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Sample records for chronic unpredictable stress-induced

  1. Unpredictable chronic mild stress not chronic restraint stress induces depressive behaviours in mice.

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    Zhu, Shenghua; Shi, Ruoyang; Wang, Junhui; Wang, Jun-Feng; Li, Xin-Min

    2014-10-01

    The chronic stress model was developed on the basis of the stress-diathesis hypothesis of depression. However, these behavioural responses associated with different stress paradigms are quite complex. This study examined the effects of two chronic stress regimens on anxiety-like and depressive behaviours. C57BL/6 mice were subjected to unpredictable chronic mild stress or to chronic restraint stress for 4 weeks. Subsequently, both anxiety-like behaviours (open field, elevated plus maze and novelty suppressed feeding) and depression-like behaviours (tail suspension, forced swim and sucrose preference) were evaluated. Both chronic stress models generated anxiety-like behaviours, whereas only unpredictable chronic mild stress could induce depressive behaviours such as increased immobility and decreased sucrose consumption. These results of the present study provide additional evidence on how chronic stress affects behavioural responses and point to the importance of the validity of animal models of chronic stress in studying depression. PMID:25089805

  2. Adaptogenic potential of curcumin in experimental chronic stress and chronic unpredictable stress-induced memory deficits and alterations in functional homeostasis.

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    Bhatia, Nitish; Jaggi, Amteshwar Singh; Singh, Nirmal; Anand, Preet; Dhawan, Ravi

    2011-07-01

    The present study was designed to investigate the role of curcumin in chronic stress and chronic unpredictable stress-induced memory deficits and alteration of functional homeostasis in mice. Chronic stress was induced by immobilizing the animal for 2 h daily for 10 days, whereas chronic unpredictable stress was induced by employing a battery of stressors of variable magnitude and time for 10 days. Curcumin was administered to drug-treated mice prior to induction of stress. Body weight, adrenal gland weight, ulcer index and biochemical levels of glucose, creatine kinase, cholesterol, corticosterone, thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) were evaluated to assess stress-induced functional changes. Memory deficits were evaluated using the elevated plus maze (EPM) model. Chronic stress and chronic unpredictable stress significantly increased the levels of corticosterone, glucose and creatine kinase and decreased cholesterol levels. Moreover, chronic stress and chronic unpredictable stress resulted in severe memory deficits along with adrenal hypertrophy, weight loss and gastric ulceration. Chronic stress and chronic unpredictable stress also increased oxidative stress assessed in terms of increase in TBARS and decrease in GSH levels. Pretreatment with curcumin (25 and 50 mg/kg p.o.) attenuated chronic stress and chronic unpredictable stress-associated memory deficits, biochemical alterations, pathological outcomes and oxidative stress. It may be concluded that curcumin-mediated antioxidant actions and decrease in corticosterone secretion are responsible for its adaptogenic and memory restorative actions in chronic and chronic unpredictable stress.

  3. Chronic unpredictable stress induces a reversible change of PER2 rhythm in the suprachiasmatic nucleus.

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    Jiang, Wen-Gao; Li, Su-Xia; Zhou, Shuang-Jiang; Sun, Yan; Shi, Jie; Lu, Lin

    2011-07-01

    Many clinical studies have shown that circadian rhythm abnormalities are strongly associated with major depression. The master clock of the circadian system in mammals is located in the suprachiasmatic nucleus (SCN) within the anterior hypothalamus, where Per1 and Per2 are essential core components of circadian rhythm oscillation. Chronic unpredictable stress (CUS) is a reliable animal model of depression with good face, predictive, and constructive validity. In the present study, we investigated the effects of CUS on the circadian expression of PER1 and PER2 in the SCN. We found that CUS led to depressive-like behavior and reduced the amplitude of PER2 oscillation in the SCN, which were blocked by 3 weeks of desipramine (DMI) treatment. 2 weeks after termination of CUS, the decreased peak of PER2 expression returned to control levels, whereas depressive-like behavior remained unchanged. Our findings suggest that the dampened amplitude of PER2 expression in the SCN may participate in the development of depressive-like behavior induced by CUS but is unlikely involved in the long-lasting effects of CUS on depressive-like behavior. PMID:21621196

  4. Neuroprotective Role of Intermittent Hypobaric Hypoxia in Unpredictable Chronic Mild Stress Induced Depression in Rats.

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    Neetu Kushwah

    Full Text Available Hypoxic exposure results in several pathophysiological conditions associated with nervous system, these include acute and chronic mountain sickness, loss of memory, and high altitude cerebral edema. Previous reports have also suggested the role of hypoxia in pathogenesis of depression and related psychological conditions. On the other hand, sub lethal intermittent hypoxic exposure induces protection against future lethal hypoxia and may have beneficial effect. Therefore, the present study was designed to explore the neuroprotective role of intermittent hypobaric hypoxia (IHH in Unpredictable Chronic Mild Stress (UCMS induced depression like behaviour in rats. The IHH refers to the periodic exposures to hypoxic conditions interrupted by the normoxic or lesser hypoxic conditions. The current study examines the effect of IHH against UCMS induced depression, using elevated plus maze (EPM, open field test (OFT, force swim test (FST, as behavioural paradigm and related histological and molecular approaches. The data indicated the UCMS induced depression like behaviour as evident from decreased exploration activity in OFT with increased anxiety levels in EPM, and increased immobility time in the FST; whereas on providing the IHH (5000m altitude, 4hrs/day for two weeks these behavioural changes were ameliorated. The morphological and molecular studies also validated the neuroprotective effect of IHH against UCMS induced neuronal loss and decreased neurogenesis. Here, we also explored the role of Brain-Derived Neurotrophic Factor (BDNF in anticipatory action of IHH against detrimental effect of UCMS as upon blocking of BDNF-TrkB signalling the beneficial effect of IHH was nullified. Taken together, the findings of our study demonstrate that the intermittent hypoxia has a therapeutic potential similar to an antidepressant in animal model of depression and could be developed as a preventive therapeutic option against this pathophysiological state.

  5. Neuroprotective Role of Intermittent Hypobaric Hypoxia in Unpredictable Chronic Mild Stress Induced Depression in Rats.

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    Kushwah, Neetu; Jain, Vishal; Deep, Satayanarayan; Prasad, Dipti; Singh, Shashi Bala; Khan, Nilofar

    2016-01-01

    Hypoxic exposure results in several pathophysiological conditions associated with nervous system, these include acute and chronic mountain sickness, loss of memory, and high altitude cerebral edema. Previous reports have also suggested the role of hypoxia in pathogenesis of depression and related psychological conditions. On the other hand, sub lethal intermittent hypoxic exposure induces protection against future lethal hypoxia and may have beneficial effect. Therefore, the present study was designed to explore the neuroprotective role of intermittent hypobaric hypoxia (IHH) in Unpredictable Chronic Mild Stress (UCMS) induced depression like behaviour in rats. The IHH refers to the periodic exposures to hypoxic conditions interrupted by the normoxic or lesser hypoxic conditions. The current study examines the effect of IHH against UCMS induced depression, using elevated plus maze (EPM), open field test (OFT), force swim test (FST), as behavioural paradigm and related histological and molecular approaches. The data indicated the UCMS induced depression like behaviour as evident from decreased exploration activity in OFT with increased anxiety levels in EPM, and increased immobility time in the FST; whereas on providing the IHH (5000m altitude, 4hrs/day for two weeks) these behavioural changes were ameliorated. The morphological and molecular studies also validated the neuroprotective effect of IHH against UCMS induced neuronal loss and decreased neurogenesis. Here, we also explored the role of Brain-Derived Neurotrophic Factor (BDNF) in anticipatory action of IHH against detrimental effect of UCMS as upon blocking of BDNF-TrkB signalling the beneficial effect of IHH was nullified. Taken together, the findings of our study demonstrate that the intermittent hypoxia has a therapeutic potential similar to an antidepressant in animal model of depression and could be developed as a preventive therapeutic option against this pathophysiological state. PMID:26901349

  6. MDMA Pretreatment Leads to Mild Chronic Unpredictable Stress-induced Impairments in Spatial Learning

    OpenAIRE

    Cunningham, Jacobi I.; Raudensky, Jamie; Tonkiss, John; Yamamoto, Bryan K.

    2009-01-01

    3,4-Methylenedioxymethamphetamine (MDMA) is a drug of abuse world-wide and a selective serotonin (5-HT) neurotoxin. An important factor in the risk of drug abuse and relapse is stress. Although multiple parallels exist between MDMA abuse and stress including effects on 5-HTergic neurotransmission, few studies have investigated the consequences of combined exposure to MDMA and chronic stress. Therefore, rats were pretreated with MDMA and exposed 7 days later to 10 days of mild chronic unpredic...

  7. Behavioural and neurochemical evaluation of Perment an herbal formulation in chronic unpredictable mild stress induced depressive model.

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    Ramanathan, M; Balaji, B; Justin, A

    2011-04-01

    Perment, a polyherbal Ayurvedic formulation that contains equal parts of Clitoria ternatea Linn., Withania somnifera Dun., Asparagus racemosus Linn., Bacopa monniera Linn., is used clinically as mood elevators. The aim of the present study was to explore the behavioural effects and to understand possible mode of action of Perment in stress induced depressive model. Chronic unpredictable mild stress (CUMS) was used to induce depression in rats. Open field exploratory behaviour, elevated plus maze, social interaction and behavioural despair tests were used to assess behaviour. Using standard protocols plasma noradrenaline, serotonin, corticosterone and brain/adrenal corticosterone levels were measured to support the behavioural effects of Perment. Exposure to CUMS for 21 days caused anxiety and depression in rats, as indicated by significant decrease in locomotor activity in the open field exploratory behaviour test and increased immobility period in the behavioural despair test. Perment predominantly exhibited antidepressant action than anxiolytic activity. Further Perment increased the plasma noradrenaline and serotonin levels in stressed rats. No significant alteration in the brain corticosterone level in stressed rats was observed with Perment treatment. However the adrenal corticosterone level is decreased with Perment. It can be concluded that the Perment formulation exhibited synergistic activity, has a significant antidepressant and anxiolytic activity, which may be mediated through adrenergic and serotonergic system activation. Currently the formulation is clinically used as anxiolytic but the present results suggest that the formulation can also be indicated in patients affected with depression. PMID:21614890

  8. A novel isoquinoline compound abolishes chronic unpredictable mild stress-induced depressive-like behavior in mice.

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    Pesarico, Ana Paula; Sartori, Gláubia; Brüning, César A; Mantovani, Anderson C; Duarte, Thiago; Zeni, Gilson; Nogueira, Cristina Wayne

    2016-07-01

    Chronic unpredictable mild stress (CUMS) elicits aspects of cognitive and behavioral alterations that can be used to model comparable aspects of depression in humans. The aim of the present study was to investigate the antidepressant-like potential of 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI), a novel isoquinoline compound, in CUMS, a model that meets face, construct and predictive criteria for validity. Swiss mice were subjected to different stress paradigms daily for a period of 35 days to induce the depressive-like behavior. The animals received concomitant FDPI (0.1 and 1mg/kg, intragastric) or paroxetine (8mg/kg, intraperitoneal) and CUMS. The behavioral tests (splash test, tail suspension test, modified forced swimming test and locomotor activity) were performed. The levels of cytokines, corticosterone and adrenocorticotropic (ACTH) hormones were determined in the mouse prefrontal cortex and serum. The synaptosomal [(3)H] serotonin (5-HT) uptake, nuclear factor (NF)-κB, tyrosine kinase receptor (TrkB) and pro-brain-derived neurotrophic factor (BDNF) levels were determined in the mouse prefrontal cortex. CUMS induced a depressive-like behavior in mice, which was demonstrated in the modified forced swimming, tail suspension and splash tests. FDPI at both doses prevented depressive-like behavior induced by CUMS, without altering the locomotor activity of mice. FDPI at the highest dose prevented the increase in the levels of NF-kB, pro-inflammatory cytokines, corticosterone and ACTH and modulated [(3)H]5-HT uptake and the proBDNF/TrkB signaling pathway altered by CUMS. The present findings demonstrated that FDPI elicited an antidepressant-like effect in a model of stress-induced depression. PMID:27036647

  9. β-Asarone Reverses Chronic Unpredictable Mild Stress-Induced Depression-Like Behavior and Promotes Hippocampal Neurogenesis in Rats

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    Haiying Dong

    2014-04-01

    Full Text Available In this study, we investigated the influence of β-asarone, the major ingredient of Acorus tatarinowii Schott, on depressive-like behavior induced by the chronic unpredictable mild stresses (CUMS paradigm and to clarify the underlying mechanisms. The results show that β-asarone treatment partially reversed the CUMS-induced depression-like behaviors in both the forced swim and sucrose preference tests. The behavioral effects were associated with increased hippocampal neurogenesis indicated by bromodeoxyuridine (BrdU immunoreactivity. β-Asarone treatment significantly increased the expression of brain-derived neurotrophic factor (BDNF at levels of transcription and translation. Moreover, CUMS caused significant reduction in ERK1/2 and CREB phosphorylation, both of which were partially attenuated by β-asarone administration. It is important to note that β-asarone treatment had no effect on total levels or phosphorylation state of any of the proteins examined in ERK1/2-CREB pathway in no stress rats, suggesting that β-asarone acts in a stress-dependent manner to block ERK1/2-CREB signaling. We did not observe a complete reversal of depression-like behaviors to control levels by β-asarone. To our knowledge, the present study is the first to demonstrate that adult neurogenesis is involved in the antidepressant-like behavioral effects of β-asarone, suggesting that β-asarone is a promising candidate for the treatment of depression.

  10. TNFα mediates stress-induced depression by upregulating indoleamine 2,3-dioxygenase in a mouse model of unpredictable chronic mild stress

    OpenAIRE

    Liu, Yu-Ning; Peng, Yun-Li; Lei-Liu,; Wu, Teng-Yun; Zhang, Yi; Lian, Yong-Jie; Yang, Yuan-Yuan; Kelley, Keith W.; Jiang, Chun-Lei; Wang, Yun-Xia

    2015-01-01

    Depression is often preceded by exposure to stressful life events. Chronic stress causes perturbations in the immune system, and up-regulates production of proinflammatory cytokines, which has been proposed to be associated with the pathogenesis of clinical depression. However, the potential mechanisms by which stress-induced proinflammatory cytokines lead to the development of depression are not well understood. Here, we sought to screen the main proinflammatory cytokines and the potential m...

  11. Cytisine, a Partial Agonist of α4β2 Nicotinic Acetylcholine Receptors, Reduced Unpredictable Chronic Mild Stress-Induced Depression-Like Behaviors

    OpenAIRE

    Han, Jing; Wang, Dong-sheng; Liu, Shui-Bing; Zhao, Ming-Gao

    2016-01-01

    Cytisine (CYT), a partial agonist of α4β2-nicotinic receptors, has been used for antidepressant efficacy in several tests. Nicotinic receptors have been shown to be closely associated with depression. However, little is known about the effects of CYT on the depression. In the present study, a mouse model of depression, the unpredictable chronic mild stress (UCMS), was used to evaluate the activities of CYT. UCMS caused significant depression-like behaviors, as shown by the decrease of total d...

  12. Cytisine, a Partial Agonist of α4β2 Nicotinic Acetylcholine Receptors, Reduced Unpredictable Chronic Mild Stress-Induced Depression-Like Behaviors.

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    Han, Jing; Wang, Dong-Sheng; Liu, Shui-Bing; Zhao, Ming-Gao

    2016-05-01

    Cytisine (CYT), a partial agonist of α4β2-nicotinic receptors, has been used for antidepressant efficacy in several tests. Nicotinic receptors have been shown to be closely associated with depression. However, little is known about the effects of CYT on the depression. In the present study, a mouse model of depression, the unpredictable chronic mild stress (UCMS), was used to evaluate the activities of CYT. UCMS caused significant depression-like behaviors, as shown by the decrease of total distances in open field test, and the prolonged duration of immobility in tail suspension test and forced swimming test. Treatment with CYT for two weeks notably relieved the depression-like behaviors in the UCMS mice. Next, proteins related to depressive disorder in the brain region of hippocampus and amygdala were analyzed to elucidate the underlying mechanisms of CYT. CYT significantly reversed the decreases of 5-HT1A, BDNF, and mTOR levels in the hippocampus and amygdala. These results imply that CYT may act as a potential anti-depressant in the animals under chronic stress. PMID:27098858

  13. The Antidepressant Effect of Angelica sinensis Extracts on Chronic Unpredictable Mild Stress-Induced Depression Is Mediated via the Upregulation of the BDNF Signaling Pathway in Rats

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    Jun Shen

    2016-01-01

    Full Text Available Angelica sinensis (AS, a traditional Chinese herbal medicine, has pharmaceutical effects on menstrual illness, cerebrovascular diseases, cardiovascular diseases, and cognitive impairments. However, until recently, few studies had explored its antidepressant effect. The current study attempts to investigate the effect of AS extracts on chronic unpredictable mild stress- (CUMS- induced depression in rats. Male SD rats were exposed to a CUMS-inducing procedure for 5 weeks, resulting in rodent depressive behaviors that included reduced sucrose consumption and lessened sucrose preference ratios in sucrose preference test, prolonged immobility times and decreased struggling time in force swim test, and decreased locomotor activity in open field test. Moreover, the expression of brain derived neurotrophic factor (BDNF and the phosphorylation of cAMP-response element binding protein (CREB and extracellular signal-regulated protein kinase (ERK 1/2 were markedly decreased in the hippocampus in depressed rats. However, chronically treating the depressed rats with AS (1 g/kg normalized their depression-related behaviors and molecular profiles. In conclusion, in the present study, we show that AS extracts exerted antidepressant effects that were mediated by the BDNF signaling pathway: in AS-treated depressed rats, the expression of the BDNF protein and the phosphorylation of its downstream targets (ERK 1/2, CREB were upregulated in the hippocampus.

  14. Hydrogen Sulfide Protects against Chronic Unpredictable Mild Stress-Induced Oxidative Stress in Hippocampus by Upregulation of BDNF-TrkB Pathway

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    Zou, Wei; Wang, Chun-Yan; Tan, Hui-Ying; Zeng, Hai-Ying; Zhang, Ping; Gu, Hong-Feng

    2016-01-01

    Chronic unpredictable mild stress (CUMS) induces hippocampal oxidative stress. H2S functions as a neuroprotectant against oxidative stress in brain. We have previously shown the upregulatory effect of H2S on BDNF protein expression in the hippocampus of rats. Therefore, we hypothesized that H2S prevents CUMS-generated oxidative stress by upregulation of BDNF-TrkB pathway. We showed that NaHS (0.03 or 0.1 mmol/kg/day) ameliorates the level of hippocampal oxidative stress, including reduced levels of malondialdehyde (MDA) and 4-hydroxy-2-trans-nonenal (4-HNE), as well as increased level of glutathione (GSH) and activity of superoxide dismutase (SOD) in the hippocampus of CUMS-treated rats. We also found that H2S upregulated the level of BDNF and p-TrkB protein in the hippocampus of CUMS rats. Furthermore, inhibition of BDNF signaling by K252a, an inhibitor of the BDNF receptor TrkB, blocked the antioxidant effects of H2S on CUMS-induced hippocampal oxidative stress. These results reveal the inhibitory role of H2S in CUMS-induced hippocampal oxidative stress, which is through upregulation of BDNF/TrkB pathway. PMID:27525050

  15. Metabonomic identification of the effects of the Zhimu-Baihe saponins on a chronic unpredictable mild stress-induced rat model of depression.

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    Du, Hongli; Wang, Keqing; Su, Li; Zhao, Hongxia; Gao, Songyan; Lin, Qishan; Ma, Xiaofang; Zhu, Baokang; Dong, Xin; Lou, Ziyang

    2016-09-01

    The herbal pair Zhimu-Baihe (Zhimu: Anemarrhena asphodeloides; Baihe: Lilium brownii var. viridulum) is a traditional Chinese medicament used for the treatment of depression. However, the relevant mechanisms of action has not been clarified. This study investigated the anti-depressant activity of the total saponins from Zhimu and Baihe and the mechanisms underlying using a chronic unpredictable mild stress (CUMS)-induced rat model of depression. High performance liquid chromatography with electrochemical detection (HPLC-ECD) was applied to determine the levels of three monoamine neurotransmitters, 5-hydroxytryptamine (5-HT), noradrenaline (NE) and dopamine (DA), in the rat hippocampus. Optimized pretreatment of samples and mass spectrometry conditions were used to analyse the metabonomic profile of the hippocampus. The 5-HT and NE levels in the CUMS group were reduced compared with the control group, whereas all groups had similar DA levels. The metabonomic profile of the hippocampus revealed 32 differential metabolites between the CUMS and control group, among which 18 metabolites were significantly recovered in the Anemarrhena saponins and Lilium saponins (AL) combination intervention group. These results suggested an anti-depressant effect of AL. Moreover, 24 metabolites in AL group were better recovered compared with the Anemarrhena saponins (AS) or Lilium saponins (LS) intervention groups, suggesting a synergetic effect of AS and LS in the treatment of depression. The anti-depressant effect might be related to the regulation of several metabolic pathways, including monoamine neurotransmitter synthesis (especially 5-HT and NE), and amino acid, fatty acid, and phospholipid metabolism in rats. PMID:27371920

  16. Neuropharmacological evaluation of a novel 5-HT3 receptor antagonist (6g on chronic unpredictable mild stress-induced changes in behavioural and brain oxidative stress parameters in mice

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    Shvetank Bhatt

    2014-01-01

    Full Text Available Aim: The aim of the study was to evaluate a novel 5 HT 3 receptor antagonist (6g on chronic stress induced changes in behavioural and brain oxidative stress parameter in mice. A complicated relationship exists among stressful stimuli, body′s reaction to stress and the onset of clinical depression. Chronic unpredictable stressors can produce a situation similar to human depression, and such animal models can be used for the preclinical evaluation of antidepressants. Materials and Methods: In the present study, a novel and potential 5-HT 3 receptor antagonist (4-benzylpiperazin-1-yl(3-methoxyquinoxalin-2-yl methanone (6g with good Log P (3.08 value and pA 2 (7.5 values, synthesized in our laboratory was investigated to study the effects on chronic unpredictable mild stress (CUMS-induced behavioural and biochemical alterations in mice. Mice were subjected to different stress paradigms daily for a period of 28 days to induce depressive-like behaviour. Results: The results showed that CUMS caused depression-like behaviour in mice, as indicated by the significant (P < 0.05 decrease in sucrose consumption and locomotor activity and increase in immobility the forced swim test. In addition, it was found that lipid peroxidation and nitrite levels were significantly (P < 0.05 increased, whereas glutathione levels, superoxide dismutase and catalase activities decreased in brain tissue of CUMS-treated mice. ′6g′ (1 and 2 mg/kg, p.o., 21 days and fluoxetine treatment (20 mg/kg, p.o., 21 days significantly (P < 0.05 reversed the CUMS-induced behavioural (increased immobility period, reduced sucrose preference and decreased locomotor activity and biochemical (increased lipid peroxidation; decreased glutathione levels, superoxide dismutase and catalase activities. However fluoxetine treatment (20 mg/kg, p.o., 21 days significantly decreased the nitrite level in the brain while ′6g′ (1 and 2 mg/kg, p.o., 21 days did not show significant (P < 0

  17. Liquiritigenin reverses depression-like behavior in unpredictable chronic mild stress-induced mice by regulating PI3K/Akt/mTOR mediated BDNF/TrkB pathway.

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    Tao, Weiwei; Dong, Yu; Su, Qiang; Wang, Hanqing; Chen, Yanyan; Xue, Wenda; Chen, Chang; Xia, Baomei; Duan, Jinao; Chen, Gang

    2016-07-15

    Major depression is a common long-lasting or recurrent psychiatric disease with high lifetime prevalence and high incidence of suicide. The main purpose of the current study was to verify whether liquiritigenin conferred an antidepressant-like effect on the depressive mouse model established by unpredictable chronic mild stress (UCMS) and explore its possible mechanism. The results of depression-related behaviors including sucrose preference test (SPT), open field test (OFT), forced swimming test (FST) and tail suspension test (TST) indicated that both liquiritigenin (7.5mg/kg, 15mg/kg) and fluoxetine (20mg/kg) dramatically improved the depression symptoms. Enzyme-linked immunosorbent assay (ELISA) revealed that treatment with liquiritigenin significantly reduced the concentrations of pro-inflammatory cytokines including interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF)-α in serum and hippocampus. Compared with the UCMS group, the administrations of liquiritigenin, increased levels of superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), and decreased Malondialdehyde (MDA) content. Meanwhile, glucocorticoids (GC) content was reduced in the liquiritigenin group, which suggested that liquiritigenin exhibiting the ameliorative effect on activated hypothalamic-pituitary-adrenal (HPA) axis stimulated with UCMS. Mice treated with liquiritigenin showed restored levels of neurotransmitter norepinephrine (NE) and serotonin (5-HT). Western blot analysis displayed up-regulated expressions of p-phosphatidylinositol 3-kinase (PI3K), p-Akt, p- mammalian target of rapamycin (mTOR), p-tropomyosin-related kinase B (TrkB), brain-derived neurotrophic factor (BDNF). Thus, it was supposed that liquiritigenin might be useful for the treatment of chronic depression possibly through PI3K/Akt/mTOR mediated BDNF/TrkB pathway. PMID:27113683

  18. Utility of the chronic unpredictable mild stress model in research on new antidepressants

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    Pekala Karolina

    2014-06-01

    Full Text Available Unpredictable chronic mild stress model was developed as an animal model of depression more than 20 years ago. Essential for this model is that after prolonged exposure of tested animals to a series of unpredictable mild stressors, a condition similar to anhedonia develops, which is observed in the majority of depressive disorders. Unpredictable chronic mild stress model is used nowadays in numerous studies related to the neurobiological and biochemical changes associated with depressive illness. Their results confirm that chronic unpredictable mild stress induces in tested animals a number of changes, which reflect those seen in depressive disorders. Because the effects of unpredictable chronic mild stress can be used in a more accurate diagnosis of the pathophysiology of depressive illness and expand knowledge of its pharmacotherapy, therefore research in this area has been continued all the time.

  19. Effect of shuyusan on neuropeptide Y and serotonin expression in the hippocampalneurons of rats with chronic mild unpredictable stress-induced depression%舒郁散对慢性应激抑郁大鼠神经肽及海马神经元5-HT表达的影响

    Institute of Scientific and Technical Information of China (English)

    陈利平; 孙艳; 王发渭; 段冬梅; 胡亚卓

    2011-01-01

    Objective To investigate the effect of Shuyusan decoction on neuropeptide Y (NPY) and serotonin (5-HT) expression in the hippocampus and plasma of rats with chronic mild unpredictable stressors depression. Methods Fifty Wistar rats were randomly divided into 5 groups, namely the normal control group, model group, fluoxetine group, and high- and low-dose Shuyusan groups. Except for those in the normal control group, all the rats were subjected to chronic mild unpredicted stress for 21 consecutive days with corresponding treatments. Open-field test was used to assess the behavioral changes of the rats. The content of NPY in the hippocampus and plasma was detected by competitive enzyme-linked immunosorbent assay, and immunocytochemistry was used to determine the expression of 5-HT in the hippocampus. Results NPY levels in the hippocampus and plasma was significantly decreased in the model group as compared with that in the normal control group (P<0.05). Treatments with fluoxetine and high-dose Shuyusan both significantly increased NPY levels in the hippocampus and plasma in the depressive rats (P<0.05), resulting also in significantly increased 5-HT-immunoreactive neurons in the cerebral cortex and hippocampus and the average optical density (P<0.05). Conclusion Shuyusan decoction can effectively increase plasma and hippocampus NPY levels and the number of 5-HT-positive neurons in the cerebral cortex and happocampus of rats with chronic mild unpredictable stress-induced depression.%目的 观察中药舒郁散对慢性应激抑郁大鼠神经肽(neuropeptide Y,NPY)及海马5-HT表达的影响.方法 50只Wistar大鼠随机分为正常对照组、模型组、百忧解组、舒郁散小剂量组、舒郁散大剂量组;对大鼠进行21 d的应激刺激建立慢性应激抑郁大鼠模型,采用open-field方法观察各组处理前、后2 min内大鼠行走路线及格子交叉点数的变化,了解大鼠行为的改变,用竞争酶联免疫分析法测定各组大鼠

  20. THE DELAYED EFFECTS OF CHRONIC UNPREDICTABLE STRESS ON ANXIETY MEASURES

    OpenAIRE

    Matuszewich, Leslie; Karney, Jared J.; Carter, Samantha R.; Janasik, Steven P.; O’Brien, Johanna L.; Friedman, Ross D.

    2006-01-01

    Previous research has found that exposure to unpredictable stress can augment anxiety in humans and animals. The appearance of anxiety symptoms in humans frequently develop after stress exposure has terminated, but few rodent studies have systematically examined the delayed anxiogenic effects of unpredictable stress. Therefore, the current study investigated whether anxiety-like behaviors in rats would increase at several time intervals following exposure to chronic unpredictable stress (CUS)...

  1. 高半胱氨酸对慢性应激性抑郁大鼠海马谷氨酸及其受体的调节%Modulation of hippocampal glutamate and NMDA/AMPA receptor by homocysteine in chronic unpredictable mild stress-induced rat depression

    Institute of Scientific and Technical Information of China (English)

    刘慧; 问黎敏; 乔卉; 安书成

    2013-01-01

    depression-like behaviors, but also decreased the Glu content induced by Hcy remarkably. These results suggest that CUMS may contribute to the production and release of Hcy via hippocampal astrocytes. Through the increase of expression of NR1/ NR2B/GluR2/3 and level of p-NMDAR, and the decrease of level of p-AMPAR, Hcy results in elevation of Glu level, which leads to depression-like behaviors in the end. In a word, the Hcy released by astrocytes plays an important role in stress-induced elevation of Glu content and variation of NMDA/AMPA receptors in hippocampus.%本文旨在探讨应激性抑郁样行为发生中海马胶质细胞释放高半胱氨酸(homocysteine,Hcy)的作用,以及与谷氨酸(glutamic acid,Glu)及其受体的关系.建立慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)性抑郁模型,海马单侧微量注射Hcy、N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体拮抗剂MK-801和α-氨基羟甲基异恶唑丙酸(α-amino-3-hudroxy-5-methylisoxazole-4-propionic acid,AMPA)受体拮抗剂NBQX,观察大鼠体重变化率,并通过糖水偏爱测试、旷场实验和悬尾实验等检测行为表现,采用高效液相色谱法(high-performance liquid chromatography,HPLC)和Western blot方法检测海马内Glu水平及其NMDA受体和AMPA受体关键亚基的变化,运用酶联免疫吸附(enzyme linked immunosorbent assay,ELISA)法测定谷氨酸NMDA受体和AMPA受体的磷酸化水平和Hcy含量.结果显示,CUMS诱发大鼠表现出明显的抑郁样行为,且海马Glu和Hcy含量、NMDA受体的NR1亚基和NR2B亚基表达及其磷酸化水平显著升高,而AMPA受体的GluR2/3亚基含量及其磷酸化水平均明显降低;正常大鼠海马微量注射Hcy,也表现出抑郁样行为,且Glu含量明显升高,NMDA受体NR1亚基和NR2B亚基及其磷酸化水平均显著升高,AMPA受体的GluR2/3亚基含量明显升高,但其磷酸化水平明显降低;CUMS和海马注射Hcy引起的抑郁样行为可被

  2. Inducible nitric oxide synthase is involved in the modulation of depressive behaviors induced by unpredictable chronic mild stress

    OpenAIRE

    Peng Yun-Li; Liu Yu-Ning; Liu Lei; Wang Xia; Jiang Chun-Lei; Wang Yun-Xia

    2012-01-01

    Abstract Background Experiences and inflammatory mediators are fundamental in the provocation of major depressive disorders (MDDs). We investigated the roles and mechanisms of inducible nitric oxide synthase (iNOS) in stress-induced depression. Methods We used a depressive-like state mouse model induced by unpredictable chronic mild stress (UCMS). Depressive-like behaviors were evaluated after 4 weeks of UCMS, in the presence and absence of the iNOS inhibitor N-(3-(aminomethyl)benzyl)acetamid...

  3. Antidepressant-like activity of gallic acid in mice subjected to unpredictable chronic mild stress.

    Science.gov (United States)

    Chhillar, Ritu; Dhingra, Dinesh

    2013-08-01

    This study was designed to evaluate antidepressant-like activity of gallic acid in Swiss young male albino mice subjected to unpredictable chronic mild stress and to explore the possible underlying mechanisms for this activity. Gallic acid (5, 10, 20 mg/kg, i.p.) and fluoxetine (10 mg/kg, i.p.) per se were administered daily to unstressed mice and other groups of mice subjected to unpredictable mild stress, 30 min after the injection for 21 successive days. The antidepressant-like activity was evaluated using forced swim test (FST) and sucrose preference test. Stress significantly increased immobility period of mice in FST. Gallic acid (10 and 20 mg/kg, i.p.) and fluoxetine significantly decreased immobility period of unstressed and stressed mice in FST and prevented the stress-induced decrease in sucrose preference, indicating significant antidepressant-like activity. There was no significant effect on locomotor activity of the mice by the drugs. Gallic acid (10 and 20 mg/kg, i.p.) significantly decreased Monoamine oxidase-A (MAO-A) activity, malondialdehyde levels, and catalase activity in unstressed mice; and significantly prevented the stress-induced decrease in reduced glutathione and catalase activity; and also significantly prevented stress-induced increase in MAO-A activity, malondialdehyde levels, plasma nitrite, and corticosterone levels. Thus, gallic acid showed antidepressant-like activity in unstressed and stressed mice probably due to its antioxidant activity and through inhibition of MAO-A activity and decrease in plasma nitrite levels. In addition, gallic acid also showed antidepressant-like activity in stressed mice probably through decrease in plasma corticosterone levels.

  4. Chronic psychosocial stress induces visceral hyperalgesia in mice.

    Science.gov (United States)

    Tramullas, Mónica; Dinan, Timothy G; Cryan, John F

    2012-05-01

    Experimental and clinical evidence has shown that chronic stress plays an important role in the onset and/or exacerbation of symptoms of functional gastrointestinal disorders. Here, we aimed to investigate whether exposure to a chronic and temporally unpredictable psychosocial stressor alters visceral and somatic nociception as well as anxiety-related behaviour. In male C57BL/6J mice, chronic stress was induced by repeated exposure to social defeat (SD, 2 h) and overcrowding (OC, 24 h) during 19 consecutive days. Visceral and somatic nociception was evaluated by colorectal distension and a hot plate, respectively. The social interaction test was used to assess social anxiety. Mice exposed to psychosocial stress developed visceral hyperalgesia and somatic hypoalgesia 24 h following the last stress session. SD/OC mice also exhibited social anxiety-like behaviour. All these changes were also associated with physiological alterations, measured as a decreased faecal pellet output and hypothalamic-pituitary-adrenal (HPA) axis disruption. Taken together, these data confirm that this mouse model of chronic psychosocial stress may be useful for studies on the pathophysiological mechanisms underlying such stress-associated disorders and to further test potential therapies.

  5. Post-training reward partially restores chronic stress induced effects in mice.

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    Sergiu Dalm

    Full Text Available Reduced responsiveness to positive stimuli is a core symptom of depression, known as anhedonia. In the present study, we assessed the expression of anhedonia in our chronic stress mouse model using a subset of read-out parameters. In line with this, we investigated in how far chronic stress would affect the facilitating effect of post-training self-administration of sugar, as we previously observed in naïve mice. Male C57BL/6J mice were repeatedly and at unpredictable times exposed to rats (no physical contact over the course of two weeks. Following novelty exploration, (non- spatial learning and memory processes with and without post-training sugar acting as reinforcer, emotionality, reward sensitivity and corticosterone levels were determined. We found that (1 the effects of chronic stress persisted beyond the period of the actual rat exposure. (2 Post-training self-administration of sugar as reinforcer improved spatial performance in naïve mice, whereas (3 in stressed mice sugar partially "normalized" the impaired performance to the level of controls without sugar. Chronic stress (4 increased behavioral inhibition in response to novelty; (5 induced dynamic changes in the pattern of circadian corticosterone secretion during the first week after rat stress and (6 increased the intake of sucrose and water. (7 Chronic stress and sugar consumed during spatial training facilitated the memory for the location of the sucrose bottle weeks later. Concluding, our chronic stress paradigm induces the expression of anhedonia in mice, at different levels of behavior. The behavioral inhibition appears to be long lasting in stressed mice. Interestingly, sugar consumed in close context with spatial learning partially rescued the stress-induced emotional and cognitive impairments. This suggests that reward can ameliorate part of the negative consequences of chronic stress on memory.

  6. Effects of Active Mastication on Chronic Stress-Induced Bone Loss in Mice

    OpenAIRE

    Azuma, Kagaku; Furuzawa, Manabu; Fujiwara, Shu; YAMADA, Kumiko; Kubo, Kin-Ya

    2015-01-01

    Chronic psychologic stress increases corticosterone levels, which decreases bone density. Active mastication or chewing attenuates stress-induced increases in corticosterone. We evaluated whether active mastication attenuates chronic stress-induced bone loss in mice. Male C57BL/6 (B6) mice were randomly divided into control, stress, and stress/chewing groups. Stress was induced by placing mice in a ventilated restraint tube (60 min, 2x/day, 4 weeks). The stress/chewing group was given a woode...

  7. Chronic stress-induced hippocampal vulnerability: the glucocorticoid vulnerability hypothesis.

    Science.gov (United States)

    Conrad, Cheryl D

    2008-01-01

    The hippocampus, a limbic structure important in learning and memory, is particularly sensitive to chronic stress and to glucocorticoids. While glucocorticoids are essential for an effective stress response, their oversecretion was originally hypothesized to contribute to age-related hippocampal degeneration. However, conflicting findings were reported on whether prolonged exposure to elevated glucocorticoids endangered the hippocampus and whether the primate hippocampus even responded to glucocorticoids as the rodent hippocampus did. This review discusses the seemingly inconsistent findings about the effects of elevated and prolonged glucocorticoids on hippocampal health and proposes that a chronic stress history, which includes repeated elevation of glucocorticoids, may make the hippocampus vulnerable to potential injury. Studies are described to show that chronic stress or prolonged exposure to glucocorticoids can compromise the hippocampus by producing dendritic retraction, a reversible form of plasticity that includes dendritic restructuring without irreversible cell death. Conditions that produce dendritic retraction are hypothesized to make the hippocampus vulnerable to neurotoxic or metabolic challenges. Of particular interest is the finding that the hippocampus can recover from dendritic retraction without any noticeable cell loss. When conditions surrounding dendritic retraction are present, the potential for harm is increased because dendritic retraction may persist for weeks, months or even years, thereby broadening the window of time during which the hippocampus is vulnerable to harm, called the 'glucocorticoid vulnerability hypothesis'. The relevance of these findings is discussed with regard to conditions exhibiting parallels in hippocampal plasticity, including Cushing's disease, major depressive disorder (MDD), and post-traumatic stress disorder (PTSD).

  8. Influence of Acupuncture on HPA Axis in a Rat Model of Chronic Stress-induced Depression

    Institute of Scientific and Technical Information of China (English)

    孙冬玮; 王珑; 孙忠人

    2007-01-01

    目的:讨抑郁症的神经生物学发病机制,揭示针刺治疗抑郁症的机理.方法:以Wistar大鼠为受试对象,采用给予孤养大鼠以长期不可预见的中等强度刺激的方法建立抑郁大鼠模型,检测应激后造成的抑郁模型大鼠行为学改变、下丘脑垂体肾上腺皮质轴(HPA)的变化,同时观察针刺干预效应及不同针法的疗效比较.结果:型组、生理盐水组血清CORT和ACTH含量明显高于正常对照组(P<0.05);手针治疗组、电针治疗组血清CORT和ACTH含量明显低于模型组(P<0.05);药物组血清CORT和ACTH含量明显低于生理盐水组(P<0.05);手针治疗组、电针治疗组、药物组比较差别无统计学意义.结论:刺百会、太冲具有较明显的抗抑郁效应,其机制可能与针刺对HPA轴的调整有关.%To investigate the neurobiological mechanism of depression pathogenesis and reveal the mechanism of acupuncture treatment of depression. Methods: Wistar rats were selected for subjects. A rat model of depression was made by individually housing with unpredicted chronic moderate stimuli. Changes in behavior and hypothalamus-pituitary-adrenocortical axis were examined in rat models of stress-induced depression. Meanwhile, the intervening effect of acupuncture was evaluated and the curative effects of different acupuncture methods compared. Results: CORT and ACTH contents of serum were significantly higher in the model and normal saline groups than in the control group (P<0.05), significantly lower in the hand acupuncture and electroacupuncture groups than in the model group (P<0.05) and significantly lower in the medication group than in the normal saline group (P<0.05). There were no significant differences between the hand acupuncture, electroacupuncture and medication groups. Conclusion: Acupuncture of Baihui(GV 20) and Taichong (LR 3) has a marked antidepressant effect. Its mechanism may be related to the regulation of HPA axis by acupuncture.

  9. The impacts of swimming exercise on hippocampal expression of neurotrophic factors in rats exposed to chronic unpredictable mild stress.

    Science.gov (United States)

    Jiang, Pei; Dang, Rui-Li; Li, Huan-De; Zhang, Li-Hong; Zhu, Wen-Ye; Xue, Ying; Tang, Mi-Mi

    2014-01-01

    Depression is associated with stress-induced neural atrophy in limbic brain regions, whereas exercise has antidepressant effects as well as increasing hippocampal synaptic plasticity by strengthening neurogenesis, metabolism, and vascular function. A key mechanism mediating these broad benefits of exercise on the brain is induction of neurotrophic factors, which instruct downstream structural and functional changes. To systematically evaluate the potential neurotrophic factors that were involved in the antidepressive effects of exercise, in this study, we assessed the effects of swimming exercise on hippocampal mRNA expression of several classes of the growth factors (BDNF, GDNF, NGF, NT-3, FGF2, VEGF, and IGF-1) and peptides (VGF and NPY) in rats exposed to chronic unpredictable mild stress (CUMS). Our study demonstrated that the swimming training paradigm significantly induced the expression of BDNF and BDNF-regulated peptides (VGF and NPY) and restored their stress-induced downregulation. Additionally, the exercise protocol also increased the antiapoptotic Bcl-xl expression and normalized the CUMS mediated induction of proapoptotic Bax mRNA level. Overall, our data suggest that swimming exercise has antidepressant effects, increasing the resistance to the neural damage caused by CUMS, and both BDNF and its downstream neurotrophic peptides may exert a major function in the exercise related adaptive processes to CUMS. PMID:25477997

  10. The Impacts of Swimming Exercise on Hippocampal Expression of Neurotrophic Factors in Rats Exposed to Chronic Unpredictable Mild Stress

    Directory of Open Access Journals (Sweden)

    Pei Jiang

    2014-01-01

    Full Text Available Depression is associated with stress-induced neural atrophy in limbic brain regions, whereas exercise has antidepressant effects as well as increasing hippocampal synaptic plasticity by strengthening neurogenesis, metabolism, and vascular function. A key mechanism mediating these broad benefits of exercise on the brain is induction of neurotrophic factors, which instruct downstream structural and functional changes. To systematically evaluate the potential neurotrophic factors that were involved in the antidepressive effects of exercise, in this study, we assessed the effects of swimming exercise on hippocampal mRNA expression of several classes of the growth factors (BDNF, GDNF, NGF, NT-3, FGF2, VEGF, and IGF-1 and peptides (VGF and NPY in rats exposed to chronic unpredictable mild stress (CUMS. Our study demonstrated that the swimming training paradigm significantly induced the expression of BDNF and BDNF-regulated peptides (VGF and NPY and restored their stress-induced downregulation. Additionally, the exercise protocol also increased the antiapoptotic Bcl-xl expression and normalized the CUMS mediated induction of proapoptotic Bax mRNA level. Overall, our data suggest that swimming exercise has antidepressant effects, increasing the resistance to the neural damage caused by CUMS, and both BDNF and its downstream neurotrophic peptides may exert a major function in the exercise related adaptive processes to CUMS.

  11. Overlapping mechanisms of stress-induced relapse to opioid use disorder and chronic pain: Clinical implications

    Directory of Open Access Journals (Sweden)

    Udi E Ghitza

    2016-05-01

    Full Text Available Over the past two decades, a steeply growing number of persons with chronic non-cancer pain have been using opioid analgesics chronically to treat it, accompanied by a markedly increased prevalence of individuals with opioid-related misuse, opioid use disorders, emergency department visits, hospitalizations, admissions to drug treatment programs, and drug overdose deaths. This opioid misuse and overdose epidemic calls for well-designed randomized-controlled clinical trials into more skillful and appropriate pain management and for developing effective analgesics which have lower abuse liability and are protective against stress induced by chronic non-cancer pain. However, incomplete knowledge regarding effective approaches to treat various types of pain has been worsened by an under-appreciation of overlapping neurobiological mechanisms of stress, stress-induced relapse to opioid use, and chronic non-cancer pain in patients presenting for care for these conditions. This insufficient knowledge base has unfortunately encouraged common prescription of conveniently-available opioid pain-relieving drugs with abuse liability, as opposed to treating underlying problems using team-based multidisciplinary, patient-centered, collaborative-care approaches for addressing pain and co-occurring stress and risk for opioid use disorder. This paper reviews recent neurobiological findings regarding overlapping mechanisms of stress-induced relapse to opioid misuse and chronic non-cancer pain, and then discusses these in the context of key outstanding evidence gaps and clinical-treatment research directions which may be pursued to fill these gaps. Such research directions, if conducted through well-designed randomized controlled trials, may substantively inform clinical practice in general medical settings on how to effectively care for patients presenting with pain-related distress and these common co-occurring conditions.

  12. Effect of baclofen on morphine-induced conditioned place preference, extinction, and stress-induced reinstatement in chronically stressed mice

    OpenAIRE

    Meng, Shanshan; Quan, Wuxing; Xu QI; Su, Zhiqiang; Yang, Shanshan

    2013-01-01

    Rationale and Objective A stress-induced increase in excitability can result from a reduction in inhibitory neurotransmission. Modulation of gamma-aminobutyric acid (GABA)ergic transmission is an effective treatment for drug seeking and relapse. This study investigated whether baclofen, a GABAB receptor agonist, had an impact on morphine-induced conditioned place preference (CPP), extinction, and stress-induced relapse in chronically stressed mice. Methods Chronic stress was induced by restra...

  13. Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders

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    Ignacio Negrón-Oyarzo

    2016-01-01

    Full Text Available Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral responses. In the present review, we integrate evidence obtained from cognitive neuroscience with neurophysiological research with animal models, to put forward a hypothesis that addresses stress-induced behavioral dysfunctions observed in stress-related neuropsychiatric disorders. We propose that chronic stress impairs mechanisms involved in neuronal functional connectivity in the PFC that are required for the formation of adaptive representations for the execution of adaptive behavioral responses. These considerations could be particularly relevant for understanding the pathophysiology of chronic stress-related neuropsychiatric disorders.

  14. The different roles of glucocorticoids in the hippocampus and hypothalamus in chronic stress-induced HPA axis hyperactivity.

    Directory of Open Access Journals (Sweden)

    Li-Juan Zhu

    Full Text Available Hypothalamus-pituitary-adrenal (HPA hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR - neuronal nitric oxide synthesis enzyme (nNOS - nitric oxide (NO pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.

  15. The different roles of glucocorticoids in the hippocampus and hypothalamus in chronic stress-induced HPA axis hyperactivity.

    Science.gov (United States)

    Zhu, Li-Juan; Liu, Meng-Ying; Li, Huan; Liu, Xiao; Chen, Chen; Han, Zhou; Wu, Hai-Yin; Jing, Xing; Zhou, Hai-Hui; Suh, Hoonkyo; Zhu, Dong-Ya; Zhou, Qi-Gang

    2014-01-01

    Hypothalamus-pituitary-adrenal (HPA) hyperactivity is observed in many patients suffering from depression and the mechanism underling the dysfunction of HPA axis is not well understood. Chronic stress has a causal relationship with the hyperactivity of HPA axis. Stress induces the over-synthesis of glucocorticoids, which will arrive at all the body containing the brain. It is still complicated whether glucocorticoids account for chronic stress-induced HPA axis hyperactivity and in which part of the brain the glucocorticoids account for chronic stress-induced HPA axis hyperactivity. Here, we demonstrated that glucocorticoids were indispensable and sufficient for chronic stress-induced hyperactivity of HPA axis. Although acute glucocorticoids elevation in the hippocampus and hypothalamus exerted a negative regulation of HPA axis, we found that chronic glucocorticoids elevation in the hippocampus but not in the hypothalamus accounted for chronic stress-induced hyperactivity of HPA axis. Chronic glucocorticoids exposure in the hypothalamus still exerted a negative regulation of HPA axis activity. More importantly, we found mineralocorticoid receptor (MR) - neuronal nitric oxide synthesis enzyme (nNOS) - nitric oxide (NO) pathway mediated the different roles of glucocorticoids in the hippocampus and hypothalamus in regulating HPA axis activity. This study suggests that the glucocorticoids in the hippocampus play an important role in the development of HPA axis hyperactivity and the glucocorticoids in the hypothalamus can't induce hyperactivity of HPA axis, revealing new insights into understanding the mechanism of depression.

  16. [Unpredictable chronic mild stress effects on antidepressants activities in forced swim test].

    Science.gov (United States)

    Kudryashov, N V; Kalinina, T S; Voronina, T A

    2015-02-01

    The experiments has been designed to study unpredictable chronic mild stress effect on anti-depressive activities of amitriptyline (10 mg/kg) and fluoxetine (20 mg/kg) in forced swim test in male outbred mice. It is shown that acute treatment with fluoxetine does not produce any antidepressant effects in mice following stress of 14 days while the sub-chronic injections of fluoxetine result in more deep depressive-like behavior. In 28 daily stressed mice, antidepressant effect of fluoxetine is observed independently of the injection rates. Amitriptyline demonstrates the antidepressant activity regardless of the duration of stress or administration scheduling, but at the same time the severity of anti-immobilization effect of amitriptyline in stressed mice is weaker in compare to non-stressed trails. Thus, the injection rates and duration of unpredictable mild chronic stress are the parameters that determine the efficiency of antidepressants in the mouse forced swimming test.

  17. Antidepressant-Like Effects of Fractions Prepared from Danzhi-Xiaoyao-San Decoction in Rats with Chronic Unpredictable Mild Stress: Effects on Hypothalamic-Pituitary-Adrenal Axis, Arginine Vasopressin, and Neurotransmitters

    Directory of Open Access Journals (Sweden)

    Li-Li Wu

    2016-01-01

    Full Text Available The aim of the present study was to investigate the antidepressant-like effects of two fractions, including petroleum ether soluble fraction (Fraction A, FA and water-EtOH soluble fraction (Fraction B, FB prepared from the Danzhi-xiaoyao-san (DZXYS by using chronic unpredictable mild stress-induced depressive rat model. The results indicated that DZXYS could ameliorate the depression-like behavior in chronic stress model of rats. The inhibition of hyperactivity of HPA axis and the modulation of monoamine and amino acid neurotransmitters in the hippocampus may be the important mechanisms underlying the action of DZXYS antidepressant-like effect in chronically stressed rats.

  18. Antidepressant-Like Effects of Fractions Prepared from Danzhi-Xiaoyao-San Decoction in Rats with Chronic Unpredictable Mild Stress: Effects on Hypothalamic-Pituitary-Adrenal Axis, Arginine Vasopressin, and Neurotransmitters

    Science.gov (United States)

    Wu, Li-Li; Liu, Yan; Pan, Yi; Su, Jun-Fang; Wu, Wei-Kang

    2016-01-01

    The aim of the present study was to investigate the antidepressant-like effects of two fractions, including petroleum ether soluble fraction (Fraction A, FA) and water-EtOH soluble fraction (Fraction B, FB) prepared from the Danzhi-xiaoyao-san (DZXYS) by using chronic unpredictable mild stress-induced depressive rat model. The results indicated that DZXYS could ameliorate the depression-like behavior in chronic stress model of rats. The inhibition of hyperactivity of HPA axis and the modulation of monoamine and amino acid neurotransmitters in the hippocampus may be the important mechanisms underlying the action of DZXYS antidepressant-like effect in chronically stressed rats.

  19. Lithium modulates the chronic stress-induced effect on blood glucose level of male rats

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    Popović Nataša

    2010-01-01

    Full Text Available In the present study we examined gross changes in the mass of whole adrenal glands and that of the adrenal cortex, as well as the serum corticosterone and glucose level of mature male Wistar rats subjected to three different treatments: animals subjected to chronic restraint-stress, animals injected with lithium (Li and chronically stressed rats treated with Li. Under all three conditions we observed hypertrophy of whole adrenals, as well as the adrenal cortices. Chronic restraint stress, solely or in combination with Li treatment, significantly elevated the corticosterone level, but did not change the blood glucose level. Animals treated only with Li exhibited an elevated serum corticosterone level and blood glucose level. The aim of our study was to investigate the modulation of the chronic stress-induced effect on the blood glucose level by lithium, as a possible mechanism of avoiding the damage caused by chronic stress. Our results showed that lithium is an agent of choice which may help to reduce stress-elevated corticosterone and replenish exhausted glucose storages in an organism.

  20. Does Chronic Unpredictable Stress during Adolescence Affect Spatial Cognition in Adulthood?

    OpenAIRE

    Chaby, Lauren E; Michael J Sheriff; Hirrlinger, Amy M.; Lim, James; Thomas B Fetherston; Braithwaite, Victoria A.

    2015-01-01

    Spatial abilities allow animals to retain and cognitively manipulate information about their spatial environment and are dependent upon neural structures that mature during adolescence. Exposure to stress in adolescence is thought to disrupt neural maturation, possibly compromising cognitive processes later in life. We examined whether exposure to chronic unpredictable stress in adolescence affects spatial ability in late adulthood. We evaluated spatial learning, reference and working memory,...

  1. The Consequences of adolescent chronic unpredictable stress exposure on brain and behavior

    OpenAIRE

    Hollis, Fiona; Isgor, Ceylan; Kabbaj, Mohamed

    2013-01-01

    There is increasing evidence for adolescence as a time period vulnerable to environmental perturbations such as stress. What is unclear is the persistent nature of the effects of stress and how specific these effects are to the type of stressor. In this review, we describe the effects of chronic, unpredictable stress (CUS) exposure during adolescence on adult behavior and brain morphology and function in animal models. We provide evidence for adolescence as a critical window for the effects o...

  2. Chronic stress induces ageing-associated degeneration in rat Leydig cells

    Institute of Scientific and Technical Information of China (English)

    Fei-Fei Wang; Qian Wang; Yong Chen; Qiang Lin; Hui-Bao Gao; Ping Zhang

    2012-01-01

    Several studies have suggested that stress and ageing exert inhibitory effects on rat Leydig cells.In a pattern similar to the normal process of Leydig cell ageing,stress-mediated increases in glucocorticoid levels inhibit steroidogenic enzyme expression that then results in decreased testosterone secretion.We hypothesized that chronic stress accelerates the degenerative changes associated with ageing in Leydig cells.To test this hypothesis,we established a model of chronic stress to evaluate stress-induced morphological and functional alterations in Brown Norway rat Leydig cells; additionally,intracellular lipofuscin levels,reactive oxygen species (ROS)levels and DNA damage were assessed.The results showed that chronic stress accelerated ageing-related changes:ultrastructural alterations associated with ageing,cellular lipofuscin accumulation,increased ROS levels and more extensive DNA damage were observed.Additionally,testosterone levels were decreased.This study sheds new light on the idea that chronic stress contributes to the degenerative changes associated with ageing in rat Leydig cells in vivo.

  3. An Efficient Chronic Unpredictable Stress Protocol to Induce Stress-Related Responses in C57BL/6 Mice

    OpenAIRE

    Monteiro, Susana; Roque, Susana; de Sá-Calçada, Daniela; Sousa, Nuno; Correia-Neves, Margarida; Cerqueira, João José

    2015-01-01

    Exposure to chronic stress can have broad effects on health ranging from increased predisposition for neuropsychiatric disorders to deregulation of immune responses. The chronic unpredictable stress (CUS) protocol has been widely used to study the impact of stress exposure in several animal models and consists in the random, intermittent, and unpredictable exposure to a variety of stressors during several weeks. CUS has consistently been shown to induce behavioral and immunological alteration...

  4. Expression of fibroblast growth factor-2 and fibroblast growth factor receptor-1 protein in the hippocampus in rats exhibiting chronic stress-induced depression

    Institute of Scientific and Technical Information of China (English)

    Gonglin Hou; Mingming Tang

    2011-01-01

    There is evidence that the expression of members of the fibroblast growth factor (FGF) protein family is altered in post-mortem brains of humans suffering from major depressive disorder. The present study examined whether the expression of fibroblast growth factor-2 (FGF2) and fibroblast growth factor receptor-1 (FGFR1) protein is altered following chronic stress in an animal model. Rats were exposed to 35 days of chronic unpredictable mild stress, and then tested using open-field and sucrose consumption tests. Compared with the control group, rats in the chronic stress group exhibited obvious depressive-like behaviors, including anhedonia, anxiety and decreased mobility. The results of western blot analysis and immunohistochemical analysis revealed a downregulation of the expression of FGF2 and FGFR1 in the hippocampus of rats, particularly in the CA1, CA3 and dentate gyrus. This decreased expression is in accord with the results of post-mortem studies in humans with major depressive disorder. These findings suggest that FGF2 and FGFR1 proteins participate in the pathophysiology of depressive-like behavior, and may play an important role in the mechanism of chronic stress-induced depression.

  5. Antidepressant-like effects of BCEF0083 in the chronic unpredictable stress models in mice

    Institute of Scientific and Technical Information of China (English)

    ZHOU Lan-lan; MING Liang; MA Chuan-geng; CHENG Yan; JIANG Qin

    2005-01-01

    Background Up to now there have been no satisfactory drugs to treat psychiatric disorders, and now bioactive compound from entomagenous fungi (BCEF0083) is a new type of bioactive compound from entomopathogenic fungi. Our previous investigations have shown that BCEF has an inhibition effect on monoamine oxidase. So, BCEF may be a latent antidepressant. This study aimed at observing the antidepressant effects and its mechanism of BCEF in the chronic unpredictable stress models in mice. Methods The antidepressant effects of BCEF were examined on the chronic unpredictable stress models in mice. Sixty mice were randomly divided to six groups. Animals were housed and isolated except saline group. Mice were exposed to different stressors per day randomly from day 1 to day 21. Body weight were weighed on day 1,day 10 and on day 21 during the 21-day stress procedure. Awarding response was detected by using method of calculating the 24-hour consumption of saccharum water. Step through test was used to evaluate the behavioral response. AVP contents in plasma were also detected by using radioimmunoassays. Results Chronic unpredictable stress resulted in a significant decrease of the body weight and could apparently cause escape behavior disturbance and gradual reduction of sensitivity to reward in animal models. Drug treatment (BCEF 25, 50, 100 mg/kg) could significantly ameliorate the decreased body weight and effectively reverse the escape behavior disturbance. The gradual reduction of sensitivity to reward, the anhedonic state, was also effectively reversed by BCEF. BCEF (50, 100 mg/kg) could also effectively restore the AVP content in the plasma.Conclusions This evidence suggests that BCEF can effectively inhibit the depression behavior and show strong antidepressant effect. BCEF can effectively restore the plasma AVP release and this may be an important mechanism of its antidepressant effect.

  6. Acute and chronic stress-induced disturbances of microglial plasticity, phenotype and function.

    Science.gov (United States)

    Walker, Frederick Rohan; Nilsson, Michael; Jones, Kimberley

    2013-10-01

    Traditionally, microglia have been considered to act as macrophages of the central nervous system. While this concept still remains true it is also becoming increasingly apparent that microglia are involved in a host of nonimmunological activities, such as monitoring synaptic function and maintaining synaptic integrity. It has also become apparent that microglia are exquisitely sensitive to perturbation by environmental challenges. The aim of the current review is to critically examine the now substantial literature that has developed around the ability of acute, sub-chronic and chronic stressors to alter microglial structure and function. The vast majority of studies have demonstrated that stress promotes significant structural remodelling of microglia, and can enhance the release of pro-inflammatory cytokines from microglia. Mechanistically, many of these effects appear to be driven by traditional stress-linked signalling molecules, namely corticosterone and norepinephrine. The specific effects of these signalling molecules are, however, complex as they can exert both inhibitory and suppressive effects on microglia depending upon the duration and intensity of exposure. Importantly, research has now shown that these stress-induced microglial alterations, rather than being epiphenomena, have broader behavioural implications, with the available evidence implicating microglia in directly regulating certain aspects of cognitive function and emotional regulation. PMID:24020974

  7. Antidepressant-Like Effects of Cordycepin in a Mice Model of Chronic Unpredictable Mild Stress

    Directory of Open Access Journals (Sweden)

    Zhang Tianzhu

    2014-01-01

    Full Text Available Cordycepin (3′-deoxyadenosine, a major bioactive component isolated from Cordyceps militaris, has multiple pharmacological activities. This study is attempted to investigate whether cordycepin (COR possesses beneficial effects on chronic unpredictable mild stress- (CUMS- induced behavioral deficits (depression-like behaviors and explore the possible mechanisms. ICR mice were subjected to chronic unpredictable mild stress for 42 consecutive days. Then, COR and fluoxetine (FLU, positive control drug were administered for 21 consecutive days at the last three weeks of CUMS procedure. The classical behavioral tests, open field test (OFT, sucrose preference test (SPT, tail suspension test (TST, and forced swimming test (FST, were applied to evaluate the antidepressant effects of COR. Then the serotonin (5-HT and noradrenaline (NE concentrations in hippocampal were evaluated by HPLC; tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6 in hippocampal were evaluated, and the proteins of TNF-α, IL-6, NF-κBP65 5-HT receptor (5-HTR, and brain-derived neurotrophic factor (BDNF in hippocampal were evaluated by Western blot. Our results indicated that 6 weeks of CUMS exposure induced significant depression-like behavior, with low 5-HT and NE levels, high TNF-α and IL-6 in brain and high hippocampal TNF-α, IL-6, P-NF-κBP65, and 5-HTR levels, and low BDNF expression levels. Whereas, chronic COR (20, 40 mg/kg treatments reversed the behavioral deficiency induced by CUMS exposure, treatment with COR normalized the change of TNF-α, IL-6, 5-HT, and NE levels, which demonstrated that COR could partially restore CUMS-induced 5-HT receptor impairments and inflammation. Besides, hippocampal BDNF expressions were also upregulated after COR treatments. In conclusion, COR remarkably improved depression-like behavior in CUMS mice and its antidepressant activity is mediated, at least in part, by the upregulating BDNF and downregulating 5-HTR levels and

  8. Effects of Shuyusan on monoamine neurotransmitters expression in a rat model of chronic stress-induced depression

    Institute of Scientific and Technical Information of China (English)

    Yuanyuan Zhang; Jianjun Jia; Liping Chen; Zhitao Han; Yulan Zhao; Honghong Zhang; Yazhuo Hu

    2011-01-01

    Shuyusan, a traditional Chinese medicine, was shown to improve depression symptoms and behavioral scores, as well as increase 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid, and 5-hydroxytryptophan levels, in a rat model of chronic stress-induced depression. However, dopamine, noradrenalin, and 3-methoxy-4-hydroxyphenylglycol expressions remained unchanged following Shuyusan treatment. Compared with the model group, the number of 5-HT-positive neurons in layers 4-5 of the frontal cortex, as well as hippocampal CA1 and CA3 regions, significantly increased following Shuyusan treatment. These results suggested that Shuyusan improved symptoms in a rat model of chronic stress-induced depression with mechanisms that involved 5-HT, 5-HT metabolite, 5-HT precursor expressions.

  9. Attenuation of Acute and Chronic Restraint Stress-induced Perturbations in Experimental Animals by Nelumbo nucifera Gaertn

    OpenAIRE

    Kulkarni, M. P.; Juvekar, A. R.

    2008-01-01

    Aqueous extract of leaves of Nelumbo nucifera was investigated on acute stress (immobilization stress)-induced biochemical alterations in Swiss mice. The animals were also subjected to acute physical stress (swimming endurance test) and acute chemical stress (writhing test) to gauge the antistress potential of the extract. Further to evaluate the antistress activity of Nelumbo nucifera in chronic stress condition, fresh Wistar rats were subjected to cold restraint stress (4° for 1 h) for 7 da...

  10. Attenuation of acute and chronic restraint stress-induced perturbations in experimental animals by Nelumbo nucifera Gaertn

    OpenAIRE

    Kulkarni M; Juvekar A

    2008-01-01

    Aqueous extract of leaves of Nelumbo nucifera was investigated on acute stress (immobilization stress)-induced biochemical alterations in Swiss mice. The animals were also subjected to acute physical stress (swimming endurance test) and acute chemical stress (writhing test) to gauge the antistress potential of the extract. Further to evaluate the antistress activity of Nelumbo nucifera in chronic stress condition, fresh Wistar rats were subjected to cold restraint stress (4° for 1 h) f...

  11. Chronic unpredictable stress decreases expression of brain-derived neurotrophic factor (BDNF in mouse ovaries: relationship to oocytes developmental potential.

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    Li-Min Wu

    Full Text Available BACKGROUND: Brain-derived neurotropic factor (BDNF was originally described in the nervous system but has been shown to be expressed in ovary tissues recently, acting as a paracrine/autocrine regulator required for developments of follicles and oocytes. Although it is generally accepted that chronic stress impairs female reproduction and decreases the expression of BDNF in limbic structures of central nervous system, which contributes to mood disorder. However, it is not known whether chronic stress affects oocytes developments, nor whether it affects expression of BDNF in ovary. METHODS: Mice were randomly assigned into control group, stressed group, BDNF-treated group and BDNF-treated stressed group. The chronic unpredictable mild stress model was used to produce psychosocial stress in mice, and the model was verified by open field test and hypothalamic-pituitary-adrenal (HPA axis activity. The methods of immunohistochemistry and western blotting were used to detect BDNF protein level and distribution. The number of retrieved oocytes, oocyte maturation, embryo cleavage and the rates of blastocyst formation after parthenogenetic activation were evaluated. RESULTS: Chronic unpredictable stress decreased the BDNF expression in antral follicles, but didn't affect the BDNF expression in primordial, primary and secondary follicles. Chronic unpredictable stress also decreased the number of retrieved oocytes and the rate of blastocyst formation, which was rescued by exogenous BDNF treatment. CONCLUSION: BDNF in mouse ovaries may be related to the decreased number of retrieved oocytes and impaired oocytes developmental potential induced by chronic unpredictable stress.

  12. Hypothalamic Proteomic Analysis Reveals Dysregulation of Glutamate Balance and Energy Metabolism in a Mouse Model of Chronic Mild Stress-Induced Depression.

    Science.gov (United States)

    Rao, Chenglong; Shi, Haiyang; Zhou, Chanjuan; Zhu, Dan; Zhao, Mingjun; Wang, Ziye; Yang, Yongtao; Chen, Jin; Liao, Li; Tang, Jianyong; Wu, You; Zhou, Jian; Cheng, Ke; Xie, Peng

    2016-09-01

    Hypothalamus-pituitary-adrenal (HPA) axis hyperactivity is observed in many patients suffering from depression. However, the mechanism underlying the dysfunction of the HPA axis is not well understood. Moreover, dysfunction of the hypothalamus, the key brain region of the HPA axis, has not been well-explored. The aim of our study was to examine possible alterations in hypothalamus protein expression in a model of depression using proteomic analysis. In order to achieve this aim, mice were exposed to chronic unpredictable mild stress (CUMS), as the paradigm results in hyperactivity of the HPA axis. Differential protein expression between the hypothalamic proteomes of CUMS and control mice was then assessed through two-dimensional electrophoresis followed by matrix-assisted laser desorption ionization-time of flight-tandem mass spectrometry. Thirty-seven proteins with a threshold of a 1.5-fold change and a p value ≤0.05 were identified as being differentially expressed between CUMS and control mice, and were quantified for bioinformatics analysis. Glycometabolism, citrate cycle (TCA cycle) and oxidation respiratory chain were found to have changed significantly. Glial fibrillary acidic protein and glutamine synthetase were further validated by Western Blot. Our results demonstrated that CUMS mice exhibited a dramatic protein change both in glutamate metabolism and energy mobilization, which may shed some light on the role of the hypothalamus in the pathology of stress-induced depression. PMID:27230881

  13. Inducible nitric oxide synthase is involved in the modulation of depressive behaviors induced by unpredictable chronic mild stress

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    Peng Yun-Li

    2012-07-01

    Full Text Available Abstract Background Experiences and inflammatory mediators are fundamental in the provocation of major depressive disorders (MDDs. We investigated the roles and mechanisms of inducible nitric oxide synthase (iNOS in stress-induced depression. Methods We used a depressive-like state mouse model induced by unpredictable chronic mild stress (UCMS. Depressive-like behaviors were evaluated after 4 weeks of UCMS, in the presence and absence of the iNOS inhibitor N-(3-(aminomethylbenzylacetamidine (1400 W compared with the control group. Immunohistochemistry was used to check the loss of Nissl bodies in cerebral cortex neurons. The levels of iNOS mRNA expression in the cortex and nitrites in the plasma were measured with real-time reverse transcription PCR (RT-PCR and Griess reagent respectively. Results Results showed that the 4-week UCMS significantly induced depressive-like behaviors, including decreased sucrose preference in a sucrose preference test, increased duration of immobility in a forced swim test, and decreased hole-searching time in a locomotor activity test. Meanwhile, in the locomotor activity test, UCMS had no effect on normal locomotor activities, such as resting time, active time and total travel distance. Furthermore, the levels of iNOS mRNA expression in the cortex and nitrites in the plasma of UCMS-exposed mice were significantly increased compared with that of the control group. Neurons of cerebral cortex in UCMS-exposed mice were shrunken with dark staining, together with loss of Nissl bodies. The above-mentioned stress-related depressive-like behaviors, increase of iNOS mRNA expression in the cortex and nitrites in the plasma, and neuron damage, could be abrogated remarkably by pretreating the mice with an iNOS inhibitor (1400 W. Moreover, neurons with abundant Nissl bodies were significantly increased in the 1400 W + UCMS group. Conclusions These results support the notion that stress-related NO (derived from iNOS may

  14. Chronic Unpredictable Stress Augments +3,4-Methylenedioxymethamphetamine (MDMA)-induced Monoamine Depletions: The Role of Corticosterone

    OpenAIRE

    Johnson, Bethann N.; Yamamoto, Bryan K.

    2009-01-01

    Exposure to stress alters the behavioral and neurochemical effects of drugs of abuse. However, it is unknown if chronic stress can affect the serotonergic depletions induced by the psychostimulant drug 3,4-methylenedioxymethamphetamine (MDMA). Rats were exposed to 10 days of chronic unpredictable stress (CUS) which resulted in the predicted elevation of basal plasma corticosterone concentrations. On the 11th day, rats received 4 challenge doses of MDMA (5 mg/kg every 2 h, i.p.) or saline. Fiv...

  15. Chronic unpredictable stress deteriorates the chemopreventive efficacy of pomegranate through oxidative stress pathway.

    Science.gov (United States)

    Hasan, Shirin; Suhail, Nida; Bilal, Nayeem; Ashraf, Ghulam Md; Zaidi, Syed Kashif; AlNohair, Sultan; Banu, Naheed

    2016-05-01

    Chronic unpredictable stress (CUS) can influence the risk and progression of cancer through increased oxidative stress. Pomegranate is known to protect carcinogenesis through its anti-oxidative properties. This study is carried out to examine whether CUS affects the chemopreventive potential of pomegranate through oxidative stress pathway. Role of CUS on early stages of 7, 12 dimethyl benz(a) anthracene (DMBA) induced carcinogenesis, and its pre-exposure effect on chemopreventive efficacy of pomegranate juice (PJ) was examined in terms of in vivo antioxidant and biochemical parameters in Swiss albino rats. Rats were divided in various groups and were subjected to CUS paradigm, DMBA administration (65 mg/kg body weight, single dose), and PJ treatment. Exposure to stress (alone) and DMBA (alone) led to increased oxidative stress by significantly decreasing the antioxidant enzymes activities and altering the glutathione (GSH), malondialdehyde (MDA), glutamate oxaloacetate transaminase (GOT), and glutamate pyruvate transaminase (GPT) levels. A significant increase in DNA damage demonstrated by comet assay was seen in the liver cells. Stress exposure to DMBA-treated rats further increased the oxidative stress and disturbed the biochemical parameters as compared to DMBA (alone)-treated rats. Chemoprevention with PJ in DMBA (alone)-treated rats restored the altered parameters. However, in the pre-stress DMBA-treated rats, the overall antioxidant potential of PJ was significantly diminished. Our results indicate that chronic stress not only increases the severity of carcinogenesis but also diminishes the anti-oxidative efficacy of PJ. In a broader perspective, special emphasis should be given to stress management and healthy diet during cancer chemoprevention. PMID:26596837

  16. Effect of Celastrus paniculatus seed oil (Jyothismati oil on acute and chronic immobilization stress induced in swiss albino mice

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    George Lekha

    2010-01-01

    Full Text Available Stress alters the homeostasis and is produced by several factors. Immobilization stress induced due to reduced floor area provided for the mobility results in the imbalance of oxidant and antioxidant status. The modern computer savvy world decreases human mobility in the working environment, leading to the formation of oxygen free radicals and if left untreated might result in severe health problems like hypertension, cardiovascular disease, premature aging and brain dysfunction. Hence, modern medicines rely upon the medicinal plants for some drugs with zero side effects. In this context, Jyothismati oil (JO, extracted from Celastrus paniculatus seeds, was used to treat acute and chronic immobilization induced experimentally. C. paniculatus plant is considered to be rich in antioxidant content and so the seed oil extract′s efficacy was tested against immobilization stress in albino mice. The animals were kept in a restrainer for short and long durations, grouped separately and fed with the drug. Animals were sacrificed and the samples were analyzed. The antioxidant enzyme levels of the animals regained and markedly increased in the acute and chronic immobilized groups, respectively. The results suggested that the extract of C. paniculatus seed was highly efficacious in reducing the stress induced by least mobility for hours.

  17. Omega-3 polyunsaturated fatty acids and chronic stress-induced modulations of glutamatergic neurotransmission in the hippocampus.

    Science.gov (United States)

    Hennebelle, Marie; Champeil-Potokar, Gaëlle; Lavialle, Monique; Vancassel, Sylvie; Denis, Isabelle

    2014-02-01

    Chronic stress causes the release of glucocorticoids, which greatly influence cerebral function, especially glutamatergic transmission. These stress-induced changes in neurotransmission could be counteracted by increasing the dietary intake of omega-3 polyunsaturated fatty acids (n-3 PUFAs). Numerous studies have described the capacity of n-3 PUFAs to help protect glutamatergic neurotransmission from damage induced by stress and glucocorticoids, possibly preventing the development of stress-related disorders such as depression or anxiety. The hippocampus contains glucocorticoid receptors and is involved in learning and memory. This makes it particularly sensitive to stress, which alters certain aspects of hippocampal function. In this review, the various ways in which n-3 PUFAs may prevent the harmful effects of chronic stress, particularly the alteration of glutamatergic synapses in the hippocampus, are summarized.

  18. Is unpredictable chronic mild stress (UCMS) a reliable model to study depression-induced neuroinflammation?

    Science.gov (United States)

    Farooq, Rai Khalid; Isingrini, Elsa; Tanti, Arnaud; Le Guisquet, Anne-Marie; Arlicot, Nicolas; Minier, Frederic; Leman, Samuel; Chalon, Sylvie; Belzung, Catherine; Camus, Vincent

    2012-05-16

    Unipolar depression is one of the leading causes of disability. The pathophysiology of depression is poorly understood. Evidence suggests that inflammation is associated with depression. For instance, pro-inflammatory cytokines are found to be elevated in the peripheral blood of depressed subjects. Cytokine immunotherapy itself is known to induce depressive symptoms. While the epidemiological and biochemical relationship between inflammation and depression is strong, little is known about the possible existence of neuroinflammation in depression. The use of animal models of depression such as the Unpredictable Chronic Mild Stress (UCMS) has already contributed to the elucidation of the pathophysiological mechanisms of depression such as decreased neurogenesis and HPA axis alterations. We used this model to explore the association of depressive-like behavior in mice with changes in peripheral pro-inflammatory cytokines IL-1β, TNFα and IL-6 level as well as the neuroinflammation by quantifying CD11b expression in brain areas known to be involved in the pathophysiology of depression. These areas include the cerebral cortex, the nucleus accumbens, the bed nucleus of the stria terminalis, the caudate putamen, the amygdala and the hippocampus. The results indicate that microglial activation is significantly increased in the infralimbic, cingulate and medial orbital cortices, nucleus accumbens, caudate putamen, amygdala and hippocampus of the mouse brain as a function of UCMS, while levels of pro-inflammatory cytokines did not differ among the groups. This finding suggests that neuroinflammation occurs in depression and may be implicated in the subject's behavioral response. They also suggest that UCMS could be a potentially reliable model to study depression-induced neuroinflammation. PMID:22465167

  19. Effects of Electroacupuncture at Auricular Concha Region on the Depressive Status of Unpredictable Chronic Mild Stress Rat Models

    OpenAIRE

    Ru-Peng Liu; Ji-Liang Fang; Pei-Jing Rong; Yufeng Zhao; Hong Meng; Hui Ben; Liang Li; Zhan-Xia Huang; Xia Li; Ying-Ge Ma; Bing Zhu

    2013-01-01

    To explore new noninvasive treatment options for depression, this study investigated the effects of electroacupuncture (EA) at the auricular concha region (ACR) of depression rat models. Depression in rats was induced by unpredictable chronic mild stress (UCMS) combined with isolation for 21 days. Eighty male Wistar rats were randomly assigned into four groups: normal, UCMS alone, UCMS with EA-ACR treatment, and UCMS with EA-ear-tip treatment. Rats under inhaled anesthesia were treated once d...

  20. Long-term changes in cognitive bias and coping response as a result of chronic unpredictable stress during adolescence

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    Lauren eChaby

    2013-07-01

    Full Text Available Animals that experience adverse events in early life often have life-long changes to their physiology and behavior. Long-term effects of stress during early life have been studied extensively, but less attention has been given to the consequences of negative experiences solely during the adolescent phase. Adolescence is a particularly sensitive period of life when regulation of the glucocorticoid stress hormone response matures and specific regions in the brain undergo considerable change. Aversive experiences during this time might, therefore, be expected to generate long-term consequences for the adult phenotype. Here we investigated the long-term effects of exposure to chronic unpredictable stress during adolescence on adult decision making, coping response, cognitive bias, and exploratory behavior in rats. Rats exposed to chronic unpredictable stress (e.g. isolation, crowding, cage tilt were compared to control animals that were maintained in standard, predictable conditions throughout development. Unpredictable stress during adolescence resulted in a suite of long-term behavioral and cognitive changes including a negative cognitive bias (F1,12 = 5.000, P < 0.05, altered coping response (T1,14 = 2.216, P = 0.04, and accelerated decision making (T1,14 = 3.245, P = 0.01. Exposure to chronic stress during adolescence also caused a short-term increase in boldness behaviors; in a novel object test 15 days after the last stressor, animals exposed to chronic unpredictable stress had decreased latencies to leave a familiar shelter and approach a novel object (T1,14 = 2.240, P = 0.04; T1,14 = 2.419, P = 0.03, respectively. The results showed that stress during adolescence has long-term impacts on behavior and cognition that affect the interpretation of ambiguous stimuli, behavioral response to adverse events, and how animals make decisions. Stress during adolescence also induced short-term changes in the way animals moved around a novel environment.

  1. Chronic early postnatal scream sound stress induces learning deficits and NMDA receptor changes in the hippocampus of adult mice.

    Science.gov (United States)

    Hu, Lili; Han, Bo; Zhao, Xiaoge; Mi, Lihua; Song, Qiang; Wang, Jue; Song, Tusheng; Huang, Chen

    2016-04-13

    Chronic scream sounds during adulthood affect spatial learning and memory, both of which are sexually dimorphic. The long-term effects of chronic early postnatal scream sound stress (SSS) during postnatal days 1-21 (P1-P21) on spatial learning and memory in adult mice as well as whether or not these effects are sexually dimorphic are unknown. Therefore, the present study examines the performance of adult male and female mice in the Morris water maze following exposure to chronic early postnatal SSS. Hippocampal NR2A and NR2B levels as well as NR2A/NR2B subunit ratios were tested using immunohistochemistry. In the Morris water maze, stress males showed greater impairment in spatial learning and memory than background males; by contrast, stress and background females performed equally well. NR2B levels in CA1 and CA3 were upregulated, whereas NR2A/NR2B ratios were downregulated in stressed males, but not in females. These data suggest that chronic early postnatal SSS influences spatial learning and memory ability, levels of hippocampal NR2B, and NR2A/NR2B ratios in adult males. Moreover, chronic early stress-induced alterations exert long-lasting effects and appear to affect performance in a sex-specific manner. PMID:27015584

  2. An efficient chronic unpredictable stress protocol to induce stress-related responses in C57BL/6 mice

    Directory of Open Access Journals (Sweden)

    Susana eMonteiro

    2015-02-01

    Full Text Available Exposure to chronic stress can have broad effects on health ranging from increased predisposition for neuropsychiatric disorders to deregulation of immune responses. The chronic unpredictable stress (CUS protocol has been widely used to study the impact of stress exposure in several animal models and consists in the random, intermittent and unpredictable exposure to a variety of stressors during several weeks. CUS has consistently been shown to induce behavioral and immunological alterations typical of the chronic stress response. Unfortunately C57BL/6 mice, one of the most widely used mouse strains, due to the great variety of genetically modified lines, seem to be resistant to the commonly used 4-week-long CUS protocol. The definition of an alternative CUS protocol allowing the use of C57BL/6 mice in chronic stress experiments is a need. Here we show that by extending the CUS protocol to 8 weeks is possible to induce a chronic stress response in C57BL/6 mice, as revealed by abrogated body weight gain, increased adrenals weight and an overactive hypothalamic-pituitary-adrenal (HPA axis with increased levels of serum corticosterone. Moreover, we also observed stress-associated behavioral alterations, including the potentiation of anxious-like and depressive-like behaviors and a reduction of exploratory behavior, as well as subtle stress-related changes in the cell population of the thymus and of the spleen.The present protocol for C57BL/6 mice consistently triggers the spectrum of CUS-induced changes observed in rats and, thus, will be highly useful to researchers that need to use this particular mouse strain as an animal model of neuropsychiatric disorders and/or immune deregulation related to chronic unpredictable stress.

  3. Orbitofrontal cortex 5-HT2A receptor mediates chronic stress-induced depressive-like behaviors and alterations of spine density and Kalirin7.

    Science.gov (United States)

    Xu, Chang; Ma, Xin-Ming; Chen, Hui-Bin; Zhou, Meng-He; Qiao, Hui; An, Shu-Cheng

    2016-10-01

    Neuroimaging studies show that patients with major depression have reduced volume of the orbitofrontal cortex (OFC). Although the serotonin (5-HT) 2A receptor, which is abundant in the OFC, has been implicated in depression, the underlying mechanisms in the development of stress-induced depression remain unclear. Kalirin-7 (Kal7) is an essential component of mature excitatory synapses for maintaining dendritic spines density, size and synaptic functions. The aim of this study was to investigate the role of orbitofrontal 5-HT and 5-HT2A receptors in depressive-like behaviors and their associations with Kal7 and dendritic spines using chronic unpredictable mild stress (CUMS), an established animal model of depression. CUMS had no effect on the levels of 5-HT or the 5-HT2A receptor in the OFC. However, CUMS or microinjection of the 5-HT2A/2C receptor agonist (±)-1-(2, 5-Dimethoxy-4-iodophenyl)- 2-aminopropane hydrochloride (DOI, 5 μg/0.5 μL) into the OFC induced depressive-like behaviors, including anhedonia in the sucrose preference test and behavioral despair in the tail suspension test, a significant reduction in body weight gain and locomotor activity in the open field test, which were accompanied by decreased expression of Kal7 and PSD95 as well as decreased density of dendritic spines in the OFC. These alterations induced by CUMS were reversed by pretreatment with the 5-HT2A receptor antagonist Ketanserin (Ket, 5 μg/0.5 μL into the OFC). These results suggest that CUMS alters structural plasticity through activation of the orbital 5-HT2A receptor and is associated with decreased expression of Kal7, thereby resulting in depressive-like behaviors in rats, suggesting an important role of Kal7 in the OFC in depression. PMID:26921771

  4. Cannabinoid modulation of chronic mild stress-induced selective enhancement of trace fear conditioning in adolescent rats.

    Science.gov (United States)

    Reich, Christian G; Iskander, Anthony N; Weiss, Michael S

    2013-10-01

    History of stress is considered a major risk factor for the development of major depression and posttraumatic stress disorder (PTSD). Elucidating the neurobiological mechanisms of Pavlovian fear conditioning may provide insight into the etiology of PTSD. In the current study, adolescent male Sprague-Dawley rats were exposed to 3 weeks of a chronic-mild-unpredictable stress (CMS) protocol. Immediately following the CMS, the animals were subjected to hippocampal-dependent (trace and contextual) and hippocampal-independent (delay) fear conditioning. CMS exposure enhanced trace freezing behavior compared to non-stress controls. This effect was not observed in contextual or delay conditioned animals. Given that the endocannabinoid system is negatively affected by CMS procedures, separate groups of stressed rats were administered the CB1 receptor agonist, ACEA (0.1 mg/kg), prior to trace fear conditioning or a memory-recall test. Regardless of administration time, ACEA significantly reduced freezing behavior in stressed animals. Furthermore, when administered during the first memory recall test, ACEA enhanced long-term extinction in both stress and non-stress groups. The results demonstrate that chronic unpredictable stress selectively enhances hippocampal-dependent episodic fear memories. Pathologies of the episodic memory and fear response may increase the susceptibility of developing PTSD. Reduction in fear responses via exogenous activation of the CB1 receptor suggests that a deficiency in the endocannabinoid system contributes to this pathology.

  5. Overexpression of Mineralocorticoid Receptors Partially Prevents Chronic Stress-Induced Reductions in Hippocampal Memory and Structural Plasticity.

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    Sofia Kanatsou

    Full Text Available Exposure to chronic stress is a risk factor for cognitive decline and psychopathology in genetically predisposed individuals. Preliminary evidence in humans suggests that mineralocorticoid receptors (MRs may confer resilience to these stress-related changes. We specifically tested this idea using a well-controlled mouse model for chronic stress in combination with transgenic MR overexpression in the forebrain. Exposure to unpredictable stressors for 21 days in adulthood reduced learning and memory formation in a low arousing hippocampus-dependent contextual learning task, but enhanced stressful contextual fear learning. We found support for a moderating effect of MR background on chronic stress only for contextual memory formation under low arousing conditions. In an attempt to understand potentially contributing factors, we studied structural plasticity. Chronic stress altered dendritic morphology in the hippocampal CA3 area and reduced the total number of doublecortin-positive immature neurons in the infrapyramidal blade of the dentate gyrus. The latter reduction was absent in MR overexpressing mice. We therefore provide partial support for the idea that overexpression of MRs may confer resilience to the effects of chronic stress on hippocampus-dependent function and structural plasticity.

  6. Physical Activity Protects the Human Brain against Metabolic Stress Induced by a Postprandial and Chronic Inflammation

    NARCIS (Netherlands)

    Pruimboom, Leo; Raison, Charles L.; Muskiet, Frits A. J.

    2015-01-01

    In recent years, it has become clear that chronic systemic low-grade inflammation is at the root of many, if not all, typically Western diseases associated with the metabolic syndrome. While much focus has been given to sedentary lifestyle as a cause of chronic inflammation, it is less often appreci

  7. Stress-induced increases in brainstem amino acid levels are prevented by chronic sodium hydrosulfide treatment.

    Science.gov (United States)

    Warenycia, M W; Kombian, S B; Reiffenstein, R J

    1990-01-01

    Neurotransmitter amino acid levels were measured in select brain regions of rats and mice after chronic treatment with sublethal doses of sodium hydrosulfide (NaHS). Brainstem aspartate, glutamate, glutamine, taurine and GABA levels increased in chronically but not acutely saline-treated rats. These increases may have been due to stress from frequent handling, and were prevented by chronic NaHS treatment (7.5 mg/kg ip every 8 hr for 3 consecutive days). In contrast, aspartate, glutamate and glutamine increased in female but not in male ICR mouse brainstems after once daily treatment with 7.0 mg/kg NaHS for 5 consecutive days. These effects of NaHS may indicate chronic low level H2S neurotoxicity. Differences between chronic and acute treatments, female and male responses, and treatment paradigms may complicate interpretations of such toxicity studies.

  8. Chronic Unpredictable Stress (CUS)-Induced Anxiety and Related Mood Disorders in a Zebrafish Model: Altered Brain Proteome Profile Implicates Mitochondrial Dysfunction

    OpenAIRE

    Sumana Chakravarty; Bommana R Reddy; Sudhakar, Sreesha R.; Sandeep Saxena; Tapatee Das; Vuppalapaty Meghah; Cherukuvada V Brahmendra Swamy; Arvind Kumar; Idris, Mohammed M.

    2013-01-01

    Anxiety and depression are major chronic mood disorders, and the etiopathology for each appears to be repeated exposure to diverse unpredictable stress factors. Most of the studies on anxiety and related mood disorders are performed in rodents, and a good model is chronic unpredictable stress (CUS). In this study, we have attempted to understand the molecular basis of the neuroglial and behavioral changes underlying CUS-induced mood disorders in the simplest vertebrate model, the zebrafish, D...

  9. Chronic stress-induced memory deficits are reversed by regular exercise via AMPK-mediated BDNF induction.

    Science.gov (United States)

    Kim, D-M; Leem, Y-H

    2016-06-01

    Chronic stress has a detrimental effect on neurological insults, psychiatric deficits, and cognitive impairment. In the current study, chronic stress was shown to impair learning and memory functions, in addition to reducing in hippocampal Adenosine monophosphate-activated protein kinase (AMPK) activity. Similar reductions were also observed for brain-derived neurotrophic factor (BDNF), synaptophysin, and post-synaptic density-95 (PSD-95) levels, all of which was counter-regulated by a regime of regular and prolonged exercise. A 21-day restraint stress regimen (6 h/day) produced learning and memory deficits, including reduced alternation in the Y-maze and decreased memory retention in the water maze test. These effects were reversed post-administration by a 3-week regime of treadmill running (19 m/min, 1 h/day, 6 days/week). In hippocampal primary culture, phosphorylated-AMPK (phospho-AMPK) and BDNF levels were enhanced in a dose-dependent manner by 5-amimoimidazole-4-carboxamide riboside (AICAR) treatment, and AICAR-treated increase was blocked by Compound C. A 7-day period of AICAR intraperitoneal injections enhanced alternation in the Y-maze test and reduced escape latency in water maze test, along with enhanced phospho-AMPK and BDNF levels in the hippocampus. The intraperitoneal injection of Compound C every 4 days during exercise intervention diminished exercise-induced enhancement of memory improvement during the water maze test in chronically stressed mice. Also, chronic stress reduced hippocampal neurogenesis (lower Ki-67- and doublecortin-positive cells) and mRNA levels of BDNF, synaptophysin, and PSD-95. Our results suggest that regular and prolonged exercise can alleviate chronic stress-induced hippocampal-dependent memory deficits. Hippocampal AMPK-engaged BDNF induction is at least in part required for exercise-induced protection against chronic stress. PMID:26975895

  10. Attenuation of acute and chronic restraint stress-induced perturbations in experimental animals by Zingiber officinale Roscoe.

    Science.gov (United States)

    Lakshmi, B V S; Sudhakar, M

    2010-02-01

    Ethanolic extract of rhizomes of Zingiber officinale was investigated on anoxia stress tolerance test in Swiss mice. The animals were also subjected to acute physical stress (swimming endurance test) to gauge the anti-stress potential of the extract. Further to evaluate the anti-stress activity of Z. officinale in chronic stress condition, fresh Wistar rats were subjected to cold restraint stress (4 degrees for 2 h) for 10 days. Stimulation of hypothalamus pituitary adrenal axis in stressful condition alters plasma glucose, triglyceride, cholesterol, BUN and corticosterone levels. There is also alteration in the blood cell counts. Pretreatment with the extract significantly ameliorated the stress-induced variations in these biochemical levels and blood cell counts in both acute and chronic stress models. The extract treated animals showed increase in swimming endurance time and increase in anoxia tolerance time in physical and anoxia stress models, respectively. Treatment groups also reverted back increase in liver, adrenal gland weights and atrophy of spleen caused by cold chronic stress and swimming endurance stress models. The results indicate that ethanolic extract of Z. officinale has significant adaptogenic activity against a variety of biochemical and physiological perturbations in different stress models. PMID:19909780

  11. Impaired Functional Connectivity in the Prefrontal Cortex: A Mechanism for Chronic Stress-Induced Neuropsychiatric Disorders

    OpenAIRE

    Ignacio Negrón-Oyarzo; Francisco Aboitiz; Pablo Fuentealba

    2016-01-01

    Chronic stress-related psychiatric diseases, such as major depression, posttraumatic stress disorder, and schizophrenia, are characterized by a maladaptive organization of behavioral responses that strongly affect the well-being of patients. Current evidence suggests that a functional impairment of the prefrontal cortex (PFC) is implicated in the pathophysiology of these diseases. Therefore, chronic stress may impair PFC functions required for the adaptive orchestration of behavioral response...

  12. Bidirectional Crosstalk between Stress-Induced Gastric Ulcer and Depression under Chronic Stress

    OpenAIRE

    Shuang Zhang; Zhiwei Xu; Yan Gao; Yonghong Wu; Zhihui Li; Haifeng Liu; Chenggang Zhang

    2012-01-01

    Stress contributes to a variety of diseases and disorders such as depression and peptic ulcer. The present study aimed to investigate the correlation between stress ulcer and depression in pathogenesis and treatment by using chronic stress depression (CSD), chronic psychological stress ulcer (CPSU) and water immersion restrain stress models in rats. Our data showed that the ulcer index of the animals after CSD exposure was significantly higher than that of controls. Depression-like behaviors ...

  13. Having your cake and eating it too: A habit of comfort food may link chronic social stress exposure and acute stress-induced cortisol hyporesponsiveness.

    Science.gov (United States)

    Stress has been tied to changes in eating behavior and food choice. Previous studies in rodents have shown that chronic stress increases palatable food intake which, in turn, increases mesenteric fat and inhibits acute stress-induced hypothalamic-pituitary-adrenal (HPA) axis activity. The effect of...

  14. Bioactive compounds from Paecilomyces tenuipes regulating the function of the hypothalamo-hypophyseal system axis in chronic unpredictable stress rats

    Institute of Scientific and Technical Information of China (English)

    YIN Yan-yan; MING Liang; ZHENG Li-fang; KAN Hong-wei; LI Chun-ru; LI Wei-ping

    2007-01-01

    Background A bioactive compound from Paecilomyces tenuipes (BGPT) has an inhibitory effect on monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) in vitro and in vivo, which indicates BCPT may be a potential antidepressant. In this study we aimed to study the antidepressant effects of BCPT in the chronic unpredictable stress(CUS) model in rats and explore underlying mechanisms in the hypothalamic-pituitary-adrenal (HPA) axis.Methods The antidepressant effects of BCPT were studied in the chronic unpredictable stress model in rats. Animals were housed isolated, except the control group. Rats were exposed daily to different random stressors from day 1 to 21.Awarding response was detected by calculating the 24-hour consumption of sucrose water. Cortisol (CORT) and adrenocorticotropic hormone (ATCH) contents in serum and arginine vasopressin (AVP) contents in the pituitary body were detected by radio immunoassays. Total RNA of hippocampus or hypothalamus was extracted and subjected to reverse transcription-polymerase chain reaction (RT-PCR) for the measurement of corticotrophin releasing hormone(CRH) mRNA or mineralocorticoid receptor (MR) mRNA and glucocorticoid receptor (GR) mRNA levels. Statistical analyses were performed using one way analysis of variance (ANOVA) followed by Student-Newman-Keuls (SNK) test.Results Chronic unpredictable stress resulted in reduction of sensitivity to reward and abnormality in the HPA axis in the animal model. BCPT improved the reward reaction as measured by increasing sucrose consumption, remarkably reduced serum CORT and ACTH levels and the AVP content in the pituitary body in the CUS-treated rats, decreased the expression of CRH mRNA, enhanced the expression of hippocampus MR mRNA, GR mRNA and decreased the ratio of MR/GR.Conclusions BCPT has potentially antidepressant-like activity and normalized the HPA axis hyperactivity in a CUS model of depression in rats. This may be an important mechanism of its antidepressant effect.

  15. Vulnerability to chronic subordination stress-induced depression-like disorders in adult 129SvEv male mice.

    Science.gov (United States)

    Dadomo, Harold; Sanghez, Valentina; Di Cristo, Luisana; Lori, Andrea; Ceresini, Graziano; Malinge, Isabelle; Parmigiani, Stefano; Palanza, Paola; Sheardown, Malcolm; Bartolomucci, Alessandro

    2011-08-01

    Exposure to stressful life events is intimately linked with vulnerability to neuropsychiatric disorders such as major depression. Pre-clinical animal models offer an effective tool to disentangle the underlying molecular mechanisms. In particular, the 129SvEv strain is often used to develop transgenic mouse models but poorly characterized as far as behavior and neuroendocrine functions are concerned. Here we present a comprehensive characterization of 129SvEv male mice's vulnerability to social stress-induced depression-like disorders and physiological comorbidities. We employed a well characterized mouse model of chronic social stress based on social defeat and subordination. Subordinate 129SvEv mice showed body weight gain, hyperphagia, increased adipose fat pads weight and basal plasma corticosterone. Home cage phenotyping revealed a suppression of spontaneous locomotor activity and transient hyperthermia. Subordinate 129SvEv mice also showed marked fearfulness, anhedonic-like response toward a novel but palatable food, increased anxiety in the elevated plus maze and social avoidance of an unfamiliar male mouse. A direct measured effect of the stressfulness of the living environment, i.e. the amount of daily aggression received, predicted the degree of corticosterone level and locomotor activity but not of the other parameters. This is the first study validating a chronic subordination stress paradigm in 129SvEv male mice. Results demonstrated remarkable stress vulnerability and establish the validity to use this mouse strain as a model for depression-like disorders. PMID:21093519

  16. Chronic hypertension aggravates heat stress-induced brain damage: possible neuroprotection by cerebrolysin.

    Science.gov (United States)

    Muresanu, Dafin Fior; Zimmermann-Meinzingen, Sibilla; Sharma, Hari Shanker

    2010-01-01

    Whole body hyperthermia (WBH) aggravates brain edema formation and cell damage in chronic hypertensive rats compared with normotensive animals. In this investigation, we examined the influence of cerebrolysin on WBH-induced edema formation and brain pathology in hypertensive and normotensive rats. Rats subjected to 4 h WBH at 38 degrees C in a biological oxygen demand (BOD) incubator showed breakdown of the blood-brain barrier (BBB), reduced cerebral blood flow (CBF), edema formation and cell injuries in several parts of the brain. These effects were further aggravated in chronic hypertensive rats (two-kidney one clip model (2K1C), for 4 weeks) subjected to WBH. Pretreatment with cerebrolysin (5 mL/kg, 24 h and 30 min before heat stress) markedly attenuated the BBB dysfunction and brain pathology in normal animals. However, in hypertensive animals, a high dose of cerebrolysin (10 mL/kg, 24 h and 30 min before heat stress) was needed to attenuate WBH-induced BBB dysfunction and brain pathology. These observations indicate that heat stress could affect differently in normal and hypertensive conditions. Furthermore, our results suggest that patients suffering from various chronic cardiovascular diseases may respond differently to hyperthermia and to neuroprotective drugs, e.g., cerebrolysin not reported earlier.

  17. Apomorphine induced conditioned place preference and sensitization is greater in rats exposed to unpredictable chronic mild stress.

    Science.gov (United States)

    Kanwal, Sumera; Ikram, Huma; Farhan, Muhammad; Haleem, Darakhshan Jabeen

    2015-11-01

    CNS stimulants are the class of the drugs that may be used to get relief from depression. Apomorphine is a D1 and D2 receptor agonist with a CNS stimulatory effect used for the treatment of Parkinson's disease is also abused. Although many drugs of abuse produce tolerance and dependence. Long term use of pshycostimulants produce reverse tolerance described as sensitization. These drugs also have a number of other beneficial effects but their therapeutic use is limited because of abuse potential. Conditioned place preference (CPP) test is used to monitor the reinforcing effect of drugs of abuse. Stress is an important factor that precipitates and potentiates addictive effects of different drugs of abuse. The present study was designed to investigate the addictive effect of apomorphine (1mg/kg) in rats previously exposed to repeated unpredictable chronic mild stress for 10 days (animal model of depression). Results from present study illustrate that unpredictable chronic mild stress potentiates the reinforcing effects of apomorphine as the number of entries and the time spent in the CPP compartment associated with drug administration is increased. Motor activity was taken as a parameter for behavioral sensitization which is induced by repeated administration of apomorphine, monitored as the number of cage crossings in light compartment of the CPP apparatus, also increased. PMID:26639488

  18. Bidirectional crosstalk between stress-induced gastric ulcer and depression under chronic stress.

    Directory of Open Access Journals (Sweden)

    Shuang Zhang

    Full Text Available Stress contributes to a variety of diseases and disorders such as depression and peptic ulcer. The present study aimed to investigate the correlation between stress ulcer and depression in pathogenesis and treatment by using chronic stress depression (CSD, chronic psychological stress ulcer (CPSU and water immersion restrain stress models in rats. Our data showed that the ulcer index of the animals after CSD exposure was significantly higher than that of controls. Depression-like behaviors were observed in rat after CPSU exposure. Fluoxetine hydrochloride significantly reduced the ulcer index of rats exposed to CPSU stress, while ranitidine inhibited depression-like behavior of the animals in CSD group. The ulcer index of rats administered with mifepristone after CPSU stress was markedly reduced compared to CPSU group, although there was no significant difference in the depression-like behavior between mifepristone-treated CSD group and naive controls. We also found that the rats exposed to CPSU or CSD stress displayed a lower level of corticosterone than naive controls, however, the acute stress (AS group showed an opposite result. Additionally, in order to study the relevance of H(2 receptors and depression, we treated the CSD group with cimetidine and famotidine respectively. The data showed that cimetidine inhibited depression-like behavior in CSD rats, and famotidine had no impact on depression. Overall our data suggested that the hypothalamic-pituitary-adrenal (HPA axis dysfunction may be the key role in triggering depression and stress ulcer. Acid-suppressing drugs and antidepressants could be used for treatment of depression and stress ulcer respectively. The occurrence of depression might be inhibited by blocking the central H(2 receptors.

  19. Chronic stress induced cognitive impairment in APP/PS-1 double transgenic mouse model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Bing HAN

    2015-08-01

    Full Text Available Objective  To observe the effect of chronic unpredictable mild stress (CUMS on the cognitive function and brain morphological changes in APP/PS-1 mice, one of the genetic mouse models of Alzheimer's disease (AD, and to investigate the possible role of environmental factors in genetic mouse model of AD. Methods  There were 22-week-old wild-type C57BL/6 male mice (control group, N = 15 and APP/PS-1 double transgenic male mice [N = 27: AD group (N = 13 and AD + CUMS group (N = 14] tested in this study. Morris water maze test was used to evaluate spatial learning and memory of the mice. Amyloid deposition in the hippocampus was determined by Congo red staining. The ultrastructure of neurons in hippocampal CA1 region was observed by transmission electron microscope (TEM.  Results  Compared with control group, AD + CUMS group had significantly longer fifth-day escape latency [(33.14 ± 14.37 s vs (21.22 ± 12.16 s; t = -2.701, P = 0.045], and significantly shortened time spent in platform quadrant [(9.74±1.35 s vs (15.02 ± 1.33 s; t = 2.639, P = 0.012] in Morris water maze test. Compared with AD group, the percentage of amyloid plaque area in hippocampal area was increased in AD + CUMS group [(0.59 ± 0.03% vs (0.04 ± 0.03%; t = -2.900, P = 0.005]. The ultrastructure of hippocampal neurons in AD group was slightly damaged: cellular membrane was intact; cell matrix was uniform; intracelluar lipofuscin could be seen; the structure of nucleus and nuclear membrane had no obvious changes; mild fusion of cristae and membrane was seen in mitochondria; Golgi apparatus was partially indistinct; endoplasmic reticulum was mildly expanded. The ultrastructure of hippocampal neurons in AD + CUMS group was obviously damaged, including blurred cell membrane, reduced low-density and high-density granules in cytoplasm, uneven cell matrix, reduced number of organelles, lipofuscin and autophagosome deposition, obvious condensation of chromatin distributing over

  20. Physiological characterization of Chlamydomonas reinhardtii acclimated to chronic stress induced by Ag, Cd, Cr, Cu and Hg ions.

    Science.gov (United States)

    Nowicka, Beatrycze; Pluciński, Bartosz; Kuczyńska, Paulina; Kruk, Jerzy

    2016-08-01

    Acclimation to heavy metal-induced stress is a complex phenomenon. Among the mechanisms of heavy metal toxicity, an important one is the ability to induce oxidative stress, so that the antioxidant response is crucial for providing tolerance to heavy metal ions. The effect of chronic stress induced by ions of five heavy metals, Ag, Cu, Cr (redox-active metals) Cd, Hg (nonredox-active metals) on the green microalga Chlamydomonas reinhardtii was examined at two levels - the biochemical (content of photosynthetic pigments and prenyllipid antioxidants, lipid peroxidation) and the physiological (growth rate, photosynthesis and respiration rates, induction of nonphotochemical quenching of chlorophyll fluorescence). The expression of the genes which encode the enzymes participating in the detoxification of reactive oxygen species (APX1, CAT1, FSD1, MSD1) was measured. The other gene measured was one required for plastoquinone and α-tocopherol biosynthesis (VTE3). The application of heavy metal ions partly inhibited growth and biosynthesis of chlorophyll. The growth inhibition was accompanied by enhanced lipid peroxidation. An increase in the content of prenyllipid antioxidants was observed in cultures exposed to Cr2O7(2-), Cd(2+) (α- and γ-tocopherol and plastoquinone) and Cu(2+) (only tocopherols). The induction of nonphotochemical quenching was enhanced in cultures exposed to Cu(2+), Cr2O7(2-) and Cd(2+), as compared to the control. Chronic heavy metal-induced stress led to changes in gene expression dependent on the type and concentration of heavy metal ions. The up-regulation of antioxidant enzymes was usually accompanied by the up-regulation of the VTE3 gene. PMID:27104807

  1. Chronic subordination stress induces hyperphagia and disrupts eating behavior in mice modeling binge-eating-like disorder

    Directory of Open Access Journals (Sweden)

    Maria eRazzoli

    2015-01-01

    Full Text Available Background: Eating disorders are associated with physical morbidity and appear to have causal factors like stressful life events and negative affect. Binge eating disorder (BED is characterized by eating in a discrete period of time a larger than normal amount of food, a sense of lack of control over eating, and marked distress. There are still unmet needs for the identification of mechanisms regulating excessive eating, which is in part due to the lack of appropriate animal models. We developed a naturalistic murine model of subordination stress induced hyperphagia associated with the development of obesity. Here we tested the hypotheses that the eating responses of subordinate mice recapitulate the BED and that limiting hyperphagia could prevent stress-associated metabolic changes. Methods: Adult male mice were exposed to a model of chronic subordination stress associated with the automated acquisition of food intake and we performed a detailed meal pattern analysis. Additionally, using a pair-feeding protocol was test the hypothesis that the manifestation of obesity and the metabolic syndrome could be prevented by limiting hyperphagia. Results: The architecture of feeding of subordinate mice was disrupted during the stress protocol due to disproportionate amount of food ingested at higher rate and with shorter satiety ratio than control mice. Subordinate mice hyperphagia was further exacerbated in response to either hunger or to the acute application of a social defeat. Notably, the obese phenotype but not the fasting hyperglycemia of subordinate mice was abrogated by preventing hyperphagia in a pair feeding paradigm. Conclusion: Overall these results support the validity of our chronic subordination stress to model binge eating disorder allowing for the determination of the underlying molecular mechanisms and the generation of testable predictions for innovative therapies, based on the understanding of the regulation and the control of food

  2. Flupirtine attenuates chronic restraint stress-induced cognitive deficits and hippocampal apoptosis in male mice.

    Science.gov (United States)

    Huang, Pengcheng; Li, Cai; Fu, Tianli; Zhao, Dan; Yi, Zhen; Lu, Qing; Guo, Lianjun; Xu, Xulin

    2015-07-15

    Chronic restraint stress (CRS) causes hippocampal neurodegeneration and hippocampus-dependent cognitive deficits. Flupirtine represents neuroprotective effects and we have previously shown that flupirtine can protect against memory impairment induced by acute stress. The present study aimed to investigate whether flupirtine could alleviate spatial learning and memory impairment and hippocampal apoptosis induced by CRS. CRS mice were restrained in well-ventilated Plexiglass tubes for 6h daily beginning from 10:00 to 16:00 for 21 consecutive days. Mice were injected with flupirtine (10mg/kg and 25mg/kg) or vehicle (10% DMSO) 30min before restraint stress for 21 days. After stressor cessation, the spatial learning and memory, dendritic spine density, injured neurons and the levels of Bcl-2, Bax, p-Akt, p-GSK-3β, p-Erk1/2 and synaptophysin of hippocampal tissues were examined. Our results showed that flupirtine significantly prevented spatial learning and memory impairment induced by CRS in the Morris water maze. In addition, flupirtine (10mg/kg and 25mg/kg) treatment alleviated neuronal apoptosis and the reduction of dendritic spine density and synaptophysin expression in the hippocampal CA1 region of CRS mice. Furthermore, flupirtine (10mg/kg and 25mg/kg) treatment significantly decreased the expression of Bax and increased the p-Akt and p-GSK-3β, and flupirtine (25mg/kg) treatment up-regulated the p-Erk1/2 in the hippocampus of CRS mice. These results suggested that flupirtine exerted protective effects on the CRS-induced cognitive impairment and hippocampal neuronal apoptosis, which is possibly associated with the activation of Akt/GSK-3β and Erk1/2 signaling pathways. PMID:25869780

  3. Chronic Subordination Stress Induces Hyperphagia and Disrupts Eating Behavior in Mice Modeling Binge-Eating-Like Disorder

    Science.gov (United States)

    Razzoli, Maria; Sanghez, Valentina; Bartolomucci, Alessandro

    2015-01-01

    Background: Eating disorders are associated with physical morbidity and appear to have causal factors like stressful life events and negative affect. Binge-eating disorder (BED) is characterized by eating in a discrete period of time a larger than normal amount of food, a sense of lack of control over eating, and marked distress. There are still unmet needs for the identification of mechanisms regulating excessive eating, which is in part due to the lack of appropriate animal models. We developed a naturalistic murine model of subordination stress-induced hyperphagia associated with the development of obesity. Here, we tested the hypotheses that the eating responses of subordinate mice recapitulate the BED and that limiting hyperphagia could prevent stress-associated metabolic changes. Methods: Adult male mice were exposed to a model of chronic subordination stress (CSS) associated with the automated acquisition of food intake and we performed a detailed meal pattern analysis. Additionally, using a pair-feeding protocol we tested the hypothesis that the manifestation of obesity and the metabolic syndrome could be prevented by limiting hyperphagia. Results: The architecture of feeding of subordinate mice was disrupted during the stress protocol due to disproportionate amount of food ingested at higher rate and with shorter satiety ratio than control mice. Subordinate mice hyperphagia was further exacerbated in response to either hunger or to the acute application of a social defeat. Notably, the obese phenotype but not the fasting hyperglycemia of subordinate mice was abrogated by preventing hyperphagia in a pair-feeding paradigm. Conclusion: Overall, these results support the validity of our CSS to model BED allowing for the determination of the underlying molecular mechanisms and the generation of testable predictions for innovative therapies, based on the understanding of the regulation and the control of food intake. PMID:25621284

  4. Bilobalide alleviates depression-like behavior and cognitive deficit induced by chronic unpredictable mild stress in mice.

    Science.gov (United States)

    Wu, Ruiyong; Shui, Li; Wang, Siyang; Song, Zhenzhen; Tai, Fadao

    2016-10-01

    Bilobalide (BB), a unique constituent of Ginkgo biloba, has powerful neuroprotection and stress-alleviating properties. However, whether BB exerts a positive effect on depression and cognitive deficit induced by chronic stress is not known. The present study was designed to investigate the influence of BB on depression and cognitive impairments induced by chronic unpredictable mild stress (CUMS) in mice. During daily exposure to stressors for 5 consecutive weeks, mice were administered BB at the doses of 0, 3, or 6 mg/kg/day intraperitoneally. We replicated the finding that CUMS induced depression-like behavior and cognitive deficits as the CUMS+vehicle (VEH) group showed a significant increase in immobility in the tail suspension test, a decrease in the discrimination index of the novel object recognition task, and increased latency to platform and decreased number of platform crossings in the Morris water maze compared with the control+VEH group. Chronic administration of BB effectively reversed these alterations. In addition, the CUMS+VEH group showed significantly higher levels of baseline serum corticosterone than those of the control+VEH group and BB dose-dependently inhibited this effect. Our results suggest that BB may be useful for inhibition of depression-like behavior and cognitive deficits, and this protective effect was possibly exerted partly through an action on the hypothalamic-pituitary-adrenal axis. PMID:27509313

  5. Chronic unpredictable stress regulates visceral adipocyte‐mediated glucose metabolism and inflammatory circuits in male rats

    OpenAIRE

    Karagiannides, Iordanes; Golovatscka, Viktoriya; Bakirtzi, Kyriaki; Sideri, Aristea; Salas, Martha; Stavrakis, Dimitris; Polytarchou, Christos; Iliopoulos, Dimitrios; Pothoulakis, Charalabos; Bradesi, Sylvie

    2014-01-01

    Abstract Chronic psychological stress is a prominent risk factor involved in the pathogenesis of many complex diseases, including major depression, obesity, and type II diabetes. Visceral adipose tissue is a key endocrine organ involved in the regulation of insulin action and an important component in the development of insulin resistance. Here, we examined for the first time the changes on visceral adipose tissue physiology and on adipocyte‐associated insulin sensitivity and function after c...

  6. Anticompulsive Activity of a New Pyrazolo[C]Pyridine Derivative GIZh-72 under Conditions of Unpredictable Chronic Mild Stress.

    Science.gov (United States)

    Kudryashov, N V; Kalinina, T S; Zhmurenko, L A; Voronina, T A

    2016-07-01

    Anticompulsive activity of a novel compound GIZh-72 (4,6-dimethyl-2-(4-chlorphenyl)-2,3-dihydro-1H-pyrazolo[4,3-C]Pyridine-3-on, chloral hydrate) in a dose of 20 mg/kg (single, subchronic, and chronic administration) in comparison with fluvoxamine (25 mg/kg) was studied in the marble burying test in the model of unpredictable chronic mild stress on BALB/c mice. GIZh-72 produced an anticompulsive effect that increased with increasing treatment duration under stress conditions in contrast to fluvoxamine that induced inversion of this effect after long-term administration. Neuroleptic activity of GIZh-72 in doses of 20 and 40 mg/kg was studied on the model of apomorphine-induced climbing in C57Bl/6 mice. In contrast to haloperidol (0.5 mg/kg), GIZh-72 exhibited no neuroleptic properties. Our results indicate that GIZh-72 holds much promise for pharmacotherapy of obsessive-compulsive disorder. PMID:27502699

  7. Effects of Electroacupuncture at Auricular Concha Region on the Depressive Status of Unpredictable Chronic Mild Stress Rat Models

    Directory of Open Access Journals (Sweden)

    Ru-Peng Liu

    2013-01-01

    Full Text Available To explore new noninvasive treatment options for depression, this study investigated the effects of electroacupuncture (EA at the auricular concha region (ACR of depression rat models. Depression in rats was induced by unpredictable chronic mild stress (UCMS combined with isolation for 21 days. Eighty male Wistar rats were randomly assigned into four groups: normal, UCMS alone, UCMS with EA-ACR treatment, and UCMS with EA-ear-tip treatment. Rats under inhaled anesthesia were treated once daily for 14 days. The results showed that blood pressure and heart rate were significantly reduced in the EA-ACR group than in the UCMS alone group or the EA-ear-tip group. The open-field test scores significantly decreased in the UCMS alone and EA-ear-tip groups but not in the EA-ACR group. Both EA treatments downregulated levels of plasma cortisol and ACTH in UCMS rats back to normal levels. The present study suggested that EA-ACR can elicit similar cardioinhibitory effects as vagus nerve stimulation (VNS, and EA-ACR significantly antagonized UCMS-induced depressive status in UCMS rats. The antidepressant effect of EA-ACR is possibly mediated via the normalization of the hypothalamic-pituitary-adrenal (HPA axis hyperactivity.

  8. Role of hippocampal p11 in the sustained antidepressant effect of ketamine in the chronic unpredictable mild stress model.

    Science.gov (United States)

    Sun, H-L; Zhou, Z-Q; Zhang, G-F; Yang, C; Wang, X-M; Shen, J-C; Hashimoto, K; Yang, J-J

    2016-01-01

    Although ketamine shows a rapid and sustained antidepressant effect, the precise mechanisms underlying its effect are unknown. Recent studies indicate a key role of p11 (also known as S100A10) in depression-like behavior in rodents. The present study aimed to investigate the role of p11 in the antidepressant-like action of ketamine in chronic unpredictable mild stress (CUMS) rat model. The open-field test, forced swimming test and sucrose preference test were performed after administration of ketamine (10 mg kg(-1)) or a combination of ketamine and ANA-12 (a tropomyosin-related kinase B (TrkB) antagonist; 0.5 mg kg(-1)). The lentivirus vector for p11 was constructed to knock down the hippocampal expression of p11. In the CUMS rats, ketamine showed a rapid (0.5 h) and sustained (72 h) antidepressant effect, and its effect was significantly blocked by co-administration of ANA-12. Furthermore, ketamine significantly increased the reduced expression of brain-derived neurotrophic factor (BDNF) in the hippocampus of CUMS rats, whereas ketamine did not affect the expression of p11 in CUMS rats 0.5 h after administration. In addition, ketamine significantly increased the reduced ratio of p-TrkB/TrkB in the hippocampus by CUMS rats, and its effect was also blocked by ANA-12. Moreover, the reduced expression of BDNF and p11 in the hippocampus of CUMS rats was significantly recovered to control levels 72 h after ketamine administration. Interestingly, knockdown of hippocampal p11 caused increased immobility time and decreased sucrose preference, which were not improved by ketamine administration. These results suggest that p11 in the hippocampus may have a key role in the sustained antidepressant effect of ketamine in the CUMS model of depression. PMID:26905413

  9. BDNF and COX-2 participate in anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress.

    Science.gov (United States)

    Wang, Jun-Ming; Yang, Lian-He; Zhang, Yue-Yue; Niu, Chun-Ling; Cui, Ying; Feng, Wei-Sheng; Wang, Gui-Fang

    2015-11-01

    Catalpol, a major compound in Rehmannia glutinosa with both medicinal and nutritional values, has been previously confirmed to shorten the duration of immobility in mice exposed to tail suspension and forced swimming tests. This study attempted to examine the anti-depressive mechanisms of catalpol in rats undergoing chronic unpredictable mild stress (CUMS) by involving brain-derived neurotrophic factor (BDNF) and cyclooxygenase-2 (COX-2). CUMS-exposed rats were given catalpol daily (5, 10, and 20mg/kg, ig) or a reference drug, fluoxetine hydrochloride (FH, 10mg/kg, ig), at 5 weeks after starting the CUMS procedure. Sucrose preference test was performed to observe depression-like behavior, and serum and brain tissues were used for neurochemical and fluorescent quantitative reverse transcription PCR analysis. CUMS induced depression-like behavior, whereas catalpol and FH administration attenuated this symptom. Moreover, CUMS caused excessively elevated levels of serum corticosterone, an index of hypothalamic-pituitary-adrenal (HPA) axis hyperactivation, in a manner attenuated by catalpol and FH administration. Catalpol administration also further decreased BDNF activities, downregulated the mRNA expression of BDNF and tropomyosin-related kinase B (TrkB), and reversed the excessive elevation in the activities and mRNA expression levels of COX-2 and prostaglandin E2 (PGE2) in the hippocampus and frontal cortex of rats undergoing CUMS. Results indicate that catalpol can ameliorate CUMS-induced depression-like behavior, and suggest its mechanisms may partially be ascribed to restoring HPA axis dysfunctions, upregulating BDNF expression and its cognate receptor TrkB, and downregulating COX-2 expression, thereby reducing PGE2 levels in the brain. PMID:26255123

  10. Involvement of glutamatergic neurotransmission in the antidepressant-like effect of zinc in the chronic unpredictable stress model of depression.

    Science.gov (United States)

    Manosso, Luana M; Moretti, Morgana; Colla, André R; Ribeiro, Camille M; Dal-Cim, Tharine; Tasca, Carla I; Rodrigues, Ana Lúcia S

    2016-03-01

    Stress and excessive glutamatergic neurotransmission have been implicated in the pathophysiology of depression. Therefore, this study was aimed at investigating the influence of zinc on depressive-like behavior induced by chronic unpredictable stress (CUS), on alterations in glutamate-induced toxicity and immunocontent of proteins involved in the control of glutamatergic neurotransmission in the hippocampus of mice. Mice were subjected to CUS procedure for 14 days. From the 8th to the 14th day, mice received zinc chloride (ZnCl2) (10 mg/kg) or fluoxetine (10 mg/kg, positive control) once a day by oral route. CUS caused a depressive-like behavior evidenced by the increased immobility time in the tail suspension test (TST), which was prevented by treatment with ZnCl2 or fluoxetine. Ex vivo exposure of hippocampal slices to glutamate (10 mM) resulted in a significant decrease on cell viability; however, neither CUS procedure nor drug treatments altered this reduction. No alterations in the immunocontents of GLT-1 and GFAP or p-Akt were observed in any experimental group. The ratio of p-Akt/AKT was also not altered in any group. However, Akt immunocontent was increased in stressed mice and in animals treated with ZnCl2 (stressed or non-stressed mice) and EAAC1 immunocontent was increased in stressed mice treated with ZnCl2, fluoxetine or vehicle and in non-stressed mice treated with ZnCl2 and fluoxetine. These findings indicate a robust effect of zinc in reversing behavioral alteration induced by CUS in mice, through a possible modulation of the glutamatergic neurotransmission, extending literature data regarding the mechanisms underlying its antidepressant-like action. PMID:26747027

  11. Evaluation of behavioural and antioxidant activity of Cytisus scoparius Link in rats exposed to chronic unpredictable mild stress

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    Harisudhan Thanukrishnan

    2008-04-01

    Full Text Available Abstract Background Various human diseases have oxidative stress as one of their component. Many herbs have been reported to exhibit properties that combat oxidative stress through their active constituents such as flavonoids, tannins, phenolic compounds etc. Cytisus scoparius (CS Link, (Family: Leguminosae, also called Sarothamnus scoparius, has been shown in invitro experiments to be endowed with anti-diabetic, hypnotic and sedative and antioxidant activity. Therefore this study was carried out to evaluate CS for its anxiolytic, antidepressant and anti-oxidant activity in stressed rats. Methods 60% methanolic extract of CS was quantified for phenolic content by Folin-Ciocalteau's method. Chronic unpredictable mild stress (CMS was employed to induce stress in rats. CS (125 and 250 mg/kg, p.o and diazepam (DZM (2 mg/kg, p.o was administered during the 21 day stress exposure period. Anxiolytic and antidepressant activities of CS were assessed in open field exploratory and behavioural despair paradigms, respectively. Plasma glucose and total lipids; endogenous antioxidant enzymes such as superoxide dismutase (SOD, catalase (CAT; non-enzymic-ascorbic acid and thiobarbituric acid reactive substances (TBARS levels were measured in brain, kidneys and adrenals using standard protocols to assess the effect of CS. Results Total phenolic content of CS was found to be 8.54 ± 0.16% w/w. CMS produced anxiogenic and depressive behaviour in experimental rats with metabolic disturbance. Significant decrease in SOD, CAT levels and increase in lipid peroxidation level was observed in stressed rats. CS administration for 21 days during stress exposure significantly increased the ambulatory behaviour and decreased the freezing time in open field behaviour. In behavioural despair test no significant alteration in the immobility period was observed. CS also improved SOD, CAT, and ascorbic acid level and controlled the lipid peroxidation in different tissues

  12. Ethology assessment and detection of serum GPX-3 levels in rat model of depression induced by chronic unpredictable mild stress

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    Chang-qiang ZHU

    2013-09-01

    Full Text Available Objective To investigate the ethological changes and detect the serum level of glutathione peroxidase (GPX-3 in a rat model of primary and recurrent depression induced by chronic unpredictable mild stress (CUMS. Methods Rats were divided into four groups: group 1(normal feeding, group 2 (CUMS, group 3 (normal + saline + normal feeding and group 4 (CUMS + fluoxetine + CUMS. The behavior of rats in the four groups was assessed by sucrose preference test and open field test. GPX-3 concentration in serum was measured by ELISA. Results A four-week of CUMS was successful in inducing a significant decrease in sucrose preference and locomotor activity in rats in treatment groups (group 2 and 4 in contrast with that of control groups (group 1 and 3 (P<0.01. After 3 weeks of fluoxetine treatment, no obvious difference was found in rats between the group 4 and group 3 in the degree of sucrose preference and locomotor activity. Subsequently, after the treated rats were re-exposed to CUMS for 4 weeks, a significant difference was found again in sucrose preference test (P<0.01 and open field test in comparison with control group (P<0.05. GPX-3 levels in the rats exposed and re-exposed to CUMS were significantly higher than those in control groups (P<0.01. Conclusions CUMS may induce depression-like symptoms in rats, and fluoxetine can alleviate the symptoms induced by CUMS. The increase in GPX-3 concentration may reduce the level of oxidative stress in depression-like rats exposed and re-exposed to CUMS, accordingly it plays a protective role in these rats.

  13. Social Isolation-Induced Aggression Potentiates Anxiety and Depressive-Like Behavior in Male Mice Subjected to Unpredictable Chronic Mild Stress

    OpenAIRE

    Xian-cang Ma; Dong Jiang; Wen-hui Jiang; Fen Wang; Min Jia; Jin Wu; Kenji Hashimoto; Yong-hui Dang; Cheng-ge Gao

    2011-01-01

    BACKGROUND: Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that social isolation in male mice results in aggressive behavior. However, it is not known how social isolation-induced aggression affects anxiety and depressive-like behavior in isolated male mice subjected to unpredictable chronic mild stress (CMS), an animal model of depression. METHODOLOGY/PRINCIPAL FIND...

  14. Pervasive and opposing effects of Unpredictable Chronic Mild Stress (UCMS) on hippocampal gene expression in BALB/cJ and C57BL/6J mouse strains

    OpenAIRE

    Malki, Karim; Mineur, Yann S.; Tosto, Maria Grazia; Campbell, James; Karia, Priya; Jumabhoy, Irfan; Sluyter, Frans; Crusio, Wim E.; Schalkwyk, Leonard C

    2015-01-01

    Background BALB/cJ is a strain susceptible to stress and extremely susceptible to a defective hedonic impact in response to chronic stressors. The strain offers much promise as an animal model for the study of stress related disorders. We present a comparative hippocampal gene expression study on the effects of unpredictable chronic mild stress on BALB/cJ and C57BL/6J mice. Affymetrix MOE 430 was used to measure hippocampal gene expression from 16 animals of two different strains (BALB/cJ and...

  15. Chronic Stress Induces Structural Alterations in Splenic Lymphoid Tissue That Are Associated with Changes in Corticosterone Levels in Wistar-Kyoto Rats

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    María Eugenia Hernandez

    2013-01-01

    Full Text Available Major depressive disorder patients present chronic stress and decreased immunity. The Wistar-Kyoto rat (WKY is a strain in which the hypothalamic-pituitary-adrenal axis is overactivated. To determine whether chronic stress induces changes in corticosterone levels and splenic lymphoid tissue, 9-week-old male rats were subject to restraint stress (3 h daily, chemical stress (hydrocortisone treatment, 50 mg/Kg weight, mixed stress (restraint plus hydrocortisone, or control treatment (without stress for 1, 4, and 7 weeks. The serum corticosterone levels by RIA and spleens morphology were analyzed. Corticosterone levels as did the structure, size of the follicles and morphology of the parenchyma (increase in red pulp in the spleen, varied depending on time and type of stressor. These changes indicate that chronic stress alters the immune response in the spleen in WKY rats by inducing morphological changes, explaining in part the impaired immunity that develops in organisms that are exposed to chronic stress.

  16. The Impacts of Swimming Exercise on Hippocampal Expression of Neurotrophic Factors in Rats Exposed to Chronic Unpredictable Mild Stress

    OpenAIRE

    Pei Jiang; Rui-Li Dang; Huan-De Li; Li-Hong Zhang; Wen-Ye Zhu; Ying Xue; Mi-Mi Tang

    2014-01-01

    Depression is associated with stress-induced neural atrophy in limbic brain regions, whereas exercise has antidepressant effects as well as increasing hippocampal synaptic plasticity by strengthening neurogenesis, metabolism, and vascular function. A key mechanism mediating these broad benefits of exercise on the brain is induction of neurotrophic factors, which instruct downstream structural and functional changes. To systematically evaluate the potential neurotrophic factors that were invol...

  17. Undefined and unpredictable responsibility

    DEFF Research Database (Denmark)

    Bove, Dorthe Gaby; Zakrisson, Ann-Britt; Midtgaard, Julie;

    2016-01-01

    ORIGINAL ARTICLE Undefined and unpredictable responsibility: a focus group studyof the experiences of informal caregiver spouses of patients withsevere COPDDorthe Gaby Bove, Ann-Britt Zakrisson, Julie Midtgaard, Kirsten Lomborg and Dorthe OvergaardAims and objectives. To explore how spouses of...... supportive interventions aimed at reducing the caregiverburden.Design. The study had a qualitative exploratory design. The data collection andanalysis were based on framework method. Framework method is a thematicmethodology and consists of five key stages: familiarisation, identifying a thematicframework......, indexing, charting and mapping & interpretation.Methods. Three focus groups were conducted in November 2013 with 22 spousesof patients with severe chronic obstructive pulmonary disease.Results. Undefined and unpredictable responsibility was found to be the overarch-ing theme describing the informal...

  18. Antidepressant-Like Behavioral, Anatomical, and Biochemical Effects of Petroleum Ether Extract from Maca (Lepidium meyenii) in Mice Exposed to Chronic Unpredictable Mild Stress

    OpenAIRE

    Ai, Zhong; Cheng, Ai-Fang; Yu, Yuan-Tao; Yu, Long-Jiang; Jin, Wenwen

    2014-01-01

    Maca has been consumed as a medical food in Peru for thousands of years, and exerts anxiolytic and antidepressant effects. Our present study aimed to evaluate the behavior and anatomical and biochemical effects of petroleum ether extract from maca (ME) in the chronic unpredictable mild stress (CUMS) model of depression in mice. Three different doses of maca extract (125, 250, and 500 mg/kg) were orally administrated in the six-week CUMS procedure. Fluoxetine (10 mg/kg) was used as a positive ...

  19. Association between chronic stress-induced structural abnormalities in Ranvier nodes and reduced oligodendrocyte activity in major depression.

    Science.gov (United States)

    Miyata, Shingo; Taniguchi, Manabu; Koyama, Yoshihisa; Shimizu, Shoko; Tanaka, Takashi; Yasuno, Fumihiko; Yamamoto, Akihide; Iida, Hidehiro; Kudo, Takashi; Katayama, Taiichi; Tohyama, Masaya

    2016-01-01

    Repeated stressful events are associated with the onset of major depressive disorder (MDD). We previously showed oligodendrocyte (OL)-specific activation of the serum/glucocorticoid-regulated kinase (SGK)1 cascade, increased expression of axon-myelin adhesion molecules, and elaboration of the oligodendrocytic arbor in the corpus callosum of chronically stressed mice. In the current study, we demonstrate that the nodes and paranodes of Ranvier in the corpus callosum were narrower in these mice. Chronic stress also led to diffuse redistribution of Caspr and Kv 1.1 and decreased the activity in white matter, suggesting a link between morphological changes in OLs and inhibition of axonal activity. OL primary cultures subjected to chronic stress resulted in SGK1 activation and translocation to the nucleus, where it inhibited the transcription of metabotropic glutamate receptors (mGluRs). Furthermore, the cAMP level and membrane potential of OLs were reduced by chronic stress exposure. We showed by diffusion tensor imaging that the corpus callosum of patients with MDD exhibited reduced fractional anisotropy, reflecting compromised white matter integrity possibly caused by axonal damage. Our findings suggest that chronic stress disrupts the organization of the nodes of Ranvier by suppressing mGluR activation in OLs, and that specific white matter abnormalities are closely associated with MDD onset. PMID:26976207

  20. Fluoxetine reverts chronic restraint stress-induced depression-like behaviour and increases neuropeptide Y and galanin expression in mice

    DEFF Research Database (Denmark)

    Christiansen, Søren Hofman Oliveira; Olesen, Mikkel Vestergaard; Wörtwein, Gitta;

    2011-01-01

    Stressful life events and chronic stress are implicated in the development of depressive disorder in humans. Neuropeptide Y (NPY) and galanin have been shown to modulate the stress response, and exert antidepressant-like effects in rodents. To further investigate these neuropeptides in depression...

  1. Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice.

    Science.gov (United States)

    Nagata, Kazufumi; Nakashima-Kamimura, Naomi; Mikami, Toshio; Ohsawa, Ikuroh; Ohta, Shigeo

    2009-01-01

    We have reported that hydrogen (H(2)) acts as an efficient antioxidant by gaseous rapid diffusion. When water saturated with hydrogen (hydrogen water) was placed into the stomach of a rat, hydrogen was detected at several microM level in blood. Because hydrogen gas is unsuitable for continuous consumption, we investigated using mice whether drinking hydrogen water ad libitum, instead of inhaling hydrogen gas, prevents cognitive impairment by reducing oxidative stress. Chronic physical restraint stress to mice enhanced levels of oxidative stress markers, malondialdehyde and 4-hydroxy-2-nonenal, in the brain, and impaired learning and memory, as judged by three different methods: passive avoidance learning, object recognition task, and the Morris water maze. Consumption of hydrogen water ad libitum throughout the whole period suppressed the increase in the oxidative stress markers and prevented cognitive impairment, as judged by all three methods, whereas hydrogen water did not improve cognitive ability when no stress was provided. Neural proliferation in the dentate gyrus of the hippocampus was suppressed by restraint stress, as observed by 5-bromo-2'-deoxyuridine incorporation and Ki-67 immunostaining, proliferation markers. The consumption of hydrogen water ameliorated the reduced proliferation although the mechanistic link between the hydrogen-dependent changes in neurogenesis and cognitive impairments remains unclear. Thus, continuous consumption of hydrogen water reduces oxidative stress in the brain, and prevents the stress-induced decline in learning and memory caused by chronic physical restraint. Hydrogen water may be applicable for preventive use in cognitive or other neuronal disorders. PMID:18563058

  2. Serum metabonomics study of anti-depressive effect of Xiao-Chai-Hu-Tang on rat model of chronic unpredictable mild stress.

    Science.gov (United States)

    Xiong, Zhili; Yang, Jie; Huang, Yue; Zhang, Kuo; Bo, Yunhai; Lu, Xiumei; Su, Guangyue; Ma, Jie; Yang, Jingyu; Zhao, Longshan; Wu, Chunfu

    2016-09-01

    Xiao-Chai-Hu-Tang (XCHT) has been proven to be effective for the clinical treatment of depression. However, the mechanisms of definite antidepressant-like effects and detailed metabolic biomarkers were still unclear in this prior study. Here, we have investigated the metabolic profiles and potential biomarkers in a chronic unpredictable mild stress model after treatment with XCHT. Metabonomics based on ultra-high performance liquid chromatography coupled with mass spectrometry was used to profile the metabolic fingerprints of serum obtained from a rat model with chronic unpredictable mild stress with and without XCHT treatment. The model rats showed a significant decrease in sucrose preference and food consumption, and these depression-like symptoms were significantly improved by XCHT. Through principal component analysis (PCA), nine potential biomarkers of tryptophan, uric acid, phenylalanine, cholic acid and lysophosphatidylcholine (C18:0 LPC, C16:0 LPC, C16:1 LPC, C18:1 LPC, C20:4 LPC) were characterized as potential biomarkers involved the pathogenesis of depression. The therapeutic effect of XCHT on depression may involve in amino acid metabolism, lipid metabolism, oxidative stress and inflammation response. The present investigation highlights that metabonomics is a valuable tool for studying the essence of depression as well as evaluating the efficacy of the corresponding drug treatment. PMID:27398633

  3. Chronic stress induces sex-specific alterations in methylation and expression of corticotropin-releasing factor gene in the rat.

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    Linda Sterrenburg

    Full Text Available BACKGROUND: Although the higher prevalence of depression in women than in men is well known, the neuronal basis of this sex difference is largely elusive. METHODS: Male and female rats were exposed to chronic variable mild stress (CVMS after which immediate early gene products, corticotropin-releasing factor (CRF mRNA and peptide, various epigenetic-associated enzymes and DNA methylation of the Crf gene were determined in the hypothalamic paraventricular nucleus (PVN, oval (BSTov and fusiform (BSTfu parts of the bed nucleus of the stria terminalis, and central amygdala (CeA. RESULTS: CVMS induced site-specific changes in Crf gene methylation in all brain centers studied in female rats and in the male BST and CeA, whereas the histone acetyltransferase, CREB-binding protein was increased in the female BST and the histone-deacetylase-5 decreased in the male CeA. These changes were accompanied by an increased amount of c-Fos in the PVN, BSTfu and CeA in males, and of FosB in the PVN of both sexes and in the male BSTov and BSTfu. In the PVN, CVMS increased CRF mRNA in males and CRF peptide decreased in females. CONCLUSIONS: The data confirm our hypothesis that chronic stress affects gene expression and CRF transcriptional, translational and secretory activities in the PVN, BSTov, BSTfu and CeA, in a brain center-specific and sex-specific manner. Brain region-specific and sex-specific changes in epigenetic activity and neuronal activation may play, too, an important role in the sex specificity of the stress response and the susceptibility to depression.

  4. Morin Mitigates Chronic Constriction Injury (CCI)-Induced Peripheral Neuropathy by Inhibiting Oxidative Stress Induced PARP Over-Activation and Neuroinflammation.

    Science.gov (United States)

    Komirishetty, Prashanth; Areti, Aparna; Sistla, Ramakrishna; Kumar, Ashutosh

    2016-08-01

    Neuropathic pain is initiated or caused due to the primary lesion or dysfunction in the nervous system and is proposed to be linked to a cascade of events including excitotoxicity, oxidative stress, neuroinflammation and apoptosis. Oxidative/nitrosative stress aggravates the neuroinflammation and neurodegeneration through poly (ADP) ribose polymerase (PARP) overactivation. Hence, the present study investigated the antioxidant and anti-inflammatory effects of the phytoconstituent; morin in chronic constriction injury (CCI) induced neuropathy. Neuropathic pain was induced by chronic constriction of the left sciatic nerve in rats, and the effect of morin (15 and 30 mg/kg, p.o.) was evaluated by measuring behavioural and biochemical changes. Mechanical, chemical and thermal stimuli confirmed the CCI-induced neuropathic pain and treatment with morin significantly improved these behavioural deficits and improved the sciatic functional index by the 14th day after CCI induction. After 14 days of CCI induction, oxidative/nitrosative stress and inflammatory markers were elevated in rat lumbar spinal cord. Oxidative stress induced PARP overactivation resulted in depleted levels of ATP and elevated levels of poly (ADP) ribose (PAR). Treatment with morin reduced the levels of nitrites, restored glutathione levels and abrogated the oxidant induced DNA damage. It also mitigated the increased levels of TNF-α and IL-6. Protein expression studies confirmed the PARP inhibition and anti-inflammatory activity of morin. Findings of this study suggest that morin, by virtue of its antioxidant properties, limited PARP overactivation and neuroinflammation and protected against CCI induced functional, behavioural and biochemical deficits. PMID:27084773

  5. Stress-induced enhancement of ethanol intake in C57BL/6J mice with a history of chronic ethanol exposure: Involvement of kappa opioid receptors

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    Rachel Ivy Anderson

    2016-02-01

    Full Text Available Our laboratory has previously demonstrated that daily forced swim stress (FSS prior to ethanol drinking sessions facilitates enhanced ethanol consumption in mice with a history of chronic intermittent ethanol (CIE vapor exposure without altering ethanol intake in air-exposed controls. Because both stress and chronic ethanol exposure have been shown to activate the dynorphin/kappa opioid receptor (KOR system, the present study was designed to explore a potential role for KORs in modulating stress effects on ethanol consumption in the CIE model of dependence and relapse drinking. After stable baseline ethanol intake was established in adult male C57BL/6J mice, subjects received chronic intermittent exposure (16 hr/day x 4 days/week to ethanol vapor (CIE group or air (CTL group. Weekly cycles of inhalation exposure were alternated with 5-day limited access drinking tests (1 hour access to 15% ethanol. Experiment 1 compared effects of daily FSS and KOR activation on ethanol consumption. CIE and CTL mice were either exposed to FSS (10 min, the KOR agonist U50,488 (5 mg/kg, or a vehicle injection (non-stressed condition prior to each daily drinking session during test weeks. FSS selectively increased drinking in CIE mice. U50,488 mimicked this effect in CIE mice, but also increased drinking in CTL mice. Experiment 2 assessed effects of KOR blockade on stress-induced drinking in CIE and CTL mice. Stressed and non-stressed mice were administered the short-acting KOR antagonist LY2444296 (0 or 5 mg/kg 30 min prior to each drinking session during test weeks. FSS selectively increased ethanol consumption in CIE mice, an effect that was abolished by LY2444296 pretreatment. In Experiment 3, CIE and CTL mice were administered one of four doses of U50,488 (0,1.25, 2.5, 5.0 mg/kg one hour prior to each daily drinking test (in lieu of FSS. All doses of U50,488 increased ethanol consumption in both CIE and CTL mice. The U50,488-induced increase in drinking was

  6. The Functional Study of a Chinese Herbal Compounded Antidepressant Medicine--Jie Yu Chu Fan Capsule on Chronic Unpredictable Mild Stress Mouse Model.

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    Lingling Ding

    Full Text Available Jie Yu Chu Fan capsule (JYCF is a new compounded Chinese herbal medicine for the treatment of depression. The present study was designed to explore the antidepressant effects and the possible mechanisms of JYCF by using chronic unpredictable mild stress (CUMS mouse model and comparing results to that of fluoxetine. Behavioral tests including an open field test, sucrose preference test and forced swim test were performed to evaluate the antidepressant effects of JYCF. The concentrations of monoamine neurotransmitters and metabolic products including norepinephrine (NE, 5-hydroxytryptamine (5-HT, dopamine (DA, 5-hydroxyindoleacetic acid (5-HIAA, homovanillic acid (HVA and 3,4-dihydroxyphenylacetic acid (DOPAC in the cerebral cortex and hippocampus of mice were determined by means of high performance liquid chromatography with electrochemical detection (HPLC-EC. The results show that a successful mouse CUMS model was established through 5 weeks of continuous unpredictable stimulation, as indicated by the significant decrease in sucrose preference and locomotor activity and increase in immobility time in the forced swim test. Chronic treatment of JYCF (1.25, 2.5 and 5 g/kg and fluoxetine (20 mg/kg significantly reversed the CUMS-induced behavioral abnormalities. JYCF (1.25, 2.5 and 5 g/kg significantly increased NE in CUMS mouse prefrontal cortex (P < 0.01, P < 0.01, P < 0.05 respectively and 5-HT in hippocampus (P < 0.05. In summary, our findings suggest that JYCF exerts comparable antidepressant-like effects to that of fluoxetine in CUMS mice. Besides, the antidepressant-like effect of JYCF is mediated by the increase of monoaminergic transmitters including 5-HT and NE.

  7. Chronic Unpredictable Stress Decreases Expression of Brain-Derived Neurotrophic Factor (BDNF) in Mouse Ovaries: Relationship to Oocytes Developmental Potential

    OpenAIRE

    Li-Min Wu; Mei-Hong Hu; Xian-Hong Tong; Hui Han; Ni Shen; Ren-Tao Jin; Wei Wang; Gui-Xiang Zhou; Guo-Ping He; Yu-Sheng Liu

    2012-01-01

    BACKGROUND: Brain-derived neurotropic factor (BDNF) was originally described in the nervous system but has been shown to be expressed in ovary tissues recently, acting as a paracrine/autocrine regulator required for developments of follicles and oocytes. Although it is generally accepted that chronic stress impairs female reproduction and decreases the expression of BDNF in limbic structures of central nervous system, which contributes to mood disorder. However, it is not known whether chroni...

  8. Epigallocatechin-3-gallate attenuates impairment of learning and memory in chronic unpredictable mild stress-treated rats by restoring hippocampal autophagic flux.

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    Hong-Feng Gu

    Full Text Available Epigallocatechin gallate (EGCG is a major polyphenol in green tea with beneficial effects on the impairment in learning and memory. Autophagy is a cellular process that protects neurons from stressful conditions. The present study was designed to investigate whether EGCG can rescue chronic unpredictable mild stress (CUMS-induced cognitive impairment in rats and whether its protective effect involves improvement of autophagic flux. As expected, our results showed that CUMS significantly impaired memory performance and inhibited autophagic flux as indicated by elevated LC3-II and p62 protein levels. At the same time, we observed an increased neuronal loss and activated mammalian target of rapamycin (mTOR/p70 ribosomal protein S6 kinase (p70S6k signaling in the CA1 regions. Interestingly, chronic treatment with EGCG (25 mg/kg, i.p. significantly improved those behavioral alterations, attenuated histopathological abnormalities in hippocampal CA1 regions, reduced amyloid beta1-42 (Aβ1-42 levels, and restored autophagic flux. However, blocking autophagic flux with chloroquine, an inhibitor of autophagic flux, reversed these effects of EGCG. Taken together, these findings suggest that the impaired autophagy in CA1 regions of CUMS rats may contribute to learning and memory impairment. Therefore, we conclude that EGCG attenuation of CUMS-induced learning and memory impairment may be through rescuing autophagic flux.

  9. An Unpredicted Side Effect of Bisphosphonates in a Patient with Chronic Renal Failure Due to Multiple Myeloma: Reversible Parkinsonism

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    Barış İşak

    2010-09-01

    Full Text Available In this report, we present a unique case in which the chemotherapeutic agent, i.e., zoledronic acid, deepened the hypocalcemia on the basis of chronic renal failure secondary to multiple myeloma and caused parkinsonism episodes. An 80-year-old female patient, who had been diagnosed as multiple myeloma and had been administered bisphosphonate therapy monthly for six months, was ad¬mitted to our emergency room with two parkinsonism episodes. Low serum calcium levels accompanied parkinsonism symptoms, which subsided with calcium replacement therapy in both episodes. Imaging did not reveal any pathology in the basal ganglia. The fact that the patient was cured both times with calcium replacement suggests that hypocalcemia was the actual cause. This can be interpreted as a unique case, reflecting the reversible functional impairment due to metabolic side effects of a chemotherapeutic agent rather than destructive changes in the basal ganglia.

  10. Exposure to sub-chronic unpredictable stress accounts for antidepressant-like effects in hamsters treated with BDNF and CNQX.

    Science.gov (United States)

    Alò, Raffaella; Mele, Maria; Fazzari, Gilda; Avolio, Ennio; Canonaco, Marcello

    2015-09-01

    Recent evidences indicate that cerebral neurotrophic factors like vascular endothelial growth factor plus signaling pathways of the glutamatergic neuroreceptor system (L-Glu) are determinant modulators of depression-like states. In the present study, the type of interaction(s) exerted by the AMPAergic antagonist, 6-cyano-7-nitroquinoxalin-2,3-dione (CNQX) and the brain derived neurotrophic factor (BDNF) on depression-like behaviors in hamsters (Mesocricetus auratus) were investigated. Sub-chronic administration of BDNF in the hippocampal dentate gyrus (DG) of stressed hamsters was responsible for very evident (pdepression states, were reduced following treatment with both compounds. Contextually, marked mRNA expression levels of the BDNF receptor (tropomyosin-related kinase B; TrkB) were detected in DG and the oriens-pyramidalis of HIP (Or-Py) while a moderate (pcaused moderate increases of the major stress protein (Hsp70) in DG and Or-Py. Conversely, while CNQX induced similar TrkB expression levels, it instead accounted for a moderate reduction of Hsp70 mRNAs in the same brain areas. Overall these results support crucial roles played by BDNF and AMPAergic neurosignaling mechanisms during distinct adaptive responses of depression- and anxiety-like states in hamsters. PMID:26409118

  11. Antidepressant-like behavioral, anatomical, and biochemical effects of petroleum ether extract from maca (Lepidium meyenii) in mice exposed to chronic unpredictable mild stress.

    Science.gov (United States)

    Ai, Zhong; Cheng, Ai-Fang; Yu, Yuan-Tao; Yu, Long-Jiang; Jin, Wenwen

    2014-05-01

    Maca has been consumed as a medical food in Peru for thousands of years, and exerts anxiolytic and antidepressant effects. Our present study aimed to evaluate the behavior and anatomical and biochemical effects of petroleum ether extract from maca (ME) in the chronic unpredictable mild stress (CUMS) model of depression in mice. Three different doses of maca extract (125, 250, and 500 mg/kg) were orally administrated in the six-week CUMS procedure. Fluoxetine (10 mg/kg) was used as a positive control drug. Maca extract (250 and 500 mg/kg) significantly decreased the duration of immobility time in the tail suspension test. After treatment with maca extract (250 and 500 mg/kg), the granule cell layer in the dentate gyrus appeared thicker. Maca extract (250 and 500 mg/kg) also induced a significant reduction in corticosterone levels in mouse serum. In mouse brain tissue, after six weeks of treatment, noradrenaline and dopamine levels were increased by maca extract, and the activity of reactive oxygen species was significantly inhibited. Serotonin levels were not significantly altered. These results demonstrated that maca extract (250 and 500 mg/kg) showed antidepressant-like effects and was related to the activation of both noradrenergic and dopaminergic systems, as well as attenuation of oxidative stress in mouse brain. PMID:24730393

  12. Antidepressant-like effects of sodium butyrate and its possible mechanisms of action in mice exposed to chronic unpredictable mild stress.

    Science.gov (United States)

    Sun, Jing; Wang, Fangyan; Hong, Guangliang; Pang, Mengqi; Xu, Hailing; Li, Haixiao; Tian, Feng; Fang, Renchi; Yao, Ye; Liu, Jiaming

    2016-04-01

    Sodium butyrate (NaB) has exhibited neuroprotective activity. This study aimed to explore that NaB exerts beneficial effects on chronic unpredictable mild stress (CUMS)-induced depression-like behaviors and its possible mechanisms. The behavioral tests including sucrose preference test (SPT), open field test (OFT), tail suspension test (TST) and forced swimming test (FST) were to evaluate the antidepressant effects of NaB. Then changes of Nissl's body in the hippocampus, brain serotonin (5-HT) concentration, brain-derived neurotrophic factor (BDNF) and tight junctions (TJs) proteins level were assessed to explore the antidepressant mechanisms. Our results showed that CUMS caused significant depression-like behaviors, neuropathological changes, and decreased brain 5-HT concentration, TJs protein levels and BDNF expression in the hippocampus. However, NaB treatment significantly ameliorated behavioral deficits of the CUMS-induced mice, increased 5-HT concentration, increased BDNF expression, and up-regulated Occludin and zonula occludens-1(ZO-1) protein levels in the hippocampus, which demonstrated that NaB could partially restore CUMS-induced blood-brain barrier (BBB) impairments. Besides, the pathologic changes were alleviated. In conclusion, these results demonstrated that NaB significantly improved depression-like behaviors in CUMS-induced mice and its antidepressant actions might be related with, at least in part, the increasing brain 5-HT concentration and BDNF expression and restoring BBB impairments. PMID:26957230

  13. Chronic unpredictable stress exacerbates lipopolysaccharide-induced activation of nuclear factor-kappaB in the frontal cortex and hippocampus via glucocorticoid secretion.

    Science.gov (United States)

    Munhoz, Carolina Demarchi; Lepsch, Lucilia B; Kawamoto, Elisa Mitiko; Malta, Marília Brinati; Lima, Larissa de Sá; Avellar, Maria Christina Werneck; Sapolsky, Robert M; Scavone, Cristoforo

    2006-04-01

    Although the anti-inflammatory actions of glucocorticoids (GCs) are well established in the periphery, these stress hormones can increase inflammation under some circumstances in the brain. The transcription factor nuclear factor-kappaB (NF-kappaB), which is inhibited by GCs, regulates numerous genes central to inflammation. In this study, the effects of stress, GCs, and NMDA receptors on lipopolysaccharide (LPS)-induced activation of NF-kappaB in the brain were investigated. One day after chronic unpredictable stress (CUS), nonstressed and CUS rats were treated with saline or LPS and killed 2 h later. CUS potentiated the increase in LPS-induced activation of NF-kappaB in frontal cortex and hippocampus but not in the hypothalamus. This stress effect was blocked by pretreatment of rats with RU-486, an antagonist of the GC receptor. MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate], an NMDA receptor antagonist, also reduced the effect of LPS in all three brain regions. However, the combined antagonism of both GC and NMDA receptors produced no further reduction in NF-kappaB activation when compared with the effect of each treatment alone. Our results indicate that stress, via GC secretion, can increase LPS-induced NF-kappaB activation in the frontal cortex and hippocampus, agreeing with a growing literature demonstrating proinflammatory effects of GCs.

  14. Unpredictable chronic mild stress exerts anxiogenic-like effects and activates neurons in the dorsal and caudal region and in the lateral wings of the dorsal raphe nucleus.

    Science.gov (United States)

    Lopes, Danielle A; Lemes, Jéssica A; Melo-Thomas, Liana; Schor, Herbert; de Andrade, José S; Machado, Carla M; Horta-Júnior, José A C; Céspedes, Isabel C; Viana, Milena B

    2016-01-15

    In previous studies, we verified that exposure to unpredictable chronic mild stress (UCMS) facilitates avoidance responses in the elevated T-maze (ETM) and increased Fos-immunoreactivity in different brain structures involved in the regulation of anxiety, including the dorsal raphe (DR). Since, it has been shown that the DR is composed of distinct subpopulations of serotonergic and non-serotonergic neurons, the present study investigated the pattern of activation of these different subnuclei of the region in response to this stress protocol. Male Wistar rats were either unstressed or exposed to the UCMS procedure for two weeks and, subsequently, analyzed for Fos-immunoreactivity (Fos-ir) in serotonergic cells of the DR. To verify if the anxiogenic effects observed in the ETM could be generalized to other anxiety models, a group of animals was also tested in the light/dark transition test after UCMS exposure. Results showed that the UCMS procedure decreased the number of transitions and increased the number of stretched attend postures in the model, an anxiogenic effect. UCMS exposure also increased Fos-ir and the number of double-labeled neurons in the mid-rostral subdivision of the dorsal part of the DR and in the mid-caudal region of the lateral wings. In the caudal region of the DR there was a significant increase in the number of Fos-ir. No significant effects were found in the other DR subnuclei. These results corroborate the idea that neurons of specific subnuclei of the DR regulate anxiety responses and are differently activated by chronic stress exposure. PMID:26462572

  15. Association between repeated unpredictable chronic mild stress (UCMS procedures with a high fat diet: a model of fluoxetine resistance in mice.

    Directory of Open Access Journals (Sweden)

    Elsa Isingrini

    Full Text Available Major depressive disorder is a debilitating disease. Unfortunately, treatment with antidepressants (ADs has limited therapeutic efficacy since resistance to AD is common. Research in this field is hampered by the lack of a reliable natural animal model of AD resistance. Depression resistance is related to various factors, including the attendance of cardiovascular risk factors and past depressive episodes. We aimed to design a rodent model of depression resistance to ADs, associating cardiovascular risk factors with repeated unpredicted chronic mild stress (UCMS. Male BALB/c mice were given either a regular (4% fat or a high fat diet (45% fat and subjected to two 7-week periods of UCMS separated by 6 weeks. From the second week of each UCMS procedure, vehicle or fluoxetine (10 mg/kg, i.p. was administrated daily. The effects of the UCMS and fluoxetine in both diet conditions were assessed using physical (coat state and body weight and behavioural tests (the reward maze test and the splash test. The results demonstrate that during the second procedure, UCMS induced behavioural changes, including coat state degradation, disturbances in self-care behaviour (splash test and anhedonia (reward maze test and these were reversed by fluoxetine in the regular diet condition. In contrast, the high-fat diet regimen prevented the AD fluoxetine from abolishing the UCMS-induced changes. In conclusion, by associating UCMS-an already validated animal model of depression-with high-fat diet regimen, we designed a naturalistic animal model of AD resistance related to a sub-nosographic clinical entity of depression.

  16. Social isolation-induced aggression potentiates anxiety and depressive-like behavior in male mice subjected to unpredictable chronic mild stress.

    Directory of Open Access Journals (Sweden)

    Xian-cang Ma

    Full Text Available BACKGROUND: Accumulating epidemiological evidence shows that life event stressors are major vulnerability factors for psychiatric diseases such as major depression. It is also well known that social isolation in male mice results in aggressive behavior. However, it is not known how social isolation-induced aggression affects anxiety and depressive-like behavior in isolated male mice subjected to unpredictable chronic mild stress (CMS, an animal model of depression. METHODOLOGY/PRINCIPAL FINDINGS: C57/B6 male mice were divided into 3 groups; non-stressed controls, in Group I; isolated mice subjected to the CMS protocol in Group II and aggression by physical contact in socially isolated mice subjected to the CMS protocol in Group III. In the sucrose intake test, ingestion of a 1% sucrose solution by mice in Groups II and III was significantly lower than in Group I. Furthermore, intake of this solution in Group III mice was significantly lower than in Group II mice. In the open field test, mice in Group III, showed reduced locomotor activity and reduced entry and retention time in the central zone, compared to Groups I and II mice. Moreover, the distances moved in 1 hour by Group III mice did not differ between night and morning. In the light/black box test, Groups II and III animals spent significantly less time in the light box compared to Group I animals. In the tail suspension test (TST and forced swimming test (FST, the immobility times of Group II and Group III mice were significantly longer than in Group I mice. In addition, immobility times in the FST were significantly longer in Group III than in Group II mice. CONCLUSIONS/SIGNIFICANCE: These findings show that social isolation-induced aggression could potentiate anxiety and depressive-like behaviors in isolated male mice subjected to CMS.

  17. Effects of Yulangsan polysaccharide on monoamine neurotransmitters, adenylate cyclase activity and brain-derived neurotrophic factor expression in a mouse model of depression induced by unpredictable chronic mild stress☆

    OpenAIRE

    Liang, Shuang; Huang, Renbin; Lin, Xing; Huang, Jianchun; Huang, Zhongshi; Liu, Huagang

    2012-01-01

    The present study established a mouse model of depression induced by unpredictable chronic mild stress. The model mice were treated with Yulangsan polysaccharide (YLSPS; 150, 300 and 600 mg/kg) for 21 days, and compared with fluoxetine-treated and normal control groups. Enzyme-linked immunosorbent assay, radioimmunity and immunohistochemical staining showed that following treatment with YLSPS (300 and 600 mg/kg), monoamine neurotransmitter levels, prefrontal cortex adenylate cyclase activity ...

  18. Unpredictable chronic stress decreases inhibitory avoidance learning in Tuebingen long-fin zebrafish: stronger effects in the resting phase than in the active phase.

    Science.gov (United States)

    Manuel, Remy; Gorissen, Marnix; Zethof, Jan; Ebbesson, Lars O E; van de Vis, Hans; Flik, Gert; van den Bos, Ruud

    2014-11-01

    Zebrafish (Danio rerio Hamilton) are increasingly used as a model to study the effects of chronic stress on brain and behaviour. In rodents, unpredictable chronic stress (UCS) has a stronger effect on physiology and behaviour during the active phase than during the resting phase. Here, we applied UCS during the daytime (active phase) for 7 and 14 days or during the night-time (resting phase) for 7 nights in an in-house-reared Tuebingen long-fin (TLF) zebrafish strain. Following UCS, inhibitory avoidance learning was assessed using a 3 day protocol where fish learn to avoid swimming from a white to a black compartment where they will receive a 3 V shock. Latencies of entering the black compartment were recorded before training (day 1; first shock) and after training on day 2 (second shock) and day 3 (no shock, tissue sampling). Fish whole-body cortisol content and expression levels of genes related to stress, fear and anxiety in the telencephalon were quantified. Following 14 days of UCS during the day, inhibitory avoidance learning decreased (lower latencies on days 2 and 3); minor effects were found following 7 days of UCS. Following 7 nights of UCS, inhibitory avoidance learning decreased (lower latency on day 3). Whole-body cortisol levels showed a steady increase compared with controls (100%) from 7 days of UCS (139%), to 14 days of UCS (174%) to 7 nights of UCS (231%), suggestive of an increasing stress load. Only in the 7 nights of UCS group did expression levels of corticoid receptor genes (mr, grα, grβ) and of bdnf increase. These changes are discussed as adaptive mechanisms to maintain neuronal integrity and prevent overload, and as being indicative of a state of high stress load. Overall, our data suggest that stressors during the resting phase have a stronger impact than during the active phase. Our data warrant further studies on the effect of UCS on stress axis-related genes, especially grβ; in mammals this receptor has been implicated in

  19. Effects of Yulangsan Polysaccharides on Behavior, Structure of Hippocampus in Mice with Chronic Stress-induced Depression%玉郎伞多糖对慢性应激抑郁小鼠行为学及海马结构的影响

    Institute of Scientific and Technical Information of China (English)

    陆玉丹; 黄仁彬; 何萍

    2013-01-01

    目的:观察玉郎伞多糖(YLSPA)对慢性应激抑郁小鼠行为学及海马结构的影响.方法:50只昆明种小鼠随机分为5组:正常对照组、模型组、氟西汀20 mg· kg-1组和YLSPA 1 200,600 mg· kg-1高、低剂量组,连续灌胃21 d,同期利用慢性不可预知温和应激加孤养模型建立小鼠抑郁症模型.采用蔗糖水消耗实验和小鼠自主活动记录仪进行行为学测定;采用脑组织切片HE染色观察海马结构的改变.结果:实验第22天,模型组小鼠的体重、活动站立次数、糖水偏爱度明显减少(与正常对照组比较,P<0.01或P<0.05),YLSPA高、低剂量组、氟西汀组均较模型组有所增加(P<0.01或P<0.05);观察HE染色切片可见慢性应激引起海马结构发生改变,细胞数量减少,玉郎伞多糖和氟西汀可对抗这种改变.结论:YLSPA具有抗抑郁作用,能改善慢性应激对小鼠海马神经元细胞的损伤.%Objective: To observe the effects of Yulangsan polysaccharides ( YLSPA ) on behavior, structure changes of hippocampus in mice with chronic stress-induced depression. Method: Fifty Kunming mice were randomly divided into 5 groups; normal control, animal model, fluoxetine 20 mg·kg-1 and YLSPA 1 200 mg · kg-1 , YLSPA 600 mg·kg-1 groups with continuous oral administration for 21 d, and chronic unpredictable mild stress ( CUMS) with isolated support was imposed simultaneously to establish mouse depression model. The behavior changes of mice were evaluated by sucrose water consumption and the spontaneous activity; the structure changes of hippocampus were detected by the brain tissue HE staining. Result: The weight, the number of active stand, the consumption and preference for sucrose solution of the animal model group were significantly decreased compared with normal control group (P <0. 01 or P < 0. 05 ) , and were increased in YLSPA group and fluoxetine group (P < 0. 01 or P <0. 05) . Chronic unpredictable mild stress with isolated

  20. Regulation of brain-derived neurotrophic factor (BDNF) in the chronic unpredictable stress rat model and the effects of chronic antidepressant treatment

    DEFF Research Database (Denmark)

    Larsen, Marianne H; Mikkelsen, Jens D; Hay-Schmidt, Anders;

    2010-01-01

    swim test in stressed rats. Present evidence suggests a role for brain-derived neurotrophic factor (BDNF) in depression. BDNF mRNA levels in the ventral and dorsal hippocampus were assessed by in situ hybridization. Exposure to CUS was not correlated with a decrease but rather with an increase in BDNF...... mRNA expression in both the dentate gyrus of the dorsal hippocampus and the CA3 region of the ventral hippocampus indicating that there is no simple link between depression-like behaviors per se and brain BDNF levels in rats. However, a significant increase in BDNF mRNA levels in the dentate gyrus...... of the dorsal hippocampus correlated with chronic antidepressant treatment emphasizing a role for BDNF in the mechanisms underlying antidepressant activity....

  1. 芒果苷对慢性应激抑郁小鼠行为及海马脑源性神经营养因子表达的影响%The effects of mangiterin on the improvement of behavior and expression of brain-derived neurotrophic factor in the hippocampus of chronic stress-induced depression model mice

    Institute of Scientific and Technical Information of China (English)

    付燕燕; 宋远见; 杨宜华; 段静雨

    2013-01-01

    Objective To explore the effects of mangiterin on behaviors and brain-derived neurotrophic factor(BDNF) of hippocampus in chronic stress depression mice.Methods 60 male mice were randomly divided into normol control group,model group,fluoxetin control group and mangiterin groups (low,medium and high dose),10 mice in each group.All mice except normal control group were singly housed and subjected to chronic stress-induced depression model for 21 consecutive days.The behaviors of mice were detected by open-field test and tail-suspension test.The expression of BDNF in the hippocampus were assessed using western blot.Results Compared with the normal group,mice exposed chronic stress showed decreased body weight((5.33 ±1.20) g),crossing lines (102 ± 18) and distances ((3425 ± 112) mm) notably decreased in open-field behavior test.The duration of immobility during tail-suspension was increased significantly.BDNF expression in the hippocampus(0.45 ± 0.03) was downregulated significantly(P< 0.01),while it was upregulated in the groups of mangiterin(P < 0.01).Mangiterin group in high dose had the similar effects to fluoxetin group(P > 0.05).Conclusion Mangiterin can ameliorate behavior impairment of chronic stress induced-depression mice and it may be related to the upregulation of BDNF expression in the hippocampus.%目的 探讨芒果苷(Mangiterin)对慢性应激抑郁模型(chronic unpredictable stress,CUS)小鼠行为学的改善作用及对海马脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)表达的影响.方法 将大鼠随机分为正常对照组,慢性应激模型组,氟西汀组,芒果苷低、中和高剂量组,共6组,每组10只.采用慢性轻度不可预见性应激配合孤养复制抑郁模型,通过旷场及悬尾实验观察行为学改变,并运用免疫印迹检测海马BDNF的表达.结果 与正常对照组比,模型组体质量增长缓慢[(5.33±1.20)g],水平穿格次数减少[(102±18)次/5 min

  2. Contextual fear induced by unpredictability in a human fear conditioning preparation is related to the chronic expectation of a threatening US

    NARCIS (Netherlands)

    D. Vansteenwegen; C. Iberico; B. Vervliet; D. Hermans

    2008-01-01

    The present study was set up to investigate cued and contextual fear in situations of (un)predictability in a human fear conditioning paradigm. Forty-nine participants were presented with two different contexts (switching on and off the central lighting of the experimental room). In the predictable

  3. 海马NMDA受体经SP-NK1受体通路参与慢性应激诱发的抑郁样行为%Hippocampal NMDA Receptor is involved in Chronic Stress Induced Depressive-Like Behaviors via SP-NK1 Receptor Pathway

    Institute of Scientific and Technical Information of China (English)

    董素平; 徐畅; 原婷婷; 安书成

    2011-01-01

    theoretic mechanisms for depression, such as monoamine neurotransmitter imbalance theory, neural plasticity theory, but none of them can fully elucidate the formation of depression. Due to weakness of the antidepressant-like effect of monoamines, glutamate (Glu)and its receptors, especially N-methyl-D-aspartic acid (NMDA) receptor, and neuropeptides such as neuropeptide Y (NPY), substance P (SP), are drawing closer attention in recent years. Here, we are attempted to explore the interaction between Glu/NMDA receptor and SP/neurokinin 1 (NK1) receptor in chronic unpredictable mild stress (CUMS)-induced depression.CUMS-induced depression model was established in 250~300g weighted 90-day old Sprague-Dawley rats. Intrahippocampal microinjection of NK1 receptor antagonist CP-96345, NMDA receptor agonist NMDA or NMDA receptor antagonist MK-801 was performed under stereotaxic guide cannula. The body weight of rats was weighed on the 1st, 7th, 14th, and 21st days during the experiment. The behavioral conducts were observed by means of sucrose consumption test, open field test and tail suspension test. The substance P (SP) and glutamate (Glu) content in hippocampus were separately determined by High performance liquid chromatography (HPLC). One-way ANOVA, LSD and repeated measures in SPSS were used in datum analysis.Our data suggest that CUMS significantly induced the depressive-like behaviors in animals and the content of SP and Glu in hippocampus had increased significantly. Microinjection of NMDA into hippocampus resulted in similar animal depressive-like behaviors and an increased SP content compared to the CON/SAL group. Intrahippocampal injections of CP-96345 or MK-801 had effectively improved the depression-like behaviors induced by CUMS, and the elevation of SP level in hippocampus was attenuated in MK-801 injection, whereas Glu level remained unchanged in CP-96345 injection.Our results imply that hippocampal NMDA receptor may contribute to chronic stress induced depressive

  4. 慢性应激引起的大鼠海马神经细胞形态结构的改变%The pathological change in the neurons of hippocampus of rat after chronic unpredictable mild stress

    Institute of Scientific and Technical Information of China (English)

    林志雄; 殷静雯; 罗旭东

    2014-01-01

    Objective:To identify The Change in the neurons of Hippocampus of Rat and depressive-like behavior after Chronic Unpredictable Mild Stress ( CUMS). Method: The mice were subjected to various unpredictable stressors during the 21 days CUMS procedures. The depressive-like behavior and pathological change was observed.Results:The number of neurons of hippocampus after stress was significantly different (P<0.01).Conclusion:Rats after chronic unpredictable mild stress appeared depressive-like behavior correlated with decreased of neurons hippocampus.%目的:探讨慢性应激引起的抑郁样行为与海马神经细胞形态结构的变化。方法:建立慢性轻度不可预见性应激大鼠抑郁模型,检测大鼠快感缺乏,行为活动减少,体质量减轻等抑郁样症状,观察海马区病理改变。结果:实验组和对照组大鼠行为学评分存在显著差异(P<0.01),实验组海马椎体细胞萎缩,神经细胞层数减少,细胞数目明显减少(P<0.01)。结论:应激可导致大鼠抑郁样行为的发生,同时影响神经细胞的生长和存活。

  5. Chronic stress induces a hyporeactivity of the autonomic nervous system in response to acute mental stressor and impairs cognitive performance in business executives.

    Science.gov (United States)

    Teixeira, Renata Roland; Díaz, Miguel Mauricio; Santos, Tatiane Vanessa da Silva; Bernardes, Jean Tofoles Martins; Peixoto, Leonardo Gomes; Bocanegra, Olga Lucia; Neto, Morun Bernardino; Espindola, Foued Salmen

    2015-01-01

    The present study examined the incidence of chronic stress in business executives (109 subjects: 75 male and 34 female) and its relationship with cortisol levels, cognitive performance, and autonomic nervous system (ANS) reactivity after an acute mental stressor. Blood samples were collected from the subjects to measure cortisol concentration. After the sample collection, the subjects completed the Lipp Inventory of Stress Symptoms for Adults and the Stroop Color-Word Test to evaluate stress and cognitive performance levels, respectively. Saliva samples were collected prior to, immediately after, and five minutes after the test. The results revealed that 90.1% of the stressed subjects experienced stress phases that are considered chronic stress. At rest, the subjects with chronic stress showed higher cortisol levels, and no gender differences were observed. No differences were found between the stressed and non-stressed subjects regarding salivary amylase activity prior to test. Chronic stress also impaired performance on the Stroop test, which revealed higher rates of error and longer reaction times in the incongruent stimulus task independently of gender. For the congruent stimulus task of the Stroop test, the stressed males presented a higher rate of errors than the non-stressed males and a longer reaction time than the stressed females. After the acute mental stressor, the non-stressed male group showed an increase in salivary alpha-amylase activity, which returned to the initial values five minutes after the test; this ANS reactivity was not observed in the chronically stressed male subjects. The ANS responses of the non-stressed vs stressed female groups were not different prior to or after the Stroop test. This study is the first to demonstrate a blunted reactivity of the ANS when male subjects with chronic psychological stress were subjected to an acute mental stressor, and this change could contribute to impairments in cognitive performance. PMID:25807003

  6. Chronic stress induces a hyporeactivity of the autonomic nervous system in response to acute mental stressor and impairs cognitive performance in business executives.

    Directory of Open Access Journals (Sweden)

    Renata Roland Teixeira

    Full Text Available The present study examined the incidence of chronic stress in business executives (109 subjects: 75 male and 34 female and its relationship with cortisol levels, cognitive performance, and autonomic nervous system (ANS reactivity after an acute mental stressor. Blood samples were collected from the subjects to measure cortisol concentration. After the sample collection, the subjects completed the Lipp Inventory of Stress Symptoms for Adults and the Stroop Color-Word Test to evaluate stress and cognitive performance levels, respectively. Saliva samples were collected prior to, immediately after, and five minutes after the test. The results revealed that 90.1% of the stressed subjects experienced stress phases that are considered chronic stress. At rest, the subjects with chronic stress showed higher cortisol levels, and no gender differences were observed. No differences were found between the stressed and non-stressed subjects regarding salivary amylase activity prior to test. Chronic stress also impaired performance on the Stroop test, which revealed higher rates of error and longer reaction times in the incongruent stimulus task independently of gender. For the congruent stimulus task of the Stroop test, the stressed males presented a higher rate of errors than the non-stressed males and a longer reaction time than the stressed females. After the acute mental stressor, the non-stressed male group showed an increase in salivary alpha-amylase activity, which returned to the initial values five minutes after the test; this ANS reactivity was not observed in the chronically stressed male subjects. The ANS responses of the non-stressed vs stressed female groups were not different prior to or after the Stroop test. This study is the first to demonstrate a blunted reactivity of the ANS when male subjects with chronic psychological stress were subjected to an acute mental stressor, and this change could contribute to impairments in cognitive

  7. Chronic stress induces a hyporeactivity of the autonomic nervous system in response to acute mental stressor and impairs cognitive performance in business executives.

    Science.gov (United States)

    Teixeira, Renata Roland; Díaz, Miguel Mauricio; Santos, Tatiane Vanessa da Silva; Bernardes, Jean Tofoles Martins; Peixoto, Leonardo Gomes; Bocanegra, Olga Lucia; Neto, Morun Bernardino; Espindola, Foued Salmen

    2015-01-01

    The present study examined the incidence of chronic stress in business executives (109 subjects: 75 male and 34 female) and its relationship with cortisol levels, cognitive performance, and autonomic nervous system (ANS) reactivity after an acute mental stressor. Blood samples were collected from the subjects to measure cortisol concentration. After the sample collection, the subjects completed the Lipp Inventory of Stress Symptoms for Adults and the Stroop Color-Word Test to evaluate stress and cognitive performance levels, respectively. Saliva samples were collected prior to, immediately after, and five minutes after the test. The results revealed that 90.1% of the stressed subjects experienced stress phases that are considered chronic stress. At rest, the subjects with chronic stress showed higher cortisol levels, and no gender differences were observed. No differences were found between the stressed and non-stressed subjects regarding salivary amylase activity prior to test. Chronic stress also impaired performance on the Stroop test, which revealed higher rates of error and longer reaction times in the incongruent stimulus task independently of gender. For the congruent stimulus task of the Stroop test, the stressed males presented a higher rate of errors than the non-stressed males and a longer reaction time than the stressed females. After the acute mental stressor, the non-stressed male group showed an increase in salivary alpha-amylase activity, which returned to the initial values five minutes after the test; this ANS reactivity was not observed in the chronically stressed male subjects. The ANS responses of the non-stressed vs stressed female groups were not different prior to or after the Stroop test. This study is the first to demonstrate a blunted reactivity of the ANS when male subjects with chronic psychological stress were subjected to an acute mental stressor, and this change could contribute to impairments in cognitive performance.

  8. Chronic desipramine prevents acute stress-induced reorganization of medial prefrontal cortex architecture by blocking glutamate vesicle accumulation and excitatory synapse increase

    DEFF Research Database (Denmark)

    Nava, Nicoletta; Treccani, Giulia; Liebenberg, Nico;

    2014-01-01

    While a clear negative influence of chronic exposure to stressful experiences has been repeatedly demonstrated, the outcome of acute stress on key brain regions has only just started to be elucidated. Although it has been proposed that acute stress may produce enhancement of brain plasticity...

  9. Effects of Repeated Citalopram Treatments on Chronic Mild Stress-Induced Growth Associated Protein-43 mRNA Expression in Rat Hippocampus

    OpenAIRE

    Park, Sang-Ha; Choi, Song-Hyen; Lee, Jimin; Kang, Seungwoo; Shin, You-Chan; Kim, Hyun-Ju; Kim, Hyun Jung; Shin, Seung Keon; Lee, Min-Soo; Shin, Kyung-Ho

    2008-01-01

    Although growth associated protein-43 (GAP-43) is known to play a significant role in the regulation of axonal growth and the formation of new neuronal connections in the hippocampus, there is only a few studies on the effects of acute stress on GAP-43 mRNA expression in the hippocampus. Moreover, the effects of repeated citalopram treatment on chronic mild stress (CMS)-induced changes in GAP-43 mRNA expression in the hippocampus have not been explored before. To explore this question, male r...

  10. 抑郁模型大鼠再应激后海马细胞支架蛋白的改变%Cytoskeletal alterations in rat hippocampus following chronic unpredictable mild stress and re-exposure to acute and chronic unpredictable mild stress

    Institute of Scientific and Technical Information of China (English)

    杨灿; 王高华; 王惠玲; 刘忠纯; 王晓萍; 朱志先

    2011-01-01

    目的 研究抑郁模型大鼠接受再次急性和慢性应激后细胞支架微管系统的动态性改变,并探讨可能的机制.方法 将40只大鼠按随机数字表法分为5组:对照组(空白对照+生理盐水),CUMS组(CUMS+生理盐水),氟西汀组(CUMS+氟西汀),急性再应激组(CUMS+氟西汀+药物清洗期+急性游泳应激),CUMS再应激组(CUMS+氟西汀+药物清洗期+CUMS).实验结束后进行行为学观察,并使用免疫印迹法( western blotting)检测大鼠海马乙酰化微管蛋白(Acet-Tub),酪氨酸化微管蛋白(Tyr-Tub),微管结合蛋白2(MAP-2)及磷酸化微管结合蛋白2(phospho-MAP-2).结果 (1)CUMS再应激组糖水偏好[ (43.38±7.84)%],总行程[(859.21±653.62)cm],运动平均速度[(2.05±0.60)cm/s]及直立次数[(0.12±0.30)次]均减少,与对照组及CUMS组相比均差异有显著性(P<0.01).急性再应激组行为与对照组比较差异无显著性.氟西汀组糖水偏好和旷场实验相关指标与对照组差异无显著性,与CUMS组差异有显著性(P<0.01).(2) CUMS再应激组Acet-Tub表达升高[(244.24±8.90)%],Tyr-Tub表达降低[ (30.92±11.00)%],与对照组及CUMS组差异均有显著性(P<0.01).MAP-2的表达与对照组及CUMS组比较差异无显著性,phospho-M AP-2的表达减少[(24.75±8.83)%],与对照组及CUMS组均差异有显著性(P<0.01).急性再应激组各蛋白水平与对照组比较差异无显著性.氟西汀组各蛋白的表达与对照组比较差异无显著性(P>0.05),与CUMS组比较差异有显著性(P<0.01).结论 动物再次暴露于CUMS后,其行为和微管动态性损害更严重,同时伴随微管相关蛋白磷酸化的变化,提示临床抑郁症的发生以及复发的町能机制.%Objective To investigate behavior and hippocampal cytoskeletal alterations following re-exposure to chronic unpredictable mild stress(CUMS) and acute swimming stress,and explore the possible mechanism.Methods 40 Male Sprague-Dawley (SD) rats were

  11. Tianeptine, olanzapine and fluoxetine show similar restoring effects on stress induced molecular changes in mice brain: An FT-IR study

    Science.gov (United States)

    Türker-Kaya, Sevgi; Mutlu, Oğuz; Çelikyurt, İpek K.; Akar, Furuzan; Ulak, Güner

    2016-05-01

    Chronic stress which can cause a variety of disorders and illness ranging from metabolic and cardiovascular to mental leads to alterations in content, structure and dynamics of biomolecules in brain. The determination of stress-induced changes along with the effects of antidepressant treatment on these parameters might bring about more effective therapeutic strategies. In the present study, we investigated unpredictable chronic mild stress (UCMS)-induced changes in biomolecules in mouse brain and the restoring effects of tianeptine (TIA), olanzapine (OLZ) and fluoxetine (FLX) on these variations, by Fourier transform infrared (FT-IR) spectroscopy. The results revealed that chronic stress causes different membrane packing and an increase in lipid peroxidation, membrane fluidity. A significant increment for lipid/protein, Cdbnd O/lipid, CH3/lipid, CH2/lipid, PO-2/lipid, COO-/lipid and RNA/protein ratios but a significant decrease for lipid/protein ratios were also obtained. Additionally, altered protein secondary structure components were estimated, such as increment in random coils and beta structures. The administration of TIA, OLZ and FLX drugs restored these stress-induced variations except for alterations in protein structure and RNA/protein ratio. This may suggest that these drugs have similar restoring effects on the consequences of stress activity in brain, in spite of the differences in their action mechanisms. All findings might have importance in understanding molecular mechanisms underlying chronic stress and contribute to studies aimed for drug development.

  12. Effects of unpredictable chronic stress on behavior and brain-derived neurotrophic factor expression in CA3 subfield and dentate gyrus of the hippocampus in different aged rats

    Institute of Scientific and Technical Information of China (English)

    LI Ying; JI Yong-juan; JIANG Hong; LIU De-xiang; ZHANG Qian; FAN Shu-jian; PAN Fang

    2009-01-01

    Background Brain-derived neurotrophic factor (BDNF) is a stress-responsive intercellular messenger modifying hypothalamic-pituitary-adrenal (HPA) axis activity. The interaction between stress and age in BDNF expression is currently not fully understood. This study was conducted to observe unpredictable stress effect on behavior and BDNF expression in CA3 subfield (CA3) and dentate gyrus of hippocampus in different aged rats. Methods Forty-eight Wistar rats of two different ages (2 months and 15 months) were randomly assigned to six groups: two control groups and four stress groups. The rats in the stress group received three weeks of unpredictable mild stress. The depression state and the stress level of the animals were determined by sucrose preference test and observation of exploratory behavior in an open field (OF) test. The expressions of BDNF in CA3 and dentate gyrus of the hippocampus were measured using immunohistochemistry. Results Age and stress had different effects on the behavior of different aged animals (age: F=6.173, P <0.05, stress: F=6.056, P <0.05). Stress was the main factor affecting sucrose preference (F=123.608, P <0.05). Decreased sucrose preference and suppressed behavior emerged directly following stress, lasting to at least the eighth day after stress in young animals (P <0.05). The older stress rats showed a lower sucrose preference than young stress rats (P <0.05). Older control rats behaved differently from the younger control animals in the OF test, spending more time in the central square (P <0.05), exhibiting fewer vertical movements (P <0.05) and less grooming (P <0.05). Following exposure to stress, older-aged rats showed no obvious changes in vertical movement and grooming. This indicates that aged rats were in an unexcited state before the stress period, and responded less to stressful stimuli than younger rats. There was significantly lower BDNF expression in the CA3 and dentate gyrus regions of the hippocampus following stress

  13. A Standardized Chinese Herbal Decoction, Kai-Xin-San, Restores Decreased Levels of Neurotransmitters and Neurotrophic Factors in the Brain of Chronic Stress-Induced Depressive Rats

    Directory of Open Access Journals (Sweden)

    Kevin Yue Zhu

    2012-01-01

    Full Text Available Kai-xin-san (KXS, a Chinese herbal decoction being prescribed by Sun Simiao in Beiji Qianjin Yaofang about 1400 years ago, contains Ginseng Radix et Rhizoma, Polygalae Radix, Acori tatarinowii Rhizoma, and Poria. KXS has been used to treat stress-related psychiatric disease with the symptoms of depression and forgetfulness in ancient China until today. However, the mechanism of its antidepression action is still unknown. Here, the chronic mild-stress-(CMS- induced depressive rats were applied in exploring the action mechanisms of KXS treatment. Daily intragastric administration of KXS for four weeks significantly alleviated the CMS-induced depressive symptoms displayed by enhanced sucrose consumption. In addition, the expressions of those molecular bio-markers relating to depression in rat brains were altered by the treatment of KXS. These KXS-regulated brain biomarkers included: (i the levels of dopamine, norepinephrine, and serotonin (ii the transcript levels of proteins relating to neurotransmitter metabolism; (iii the transcript levels of neurotrophic factors and their receptors. The results suggested that the anti-depressant-like action of KXS might be mediated by an increase of neurotransmitters and expression of neurotrophic factors and its corresponding receptors in the brain. Thus, KXS could serve as alternative medicine, or health food supplement, for patients suffering from depression.

  14. Effects of Yulangsan polysaccharide on monoamine neurotransmitters, adenylate cyclase activity and brain-derived neurotrophic factor expression in a mouse model of depression induced by unpredictable chronic mild stress

    Institute of Scientific and Technical Information of China (English)

    Shuang Liang; Renbin Huang; Xing Lin; Jianchun Huang; Zhongshi Huang; Huagang Liu

    2012-01-01

    The present study established a mouse model of depression induced by unpredictable chronic mild stress. The model mice were treated with Yulangsan polysaccharide (YLSPS; 150, 300 and 600 mg/kg) for 21 days, and compared with fluoxetine-treated and normal control groups. Enzyme-linked immunosorbent assay, radioimmunity and immunohistochemical staining showed that following treatment with YLSPS (300 and 600 mg/kg), monoamine neurotransmitter levels, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression were significantly elevated, and depression-like behaviors were improved. Open-field and novelty-suppressed feeding tests showed that mouse activity levels were increased and feeding latency was shortened following treatment. Our results indicate that YLSPS inhibits depression by upregulating monoamine neurotransmitters, prefrontal cortex adenylate cyclase activity and hippocampal brain-derived neurotrophic factor expression.

  15. Stress induced changes in testis function.

    Science.gov (United States)

    López-Calderón, A; Ariznavarreta, C; González-Quijano, M I; Tresguerres, J A; Calderón, M D

    1991-01-01

    The mechanism through which chronic stress inhibits the hypothalamic-pituitary-testicular axis has been investigated. Chronic restraint stress decreases testosterone secretion, an effect that is associated with a decrease in plasma gonadotropin levels. In chronically stressed rats there was a decrease in hypothalamic luteinizing hormone-releasing hormone (LHRH) content and the response on plasma gonadotropins to LHRH administration was enhanced. Thus the inhibitory effect of chronic stress on plasma LH and FSH levels seems not to be due to a reduction in pituitary responsiveness to LHRH, but rather to a modification in LHRH secretion. It has been suggested that beta-endorphin might interfere with hypothalamic LHRH secretion during stress. Chronic immobilization did not modify hypothalamic beta-endorphin, while an increase in pituitary beta-endorphin secretion was observed. Since we cannot exclude that changes in beta-endorphin secreted by the pituitary or other opioids may play some role in the stress-induced decrease in LHRH secretion, the effect of naltrexone administration on plasma gonadotropin was studied in chronically stressed rats. Naltrexone treatment did not modify the decrease in plasma concentrations of LH or FSH. These findings suggest that the inhibitory effect of restraint on the testicular axis is exerted at hypothalamic level by some mechanism other than opioids. PMID:1958548

  16. Pathological Mechanism Research in Chronic Unpredictable Mild Stress of Rats%慢性温和不可预知性刺激致大鼠抑郁症模型的病理机制研究进展

    Institute of Scientific and Technical Information of China (English)

    赵瑞; 杜冠华

    2011-01-01

    Depression is a psychological disorder characterized by behavioral, neurochemical and other physiological abnormities. Chronic exposure to mild unpredictable stress (CUMS) has previously been found to cause an antidepressant-reversible decrease in the consumption of palatable sweet solutions, at the same time biochemical disturbances induced by the CUMS procedure were similar to those found in human depression. We review the pathological changes of the animal model of depression ( CUMS). It reflected in some persistent molecular pathologys, such as the changes in receptor , signal transduction.%抑郁症是一种伴有行为学、神经化学和其他生理病理导演的心理障碍.慢性暴露于轻度不可预见性应激(CUMS)已被证实可以导致抑郁薅行为,包括糖水消耗减少等.并且CUMS引起的一系列生化改变类似于人类的抑郁症.我们综述了CUMS致抑郁症动物模型的病理变化,包括了受体、信号转导系统等方面的病理改变.

  17. 慢性不可预知性应激对大鼠实验性牙周炎预后的影响%Effect of chronic unpredictable stress on the healing process of experimental periodontitis in rats

    Institute of Scientific and Technical Information of China (English)

    赵雅娟; 张旻; 黄飞; 崔敏; 陈永进

    2012-01-01

    AIM: To investigate the effect of chronic unpredictable stress on the healing process of experi- mental periodontitis in rats. METHODS: Thirty-two out of one hundred and twenty-eight male Sprague-Dawley rats were randomly selected as control group; the rest of the rats were operated by placing a silk ligature around cervix of the right second maxillary molar to induce experimental periodontitis. After four weeks, sulcus bleeding index(SBI) and periodontal probe depth (PD) were used to testify the animal model. Then the ligature was removed and the rats were randomly divided into periodontitis group; periodontitis and stress group; periodontitis and stress + drug group. Chronic unpredictable stress was given to the rats in stress group and drug group everyday from week S. Also, fluoxetine was given to drug group 5mg/Kg daily. The rats in every group were sacrificed at week 4, 5, 6, 8. The body weight gained, behavior tests and serum tests were used to testify stressed condition. Histological examinations were used to e-valuate the changes of periodontal tissues. RRSULTS: The stressed rats showed less body weight gained, affective -like behavioral changes and increased serum corticosterone ( CORT) and adrenocorticotropic hormone (ACTH) (P < 0.05). The surface of inflammatory infiltrate, alveolar bone loss and osteoclast numbers at week 6 and 8, and the attachment loss at week 8 of the stress group were significantly higher than those of periodontitis group (P <0.05). The surface of inflammatory infiltrate and alveolar bone loss at week 6 and 8, and the osteoclast numbers at week 8 of the drug group were significantly lower than those of the stress group( P < 0.05). CONCLUSION: Chronic unpredictable stress can result in delayed healing of the periodontal tissue in periodontitis while fluoxetine might antagonize the stress and alleviate its negative effect.%目的:探讨慢性不可预知性复合心理应激对大鼠实验性牙周炎模型牙周组织愈

  18. 慢性不可预知温和应激抑郁小鼠模型的建立%Establishment of Chronic Unpredictable Mild Stress Mice Model of Depression

    Institute of Scientific and Technical Information of China (English)

    张臣颢; 张曼芳; 谢青莲; 成志恒; 邹洪; 金玫蕾

    2011-01-01

    抑郁症是一种以情绪低落为主要症状的情感性精神障碍.利用慢性不可预知温和应激建立抑郁症小鼠模型,以蔗糖水消耗实验作为抑郁核心症状之一——快感缺乏的检测方法.将4周龄雄性小鼠(C57BL/6)持续6周暴露于一系列轻度应激中,每周检测蔗糖水消耗.应激包括:令小鼠恐惧的气味、噪音、饲养笼倾斜、潮湿的垫料、无垫料的新饲养笼、照明过夜以及短暂的同笼饲养.前3周模型组每天随机应用2个不同的应激,后3周应用3个不同的应激.结果:随着应激强度的增加,模型组对蔗糖水的摄取量显著低于对照组.由此表明,慢性不可预知性温和应激能导致小鼠出现对奖赏的反应性下降,快感缺乏等抑郁症状.%Depression is a chronic mental disorder mainly characterized by depressed mood. A series of chronic unpredictable mild stresses (CUMS) was used to set up a mice model of depression. And sucrose consumption test was adopted to estimate the anhedonia, one of the core symptoms of human depression. Mice (C57BL/6) were exposed to CUMS over 6 weeks, and anhedonia was evaluated by weekly monitoring sucrose intake. The stressors included that soiled cage with aversive odour, noise, cage tilt, damp bedding, illumination overnight, paired-housing. Week 1-3, two stressors was used daily. Week 4-6, three stressors was used. The results showed that, with the increasing of the stress frequency, sucrose consumption of the stress group was statistically decreased compared with the control group. This indicated that CUMS causes a decrease in responsiveness to rewards, which reflected the key symptom of depression-anhedonia.

  19. 重复经颅磁刺激对慢性应激抑郁模型大鼠行为及海马神经元凋亡的影响%Effect of repetitive transcranial magnetic stimulation on the improvement of behaviors and neuronal apoptosis in rats with chronic stress induced depression

    Institute of Scientific and Technical Information of China (English)

    赵琳; 白冰; 任慧聪; 李文强; 张朝辉

    2015-01-01

    behaviors and hippocampus neuronal apoptosis in rats with chronic stress-induced depression.Methods 40 male SD rats of SPF grade were randomly divided into normol control group (n =8) and model preparation group (n =30) after screening.Rats in model preparation group were singly housed and given chronic unpredictable mild stress(CUMS) to build depression model.Excluding unsuccessful modeling rats,the model preparation group was divided into three groups:model group(n=8,without any treatment),rTMS group (n=8,with the intervention of 10 Hz rTMS) and shame group (n=8,simulation of rTMS environment without rTMS stimulus).The changes of behaviors in each group were detected by weight measurement,sucrose consumption test and open-field test.The changes of morphology of hippocampal neurons were detected by Nissl's staining.The changes of Bax in hippocampal neuron were detected by Immunohistochemical staining.Results (1) Behavioral results showed stress for 21 d could make rat behavior scores decrease significantly(all P<0.05),and rTMS intervention could significantly improve their behavior scores (all P<0.01).Compared with model group,the weight reduction rate (0.32±0.05)%,the score of sucrose consumption test(7.03 ± 1.02) and the score of open field test(8212.41 ± 1416.15,8.75 ± 1.58) in rTMS group was higher(P <0.01).(2) Nissl staining showed stress for 21 d could make the number of hippocampal CA3 neurons was reduced,cell morphology was poor,and the number of Nissl bodies was reduced.rTMS intervention could increase the number of hippocampal CA3 neurons,cell morphology was integral and the number of Nissl bodies was increased.(3) Immunohistochemistry results showed stress for 21 d could cause the number of Bax cell were significantly increased(P<0.01),and rTMS intervention can make the number of Bax cell were significantly lower(P<0.01).Conclusion rTMS intervention improves the depressive behavior in chronic stress depression model rats and inhibits the

  20. 海马BDNF和iNOS与慢性应激性抑郁的关系%Sequental Involvement of Hippocampal BDNF and Inducible Nitric Oxide in Depression Induced by Chronic Unpredicted Mild Stress

    Institute of Scientific and Technical Information of China (English)

    王丹

    2010-01-01

    建立慢性不可预见性抑郁动物模型,采用液体消耗实验(fluid consumption test,FCT)、敞箱实验(Open field test,OFT)和强迫游泳(Forced swimming test,FST)等方法进行行为学测试,并用免疫组织化学的方法检测海马BDNF和iNOS的表达,运用腹腔注射药物的方法探索BDNF和iNOS的作用与关系.探讨了海马脑源性神经营养因子(BDNF)和诱导型一氧化氮合酶(iNOS)在慢性应激诱导的抑郁症中的关系,及抑郁症的发病机制.与对照组相比,慢性不可预见性应激(Chronic unpredicted mild stress ,CUMS)组大鼠的行为学表现能力下降,BDNF表达下降(n=8,P<0.01),iNOS的表达升高(n=8,P<0.01);阻断内源性BDNF大鼠的行为学表现能力也下降,iNOS的表达升高(n=7,P<0.01);而海马微量注射iNOS的抑制剂SMT均可反转CUMS和BDNF抑制剂所导致的行为学表现能力下降的现象.慢性不可预见性应激引起海马BDNF表达下降,NO过高而导致抑郁.BDNF对神经元具有保护作用, BDNF的抗抑郁作用可能是通过抑制iNOS的表达而起作用的.提示BDNF等神经保护因子通过抑制iNOS的过量表达而保护脑组织可能是治疗抑郁症的一个重要途径.

  1. Behavioral and hippocampal cytoskeletal alterations in rats following chronic unpredictable mild stress and fluoxetine treatment%慢性应激及氟西汀治疗后大鼠海马细胞支架的改变

    Institute of Scientific and Technical Information of China (English)

    杨灿; 王高华; 王惠玲; 王晓萍; 刘忠纯; 朱志先

    2010-01-01

    目的 探讨慢性不可预见性应激及氟西汀治疗后大鼠细胞支架微管系统的动态性变化及其可能机制.方法 将24只大鼠按随机数字表法分为对照组(空白对照+生理盐水)、慢性不可预见性温和应激(CUMS)组(CUMS+生理盐水)和氟西汀组(CUMS+氟西汀),每组8只.对大鼠进行连续21 d CUMS后,氟西汀组给予氟西汀(10 mg/kg)治疗21 d,对照组和CUMS组给予生理盐水.实验结束后进行行为学观察,并使用免疫印迹法(western blot)检测大鼠海马乙酰化微管蛋白(Acet-Tub),酪氨酸化微管蛋白(Tyr-Tub),微管结合蛋白2(MAP-2)及磷酸化微管结合蛋白2(phospho-MAP-2).结果 (1)CUMS组糖水偏好[(55.13±11.80)%],总行程[(2736.59±511.20)cm],运动平均速度[(5.69±1.08)cm/s]及直立次数[(2.50±2.00)次]均低于对照组,差异有统计学意义(P<0.01);氟西汀组上述指标与对照组比较差异无统计学意义(P>0.05).(2)CUMS组与对照组相比,Acet-Tub表达升高[(171.84±10.34)%],Tyr-Tub[(62.06±9.24)%]和phospho-MAP-2[(68.81±8.93)%]的表达降低,差异有统计学意义(P均<0.01),MAP-2的表达与对照组比较无统计学意义(P>0.05);经氟西汀治疗后,Acet-Tub的表达降低为[(96.18±8.92)%],Tyr-Tub和phospho-MAP-2的表达分别升高为[(95.06±8.00)%]、[(100.60±7.30)%],与对照组比较均无统计学意义(P>0.05).结论 慢性应激后微管动态性减低,神经可塑性受损,氟西汀可以逆转海马的这些损伤,上述过程可能与微管相关蛋白磷酸化水平的变化有关.%Objective To investigate behavior and hippocampal cytoskeletal alterations in rats following chronic unpredictable mild stress and fluoxetine treatment, and explore the possible mechanism. Methods Twenty four male Sprague-Dawley (SD) rats were divided into three groups, with 8 exposed to 21 consecutive days of chronic unpredicted mild stresses (CUMS) and treated with vehicle, 8 exposed to CUMS and treated with fluoxetine, and 8 as

  2. Analysis of expression of brain-derived neurotrophic factor in rats with chronic unpredictable mild stress%慢性应激大鼠脑源性营养因子的表达分析

    Institute of Scientific and Technical Information of China (English)

    王静华; 肖泽萍; 肖世富; 彭素芳; 董晓蔚; 禹顺英; 李华芳; 李霞

    2012-01-01

    目的 探讨慢性不可预知轻度应激(CUMS)大鼠模型各脑区脑源性神经营养因子(BDNF)的表达及抗抑郁药对BDNF表达的影响.方法 将24只雄性SD大鼠随机分为三组(n=8):A组为对照组;B组为CUMS应激组;C组为CUMS应激+西太普兰用药组(每天腹腔注射西酞普兰水溶液2 mL,10 mg/kg).实验为期6周,每周称量大鼠体质量,每3周测试大鼠的糖水偏爱度,造模前及造模6周末通过旷场试验评价大鼠行为.6周后处死大鼠获取脑组织,采用Real-Time PCR检测各脑区BDNFmRNA表达水平.结果 第6周末,B组大鼠的糖水偏爱度明显低于A、C两组(P<0.05)且行为增多.应激实验开始后,B、C两组大鼠体质量均明显低于A组(P<0.05).B组BDNF mRNA在海马中的表达高于A组,但差异无统计学意义(P=0.07);C组纹状体中BDNF mRNA表达明显低于A组(P<0.05).结论 慢性应激可能引起海马BDNF表达升高,抗抑郁药物可能导致纹状体BDNF表达降低.%Objective To investigate the expression of brain-derived neurotrophic factor ( BDNF) in different areas of brain in rats with chronic unpredictable mild stress ( CUMS), and explore the effects of antidepressant on expression of BDNF. Methods Twenty-four male SD rats were randomly assigned to control group ( group A) , CUMS group ( group B) and CUMS + citalpram group (intraperitoneal injection of citalpram 2 mL once a day, 10 nig/kg) (group C), with 8 rats in each group. The experiment lasted for 6 weeks. Body weight was measured each week, sugar preference was evaluated every 3 weeks, and behavior of rats was assessed through open field tests before model establishment and 6 weeks after model establishment. Animals were sacrificed after 6 weeks, brain tissues were obtained, and Real-Time PCR was employed to detect the expression of BDNF mRNA in different areas of brain. Results At the end of the sixth week, rats in group B had significantly lower sugar preference than group A Bnd group C

  3. Stress-induced neuroinflammation: mechanisms and new pharmacological targets

    Directory of Open Access Journals (Sweden)

    C.D. Munhoz

    2008-12-01

    Full Text Available Stress is triggered by numerous unexpected environmental, social or pathological stimuli occurring during the life of animals, including humans, which determine changes in all of their systems. Although acute stress is essential for survival, chronic, long-lasting stress can be detrimental. In this review, we present data supporting the hypothesis that stress-related events are characterized by modifications of oxidative/nitrosative pathways in the brain in response to the activation of inflammatory mediators. Recent findings indicate a key role for nitric oxide (NO and an excess of pro-oxidants in various brain areas as responsible for both neuronal functional impairment and structural damage. Similarly, cyclooxygenase-2 (COX-2, another known source of oxidants, may account for stress-induced brain damage. Interestingly, some of the COX-2-derived mediators, such as the prostaglandin 15d-PGJ2 and its peroxisome proliferator-activated nuclear receptor PPARγ, are activated in the brain in response to stress, constituting a possible endogenous anti-inflammatory mechanism of defense against excessive inflammation. The stress-induced activation of both biochemical pathways depends on the activation of the N-methyl-D-aspartate (NMDA glutamate receptor and on the activation of the transcription factor nuclear factor kappa B (NFκB. In the case of inducible NO synthase (iNOS, release of the cytokine TNF-α also accounts for its expression. Different pharmacological strategies directed towards different sites in iNOS or COX-2 pathways have been shown to be neuroprotective in stress-induced brain damage: NMDA receptor blockers, inhibitors of TNF-α activation and release, inhibitors of NFκB, specific inhibitors of iNOS and COX-2 activities and PPARγ agonists. This article reviews recent contributions to this area addressing possible new pharmacological targets for the treatment of stress-induced neuropsychiatric disorders.

  4. A PET study on brain of chronic unpredictable mild stimulations (CUMS)-induced depressive rats%慢性不可预见性温和刺激抑郁症模型大鼠的脑PET成像研究

    Institute of Scientific and Technical Information of China (English)

    刘金鹏; 刘华; 高峻钰; 刘少君

    2015-01-01

    目的:通过PET成像技术研究慢性不可预见性温和刺激( CUMS)致抑郁症大鼠的全脑代谢特点。方法实验组大鼠给予CUMS 4周后,通过糖水偏嗜度、自发活动距离、体质量等指标分为刺激后抑郁大鼠( D组)及刺激后非抑郁大鼠( ND组),并与正常对照组大鼠( CON组)一起行PET检查,比较不同组大鼠之间全脑的代谢变化。结果(1)D组大鼠的双侧S1、丘脑、苍白球、岛叶、M2、左屏状核较CON组代谢升高,右侧下丘、胼胝体压部、小脑则代谢降低;(2)D组大鼠双侧海马CA3区、M1、M2、纹状体、S1、嗅球等区较ND组代谢增高,左侧楔状核及海马则代谢降低;(3) ND组大鼠与CON组相比,无代谢升高的脑区,而外侧隔核、双侧纹状体、下丘脑室旁核、双侧S1、右侧苍白球则代谢降低。结论以前囟后4 mm处为界,抑郁大鼠脑代谢特点是前高后低,左右大致对称。抑郁症的发生可能与多个脑区功能的异常相互作用有关。%Objective To observe the metabolic changes in the whole brain of chronic unpredictable mild stimulations ( CUMS)-induced depressive rats using PET imaging technology.Methods After 4 weeks’ of CUMS, rats of experimental group were divided into two groups:Group D( depression) and Group ND( no depression) , according to the degree of sugar addiction, distance of spontaneous activity and relative body mass.Then metabolic changes in the whole brain of these rats and those in control group ( CON) were observed using PET technology, and the differences were companred between the threegroups.Results (1)ComparedwithGroupCON,metabolismofGroupDwaselevatedinbilateralS1,thalamus, globus pallidus, insula, M2 and left claustrum, but descended in right inferior colliculus, splenium of corpus callosum and cerebellum.(2) Metabolism of Group D increased in the bilateral CA3 region of hippocampus, M1, M2, striatum, S1 and olfactory bulb

  5. Chronic stress disrupts neural coherence between cortico-limbic structures

    Directory of Open Access Journals (Sweden)

    João Filipe Oliveira

    2013-02-01

    Full Text Available Chronic stress impairs cognitive function, namely on tasks that rely on the integrity of cortico-limbic networks. To unravel the functional impact of progressive stress in cortico-limbic networks we measured neural activity and spectral coherences between the ventral hippocampus (vHIP and the medial prefrontal cortex (mPFC in rats subjected to short term (STS and chronic unpredictable stress (CUS. CUS exposure consistently disrupted the spectral coherence between both areas for a wide range of frequencies, whereas STS exposure failed to trigger such effect. The chronic stress-induced coherence decrease correlated inversely with the vHIP power spectrum, but not with the mPFC power spectrum, which supports the view that hippocampal dysfunction is the primary event after stress exposure. Importantly, we additionally show that the variations in vHIP-to-mPFC coherence and power spectrum in the vHIP correlated with stress-induced behavioral deficits in a spatial reference memory task. Altogether, these findings result in an innovative readout to measure, and follow, the functional events that underlie the stress-induced reference memory impairments.

  6. Regulatory effect of heat shock protein 70 in stress-induced rat intestinal epithelial barrier dysfunction

    Directory of Open Access Journals (Sweden)

    Ping-Chang Yang

    2009-01-01

    Full Text Available Background : Psychological stress is one of the factors associated with many human diseases; the mechanisms need to be further understood. Methods : Rats were subjected to chronic water avoid stress. Intestinal epithelial heat shock protein (HSP 70 was evaluated. The intestinal epithelial permeability was examined with Ussing chamber technique. Results : HSP70 was detected in normal intestinal epithelial cells. Psychological stress decreased HSP70 in the intestinal epithelial cells that correlated with the stress-induced intestinal epithelial hyperpermeability. Pretreatment with HSP70 abrogated stress-induced intestinal barrier dysfunction. Conclusions : Chronic stress inhibits HSP70 activity in rat intestinal epithelial layer that is associated with intestinal epithelial barrier dysfunction, which can be prevented by pretreatment with HSP70 protein. (Yang PC, Tu YH, Perdue MH, Oluwole C, Struiksma S. Regulatory effect of heat shock protein 70 in stress-induced rat intestinal epithelial barrier dysfunction.

  7. NEUROPROTECTIVE EFFECT OF CURCUMIN ON RATS UNDER CHRONIC UNPREDICTABLE MILD STRESS%姜黄素预处理对慢性心理应激大鼠中枢神经的保护作用

    Institute of Scientific and Technical Information of China (English)

    安改红; 陈学伟; 王静; 刘洪涛; 张娜; 徐传香; 佘晓俊; 崔博; 马强

    2013-01-01

    目的 观察姜黄素预处理对慢性应激大鼠行为学、单胺类递质水平及血清糖皮质激素的影响,为评价姜黄素对慢性心理应激大鼠中枢神经的保护作用提供依据.方法 48只Wistar大鼠随机分为对照组、慢性应激组、氟西汀干预组、姜黄素(低、中、高剂量)干预组,每天应激前1h灌胃给药.对大鼠进行28 d应激刺激建立慢性不可预知性慢性应激模型.旷场试验测定大鼠行为学指标;糖水试验测定大鼠“快感缺乏”;高效液相-电化学检测法测定海马单胺类递质;ELISA检测血清糖皮质激素.结果 慢性应激组大鼠的体质量、旷场活动性和糖水偏嗜度均明显低于对照组(P<0.05,P<0.01);海马5-HT含量下降(P<0.05),血清糖皮质激素水平升高(P<0.01).3个剂量姜黄素组大鼠体质量于第4周分别为(310.60±21.35)、(315.60±23.73)和(319.91±18.76)g,高于慢性应激组[(270.24±19.60)g,P<0.05];旷场竖立时间分别为(18.86±9.49)、(24.14±4.38)和(24.14±5.41)s,高于慢性应激组[(11.00±9.20)s,P<0.05];血清糖皮质激素水平分别为(567.94±22.54)、(338.62±63.79)和(259.96± 17.79)ng/L,低于慢性应激组[(908.57±22.86) ng/L,P<0.01].实验后低、中剂量组海马5-HT含量分别为(1063.89±149.61)和(1340.96±42.62) ng/g,高于慢性应激组[(941.23±80.00) ng/g,P<0.05].结论 姜黄素预处理可改善慢性不可预知性应激大鼠抑郁状态,起到中枢神经保护作用,其作用机制可能与单胺类递质水平的增加和调节HPA轴活性有关.%Objective To observe the effect of curcumin on behavior,monoamine neurotransmitter,and serum glucocorticoid of rats under chronic unpredictable mild stress (CUMS) ,in order to provide theoretical basis for assessing the neuroprotection of curcumin. Methods Forty-eight male Wistar rats were randomly divided into six groups: normal control group, stress group, curcumin groups (low, moderate, high dose) ,and

  8. Unpredictability and the transmission of numbers

    CERN Document Server

    Myers, John M

    2015-01-01

    Curiously overlooked in physics is its dependence on the transmission of numbers. For example the transmission of numerical clock readings is implicit in the concept of a coordinate system. The transmission of numbers and other logical distinctions is often achieved over a computer-mediated communications network in the face of an unpredictable environment. By unpredictable we mean something stronger than the spread of probabilities over given possible outcomes, namely an opening to unforeseeable possibilities. Unpredictability, until now overlooked in theoretical physics, makes the transmission of numbers interesting. Based on recent proofs within quantum theory that provide a theoretical foundation to unpredictability, here we show how regularities in physics rest on a background of channels over which numbers are transmitted. As is known to engineers of digital communications, numerical transmissions depend on coordination reminiscent of the cycle of throwing and catching by players tossing a ball back and...

  9. Stress-induced structural remodeling in hippocampus: Prevention by lithium treatment

    Science.gov (United States)

    Wood, Gwendolyn E.; Young, L. Trevor; Reagan, Lawrence P.; Chen, Biao; McEwen, Bruce S.

    2004-03-01

    Chronic restraint stress, psychosocial stress, as well as systemic or oral administration of the stress-hormone corticosterone induces a morphological reorganization in the rat hippocampus, in which adrenal steroids and excitatory amino acids mediate a reversible remodeling of apical dendrites on CA3 pyramidal cell neurons of the hippocampus. This stress-induced neuronal remodeling is accompanied also by behavioral changes, some of which can be prevented with selective antidepressant and anticonvulsive drug treatments. Lithium is an effective treatment for mood disorders and has neuroprotective effects, which may contribute to its therapeutic properties. Thus, we wanted to determine whether lithium treatment could prevent the effects of chronic stress on CA3 pyramidal cell neuroarchitecture and the associated molecular and behavioral measures. Chronic lithium treatment prevented the stress-induced decrease in dendritic length, as well as the stress-induced increase in glial glutamate transporter 1 (GLT-1) mRNA expression and the phosphorylation of cAMP-response element binding in the hippocampus. Lithium treatment, however, did not prevent stress effects on behavior in the open field or the plus-maze. These data demonstrate that chronic treatment with lithium can protect the hippocampus from potentially deleterious effects of chronic stress on glutamatergic activation, which may be relevant to its therapeutic efficacy in the treatment of major depressive disorder and bipolar disorder.

  10. 慢性不可预测性温和应激对大鼠行为及海马微管蛋白表达的影响%The Impact of Chronic Unpredictable Mild Stress on Behavior and Tubulin Expression of Hippocampus in Rats

    Institute of Scientific and Technical Information of China (English)

    张学平; 胡尚平; 王高华; 杨灿

    2013-01-01

    Objective To explore the impact of chronic unpredictable mild stress on behaviors and hippocam-pal neurons microtubules. Methods Twenty - four male rats were randomly divided into three groups, with 8 rats as chronic unpredicted mild stresses group (CUMS) , 8 rats as the fluoxetine administrated group and 8 as normal controls. After 6 weeks ,behavioral changes in these rats were analyzed in an open -field paradigm. The expression of hippocampal cytoskeletal microtubulin ( Acet - Tub or Tyr - Tub ) were analyzed using Western Blot. Results (1) Compared with the normal rats, sucrose prefereneet total traveling distance, velocity and frequencies of rearing were significantly reduced in the depressed rats( P < 0. 01); Behavioral changes could be reversed after 21 day fluoxetine treatment;( 2) The western blotting results showed that compared with the normal rats, the Acet - Tub expression of CUMS group showed a significant increase ( P < 0. 01) and Tyr - Tub expression of CUMS group was significantly decreased following CUMS stress ( P < 0. 01 ). Conclusion These findings provide evidence that rats exposed to chronic unpredicted mild stresses showed impairment of cytoskeletal microtubular dynamic and structural neuronal plasticity, providing insight into the role of cytoskeleton in the depression.%目的 研究慢性不可预测性温和应激对大鼠行为及海马微管蛋白表达的影响.方法 将SD雄性大鼠24只随机分为对照组、慢性不可预测性温、应激组(chronic unpredicted mild stress,CUMS组)和氟西汀组,每组8只.在实验结束后对三组大鼠进行行为学观察,检测海马微管蛋白的表达.结果 CUMS组大鼠总行程、平均运动速度、直立次数及糖水偏好低于对照组(P<0.01);氟西汀组行为学评价指标与对照组比较差异无统计学意义(P>0.05).免疫印迹结果显示CUMS组海马乙酰化微管蛋白(Acet-Tub)表达升高,酪氨酸化微管蛋白(Tyr-Tub)表达减低,与对照组

  11. 慢性应激抑郁型黄褐斑动物模型建立与现有模型的比较研究%Establishment of Chloasma Guinea pig Model with chronic unpredictable mild stress depression and comparative study of it with existent models

    Institute of Scientific and Technical Information of China (English)

    杨鹏; 杨慧兰; 麦跃; 戴勇; 孙林潮; 鲁东平

    2013-01-01

    Objective To establish and authenticate the Chloasma Guinea pig Model with chronic unpredictable mild stress depression and comparative study of it with existent models. Methods After the injection of progesterone,chronic unpredictable sequence of mild stressors stimulated them and gave them partially ultraviolet radiation. Results The Guinea pig model of depression had been established successfully at 28th day.Multiple models of progesterone injection and ultraviolet radiation compounding with chronic unpredictable sequence of mild stressors can heighten MDA,depress SOD,and increase melanocytes of skin. Meanwhile,the ethology of this model showed it's syndrome of Depressive position.The guinea pig showed reduced squares crossing and rearing in open-field test, a significantly reduced consumption of preference for sucrose solutions and an increased pure water consumption as compared with control group. Conclusion The multiple factor Chloasma model of chronic unpredictable mild stress depression has been built successfully. Compared with other existing models of MDA,SOD and skin melanocytes objective indicators of change closer to human Chloasma lesions.%目的:建立并验证慢性应激抑郁型黄褐斑动物模型,并与现有其他模型进行比较.方法:在注射黄体酮同时,进行慢性轻度不可预见的应激刺激,并紫外线局部照射.结果:黄体酮+紫外线+慢性应激抑郁法造模较其他方法更能导致皮肤丙二醛(Malondialdehyde,MDA)升高和超氧化物歧化酶(Superoxide dismutase,SOD)降低以及皮肤黑素细胞的增加,并且具有抑郁症的行动学表现.与空白组比较,经慢性轻度不可预见性应激刺激的动物体重显著下降,敞箱试验中穿格次数、理毛时间和次数、直立次数得分显著下降,液体消耗试验中糖水消耗和糖水偏爱百分比明显下降,而纯水消耗显著提高.结论:黄体酮+紫外线+慢性应激抑郁法建立的抑郁型黄褐斑豚鼠多因素模型

  12. Unpredictability and the transmission of numbers

    Science.gov (United States)

    Myers, John M.; Madjid, F. Hadi

    2016-03-01

    Curiously overlooked in physics is its dependence on the transmission of numbers. For example, the transmission of numerical clock readings is implicit in the concept of a coordinate system. The transmission of numbers and other logical distinctions is often achieved over a computer-mediated communications network in the face of an unpredictable environment. By unpredictable we mean something stronger than the spread of probabilities over given possible outcomes, namely an opening to unforeseeable possibilities. Unpredictability, until now overlooked in theoretical physics, makes the transmission of numbers interesting. Based on recent proofs within quantum theory that provide a theoretical foundation to unpredictability, here we show how regularities in physics rest on a background of channels over which numbers are transmitted. As is known to engineers of digital communications, numerical transmissions depend on coordination reminiscent of the cycle of throwing and catching by players tossing a ball back and forth. In digital communications, the players are computers, and the required coordination involves unpredictably adjusting "live clocks" that step these computers through phases of a cycle. We show how this phasing, which we call logical synchronization, constrains number-carrying networks, and, if a spacetime manifold in invoked, put "stripes" on spacetime. Via its logically synchronized channels, a network of live clocks serves as a reference against which to locate events. Such a network in any case underpins a coordinate frame, and in some cases the direct use of a network can be tailored to investigate an unpredictable environment. Examples include explorations of gravitational variations near Earth.

  13. Physical Exercise Counteracts Stress-induced Upregulation of Melanin-concentrating Hormone in the Brain and Stress-induced Persisting Anxiety-like Behaviors.

    Science.gov (United States)

    Kim, Tae-Kyung; Han, Pyung-Lim

    2016-08-01

    Chronic stress induces anxiety disorders, whereas physical exercise is believed to help people with clinical anxiety. In the present study, we investigated the mechanisms underlying stress-induced anxiety and its counteraction by exercise using an established animal model of anxiety. Mice treated with restraint for 2 h daily for 14 days exhibited anxiety-like behaviors, including social and nonsocial behavioral symptoms, and these behavioral impairments lasted for more than 12 weeks after the stress treatment was removed. Despite these lasting behavioral changes, wheel-running exercise treatment for 1 h daily from post-stress days 1 - 21 counteracted anxiety-like behaviors, and these anxiolytic effects of exercise persisted for more than 2 months, suggesting that anxiolytic effects of exercise stably induced. Repeated restraint treatment up-regulated the expression of the neuropeptide, melanin-concentrating hormone (MCH), in the lateral hypothalamus, hippocampus, and basolateral amygdala, the brain regions important for emotional behaviors. In an in vitro study, treatment of HT22 hippocampal cells with glucocorticoid increased MCH expression, suggesting that MCH upregulation can be initially triggered by the stress hormone, corticosterone. In contrast, post-stress treatment with wheel-running exercise reduced the stress-induced increase in MCH expression to control levels in the lateral hypothalamus, hippocampus and basolateral amygdala. Administration of an MCH receptor antagonist (SNAP94847) to stress-treated mice was therapeutic against stress-induced anxiety-like behaviors. These results suggest that repeated stress produces long-lasting anxiety-like behaviors and upregulates MCH in the brain, while exercise counteracts stress-induced MCH expression and persisting anxiety-like behaviors. PMID:27574483

  14. 舒郁散对慢性应激抑郁大鼠行为及海马糖皮质激素受体表达的影响%Effect of Suyusan on the Behavior and Glucocorticoid Receptor Expression in Hippocampus with Chronic Unpredictable Mild Stress induced Depression Rats

    Institute of Scientific and Technical Information of China (English)

    陈利平; 王发渭; 段冬梅; 孙志高; 许成勇

    2014-01-01

    目的 观察舒郁散对慢性不可预见性应激(CUMS)抑郁大鼠的行为变化及对大鼠脑组织肿瘤坏死因子-α (TNF-α)含量、海马内糖皮质激素受体表达的影响.方法 50只Wistar大鼠随机分为正常对照组、模型组、百忧解组、舒郁散小剂量组、舒郁散大剂量组.对大鼠进行21 d的CUMS刺激,采用糖水实验、悬尾实验观察大鼠的行为改变,用ELISA法测大鼠脑组织TNF-α含量,免疫组化观察大鼠海马GR表达.结果 百忧解组、舒郁散大剂量组大鼠的尾悬不动时间明显延长、糖水消耗百分率明显下降,与模型组比差异显著(P<0.01).百忧解、舒郁散大剂量治疗组大鼠悬尾不动时间明显减少,糖水消耗量明显增加,与模型组比差异显著(P< 0.05).百忧解、舒郁散大剂量治疗组大鼠脑组织TNF-α含量显著降低,与模型组比差异显著(P<0.05).模型组海马GR免疫反应阳性神经元数目明显减少,百忧解组、舒郁散大剂量组海马GR免疫反应阳性神经元数目明显增加,平均光密度明显增强,与模型组比差异显著(P<0.05).结论 动物行为学显示舒郁散具有抗抑郁作用,这种作用与降低CUMS抑郁大鼠脑组织TNF-α含量,增强海马糖皮质激素受体表达有关,上述作用与其剂量呈正相关.

  15. Repeated Short-term (2h×14d) Emotional Stress Induces Lasting Depression-like Behavior in Mice

    OpenAIRE

    Kim, Kyoung-Shim; Kwon, Hye-Joo; Baek, In-Sun; Han, Pyung-Lim

    2012-01-01

    Chronic behavioral stress is a risk factor for depression. To understand chronic stress effects and the mechanism underlying stress-induced emotional changes, various animals model have been developed. We recently reported that mice treated with restraints for 2 h daily for 14 consecutive days (2h-14d or 2h×14d) show lasting depression-like behavior. Restraint provokes emotional stress in the body, but the nature of stress induced by restraints is presumably more complex than emotional stress...

  16. Chronic mild stress induces depression-like behavior of rats%慢性应激性刺激对大鼠行为的影响——抑郁症模型的建立

    Institute of Scientific and Technical Information of China (English)

    姚莉红; 成翔; 张蕾; 衣昕; 郭玉秀; 秦建兵; 金国华; 张新化

    2013-01-01

    目的:以慢性应激性刺激(chronic mild stress,CMS)制作抑郁症动物模型,并以多种方式检测模型鼠的行为学变化,以期获得理想的动物模型.方法:对SD大鼠给予不可预知的慢性应激性刺激,包括:日夜颠倒;笼子弄脏;将笼子倾斜45°;限制它的活动;夜间不给予充足的食物;停止或减少对其水的供应等.每项刺激持续时间≥20 min,每2次刺激间隔时间≥16h,为时5周.在刺激结束后,立即进行行为学测试,包括悬尾实验(tail suspension test,TST);强迫游泳实验(forced swim test,FST);蔗糖饮水实验(sucrose preference test,SPT).结果:经过CMS处理的大鼠在悬尾试验中的不动时间明显大于未经过CMS实验处理的大鼠的不动时间(P<0.05).在强迫游泳实验中,经过CMS处理的大鼠不动次数大于未经CMS实验的大鼠的次数,游泳的次数明显少于未经CMS实验处理的大鼠的游泳次数.未经CMS实验的大鼠蔗糖摄入百分比为(72.10±5.24)%,而经过CMS实验大鼠的摄入蔗糖水百分比为(52.98± 11.14)%,明显低于对照组(P<0.05).结论:不可预知的缓慢刺激长时间施加到啮齿类动物,可以模拟出类似抑郁症的相关症状.

  17. A comparative study on behavior changes and cerebral morphology and function of chronic restraint stress mice and chronic unpredictable mild stress mice%慢性束缚与慢性不可预期温和应激抑郁模型小鼠的行为学比较及其发生机制研究

    Institute of Scientific and Technical Information of China (English)

    廖莎; 周佳; 平锋锋; 王倩; 郝娣; 尚靖

    2012-01-01

    【Objective】 The aim of this study was to explore the pathogenesis of depression by comparing the effects of chronic restraint stress(CRS) and chronic unpredictable mild stress(CUMS) on behavior and cerebral morphology of C57BL/6 mice.【Method】 Mice were randomly divided into the normal control(NC) group,CRS group,and CUMS group.After 3 weeks of stress exposure,open-field test,tail suspension test,and forced swimming test were taken to evaluate the behavior changes of mice.In addition,the cerebral morphology and function changes were investigated by HE staining and immuno-histochemistry analysis.The MAO activity of mice hippocampus was analyzed by fluorescence spectrophotometry.【Result】 The results showed that compared to the NC group,the crossing frequency,hearing frequency and body weight were all decreased significantly in the CRS group,whereas no significant changes in the CUMS group(P0.05).However,the results of tail suspension test and forced swimming test showed that there was a significant increase in the percent of immobility time in the CUMS group compared to the NC group(P0.01).In addition,except the hippocampus CA1 region in the CRS group,the CA1,CA3 and dentate gyrus regions of hippocampus were all atrophied in both stressed groups.Furthermore,the expression of 5-HT1A receptor in hippocampus was decreased and the MAO activity was up-regulated in both CRS and CUMS group.【Conclusion】 The results showed that both CRS and CUMS can induce depressive-like behaviors in C57BL/6 mice.CRS mainly suppresses the exploratory behavior while CUMS induced typical behavioral despair.This praxiology distinction may be relative to the differences in cerebral morphology and function of treated mice between two stressed groups.%【目的】通过比较慢性束缚应激(Chronic restraint stress,CRS)与慢性不可预期温和应激(Chronic unpredictable mild stress,CUMS)对C57BL/6小鼠行为学指标及大脑海马区相关功能的影响,探讨抑

  18. STRESS INDUCED OBESITY: LESSONS FROM RODENT MODELS OF STRESS

    Directory of Open Access Journals (Sweden)

    Zachary Robert Patterson

    2013-07-01

    Full Text Available Stress is defined as the behavioral and physiological responses generated in the face of, or in anticipation of, a perceived threat. The stress response involves activation of the sympathetic nervous system and recruitment of the hypothalamic-pituitary-adrenal (HPA axis. When an organism encounters a stressor (social, physical, etc., these endogenous stress systems are stimulated in order to generate a fight-or-flight response, and manage the stressful situation. As such, an organism is forced to liberate energy resources in attempt to meet the energetic demands posed by the stressor. A change in the energy homeostatic balance is thus required to exploit an appropriate resource and deliver useable energy to the target muscles and tissues involved in the stress response. Acutely, this change in energy homeostasis and the liberation of energy is considered advantageous, as it is required for the survival of the organism. However, when an organism is subjected to a prolonged stressor, as is the case during chronic stress, a continuous irregularity in energy homeostasis is considered detrimental and may lead to the development of metabolic disturbances such as cardiovascular disease, type II diabetes mellitus and obesity. This concept has been studied extensively using animal models, and the neurobiological underpinnings of stress induced metabolic disorders are beginning to surface. However, different animal models of stress continue to produce divergent metabolic phenotypes wherein some animals become anorexic and loose body mass while others increase food intake and body mass and become vulnerable to the development of metabolic disturbances. It remains unclear exactly what factors associated with stress models can be used to predict the metabolic outcome of the organism. This review will explore a variety of rodent stress models and discuss the elements that influence the metabolic outcome in order to further our understanding of stress-induced

  19. Regulatory effect of heat shock protein 70 in stress-induced rat intestinal epithelial barrier dysfunction

    Directory of Open Access Journals (Sweden)

    Stevie Struiksma

    2009-06-01

    Full Text Available Background: Psychological stress is one of the factors associated with many human diseases; the mechanisms need to be further understood. Methods: Rats were subjected to chronic water avoid stress. Intestinal epithelial heat shock protein (HSP 70 was evaluated. The intestinal epithelial permeability was examined with Ussing chamber technique. Results: HSP70 was detected in normal intestinal epithelial cells. Psychological stress decreased HSP70 in the intestinal epithelial cells that correlated with the stress-induced intestinal epithelial hyperpermeability. Pretreatment with HSP70 abrogated stress-induced intestinal barrier dysfunction. Conclusions: Chronic stress inhibits HSP70 activity in rat intestinal epithelial layer that is associated with intestinal epithelial barrier dysfunction, which can be prevented by pretreatment with HSP70 protein.

  20. A Case of Anorexia Nervosa Complicated With Strongly Suspected Stress-Induced Cardiomyopathy and Mural Thrombus

    OpenAIRE

    Kim, Kyung-Hee; Youn, Ho-Joong; Lee, Wook-Hyun; Kim, Jin-Suk; Kim, Jae-Gyung; Park, Ha-Wook; Min, Jinsoo; Kim, Gee-Hee; Jung, Hae-Ok

    2011-01-01

    Stress-induced cardiomyopathy is a unique reversible cardiovascular disease precipitated by acute emotional or physical stress. It is associated with a high prevalence of chronic anxiety disorder that precedes the onset of cardiomyopathy, as well as comorbid cardiovascular risk factors that are similar to the ST segment elevation of myocardial infarction. A thirty-five-year-old woman suffering from anorexia nervosa visited our hospital complaining of severe general weakness. She was diagnosed...

  1. Ghrelin mediates stress-induced food-reward behavior in mice

    OpenAIRE

    Chuang, Jen-Chieh; Perello, Mario; Sakata, Ichiro; Osborne-Lawrence, Sherri; Savitt, Joseph M.; Lutter, Michael; Zigman, Jeffrey M.

    2011-01-01

    The popular media and personal anecdotes are rich with examples of stress-induced eating of calorically dense “comfort foods.” Such behavioral reactions likely contribute to the increased prevalence of obesity in humans experiencing chronic stress or atypical depression. However, the molecular substrates and neurocircuits controlling the complex behaviors responsible for stress-based eating remain mostly unknown, and few animal models have been described for probing the mechanisms orchestrati...

  2. Cognition in harsh and unpredictable environments

    NARCIS (Netherlands)

    Frankenhuis, W.E.; Panchanathan, K.; Nettle, D.

    2016-01-01

    In environments that are harsh and unpredictable, people are typically more vigilant, act more impulsively, and discount the future more. In this paper, we argue that these behaviors reflect a present-orientation produced by biological adaptations, despite potential harm to health and wellbeing. We

  3. Effect of intravenous human immunoglobulin G on hippocampal function of depressive model rats subjected to chronic unpredictable stress%静脉输注人免疫球蛋白G对慢性不可预料应激抑郁模型大鼠海马功能的影响

    Institute of Scientific and Technical Information of China (English)

    王晟; 徐丽芳

    2014-01-01

    目的:探讨静脉输注人免疫球蛋白G(IgG)对慢性不可预料应激抑郁模型大鼠海马功能的影响。方法对慢性不可预料应激抑郁模型大鼠分别给予静脉输注人IgG+应激( IgG组)和单纯应激( CUS组)处理,对照组不行任何处理。分别采用悬尾实验、糖水偏好实验、强迫游泳实验、自主活动实验和5-溴脱氧尿嘧啶核苷(BrdU)标记海马齿状回神经元,检测神经元再生情况。结果 IgG组及对照组糖水偏好消耗显著大于 CUS 组( P均<0.01);悬尾实验、强迫游泳实验和自主活动实验不动时间IgG组及对照组显著小于CUS组(P均<0.01);IgG组海马区域BrdU阳性细胞数与CUS组比较有统计学差异( P<0.01)。结论静脉输注人IgG对慢性不可预料应激造成的大鼠抑郁样行为具有改善作用;可保护海马的神经元再生功能。%Objective To investigate the effect of intravenous human immunoglobulin G ( IgG) on depressive model rats subjected to chronic unpredictable stress .Methods Depressive model rats subjected to chronic unpredictable stress were randomly divided into 3 groups: intravenous immunoglobulin G ( IVIG) +stress group ( IVIG group), stress-only group ( CUS group) and the control group without any treatment .Tail suspension test , sucrose preference test , forces swimming test, locomotor activity and BrdU labeling neuron of hippocampal dentate gyrus based neurogenesis were used to analyze the effect of IVIG on depressive model rats .Results Sucrose consumption in the IVIG group and control group was significantly less than that of the CUS group (P<0.01), while duration of immobility of tail suspension test , forced swimming test and lo-comotor activity was significantly shorter than that of the CUS group (all P<0.01).The difference of BrdU positive cell number in the hippocampus between the two groups was significant (P<0.01).Conclusion IVIG can improve the depres

  4. Protective effect of Labisia pumila on stress-induced behavioral, biochemical, and immunological alterations.

    Science.gov (United States)

    Kour, Kiranjeet; Sharma, Neelam; Chandan, Bal Krishan; Koul, Surrinder; Sangwan, Payare Lal; Bani, Sarang

    2010-10-01

    The aim of the present study was to investigate the antistress potential of LABISIA PUMILA aqueous extract (LPPM/A003) using a battery of tests widely employed in different stressful situations. Pretreatment of experimental animals with LPPM/A003 caused an increase in the swimming endurance and hypoxia time and also showed the recovery of physical stress-induced depletion of neuromuscular coordination and scopolamine induced memory deficit. LPPM/A003 at graded doses reversed the chronic restraint stress (RST), induced depletion of CD4 (+) and CD8 (+) T lymphocytes, NK cell population, and corresponding cytokines expression besides downregulating the stress-induced increase in plasma corticosterone, a major stress hormone. In addition, LPPM/A003 reversed the chronic stress-induced increase in adrenal gland weight, serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), and hepatic lipid peroxidation (LP) levels and augmented the RST induced decrease in hepatic glutathione (GSH), thymus and spleen weight. Thus, we conclude that LPPM/A003 has the ability to reverse the alterations produced by various stressful stimuli and therefore restores homeostasis. PMID:20217640

  5. Protective effect of Labisia pumila on stress-induced behavioral, biochemical, and immunological alterations.

    Science.gov (United States)

    Kour, Kiranjeet; Sharma, Neelam; Chandan, Bal Krishan; Koul, Surrinder; Sangwan, Payare Lal; Bani, Sarang

    2010-10-01

    The aim of the present study was to investigate the antistress potential of LABISIA PUMILA aqueous extract (LPPM/A003) using a battery of tests widely employed in different stressful situations. Pretreatment of experimental animals with LPPM/A003 caused an increase in the swimming endurance and hypoxia time and also showed the recovery of physical stress-induced depletion of neuromuscular coordination and scopolamine induced memory deficit. LPPM/A003 at graded doses reversed the chronic restraint stress (RST), induced depletion of CD4 (+) and CD8 (+) T lymphocytes, NK cell population, and corresponding cytokines expression besides downregulating the stress-induced increase in plasma corticosterone, a major stress hormone. In addition, LPPM/A003 reversed the chronic stress-induced increase in adrenal gland weight, serum alanine aminotransferase (ALT), alkaline phosphatase (ALP), and hepatic lipid peroxidation (LP) levels and augmented the RST induced decrease in hepatic glutathione (GSH), thymus and spleen weight. Thus, we conclude that LPPM/A003 has the ability to reverse the alterations produced by various stressful stimuli and therefore restores homeostasis.

  6. Hyperhomocysteinemia is a result, rather than a cause, of depression under chronic stress.

    Directory of Open Access Journals (Sweden)

    Shen Chengfeng

    Full Text Available BACKGROUND: Although the accumulation of homocysteine (Hcy has been implicated in the pathogenesis of depression, whether Hcy is directly involved and acts as the primary cause of depressive symptoms remains unclear. The present study was designed to clarify whether increased Hcy plays an important role in stress-induced depression. RESULTS: We employed the chronic unpredictable mild stress model (CUMS of depression for 8 weeks to observe changes in the plasma Hcy level in the development of depression. The results showed that Wistar rats exposed to a series of mild, unpredictable stressors for 4 weeks displayed depression-like symptoms such as anhedonia (decreased sucrose preferences and a decreased 5-Hydroxy Tryptophan (5-HT concentration in the hippocampus. At the end of 8 weeks, the plasma Hcy level increased in the CUMS rats. The anti-depressant sertraline could decrease the plasma Hcy level and improve the depression-like symptoms in the CUMS rats. RhBHMT, an Hcy metabolic enzyme, could decrease the plasma Hcy level significantly, although it could not improve the depressive symptoms in the CUMS rats. CONCLUSIONS: The results obtained from the experiments did not support the hypothesis that the increased Hcy concentration mediated the provocation of depression in CUMS rats, and the findings suggested that the increased Hcy concentration in the plasma might be the result of stress-induced depression.

  7. Macrophage migration inhibitory factor is an endogenous regulator of stress-induced extramedullary erythropoiesis.

    Science.gov (United States)

    Vignjević Petrinović, Sanja; Budeč, Mirela; Marković, Dragana; Gotić, Mirjana; Mitrović Ajtić, Olivera; Mojsilović, Slavko; Stošić-Grujičić, Stanislava; Ivanov, Milan; Jovčić, Gordana; Čokić, Vladan

    2016-09-01

    Macrophage migration inhibitory factor is a well-known proinflammatory cytokine that is released during systemic stress response. Although MIF can affect erythrocyte production, the role of this cytokine in stress-induced erythropoiesis is completely unknown. To extend our previous findings showing that chronic psychological stress stimulates extramedullary erythropoiesis, here we examined whether MIF is involved in the control of stress-induced erythropoietic response. Adult male C57BL/6 wild-type (WT) and MIF-KO (knock-out) mice were subjected to 2-h daily restraint stress for either 7 or 14 consecutive days. The number of erythroid progenitors and CD71/Ter119 profile of erythroid precursors were analyzed in the bone marrow and spleen. Additionally, MIF protein expression was assessed in WT mice. Our results demonstrated that chronic restraint stress enhanced the number of both erythroid progenitors and precursors in the spleen. Stress-induced increase in the number of splenic late erythroid progenitors as well as in the percentage of CD71(+)Ter119(+)-double-positive precursors was significantly more pronounced in MIF-KO mice compared to WT animals. Furthermore, repeatedly stressed WT animals demonstrated an augmented MIF expression in the spleen. Unlike the spleen, the bone marrow of chronically stressed WT mice exhibited less prominent changes in erythropoietic stress response and no significant alteration in MIF expression. In addition, MIF deficiency did not influence the bone marrow erythropoiesis in stressed animals. These findings suggest that MIF regulates extramedullary erythropoiesis by inhibiting an overexpansion of splenic immature erythroid cells during chronic stress and indicate a novel role for this cytokine under chronic stress conditions. PMID:27129368

  8. Stress-induced glucocorticoids as a neuroendocrine alarm signal of danger.

    Science.gov (United States)

    Frank, Matthew G; Watkins, Linda R; Maier, Steven F

    2013-10-01

    A considerable number of studies demonstrate that acute and chronic stressors prime CNS innate immune responses to subsequent pro-inflammatory challenges and that glucocorticoids mediate, in part, stress-induced sensitization of pro-inflammatory immune responses. Here, we explore the notion that GCs produce a persisting sensitization of CNS innate immune effectors (e.g. microglia) so that they will generate a potentiated pro-inflammatory response after the GC rise has dissipated, thereby enhancing the sickness response to infection or injury and maximizing the animal's ability to neutralize danger. The stress-induced GC response is conceptualized here as an neuroendocrine warning signal or alarmin to the innate immune system, which prepares or sensitizes the innate immune response to potential danger. Thus, a new understanding of the stress response and its function (priming CNS innate immune responses to infection or injury during a fight/flight emergency) would be suggested.

  9. A study on anti-stress property of Nardostachys jatamamsi on stress induced Drosophila melanogaster

    Directory of Open Access Journals (Sweden)

    Shilpashree R.

    2011-09-01

    Full Text Available Stress is a feeling that’s created when we react to particular events. It s the body’s way of rising to a challenge and preparing to meet a tough situation with focus, strength, stamina, and heightened alertness. As a result of the stress immune system can be suppressed by chronic stress opening to increased infections and increasing the risk of autoimmune diseases. So one has to learn away to overcome stress. Here is an attempt made to overcome the stress induced in Drosophila melanogaster a model organism, in this study. Methotrexate is used to induce the stress at different concentration taking different group of flies and a Nardostachys jatamamsi plant extract having antistress property is used to relieve the stress induced. This stress relieve measured by the various stress related enzymes like catalase and Superoxide dismutase by this antistress property of the plant Nardostachys jatamamsi was shown.

  10. Stress induced phase transitions in silicon

    Science.gov (United States)

    Budnitzki, M.; Kuna, M.

    2016-10-01

    Silicon has a tremendous importance as an electronic, structural and optical material. Modeling the interaction of a silicon surface with a pointed asperity at room temperature is a major step towards the understanding of various phenomena related to brittle as well as ductile regime machining of this semiconductor. If subjected to pressure or contact loading, silicon undergoes a series of stress-driven phase transitions accompanied by large volume changes. In order to understand the material's response for complex non-hydrostatic loading situations, dedicated constitutive models are required. While a significant body of literature exists for the dislocation dominated high-temperature deformation regime, the constitutive laws used for the technologically relevant rapid low-temperature loading have severe limitations, as they do not account for the relevant phase transitions. We developed a novel finite deformation constitutive model set within the framework of thermodynamics with internal variables that captures the stress induced semiconductor-to-metal (cd-Si → β-Si), metal-to-amorphous (β-Si → a-Si) as well as amorphous-to-amorphous (a-Si → hda-Si, hda-Si → a-Si) transitions. The model parameters were identified in part directly from diamond anvil cell data and in part from instrumented indentation by the solution of an inverse problem. The constitutive model was verified by successfully predicting the transformation stress under uniaxial compression and load-displacement curves for different indenters for single loading-unloading cycles as well as repeated indentation. To the authors' knowledge this is the first constitutive model that is able to adequately describe cyclic indentation in silicon.

  11. Role of brain-derived neurotrophic factor and neuronal nitric oxide synthase in stress-induced depression

    Institute of Scientific and Technical Information of China (English)

    Dan Wang; Shucheng An

    2008-01-01

    BACKGROUND: Accumulated evidence indicates an important role for hippocampal dendrite atrophy in development of depression, while brain-derived neurotrophic factor (BDNF) participates in hippocampal dendrite growth. OBJECTIVE: To discuss the role of BDNF and neuronal nitric oxide synthase (nNOS) in chronic and unpredictable stress-induced depression and the pathogenesis of depression.DESIGN, TIME AND SETTING: Randomized, controlled animal experiment. The experiment was carried out from October 2006 to May 2007 at the Department of Animal Physiology, College of Life Science, Shaanxi Normal University.MATERIALS: Thirty-seven male Sprague-Dawley rats weighing 250-300 g at the beginning of the experiment were obtained from Shaanxi Provincial Institute of Traditional Chinese Medicine (Xi'an, China). BDNF antibody and nNOS antibody were provided by Santa Cruz (USA). K252a (BDNF inhibitor) and 7-NI (nNOS inhibitor) were provided by Sigma (USA). METHODS: Animals were randomly divided into five groups: Control group, chronic unpredicted mild stress (CUMS) group, K252a group, K252a+7-NI group and 7-NI+CUMS group. While the Control, K252a and K252a+7-NI groups of rats not subjected to stress had free access to food and water, other groups of rats were subjected to nine stressors randomly applied for 21 days, with each stressor applied 2-3 times. On days 1, 7, 14 and 21 during CUMS, rats received microinjection of 1 μL of physiological saline in the Control and CUMS groups, 1 μL of K252a in the K252a group, 1 μL of K252a and 7-NI in the K252a+7-NI group, and 1 μL of 7-NI in the 7-NI+CUMS group. We observed a variety of alterations in sucrose preference, body weight change, open field test and forced swimming test, and observed the expression of BDNF and nNOS in rat hippocampus by immunohistochemistry;RESULTS: Compared with the Control group, the behavior of the CUMS rats was significantly depressed, the expression of BDNF decreased (P < 0.01) but the expression of n

  12. 舒郁宁心方对慢性应激抑郁模型大鼠行为学及海马BDNF、TrkB表达的影响%Effects of Shuyu Ningxin Recipe on the Praxiology and the Expressions of Hippocampal BDNF and TrkB of Model Rats with Chronic Stress-induced Depression

    Institute of Scientific and Technical Information of China (English)

    孙志高; 黄泉智; 许成勇; 陈利平

    2013-01-01

    目的 观察舒郁宁心方对慢性应激抑郁模型大鼠行为学以及海马脑源性神经营养因子(brainderived neurotrophic factor,BDNF)及其主要受体酪氨酸激酶B(tyrosine kinase B,TrkB)表达的影响,探讨其抗抑郁机制.方法 将60只成年SD大鼠随机分为正常对照组、模型组、西药组及中药大、中、小剂量组,每组10只.对大鼠进行21天的应激刺激建立慢性应激抑郁模型.除正常对照组外,其他5组大鼠在造模第22天开始灌胃,模型组灌胃生理盐水,中药大、中、小剂量组分别给予25.0、7.5、2.5 g/kg舒郁宁心方灌胃;西药组给予盐酸氟西汀混悬液(12 mg/kg)灌胃;均连续给药3周.分别于O(造模前)、3周(造模成功后)、6周(给药结束后)测定每只大鼠体重;敞箱实验检测大鼠行为学;强迫游泳实验记录大鼠5min内不动时间.实验结束后脑区取材,测定大鼠脑组织中BDNF及TrkB表达水平.结果 与正常对照组比较,模型组大鼠体重增长缓慢,行为学指标下降,强迫游泳不动时间延长,海马BDNF及TrkB表达减弱,差异均有统计学意义(P <0.05,P<0.01).给药结束后,中药大剂量组和西药组大鼠体重增加,大鼠行为学改善,强迫游泳不动时间缩短,海马BDNF、TrkB表达增强,与模型组比较,差异均有统计学意义(P<0.05,P <0.01).结论 舒郁宁心方可能通过改善脑组织BDNF和TrkB的表达水平发挥抗抑郁作用.%Objective To observe the effects of Shuyu Ningxin Recipe (SNR) on the praxiology and the expressions of hippocampal brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase B (TrkB) of model rats with chronic stress-induced depression, thus exploring its anti-depression mechanisms. Methods Sixty adult SD rats were randomly divided into 6 groups, i.e., the normal control group, the model group, the fluoxetine group, the high dose SNR group, the medium dose SNR group, and the low dose SNR group, 10 in each

  13. Fluvoxamine Attenuated Endoplasmic Reticulum Stress-Induced Leptin Resistance

    OpenAIRE

    Hosoi, Toru; Miyahara, Tsuyoshi; Kayano, Takaaki; Yokoyama, Shota; Ozawa, Koichiro

    2012-01-01

    Increasing evidence indicates that endoplasmic reticulum stress (ER stress) is involved in the development of metabolic syndrome. However, pharmacological treatments targeting ER stress are not well understood. In the present study, we found that fluvoxamine, a selective serotonin reuptake inhibitor used for depression, can attenuate ER stress-induced “leptin resistance,” i.e., insensitivity to the anti-obesity hormone leptin. Treatment with tunicamycin, an ER stress-inducing reagent, caused ...

  14. Stress-induced enhancement of leukocyte trafficking into sites of surgery or immune activation

    Science.gov (United States)

    Viswanathan, Kavitha; Dhabhar, Firdaus S.

    2005-04-01

    Effective immunoprotection requires rapid recruitment of leukocytes into sites of surgery, wounding, infection, or vaccination. In contrast to immunosuppressive chronic stressors, short-term acute stressors have immunoenhancing effects. Here, we quantify leukocyte infiltration within a surgical sponge to elucidate the kinetics, magnitude, subpopulation, and chemoattractant specificity of an acute stress-induced increase in leukocyte trafficking to a site of immune activation. Mice acutely stressed before sponge implantation showed 200-300% higher neutrophil, macrophage, natural killer cell, and T cell infiltration than did nonstressed animals. We also quantified the effects of acute stress on lymphotactin- (LTN; a predominantly lymphocyte-specific chemokine), and TNF-- (a proinflammatory cytokine) stimulated leukocyte infiltration. An additional stress-induced increase in infiltration was observed for neutrophils, in response to TNF-, macrophages, in response to TNF- and LTN, and natural killer cells and T cells in response to LTN. These results show that acute stress initially increases trafficking of all major leukocyte subpopulations to a site of immune activation. Tissue damage-, antigen-, or pathogen-driven chemoattractants subsequently determine which subpopulations are recruited more vigorously. Such stress-induced increases in leukocyte trafficking may enhance immunoprotection during surgery, vaccination, or infection, but may also exacerbate immunopathology during inflammatory (cardiovascular disease or gingivitis) or autoimmune (psoriasis, arthritis, or multiple sclerosis) diseases. chemokine | psychophysiological stress | surgical sponge | wound healing | lymphotactin

  15. Effects of maternal rats exposed to chronic unpredictable stress before pregnancy on the behaviors and brain monamine of their adult male offspring%母鼠孕前慢性应激对成年雄性子代行为学和脑区单胺递质的影响

    Institute of Scientific and Technical Information of China (English)

    李海红; 张磊; 方泽漫; 吴彩茹; 朱琴; 黄庆军

    2010-01-01

    目的 研究母鼠孕前慢性应激对成年雄性子代行为学和脑内单胺类神经递质的影响.方法 16只成年雌性SD大鼠随机分为正常对照组和慢性不可预见性应激组(CUS),CUS组大鼠每天接受一种应激,共21d,正常对照组不接受任何应激.应激结束后10 d,2组大鼠均与同种SD雄性大鼠合笼,以成年2月龄雄性子代作为研究对象.用糖水消耗实验测量快感缺失,Morris水迷宫检测空间记忆能力,高效液相色谱法测量海马、下丘脑和前额皮质单胺递质的含量.结果 糖水消耗实验示正常对照组子代的糖水消耗量和糖水消耗百分比均显著高于CUS组子代[糖水消耗量:(10.23±4.12)g,(6.48±3.19)g;糖水消耗百分比:(85.43±20.15)%,(60.98±24.65)%](P<0.05).Morris水迷宫检测示2组的逃避潜伏期无差异,但空间探索测试中正常对照组子代[(4.17±2.29)次]穿越平台的次数明显多CUS组子代[(1.64±1.69)次](P<0.05).CUS组子代[(500.17±80.94)ng/g脑组织]下丘脑5-羟色胺的含量低于正常对照组子代[(569.63±50.91)ng/g脑组织](P<0.05),而CUS组子代[(2315.01±1397.12)ng/g脑组织]海马去甲肾上腺素的含量却要高于正常对照组子代[(907.56±207.27)ng/g脑组织](P<0.05).结论 母鼠孕前慢性应激或抑郁会造成成年雄性子代的快感缺失和空间记忆力下降,以及脑内单胺类神经递质异常.%Objective To examine the effects of maternal rats exposed to chronic unpredictable stress before pregnancy on the behaviors and brain monamine of their adult male offspring.Methods Sixteen SD rats were divided into chronic unpredictable stress (CUS) group and controls.CUS rats were exposed to 21 days chronic unpredictable stressors ,and the controls were stress-free.Ten days after the last stressor, all the female rats were caged with sexually experienced males of the same strain.Then we performed the following experiments on the two months male progeny, sucrose consumption

  16. Role of glia in stress-induced enhancement and impairment of memory

    Directory of Open Access Journals (Sweden)

    Jiah ePearson-Leary

    2016-01-01

    Full Text Available Both acute and chronic stress profoundly affects hippocampally-dependent learning and memory: moderate stress generally enhances, while chronic or extreme stress can impair, neural and cognitive processes. Within the brain, stress elevates both norepinephrine and glucocorticoids, and both affect several genomic and signaling cascades responsible for modulating memory strength. Memories formed at times of stress can be extremely strong, yet stress can also impair memory to the point of amnesia. Often overlooked in consideration of the impact of stress on cognitive processes, and specifically memory, is the important contribution of glia as a target for stress-induced changes. Astrocytes, microglia, and oligodendrocytes all have unique contributions to learning and memory. Furthermore, these three types of glia express receptors for both norepinephrine and glucocorticoids and are hence immediate targets of stress hormone actions. It is becoming increasingly clear that inflammatory cytokines and immunomodulatory molecules released by glia during stress may promote many of the behavioral effects of acute and chronic stress. In this review, the role of traditional genomic and rapid hormonal mechanisms working in concert with glia to affect stress-induced learning and memory will be emphasized.

  17. Role of Glia in Stress-Induced Enhancement and Impairment of Memory

    Science.gov (United States)

    Pearson-Leary, Jiah; Osborne, Danielle Maria; McNay, Ewan C.

    2016-01-01

    Both acute and chronic stress profoundly affect hippocampally-dependent learning and memory: moderate stress generally enhances, while chronic or extreme stress can impair, neural and cognitive processes. Within the brain, stress elevates both norepinephrine and glucocorticoids, and both affect several genomic and signaling cascades responsible for modulating memory strength. Memories formed at times of stress can be extremely strong, yet stress can also impair memory to the point of amnesia. Often overlooked in consideration of the impact of stress on cognitive processes, and specifically memory, is the important contribution of glia as a target for stress-induced changes. Astrocytes, microglia, and oligodendrocytes all have unique contributions to learning and memory. Furthermore, these three types of glia express receptors for both norepinephrine and glucocorticoids and are hence immediate targets of stress hormone actions. It is becoming increasingly clear that inflammatory cytokines and immunomodulatory molecules released by glia during stress may promote many of the behavioral effects of acute and chronic stress. In this review, the role of traditional genomic and rapid hormonal mechanisms working in concert with glia to affect stress-induced learning and memory will be emphasized. PMID:26793072

  18. Chronic mild stress and antidepressant treatment alter 5-HT1A receptor expression by modifying DNA methylation of a conserved Sp4 site.

    Science.gov (United States)

    Le François, Brice; Soo, Jeremy; Millar, Anne M; Daigle, Mireille; Le Guisquet, Anne-Marie; Leman, Samuel; Minier, Frédéric; Belzung, Catherine; Albert, Paul R

    2015-10-01

    The serotonin 1A receptor (5-HT1A), a critical regulator of the brain serotonergic tone, is implicated in major depressive disorder (MDD) where it is often found to be dys-regulated. However, the extent to which stress and antidepressant treatment impact 5-HT1A expression in adults remains unclear. To address this issue, we subjected adult male BALB/c mice to unpredictable chronic mild stress (UCMS) to induce a depression-like phenotype that was reversed by chronic treatment with the antidepressant imipramine. In prefrontal cortex (PFC) and midbrain tissue, UCMS increased 5-HT1A RNA and protein levels, changes that are expected to decrease the brain serotonergic activity. The stress-induced increase in 5-HT1A expression was paralleled by a specific increase in DNA methylation of the conserved -681 CpG promoter site, located within a Sp1-like element. We show that the -681 CpG site is recognized and repressed by Sp4, the predominant neuronal Sp1-like factor and that Sp4-induced repression is attenuated by DNA methylation, despite a stress-induced increase in PFC Sp4 levels. These results indicate that adult life stress induces DNA methylation of a conserved promoter site, antagonizing Sp4 repression to increase 5-HT1A expression. Chronic imipramine treatment fully reversed the UCMS-induced increase in methylation of the -681 CpG site in the PFC but not midbrain of stressed animals and also increased 5-HT1A expression in the PFC of control animals. Incomplete reversal by imipramine of stress-induced changes in 5-HT1A methylation and expression indicates a persistence of stress vulnerability, and that sustained reversal of behavioral impairments may require additional pathways. PMID:26188176

  19. 慢性应激性抑郁对大鼠皮下种植性肿瘤Walker256的影响及其作用机制%Effect of Chronic Stress-induced Depression on Subcutaneously Implanted Walker 256 Tumors in Rats and Its Mechanism

    Institute of Scientific and Technical Information of China (English)

    王双彪; 姜达; 张增叶

    2013-01-01

    间的慢性应激性抑郁可显著缩短荷瘤大鼠的生存期,其作用机制可能与脾脏等免疫器官萎缩、血清皮质醇、IL-6水平升高造成机体免疫内分泌功能紊乱,机体内环境的稳定遭到破坏有关.%Objective To observe the effect of chronic stress-induced depression on subcutaneously implanted Walker 256 tumors in rats,and to explore its possible mechanism.Methods Rat models of chronic stress-induced depression and subcutaneous implanted tumors were established in this study.Forty-eight female SD rats were randomly divided into four groups,with 12 rats in each group.Group A was only inoculated with Walker 256 carcinosarcoma cells,without stress before and after inoculation;Group B was given various stress treatments for 16 days after inoculation with Walker 256 carcinosarcoma cells;Group C was given various stress treatments for 16 days before inoculation with Walker 256 carcinosarcoma cells;Group D was given various stress treatments for 16 days both before and after inoculation with Walker 256 carcinosarcoma cells.The survival,behavior indexes,spleen weight,tumor weight,serum cortisol levels and interleukin-6 (IL-6) levels were measured after inoculation.Results Compared with group A,movement time,movement distance and central regional movement time significantly decreased but rest time and peripheral regional movement time significantly increased in group B,C and D (P<0.05).Compared with group B or C,movement distance significantly decreased in group D (P<0.05).In addition,movement time,rest time,central regional movement time and peripheral regional movement time in group D were longer than those in group B or C,but differences were not significant (P>0.05).Compared with group A,survival time and spleen weight obviously decreased but IL-6 levels obviously increased in group D (P<0.05).However,no significant differences were found among group A,B and C (P>0.05).Compared with group A,serum cortisol levels

  20. Intrathecal Clonidine Pump Failure Causing Acute Withdrawal Syndrome With 'Stress-Induced' Cardiomyopathy.

    Science.gov (United States)

    Lee, Hwee Min D; Ruggoo, Varuna; Graudins, Andis

    2016-03-01

    Clonidine is a central alpha(2)-agonist antihypertensive used widely for opioid/alcohol withdrawal, attention deficit hyperactivity disorder and chronic pain management. We describe a case of clonidine withdrawal causing life-threatening hypertensive crisis and stress-induced cardiomyopathy. A 47-year-old man with chronic back pain, treated with clonidine for many years via intrathecal pump (550 mcg/24 h), presented following a collapse and complaining of sudden worsening of back pain, severe headache, diaphoresis, nausea and vomiting. A few hours prior to presentation, his subcutaneous pump malfunctioned. On presentation, vital signs included pulse 100 bpm, BP 176/103 mmHg, temperature 37.8 °C and O2 saturation 100 % (room air). Acute clonidine withdrawal with hypertensive crisis was suspected. Intravenous clonidine loading dose and a 50 mcg/h infusion were commenced. Five hours later, severe chest pain, dyspnoea, tachycardia, hypoxia, with BP 180/120 mmHg and pulmonary edema ensued. ECG showed sinus tachycardia with no ST elevation. Repeated intravenous clonidine doses were given (25 mcg every 5-10 min), with ongoing clonidine infusion to control blood pressure. Glyceryl trinitrate infusion, positive pressure ventilation and intravenous benzodiazepines were added. Bedside echocardiogram showed stress-induced cardiomyopathy pattern. Serum troponin-I was markedly elevated. His coronary angiography showed minor irregularities in the major vessels. Over the next 3 days in the ICU, drug infusions were weaned. Discharge was 12 days later on oral clonidine, metoprolol, perindopril, aspirin and oxycodone-SR. Two months later, his echocardiogram was normal. The intrathecal pump was removed. We report a case of stress-induced cardiomyopathy resulting from the sudden cessation of long-term intrathecal clonidine. This was managed by re-institution of clonidine and targeted organ-specific therapies. PMID:26370679

  1. Stress-Induced Drinking in Parents of Adolescents with Externalizing Symptomatology: The Moderating Role of Parent Social Support

    OpenAIRE

    Handley, Elizabeth D.; Chassin, Laurie

    2008-01-01

    Parenting adolescents with externalizing symptomatology has been repeatedly shown to be stress-inducing for parents. One possible coping strategy for parents dealing with this chronic stress may be drinking. The current study extended previous research by examining the prospective relations between adolescents' externalizing behaviors and parents' negative affect and alcohol consumption. Additionally, the present study tested whether this mediated effect is a function of parental social suppo...

  2. Effect of exercise on chronic stress-induced abnormal behaviors and neuroendocrine function in elderly depression-like rats%运动对慢性应激所致抑郁样老年大鼠行为异常及神经内分泌的影响

    Institute of Scientific and Technical Information of China (English)

    王桂华; 栾海云; 杨丽娟; 王敏; 张慧

    2013-01-01

    目的 探讨运动对慢性不可预见温和应激(CUMS)抑郁老年大鼠行为学及血清皮质醇和促肾上腺皮质激素(ACTH)浓度的影响.方法 50只雄性老年SD大鼠随机分为对照组、CUMS组、低强度跑台运动训练(LITT)组、中等强度跑台运动训练(MITT)组、高强度跑台运动训练(HITT)组.采用CUMS加孤养复制老年大鼠抑郁模型.采用旷场实验得分和强迫游泳实验评价各组大鼠行为学改变,分别采用ELISA和放射免疫方法检测血清皮质醇、ACTH浓度.结果 与对照组比较,CUMS组大鼠血清皮质醇和ACTH浓度增高(P<0.01);与CUMS组比较,LITT组、MITT组和HITT组大鼠水平运动和垂直运动增多、清理次数增加,中央格停留时间缩短,血清皮质醇和ACTH浓度降低(P<0.05,P<0.01).结论 CUMS可使老年大鼠行为及内分泌发生异常改变,引起抑郁;适度的运动可调节CUMS引起的下丘脑-垂体-肾上腺轴功能亢进,具有抗抑郁及降低抑郁程度的作用.%Objective To study the effect of exercise on chronic unpredictable mild stress(CUMS) induced abnormal behaviors and serum cortisol ( CORT) and adrenocorticotropic hormone (ACTH) levels in elderly depression-like rats. Methods Fifty elderly male SD rats were random ly divided into control group,model group,low intensity treadmill training(LITT)group,medium intensity treadmill training( MITT) group, and high intensity treadmill training(HITT)group(10 in each group). A rat depression model was induced by CUMS. Bahaviors of rats were assessed ac cording to the open field test and forced swimming test scores. Serum CORT and ACTH levels in different groups were measured by RIA and ELISA,respectively. Results The body weight gain was slower,the horizontal and vertical exercise scores and the modified scores were significantly lower,the central retention time was significantly longer,the serum CORT and ACTH levels were significantly higher in CUMS group than in control group

  3. Influence of Electroacupuncture on Hippocampal Somatostatin (SS) and SS mRNA Expression in Chronic Stress-induced Depression Rats%电针对抑郁大鼠行为学、海马生长抑素及其mRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    朱艺; 白春艳; 卓廉士; 冯雯琪

    2009-01-01

    Objective To study the underlying mechanism of electroacupuncture (EA) in relieving depression. Methods A total of 30 Wistar rats were randomly divided into normal control group (n = 10), model group (n = 10) and EA group (n = 10). Depression model was established by lonely raising and chronic unpredictable mild stress for 21 days. EA (2 Hz, 1 mA) was applied to "Baihui" (GV 20) and "Sanyinjiao" (SP 6) for 20 min, once daily for 14 days. The expression (option density) of hippocampal somatostatin (SS) and SS mRNA was detected by using immunohistochemistry and reversed transcription-polymerase chain reaction (RT-PCR) techniques respectively. Results Compared to normal control group, the crossing movement and rearing movement times of open-field test, and sucrose consumption in model group decreased significantly (P<0. 01), and hippocampal SS and SS mRNA expressions were downregulated remarkably (P<0. 05). Compared to model group, the crossing movement and rearing movement times in EA group increased considerably (P<0. 01), and hippocampal SS and SS mRNA expressions were upregulated remarkably (P<0. 05). No significant difference was found between EA and normal control groups in SS and SS mRNA expression. Conclusion EA can effectively improve depression rats' behavior activity and upregu-late hippocampal SS and SS mRNA expression.%目的:观察电针对抑郁大鼠行为学、海马生长抑素(somatostatin,SS)及SS mRNA表达的影响,探讨电针治疗抑郁症的可能机制.方法:30只健康Wistar大鼠,随机分为正常组、模型组和电针组,每组10只.慢性应激法刺激造抑郁大鼠模型,电针"百会""三阴交",每日1次,每次20 min,连续14 d.使用开野试验和糖水试验检测大鼠行为学变化,使用免疫组化法和逆转录多聚酶链反应法测定SS及SS mRNA的表达.结果:造模后模型组大鼠水平和垂直运动次数、糖水摄入量与正常组比较均降低(P<0.01),治疗后电针组的水平、垂直运动次

  4. A new murine model of stress-induced complex atherosclerotic lesions

    Directory of Open Access Journals (Sweden)

    Amir H. Najafi

    2013-03-01

    The primary purpose of this investigation was to determine whether ApoE−/− mice, when subjected to chronic stress, exhibit lesions characteristic of human vulnerable plaque and, if so, to determine the time course of such changes. We found that the lesions were remarkably similar to human vulnerable plaque, and that the time course of lesion progression raised interesting insights into the process of plaque development. Lard-fed mixed-background ApoE−/− mice exposed to chronic stress develop lesions with large necrotic core, thin fibrous cap and a high degree of inflammation. Neovascularization and intraplaque hemorrhage are observed in over 80% of stressed animals at 20 weeks of age. Previously described models report a prevalence of only 13% for neovascularization observed at a much later time point, between 36 and 60 weeks of age. Thus, our new stress-induced model of advanced atherosclerotic plaque provides an improvement over what is currently available. This model offers a tool to further investigate progression of plaque phenotype to a more vulnerable phenotype in humans. Our findings also suggest a possible use of this stress-induced model to determine whether therapeutic interventions have effects not only on plaque burden, but also, and importantly, on plaque vulnerability.

  5. Tissue plasminogen activator and plasminogen mediate stress-induced decline of neuronal and cognitive functions in the mouse hippocampus.

    Science.gov (United States)

    Pawlak, Robert; Rao, B S Shankaranarayana; Melchor, Jerry P; Chattarji, Sumantra; McEwen, Bruce; Strickland, Sidney

    2005-12-13

    Repeated stress can impair function in the hippocampus, a brain structure essential for learning and memory. Although behavioral evidence suggests that severe stress triggers cognitive impairment, as seen in major depression or posttraumatic stress disorder, little is known about the molecular mediators of these functional deficits in the hippocampus. We report here both pre- and postsynaptic effects of chronic stress, manifested as a reduction in the number of NMDA receptors, dendritic spines, and expression of growth-associated protein-43 in the cornu ammonis 1 region. Strikingly, the stress-induced decrease in NMDA receptors coincides spatially with sites of plasminogen activation, thereby predicting a role for tissue plasminogen activator (tPA) in this form of stress-induced plasticity. Consistent with this possibility, tPA-/- and plasminogen-/- mice are protected from stress-induced decrease in NMDA receptors and reduction in dendritic spines. At the behavioral level, these synaptic and molecular signatures of stress-induced plasticity are accompanied by impaired acquisition, but not retrieval, of hippocampal-dependent spatial learning, a deficit that is not exhibited by the tPA-/- and plasminogen-/- mice. These findings establish the tPA/plasmin system as an important mediator of the debilitating effects of prolonged stress on hippocampal function at multiple levels of neural organization.

  6. Role of Hippocampal 5-HT1A Receptor and Its Modulation to NMDA Receptor and AMPA Receptor in Depression Induced by Chronic Unpredictable Mild Stress%应激性抑郁样行为发生中海马5-羟色胺1A受体的作用及其对NMDA受体和AMPA受体的调节

    Institute of Scientific and Technical Information of China (English)

    问黎敏; 安书成; 刘慧

    2012-01-01

    为探讨慢性不可预见性温和应激(chronic unpredictable mild stress,CUMS)诱发抑郁样行为发生中海马5-羟色胺1A受体(5-hydroxytryptamine receptor 1A,5-HT1AR)表达与作用,及其对谷氨酸N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体和α-氨基羟甲基异恶唑丙酸(α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid,AMPA)受体的影响.通过建立CUMS动物模型,给应激抑郁模型大鼠海马微量注射5-HT1A受体激动剂、给正常大鼠海马微量注射5-HT1A受体拮抗剂,测量大鼠体重变化率,并采用糖水偏爱测试、旷场实验和悬尾实验等方法对大鼠进行行为学检测,运用Western blot和ELISA方法检测大鼠海马组织中5-HT1AR和NMDAR和AMPAR的关键亚基的表达以及磷酸化水平.结果显示,与对照组相比,CUMS组大鼠表现出抑郁样行为,海马5-HT1AR、AMPA受体的GluR2/3亚基表达及磷酸化明显降低,NMDA受体的NR1和NR2B亚基表达及磷酸化显著增加;正常大鼠海马微量注射5-HT1A受体拮抗剂WAY100635,动物行为学表现及AMPA受体、NMDA受体表达及磷酸化水平均与CUMS组相同;注射5-HT1A受体激动剂8-OH-DPAT能逆转应激诱导的上述改变.以上结果表明,CUMS诱发抑郁榉行为与海马5-HT1AR表达下降,AMPAR表达量及磷酸化水平降低,NMDAR表达量及磷酸化水平升高有关.5-HT通过5-HT1AR产生抗抑郁作用.5-HT1AR激动剂抗抑郁作用与降低NMDAR表达量及磷酸化水平,提高AMPAR表达量及磷酸化水平密切相关.%Stressors markedly influence central neurochemical and hormonal processes and thus play a pivotal role in the occurrence of depressive illnesses. As the center for stress response and the potential target for stressfulprovocation, the hippocampus is becoming a focus in depression research. Although a large number of behavioral paradigms have been proposed as animal models of depression, only a few are considered potentially useful research tools with

  7. 孕前慢性应激对母鼠及其子代行为学和海马神经元再生的影响%Effects of maternal rats exposed to chronic unpredictable stress before pregnancy on the postpartum behavior and neurobiology of themselves and their progency

    Institute of Scientific and Technical Information of China (English)

    刘彬; 王克; 董继承; 郑占杰; 姜桂兰

    2013-01-01

    Objective To determine the effects of maternal rats exposed to chronic unpredictable stress before pregnancy on the behavior and neurobiology of the mother and their offspring.Methods Two-month Virgin female Sprague-Dawley(SD) rats were applied to study.Females were housed with sexually experienced males (ratio 3:1) for propagation after 21-day chronic unpredictable stress.The behaviors of rats and their two-month-offspring were tested.The two-month rats were injected intraperitoneally with BrdU,then the brains were removed and 20 μm frozen sections were used to detect the neurogenesis of hippocampus.Results 1.Open field test:after lactation,CUS + Pre group ((720.52 ± 238.99) cm),CUS group ((995.62 ± 191.77) cm),CON group ((464.95 ±210.11)cm) and CON + Pre group((740.76 ± 281.48)cm) had statistic difference in total distance(P < 0.05).The total distance((1281.10 ±247.89)cm) and border distance((1153.20 ±238.19)cm) in female two-monthprogeny were higher than these in male two-month-progeny ((1074.70 ± 263.35) cm,(957.28 ± 82.94) cm) in CUS + Pre group (P < 0.05).2.Sucrose consumption test:after lactation,the sucrose intake ((13.00 ± 3.46) g)and sucrose consumption percentage((87.00 ±9.01)%) in CUS + Pre group were higher than that in CUS group ((8.13 ± 3.36) g,(79.06 ± 6.45) %,P < 0.05).The sucrose intake ((12.43 ± 3.31) g) and sucrose consumption percentage((86.90 ± 5.80)%) in CON group were higher than that in CUS group ((8.13 ± 3.36) g,(79.06 ± 6.45) %,P < 0.05).The sucrose intake ((14.71 ± 4.39) g) and sucrose consumption percentage ((91.54 ± 1.89) %) in CON + Pre group were significantly higher than those in CUS group ((8.13 ± 3.36) g,(79.06 ± 6.45) %) (P < 0.01).3.Immunohistochemistry:there was no statistic difference on the new neuron in dentate gyrus of hippocampus in both female and male two-month-progeny of CUS group and CON group((1.18 ±0.37) cells,(1.24 ± 0.41) cells,(1.38 ± 0.47) cells,(1.41 ± 0.35) cells

  8. 慢性不可预见性温和应激后大鼠行为及微管相关蛋白tau磷酸化的改变%Behavioral and tau protein alterations in rats following chronic unpredictable mild stress

    Institute of Scientific and Technical Information of China (English)

    杨灿; 王高华; 王惠玲; 刘忠纯; 朱志先

    2013-01-01

    目的 研究慢性不可预见性温和应激所致的动物行为学改变及微管相关蛋白tau磷酸化的改变.方法 将大鼠随机分为慢性不可预见性温和应激抑郁(CUMS)组和对照组,对模型组大鼠进行连续21d的慢性不可预见性应激.进行行为学观察,使用western blotting检测总tau,tau磷酸化(Ser356,Thr231)水平的改变.结果 CUMS组大鼠慢性应激后糖水偏好及自主活动显著减低,与对照组比较差异有统计学意义(P<0.05);CUMS组大鼠慢性应激后海马tau磷酸化表达升高,与对照组比较差异有统计学意义(P<0.05).结论 慢性应激后微管相关蛋白tau磷酸化水平升高,神经可塑性受损,提示了新的抑郁症和阿尔茨海默病联系的生化机制.%Objective To investigate the behavior and hippocampal microtubule-associated proteins tau alterations.Methods Sixteen rats were divided into two groups,with 8 exposed to 21 consecutive days of chronic unpredicted mild stresses (CUMS) as depression models,and 8 as normal controls.Behavioral changes in these rats were analyzed in sucrose preference and open-field paradigm,and compared to a control group of normal rats.The expressions of hippocampal cytoskeletal microtubule-associated proteins p-tau were analyzed using Western Blot.Results (1)Compared with the normal rats,sucrose preference,total traveling distance,velocity and frequencies of rearing were reduced (P <0.05)in the depressed rats; (2) Compared with the normal rats,the p-tau expression of CUMS group showed a obvious increase (P <0.05) in rats submitted to CUMS,which had statistical significance.Conclusions These findings provide evidence that rats exposed to CUMS showed increased p-tau expression which suggests impairment of structural neuronal plasticity,providing insight into the link between depression and Alzheimer disease.

  9. Effects of chronic mild stress on apomorphine induced behavioral sensitization in different brain regions of rats in relation to serotonin change

    OpenAIRE

    Muhammad Farhan; Darakshan Jabeen Haleem

    2015-01-01

    Background: The impacts of unpredictable stressors have influence on neurochemical and behavioral parameters in laboratory animals. Stress induced behavioral changes particularly those associated with anxiety like behavior may activate topographically organized mesolimbic cortical serotonergic system. This study was designed to investigate the influence of unpredictable stress on behavioral and neurochemical parameters in apomorphine treated rats. Methods: Initially, the animals were divid...

  10. Vertical leadership in highly complex and unpredictable health systems.

    Science.gov (United States)

    Till, Alex; Dutta, Nina; McKimm, Judy

    2016-08-01

    This article explores how the concept of vertical leadership development might help health organizations cope with and thrive within highly complex and unpredictable health systems, looking at concepts of VUCA (volatility, uncertainty, complexity and ambiguity) and RUPT (rapid, unpredictable, paradoxical and tangled). PMID:27487058

  11. Serotonergic systems in the balance: CRHR1 and CRHR2 differentially control stress-induced serotonin synthesis.

    Science.gov (United States)

    Donner, Nina C; Siebler, Philip H; Johnson, Danté T; Villarreal, Marcos D; Mani, Sofia; Matti, Allison J; Lowry, Christopher A

    2016-01-01

    Anxiety and affective disorders are often associated with hypercortisolism and dysfunctional serotonergic systems, including increased expression of TPH2, the gene encoding the rate-limiting enzyme of neuronal serotonin synthesis. We previously reported that chronic glucocorticoid exposure is anxiogenic and increases rat Tph2 mRNA expression, but it was still unclear if this also translates to increased TPH2 protein levels and in vivo activity of the enzyme. Here, we found that adult male rats treated with corticosterone (CORT, 100 μg/ml) via the drinking water for 21 days indeed show increased TPH2 protein expression in the dorsal and ventral part of the dorsal raphe nucleus (DRD, DRV) during the light phase, abolishing the enzyme's diurnal rhythm. In a second study, we systemically blocked the conversion of 5-hydroxytryptophan (5-HTP) to serotonin immediately before rats treated with CORT or vehicle were either exposed to 30 min acoustic startle stress or home cage control conditions. This allowed us to measure 5-HTP accumulation as a direct readout of basal versus stress-induced in vivo TPH2 activity. As expected, basal TPH2 activity was elevated in the DRD, DRV and MnR of CORT-treated rats. In response to stress, a multitude of serotonergic systems reacted with increased TPH2 activity, but the stress-, anxiety-, and learned helplessness-related dorsal and caudal DR (DRD/DRC) displayed stress-induced increases in TPH2 activity only after chronic CORT-treatment. To address the mechanisms underlying this region-specific CORT-dependent sensitization, we stereotaxically implanted CORT-treated rats with cannulae targeting the DR, and pharmacologically blocked either corticotropin-releasing hormone receptor type 1 (CRHR1) or type 2 (CRHR2) 10 min prior to acoustic startle stress. CRHR2 blockade prevented stress-induced increases of TPH2 activity within the DRD/DRC, while blockade of CRHR1 potentiated stress-induced TPH2 activity in the entire DR. Stress-induced TPH2

  12. Serotonergic involvement in stress-induced vasopressin and oxytocin secretion

    DEFF Research Database (Denmark)

    Jørgensen, Henrik; Knigge, Ulrich; Kjaer, Andreas;

    2002-01-01

    OBJECTIVE: To investigate the involvement of serotonin (5-hydroxytryptamine - 5-HT) receptors in mediation of stress-induced arginine vasopressin (AVP) and oxytocin (OT) secretion in male rats. DESIGN: Experiments on laboratory rats with control groups. METHODS: Different stress paradigms were...

  13. Implication of snail in metabolic stress-induced necrosis.

    Directory of Open Access Journals (Sweden)

    Cho Hee Kim

    Full Text Available BACKGROUND: Necrosis, a type of cell death accompanied by the rupture of the plasma membrane, promotes tumor progression and aggressiveness by releasing the pro-inflammatory and angiogenic cytokine high mobility group box 1. It is commonly found in the core region of solid tumors due to hypoxia and glucose depletion (GD resulting from insufficient vascularization. Thus, metabolic stress-induced necrosis has important clinical implications for tumor development; however, its regulatory mechanisms have been poorly investigated. METHODOLOGY/PRINCIPAL FINDINGS: Here, we show that the transcription factor Snail, a key regulator of epithelial-mesenchymal transition, is induced in a reactive oxygen species (ROS-dependent manner in both two-dimensional culture of cancer cells, including A549, HepG2, and MDA-MB-231, in response to GD and the inner regions of a multicellular tumor spheroid system, an in vitro model of solid tumors and of human tumors. Snail short hairpin (sh RNA inhibited metabolic stress-induced necrosis in two-dimensional cell culture and in multicellular tumor spheroid system. Snail shRNA-mediated necrosis inhibition appeared to be linked to its ability to suppress metabolic stress-induced mitochondrial ROS production, loss of mitochondrial membrane potential, and mitochondrial permeability transition, which are the primary events that trigger necrosis. CONCLUSIONS/SIGNIFICANCE: Taken together, our findings demonstrate that Snail is implicated in metabolic stress-induced necrosis, providing a new function for Snail in tumor progression.

  14. Stress-induced sensitization of the limbic system in ovariectomized rats is partly restored by cyclic 17 beta-estradiol administration

    NARCIS (Netherlands)

    Gerrits, M; Bakker, PL; Koch, T; Ter Horst, GJ

    2006-01-01

    Chronic stress induces neurobiological alterations which have consequences for subsequent stress handling. In the current experiment, ovariectomized rats were subjected daily to a stressor for 21 days. Thereafter, the rats were treated for 21 days with 17 beta-estradiol benzoate (10 mu g/250 g, once

  15. Effects of Chaihu Shugan San on behavior and CRHmRNA expression in the brain of mice with chronic mild unpredicted stress depression%柴胡疏肝散对慢性应激抑郁模型小鼠行为与脑促肾上腺皮质激素释放激素基因表达的影响

    Institute of Scientific and Technical Information of China (English)

    张春虎; 胡随瑜; 李云辉; 黄熙; 邓颖; 王杨

    2011-01-01

    Objective To investigate the effects of Chaihu Shugan San(CHSGS) ,a compound traditional Chinese herbal medicine,on the behavior and plasma levels of corticosterone level and corticotrophin releasing hormone ( CRH) mRNA expression in the prefrontal cortex and the hypothalamus of mice with chronic mild unpredicted stress depression. Methods 40 adult male Kunming mice were randomly divided into 4 groups: the normal control group,the model control group,the fluoxetine group and CHSGS group. Except the normal control group, mice were exposed to an unpredicted sequence of mild stressor for continuous 21 days to induce depression. Since the 8th day, mice were intragastrically administered with equal volume agents respectively for 14 days (normal saline for the normal control group and the model group,fluoxetine(2. 6 mg · kg-1 ) for fluoxetine group and CHSGS (8.45 g · kg-1) for CHSGS group). Body weight and behaviors were investigated,the plasma levels of CORT in different groups were detected by radioimmunoassay, and the mRNA expression in the prefrontal cortex and the hypothalamus were semiquantified by the RT-PCR method. Results In comparision with the model group, body weight changes ( (13.22 ±3.57)g) and consumption of sucrose solution((1. 90 ±0. 74) ml) of CHSGS groups were significantly increased, and the duration of immobility during the forced swimming ((62.20±13.73)s) and tail suspension((58. 10 ± 11.71 )s) ,the levels of plasma CORT((12.61 ±4.63)ng/L) and the CRHmRNA expression in the prefrontal cortex(0.34 ±0.10) and the hypothalamus(0.70 ±0.09) were significantly decreased. Conclusion CHSGS can reverse the depressive behavior, reduced the levels of plasma CORT and down-regulated CRHmRNA expression in the prefrontal cortex and the hypothalamus of the depressive mouse caused chronic stress.%目的 研究柴胡疏肝散对慢性应激抑郁模型小鼠行为学和血浆皮质醇水平及额叶皮质、下丘脑促肾上腺皮质激素释放激

  16. 音乐治疗对慢性应激大鼠脑内5-羟色胺及微管蛋白的影响%Effects of the music therapy on the serotonin and tubulin in brain tissue of chronic unpredictable mild stress rats

    Institute of Scientific and Technical Information of China (English)

    吴涵; 牟晓洁

    2014-01-01

    目的 探讨音乐治疗对慢性轻度不可预测性应激(CUMS)大鼠脑内前额叶、海马、下丘脑等脑区5-羟色胺及微管蛋白的水平及可能作用机制.方法 随机将24只SD雄性大鼠分为音乐治疗应激组(n=8)、应激组(n=8)和正常对照组(n=8).采用慢性轻度不可预测性应激(CUMS)模型连续刺激大鼠21 d,音乐治疗应激组在应激的同时给予音乐治疗.实验结束后对每组大鼠进行行为学观察,然后处死大鼠,检测下丘脑、海马和前额叶皮质中5-羟色胺(5-HT)及其代谢产物5-羟吲哚乙酸(5-HIAA)的含量和微管蛋白的表达.结果 旷场试验的中央格停留时间比较,应激组大鼠显著低于对照组(P<0.01),而音乐治疗应激组与对照组相比差异无统计学意义(P>0.05).与应激组相比,对照组和音乐治疗应激组的海马、前额叶中5-HT及5-HIAA含量均显著升高(P<0.01);但三组下丘脑中5-HT及5-HIAA含量差异无统计学意义(P>0.05).与应激组相比,对照组和音乐治疗应激组的海马中乙酰化微管蛋白表达均显著降低(P<0.01),酪氨酸化微管蛋白表达均显著升高(P<0.01);但三组的前额叶和下丘脑中乙酰化微管蛋白、酪氨酸化微管蛋白表达差异无统计学意义(P>0.05).结论 音乐治疗能改善应激所致的前额叶、海马5-羟色胺水平的低下和海马微管蛋白的降低.%Objective To study the effect of the music therapy on the serotonin and tubulin in frontal cortex,hippocampus and hypothalamus of chronic unpredictable mild stress (CUMS) rats,and to explore the neurobiology of the music therapy on stress disorders.Methods Twenty-four male Sprague-Dawley rats were randomly divided equally to music therapy stress group(n=8),stress group(n=8) and normal control group(n=8).Mild chronic unpredictable stress was used for 21 days in a continuous stimulation pattern to establish the CUMS model.The 5-HT,5-HIAA and tubulin levels in the the frontal cortex

  17. 慢性不可预见性应激易感性差异的5-羟色胺转运体和5-羟色胺受体机制研究%Mechanisms of serotonin transporter and serotonin 1A receptor in the different susceptibility of chronic unpredictable stress

    Institute of Scientific and Technical Information of China (English)

    刘杰; 王瑛; 贾梅志; 王晓慧; 张尚荣; 尚士渲

    2013-01-01

    Objective To investigate the expression of serotonin transporter (5-HTT) and serotonin 1A treceptor (5-HT1 A R) located in the chronic unpredictable stress (CUS)-relative brain areas (mPFC,VTA,NAc) in high and low CUS susceptibility rats,thus to unveil the possible mechanism lead to the different CUS susceptibility.Methods One hundred and fifty male Sprague-Dawley rats were randomly assigned into experiment group (n =120) and control group (n =30).Rats in experiment group were trained according to established CUS procedure.OFT and FST were used to assess the different susceptibility to CUS:high susceptibility group (H group)and low susceptibility group (L group).After the model was established,rats were scarified and cardio-perfused,and the brains were removed and sliced up coronarily.The sections including ventral tegmental area (VTA),nucleus accumben (NAc),medial prefrontal cortex (mPFC) were selected.The mRNA levels of 5-HTT and 5-HT1AR in the regions were estimated with in situ hybridization.Results The expression of 5-HTT in H group were significantly lower than that of in the control and L group in all regions (mPFC:169.20 ± 8.23 vs 143.53 ±5.31 ; Nac:177.41 ± 5.68 vs 158.65 ± 5.24 ; VTA:174.16 ± 5.61 vs 158.65 ± 4.85),and the difference between the H and L group was significant(P<0.01) ;however,the expression of 5-HT1AR in H group were significantly higher than that of in the control and L group in all regions (mPFC:113.98 ± 7.46 vs 125.90 ± 3.30 ; Nac:112.11± 5.50 vs 125.06 ± 3.97 ;VTA:103.11 ± 6.05 vs 115.57 ± 3.19),and the difference between the H and L group was significant (P< 0.01).Conclusion The overexpression of 5-HT1AR and down regulation of 5-HTT in the circuit of VTA-NAc-mPFC may be the basis of the high susceptibility to CUS.%目的 探讨大鼠慢性不可预见性应激(Chronic Unpredictable Stress,CUS)易感性差异的中脑边缘系统5-羟色胺转运体(5-HTT)和5-羟色胺1A受体(5-HT1AR)机制.方法 150只雄性Sprague

  18. Expression of 11β-hydroxysteroid dehydrogenase type 1 on hippocampus of rat with chronic unpredictable mild stress%11β-羟基类固醇脱氢酶-1在慢性温和应激抑郁大鼠海马组织中的表达

    Institute of Scientific and Technical Information of China (English)

    程世翔; 涂悦; 张赛; 文立; 刘晓智

    2012-01-01

    Objective To investigate the roles of 11 β-hydroxysteroid dehydrogenase type 1 ( 11 β-HSD1 )on hippocampus of rat with chronic unpredictable mild stress (CUMS).Methods Twenty-four male SpragueDawley rats were randomly divided into control group and depressive model group. Chronic unpredictable mild stress (CUMS) was used to make up depressive animal model.Behavioral changes were recorded by body weight measuring,sucrose consumption test (SCT) and open field test (OFT),respectively.The mRNA transcription of 11β-HSD1 in hippocampus tissues of the rats were detected by real-time RT-PCR,and the protein expression of 11β-HSD1 were detected by western blot and immunofluorescence.Results Bcforc starting CUMS protocol,the rats exhibited equivalent weight and sucrose consumption.Twenty-eight days after CUMS protocol,behavior parameters such as body weight,sucrose consumption,nunber of crossing,and number of rearing were significantly decreased in rats exposed to CUMS group compared with control group (P < 0.05,P < 0.01 ).Correspondingly,realtime RT-PCR assays showed the mRNA expression of 11 β-HSD1 in the hippocampus of CUMS group,which was (31 ±9) % lower than that of control group.Meanwhile,the protein expression of it in CUMS group was lower than that of control group (P < 0.05 ).Inmunofluorescence revealed that the number of positive 11 3-HSD1 cells was high (223 ± 13) in the control group,while the number was decreased prominently (92 ± 11 ) in the CUMS group (P < 0.01 ).Conclusion Depressive behavior of rats is induced and the expression of 11 β-HSD1 in the hippocampus is decreased prominently by CUMS,the mechanism of which is at least related to the low expression of 11β-HSD1 and disturbance of glucocorticoid metabolism caused by CUMS.%目的 应用慢性温和不可预知刺激( CUMS)建立抑郁症动物模型,探讨大鼠海马组织中11β-羟基类固醇脱氢酶-1(11β-HSD1)蛋白表达以及抑郁症的发病机制.方法 将24只Sprague

  19. Orbitofrontal Cortex 5-HT1A Receptor Modulate Glutamate and GABA in Depression Induced by Chronic Unpredictable Mild Stress%应激性抑郁样行为发生中眶额叶5-HT1A受体对谷氨酸和γ-氨基丁酸的调节

    Institute of Scientific and Technical Information of China (English)

    李江娜; 安书成; 李珍

    2015-01-01

    Stress response and depression have a crucial impact on modern society. Although the symptoms are well characterized, the molecular mechanisms underlying depression are largely unknown. Currently, the monoaminergic systems, especially serotonergic systems, have received the most attention in the research of depression. Accumulating evidence suggests that the glutamatergic and GABAergic system play an important role in the neurobiology and treatment of this disease. Multiple studies have shown that serotonin (5-HT) could modulate the neurotransmission of glutamic acid (Glu) and gamma-aminobutyric acid (GABA). The orbitofrontal cortex (OFC), which is involved in the pathophysiology and treatment of depression, plays a critical role in the control of higher brain functions and it mainly receives a dense 5-HT innervation from the dorsal raphe nucleus. There exist some 5-HT1A receptors on glutamatergic neurons and GABAergic neurons in the OFC. The purpose of this research was to elucidate the modulatory action of 5-HT1A receptor on the functions of Glu and GABA, which are the principal neurotransmitters mediating excitatory and inhibitory signals in the OFC respectively, in a well-established animal model of depression induced by chronic unpredictable mild stress (CUMS). We used CUMS in rat to mimic the core symptoms in human. Using the pharmacology approaches by microinjecting of 5-HT1A receptor agonist 8-OH-DPAT and its antagonist WAY100635 to the OFC, we detected behavioral changes by using behavior tests including sucrose preference test, open field test and tail suspension test. In addition, high-performance liquid chromatography (HPLC) was used to detect the level of neurotransmitters such as 5-HT, Glu and GABA in the OFC, respectively. CUMS group showed a variety of behavioral characteristics of depression, including a significant reduction in the sucrose preference, and locomotion, rearing and grooming in the open field test, and a significant increase in

  20. Stress-Induced Premature Senescence or Stress-Induced Senescence-Like Phenotype: One In Vivo Reality, Two Possible Definitions?

    Directory of Open Access Journals (Sweden)

    Olivier Toussaint

    2002-01-01

    Full Text Available No consensus exists so far on the definition of cellular senescence. The narrowest definition of senescence is irreversible growth arrest triggered by telomere shortening counting cell generations (definition 1. Other authors gave an enlarged functional definition encompassing any kind of irreversible arrest of proliferative cell types induced by damaging agents or cell cycle deregulations after overexpression of proto-oncogenes (definition 2. As stress increases, the proportion of cells in “stress-induced premature senescence-like phenotype” according to definition 1 or “stress-induced premature senescence,” according to definition 2, should increase when a culture reaches growth arrest, and the proportion of cells that reached telomere-dependent replicative senescence due to the end-replication problem should decrease. Stress-induced premature senescence-like phenotype and telomere-dependent replicatively senescent cells share basic similarities such as irreversible growth arrest and resistance to apoptosis, which may appear through different pathways. Irreversible growth arrest after exposure to oxidative stress and generation of DNA damage could be as efficient in avoiding immortalisation as “telomere-dependent” replicative senescence. Probabilities are higher that the senescent cells (according to definition 2 appearing in vivo are in stress-induced premature senescence rather than in telomere-dependent replicative senescence. Examples are given suggesting these cells affect in vivo tissue (pathophysiology and aging.

  1. Dysregulation of Prefrontal Cortex-Mediated Slow-Evolving Limbic Dynamics Drives Stress-Induced Emotional Pathology.

    Science.gov (United States)

    Hultman, Rainbo; Mague, Stephen D; Li, Qiang; Katz, Brittany M; Michel, Nadine; Lin, Lizhen; Wang, Joyce; David, Lisa K; Blount, Cameron; Chandy, Rithi; Carlson, David; Ulrich, Kyle; Carin, Lawrence; Dunson, David; Kumar, Sunil; Deisseroth, Karl; Moore, Scott D; Dzirasa, Kafui

    2016-07-20

    Circuits distributed across cortico-limbic brain regions compose the networks that mediate emotional behavior. The prefrontal cortex (PFC) regulates ultraslow (depressive disorder (MDD). To uncover the mechanism whereby stress-induced changes in PFC circuitry alter emotional networks to yield pathology, we used a multi-disciplinary approach including in vivo recordings in mice and chronic social defeat stress. Our network model, inferred using machine learning, linked stress-induced behavioral pathology to the capacity of PFC to synchronize amygdala and VTA activity. Direct stimulation of PFC-amygdala circuitry with DREADDs normalized PFC-dependent limbic synchrony in stress-susceptible animals and restored normal behavior. In addition to providing insights into MDD mechanisms, our findings demonstrate an interdisciplinary approach that can be used to identify the large-scale network changes that underlie complex emotional pathologies and the specific network nodes that can be used to develop targeted interventions. PMID:27346529

  2. Are seabirds foraging for unpredictable resources?

    Science.gov (United States)

    Weimerskirch, Henri

    2007-02-01

    It is generally assumed that the extreme life history traits of pelagic seabirds, such as low fecundity or slow growth of chicks, result from the difficulties obtaining energy at sea from unpredictable and patchily distributed resources. However, little information on seabird prey distribution and availability exists to sustain this widely accepted hypothesis. Using tracking studies of 68 sub-populations of flying seabirds, I examine whether it is possible to gain information on the predictability of their marine resources. Because prey are clustered from fine to large scale in nested unities, from swarms to patches and concentrations of patches, it is important to take into account spatial scale. In temperate and polar regions, at large and meso-scales, seabirds appear to have a good knowledge of the location and concentrations of patches and generally use a commuting type of trip to reach foraging zones. Predictability appears to be high at large and meso-scales, with individuals from each sub-population heading in a particular direction from the colony to reach favoured habitats of known enhanced productivity such as shelf edges, frontal zones, upwellings. Within these mesoscale features, the animals use an area-restricted search behaviour to search for patches and swarms at finer scales. Using information on foraging site fidelity of individual birds, I show that differences in predictability at coarse scales are related to the distance and time spent foraging, and in particular to the specific types of foraging habitat. Some habitats appear to be more predictable than others: birds return consistently to the same coarse-scale sectors on shelf edges, whereas predictability is low in oceanic waters, even in frontal zones. Preliminary results on tropical species suggest that the environment here is less predictable in tropic than in temperate or polar zones. This review highlights that patchiness and predictability of marine resources are complex notions

  3. Effects of Mongolian Pharmaceutical Betel Shisanwei Ingredients Pill on hypothalamic-pituitary-adrenal axis negative feedback function in rat models of chronic stress-induced depression%慢性应激抑郁模型大鼠下丘脑-垂体-肾上腺轴负反馈功能与蒙药槟榔十三味丸的干预

    Institute of Scientific and Technical Information of China (English)

    包伍叶; 范盎然; 白亮凤; 佟海英; 于雪; 乌吉斯古冷; 李婧; 胡日乐巴根; 张月

    2014-01-01

    BACKGROUND:Mongolian Pharmaceutical Betel Shisanwei Ingredients Pil has achieved good clinical efficacy, but the underlying mechanism remains unclear. OBJECTIVE: To study the effects of Mongolian Pharmaceutical Betel Shisanwei Ingredients Pil on the hypothalamic-pituitary-adrenal axis negative feedback function in the chronic depressed rats, and to explore anti-depression mechanisms of Mongolian Pharmaceutical Betel Shisanwei ingredients pil. METHODS: Eighty male Wistar rats were randomly divided into ten groups according to the sugar consumption test (with eight rats in each group): normal control group, model group, fluoxetine group, high-, medium- and low-dose Betel Shisanwei Ingredients Pil groups, RU486 group, high-, medium- and low-dose Betel Shisanwei Ingredients Pil plus RU486 groups. Except normal control group, the other groups were treated with the chronic unpredictable mild stress stimulation combined with lonely rising, to establish depression models. In the meantime, rats of the high-, medium- and low-dose Betel Shisanwei Ingredients Pil groups were given oral gavage of Betel Shisanwei Ingredients Pil (0.2, 0.4, 0.8 g/kg) for 28 days; rats of the normal control group and model group were intragstricaly administered with sodium carboxymethyl celulose; rats of RU486 group were given abdominal subcutaneous injection of RU486 from day 21 after modeling; rats of the high-, medium- and low-dose Betel Shisanwei Ingredients Pil plus RU486 groups were intragstricaly administered with Betel Shisanwei Ingredients Pil (0.2, 0.4, 0.8 g/kg) and subcutaneous injection of RU486 from day 21. RESULTS AND CONCLUSION:Compared with normal control group, cortisone content increased significantly (P < 0.05), the expression of glucocorticoid receptor mRNA in hippocampus, hypothalamus and pituitary gland decreased significantly, and hypothalamic corticotrophin releasing hormone mRNA expression increased significantly in the model group and RU486 group. Compared with model

  4. TRH and TRH receptor system in the basolateral amygdala mediate stress-induced depression-like behaviors.

    Science.gov (United States)

    Choi, Juli; Kim, Ji-eun; Kim, Tae-Kyung; Park, Jin-Young; Lee, Jung-Eun; Kim, Hannah; Lee, Eun-Hwa; Han, Pyung-Lim

    2015-10-01

    Chronic stress is a potent risk factor for depression, but the mechanism by which stress causes depression is not fully understood. To investigate the molecular mechanism underlying stress-induced depression, C57BL/6 inbred mice were treated with repeated restraint to induce lasting depressive behavioral changes. Behavioral states of individual animals were evaluated using the forced swim test, which measures psychomotor withdrawals, and the U-field test, which measures sociability. From these behavioral analyses, individual mice that showed depression-like behaviors in both psychomotor withdrawal and sociability tests, and individuals that showed a resiliency to stress-induced depression in both tests were selected. Among the neuropeptides expressed in the amygdala, thyrotropin-releasing hormone (TRH) was identified as being persistently up-regulated in the basolateral amygdala (BLA) in individuals exhibiting severe depressive behaviors in the two behavior tests, but not in individuals displaying a stress resiliency. Activation of TRH receptors by local injection of TRH in the BLA in normal mice produced depressive behaviors, mimicking chronic stress effects, whereas siRNA-mediated suppression of either TRH or TRHR1 in the BLA completely blocked stress-induced depressive symptoms. The TRHR1 agonist, taltirelin, injection in the BLA increased the level of p-ERK, which mimicked the increased p-ERK level in the BLA that was induced by treatment with repeated stress. Stereotaxic injection of U0126, a potent inhibitor of the ERK pathway, within the BLA blocked stress-induced behavioral depression. These results suggest that repeated stress produces lasting depression-like behaviors via the up-regulation of TRH and TRH receptors in the BLA.

  5. Identification of 30 protein species involved in replicative senescence and stress-induced premature senescence

    DEFF Research Database (Denmark)

    Dierick, Jean François; Kalume, Dário E; Wenders, Frédéric;

    2002-01-01

    Exposure of human proliferative cells to subcytotoxic stress triggers stress-induced premature senescence (SIPS) which is characterized by many biomarkers of replicative senescence. Proteomic comparison of replicative senescence and stress-induced premature senescence indicates that, at the level...

  6. Effects of Chronic Unpredictable Mild Stress with Different Time Courses on Neuroplasticity-related Proteins Expression in Rat Hippocampus%不同时程的慢性不可预计温和应激对大鼠海马神经可塑性相关蛋白水平的影响

    Institute of Scientific and Technical Information of China (English)

    肖玲; 舒畅; 唐记华; 王晓萍; 王高华

    2013-01-01

    Objective:To explore the effect of different time courses of chronic unpredictable mild stress on neu-roplasticity-related proteins expression in the adult rat hippocampus. Methods:Twenty-four rats were randomly divided into four groups with 6 rats in each group:the control group, rats without stress;M1 group in which rats were subjected to CUMS for 1 week; M2 group, in which rats were subjected to CUMS for 2 weeks; and M3 group in which rats were subjected to CUMS for 3 weeks. The levels of brain-derived neurotrophic factor (BD-NF), cAMP response element binding protein (CREB), B-cell lymphoma-2 (Bcl-2) protein in the hippocampus were detected using Weston blot. Results:when compared to the expression of BDNF, CREB, and Bcl-2 proteins in the controlled group, those in the M1 and M3 groups were significantly decreased ( <0.05), and there was no different changes in those protein in the M2 group. The amounts of BDNF, CREB, and Bcl-2 protein showed no significant difference between the M1 group and M3 group. Conclusion:Different time courses of CUMS might affect the expression of proteins implicated in neuroplasticity, providing insight into the role of neuroplasticity-related proteins in the depression.%目的:探讨不同时程的慢性不可预计温和应激对大鼠海马区神经可塑性相关蛋白水平的影响。方法:24只大鼠随机分为4组,各6只:正常对照组、应激1周组、应激2周组、应激3周组,分别给予应激0、1、2、 3周。采用Western blot 方法检测海马脑源性神经营养因子(BDNF)、cAMP 反应元件结合蛋白(CREB)、B 淋巴细胞瘤-2(Bcl-2)的蛋白水平。结果:与正常对照组对比,应激1周组、应激3周组的BDNF、CREB、 Bcl-2的蛋白水平较低(<0.05),应激2周组无明显差异;应激1周组和应激3周组之间的BDNF、CREB、 Bcl-2蛋白水平无明显差异。结论:海马区的神经可塑性相关蛋白BDNF、CREB、Bcl-2的水平变化可能

  7. 人参皂苷对慢性应激抑郁模型大鼠行为学及HPA轴、BDNF的影响%Effects of ginsenosides on hypothalamic-pituitary-adrenal function and brain-derived neurotrophic factor in rats exposed to chronic unpredictable mild stress

    Institute of Scientific and Technical Information of China (English)

    刘丽琴; 罗艳; 张瑞睿; 郭建友

    2011-01-01

    Gingseng is commonly used in traditional Chinese medicine community for the treatment of depression-like dis, orders. Ginsenosides is considered to be the major active components of ginseng. Previous studies have demonstrated that ginsenosides produced antidepressant-like action in various mouse models of behavioral despair. The present study aimed to examine whether ginsenosides could affect the chronic unpredictable mild stress (CUMS)-induced depression in rats. The mechanism(s) underlying the antidepressant-like action was investigated by measuring serum corticesterone level, glucocorticoid receptor ( GR), mineralocorticoid receptor (MR) and brain-derived neurotrophic factor (BDNF) mRNA levels in brain tissues. CUMS, being lasted for 6 weeks, caused depression-like behavior in rats, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. Whereas serum corticosterone level was significantly increased in rats exposed to CUMS, expressions of GR mRNA in hippocampus, and BDNF mRNA in hippocampus and frontal cortex, were decreased in CUMS-treated rats. Daily intragastric administration of ginsenosides (12. 5, 25, 50 mg · kg-1) during the six weeks of CUMS significantly suppressed behavioral and biochemical changes induced by CUMS. However, there was no significant difference in MR mRNA level among groups. The results suggest that the antidepressant-like action of ginsenosides is likely mediated by modulating the function of hypothalamic- pituitary -adrenal axis and increasing the expression of BDNF in brain tissues.%目的:探讨人参皂苷对慢性应激所致大鼠抑郁模型的干预作用.方法:通过测定大鼠血清中皮质酮(COR)、糖皮质激素受体(GR)、盐皮质激素受体(MR)和脑组织中神经营养(BDNF)的mRNA表达水平,探讨人参皂苷的抗抑郁机制.结果:与正常组大鼠比较,经过慢性应激6周后大鼠糖水偏好显著下降,强迫游泳测试不动时间

  8. Health Related Quality of Life of Chronic Liver Patients: A Dutch Population-Based Study

    NARCIS (Netherlands)

    S.M. van der Plas (Simone)

    2004-01-01

    markdownabstract__Abstract__ Chronic illnesses form a spectrum of diseases. Some chronic illnesses are poorly understood and unpredictable, some are understood and manageable, some are progressively disabling and some are life threatening. Nevertheless, for all chronic patients chronic illnesses ha

  9. Fluvoxamine attenuated endoplasmic reticulum stress-induced leptin resistance

    Directory of Open Access Journals (Sweden)

    Toru eHosoi

    2012-01-01

    Full Text Available Increasing evidence indicates that endoplasmic reticulum stress (ER stress is involved in the development of metabolic syndrome. However, pharmacological treatments targeting ER stress are not well understood. In the present study, we found that fluvoxamine, a selective serotonin reuptake inhibitor used for depression, can attenuate ER stress-induced leptin resistance, i.e. insensitivity to the anti-obesity hormone leptin. Treatment with tunicamycin, an ER stress-inducing reagent, caused cell death which was significantly inhibited by fluvoxamine. Leptin activates JAK2-STAT3 signaling. ER stress caused an impairment of leptin-induced STAT3 phosphorylation which was reversed by fluvoxamine. Fluvoxamine would be a novel leptin-sensitizing drug, which targets ER stress.

  10. Oxidative stress induces mitochondrial fragmentation in frataxin-deficient cells

    International Nuclear Information System (INIS)

    Highlights: ► Yeast frataxin-deficiency leads to increased proportion of fragmented mitochondria. ► Oxidative stress induces complete mitochondrial fragmentation in Δyfh1 cells. ► Oxidative stress increases mitochondrial fragmentation in patient fibroblasts. ► Inhibition of mitochondrial fission in Δyfh1 induces oxidative stress resistance. -- Abstract: Friedreich ataxia (FA) is the most common recessive neurodegenerative disease. It is caused by deficiency in mitochondrial frataxin, which participates in iron–sulfur cluster assembly. Yeast cells lacking frataxin (Δyfh1 mutant) showed an increased proportion of fragmented mitochondria compared to wild-type. In addition, oxidative stress induced complete fragmentation of mitochondria in Δyfh1 cells. Genetically controlled inhibition of mitochondrial fission in these cells led to increased resistance to oxidative stress. Here we present evidence that in yeast frataxin-deficiency interferes with mitochondrial dynamics, which might therefore be relevant for the pathophysiology of FA.

  11. Serotonergic involvement in stress-induced vasopressin and oxytocin secretion

    DEFF Research Database (Denmark)

    Jørgensen, Henrik; Knigge, Ulrich; Kjaer, Andreas;

    2002-01-01

    OBJECTIVE: To investigate the involvement of serotonin (5-hydroxytryptamine - 5-HT) receptors in mediation of stress-induced arginine vasopressin (AVP) and oxytocin (OT) secretion in male rats. DESIGN: Experiments on laboratory rats with control groups. METHODS: Different stress paradigms were...... applied after pretreatment with intracerebroventricular infusion of saline or different 5-HT antagonists. RESULTS: Restraint stress (5 min), hypotensive hemorrhage or dehydration for 24 h increased AVP secretion fivefold and OT secretion threefold. Swim stress for 3 min had no effect on AVP secretion......, but increased OT secretion threefold. Ether vapor or hypoglycemia had no effect on AVP or OT secretion. The restraint stress-induced AVP response was inhibited by pretreatment with the 5-HT(2A+2C) antagonists ketanserin (KET) and LY-53857 (LY) and the 5-HT(3+4) antagonist ICS-205930 (ICS), whereas the 5-HT(1A...

  12. [Unpredictable risk and damage compensation in civil process].

    Science.gov (United States)

    Vayre, P

    1998-04-01

    UNPREDICTABLE RISK DEFINITION: Any medical or surgical action with diagnostic or therapeutic purpose involves a potential risk of complication, unrelated to the initial pathology or a technical error, but could lead to death or disability. Proof of unpredictable risk without initial fault requires a careful examination of each case by a judicial expert in order to eliminate the complications related to an unskilled surgeon or to poor postoperative care. UNPREDICTABLE RISK COMPENSATION: Conclusions of the Academy: In current French common law, damage compensation can only be obtained in cases where all possible medical means are not implemented and professional fault can be proven. It is illogical to extend the civil responsibility of the practitioner to an obligation of procedural result. In the absence of fault, damage compensation does not come under the civil responsibility of the surgeon. A special insurance system for unpredictable risk has to be created using the principles of mutual insurance.

  13. Neural circuitry of stress-induced insomnia in rats

    OpenAIRE

    Cano, Georgina; Mochizuki, Takatoshi; Saper, Clifford B.

    2008-01-01

    Sleep architecture is often disturbed following a stressful event; nevertheless, little is known about the brain circuitry responsible for the sleep perturbations induced by stress. We exposed rats to a psychological stressor (cage exchange) that initially causes an acute stress response, but several hours later generates a pattern of sleep disturbances similar to that observed in stress-induced insomnia in humans: increased sleep latency, decreased nREM and REM sleep, increased fragmentation...

  14. Salubrious effects of oxytocin on social stress-induced deficits

    OpenAIRE

    Smith, Adam S.; Wang, Zuoxin

    2011-01-01

    Social relationships are a fundamental aspect of life, affecting social, psychological, physiological, and behavioral functions. While social interactions can attenuate stress and promote health, disruption, confrontations, isolation, or neglect in the social environment can each be major stressors. Social stress can impair the basal function and stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing function of multiple biological systems and posing a risk to m...

  15. Shear stress-induced improvement of red blood cell deformability

    OpenAIRE

    Meram, Ece; Yılmaz, Bahar D.; Bas, Ceren; Atac, Nazlı; Yalçın, Ö.; Başkurt, Oguz K.; Meiselman, Herbert J.

    2013-01-01

    Classically, it is known that red blood cell (RBC) deformability is determined by the geometric and material properties of these cells. Experimental evidence accumulated during the last decade has introduced the concept of active regulation of RBC deformability. This regulation is mainly related to altered associations between membrane skeletal proteins and integral proteins, with the latter serving to anchor the skeleton to the lipid matrix. It has been hypothesized that shear stress induces...

  16. Potential role of punicalagin against oxidative stress induced testicular damage

    Directory of Open Access Journals (Sweden)

    Faiza Rao

    2016-01-01

    Full Text Available Punicalagin is isolated from pomegranate and widely used for the treatment of different diseases in Chinese traditional medicine. This study aimed to evaluate the effect of Punicalagin (purity ≥98% on oxidative stress induced testicular damage and its effect on fertility. We detected the antioxidant potential of punicalagin in lipopolysaccharide (LPS induced oxidative stress damage in testes, also tried to uncover the boosting fertility effect of Punicalagin (PU against oxidative stress-induced infertility. Results demonstrated that 9 mg kg−1 for 7 days treatment significantly decreases LPS induced oxidative damage in testes and nitric oxide production. The administration of oxidative stress resulted in a significant reduction in testes antioxidants GSH, T-SOD, and CAT raised LPO, but treatment with punicalagin for 7 days increased antioxidant defense GSH, T-SOD, and CAT by the end of the experiment and reduced LPO level as well. PU also significantly activates Nrf2, which is involved in regulation of antioxidant defense systems. Hence, the present research categorically elucidates the protective effect of punicalagin against LPS induced oxidative stress induced perturbation in the process of spermatogenesis and significantly increased sperm health and number. Moreover, fertility success significantly decreased in LPS-injected mice compared to controls. Mice injected with LPS had fertility indices of 12.5%, while others treated with a combination of PU + LPS exhibited 75% indices. By promoting fertility and eliminating oxidative stress and inflammation, PU may be a useful nutrient for the treatment of infertility.

  17. OGG1 is essential in oxidative stress induced DNA demethylation.

    Science.gov (United States)

    Zhou, Xiaolong; Zhuang, Ziheng; Wang, Wentao; He, Lingfeng; Wu, Huan; Cao, Yan; Pan, Feiyan; Zhao, Jing; Hu, Zhigang; Sekhar, Chandra; Guo, Zhigang

    2016-09-01

    DNA demethylation is an essential cellular activity to regulate gene expression; however, the mechanism that triggers DNA demethylation remains unknown. Furthermore, DNA demethylation was recently demonstrated to be induced by oxidative stress without a clear molecular mechanism. In this manuscript, we demonstrated that 8-oxoguanine DNA glycosylase-1 (OGG1) is the essential protein involved in oxidative stress-induced DNA demethylation. Oxidative stress induced the formation of 8-oxoguanine (8-oxoG). We found that OGG1, the 8-oxoG binding protein, promotes DNA demethylation by interacting and recruiting TET1 to the 8-oxoG lesion. Downregulation of OGG1 makes cells resistant to oxidative stress-induced DNA demethylation, while over-expression of OGG1 renders cells susceptible to DNA demethylation by oxidative stress. These data not only illustrate the importance of base excision repair (BER) in DNA demethylation but also reveal how the DNA demethylation signal is transferred to downstream DNA demethylation enzymes. PMID:27251462

  18. Histone deacetylase inhibition abolishes stress-induced spatial memory impairment.

    Science.gov (United States)

    Vargas-López, Viviana; Lamprea, Marisol R; Múnera, Alejandro

    2016-10-01

    Acute stress induced before spatial training impairs memory consolidation. Although non-epigenetic underpinning of such effect has been described, the epigenetic mechanisms involved have not yet been studied. Since spatial training and intense stress have opposite effects on histone acetylation balance, it is conceivable that disruption of such balance may underlie acute stress-induced spatial memory consolidation impairment and that inhibiting histone deacetylases prevents such effect. Trichostatin-A (TSA, a histone deacetylase inhibitor) was used to test its effectiveness in preventing stress' deleterious effect on memory. Male Wistar rats were trained in a spatial task in the Barnes maze; 1-h movement restraint was applied to half of them before training. Immediately after training, stressed and non-stressed animals were randomly assigned to receive either TSA (1mg/kg) or vehicle intraperitoneal injection. Twenty-four hours after training, long-term spatial memory was tested; plasma and brain tissue were collected immediately after the memory test to evaluate corticosterone levels and histone H3 acetylation in several brain areas. Stressed animals receiving vehicle displayed memory impairment, increased plasma corticosterone levels and markedly reduced histone H3 acetylation in prelimbic cortex and hippocampus. Such effects did not occur in stressed animals treated with TSA. The aforementioned results support the hypothesis that acute stress induced-memory impairment is related to histone deacetylation. PMID:27544851

  19. Unpredictability and Nonlinearity in Complexity Theory: A Critical Appraisal

    OpenAIRE

    Kemp, Stephen

    2009-01-01

    This piece explores potential problems with the focus on unpredictability and nonlinearity within complexity theory. Whilst not completely rejecting the application of ideas of nonlinearity and unpredictability within the social sciences, I argue that greater empirical and conceptual care is needed. The arguments made are illustrated by a critical examination of cases from John Urry's Global Complexity, including the dominance of the petroleum-fuelled car in the 20th century and the prevalenc...

  20. Restoration of hippocampal growth hormone reverses stress-induced hippocampal impairment

    Directory of Open Access Journals (Sweden)

    Caitlin M. Vander Weele

    2013-06-01

    Full Text Available Though growth hormone (GH is synthesized by hippocampal neurons, where its expression is influenced by stress exposure, its function is poorly characterized. Here, we show that a regimen of chronic stress that impairs hippocampal function in rats also leads to a profound decrease in hippocampal GH levels. Restoration of hippocampal GH in the dorsal hippocampus via viral-mediated gene transfer completely reversed stress-related impairment of two hippocampus-dependent behavioral tasks, auditory trace fear conditioning and contextual fear conditioning, without affecting hippocampal function in unstressed control rats. GH overexpression reversed stress-induced decrements in both fear acquisition and long-term fear memory. These results suggest that loss of hippocampal GH contributes to hippocampal dysfunction following prolonged stress and demonstrate that restoring hippocampal GH levels following stress can promote stress resilience.

  1. Calcium channel blocker prevents stress-induced activation of renin and aldosterone in conscious pig

    International Nuclear Information System (INIS)

    A considerable amount of data suggest the involvement of calcium-mediated processes in the activation of the renin-angiotensin-aldosterone (RAA) cascade. To investigate the effect of calcium-channel inhibition on the RAA system, the authors studied 21 conscious pigs. Blood renin and aldosterone levels increased by subjecting animals to 24 hours of immobilization stress. Renin and aldosterone levels were repeatedly measured by radioimmunoassay in blood samples taken periodically over 24 hours from a chronically implanted arterial cannula. Pretreatment of the animals (N = 11) with nisoldipine, 2 x 20 mg p.o. daily for 2 days before and on the day of immobilization, transiently attenuated the stress-induced increase of plasma renin activity and completely prevented the rise of aldosterone, as compared to nontreated controls (N = 10). The finding that nisoldipine suppresses RAA activation induced by a nonpharmacologic stimulus in the conscious intact animal may have clinical implications

  2. Calcium channel blocker prevents stress-induced activation of renin and aldosterone in conscious pig

    Energy Technology Data Exchange (ETDEWEB)

    Ceremuzynski, L.K.; Klos, J.; Barcikowski, B.; Herbaczynska-Cedro, K. (Department of Cardiology, Postgraduate Medical School, Warsaw (Poland))

    1991-06-01

    A considerable amount of data suggest the involvement of calcium-mediated processes in the activation of the renin-angiotensin-aldosterone (RAA) cascade. To investigate the effect of calcium-channel inhibition on the RAA system, the authors studied 21 conscious pigs. Blood renin and aldosterone levels increased by subjecting animals to 24 hours of immobilization stress. Renin and aldosterone levels were repeatedly measured by radioimmunoassay in blood samples taken periodically over 24 hours from a chronically implanted arterial cannula. Pretreatment of the animals (N = 11) with nisoldipine, 2 {times} 20 mg p.o. daily for 2 days before and on the day of immobilization, transiently attenuated the stress-induced increase of plasma renin activity and completely prevented the rise of aldosterone, as compared to nontreated controls (N = 10). The finding that nisoldipine suppresses RAA activation induced by a nonpharmacologic stimulus in the conscious intact animal may have clinical implications.

  3. Aberrant sialylation causes dilated cardiomyopathy and stress-induced heart failure.

    Science.gov (United States)

    Deng, Wei; Ednie, Andrew R; Qi, Jianyong; Bennett, Eric S

    2016-09-01

    Dilated cardiomyopathy (DCM), the third most common cause of heart failure, is often associated with arrhythmias and sudden cardiac death if not controlled. The majority of DCM is of unknown etiology. Protein sialylation is altered in human DCM, with responsible mechanisms not yet described. Here we sought to investigate the impact of clinically relevant changes in sialylation on cardiac function using a novel model for altered glycoprotein sialylation that leads to DCM and to chronic stress-induced heart failure (HF), deletion of the sialyltransferase, ST3Gal4. We previously reported that 12- to 20-week-old ST3Gal4 (-/-) mice showed aberrant cardiac voltage-gated ion channel sialylation and gating that contribute to a pro-arrhythmogenic phenotype. Here, echocardiography supported by histology revealed modest dilated and thinner-walled left ventricles without increased fibrosis in ST3Gal4 (-/-) mice starting at 1 year of age. Cardiac calcineurin expression in younger (16-20 weeks old) ST3Gal4 (-/-) hearts was significantly reduced compared to WT. Transverse aortic constriction (TAC) was used as a chronic stressor on the younger mice to determine whether the ability to compensate against a pathologic insult is compromised in the ST3Gal4 (-/-) heart, as suggested by previous reports describing the functional implications of reduced cardiac calcineurin levels. TAC'd ST3Gal4 (-/-) mice presented with significantly reduced systolic function and ventricular dilation that deteriorated into congestive HF within 6 weeks post-surgery, while constricted WT hearts remained well-adapted throughout (ejection fraction, ST3Gal4 (-/-) = 34 ± 5.2 %; WT = 53.8 ± 7.4 %; p stress-induced HF. PMID:27506532

  4. 高脂血症叠加慢性不可预见性应激模型大鼠open-field行为学特征分析%Open-field behavioral study in rat hyperlipidemia combined with chronic unpredictable mild stress model

    Institute of Scientific and Technical Information of China (English)

    胡华; 张迎春; 许烨勍; 刘春风; 王立伟

    2015-01-01

    Objective To investigate behavioral changes in a rat hyperlipidemia model induced by high lipid feed combined with depression by Chronic Unpredictable Mild Stress (CUMS).Methods A total of 40 rats were randomly divided into control (CON),control feed for 9 weeks followed by CUMS for 4 weeks (CON + CUMS),high fat diet (HFD) and high lipid feed for 9 weeks followed by CUMS for 4 weeks (HFD + CUMS) (n =10 each).Open-field test was individually measured at baseline,week 9 and week 13.Results (1) Serum lipids:total cholesterol [(2.67 ± 0.04) mmol/L,(2.68 ± 0.02) mmol/L] and low density lipoprotein [(1.08 ± 0.03) mmol/L,(1.06 ± 0.01) mmol/L] of HFD and HFD + CUMS were both significantly higher than those of CON and CON + CUMS [(1.78 ± 0.12) mmol/L,(0.79 ± 0.04) mmol/L;(1.76 ±0.09)mmol/L,(0.76 ±0.06)mmol/L,all P <0.01].(2) Open-field test:at week 13,compared to CON rats,CON + CUMS rats exhibited enhanced locomotor activity during the first minute,reduced activity in the center squares and rearing,and increased the number of grooming and defecation (all P < 0.05).In comparison to the CON rats,a decrease in total squares in 5 min,central squares and peripheral squares was observed in HFD rats at week 13 (all P < 0.05).However,compared with HFD,CON,CON + CUMS rats,when high lipid feed for 9 weeks combined with depression,significant decrease activities in total squares in 5 min,central squares and peripheral squares were observed in HFD + CUMS rats at week 13.Besides these,the number of rearing was reduced,however,locomotor activity during the first minute and the number of grooming and defecation was significantly increased (all P < 0.001).Conclusion Under uncontrolled hyperlipidemia,severe depressive symptoms will present more early once exposure to a series of chronic stressors followed by significant autonomic nervous dysfunctional symptoms.%目的 观察高脂血症叠加抑郁症大鼠open-field行为学特征.方法 40只SD大鼠按随机数字表法

  5. Post-traumatic and stress-induced osteolysis of the distal clavicle: MR imaging findings in 17 patients

    Energy Technology Data Exchange (ETDEWEB)

    Puente, R. de la [Department of Radiology, University of California San Diego and Veterans Affairs Medical Center, San Diego, CA (United States)]|[Servicio de Radioloxia, CXH Cristal Pinor, Ourense (Spain); Boutin, R.D. [Department of Radiology, University of California San Diego and Veterans Affairs Medical Center, San Diego, CA (United States)]|[Department of Radiology, Veterans Affairs Medical Center, San Diego, CA (United States); Theodorou, D.J.; Hooper, A.; Resnick, D. [Department of Radiology, University of California San Diego and Veterans Affairs Medical Center, San Diego, CA (United States); Schweitzer, M. [Department of Radiology, Thomas Jefferson University Hospital, Philadelphia, PA (United States)

    1999-04-01

    Objective. To describe the MR imaging findings in patients with osteolysis of the distal clavicle and to compare the MR imaging appearance of clavicular osteolysis following acute injury with that related to chronic stress. Design and patients. MR imaging examinations were reviewed in 17 patients (14 men, 3 women; ages 16-55 years) with the diagnosis of post-traumatic or stress-induced osteolysis of the clavicle. A history of a single direct injury was present in seven patients and a history of weight-lifting, participation in sports, or repetitive microtrauma was present in 10 patients. Results. MR imaging showed edema in the distal clavicle in 17 patients and, of these, eight also had edema in the acromion. The edema was most evident in STIR and fat-suppressed T2-weighted pulse sequences. Other findings about the acromioclavicular (AC) joint were prominence of the joint capsule in 14, joint fluid in eight, cortical irregularity in 12, and bone fragmentation in six patients. No differences in the MR imaging features of post-traumatic and stress-induced osteolysis of the distal clavicle were observed. Conclusion. Post-traumatic and stress-induced osteolysis of the distal clavicle have similar appearances on MR imaging, the most common and conspicuous MR imaging feature being increased T2 signal intensity in the distal clavicle. (orig.) With 5 figs., 1 tab., 19 refs.

  6. URB597 inhibits oxidative stress induced by alcohol binging in the prefrontal cortex of adolescent rats.

    Science.gov (United States)

    Pelição, Renan; Santos, Matheus C; Freitas-Lima, Leandro C; Meyrelles, Silvana S; Vasquez, Elisardo C; Nakamura-Palacios, Ester M; Rodrigues, Lívia C M

    2016-06-15

    Heavy episodic drinking (binging), which is highly prevalent among teenagers, results in oxidative damage. Because the prefrontal cortex (PFC) is not completely mature in adolescents, this brain region may be more vulnerable to the effects of alcohol during adolescence. As endocannabinoids may protect the immature PFC from the harmful effects of high doses of alcohol, this study investigated the effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597 on oxidative stress induced by acute or chronic binge alcohol intake in adolescent rats. At 40min after intraperitoneal pre-treatment with URB597 (0.3mg/kg) or vehicle (Veh), ethanol (EtOH; 3 or 6g/kg, intragastrically) or distilled water (DW) was administered in 3 consecutive sessions (acute binging) or 3 consecutive sessions over 4 weeks (chronic binging). Oxidative stress in PFC slices in situ was measured by dihydroethidium fluorescence staining. At the higher EtOH dose (6g/kg), pre-treatment with URB597 significantly reduced (peffect of endocannabinoids to suppress acute and chronic binge alcohol intake-induced oxidative stress in the PFC of adolescent rats. PMID:27150075

  7. Lateral stress-induced propagation characteristics in photonic crystal fibres

    Institute of Scientific and Technical Information of China (English)

    Tian Hong-Da; Yu Zhong-Yuan; Han Li-Hong; Liu Yu-Min

    2009-01-01

    Using the finite element method, this paper investigates lateral stress-induced propagation characteristics in a pho-tonic crystal fibre of hexagonal symmetry. The results of simulation show the strong stress dependence of effective index of the fundamental guided mode, phase modal birefringence and confinement loss. It also finds that the contribution of the geometrical effect that is related only to deformation of the photonic crystal fibre and the stress-related contribution to phase modal birefringence and confinement loss are entirely different. Furthermore, polarization-dependent stress sensitivity of confinement loss is proposed in this paper.

  8. Stress Induced Phase Transition of Iron-Rhodium Alloys

    OpenAIRE

    Takahashi, M; Oshima, R.

    1995-01-01

    Stress-induced phase transitions(B2-L10, B2-fcc) on an FeRh alloy were investigated with X-ray diffraction (XRD) and transmission electron microscopy(TEM). An Fe-50.5at%Rh alloy was rolled to 80µm thickness, and annealed at 1370K for 173ks. Annealed sample sheets were cold rolled at various rolling rates, and changes of the sample alloy on the phase state were investigated with XRD. The L10 phase appeared in the early stage of cold work. With heavy work appearance of the fcc phase and consequ...

  9. Neuromodulator and Emotion Biomarker for Stress Induced Mental Disorders

    Directory of Open Access Journals (Sweden)

    Simeng Gu

    2016-01-01

    Full Text Available Affective disorders are a leading cause of disabilities worldwide, and the etiology of these many affective disorders such as depression and posttraumatic stress disorder is due to hormone changes, which includes hypothalamus-pituitary-adrenal axis in the peripheral nervous system and neuromodulators in the central nervous system. Consistent with pharmacological studies indicating that medical treatment acts by increasing the concentration of catecholamine, the locus coeruleus (LC/norepinephrine (NE system is regarded as a critical part of the central “stress circuitry,” whose major function is to induce “fight or flight” behavior and fear and anger emotion. Despite the intensive studies, there is still controversy about NE with fear and anger. For example, the rats with LC ablation were more reluctant to leave a familiar place and took longer to consume the food pellets in an unfamiliar place (neophobia, i.e., fear in response to novelty. The reason for this discrepancy might be that NE is not only for flight (fear, but also for fight (anger. Here, we try to review recent literatures about NE with stress induced emotions and their relations with mental disorders. We propose that stress induced NE release can induce both fear and anger. “Adrenaline rush or norepinephrine rush” and fear and anger emotion might act as biomarkers for mental disorders.

  10. STRESS INDUCED NITROGEN DIFFUSION IN NITRITED CoCr ALLOY

    Directory of Open Access Journals (Sweden)

    AKVILĖ PETRAITIENĖ

    2015-03-01

    Full Text Available In the present study the nitrogen transport mechanism in plasma nitrited CoCr alloy at moderate temperature ( 400ºC is explained by non-Fickian diffusion model. This mechanism is considered by stress induced diffusion model. The model involves diffusion of nitrogen induced by internal stresses created during nitriding process. The model considers the diffusion of nitrogen in the presence of  internal stresses gradient induced by penetrating nitrogen as the next driving force of diffusion after concentration gradient. This model is commonly used for analysis of stainless steel nitriding, however, in this work it is shown that the same nitrogen penetration mechanism takes place in CoCr alloy. For mathematical description of stress induced diffusion process the equation of baro-diffusion is used which involves concentration dependant baro-diffusion concentration. For calculation of stress gradient it is assumed that stress depth profile linearly relates with nitrogen concentration depth profile. The fitting is done using experimental curves of nitrogen depth profiles for medical grade CoCr alloy (ISO 5831-12 nitrited at 400 ºC temperature. The experimental curves are taken from literature. The nitriding duration was 2h, 6h, 20h. Calculated nitrogen depth profiles in CoCr alloy are in good agreement with experimental nitrogen depth profiles.  The diffusion coefficient D is found from fitting of experimental data.DOI: http://dx.doi.org/10.5755/j01.ms.21.1.5711

  11. Stress-induced cardiomyopathy (Takotsubo – broken heart and mind?

    Directory of Open Access Journals (Sweden)

    Redfors B

    2013-04-01

    Full Text Available Björn Redfors, Yangzhen Shao, Elmir Omerovic Department of Molecular and Clinical Medicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden Abstract: Stress-induced cardiomyopathy (SIC, also known as Takotsubo cardiomyopathy, is characterized by severe but potentially reversible regional left ventricular wall motion abnormalities, ie, akinesia, in the absence of explanatory angiographic evidence of a coronary occlusion. The typical pattern is that of an akinetic apex with preserved contractions in the base, but other variants are also common, including basal or midmyocardial akinesia with preserved apical function. The pathophysiology of SIC remains largely unknown but catecholamines are believed to play a pivotal role. The diverse array of triggering events that have been linked to SIC are arbitrarily categorized as either emotional or somatic stressors. These categories can be considered as different elements of a continuous spectrum, linked through the interface of neurology and psychiatry. This paper reviews our current knowledge of SIC, with focus on the intimate relationship between the brain and the heart. Keywords: stress-induced cardiomyopathy, takotsubo cardiomyopathy, catecholamine, cerebral injury, emotional stress, somatic stress

  12. Oxidative stress induces mitochondrial fragmentation in frataxin-deficient cells

    Energy Technology Data Exchange (ETDEWEB)

    Lefevre, Sophie [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); ED515 UPMC, 4 place Jussieu 75005 Paris (France); Sliwa, Dominika [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); Rustin, Pierre [Inserm, U676, Physiopathology and Therapy of Mitochondrial Disease Laboratory, 75019 Paris (France); Universite Paris-Diderot, Faculte de Medecine Denis Diderot, IFR02 Paris (France); Camadro, Jean-Michel [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France); Santos, Renata, E-mail: santos.renata@ijm.univ-paris-diderot.fr [Mitochondria, Metals and Oxidative Stress Laboratory, Institut Jacques Monod, CNRS-Universite Paris-Diderot, Sorbonne Paris Cite, 15 rue Helene Brion, 75205 Paris cedex 13 (France)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer Yeast frataxin-deficiency leads to increased proportion of fragmented mitochondria. Black-Right-Pointing-Pointer Oxidative stress induces complete mitochondrial fragmentation in {Delta}yfh1 cells. Black-Right-Pointing-Pointer Oxidative stress increases mitochondrial fragmentation in patient fibroblasts. Black-Right-Pointing-Pointer Inhibition of mitochondrial fission in {Delta}yfh1 induces oxidative stress resistance. -- Abstract: Friedreich ataxia (FA) is the most common recessive neurodegenerative disease. It is caused by deficiency in mitochondrial frataxin, which participates in iron-sulfur cluster assembly. Yeast cells lacking frataxin ({Delta}yfh1 mutant) showed an increased proportion of fragmented mitochondria compared to wild-type. In addition, oxidative stress induced complete fragmentation of mitochondria in {Delta}yfh1 cells. Genetically controlled inhibition of mitochondrial fission in these cells led to increased resistance to oxidative stress. Here we present evidence that in yeast frataxin-deficiency interferes with mitochondrial dynamics, which might therefore be relevant for the pathophysiology of FA.

  13. Endocannabinoid Modulation of Predator Stress-Induced Long-Term Anxiety in Rats.

    Science.gov (United States)

    Lim, James; Igarashi, Miki; Jung, Kwang-Mook; Butini, Stefania; Campiani, Giuseppe; Piomelli, Daniele

    2016-04-01

    Individuals who experience life-threatening psychological trauma are at risk of developing a series of chronic neuropsychiatric pathologies that include generalized anxiety, depression, and drug addiction. The endocannabinoid system has been implicated in the modulation of these responses by regulating the activity of the amygdala and the hypothalamic-pituitary-adrenal axis. However, the relevance of this signaling complex to the long-term consequences of traumatic events is unclear. Here we use an animal model of predatory stress-induced anxiety-like behavior to investigate the role of the endocannabinoid system in the development of persistent anxiety states. Our main finding is that rats exposed to the fox pheromone 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a life-threatening stimulus for rodents, display a marked and selective increase in the mobilization of the endocannabinoid, 2-arachidonoyl-sn-glycerol (2-AG), in the amygdala. This effect lasts for at least 14 days after the stress has occurred. In addition, systemic or local pharmacological inhibition of monoacylglycerol lipase (MGL)-a lipid hydrolase that degrades 2-AG in presynaptic nerve terminals-elevates 2-AG levels and suppresses the anxiety-like behavior elicited by exposure to TMT. The results suggest that predator threat triggers long-term changes in 2-AG-mediated endocannabinoid signaling in the amygdala, and that pharmacological interventions targeting MGL might provide a therapeutic strategy for the treatment of chronic brain disorders initiated by trauma. PMID:26361059

  14. κ Opioid Receptor Antagonism and Prodynorphin Gene Disruption Block Stress-Induced Behavioral Responses

    OpenAIRE

    McLaughlin, Jay P.; Marton-Popovici, Monica; Chavkin, Charles

    2003-01-01

    Previous studies have demonstrated that stress may increase prodynorphin gene expression, and κ opioid agonists suppress drug reward. Therefore, we tested the hypothesis that stress-induced release of endogenous dynorphin may mediate behavioral responses to stress and oppose the rewarding effects of cocaine. C57Bl/6 mice subjected to repeated forced swim testing (FST) using a modified Porsolt procedure at 30°C showed a characteristic stress-induced immobility response and a stress-induced ana...

  15. Translational and posttranslational regulation of XIAP by eIF2α and ATF4 promotes ER stress-induced cell death during the unfolded protein response.

    Science.gov (United States)

    Hiramatsu, Nobuhiko; Messah, Carissa; Han, Jaeseok; LaVail, Matthew M; Kaufman, Randal J; Lin, Jonathan H

    2014-05-01

    Endoplasmic reticulum (ER) protein misfolding activates the unfolded protein response (UPR) to help cells cope with ER stress. If ER homeostasis is not restored, UPR promotes cell death. The mechanisms of UPR-mediated cell death are poorly understood. The PKR-like endoplasmic reticulum kinase (PERK) arm of the UPR is implicated in ER stress-induced cell death, in part through up-regulation of proapoptotic CCAAT/enhancer binding protein homologous protein (CHOP). Chop((-)/(-)) cells are partially resistant to ER stress-induced cell death, and CHOP overexpression alone does not induce cell death. These findings suggest that additional mechanisms regulate cell death downstream of PERK. Here we find dramatic suppression of antiapoptosis XIAP proteins in response to chronic ER stress. We find that PERK down-regulates XIAP synthesis through eIF2α and promotes XIAP degradation through ATF4. Of interest, PERK's down-regulation of XIAP occurs independently of CHOP activity. Loss of XIAP leads to increased cell death, whereas XIAP overexpression significantly enhances resistance to ER stress-induced cell death, even in the absence of CHOP. Our findings define a novel signaling circuit between PERK and XIAP that operates in parallel with PERK to CHOP induction to influence cell survival during ER stress. We propose a "two-hit" model of ER stress-induced cell death involving concomitant CHOP up-regulation and XIAP down-regulation both induced by PERK.

  16. Oxidative stress-induced autophagy: Role in pulmonary toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Malaviya, Rama [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Jeffrey D. [Department of Environmental and Occupational Medicine, Robert Wood Johnson Medical School, Rutgers University, Piscataway, NJ 08854 (United States); Laskin, Debra L., E-mail: laskin@eohsi.rutgers.edu [Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854 (United States)

    2014-03-01

    Autophagy is an evolutionarily conserved catabolic process important in regulating the turnover of essential proteins and in elimination of damaged organelles and protein aggregates. Autophagy is observed in the lung in response to oxidative stress generated as a consequence of exposure to environmental toxicants. Whether autophagy plays role in promoting cell survival or cytotoxicity is unclear. In this article recent findings on oxidative stress-induced autophagy in the lung are reviewed; potential mechanisms initiating autophagy are also discussed. A better understanding of autophagy and its role in pulmonary toxicity may lead to the development of new strategies to treat lung injury associated with oxidative stress. - Highlights: • Exposure to pulmonary toxicants is associated with oxidative stress. • Oxidative stress is known to induce autophagy. • Autophagy is upregulated in the lung following exposure to pulmonary toxicants. • Autophagy may be protective or pathogenic.

  17. REPEATED ACUTE STRESS INDUCED ALTERATIONS IN CARBOHYDRATE METABOLISM IN RAT

    Directory of Open Access Journals (Sweden)

    Nirupama R.

    2010-09-01

    Full Text Available Acute stress induced alterations in the activity levels of rate limiting enzymes and concentration of intermediates of different pathways of carbohydrate metabolism have been studied. Adult male Wistar rats were restrained (RS for 1 h and after an interval of 4 h they were subjected to forced swimming (FS exercise and appropriate controls were maintained. Five rats were killed before the commencement of the experiment (initial controls, 5 control and equal number of stressed rats were killed 2 h after RS and remaining 5 rats in each group were killed 4 h after FS. There was a significant increase in the adrenal 3β- hydroxy steroid dehydrogenase activity following RS, which showed further increase after FS compared to controls and thereby indicated stress response of rats. There was a significant increase in the blood glucose levels following RS which showed further increase and reached hyperglycemic condition after FS. The hyperglycemic condition due to stress was accompanied by significant increases in the activities of glutamate- pyruvate transaminase, glutamate- oxaloacetate transaminase, glucose -6- phosphatase and lactate dehydrogenase and significant decrease in the glucose -6- phosphate dehydrogenase and pyruvate dehydrogenase activities, whereas pyruvate kinase activity did not show any alteration compared to controls. Further, the glycogen and total protein contents of the liver were decreased whereas those of pyruvate and lactate showed significant increase compared to controls after RS as well as FS.The results put together indicate that acute stress induced hyperglycemia results due to increased gluconeogenesis and glycogenolysis without alteration in glycolysis. The study first time reveals that after first acute stress exposure, the subsequent stressful experience augments metabolic stress response leading to hyperglycemia. The results have relevance to human health as human beings are exposed to several stressors in a day and

  18. Understanding stress-induced immunosuppression: exploration of cytokine and chemokine gene profiles in chicken peripheral leukocytes.

    Science.gov (United States)

    Shini, S; Huff, G R; Shini, A; Kaiser, P

    2010-04-01

    At present, the poultry meat and egg industry has gained a lot of ground, being viewed as a provider of a healthy alternative to red meat and other protein sources. If this trend is to be maintained, solutions must be found to improve resistance of chickens to disease, which often is weakened by stressful conditions. In poultry, stress-induced immunosuppression is manifested by failures in vaccination and increased morbidity and mortality of flocks. Currently, several modern cellular and molecular approaches are being used to explore the status of the immune system during stress and disease. It is likely that these new techniques will lead to the development of new strategies for preventing and controlling immunosuppression in poultry. Using quantitative reverse transcription-PCR assays, a broad spectrum of cytokine, chemokine, and their receptor genes can be quantified in birds and then be used as markers to assess the effects of stress on the immune system. Currently, we are investigating immune and endocrine interactions in the chicken, in particular the cells and molecules that are known to be involved in such interactions in mammals. We have evaluated the effects of corticosterone administration in drinking water on peripheral lymphocyte and heterophil cytokine and chemokine gene profiles. In particular, there seems to be effects on cytokine and chemokine mRNA expression levels in both lymphocytes and heterophils, especially expression of the proinflammatory cytokines interleukin (IL)-1beta, IL-6, and IL-18 and chemokines C-C motif, ligand 1 inflammatory (CCLi1); C-C motif, ligand 2 inflammatory (CCLi2); C-C motif, ligand 5 (CCL5); C-C motif, ligand 16 (CCL16); C-X-C motif ligand 1 inflammatory (CXCLi1); and C-X-C motif ligand 2 inflammatory (CXCLi2), which are initially upregulated and are potentially involved in modulating the adaptive immune response. A chronic treatment with corticosterone downregulates proinflammatory cytokines and chemokines, suggesting

  19. Trailing the unpredictable pathways of European Union lifelong learning policy

    DEFF Research Database (Denmark)

    Cort, Pia

    2014-01-01

    Since 2000 the concept of Europeanization has gained importance as a way of conceptualizing the changes in education and training policy in the European Union. Not least the introduction of the Open Method of Coordination in education and training has launched important policy processes through...... which the usual distinctions between policy-making, policy decision and policy implementation are changing. Policy pathways have become unpredictable as ‘transnational flows and networks of people, ideas and practices across European borders’ (Lawn & Grek, 2012, p. 8) have intensified and drawn together...... actors within the new structures of a European education space. The aim of this chapter is to offer a tentative proposal on how to study the unpredictable pathways of EU LLL policy. The methodology of policy trailing and the use of the mixed methods of discourse analysis and narrative inquiry...

  20. Unpredictable feeding impairs glucose tolerance in growing lambs.

    Directory of Open Access Journals (Sweden)

    Anne L Jaquiery

    Full Text Available Irregular eating is associated with insulin resistance and metabolic disease in adults but may affect young, growing children differently. We investigated the metabolic effects of unpredictable feeding in female juvenile lambs randomly assigned to receive, for six weeks, maintenance feed given twice daily in equal portions (Control Group, C; n = 24 or the same weekly feed amount in aliquots of variable size at unpredictable times (Unpredictable Group, U; n = 21. Intravenous glucose tolerance tests (IVGTT, insulin tolerance tests (ITT, and measurement of diurnal plasma cortisol concentrations were performed pre and post the dietary intervention. Groups were compared using t test and RM ANOVA. Weight gain was similar in both groups (C 18 ± 2%; U 16 ± 2% of initial body weight. Glucose area under the curve (AUC was unchanged in C (AUC pre 818 ± 34, post 801 ± 33 mmol.min.l(-1, but increased by 20% in U (pre 830 ± 25, post 1010 ± 19 mmol.min.l(-1; p<0.0001, with an inadequate insulin response to glucose load (log(AUC insulin first 40 minutes post intervention C 1.49 ± 0.04 vs U 1.36 ± 0.04 ng.min.ml(-1; p = 0.03. Insulin tolerance and diurnal variation of plasma cortisol concentrations were not different between groups. Unpredictable feeding impairs insulin response to glucose in growing lambs despite high quality food and normal weight gain. Irregular eating warrants investigation as a potentially remediable risk factor for disordered glucose metabolism.

  1. CPG Control for Biped Hopping Robot in Unpredictable Environment

    Institute of Scientific and Technical Information of China (English)

    Tingting Wang; Wei Guo; Mantian Li; Fusheng Zha; Lining Sun

    2012-01-01

    A CPG control mechanism is proposed for hopping motion control of biped robot in unpredictable environment.Based on analysis of robot motion and biological observation of animal's control mechanism,the motion control task is divided into two simple parts:motion sequence control and output force control.Inspired by a two-level CPG model,a two-level CPG control mechanism is constructed to coordinate the drivers of robot joint,while various feedback information are introduced into the control mechanism.Interneurons within the control mechanism are modeled to generate motion rhythm and pattern promptly for motion sequence control; motoneurons are modeled to control output forces of joint drivers in real time according to feedbacks.The control system can perceive changes caused by unknown perturbations and environment changes according to feedback information,and adapt to unpredictable environment by adjusting outputs of neurons.The control mechanism is applied to a biped hopping robot in unpredictable environment on simulation platform,and stable adaptive motions are obtained.

  2. Clocking in the face of unpredictability beyond quantum uncertainty

    Science.gov (United States)

    Madjid, F. Hadi; Myers, John M.

    2015-05-01

    In earlier papers we showed unpredictability beyond quantum uncertainty in atomic clocks, ensuing from a proven gap between given evidence and explanations of that evidence. Here we reconceive a clock, not as an isolated entity, but as enmeshed in a self-adjusting communications network adapted to one or another particular investigation, in contact with an unpredictable environment. From the practical uses of clocks, we abstract a clock enlivened with the computational capacity of a Turing machine, modified to transmit and to receive numerical communications. Such "live clocks" phase the steps of their computations to mesh with the arrival of transmitted numbers. We lift this phasing, known in digital communications, to a principle of logical synchronization, distinct from the synchronization defined by Einstein in special relativity. Logical synchronization elevates digital communication to a topic in physics, including applications to biology. One explores how feedback loops in clocking affect numerical signaling among entities functioning in the face of unpredictable influences, making the influences themselves into subjects of investigation. The formulation of communications networks in terms of live clocks extends information theory by expressing the need to actively maintain communications channels, and potentially, to create or drop them. We show how networks of live clocks are presupposed by the concept of coordinates in a spacetime. A network serves as an organizing principle, even when the concept of the rigid body that anchors a special-relativistic coordinate system is inapplicable, as is the case, for example, in a generic curved spacetime.

  3. Cordycepin prevents oxidative stress-induced inhibition of osteogenesis.

    Science.gov (United States)

    Wang, Feng; Yin, Peipei; Lu, Ye; Zhou, Zubin; Jiang, Chaolai; Liu, Yingjie; Yu, Xiaowei

    2015-11-01

    Oxidative stress is known to be involved in impairment of osteogenesis and age-related osteoporosis. Cordycepin is one of the major bioactive components of Cordyceps militaris that has been shown to exert antioxidant and anti-inflammatory activities. However, there are few reports available regarding the effects of cordycepin on osteogenesis and the underlying mechanism. In this study, we investigated the potential osteoprotective effects of cordycepin and its mechanism systematically using both in vitro model as well as in vivo mouse models. We discovered that hydrogen peroxide (H2O2)-induced inhibition of osteogenesis which was rescued by cordycepin treatment in human bone marrow mesenchymal stem cells (BM-MSCs). Cordycepin exerted its protective effects partially by increasing or decreasing expression of osteogenic and osteoclastogenesis marker genes. Treatment with cordycepin increased Wnt-related genes' expression whereas supplementation of Wnt pathway inhibitor reversed its protective effects. In addition, administration of cordycepin promoted osteogenic differentiation of BM-MSCs by reducing oxidative stress in both ovariectomized and aged animal models. Taken together, these results support the protective effects of cordycepin on oxidative stress induced inhibition of osteogenesis by activation of Wnt pathway. PMID:26462178

  4. Oxidative Stress Induces Senescence in Cultured RPE Cells.

    Science.gov (United States)

    Aryan, Nona; Betts-Obregon, Brandi S; Perry, George; Tsin, Andrew T

    2016-01-01

    The aim of this research is to determine whether oxidative stress induces cellular senescence in human retinal pigment epithelial cells. Cultured ARPE19 cells were subjected to different concentrations of hydrogen peroxide to induce oxidative stress. Cells were seeded into 24-well plates with hydrogen peroxide added to cell medium and incubated at 37°C + 5% CO2 for a 90-minute period [at 0, 300, 400 and 800 micromolar (MCM) hydrogen peroxide]. The number of viable ARPE19 cells were recorded using the Trypan Blue Dye Exclusion Method and cell senescence was measured by positive staining for senescence-associated beta-galactosidase (SA-beta-Gal) protein. Without hydrogen peroxide treatment, the number of viable ARPE19 cells increased significantly from 50,000 cells/well to 197,000 within 72 hours. Treatment with hydrogen peroxide reduced this level of cell proliferation significantly (to 52,167 cells at 400 MCM; to 49,263 cells at 800 MCM). Meanwhile, cells with a high level of positive senescence-indicator SA-Beta-Gal-positive staining was induced by hydrogen peroxide treatment (from a baseline level of 12% to 80% at 400 MCM and at 800 MCM). Our data suggests that oxidative stress from hydrogen peroxide treatment inhibited ARPE19 cell proliferation and induced cellular senescence. PMID:27651846

  5. Effects of Kombucha on oxidative stress induced nephrotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Gharib Ola

    2009-11-01

    Full Text Available Abstract Background Trichloroethylene (TCE may induce oxidative stress which generates free radicals and alters antioxidants or oxygen-free radical scavenging enzymes. Methods Twenty male albino rats were divided into four groups: (1 the control group treated with vehicle, (2 Kombucha (KT-treated group, (3 TCE-treated group and (4 KT/TCE-treated group. Kidney lipid peroxidation, glutathione content, nitric oxide (NO and total blood free radical concentrations were evaluated. Serum urea, creatinine level, gamma-glutamyl transferase (GGT and lactate dehydrogenase (LDH activities were also measured. Results TCE administration increased the malondiahyde (MDA and NO contents in kidney, urea and creatinine concentrations in serum, total free radical level in blood and GGT and LDH activities in serum, whereas it decreased the glutathione (GSH level in kidney homogenate. KT administration significantly improved lipid peroxidation and oxidative stress induced by TCE. Conclusion The present study indicates that Kombucha may repair damage caused by environmental pollutants such as TCE and may be beneficial to patient suffering from renal impairment.

  6. Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

    Directory of Open Access Journals (Sweden)

    Magdalena Cristóbal-García

    2015-01-01

    Full Text Available We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks and short-term (3 weeks effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW, OA+Allopurinol (AP, 150 mg/L drinking water, OA+Tempol (T, 15 mg/kg BW, or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase and oxidative stress markers (lipid and protein oxidation along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident.

  7. The involvement of homocysteine in stress-induced Aβ precursor protein misprocessing and related cognitive decline in rats.

    Science.gov (United States)

    Xie, Fang; Zhao, Yun; Ma, Jing; Gong, Jing-Bo; Wang, Shi-Da; Zhang, Liang; Gao, Xiu-Jie; Qian, Ling-Jia

    2016-09-01

    Chronic stress is a risk factor in the development of cognitive decline and even Alzheimer's disease (AD), although its underlying mechanism is not fully understood. Our previous data demonstrated that the level of homocysteine (Hcy) was significantly elevated in the plasma of stressed animals, which suggests the possibility that Hcy is a link between stress and cognitive decline. To test this hypothesis, we compared the cognitive function, plasma concentrations of Hcy, and the brain beta-amyloid (Aβ) level between rats with or without chronic unexpected mild stress (CUMS). A lower performance by rats in behavioral tests indicated that a significant cognitive decline was induced by CUMS. Stress also disturbed the normal processing of Aβ precursor protein (APP) and resulted in the accumulation of Aβ in the brains of rats, which showed a positive correlation with the hyperhomocysteinemia (HHcy) that appeared in stressed rats. Hcy-targeting intervention experiments were used to verify further the involvement of Hcy in stress-induced APP misprocessing and related cognitive decline. The results showed that diet-induced HHcy could mimic the cognitive impairment and APP misprocessing in the same manner as CUMS, while Hcy reduction by means of vitamin B complex supplements and betaine could alleviate the cognitive deficits and dysregulation of Aβ metabolism in CUMS rats. Taken together, the novel evidence from our present study suggests that Hcy is likely to be involved in chronic stress-evoked APP misprocessing and related cognitive deficits. Our results also suggested the possibility of Hcy as a target for therapy and the potential value of vitamin B and betaine intake in the prevention of stress-induced cognitive decline.

  8. The involvement of homocysteine in stress-induced Aβ precursor protein misprocessing and related cognitive decline in rats.

    Science.gov (United States)

    Xie, Fang; Zhao, Yun; Ma, Jing; Gong, Jing-Bo; Wang, Shi-Da; Zhang, Liang; Gao, Xiu-Jie; Qian, Ling-Jia

    2016-09-01

    Chronic stress is a risk factor in the development of cognitive decline and even Alzheimer's disease (AD), although its underlying mechanism is not fully understood. Our previous data demonstrated that the level of homocysteine (Hcy) was significantly elevated in the plasma of stressed animals, which suggests the possibility that Hcy is a link between stress and cognitive decline. To test this hypothesis, we compared the cognitive function, plasma concentrations of Hcy, and the brain beta-amyloid (Aβ) level between rats with or without chronic unexpected mild stress (CUMS). A lower performance by rats in behavioral tests indicated that a significant cognitive decline was induced by CUMS. Stress also disturbed the normal processing of Aβ precursor protein (APP) and resulted in the accumulation of Aβ in the brains of rats, which showed a positive correlation with the hyperhomocysteinemia (HHcy) that appeared in stressed rats. Hcy-targeting intervention experiments were used to verify further the involvement of Hcy in stress-induced APP misprocessing and related cognitive decline. The results showed that diet-induced HHcy could mimic the cognitive impairment and APP misprocessing in the same manner as CUMS, while Hcy reduction by means of vitamin B complex supplements and betaine could alleviate the cognitive deficits and dysregulation of Aβ metabolism in CUMS rats. Taken together, the novel evidence from our present study suggests that Hcy is likely to be involved in chronic stress-evoked APP misprocessing and related cognitive deficits. Our results also suggested the possibility of Hcy as a target for therapy and the potential value of vitamin B and betaine intake in the prevention of stress-induced cognitive decline. PMID:27435080

  9. Chronic Restraint Stress Induced Anxiety-and Depression-like Behaviors in Spontaneously Hypertensive Rats%慢性束缚应激诱导自发性高血压大鼠出现抑郁焦虑样行为

    Institute of Scientific and Technical Information of China (English)

    曹爽; 丁建伟; 李炳; 袁丽粉; 杜勤

    2014-01-01

    目的 探讨自发性高血压大鼠(SHR)在慢性束缚应激(Chronic Restraint Stress,CRS)时抑郁焦虑样行为学改变. 方法 雄性SHR大鼠16只,随机分为对照组(CON,n=8)和慢性束缚应激组(CRS,n=8).通过旷场试验(Open Field test,OFT)、强迫游泳实验(Forced Swimming test,FST)、高架十字迷宫试验(Elevated Plus Maze,EPM)评价其抑郁焦虑样行为,同时比较SHR血压变化及血清ACTH水平.结果 束缚4周后,与对照组相比,CRS组的SHR在OFT中直立次数及总位移均显著降低(P<0.05),FST中不动时间显著延长(P<0.05),EPM中开臂滞留时间百分比显著下降(P<0.05). 结论 慢性束缚应激可诱导SHR出现抑郁焦虑样行为.

  10. [On the mechanism of noopept action: decrease in activity of stress-induced kinases and increase in expression of neutrophines].

    Science.gov (United States)

    Ostrovskaia, R U; Vakhitova, Iu V; Salimgareeva, M Kh; Iamidanov, R S; Sadovnikov, S V; Kapitsa, I G; Seredenin, S B

    2010-12-01

    The influence of noopept (N-phenylacetyl-L-prolylglycine ethyl ester, GVS-111)--a drug combining the nootrope and neuroprotector properties--on the activity of mitogen-activated protein kinases (MAPKs) and the level of NGF and BDNF gene and protein expression in the frontal cortex, hippocampus, and hypothalamus has been studied in rats. Under conditions of chronic administration (28 days, 0.5 mg/day, i.p.), noopept decreased the activity of stress-induced kinases (SAPK/JNK 46/54 and pERK1/2) in rat hippocampus and increases the level of mRNA of the BDNF gene in both hypothalamus and hippocampus. The content of BDNF protein in the hypothalamus was also somewhat increased. In the context of notions about the activation of stress-induced kinases, as an important factor of amyloidogenesis and tau-protein deposition in brain tissue, and the role of deficiency of the neurotrophic factors in the development of neurodegenerative processes, the observed decrease in the activity of stress-activated MAPKs and increased expression of BDNF as a result of noopept administration suggest thatthis drug hasaspecific activity withrespect to some pathogenetic mechanisms involved in the Alzheimer disease. PMID:21395007

  11. Critical features of acute stress-induced cross-sensitization identified through the hypothalamic-pituitary-adrenal axis output.

    Science.gov (United States)

    Belda, Xavier; Nadal, Roser; Armario, Antonio

    2016-01-01

    Stress-induced sensitization represents a process whereby prior exposure to severe stressors leaves animals or humans in a hyper-responsive state to further stressors. Indeed, this phenomenon is assumed to be the basis of certain stress-associated pathologies, including post-traumatic stress disorder and psychosis. One biological system particularly prone to sensitization is the hypothalamic-pituitary-adrenal (HPA) axis, the prototypic stress system. It is well established that under certain conditions, prior exposure of animals to acute and chronic (triggering) stressors enhances HPA responses to novel (heterotypic) stressors on subsequent days (e.g. raised plasma ACTH and corticosterone levels). However, such changes remain somewhat controversial and thus, the present study aimed to identify the critical characteristics of the triggering and challenging stressors that affect acute stress-induced HPA cross-sensitization in adult rats. We found that HPA cross-sensitization is markedly influenced by the intensity of the triggering stressor, whereas the length of exposure mainly affects its persistence. Importantly, HPA sensitization is more evident with mild than strong challenging stressors, and it may remain unnoticed if exposure to the challenging stressor is prolonged beyond 15 min. We speculate that heterotypic HPA sensitization might have developed to optimize biologically adaptive responses to further brief stressors. PMID:27511270

  12. Antidepressant-like effects and possible mechanisms of amantadine on cognitive and synaptic deficits in a rat model of chronic stress.

    Science.gov (United States)

    Yu, Mei; Zhang, Yuan; Chen, Xiaoyu; Zhang, Tao

    2016-01-01

    The aim of this study was to examine whether amantadine (AMA), as a low-affinity noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, is able to improve cognitive deficits caused by chronic stress in rats. Male Wistar rats were divided into four groups: control, control + AMA, stress and stress + AMA groups. The chronic stress model combined chronic unpredictable stress (CUS) with isolated feeding. Animals were exposed to CUS continued for 21 days. AMA (25 mg/kg) was administrated p.o. for 20 days from the 4th day of CUS to the 23rd. Weight and sucrose consumption were measured during model establishing period. Spatial memory was evaluated using the Morris water maze (MWM) test. Following MWM testing, both long-term potentiation (LTP) and depotentiation were recorded in the hippocampal CA1 region. NR2B and postsynaptic density protein 95 (PSD-95) proteins were measured by Western-blot analysis. AMA increased weight and sucrose consumption of stressed rats. Spatial memory and reversal learning in stressed rats were impaired relative to controls, whereas AMA significantly attenuated cognitive impairment. AMA also mitigated the chronic stress-induced impairment of hippocampal synaptic plasticity, in which both the LTP and depotentiation were significantly inhibited in stressed rats. Moreover, AMA enhanced the expression of hippocampal NR2B and PSD-95 in stressed rats. The data suggest that AMA may be an effective therapeutic agent for depression-like symptoms and associated cognitive disturbances.

  13. Antidepressant-like effects and possible mechanisms of amantadine on cognitive and synaptic deficits in a rat model of chronic stress.

    Science.gov (United States)

    Yu, Mei; Zhang, Yuan; Chen, Xiaoyu; Zhang, Tao

    2016-01-01

    The aim of this study was to examine whether amantadine (AMA), as a low-affinity noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, is able to improve cognitive deficits caused by chronic stress in rats. Male Wistar rats were divided into four groups: control, control + AMA, stress and stress + AMA groups. The chronic stress model combined chronic unpredictable stress (CUS) with isolated feeding. Animals were exposed to CUS continued for 21 days. AMA (25 mg/kg) was administrated p.o. for 20 days from the 4th day of CUS to the 23rd. Weight and sucrose consumption were measured during model establishing period. Spatial memory was evaluated using the Morris water maze (MWM) test. Following MWM testing, both long-term potentiation (LTP) and depotentiation were recorded in the hippocampal CA1 region. NR2B and postsynaptic density protein 95 (PSD-95) proteins were measured by Western-blot analysis. AMA increased weight and sucrose consumption of stressed rats. Spatial memory and reversal learning in stressed rats were impaired relative to controls, whereas AMA significantly attenuated cognitive impairment. AMA also mitigated the chronic stress-induced impairment of hippocampal synaptic plasticity, in which both the LTP and depotentiation were significantly inhibited in stressed rats. Moreover, AMA enhanced the expression of hippocampal NR2B and PSD-95 in stressed rats. The data suggest that AMA may be an effective therapeutic agent for depression-like symptoms and associated cognitive disturbances. PMID:26466744

  14. Effects of chronic mild stress on apomorphine induced behavioral sensitization in different brain regions of rats in relation to serotonin change

    Directory of Open Access Journals (Sweden)

    Muhammad Farhan

    2015-11-01

    Full Text Available Background: The impacts of unpredictable stressors have influence on neurochemical and behavioral parameters in laboratory animals. Stress induced behavioral changes particularly those associated with anxiety like behavior may activate topographically organized mesolimbic cortical serotonergic system. This study was designed to investigate the influence of unpredictable stress on behavioral and neurochemical parameters in apomorphine treated rats. Methods: Initially, the animals were divided into two groups as Unstressed and stressed (uncontrollable chronic mild stress or UCMS. Both groups of animals were subdivided into two groups; i.e. saline and apomorphine administrated animals at dose 1.0 mg/kg. Behavioral manipulations was observed by monitoring the locomotor activity and exploratory activity. Neurochemical estimation of 5-hydroxytryptamine (5-HT was done by High performance liquid chromatography (HPLC. Animals were decapitated 24hr post apomorphine injection and different regions of brain (dorsal and ventral striatum, of animals were collected and stored at -70°C. Results: This preclinical study showed that the UCMS induced hypophagia were promoted in apomorphine administrated animals. Apomorphine induced hyperlocomotion were more prominent in unstressed animals than that of stressed groups. It implies that apomorphine is effective in the retrieval from UCMS induced depressive symptoms in rats. Neurochemical study showed decreased level of 5-HT in unstressed animals than stressed animals in response to apomorphine administration. Conclusion: This study, therefore establish the relation between stress and addiction at behavioral as well as neurochemical level to better understand the idea whether intolerable stress promotes addiction.

  15. Sensitivity of the prefrontal GABAergic system to chronic stress in male and female mice: Relevance for sex differences in stress-related disorders.

    Science.gov (United States)

    Shepard, Ryan; Page, Chloe E; Coutellier, Laurence

    2016-09-22

    Stress-induced modifications of the prefrontal cortex (PFC) are believed to contribute to the onset of mood disorders, such as depression and anxiety, which are more prevalent in women. In depression, the PFC is hypoactive; however the origin of this hypoactivity remains unclear. Possibly, stress could impact the prefrontal GABAergic inhibitory system that, as a result, impairs the functioning of downstream limbic structures controlling emotions. Preclinical evidence indicates that the female PFC is more sensitive to the effects of stress. These findings suggest that exposure to stress could lead to sex-specific alterations in prefrontal GABAergic signaling, which contribute to sex-specific abnormal functioning of limbic regions. These limbic changes could promote the onset of depressive and anxiety behaviors in a sex-specific manner, providing a possible mechanism mediating sex differences in the clinical presentation of stress-related mood disorders. We addressed this hypothesis using a mouse model of stress-induced depressive-like behaviors: the unpredictable chronic mild stress (UCMS) paradigm. We observed changes in prefrontal GABAergic signaling after exposure to UCMS most predominantly in females. Increased parvalbumin (PV) expression and decreased prefrontal neuronal activity were correlated in females with severe emotionality deficit following UCMS, and with altered activity of the amygdala. In males, small changes in emotionality following UCMS were associated with minor changes in prefrontal PV expression, and with hypoactivity of the nucleus accumbens. Our data suggest that prefrontal hypoactivity observed in stress-related mood disorders could result from stress-induced increases in PV expression, particularly in females. This increased vulnerability of the female prefrontal PV system to stress could underlie sex differences in the prevalence and symptomatology of stress-related mood disorders. PMID:27365172

  16. Stress-induced core temperature changes in pigeons (Columba livia).

    Science.gov (United States)

    Bittencourt, Myla de Aguiar; Melleu, Fernando Falkenburger; Marino-Neto, José

    2015-02-01

    Changes in body temperature are significant physiological consequences of stressful stimuli in mammals and birds. Pigeons (Columba livia) prosper in (potentially) stressful urban environments and are common subjects in neurobehavioral studies; however, the thermal responses to stress stimuli by pigeons are poorly known. Here, we describe acute changes in the telemetrically recorded celomatic (core) temperature (Tc) in pigeons given a variety of potentially stressful stimuli, including transfer to a novel cage (ExC) leading to visual isolation from conspecifics, the presence of the experimenter (ExpR), gentle handling (H), sham intracelomatic injections (SI), and the induction of the tonic immobility (TI) response. Transfer to the ExC cage provoked short-lived hyperthermia (10-20 min) followed by a long-lasting and substantial decrease in Tc, which returned to baseline levels 2 h after the start of the test. After a 2-hour stay in the ExC, the other potentially stressful stimuli evoked only weak, marginally significant hyperthermic (ExpR, IT) or hypothermic (SI) responses. Stimuli delivered 26 h after transfer to the ExC induced definite and intense increases in Tc (ExpR, H) or hypothermic responses (SI). These Tc changes appear to be unrelated to modifications in general activity (as measured via telemetrically recorded actimetric data). Repeated testing failed to affect the hypothermic responses to the transference to the ExC, even after nine trials and at 1- or 8-day intervals, suggesting that the social (visual) isolation from conspecifics may be a strong and poorly controllable stimulus in this species. The present data indicated that stress-induced changes in Tc may be a consistent and reliable physiological parameter of stress but that they may also show stressor type-, direction- and species-specific attributes.

  17. Role for MMP-9 in stress-induced downregulation of nectin-3 in hippocampal CA1 and associated behavioural alterations.

    Science.gov (United States)

    van der Kooij, Michael A; Fantin, Martina; Rejmak, Emilia; Grosse, Jocelyn; Zanoletti, Olivia; Fournier, Celine; Ganguly, Krishnendu; Kalita, Katarzyna; Kaczmarek, Leszek; Sandi, Carmen

    2014-01-01

    Chronic stress is a risk factor for the development of psychopathologies characterized by cognitive dysfunction and deregulated social behaviours. Emerging evidence suggests a role for cell adhesion molecules, including nectin-3, in the mechanisms that underlie the behavioural effects of stress. We tested the hypothesis that proteolytic processing of nectins by matrix metalloproteinases (MMPs), an enzyme family that degrades numerous substrates, including cell adhesion molecules, is involved in hippocampal effects induced by chronic restraint stress. A reduction in nectin-3 in the perisynaptic CA1, but not in the CA3, compartment is observed following chronic stress and is implicated in the effects of stress in social exploration, social recognition and a CA1-dependent cognitive task. Increased MMP-9-related gelatinase activity, involving N-methyl-D-aspartate receptor, is specifically found in the CA1 and involved in nectin-3 cleavage and chronic stress-induced social and cognitive alterations. Thus, MMP-9 proteolytic processing emerges as an important mediator of stress effects in brain function and behaviour. PMID:25232752

  18. Phase Stability and Stress-Induced Transformations in Beta Titanium Alloys

    Science.gov (United States)

    Kolli, R. Prakash; Joost, William J.; Ankem, Sreeramamurthy

    2015-06-01

    In this article, we provide a brief review of the recent developments related to the relationship between phase stability and stress-induced transformations in metastable body-centered-cubic β-phase titanium alloys. Stress-induced transformations occur during tensile, compressive, and creep loading and influence the mechanical response. These transformations are not fully understood and increased understanding of these mechanisms will permit future development of improved alloys for aerospace, biomedical, and energy applications. In the first part of this article, we review phase stability and discuss a few recent developments. In the second section, we discuss the current status of understanding stress-induced transformations and several areas that require further study. We also provide our perspective on the direction of future research efforts. Additionally, we address the occurrence of the hcp ω-phase and the orthorhombic α″-martensite phase stress-induced transformations.

  19. Catalase activity as a biomarker for mild-stress-induced robustness in Bacillus weihenstephanensis

    NARCIS (Netherlands)

    Besten, den H.M.W.; Effraimidou, S.; Abee, T.

    2013-01-01

    Microorganisms are able to survive and grow in changing environments by activating stress adaptation mechanisms which may enhance bacterial robustness. Stress-induced enhanced robustness complicates the predictability of microbial inactivation. Using psychrotolerant Bacillus weihenstephanensis strai

  20. Stress-induced cortisol is associated with generation of non-negative interpretations during cognitive reappraisal

    OpenAIRE

    Tsumura, Hideki; Sensaki, Jun; Shimada, Hironori

    2015-01-01

    Background Enhanced processing of emotional stimuli after stress exposure is reported to be associated with stress-induced cortisol. Because enhanced emotional information processing could make cognitive emotion regulation more difficult, it was hypothesized that stress-induced cortisol would be associated with non-negative interpretation generation associated with the cognitive reappraisal processes. Methods A total of 36 participants (Mean age = 21.3 years, SD = 1.8) watched video clips of ...

  1. Permanent lesion in rostral ventromedial medulla potentiates swim stress-induced analgesia in formalin test

    OpenAIRE

    Ali Shamsizadeh; Neda Soliemani; Mohammad Mohammad-Zadeh; Hassan Azhdari-

    2014-01-01

    Objective(s): There are many reports about the role of rostral ventromedial medulla (RVM) in modulating stress-induced analgesia (SIA). In the previous study we demonstrated that temporal inactivation of RVM by lidocaine potentiated stress-induced analgesia. In this study, we investigated the effect of permanent lesion of the RVM on SIA by using formalin test as a model of acute inflammatory pain. Materials and Methods: Three sets of experiments were conducted: (1) Application of stress proto...

  2. Interactions Between Endocannabinoids and Stress-Induced Decreased Sensitivity to Natural Reward

    OpenAIRE

    Rademacher, David J.; Hillard, Cecilia J.

    2006-01-01

    Since endocannabinoids modulate reward processing and the stress response, we tested the hypothesis that endocannabinoids regulate stress-induced decreased sensitivity to natural reward. Restraint was used to produce stress-induced reductions in sucrose consumption and preference in male mice. Central cannabinoid receptor (CB1) signaling was modulated pharmacologically prior to the application of stress. The preference for sucrose over water was significantly decreased in mice exposed to rest...

  3. Studies on effect of stress preconditioning in restrain stress-induced behavioral alterations.

    Science.gov (United States)

    Kaur, Rajneet; Jaggi, Amteshwar Singh; Singh, Nirmal

    2010-02-01

    Stress preconditioning has been documented to confer on gastroprotective effects on stress-induced gastric ulcerations. However, the effects of prior exposure of stress preconditioning episodes on stress-induced behavioral changes have not been explored yet. Therefore the present study was designed to investigate the ameliorative effects of stress preconditioning in immobilization stress-induced behavioral alterations in rats. The rats were subjected to restrain stress by placing in restrainer (5.5 cm in diameter and 18 cm in length) for 3.5 h. Stress preconditioning was induced by subjecting the rats to two cycles of restraint and restrain-free periods of 15 min each. Furthermore, a similar type of stress preconditioning was induced using different time cycles of 30 and 45 min. The extent and severity of the stress-induced behavioral alterations were assessed using different behavioral tests such as hole-board test, social interaction test, open field test, and actophotometer. Restrain stress resulted in decrease in locomotor activity, frequency of head dips and rearing in hole board, line crossing and rearing in open field, and decreased following and increased avoidance in social interaction test. Stress preconditioning with two cycles of 15, 30 or 45 min respectively, did not attenuate stress-induced behavioral changes to any extent. It may be concluded that stress preconditioning does not seem to confer any protective effect in modulating restrain stress-induced behavioral alterations.

  4. Inhibition of telomerase causes vulnerability to endoplasmic reticulum stress-induced neuronal cell death.

    Science.gov (United States)

    Hosoi, Toru; Nakatsu, Kanako; Shimamoto, Akira; Tahara, Hidetoshi; Ozawa, Koichiro

    2016-08-26

    Endoplasmic reticulum (ER) stress is implicated in several diseases, such as cancer and neurodegenerative diseases. In the present study, we investigated the possible involvement of telomerase in ER stress-induced cell death. ER stress-induced cell death was ameliorated in telomerase reverse transcriptase (TERT) over-expressing MCF7 cells (MCF7-TERT cell). Telomerase specific inhibitor, BIBR1532, reversed the inhibitory effect of TERT on ER stress-induced cell death in MCF7-TERT cells. These findings suggest that BIBR1532 may specifically inhibit telomerase activity, thereby inducing cell death in ER stress-exposed cells. TERT was expressed in the SH-SY5Y neuroblastoma cell line. To analyze the possible involvement of telomerase in ER stress-induced neuronal cell death, we treated SH-SY5Y neuroblastoma cells with BIBR1532 and analyzed ER stress-induced cell death. We found that BIBR1532 significantly enhanced the ER stress-induced neuronal cell death. These findings suggest that inhibition of telomerase activity may enhance vulnerability to neuronal cell death caused by ER stress. PMID:27443785

  5. Role of melatonin in modulation of oxidative stress induced by delta-

    Directory of Open Access Journals (Sweden)

    El-Sawi, MR, Badawy, ME and El-Gharieb, NM.

    2007-09-01

    Full Text Available Backgrounds: Delta-aminolevulinic acid (ALA is a heme precursor that accumulates in acute intermittent porphyria (AIP due to enzymatic deficiencies in the heme biosynthetic pathway, its accumulation has been associated with several symptoms because it works as an endogenous source of reactive oxygen species, which can exert oxidative damage to cell structures. The present work was designed to examine the ability of melatonin, a well known antioxidant and a free radical scavenger secreted from the pineal gland, to revert ALA-promoted damage in brain, liver and kidney of rats. Results: The present data demonstrated that chronically ALA-treated rats (40 mg / kg body wt day after day for 14 days exhibited very highly significant increases in malondialdehyde (MDA and protein carbonyl (PC whereas the level of glutathione (GSH was significantly diminished in the tissue homogenates of all tested organs (brain, kidney & liver. Among antioxidant enzymes, superoxide dismutase (SOD, catalase (CAT, glutathione reductase (GSH-Rd, glutathione-S-transferase (GST activities were significantly diminished by ALA treatment. Intraperitoneal injection of melatonin (10 mg / kg body weight, every day for 14 consecutive days significantly ameliorated all the tested parameters. Melatonin moderately increased SOD, CAT, GSH-Rd and GST activities, thereby counteracting the oxidative stress induced by ALA. Nevertheless, exogenous ALA caused a strong net rise in MDA and PC and a significant decrease in GSH when given together with ALA, melatonin antagonized these effects and largely protected the integrity of tissue structures. From the present data, the protection of melatonin against ALA oxidative stress is obviously, so it is well recommended to use melatonin in patients suffering from symptoms related to ALA accumulation

  6. Managing the continuum certainty, uncertainty, unpredictability in large engineering projects

    CERN Document Server

    Caron, Franco

    2013-01-01

    The brief will describe how to develop a risk analysis applied to a project , through a sequence of steps: risk management planning, risk identification, risk classification, risk assessment, risk quantification, risk response planning, risk monitoring and control, process close out and lessons learning. The project risk analysis and management process will be applied to large engineering projects, in particular related to the oil and gas industry. The brief will address the overall range of possible events affecting the project moving from certainty (project issues) through uncertainty (project risks) to unpredictability (unforeseeable events), considering both negative and positive events. Some quantitative techniques (simulation, event tree, Bayesian inference, etc.) will be used to develop risk quantification. The brief addresses a typical subject in the area of project management, with reference to large engineering projects concerning the realization of large plants and infrastructures. These projects a...

  7. Acute and Chronic Stress-Induced Disturbances of Microglial Plasticity, Phenotype and Function

    OpenAIRE

    Walkera, Frederick Rohan; Nilsson, Michael; Jones, Kimberley

    2013-01-01

    Traditionally, microglia have been considered to act as macrophages of the central nervous system. While this concept still remains true it is also becoming increasingly apparent that microglia are involved in a host of non-immunological activities, such as monitoring synaptic function and maintaining synaptic integrity. It has also become apparent that microglia are exquisitely sensitive to perturbation by environmental challenges. The aim of the current review is to critically examine the n...

  8. NLRP3 Inflammasome Mediates Chronic Mild Stress-Induced Depression in Mice via Neuroinflammation

    OpenAIRE

    Zhang, Yi; Liu, Lei; Liu, Yun-Zi; Shen, Xiao-Liang; Wu, Teng-Yun; Zhang, Ting; Wang, Wei; Wang, Yun-Xia; Jiang, Chun-Lei

    2015-01-01

    Background: Evidence from both clinical and experimental research indicates that the immune-brain interaction plays a pivotal role in the pathophysiology of depression. A multi-protein complex of the innate immune system, the NLRP3 inflammasome regulates cleavage and secretion of proinflammatory cytokine interleukin-1β. The inflammasome detects various pathogen-associated molecule patterns and damage-associated molecule patterns, which then leads to a series of immune-inflammatory reactions. ...

  9. Aneuploidy as a mechanism for stress-induced liver adaptation.

    Science.gov (United States)

    Duncan, Andrew W; Hanlon Newell, Amy E; Bi, Weimin; Finegold, Milton J; Olson, Susan B; Beaudet, Arthur L; Grompe, Markus

    2012-09-01

    Over half of the mature hepatocytes in mice and humans are aneuploid and yet retain full ability to undergo mitosis. This observation has raised the question of whether this unusual somatic genetic variation evolved as an adaptive mechanism in response to hepatic injury. According to this model, hepatotoxic insults select for hepatocytes with specific numerical chromosome abnormalities, rendering them differentially resistant to injury. To test this hypothesis, we utilized a strain of mice heterozygous for a mutation in the homogentisic acid dioxygenase (Hgd) gene located on chromosome 16. Loss of the remaining Hgd allele protects from fumarylacetoacetate hydrolase (Fah) deficiency, a genetic liver disease model. When adult mice heterozygous for Hgd and lacking Fah were exposed to chronic liver damage, injury-resistant nodules consisting of Hgd-null hepatocytes rapidly emerged. To determine whether aneuploidy played a role in this phenomenon, array comparative genomic hybridization (aCGH) and metaphase karyotyping were performed. Strikingly, loss of chromosome 16 was dramatically enriched in all mice that became completely resistant to tyrosinemia-induced hepatic injury. The frequency of chromosome 16-specific aneuploidy was approximately 50%. This result indicates that selection of a specific aneuploid karyotype can result in the adaptation of hepatocytes to chronic liver injury. The extent to which aneuploidy promotes hepatic adaptation in humans remains under investigation.

  10. Apoplastic reactive oxygen species transiently decrease auxin signaling and cause stress-induced morphogenic response in Arabidopsis.

    Science.gov (United States)

    Blomster, Tiina; Salojärvi, Jarkko; Sipari, Nina; Brosché, Mikael; Ahlfors, Reetta; Keinänen, Markku; Overmyer, Kirk; Kangasjärvi, Jaakko

    2011-12-01

    Reactive oxygen species (ROS) are ubiquitous signaling molecules in plant stress and development. To gain further insight into the plant transcriptional response to apoplastic ROS, the phytotoxic atmospheric pollutant ozone was used as a model ROS inducer in Arabidopsis (Arabidopsis thaliana) and gene expression was analyzed with microarrays. In contrast to the increase in signaling via the stress hormones salicylic acid, abscisic acid, jasmonic acid (JA), and ethylene, ROS treatment caused auxin signaling to be transiently suppressed, which was confirmed with a DR5-uidA auxin reporter construct. Transcriptomic data revealed that various aspects of auxin homeostasis and signaling were modified by apoplastic ROS. Furthermore, a detailed analysis of auxin signaling showed that transcripts of several auxin receptors and Auxin/Indole-3-Acetic Acid (Aux/IAA) transcriptional repressors were reduced in response to apoplastic ROS. The ROS-derived changes in the expression of auxin signaling genes partially overlapped with abiotic stress, pathogen responses, and salicylic acid signaling. Several mechanisms known to suppress auxin signaling during biotic stress were excluded, indicating that ROS regulated auxin responses via a novel mechanism. Using mutants defective in various auxin (axr1, nit1, aux1, tir1 afb2, iaa28-1, iaa28-2) and JA (axr1, coi1-16) responses, ROS-induced cell death was found to be regulated by JA but not by auxin. Chronic ROS treatment resulted in altered leaf morphology, a stress response known as "stress-induced morphogenic response." Altered leaf shape of tir1 afb2 suggests that auxin was a negative regulator of stress-induced morphogenic response in the rosette.

  11. THE ROLE OF NITRIC OXIDE IN STRESS-INDUCED GASTRIC DAMAGE IN CHOLESTATIC RATS

    Directory of Open Access Journals (Sweden)

    Sh. Sadr

    1999-07-01

    Full Text Available In this study the effect of nitric oxide synthesis inhibition on stress-induced gastric damage was evaluated in bile duel ligated, sham operated and unoperated rats. Animals were injected intraperitoneally with NG-nitro-L-arginine methylester (L-NAME, 40 mglkg, L-argininc, 200 mg/kg or saline, 30 min before water-immersion stress. One hour after water immersion, the animals were killed and their stomachs were removed for measurement of gastric mucosal damage. Tfie results showed that L-NAME significantly enhances the development of gastric mucosal lesion in sham operated and unoperated rats, while in bile duct ligated animals, L-NAME decreases and L-arginine enhances the potentiation of stress-induced gastric mucosal damage. The results suggest that inhibition of nitric oxide synthase with L-NAME has different effects on stress-induced gastric damage in cholestatic rats compared with normal animals.

  12. Disease in a more variable and unpredictable climate

    Science.gov (United States)

    McMahon, T. A.; Raffel, T.; Rohr, J. R.; Halstead, N.; Venesky, M.; Romansic, J.

    2014-12-01

    Global climate change is shifting the dynamics of infectious diseases of humans and wildlife with potential adverse consequences for disease control. Despite this, the role of global climate change in the decline of biodiversity and the emergence of infectious diseases remains controversial. Climate change is expected to increase climate variability in addition to increasing mean temperatures, making climate less predictable. However, few empirical or theoretical studies have considered the effects of climate variability or predictability on disease, despite it being likely that hosts and parasites will have differential responses to climatic shifts. Here we present a theoretical framework for how temperature variation and its predictability influence disease risk by affecting host and parasite acclimation responses. Laboratory experiments and field data on disease-associated frog declines in Latin America support this framework and provide evidence that unpredictable temperature fluctuations, on both monthly and diurnal timescales, decrease frog resistance to the pathogenic chytrid fungus Batrachochytrium dendrobatidis (Bd). Furthermore, the pattern of temperature-dependent growth of the fungus on frogs was inconsistent with the pattern of Bd growth in culture, emphasizing the importance of accounting for the host-parasite interaction when predicting climate-dependent disease dynamics. Consistent with our laboratory experiments, increased regional temperature variability associated with global El Niño climatic events was the best predictor of widespread amphibian losses in the genus Atelopus. Thus, incorporating the effects of small-scale temporal variability in climate can greatly improve our ability to predict the effects of climate change on disease.

  13. Regular moderate or intense exercise prevents depression-like behavior without change of hippocampal tryptophan content in chronically tryptophan-deficient and stressed mice.

    Directory of Open Access Journals (Sweden)

    Hosung Lee

    Full Text Available Regular exercise has an antidepressant effect in human subjects. Studies using animals have suggested that the antidepressant effect of exercise is attributable to an increase of brain 5-hydroxytryptamine (5-HT; however, the precise mechanism underlying the antidepressant action via exercise is unclear. In contrast, the effect of 5-HT on antidepressant activity has not been clarified, in part because the therapeutic response to antidepressant drugs has a time lag in spite of the rapid increase of brain 5-HT upon administration of these drugs. This study was designed to investigate the contribution of brain 5-HT to the antidepressant effect of exercise. Mice were fed a tryptophan-deficient diet and stressed using chronic unpredictable stress (CUS for 4 weeks with or without the performance of either moderate or intense exercise on a treadmill 3 days per week. The findings demonstrated that the onset of depression-like behavior is attributable not to chronic reduction of 5-HT but to chronic stress. Regular exercise, whether moderate or intense, prevents depression-like behavior with an improvement of adult hippocampal cell proliferation and survival and without the recovery of 5-HT. Concomitantly, the mice that exercised showed increased hippocampal noradrenaline. Regular exercise prevents the impairment of not long-term memory but short-term memory in a 5-HT-reduced state. Together, these findings suggest that: (1 chronic reduction of brain 5-HT may not contribute to the onset of depression-like behavior; (2 regular exercise, whether moderate or intense, prevents the onset of chronic stress-induced depression-like behavior independent of brain 5-HT and dependent on brain adrenaline; and (3 regular exercise prevents chronic tryptophan reduction-induced impairment of not long-term but short-term memory.

  14. Antioxidant effect of phycocyanin on oxidative stress induced with monosodium glutamate in rats

    Directory of Open Access Journals (Sweden)

    Telma Elita Bertolin

    2011-08-01

    Full Text Available The objective of this work was to study the antioxidant effect of phycocyanin on the oxidative stress induced by monosodium glutamate in the rats. The tests were performed with 32 rats of Wistar breed, divided into four groups, which were administered saline solution of phycocyanin, monosodium glutamate and monosodium glutamate plus phycocyanin. Sulfhydryl groups and the secondary substances derived from lipid oxidation were determined through the level of TBA. The evaluation of these values and the level of sulfhydryl showed that the administration of phycocyanin presented significant antioxidant effect (p < 0.05 reducing the oxidative stress induced by the monosodium glutamate in vivo.

  15. OXIDATIVE STRESS INDUCED ULCER PROTECTED BY NATURAL ANTIOXIDANTS: A REVIEW

    Directory of Open Access Journals (Sweden)

    Gupta Priya

    2012-05-01

    Full Text Available Oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive intermediates, which ultimately leads to oxidative deterioration of protein, lipid and DNA. In humans, oxidative stress is involved in pathology of many diseases, such as atherosclerosis, Parkinson’s disease, heart failure, myocardial infarction, and chronic fatigue syndrome. Reactive oxygen species (ROS can be beneficial, as they are used by the immune system as a way to attack and kill pathogens. To counteract oxidative stress, the body produces an armory of antioxidants to defend itself. It's the job of antioxidants to neutralize free radicals that can harm the cells. Body's internal production of antioxidants is not enough to neutralize all the free radicals. It’s a well-known fact that ROS are involved in the aetio-pathogenesis of the inflammatory and ulcerative lesions of the gastrointestinal tract. The present review focuses on the studies where oxidative damage due to stress has been linked causally to loss of cell integrity mainly in peptic ulcer cured by natural antioxidants.

  16. Scintigraphic appearance of stress-induced trauma of the dorsal cortex of the third metacarpal bone in racing Thoroughbred horses: 121 cases (1978-1986)

    International Nuclear Information System (INIS)

    Review of 121 bone scintigrams obtained on racing Thoroughbred horses with clinical histories indicative of forelimb lameness revealed 3 scintigraphic patterns of stress-induced trauma to the dorsal cortex of the third metacarpal bone: (1) focal, intense uptake associated with recent stress fracture; (2) regional uptake of varying intensity or a mixed pattern of uptake associated with chronic stress fracture; and (3) diffuse, mild to moderate uptake associated with periostitis (bucked shins). The latter scintigraphic pattern appeared to be an exaggerated manifestation of the normal remodeling process evident in immature horses (2 to 3 years old). Scintigraphy was most helpful in identifying radiographically occult stress fractures, determining the extent of cortical involvement before surgical intervention in cases of chronic stress fractures, and monitoring the fracture healing process

  17. Unpredictability of lymphatic drainage patterns in melanoma patients.

    Science.gov (United States)

    Statius Muller, Markwin G; Hennipman, Feitse A; van Leeuwen, Paul A M; Pijpers, Rik; Vuylsteke, Ronald J; Meijer, Sybren

    2002-02-01

    We analysed the localisations of sentinel nodes (SN) found with the SN procedure to compare these sites with those that would have been predicted by conventional clinical descriptions of cutaneous lymphatic drainage. We assessed the surplus value of performing the SN procedure in melanoma patients who underwent regional nodal surgery. The SN procedure was performed in 348 patients with melanomas who were referred to our institute between 1993 and 1999. The localisations of the melanomas with the corresponding SNs were meticulously recorded on drawings of the human body and grouped according to the conventional descriptions. Predictability of lymph drainage was defined as the percentage of melanomas whose draining pattern was to the ipsilateral nearest basin, without simultaneous drainage to other basins or to an interval node. In all patients the SN procedure visualised at least one SN. We found 410 lymphatic basins in 347 patients. These basins included basins that could not have been predicted by the conventional clinical descriptions, such as multiple basins and contralateral drainage sites. For the head/neck region, SNs could be found in any of the basins described in the literature. The trunk's drainage predictability depended strongly on the melanoma localisation, ranging from 0% in the midline to 92% in one of the upper quadrants. The lower extremities had a high predictability of almost 100%, and predictability of drainage for the upper extremities ranged from 77% to 100%. In total, 34% of the patients had a cutaneous lymphatic drainage that was unpredictable, either totally or partially. We therefore conclude that an SN procedure is indispensable if the drainage site(s) are to be accurately identified. PMID:11930886

  18. Intrusions of a drowsy mind: Neural markers of phenomenological unpredictability

    Directory of Open Access Journals (Sweden)

    Valdas eNoreika

    2015-03-01

    Full Text Available The transition from a relaxed to a drowsy state of mind is often accompanied by hypnagogic experiences: most commonly, perceptual imagery, but also linguistic intrusions, i.e. the sudden emergence of unpredictable anomalies in the stream of inner speech. This study has sought to describe the contents of such intrusions, to verify their association with the progression of sleep onset, and to investigate the electroencephalographic processes associated with linguistic intrusions as opposed to more common hypnagogic perceptual imagery. A single participant attended 10 experimental sessions in the EEG laboratory, where he was allowed to drift into a drowsy state of mind, while maintaining metacognition of his own experiences. Once a linguistic intrusion or a noticeable perceptual image occurred, the participant pressed a button and reported it verbally. An increase in the EEG-defined depth of drowsiness as assessed by the Hori system of sleep onset was observed in the last 20 sec before a button press. Likewise, EEG Dimension of Activation values decreased before the button press, indicating that the occurrence of cognitively incongruous experiences coincides with the rapid change of EEG predictability patterns. EEG hemispheric asymmetry analysis showed that linguistic intrusions had a higher alpha and gamma power in the left hemisphere electrodes, whereas perceptual imagery reports were associated with a higher beta power over the right hemisphere. These findings indicate that the modality as well as the incongruence of drowsiness-related hypnagogic experiences is strongly associated with distinct EEG signatures in this participant. Sleep onset may provide a unique possibility to study the neural mechanisms accompanying the fragmentation of the stream of consciousness in healthy individuals.

  19. Activation of sensory nerves participates in stress-induced histamine release from mast cells in rats.

    Science.gov (United States)

    Huang, Z L; Mochizuki, T; Watanabe, H; Maeyama, K

    1999-08-01

    To elucidate the mechanism by which stress induces rapid histamine release from mast cells, Wistar rats, pretreated as neonates with capsaicin, were subjected to immobilization stress for 2 h, and histamine release was measured in paws of anesthetized rats by using in vivo microdialysis after activation of sensory nerves by electrical or chemical stimulation. Immobilization stress studies indicated that in control rats stress induced a 2.7-fold increase in the level of plasma histamine compared to that in freely moving rats. Whereas pretreatment with capsaicin significantly decreased stress-induced elevation of plasma histamine. Microdialysis studies showed that electrical stimulation of the sciatic nerve resulted in a 4-fold increase of histamine release in rat paws. However, this increase was significantly inhibited in rats pretreated with capsaicin. Furthermore, injection of capsaicin into rat paw significantly increased histamine release in a dose-dependent manner. These results suggest that activation of sensory nerves participates in stress-induced histamine release from mast cells. PMID:10462124

  20. Dynamic OCT of mentally stress-induced sweating in sweat glands of the human finger tip

    Science.gov (United States)

    Ohmi, Masato; Ueda, Yoshihiro; Haruna, Masamitsu

    2007-02-01

    We demonstrate in-vivo imaging of sweat glands of human finger tip using the dynamic optical coherence tomography (OCT). Mentally-stress-induced sweating in sweat glands of human finger tip can be observed clearly in time-sequential OCT images. In the experiment, a sweat pore opened clearly on the skin surface according to a stimulus of sound.

  1. The ER stress inducer DMC enhances TRAIL-induced apoptosis in glioblastoma

    NARCIS (Netherlands)

    van Roosmalen, Ingrid A. M.; Dos Reis, Carlos R; Setroikromo, Rita; Yuvaraj, Saravanan; Joseph, Justin V.; Tepper, Pieter G.; Kruyt, Frank A. E.; Quax, Wim J.

    2014-01-01

    Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumour in humans and is highly resistant to current treatment modalities. We have explored the combined treatment of the endoplasmic reticulum (ER) stress-inducing agent 2,5-dimethyl-celecoxib (DMC) and TNF-related apoptosis-induci

  2. Stress-induced activation of brown adipose tissue prevents obesity in conditions of low adaptive thermogenesis

    Directory of Open Access Journals (Sweden)

    Maria Razzoli

    2016-01-01

    Conclusion: Our findings demonstrate that thermogenesis and BAT function are determinant of the resilience or vulnerability to stress-induced obesity. Our data support a model in which adrenergic and purinergic pathways exert complementary/synergistic functions in BAT, thus suggesting an alternative to βARs agonists for the activation of human BAT.

  3. Central anandamide deficiency predicts stress-induced anxiety: behavioral reversal through endocannabinoid augmentation.

    Science.gov (United States)

    Bluett, R J; Gamble-George, J C; Hermanson, D J; Hartley, N D; Marnett, L J; Patel, S

    2014-07-08

    Stress is a major risk factor for the development of mood and anxiety disorders; elucidation of novel approaches to mitigate the deleterious effects of stress could have broad clinical applications. Pharmacological augmentation of central endogenous cannabinoid (eCB) signaling may be an effective therapeutic strategy to mitigate the adverse behavioral and physiological consequences of stress. Here we show that acute foot-shock stress induces a transient anxiety state measured 24 h later using the light-dark box assay and novelty-induced hypophagia test. Acute pharmacological inhibition of the anandamide-degrading enzyme, fatty acid amide hydrolase (FAAH), reverses the stress-induced anxiety state in a cannabinoid receptor-dependent manner. FAAH inhibition does not significantly affect anxiety-like behaviors in non-stressed mice. Moreover, whole brain anandamide levels are reduced 24 h after acute foot-shock stress and are negatively correlated with anxiety-like behavioral measures in the light-dark box test. These data indicate that central anandamide levels predict acute stress-induced anxiety, and that reversal of stress-induced anandamide deficiency is a key mechanism subserving the therapeutic effects of FAAH inhibition. These studies provide further support that eCB-augmentation is a viable pharmacological strategy for the treatment of stress-related neuropsychiatric disorders.

  4. Adolescent Personality : Associations With Basal, Awakening, and Stress-Induced Cortisol Responses

    NARCIS (Netherlands)

    Laceulle, Odilia M.; Nederhof, Esther; van Aken, Marcel A. G.; Ormel, Johan

    2015-01-01

    The purpose of the present study was to investigate the associations between personality facets and hypothalamic-pituitary-adrenal (HPA) axis functioning. Previous studies have mainly focussed on stress-induced HPA-axis activation. We hypothesized that other characteristics of HPA-axis functioning w

  5. Influenza a virus host shutoff disables antiviral stress-induced translation arrest.

    Directory of Open Access Journals (Sweden)

    Denys A Khaperskyy

    2014-07-01

    Full Text Available Influenza A virus (IAV polymerase complexes function in the nucleus of infected cells, generating mRNAs that bear 5' caps and poly(A tails, and which are exported to the cytoplasm and translated by host machinery. Host antiviral defences include mechanisms that detect the stress of virus infection and arrest cap-dependent mRNA translation, which normally results in the formation of cytoplasmic aggregates of translationally stalled mRNA-protein complexes known as stress granules (SGs. It remains unclear how IAV ensures preferential translation of viral gene products while evading stress-induced translation arrest. Here, we demonstrate that at early stages of infection both viral and host mRNAs are sensitive to drug-induced translation arrest and SG formation. By contrast, at later stages of infection, IAV becomes partially resistant to stress-induced translation arrest, thereby maintaining ongoing translation of viral gene products. To this end, the virus deploys multiple proteins that block stress-induced SG formation: 1 non-structural protein 1 (NS1 inactivates the antiviral double-stranded RNA (dsRNA-activated kinase PKR, thereby preventing eIF2α phosphorylation and SG formation; 2 nucleoprotein (NP inhibits SG formation without affecting eIF2α phosphorylation; 3 host-shutoff protein polymerase-acidic protein-X (PA-X strongly inhibits SG formation concomitant with dramatic depletion of cytoplasmic poly(A RNA and nuclear accumulation of poly(A-binding protein. Recombinant viruses with disrupted PA-X host shutoff function fail to effectively inhibit stress-induced SG formation. The existence of three distinct mechanisms of IAV-mediated SG blockade reveals the magnitude of the threat of stress-induced translation arrest during viral replication.

  6. Influenza a virus host shutoff disables antiviral stress-induced translation arrest.

    Science.gov (United States)

    Khaperskyy, Denys A; Emara, Mohamed M; Johnston, Benjamin P; Anderson, Paul; Hatchette, Todd F; McCormick, Craig

    2014-07-01

    Influenza A virus (IAV) polymerase complexes function in the nucleus of infected cells, generating mRNAs that bear 5' caps and poly(A) tails, and which are exported to the cytoplasm and translated by host machinery. Host antiviral defences include mechanisms that detect the stress of virus infection and arrest cap-dependent mRNA translation, which normally results in the formation of cytoplasmic aggregates of translationally stalled mRNA-protein complexes known as stress granules (SGs). It remains unclear how IAV ensures preferential translation of viral gene products while evading stress-induced translation arrest. Here, we demonstrate that at early stages of infection both viral and host mRNAs are sensitive to drug-induced translation arrest and SG formation. By contrast, at later stages of infection, IAV becomes partially resistant to stress-induced translation arrest, thereby maintaining ongoing translation of viral gene products. To this end, the virus deploys multiple proteins that block stress-induced SG formation: 1) non-structural protein 1 (NS1) inactivates the antiviral double-stranded RNA (dsRNA)-activated kinase PKR, thereby preventing eIF2α phosphorylation and SG formation; 2) nucleoprotein (NP) inhibits SG formation without affecting eIF2α phosphorylation; 3) host-shutoff protein polymerase-acidic protein-X (PA-X) strongly inhibits SG formation concomitant with dramatic depletion of cytoplasmic poly(A) RNA and nuclear accumulation of poly(A)-binding protein. Recombinant viruses with disrupted PA-X host shutoff function fail to effectively inhibit stress-induced SG formation. The existence of three distinct mechanisms of IAV-mediated SG blockade reveals the magnitude of the threat of stress-induced translation arrest during viral replication.

  7. Antidepressant- like effects of BCEF0083 in the chronic unpredictable stress models

    Institute of Scientific and Technical Information of China (English)

    LanlanZhou; LiangMING; ChuangengMa; YanCheng; QinJiang

    2004-01-01

    AIM: Depression is a complicated disease, There are no satisfactory drugs to therapy depression so far. BCEF is a new type of bioactive compounds from entomogenous fungi. Depression animal models are effective to evaluate the antidepressant property of drugs. Several animal models of depression have been inn'oduced, however, only a few have been

  8. Stress Induces the Danger-Associated Molecular Pattern HMGB-1 in the Hippocampus of Male Sprague Dawley Rats: A Priming Stimulus of Microglia and the NLRP3 Inflammasome

    Science.gov (United States)

    Frank, Matthew G.; Tracey, Kevin J.; Watkins, Linda R.; Maier, Steven F.

    2015-01-01

    Exposure to acute and chronic stressors sensitizes the proinflammatory response of microglia to a subsequent immune challenge. However, the proximal signal by which stressors prime microglia remains unclear. Here, high mobility group box-1 (HMGB-1) protein was explored as a potential mediator of stress-induced microglial priming and whether HMGB-1 does so via the nucleotide-binding domain, leucine-rich repeat, pyrin domain containing protein 3 (NLRP3) inflammasome. Exposure to 100 inescapable tail shocks (ISs) increased HMGB-1 and NLRP3 protein in the hippocampus and led isolated microglia to release HMGB-1 ex vivo. To determine whether HMGB-1 signaling is necessary for stress-induced sensitization of microglia, the HMGB-1 antagonist BoxA was injected into the cisterna magna before IS. Hippocampal microglia were isolated 24 h later and stimulated with LPS ex vivo to probe for stress-induced sensitization of proinflammatory responses. Previous IS potentiated gene expression of NLRP3 and proinflammatory cytokines to LPS, that is, microglia were sensitized. Treatment with BoxA abolished this effect. To determine whether HMGB-1 is sufficient to prime microglia, IS was replaced with intracerebral administration of disulfide or fully reduced HMGB-1. Intracerebral disulfide HMGB-1 mimicked the effect of the stressor, because microglia isolated from HMGB-1-treated rats expressed exaggerated NLRP3 and proinflammatory cytokine expression after LPS treatment, whereas fully reduced HMGB-1 had no effect. The present results suggest that the CNS innate immune system can respond to an acute stressor as if it were cellular damage, thereby releasing the danger signal HMGB-1 in the brain to prime microglia by acting on the NLRP3 inflammasome, in preparation for a later immune challenge. PMID:25568124

  9. Sensitivity to stress-induced reproductive dysfunction is associated with a selective but not a generalized increase in activity of the adrenal axis.

    Science.gov (United States)

    Herod, S M; Dettmer, A M; Novak, M A; Meyer, J S; Cameron, J L

    2011-01-01

    Stress-induced reproductive dysfunction is a relatively common cause of infertility in women. In response to everyday life stress, some individuals readily develop reproductive dysfunction (i.e., they are stress sensitive), whereas others are more stress resilient. Female cynomolgus monkeys, when exposed to mild combined psychosocial and metabolic stress (change in social environment + 20% reduced calorie diet), can be categorized as stress sensitive (SS; they rapidly become anovulatory in response to stress), medium stress resilient (MSR; they slowly become anovulatory in response to prolonged stress), or highly stress resilient (HSR; they maintain normal menstrual cycles in response to stress). In this study, we examined whether increased sensitivity to stress-induced reproductive dysfunction is associated with elevated adrenal axis activity by measuring 1) the diurnal release of ACTH and cortisol, 2) ACTH and cortisol in response to an acute psychological stress, 3) the percent suppression of cortisol in response to dexamethasone negative feedback, 4) the diurnal release of ACTH and cortisol following exposure to mild psychosocial and metabolic stress, 5) the concentration of cortisol in hair, and 6) adrenal weight. SS monkeys (n = 5) did not differ from MSR (n = 5) or HSR (n = 7) monkeys in any measurement of baseline HPA axis activity or the integrated measurements of chronic HPA axis activity. However, MSR + SS monkeys (n = 10) did secrete more cortisol than HSR monkeys during the daytime hours (1000-1800) following exposure to a novel social environment and reduced diet. We conclude that increased activity of the HPA axis is unlikely to be the primary mechanism causing increased sensitivity to stress-induced reproductive dysfunction.

  10. The antidepressant roles of Wnt2 and Wnt3 in stress-induced depression-like behaviors

    Science.gov (United States)

    Zhou, W-J; Xu, N; Kong, L; Sun, S-C; Xu, X-F; Jia, M-Z; Wang, Y; Chen, Z-Y

    2016-01-01

    Wnts-related signaling pathways have been reported to play roles in the pathogenesis of stress-induced depression-like behaviors. However, there is relatively few direct evidence to indicate the effect of Wnt ligands on this process. Here, we investigated the role of Wnts in mediating chronic restraint stress (CRS)-induced depression-like behaviors. We found that CRS induced a significant decrease in the expression of Wnt2 and Wnt3 in the ventral hippocampus (VH) but not in the dorsal hippocampus. Knocking down Wnt2 or Wnt3 in the VH led to impaired Wnt/β-catenin signaling, neurogenesis deficits and depression-like behaviors. In contrast, overexpression of Wnt2 or Wnt3 reversed CRS-induced depression-like behaviors. Moreover, Wnt2 and Wnt3 activated cAMP response element-binding protein (CREB) and there was CREB-dependent positive feedback between Wnt2 and Wnt3. Finally, fluoxetine treatment increased Wnt2 and Wnt3 levels in the VH and knocking down Wnt2 or Wnt3 abolished the antidepressant effect of fluoxetine. Taken together, our study indicates essential roles for Wnt2 and Wnt3 in CRS-induced depression-like behaviors and antidepressant. PMID:27622936

  11. APACHE II score, rather than cardiac function, may predict poor prognosis in patients with stress-induced cardiomyopathy.

    Science.gov (United States)

    Joe, Byung-Hyun; Jo, Uk; Kim, Hyun-Soo; Park, Chang-Bum; Hwang, Hui-Jeong; Sohn, Il-Suk; Jin, Eun-Sun; Cho, Jin-Man; Park, Jeong-Hwan; Kim, Chong-Jin

    2012-01-01

    While the disease course of stress-induced cardiomyopathy (SIC) is usually benign, it can be fatal. The prognostic factors to predict poorer outcome are not well established, however. We analyzed the Acute Physiology And Chronic Health Evaluation (APACHE) II score to assess its value for predicting poor prognosis in patients with SIC. Thirty-seven consecutive patients with SIC were followed prospectively during their hospitalization. Clinical factors, including APACHE II score, coronary angiogram, echocardiography and cardiac enzymes at presentation were analyzed. Of the 37 patients, 27 patients (73%) were women. The mean age was 66.1 ± 15.6 yr, and the most common presentation was chest pain (38%). Initial echocardiographic left ventricular ejection fraction (EF) was 42.5% ± 9.3%, and the wall motion score index (WMSI) was 1.9 ± 0.3. Six patients (16%) expired during the follow-up period of hospitalization. Based on the analysis of characteristics and clinical factors, the only predictable variable in prognosis was APACHE II score. The patients with APACHE II score greater than 20 had tendency to expire than the others (P = 0.001). Based on present study, APACHE II score more than 20, rather than cardiac function, is associated with mortality in patients with SIC.

  12. Inhibition of phosphodiesterase-4 reverses the cognitive dysfunction and oxidative stress induced by Aβ25-35 in rats.

    Science.gov (United States)

    Zhuo, Yeye; Guo, Haibiao; Cheng, Yufang; Wang, Chuang; Wang, Canmao; Wu, Jingang; Zou, Zhengqiang; Gan, Danna; Li, Yiwen; Xu, Jiangping

    2016-08-01

    Phosphodiesterase-4 (PDE4) inhibitors prevent the breakdown of the second messenger cAMP and have been demonstrated to improve learning in several animal models of cognition. In this study, we explored the antioxidative effects of rolipram in Alzheimer's disease (AD) by using bilateral Aβ25-35 injection into the hippocampus of rats, which were used as an AD model. Rats received 3 intraperitoneal (i.p.) doses of rolipram (0.1, 0.5 and 1.25 mg/kg) daily after the injection of Aβ25-35 for 25 days. Chronic administration of rolipram prevented the memory impairments induced by Aβ25-35, as assessed using the passive avoidance test and the Morris water maze test. Furthermore, rolipram significantly reduced the oxidative stress induced by Aβ25-35, as evidenced by the decrease in the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and restored the reduced GSH levels and superoxide dismutase (SOD) activity. Moreover, western blotting and real-time reverse transcription polymerase chain reaction (RT-PCR) analysis showed that rolipram remarkably upregulated thioredoxin (Trx) and inhibited the inducible nitric oxide synthase/nitric oxide (iNOS/NO) pathway in the hippocampus. These results demonstrated that rolipram improved the learning and memory abilities in an Aβ25-35-induced AD rat model. The mechanism underlying these effects may be due to the noticeable antioxidative effects of rolipram. PMID:26920899

  13. Psychosocial stress induces hyperphagia and exacerbates diet-induced insulin resistance and the manifestations of the Metabolic Syndrome.

    Science.gov (United States)

    Sanghez, Valentina; Razzoli, Maria; Carobbio, Stefania; Campbell, Mark; McCallum, Jacob; Cero, Cheryl; Ceresini, Graziano; Cabassi, Aderville; Govoni, Paolo; Franceschini, Paolo; de Santis, Valentina; Gurney, Allison; Ninkovic, Ivana; Parmigiani, Stefano; Palanza, Paola; Vidal-Puig, Antonio; Bartolomucci, Alessandro

    2013-12-01

    Stress and hypercaloric food are recognized risk factors for obesity, Metabolic Syndrome (MetS) and Type 2 Diabetes (T2D). Given the complexity of these metabolic processes and the unavailability of animal models, there is poor understanding of their underlying mechanisms. We established a model of chronic psychosocial stress in which subordinate mice are vulnerable to weight gain while dominant mice are resilient. Subordinate mice fed a standard diet showed marked hyperphagia, high leptin, low adiponectin, and dyslipidemia. Despite these molecular signatures of MetS and T2D, subordinate mice fed a standard diet were still euglycemic. We hypothesized that stress predisposes subordinate mice to develop T2D when synergizing with other risk factors. High fat diet aggravated dyslipidemia and the MetS thus causing a pre-diabetes-like state in subordinate mice. Contrary to subordinates, dominant mice were fully protected from stress-induced metabolic disorders when fed both a standard- and a high fat-diet. Dominant mice showed a hyperphagic response that was similar to subordinate but, unlike subordinates, showed a significant increase in VO2, VCO2, and respiratory exchange ratio when compared to control mice. Overall, we demonstrated a robust stress- and social status-dependent effect on the development of MetS and T2D and provided insights on the physiological mechanisms. Our results are reminiscent of the effect of the individual socioeconomic status on human health and provide an animal model to study the underlying molecular mechanisms.

  14. BUILDING A MOVEMENT OF MAGNETO AND LEVITATING TRAINS IN AN UNPREDICTABLE ENVIRONMENT

    Directory of Open Access Journals (Sweden)

    V. A. Polyakov

    2009-07-01

    Full Text Available The method of constructing the goal-directed dynamics of magnet-levitation train is offered. The components of its motion are divided on useful and parasitic. Their situation is expected unpredictable.

  15. Short-term environmental enrichment is sufficient to counter stress-induced anxiety and associated structural and molecular plasticity in basolateral amygdala.

    Science.gov (United States)

    Ashokan, Archana; Hegde, Akshaya; Mitra, Rupshi

    2016-07-01

    Moderate levels of anxiety enable individual animals to cope with stressors through avoidance, and could be an adaptive trait. However, repeated stress exacerbates anxiety to pathologically high levels. Dendritic remodeling in the basolateral amygdala is proposed to mediate potentiation of anxiety after stress. Similarly, modulation of brain-derived neurotrophic factor is thought to be important for the behavioral effects of stress. In the present study, we investigate if relatively short periods of environmental enrichment in adulthood can confer resilience against stress-induced anxiety and concomitant changes in neuronal arborisation and brain derived neurotrophic factor within basolateral amygdala. Two weeks of environmental enrichment countermanded the propensity of increased anxiety following chronic immobilization stress. Environmental enrichment concurrently reduced dendritic branching and spine density of projection neurons of the basolateral amygdala. Moreover, stress increased abundance of BDNF mRNA in the basolateral amygdala in agreement with the dendritic hypertrophy post-stress and role of BDNF in promoting dendritic arborisation. In contrast, environmental enrichment prevented stress-induced rise in the BDNF mRNA abundance. Gain in body weights and adrenal weights remained unaffected by exposure to environmental enrichment. These observations suggest that a short period of environmental enrichment can provide resilience against maladaptive effects of stress on hormonal, neuronal and molecular mediators of anxiogenesis. PMID:27128967

  16. Unpredictable neonatal stress enhances adult anxiety and alters amygdala gene expression related to serotonin and GABA

    OpenAIRE

    Sarro, Emma C.; Sullivan, Regina M.; Barr, Gordon

    2013-01-01

    Anxiety-related disorders are among the most common psychiatric illnesses, thought to have both genetic and environmental causes. Early-life trauma, such as abuse from a caregiver, can be predictable or unpredictable, each resulting in increased prevalence and severity of a unique set of disorders. In this study, we examined the influence of early unpredictable trauma on both the behavioral expression of adult anxiety and gene expression within the amygdala. Neonatal rats were exposed to unpa...

  17. Cardioprotective and Antioxidant Influence of Aqueous Extracts from Sesamum indicum Seeds on Oxidative Stress Induced by Cadmium in Wistar Rats

    Science.gov (United States)

    Oyinloye, Babatunji Emmanuel; Ajiboye, Basiru Olaitan; Ojo, Oluwafemi Adeleke; Nwozo, Sarah Onyenibe; Kappo, Abidemi Paul

    2016-01-01

    Background: Oxidative stress has been implicated in the pathogenesis of several acute and chronic diseases of the heart as a result of indiscriminate exposure to cardiotoxic heavy metals. The study reported here was designed to evaluate the possible ameliorative effect of aqueous extracts from Sesamum indicum (SI) seeds on oxidative stress induced by cadmium (Cd) in Wistar rats. Materials and Methods: Daily administration of Cd (200 mg/L Cd as CdCl2) in the animals’ main drinking water for 21 days led to oxidative stress. Thereafter, the ameliorative effects were assessed by measuring biochemical parameters such as extent of lipid peroxidation (LPO), lipid profile, and enzymatic and nonenzymatic antioxidants, as well as serum aminotransferase activities. Results: Treatment with SI extract elicited notable reduction in serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels as well as concomitant increase in high-density lipoprotein cholesterol. SI extract also reversed the elevations witnessed in serum aminotransferase activities, LPO level, and ameliorated enzymatic and nonenzymatic antioxidant status in the heart of Cd-exposed rats. Conclusion: Thus, SI appears to be an attractive candidate with potential for the novel treatment of cardiotoxicity and management of oxidative stress arising from Cd exposure. SUMMARY Cadmium (200 mg/L) exposure in drinking water caused pronounced oxidative stress and cardiac tissue damage in animal modelAqueous extract of Sesamum indicum (SI) seeds at a dose of 200 or 400 mg/kg body weight exhibited a significant reversal effect in all biochemical parameters measured such as extent of lipid peroxidation, lipid profile, and enzymatic and nonenzymatic antioxidants, as well as serum aminotransferase activitiesAqueous extract of SI seeds possess antioxidant and cardioprotective potential in a dose-dependent manner, thus conferring protection against oxidative stress induced by cadmium. Abbreviation used

  18. Nordihydroguaiaretic Acid Attenuates the Oxidative Stress-Induced Decrease of CD33 Expression in Human Monocytes

    Directory of Open Access Journals (Sweden)

    Silvia Guzmán-Beltrán

    2013-01-01

    Full Text Available Nordihydroguaiaretic acid (NDGA is a natural lignan with recognized antioxidant and beneficial properties that is isolated from Larrea tridentata. In this study, we evaluated the effect of NDGA on the downregulation of oxidant stress-induced CD33 in human monocytes (MNs. Oxidative stress was induced by iodoacetate (IAA or hydrogen peroxide (H2O2 and was evaluated using reactive oxygen species (ROS production, and cell viability. NDGA attenuates toxicity, ROS production and the oxidative stress-induced decrease of CD33 expression secondary to IAA or H2O2 in human MNs. It was also shown that NDGA (20 μM attenuates cell death in the THP-1 cell line that is caused by treatment with either IAA or H2O2. These results suggest that NDGA has a protective effect on CD33 expression, which is associated with its antioxidant activity in human MNs.

  19. Inonotus obliquus protects against oxidative stress-induced apoptosis and premature senescence.

    Science.gov (United States)

    Yun, Jong Seok; Pahk, Jung Woon; Lee, Jong Seok; Shin, Won Cheol; Lee, Shin Young; Hong, Eock Kee

    2011-05-01

    In this study, we investigated the cytoprotective effects of Inonotus obliquus against oxidative stress-induced apoptosis and premature senescence. Pretreatment with I. obliquus scavenged intracellular ROS and prevented lipid peroxidation in hydrogen peroxide-treated human fibroblasts. As a result, I. obliquus exerted protective effects against hydrogen peroxide-induced apoptosis and premature senescence in human fibroblasts. In addition, I. obliquus suppressed UV-induced morphologic skin changes, such as skin thickening and wrinkle formation, in hairless mice in vivo and increased collagen synthesis through inhibition of MMP-1 and MMP-9 activities in hydrogen peroxide-treated human fibroblasts. Taken together, these results demonstrate that I. obliquus can prevent the aging process by attenuating oxidative stress in a model of stress-induced premature senescence. PMID:21359681

  20. Endoplasmic reticulum stress-induced autophagy determines the susceptibility of melanoma cells to dabrafenib

    Science.gov (United States)

    Ji, Chao; Zhang, Ziping; Chen, Lihong; Zhou, Kunli; Li, Dongjun; Wang, Ping; Huang, Shuying; Gong, Ting; Cheng, Bo

    2016-01-01

    Melanoma is one of the deadliest skin cancers and accounts for most skin-related deaths due to strong resistance to chemotherapy drugs. In the present study, we investigated the mechanisms of dabrafenib-induced drug resistance in human melanoma cell lines A375 and MEL624. Our studies support that both endoplasmic reticulum (ER) stress and autophagy were induced in the melanoma cells after the treatment with dabrafenib. In addition, ER stress-induced autophagy protects melanoma cells from the toxicity of dabrafenib. Moreover, inhibition of both ER stress and autophagy promote the sensitivity of melanoma cells to dabrafenib. Taken together, the data suggest that ER stress-induced autophagy determines the sensitivity of melanoma cells to dabrafenib. These results provide us with promising evidence that the inhibition of autophagy and ER stress could serve a therapeutic effect for the conventional dabrafenib chemotherapy. PMID:27536070

  1. Immobilization stress-induced anorexia is mediated independent of MyD88.

    Science.gov (United States)

    Hosoi, Toru; Yamawaki, Yosuke; Kimura, Hitomi; Ozawa, Koichiro

    2016-09-01

    MyD88 is an adaptor protein for the toll-like receptor, which is involved in regulating innate immune function. Lipopolysaccharide-induced activation of toll-like receptor 4 signaling induces hypothalamic signal transducer and activator of transcription 3 (STAT3) phosphorylation and anorexia through MyD88. In the present study, we investigated the possible role of MyD88 in psychological stress-induced anorexia. We found that immobilization stress inhibited food intake in both wild-type mice and MyD88-deficient mice. Immobilization stress slightly increased STAT3 phosphorylation in the hypothalamus, but it was weaker than the lipopolysaccharide-induced increase in STAT3 phosphorylation. These observations suggest that the mechanisms involved in psychological stress-induced anorexia may be regulated differently from those involved in anorexia that is induced by infection. PMID:27391428

  2. A Method for Psychosocial Stress-Induced Reinstatement of Cocaine Seeking in Rats.

    Science.gov (United States)

    Manvich, Daniel F; Stowe, Taylor A; Godfrey, Jodi R; Weinshenker, David

    2016-06-01

    We describe a novel preclinical model of stress-induced relapse to cocaine use in rats using social defeat stress, an ethologically valid psychosocial stressor in rodents that closely resembles stressors that promote craving and relapse in humans. Rats self-administered cocaine for 20 days. On days 11, 14, 17, and 20, animals were subjected to social defeat stress or a nonstressful control condition following the session, with discrete environmental stimuli signaling the impending event. After extinction training, reinstatement was assessed following re-exposure to these discrete cues. Animals re-exposed to psychosocial stress-predictive cues exhibited increased serum corticosterone and significantly greater reinstatement of cocaine seeking than the control group, and active coping behaviors during social defeat episodes were associated with subsequent reinstatement magnitude. These studies are the first to describe an operant model of psychosocial stress-induced relapse in rodents and lay the foundation for future work investigating its neurobiological underpinnings.

  3. Stress-Induced Depressive Behaviors Require a Functional NLRP3 Inflammasome.

    Science.gov (United States)

    Alcocer-Gómez, Elísabet; Ulecia-Morón, Cristina; Marín-Aguilar, Fabiola; Rybkina, Tatyana; Casas-Barquero, Nieves; Ruiz-Cabello, Jesús; Ryffel, Bernhard; Apetoh, Lionel; Ghiringhelli, François; Bullón, Pedro; Sánchez-Alcazar, José Antonio; Carrión, Angel M; Cordero, Mario D

    2016-09-01

    Depression is a major public health concern in modern society, yet little is known about the molecular link between this condition and neuroinflammation. The inflammasome complex was recently shown to be implicated in depression. The present study shows the implication of NLRP3 inflammasome in animal model of stress-induced depression. Accordingly, we show here that in the absence of a NLRP3 inflammasome, prolonged stress does not provoke depressive behaviors or microglial activation in mice or dampen hippocampal neurogenesis. Indeed, NLRP3 deletion or inhibition of microglial activation impairs the stress-induced alterations associated with depression. According to these findings in animal model, the inflammasome could be a target for new therapeutic interventions to prevent depression in patients. PMID:26362308

  4. Mitochondrial calcium uniporter protein MCU is involved in oxidative stress-induced cell death.

    Science.gov (United States)

    Liao, Yajin; Hao, Yumin; Chen, Hong; He, Qing; Yuan, Zengqiang; Cheng, Jinbo

    2015-06-01

    Mitochondrial calcium uniporter (MCU) is a conserved Ca(2+) transporter at mitochondrial in eukaryotic cells. However, the role of MCU protein in oxidative stress-induced cell death remains unclear. Here, we showed that ectopically expressed MCU is mitochondrial localized in both HeLa and primary cerebellar granule neurons (CGNs). Knockdown of endogenous MCU decreases mitochondrial Ca(2+) uptake following histamine stimulation and attenuates cell death induced by oxidative stress in both HeLa cells and CGNs. We also found MCU interacts with VDAC1 and mediates VDAC1 overexpression-induced cell death in CGNs. This finding demonstrates that MCU-VDAC1 complex regulates mitochondrial Ca(2+) uptake and oxidative stress-induced apoptosis, which might represent therapeutic targets for oxidative stress related diseases.

  5. Protective effect of stress-induced liver damage by saponin fraction from Codonopsis lanceolata.

    Science.gov (United States)

    Kim, Min Ho; Lee, Jaehwi; Yoo, Dae Sung; Lee, Yong Gyu; Byeon, Se Eun; Hong, Eock Kee; Cho, Jae Youl

    2009-10-01

    Saponins are valuable principles found in various herbal medicine with pharmaceutical, cosmetical and nutraceutical merits. In this study, we evaluated the protective role of saponin fraction (Cl-SF), prepared from Codonopsis lanceolata, an ethnopharmacologically famous plant in Korea, China and Japan, on water immersion stress-induced liver damage and radical generation. Cl-SF clearly decreased the up-regulated levels of serum glutamate-oxalacetate transaminase and glutamate-pyruvate-transaminase induced by water-immersed stress conditions. Furthermore, Cl-SF seemed to block the stress-induced radicals. Thus, Griess and DPPH assays revealed that Cl-SF significantly suppressed both radical generation in sodium nitroprusside-treated RAW264.7 cells and nitric oxide production in LPS-treated RAW264.7 cells. Therefore, these results suggest that Cl-SF may be considered as a promising stress-regulatory principle with radical scavenging actions. PMID:19898808

  6. Chemical chaperone 4-phenylbutyrate prevents endoplasmic reticulum stress induced by T17M rhodopsin

    OpenAIRE

    Jiang, Haibo; Xiong, Siqi; Xia, Xiaobo

    2014-01-01

    Background Rhodopsin mutations are associated with the autosomal dominant form of retinitis pigmentosa. T17M mutation in rhodopsin predisposes cells to endoplasmic reticulum (ER) stress and induces cell death. This study aimed to examine whether chemical chaperone 4-phenylbutyrate prevents ER stress induced by rhodopsin T17M. Results ARPE-19 cells were transfected with myc-tagged wild-type (WT) and T17M rhodopsin constructs. Turnover of WT and T17M rhodopsin was measured by cycloheximide chas...

  7. Inonotus obliquus Protects against Oxidative Stress-Induced Apoptosis and Premature Senescence

    OpenAIRE

    Yun, Jong Seok; Pahk, Jung Woon; Lee, Jong Seok; Shin, Won Cheol; Lee, Shin Young; Hong, Eock Kee

    2011-01-01

    In this study, we investigated the cytoprotective effects of Inonotus obliquus against oxidative stress-induced apoptosis and premature senescence. Pretreatment with I. obliquus scavenged intracellular ROS and prevented lipid peroxidation in hydrogen peroxide-treated human fibroblasts. As a result, I. obliquus exerted protective effects against hydrogen peroxide-induced apoptosis and premature senescence in human fibroblasts. In addition, I. obliquus suppressed UV-induced morphologic skin cha...

  8. Angiotensin II Receptor Blocker Ameliorates Stress-Induced Adipose Tissue Inflammation and Insulin Resistance

    OpenAIRE

    Motoharu Hayashi; Kyosuke Takeshita; Yasuhiro Uchida; Koji Yamamoto; Ryosuke Kikuchi; Takayuki Nakayama; Emiko Nomura; Xian Wu Cheng; Tadashi Matsushita; Shigeo Nakamura; Toyoaki Murohara

    2014-01-01

    A strong causal link exists between psychological stress and insulin resistance as well with hypertension. Meanwhile, stress-related responses play critical roles in glucose metabolism in hypertensive patients. As clinical trials suggest that angiotensin-receptor blocker delays the onset of diabetes in hypertensive patients, we investigated the effects of irbesartan on stress-induced adipose tissue inflammation and insulin resistance. C57BL/6J mice were subjected to 2-week intermittent restra...

  9. Antioxidant effect of phycocyanin on oxidative stress induced with monosodium glutamate in rats

    OpenAIRE

    Telma Elita Bertolin; Daniele Farias; Cíntia Guarienti; Fernanda Tais Souza Petry; Luciane Maria Colla; Jorge Alberto Vieira Costa

    2011-01-01

    The objective of this work was to study the antioxidant effect of phycocyanin on the oxidative stress induced by monosodium glutamate in the rats. The tests were performed with 32 rats of Wistar breed, divided into four groups, which were administered saline solution of phycocyanin, monosodium glutamate and monosodium glutamate plus phycocyanin. Sulfhydryl groups and the secondary substances derived from lipid oxidation were determined through the level of TBA. The evaluation of these values ...

  10. Oxidative Stress Induces Endothelial Cell Senescence via Downregulation of Sirt6

    OpenAIRE

    Rong Liu; Hua Liu; Yonju Ha; Tilton, Ronald G.; Wenbo Zhang

    2014-01-01

    Accumulating evidence has shown that diabetes accelerates aging and endothelial cell senescence is involved in the pathogenesis of diabetic vascular complications, including diabetic retinopathy. Oxidative stress is recognized as a key factor in the induction of endothelial senescence and diabetic retinopathy. However, specific mechanisms involved in oxidative stress-induced endothelial senescence have not been elucidated. We hypothesized that Sirt6, which is a nuclear, chromatin-bound protei...

  11. Urban stress-induced biogenic VOC emissions impact secondary aerosol formation in Beijing

    OpenAIRE

    Ghirardo, A.; Xie, J; Zheng, X; Wang, Y.; Grote, R.; Block, K.; J. Wildt; Mentel, T.; Kiendler-Scharr, A.; M. Hallquist; Butterbach-Bahl, K.; J.-P. Schnitzler

    2015-01-01

    Trees can significantly impact the urban air chemistry by the uptake and emission of reactive biogenic volatile organic compounds (BVOCs), which are involved in ozone and particle formation. Here we present the emission potentials of "constitutive" (cBVOCs) and "stress-induced" BVOCs (sBVOCs) from the dominant broadleaf woody plant species in the megacity of Beijing. Based on an inventory of BVOC emissions and the tree census, we assessed the potential impact ...

  12. Urban stress-induced biogenic VOC emissions and SOA-forming potentials in Beijing

    OpenAIRE

    Ghirardo, Andrea; Xie, Junfei; Zheng, Xunhua; Wang, Yuesi; Grote, Rüdiger; Block, Katja; Wildt, Jürgen; Mentel, Thomas; Kiendler-Scharr, Astrid; Hallquist, Mattias; Butterbach-Bahl, Klaus; Schnitzler, Jörg-Peter

    2016-01-01

    Trees can significantly impact the urban air chemistry by the uptake and emission of reactive biogenic volatile organic compounds (BVOCs), which are involved in ozone and particle formation. Here we present the emission potentials of "constitutive" (cBVOCs) and "stress-induced" BVOCs (sBVOCs) from the dominant broadleaf woody plant species in the megacity of Beijing. Based on the municipal tree census and cuvette BVOC measurements on leaf level, we built an inventory of BVOC...

  13. Effects of L-citrulline diet on stress-induced cold hypersensitivity in mice

    Directory of Open Access Journals (Sweden)

    Yoshinori Kobayashi

    2014-01-01

    Full Text Available Background: L-citrulline is an amino acid discovered in watermelon (Citrullus lanatus, Cucurbitaceae and is a known component of the nitric oxide (NO cycle that plays an important role in adjusting blood circulation and supplying NO and a key component of the endothelium-derived relaxing factor. Objective: The objective of this study is to evaluate the effect of L-citrulline on a newly established stress-induced cold hypersensitivity mouse model. Materials and Methods: When normal mice were forced to swim in water at 25°C for 15 min, their core body temperature dropped to 28.9°C, and then quickly recovered to normal temperature after the mice were transferred to a dry cage at room temperature (25°C. A 1-h immobilization before swimming caused the core body temperature to drop to ca. 24.1°C (4.8°C lower than normal mice, and the speed of core body temperature recovery dropped to 57% of the normal control. We considered this delay in recovery from hypothermia to be a sign of stress-induced cold hypersensitivity. Similar cold hypersensitivity was induced by administration of 50 mM L-NG-nitroarginine methyl ester, a NO synthesis inhibitor. Results: In this study, we showed that recovery speed from the stress-induced hypothermia remarkably improved in mice fed a 1% L-citrulline-containing diet for 20 days. Furthermore, the nonfasting blood level of L-arginine and L-citrulline increased significantly in the L-citrulline diet group, and higher serum nitrogen oxide levels were observed during recovery from the cold. Conclusions: These results suggested that oral L-citrulline supplementation strengthens vascular endothelium function and attenuates stress-induced cold hypersensitivity by improving blood circulation.

  14. Depressive Symptoms Are Associated with Mental Stress-Induced Myocardial Ischemia after Acute Myocardial Infarction

    OpenAIRE

    Jingkai Wei; Pratik Pimple; Shah, Amit J.; Cherie Rooks; Douglas Bremner, J.; Nye, Jonathon A.; Ijeoma Ibeanu; Nancy Murrah; Lucy Shallenberger; Paolo Raggi; Viola Vaccarino

    2014-01-01

    Objectives Depression is an adverse prognostic factor after an acute myocardial infarction (MI), and an increased propensity toward emotionally-driven myocardial ischemia may play a role. We aimed to examine the association between depressive symptoms and mental stress-induced myocardial ischemia in young survivors of an MI. Methods We studied 98 patients (49 women and 49 men) age 38–60 years who were hospitalized for acute MI in the previous 6 months. Patients underwent myocardial perfusion ...

  15. EVALUATION OF ANXIOLYTIC POTENTIAL OF ETHANOLIC EXTRACT HYPERICUM HOOKERIANUM IN STRESS INDUCED SWISS ALBINO MICE

    Directory of Open Access Journals (Sweden)

    S.Subakanmani

    2012-04-01

    Full Text Available The aim of the present work is evaluate to Anxiolytic profile of Hypericum hookerianum in stress induced Swiss albino mice. The study was carried out using Swiss albino mice (25- 30 g. The Anxiolytic effect of aerial parts of ethanolic extract of Hypericum hookerianum was evaluated by using behavioral analysis like Elevated plus maze (EPM test, Open Field Test (OFT, Hole Board Test (HBT, Light dark exploration Test (LDE in restraint stress induced animals. Behavioral test parameters for anxiety were assessed followed by biochemical parameters (lipid per oxidation, super oxide dismutase, catalase, glutathione per oxidase, reduced glutathione, etc. and Diazepam 1 mg/kg served as a standard Anxiolytic drug, administered intraperitonealy. The results were shown that, ethanolic extract of H.hookerianum (Hh 100mg/kg and Hh 200 mg/kg, p.o. significantly increased the percentage of time spent and number of entries in open arm in EPM. In LDE, the extract produced significant increase in time spent, number of crossing and decrease in the duration of immobility in light box. In OFT, the extract showed significant increase in number of rearings, assisted rearings and number of square crossed, all of which are demonstrations of exploratory behavior. Biochemical analyses revealed an increase in lipid per oxidation, depletion of super oxide dismutase, reduced glutathione, catalase activity and glutathione per oxidase in stress induced animals as compared to unstressed animal. Six days treatment of Hh (100 mg/kg, 200 mg/kg comparable with Diazepam, significantly attenuated restraint stress-induced behavioral and oxidative damage. The results of the present study suggest that an ethanolic extract of H.hookerianum may possess Anxiolytic activity in stressed animals and provide a scientific evidence for its traditional claim.

  16. Salt stress-induced cell death in the unicellular green alga Micrasterias denticulata

    OpenAIRE

    Affenzeller, Matthias Josef; Darehshouri, Anza; Andosch, Ancuela; Lütz, Cornelius; LÜTZ-MEINDL, URSULA

    2009-01-01

    Programmed cell death (PCD) is a key element in normal plant growth and development which may also be induced by various abiotic and biotic stress factors including salt stress. In the present study, morphological, biochemical, and physiological responses of the theoretically immortal unicellular freshwater green alga Micrasterias denticulata were examined after salt (200 mM NaCl or 200 mM KCl) and osmotic stress induced by iso-osmotic sorbitol. KCl caused morphological changes such as cytopl...

  17. Binary stress induces an increase in indole alkaloid biosynthesis in Catharanthus roseus

    OpenAIRE

    Wei ZHU; Yang, Bingxian; Komatsu, Setsuko; Lu, Xiaoping; Li, Ximin; Tian, Jingkui

    2015-01-01

    Catharanthus roseus is an important medicinal plant, which produces a variety of indole alkaloids of significant pharmaceutical relevance. In the present study, we aimed to investigate the potential stress-induced increase of indole alkaloid biosynthesis in C. roseus using proteomic technique. The contents of the detectable alkaloids ajmalicine, vindoline, catharanthine, and strictosidine in C. roseus were significantly increased under binary stress. Proteomic analysis revealed that the abund...

  18. Binary Stress Induces an Increase in Indole Alkaloid Biosynthesis in Catharanthus roseus

    OpenAIRE

    Wei eZhu; Bingxian eYang; Setsuko eKomatsu; Xiaoping eLu; Ximin eLi; Jingkui eTian

    2015-01-01

    Catharanthus roseus is an important medicinal plant, which produces a variety of indole alkaloids of significant pharmaceutical relevance. In the present study, we aimed to investigate the potential stress-induced increase of indole alkaloid biosynthesis in C. roseus using proteomic technique. The contents of the detectable alkaloids ajmalicine, vindoline, catharanthine, and strictosidine in C. roseus were significantly increased under binary stress. Proteomic analysis revealed that the abund...

  19. Central anandamide deficiency predicts stress-induced anxiety: behavioral reversal through endocannabinoid augmentation

    OpenAIRE

    Bluett, R J; Gamble-George, J C; Hermanson, D J; Hartley, N D; Marnett, L J; Patel, S.

    2014-01-01

    Stress is a major risk factor for the development of mood and anxiety disorders; elucidation of novel approaches to mitigate the deleterious effects of stress could have broad clinical applications. Pharmacological augmentation of central endogenous cannabinoid (eCB) signaling may be an effective therapeutic strategy to mitigate the adverse behavioral and physiological consequences of stress. Here we show that acute foot-shock stress induces a transient anxiety state measured 24 h later using...

  20. Altered microglia morphology and higher resilience to stress-induced depression-like behavior in CX3CR1-deficient mice.

    Science.gov (United States)

    Hellwig, Sabine; Brioschi, Simone; Dieni, Sandra; Frings, Lars; Masuch, Annette; Blank, Thomas; Biber, Knut

    2016-07-01

    Microglia are suggested to be involved in several neuropsychiatric diseases. Indeed changes in microglia morphology have been reported in different mouse models of depression. A crucial regulatory system for microglia function is the well-defined CX3C axis. Thus, we aimed to clarify the role of microglia and CX3CR1 in depressive behavior by subjecting CX3CR1-deficient mice to a particular chronic despair model (CDM) paradigm known to exhibit face validity to major depressive disorder. In wild-type mice we observed the development of chronic depressive-like behavior after 5days of repetitive swim stress. 3D-reconstructions of Iba-1-labeled microglia in the dentate molecular layer revealed that behavioral effects were associated with changes in microglia morphology towards a state of hyper-ramification. Chronic treatment with the anti-depressant venlafaxine ameliorated depression-like behavior and restored microglia morphology. In contrast, CX3CR1 deficient mice showed a clear resistance to either (i) stress-induced depressive-like behavior, (ii) changes in microglia morphology and (iii) antidepressant treatment. Our data point towards a role of hyper-ramified microglia in the etiology of chronic depression. The lack of effects in CX3CR1 deficient mice suggests that microglia hyper-ramification is controlled by neuron-microglia signaling via the CX3C axis. However, it remains to be elucidated how hyper-ramified microglia contribute to depressive-like behavior. PMID:26576722

  1. Cordyceps militaris Extract Protects Human Dermal Fibroblasts against Oxidative Stress-Induced Apoptosis and Premature Senescence

    Directory of Open Access Journals (Sweden)

    Jun Myoung Park

    2014-09-01

    Full Text Available Oxidative stress induced by reactive oxygen species (ROS is the major cause of degenerative disorders including aging and disease. In this study, we investigated whether Cordyceps militaris extract (CME has in vitro protective effects on hydrogen peroxide-induced oxidative stress in human dermal fibroblasts (HDFs. Our results showed that the 2,2-diphenyl-1-picrylhydrazyl (DPPH radical scavenging activity of CME was increased in a dose-dependent manner. We found that hydrogen peroxide treatment in HDFs increased ROS generation and cell death as compared with the control. However, CME improved the survival of HDFs against hydrogen peroxide-induced oxidative stress via inhibition of intracellular ROS production. CME treatment inhibited hydrogen peroxide-induced apoptotic cell death and apoptotic nuclear condensation in HDFs. In addition, CME prevented hydrogen peroxide-induced SA-β-gal-positive cells suggesting CME could inhibit oxidative stress-induced premature senescence. Therefore, these results suggest that CME might have protective effects against oxidative stress-induced premature senescence via scavenging ROS.

  2. CRH engagement of the locus coeruleus noradrenergic system mediates stress-induced anxiety

    Science.gov (United States)

    McCall, Jordan G.; Al-Hasani, Ream; Siuda, Edward R.; Hong, Daniel Y.; Norris, Aaron J.; Ford, Christopher P.; Bruchas, Michael R.

    2015-01-01

    Summary The locus coeruleus noradrenergic (LC-NE) system is one of the first systems engaged following a stressful event. While numerous groups have demonstrated that LC-NE neurons are activated by many different stressors, the underlying neural circuitry and the role of this activity in generating stress-induced anxiety has not been elucidated. Using a combination of in vivo chemogenetics, optogenetics, and retrograde tracing we determine that increased tonic activity of the LC-NE system is necessary and sufficient for stress-induced anxiety and aversion. Selective inhibition of LC-NE neurons during stress prevents subsequent anxiety-like behavior. Exogenously increasing tonic, but not phasic, activity of LC-NE neurons is alone sufficient for anxiety-like and aversive behavior. Furthermore, endogenous corticotropin releasing hormone+ (CRH+) LC inputs from the amygdala increase tonic LC activity, inducing anxiety-like behaviors. These studies position the LC-NE system as a critical mediator of acute stress-induced anxiety and offer a potential intervention for preventing stress-related affective disorders. PMID:26212712

  3. Oxidative Stress Induces Endothelial Cell Senescence via Downregulation of Sirt6

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    Rong Liu

    2014-01-01

    Full Text Available Accumulating evidence has shown that diabetes accelerates aging and endothelial cell senescence is involved in the pathogenesis of diabetic vascular complications, including diabetic retinopathy. Oxidative stress is recognized as a key factor in the induction of endothelial senescence and diabetic retinopathy. However, specific mechanisms involved in oxidative stress-induced endothelial senescence have not been elucidated. We hypothesized that Sirt6, which is a nuclear, chromatin-bound protein critically involved in many pathophysiologic processes such as aging and inflammation, may have a role in oxidative stress-induced vascular cell senescence. Measurement of Sirt6 expression in human endothelial cells revealed that H2O2 treatment significantly reduced Sirt6 protein. The loss of Sirt6 was associated with an induction of a senescence phenotype in endothelial cells, including decreased cell growth, proliferation and angiogenic ability, and increased expression of senescence-associated β-galactosidase activity. Additionally, H2O2 treatment reduced eNOS expression, enhanced p21 expression, and dephosphorylated (activated retinoblastoma (Rb protein. All of these alternations were attenuated by overexpression of Sirt6, while partial knockdown of Sirt6 expression by siRNA mimicked the effect of H2O2. In conclusion, these results suggest that Sirt6 is a critical regulator of endothelial senescence and oxidative stress-induced downregulation of Sirt6 is likely involved in the pathogenesis of diabetic retinopathy.

  4. The Anti-apoptotic Effect of Ghrelin on Restraint Stress-Induced Thymus Atrophy in Mice.

    Science.gov (United States)

    Lee, Jun Ho; Kim, Tae-Jin; Kim, Jie Wan; Yoon, Jeong Seon; Kim, Hyuk Soon; Lee, Kyung-Mi

    2016-08-01

    Thymic atrophy is a complication that results from exposure to many environmental stressors, disease treatments, and microbial challenges. Such acute stress-associated thymic loss can have a dramatic impact on the host's ability to replenish the necessary naïve T cell output to reconstitute the peripheral T cell numbers and repertoire to respond to new antigenic challenges. We have previously reported that treatment with the orexigenic hormone ghrelin results in an increase in the number and proliferation of thymocytes after dexamethasone challenge, suggesting a role for ghrelin in restraint stress-induced thymic involution and cell apoptosis and its potential use as a thymostimulatory agent. In an effort to understand how ghrelin suppresses thymic T cell apoptosis, we have examined the various signaling pathways induced by receptor-specific ghrelin stimulation using a restraint stress mouse model. In this model, stress-induced apoptosis in thymocytes was effectively blocked by ghrelin. Western blot analysis demonstrated that ghrelin prevents the cleavage of pro-apoptotic proteins such as Bim, Caspase-3, and PARP. In addition, ghrelin stimulation activates the Akt and Mitogen-activated protein kinases (MAPK) signaling pathways in a time/dose-dependent manner. Moreover, we also revealed the involvement of the FoxO3a pathway in the phosphorylation of Akt and ERK1/2. Together, these findings suggest that ghrelin inhibits apoptosis by modulating the stress-induced apoptotic signal pathway in the restraint-induced thymic apoptosis. PMID:27574503

  5. Secondary aerosol formation from stress-induced biogenic emissions and possible climate feedbacks

    Directory of Open Access Journals (Sweden)

    Th. F. Mentel

    2013-09-01

    Full Text Available Atmospheric aerosols impact climate by scattering and absorbing solar radiation and by acting as ice and cloud condensation nuclei. Biogenic secondary organic aerosols (BSOAs comprise an important component of atmospheric aerosols. Biogenic volatile organic compounds (BVOCs emitted by vegetation are the source of BSOAs. Pathogens and insect attacks, heat waves and droughts can induce stress to plants that may impact their BVOC emissions, and hence the yield and type of formed BSOAs, and possibly their climatic effects. This raises questions of whether stress-induced changes in BSOA formation may attenuate or amplify effects of climate change. In this study we assess the potential impact of stress-induced BVOC emissions on BSOA formation for tree species typical for mixed deciduous and Boreal Eurasian forests. We studied the photochemical BSOA formation for plants infested by aphids in a laboratory setup under well-controlled conditions and applied in addition heat and drought stress. The results indicate that stress conditions substantially modify BSOA formation and yield. Stress-induced emissions of sesquiterpenes, methyl salicylate, and C17-BVOCs increase BSOA yields. Mixtures including these compounds exhibit BSOA yields between 17 and 33%, significantly higher than mixtures containing mainly monoterpenes (4–6% yield. Green leaf volatiles suppress SOA formation, presumably by scavenging OH, similar to isoprene. By classifying emission types, stressors and BSOA formation potential, we discuss possible climatic feedbacks regarding aerosol effects. We conclude that stress situations for plants due to climate change should be considered in climate–vegetation feedback mechanisms.

  6. Quantification of stress-induced damage and post-fire response of 5083 aluminum alloy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Y., E-mail: yanyun@vt.edu [Department of Engineering Science & Mechanics, Virginia Tech, Blacksburg, VA 24061 (United States); Puplampu, S.B. [Department of Civil and Environmental Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Summers, P.T.; Lattimer, B.Y. [Department of Mechanical Engineering, Virginia Tech, Blacksburg, VA 24061 (United States); Penumadu, D. [Department of Civil and Environmental Engineering, University of Tennessee, Knoxville, TN 37996 (United States); Case, S.W. [Department of Engineering Science & Mechanics, Virginia Tech, Blacksburg, VA 24061 (United States)

    2015-08-12

    One of the major concerns regarding the use of lightweight materials in ship construction is the response of those materials to fire scenarios, including the residual structural performance after a fire event. This paper presents a study on creep damage evolution in 5083 marine-grade aluminum alloy and its impact on residual mechanical behavior. Tests conducted at 400 °C and pre-selected tensile stress levels were interrupted at target amplitudes of accumulated engineering creep strains to investigate the stress-induced damage using ex-situ characterization. Two-dimensional optical and electron microscopy and three-dimensional X-ray tomography were utilized on samples extracted from these test specimens to characterize the external and internal creep damage. The stress-induced damage is primarily manifested as cavitation and dynamic microstructural evolution. Cavitation morphology, orientation and grain structure evolution were investigated on three perpendicular sample surfaces. A 3D examination of the damage state provided consistent damage information to that obtained from the 2D analysis. The post-fire mechanical properties were also evaluated and linked to the microstructural change. The competing processes of cavitation and grain structure evolution were investigated to develop an understanding of the stress-induced damage associated with high temperature creep.

  7. Stress Induced Mechano-electrical Writing-Reading of Polymer Film Powered by Contact Electrification Mechanism

    Science.gov (United States)

    Goswami, Sumita; Nandy, Suman; Calmeiro, Tomás R.; Igreja, Rui; Martins, Rodrigo; Fortunato, Elvira

    2016-01-01

    Mechano-electrical writing and reading in polyaniline (PANI) thin film are demonstrated via metal-polymer contact electrification mechanism (CEM). An innovative conception for a non-destructive self-powered writable-readable data sheet is presented which can pave the way towards new type of stress induced current harvesting devices. A localized forced deformation of the interface has been enacted by pressing the atomic force microscopic probe against the polymer surface, allowing charge transfer between materials interfaces. The process yields a well-defined charge pattern by transmuting mechanical stress in to readable information. The average of output current increment has been influenced from 0.5 nA to 15 nA for the applied force of 2 nN to 14 nN instead of electrical bias. These results underscore the importance of stress-induced current harvesting mechanism and could be scaled up for charge patterning of polymer surface to writable-readable data sheet. Time evolutional current distribution (TECD) study of the stress-induced patterned PANI surface shows the response of readability of the recorded data with time.

  8. Caffeine acts through neuronal adenosine A2A receptors to prevent mood and memory dysfunction triggered by chronic stress.

    Science.gov (United States)

    Kaster, Manuella P; Machado, Nuno J; Silva, Henrique B; Nunes, Ana; Ardais, Ana Paula; Santana, Magda; Baqi, Younis; Müller, Christa E; Rodrigues, Ana Lúcia S; Porciúncula, Lisiane O; Chen, Jiang Fan; Tomé, Ângelo R; Agostinho, Paula; Canas, Paula M; Cunha, Rodrigo A

    2015-06-23

    The consumption of caffeine (an adenosine receptor antagonist) correlates inversely with depression and memory deterioration, and adenosine A2A receptor (A2AR) antagonists emerge as candidate therapeutic targets because they control aberrant synaptic plasticity and afford neuroprotection. Therefore we tested the ability of A2AR to control the behavioral, electrophysiological, and neurochemical modifications caused by chronic unpredictable stress (CUS), which alters hippocampal circuits, dampens mood and memory performance, and enhances susceptibility to depression. CUS for 3 wk in adult mice induced anxiogenic and helpless-like behavior and decreased memory performance. These behavioral changes were accompanied by synaptic alterations, typified by a decrease in synaptic plasticity and a reduced density of synaptic proteins (synaptosomal-associated protein 25, syntaxin, and vesicular glutamate transporter type 1), together with an increased density of A2AR in glutamatergic terminals in the hippocampus. Except for anxiety, for which results were mixed, CUS-induced behavioral and synaptic alterations were prevented by (i) caffeine (1 g/L in the drinking water, starting 3 wk before and continued throughout CUS); (ii) the selective A2AR antagonist KW6002 (3 mg/kg, p.o.); (iii) global A2AR deletion; and (iv) selective A2AR deletion in forebrain neurons. Notably, A2AR blockade was not only prophylactic but also therapeutically efficacious, because a 3-wk treatment with the A2AR antagonist SCH58261 (0.1 mg/kg, i.p.) reversed the mood and synaptic dysfunction caused by CUS. These results herald a key role for synaptic A2AR in the control of chronic stress-induced modifications and suggest A2AR as candidate targets to alleviate the consequences of chronic stress on brain function. PMID:26056314

  9. Prenatal stress induces spatial memory deficits and epigenetic changes in the hippocampus indicative of heterochromatin formation and reduced gene expression

    Science.gov (United States)

    Benoit, Jamie D.; Rakic, Pasko; Frick, Karyn M.

    2015-01-01

    Stress during pregnancy has a wide variety of negative effects in both human [1] and animal offspring [2]. These effects are especially apparent in various forms of learning and memory such as object recognition [3] and spatial memory [4]. The cognitive effects of prenatal stress (PNS) may be mediated through epigenetic changes such as histone acetylation and DNA methylation [5]. As such, the present study investigated the effects of chronic unpredictable PNS on memory and epigenetic measures in adult offspring. Mice that underwent PNS exhibited impaired spatial memory in the Morris water maze, as well as sex-specific changes in levels of DNA methyltransferase (DNMT) 1 protein, and acetylated histone H3 (AcH3) in the hippocampus, and serum corticosterone. Male mice exposed to PNS exhibited decreased hippocampal AcH3, whereas female PNS mice displayed a further reduction in AcH3, as well as heightened hippocampal DNMT1 protein levels and corticosterone levels. These data suggest that PNS may epigenetically reduce transcription in the hippocampus, particularly in females in whom this effect may be related to increased baseline stress hormone levels, and which may underlie the sexual dimorphism in rates of mental illness in humans. PMID:25496779

  10. Lanthanum Prevents Salt Stress-induced Programmed Cell Death in Rice Root Tip Cells by Controlling Early Induction Events

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    In a previous study, a salt stress-induced programmed cell death (PCD) model was established in rice root tip cells. Here,by using Wuyunjing 8th rice seedlings, the effects of lanthanum on salt stress-induced PCD early events were studied. The peroxidase (APX). Imidazole (20 mmol/L), the inhibitor of nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase), could alleviate the occurrence of PCD obviously, and such alleviation could be enhanced by the addition of La3+,indicating the involvement of NADPH oxidase in the salt stress-induced PCD process. Taken together, lanthanum could prevent salt stress-induced PCD occurrence in the rice root tip cells by blocking the calcium influx under stress, which was followed by inhibiting calcium-dependent NADPH oxidase activity to prevent O2·-production and, enhancing the cytosolic antioxidative enzyme activities to scavenge the reactive oxygen species.

  11. Influence of Momordica charantia on oxidative stress-induced perturbations in brain monoamines and plasma corticosterone in albino rats

    Directory of Open Access Journals (Sweden)

    Ch. Naga Kavitha

    2011-01-01

    Conclusions: This study reveals the antistress activity of MC as it significantly reverted the stress-induced changes, and the activity might be attributed to its antioxidant activity since stress is known to involve several oxidative mechanisms.

  12. Administration of orexin receptor 1 antagonist into the rostral ventromedial medulla increased swim stress-induced antinociception in rat

    OpenAIRE

    Neda Soliemani; Alireza Moslem; Ali Shamsizadeh; Hassan Azhdari-Zarmehri

    2016-01-01

    Objective(s): Intracerebroventricular injection of orexin-A (hypocretin-1) antagonist has been shown to inhibit stress-induced analgesia. However the locations of central sites that may mediate these effects have not been totally demonstrated. This study was performed to investigate the role of rostral ventromedial medulla (RVM) orexin receptor 1 in stress-induced analgesia (SIA). Materials and Methods: Forced swim stress in water was employed to adult male rats (200-250 g). Nociceptive respo...

  13. Stress-induced decrease of uterine blood flow in sheep is mediated by alpha 1-adrenergic receptors.

    Science.gov (United States)

    Dreiling, Michelle; Bischoff, Sabine; Schiffner, Rene; Rupprecht, Sven; Kiehntopf, Michael; Schubert, Harald; Witte, Otto W; Nathanielsz, Peter W; Schwab, Matthias; Rakers, Florian

    2016-09-01

    Prenatal maternal stress can be transferred to the fetus via a catecholamine-dependent decrease of uterine blood flow (UBF). However, it is unclear which group of adrenergic receptors mediates this mechanism of maternal-fetal stress transfer. We hypothesized that in sheep, alpha 1-adrenergic receptors may play a key role in catecholamine mediated UBF decrease, as these receptors are mainly involved in peripheral vasoconstriction and are present in significant number in the uterine vasculature. After chronic instrumentation at 125 ± 1 days of gestation (dGA; term 150 dGA), nine pregnant sheep were exposed at 130 ± 1 dGA to acute isolation stress for one hour without visual, tactile, or auditory contact with their flockmates. UBF, blood pressure (BP), heart rate (HR), stress hormones, and blood gases were determined before and during this isolation challenge. Twenty-four hours later, experiments were repeated during alpha 1-adrenergic receptor blockage induced by a continuous intravenous infusion of urapidil. In both experiments, ewes reacted to isolation with an increase in serum norepinephrine, cortisol, BP, and HR as typical signs of activation of sympatho-adrenal and the hypothalamic-pituitary-adrenal axis. Stress-induced UBF decrease was prevented by alpha 1-adrenergic receptor blockage. We conclude that UBF decrease induced by maternal stress in sheep is mediated by alpha 1-adrenergic receptors. Future studies investigating prevention strategies of impact of prenatal maternal stress on fetal health should consider selective blockage of alpha 1-receptors to interrupt maternal-fetal stress transfer mediated by utero-placental malperfusion.

  14. Acute restraint stress induces specific changes in nitric oxide production and inflammatory markers in the rat hippocampus and striatum.

    Science.gov (United States)

    Chen, Hsiao-Jou Cortina; Spiers, Jereme G; Sernia, Conrad; Lavidis, Nickolas A

    2016-01-01

    Chronic mild stress has been shown to cause hippocampal neuronal nitric oxide synthase (NOS) overexpression and the resultant nitric oxide (NO) production has been implicated in the etiology of depression. However, the extent of nitrosative changes including NOS enzymatic activity and the overall output of NO production in regions of the brain like the hippocampus and striatum following acute stress has not been characterized. In this study, outbred male Wistar rats aged 6-7 weeks were randomly allocated into 0 (control), 60, 120, or 240 min stress groups and neural regions were cryodissected for measurement of constitutive and inducible NOS enzymatic activity, nitrosative status, and relative gene expression of neuronal and inducible NOS. Hippocampal constitutive NOS activity increased initially but was superseded by the inducible isoform as stress duration was prolonged. Interestingly, hippocampal neuronal NOS and interleukin-1β mRNA expression was downregulated, while the inducible NOS isoform was upregulated in conjunction with other inflammatory markers. This pro-inflammatory phenotype within the hippocampus was further confirmed with an increase in the glucocorticoid-antagonizing macrophage migration inhibitory factor, Mif, and the glial surveillance marker, Ciita. This indicates that despite high levels of glucocorticoids, acute stress sensitizes a neuroinflammatory response within the hippocampus involving both pro-inflammatory cytokines and inducible NOS while concurrently modulating the immunophenotype of glia. Furthermore, there was a delayed increase in striatal inducible NOS expression while no change was found in other pro-inflammatory mediators. This suggests that short term stress induces a generalized increase in inducible NOS signaling that coincides with regionally specific increased markers of adaptive immunity and inflammation within the brain.

  15. Muscimol microinjection into cerebellar fastigial nucleus exacerbates stress-induced gastric mucosal damage in rats

    Institute of Scientific and Technical Information of China (English)

    Jin-zhou ZHU; Su-juan FEI; Jian-fu ZHANG; Sheng-ping ZHU; Zhang-bo LIU; Ting-ting LI; Xiao QIAO

    2013-01-01

    Aim: To investigate the effects of microinjection of the GABAA receptor agonist muscimol into cerebellar fastigial nucleus (FN) on stressinduced gastric mucosal damage and the underlying mechanism in rats.Methods: Stress-induced gastric mucosal damage was induced in adult male SD rats by restraining and immersing them in cold water for 3 h.GABAA receptor agonist or antagonist was microinjected into the lateral FN.The decussation of superior cerebellar peduncle (DSCP) was electrically destroyed and the lateral hypothalamic area (LHA) was chemically ablated by microinjection of kainic acid.The pathological changes in the gastric mucosa were evaluated using TUNEL staining,immunohistochemistry staining and Western blotting.Results: Microinjection of muscimol (1.25,2.5,and 5.0 μg) into FN significantly exacerbated the stress-induced gastric mucosal damage in a dose-dependent manner,whereas microinjection of GABAA receptor antagonist bicuculline attenuated the damage.The intensifying effect of muscimol on gastric mucosal damage was abolished by electrical lesion of DSCP or chemical ablation of LHA performed 3 d before microinjection of muscimol.Microinjection of muscimol markedly increased the discharge frequency of the greater splanchnic nerve,significantly increased the gastric acid volume and acidity,and further reduced the gastric mucosal blood flow.In the gastric mucosa,further reduced proliferation cells,enhanced apoptosis,and decreased anti-oxidant levels were observed following microinjection of muscimol.Conclusion: Cerebellar FN participates in the regulation of stress-induced gastric mucosal damage,and cerebello-hypothalamic circuits contribute to the process.

  16. GAD65 haplodeficiency conveys resilience in animal models of stress-induced psychopathology

    Directory of Open Access Journals (Sweden)

    Iris eMüller

    2014-08-01

    Full Text Available GABAergic mechanisms are critically involved in the control of fear and anxiety, but their role in the development of stress-induced psychopathologies, including post-traumatic stress disorder (PTSD and mood disorders is not sufficiently understood. We studied these functions in two established mouse models of risk factors for stress-induced psychopathologies employing variable juvenile stress and/or social isolation. A battery of emotional tests in adulthood revealed the induction of contextually generalized fear, anxiety, hyperarousal and depression-like symptoms in these paradigms. These reflect the multitude and complexity of stress effects in human PTSD patients. With factor analysis we were able to identify parameters that reflect these different behavioral domains in stressed animals and thus provide a basis for an integrated scoring of affectedness more closely resembling the clinical situation than isolated parameters. To test the applicability of these models to genetic approaches we further tested the role of GABA using heterozygous mice with targeted mutation of the GABA synthesizing enzyme GAD65 (GAD65+/- mice, which show a delayed postnatal increase in tissue GABA content in limbic and cortical brain areas. Unexpectedly, GAD65(+/- mice did not show changes in exploratory activity regardless of the stressor type and were after the variable juvenile stress procedure protected from the development of contextual generalization in an auditory fear conditioning experiment. Our data demonstrate the complex nature of behavioral alterations in rodent models of stress-related psychopathologies and suggest that GAD65 haplodeficiency, likely through its effect on the postnatal maturation of GABAergic transmission, conveys resilience to some of these stress-induced effects.

  17. Pattern of Stress-Induced Hyperglycemia according to Type of Diabetes: A Predator Stress Model

    Directory of Open Access Journals (Sweden)

    Jin-Sun Chang

    2013-12-01

    Full Text Available BackgroundWe aimed to quantify stress-induced hyperglycemia and differentiate the glucose response between normal animals and those with diabetes. We also examined the pattern in glucose fluctuation induced by stress according to type of diabetes.MethodsTo load psychological stress on animal models, we used a predator stress model by exposing rats to a cat for 60 minutes and measured glucose level from the beginning to the end of the test to monitor glucose fluctuation. We induced type 1 diabetes model (T1D for ten Sprague-Dawley rats using streptozotocin and used five Otsuka Long-Evans Tokushima Fatty rats as obese type 2 diabetes model (OT2D and 10 Goto-Kakizaki rats as nonobese type 2 diabetes model (NOT2D. We performed the stress loading test in both the normal and diabetic states and compared patterns of glucose fluctuation among the three models. We classified the pattern of glucose fluctuation into A, B, and C types according to speed of change in glucose level.ResultsIncrease in glucose, total amount of hyperglycemic exposure, time of stress-induced hyperglycemia, and speed of glucose increase were significantly increased in all models compared to the normal state. While the early increase in glucose after exposure to stress was higher in T1D and NOT2D, it was slower in OT2D. The rate of speed of the decrease in glucose level was highest in NOT2D and lowest in OT2D.ConclusionThe diabetic state was more vulnerable to stress compared to the normal state in all models, and the pattern of glucose fluctuation differed among the three types of diabetes. The study provides basic evidence for stress-induced hyperglycemia patterns and characteristics used for the management of diabetes patients.

  18. Long term sex-dependent psychoneuroendocrine effects of maternal deprivation and juvenile unpredictable stress in rats.

    Science.gov (United States)

    Llorente, R; Miguel-Blanco, C; Aisa, B; Lachize, S; Borcel, E; Meijer, O C; Ramirez, M J; De Kloet, E R; Viveros, M P

    2011-04-01

    We have analysed the long-term psychoneuroendocrine effects of maternal deprivation (MD) [24 h at postnatal day (PND) 9] and/or exposure to chronic unpredictable stress (CUS) during the periadolescent period (PND 28 to PND 43) in male and female Wistar rats. Animals were tested in the elevated plus maze (EPM, anxiety) at PND 44 and in two memory tests, spontaneous alternation and novel object recognition (NOT) in adulthood. The expression of hippocampal glucocorticoid (GR) and mineralocorticoid (MR) receptors, as well as of synaptophysin, neural cell adhesion molecule and brain-derived neurotrophic factor, was analysed by in situ hybridisation in selected hippocampal regions. Endocrine determinations of leptin, testosterone and oestradiol plasma levels were carried out by radioimmunoassay. Young CUS animals showed decreased anxiety behaviour in the EPM (increased percentage of time and entries in the open arms) irrespective of neonatal treatment. Memory impairments were induced by the two stressful treatments as was revealed by the NOT, with males being most clearly affected. Although each stressful procedure, when considered separately, induced different (always decrements) effects on the three synaptic molecules analysed and affected males and females differently, the combination of MD and CUS induced an unique disruptive effect on the three synaptic plasticity players. MD induced a long-term significant decrease in hippocampal GR only in males, whereas CUS tended to increase MR in males and decrease MR in females. Both neonatal MD and periadolescent CUS induced marked reductions in testosterone and oestradiol in males, whereas MD male animals also showed significantly decreased leptin levels. By contrast, in females, none of the hormones analysed was altered by any of the stressful procedures. Taking our data together in support of the 'two-hit' hypothesis, MD during neonatal life and/or exposure to CUS during the periadolescent period induced a permanent

  19. FCJ-178 Network Affordances: The unpredictable parameters of a Hong Kong SPEED SHOW

    Directory of Open Access Journals (Sweden)

    Audrey Samson

    2015-06-01

    Full Text Available This paper examines the notion of network affordance within the context of network art. We expand on the notion of affordances, (Gibson, 1977; Gaver, 1996 to include ecological and computational parameters of unpredictability. We illustrate the notion of unpredictability by considering four specific works that were included in a network art exhibition, SPEED SHOW [2.0] Hong Kong (2013. The paper discusses how the artworks are contingent upon the parametric relations (Parisi, 2013 of the network. We introduce network affordance as a dynamic framework that could articulate the experience of tension arising from the (visible symbolic representation of computational processes and its hidden occurrences.

  20. How to create a health care organization that can succeed in an unpredictable future.

    Science.gov (United States)

    Olden, Peter C; Haynos, Jessika

    2013-01-01

    For those who manage organizations, it has been said that success does not come from predicting the future but instead comes from creating an organization that can succeed in an unpredictable future. Managers are responsible for creating such an organization. To do that, managers can apply management-related principles and methods. This article explains selected principles of organization structure, human resources, culture, decision making, and change management and how to apply them to health care organizations. If done well, that will help such organizations succeed in an unpredictable future.

  1. [Predicting suicide or predicting the unpredictable in an uncertain world: Reinforcement Learning Model-Based analysis].

    Science.gov (United States)

    Desseilles, Martin

    2012-01-01

    In general, it appears that the suicidal act is highly unpredictable with the current scientific means available. In this article, the author submits the hypothesis that predicting suicide is complex because it results in predicting a choice, in itself unpredictable. The article proposes a Reinforcement learning model-based analysis. In this model, we integrate on the one hand, four ascending modulatory neurotransmitter systems (acetylcholine, noradrenalin, serotonin, and dopamine) with their regions of respective projections and afferences, and on the other hand, various observations of brain imaging identified until now in the suicidal process.

  2. Stress-Induced Stroke and Stomach Cancer: Sex Differences in Oxygen Saturation.

    Science.gov (United States)

    Ulanova, Maria; Gekalyuk, Artem; Agranovich, Ilana; Khorovodov, Alexander; Rezunbaeva, Victoria; Borisova, Ekaterina; Sharif, Aly Esmat; Navolokin, Nikita; Shuvalova, Ekaterina; Semyachkina-Glushkovskaya, Oxana

    2016-01-01

    Sex differences in stress-related diseases such as stroke and stomach cancer are well established, but the mechanisms underlying this phenomenon remain unknown. Despite the fact that sexual hormones play an important role in the high resistance of females to harmful effects of stress compared with males, the regulation of oxygenation status can be a potential factor, which might explain sex differences in stress-induced cerebrovascular catastrophes in newborn rats and in mutagens activation in adult rats with stomach cancer. PMID:27526135

  3. Stress-Induced Phase Transformation in Incompressible Materials and Stability of Multi-Phase Deformation

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The stress-induced phase transformation in incompressible materials and the interfacial stability of multi-phase deformation were studied. The existence of multi-phase deformation was determined through exploring whether the material would lose the strong ellipticity at some deformation gradient.Then, according to the stability criterion which is based on a quasi-static approach, the stability of the multi-phase deformation in incompressible materials was investigated by studying the growth/decay behaviour of the interface in the undeformed configuration when it is perturbed. At last, the way to define multi-phase deformation in incompressible materials was concluded and testified by a corresponding numerical example.

  4. Thermal Stress-Induced Birefringence in Borate Glass Irradiated by Femtosecond Laser Pulses

    Institute of Scientific and Technical Information of China (English)

    DAI Ye; YU Bing-Kun; LU Bo; QIU Jian-Rong; YAN Xiao-Na; JIANG Xiong-Wei; ZHU Cong-Shan

    2005-01-01

    @@ Thermal stress-induced birefringence in borate glass which has been irradiated by 800-nm femtosecond laser pulses is observed under cross-polarized light. Due to the high temperature and pressure formed in the focal volume, the material at the edge of the micro-modified region is compressed between the expanding region and the unheated one, then stress emerges. Raman spectroscopy is used to investigate the stress distribution in the micro-modified region and indicates the redistributions of density and refractive index by Raman peak shift. We suggest that this technique can develop waveguide polarizers and Fresnel zone plates in integrated optics.

  5. Angiotensin II receptor blocker ameliorates stress-induced adipose tissue inflammation and insulin resistance.

    Directory of Open Access Journals (Sweden)

    Motoharu Hayashi

    Full Text Available A strong causal link exists between psychological stress and insulin resistance as well with hypertension. Meanwhile, stress-related responses play critical roles in glucose metabolism in hypertensive patients. As clinical trials suggest that angiotensin-receptor blocker delays the onset of diabetes in hypertensive patients, we investigated the effects of irbesartan on stress-induced adipose tissue inflammation and insulin resistance. C57BL/6J mice were subjected to 2-week intermittent restraint stress and orally treated with vehicle, 3 and 10 mg/kg/day irbesartan. The plasma concentrations of lipid and proinflammatory cytokines [Monocyte Chemoattractant Protein-1 (MCP-1, tumor necrosis factor-α, and interleukin-6] were assessed with enzyme-linked immunosorbent assay. Monocyte/macrophage accumulation in inguinal white adipose tissue (WAT was observed with CD11b-positive cell counts and mRNA expressions of CD68 and F4/80 using immunohistochemistry and RT-PCR methods respectively. The mRNA levels of angiotensinogen, proinflammatory cytokines shown above, and adiponectin in WAT were also assessed with RT-PCR method. Glucose metabolism was assessed by glucose tolerance tests (GTTs and insulin tolerance tests, and mRNA expression of insulin receptor substrate-1 (IRS-1 and glucose transporter 4 (GLUT4 in WAT. Restraint stress increased monocyte accumulation, plasma free fatty acids, expression of angiotensinogen and proinflammatory cytokines including MCP-1, and reduced adiponectin. Irbesartan reduced stress-induced monocyte accumulation in WAT in a dose dependent manner. Irbesartan treatment also suppressed induction of adipose angiotensinogen and proinflammatory cytokines in WAT and blood, and reversed changes in adiponectin expression. Notably, irbesartan suppressed stress-induced reduction in adipose tissue weight and free fatty acid release, and improved insulin tolerance with restoration of IRS-1 and GLUT4 mRNA expressions in WAT. The results

  6. Permanent lesion in rostral ventromedial medulla potentiates swim stress-induced analgesia in formalin test

    Directory of Open Access Journals (Sweden)

    Ali Shamsizadeh

    2014-03-01

    Results: In the unstressed rats, permanent lesion of the RVM by R-SKF38393 decreased formalin-induced nociceptive behaviors in phase 1, while in stressed rats, injection of R-SKF38393 into the RVM potentiated swim stress-induced antinociception in phase 1 and interphase, phase 2A of formalin test. Furthermore, R-SKF38393 had pronociceptive effects in phase2B whereas injections of R-SKF38393 resulted in significant difference in nociceptive bahaviours in all phases of formalin test (P

  7. IL-13 Augments Compressive Stress-Induced Tissue Factor Expression in Human Airway Epithelial Cells.

    Science.gov (United States)

    Mitchel, Jennifer A; Antoniak, Silvio; Lee, Joo-Hyeon; Kim, Sae-Hoon; McGill, Maureen; Kasahara, David I; Randell, Scott H; Israel, Elliot; Shore, Stephanie A; Mackman, Nigel; Park, Jin-Ah

    2016-04-01

    Tissue factor (TF) is best known as a cellular initiator of coagulation, but it is also a multifunctional protein that has been implicated in multiple pathophysiologic conditions, including asthma. In the lung, airway epithelial cells express TF, but it is unknown how TF expression is regulated by asthma-associated mediators. We investigated the role of IL-13, a type 2 cytokine, alone and in combination with compressive stress, which mimics asthmatic bronchoconstriction, on TF expression and release of TF-positive extracellular vesicles from primary normal human bronchial epithelial cells. Well-differentiated normal human bronchial epithelial cells were treated with IL-13 and compressive stress, alone and in combination. TF mRNA, protein and activity were measured in the cells and conditioned media. TF was also measured in the bronchoalveolar lavage (BAL) fluid of allergen-challenged mice and patients with asthma. IL-13 and compressive stress increased TF expression, but only compressive stress induced TF-positive extracellular vesicle release. Pretreatment with IL-13 augmented compressive stress-induced TF expression and release. TF protein and activity in BAL fluid were increased in allergen-sensitized and -challenged mice. TF was elevated in the BAL fluid of patients with mild asthma after an allergen challenge. Our in vitro and in vivo data indicate close cooperation between mechanical and inflammatory stimuli on TF expression and release of TF-positive extracellular vesicles in the lungs, which may contribute to pathophysiology of asthma. PMID:26407210

  8. Stress-induced alternative gene splicing in mind-body medicine.

    Science.gov (United States)

    Rossi, Ernest Lawrence

    2004-01-01

    Recent research documents how psychosocial stress can alter the expression of the acetylcholinesterase gene to generate at least 3 alternative proteins that are implicated in a wide variety of normal mind-body functions, as well as pathologies. These range from early embryological development, plasticity of the brain in adulthood, post-traumatic stress disorder (PTSD), and stress-associated dysfunctions of the central nervous, endocrine, and immune systems, to age-related neuropathologies. Such stress-induced alternative gene splicing is proposed here as a major mind-body pathway of psychosocial genomics-the modulation of gene expression by creative psychological, social, and cultural processes. We explore the types of research that are now needed to investigate how stress-induced alternative splicing of the acetylcholinesterase gene may play a pivotal role in the deep psychobiology of psychotherapy, meditation, spiritual rituals, and the experiencing of positive humanistic values that have been associated with mind-body medicine, such as compassion, beneficence, serenity, forgiveness, and gratitude. PMID:15356952

  9. Protective effects of parecoxib on rat primary astrocytes from oxidative stress induced by hydrogen peroxide* #

    Science.gov (United States)

    Ling, Yun-zhi; Li, Xiao-hong; Yu, Li; Zhang, Ye; Liang, Qi-sheng; Yang, Xiao-di; Wang, Hong-tao

    2016-01-01

    Objective: To investigate the protective effects of parecoxib from oxidative stress induced by hydrogen peroxide (H2O2) in rat astrocytes in vitro. Methods: All experiments included 4 groups: (1) negative control (NC) group, without any treatment; (2) H2O2 treatment group, 100 μmol/L H2O2 treatment for 24 h; (3) and (4) parecoxib pretreatment groups, 80 and 160 μmol/L parecoxib treatment for 24 h, respectively, and then treated with 100 μmol/L H2O2. Several indices were investigated, and the expressions of Bax, Bcl-2, and brain-derived neurotrophic factor (BDNF) were quantified. Results: Compared to the NC group, exposure to H2O2 resulted in significant morphological changes, which could be reversed by pretreatment of parecoxib. In addition, H2O2 treatment led to loss of viability (P=0.026) and increased intracellular reactive oxygen species (ROS) levels (P<0.001), and induced apoptosis (P<0.01) in the primary astrocytes relative to the NC group. However, in the parecoxib pretreatment groups, all the above changes reversed significantly (P<0.05) as compared to the H2O2 treatment group, and were nearly unchanged when compared to the NC group. Mechanical investigation showed that dysregulated Bax, Bcl-2, and BDNF could be implicated in these changes. Conclusions: Our results indicated that parecoxib provided a protective effect from oxidative stress induced by exposure to H2O2. PMID:27604861

  10. Thermal Stress-Induced Depolarization Loss in Conventional and Panda-Shaped Photonic Crystal Fiber Lasers

    Science.gov (United States)

    Mousavi, Seyedeh Laleh; Sabaeian, Mohammad

    2016-10-01

    We report on the modeling of the depolarization loss in the conventional and panda-shaped photonic crystal fiber lasers (PCFLs) due to the self-heating of the fiber, which we call it thermal stress-induced depolarization loss (TSIDL). We first calculated the temperature distribution over the fiber cross sections and then calculated the thermal stresses/strains as a function of heat load per meter. Thermal stress-induced birefringence (TSIB), which is defined as | n x - n y |, in the core and cladding regions was calculated. Finally, TSIDL was calculated for the conventional and panda-shaped PCFLs as a function of fiber length and, respectively, saturated values of 22 and 25 % were obtained which were independent of heat load per meter. For panda-shaped PCFLs, prior to being saturated, an oscillating and damping behavior against the fiber length was seen where in some lengths reached 35 %. The results are close to an experimental value of 30 % reported for a pulsed PCFL (Limpert et al., Opt Express 12:1313-1319, 2004) where the authors reported a degree of polarization of 70 % (i.e., a depolarization of 30 %). The most important result of this work is a saturation behavior of TSIDL at long-enough lengths of the fiber laser which is independent of heat load per meter. To our knowledge, this the first report of TSIBL for PCFLs.

  11. Stress-Induced Fracturing of Reservoir Rocks: Acoustic Monitoring and μCT Image Analysis

    Science.gov (United States)

    Pradhan, Srutarshi; Stroisz, Anna M.; Fjær, Erling; Stenebråten, Jørn F.; Lund, Hans K.; Sønstebø, Eyvind F.

    2015-11-01

    Stress-induced fracturing in reservoir rocks is an important issue for the petroleum industry. While productivity can be enhanced by a controlled fracturing operation, it can trigger borehole instability problems by reactivating existing fractures/faults in a reservoir. However, safe fracturing can improve the quality of operations during CO2 storage, geothermal installation and gas production at and from the reservoir rocks. Therefore, understanding the fracturing behavior of different types of reservoir rocks is a basic need for planning field operations toward these activities. In our study, stress-induced fracturing of rock samples has been monitored by acoustic emission (AE) and post-experiment computer tomography (CT) scans. We have used hollow cylinder cores of sandstones and chalks, which are representatives of reservoir rocks. The fracture-triggering stress has been measured for different rocks and compared with theoretical estimates. The population of AE events shows the location of main fracture arms which is in a good agreement with post-test CT image analysis, and the fracture patterns inside the samples are visualized through 3D image reconstructions. The amplitudes and energies of acoustic events clearly indicate initiation and propagation of the main fractures. Time evolution of the radial strain measured in the fracturing tests will later be compared to model predictions of fracture size.

  12. Involvement of Protein Phosphorylation in Water Stress-induced Antioxidant Defense in Maize Leaves

    Institute of Scientific and Technical Information of China (English)

    Shu-cheng Xu; Hai-dong Ding; Feng-xia Su; A-ying Zhang; Ming-yi Jiang

    2009-01-01

    Using pharmacological and biochemical approaches, the role of protein phosphorylation and the interrelationship between water stress-enhanced kinase activity, antioxidant enzyme activity, hydrogen peroxide (H2O2) accumulation and endogenous abscisic acid in maize (Zea mays L.) leaves were investigated. Water-stress upregulated the activities of total protein phosphorylation and Ca2+ -dependent protein kinase, and the upregulation was blocked in abscisic acid-deficient vp5 mutant. Furthermore, pretreatments with a nicotinamide adenine dinucleotide phosphate oxidase inhibitor and a scavenger of H2O2 significantly reduced the increased activities of total protein kinase and Ca2+-dependent protein kinase in maize leaves exposed to water stress. Pretreatments with different protein kinase inhibitors also reduced the water stress-induced H2O2 production and the water stress-enhanced activities of antioxidant enzymes such as superoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase. The data suggest that protein phosphorylation and H2O2 generation are required for water stress-induced antioxidant defense in maize leaves and that crosstalk between protein phosphorylation and H2O2 generation may occur.

  13. Effective prevention of stress-induced sweating and axillary malodour formation in teenagers.

    Science.gov (United States)

    Martin, A; Hellhammer, J; Hero, T; Max, H; Schult, J; Terstegen, L

    2011-02-01

    Emotional sweating and malodour production represent a relevant challenge to today's antiperspirant (AP) and deodorant products as stress in everyday life increases continuously. The aim of this study was to investigate stress-induced sweating in teenagers who are known to experience various stressful situations, e.g. exams at school or job interviews. To induce emotional sweating in 20 female and 20 male adolescents (16-18 years of age), we applied the Trier Social Stress Test (TSST), considered today to be the most reliable and standardized stress protocol. In this study, we demonstrate that the TSST induces high amounts of sweat and strong axillary malodour in the tested age group. Notably, male teenagers showed significantly higher stress-induced odour scores than female subjects, although no gender differences were detected concerning other physiological stress markers. Testing of a novel deodorant/AP product developed to specifically address the needs of adolescent consumers revealed excellent deodorant and AP efficacy under the challenging conditions of the TSST. PMID:20646085

  14. Efficacy of enteral diets in the prevention of stress-induced gastric erosions in rats.

    Science.gov (United States)

    Sriram, K; Abrahamian, V; Kaminski, M V; Santiago, G C

    1987-04-01

    This study compares the prophylactic effects of two different diets and routes of feeding on restraint stress-induced gastric erosions in the rat. Thirty male Sprague-Dawley rats were food-deprived and immobilized for 24 hours using a steel wire mesh. A small silicone tube was placed into either the proximal jejunum or the stomach via a laparotomy. There were three groups of ten rats (five jejunum-fed, five stomach-fed), receiving infusions (50 ml/24 h) of: (A) normal saline; (B) free amino acids (Vivonex HN, Norwich Eaton Pharmaceuticals) (60 cal and 0.318 G nitrogen); or (C) a peptide diet, with the nitrogen source as lactalbumin hydrolysate, otherwise identical to B. Gastric acidity was measured every 4 hours. At 24 hours, blood was collected and serum gastrin levels determined. The animals were then sacrificed and the stomachs examined. The results were analyzed using one-way analysis of variance. Fewer gastric erosions and lower serum gastrin levels and gastric acidity were found in animals fed diets B and C, versus animals fed normal saline (p less than 0.05). There was no difference between groups B and C. Our results also show that enteral diets using the jejunal route are better than those using the gastric route in reducing the incidence of stress-induced gastric erosions in rats. PMID:3108349

  15. Mitofusin-2 protects against cold stress-induced cell injury in HEK293 cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Wenbin; Chen, Yaomin; Yang, Qun; Che, Honglei; Chen, Xiangjun; Yao, Ting; Zhao, Fang; Liu, Mingchao; Ke, Tao [Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Chen, Jingyuan, E-mail: jy_chen@fmmu.edu.cn [Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China); Luo, Wenjing, E-mail: luowenj@fmmu.edu.cn [Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, Xi' an 710032 (China)

    2010-06-25

    Mitochondrial impairment is hypothesized to contribute to cell injury during cold stress. Mitochondria fission and fusion are closely related in the function of the mitochondria, but the precise mechanisms whereby these processes regulate cell injury during cold stress remain to be determined. HEK293 cells were cultured in a cold environment (4.0 {+-} 0.1 {sup o}C) for 2, 4, 8, or 12 h. Western blot analyses showed that these cells expressed decreased fission-related protein Drp1 and increased fusion-related protein Mfn2 at 4 h; meanwhile, electron microscopy analysis revealed large and long mitochondrial morphology within these cells, indicating increased mitochondrial fusion. With silencing of Mfn2 but not of Mfn1 by siRNA promoted cold-stress-induced cell death with decreased ATP production in HEK293 cells. Our results show that increased expression of Mfn2 and mitochondrial fusion are important for mitochondrial function as well as cell survival during cold stress. These findings have important implications for understanding the mechanisms of mitochondrial fusion and fission in cold-stress-induced cell injury.

  16. Stress-induced twin boundary motion in NiMnGa-polymer-composites

    Energy Technology Data Exchange (ETDEWEB)

    Scheerbaum, Nils; Hinz, Dietrich; Liu, Jian; Gutfleisch, Oliver; Schultz, Ludwig [IFW Dresden, Institut fuer Metallische Werkstoffe, P.O. Box 270116, D-01171 Dresden (Germany); Skrotzki, Werner [Technische Universitaet Dresden, Institut fuer Strukturphysik, D-01062 Dresden (Germany)

    2007-07-01

    Composites were prepared by embedding magnetic shape memory (MSM) particles in a polyester matrix. Single-crystalline MSM particles were obtained by mortar grinding of melt-extracted and subsequently annealed Ni{sub 50.9}Mn{sub 27.1}Ga{sub 22.0} (at.%) fibres. The crystal structure of the martensite is tetragonal (5M) and of uniaxial magnetocrystalline anisotropy with c being the short and easy magnetisation axis. Previous magnetic characterisation of these composites showed indirect evidence for stress-induced twin boundary motion in the MSM particles, as the compressed composite becomes easier to magnetise in the direction of compression. Therefore, the texture of the embedded Ni-Mn-Ga particles is investigated before and after compression by means of synchrotron radiation. In the initial state, the MSM particles have a random texture, i.e. there is no preferred orientation of the c-axis. After a 30% compression of the composite, the MSM particles have a [004]-fibre texture in direction of compression. This confirms stress-induced twin boundary motion.

  17. Thermal Stress-Induced Depolarization Loss in Conventional and Panda-Shaped Photonic Crystal Fiber Lasers

    Science.gov (United States)

    Mousavi, Seyedeh Laleh; Sabaeian, Mohammad

    2016-07-01

    We report on the modeling of the depolarization loss in the conventional and panda-shaped photonic crystal fiber lasers (PCFLs) due to the self-heating of the fiber, which we call it thermal stress-induced depolarization loss (TSIDL). We first calculated the temperature distribution over the fiber cross sections and then calculated the thermal stresses/strains as a function of heat load per meter. Thermal stress-induced birefringence (TSIB), which is defined as |n x - n y |, in the core and cladding regions was calculated. Finally, TSIDL was calculated for the conventional and panda-shaped PCFLs as a function of fiber length and, respectively, saturated values of 22 and 25 % were obtained which were independent of heat load per meter. For panda-shaped PCFLs, prior to being saturated, an oscillating and damping behavior against the fiber length was seen where in some lengths reached 35 %. The results are close to an experimental value of 30 % reported for a pulsed PCFL (Limpert et al., Opt Express 12:1313-1319, 2004) where the authors reported a degree of polarization of 70 % (i.e., a depolarization of 30 %). The most important result of this work is a saturation behavior of TSIDL at long-enough lengths of the fiber laser which is independent of heat load per meter. To our knowledge, this the first report of TSIBL for PCFLs.

  18. Peripheral and central CB1 cannabinoid receptors control stress-induced impairment of memory consolidation.

    Science.gov (United States)

    Busquets-Garcia, Arnau; Gomis-González, Maria; Srivastava, Raj Kamal; Cutando, Laura; Ortega-Alvaro, Antonio; Ruehle, Sabine; Remmers, Floortje; Bindila, Laura; Bellocchio, Luigi; Marsicano, Giovanni; Lutz, Beat; Maldonado, Rafael; Ozaita, Andrés

    2016-08-30

    Stressful events can generate emotional memories linked to the traumatic incident, but they also can impair the formation of nonemotional memories. Although the impact of stress on emotional memories is well studied, much less is known about the influence of the emotional state on the formation of nonemotional memories. We used the novel object-recognition task as a model of nonemotional memory in mice to investigate the underlying mechanism of the deleterious effect of stress on memory consolidation. Systemic, hippocampal, and peripheral blockade of cannabinoid type-1 (CB1) receptors abolished the stress-induced memory impairment. Genetic deletion and rescue of CB1 receptors in specific cell types revealed that the CB1 receptor population specifically in dopamine β-hydroxylase (DBH)-expressing cells is both necessary and sufficient for stress-induced impairment of memory consolidation, but CB1 receptors present in other neuronal populations are not involved. Strikingly, pharmacological manipulations in mice expressing CB1 receptors exclusively in DBH(+) cells revealed that both hippocampal and peripheral receptors mediate the impact of stress on memory consolidation. Thus, CB1 receptors on adrenergic and noradrenergic cells provide previously unrecognized cross-talk between central and peripheral mechanisms in the stress-dependent regulation of nonemotional memory consolidation, suggesting new potential avenues for the treatment of cognitive aspects on stress-related disorders. PMID:27528659

  19. Secondary aerosol formation from stress-induced biogenic emissions and possible climate feedbacks

    Directory of Open Access Journals (Sweden)

    Th. F. Mentel

    2013-03-01

    Full Text Available Atmospheric aerosols impact climate by scattering and absorbing solar radiation and by acting as ice and cloud condensation nuclei. Secondary organic aerosols (SOA comprise an important component of atmospheric aerosols. Biogenic volatile organic compounds (BVOC emitted by vegetation are a major source of SOA. Pathogens and insect attacks, heat waves and droughts can induce stress to plants that may impact their BVOC emissions, and hence the yield and type of formed SOA, and possibly their climatic effects. This raises questions whether stress-induced changes in SOA formation may attenuate or amplify effects of climate change. In this study we assess the potential impact of stress-induced BVOC emissions on SOA formation for tree species typical for mixed deciduous and Boreal Eurasian forests. We studied the photochemical SOA formation for infested plants in a laboratory setup under well-controlled conditions and applied in addition heat and drought stress. The results indicate that stress conditions substantially modify SOA formation. While sesquiterpenes, methyl salicylate, and C17-BVOC increase SOA yield, green leaf volatiles suppress SOA formation. By classifying emission types, stressors and SOA formation potential, we propose possible climatic feedbacks regarding aerosol effects. We conclude that stress situations for plants due to climate change should be considered in climate-vegetation feedback mechanisms.

  20. Romo1 expression contributes to oxidative stress-induced death of lung epithelial cells

    International Nuclear Information System (INIS)

    Highlights: •Romo1 mediates oxidative stress-induced mitochondrial ROS production. •Romo1 induction by oxidative stress plays an important role in oxidative stress-induced apoptosis. •Romo1 overexpression correlates with epithelial cell death in patients with IPF. -- Abstract: Oxidant-mediated death of lung epithelial cells due to cigarette smoking plays an important role in pathogenesis in lung diseases such as idiopathic pulmonary fibrosis (IPF). However, the exact mechanism by which oxidants induce epithelial cell death is not fully understood. Reactive oxygen species (ROS) modulator 1 (Romo1) is localized in the mitochondria and mediates mitochondrial ROS production through complex III of the mitochondrial electron transport chain. Here, we show that Romo1 mediates mitochondrial ROS production and apoptosis induced by oxidative stress in lung epithelial cells. Hydrogen peroxide (H2O2) treatment increased Romo1 expression, and Romo1 knockdown suppressed the cellular ROS levels and cell death triggered by H2O2 treatment. In immunohistochemical staining of lung tissues from patients with IPF, Romo1 was mainly localized in hyperplastic alveolar and bronchial epithelial cells. Romo1 overexpression was detected in 14 of 18 patients with IPF. TUNEL-positive alveolar epithelial cells were also detected in most patients with IPF but not in normal controls. These findings suggest that Romo1 mediates apoptosis induced by oxidative stress in lung epithelial cells

  1. Transgenerational inheritance or resetting of stress-induced epigenetic modifications: two sides of the same coin.

    Directory of Open Access Journals (Sweden)

    Penny J Tricker

    2015-09-01

    Full Text Available The transgenerational inheritance of stress-induced epigenetic modifications is still controversial. Despite several examples of defence ‘priming’ and induced genetic rearrangements, the involvement and persistence of transgenerational epigenetic modifications is not known to be general. Here I argue that non-transmission of epigenetic marks through meiosis may be regarded as an epigenetic modification in itself, and that we should understand the implications for plant evolution in the context of both selection for and selection against transgenerational epigenetic memory. Recent data suggest that both epigenetic inheritance and resetting are mechanistically directed and targeted. Stress-induced epigenetic modifications may buffer against DNA sequence-based evolution to maintain plasticity, or may form part of plasticity’s adaptive potential. To date we have tended to concentrate on the question of whether and for how long epigenetic memory persists. I argue that we should now re-direct our question to investigate the differences between where it persists and where it does not, to understand the higher order evolutionary methods in play and their contribution.

  2. Romo1 expression contributes to oxidative stress-induced death of lung epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Jung Ar [Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul 135-270 (Korea, Republic of); Chung, Jin Sil [Laboratory of Molecular Cell Biology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of); Cho, Sang-Ho [Department of Pathology, Pochon CHA University, College of Medicine, Gyeonggi-do (Korea, Republic of); Kim, Hyung Jung, E-mail: khj57@yuhs.ac.kr [Department of Internal Medicine, Yonsei University College of Medicine, Yonsei University Health System, Seoul 135-270 (Korea, Republic of); Yoo, Young Do, E-mail: ydy1130@korea.ac.kr [Laboratory of Molecular Cell Biology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713 (Korea, Republic of)

    2013-09-20

    Highlights: •Romo1 mediates oxidative stress-induced mitochondrial ROS production. •Romo1 induction by oxidative stress plays an important role in oxidative stress-induced apoptosis. •Romo1 overexpression correlates with epithelial cell death in patients with IPF. -- Abstract: Oxidant-mediated death of lung epithelial cells due to cigarette smoking plays an important role in pathogenesis in lung diseases such as idiopathic pulmonary fibrosis (IPF). However, the exact mechanism by which oxidants induce epithelial cell death is not fully understood. Reactive oxygen species (ROS) modulator 1 (Romo1) is localized in the mitochondria and mediates mitochondrial ROS production through complex III of the mitochondrial electron transport chain. Here, we show that Romo1 mediates mitochondrial ROS production and apoptosis induced by oxidative stress in lung epithelial cells. Hydrogen peroxide (H{sub 2}O{sub 2}) treatment increased Romo1 expression, and Romo1 knockdown suppressed the cellular ROS levels and cell death triggered by H{sub 2}O{sub 2} treatment. In immunohistochemical staining of lung tissues from patients with IPF, Romo1 was mainly localized in hyperplastic alveolar and bronchial epithelial cells. Romo1 overexpression was detected in 14 of 18 patients with IPF. TUNEL-positive alveolar epithelial cells were also detected in most patients with IPF but not in normal controls. These findings suggest that Romo1 mediates apoptosis induced by oxidative stress in lung epithelial cells.

  3. Effects of Cynodon dactylon on Stress-Induced Infertility in Male Rats.

    Science.gov (United States)

    Chidrawar, Vr; Chitme, Hr; Patel, Kn; Patel, Nj; Racharla, Vr; Dhoraji, Nc; Vadalia, Kr

    2011-01-01

    Cynodon dactylon (Family: Poaceae) is known to be a tackler in Indian mythology and is offered to Lord Ganesha. It is found everywhere, even on waste land, road side, dry places, and spreads vigorously on cultivated ground. This study was carried out with an objective to test if the constituents of this plant are useful in coping stress-induced sexual In this study, we considered immobilization stress to induce male infertility and the effect of C. dactylon in restoration of the dysfunction was evaluated by considering sexual behavioral observations, sexual performance, fructose content of the seminal vesicles, epididymal sperm concentration and histopathological examinations as parameters. Treatment of rats under stress with methanolic extract of C. dactylon has shown a promising effect in overcoming stress-induced sexual dysfunction, sexual performance, fructose content, sperm concentration and its effect on accessory sexual organs and body weight. We conclude that active constituents of C. dactylon present in methanolic extract have a potent aphrodisiac and male fertility activity. PMID:21607051

  4. Fat or lean: adjustment of endogenous energy stores to predictable and unpredictable changes in allostatic load

    Science.gov (United States)

    Schultner, Jannik; Kitaysky, Alexander S.; Welcker, Jorg; Hatch, Scott

    2013-01-01

    1. The ability to store energy endogenously is an important ecological mechanism that allows animals to buffer predictable and unpredictable variation in allostatic load. The secretion of glucocorticoids, which reflects changes in allostatic load, is suggested to play a major role in the adjustment of endogenous stores to these varying conditions.

  5. Title: Sex differences in stress-induced social withdrawal: role of brain derived neurotrophic factor in the bed nucleus of the stria terminalis

    Directory of Open Access Journals (Sweden)

    Gian David Greenberg

    2014-01-01

    Full Text Available Depression and anxiety disorders are more common in women than men, and little is known about the neurobiological mechanisms that contribute to this disparity. Recent data suggest that stress-induced changes in neurotrophins have opposing effects on behavior by acting in different brain networks. Social defeat has been an important approach for understanding neurotrophin action, but low female aggression levels in rats and mice have limited the application of these methods primarily to males. We examined the effects of social defeat in monogamous California mice (Peromyscus californicus, a species in which both males and females defend territories. We demonstrate that defeat stress increases mature brain-derived neurotrophic factor (BDNF protein but not mRNA in the bed nucleus of the stria terminalis (BNST in females but not males. Changes in BDNF protein were limited to anterior subregions of the BNST, and there were no changes in the adjacent nucleus accumbens (NAc. The effects of defeat on social withdrawal behavior and BDNF were reversed by chronic, low doses of the antidepressant sertraline. However, higher doses of sertraline restored social withdrawal and elevated BDNF levels. Acute treatment with a low dose of sertraline failed to reverse the effects of defeat. Infusions of the selective tyrosine-related kinase B receptor (TrkB antagonist ANA-12 into the anterior BNST specifically increased social interaction in stressed females but had no effect on behavior in females naïve to defeat. These results suggest that stress-induced increases in BDNF in the anterior BNST contribute to the exaggerated social withdrawal phenotype observed in females.

  6. Metformin prevents endoplasmic reticulum stress-induced apoptosis through AMPK-PI3K-c-Jun NH2 pathway

    Science.gov (United States)

    Jung, T.W.; Lee, M.W.; Lee, Y.-J.; Kim, S.M.

    2012-01-01

    Type 2 diabetes mellitus is thought to be partially associated with endoplasmic reticulum (ER) stress toxicity on pancreatic beta cells and the result of decreased insulin synthesis and secretion. In this study, we showed that a well-known insulin sensitizer, metformin, directly protects against dysfunction and death of ER stress-induced NIT-1 cells (a mouse pancreatic beta cell line) via AMP-activated protein kinase (AMPK) and phosphatidylinositol-3 (PI3) kinase activation. We also showed that exposure of NIT-1 cells to metformin (5mM) increases cellular resistance against ER stress-induced NIT-1 cell dysfunction and death. AMPK and PI3 kinase inhibitors abolished the effect of metformin on cell function and death. Metformin-mediated protective effects on ER stress-induced apoptosis were not a result of an unfolded protein response or the induced inhibitors of apoptotic proteins. In addition, we showed that exposure of ER stressed-induced NIT-1 cells to metformin decreases the phosphorylation of c-Jun NH(2) terminal kinase (JNK). These data suggest that metformin is an important determinant of ER stress-induced apoptosis in NIT-1 cells and may have implications for ER stress-mediated pancreatic beta cell destruction via regulation of the AMPK-PI3 kinase-JNK pathway.

  7. The 5-HT1A agonists 8-OH-DPAT, buspirone and ipsapirone attenuate stress-induced anorexia in rats.

    Science.gov (United States)

    Dourish, C T; Kennett, G A; Curzon, G

    1987-01-01

    The effects of 5-HT agonists and antagonists, benzodiazepine anxiolytics and tricyclic antidepressants on restraint stress-induced anorexia in rats were examined. The selective 5-HT(1A) agonists 8-hydroxy-2-(di- n-propylamino)tetralin (8-OH-DPAT), buspirone and ipsapirone, when injected 2 h after the termination of stress, attenuated stress-induced anor exia and body weight loss. The effects of 8-OH-DPAT on stress-induced anorexia were blocked by the 5-HT(1A) antagonist spiperone but not by the 5-HT(2) antagonist ketanserin. The preferential 5-HT(1B) agonists RU-24969 and quipazine induced anorexia in unstressed rats and tended to supplement the anorectic effects of stress. The benzodiazepines chlordiazepoxide and diazepam and the 5-HT antagonist cyproheptadine had no effect on stress-induced anorexia, when given (like the 5-HT(1A) agonists) 2 h after the stress. Similarly, daily injection for 2 weeks of the tricyclic antidepressants desipramine and sertraline had no beneficial effect. The data suggest that 8-OH-DPAT, buspirone and ipsapirone attenuate stress-induced anorexia in rodents by a hyperphagic action on 5-HT(1A) receptors. PMID:22158750

  8. Uncontrollable and unpredictable stress interacts with subclinical depression and anxiety scores in determining anxiety response.

    Science.gov (United States)

    Havranek, Michael M; Bolliger, Bianca; Roos, Sophie; Pryce, Christopher R; Quednow, Boris B; Seifritz, Erich

    2016-01-01

    According to learned helplessness theory, uncontrollable stress is assumed to be a critical etiological factor in the pathogenesis of depression. In contrast, unpredictability of stressors is assumed to facilitate the development of sustained anxiety. Despite the frequent co-morbidity of depression and anxiety disorders, these two factors have rarely been studied simultaneously in humans. Therefore, we investigated whether there are interaction effects of uncontrollability and unpredictability on anxiety response in healthy participants. Seventy-nine healthy participants performed a visual dot probe task with emotional faces, while receiving mild electrical shocks in four different conditions (2 × 2 factorial design). In (un)controllable conditions, participants were (not) able to attenuate shock intensity. In (un)predictable conditions, participants were (not) able to anticipate shock occurrence. Before the experiment, participants' subclinical depression and anxiety scores were measured using the Beck Depression and Anxiety Inventories (BDI/BAI). During the experiment, continuous skin conductance and self-reported state anxiety were assessed and attentional biases towards angry faces were calculated. As expected, participants showed greater anxiety in uncontrollable compared to controllable and in unpredictable compared to predictable conditions. Additionally, anxiety decreased within the test sessions in participants with low BDI/BAI scores but not in participants with higher BDI/BAI scores. Most importantly, controllability and predictability interacted with each other and with BDI/BAI scores with regard to anxiety. Our results provide evidence that uncontrollability and unpredictability of stressors not only have separate but also interaction effects on several anxiety measures in susceptible individuals and may provide insights into the psychological mechanisms underlying a depressive/anxiety co-morbidity.

  9. Biologically Synthesized Gold Nanoparticles Ameliorate Cold and Heat Stress-Induced Oxidative Stress in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Xi-Feng Zhang

    2016-06-01

    Full Text Available Due to their unique physical, chemical, and optical properties, gold nanoparticles (AuNPs have recently attracted much interest in the field of nanomedicine, especially in the areas of cancer diagnosis and photothermal therapy. Because of the enormous potential of these nanoparticles, various physical, chemical, and biological methods have been adopted for their synthesis. Synthetic antioxidants are dangerous to human health. Thus, the search for effective, nontoxic natural compounds with effective antioxidative properties is essential. Although AuNPs have been studied for use in various biological applications, exploration of AuNPs as antioxidants capable of inhibiting oxidative stress induced by heat and cold stress is still warranted. Therefore, one goal of our study was to produce biocompatible AuNPs using biological methods that are simple, nontoxic, biocompatible, and environmentally friendly. Next, we aimed to assess the antioxidative effect of AuNPs against oxidative stress induced by cold and heat in Escherichia coli, which is a suitable model for stress responses involving AuNPs. The response of aerobically grown E. coli cells to cold and heat stress was found to be similar to the oxidative stress response. Upon exposure to cold and heat stress, the viability and metabolic activity of E. coli was significantly reduced compared to the control. In addition, levels of reactive oxygen species (ROS and malondialdehyde (MDA and leakage of proteins and sugars were significantly elevated, and the levels of lactate dehydrogenase activity (LDH and adenosine triphosphate (ATP significantly lowered compared to in the control. Concomitantly, AuNPs ameliorated cold and heat-induced oxidative stress responses by increasing the expression of antioxidants, including glutathione (GSH, glutathione S-transferase (GST, super oxide dismutase (SOD, and catalase (CAT. These consistent physiology and biochemical data suggest that AuNPs can ameliorate cold and

  10. Protective role of metallothionein in stress-induced gastric ulcer in rats

    Institute of Scientific and Technical Information of China (English)

    Ping Jiang; Lin Chang; Chun-Shui Pan; Yong-Fen Qi; Chao-Shu Tang

    2005-01-01

    AIM: To illustrate the pathophysiological role of metallothionein (MT) in gastric ulcer induced by stress. METHODS: Wistar rats underwent water-immersionrestraint (WIR) stress, ZnSO4 (an MT inducer) treatment, WIR+ZnSO4 or WIR+MT, and the ulcer index (UI) was estimated in excised stomach and liver tissues. The mRNA level of gastric MT was determined by semi-quantitative RT-PCR. The MT content in gastric and hepatic tissues was determined by Cd/hemoglobin affinity assay. The lipid peroxidation products malondialdehyde (MDA) and conjugated dienes (CD) were estimated by use of thiobarbituric acid reactive species and ultraviolet spectrophotometry. RESULTS: WIR stress induced severe gastric mucosal lesions in rats. Compared with control rats, stressed rats had increased lipid peroxide content in serum and stomach and liver tissues. MDA content was increased by 34%, 21% and 29% and CD level by 270%, 83% and 28%, respectively. MT content in the stomach and liver was increased by 0.74- and 1.8-fold, and the MT-mRNA level in the stomach was increased by 26%. Pretreatment with ZnSO4 prevented gastric lesion development (the UI was 87% lower than that without pretreatment), and the MDA and CD content in serum and tissues was lower. The MT content in the liver was double in rats that were not pretreated, and the MT mRNA level in the stomach was 35% higher. MT administration 1 h before the WIR stress prevented gastric lesion development (the UI decreased by 47% compared with that in rats not pretreated), and the MDA and CD content in serum and tissues was significantly lower. CONCLUSION: In WIR-stressed rats, the MT level was increased in serum and in stomach and liver tissues. Pre-administration of exogenous MT or pre-induction of endogenous MT can protect the gastric mucosa against stress-induced ulcers and inhibits the formation of stressinduced lipid peroxide. MT could have a gastroprotective effect and might be a new interventive and therapeutic target in stress-induced

  11. Unpredictably Stable

    DEFF Research Database (Denmark)

    Failla, Virgilio; Melillo, Francesca; Reichstein, Toke

    2014-01-01

    Is entrepreneurship a more stable career choice for high employment turnover individuals? We find that a transition to entrepreneurship induces a shift towards stayer behavior and identify job matching, job satisfaction and lock-in effects as main drivers. These findings have major implications...

  12. Unpredictably Stable

    DEFF Research Database (Denmark)

    Failla, Virgilio; Melillo, Francesca; Reichstein, Toke

    is tested on matched employer-employee data from the entire Danish population. The analysis reveals that self-employed stay longer in their employment status compared to individuals in paid-employment. This effect is not explained by reduced attractiveness to the wage sector (lock-in effect). We interpret...

  13. Unpredictably Stable

    DEFF Research Database (Denmark)

    Failla, Virgilio; Melillo, Francesca; Reichstein, Toke

    Does entrepreneurship lower individuals? employment turnover rates? The paper offers two reasons why this is the case - a matching mechanism and a lock-in effect. The paper offers theoretical justifications and seeks to empirically disentangle the two mechanisms. A matched employer-employee data...... due to reduced attractiveness in the wage sector and sunk costs related lock-in effects. Results, however, also indicate that entrepreneurship may resolve mismatches of individuals in the labor market. This counterintuitive finding - self-employment yields greater employment stability - has...

  14. A Detailed Observation on Successive Stress-Induced Martensite Transformation in CuAlMnZnZr Alloy Polycrystalline Above Af

    Institute of Scientific and Technical Information of China (English)

    Li Zhou; Wang Ming-pu; Tang Wang; Guo Ming-xing

    2004-01-01

    The successive stress-induced martensite morphologies and mechanisms in polycrystalline CuAlMnZnZr samples have been examined. By applying stress to the uniform β1 matrix, two or more orientation plates of M18R martensite are stress-induced in a grain. With further increasing stress, one orientation plate depletes the other and coalesces into a single region in some view field. The mechanisms by which these are developed have been ascertained, and include variant-variant coalescence, stress-induced martensite to martensite transformation and the complicated cross-like stress-induced martensite formation.

  15. Widespread rearrangement of 3D chromatin organization underlies polycomb-mediated stress-induced silencing.

    Science.gov (United States)

    Li, Li; Lyu, Xiaowen; Hou, Chunhui; Takenaka, Naomi; Nguyen, Huy Q; Ong, Chin-Tong; Cubeñas-Potts, Caelin; Hu, Ming; Lei, Elissa P; Bosco, Giovanni; Qin, Zhaohui S; Corces, Victor G

    2015-04-16

    Chromosomes of metazoan organisms are partitioned in the interphase nucleus into discrete topologically associating domains (TADs). Borders between TADs are formed in regions containing active genes and clusters of architectural protein binding sites. The transcription of most genes is repressed after temperature stress in Drosophila. Here we show that temperature stress induces relocalization of architectural proteins from TAD borders to inside TADs, and this is accompanied by a dramatic rearrangement in the 3D organization of the nucleus. TAD border strength declines, allowing for an increase in long-distance inter-TAD interactions. Similar but quantitatively weaker effects are observed upon inhibition of transcription or depletion of individual architectural proteins. Heat shock-induced inter-TAD interactions result in increased contacts among enhancers and promoters of silenced genes, which recruit Pc and form Pc bodies in the nucleolus. These results suggest that the TAD organization of metazoan genomes is plastic and can be reconfigured quickly. PMID:25818644

  16. Deep-Trap Stress Induced Leakage Current Model for Nominal and Weak Oxides

    Science.gov (United States)

    Kamohara, Shiro; Hu, Chenming; Okumura, Tsugunori

    2008-08-01

    We have developed a model of the stress-induced leakage current (SILC) based on the inelastic trap-assisted tunneling (ITAT) by introducing a trap with a deep energy level of 3.6 eV from the bottom of the conduction band. This model can explain both of two field dependencies, i.e., a field dependence of the direct tunneling (DT) for A-mode SILC and that of the Fowler-Nordheim (FN) tunneling for B-mode SILC by analytical equations of a common form. For simple analytical equations, we introduce the most favorable trap position (MFTP), which gives the largest contribution to the leakage current. The trap area density for A-mode SILC of around 1×1010 cm-2 and the area density of the leakage paths for B-mode SILC of 1×102 cm-2 were obtained by comparisons between the experimental results and the present model.

  17. Resistance of LaCl3 to Oxidative Stress Induced by 2, 4-Dichlorophenoxy

    Institute of Scientific and Technical Information of China (English)

    Jia Yanxia; Gao Yongsheng; Zeng Fuli

    2005-01-01

    Cucumber seedlings were sprayed with different concentrations of LaCl3 for 3 d continuously. After 7 d of this treatment, the plants were treated with 1200 mg·L-1 2,4-dichlorophennoxy(2,4-D) for 24 h. The leaves were harvested and rinsed with 5 mmol · L-1 EDTA. The concentrations of photosynthetic pigments, soluble protein and metabolites related to oxidative stress and the activities of antioxidant enzymes in leaves were assayed. The results show that the treatment with appropriate concentration of LaCl3 has resistant effect on oxidative stress induced by 2, 4-D. Proper concentration of LaCl3 promotes the activity of antioxidant system in plants and alleviates the damage caused by 2, 4-D.

  18. Estrogen in prefrontal cortex blocks stress-induced cognitive impairments in female rats.

    Science.gov (United States)

    Yuen, Eunice Y; Wei, Jing; Yan, Zhen

    2016-06-01

    Animal and human studies have found that males and females show distinct stress responses. Recent studies suggest the contribution of estrogen in the brain to this sexual dimorphism. Repeated stress has been found to impair cognitive behaviors via suppressing glutamatergic transmission and glutamate receptor surface expression in pyramidal neurons of prefrontal cortex (PFC) in male rats. On the contrary, female rats exposed to the same stress paradigms show normal synaptic function and PFC-mediated cognition. The level of aromatase, the enzyme for the biosynthesis of estrogen, is significantly higher in the PFC of females than males. The stress-induced glutamatergic deficits and memory impairment are unmasked by blocking estrogen receptors or aromatase in females, suggesting a protective role of estrogen against the detrimental effects of repeated stress. PMID:26321384

  19. Effect of Paclobutrazol on Water Stress-Induced Abscisic Acid in Apple Seedling Leaves

    Science.gov (United States)

    Wang, Shiow Y.; Sun, Tung; Ji, Zuo L.; Faust, Miklos

    1987-01-01

    Abscisic acid (ABA) was quantitated by enzyme-linked immunosorbent assay (ELISA) in water-stressed leaves from control apple seedlings, and also from apple seedlings treated for 28 days with paclobutrazol ([2RS, 3RS]-1-[4-chlorophenyl]-4,4-dimethyl-2-[1,2,4-triazol-1-yl] pentan-3-ol). The ELISA quantitative estimates were also validated by gas chromatography-electron capture detector and lettuce seed germination inhibition bioassay. Paclobutrazol treatment reduced endogenous ABA levels by about one-third, and prevented the marked accumulation of water-stress-induced ABA that occurred in untreated seedlings. The presence of ABA in the apple leaf extracts was confirmed by gas chromatography-mass spectrometry. PMID:16665559

  20. Stress induced and magnetic field enhanced twin variants reorientation in NiMnGa single crystal

    Energy Technology Data Exchange (ETDEWEB)

    Wang Jingmin; Jiang Chengbao; Xu Huibin [School of Materials Science and Engineering, Beijing Univ. of Aeronautics and Astronautics, Beijing, BJ (China)

    2005-07-01

    The behavior of twin variants reorientation in Ni{sub 50}Mn{sub 27.5}Ga{sub 22.5} single crystal under the applied mechanical stress and magnetic field was investigated. Through three times of compression, the twinning stress was reduced from 4.4 MPa to 0.4 MPa, and 2.5% stress induced strain was obtained. During the succedent MFIS measurement, with the increase of measurement number of times, the critical field ({mu}{sub 0}H){sub c} at which the MFIS jumps became lower, and the corresponding jumping magnetostrain, and the maximal magnetostrain ascended. At last, a quasi single-variant state was realized, and the sample showed repeatable 6.21% MFIS, which is close to the theoretical value (1-c/a){sup *}100%. The results are discussed from the point of martensitic microstructure evolution. (orig.)

  1. Quantum mechanics based multiscale modeling of stress-induced phase transformations in iron

    Science.gov (United States)

    Lew, A.; Caspersen, K.; Carter, E. A.; Ortiz, M.

    2006-06-01

    The ground state crystal structure of Fe, ferromagnetic body-centered cubic (bcc), undergoes a stress-induced martensitic phase transformation to a hexagonally close-packed (hcp) structure. Both bcc and hcp have been observed to coexist over a large range deformations, such that the nonlinearities in the constitutive behavior of each phase need to be included for an accurate description. We present herein a methodology to construct high-fidelity quantum mechanics based nonlinear elastic energy densities, amenable to be included in microstructural optimization procedures like sequential lamination. We use the model to show that the transition pressure (TP) has a strong dependence on relatively small amounts of shear deformation, and to investigate the value of the TP under uniaxial compressions, presumably found in shock-loaded materials. Results hint that more complex deformation patterns may need be present to be consistent with measured experimental values.

  2. Relaxation of surface stress induced by an organic adsorbate: PTCDA on vicinal Ag(111)

    Energy Technology Data Exchange (ETDEWEB)

    Pollinger, Florian; Vrdoljak, Pavo; Fertig, Dominik; Schmitt, Stefan; Kumpf, Christian; Schoell, Achim; Umbach, Eberhard [Universitaet Wuerzburg, Experimentelle Physik II, Am Hubland, 97074 Wuerzburg (Germany); Tian, Zhen; Sander, Dirk; Kirschner, Juergen [Max-Planck-Institut fuer Mikrostrukturphysik, Weinberg 2, 06120 Halle (Germany)

    2007-07-01

    Self-organization of metallic surfaces on large scales can be induced by the adsorption of organic molecules and has been observed in several experiments. One example is the growth of 3,4,9,10-perylenetetracarboxylic-acid dianhydride (PTCDA) on stepped (8.5 -vicinal) Ag(111) surfaces. At elevated temperatures, the adsorbate molecules lead to a bunching of substrate steps, which agglomerate to facets of critical sizes. The facets arrange in a coverage-dependent grating-like pattern on a mesoscopic length scale. The resulting order requires a long-range interaction which is mediated by the substrate. It can be explained by a change of surface stress induced by the adsorbate layer. Experimentally, such a change is directly accessible by an optical cantilever bending technique. We monitored the bending of a faceting thin Ag(10 8 7) crystal with this method in order to quantify the occurring relaxation of surface stress.

  3. Preventing hydrogen embrittlement in stainless steel by means of compressive stress induced by cavitation peening

    Directory of Open Access Journals (Sweden)

    Osamu Takakuwa

    2015-07-01

    Full Text Available In this paper, it has been demonstrated that compressive residual stress induced by cavitation peening which is one of the mechanical surface modification techniques can reduce invasion of the surface of austenitic stainless steel by hydrogen. Cavitation peening was done with employing a cavitating jet in air. The specimens were prepared with different processing time of cavitation peening. Then, stress measurement was performed using an X-ray diffraction analysis. After that, the surface was charged with hydrogen employing a cathodic charging method. Hydrogen content was evaluated by a thermal desorption analysis using a gas chromatography. From the obtained results, hydrogen content was reduced along with increase in compressive residual stress at surface. In particular hydrogen content became to 15% at processing time of 2 s/mm introducing compressive residual stress of 378 MPa. In short, cavitation peening can drastically prevent invasion by hydrogen.

  4. Nutritional stress induces exchange of cell material and energetic coupling between bacterial species.

    Science.gov (United States)

    Benomar, Saida; Ranava, David; Cárdenas, María Luz; Trably, Eric; Rafrafi, Yan; Ducret, Adrien; Hamelin, Jérôme; Lojou, Elisabeth; Steyer, Jean-Philippe; Giudici-Orticoni, Marie-Thérèse

    2015-02-23

    Knowledge of the behaviour of bacterial communities is crucial for understanding biogeochemical cycles and developing environmental biotechnology. Here we demonstrate the formation of an artificial consortium between two anaerobic bacteria, Clostridium acetobutylicum (Gram-positive) and Desulfovibrio vulgaris Hildenborough (Gram-negative, sulfate-reducing) in which physical interactions between the two partners induce emergent properties. Molecular and cellular approaches show that tight cell-cell interactions are associated with an exchange of molecules, including proteins, which allows the growth of one partner (D. vulgaris) in spite of the shortage of nutrients. This physical interaction induces changes in expression of two genes encoding enzymes at the pyruvate crossroads, with concomitant changes in the distribution of metabolic fluxes, and allows a substantial increase in hydrogen production without requiring genetic engineering. The stress induced by the shortage of nutrients of D. vulgaris appears to trigger the interaction.

  5. Stress-induced phase transformation and optical coupling of silver nanoparticle superlattices into mechanically stable nanowires

    Science.gov (United States)

    Li, Binsong; Wen, Xiaodong; Li, Ruipeng; Wang, Zhongwu; Clem, Paul G.; Fan, Hongyou

    2014-06-01

    One-dimensional silver materials display unique optical and electrical properties with promise as functional blocks for a new generation of nanoelectronics. To date, synthetic approaches and property engineering of silver nanowires have primarily focused on chemical methods. Here we report a simple physical method of metal nanowire synthesis, based on stress-induced phase transformation and sintering of spherical Ag nanoparticle superlattices. Two phase transformations of nanoparticles under stress have been observed at distinct length scales. First, the lattice dimensions of silver nanoparticle superlattices may be reversibly manipulated between 0-8 GPa compressive stresses to enable systematic and reversible changes in mesoscale optical coupling between silver nanoparticles. Second, stresses greater than 8 GPa induced an atomic lattice phase transformation, which induced sintering of silver nanoparticles into micron-length scale nanowires. The nanowire synthesis mechanism displays a dependence on both nanoparticle crystal surface orientation and presence of particular grain boundaries to enable nanoparticle consolidation into nanowires.

  6. Developmentally and stress-induced small heat shock proteins in cork oak somatic embryos.

    Science.gov (United States)

    Puigderrajols, Pere; Jofré, Anna; Mir, Gisela; Pla, Maria; Verdaguer, Dolors; Huguet, Gemma; Molinas, Marisa

    2002-06-01

    The timing and tissue localization of small heat shock proteins (sHSPs) during cork oak somatic embryo development was investigated under normal growing culture conditions and in response to stress. Western blot analyses using polyclonal antibodies raised against cork oak recombinant HSP17 showed a transient accumulation of class I sHSPs during somatic embryo maturation and germination. Moreover, the amount of protein increased at all stages of embryo development in response to exogenous stress. The developmentally accumulated proteins localized to early differentiating, but not the highly dividing, regions of the root and shoot apical meristems. By contrast, these highly dividing regions were strongly immunostained after heat stress. Findings support the hypothesis of a distinct control for developmentally and stress-induced accumulation of class I sHSPs. The possible role of sHSPs is discussed in relation to their tissue specific localization.

  7. Stress induced martensite at the crack tip in NiTi alloys during fatigue loading

    Directory of Open Access Journals (Sweden)

    E. Sgambitterra

    2014-10-01

    Full Text Available Crack tip stress-induced phase transformation mechanisms in nickel-titanium alloys (NiTi were analyzed by Digital Image Correlation (DIC, under fatigue loads. In particular, Single Edge Crack (SEC specimens, obtained from a commercial pseudoelastic NiTi sheet, and an ad-hoc experimental setup were used, for direct measurements of the near crack tip displacement field by the DIC technique. Furthermore, a fitting procedure was developed to calculate the mode I Stress Intensity Factor (SIF, starting from the measured displacement field. Finally, cyclic tensile tests were performed at different operating temperature, in the range 298-338 K, and the evolution of the SIF was studied, which revealed a marked temperature dependence.

  8. [Practicing subnarcotic xenon dose inhalation in spa treatment of posttraumatic stress-induced disorders].

    Science.gov (United States)

    Igoshina, T V; Kotrovskaya, T I; Bubeev, Yu A; Schastlivtseva, D V; Potapov, A V

    2014-01-01

    Purpose of the investigation was to compare and contrast effectiveness of xenon therapy of stress-induced neurotic disorders and traditional spa-based therapy. Patients of the experimental and control groups were people of risky professions who received drug therapy, psychotherapy and physiotherapy. The experimental group was additionally treated by inhalation therapeutic doses of medical xenon. Comparative analysis of qualitative and quantitative parameters of electroencephalogram (EEG), blood oxygen level, heart rate and blood pressure were compared in the groups before and after treatment. Recovery of the central nervous system functions, activation of parasympathetic involvement, abatement of main psychopathological and somatovegetative disorders in the experimental group were considered as signs of psychic improvement and return to the gestalt behavior. PMID:26036001

  9. Inflammatory cytokines protect retinal pigment epithelial cells from oxidative stress-induced death

    DEFF Research Database (Denmark)

    Juel, Helene B; Faber, Carsten; Svendsen, Signe Goul;

    2013-01-01

    -cultured with activated T cells, or treated with cytokines showed increased expression of anti-oxidative genes, with upregulation of superoxide dismutase 2 protein following PCM treatment. CONCLUSION: Oxidative stress-induced cell death was reduced by concomitant inflammatory stress. This is likely due to the cytokine......PURPOSE: To investigate the effects of inflammatory factors and oxidative stress on cell survival of the human retinal pigment epithelial (RPE) cell line, ARPE-19. METHODS: Confluent RPE cells were treated with peripheral blood mononuclear cells-conditioned medium (PCM), H2O2, NaIO3, interferon...... expression of anti-oxidative enzymes, and protein expression was validated by immunoblotting. RESULTS: Viability of RPE cells was reduced by exposure to inflammatory agents (PCM, IFNγ+/-TNFα) or to oxidative agents (H2O2 or NaIO3). Unexpectedly, cells treated with either H2O2 or NaIO3 were partially...

  10. Reno-protective effect of garlic extract against immobilization stress induced changes in rats

    Institute of Scientific and Technical Information of China (English)

    Syed; Kashif; Zaidi; Shakeel; Ahmed; Ansari; Ghulam; Md.Ashraf; Mohammad; Alam; Jafri; Shams; Tabrez; Naheed; Banu

    2015-01-01

    Objective: To examine immobilization stress-induced antioxidant defense alterations in rat kidney and the antioxidant effects of aqueous garlic extract in pre and post stress extract treatments. Methods: Albino rats were treated with aqueous extract of garlic both before and 6 h of immobilization stress. Pro-oxidant eminence of rat kidney was assessed by determining the levels of glutathione, thiobarbituric acid reactive substances, aspartate aminotransferase, alanine aminotransferase, glucose, uric acid, alkaline phosphatase and antioxidant enzymes activities. Results: In response to 6 h of immobilization stress, a significant rise in the level of kidney enzymes was recorded. However, antioxidant enzyme activities showed a sharp decline. Conclusions: The extract treatment before and after the stress reverted the activities of above mentioned enzymes towards their control values. Hence, garlic extract can be given as nutritional supplement for scavenging the free radicals generated in rat kidney.

  11. Stress-induced hemorrhagic gastric ulcer after successful Helicobacter pylori eradication: two case reports

    Directory of Open Access Journals (Sweden)

    Miyamoto Mitsuaki

    2011-06-01

    Full Text Available Abstract Introduction Helicobacter pylori infection is a major cause of gastric ulcers, and Helicobacter pylori eradication drastically reduces ulcer recurrence. It has been reported, however, that severe physical stress is closely associated with gastric ulceration even in Helicobacter pylori -negative patients. Case presentation We report the cases of a 47-year-old Japanese man and a 69-year-old Japanese man who developed psychological stress-induced hemorrhagic gastric ulcers, in both of whom Helicobacter pylori had been successfully eradicated. Conclusion Our cases strongly suggest that not only physical but also psychological stress is still an important pathogenic factor for peptic ulceration and accordingly that physicians should pay attention to the possible presence of psychological stress in the management of patients with peptic ulcers.

  12. Stress-induced cognitive dysfunction: hormone-neurotransmitter interactions in the prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Rebecca M Shansky

    2013-04-01

    Full Text Available The mechanisms and neural circuits that drive emotion and cognition are inextricably linked. Activation of the hypothalamic-pituitary-adrenal (HPA axis as a result of stress or other causes of arousal initiates a flood of hormone and neurotransmitter release throughout the brain, affecting the way we think, decide, and behave. This review will focus on factors that influence the function of the prefrontal cortex (PFC, a brain region that governs higher-level cognitive processes and executive function. The PFC becomes markedly impaired by stress, producing measurable deficits in working memory. These deficits arise from the interaction of multiple neuromodulators, including glucocorticoids, catecholamines, and gonadal hormones; here we will discuss the non- human primate and rodent literature that has furthered our understanding of the circuitry, receptors, and signaling cascades responsible for stress-induced prefrontal dysfunction.

  13. CHARACTERISTICS OF STRESS-INDUCED TRANSFORMATION AND MICROSTRUCTURE EVOLUTION IN Cu-BASED SMA

    Institute of Scientific and Technical Information of China (English)

    Cheng Peng; Xingyao Wang; Yongzhong Huo

    2008-01-01

    The mechanical behavior of shape memory alloys (SMAs) is closely related to the formation and evolution of its microstructures. Through theoretical analysis and experimental ob-servations, it was found that the stress-induced martensitic transformation process of single crys-tal Cu-based SMA under uniaxial tension condition consisted of three periods: nucleation, mixed nucleation and growth, and merging due to growth. During the nucleation, the stress dropped rapidly and the number of interfaces increased very fast while the phase fraction increased slowly.In the second period, both the stress and the interface number changed slightly but the phase fraction increased dramatically. Finally, the stress and the phase fraction changed slowly while the number of interfaces decreased quickly. Moreover, it was found that the transformation could be of multi-stage: sharp stress drops at several strains and correspondingly, the nucleation and growth process occurred quasi-independently in several parts of the sample.

  14. Effects of cerebrolysin administration on oxidative stress-induced apoptosis in lymphocytes from CADASIL patients.

    Science.gov (United States)

    Formichi, Patrizia; Radi, Elena; Battisti, Carla; Di Maio, Giuseppe; Dotti, Maria Teresa; Muresanu, Dafin; Federico, Antonio

    2013-04-01

    Cerebrolysin (Cere) is a peptidergic nootropic drug with neurotrophic properties which has been used to treat dementia and sequelae of stroke. Use of Cere prevents nuclear structural changes typical of apoptosis and significantly reduces the number of apoptotic cells after several apoptotic stimuli. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary disease caused by mutations of the Notch3 gene encoding the Notch3 protein. Notch3 is involved in the regulation of apoptosis, modulating Fas-Ligand (Fas-L)- induced apoptosis. The aim of this study was to evaluate the in vitro protective effects of Cere against oxidative stress-induced apoptosis in cells from CADASIL patients. We used peripheral blood lymphocytes (PBLs) from 15 CADASIL patients (age range 34-70 years); 2-deoxy-D-ribose (dRib), a highly reducing sugar, was used as paradigm pro-apoptotic stimulus. Apoptosis was analyzed by flow cytometry and fluorescence microscopy. Administration of Cere to PBLs from CADASIL patients cultured under standard conditions had no effect on the percentage of apoptotic cells. Administration of Cere to PBLs cultured with dRib caused a significant decrease in apoptosis after 48 h of culture in only 5 patients, whereas in the other 10 patients, Cere treatment was not associated with any significant difference in the percentage of apoptosis. This result showed a protective effect of Cere against oxidative stress-induced apoptosis only in 30 % of the CADASIL patients, suggesting that the Notch3 gene probably does not influence the anti-apoptotic properties of Cere in vitro. PMID:22878905

  15. Combination of Neurofeedback Technique with Music Therapy for Effective Correction of Stress-Induced Disorders

    Directory of Open Access Journals (Sweden)

    Fedotchev A.I.

    2014-09-01

    Full Text Available The aim of the investigation was to evaluate the applicability and efficacy of music presentations controlled by feedback signals from the narrow-band electroencephalographic (EEG oscillators of a patient to correct functional stress-induced disturbances. Materials and Methods. We revealed dominant narrow-band (0.4–0.6 Hz oscillators in the theta (4–8 Hz and alpha (8–13 Hz EEG bands in 18 volunteers suffering from stress-induced disorders. During two examinations the subjects were presented with classical music. However, the music was interrupted for 3 s if the current amplitude of subject’s theta EEG oscillator exceeded the initial level, or if the current amplitude of subject’s alpha EEG oscillator did not reach the initial level. The subjects were asked to find and maintain the functional state in which the music was played continuously. Music playing time, the changes in EEG rhythm power, and the shifts in subjective estimations of health, activity and mood from the beginning to the end of each session were recorded. Results. Marked EEG normalization, reduction of stress sensations and positive shifts in mental and emotional state of the patient were found under the influence of music controlled by a feedback from theta or alpha EEG oscillators of a patient as early as by the end of the first treatment procedure. Conclusion. Improved efficiency of applied music therapy caused by its interaction with the relevant individual characteristics of the bioelectrical brain activity suggests the possibility for a successful use of such effects in a wide range of medical rehabilitation procedures.

  16. Hepcidin is an antibacterial, stress-inducible peptide of the biliary system.

    Directory of Open Access Journals (Sweden)

    Pavel Strnad

    Full Text Available BACKGROUND/AIMS: Hepcidin (gene name HAMP, an IL-6-inducible acute phase peptide with antimicrobial properties, is the key negative regulator of iron metabolism. Liver is the primary source of HAMP synthesis, but it is also produced by other tissues such as kidney or heart and is found in body fluids such as urine or cerebrospinal fluid. While the role of hepcidin in biliary system is unknown, a recent study demonstrated that conditional gp130-knockout mice display diminished hepcidin levels and increased rate of biliary infections. METHODS: Expression and localization of HAMP in biliary system was analyzed by real time RT-PCR, in-situ hybridization, immunostaining and -blotting, while prohepcidin levels in human bile were determined by ELISA. RESULTS: Hepcidin was detected in mouse/human gallbladder and bile duct epithelia. Biliary HAMP is stress-inducible, in that it is increased in biliary cell lines upon IL-6 stimulation and in gallbladder mucosa of patients with acute cholecystitis. Hepcidin is also present in the bile and elevated prohepcidin levels were observed in bile of primary sclerosing cholangitis (PSC patients with concurrent bacterial cholangitis compared to PSC subjects without bacterial infection (median values 22.3 vs. 8.9; p = 0.03. In PSC-cholangitis subjects, bile prohepcidin levels positively correlated with C-reactive protein and bilirubin levels (r = 0.48 and r = 0.71, respectively. In vitro, hepcidin enhanced the antimicrobial capacity of human bile (p<0.05. CONCLUSION: Hepcidin is a stress-inducible peptide of the biliary epithelia and a potential marker of biliary stress. In the bile, hepcidin may serve local functions such as protection from bacterial infections.

  17. Structural basis of how stress-induced MDMX phosphorylation activates p53.

    Science.gov (United States)

    Chen, X; Gohain, N; Zhan, C; Lu, W-Y; Pazgier, M; Lu, W

    2016-04-14

    The tumor-suppressor protein p53 is tightly controlled in normal cells by its two negative regulators--the E3 ubiquitin ligase MDM2 and its homolog MDMX. Under stressed conditions such as DNA damage, p53 escapes MDM2- and MDMX-mediated functional inhibition and degradation, acting to prevent damaged cells from proliferating through induction of cell cycle arrest, DNA repair, senescence or apoptosis. Ample evidence suggests that stress signals induce phosphorylation of MDM2 and MDMX, leading to p53 activation. However, the structural basis of stress-induced p53 activation remains poorly understood because of the paucity of technical means to produce site-specifically phosphorylated MDM2 and MDMX proteins for biochemical and biophysical studies. Herein, we report total chemical synthesis, via native chemical ligation, and functional characterization of (24-108)MDMX and its Tyr99-phosphorylated analog with respect to their ability to interact with a panel of p53-derived peptide ligands and PMI, a p53-mimicking but more potent peptide antagonist of MDMX, using FP and surface plasmon resonance techniques. Phosphorylation of MDMX at Tyr99 weakens peptide binding by approximately two orders of magnitude. Comparative X-ray crystallographic analyses of MDMX and of pTyr99 MDMX in complex with PMI as well as modeling studies reveal that the phosphate group of pTyr99 imposes extensive steric clashes with the C-terminus of PMI or p53 peptide and induces a significant lateral shift of the peptide ligand, contributing to the dramatic decrease in the binding affinity of MDMX for p53. Because DNA damage activates c-Abl tyrosine kinase that phosphorylates MDMX at Tyr99, our findings afford a rare glimpse at the structural level of how stress-induced MDMX phosphorylation dislodges p53 from the inhibitory complex and activates it in response to DNA damage. PMID:26148237

  18. Urban stress-induced biogenic VOC emissions and SOA-forming potentials in Beijing

    Science.gov (United States)

    Ghirardo, Andrea; Xie, Junfei; Zheng, Xunhua; Wang, Yuesi; Grote, Rüdiger; Block, Katja; Wildt, Jürgen; Mentel, Thomas; Kiendler-Scharr, Astrid; Hallquist, Mattias; Butterbach-Bahl, Klaus; Schnitzler, Jörg-Peter

    2016-03-01

    Trees can significantly impact the urban air chemistry by the uptake and emission of reactive biogenic volatile organic compounds (BVOCs), which are involved in ozone and particle formation. Here we present the emission potentials of "constitutive" (cBVOCs) and "stress-induced" BVOCs (sBVOCs) from the dominant broadleaf woody plant species in the megacity of Beijing. Based on the municipal tree census and cuvette BVOC measurements on leaf level, we built an inventory of BVOC emissions, and assessed the potential impact of BVOCs on secondary organic aerosol (SOA) formation in 2005 and 2010, i.e., before and after realizing the large tree-planting program for the 2008 Olympic Games. We found that sBVOCs, such as fatty acid derivatives, benzenoids, and sesquiterpenes, constituted a significant fraction ( ˜ 40 %) of the total annual BVOC emissions, and we estimated that the overall annual BVOC budget may have doubled from ˜ 4.8 × 109 g C year-1 in 2005 to ˜ 10.3 × 109 g C year-1 in 2010 due to the increase in urban greening, while at the same time the emission of anthropogenic VOCs (AVOCs) decreased by 24 %. Based on the BVOC emission assessment, we estimated the biological impact on SOA mass formation potential in Beijing. Constitutive and stress-induced BVOCs might produce similar amounts of secondary aerosol in Beijing. However, the main contributors of SOA-mass formations originated from anthropogenic sources (> 90 %). This study demonstrates the general importance to include sBVOCs when studying BVOC emissions. Although the main problems regarding air quality in Beijing still originate from anthropogenic activities, the present survey suggests that in urban plantation programs, the selection of low-emitting plant species has some potential beneficial effects on urban air quality.

  19. Dispositional optimism and stress-induced changes in immunity and negative mood.

    Science.gov (United States)

    Brydon, Lena; Walker, Cicely; Wawrzyniak, Andrew J; Chart, Henrik; Steptoe, Andrew

    2009-08-01

    Evidence suggests that optimism may be protective for health during times of heightened stress, yet the mechanisms involved remain unclear. In a double-blind placebo-controlled study, we recently showed that acute psychological stress and an immune stimulus (Typhim-Vi typhoid vaccine) synergistically increased serum levels of interleukin-6 (IL-6) and negative mood in 59 healthy men. Here we carried out further analysis of this sample to investigate the relationship between dispositional optimism and stress-induced changes in immunity and mood. Volunteers were randomly assigned to one of four experimental conditions in which they received either typhoid vaccine or saline placebo, and then rested or completed two mental tasks. In the stress condition, optimism was inversely related to IL-6 responses, independent of age, BMI, trait CES-D depression and baseline IL-6. This relationship was present across both stress groups (combining vaccine and placebo) and was not present in the vaccine/stress group alone, suggesting that optimism protects against the inflammatory effects of stress rather than vaccine per se. Typhoid vaccine induced a significant increase in participants' circulating anti-Vi antibody levels. Stress had no effect on antibody responses overall. However, in the vaccine/stress group, there was a strong positive association between optimism and antibody responses, indicating that stress accentuated the antibody response to vaccine in optimists. Across the complete sample, more optimistic individuals had smaller increases in negative mood and less reduction in mental vigour. Together these findings suggest that optimism may promote health, by counteracting stress-induced increases in inflammation and boosting the adjuvant effects of acute stress.

  20. Depressive symptoms are associated with mental stress-induced myocardial ischemia after acute myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Jingkai Wei

    Full Text Available Depression is an adverse prognostic factor after an acute myocardial infarction (MI, and an increased propensity toward emotionally-driven myocardial ischemia may play a role. We aimed to examine the association between depressive symptoms and mental stress-induced myocardial ischemia in young survivors of an MI.We studied 98 patients (49 women and 49 men age 38-60 years who were hospitalized for acute MI in the previous 6 months. Patients underwent myocardial perfusion imaging at rest, after mental stress (speech task, and after exercise or pharmacological stress. A summed difference score (SDS, obtained with observer-independent software, was used to quantify myocardial ischemia under both stress conditions. The Beck Depression Inventory-II (BDI-II was used to measure depressive symptoms, which were analyzed as overall score, and as separate somatic and cognitive depressive symptom scores.There was a significant positive association between depressive symptoms and SDS with mental stress, denoting more ischemia. After adjustment for demographic and lifestyle factors, disease severity and medications, each incremental depressive symptom was associated with 0.14 points higher SDS. When somatic and cognitive depressive symptoms were examined separately, both somatic [β = 0.17, 95% CI: (0.04, 0.30, p = 0.01] and cognitive symptoms [β = 0.31, 95% CI: (0.07, 0.56, p = 0.01] were significantly associated with mental stress-induced ischemia. Depressive symptoms were not associated with ischemia induced by exercise or pharmacological stress.Among young post-MI patients, higher levels of both cognitive and somatic depressive symptoms are associated with a higher propensity to develop myocardial ischemia with mental stress, but not with physical (exercise or pharmacological stress.

  1. Poly(ADP-ribose) polymerase-1 protects from oxidative stress induced endothelial dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Gebhard, Catherine; Staehli, Barbara E. [Cardiovascular Research, Physiology Institute, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Cardiology, Cardiovascular Center, University Hospital Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Shi, Yi; Camici, Giovanni G.; Akhmedov, Alexander; Hoegger, Lisa; Lohmann, Christine [Cardiovascular Research, Physiology Institute, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Matter, Christian M. [Cardiovascular Research, Physiology Institute, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Cardiology, Cardiovascular Center, University Hospital Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); Hassa, Paul O.; Hottiger, Michael O. [Institute of Veterinary Biochemistry and Molecular Biology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Malinski, Tadeusz [Department of Chemistry and Biochemistry, Ohio University, Athens, OH (United States); Luescher, Thomas F. [Cardiovascular Research, Physiology Institute, University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Winterthurerstrasse 190, 8057 Zurich (Switzerland); Cardiology, Cardiovascular Center, University Hospital Zurich, Raemistrasse 100, 8091 Zurich (Switzerland); and others

    2011-11-04

    Highlights: Black-Right-Pointing-Pointer The nuclear enzyme PARP-1 is a downstream effector of oxidative stress. Black-Right-Pointing-Pointer PARP-1 protects from oxidative stress induced endothelial dysfunction. Black-Right-Pointing-Pointer This effect is mediated through inhibition of vasoconstrictor prostanoid production. Black-Right-Pointing-Pointer Thus, PARP-1 may play a protective role as antioxidant defense mechanism. -- Abstract: Background: Generation of reactive oxygen species (ROS) is a key feature of vascular disease. Activation of the nuclear enzyme poly (adenosine diphosphate [ADP]-ribose) polymerase-1 (PARP-1) is a downstream effector of oxidative stress. Methods: PARP-1(-/-) and PARP-1(+/+) mice were injected with paraquat (PQ; 10 mg/kg i.p.) to induce intracellular oxidative stress. Aortic rings were suspended in organ chambers for isometric tension recording to analyze vascular function. Results: PQ treatment markedly impaired endothelium-dependent relaxations to acetylcholine in PARP-1(-/-), but not PARP-1(+/+) mice (p < 0.0001). Maximal relaxation was 45% in PQ treated PARP-1(-/-) mice compared to 79% in PARP-1(+/+) mice. In contrast, endothelium-independent relaxations to sodium nitroprusside (SNP) were not altered. After PQ treatment, L-NAME enhanced contractions to norepinephrine by 2.0-fold in PARP-1(-/-) mice, and those to acetylcholine by 3.3-fold, respectively, as compared to PARP-1(+/+) mice. PEG-superoxide dismutase (SOD) and PEG-catalase prevented the effect of PQ on endothelium-dependent relaxations to acetylcholine in PARP-1(-/-) mice (p < 0.001 vs. PQ treated PARP-1(+/+) mice. Indomethacin restored endothelium-dependent relaxations to acetylcholine in PQ treated PARP-1(-/-) mice (p < 0.05 vs. PQ treated PARP-1(+/+). Conclusion: PARP-1 protects from acute intracellular oxidative stress induced endothelial dysfunction by inhibiting ROS induced production of vasoconstrictor prostanoids.

  2. Effects of cerebrolysin administration on oxidative stress-induced apoptosis in lymphocytes from CADASIL patients.

    Science.gov (United States)

    Formichi, Patrizia; Radi, Elena; Battisti, Carla; Di Maio, Giuseppe; Dotti, Maria Teresa; Muresanu, Dafin; Federico, Antonio

    2013-04-01

    Cerebrolysin (Cere) is a peptidergic nootropic drug with neurotrophic properties which has been used to treat dementia and sequelae of stroke. Use of Cere prevents nuclear structural changes typical of apoptosis and significantly reduces the number of apoptotic cells after several apoptotic stimuli. Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary disease caused by mutations of the Notch3 gene encoding the Notch3 protein. Notch3 is involved in the regulation of apoptosis, modulating Fas-Ligand (Fas-L)- induced apoptosis. The aim of this study was to evaluate the in vitro protective effects of Cere against oxidative stress-induced apoptosis in cells from CADASIL patients. We used peripheral blood lymphocytes (PBLs) from 15 CADASIL patients (age range 34-70 years); 2-deoxy-D-ribose (dRib), a highly reducing sugar, was used as paradigm pro-apoptotic stimulus. Apoptosis was analyzed by flow cytometry and fluorescence microscopy. Administration of Cere to PBLs from CADASIL patients cultured under standard conditions had no effect on the percentage of apoptotic cells. Administration of Cere to PBLs cultured with dRib caused a significant decrease in apoptosis after 48 h of culture in only 5 patients, whereas in the other 10 patients, Cere treatment was not associated with any significant difference in the percentage of apoptosis. This result showed a protective effect of Cere against oxidative stress-induced apoptosis only in 30 % of the CADASIL patients, suggesting that the Notch3 gene probably does not influence the anti-apoptotic properties of Cere in vitro.

  3. Antioxidant Activity of Cabbage and/or Carrot Against Oxidative Stress Induced by Gamma Irradiation in Male Albino Rats

    International Nuclear Information System (INIS)

    Several studies indicated that diets rich in fruits and vegetables are protective against diseases, and populations that consume such diets have higher plasma antioxidants and exhibit lower risk of cancer and cardiovascular diseases. Vegetable is considered major dietary source of fibers and antioxidants such as polyphenols, flavonoids and carotenoids that can protect against different dietary disorders. The present study was carried out to investigate the potential protective effects of cabbage and/or carrot against oxidative stress induced by gamma irradiation in male albino rats. Chemical composition and phenolic contents in cabbage and carrot were determined. Male albino rats were exposed to 5 Gy (single dose with rate 0.46 Gy/min) of whole body gamma irradiation. Thirty five rats were randomly divided into five groups as follow: group 1: control (rats fed on balanced diet for 6 weeks), group 2: irradiated (rats were exposed to whole gamma irradiation and fed on balanced diet for 6 weeks) and groups 3, 4 and 5: irradiated rats fed on balanced diet and received cabbage 15%, carrot 15% and a combination of cabbage and carrot, respectively. The results obtained revealed that the administration of cabbage and/or carrot diet significantly reduced the changes induced by gamma irradiation in the serum level of glucose and liver function parameters; serum aminotransferases (AST, ALT), alkaline phosphatase (ALP), total protein and albumin. In addition, significant improvements were observed in the serum levels of total cholesterol (TC), triglycerides (TG), low density lipoprotein-cholesterol (LDL-C) and high density lipoprotein-cholesterol (HDL-C). Significant enhancement in hepatic antioxidant enzymes; superoxide dismutase (SOD) and catalase (CAT), was observed. The levels of reduced glutathione (GSH) associated with remarkable decrease in the level of lipid peroxidation (TBARS) were observed. Accordingly, it could be concluded that consumption of cabbage and/or carrot

  4. Foundations of Nonlinear Dynamics or Real Dynamics, Ideal Dynamics, Unpredictable Dynamics and the "Schroedinger's Cat Paradox"

    OpenAIRE

    Oleg, Kupervasser

    2005-01-01

    The paper discusses the basic paradoxes of thermodynamics and quantum mechanics. The approaches to solution of these paradoxes are suggested. The first one relies on the influence of the external observer (environment), which disrupts the correlations in the system. The second one is based on the limits of self-knowledge of the system in case of both the external observer and the environment is included in the considered system. The concepts of Real Dynamics, Ideal Dynamics, and Unpredictable...

  5. Base of nonlinear dynamics or Real Dynamics, Ideal Dynamics, Unpredictable Dynamics and "Schrodinger cat"

    OpenAIRE

    Kupervasser, Oleg

    2004-01-01

    In the paper paradoxes underlying thermodynamics and a quantum mechanics are discussed. Their solution is given from the point of view of influence of the exterior observer (surrounding medium) destroying correlations of system, or boundedness of self-knowledge of system in a case when both the observer, and a surrounding medium are included in system. Concepts Real Dynamics, Ideal Dynamics and Unpredictable Dynamics are entered. Consideration an appearance of a life is given from the point o...

  6. Predictive Physiological Anticipation Preceding Seemingly Unpredictable Stimuli: A Meta-Analysis

    OpenAIRE

    Julia eMossbridge; Patrizio E Tressoldi; Jessica eUtts

    2012-01-01

    This meta-analysis of 26 reports published between 1978 and 2010 tests an unusual hypothesis: for stimuli of two or more types that are presented in an order designed to be unpredictable and that produce different post-stimulus physiological activity, the direction of pre-stimulus physiological activity reflects the direction of post-stimulus physiological activity, resulting in an unexplained anticipatory effect. The reports we examined used one of two paradigms: (1) randomly ordered present...

  7. Pulling Information from Social Media in the Aftermath of Unpredictable Disasters

    OpenAIRE

    Del Vigna, Fabio; Cresci, Stefano; Marchetti, Andrea; Tesconi, Maurizio; Avvenuti, Marco

    2015-01-01

    Social media have become a primary communication channel among people and are continuously overwhelmed by huge volumes of User Generated Content. This is especially true in the aftermath of unpredictable disasters, when users report facts, descriptions and photos of the unfolding event. This material contains actionable information that can greatly help rescuers to achieve a better response to crises, but its volume and variety render manual processing unfeasible. This paper reports the exper...

  8. Adaptive phenotypic plasticity and resilience of vertebrates to increasing climatic unpredictability

    OpenAIRE

    Canale, C I; Henry, P Y

    2010-01-01

    As ecosystems undergo global changes, there is increasing interest in understanding how organisms respond to changing environments. Recent evidence drawn from available vertebrate studies suggests that most of the phenotypic responses to climate change would be due to plasticity. We hypothesize that organisms that have evolved in unpredictable environments inform us about the mechanisms of phenotypic plasticity which provide an adaptive response to climate instability. As climate changes incr...

  9. Chronic subordination stress induces hyperphagia and disrupts eating behavior in mice modeling binge-eating-like disorder

    OpenAIRE

    Maria eRazzoli; Valentina eSanghez; Alessandro eBartolomucci

    2015-01-01

    Background: Eating disorders are associated with physical morbidity and appear to have causal factors like stressful life events and negative affect. Binge eating disorder (BED) is characterized by eating in a discrete period of time a larger than normal amount of food, a sense of lack of control over eating, and marked distress. There are still unmet needs for the identification of mechanisms regulating excessive eating, which is in part due to the lack of appropriate animal models. We devel...

  10. Chronic Subordination Stress Induces Hyperphagia and Disrupts Eating Behavior in Mice Modeling Binge-Eating-Like Disorder

    OpenAIRE

    Razzoli, Maria; Sanghez, Valentina; Bartolomucci, Alessandro

    2015-01-01

    Background: Eating disorders are associated with physical morbidity and appear to have causal factors like stressful life events and negative affect. Binge-eating disorder (BED) is characterized by eating in a discrete period of time a larger than normal amount of food, a sense of lack of control over eating, and marked distress. There are still unmet needs for the identification of mechanisms regulating excessive eating, which is in part due to the lack of appropriate animal models. We devel...

  11. Defensive activation to (un)predictable interoceptive threat: The NPU respiratory threat test (NPUr).

    Science.gov (United States)

    Schroijen, Mathias; Fantoni, Simona; Rivera, Carmen; Vervliet, Bram; Schruers, Koen; van den Bergh, Omer; van Diest, Ilse

    2016-06-01

    Potentially life-threatening interoceptive sensations easily engage the behavioral defensive system. Resulting fear and anxiety toward interoceptive threat are functionally distinct states that are hypothesized to play a prominent role in the etiology of panic disorder. The present study aimed to investigate whether fear- and anxiety-potentiated startle responses occur to predictable and unpredictable interoceptive threat, respectively. Therefore, we modified the NPU threat test (Schmitz & Grillon, ) and replaced the aversive electrocutaneous stimulus with an aversive interoceptive stimulus (a breathing occlusion, making it briefly impossible to breathe). Healthy participants (N = 48) underwent three instructed conditions. A visual cue signaled the occlusion in the predictable condition (P), whereas another cue was unrelated to the occurrence of the occlusion in the unpredictable condition (U). The safe condition (N) also had a visual cue, but no occlusion. Both fear- and anxiety-potentiated startle blink responses were observed in response to predictable and unpredictable respiratory threat, respectively. The current study presents and validates the NPU respiratory threat test (NPUr) as an ecologically valid paradigm to study both anxiety and fear in response to a panic-relevant interoceptive threat. The paradigm allows future testing of contextual generalization, investigation of different clinical groups, and more explicit comparisons of defensive responding to interoceptive versus exteroceptive threats.

  12. Estrogen receptor-a in the medial amygdala prevents stress-induced elevations in blood pressure in females

    Science.gov (United States)

    Psychological stress contributes to the development of hypertension in humans. The ovarian hormone, estrogen, has been shown to prevent stress-induced pressor responses in females by unknown mechanisms. Here, we showed that the antihypertensive effects of estrogen during stress were blunted in femal...

  13. Possible Involvement of TLRs and Hemichannels in Stress-Induced CNS Dysfunction via Mastocytes, and Glia Activation

    OpenAIRE

    Adam Aguirre; Maturana, Carola J.; Paloma A. Harcha; Sáez, Juan C.

    2013-01-01

    In the central nervous system (CNS), mastocytes and glial cells (microglia, astrocytes and oligodendrocytes) function as sensors of neuroinflammatory conditions, responding to stress triggers or becoming sensitized to subsequent proinflammatory challenges. The corticotropin-releasing hormone and glucocorticoids are critical players in stress-induced mastocyte degranulation and potentiation of glial inflammatory responses, respectively. Mastocytes and glial cells express different toll-like re...

  14. Stress Induces AMP-Dependent Loss of Potency Factors Id2 and Cdx2 in Early Embryos and Stem Cells

    NARCIS (Netherlands)

    Xie, Yufen; Awonuga, Awoniyi; Liu, Jian; Rings, Edmond; Puscheck, Elizabeth Ella; Rappolee, Daniel A.

    2013-01-01

    The AMP-activated protein kinase (AMPK) mediates rapid, stress-induced loss of the inhibitor of differentiation (Id) 2 in blastocysts and trophoblast stem cells (TSC), and a lasting differentiation in TSC. However, it is not known if AMPK regulates other potency factors or regulates them before the

  15. Chronic pancreatitis

    Science.gov (United States)

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

  16. Effect of water deprivation on baseline and stress-induced corticosterone levels in the Children's python (Antaresia childreni).

    Science.gov (United States)

    Dupoué, Andréaz; Angelier, Frédéric; Lourdais, Olivier; Bonnet, Xavier; Brischoux, François

    2014-02-01

    Corticosterone (CORT) secretion is influenced by endogenous factors (e.g., physiological status) and environmental stressors (e.g., ambient temperature). Heretofore, the impact of water deprivation on CORT plasma levels has not been thoroughly investigated. However, both baseline CORT and stress-induced CORT are expected to respond to water deprivation not only because of hydric stress per se, but also because CORT is an important mineralocorticoid in vertebrates. We assessed the effects of water deprivation on baseline CORT and stress-induced CORT, in Children's pythons (Antaresia childreni), a species that experiences seasonal droughts in natural conditions. We imposed a 52-day water deprivation on a group of unfed Children's pythons (i.e., water-deprived treatment) and provided water ad libitum to another group (i.e., control treatment). We examined body mass variations throughout the experiment, and baseline CORT and stress-induced CORT at the end of the treatments. Relative body mass loss averaged ~10% in pythons without water, a value 2 to 4 times higher compared to control snakes. Following re-exposition to water, pythons from the water-deprived treatment drank readily and abundantly and attained a body mass similar to pythons from the control treatment. Together, these results suggest a substantial dehydration as a consequence of water deprivation. Interestingly, stress-induced but not baseline CORT level was significantly higher in water-deprived snakes, suggesting that baseline CORT might not respond to this degree of dehydration. Therefore, possible mineralocorticoid role of CORT needs to be clarified in snakes. Because dehydration usually induces adjustments (reduced movements, lowered body temperature) to limit water loss, and decreases locomotor performances, elevated stress-induced CORT in water-deprived snakes might therefore compensate for altered locomotor performances. Future studies should test this hypothesis.

  17. Dependence of stress-induced omega transition and mechanical twinning on phase stability in metastable β Ti–V alloys

    Energy Technology Data Exchange (ETDEWEB)

    Wang, X.L.; Li, L.; Mei, W.; Wang, W.L.; Sun, J., E-mail: jsun@sjtu.edu.cn

    2015-09-15

    Tensile properties and deformation microstructures of a series of binary β Ti–16–22V alloys have been investigated. The results show that the plastic deformation mode changes from the plate-like stress-induced ω phase transformation with a special habit plane of (− 5052){sub ω}//(3 − 3 − 2){sub β} to (332)<113> type deformation twinning with increasing the content of vanadium in the β Ti–16–22 wt.% V alloys. The plate-like stress-induced ω phase has a special orientation relationship with the β phase matrix, i.e., [110]{sub β}//[− 12 − 10]{sub ω}, (3 − 3 − 2){sub β}//(− 5052){sub ω} and (− 55 − 4){sub β}//(30 − 31){sub ω}. The alloys plastically deformed by stress-induced ω phase transformation exhibit relatively higher yield strength than those deformed via (332)<113> type deformation twinning. It can be concluded that the stability of β phase plays a significant role in plastic deformation mode, i.e., stress-induced ω phase transformation or (332)<113> type deformation twinning, which governs the mechanical property of the β Ti–16–22 wt.% V alloys. - Highlights: • Tensile properties and deformed microstructures of β Ti–16–22V alloys were studied. • Stress-induced ω phase transformation and (332)<113> twinning occur in the alloys. • Stability of β phase plays a significant role in plastic deformation mode. • Plastic deformation mode governs the mechanical property of the alloys.

  18. Cerebrolysin administration reduces oxidative stress-induced apoptosis in lymphocytes from healthy individuals.

    Science.gov (United States)

    Formichi, Patrizia; Radi, Elena; Battisti, Carla; Di Maio, Giuseppe; Muresanu, Dafin; Federico, Antonio

    2012-11-01

    Cerebrolysin is the only drug available for clinical use containing active fragments of some important neurotrophic factors obtained from purified porcine brain proteins, which has long been used for the treatment of dementia and stroke sequels. Cerebrolysin has growth factor-like activities and promotes neuronal survival and sprouting, however, its molecular mechanism still needs to be determined. It has been shown that Cerebrolysin may interact with proteolytic pathways linked to apoptosis. Administration of Cerebrolysin significantly reduces the number of apoptotic neurons after glutamate exposure. Furthermore, it has been reported that Cerebrolysin inhibits free radicals formation and lipid peroxidation. In vitro we evaluated the protective effects of Cerebrolysin towards spontaneous and induced apoptotic death in cells from healthy individuals. Peripheral blood lymphocytes (PBLs) from 10 individuals were used as cell model; 2-deoxy-D-ribose (dRib), a highly reducing sugar, was used as paradigm pro-apoptotic stimulus. Apoptosis was analysed using flow cytometry and fluorescence microscopy. Our results showed that Cerebrolysin significantly reduced the number of apoptotic PBLs after dRib treatment, although it had no significative effects on cells cultured in standard conditions. Our work showed a protective effect of Cerebrolysin on oxidative stress-induced apoptosis and suggested that PBLs can be used as an easy obtainable and handy cell model to verify Cerebrolysin effects in neurodegenerative pathologies. PMID:22882711

  19. Chaperone-Targeting Cytotoxin and Endoplasmic Reticulum Stress-Inducing Drug Synergize to Kill Cancer Cells

    Directory of Open Access Journals (Sweden)

    Joseph M. Backer

    2009-11-01

    Full Text Available Diverse physiological and therapeutic insults that increase the amount of unfolded or misfolded proteins in the endoplasmic reticulum (ER induce the unfolded protein response, an evolutionarily conserved protective mechanism that manages ER stress. Glucose-regulated protein 78/immunoglobulin heavy-chain binding protein (GRP78/BiP is an ER-resident protein that plays a central role in the ER stress response and is the only known substrate of the proteolytic A subunit (SubA of a novel bacterial AB5 toxin. Here, we report that an engineered fusion protein, epidermal growth factor (EGF-SubA, combining EGF and SubA, is highly toxic to growing and confluent epidermal growth factor receptor-expressing cancer cells, and its cytotoxicity is mediated by a remarkably rapid cleavage of GRP78/BiP. Systemic delivery of EGF-SubA results in a significant inhibition of human breast and prostate tumor xenografts in mouse models. Furthermore, EGF-SubA dramatically increases the sensitivity of cancer cells to the ER stress-inducing drug thapsigargin, and vice versa, demonstrating the first example of mechanism-based synergism in the action of a cytotoxin and an ER-targeting drug.

  20. Analysis of the stress-inducible transcription factor SsNAC23 in sugarcane plants

    Directory of Open Access Journals (Sweden)

    Renata Fava Ditt

    2011-08-01

    Full Text Available Stresses such as cold and drought can impair plant yield and induce a highly complex array of responses. Sugarcane (Saccharum spp. is cultivated in tropical and subtropical areas and is considered a cold-sensitive plant. We previously showed that cold stress induces the expression of several genes in in vitro sugarcane plantlets. Here we characterize one of those genes, SsNAC23, a member of the NAC family of plant-specific transcription factors, which are induced by low temperature and other stresses in several plant species. The expression of SsNAC23 was induced in sugarcane plants exposed to low temperatures (4ºC. With the aim of further understanding the regulatory network in response to stress, we used the yeast two-hybrid system to identify sugarcane proteins that interact with SsNAC23. Using SsNAC23 as bait, we screened a cDNA expression library of sugarcane plants submitted to 4ºC for 48 h. Several interacting partners were identified, including stress-related proteins, increasing our knowledge on how sugarcane plants respond to cold stress. One of these interacting partners, a thioredoxin h1, offers insights into the regulation of SsNAC23 activity.

  1. Exposure to HT-2 toxin causes oxidative stress induced apoptosis/autophagy in porcine oocytes

    Science.gov (United States)

    Zhang, Yue; Han, Jun; Zhu, Cheng-Cheng; Tang, Feng; Cui, Xiang-Shun; Kim, Nam-Hyung; Sun, Shao-Chen

    2016-01-01

    T-2 toxin is a main type A trichothecene mycotoxin which is the most toxic trichothecence. T-2 toxin has posed various toxic effects on human and animals in vigorous cell proliferation tissues like lymphoid, hematopoietic and gastrointestinal tissues, while HT-2 toxin is the major metabolite which is deacetylated by T-2 toxin. In this study, we focused on the toxic effects of HT-2 on porcine oocyte maturation. We treated the porcine oocyte with HT-2 toxin in vitro, and we first found that HT-2 treatment inhibited porcine oocyte polar body extrusion and cumulus cell expansion. We observed the disrupted meiotic spindle morphology after treatment, which might be due to the reduced p-MAPK protein level. Actin distribution was also disturbed, indicating that HT-2 affects cytoskeleton of porcine oocytes. We next explored the causes for the failure of oocyte maturation after HT-2 treatment. We found that HT-2 treated oocytes showed the increased ROS level, which indicated that oxidative stress had occurred. We also detected autophagy as well as early apoptosis in the treatment oocytes. Due to the fact that oxidative stress could induced apoptosis, our results indicated that HT-2 toxin caused oxidative stress induced apoptosis and autophagy, which further affected porcine oocyte maturation. PMID:27658477

  2. Salt Stress-induced Programmed Cell Death in Rice Root Tip Cells

    Institute of Scientific and Technical Information of China (English)

    Jian-You Li; Ai-Liang Jiang; Wei Zhang

    2007-01-01

    Salt stressed rice root tips were used to investigate the changes of reactive oxygen species (ROS) and antioxidant enzymes at the early stages of programmed cell death (PCD). The results indicated that 500 mmol/L NaCl treatment could lead to specific features of PCD in root tips, such as DNA ladder, nuclear condense and deformation, and transferase mediated dUTP nick end labeling positive reaction, which were initiated at 4 h of treatment and progressed thereafter. Cytochrome c release from mitochondria into cytoplasm was also observed, which occurred at 2 h and was earlier than the above nuclear events. In the very early phase of PCD, an immediate burst in hydrogen peroxide and superoxide anion production rate was accompanied by two-phase changes of superoxide dismutases and ascorbate peroxidase. A short period of increase in the activity was followed by prolonged impairment. Thus,we conclude that salt can induce PCD in rice root tip cells, and propose that in the early phase of rice root tip cell PCD, salt stress-induced oxidative burst increased the antioxidant enzyme activity, which, In turn, scavenged the ROS and abrogated PCD. Also, when the stress is prolonged, the antioxidant system is damaged and accumulated ROS induces the PCD process, which leads to cytochrome c release and nuclear change.

  3. Neighborhood matters: divergent patterns of stress-induced plasticity across the brain.

    Science.gov (United States)

    Chattarji, Sumantra; Tomar, Anupratap; Suvrathan, Aparna; Ghosh, Supriya; Rahman, Mohammed Mostafizur

    2015-10-01

    The fact that exposure to severe stress leads to the development of psychiatric disorders serves as the basic rationale for animal models of stress disorders. Clinical and neuroimaging studies have shown that three brain areas involved in learning and memory--the hippocampus, amygdala and prefrontal cortex--undergo distinct structural and functional changes in individuals with stress disorders. These findings from patient studies pose several challenges for animal models of stress disorders. For instance, why does stress impair cognitive function, yet enhance fear and anxiety? Can the same stressful experience elicit contrasting patterns of plasticity in the hippocampus, amygdala and prefrontal cortex? How does even a brief exposure to traumatic stress lead to long-lasting behavioral abnormalities? Thus, animal models of stress disorders must not only capture the unique spatio-temporal features of structural and functional alterations in these brain areas, but must also provide insights into the underlying neuronal plasticity mechanisms. This Review will address some of these key questions by describing findings from animal models on how stress-induced plasticity varies across different brain regions and thereby gives rise to the debilitating emotional and cognitive symptoms of stress-related psychiatric disorders. PMID:26404711

  4. Stress-induced interaction between p38 MAPK and HSP70

    International Nuclear Information System (INIS)

    Highlights: ► HSP70 interacts to p38 MAPK in vitro and in vivo. ► HSP70 co-localizes with p38 MAPK in the nucleus upon stress. ► HSP70 is involved in the nuclear phosphorylation of MK2 by p38 MAPK. -- Abstract: p38 MAPK, one of the four MAPK subfamilies in mammalian cells, is activated by environmental stresses and pro-inflammatory cytokines, playing fundamental roles in many biological processes. Despite all that is known on the structure and functions of p38, many questions still exist. The coupling of activation and nuclear translocation represents an important aspect of p38 signaling. In our effort in exploring the potential chaperone for p38 translocation, we performed an endogenous pull-down assay and identified HSP70 as a potential interacting protein of p38. We confirmed the interaction between p38 and HSP70 in vitro and in vivo, and identified their interaction domains. We also showed stress-induced nuclear co-localization of these two proteins. Our preliminary result indicated that HSP70 was related to the phosphorylation of MK2, a specific nuclear downstream target of p38, suggesting HSP70 is a potential chaperone for the nuclear translocation of p38.

  5. Micromechanical modeling of stress-induced strain in polycrystalline Ni–Mn–Ga by directional solidification

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Yuping, E-mail: zhuyuping@126.com [Seismic Observation and Geophysical Imaging Laboratory, Institute of Geophysics, China Earthquake Administration, Beijing 100081 (China); Shi, Tao; Teng, Yao [Faculty of Civil Engineering and Mechanics, Jiangsu University, Zhenjiang 212013 (China)

    2015-10-05

    Highlights: • A micromechanical model of directional solidification Ni–Mn–Ga is developed. • The stress–strain curves in different directions are tested. • The martensite Young’s moduli in different directions are predicted. • The macro reorientation strains in different directions are investigated. - Abstract: Polycrystalline ferromagnetic shape memory alloy Ni–Mn–Ga produced by directional solidification possess unique properties. Its compressive stress–strain behaviors in loading–unloading cycle show nonlinear and anisotropic. Based on the self-consistent theory and thermodynamics principle, a micromechanical constitutive model of polycrystalline Ni–Mn–Ga by directional solidification is developed considering the generating mechanism of the macroscopic strain and anisotropy. Then, the stress induced strains at different angles to solidification direction are calculated, and the results agree well with the experimental data. The predictive curves of martensite Young’s modulus and macro reorientation strain in different directions are investigated. It may provide theoretical guidance for the design and use of ferromagnetic shape memory alloy.

  6. Genome wide transcriptional response of Saccharomyces cerevisiae to stress-induced perturbations

    Directory of Open Access Journals (Sweden)

    Hilal eTaymaz-Nikerel

    2016-02-01

    Full Text Available Cells respond to environmental and/or genetic perturbations in order to survive and proliferate. Characterization of the changes after various stimuli at different -omics levels is crucial to comprehend the adaptation of cells to changing conditions. Genome wide quantification and analysis of transcript levels, the genes affected by perturbations, extends our understanding of cellular metabolism by pointing out the mechanisms that play role in sensing the stress caused by those perturbations and related signaling pathways, and in this way guides us to achieve endeavors such as rational engineering of cells or interpretation of disease mechanisms. Saccharomyces cerevisiae as a model system has been studied in response to different perturbations and corresponding transcriptional profiles were followed either statically or/and dynamically, short- and long- term. This review focuses on response of yeast cells to diverse stress inducing perturbations including nutritional changes, ionic stress, salt stress, oxidative stress, osmotic shock, as well as to genetic interventions such as deletion and over-expression of genes. It is aimed to conclude on common regulatory phenomena that allow yeast to organize its transcriptomic response after any perturbation under different external conditions.

  7. Prevalence and risk factors of stress-induced gastrointestinal bleeding in critically ill children

    Institute of Scientific and Technical Information of China (English)

    Chookhuan Nithiwathanapong; Sanit Reungrongrat; Nuthapong Ukarapol

    2005-01-01

    AIM: To assess the frequency and the risk factors of stress-induced gastrointestinal (GI) bleeding in children admitted to a pediatric intensive care unit (PICU).METHODS: The medical records of children aged between 1 month and 15 years admitted to the PICU between January 2002 and December 2002 were reviewed.Demographic data, indications for PICU admission, principle diagnosis, and basic laboratory investigations were recorded. Previously described factors for stress ulcer bleeding (mechanical ventilation, sepsis, acute respiratory distress syndrome, renal insufficiency, coagulopathy,thrombocytopenia, and intracranial pathology) were used as independent variables in a multivariate analysis.RESULTS: One hundred and seventy of two hundred and five medical records were eligible for review. The most common indication for PICU admission was respiratory failure (48.8%). Twenty-five children received stress ulcer bleeding prophylaxis with ranitidine. The incidence of stress ulcer bleeding was 43.5%, in which 5.3% were clinically significant bleeding. Only mechanical ventilation and thrombocytopenia were significantly associated with stress ulcer bleeding using the univariate analysis.The odds ratio and 95% confidence intervals were 5.13(1.86-14.12) and 2.26 (1.07-4.74), respectively. However, the logistic regression analysis showed that mechanicai ventilation was the only significant risk factor with the odds ratio of 14.1.CONCLUSION: The incidence of gastrointestinal bleeding was high in critically ill children. Mechanical ventilation was an important risk factor for gastrointestinal bleeding.

  8. Collectin-11 detects stress-induced L-fucose pattern to trigger renal epithelial injury.

    Science.gov (United States)

    Farrar, Conrad A; Tran, David; Li, Ke; Wu, Weiju; Peng, Qi; Schwaeble, Wilhelm; Zhou, Wuding; Sacks, Steven H

    2016-05-01

    Physiochemical stress induces tissue injury as a result of the detection of abnormal molecular patterns by sensory molecules of the innate immune system. Here, we have described how the recently discovered C-type lectin collectin-11 (CL-11, also known as CL-K1 and encoded by COLEC11) recognizes an abnormal pattern of L-fucose on postischemic renal tubule cells and activates a destructive inflammatory response. We found that intrarenal expression of CL-11 rapidly increases in the postischemic period and colocalizes with complement deposited along the basolateral surface of the proximal renal tubule in association with L-fucose, the potential binding ligand for CL-11. Mice with either generalized or kidney-specific deficiency of CL-11 were strongly protected against loss of renal function and tubule injury due to reduced complement deposition. Ex vivo renal tubule cells showed a marked capacity for CL-11 binding that was induced by cell stress under hypoxic or hypothermic conditions and prevented by specific removal of L-fucose. Further analysis revealed that cell-bound CL-11 required the lectin complement pathway-associated protease MASP-2 to trigger complement deposition. Given these results, we conclude that lectin complement pathway activation triggered by ligand-CL-11 interaction in postischemic tissue is a potent source of acute kidney injury and is amenable to sugar-specific blockade.

  9. Evaluation of Stress-Inducing Factors of Educational Environment in Hamadan Dentistry School’s Students

    Directory of Open Access Journals (Sweden)

    M. Dalband

    2007-01-01

    Full Text Available ntroduction & Objective: The aim of this study was to evaluate stressor factors of educational environment in Hamadan dental school’s students in year 2002.Materials & Methods: The study design was descriptive, cross-sectional and it was accomplished using a questionnaire which was taken from DES (dental environment stress questionnaire. According to restricted number of statistical population all members of population (154 students were evaluated as samples and this study was a survey one. Results: The results of this study indicated that most stressfull factors in dental students has been related to class work with mean score 3.18±0.83 and faculty-student relationship with mean score 3.05±0.83. Female students showed more total stress than male students (2.73 vs. 2.44. The fourth-year students had the most stress rate in all students of different years (3.05 and preclinical and clinical factors were the most stress-inducing factors of these students (3.63.Conclusion: It is concluded that the environment of Hamadan dental school and the process of education in the field of dentistry is potentially stressful. Also there is a reverse relationship between level of stress in students and their academic efficiencies.

  10. Stress-induced changes in the analgesic and thermic effects of morphine administered centrally.

    Science.gov (United States)

    Appelbaum, B D; Holtzman, S G

    1985-12-01

    Stress (e.g. restraint) potentiates analgesia and changes in body temperature induced by morphine administered systemically to rats. In order to determine if stress-induced potentiation of these effects of morphine are mediated within the central nervous system, restrained and unstressed groups of rats were injected in the lateral ventricle (i.c.v.) with graded doses of morphine, and their analgesic and body temperature responses were measured. Compared to unstressed animals, restrained rats had a greater analgesic response at each dose of morphine, characterized by an increase in both the magnitude and duration of the drug effect. The unstressed group of rats responded consistently to 1.0-100 micrograms of morphine with a 1.5-2.0 degrees C increase in core temperature. Restrained rats had either a smaller increase in body temperature or a hypothermia at these doses of morphine. Thus, restraint stress can modify the effects of morphine administered i.c.v. on analgesia and body temperature in a manner similar to that seen after systemic administration of morphine, indicating that this phenomenon is mediated centrally. PMID:4075121

  11. Collectin-11 detects stress-induced L-fucose pattern to trigger renal epithelial injury.

    Science.gov (United States)

    Farrar, Conrad A; Tran, David; Li, Ke; Wu, Weiju; Peng, Qi; Schwaeble, Wilhelm; Zhou, Wuding; Sacks, Steven H

    2016-05-01

    Physiochemical stress induces tissue injury as a result of the detection of abnormal molecular patterns by sensory molecules of the innate immune system. Here, we have described how the recently discovered C-type lectin collectin-11 (CL-11, also known as CL-K1 and encoded by COLEC11) recognizes an abnormal pattern of L-fucose on postischemic renal tubule cells and activates a destructive inflammatory response. We found that intrarenal expression of CL-11 rapidly increases in the postischemic period and colocalizes with complement deposited along the basolateral surface of the proximal renal tubule in association with L-fucose, the potential binding ligand for CL-11. Mice with either generalized or kidney-specific deficiency of CL-11 were strongly protected against loss of renal function and tubule injury due to reduced complement deposition. Ex vivo renal tubule cells showed a marked capacity for CL-11 binding that was induced by cell stress under hypoxic or hypothermic conditions and prevented by specific removal of L-fucose. Further analysis revealed that cell-bound CL-11 required the lectin complement pathway-associated protease MASP-2 to trigger complement deposition. Given these results, we conclude that lectin complement pathway activation triggered by ligand-CL-11 interaction in postischemic tissue is a potent source of acute kidney injury and is amenable to sugar-specific blockade. PMID:27088797

  12. Magnetization processes during field and stress induced twin boundary motion in NiMnGa

    Energy Technology Data Exchange (ETDEWEB)

    Neudert, Andreas; Lai, Yiu-Wai; Schaefer, Rudolf; McCord, Jeffrey [IFW Dresden (Germany)

    2010-07-01

    We have studied the twin boundary motion in bulk single crystals of the ferromagnetic shape memory alloy NiMnGa using polarized light microscopy. Magnetic domains were imaged by using magnetic indicator films that are placed on top of the sample. Those indicator films consist of a soft-magnetic garnet film that senses the out of plane stray field of the sample. Twin boundaries can be moved by either applying a magnetic field or a mechanical stress to the sample, but there are qualitative differences between the two mechanisms. After moving a twin boundary by applying an external magnetic field, the domain state consists of wide antiparallel domains with 180 domain walls. Moving the twin boundary by applying external stress results in a different domain state. Here the magnetization rotates as the twin boundary passes through and a patchy domain structure is created. After demagnetizing the sample in a decaying ac magnetic field the domain state consists of mainly 180 domain walls again. This suggests that the magnetization after stress-induced reversal is not in a global energy minimum and rather trapped in local minima. The involved energies and effective fields for the two mechanisms are discussed in the presentation.

  13. Influence of reaction stresses induced by dislocation slips on the orientation evolution in bcc metals

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    A plastic deformation model for bcc metals is proposed in consideration of reaction stresses. The shear strains and the corresponding reaction stresses induced by the activation of dislocations are calculated in the model, which will influence the following dislocation activation. The rolling texture in bcc metals is simulated up to 80% reduction, while the ratio of critical resolved shear stresses between the dislocations slipping on the {110} and {112} planes is chosen as 0.95. The corresponding calculation is also conducted with the activation of second dislocation, if the difference between the orientation factor of the two dislocations with maximal orientation factors is lower than 5%. It is shown that the simulated texture is closer to that of the 80% rolled interstitial free steels than other modeling. It is believed that the new model can give more attention to both of the strain and stress continuities during the plastic deformation of polycrystalline metals, and therefore approaches closer to the real deformation process in bcc metals.

  14. Stress Induced Effects for Advanced Polarization Control in Silicon Photonics Components

    Directory of Open Access Journals (Sweden)

    P. Waldron

    2008-06-01

    Full Text Available We review the use of the oxide cladding stress-induced photoelastic effect to modify the polarization dependent properties in silicon-on-insulator (SOI waveguide components, and highlight characteristics particular to this high index contrast (HIC systems. The birefringence in SOI waveguides has its origin in the electromagnetic boundary conditions at the waveguide boundaries, and can be further modified by the presence of stress in the waveguiding materials. With typical stress levels in SiO2 films, which are often used as the upper cladding, the waveguide effective index can be altered anisotropically up to the order of 10−3 for ridges with heights ranging from 1 μm to 5 μm. This effect can be used effectively to counter the waveguide geometrical birefringence, allowing the waveguide cross-section profiles to be optimized for design criteria other than null geometrical birefringence. Design strategies are developed for using stress engineering to achieve a variety of functions. Polarization insensitive arrayed waveguide gratings (AWGs, polarization insensitive ring resonators, and polarization splitters and filters are demonstrated using these design principles.

  15. Identification of a Benzamide Derivative that Inhibits Stress-Induced Adrenal Corticosteroid Synthesis

    Directory of Open Access Journals (Sweden)

    Jing Xu

    2009-09-01

    Full Text Available Elevated serum glucocorticoid levels contribute to the progression of many diseases, including depression, Alzheimer’s disease, hypertension, and acquired immunodeficiency syndrome. Here we show that the benzamide derivative N-[2-(4-cyclopropanecarbonyl-3-methyl-piperazin-1-yl-1-(tert-butyl-1H-indol-3-yl-methyl-2-oxo-ethyl]-4-nitrobenzamide (SP-10 inhibits dibutyryl cyclic AMP (dbcAMP-induced corticosteroid synthesis in a dose-dependent manner in Y-1 adrenal cortical mouse tumor cells, without affecting basal steroid synthesis and reduced stress-induced corticosterone increases in rats without affecting the physiological levels of the steroid in blood. SP-10 did not affect cholesterol transport and metabolism by the mitochondria but was unexpectedly found to increase 3-hydroxy-3-methylglutaryl-coenzyme A, low density lipoprotein receptor, and scavenger receptor class B type I (SR-BI expression. However, it also markedly reduced dbcAMP-induced NBD-cholesterol uptake, suggesting that this is a compensatory mechanism aimed at maintaining cholesterol levels. SP-10 also induced a redistribution of filamentous (F- and monomeric (G- actin, leading to decreased actin levels in the submembrane cytoskeleton suggesting that SP-10-induced changes in actin distribution might prevent the formation of microvilli–cellular structures required for SRBI-mediated cholesterol uptake in adrenal cells.

  16. Impaired endothelial shear stress induces podosome assembly via VEGF up-regulation.

    Science.gov (United States)

    Fey, Theres; Schubert, Kai Michael; Schneider, Holger; Fein, Evelyn; Kleinert, Eike; Pohl, Ulrich; Dendorfer, Andreas

    2016-08-01

    Podosomes are dynamic cytoskeletal membrane structures with local adhesive and proteolytic activity. They are critically involved in angiogenesis and vascular adaptive growth. Here, we studied in HUVECs and murine small vessels whether shear stress controls podosome assembly and local proteolytic activity. Podosomes were characterized by immunohistochemistry, and their proteolytic activity was assessed as degradation imprints in fluorescent gelatin that was used as growth substrate. Compared with controls (10 dyn/cm(2)), the number of podosomes formed per time was doubled when cells were exposed to low shear stress (0.3 dyn/cm(2)) or even increased 5-fold under static conditions. This was a result of an enhanced expression of VEGF after reduction of shear stress. Consequently, enhanced podosome formation could be prevented by a VEGF receptor antagonist as well by interruption of VEGF signaling via inhibition of PI3K, Src, or p38. Increase of podosome assembly went along with significantly augmented cell motility. In vivo experiments in mouse arteries confirmed increased endothelial podosome numbers when shear stress was abolished by vessel occlusion. We conclude that shear stress, by reducing VEGF release, inhibits podosome assembly. Hence, endothelial cell-mediated matrix proteolysis and migratory activity are inhibited, thereby stabilizing the structure of the vessel wall.-Fey, T., Schubert, K. M., Schneider, H., Fein, E., Kleinert, E., Pohl, U., Dendorfer, A. Impaired endothelial shear stress induces podosome assembly via VEGF up-regulation.

  17. Stress induced anisotropy in CoFeMn soft magnetic nanocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Leary, AM; Keylin, V; Ohodnicki, PR; McHenry, ME

    2015-05-07

    The use of processing techniques to create magnetic anisotropy in soft magnetic materials is a well-known method to control permeability and losses. In nanocomposite materials, field annealing below the Curie temperature results in uniaxial anisotropy energies up to similar to 2 kJ/m(3). Higher anisotropies up to similar to 10 kJ/m(3) result after annealing Fe-Si compositions under stress due to residual stress in the amorphous matrix acting on body centered cubic crystals. This work describes near zero magnetostriction Co80-x-yFexMnyNb4B14Si2 soft magnetic nanocomposites, where x and y < 8 at. % with close packed crystalline grains that show stress induced anisotropies up to similar to 50 kJ/m(3) and improved mechanical properties with respect to Fe-Si compositions. Difference patterns measured using transmission X-ray diffraction show evidence of affine strain with respect to the stress axis. (C) 2015 AIP Publishing LLC.

  18. Stress induced anisotropy in CoFeMn soft magnetic nanocomposites

    Energy Technology Data Exchange (ETDEWEB)

    Leary, A. M., E-mail: leary@cmu.edu; Keylin, V.; McHenry, M. E. [Materials Science and Engineering Department, Carnegie Mellon University, 5000 Forbes Ave., Pittsburgh, Pennsylvania 15213 (United States); Ohodnicki, P. R. [Functional Materials Development Division, National Energy Technology Laboratory (NETL), 626 Cochrans Mill Road, Pittsburgh, Pennsylvania 15236 (United States)

    2015-05-07

    The use of processing techniques to create magnetic anisotropy in soft magnetic materials is a well-known method to control permeability and losses. In nanocomposite materials, field annealing below the Curie temperature results in uniaxial anisotropy energies up to ∼2 kJ/m{sup 3}. Higher anisotropies up to ∼10 kJ/m{sup 3} result after annealing Fe-Si compositions under stress due to residual stress in the amorphous matrix acting on body centered cubic crystals. This work describes near zero magnetostriction Co{sub 80−x−y}Fe{sub x}Mn{sub y}Nb{sub 4}B{sub 14}Si{sub 2} soft magnetic nanocomposites, where x and y < 8 at.% with close packed crystalline grains that show stress induced anisotropies up to ∼50 kJ/m{sup 3} and improved mechanical properties with respect to Fe-Si compositions. Difference patterns measured using transmission X-ray diffraction show evidence of affine strain with respect to the stress axis.

  19. Seagrass proliferation precedes mortality during hypo-salinity events: a stress-induced morphometric response.

    Science.gov (United States)

    Collier, Catherine J; Villacorta-Rath, Cecilia; van Dijk, Kor-jent; Takahashi, Miwa; Waycott, Michelle

    2014-01-01

    Halophytes, such as seagrasses, predominantly form habitats in coastal and estuarine areas. These habitats can be seasonally exposed to hypo-salinity events during watershed runoff exposing them to dramatic salinity shifts and osmotic shock. The manifestation of this osmotic shock on seagrass morphology and phenology was tested in three Indo-Pacific seagrass species, Halophila ovalis, Halodule uninervis and Zostera muelleri, to hypo-salinity ranging from 3 to 36 PSU at 3 PSU increments for 10 weeks. All three species had broad salinity tolerance but demonstrated a moderate hypo-salinity stress response--analogous to a stress induced morphometric response (SIMR). Shoot proliferation occurred at salinities seagrasses, being detectable due to the fine resolution of salinity treatments tested. The detection of SIMR demonstrates the need for caution in interpreting in-situ changes in shoot density as shoot proliferation could be interpreted as a healthy or positive plant response to environmental conditions, when in fact it could signal pre-mortality stress. PMID:24705377

  20. Arabidopsis FORGETTER1 mediates stress-induced chromatin memory through nucleosome remodeling

    Science.gov (United States)

    Brzezinka, Krzysztof; Altmann, Simone; Czesnick, Hjördis; Nicolas, Philippe; Gorka, Michal; Benke, Eileen; Kabelitz, Tina; Jähne, Felix; Graf, Alexander; Kappel, Christian; Bäurle, Isabel

    2016-01-01

    Plants as sessile organisms can adapt to environmental stress to mitigate its adverse effects. As part of such adaptation they maintain an active memory of heat stress for several days that promotes a more efficient response to recurring stress. We show that this heat stress memory requires the activity of the FORGETTER1 (FGT1) locus, with fgt1 mutants displaying reduced maintenance of heat-induced gene expression. FGT1 encodes the Arabidopsis thaliana orthologue of Strawberry notch (Sno), and the protein globally associates with the promoter regions of actively expressed genes in a heat-dependent fashion. FGT1 interacts with chromatin remodelers of the SWI/SNF and ISWI families, which also display reduced heat stress memory. Genomic targets of the BRM remodeler overlap significantly with FGT1 targets. Accordingly, nucleosome dynamics at loci with altered maintenance of heat-induced expression are affected in fgt1. Together, our results suggest that by modulating nucleosome occupancy, FGT1 mediates stress-induced chromatin memory. DOI: http://dx.doi.org/10.7554/eLife.17061.001 PMID:27680998

  1. Salt stress-induced cell death in the unicellular green alga Micrasterias denticulata.

    Science.gov (United States)

    Affenzeller, Matthias Josef; Darehshouri, Anza; Andosch, Ancuela; Lütz, Cornelius; Lütz-Meindl, Ursula

    2009-01-01

    Programmed cell death (PCD) is a key element in normal plant growth and development which may also be induced by various abiotic and biotic stress factors including salt stress. In the present study, morphological, biochemical, and physiological responses of the theoretically immortal unicellular freshwater green alga Micrasterias denticulata were examined after salt (200 mM NaCl or 200 mM KCl) and osmotic stress induced by iso-osmotic sorbitol. KCl caused morphological changes such as cytoplasmic vacuolization, extreme deformation of mitochondria, and ultrastructural changes of Golgi and ER. However, prolonged salt stress (24 h) led to the degradation of organelles by autophagy, a special form of PCD, both in NaCl- and KCl-treated cells. This was indicated by the enclosure of organelles by ER-derived double membranes. DNA of NaCl- and KCl-stressed cells but not of sorbitol-treated cells showed a ladder-like pattern on agarose gel, which means that the ionic rather than the osmotic component of salt stress leads to the activation of the responsible endonuclease. DNA laddering during salt stress could be abrogated by addition of Zn(2+). Neither cytochrome c release from mitochondria nor increase in caspase-3-like activity occurred after salt stress. Reactive oxygen species could be detected within 5 min after the onset of salt and osmotic stress. Respiration, photosynthetic activity, and pigment composition indicated an active metabolism which supports programmed rather than necrotic cell death in Micrasterias after salt stress. PMID:19213813

  2. Salt stress-induced cell death in the unicellular green alga Micrasterias denticulata

    Science.gov (United States)

    Affenzeller, Matthias Josef; Darehshouri, Anza; Andosch, Ancuela; Lütz, Cornelius; Lütz-Meindl, Ursula

    2009-01-01

    Programmed cell death (PCD) is a key element in normal plant growth and development which may also be induced by various abiotic and biotic stress factors including salt stress. In the present study, morphological, biochemical, and physiological responses of the theoretically immortal unicellular freshwater green alga Micrasterias denticulata were examined after salt (200 mM NaCl or 200 mM KCl) and osmotic stress induced by iso-osmotic sorbitol. KCl caused morphological changes such as cytoplasmic vacuolization, extreme deformation of mitochondria, and ultrastructural changes of Golgi and ER. However, prolonged salt stress (24 h) led to the degradation of organelles by autophagy, a special form of PCD, both in NaCl- and KCl-treated cells. This was indicated by the enclosure of organelles by ER-derived double membranes. DNA of NaCl- and KCl-stressed cells but not of sorbitol-treated cells showed a ladder-like pattern on agarose gel, which means that the ionic rather than the osmotic component of salt stress leads to the activation of the responsible endonuclease. DNA laddering during salt stress could be abrogated by addition of Zn2+. Neither cytochrome c release from mitochondria nor increase in caspase-3-like activity occurred after salt stress. Reactive oxygen species could be detected within 5 min after the onset of salt and osmotic stress. Respiration, photosynthetic activity, and pigment composition indicated an active metabolism which supports programmed rather than necrotic cell death in Micrasterias after salt stress. PMID:19213813

  3. Binary stress induces an increase in indole alkaloid biosynthesis in Catharanthus roseus.

    Science.gov (United States)

    Zhu, Wei; Yang, Bingxian; Komatsu, Setsuko; Lu, Xiaoping; Li, Ximin; Tian, Jingkui

    2015-01-01

    Catharanthus roseus is an important medicinal plant, which produces a variety of indole alkaloids of significant pharmaceutical relevance. In the present study, we aimed to investigate the potential stress-induced increase of indole alkaloid biosynthesis in C. roseus using proteomic technique. The contents of the detectable alkaloids ajmalicine, vindoline, catharanthine, and strictosidine in C. roseus were significantly increased under binary stress. Proteomic analysis revealed that the abundance of proteins related to tricarboxylic acid cycle and cell wall was largely increased; while, that of proteins related to tetrapyrrole synthesis and photosynthesis was decreased. Of note, 10-hydroxygeraniol oxidoreductase, which is involved in the biosynthesis of indole alkaloid was two-fold more abundant in treated group compared to the control. In addition, mRNA expression levels of genes involved in the indole alkaloid biosynthetic pathway indicated an up-regulation in their transcription in C. roseus under UV-B irradiation. These results suggest that binary stress might negatively affect the process of photosynthesis in C. roseus. In addition, the induction of alkaloid biosynthesis appears to be responsive to binary stress. PMID:26284098

  4. Binary Stress Induces an Increase in Indole Alkaloid Biosynthesis in Catharanthus roseus

    Directory of Open Access Journals (Sweden)

    Wei eZhu

    2015-07-01

    Full Text Available Catharanthus roseus is an important medicinal plant, which produces a variety of indole alkaloids of significant pharmaceutical relevance. In the present study, we aimed to investigate the potential stress-induced increase of indole alkaloid biosynthesis in C. roseus using proteomic technique. The contents of the detectable alkaloids ajmalicine, vindoline, catharanthine, and strictosidine in C. roseus were significantly increased under binary stress. Proteomic analysis revealed that the abundance of proteins related to tricarboxylic acid cycle and cell wall was largely increased; while, that of proteins related to tetrapyrrole synthesis and photosynthesis was decreased. Of note, 10-hydroxygeraniol oxidoreductase, which is involved in the biosynthesis of indole alkaloid was two-fold more abundant in treated group compared to that in control. In addition, mRNA expression levels of genes involved in the indole alkaloid biosynthetic pathway indicated an up-regulation in their transcription in C. roseus under UV-B irradiation. These results suggest that binary stress might negatively affect the process of photosynthesis in C. roseus. In addition, the induction of alkaloid biosynthesis appears to be responsive to binary stress.

  5. Cerebrolysin administration reduces oxidative stress-induced apoptosis in lymphocytes from healthy individuals.

    Science.gov (United States)

    Formichi, Patrizia; Radi, Elena; Battisti, Carla; Di Maio, Giuseppe; Muresanu, Dafin; Federico, Antonio

    2012-11-01

    Cerebrolysin is the only drug available for clinical use containing active fragments of some important neurotrophic factors obtained from purified porcine brain proteins, which has long been used for the treatment of dementia and stroke sequels. Cerebrolysin has growth factor-like activities and promotes neuronal survival and sprouting, however, its molecular mechanism still needs to be determined. It has been shown that Cerebrolysin may interact with proteolytic pathways linked to apoptosis. Administration of Cerebrolysin significantly reduces the number of apoptotic neurons after glutamate exposure. Furthermore, it has been reported that Cerebrolysin inhibits free radicals formation and lipid peroxidation. In vitro we evaluated the protective effects of Cerebrolysin towards spontaneous and induced apoptotic death in cells from healthy individuals. Peripheral blood lymphocytes (PBLs) from 10 individuals were used as cell model; 2-deoxy-D-ribose (dRib), a highly reducing sugar, was used as paradigm pro-apoptotic stimulus. Apoptosis was analysed using flow cytometry and fluorescence microscopy. Our results showed that Cerebrolysin significantly reduced the number of apoptotic PBLs after dRib treatment, although it had no significative effects on cells cultured in standard conditions. Our work showed a protective effect of Cerebrolysin on oxidative stress-induced apoptosis and suggested that PBLs can be used as an easy obtainable and handy cell model to verify Cerebrolysin effects in neurodegenerative pathologies.

  6. COX7AR is a Stress-inducible Mitochondrial COX Subunit that Promotes Breast Cancer Malignancy.

    Science.gov (United States)

    Zhang, Kezhong; Wang, Guohui; Zhang, Xuebao; Hüttemann, Philipp P; Qiu, Yining; Liu, Jenney; Mitchell, Allison; Lee, Icksoo; Zhang, Chao; Lee, Jin-Sook; Pecina, Petr; Wu, Guojun; Yang, Zeng-Quan; Hüttemann, Maik; Grossman, Lawrence I

    2016-01-01

    Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, plays a key role in regulating mitochondrial energy production and cell survival. COX subunit VIIa polypeptide 2-like protein (COX7AR) is a novel COX subunit that was recently found to be involved in mitochondrial supercomplex assembly and mitochondrial respiration activity. Here, we report that COX7AR is expressed in high energy-demanding tissues, such as brain, heart, liver, and aggressive forms of human breast cancer cells. Under cellular stress that stimulates energy metabolism, COX7AR is induced and incorporated into the mitochondrial COX complex. Functionally, COX7AR promotes cellular energy production in human mammary epithelial cells. Gain- and loss-of-function analysis demonstrates that COX7AR is required for human breast cancer cells to maintain higher rates of proliferation, clone formation, and invasion. In summary, our study revealed that COX7AR is a stress-inducible mitochondrial COX subunit that facilitates human breast cancer malignancy. These findings have important implications in the understanding and treatment of human breast cancer and the diseases associated with mitochondrial energy metabolism. PMID:27550821

  7. COX7AR is a Stress-inducible Mitochondrial COX Subunit that Promotes Breast Cancer Malignancy

    Science.gov (United States)

    Zhang, Kezhong; Wang, Guohui; Zhang, Xuebao; Hüttemann, Philipp P.; Qiu, Yining; Liu, Jenney; Mitchell, Allison; Lee, Icksoo; Zhang, Chao; Lee, Jin-sook; Pecina, Petr; Wu, Guojun; Yang, Zeng-quan; Hüttemann, Maik; Grossman, Lawrence I.

    2016-01-01

    Cytochrome c oxidase (COX), the terminal enzyme of the mitochondrial respiratory chain, plays a key role in regulating mitochondrial energy production and cell survival. COX subunit VIIa polypeptide 2-like protein (COX7AR) is a novel COX subunit that was recently found to be involved in mitochondrial supercomplex assembly and mitochondrial respiration activity. Here, we report that COX7AR is expressed in high energy-demanding tissues, such as brain, heart, liver, and aggressive forms of human breast cancer cells. Under cellular stress that stimulates energy metabolism, COX7AR is induced and incorporated into the mitochondrial COX complex. Functionally, COX7AR promotes cellular energy production in human mammary epithelial cells. Gain- and loss-of-function analysis demonstrates that COX7AR is required for human breast cancer cells to maintain higher rates of proliferation, clone formation, and invasion. In summary, our study revealed that COX7AR is a stress-inducible mitochondrial COX subunit that facilitates human breast cancer malignancy. These findings have important implications in the understanding and treatment of human breast cancer and the diseases associated with mitochondrial energy metabolism. PMID:27550821

  8. Protective effects of Sesamum indicum extract against oxidative stress induced by vanadium on isolated rat hepatocytes.

    Science.gov (United States)

    Hosseini, Mir-Jamal; Shahraki, Jafar; Tafreshian, Saman; Salimi, Ahmad; Kamalinejad, Mohammad; Pourahmad, Jalal

    2016-08-01

    Vanadium toxicity is a challenging problem to human and animal health with no entirely understanding cytotoxic mechanisms. Previous studies in vanadium toxicity showed involvement of oxidative stress in isolated liver hepatocytes and mitochondria via increasing of ROS formation, release of cytochrome c and ATP depletion after incubation with different concentrations (25-200 µM). Therefore, we aimed to investigate the protective effects of Sesamum indicum seed extract (100-300 μg/mL) against oxidative stress induced by vanadium on isolated rat hepatocytes. Our results showed that quite similar to Alpha-tocopherol (100 µM), different concentrations of extract (100-300 μg/mL) protected the isolated hepatocyte against all oxidative stress/cytotoxicity markers induced by vanadium in including cell lysis, ROS generation, mitochondrial membrane potential decrease and lysosomal membrane damage. Besides, vanadium induced mitochondrial/lysosomal toxic interaction and vanadium reductive activation mediated by glutathione in vanadium toxicity was significantly (P < 0.05) ameliorated by Sesamum indicum extracts. These findings suggested a hepato-protective role for extracts against liver injury resulted from vanadium toxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 979-985, 2016. PMID:25727928

  9. Moesin and stress-induced phosphoprotein-1 are possible sero-diagnostic markers of psoriasis.

    Directory of Open Access Journals (Sweden)

    Hideki Maejima

    Full Text Available To identify diagnostic markers for psoriasis vulgaris and psoriatic arthritis, autoantibodies in sera from psoriasis vulgaris and psoriatic arthritis patients were screened by two-dimensional immunoblotting (2D-IB. Based on 2D-IB and MADLI TOF/TOF-MS analyses, eleven proteins each in psoriasis vulgaris and psoriatic arthritis were identified as autoantigens. Furthermore, serum levels of moesin, keratin 17 (K17, annexin A1 (ANXA1, and stress-induced phophoprotein-1 (STIP1, which were detected as autoantigens, were studied by dot blot analysis with psoriasis patients and healthy controls. The levels of moesin and STIP1 were significantly higher in sera from patients with psoriasis vulgaris than in the controls (moesin: P<0.05, STIP1: P<0.005. The area under the curve (AUC for moesin and STIP1 between patients with psoraisis vulgaris and controls was 0.747 and 0.792, respectively. STIP1 and K17 levels were significantly higher in sera from patients with psoriatic arthritis than in those with psoriasis vulgaris (P<0.05 each. The AUC for STIP1 and K17 between patients with psoriatic arthritis and psoriasis vulgaris was 0.69 and 0.72, respectively. The STIP1 or moesin, CK17 serum level was not correlated with disease activity of psoriasis patients. These data suggest that STIP1 and moesin may be novel and differential sero-diagnostic markers for psoriasis vulgaris and psoriatic arthritis.

  10. Age-dependent oxidative stress-induced DNA damage in Down's lymphocytes

    International Nuclear Information System (INIS)

    The aim of the present study was to investigate the oxidative status of lymphocytes from children (n = 7) and adults (n = 18) with Down's syndrome (DS). The basal oxidative condition, the vulnerability to in vitro hydrogen peroxide exposure, and the repair capacity were measured by means of the damage-specific alkaline comet assay. Significantly and age-independently elevated numbers of single strand breaks and oxidized bases (pyrimidines and purines) were found in the nuclear DNA of the lymphocytes in the DS group in the basal condition. These results may support the role of an increased level of endogenous oxidative stress in DS and are similar to those previously demonstrated in Alzheimer's disease. In the in vitro oxidative stress-induced state, a markedly higher extent of DNA damage was observed in DS children as compared with age- and gender-matched healthy controls, suggesting that young trisomic lymphocytes are more sensitive to oxidative stress than normal ones. However, the repair ability itself was not found to be deteriorated in either DS children or DS adults

  11. Effect of Gelam Honey on the Oxidative Stress-Induced Signaling Pathways in Pancreatic Hamster Cells

    Directory of Open Access Journals (Sweden)

    Kalaivani Batumalaie

    2013-01-01

    Full Text Available Background. Oxidative stress induced by reactive oxygen and nitrogen species is critically involved in the impairment of β-cell function during the development of diabetes. Methods. HIT-T15 cells were cultured in 5% CO2 and then preincubated with Gelam honey extracts (20, 40, 60, and 80 µg/mL as well as quercetin (20, 40, 60, and 80 µM, prior to stimulation by 20 and 50 mM of glucose. Cell lysate was collected to determine the effect of honey extracts and quercetin on the stress activated NF-κB, MAPK pathways, and the Akt (ser473 activated insulin signaling pathway. Results. HIT-T15 cells cultured under hyperglycemic conditions demonstrated insulin resistance with a significant increase in the levels of MAPK, NF-κB, and IRS-1 serine phosphorylation (ser307; however, Akt expression and insulin contents are significantly decreased. Pretreatment with quercetin and Gelam honey extract improved insulin resistance and insulin content by reducing the expression of MAPK, NF-κB, and IRS-1 serine phosphorylation (ser307 and increasing the expression of Akt significantly. Conclusion. Gelam honey-induced differential expression of MAPK, NF-κB, IRS-1 (ser307, and Akt in HIT-T15 cells shows that Gelam honey exerts protective effects against diabetes- and hyperglycemia-induced oxidative stress by improving insulin content and insulin resistance.

  12. A preliminary study of the effects of individual response to challenge tests and stress induced by humans on learning performance of weaned piglets (Sus scrofa).

    Science.gov (United States)

    Brajon, Sophie; Laforest, Jean-Paul; Schmitt, Océane; Devillers, Nicolas

    2016-08-01

    This study investigated whether individual behavioural characteristics of piglets and stress induced by experience with humans can influence learning performance. After weaning, piglets received a chronic experience with humans to modulate their emotional state: rough (ROU), gentle (GEN), or minimal (MIN) experience. Simultaneously, they were trained on a discrimination task. Afterward, their behaviour during challenge tests was assessed. The first learning step of the task involved associating a positive sound cue with a response (approach a trough) and success of piglets depended mostly on motivation to seek for reward. Although the experience with humans did not have direct effect, the degree of fear of handler, measured based on their reactivity to a human approach test, was related to motivation to seek rewards and learning speed of this first step in stressed ROU piglets, but not in MIN and GEN piglets. In contrast, the second learning step was more cognitively challenging, since it involved discrimination learning, including negative cues during which piglets had to learn to avoid the trough. Locomotion activity, measured during an open-field test, was associated with performance of the discrimination learning. To conclude, fearfulness towards humans and locomotion activity are linked with learning performance in relation to task complexity, highlighting the necessity to take into account these factors in animal research and management. PMID:27246576

  13. Antidepressant-like Effect of l-perillaldehyde in Stress-induced Depression-like Model Mice through Regulation of the Olfactory Nervous System

    Directory of Open Access Journals (Sweden)

    N. Ito

    2011-01-01

    Full Text Available Perillae Herba (a leaf of Perilla frutescens has been prescribed as one of the component herbs in certain Kampo (Japanese herbal medicines that are used clinically for the improvement of depressive mood. l-Perillaldehyde (PAH is a major component in the essential oil containing in Perillae Herba, but its antidepressant-like effect has not been reported. To clarify the antidepressant-like effect of PAH, the inhaled effect of PAH on stress-induced depression-like model mice prepared by subjection to a combination of forced swimming and chronic mild stresses was investigated. The degree of the depression-like state was measured by the animal's duration of immobility using a forced swimming test. Inhalation of PAH (0.0965 and 0.965 mg/mouse/day, 9 days significantly shortened the duration of immobility of the depression-like model mice and did not affect locomotor activity. However, another odor substance, cinnamaldehyde containing in Cinnamomi Cortex, exhibited no reduction in the immobility. The reduction in the immobility induced by the inhalation of PAH was prevented on anosmia-induced mice prepared by intranasal irrigation with zinc sulfate. These results suggest that the inhalation of PAH shows antidepressant-like activity through the olfactory nervous function.

  14. Hereditary chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Mössner Joachim

    2007-01-01

    Full Text Available Abstract Hereditary chronic pancreatitis (HCP is a very rare form of early onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. As well, diagnostic criteria and treatment of HCP resemble that of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, most patients have a mild disease. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2, the serine protease inhibitor, Kazal type 1 (SPINK1 and the cystic fibrosis transmembrane conductance regulator (CFTR have been found to be associated with chronic pancreatitis (idiopathic and hereditary as well. Genetic testing should only be performed in carefully selected patients by direct DNA sequencing and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. Pancreatic cancer risk is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer.

  15. Feeding and growth of Japanese quail (Coturnix c. japonica) chicks with unpredictable food access

    OpenAIRE

    Boon, P.; Visser, GH; Daan, S

    1999-01-01

    We investigated the effect of unpredictable feeding times on feeding activity and body mass gain in fast growing Japanese quail (Coturnix c. japonica) from 7 to 31 d of age. Quail chicks were subjected to a long day length (18L:6D) with ad libitum food during (1) 17.5 h of the light period, starting 0.5 h after lights-on (group A, n = 14), (2) 6 h of the light period, starting 0.5 h after lights-on (group B, n = 14), and (3) 6 h of the light period, starting pseudorandomly either 0.5, 6, or 1...

  16. Chronic Diarrhea

    Science.gov (United States)

    ... infections that cause chronic diarrhea be prevented? Chronic Diarrhea What is chronic diarrhea? Diarrhea that lasts for more than 2-4 ... represent a life-threatening illness. What causes chronic diarrhea? Chronic diarrhea has many different causes; these causes ...

  17. Inducible nitric oxide synthase inhibition attenuates physical stress-induced lung hyper-responsiveness and oxidative stress in animals with lung inflammation.

    Science.gov (United States)

    Marques, Ricardo Henrique; Reis, Fabiana G; Starling, Claudia M; Cabido, Claudia; de Almeida-Reis, Rafael; Dohlnikoff, Marisa; Prado, Carla M; Leick, Edna A; Martins, Mílton A; Tibério, Iolanda F L C

    2012-01-01

    Mechanisms involved in stress-induced asthmatic alterations have been poorly characterised. We assessed whether inducible nitric oxide synthase (iNOS) inhibition modulates the stress-amplified lung parenchyma responsiveness, oxidative stress and extracellular matrix remodelling that was previously increased by chronic lung inflammation. Guinea pigs were subjected to 7 exposures to ovalbumin (1-5 mg/ml) or saline (OVA and SAL groups) over 4 weeks. To induce behavioural stress, animals were subjected to a forced swimming protocol (5 times/week, over 2 weeks; SAL-Stress and OVA-Stress groups) 24 h after the 4th inhalation. 1400W (iNOS-specific inhibitor) was administered intraperitoneally in the last 4 days of the protocol (SAL-1400W, OVA-1400W, SAL-Stress+1400W and OVA-Stress+1400W groups). Seventy-two hours after the last inhalation, animals were anaesthetised and exsanguinated, and adrenal glands were removed. Lung tissue resistance and elastance were evaluated by oscillatory mechanics and submitted for histopathological evaluation. Stressed animals had higher adrenal weights compared to non-stressed groups, which were reduced by 1400W treatment. Behavioural stress in sensitised animals amplified the resistance and elastance responses after antigen challenge, numbers of eosinophils and iNOS+ cells, actin content and 8-iso-PGF2α density in the distal lung compared to the OVA group. 1400W treatment in ovalbumin-exposed and stressed animals reduced lung mechanics, iNOS+ cell numbers and 8-iso-PGF2α density compared to sensitised and stressed animals that received vehicle treatment. We concluded that stress amplifies the distal lung constriction, eosinophilic inflammation, iNOS expression, actin content and oxidative stress previously induced by chronic lung inflammation. iNOS-derived NO contributes to stress-augmented lung tissue functional alterations in this animal model and is at least partially due to activation of the oxidative stress pathway. PMID:22262048

  18. Role of Glia in Stress-Induced Enhancement and Impairment of Memory

    OpenAIRE

    Jiah ePearson-Leary; Danielle Maria Osborne; Ewan eMcnay

    2016-01-01

    Both acute and chronic stress profoundly affects hippocampally-dependent learning and memory: moderate stress generally enhances, while chronic or extreme stress can impair, neural and cognitive processes. Within the brain, stress elevates both norepinephrine and glucocorticoids, and both affect several genomic and signaling cascades responsible for modulating memory strength. Memories formed at times of stress can be extremely strong, yet stress can also impair memory to the point of amnesi...

  19. Development of a stress inducer for the test of radiation resistivity of organic materials used under the strain

    Energy Technology Data Exchange (ETDEWEB)

    Nunome, Keichi; Okazaki, Masaharu; Tai, Yutaka (Government Industrial Research Inst., Nagoya (Japan))

    1991-06-01

    A stress inducer for testing the radiation resistivity of organic materials under the strain was developed. The apparatus consists of, (1) stepping motor control system, which is set outside the radiation room, (2) stepping motor protected from radiation in a lead box inside the radiation room, and (3) stress inducing head which is set near the radiation source of {sup 60}Co. Two kinds of stresses, due to either bending or twisting of the sample, can be generated in the test piece during the simultaneous irradiation. As a test run of the apparatus, low density polyethylene rods were irradiated under the stress due to bending to the sample. Changes in the 'hardness' of the material were evaluated by {sup 13}C spin relaxation using high resolution solid state MMR technique. (author).

  20. Molecular dynamics simulations of stress-induced phase transformations and grain nucleation at crack tips in Fe

    Science.gov (United States)

    Latapie, A.; Farkas, D.

    2003-09-01

    The molecular dynamics simulation technique is used to study a stress-induced new grain formation mechanism at the crack tip of a nanocrystalline alpha-iron sample at temperatures ranging from 100 to 600 K. The stress-induced formation of new bcc grains, created inside existing grains, is found to occur through a metastable bcc to fcc phase transformation at the crack tip of the sample. A Nishiyama-Wassermann orientation relationship is found between the original bcc grain and the fcc phase and a Kurdjumov-Sachs orientation relationship is found between the new bcc grain created and the fcc transition phase. The new grain nucleation is observed to increase with increasing temperature and stacking faults associated with the fcc phase are observed at the higher temperatures.

  1. Per capita interactions and stress tolerance drive stress-induced changes in biodiversity effects on ecosystem functions.

    Science.gov (United States)

    Baert, Jan M; Janssen, Colin R; Sabbe, Koen; De Laender, Frederik

    2016-01-01

    Environmental stress changes the relationship between biodiversity and ecosystem functions, but the underlying mechanisms are poorly understood. Because species interactions shape biodiversity-ecosystem functioning relationships, changes in per capita interactions under stress (as predicted by the stress gradient hypothesis) can be an important driver of stress-induced changes in these relationships. To test this hypothesis, we measure productivity in microalgae communities along a diversity and herbicide gradient. On the basis of additive partitioning and a mechanistic community model, we demonstrate that changes in per capita interactions do not explain effects of herbicide stress on the biodiversity-productivity relationship. Instead, assuming that the per capita interactions remain unaffected by stress, causing species densities to only change through differences in stress tolerance, suffices to predict the stress-induced changes in the biodiversity-productivity relationship and community composition. We discuss how our findings set the stage for developing theory on how environmental stress changes biodiversity effects on ecosystem functions. PMID:27534986

  2. Stress-induced deformation at Ap~Mp and thermal cycling behavior of Cu-Al-Ni single crystals

    Institute of Scientific and Technical Information of China (English)

    陈庆福; 蔡伟; 赵连城

    2001-01-01

    Stress-induced deformation in Ap~Mp and concomitant shape recovery behavior of Cu-13.4Al-4.0Ni single crystals were studied. Abnormal high stress-induced deformation exists in Ap~Mp under the conditions of either heating with load or cooling with load. The recovered deformation is successively composed of four parts, the recoveries from superelasticity, normal reverse transformation, thermally activated reverse transformation of partially stabilized martensite and reverse transformation of stabilized martensite by over-heating. With increasing cycling number, the recovery part from normal reverse transformation decreases, while that from reverse transformation of stabilized martensite by over-heating increases, which shows a typical stabilization of martensite.

  3. Predictable Chronic Mild Stress Improves Mood, Hippocampal Neurogenesis and Memory

    OpenAIRE

    Parihar, Vipan K; Hattiangady, Bharathi; Kuruba, Ramkumar; Shuai, Bing; Shetty, Ashok K.

    2009-01-01

    Maintenance of neurogenesis in the adult hippocampus is important for functions such as mood and memory. As exposure to unpredictable chronic stress (UCS) results in decreased hippocampal neurogenesis, enhanced depressive- and anxiety-like behaviors and memory dysfunction, it is believed that declined hippocampal neurogenesis mainly underlies the behavioral and cognitive abnormalities after UCS. However, the effects of predictable chronic mild stress (PCMS) such as the routine stress experien...

  4. Systematic control of stress-induced anisotropy in pseudomorphic iron garnet thin films

    Energy Technology Data Exchange (ETDEWEB)

    Kubota, M., E-mail: Masashi.Kubota@dsn.rohm.co.jp [Correlated Electron Research Group (CERG) and Cross-Correlated Materials Research Group (CMRG), RIKEN Advanced Science Institute, Wako, Saitama 351-0198 (Japan); Power Electronics R and D Unit, ROHM Co., Ltd., Kyoto 615-8585 (Japan); Shibuya, K.; Tokunaga, Y. [Correlated Electron Research Group (CERG) and Cross-Correlated Materials Research Group (CMRG), RIKEN Advanced Science Institute, Wako, Saitama 351-0198 (Japan); Kagawa, F. [Department of Applied Physics and Quantum Phase Electronics Center (QPEC), University of Tokyo, Bunkyo, Tokyo 113-8656 (Japan); CREST, Japan Science and Technology Agency, Bunkyo, Tokyo 113-8656 (Japan); Tsukazaki, A. [Department of Applied Physics and Quantum Phase Electronics Center (QPEC), University of Tokyo, Bunkyo, Tokyo 113-8656 (Japan); PRESTO, Japan Science and Technology Agency, Bunkyo, Tokyo 113-8656 (Japan); Tokura, Y.; Kawasaki, M. [Correlated Electron Research Group (CERG) and Cross-Correlated Materials Research Group (CMRG), RIKEN Advanced Science Institute, Wako, Saitama 351-0198 (Japan); Department of Applied Physics and Quantum Phase Electronics Center (QPEC), University of Tokyo, Bunkyo, Tokyo 113-8656 (Japan)

    2013-08-15

    Iron garnets are one of the most well-studied magnetic materials that enabled magnetic bubble memories and magneto-optical devices employing films with a perpendicular easy axis. However, most studies have been conducted on rather thick films (>1 μm), and it has not been elucidated whether it is possible to align the magnetic easy axis perpendicular to the film plane for much thinner (<100 nm) films by overcoming shape anisotropy. We studied the effects of epitaxial strain and film composition on the magnetic properties of 50-nm-thick garnet thin films grown by pulsed-laser deposition. Y{sub 3}Fe{sub 5}O{sub 12} was selected as the most prototypical garnet and Sm{sub 3−x}Tm{sub x}Fe{sub 5}O{sub 12} (x=1, 2, 3) was selected in view of its negatively large magnetostriction constants. We employed (111) planes of single crystalline Gd{sub 3}Ga{sub 5}O{sub 12} and (CaGd){sub 3}(MgGaZr){sub 5}O{sub 12} substrates to tune the epitaxial strain. Thin films with a pseudomorphic structure were fabricated with the in-plane strain (ε{sub //}) ranging from −1.5% to +0.5%, corresponding to the stress-induced anisotropy field (H{sub A}) ranging from −40 kOe to +25 kOe, respectively. The magnetization ratio of the out-of-plane to in-plane component (M{sub ⊥}/M{sub //}) systematically varied in accord with H{sub A}, yielding M{sub ⊥}/M{sub //} >1 for thin films with H{sub A} values larger than 20 kOe. Among the films grown, Tm{sub 3}Fe{sub 5}O{sub 12} on Gd{sub 3}Ga{sub 5}O{sub 12} showed the largest ε{sub //} and H{sub A} values of +0.5% and +25 kOe, respectively, to realize an apparently perpendicular easy axis, confirmed by a large M{sub ⊥}/M{sub //} value of 7.8. Further, magnetic force microscope images showed a maze pattern typical of a perpendicularly magnetized film. These results reveal a method for tailoring the magnetic anisotropy of garnet ultrathin films by utilizing epitaxial strain. These thin films may be utilized to obtain nanoscale magnetic bubbles

  5. The role of losartan and enalapril in the protection against stress-induced gastric mucosal ulceration in rats

    OpenAIRE

    Ahmed, Sanaa A.; Mahmoud H. Abdel-Rahim; Hytham M. Abdel-latif

    2016-01-01

    Background: Angiotensin II (ANG II) is a stress hormone and its level dramatically increases in the stomach during stress. In addition, it generates reactive oxygen species (ROS) with cellular damage and inflammation. So the aim of this study is to evaluate the mechanism of losartan and enalapril in the prevention of stress-induced gastric ulcer through their action on mucosal prostaglandin (PGs) and antioxidant enzymes and compare between them. Methods: Thirty- six adult male wistar albin...

  6. Overexpression of an ABA biosynthesis gene using a stress-inducible promoter enhances drought resistance in petunia

    OpenAIRE

    Estrada-Melo, Alejandro C; Chao,; Reid, Michael S; Cai-Zhong Jiang

    2015-01-01

    The response of plants to drought stress includes reduced transpiration as stomates close in response to increased abscisic acid (ABA) concentrations. Constitutive overexpression of 9-cis-epoxycarotenoid dioxygenase (NCED), a key enzyme in ABA biosynthesis, increases drought resistance, but causes negative pleiotropic effects on plant growth and development. We overexpressed the tomato NCED (LeNCED1) in petunia plants under the control of a stress-inducible promoter, rd29A. Under water stress...

  7. Ursolic acid protects monocytes against metabolic stress-induced priming and dysfunction by preventing the induction of Nox4

    Directory of Open Access Journals (Sweden)

    Sarah L. Ullevig

    2014-01-01

    Conclusion: UA protects THP-1 monocytes against dysfunction by suppressing metabolic stress-induced Nox4 expression, thereby preventing the Nox4-dependent dysregulation of redox-sensitive processes, including actin turnover and MAPK-signaling, two key processes that control monocyte migration and adhesion. This study provides a novel mechanism for the anti-inflammatory and athero- and renoprotective properties of UA and suggests that dysfunctional blood monocytes may be primary targets of UA and related compounds.

  8. Basal and stress-inducible expression of HSPA6 in human keratinocytes is regulated by negative and positive promoter regions

    OpenAIRE

    Ramirez, Vincent P.; Stamatis, Michael; Shmukler, Anastasia; Aneskievich, Brian J.

    2014-01-01

    Epidermal keratinocytes serve as the primary barrier between the body and environmental stressors. They are subjected to numerous stress events and are likely to respond with a repertoire of heat shock proteins (HSPs). HSPA6 (HSP70B′) is described in other cell types with characteristically low to undetectable basal expression, but is highly stress induced. Despite this response in other cells, little is known about its control in keratinocytes. We examined endogenous human keratinocyte HSPA6...

  9. Deformation behavior after stress-induced martensite transformation in a Ti-50.8 at.% Ni alloy

    Directory of Open Access Journals (Sweden)

    Wang Xiebin

    2015-01-01

    Full Text Available In this study, the deformation behavior of a Ti-50.8 at.% Ni thin wire, which was subjected to different heat treatments, was investigated by means of uniaxial tensile tests. Considerable ductility (tensile elongation >50% and a large variation of the stress-strain relations are observed after different heat treatments, especially in the stage after the stress-induced martensite transformation plateau. A possible explanation for the observed phenomenon is discussed in this work.

  10. Nitric Oxide Reduces Hydrogen Peroxide Accumulation Involved in Water Stress-induced Subcellular Anti-oxidant Defense in Maize Plants

    Institute of Scientific and Technical Information of China (English)

    Jianrong Sang; Mingyi Jiang; Fan Lin; Shucheng Xu; Aying Zhang; Mingpu Tan

    2008-01-01

    Nitric oxide (NO) Is a bioactive molecule involved in many biological events, and has been reported as pro-oxidant as well as anti-oxidant in plants. In the present study, the sources of NO production under water stress, the role of NO in water stress-induced hydrogen peroxide (H2O2) accumulation and subcellular activities of anti-oxidant enzymes in leaves of maize (Zea mays L.) plants were investigated. Water stress Induced defense increases in the generation of NO In maize mesphyll cells and the activity of nitric oxide synthase (NOS) in the cytosolic and microsomal fractions of maize leaves. Water stress-induced defense increases in the production of NO were blocked by pretreatments with Inhibitors of NOS and nitrate reductase (NR), suggesting that NO is produced from NOS and NR in leaves of maize plants exposed to water stress. Water stress also induced increases in the activities of the chloroplastic and cytosolic anti-oxidant enzymes superoxide dismutase (SOD), ascorbate peroxidass (APX), and glutathione reductase (GR), and the increases in the activities of anti-oxidant enzymes were reduced by pretreatments with inhibitors of NOS and NR. Exogenous NO increases the activities of water stress-induced subcellular anti-oxidant enzymes, which decreases accumulation of H2O2. Our results suggest that NOS and NR are involved in water strese-induced NO production and NOS is the major source of NO. The potential ability of NO to scavenge H2O2 is, at least in part, due to the induction of a subcellular anti-oxidant defense.

  11. The Effects of Puerariae Flos on Stress-induced Deficits of Learning and Memory in Ovariectomized Female Rats

    OpenAIRE

    Park, Hyun-Jung; Han, Seung-Moo; Yoon, Won Ju; Kim, Kyung-Soo; Shim, Insop

    2009-01-01

    Puerariae flos (PF) is a traditional oriental medicinal plant and has clinically been prescribed for a long time. The purpose of the present study was to examine the effect of PF on repeated stress-induced alterations of learning and memory on a Morris water maze (MWM) test in ovariectomized (OVX) female rats. The changes in the reactivity of the cholinergic system were assessed by measuring the immunoreactive neurons of choline acetyltransferase (ChAT) in the hippocampus after behavioral tes...

  12. Anti-EGFL7 antibodies enhance stress-induced endothelial cell death and anti-VEGF efficacy

    OpenAIRE

    Johnson, Leisa; Huseni, Mahrukh; Smyczek, Tanya; Lima, Anthony; Yeung, Stacey; Cheng, Jason H.; Molina, Rafael; Kan, David; De Mazière, Ann; Klumperman, Judith; Kasman, Ian; Zhang, Yin; Dennis, Mark S; Eastham-Anderson, Jeffrey; Jubb, Adrian M.

    2013-01-01

    Many oncology drugs are administered at their maximally tolerated dose without the knowledge of their optimal efficacious dose range. In this study, we describe a multifaceted approach that integrated preclinical and clinical data to identify the optimal dose for an antiangiogenesis agent, anti-EGFL7. EGFL7 is an extracellular matrix–associated protein expressed in activated endothelium. Recombinant EGFL7 protein supported EC adhesion and protected ECs from stress-induced apoptosis. Anti-EGFL...

  13. Inheritable effect of unpredictable maternal separation on behavioral responses in mice

    Directory of Open Access Journals (Sweden)

    Isabelle C Weiss

    2011-02-01

    Full Text Available The long-term impact of early stress on behavior and emotions is well documented in humans, and can be modeled in experimental animals. In mice, maternal separation during early postnatal development induces poor and disorganized maternal care, and results in behavioral deficits that persist through adulthood. Here, we examined the long-term effect of unpredictable maternal separation combined with maternal stress (MSUS on behavior and its transmissibility. We report that unpredictable maternal separation from birth to postnatal day (PND 14 in C57Bl/6J mice has mild behavioral effects in the animals when adult, but that its combination with maternal stress exacerbates this effect. Further, the behavioral deficits are transmitted to the following generation through females, an effect that is independent of maternal care and is not affected by cross-fostering. The combined manipulation does not alter basic components of the HPA axis but decreases the expression of the corticotropin releasing factor receptor 2 (CRFR2 in several nuclei of the amygdala and the hypothalamus in the brain of maternal-separated females. These results suggest a non-genomic mode of transmission of the impact of early stress in mice.

  14. Controllability modulates the neural response to predictable but not unpredictable threat in humans.

    Science.gov (United States)

    Wood, Kimberly H; Wheelock, Muriah D; Shumen, Joshua R; Bowen, Kenton H; Ver Hoef, Lawrence W; Knight, David C

    2015-10-01

    Stress resilience is mediated, in part, by our ability to predict and control threats within our environment. Therefore, determining the neural mechanisms that regulate the emotional response to predictable and controllable threats may provide important new insight into the processes that mediate resilience to emotional dysfunction and guide the future development of interventions for anxiety disorders. To better understand the effect of predictability and controllability on threat-related brain activity in humans, two groups of healthy volunteers participated in a yoked Pavlovian fear conditioning study during functional magnetic resonance imaging (fMRI). Threat predictability was manipulated by presenting an aversive unconditioned stimulus (UCS) that was either preceded by a conditioned stimulus (i.e., predictable) or by presenting the UCS alone (i.e., unpredictable). Similar to animal model research that has employed yoked fear conditioning procedures, one group (controllable condition; CC), but not the other group (uncontrollable condition; UC) was able to terminate the UCS. The fMRI signal response within the dorsolateral prefrontal cortex (PFC), dorsomedial PFC, ventromedial PFC, and posterior cingulate was diminished during predictable compared to unpredictable threat (i.e., UCS). In addition, threat-related activity within the ventromedial PFC and bilateral hippocampus was diminished only to threats that were both predictable and controllable. These findings provide insight into how threat predictability and controllability affects the activity of brain regions (i.e., ventromedial PFC and hippocampus) involved in emotion regulation, and may have important implications for better understanding neural processes that mediate emotional resilience to stress.

  15. Effect of temperature on oxidative stress induced by lead in the leaves of Plantago major L.

    Science.gov (United States)

    Balakhnina, Tamara I.; Borkowska, Aneta; Nosalewicz, Magdalena; Nosalewicz, Artur; Włodarczyk, Teresa M.; Kosobryukhov, Anatoly A.; Fomina, Irina R.

    2016-07-01

    Fluctuation of the summer day-time temperatures in the mid-latitudes in a range from 16 to 30°C should not have irreversible negative effects on plants, but may influence metabolic processes including the oxidative stress. To test the effect of moderately high temperature on oxidative stress induced by lead in the leaves of Plantago major L.; the plants were incubated in a water solution of 0, 150, 450, and 900 μM Pb (NO3)2 at 20 and 28°C. Plant reactions were evaluated by the content of thiobarbituric acid reactive substances and ascorbate peroxidase and glutathione reductase activities in leaves after 2, 24, 48, and 72 h. The Pb concentration in the leaves rose with the increase in the Pb content and was higher at 20°C. The increase in stomatal resistance caused by Pb was higher at 28°C. The contents of TBARS increased after 2 h of plant exposure to Pb and the increase was the highest at 900 μM Pb, 28°C. The AsP activity increased up to 50% after 24 h of Pb-treatment at 28°C; the highest increase in glutathione reductase activity was observed after 72 h at 20°C. Thus, the moderately high temperature 28°C compared with optimal 20°C caused a decrease in Pb accumulation in Plantago leaves but amplified the negative effects of lead, especially in the beginning of stress development.

  16. Stress-induced chemical detection using flexible metal-organic frameworks.

    Energy Technology Data Exchange (ETDEWEB)

    Allendorf, Mark D.; Hesketh, Peter J. (Georgia Institute of Technology, Atlanta, GA); Gall, Kenneth A. (Georgia Institute of Technology, Atlanta, GA); Choudhury, A. (Georgia Institute of Technology, Atlanta, GA); Pikarsky, J. (Georgia Institute of Technology, Atlanta, GA); Andruszkiewicz, Leanne (Georgia Institute of Technology, Atlanta, GA); Houk, Ronald J. T.; Talin, Albert Alec (National Institute of Standards & Technology, Gaithersburg, MD)

    2009-09-01

    In this work we demonstrate the concept of stress-induced chemical detection using metal-organic frameworks (MOFs) by integrating a thin film of the MOF HKUST-1 with a microcantilever surface. The results show that the energy of molecular adsorption, which causes slight distortions in the MOF crystal structure, can be efficiently converted to mechanical energy to create a highly responsive, reversible, and selective sensor. This sensor responds to water, methanol, and ethanol vapors, but yields no response to either N{sub 2} or O{sub 2}. The magnitude of the signal, which is measured by a built-in piezoresistor, is correlated with the concentration and can be fitted to a Langmuir isotherm. Furthermore, we show that the hydration state of the MOF layer can be used to impart selectivity to CO{sub 2}. We also report the first use of surface-enhanced Raman spectroscopy to characterize the structure of a MOF film. We conclude that the synthetic versatility of these nanoporous materials holds great promise for creating recognition chemistries to enable selective detection of a wide range of analytes. A force field model is described that successfully predicts changes in MOF properties and the uptake of gases. This model is used to predict adsorption isotherms for a number of representative compounds, including explosives, nerve agents, volatile organic compounds, and polyaromatic hydrocarbons. The results show that, as a result of relatively large heats of adsorption (> 20 kcal mol{sup -1}) in most cases, we expect an onset of adsorption by MOF as low as 10{sup -6} kPa, suggesting the potential to detect compounds such as RDX at levels as low as 10 ppb at atmospheric pressure.

  17. Oxidative stress induces persistent telomeric DNA damage responsible for nuclear morphology change in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Elisa Coluzzi

    Full Text Available One main function of telomeres is to maintain chromosome and genome stability. The rate of telomere shortening can be accelerated significantly by chemical and physical environmental agents. Reactive oxygen species are a source of oxidative stress and can produce modified bases (mainly 8-oxoG and single strand breaks anywhere in the genome. The high incidence of guanine residues in telomeric DNA sequences makes the telomere a preferred target for oxidative damage. Our aim in this work is to evaluate whether chromosome instability induced by oxidative stress is related specifically to telomeric damage. We treated human primary fibroblasts (MRC-5 in vitro with hydrogen peroxide (100 and 200 µM for 1 hr and collected data at several time points. To evaluate the persistence of oxidative stress-induced DNA damage up to 24 hrs after treatment, we analysed telomeric and genomic oxidative damage by qPCR and a modified comet assay, respectively. The results demonstrate that the genomic damage is completely repaired, while the telomeric oxidative damage persists. The analysis of telomere length reveals a significant telomere shortening 48 hrs after treatment, leading us to hypothesise that residual telomere damage could be responsible for the telomere shortening observed. Considering the influence of telomere length modulation on genomic stability, we quantified abnormal nuclear morphologies (Nucleoplasmic Bridges, Nuclear Buds and Micronuclei and observed an increase of chromosome instability in the same time frame as telomere shortening. At subsequent times (72 and 96 hrs, we observed a restoration of telomere length and a reduction of chromosome instability, leaving us to conjecture a correlation between telomere shortening/dysfunction and chromosome instability. We can conclude that oxidative base damage leads to abnormal nuclear morphologies and that telomere dysfunction is an important contributor to this effect.

  18. Isolation and Expression Analysis of a Novel Abiotic Stress-Induced Gene W89 from Wheat

    Institute of Scientific and Technical Information of China (English)

    ZHANG Rui-yue; XU Zhao-shi; LI Lian-cheng; CHEN Ming; MA You-zhi

    2007-01-01

    Water stress and cold stress are important factors restricting plant growth. However, there is little knowledge on the function of stress-responsive genes in plants. Therefore, it is necessary to clone some important genes to study the mechanism of plant adaptation to abiotic stress for improvement of plant resistance. A putative water stress-induced gene, W89, was cloned from the cDNA library of drought-treated wheat seedlings by phage hybridization in situ, and its entire length was obtained using 5'-rapid amplification of cDNA ends (RACE) and reverse transcription-polymerase chain reaction (RT-PCR). The full-length cDNA of W89 consists of 2 392 bp and contains a 1 896 bp open reading frame (ORF) encoding a 631 amino acid protein. Southern blot analysis indicated that W89 was a single-copy gene. RT-PCR analysis revealed that the expression of W89 was upregulated by drought, cold, and abscisic acid (ABA). Amino acid sequence analysis discovered that W89 had a conserved region of DUF248 (pfam03141), which contained a methyltransferase domain with a sterile alpha motif (SAM)-binding motif. Phylogenetic analysis showed that W89 was 66% identical to Oryza sativa dehydration-responsive protein (BAD67956). It was supposed that W89 was a novel dehydration-responsive protein encoding gene. On the basis of the functions of methyltransferase and the SAM-binding motif, the SAM-binding motif of W89 was supposed to be connected with other proteins or transcription factors to transduce stress signals and finally regulate the expression of stress-responsive genes on the early stage of drought stress.

  19. Salt stress induces internalization of plasma membrane aquaporin into the vacuole in Arabidopsis thaliana.

    Science.gov (United States)

    Ueda, Masamichi; Tsutsumi, Nobuhiro; Fujimoto, Masaru

    2016-06-10

    Salt stress is a major environmental stress for plants, causing hyperosmotic, ionic and drought-like stresses. Plasma membrane intrinsic protein 2;1 (PIP2;1), which forms a water channel that regulates water flux thorough the plasma membrane (PM), is constitutively trafficked between the PM and the trans-Golgi network (TGN) in Arabidopsis thaliana. Salt stress is known to relocalize PIP2;1 to intracellular compartments, probably to decrease the water permeability of the root. However, the destination of internalized PIP2;1 and the mechanism by which PIP2;1 is internalized remain unclear. Here, we examined the effects of salt stress and inhibitors of endocytosis on the intracellular localization of green fluorescent protein-fused PIP2;1 (GFP-PIP2;1) in Arabidopsis thaliana root epidermal cells. Salt stress decreased the fluorescence of GFP-PIP2;1 at the PM and increased it in the vacuolar lumen as shown by staining of the vacuolar membrane. The internalization of PIP2;1 was suppressed by an inhibitor of clathrin-mediated endocytosis and by inhibitors of two kinases that appear to have roles in salt stress, phosphatidylinositol 3-kinase (PI3K) and phosphatidylinositol 4-kinase (PI4K). Inhibiting PI4K suppressed the salt-induced endocytosis of GFP-PIP2;1 at the PM, whereas inhibiting PI3K suppressed the trafficking of GFP-PIP2;1 after its internalization. These results suggest that salt stress induces the internalization of PIP2;1 from the PM to the vacuolar lumen, and that these processes are dependent on clathrin, PI3K and PI4K. PMID:27163638

  20. Role of residual stresses induced by double peening on fatigue durability of automotive leaf springs

    International Nuclear Information System (INIS)

    Highlights: ► Proper choice of peening media is needed for higher fatigue strength in leaf springs. ► Optimum double-peening condition for leaf springs: 0.8 mm shot, followed by 0.3 mm. ► Fatigue life correlates with residual stress levels at the surface (up to 0.02 mm). ► Residual stress profile below 0.02 mm has no measurable effect over fatigue life. ► Failure of the investigated parts is nucleation-controlled. - Abstract: Improvement of fatigue life in parts subjected to cyclic stresses by application of mechanical surface treatment processes is already well known, both in the industry and in the academy. Dealing with automotive springs, the shot peening process becomes an essential step in manufacturing. In the case of leaf springs, however, a systematic investigation of the effect of shot peening on fatigue life is still required. The aim of the present work is to improve the knowledge on the role of shot peening in manufacturing leaf springs for vehicles, through the analysis of residual stresses by X-ray diffraction and fatigue tests on a series of samples that were subject to ten different peening schedules. Among the investigated processes, the usage of 0.8 mm diameter cast steel shot followed by a second peening with 0.3 mm diameter cast steel shot leads to optimal performance, regarding fatigue life. X-ray diffraction analysis shows that this improved performance may be attributed to residual compressive stress maintained until a depth of 0.02 mm below the surface, which directly influences fatigue crack nucleation. Residual stresses induced by shot peening in larger depths have no influence on the sample’s fatigue life

  1. Oxidative stress induces caveolin 1 degradation and impairs caveolae functions in skeletal muscle cells.

    Directory of Open Access Journals (Sweden)

    Alexis Mougeolle

    Full Text Available Increased level of oxidative stress, a major actor of cellular aging, impairs the regenerative capacity of skeletal muscle and leads to the reduction in the number and size of muscle fibers causing sarcopenia. Caveolin 1 is the major component of caveolae, small membrane invaginations involved in signaling and endocytic trafficking. Their role has recently expanded to mechanosensing and to the regulation of oxidative stress-induced pathways. Here, we increased the amount of reactive oxidative species in myoblasts by addition of hydrogen peroxide (H2O2 at non-toxic concentrations. The expression level of caveolin 1 was significantly decreased as early as 10 min after 500 μM H2O2 treatment. This reduction was not observed in the presence of a proteasome inhibitor, suggesting that caveolin 1 was rapidly degraded by the proteasome. In spite of caveolin 1 decrease, caveolae were still able to assemble at the plasma membrane. Their functions however were significantly perturbed by oxidative stress. Endocytosis of a ceramide analog monitored by flow cytometry was significantly diminished after H2O2 treatment, indicating that oxidative stress impaired its selective internalization via caveolae. The contribution of caveolae to the plasma membrane reservoir has been monitored after osmotic cell swelling. H2O2 treatment increased membrane fragility revealing that treated cells were more sensitive to an acute mechanical stress. Altogether, our results indicate that H2O2 decreased caveolin 1 expression and impaired caveolae functions. These data give new insights on age-related deficiencies in skeletal muscle.

  2. Restraint stress-induced morphological changes at the blood-brain barrier in adult rats

    Directory of Open Access Journals (Sweden)

    Petra eSántha

    2016-01-01

    Full Text Available Stress is well known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognised in the development of neurodegenerative disorders, such as Alzheimer’s disease, dysfunction of the blood-brain barrier has been linked to stress-related psychiatric diseases only recently. In the present study the effects of restraint stress with different duration (1, 3 and 21 days were investigated on the morphology of the blood-brain barrier in male adult Wistar rats. Frontal cortex and hippocampus sections were immunostained for markers of brain endothelial cells (claudin-5, occludin and glucose transporter-1 and astroglia (GFAP. Staining pattern and intensity were visualized by confocal microscopy and evaluated by several types of image analysis. The ultrastructure of brain capillaries was investigated by electron microscopy. Morphological changes and intensity alterations in brain endothelial tight junction proteins claudin-5 and occludin were induced by stress. Following restraint stress significant increases in the fluorescence intensity of glucose transporter-1 were detected in brain endothelial cells in the frontal cortex and hippocampus. Significant reductions in GFAP fluorescence intensity were observed in the frontal cortex in all stress groups. As observed by electron microscopy, one-day acute stress induced morphological changes indicating damage in capillary endothelial cells in both brain regions. After 21 days of stress thicker and irregular capillary basal membranes in the hippocampus and edema in astrocytes in both regions were seen. These findings indicate that stress exerts time-dependent changes in the staining pattern of tight junction proteins occludin, claudin-5 and glucose transporter-1 at the level of brain capillaries and in the ultrastructure of brain endothelial cells and astroglial endfeet, which may contribute to neurodegenerative processes

  3. Seagrass proliferation precedes mortality during hypo-salinity events: a stress-induced morphometric response.

    Directory of Open Access Journals (Sweden)

    Catherine J Collier

    Full Text Available Halophytes, such as seagrasses, predominantly form habitats in coastal and estuarine areas. These habitats can be seasonally exposed to hypo-salinity events during watershed runoff exposing them to dramatic salinity shifts and osmotic shock. The manifestation of this osmotic shock on seagrass morphology and phenology was tested in three Indo-Pacific seagrass species, Halophila ovalis, Halodule uninervis and Zostera muelleri, to hypo-salinity ranging from 3 to 36 PSU at 3 PSU increments for 10 weeks. All three species had broad salinity tolerance but demonstrated a moderate hypo-salinity stress response--analogous to a stress induced morphometric response (SIMR. Shoot proliferation occurred at salinities <30 PSU, with the largest increases, up to 400% increase in shoot density, occurring at the sub-lethal salinities <15 PSU, with the specific salinity associated with peak shoot density being variable among species. Resources were not diverted away from leaf growth or shoot development to support the new shoot production. However, at sub-lethal salinities where shoots proliferated, flowering was severely reduced for H. ovalis, the only species to flower during this experiment, demonstrating a diversion of resources away from sexual reproduction to support the investment in new shoots. This SIMR response preceded mortality, which occurred at 3 PSU for H. ovalis and 6 PSU for H. uninervis, while complete mortality was not reached for Z. muelleri. This is the first study to identify a SIMR in seagrasses, being detectable due to the fine resolution of salinity treatments tested. The detection of SIMR demonstrates the need for caution in interpreting in-situ changes in shoot density as shoot proliferation could be interpreted as a healthy or positive plant response to environmental conditions, when in fact it could signal pre-mortality stress.

  4. Thermal stress induced voids in nanoscale copper interconnects by in-situ TEM heating

    Science.gov (United States)

    An, Jin Ho

    Stress induced void formation in Cu interconnects, due to thermal stresses generated during the processing of semiconductors, is an increasing reliability issue in the semiconductor industry as Cu interconnects are being downscaled to follow the demand for faster chip speed. In this work, 1.8 micron and 180 nm wide Cu interconnects, fabricated by Freescale Semiconductors, were subjected to thermal cycles, in-situ in the TEM, to investigate the stress relaxation mechanisms as a function of interconnect linewidth. The experiments show that the 1.8 micron Cu interconnect lines relax the thermal stresses through dislocation nucleation and motion while the Cu interconnect 180 nm lines exhibit void formation. Void formation in 180 nm lines occurs predominantly at triple junctions where the Ta diffusion barrier meets a Cu grain boundary. In order to understand void formation in 180 nm lines, the grain orientation and local stresses are determined. In particular, Nanobeam Diffraction (NBD) in the TEM is used to obtain the diffraction pattern of each grain, from which the crystal orientation is evaluated by the ACT (Automated Crystallography for TEM) software. In addition, 2D Finite Element Method (FEM) simulations are performed using the Object Oriented Finite Modeling (OOF2) software to correlate grain orientation with local stresses, and consequently void formation. According to the experimental and simulation results obtained, void formation in 180nm Cu interconnects does not seem to be solely dependent on local stresses, but a combination of diffusion paths available, stress gradients and possibly the presence of defects. In addition, based on the in-situ TEM observations, void growth seems to occur through grain boundary and/or interfacial diffusion. However, in-situ STEM observations of fully opened voids post-failure show pileup of material at the Cu grain surfaces. This means that surface or interface diffusion is also very active during void growth in the presence

  5. The Batten disease gene CLN3 confers resistance to endoplasmic reticulum stress induced by tunicamycin

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Dan, E-mail: danw@bjmu.edu.cn [Department of Medical Genetics, Peking University Health Science Center, No 38 Xueyuan Road, Haidian district, Beijing 100191 (China); Liu, Jing; Wu, Baiyan [Department of Medical Genetics, Peking University Health Science Center, No 38 Xueyuan Road, Haidian district, Beijing 100191 (China); Tu, Bo; Zhu, Weiguo [Department of Biochemistry and Molecular Biology, Peking University Health Science Center, No 38 Xueyuan Road, Haidian district, Beijing 100191 (China); Luo, Jianyuan, E-mail: jluo@som.umaryland.edu [Department of Medical Genetics, Peking University Health Science Center, No 38 Xueyuan Road, Haidian district, Beijing 100191 (China); Department of Medical and Research Technology, School of Medicine, University of Maryland, Baltimore 21201 (United States)

    2014-04-25

    Highlights: • The work reveals a protective properties of CLN3 towards TM-induced apoptosis. • CLN3 regulates expression of the GRP78 and the CHOP in response to the ER stress. • CLN3 plays a specific role in the ERS response. - Abstract: Mutations in CLN3 gene cause juvenile neuronal ceroid lipofuscinosis (JNCL or Batten disease), an early-onset neurodegenerative disorder that is characterized by the accumulation of ceroid lipofuscin within lysosomes. The function of the CLN3 protein remains unclear and is presumed to be related to Endoplasmic reticulum (ER) stress. To investigate the function of CLN3 in the ER stress signaling pathway, we measured proliferation and apoptosis in cells transfected with normal and mutant CLN3 after treatment with the ER stress inducer tunicamycin (TM). We found that overexpression of CLN3 was sufficient in conferring increased resistance to ER stress. Wild-type CLN3 protected cells from TM-induced apoptosis and increased cell proliferation. Overexpression of wild-type CLN3 enhanced expression of the ER chaperone protein, glucose-regulated protein 78 (GRP78), and reduced expression of the proapoptotic protein CCAAT/-enhancer-binding protein homologous protein (CHOP). In contrast, overexpression of mutant CLN3 or siRNA knockdown of CLN3 produced the opposite effect. Together, our data suggest that the lack of CLN3 function in cells leads to a failure of management in the response to ER stress and this may be the key deficit in JNCL that causes neuronal degeneration.

  6. Increased limbic phosphorylated extracellular-regulated kinase 1 and 2 expression after chronic stress is reduced by cyclic 17 beta-estradiol administration

    NARCIS (Netherlands)

    Gerrits, M.; Westenbroek, C.; Koch, T.; Grootkarzijn, A.; Ter Horst, G. J.

    2006-01-01

    Chronic stress induced neuronal changes that may have consequences for subsequent stress responses. For example, chronic stress in rats rearranges dendritic branching patterns and disturbs the phosphorylation of extracellular-regulated kinase 1 and 2 (ERK) 1/2 throughout the limbic system. Stress-in

  7. Aloin Protects Skin Fibroblasts from Heat Stress-Induced Oxidative Stress Damage by Regulating the Oxidative Defense System.

    Science.gov (United States)

    Liu, Fu-Wei; Liu, Fu-Chao; Wang, Yu-Ren; Tsai, Hsin-I; Yu, Huang-Ping

    2015-01-01

    Oxidative stress is commonly involved in the pathogenesis of skin damage induced by environmental factors, such as heat stress. Skin fibroblasts are responsible for the connective tissue regeneration and the skin recovery from injury. Aloin, a bioactive compound in Aloe vera, has been reported to have various pharmacological activities, such as anti-inflammatory effects. The aim of this study was to investigate the protective effect of aloin against heat stress-mediated oxidative stress in human skin fibroblast Hs68 cells. Hs68 cells were first incubated at 43°C for 30 min to mimic heat stress. The study was further examined if aloin has any effect on heat stress-induced oxidative stress. We found that aloin protected Hs68 cells against heat stress-induced damage, as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assay. Aloin protected Hs68 cells by regulating reactive oxygen species production and increasing the levels of glutathione, cytosolic and mitochondrial superoxide dismutase. Aloin also prevented the elevation of thiobarbituric acid reactive substances and the reduction of 8-OH-dG induced by heat stress. These results indicated that aloin protected human skin fibroblasts from heat stress-induced oxidative stress damage by regulating the oxidative defense system. PMID:26637174

  8. SIRT1 sensitizes hepatocellular carcinoma cells expressing hepatitis B virus X protein to oxidative stress-induced apoptosis

    International Nuclear Information System (INIS)

    Highlights: ► Up-regulation of SIRT1 protein and activity sensitizes Hep3B-HBX cells to oxidative stress-induced apoptosis. ► Nuclear localization of SIRT1 is not required for oxidation-induced apoptosis. ► Ectopic expression and enhanced activity of SIRT1 attenuate JNK phosphorylation. ► Inhibition of SIRT1 activity restores resistance to oxidation-induced apoptosis through JNK activation. -- Abstract: We previously showed that SIRT1 deacetylase inhibits proliferation of hepatocellular carcinoma cells expressing hepatitis B virus (HBV) X protein (HBX), by destabilization of β-catenin. Here, we report another role for SIRT1 in HBX-mediated resistance to oxidative stress. Ectopic expression and enhanced activity of SIRT1 sensitize Hep3B cells stably expressing HBX to oxidative stress-induced apoptosis. SIRT1 mutant analysis showed that nuclear localization of SIRT1 is not required for sensitization of oxidation-mediated apoptosis. Furthermore, ectopic expression of SIRT1 and treatment with resveratrol (a SIRT1 activator) attenuated JNK phosphorylation, which is a prerequisite for resistance to oxidative stress-induced apoptosis. Conversely, suppression of SIRT1 activity with nicotinamide inhibited the effect of resveratrol on JNK phosphorylation, leading to restoration of resistance to oxidation-induced apoptosis. Taken together, these results suggest that up-regulation of SIRT1 under oxidative stress may be a therapeutic strategy for treatment of hepatocellular carcinoma cells related to HBV through inhibition of JNK activation.

  9. Aloin Protects Skin Fibroblasts from Heat Stress-Induced Oxidative Stress Damage by Regulating the Oxidative Defense System.

    Directory of Open Access Journals (Sweden)

    Fu-Wei Liu

    Full Text Available Oxidative stress is commonly involved in the pathogenesis of skin damage induced by environmental factors, such as heat stress. Skin fibroblasts are responsible for the connective tissue regeneration and the skin recovery from injury. Aloin, a bioactive compound in Aloe vera, has been reported to have various pharmacological activities, such as anti-inflammatory effects. The aim of this study was to investigate the protective effect of aloin against heat stress-mediated oxidative stress in human skin fibroblast Hs68 cells. Hs68 cells were first incubated at 43°C for 30 min to mimic heat stress. The study was further examined if aloin has any effect on heat stress-induced oxidative stress. We found that aloin protected Hs68 cells against heat stress-induced damage, as assessed by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assay. Aloin protected Hs68 cells by regulating reactive oxygen species production and increasing the levels of glutathione, cytosolic and mitochondrial superoxide dismutase. Aloin also prevented the elevation of thiobarbituric acid reactive substances and the reduction of 8-OH-dG induced by heat stress. These results indicated that aloin protected human skin fibroblasts from heat stress-induced oxidative stress damage by regulating the oxidative defense system.

  10. Nitric Oxide Plays a Central Role in Water Stress-Induced Tanshinone Production in Salvia miltiorrhiza Hairy Roots

    Directory of Open Access Journals (Sweden)

    Xuhong Du

    2015-04-01

    Full Text Available Nitric oxide (NO, a well-known signaling molecule plays an important role in abiotic and biotic stress-induced production of plant secondary metabolites. In this study, roles of NO in water stress-induced tanshinone production in Salvia miltiorrhiza hairy roots were investigated. The results showed that accumulations of four tanshinone compounds in S. miltiorrhiza hairy roots were significantly stimulated by sodium nitroprusside (SNP, a NO donor at 100 μM. Effects of SNP were just partially arrested by the mevalonate (MVA pathway inhibitor (mevinolin, but were completely inhibited by the 2-C-methyl-d-erythritol-4-phosphate pathway (MEP inhibitor (fosmidomycin. The increase of tanshinone accumulation and the up-regulation of HMGR and DXR expression by PEG and ABA treatments were partially inhibited by an inhibitor of NO biosynthesis (Nω-nitro-L-arginine methyl ester (L-NAME and a NO scavenger (2-(4-Carboxyphenyl- 4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (c-PTIO. Simultaneously, NO generation in the hairy roots was triggered by PEG and ABA, and the effects were also arrested by c-PTIO and L-NAME. These results indicated that NO signaling probably plays a central role in water stress-induced tanshinone production in S. miltiorrhiza hairy roots. SNP mainly stimulated the MEP pathway to increase tanshinone accumulation.

  11. Studying the cytotoxicity and oxidative stress induced by two kinds of bentonite particles on human B lymphoblast cells in vitro.

    Science.gov (United States)

    Zhang, Meibian; Lu, Yezhen; Li, Xiaoxue; Chen, Qing; Lu, Longxi; Xing, Mingluan; Zou, Hua; He, Jiliang

    2010-02-12

    The aim of the present study was to evaluate the cytotoxicity and oxidative stress induced by native and active bentonite particles (BPs) on human B lymphoblast cells using seven assays. Our results showed that the order of cytotoxicity was: active BPs>native BPs>quartz particles (DQ-12)>gypsum, according to the IC50 values in CCK-8 assay and neutral red uptake (NRU) assay. The lactate dehydrogenase (LDH) leakage, the proportions of early apoptotic cells, the reactive oxygen species (ROS) generation, the superoxide dismutase (SOD) inhibition and the malondialdehyde (MDA) release in the native and active BPs groups were significantly higher than those in the gypsum and DQ-12 groups (Pstress induced by active BPs was significantly higher than that induced by native BPs (Pstress on human B lymphoblast cells in vitro. The cytotoxic difference between active BPs and native BPs may be associated with the adsorption capacity of BPs and oxidative stress induced by BPs to a certain extent. The insoluble particle fractions may play a main role in the cytotoxic effects and oxidative stress induced by BPs.

  12. Neuropeptide FF and related peptides attenuates warm-, but not cold-water swim stress-induced analgesia in mice.

    Science.gov (United States)

    Li, Ning; Han, Zheng-lan; Fang, Quan; Wang, Zi-long; Tang, Hong-zhu; Ren, Hui; Wang, Rui

    2012-08-01

    Neuropeptide FF (NPFF) belongs to a neuropeptide family including two receptors (NPFF(1) and NPFF(2)). NPFF system has been reported to play important roles in pain transmission. The aim of the present study was to investigate the roles of NPFF related peptides and their receptors in swim stress-induced analgesia (SIA). Nociceptive test was performed in mice stressed by forced swimming in water at 15 °C (cold water swimming) or 32 °C (warm water swimming). Warm water swimming produced a naloxone-mediated antinociceptive effect. This warm water swim SIA was dose-dependently antagonized by i.c.v. injection of NPFF and two related peptides (3-30 nmol), NPVF and dNPA, which exhibited the highest selectivities for NPFF(1) and NPFF(2) receptors, respectively. Moreover, the selective NPFF receptor antagonist RF9 (30 nmol) was inactive by itself, but prevented the effects of NPFF and related peptides. Cold-water swimming produced a wilder analgesic effect that was blocked by MK-801, but not naloxone. However, NPFF system failed to modify the cold water swim stress-induced analgesia. These findings demonstrated that NPFF and related peptides attenuated opioid-mediated form of SIA via NPFF receptors in the brain, but not non-opioid swim stress-induced analgesia. These data further support an anti-opioid character of NPFF system.

  13. Prickly pear cactus (Opuntia ficus indica var. saboten) protects against stress-induced acute gastric lesions in rats.

    Science.gov (United States)

    Kim, Seung Hyun; Jeon, Byung Ju; Kim, Dae Hyun; Kim, Tae Il; Lee, Hee Kyoung; Han, Dae Seob; Lee, Jong-Hwan; Kim, Tae Bum; Kim, Jung Wha; Sung, Sang Hyun

    2012-11-01

    The protective activity of prickly pear cactus (Opuntia ficus indica var. saboten) fruit juice and its main constituent, betanin, were evaluated against stress-induced acute gastric lesions in rats. After 6 h of water immersion restraint stress (WIRS), gastric mucosal lesions with bleeding were induced in Sprague-Dawley rats. Pretreatment of a lyophilized powder containing O. ficus indica var. saboten fruit juice and maltodextrin (OFSM) and betanin significantly reduced stress lesions (800-1600 mg/kg). Both OFSM and betanin effectively prevented the decrease in gastric mucus content as detected by alcian blue staining. In addition, OFSM significantly suppressed WIRS-induced increases in the level of gastric mucosal tumor necrosis factor-α and myeloperoxidase (MPO). Betanin alone was only effective in decreasing MPO. These results revealed the protective activity of OFSM against stress-induced acute gastric lesions and that betanin may contribute to OFSM's gastric protective activity, at least in part. When OFSM and betanin were taken together, OFSM exerted gastroprotective activity against stress-induced gastric lesions by maintaining gastric mucus, which might be related to the attenuation of MPO-mediated damage and proinflammatory cytokine production.

  14. Stress-induced sphingolipid signaling: role of type-2 neutral sphingomyelinase in murine cell apoptosis and proliferation.

    Directory of Open Access Journals (Sweden)

    Raphael Devillard

    Full Text Available BACKGROUND: Sphingomyelin hydrolysis in response to stress-inducing agents, and subsequent ceramide generation, are implicated in various cellular responses, including apoptosis, inflammation and proliferation, depending on the nature of the different acidic or neutral sphingomyelinases. This study was carried out to investigate whether the neutral Mg(2+-dependent neutral sphingomyelinase-2 (nSMase2 plays a role in the cellular signaling evoked by TNFalpha and oxidized LDLs, two stress-inducing agents, which are mitogenic at low concentrations and proapoptotic at higher concentrations. METHODOLOGY AND PRINCIPAL FINDINGS: For this purpose, we used nSMase2-deficient cells from homozygous fro/fro (fragilitas ossium mice and nSMase2-deficient cells reconstituted with a V5-tagged nSMase2. We report that the genetic defect of nSMase2 (in fibroblasts from fro/fro mice does not alter the TNFalpha and oxidized LDLs-mediated apoptotic response. Likewise, the hepatic toxicity of TNFalpha is similar in wild type and fro mice, thus is independent of nSMase2 activation. In contrast, the mitogenic response elicited by low concentrations of TNFalpha and oxidized LDLs (but not fetal calf serum requires nSMase2 activation. CONCLUSION AND SIGNIFICANCE: nSMase2 activation is not involved in apoptosis mediated by TNFalpha and oxidized LDLs in murine fibroblasts, and in the hepatotoxicity of TNFalpha in mice, but is required for the mitogenic response to stress-inducing agents.

  15. HDAC2 selectively regulates FOXO3a-mediated gene transcription during oxidative stress-induced neuronal cell death.

    Science.gov (United States)

    Peng, Shengyi; Zhao, Siqi; Yan, Feng; Cheng, Jinbo; Huang, Li; Chen, Hong; Liu, Qingsong; Ji, Xunming; Yuan, Zengqiang

    2015-01-21

    All neurodegenerative diseases are associated with oxidative stress-induced neuronal death. Forkhead box O3a (FOXO3a) is a key transcription factor involved in neuronal apoptosis. However, how FOXO3a forms complexes and functions in oxidative stress processing remains largely unknown. In the present study, we show that histone deacetylase 2 (HDAC2) forms a physical complex with FOXO3a, which plays an important role in FOXO3a-dependent gene transcription and oxidative stress-induced mouse cerebellar granule neuron (CGN) apoptosis. Interestingly, we also found that HDAC2 became selectively enriched in the promoter region of the p21 gene, but not those of other target genes, and inhibited FOXO3a-mediated p21 transcription. Furthermore, we found that oxidative stress reduced the interaction between FOXO3a and HDAC2, leading to an increased histone H4K16 acetylation level in the p21 promoter region and upregulated p21 expression in a manner independent of p53 or E2F1. Phosphorylation of HDAC2 at Ser 394 is important for the HDAC2-FOXO3a interaction, and we found that cerebral ischemia/reperfusion reduced phosphorylation of HDAC2 at Ser 394 and mitigated the HDAC2-FOXO3a interaction in mouse brain tissue. Our study reveals the novel regulation of FOXO3a-mediated selective gene transcription via epigenetic modification in the process of oxidative stress-induced cell death, which could be exploited therapeutically.

  16. The effects of feeding unpredictability and classical conditioning on pre-release training of white-lipped peccary (Mammalia, Tayassuidae.

    Directory of Open Access Journals (Sweden)

    Selene S C Nogueira

    Full Text Available Some authors have suggested that environmental unpredictability, accompanied by some sort of signal for behavioral conditioning, can boost activity or foster exploratory behavior, which may increase post-release success in re-introduction programs. Thus, using white-lipped peccary (Tayassu pecari, a vulnerable Neotropical species, as a model, we evaluated an unpredictable feedin