, and to define regions of low wall shear stress and high mechanical stress. The right carotid bifurcations of five healthy male volunteers were investigated using a novel non-invasive technique which integrates magnetic resonance angiography, ultrasonography, tonometry and state-of-the-art computational fluid dynamics and solid mechanics models. Significant inter-subject variations in patterns as well as magnitude of wall shear stress and mechanical stress were found. In spite of individual variabilities, this study revealed that some regions of the artery wall are exposed simultaneously to low wall shear stress and high mechanical stress and that these regions correspond to areas where atherosclerotic plaque develops. The coexistence of regions of low wall shear stress and high tensile stress may be an important determinant of the formation of atheroma in human arteries.     

Stress granules: RNP-containing cytoplasmic bodies arising in stress: Structure and mechanism of organization

The review considers recent data on stress granules, which are dense RNP-containing cytoplasmic bodies that arise under stress conditions, e.g., in heat shock, UV irradiation, energy depletion, and oxidative stress. There is evidence that stress granules accumulate incomplete initiation complexes containing mRNA associated with proteins, small ribosomal subunits, and some translation initiation factors, and that stress granules are formed when cells are depleted of the ternary complex (eIF2-tRNA^Met-GTP), in particular, upon eIF2A phosphorylation or a decrease in GTP. Large ribosomal subunits and the ternary complex are absent from stress granules. The structural basis of stress granules is known. It is probable, however, that RNA-binding protein TIA-1, which normally occurs in the nucleus, forms prion-like aggregates that serve as scaffolds for other components of stress granules. The cytoskeleton facilitates the accumulation of stress granule components in local cytoplasmic sites. Studies of the formation and composition of stress granules are important for a better understanding of the regulation of translation initiation in vivo and the mechanisms of the cell response to stress factors.     

Role of viscoelastic properties of differentiated SH-SY5Y human neuroblastoma cells in cyclic shear stress injury

Shear stress and strain lead to neurodegeneration in vivo during head injury, glaucoma, and certain repetitive motion disorders. In vitro, shear stress and strain have been shown to lead to cell injury in a number of models using neurons and neuron-like cells. In the present study we examined the relationship between shear stress, strain, and the extent of cell injury in a cyclic shear stress induced model of cell injury using differentiated SH-SY5Y (human neuroblastoma) cells. Shear stress led to cell strain that increased with increasing stress and diminished upon cessation of shear. Strain rate during cyclic application of shear stress increased by over an order of magnitude from the first to all subsequent cycles, suggesting that the cell and/or its polymer network became more elastic upon cyclic shear stress application. To support this conclusion we measured the degree of cytoskeletal polymerization before and after exposure of cells to cyclic shear stress and found that the fraction of polymerized tubulin in the cell relative to total tubulin decreased by a factor of 2 after six cycles of shear stress. The extent of injury, as indicated by the fraction of cells with fragmented DNA, was three times higher for cyclic shear stress than for steady shear stress and may be related to the change in strain rate and/or cytoskeletal reorganization associated with cyclic stress. These findings may aid in understanding the mechanism by which neurons and neuron-like cells respond to cyclic shear stress and strain and lead to new treatments for disease or injury arising from the exposure of neurons to abnormal cyclic or repetitive stress and strain.     

Differential role of microenvironment in microencapsulation for improved cell tolerance to stress

The effect of the microenvironment in alginate–chitosan–alginate (ACA) microcapsules with liquid core (LCM) and solid core (SCM) on the physiology and stress tolerance of Sacchromyces cerevisiae was studied. The suspended cells were used as control. Cells cultured in liquid core microcapsules showed a nearly twofold increase in the intracellular glycerol content, trehalose content, and the superoxide dismutase (SOD) activity, which are stress tolerance substances, while SCM did not cause the significant physiological variation. In accordance with the physiological modification after being challenged with osmotic stress (NaCl), oxidative stress (H₂O₂), ethanol stress, and heat shock stress, the cell survival in LCM was increased. However, SCM can only protect the cells from damaging under ethanol stress. Cells released from LCM were more resistant to hyperosmotic stress, oxidative stress, and heat shock stress than cells liberated from SCM. Based on reasonable analysis, a method was established to estimate the effect of microenvironment of LCM and SCM on the protection of cells against stress factors. It was found that the resistance of LCM to hyperosmotic stress, oxidative stress, and heat shock stress mainly depend on the domestication effect of LCM’s microenvironment. The physical barrier of LCM constituted by alginate–chitosan membrane and liquid alginate matrix separated the cells from the damage of oxidative stress and ethanol stress. The significant tolerance against ethanol stress of SCM attributed to the physical barrier consists of solid alginate–calcium matrix and alginate–chitosan membrane.     

Initial stress in biomechanical models of atherosclerotic plaques

Rupture of atherosclerotic plaques is the underlying cause for the majority of acute strokes and myocardial infarctions. Rupture of the plaque occurs when the stress in the plaque exceeds the strength of the material locally. Biomechanical stress analyses are commonly based on pressurized geometries, in most cases measured by in-vivo MRI. The geometry is therefore not stress-free. The aim of this study is to identify the effect of neglecting the initial stress state on the plaque stress distribution. Fifty 2D histological sections (7 patients, 9 diseased coronary artery segments), perfusion fixed at 100 mmHg, were segmented and finite element models were created. The Backward Incremental method was applied to determine the initial stress state and the zero-pressure state. Peak plaque and cap stresses were compared with and without initial stress. The effect of initial stress on the peak stress was related to the minimum cap thickness, maximum necrotic core thickness, and necrotic core angle. When accounting for initial stress, the general relations between geometrical features and peak cap stress remain intact. However, on a patient-specific basis, accounting for initial stress has a different effect on the absolute cap stress for each plaque. Incorporating initial stress may therefore improve the accuracy of future stress based rupture risk analyses for atherosclerotic plaques.     

The effects of water and multi-nutrient stress on xylem sap chemistry,photosynthesis and transpiration of seedlings of two Eucalypts

Summary Ten seedlings each of Eucalyptus kitsoniana Maiden and Eucalyptus globulus Labill. were subjected to two levels of water stress and two levels of nutrient stress (macro and micro-nutrients) in a greenhouse for 3 weeks. The objectives were to determine the degree to which seedlings show differences in sap chemistry, photosynthesis and transpiration that relate to the environments in which these two species live. Whole plants were then extracted for xylem sap using a pressure chamber and the sap was analyzed for 14 elements using an inductively coupled plasma spectrometer and a nitrometer. For E. kitsoniana water and nutrient stress, applied separately or in combination, significantly reduced leaf conductance, transpiration, photosynthesis and midday water potential. Nutrient stress alone had less effect than water stress on most functions measured. Water stress alone reduced the root/shoot ratio; the combination of water and nutrient stress increased the root/shoot ratio, primarily because of reduced shoot weight. In E. kitsoniana, water stress alone or in combination with nutrient stress increased the xylem sap concentrations of B and Si. Multi-nutrient stress alone, or in combination with water stress, significantly decreased sap Zn and K. For this species, sap N was decreased by nutrient stress, but increased by water stress. E. globulus had significantly lower transpiration rates and less root mass than E. kitsoniana. Slightly lower leaf conductance and photosynthesis were not significant in E. globulus compared to E. kitsoniana. Water and nutrient stress reduced conductance, transpiration (except for nutrient stress) and photosynthesis, and the effects of water stress on E. globulus were greater than the effects of nutrient stress. Midday water potential was reduced by water stress. Water or nutrient stress alone did not alter seedling root/shoot ratio, but the combination of water and nutrient stress significantly increased the root/shoot ratio for both species. For E. globulus, sap concentrations of Mn, Na, Si and K were increased by water stress (alone or in combination with nutrient stress). Sap N increased with water stress or combined stresses, but decreased under nutrient stress alone. When the two species were compared, E. globulus generally had lower or similar nutrient concentrations in the sap, with Ca, Mg, Mn and P significantly lower than in E. kitsoniana. Seedlings of these two species show strong site adaptations to water and nutrient availability.     

Amyotrophic lateral sclerosis-linked FUS/TLS alters stress granule assembly and dynamics

Background

Amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma/translocated in liposarcoma (FUS/TLS or FUS) is concentrated within cytoplasmic stress granules under conditions of induced stress. Since only the mutants, but not the endogenous wild-type FUS, are associated with stress granules under most of the stress conditions reported to date, the relationship between FUS and stress granules represents a mutant-specific phenotype and thus may be of significance in mutant-induced pathogenesis. While the association of mutant-FUS with stress granules is well established, the effect of the mutant protein on stress granules has not been examined. Here we investigated the effect of mutant-FUS on stress granule formation and dynamics under conditions of oxidative stress.

Results

We found that expression of mutant-FUS delays the assembly of stress granules. However, once stress granules containing mutant-FUS are formed, they are more dynamic, larger and more abundant compared to stress granules lacking FUS. Once stress is removed, stress granules disassemble more rapidly in cells expressing mutant-FUS. These effects directly correlate with the degree of mutant-FUS cytoplasmic localization, which is induced by mutations in the nuclear localization signal of the protein. We also determine that the RGG domains within FUS play a key role in its association to stress granules. While there has been speculation that arginine methylation within these RGG domains modulates the incorporation of FUS into stress granules, our results demonstrate that this post-translational modification is not involved.

Conclusions

Our results indicate that mutant-FUS alters the dynamic properties of stress granules, which is consistent with a gain-of-toxic mechanism for mutant-FUS in stress granule assembly and cellular stress response.

     

The stressed synovium

This review focuses on the mechanisms of stress response in the synovial tissue of rheumatoid arthritis. The major stress factors, such as heat stress, shear stress, proinflammatory cytokines and oxidative stress, are discussed and reviewed, focusing on their potential to induce a stress response in the synovial tissue. Several pathways of stress signalling molecules are found to be activated in the synovial membrane of rheumatoid arthritis; of these the most important examples are heat shock proteins, mitogen-activated protein kinases, stress-activated protein kinases and molecules involved in the oxidative stress pathways. The expression of these pathways in vitro and in vivo as well as the consequences of stress signalling in the rheumatoid synovium are discussed. Stress signalling is part of a cellular response to potentially harmful stimuli and thus is essentially involved in the process of synovitis. Stress signalling pathways are therefore new and promising targets of future anti-rheumatic therapies.     

Osmotic induction of stress-responsive gene expression in the lobster Homarus americanus

The American lobster, Homarus americanus, encounters osmotic stress throughout its life cycle. To understand the molecular basis of osmotic stress responses in vivo, we used homologous cDNA probes to characterize the mRNA patterns of lobster HSP70 (=70-kDa heat-shock protein), HSP90 (=90-kDa heat-shock protein), and polyubiquitin during hypo- and hyper-osmotic stress in abdominal muscle and hepatopancreas (a digestive tissue) at 30, 60, and 120 min of osmotic stress. Hypo- and hyper-osmotic stress significantly increased the levels of the mRNAs encoding HSP70 and HSP90 in abdominal muscle. Hyper-osmotic stress increased HSP90 mRNA levels in hepatopancreas, but hypo-osmotic stress did not. Both abdominal muscle and hepatopancreas exhibited significant changes in polyubiquitin gene expression during osmotic stress. In abdominal muscle, polyubiquitin mRNA levels increased during both hypo- and hyper-osmotic stress. Hepatopancreas, however, showed a significant elevation in polyubiquitin mRNA only during hypo-osmotic stress.