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.     

Photosynthetic Enzymes of the C4 Grass Setaria sphacelata Under Water Stress: A Comparison Between Rapidly and Slowly Imposed Water Deficit

Two stress imposing systems were used: a rapid stress developed by allowing excised leaves to loose water by transpiration, and a slow stress developed by withholding watering of potted plants. Carboxylating enzymes reacted differently on both types of stress. Rapid stress increased ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBPCO) activation, but both activities (initial and total) showed little variation with stress. Under slow stress the activation did not change, although both activities decreased much under stress. Phosphoenolpyruvate carboxylase (PEPC) showed a deep decrease of activity under rapid stress, nevertheless, a certain recovery was found under extreme stress. On the other hand, under slow stress the activity of PEPC showed a linear increase with decreasing relative water content. The ratio between physiological and maximal activity increased slightly under both types of stress. The activity of malic enzyme did not change under rapid stress, and decreased linearly under slow stress.     

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.     

Antitoxin MqsA helps mediate the bacterial general stress response

Although it is well recognized that bacteria respond to environmental stress through global networks, the mechanism by which stress is relayed to the interior of the cell is poorly understood. Here we show that enigmatic toxin-antitoxin systems are vital in mediating the environmental stress response. Specifically, the antitoxin MqsA represses rpoS, which encodes the master regulator of stress. Repression of rpoS by MqsA reduces the concentration of the internal messenger 3,5-cyclic diguanylic acid, leading to increased motility and decreased biofilm formation. Furthermore, the repression of rpoS by MqsA decreases oxidative stress resistance via catalase activity. Upon oxidative stress, MqsA is rapidly degraded by Lon protease, resulting in induction of rpoS. Hence, we show that external stress alters gene regulation controlled by toxin-antitoxin systems, such that the degradation of antitoxins during stress leads to a switch from the planktonic state (high motility) to the biofilm state (low motility).     

Stress activation of Bacillus subtilis sigma B can occur in the absence of the sigma B negative regulator RsbX.

Environmental stress activates sigma B, the general stress response sigma factor of Bacillus subtilis, by a pathway that is negatively controlled by the RsbX protein. To determine whether stress activation of sigma B occurs by a direct effect of stress on RsbX, we constructed B. subtilis strains which synthesized various amounts of RsbX or lacked RsbX entirely and subjected these strains to ethanol stress. Based on the induction of a sigma B-dependent promoter, stress activation of sigma B can occur in the absence of RsbX. Higher levels of RsbX failed to detectably influence stress induction, but reduced levels of RsbX resulted in greater and longer-lived sigma B activation. The data suggest that RsbX is not a direct participant in the sigma B stress induction process but rather serves as a device to limit the magnitude of the stress response.     

microRNA在植物逆境胁迫应答中的作用

逆境胁迫严重影响着全世界范围内的作物产量。为减少逆境胁迫损伤,植物在长期的进化过程中形成了多级别（转录、转录后和翻译、翻译后）的基因表达调控应答机制。最近研究发现,内源microRNA（miRNA）在植物逆境胁迫应答中具有重要的调节作用。在逆境胁迫发生时,一些miRNA会表达上调,而另一些miRNA会表达下调;miRNA正是通过下调胁迫应答过程的负调节子靶基因和上调胁迫应答过程中的正调节子靶基因,来执行生理调控功能。通过综述miRNA在植物逆境应答中的作用,以期全面的了解逆境胁迫调控网络。     

Salt stress and hyperosmotic stress regulate the expression of different sets of genes in Synechocystis sp. PCC 6803.

Acclimation of microorganisms to environmental stress is closely related to the expression of various genes. We report here that salt stress and hyperosmotic stress have different effects on the cytoplasmic volume and gene expression in Synechocystis sp. PCC 6803. DNA microarray analysis indicated that salt stress strongly induced the genes for some ribosomal proteins. Hyperosmotic stress strongly induced the genes for 3-ketoacyl-acyl carrier protein reductase and rare lipoprotein A. Genes whose expression was induced both by salt stress and by hyperosmotic stress included those for heat-shock proteins and the enzymes for the synthesis of glucosylglycerol. We also found that each kind of stress induced a number of genes for proteins of unknown function. Our findings suggest that Synechocystis recognizes salt stress and hyperosmotic stress as different stimuli, although mechanisms common to the responses to each form of stress might also contribute to gene expression.     

A transgenic mouse model for monitoring endoplasmic reticulum stress

Endoplasmic reticulum (ER) stress is caused by the accumulation of unfolded proteins in the ER lumen, and is associated with vascular and neurodegenerative diseases. Although the connection between ER stress and some disease-related proteins has been studied using animal models of these diseases, no in vivo data concerning ER stress are available. Here we report a new method for monitoring ER stress in vivo, based on XBP-1 mRNA splicing by inositol requiring-1 (IRE-1) during ER stress. The stress indicator was constructed by fusing XBP-1 and venus, a variant of green fluorescent protein. During stress, the spliced indicator mRNA is translated into an XBP-1-venus fusion protein, which can be detected by its fluorescence. We used transgenic animals expressing the ER stress indicator to show that it can be used to monitor physiological and pathological ER stress in vivo.     

Stress-responsive hypothalamic-nucleus accumbens regulation may vary depending on stressors

This study was conducted to determine if the stress-responsive hypothalamic-nucleus accumbens (NAc) regulation is a stressor specific event. Male SD rats were subjected to restraint or cold stress for 2 h, and then mRNA expression of corticotropin-releasing hormone (CRH) in the hypothalamic paraventricular nucleus (PVN) was examined by in situ hybridization and the plasma corticosterone levels by radioimmunoassay. Neuronal activations in the PVN and the NAc were examined by c-Fos immunohistochemistry and the brain GABA contents by HPLC. Both restraint and cold stresses increased c-Fos expression in the PVN and the plasma corticosterone; however, CRH expression in PVN was increased only by restraint, but not by cold, stress. Restraint stress significantly increased the NAc neuronal activation, but cold stress failed to do so. Restraint stress increased the NAc-GABA contents and cold stress did the hypothalamic GABA. Results suggest that the HPA axis regulation responding to restraint stress, but not cold stress, may involve the NAc neuronal activation in relation with GABAergic neurotransmission. Additionally, CRH expression in the PVN may not play a major role in the elevation of plasma corticosterone responding to cold stress.     

Individual behavioral and autonomic response to emotional stress in humans

Healthy subjects (n = 53) performed a sound version of the proof-reading test under normal conditions and in the state of emotional stress. Stress resistance was evaluated by the overall number of errors. The propensity to active or passive response to stress was evaluated by the number of "false alarms" and signal omissions. The reaction pattern to emotional stress in stress-resistant subjects, irrespective of their behavioral features, consisted in an increase in sympathetic effects on the cardiac rhythm and a decrease in the reaction time to significant signals. In subjects with low stress resistance, no statistically significant changes in the level of sympathetic tone and reaction time were revealed in the state of stress. Subjects with active behavioral response to stress, irrespective of their level of stress resistance, were characterized by aggressiveness, boldness and independence. Subjects with passive response to stress were inclined to conformism, dependence, and passivity.     

Dynamic changes in small nuclear ribonucleoproteins of heat-stressed and thermotolerant HeLa cells

Living organisms when subjected to various forms of environmental stress mount a physiological response to survive the long- and short-term ill-effects of the stress. The stress response may involve selective shut down of non-essential metabolic activities and the repair of macromolecular damage resulting from the stress. Messenger RNA splicing in cultured HeLa cells is one of the processes inhibited by heat stress. Splicing is protected from such inhibition in stress-preconditioned cells that have acquired a tolerant state characterised by increased cell survival and resistance to other environmental stresses. Stress tolerant cells have heat shock proteins (HSPs) that had been induced by the preconditioning process. To examine the biochemical changes induced by stress in the splicing apparatus, we analysed the small nuclear ribonucleoprotein (snRNP) particles associated with spliceosomes in normal, stressed, and stress tolerant cells. We show that (a) the spliceosomal component U4/U5/U6 snRNP particle is disassembled by heat stress into intermediates of splicing assembly, (b) prior induction of stress tolerance protects the structural and functional integrity of snRNPs if cells are subsequently exposed to a severe stress and (c) a novel 65 kDa protein is associated with small nuclear ribonucleoprotein particles in stress tolerant cells.     

Characterization of the Adaptive Response to Trichloroethylene-Mediated Stresses in Ralstonia pickettii PKO1

In Ralstonia pickettii PKO1, a denitrifying toluene oxidizer that carries a toluene-3-monooxygenase (T3MO) pathway, the biodegradation of toluene and trichloroethylene (TCE) by the organism is induced by TCE at high concentrations. In this study, the effect of TCE preexposure was studied in the context of bacterial protective response to TCE-mediated toxicity in this organism. The results of TCE degradation experiments showed that cells induced by TCE at 110 mg/liter were more tolerant to TCE-mediated stress than were those induced by TCE at lower concentrations, indicating an ability of PKO1 to adapt to TCE-mediated stress. To characterize the bacterial protective response to TCE-mediated stress, the effect of TCE itself (solvent stress) was isolated from TCE degradation-dependent stress (toxic intermediate stress) in the subsequent chlorinated ethylene toxicity assays with both nondegradable tetrachloroethylene and degradable TCE. The results of the toxicity assays showed that TCE preexposure led to an increase in tolerance to TCE degradation-dependent stress rather than to solvent stress. The possibility that such tolerance was selected by TCE degradation-dependent stress during TCE preexposure was ruled out because a similar extent of tolerance was observed in cells that were induced by toluene, whose metabolism does not produce any toxic products. These findings suggest that the adaptation of TCE-induced cells to TCE degradation-dependent stress was caused by the combined effects of solvent stress response and T3MO pathway expression.     

Recoil and stiffening by adherent leukocytes in response to fluid shear

Prolonged exposure to fluid shear stress alters leukocyte functions associated with the immune response. We examined the initial response of freshly isolated human leukocytes to fluid shear stress under high magnification. Adherent leukocytes exhibit a rapid biomechanical response to physiological levels of fluid shear stress. After passive displacement in the direction of a constant fluid shear stress, adherent leukocytes actively recoil back in the opposite direction of the fluid flow. Recoil is observed within seconds of the applied fluid shear stress. Simultaneously, fluid shear stress induces a stiffening of the cell. The immediate cell displacement in response to a step increase in fluid shear stress is greatly attenuated in subsequent steps compared to the initial fluid shear stress step. Recoil is not mediated by actin polymerization-dependent mechanisms, as cytochalasin D had no effect on this early response. However, stiffening was determined in part by an intact actin cytoskeleton. Inhibiting myosin force generation with ML-7 abolished the recoil and stiffening responses, implicating force generation by myosin as an important contributor to the early leukocyte response to fluid shear stress. This initial shear stress response may be particularly important in facilitating leukocyte attachment under sustained fluid shear stress by the flowing blood in the microcirculation.     

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.     

Bundle sheath chloroplasts of rice are more sensitive to drought stress than mesophyll chloroplasts

We investigated the effects of drought stress on the ultrastructure of chloroplasts in rice plants. After the seedlings were grown in a glasshouse for 1 month, they were treated for drought stress using two methods. One drought treatment was imposed by reducing the water supply to the plants for 1 month. The other was imposed by withholding water for 2 weeks to examine the withering process of leaves by drought stress. The ultrastructural changes of chloroplasts in bundle sheath cells were more prominent than those in mesophyll cells under both drought stress treatments. Ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) content in bundle sheath chloroplasts reduced more dramatically than in mesophyll chloroplasts by drought stress. Although a slight swelling of thylakoids was sometimes observed in bundle sheath chloroplasts in moderate stress for 1 month, the thylakoids were less affected by drought stress than chloroplast envelope. These results suggest that chloroplasts in bundle sheath cells were more sensitive to drought stress than those in mesophyll cells and the thylakoids were less damaged by drought stress compared with chloroplast envelope.     

Focus: The Science of Stress: The Impact of Maternal Antioxidants on Prenatal Stress Effects on Offspring Neurobiology and Behavior

Prenatal stress is a neuropsychiatric risk factor, and effects may be mediated by prenatal oxidative stress. Cell types in the brain sensitive to oxidative stress—cortical microglia and cortical and hippocampal interneurons—may be altered by oxidative stress generated during prenatal stress and may be neurobiological substrates for altered behavior. Our objective was to determine the critical nature of oxidative stress in prenatal stress effects by manipulating prenatal antioxidants. CD1 mouse dams underwent restraint embryonic day 12 to 18 three times daily or no stress and received intraperitoneal injections before each stress period of vehicle, N-acetylcysteine (200 mg/kg daily), or astaxanthin (30 mg/kg before first daily stress, 10 mg/kg before second/third stresses). Adult male and female offspring behavior, microglia, and interneurons were assessed. Results supported the hypothesis that prenatal stress-induced oxidative stress affects microglia; microglia ramification increased after prenatal stress, and both antioxidants prevented these effects. In addition, N-acetylcysteine or astaxanthin was effective in preventing distinct male and female interneuron changes; decreased female medial frontal cortical parvalbumin interneurons was prevented by either antioxidant; increased male medial frontal cortical parvalbumin interneurons was prevented by N-acetylcysteine and decreased male hippocampal GAD67GFP+ cells prevented by astaxanthin. Prenatal stress-induced increased anxiety-like behavior and decreased sociability were not prevented by prenatal antioxidants. Sensorimotor gating deficits in males was partially prevented by prenatal astaxanthin. This study demonstrates the importance of oxidative stress for persistent impacts on offspring cortical microglia and interneurons, but did not link these changes with anxiety-like, social, and sensorimotor gating behaviors.