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Sample records for chronic unpredictable stress

  1. 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)...

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

    Science.gov (United States)

    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

  3. 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.

  4. 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.

  5. 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...

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

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    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.

  7. 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...

  8. 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,...

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

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    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

  10. 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.

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

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    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.

  12. 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.

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

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    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.

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

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    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

  15. 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...

  16. 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.

  17. 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...

  18. 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

  19. 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.

  20. 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

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

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    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

  2. 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...

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

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    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...

  4. 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...

  5. 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.

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

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    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

  7. 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...

  8. 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

  9. 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

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

    Science.gov (United States)

    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

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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.

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

    Science.gov (United States)

    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

  18. 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...

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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...

  4. 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...

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

    Science.gov (United States)

    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

  6. 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 ...

  7. 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

  8. 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...

  9. 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.

  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. 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.

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

    Science.gov (United States)

    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 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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

  18. 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

  19. 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...

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

    OpenAIRE

    Harisudhan Thanukrishnan; Babu Chidambaram; Nirmal Jayabalan; Ramanathan Muthiah

    2008-01-01

    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 carri...

  1. 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

  2. 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

  3. 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...

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

    OpenAIRE

    Victoria Braithwaite

    2013-01-01

    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. ...

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

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    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.

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

    Science.gov (United States)

    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

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

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    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.

  8. 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

  9. 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....

  10. 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

  11. 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。

  12. 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

  13. 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.

  14. 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

  15. 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.

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

    Science.gov (United States)

    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

  17. 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.

  18. 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

  19. 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

  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. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  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. 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...

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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.

  16. 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

  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. Chronic stress, cortical plasticity and neuroecology.

    Science.gov (United States)

    Reser, Jared Edward

    2016-08-01

    Prolonged psychological stress and accompanying elevations in blood cortisol are known to induce hypometabolism and decreasing synaptic density in the hippocampus and the prefrontal cortex (PFC). This article evaluates and explores evidence supporting the hypothesis that these, and other, selective effects of prolonged stress constitute a neuroecological program that adaptively modifies behavior in mammals experiencing adverse conditions. Three complementary hypotheses are proposed: (1) chronic stress signifies that the prevailing environment is life-threatening, indicating that the animal should decrease activity in brain areas capable of inhibiting the stress axis; (2) stress signifies that the environment is unpredictable, that high-level cognition may be less effective, and that the animal should increase its reliance on defensive, procedural and instinctual behaviors mediated by lower brain centers; and (3) stress indicates that environmental events are proving difficult to systemize based on delayed associations, and thus the maintenance of contextual, task-relevant information in the PFC need not be maintained for temporally-extended periods. Humans, along with countless other species of vertebrates, have been shown to make predictive, adaptive responses to chronic stress in many systems including metabolic, cardiovascular, neuroendocrine, and even amygdalar and striatal systems. It is proposed in this article that humans and other mammals may also have an inducible, cerebrocortical response to pronounced stress that mediates a transition from time-intensive, explicit (controlled/attentional/top-down) processing of information to quick, implicit (automatic/preattentive/bottom-up) processing. PMID:27334119

  20. 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

  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

    The study was to investigate the role of homocysteine (Hey) which was released by hippocampal glial cells and its relationship with NMDA receptor and AMPA receptor in depression induced by chronic unpredictable mild stress (CUMS), and explore the mechanism of changes of Glu/Glu receptor in glial cells and neurons. CUMS-induced depression model was established. The body weight of rats was weighed on the 1st, 7th, 14th, and 21st days during the experiment. The behavioral performances were observed by means of sucrose consumption test, open field test and tail suspension test. Intrahippocampal microinjection of Hcy, NMDA receptor antagonist MK-801 and AMPA receptor antagonist NBQX was performed under stereotaxic guide cannula. The concentration of Glu and the expression of its receptors' subunits were detected respectively by high performance liquid chromatography (HPLC) and Western blot. The Hey content and the levels of phosphorylation of NMDA receptor and AMPA receptor in hippocampus were separately determined by enzyme linked immunosorbent assay (ELISA). The results showed that CUMS significantly induced the depression-like behaviors in rats, and the content of Glu and Hcy, the expression of NMDA receptors' subunits NR1/NR2B and the level of phosphorylation of NMDA receptor (p-NMDAR) in hippocampus increased significantly, while the expression of AMPA receptors' subunits GluR2/3 and the level of phosphorylation of AMPA receptor (p-AMPAR) decreased significantly. Microinjection of Hcy into hippocampus resulted in similar animal depression-like behaviors and increased Glu content compared to the CON/SAL group, the expression of NRl/NR2B/GluR2/3 and the level of p-NMDAR increased significantly, but the level of p-AMPAR reduced observably. Intrahippocampal injections of MK-801 effectively improved the depression-like behaviors induced by CUMS and Hcy, and attenuated the elevation of Glu content induced by Hcy in hippocampus, whereas NBQX could not improve the

  2. 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...

  3. 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 ...

  4. 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

  5. Effects of Unpredictable Variable Prenatal Stress (UVPS) on Bdnf DNA Methylation and Telomere Length in the Adult Rat Brain

    Science.gov (United States)

    Blaze, Jennifer; Asok, A.; Moyer, E. L.; Roth, T. L.; Ronca, A. E.

    2015-01-01

    In utero exposure to stress can shape neurobiological and behavioral outcomes in offspring, producing vulnerability to psychopathology later in life. Animal models of prenatal stress likewise have demonstrated long-­-term alterations in brain function and behavioral deficits in offspring. For example, using a rodent model of unpredictable variable prenatal stress (UVPS), in which dams are exposed to unpredictable, variable stress across pregnancy, we have found increased body weight and anxiety-­-like behavior in adult male, but not female, offspring. DNA methylation (addition of methyl groups to cytosines which normally represses gene transcription) and changes in telomere length (TTAGGG repeats on the ends of chromosomes) are two molecular modifications that result from stress and could be responsible for the long-­-term effects of UVPS. Here, we measured methylation of brain-­-derived neurotrophic factor (bdnf), a gene important in development and plasticity, and telomere length in the brains of adult offspring from the UVPS model. Results indicate that prenatally stressed adult males have greater methylation in the medial prefrontal cortex (mPFC) compared to non-­-stressed controls, while females have greater methylation in the ventral hippocampus compared to controls. Further, prenatally stressed males had shorter telomeres than controls in the mPFC. These findings demonstrate the ability of UVPS to produce epigenetic alterations and changes in telomere length across behaviorally-­-relevant brain regions, which may have linkages to the phenotypic outcomes.

  6. 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

  7. Perception of Sentence Stress in Speech Correlates with the Temporal Unpredictability of Prosodic Features

    Science.gov (United States)

    Kakouros, Sofoklis; Räsänen, Okko

    2016-01-01

    Numerous studies have examined the acoustic correlates of sentential stress and its underlying linguistic functionality. However, the mechanism that connects stress cues to the listener's attentional processing has remained unclear. Also, the learnability versus innateness of stress perception has not been widely discussed. In this work, we…

  8. Chronic Psychosocial Stress and Hypertension

    OpenAIRE

    Spruill, Tanya M.

    2010-01-01

    Genetic and behavioral factors do not fully explain the development of hypertension, and there is increasing evidence suggesting that psychosocial factors may also play an important role. Exposure to chronic stress has been hypothesized as a risk factor for hypertension, and occupational stress, stressful aspects of the social environment, and low socioeconomic status have each been studied extensively. The study of discrimination is a more recent and rapidly growing area of investigation and...

  9. Prenatal stress effects in a wild, long-lived primate: predictive adaptive responses in an unpredictable environment.

    Science.gov (United States)

    Berghänel, Andreas; Heistermann, Michael; Schülke, Oliver; Ostner, Julia

    2016-09-28

    Prenatal maternal stress affects offspring phenotype in numerous species including humans, but it is debated whether these effects are evolutionarily adaptive. Relating stress to adverse conditions, current explanations invoke either short-term developmental constraints on offspring phenotype resulting in decelerated growth to avoid starvation, or long-term predictive adaptive responses (PARs) resulting in accelerated growth and reproduction in response to reduced life expectancies. Two PAR subtypes were proposed, acting either on predicted internal somatic states or predicted external environmental conditions, but because both affect phenotypes similarly, they are largely indistinguishable. Only external (not internal) PARs rely on high environmental stability particularly in long-lived species. We report on a crucial test case in a wild long-lived mammal, the Assamese macaque (Macaca assamensis), which evolved and lives in an unpredictable environment where external PARs are probably not advantageous. We quantified food availability, growth, motor skills, maternal caretaking style and maternal physiological stress from faecal glucocorticoid measures. Prenatal maternal stress was negatively correlated to prenatal food availability and led to accelerated offspring growth accompanied by decelerated motor skill acquisition and reduced immune function. These results support the 'internal PAR' theory, which stresses the role of stable adverse internal somatic states rather than stable external environments. PMID:27655764

  10. Prenatal stress effects in a wild, long-lived primate: predictive adaptive responses in an unpredictable environment

    Science.gov (United States)

    Heistermann, Michael; Schülke, Oliver; Ostner, Julia

    2016-01-01

    Prenatal maternal stress affects offspring phenotype in numerous species including humans, but it is debated whether these effects are evolutionarily adaptive. Relating stress to adverse conditions, current explanations invoke either short-term developmental constraints on offspring phenotype resulting in decelerated growth to avoid starvation, or long-term predictive adaptive responses (PARs) resulting in accelerated growth and reproduction in response to reduced life expectancies. Two PAR subtypes were proposed, acting either on predicted internal somatic states or predicted external environmental conditions, but because both affect phenotypes similarly, they are largely indistinguishable. Only external (not internal) PARs rely on high environmental stability particularly in long-lived species. We report on a crucial test case in a wild long-lived mammal, the Assamese macaque (Macaca assamensis), which evolved and lives in an unpredictable environment where external PARs are probably not advantageous. We quantified food availability, growth, motor skills, maternal caretaking style and maternal physiological stress from faecal glucocorticoid measures. Prenatal maternal stress was negatively correlated to prenatal food availability and led to accelerated offspring growth accompanied by decelerated motor skill acquisition and reduced immune function. These results support the ‘internal PAR’ theory, which stresses the role of stable adverse internal somatic states rather than stable external environments. PMID:27655764

  11. From Memory Impairment to Posttraumatic Stress Disorder-Like Phenotypes: The Critical Role of an Unpredictable Second Traumatic Experience.

    Science.gov (United States)

    Finsterwald, Charles; Steinmetz, Adam B; Travaglia, Alessio; Alberini, Cristina M

    2015-12-01

    Arousal and stress critically regulate memory formation and retention. Increasing levels of stress produce an inverted U-shaped effect on cognitive performance, including the retention of explicit memories, and experiencing a severe stress during a traumatic event may lead to posttraumatic stress disorder (PTSD). The molecular mechanisms underlying the impairing effect of a severe stress on memory and the key contribution of traumatic experiences toward the development of PTSD are still unknown. Here, using increasing footshock intensities in an inhibitory avoidance paradigm, we reproduced the inverted U-shaped curve of memory performance in rats. We then show that the inverted U profile of memory performance correlates with an inverted U profile of corticosterone level in the circulation and of brain-derived neurotrophic factor, phosphorylated tropomyosin-receptor kinase B, and methyl CpG binding protein in the dorsal hippocampus. Furthermore, training with the highest footshock intensity (traumatic experience) led to a significant elevation of hippocampal glucocorticoid receptors. Exposure to an unpredictable, but not to a predictable, highly stressful reminder shock after a first traumatic experience resulted in PTSD-like phenotypes, including increased memory of the trauma, high anxiety, threat generalization, and resistance to extinction. Systemic corticosterone injection immediately after the traumatic experience, but not 3 d later, was sufficient to produce PTSD-like phenotypes. We suggest that, although after a first traumatic experience a suppression of the corticosterone-dependent response protects against the development of an anxiety disorder, experiencing more than one trauma (multiple hits) is a critical contributor to the etiology of PTSD. PMID:26631471

  12. 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.

  13. 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.

  14. 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...

  15. Chronic stress effects in contralateral medial pterygoid muscle of rats with occlusion alteration.

    Science.gov (United States)

    Loyola, Bruno Melo; Nascimento, Glauce Crivelaro; Fernández, Rodrigo Alberto Restrepo; Iyomasa, Daniela Mizusaki; Pereira, Yamba Carla Lara; Leite-Panissi, Christie Ramos Andrade; Issa, João Paulo Mardegan; Iyomasa, Mamie Mizusaki

    2016-10-01

    Temporomandibular disorder (TMD) has a high prevalence in our society, characterized by a severe pain condition of the masticatory muscles and temporomandibular joint. Despite the indication of multiple factor initiators of TMD, there is still controversy about its etiology and its pathophysiology is poorly understood. Using rats as experimental animals we investigated the effect of unpredictable chronic stress with or without unilateral molar extraction on the contralateral medial pterygoid muscle. Our hypothesis is that these two factors induce changes in morphology, oxidative metabolism and oxidative stress of muscle fibers. Young adult male Wistar rats (±200g) were divided into four groups: a group with extraction and unpredictable chronic stress (E+US); with extraction and without stress (E+C); without extraction and with unpredictable chronic stress (NO+US); and a control group without either extraction or stress (NO+C). The animals were subjected to unilateral extraction of the upper left molars, under intraperitoneal anesthesia with 4% Xylazine (10mg/kg) and 10% Ketamine (80mg/kg) on day zero. The rats of groups E+US and NO+US were submitted to different protocols of stress, from the 14th day after the extraction. The protocols were different every day for five consecutive days, which were repeated from the 6th day for five days more. Contralateral medial pterygoid muscles were obtained on the 24th day after the start of the experiment for morphological, metabolic, capillary density, and oxidative stress analysis. The data from capillary density showed a decrease of capillaries in animals subjected to dental extraction, compared with those without extraction and an increase of laminin expression in the group submitted to the unpredictable chronic stress when compared to the unexposed to stress. SDH test revealed a decrease of light fibers in the group submitted to unilateral extraction of molars, compared with this area in the control group. In E+US and NO

  16. Chronic Mild Prenatal Stress Exacerbates the Allergen-Induced Airway Inflammation in Rats

    Directory of Open Access Journals (Sweden)

    Paulo J. Nogueira

    1999-01-01

    Full Text Available The effects of chronic mild prenatal stress on leukocyte infiltration into the airways was investigated in rat offspring. The chronic prenatal stress consisted of transitory and variable changes in the rat's living conditions. Offspring at adult age were actively sensitized (day 0 and intratracheally challenged (day 14 with ovalbumin. Bronchoalveolar lavage was performed in the offspring at 48 h after intratracheal challenge with ovalbumin. A significant increase in total leukocyte infiltration was observed in the nonstressed offspring group and this was associated with a marked recruitment of eosinophils without a significant effect on the influx of neutrophils and mononuclear cells. In the prenatal stressed offspring, the counts of both total leukocyte and eosinophils, as well as mononuclear cells, was increased by 50% compared to the non-stressed offspring. We provide here the first experimental evidence that chronic mild unpredictable prenatal stress produces a marked increase in the allergen-induced airway inflammation in the rat offspring.

  17. Perceived chronic stress, health and cognition

    OpenAIRE

    Öhman, Lena

    2006-01-01

    The aim of this licentiate thesis was to examine consequences of chronic stress for stressrelated diseases and to investigate the chronic stress – cognition relationship. In the first study data covering ten years was used from the Betula Prospective Cohort Study (Nilsson et al., 1997). Based on the ratings on a stress scale, matched samples between 40 and 65 years of age were divided into a high and low stress group. The reported incidence of cardiovascular, diabetes, psychiatric, tumor, and...

  18. Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress

    OpenAIRE

    Son, Hyeon; Banasr, Mounira; Choi, Miyeon; Chae, Seung Yeon; Licznerski, Pawel; Lee, Boyoung; Voleti, Bhavya; Li, Nanxin; LePack, Ashley; Fournier, Neil M.; Lee, Ka Rim; Lee, In Young; Kim, Juhyun; Kim, Joung-Hun; Kim, Yong Ho

    2012-01-01

    Decreased neuronal dendrite branching and plasticity of the hippocampus, a limbic structure implicated in mood disorders, is thought to contribute to the symptoms of depression. However, the mechanisms underlying this effect, as well as the actions of antidepressant treatment, remain poorly characterized. Here, we show that hippocampal expression of neuritin, an activity-dependent gene that regulates neuronal plasticity, is decreased by chronic unpredictable stress (CUS) and that antidepressa...

  19. Predictable chronic mild stress improves mood, hippocampal neurogenesis and memory.

    Science.gov (United States)

    Parihar, V K; Hattiangady, B; Kuruba, R; Shuai, B; Shetty, A K

    2011-02-01

    Maintenance of neurogenesis in 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 experienced in day-to-day life on functions such as mood, memory and hippocampal neurogenesis are unknown. Using FST and EPM tests on a prototype of adult rats, we demonstrate that PCMS (comprising 5 min of daily restraint stress for 28 days) decreases depressive- and anxiety-like behaviors for prolonged periods. Moreover, we illustrate that decreased depression and anxiety scores after PCMS are associated with ~1.8-fold increase in the production and growth of new neurons in the hippocampus. Additionally, we found that PCMS leads to enhanced memory function in WMT as well as NORT. Collectively, these findings reveal that PCMS is beneficial to adult brain function, which is exemplified by increased hippocampal neurogenesis and improved mood and cognitive function.

  20. Pre-stress performance in an instrumental training predict post-stress behavioral alterations in chronically stressed rats

    Directory of Open Access Journals (Sweden)

    Yoshio eIguchi

    2015-05-01

    Full Text Available Stress is a major factor in the development of major depressive disorder (MDD, but few studies have assessed individual risk based on pre-stress traits. In this study, we employed appetitive instrumental lever pressing with a progressive ratio schedule to assess the individual pre-stress behavioral and cognitive traits in experimentally naïve Sprague–Dawley rats. Based on the behavioral data, the animals were classified into four subgroups (Low Motivation, Quick Learner, Slow Learner, and Hypermotivation, and exposed to chronic unpredictable stress (CUS before monitoring their post-stress responses once each week for 4 weeks to identify early- and late-appearing CUS-induced behavioral phenotypes. The four subgroups exhibited different behavioral phenotypes after CUS. Therefore, we identified distinct relationships between pre-stress traits and the post-stress phenotypes in each subgroup. In addition, many of the CUS-induced phenotypes in rats corresponded to symptoms in human MDD or they had putative relationships with them. We concluded that the consequences of stress may be predicted before stress exposure by determining the pre-stress traits of each individual.

  1. Chronic stress in adulthood followed by intermittent stress impairs spatial memory and the survival of newborn hippocampal cells in aging animals: prevention by FGL, a peptide mimetic of neural cell adhesion molecule

    DEFF Research Database (Denmark)

    Borcel, Erika; Pérez-Alvarez, Laura; Herrero, Ana Isabel;

    2008-01-01

    In this study, we examined whether chronic stress in adulthood can exert long-term effects on spatial-cognitive abilities and on the survival of newborn hippocampal cells in aging animals. Male Wistar rats were subjected to chronic unpredictable stress at midlife (12 months old) and then reexposed...... each week to a stress stimulus. When evaluated in the water maze at the early stages of aging (18 months old), chronic unpredictable stress accelerated spatial-cognitive decline, an effect that was accompanied by a reduction in the survival of newborn cells and in the number of adult granular cells......, a peptide mimetic of neural cell adhesion molecule, during the 4 weeks of continuous stress not only prevented the deleterious effects of chronic stress on spatial memory, but also reduced the survival of the newly generated hippocampal cells in aging animals. FGL treatment did not, however, prevent...

  2. Longevity factor klotho and chronic psychological stress

    OpenAIRE

    Prather, A A; Epel, E S; Arenander, J; Broestl, L; Garay, B I; Wang, D; Dubal, D B

    2015-01-01

    Chronic psychological stress is associated with accelerated aging and premature morbidity and mortality; however, the biology linking chronic psychological stress and its maladaptive effects remains largely unknown. Klotho is a pleiotropic hormone that regulates the aging process and promotes better brain and body health. Whether klotho is linked to psychosocial stress or its negative impact in humans has not been investigated. To address this gap, we recruited 178 healthy women who were eith...

  3. Oxidative Stress Adaptation with Acute, Chronic and Repeated Stress

    OpenAIRE

    Pickering, Andrew. M.; Vojtovich, Lesya; Tower, John; Davies, Kelvin J. A.

    2012-01-01

    Oxidative stress adaptation or hormesis is an important mechanism by which cells and organisms respond to, and cope with, environmental and physiological shifts in the level of oxidative stress. Most studies of oxidative stress adaption have been limited to adaptation induced by acute stress. In contrast, many if not most environmental and physiological stresses are either repeated or chronic. In this study we find that both cultured mammalian cells, and the fruit fly Drosophila melanogaster,...

  4. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Chronic stress does not further exacerbate the abnormal psychoneuroendocrine phenotype of Cbg-deficient male mice.

    Science.gov (United States)

    de Medeiros, Gabriela F; Minni, Amandine M; Helbling, Jean-Christophe; Moisan, Marie-Pierre

    2016-08-01

    Chronic stress leads to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis which can constitute a base for pathophysiological consequences. Using mice totally deficient in Corticosteroid binding globulin (CBG), we have previously demonstrated the important role of CBG in eliciting an adequate response to an acute stressor. Here, we have studied its role in chronic stress situations. We have submitted Cbg ko and wild-type (WT) male mice to two different chronic stress paradigms - the unpredictable chronic mild stress and the social defeat. Then, their impact on neuroendocrine function - through corticosterone and CBG measurement - and behavioral responses - via anxiety and despair-like behavioral tests - was evaluated. Both chronic stress paradigms increased the display of despair-like behavior in WT mice, while that from Cbg ko mice - which was already high - was not aggravated. We have also found that control and defeated (stressed) Cbg ko mice show no difference in the social interaction test, while defeated WT mice reduce their interaction time when compared to unstressed WT mice. Interestingly, the same pattern was observed for corticosterone levels, where both chronic stress paradigms lowered the corticosterone levels of WT mice, while those from Cbg ko mice remained low and unaltered. Plasma CBG binding capacity remained unaltered in WT mice regardless of the stress paradigm. Through the use of the Cbg ko mice, which only differs genetically from WT mice by the absence of CBG, we demonstrated that CBG is crucial in modulating the effects of stress on plasma corticosterone levels and consequently on behavior. In conclusion, individuals with CBG deficiency, whether genetically or environmentally-induced, are vulnerable to acute stress but do not have their abnormal psychoneuroendocrine phenotype further affected by chronic stress. PMID:27153522

  7. Chronic stress suppresses the expression of cutaneous hypothalamic-pituitary-adrenocortical axis elements and melanogenesis.

    Directory of Open Access Journals (Sweden)

    Silin Pang

    Full Text Available Chronic stress can affect skin function, and some skin diseases might be triggered or aggravated by stress. Stress can activate the central hypothalamic-pituitary-adrenocortical (HPA axis, which causes glucocorticoid levels to increase. The skin has HPA axis elements that react to environmental stressors to regulate skin functions, such as melanogenesis. This study explores the mechanism whereby chronic stress affects skin pigmentation, focusing on the HPA axis, and investigates the role of glucocorticoids in this pathway. We exposed C57BL/6 male mice to two types of chronic stress, chronic restraint stress (CRS and chronic unpredictable mild stress (CUMS. Mice subjected to either stress condition showed reduced melanogenesis. Interestingly, CRS and CUMS triggered reductions in the mRNA expression levels of key factors involved in the HPA axis in the skin. In mice administered corticosterone, decreased melanin synthesis and reduced expression of HPA axis elements were observed. The reduced expression of HPA axis elements and melanogenesis in the skin of stressed mice were reversed by RU486 (a glucocorticoid receptor antagonist treatment. Glucocorticoids had no significant inhibitory effect on melanogenesis in vitro. These results suggest that, high levels of serum corticosterone induced by chronic stress can reduce the expression of elements of the skin HPA axis by glucocorticoid-dependent negative feedback. These activities can eventually result in decreased skin pigmentation. Our findings raise the possibility that chronic stress could be a risk factor for depigmentation by disrupting the cutaneous HPA axis and should prompt dermatologists to exercise more caution when using glucocorticoids for treatment.

  8. Chronic stress does not further exacerbate the abnormal psychoneuroendocrine phenotype of Cbg-deficient male mice.

    Science.gov (United States)

    de Medeiros, Gabriela F; Minni, Amandine M; Helbling, Jean-Christophe; Moisan, Marie-Pierre

    2016-08-01

    Chronic stress leads to a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis which can constitute a base for pathophysiological consequences. Using mice totally deficient in Corticosteroid binding globulin (CBG), we have previously demonstrated the important role of CBG in eliciting an adequate response to an acute stressor. Here, we have studied its role in chronic stress situations. We have submitted Cbg ko and wild-type (WT) male mice to two different chronic stress paradigms - the unpredictable chronic mild stress and the social defeat. Then, their impact on neuroendocrine function - through corticosterone and CBG measurement - and behavioral responses - via anxiety and despair-like behavioral tests - was evaluated. Both chronic stress paradigms increased the display of despair-like behavior in WT mice, while that from Cbg ko mice - which was already high - was not aggravated. We have also found that control and defeated (stressed) Cbg ko mice show no difference in the social interaction test, while defeated WT mice reduce their interaction time when compared to unstressed WT mice. Interestingly, the same pattern was observed for corticosterone levels, where both chronic stress paradigms lowered the corticosterone levels of WT mice, while those from Cbg ko mice remained low and unaltered. Plasma CBG binding capacity remained unaltered in WT mice regardless of the stress paradigm. Through the use of the Cbg ko mice, which only differs genetically from WT mice by the absence of CBG, we demonstrated that CBG is crucial in modulating the effects of stress on plasma corticosterone levels and consequently on behavior. In conclusion, individuals with CBG deficiency, whether genetically or environmentally-induced, are vulnerable to acute stress but do not have their abnormal psychoneuroendocrine phenotype further affected by chronic stress.

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

    Directory of Open Access Journals (Sweden)

    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.

  10. Effects of Chronic Stress on Cognition in Male SAMP8 Mice

    Directory of Open Access Journals (Sweden)

    Jinhua Wang

    2016-08-01

    Full Text Available Background/Aims: Chronic stress can lead to cognitive impairment. Senescence-accelerated mouse prone 8 (SAMP8 is a naturally occurring animal model that is useful for investigating the neurological mechanisms of Alzheimer's disease. Here we investigated the impact and mechanisms of chronic stress on cognition in male SAMP8 mice. Methods: Male 6-month- old SAMP8 and SAMR1 (senescence-accelerated mouse resistant 1 mice strains were randomly divided into 4 groups. Mice in the unpredictable chronic mild stress (UCMS groups were exposed to diverse stressors for 4 weeks. Then, these mice performed Morris water maze (MWM test to assess the effect of UCMS on learning and memory. To explore the neurological mechanisms of UCMS on cognition in mice, we evaluated changes in the expression of postsynaptic density 95 (PSD95 and synaptophysin (SYN, which are essential proteins for synaptic plasticity. Five mice from each group were randomly chosen for reverse transcription polymerase chain reaction (RT-PCR and western blotting analysis of SYN and PSD95. Results: The Morris water maze experiment revealed that the cognitive ability of the SAMP8 mice decreased with brain aging, and that chronic stress aggravated this cognitive deficit. In addition, chronic stress decreased the mRNA and protein expression of SYN and PSD95 in the hippocampus of the SAMP8 mice; however, the SAMR1 mice were unaffected. Conclusion: Our results demonstrate that decreased cognition and synaptic plasticity are related to aging. Moreover, we show that chronic stress aggravated this cognitive deficit and decreased SYN and PSD95 expression in the SAMP8 mice. Furthermore, the SAMP8 mice were more vulnerable to the detrimental effects of chronic stress on cognition than the SAMR1 mice. Our results suggest that the neurological mechanisms of chronic stress on cognition might be associated with a decrease in hippocampal SYN and PSD95 expression, which is critical for structural synaptic

  11. Changes in proinflammatory cytokines and white matter in chronically stressed rats

    Directory of Open Access Journals (Sweden)

    Yang P

    2015-03-01

    Full Text Available Ping Yang,1 Zhenyong Gao,1 Handi Zhang,1 Zeman Fang,1 Cairu Wu,1 Haiyun Xu,1,2 Qing-Jun Huang1 1Mental Health Center, 2Department of Anatomy, Shantou University Medical College, Shantou, Guangdong, People’s Republic of China Abstract: Although the pathogenesis of depression, an incapacitating psychiatric ailment, remains largely unknown, previous human and animal studies have suggested that both proinflammatory cytokines and altered oligodendrocytes play important roles in the condition. This study examined these two factors in the brains of rats following unpredictable chronic mild stress for 4 weeks, with the hypothesis that chronic stress may affect oligodendrocytes and elevate proinflammatory cytokines in the brain. After suffering unpredictable stressors for 4 weeks, the rats showed depression-like behaviors, including decreased locomotion in the open field, increased immobility time in the forced swim test, and decreased sucrose consumption and less sucrose preference when compared with controls. Immunohistochemical staining of brain sections showed higher immunoreactivity of proinflammatory cytokines in certain brain regions of stressed rats compared with controls; lower immunoreactivity of myelin basic protein and fewer mature oligodendrocytes were seen in the prefrontal cortex, but no demyelination was detected. These results are interpreted and discussed in the context of recent findings from human and animal studies. Keywords: cytokines, depression, myelination, oligodendrocytes, stress 

  12. Octreotide ameliorates gastric lesions in chronically mild stressed rats

    Institute of Scientific and Technical Information of China (English)

    Noha N Nassar; Mona F Schaalan; Hala F Zaki; Dalaal M Abdallah

    2011-01-01

    AIM: To evaluate the effect of chronic mild stress (CMS) on the emergence of gastric ulcers and possible modulation by octreotide, a synthetic somatostatin analogue. METHODS: Adult male Wistar rats were subjected to nine different unpredictable random stress procedures for 21 d, a multifactorial interactional animal model for CMS. Octreotide was administered daily for 21 d at two dose levels (50 and 90 μg/kg) before exposure to stress procedure. Macro-and microscopical assessments were made, in addition to quantification of plasma corticosterone and gastric mucosal inflammatory, oxidative stress, and apoptotic biomarkers. RESULTS: Exposure to CMS elevated plasma corticosterone (28.3 ± 0.6 μg/dL, P = 0.002), an event that was accompanied by gastric lesions (6.4 ± 0.16 mm,P = 0.01) and confirmed histopathologically. Moreover, the insult elevated gastric mucosal lipid peroxides (13 ± 0.5 nmol/g tissue, P = 0.001), tumor necrosis factor-α(3008.6 ± 78.18 pg/g tissue, P < 0.001), prostaglandin E2 (117.1 ± 4.31 pg/g tissue, P = 0.002), and caspase-3 activity (2.4 ± 0.14 OD/mg protein, P = 0.002). Conversely, CMS mitigated interleukin-10 (627.9 ± 12.82 pg/g tissue, P = 0.001). Furthermore, in animals exposed to CMS, octreotide restored plasma corticosterone (61% and 71% from CMS, P = 0.002) at both dose levels. These beneficial effects were associated with a remarkable suppression of gastric lesions (38% and 9% from CMS, P = 0.01) and reversal of derangements in gastric mucosa. CONCLUSION: The current investigation provides evidence that exposure to CMS induces gastric ulceration, which was alleviated by administration of octreotide possibly possessing antioxidant, anti-inflammatory, and anti-apoptotic actions.

  13. 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.

  14. Dysfunctional stress responses in chronic pain.

    Science.gov (United States)

    Woda, Alain; Picard, Pascale; Dutheil, Frédéric

    2016-09-01

    Many dysfunctional and chronic pain conditions overlap. This review describes the different modes of chronic deregulation of the adaptive response to stress which may be a common factor for these conditions. Several types of dysfunction can be identified within the hypothalamo-pituitary-adrenal axis: basal hypercortisolism, hyper-reactivity, basal hypocortisolism and hypo-reactivity. Neuroactive steroid synthesis is another component of the adaptive response to stress. Dehydroepiandrosterone (DHEA) and its sulfated form DHEA-S, and progesterone and its derivatives are synthetized in cutaneous, nervous, and adipose cells. They are neuroactive factors that act locally. They may have a role in the localization of the symptoms and their levels can vary both in the central nervous system and in the periphery. Persistent changes in neuroactive steroid levels or precursors can induce localized neurodegeneration. The autonomic nervous system is another component of the stress response. Its dysfunction in chronic stress responses can be expressed by decreased basal parasympathethic activity, increased basal sympathetic activity or sympathetic hyporeactivity to a stressful stimulus. The immune and genetic systems also participate. The helper-T cells Th1 secrete pro-inflammatory cytokines such as IL-1-β, IL-2, IL-6, IL-8, IL-12, IFN-γ, and TNF-α, whereas Th2 secrete anti-inflammatory cytokines: IL-4, IL-10, IGF-10, IL-13. Chronic deregulation of the Th1/Th2 balance can occur in favor of anti- or pro-inflammatory direction, locally or systemically. Individual vulnerability to stress can be due to environmental factors but can also be genetically influenced. Genetic polymorphisms and epigenetics are the main keys to understanding the influence of genetics on the response of individuals to constraints. PMID:27262345

  15. Simotang enhances gastrointestinal motility, motilin and cholecystokinin expression in chronically stressed mice

    Institute of Scientific and Technical Information of China (English)

    Guang-Xian Cai; Bai-Yan Liu; Jian Yi; Xue-Mei Chen; Fu-Ling Liu

    2011-01-01

    AIM: To investigate the effect of Simotang (Decoction of Four Powered Drugs) on gastrointestinal motility, motilin and cholecystokinin expression in chronically stressed mice. METHODS: Forty mice were randomly divided into control group, stress group (model group), mosapride group and Simotang group, 10 in each group. A variety of unpredictable stimulations were used to induce chronic stress in mice. Then, the mice were treated with distilled water, mosapride or Simotang for 7 d. Gastric emptying and intestinal propulsion function were detected. Serum level of motilin was measured by enzyme-linked immunosorbent assay. Expression of cholecystokinin (CCK) in intestine, spinal cord and brain of mice was detected by immunohistochemistry and semi-quantitative reverse transcription polymerase chain reaction, respectively. RESULTS: Simotang improved the gastric emptying and intestinal propulsion in chronically stressed mice. Furthermore, the serum motilin level was significantly higher and the expression levels of CCK-positive cells and genes were significantly lower in intestine, spinal cord and brain of Simotang group than in those of model group (P < 0.05). No significant difference was found in serum motilin level and expression levels of CCK-positive cells and genes between the mosapride and Simotang groups. CONCLUSION: Simotang enhances the gastrointestinal motility in chronically stressed mice by regulating the serum motilin level and the expression of cholecystokinin.

  16. 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

  17. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Japanese quail's genetic background modulates effects of chronic stress on emotional reactivity but not spatial learning.

    Directory of Open Access Journals (Sweden)

    Agathe Laurence

    Full Text Available Chronic stress is known to enhance mammals' emotional reactivity and alters several of their cognitive functions, especially spatial learning. Few studies have investigated such effects in birds. We investigated the impact of a two-week stress on Japanese quail's emotional reactivity and spatial learning. Quail is an avian model widely used in laboratory studies and for extrapolation of data to other poultry species. As sensitivity to chronic stress can be modulated by intrinsic factors, we tested juvenile female Japanese quail from three lines, two of them divergently selected on tonic immobility duration, an indicator of general fearfulness. The different emotional reactivity levels of quail belonging to these lines can be revealed by a large variety of tests. Half of the birds were submitted to repeated unpredictable aversive events for two weeks, whereas the other half were left undisturbed. After this procedure, two tests (open field and emergence tests evaluated the emotional reactivity of treated and control quails. They were then trained in a T-maze for seven days and their spatial learning was tested. The chronic stress protocol had an impact on resting, preening and foraging in the home cage. As predicted, the emotional reactivity of treated quails, especially those selected for long tonic immobility duration, was higher. Our spatial learning data showed that the treatment enhanced acquisition but not memorization. However, intrinsic fearfulness did not seem to interact with the treatment in this test. According to an inverted U-shaped relationship between stress and cognition, chronic stress can improve the adaptability of birds to a stressful environment. We discussed the mechanisms possibly implied in the increase of emotional reactivity and spatial abilities.

  20. Chronic pain, perceived stress, and cellular aging: an exploratory study

    Directory of Open Access Journals (Sweden)

    Sibille Kimberly T

    2012-02-01

    Full Text Available Abstract Background Chronic pain conditions are characterized by significant individual variability complicating the identification of pathophysiological markers. Leukocyte telomere length (TL, a measure of cellular aging, is associated with age-related disease onset, psychosocial stress, and health-related functional decline. Psychosocial stress has been associated with the onset of chronic pain and chronic pain is experienced as a physical and psychosocial stressor. However, the utility of TL as a biological marker reflecting the burden of chronic pain and psychosocial stress has not yet been explored. Findings The relationship between chronic pain, stress, and TL was analyzed in 36 ethnically diverse, older adults, half of whom reported no chronic pain and the other half had chronic knee osteoarthritis (OA pain. Subjects completed a physical exam, radiographs, health history, and psychosocial questionnaires. Blood samples were collected and TL was measured by quantitative polymerase chain reaction (qPCR. Four groups were identified characterized by pain status and the Perceived Stress Scale scores: 1 no pain/low stress, 2 no pain/high stress, chronic pain/low stress, and 4 chronic pain/high stress. TL differed between the pain/stress groups (p = 0.01, controlling for relevant covariates. Specifically, the chronic pain/high stress group had significantly shorter TL compared to the no pain/low stress group. Age was negatively correlated with TL, particularly in the chronic pain/high stress group (p = 0.03. Conclusions Although preliminary in nature and based on a modest sample size, these findings indicate that cellular aging may be more pronounced in older adults experiencing high levels of perceived stress and chronic pain.

  1. Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress.

    Science.gov (United States)

    Son, Hyeon; Banasr, Mounira; Choi, Miyeon; Chae, Seung Yeon; Licznerski, Pawel; Lee, Boyoung; Voleti, Bhavya; Li, Nanxin; Lepack, Ashley; Fournier, Neil M; Lee, Ka Rim; Lee, In Young; Kim, Juhyun; Kim, Joung-Hun; Kim, Yong Ho; Jung, Sung Jun; Duman, Ronald S

    2012-07-10

    Decreased neuronal dendrite branching and plasticity of the hippocampus, a limbic structure implicated in mood disorders, is thought to contribute to the symptoms of depression. However, the mechanisms underlying this effect, as well as the actions of antidepressant treatment, remain poorly characterized. Here, we show that hippocampal expression of neuritin, an activity-dependent gene that regulates neuronal plasticity, is decreased by chronic unpredictable stress (CUS) and that antidepressant treatment reverses this effect. We also show that viral-mediated expression of neuritin in the hippocampus produces antidepressant actions and prevents the atrophy of dendrites and spines, as well as depressive and anxiety behaviors caused by CUS. Conversely, neuritin knockdown produces depressive-like behaviors, similar to CUS exposure. The ability of neuritin to increase neuroplasticity is confirmed in models of learning and memory. Our results reveal a unique action of neuritin in models of stress and depression, and demonstrate a role for neuroplasticity in antidepressant treatment response and related behaviors. PMID:22733766

  2. Nature of stress: differential effects on brain acetylcholinesterase activity and memory in rats.

    Science.gov (United States)

    Das, Amitava; Rai, Deepak; Dikshit, Madhu; Palit, Gautam; Nath, Chandishwar

    2005-09-16

    Effect of acute, chronic-predictable and chronic-unpredictable stress on memory and acetylcholinesterase (AChE) was investigated in rats. The animals were subjected to 3 type of stressors--(1) acute immobilization stress, (2) chronic-predictable stress i.e., immobilization daily for 5 consecutive days and (3) chronic-unpredictable stress that included reversal of light/dark cycle, over-night fasting, forced-swimming, immobilization and forced exercise in random unpredictable manner daily for 5 consecutive days. Learning and memory function was studied by single trial Passive avoidance test. AChE activity was assayed spectrophotometrically in the detergent (DS) and salt (SS) soluble fractions in different brain regions. Learning was obtained in acute and chronic-predictable stress groups but not in chronic-unpredictable group. Acute, chronic-predictable and chronic-unpredictable stress caused significant decrease in AChE activity in the DS fraction of cortex, hippocampus and hypothalamus as compared to control. Results indicate that AChE in DS fraction is predominantly affected in stressed and stressed-trained group but cognition is affected only by chronic-unpredictable stress. In acute and chronic-predictable groups the decreased AChE activity in the hippocampal DS fraction during learning may be responsible to maintain cognitive function by enhancing the cholinergic activity. PMID:16098992

  3. Opposing actions of chronic stress and chronic nicotine on striatal function in mice

    OpenAIRE

    Salas, Ramiro; De Biasi, Mariella

    2008-01-01

    Stress is a major risk factor in drug addiction development and relapse. Virtually all drugs of abuse act by increasing extracellular dopamine levels in the striatum. To gain an understanding of the interaction between stress and drug exposure, we studied the effects of concomitant chronic nicotine and chronic stress exposure on mouse striatal dopamine levels.

  4. Increased Risk Taking in Relation to Chronic Stress in Adults

    Science.gov (United States)

    Ceccato, Smarandita; Kudielka, Brigitte M.; Schwieren, Christiane

    2016-01-01

    Chronic stress is a public health problem that affects a significant part of the population. While the physiological damage it causes is under ongoing scrutiny, its behavioral effects have been overlooked. This is one of the first studies to examine the relation between chronic stress and decision-making, using a standard lottery paradigm. We measured risk taking in the gain domain through binary choices between financially incentivized lotteries. We then measured self-reported chronic stress with the Trier Inventory for the Assessment of Chronic Stress (TICS). We additionally collected hair samples in a subsample of volunteers, in order to quantify accumulation of the stress hormone cortisol. We discovered a significant positive, though modest, correlation between self-reported chronic stress and risk taking that is stronger for women than for men. This confirms part of the findings in acute stress research that show a connection between higher stress and increased risk taking. However, unlike the biologically-based results from acute stress research, we did not identify a significant relation between hair cortisol and behavior. In line with previous literature, we found a clear gender difference in risk taking and self-reports: women generally take less risk and report slightly higher stress levels than men. We conclude that perceived chronic stress can impact behavior in risky situations. PMID:26858663

  5. Agmatine increases proliferation of cultured hippocampal progenitor cells and hippocampal neurogenesis in chronically stressed mice

    Institute of Scientific and Technical Information of China (English)

    Yun-feng LI; Hong-xia CHEN; Ying LIU; You-zhi ZHANG; Yan-qin LIU; Jin LI

    2006-01-01

    Aim:To explore the mechanism of agmatine's antidepressant action.Methods: Male mice were subjected to a variety of unpredictable stressors on a daily basis over a 24-d period.The open-field behaviors of the mice were displayed and recorded using a Videomex-V image analytic system automatically.For bromodeoxyuridine (BrdU;thymidine analog as a marker for dividing cells) labeling,the mice were injected with BrdU (100 mg/kg,ip,twice per d for 2 d),and the hippocampal neurogenesis in stressed mice was measured by immunohistochemistry.The proliferation of cultured hippocampal progenitor cells from neonatal rats was determined by colorimetric assay (cell counting kit-8) and 3H-thymidine incorporation assay.Results:After the onset of chronic stress,the locomotor activity of the mice in the open field significantly decreased,while coadministration of agmatine 10 mg/kg (po) blocked it.Furthermore,the number of BrdU-labeled cells in the hippocampal dentate gyrus significantly decreased in chronically stressed mice, which was also blocked by chronic coadministration with agmatine 10 mg/kg (po). Four weeks after the BrdU injection, some of the new born cells matured and became neurons, as determined by double labeling for BrdU and neuron specific enolase (NSE), a marker for mature neurons.In vitro treatment with agmatine 0.1-10 μmo1/L for 3 d significantly increased the proliferation of the cultured hippocampal progenitor cells in a dose-dependent manner.Conclusion:We have found that agmatine increases proliferation of hippocampal progenitor cells in vitro and the hippocampal neurogenesis in vivo in chronically stressed mice.This may be one of the important mechanisms involved in agmatine's antidepressant action.

  6. The impact of chronic stress on the rat brain lipidome

    OpenAIRE

    Oliveira, Tiago Gil; Chan, Robin B.; Bravo, Francisca Vaz; Miranda, André; Silva, Rita Ribeiro; Zhou, Bowen; Marques, Fernanda; Pinto, Vítor; Cerqueira, João José; Di Paolo, Gilbert; Sousa, Nuno

    2015-01-01

    Chronic stress is a major risk factor for several human disorders that affect modern societies. The brain is a key target of chronic stress. In fact, there is growing evidence indicating that exposure to stress affects learning and memory, decision making and emotional responses, and may even predispose for pathological processes, such as Alzheimer’s disease (AD) and depression. Lipids are a major constituent of the brain, and specifically signaling lipids have been shown to regulate brain fu...

  7. Chronic Stress and Suicidal Thinking Among Medical Students

    OpenAIRE

    Anna Rosiek; Aleksandra Rosiek-Kryszewska; Łukasz Leksowski; Krzysztof Leksowski

    2016-01-01

    Introduction: The subject of chronic stress and ways of dealing with it are very broad. The aim of this study was to analyze stress and anxiety and their influence on suicidal thinking among medical students. Materials and Methods: The study was conducted in the years 2014 to 2015 in Poland, at the Medical University—Nicolaus Copernicus University, Collegium Medicum. The objective of this study was to assess chronic stress and suicidal thinking among students and how students cope with this h...

  8. Chronic mild stress impact: are females more vulnerable?

    Science.gov (United States)

    Dalla, C; Antoniou, K; Drossopoulou, G; Xagoraris, M; Kokras, N; Sfikakis, A; Papadopoulou-Daifoti, Z

    2005-01-01

    Despite the knowledge that women are more susceptible than men to stress-related mental illness, such as major depression, there is no comprehensive estimation of the role of gender in the detrimental effects of chronic stress that might cause depression. Sex differences regarding the association of behavioral parameters with serotonergic and hypothalamic-pituitary-adrenal axis activities were investigated in the chronic mild stress model of depression. Additionally, the impact of chronic mild stress exposure on an additional/novel short-term stressful procedure, such as the forced swim test was examined in male and female rats. Female rats were found to be more vulnerable to chronic mild stress and that was depicted with disruption of sucrose intake, decreases in open field activity, increased corticosterone levels, alteration in estrous cycle and decreased serotonergic activity in hippocampus and hypothalamus. On the contrary, in males the current chronic mild stress protocol elicited only behavioral changes, such as disruption in sucrose intake and decreased open field activity. Interestingly, in response to forced swim test, females previously subjected to chronic mild stress, were found to cope better by exhibiting increased active behavior in the second forced swim test session and higher hypothalamic serotonergic activity in comparison with corresponding males. On the other hand, males were more affected by previous chronic mild stress exposure and that was manifested by decreased active behavior in the first forced swim test session and increased corticosterone levels following second forced swim test session. These data indicate that although females are more vulnerable in the application of chronic mild stress than males, in response to an additional-novel stressor (forced swim test) they show better response. Therefore, both sex/gender and combination of stressful procedures should be carefully considered in the study of the pathophysiology of stress

  9. Public Health Burden of Chronic Stress in a Transforming Society

    OpenAIRE

    Kopp, Mária S

    2007-01-01

    In this paper chronic stress is proposed as an integrating model that can be applied to the explanation of the suddenly changing patterns of premature mortality rates in transforming societies of Central-Eastern-Europe, especially in Hungary. The temporal factor in existing stress models is often neglected. Chronic stress has been shown to lead to typical pathogenetic results in animal experiments. Literature and the different models in the field of psychology, behavioural sciences, and epide...

  10. 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 ...

  11. Predictable Chronic Mild Stress in Adolescence Increases Resilience in Adulthood

    OpenAIRE

    Suo, Lin; Zhao, Liyan; Si, Jijian; Liu, Jianfeng; Zhu, Weili; Chai, Baisheng; Zhang, Yan; Feng, Jiajia; Ding, Zengbo; Luo, Yixiao; Shi, Haishui; Shi, Jie; Lu, Lin

    2013-01-01

    Stress in adolescence has been widely demonstrated to have a lasting impact in humans and animal models. Developmental risk and protective factors play an important role in the responses to stress in adulthood. Mild-to-moderate stress in adolescence may resist the negative impacts of adverse events in adulthood. However, little research on resilience has been conducted. In this study, we used a predictable chronic mild stress (PCMS) procedure (5 min of daily restraint stress for 28 days) in a...

  12. Chronic and Episodic Stress in Children of Depressed Mothers.

    Science.gov (United States)

    Feurer, Cope; Hammen, Constance L; Gibb, Brandon E

    2016-01-01

    The goal of this study was to examine chronic and episodic stress in children of mothers with and without a history of major depressive disorder (MDD) during the children's lives. Participants were 255 mothers selected according to their history of MDD (present vs. absent during child's life) and their children (age 8-14; 53% girls, 81% Caucasian). Mothers' and children's histories of MDD were assessed using diagnostic interviews, and their depressive symptoms were assessed via self-report measures. Children's levels of chronic and episodic stress were assessed using a semistructured contextual threat interview. Children of mothers with a history of recurrent MDD, compared to single MDD or no depression, experienced more chronic stress within several domains including peers, mother-child relations, and other family member relations as well as greater episodic dependent interpersonal stress. Each of these group differences was maintained after excluding children with a history of MDD themselves and controlling for their current depressive symptoms. However, only the group difference in chronic peer stress was maintained when controlling for mothers' current depression. The results suggest that children exposed to recurrent maternal MDD experience higher levels of both chronic and episodic stress, at least some of which they contribute to themselves (dependent interpersonal stress) and which is at least partially independent of the effects of children's depression. In addition, much of this stress is associated primarily with current depression in the mother, though it appears that chronic peer stress may remain elevated even after the remission of maternal depression. PMID:25496371

  13. Chronic stress, catecholamines, and sleep disturbance at Three Mile Island

    International Nuclear Information System (INIS)

    The present study was concerned with the relationship between chronic stress and sleep disturbance. Previous research has provided evidence of chronic stress responding among people living near the Three Mile Island nuclear generating facility. Compared to control subjects, the TMI group has exhibited greater symptom reporting, poorer performance on behavioral measures of concentration, and elevated levels of urinary norepinephrine and epinephrine. Other research has suggested a relationship between arousal and insomnia. The extent to which stress and sleep disturbances were experienced by residents at TMI was examined and compared to levels of stress and sleep disturbance among a group of control subjects. The relationship between stress and sleep disturbances was also examined. Results indicated that TMI area residents exhibited more stress than the controls and reported greater disturbance of sleep. Modest relationships among stress and sleep measures suggested that the symptoms of stress measured in this study were not primary determinants of sleep problems

  14. Subacute stress and chronic stress interact to decrease intestinal barrier function in rats.

    Science.gov (United States)

    Lauffer, Adriana; Vanuytsel, Tim; Vanormelingen, Christophe; Vanheel, Hanne; Salim Rasoel, Shadea; Tóth, Joran; Tack, Jan; Fornari, Fernando; Farré, Ricard

    2016-01-01

    Psychological stress increases intestinal permeability, potentially leading to low-grade inflammation and symptoms in functional gastrointestinal disorders. We assessed the effect of subacute, chronic and combined stress on intestinal barrier function and mast cell density. Male Wistar rats were allocated to four experimental groups (n = 8/group): 1/sham; 2/subacute stress (isolation and limited movement for 24 h); 3/chronic crowding stress for 14 days and 4/combined subacute and chronic stress. Jejunum and colon were collected to measure: transepithelial electrical resistance (TEER; a measure of epithelial barrier function); gene expression of tight junction molecules; mast cell density. Plasma corticosterone concentration was increased in all three stress conditions versus sham, with highest concentrations in the combined stress condition. TEER in the jejunum was decreased in all stress conditions, but was significantly lower in the combined stress condition than in the other groups. TEER in the jejunum correlated negatively with corticosterone concentration. Increased expression of claudin 1, 5 and 8, occludin and zonula occludens 1 mRNAs was detected after subacute stress in the jejunum. In contrast, colonic TEER was decreased only after combined stress, and the expression of tight junction molecules was unaltered. Increased mast cell density was observed in the chronic and combined stress condition in the colon only. In conclusion, our data show that chronic stress sensitizes the gastrointestinal tract to the effects of subacute stress on intestinal barrier function; different underlying cellular and molecular alterations are indicated in the small intestine versus the colon.

  15. Physical activity buffers fatigue only under low chronic stress.

    Science.gov (United States)

    Strahler, Jana; Doerr, Johanna M; Ditzen, Beate; Linnemann, Alexandra; Skoluda, Nadine; Nater, Urs M

    2016-09-01

    Fatigue is one of the most commonly reported complaints in the general population. As physical activity (PA) has been shown to have beneficial effects, we hypothesized that everyday life PA improves fatigue. Thirty-three healthy students (21 women, 22.8 ± 3.3 years, 21.7 ± 2.3 kg/m(2)) completed two ambulatory assessment periods. During five days at the beginning of the semester (control condition) and five days during final examination preparation (examination condition), participants repeatedly reported on general fatigue (awakening, 10 am, 2 pm, 6 pm and 9 pm) by means of an electronic diary, collected saliva samples for the assessment of cortisol and α-amylase immediately after providing information on fatigue and wore a triaxial accelerometer to continuously record PA. Self-perceived chronic stress was assessed as a moderator. Using hierarchical linear modeling, including PA, condition (control vs. examination), sex and chronic stress as predictors, PA level during the 15 min prior to data entry did not predict momentary fatigue level. Furthermore, there was no effect of condition. However, a significant cross-level interaction of perceived chronic stress with PA was observed. In fact, the (negative) relationship between PA and fatigue was stronger in those participants with less chronic stress. Neither cortisol nor α-amylase was significantly related to physical activity or fatigue. Our study showed an immediate short-term buffering effect of everyday life PA on general fatigue, but only when experiencing lower chronic stress. There seems to be no short-term benefit of PA in the face of higher chronic stress. These findings highlight the importance of considering chronic stress when evaluating the effectiveness of PA interventions in different target populations, in particular among chronically stressed and fatigued subjects.

  16. The context specificity of anxiety responses induced by chronic psychosocial stress in rats: a shift from anxiety to social phobia?

    Science.gov (United States)

    Barsy, Boglárka; Leveleki, Csilla; Zelena, Dóra; Haller, József

    2010-05-01

    The aim of the present study was to evaluate whether the anxiety-increasing effects of chronic psychosocial stress generalize to non-social (i.e. heterotypic) stressful situations. To investigate this issue, we repeatedly exposed rats to predictable or unpredictable psychosocial stress for 5 or 12 days and examined their anxiety in two markedly different contexts: the elevated plus maze and social interaction tests. Psychosocial stress and the social interaction test were administered under highly similar conditions, i.e. the two situations were homotypic. Psychosocial stress did not affect anxiety in the elevated plus-maze under any condition, but markedly increased anxiety in the social interaction test. In contrast, repeated restraint-a non-social stressor heterotypic to both the elevated plus maze and social interaction tests-increased plus-maze anxiety, demonstrating that anxiety in this test was sensitive to repeated restraint, and the effects were manifested in heterotypic situations. Thus, the anxiety-related effects of chronic psychosocial stress-unlike those of the chronic non-social stressor-were context-dependent. This is reminiscent of phobic anxiety, which manifests in specific situations only. In addition, behavior in the social interaction test showed changes that went beyond simple anxiogenesis. Socially stressed rats spent nearly 40% of total time in aggressive interactions. Based on recent data showing that social phobics are prone to violence under social pressure, and also based on the situation-dependent effects of the social stressor, we suggest that chronic psychosocial stress leads to a behavioral profile akin to social phobia.

  17. 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.

  18. 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

  19. Emotionality modulates the effect of chronic stress on feeding behaviour in birds.

    Directory of Open Access Journals (Sweden)

    Angélique Favreau-Peigné

    Full Text Available Chronic stress is a long-lasting negative emotional state that induces negative consequences on animals' psycho-physiological state. This study aimed at assessing whether unpredictable and repeated negative stimuli (URNS influence feeding behaviour in quail. Sixty-four quail were exposed to URNS from day 17 to 40, while 64 quail were undisturbed. Two lines divergently selected on their inherent emotionality were used to assess the effect of genetic factors on the sensitivity to URNS. All quail were submitted to a sequential feeding procedure (using two diets of different energetic values which placed them in a contrasting situation. Behavioural tests were performed to assess the emotional reactivity of the two lines. Results confirmed that differences exist between them and that their emotional reactivity was enhanced by URNS. Diet preferences, motivation and daily intake were also measured. URNS did not change the preferences for the hypercaloric diet compared to the hypocaloric diet in choice tests, but they reduced daily intakes in both lines. Motivations for each diet were differently affected by URNS: they decreased the motivation to eat the hypercaloric diet in quail selected for their low inherent fearfulness whereas they increased the motivation to eat the hypocaloric diet in quail selected for their high inherent fearfulness, which suggested a devaluation process in the former and a compensatory behaviour in the later. Growth was furthermore reduced and laying delayed by URNS in both lines. In conclusion, the exposure to URNS induced interesting changes in feeding behaviour added with an increase in emotional reactivity and an alteration of production parameters. This confirms that both lines of quail experienced a chronic stress state. However differences in feed motivation and emotional reactivity between lines under chronic stress suggested that they experienced different emotional state and use different ways to cope with it

  20. Chronic stress effects on hippocampal structure and synaptic function: relevance for depression and normalization by anti-glucocorticoid treatment

    Directory of Open Access Journals (Sweden)

    Harmen J Krugers

    2010-07-01

    Full Text Available Exposure of an organism to environmental challenges activates two hormonal systems that help the organism to adapt. As part of this adaptational process, brain processes are changed such that appropriate behavioral strategies are selected that allow optimal performance at the short term, while relevant information is stored for the future. Over the past years it has become evident that chronic uncontrollable and unpredictable stress also exerts profound effects on structure and function of limbic neurons, but the impact of chronic stress is not a mere accumulation of repeated episodes of acute stress exposure. Dendritic trees are reduced in some regions but expanded in others, and cells are generally exposed to a higher calcium load upon depolarization. Synaptic strengthening is largely impaired. Neurotransmitter responses are also changed, e.g. responses to serotonin. We here discuss: a the main cellular effects after chronic stress with emphasis on the hippocampus, b how such effects could contribute to the development of psychopathology in genetically vulnerable individuals, and c their normalization by brief treatment with anti-glucocorticoids.

  1. 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.

  2. Prolactin and its receptors in the chronic mild stress rat model of depression.

    Science.gov (United States)

    Faron-Górecka, A; Kuśmider, M; Kolasa, M; Zurawek, D; Gruca, P; Papp, M; Szafran, K; Solich, J; Pabian, P; Romańska, I; Antkiewicz-Michaluk, L; Dziedzicka-Wasylewska, M

    2014-03-25

    Prolactin (PRL) exhibits many physiological functions with wide effects on the central nervous system including stress responses. Our study aimed to investigate the effect of chronic unpredictable mild stress (CMS) - which is a good animal model of depression - on PRL receptor (PRLR) expression in the rat brain. Rats were exposed to CMS for two weeks and subsequently to CMS in combination with imipramine (IMI) treatment for five consecutive weeks. Behavioral deficit measured in anhedonic animals is a reduced intake of sucrose solution. Two weeks of CMS procedure allowed the selection of animals reactive to stress and displaying anhedonia, and the group which is considered as stress-non-reactive as far as behavioral measures are concerned. In this group the elevated level of PRL in plasma was observed, decrease in dopamine release in the hypothalamus, increase in [(125)I]PRL binding to PRLR in the choroid plexus, increase of mRNA encoding the long form of PRLR in the arcuate nucleus and the decrease of mRNA encoding its short form, and decrease in the mRNA encoding dopamine D2 receptor. All these alterations indicate these parameters as involved in the phenomenon of stress-resilience. The prolongation of the CMS procedure for additional five weeks shows the form of habituation to the stressful conditions. The most interesting result, however, was the up-regulation of PRLR in the choroid plexus of rats subjected to full CMS procedure combined with treatment with IMI, which may speak in favor of the role of this receptor in the mechanisms of antidepressant action.

  3. Chronic Stress and Suicidal Thinking Among Medical Students

    Directory of Open Access Journals (Sweden)

    Anna Rosiek

    2016-02-01

    Full Text Available Introduction: The subject of chronic stress and ways of dealing with it are very broad. The aim of this study was to analyze stress and anxiety and their influence on suicidal thinking among medical students. Materials and Methods: The study was conducted in the years 2014 to 2015 in Poland, at the Medical University—Nicolaus Copernicus University, Collegium Medicum. The objective of this study was to assess chronic stress and suicidal thinking among students and how students cope with this huge problem. Descriptive statistics and chi-square analyses were conducted to detect differences. Results: Analyses showed that students’ life is full of stressors. Students toward the end of their education cope better with stress than students starting their university studies. Chronic stress has a strong impact on mental health and suicidal thinking among students. Conclusions: The results of the study confirmed that chronic stress and anxiety have a negative influence on mental health and also confirm a relation to suicidal thinking in medical students. Students cope with stress by listening to music, talking to relatives or people close to them, resting or engaging in sports, with cycling, running and swimming being the most common methods used to affect suicidal thinking.

  4. Adult Neurogenesis, Chronic Stress and Depression

    NARCIS (Netherlands)

    P.J. Lucassen; C.A. Oomen; M. Schouten; J.M. Encinas; C.P. Fitzsimons

    2016-01-01

    A major risk factor for depression in vulnerable individuals is exposure to stress during critical periods. Stress affects mood and cognition and is also one of the best known inhibitors of adult neurogenesis that has been associated with hippocampal changes and atrophy, common findings in major dep

  5. Maternal Deprivation Enhances Behavioral Vulnerability to Stress Associated with miR-504 Expression in Nucleus Accumbens of Rats

    OpenAIRE

    Yi Zhang; Xiongzhao Zhu; Mei Bai; Li Zhang; Liang Xue; Jinyao Yi

    2013-01-01

    OBJECTIVE: In this study, the effect of maternal deprivation (MD) and chronic unpredictable stress (CUS) in inducing depressive behaviors and associated molecular mechanism were investigated in rats. METHODS: Maternal deprivation was established by separating pups from their mothers for 6 hours daily from postnatal day 1 to day 14. Chronic unpredictable stress was established by water deprivation, elevated open platform, food deprivation, restraint stress and electric foot shock. The depressi...

  6. Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

    International Nuclear Information System (INIS)

    Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD). In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS) and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD

  7. Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

    Energy Technology Data Exchange (ETDEWEB)

    Yang, C.; Guo, X. [Wuhan University, Renmin Hospital, Department of Psychiatry, Wuhan, China, Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan (China); Wang, G.H. [Wuhan University, Renmin Hospital, Department of Psychiatry, Wuhan, China, Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan (China); Wuhan University, Institute of Neuropsychiatry, Wuhan, China, Institute of Neuropsychiatry, Wuhan University, Wuhan (China); Wang, H.L.; Liu, Z.C.; Liu, H.; Zhu, Z.X.; Li, Y. [Wuhan University, Renmin Hospital, Department of Psychiatry, Wuhan, China, Department of Psychiatry, Renmin Hospital, Wuhan University, Wuhan (China)

    2014-03-03

    Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD). In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS) and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD.

  8. Changes in tau phosphorylation levels in the hippocampus and frontal cortex following chronic stress

    Directory of Open Access Journals (Sweden)

    C. Yang

    2014-03-01

    Full Text Available Studies have indicated that early-life or early-onset depression is associated with a 2- to 4-fold increased risk of developing Alzheimers disease (AD. In AD, aggregation of an abnormally phosphorylated form of the tau protein may be a key pathological event. Tau is known to play a major role in promoting microtubule assembly and stabilization, and in maintaining the normal morphology of neurons. Several studies have reported that stress may induce tau phosphorylation. The main aim of the present study was to investigate possible alterations in the tau protein in the hippocampus and frontal cortex of 32 male Sprague-Dawley rats exposed to chronic unpredictable mild stress (CUMS and then re-exposed to CUMS to mimic depression and the recurrence of depression, respectively, in humans. We evaluated the effects of CUMS, fluoxetine, and CUMS re-exposure on tau and phospho-tau. Our results showed that a single exposure to CUMS caused a significant reduction in sucrose preference, indicating a state of anhedonia. The change in behavior was accompanied by specific alterations in phospho-tau protein levels, but fluoxetine treatment reversed the CUMS-induced impairments. Moreover, changes in sucrose preference and phospho-tau were more pronounced in rats re-exposed to CUMS than in those subjected to a single exposure. Our results suggest that changes in tau phosphorylation may contribute to the link between depression and AD.

  9. Sex differences in synaptic plasticity in stress-responsive brain regions following chronic variable stress

    OpenAIRE

    Carvalho-Netto, Eduardo F.; Myers, Brent; Jones, Kenneth; Solomon, Matia B.; Herman, James P.

    2011-01-01

    Increased stress responsiveness is implicated in the etiology of mood and anxiety disorders, including depression and post-traumatic stress disorder. Additionally, stress-related affective disorders have a higher incidence in women than men. Chronic stress in rodents produces numerous neuromorphological changes in a variety of limbic brain regions. Here, we examined the sex-dependent differences in presynaptic innervation of the paraventricular nucleus of the hypothalamus (PVN), prefrontal co...

  10. Chronic Kidney Disease—Effect of Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Subha Palaneeswari Meenakshi Sundaram

    2014-01-01

    Full Text Available Chronic kidney disease (CKD is a growing health problem with increasing incidence. The annual mortality of end-stage renal disease patients is about 9%, which is 10–20 fold higher than the general population, approximately 50% of these deaths are due to cardiovascular (CV disease. CV risk factors, such as diabetes, hypertension, and hyperlipidemia, are strongly associated with poor outcome. Many other nontraditional risk factors such as inflammation, infection, oxidative stress, anemia, and malnutrition are also present. In this review we will focus on the role of oxidative stress in chronic kidney disease.

  11. [Carbonyl stress and oxidatively modified proteins in chronic renal failure].

    Science.gov (United States)

    Bargnoux, A-S; Morena, M; Badiou, S; Dupuy, A-M; Canaud, B; Cristol, J-P

    2009-01-01

    Oxidative stress is commonly observed in chronic renal failure patients resulting from an unbalance between overproduction of reactive oxygen species and impairement of defense mechanisms. Proteins appear as potential targets of uremia-induced oxidative stress and may undergo qualitative modifications. Proteins could be directly modified by reactive oxygen species which leads to amino acid oxydation and cross-linking. Proteins could be indirectly modified by reactive carbonyl compounds produced by glycoxidation and lipo-peroxidation. The resulting post-traductional modifications are known as carbonyl stress. In addition, thiols could be oxidized or could react with homocystein leading to homocysteinylation. Finally, tyrosin could be oxidized by myeloperoxidase leading to advanced oxidative protein products (AOPP). Oxidatively modified proteins are increased in chronic renal failure patients and may contribute to exacerbate the oxidative stress/inflammation syndrome. They have been involved in long term complications of uremia such as amyloidosis and accelerated atherosclerosis. PMID:19297289

  12. Chronic stress does not impair liver regeneration in rats

    DEFF Research Database (Denmark)

    Andersen, Kasper J; Knudsen, Anders Riegels; Wiborg, Ove;

    2015-01-01

    a 70 % partial hepatectomy (PHx). The animals were evaluated on postoperative day 2 or 4. Blood samples were collected to examine circulating markers of inflammation and liver cell damage. Additionally, liver tissues were sampled to evaluate liver weight and regeneration rate. RESULTS: None......BACKGROUND: Although wound healing is a simple regenerative process that is critical after surgery, it has been shown to be impaired under psychological stress. The liver has a unique capacity to regenerate through highly complex mechanisms. The aim of this study was to investigate the effects...... of chronic stress, which may induce a depression-like state, on the complex process of liver regeneration in rats. METHODS: Twenty rats were included in this study. The animals received either a standard housing protocol or were subjected to a Chronic Mild Stress (CMS) stress paradigm. All rats underwent...

  13. 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

  14. Interaction of Metabolic Stress with Chronic Mild Stress in Altering Brain Cytokines and Sucrose Preference

    OpenAIRE

    Remus, Jennifer L.; Stewart, Luke T.; Camp, Robert M.; Novak, Colleen M.; Johnson, John D.

    2015-01-01

    There is growing evidence that metabolic stressors increase an organism’s risk of depression. Chronic mild stress is a popular animal model of depression and several serendipitous findings have suggested that food deprivation prior to sucrose testing in this model is necessary to observe anhedonic behaviors. Here, we directly tested this hypothesis by exposing animals to chronic mild stress and used an overnight two bottle sucrose test (food ad libitum) on day 5 and 10, then food and water de...

  15. Epigenetic Effect of Chronic Stress on Dopamine Signaling and Depression

    OpenAIRE

    Sofia Moriam; Mahbub E. Sobhani

    2013-01-01

    Because of the complex causal factors leading to depression, epigenetics is of considerable interest for the understanding effect of stress in depression. Dopamine is a key neurotransmitter important in many physiological functions, including motor control, mood, and the reward pathway. These factors lead many drugs to target Dopamine receptors in treating depressive disorders. In this review, we try to portray how chronic stress as an epigenetic factor changes the gene regulation pattern by ...

  16. Balancing food and predator pressure induces chronic stress in songbirds.

    OpenAIRE

    Clinchy, Michael; Zanette, Liana; Boonstra, Rudy; Wingfield, John C.; Smith, James N. M.

    2004-01-01

    The never-ending tension between finding food and avoiding predators may be the most universal natural stressor wild animals experience. The 'chronic stress' hypothesis predicts: (i) an animal's stress profile will be a simultaneous function of food and predator pressures given the aforesaid tension; and (ii) these inseparable effects on physiology will produce inseparable effects on demography because of the resulting adverse health effects. This hypothesis was originally proposed to explain...

  17. The influence of chronic stress on T cell immunity

    OpenAIRE

    Sommershof, Annette

    2010-01-01

    Chronic environmental and psychological stress has long been suspected to increase the susceptibility and outcome of numerous infectious and inflammatory diseases. The release of neurotransmitters (catecholamines) and adrenal hormones (glucocorticoids) has been well documented as the basis for a connection between the central nervous system and peripheral components of the immune system. Glucocorticoids, the end products of stress-induced neuroendocrine pathways and the hypothalamic-pituitary...

  18. Chronic stress and pituitary-adrenal function in female pigs.

    OpenAIRE

    Janssens, C.J.J.C.

    1994-01-01

    IntroductionThe main purpose of the studies described in this thesis was to gain more insight in the regulation of the hypothalamic-pituitary-adrenocorticaI (HPA) system and the mechanisms underlying adaptation to chronic stress in female pigs. The function of the HPA axis, which coordinates multiple neuroendocrine and metabolic responses to stressors, has been subject of extensive basic and clinical research. HPA-activation by stressful stimuli results in an increase in circulating adrenocor...

  19. Chronic Stress Facilitates the Development of Deep Venous Thrombosis

    Directory of Open Access Journals (Sweden)

    Tao Dong

    2015-01-01

    Full Text Available The increasing pressure of modern social life intensifies the impact of stress on the development of cardiovascular diseases, which include deep venous thrombosis (DVT. Renal sympathetic denervation has been applied as one of the clinical approaches for the treatment of drug-resistant hypertension. In addition, the close relationship between oxidative stress and cardiovascular diseases has been well documented. The present study is designed to explore the mechanism by which the renal sympathetic nerve system and the oxidative stress affect the blood coagulation system in the development of DVT. Chronic foot shock model in rats was applied to mimic a state of physiological stress similar to humans. Our results showed that chronic foot shock procedure could promote DVT which may be through the activation of platelets aggregation. The aggravation of DVT and activation of platelets were alleviated by renal sympathetic denervation or antioxidant (Tempol treatment. Concurrently, the denervation treatment could also reduce the levels of circulating oxidation factors in rats. These results demonstrate that both the renal sympathetic nerve system and the oxidative stress contribute to the development of DVT in response to chronic stress, which may provide novel strategy for treatment of clinic DVT patients.

  20. Neural control of chronic stress adaptation

    OpenAIRE

    James eHerman

    2013-01-01

    Stress initiates adaptive processes that allow the organism to physiologically cope with prolonged or intermittent exposure to real or perceived threats. A major component of this response is repeated activation of glucocorticoid secretion by the hypothalamo-pituitary-adrenocortical (HPA) axis, which promotes redistribution of energy in a wide range of organ systems, including the brain. Prolonged or cumulative increases in glucocorticoid secretion can reduce benefits afforded by enhanced s...

  1. Chronic stress and pituitary-adrenal function in female pigs.

    NARCIS (Netherlands)

    Janssens, C.J.J.C.

    1994-01-01

    IntroductionThe main purpose of the studies described in this thesis was to gain more insight in the regulation of the hypothalamic-pituitary-adrenocorticaI (HPA) system and the mechanisms underlying adaptation to chronic stress in female pigs. The function of the HPA axis, which coordinates multipl

  2. Effects of chronic stress on sleep in rats.

    Science.gov (United States)

    Kant, G J; Pastel, R H; Bauman, R A; Meininger, G R; Maughan, K R; Robinson, T N; Wright, W L; Covington, P S

    1995-02-01

    The present study was conducted to determine the effects of chronic stress on sleep using a rodent paradigm of around-the-clock signalled intermittent foot shock in which some rats can pull a chain to avoid/escape shock while another group of rats is yoked to the first group. We measured sleep using telemetry; four-channel EEG was collected 24 h/day in rats during 2 prestress days; days 1, 2, 3, 7, and 14 during chronic stress; and 3 poststress days. States of REM sleep, non-REM (NREM) sleep, and waking were scored for each 15-s period of the EEG recordings. During the prestress period, rats slept (REM plus NREM) 55% of available time during the light hours and 34% of the dark hours with the remainder represented by waking. On the first day of stress, total sleep and, especially REM sleep, decreased markedly. By the second day of stress, only REM sleep in the controllable stress group (but not the uncontrollable stress group) was still significantly decreased compared to prestress levels, and REM sleep returned to baseline levels by day 7 of stress. The recovery of sleep quantity was accomplished by increased sleep during the dark hours, resulting in a long-lasting disruption of normal circadian sleep patterning.

  3. 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).

  4. Low maternal care exacerbates adult stress susceptibility in the chronic mild stress rat model of depression

    DEFF Research Database (Denmark)

    Henningsen, Kim; Dyrvig, Mads; Bouzinova, Elena V;

    2012-01-01

    In the present study we report the finding that the quality of maternal care, in early life, increased the susceptibility to stress exposure in adulthood, when rats were exposed to the chronic mild stress paradigm. Our results indicate that high, as opposed to low maternal care, predisposed rats...... to a differential stress-coping ability. Thus rats fostered by low maternal care dams became more prone to adopt a stress-susceptible phenotype developing an anhedonic-like condition. Moreover, low maternal care offspring had lower weight gain and lower locomotion, with no additive effect of stress. Subchronic...... exposure to chronic mild stress induced an increase in faecal corticosterone metabolites, which was only significant in rats from low maternal care dams. Examination of glucocorticoid receptor exon 17 promoter methylation in unchallenged adult, maternally characterized rats, showed an insignificant...

  5. Plasma neurotransmitters and cortisol in chronic illness: role of stress.

    Science.gov (United States)

    Lechin, F; van der Dijs, B; Lechin, A; Orozco, B; Lechin, M; Báez, S; Rada, I; León, G; Acosta, E

    1994-01-01

    We routinely measured plasma neurotransmitters and hormone levels in order to investigate the role of stress on many types of diseases. In this study, we present results obtained from patients with severe chronic diseases. The study sample consisted of 88 patients (asthmatics, ulcerative colitis, Crohn's disease, chronic active hepatitis, chronic relapsing hepatitis, multiple sclerosis, trigeminal neuralgia, systemic lupus erithematous, and rheumatoid arthritis), and their respective controls. Noradrenaline (NA), adrenaline (Ad), dopamine (DA), platelet-serotonin (pS), free-serotonin (fS), growth hormone (GH) and cortisol (CRT) were determined during both exacerbation and improvement periods. A profile compatible with uncoping stress disorder (raised NA-Ad-DA + fS + CRT as well as low pS and NA/Ad ratio) was found during exacerbation periods when compared with improvement, as seen in controls. However, during improvement periods the neurochemical profile remained significantly different from that of normal controls. The neurochemical plus hormonal plasma profiles registered in chronic illness, both during exacerbation and improvement periods, strongly suggest that an uncoping stress mechanism underlies diseases of these patients. PMID:7996062

  6. Effect of Chronic Psychological Stress on Liver Metastasis of Colon Cancer in Mice

    OpenAIRE

    Lu Zhao; Jianhua Xu; Fang Liang; Ao Li; Yong Zhang; Jue Sun

    2015-01-01

    Metastasis to the liver is a main factor in colorectal cancer mortality. Previous studies suggest that chronic psychological stress is important in cancer progression, but its effect on liver metastasis has not been investigated. To address this, we established a liver metastasis model in BALB/c nude mice to investigate the role of chronic stress in liver metastasis. Our data suggest that chronic stress elevates catecholamine levels and promotes liver metastasis. Chronic stress was also assoc...

  7. 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...

  8. Chronic subordinate colony housing (CSC as a model of chronic psychosocial stress in male rats.

    Directory of Open Access Journals (Sweden)

    Kewir D Nyuyki

    Full Text Available Chronic subordinate colony housing (CSC is an adequate and reliable mouse model of chronic psychosocial stress, resulting in reduced body weight gain, reduced thymus and increased adrenal weight, long-lasting anxiety-like behaviour, and spontaneous colitis. Furthermore, CSC mice show increased corticotrophin (ACTH responsiveness to acute heterotypic stressors, suggesting a general mechanism which allows a chronically-stressed organism to adequately respond to a novel threat. Therefore, the aim of the present study was to extend the CSC model to another rodent species, namely male Wistar rats, and to characterize relevant physiological, immunological, and behavioural consequences; placing particular emphasis on changes in hypothalamo-pituitary-adrenal (HPA axis responsiveness to an acute heterotypic stressor. In line with previous mouse data, exposure of Wistar rats to 19 days of CSC resulted in a decrease in body weight gain and absolute thymus mass, mild colonic barrier defects and intestinal immune activation. Moreover, no changes in stress-coping behaviour or social preference were seen; again in agreement with the mouse paradigm. Most importantly, CSC rats showed an increased plasma corticosterone response to an acute heterotypic stressor (open arm, 5 min despite displaying similar basal levels and similar basal and stressor-induced plasma ACTH levels. In contrast to CSC mice, anxiety-related behaviour and absolute, as well as relative adrenal weights remained unchanged in CSC rats. In summary, the CSC paradigm could be established as an adequate model of chronic psychosocial stress in male rats. Our data further support the initial hypothesis that adrenal hyper-responsiveness to ACTH during acute heterotypic stressors represents a general adaptation, which enables a chronically-stressed organism to adequately respond to novel challenges.

  9. 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...

  10. 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.

  11. Effect of chronic psychosocial stress on nonalcoholic steatohepatitis in mice.

    Science.gov (United States)

    Czech, Barbara; Neumann, Inga D; Müller, Martina; Reber, Stefan O; Hellerbrand, Claus

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation which may progress towards inflammation (nonalcoholic steatohepatitis (NASH)). NAFLD is regarded as a consequence of a sedentary, food-abundant lifestyle which, in the modern world, often coincides with chronically high levels of perceived psychosocial stress. Here, we aimed to characterize the effect of chronic psychosocial stress on the development of NAFLD/NASH in male mice either fed with standard chow or NASH-inducing high fat diet. Chronic psychosocial stress was induced by chronic subordinate colony housing (CSC), a pre-clinically validated paradigm relevant for human affective and somatic disorders. Single housed (SHC) mice served as controls. Under standard chow conditions CSC mice revealed lower hepatic triglyceride levels but higher hepatic TNFα, MCP-1 and HMOX mRNA expression, while serum transaminase levels did not significantly differ from SHC mice. Under the NASH-inducing high-fat diet CSC and SHC mice showed similar body weight-gain and serum levels of glucose and adiponectin. Moreover, liver histology as well as TNFα, MCP-1 and HMOX expression were similar in CSC and SHC mice fed with HFD. Surprisingly, CSC showed even significantly lower transaminase levels than SHC mice fed with the same NASH-inducing diet. Together, these data indicate that under normal dietary conditions the CSC model induces noticeable hepatic oxidative stress and inflammation without causing manifest hepatocellular injury. In contrast, CSC exhibited a protective effect on hepatocellular injury in a dietary NASH-model. Identification of the underlying mechanisms of this phenomenon may lead to novel therapeutic strategies to prevent progression of NAFLD.

  12. Chronic forced swim stress produces subsensitivity to nicotine.

    Science.gov (United States)

    Peck, J A; Dilsaver, S C; McGee, M

    1991-03-01

    Twice daily injections of saline reduce the thermic response to nicotine in the rat. The authors hypothesized that this was due to the stress of twice-daily handling and injection. However, the injection of saline is not a classic stressor. The hypothesis that stress blunts thermic responsiveness to nicotine was, therefore, tested using a classic form of chronic inescapable stress. Rats (n = 12) were subjected to a 14-day, twice daily course of inescapable cold water swim stress using a repeated measures design. Thermic responsiveness of nicotine was measured at baseline and every 7 days thereafter for 49 days. The mean response to nicotine (1.0 mg/kg IP) differed significantly across time, F(7,88) = 10.6, p less than 0.0001. Mean thermic responsiveness (+/- SEM) decreased from -0.75 +/- 0.09 at baseline to -0.41 +/- 0.18 degrees C (54.7% of baseline) following 14 days of forced swim stress. This change was not significant. However, the thermic response to nicotine was -0.14 +/- 0.13 degrees C (p less than 0.05), +0.55 +/- 0.12 degrees C (p less than 0.05), and +0.04 +/- 0.11 degrees C (p less than 0.05) 7, 14, and 21 days following the discontinuation of forced swim stress. The mean response did not differ from baseline 28 days following the last session of forced swim stress. The data suggest that in the recovery phase the animals ceased to be sensitive to nicotine. These findings support the hypothesis that a chronic stressor can produce subsensitivity to nicotine. PMID:2068187

  13. Mindfulness-based stress reduction for people with chronic diseases.

    Science.gov (United States)

    Merkes, Monika

    2010-01-01

    Mindfulness-based stress reduction (MBSR) is a structured group program that uses mindfulness meditation to improve well-being and alleviate suffering. This article reviews the impact of MBSR for people with chronic diseases. The review includes original research that was published in English and peer-reviewed and reported outcomes for adults with chronic diseases who had participated in an MBSR program. Fifteen studies were identified. Outcomes related to mental and physical health, well-being, and quality of life. The studies included different research designs, and used self-report and physiological outcome measures. Participants' clinical diagnoses included fibromyalgia, chronic pain, rheumatoid arthritis, type 2 diabetes, chronic fatigue syndrome, multiple chemical sensitivity, and cardiovascular diagnoses. All 15 studies found that participation in an MBSR program resulted in improvements. No negative change was reported between baseline and follow up. Outcomes in regard to specific variables were difficult to compare and equivocal. Overall, positive change predominated. Chronic diseases are associated with a range of unwelcome psychological and physical consequences. Participation in an MBSR program is likely to result in coping better with symptoms, improved overall well-being and quality of life, and enhanced health outcomes. As an adjunct to standard care, MBSR has potential for much wider application in Australian primary care settings.

  14. Chronic stress, leukocyte subpopulations, and humoral response to latent viruses

    Energy Technology Data Exchange (ETDEWEB)

    McKinnon, W.; Weisse, C.S.; Reynolds, C.P.; Bowles, C.A.; Baum, A. (Uniformed Services Univ. of the Health Sciences, Bethesda, MD (USA))

    1989-01-01

    Psychological stress has been shown to affect immune system status and function, but most studies of this relationship have focused on acute stress and/or laboratory situations. The present study compared total numbers of leukocytes and lymphocyte subpopulations (determined by flow cytometry) and antibody titers to latent and nonlatent viruses among a group of chronically stressed individuals living near the damaged Three Mile Island (TMI) nuclear power plant with those of a demographically comparable control group. Urinary catecholamine and cortisol levels were also examined. Residents of the TMI area exhibited greater numbers of neutrophils, which were positively correlated with epinephrine levels. The TMI group also exhibited fewer B lymphocytes, T-suppressor/cytotoxic lymphocytes, and natural killer cells. Antibody titers to herpes simplex were significantly different across groups as well, whereas titers to nonlatent rubella virus as well as IgG and IgM levels were comparable.

  15. Medication overuse, healthy lifestyle behaviour and stress in chronic headache

    DEFF Research Database (Denmark)

    Westergaard, Maria Lurenda; Glümer, Charlotte; Hansen, Ebba Holme;

    2016-01-01

    AIM: This cross-sectional study investigated associations between chronic headache (CH) with and without medication overuse, healthy lifestyle behaviour, and stress. METHODS: Questionnaires were sent to 129,150 adults. Those with headache ≥15 days per month for three months were classified...... as having CH then further described as having medication-overuse headache (MOH) or CH without medication overuse. Associations between headache and daily smoking, physical inactivity, obesity, excessive drinking, illicit drug use, and high stress were analysed by logistic regression. RESULTS: CH...... with and without medication overuse (prevalence 1.8% and 1.6%, respectively) had strong, graded associations with stress. Associations with daily smoking, physical inactivity, and obesity were significant only for MOH. Odds for MOH were highest among people who had all three factors compared to those who had none...

  16. Chronic stress, leukocyte subpopulations, and humoral response to latent viruses

    International Nuclear Information System (INIS)

    Psychological stress has been shown to affect immune system status and function, but most studies of this relationship have focused on acute stress and/or laboratory situations. The present study compared total numbers of leukocytes and lymphocyte subpopulations (determined by flow cytometry) and antibody titers to latent and nonlatent viruses among a group of chronically stressed individuals living near the damaged Three Mile Island (TMI) nuclear power plant with those of a demographically comparable control group. Urinary catecholamine and cortisol levels were also examined. Residents of the TMI area exhibited greater numbers of neutrophils, which were positively correlated with epinephrine levels. The TMI group also exhibited fewer B lymphocytes, T-suppressor/cytotoxic lymphocytes, and natural killer cells. Antibody titers to herpes simplex were significantly different across groups as well, whereas titers to nonlatent rubella virus as well as IgG and IgM levels were comparable

  17. Potential oxidative stress in children with chronic constipation

    Institute of Scientific and Technical Information of China (English)

    Jun-Fu Zhou; Jian-Guo Lou; Sheng-Li Zhou; Ji-Yue Wang

    2005-01-01

    AIM: To investigate the potential oxidative stress in children with -chronic constipation and to explore its mechanisms.METHODS: Seventy children with chronic constipation and 70 age- and sex-matched healthy children were enrolled in a randomized controlled study. Plasma levels of vitamins C and E, activities of superoxide dismutase and catalase and lipoperoxide level in erythrocytes were determined by spectrophotometry.RESULTS: Compared with healthy children whose vitamin C,vitamin E, superoxide dismutase, catalase and lipoperoxide were 58.35±14.42 μmol/L, 27.15±6.55 μmol/L, 2 206±171U/(g· Hb), 327.3±82.2 K/(g·Hb) and 19.18±4.27 nmol/(g·Hb)respectively, the levels of vitamin C, vitamin E, the activity of superoxide dismutase, and catalase in the children with chronic constipation significantly decreased [46.59±11.51 μmol/L,20.65±4.80 μmol/L, 1943±147 U/(g·Hb) and 269.3±67.8 K/(g·Hb),respectively P<0.01], while the lipoperoxide significantly increased [25.22±5.01 nmol/(g·Hb), P<0.01]. With a prolonged course of disease, the levels of vitamin C, vitamin E, the activity of superoxide dismutase and catalase in the children with chronic constipation gradually decreased,while the level of lipoperoxide gradually increased.CONCLUSION: Chronic constipation can cause potential oxidative stress in children.

  18. Psychological impact of chronic hepatitis C: Comparison with other stressful life events and chronic diseases

    Institute of Scientific and Technical Information of China (English)

    Laurent Castera; Aymery Constant; Pierre-Henri Bernard; Victor de Ledinghen; Patrice Couzigou

    2006-01-01

    AIM: To examine the psychological impact of chronic hepatitis C (CHC) diagnosis in a large cohort of CHC patients as compared with other stressful life events and chronic diseases carrying a risk of life-threatening complications.METHODS: One hundred and eighty-five outpatients with compensated CHC were asked to self-grade, using a 100-mm visual analogue scale (VAS), the degree of stress caused by the learning of CHC diagnosis and the perceived severity of their disease. Diagnosis-related stress was compared to four other stressful life events and perceived CHC severity was compared to four other common chronic diseases.RESULTS: Learning of CHC diagnosis was considered a major stressful event (mean ± SD scores: 72±25),significantly less than death of a loved-one (89±13,P<0.0001) and divorce (78± 23, P<0.007), but more than job dismissal (68 ± 30, P<0.04) and home removal (26±24, P< 0.0001). CHC was considered a severe disease (74±19), after AIDS (94±08, P<0.001) and cancer (91±11, P<0.001), but before diabetes (66±23,P<0.001) and hypertension (62±20, P<0.001).Perceived CHC severity was not related to the actual severity of liver disease, assessed according to Metavir fibrosis score. In multivariate analysis, diagnosisrelated stress was related to perceived disease severity (P< 0.001), trait anxiety (P< 0.001) and infection through blood transfusion (P< 0.001).CONCLUSION: Our results show the considerable psychological and emotional burden that a diagnosis of CHC represents, even in the absence of significant liver disease. They should be taken into account when announcing a diagnosis of CHC in order to reduce its negative effects.

  19. Increased oxidative stress following acute and chronic high altitude exposure.

    Science.gov (United States)

    Jefferson, J Ashley; Simoni, Jan; Escudero, Elizabeth; Hurtado, Maria-Elena; Swenson, Erik R; Wesson, Donald E; Schreiner, George F; Schoene, Robert B; Johnson, Richard J; Hurtado, Abdias

    2004-01-01

    The generation of reactive oxygen species is typically associated with hyperoxia and ischemia reperfusion. Recent evidence has suggested that increased oxidative stress may occur with hypoxia. We hypothesized that oxidative stress would be increased in subjects exposed to high altitude hypoxia. We studied 28 control subjects living in Lima, Peru (sea level), at baseline and following 48 h exposure to high altitude (4300 m). To assess the effects of chronic altitude exposure, we studied 25 adult males resident in Cerro de Pasco, Peru (altitude 4300 m). We also studied 27 subjects living in Cerro de Pasco who develop excessive erythrocytosis (hematocrit > 65%) and chronic mountain sickness. Acute high altitude exposure led to increased urinary F(2)-isoprostane, 8-iso PGF(2 alpha) (1.31 +/- 0.8 microg/g creatinine versus 2.15 +/- 1.1, p = 0.001) and plasma total glutathione (1.29 +/- 0.10 micromol versus 1.37 +/- 0.09, p = 0.002), with a trend to increased plasma thiobarbituric acid reactive substance (TBARS) (59.7 +/- 36 pmol/mg protein versus 63.8 +/- 27, p = NS). High altitude residents had significantly elevated levels of urinary 8-iso PGF(2 alpha) (1.3 +/- 0.8 microg/g creatinine versus 4.1 +/- 3.4, p = 0.007), plasma TBARS (59.7 +/- 36 pmol/mg protein versus 85 +/- 28, p = 0.008), and plasma total glutathione (1.29 +/- 0.10 micromol versus 1.55 +/- 0.19, p < 0.0001) compared to sea level. High altitude residents with excessive erythrocytosis had higher levels of oxidative stress compared to high altitude residents with normal hematological adaptation. In conclusion, oxidative stress is increased following both acute exposure to high altitude without exercise and with chronic residence at high altitude.

  20. Chronic stress, cortisol dysfunction, and pain: a psychoneuroendocrine rationale for stress management in pain rehabilitation.

    Science.gov (United States)

    Hannibal, Kara E; Bishop, Mark D

    2014-12-01

    Pain is a primary symptom driving patients to seek physical therapy, and its attenuation commonly defines a successful outcome. A large body of evidence is dedicated to elucidating the relationship between chronic stress and pain; however, stress is rarely addressed in pain rehabilitation. A physiologic stress response may be evoked by fear or perceived threat to safety, status, or well-being and elicits the secretion of sympathetic catecholamines (epinephrine and norepinepherine) and neuroendocrine hormones (cortisol) to promote survival and motivate success. Cortisol is a potent anti-inflammatory that functions to mobilize glucose reserves for energy and modulate inflammation. Cortisol also may facilitate the consolidation of fear-based memories for future survival and avoidance of danger. Although short-term stress may be adaptive, maladaptive responses (eg, magnification, rumination, helplessness) to pain or non-pain-related stressors may intensify cortisol secretion and condition a sensitized physiologic stress response that is readily recruited. Ultimately, a prolonged or exaggerated stress response may perpetuate cortisol dysfunction, widespread inflammation, and pain. Stress may be unavoidable in life, and challenges are inherent to success; however, humans have the capability to modify what they perceive as stressful and how they respond to it. Exaggerated psychological responses (eg, catastrophizing) following maladaptive cognitive appraisals of potential stressors as threatening may exacerbate cortisol secretion and facilitate the consolidation of fear-based memories of pain or non-pain-related stressors; however, coping, cognitive reappraisal, or confrontation of stressors may minimize cortisol secretion and prevent chronic, recurrent pain. Given the parallel mechanisms underlying the physiologic effects of a maladaptive response to pain and non-pain-related stressors, physical therapists should consider screening for non-pain-related stress to

  1. 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

  2. Therapeutic effects of stress-programmed lymphocytes transferred to chronically stressed mice.

    Science.gov (United States)

    Scheinert, Rachel B; Haeri, Mitra H; Lehmann, Michael L; Herkenham, Miles

    2016-10-01

    Our group has recently provided novel insights into a poorly understood component of intercommunication between the brain and the immune system by showing that psychological stress can modify lymphocytes in a manner that may boost resilience to psychological stress. To demonstrate the influence of the adaptive immune system on mood states, we previously showed that cells from lymph nodes of socially defeated mice, but not from unstressed mice, conferred anxiolytic and antidepressant-like effects and elevated hippocampal cell proliferation when transferred into naïve lymphopenic Rag2(-/-) mice. In the present study, we asked whether similar transfer could be anxiolytic and antidepressant when done in animals that had been rendered anxious and depressed by chronic psychological stress. First, we demonstrated that lymphopenic Rag2(-/-) mice and their wild-type C57BL/6 mouse counterparts had similar levels of affect normally. Second, we found that following chronic (14days) restraint stress, both groups displayed an anxious and depressive-like phenotype and decreased hippocampal cell proliferation. Third, we showed that behavior in the open field test and light/dark box was normalized in the restraint-stressed Rag2(-/-) mice following adoptive transfer of lymph node cells from green fluorescent protein (GFP) expressing donor mice previously exposed to chronic (14days) of social defeat stress. Cells transferred from unstressed donor mice had no effect on behavior. Immunolabeling of GFP+ cells confirmed that tissue engraftment had occurred at 14days after transfer. We found GFP+ lymphocytes in the spleen, lymph nodes, blood, choroid plexus, and meninges of the recipient Rag2(-/-) mice. The findings suggest that the adaptive immune system may play a key role in promoting recovery from chronic stress. The data support using lymphocytes as a novel therapeutic target for anxiety states. PMID:27109071

  3. Effects of Chronic Central Arginine Vasopressin (AVP on Maternal Behavior in Chronically Stressed Rat Dams

    Directory of Open Access Journals (Sweden)

    Benjamin C. Nephew

    2012-11-01

    Full Text Available Exposure of mothers to chronic stressors during pregnancy or the postpartum period often leads to the development of depression, anxiety, or other related mood disorders. The adverse effects of mood disorders are often mediated through maternal behavior and recent work has identified arginine vasopressin (AVP as a key neuropeptide hormone in the expression of maternal behavior in both rats and humans. Using an established rodent model that elicits behavioral and physiological responses similar to human mood disorders, this study tested the effectiveness of chronic AVP infusion as a novel treatment for the adverse effects of exposure to chronic social stress during lactation in rats. During early (day 3 and mid (day 10 lactation, AVP treatment significantly decreased the latency to initiate nursing and time spent retrieving pups, and increased pup grooming and total maternal care (sum of pup grooming and nursing. AVP treatment was also effective in decreasing maternal aggression and the average duration of aggressive bouts on day 3 of lactation. Central AVP may be an effective target for the development of treatments for enhancing maternal behavior in individuals exposed to chronic social stress.

  4. Effects of Chronic Central Arginine Vasopressin (AVP) on Maternal Behavior in Chronically Stressed Rat Dams

    Science.gov (United States)

    Coverdill, Alexander J.; McCarthy, Megan; Bridges, Robert S.; Nephew, Benjamin C.

    2012-01-01

    Exposure of mothers to chronic stressors during pregnancy or the postpartum period often leads to the development of depression, anxiety, or other related mood disorders. The adverse effects of mood disorders are often mediated through maternal behavior and recent work has identified arginine vasopressin (AVP) as a key neuropeptide hormone in the expression of maternal behavior in both rats and humans. Using an established rodent model that elicits behavioral and physiological responses similar to human mood disorders, this study tested the effectiveness of chronic AVP infusion as a novel treatment for the adverse effects of exposure to chronic social stress during lactation in rats. During early (day 3) and mid (day 10) lactation, AVP treatment significantly decreased the latency to initiate nursing and time spent retrieving pups, and increased pup grooming and total maternal care (sum of pup grooming and nursing). AVP treatment was also effective in decreasing maternal aggression and the average duration of aggressive bouts on day 3 of lactation. Central AVP may be an effective target for the development of treatments for enhancing maternal behavior in individuals exposed to chronic social stress. PMID:24349762

  5. 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.

  6. Nitric oxide synthase and nitric oxide alterations in chronically stressed rats: a model for nitric oxide in major depressive disorder.

    Science.gov (United States)

    Gao, Shang-Feng; Lu, Yun-Rong; Shi, Li-Gen; Wu, Xue-Yan; Sun, Bo; Fu, Xin-Yan; Luo, Jian-Hong; Bao, Ai-Min

    2014-09-01

    Nitric oxide (NO) and NO synthase-1 (NOS1) are involved in the stress response and in depression. We compared NOS-NO alterations in rats exposed to chronic unpredictable stress (CUS) with alterations in major depressive disorder (MDD) in humans. In the hypothalamus of male CUS rats we determined NOS activity, and in the paraventricular nucleus (PVN) we determined NOS1-immunoreactive (ir) cell densities and co-localization of NOS1 with stress-related neuropeptides corticotropin-releasing hormone (CRH), vasopressin (AVP) or oxytocin (OXT). We measured plasma NO levels and cortisol in male medicine-naïve MDD patients and plasma NO and corticosterone (CORT) in CUS rats. In the CUS rat total NOS activity in the hypothalamus (P=0.018) and NOS1-ir cell density in the PVN were both significantly decreased (P=0.018), while NOS1 staining was mainly expressed in OXT-ir neurons in this nucleus. Interestingly, plasma NO levels were significantly increased both in male CUS rats (P=0.001) and in male MDD patients (Pdepression.

  7. Usefulness of salivary alpha amylase as a biomarker of chronic stress and stress related oral mucosal changes ' a pilot study

    OpenAIRE

    Vineetha, Ravindranath; Pai, Keerthilatha M; Vengal, Manoj; Gopalakrishna, Kodyalamoole; Narayanakurup, Dinesh

    2014-01-01

    Introduction: Salivary biomarkers are suggested to provide a reliable, noninvasive and objective measurement of chronic psychosocial stress and helps in assessment of pivotal role of stress in causation or precipitation of multitude of health problems. Objectives: To evaluate the usefulness of salivary alpha amylase activity as an objective indicator of chronic stress and to find out any correlation between stress- related mucosal complaints and its levels. Study Design: Study was conducted a...

  8. 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...

  9. Stress coping mechanisms in patients with chronic dermatoses

    Directory of Open Access Journals (Sweden)

    Korabel, Hanna

    2013-09-01

    Full Text Available Objective. The results of numerous studies of today confirm that persons suffering from psychosomatic disorders are not able to effectively cope with stress. The experience of stress is also frequently combined with the occurrence or aggravation of various skin diseases. The goal of our study was to identify the predominantways of coping with stress in the group of patients with chronic dermatoses.Methods. The group under study included patients receiving treatment in the Dermatology Clinic of Collegium Medicum, Jagiellonian University. They were either hospitalized patients or those who came for control examinations at the Outpatient Clinic. Evaluation of the forms of coping with stress was conducted with the help of the Endler and Parker Questionnaire – CISS.Results. They significantly more often apply the style of coping focused on avoiding (p-value= 0.0056. It also turned out that the patients in the dermatological groups manifested a constant tendency to get involved in vicarious activities (p-value=0.0247.Discussion. The results of the presented study indicate that there is a statistically significant difference between the patients with dermatological disorders and those in the control group as regards their ways of coping with stress.Conclusion. The results obtained in the discussed study may be a starting point for designing a complex support for the patients with skin diseases. The therapeutic technique that may prove helpful for this group of patients is the cognitive-behavioral therapy (CTB.

  10. 3, 4-methylenedioximethamphetamin reverses anxiety induced by chronic mild stress

    Directory of Open Access Journals (Sweden)

    Laura Andrea León A

    2013-01-01

    Full Text Available Here we report the effects of subchronic 3, 4 methylenedioximethamphetamine (MDMA on the elevated plusmaze, a widely used animal model of anxiety. Rats exposed to a mild chronic stress (MCS protocol received intracerebroventricular microinjections of the selective serotonin reuptake inhibitor (SSRI – fluoxetine (2.0 ug/ul or MDMA, (2.0 ug/ul for seven days. On the eighth day rats were tested in the elevated plus-maze. Our results showed that sub chronic MDMA interacted with MCS leading to a decrease in anxiety related behaviors including: percentage of open arms entries (F [2, 26] = 4.00; p = 0.031, time spent in the open arms (F [2, 26] = 3.656; p = 0.040 and time spent in the open arms extremities (F [2, 26] = 5.842; p = 0.008. These results suggest a potential effect of MDMA in the reversion of the emotional significance of aversive stimuli.

  11. 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

  12. Central oxytocin is involved in restoring impaired gastric motility following chronic repeated stress in mice

    OpenAIRE

    Babygirija, Reji; Zheng, Jun; Ludwig, Kirk; Takahashi, Toku

    2009-01-01

    Accumulation of continuous life stress (chronic stress) often causes gastric symptoms. The development of gastric symptoms may depend on how humans adapt to the stressful events in their daily lives. Although acute stress delays gastric emptying and alters upper gastrointestinal motility in rodents, the effects of chronic stress on gastric motility and its adaptation mechanism remains unclear. Central oxytocin has been shown to have antistress effects. We studied whether central oxytocin is i...

  13. Enhancement of Latent Inhibition by Chronic Mild Stress in Rats Submitted to Emotional Response Conditioning

    OpenAIRE

    Liana Lins Melo; de Moraes Ferrari, Elenice A.; Nancy Airoldi Teixeira; Guy Sandner

    2003-01-01

    This work evaluated the influence of chronic mild stress on latent inhibition (LI) in rats, using a conditioned emotional response (CER) procedure. Rats were assigned to four groups: a non pre-exposed control group (NPC), a non pre-exposed stressed group (NPS), a preexposed control group (PC), and a pre-exposed stressed group (PS). Stressed animals were submitted to a chronic mild stress (CMS) regimen for three weeks. The off-baseline conditioned emotional response procedure had four phases: ...

  14. 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.

  15. 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

  16. Influence of imipramine on the duration of immobility in chronic forced-swim-stressed rats.

    OpenAIRE

    Kitamura, Yoshihisa; Araki,Hiroaki; Nagatani,Tadashi; Takao,Katsuyuki; Shibata, Kazuhiko; Gomita,Yutaka

    2004-01-01

    We studied the influence of imipramine on the duration of immobility in chronic forced-swim-stressed rats. Both single and chronic administration of imipramine potently shortened immobility in naive rats during forced-swim testing. However, chronic, 14-day forced-swim stress testing blocked the immobility-decreasing effect induced by a single administration of imipramine. When imipramine was administered for 14 days concurrently with forced-swim stress testing, immobility was shorten...

  17. Stressful Presentations: Mild Chronic Cold Stress in Mice Influences Baseline Properties of Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Kathleen Marie Kokolus

    2014-02-01

    Full Text Available The ability of dendritic cells to stimulate and regulate T cells is critical to effective anti-tumor immunity. Therefore, it is important to fully recognize any inherent factors which may influence DC function under experimental conditions, especially in laboratory mice since they are used so heavily to study immune responses. Physiological stress is well recognized to impair several arms of immune protection. The goals of this report are to briefly summarize previous work revealing how DCs respond to various forms of physiologically relevant stress and to present new data highlighting the potential for chronic mild cold stress inherent in mice housed at standard ambient temperatures required for laboratory mice to influence baseline DCs properties. Since recent data from our group shows that CD8+ T cell function is altered by mild chronic cold stress and since DC function is crucial for CD8+ T cell activation, we wondered whether mild cold stress may also be influencing DC properties. We found increased numbers of splenic DCs (CD11c+ in cold stressed mice compared to mice housed at a thermoneutral temperature, which significantly reduces cold stress. However, many of the DCs which are expanded in cold stressed mice express an immature phenotype. We also found that antigen presentation and ability of splenocytes to activate T cells were impaired compared to that seen in DCs isolated from mice at thermoneutrality. The new data presented here strongly suggest that the housing temperature of mice can affect fundamental properties of DC function which in turn could be influencing the response of DCs to added experimental stressors or other treatments.

  18. Influence of imipramine on the duration of immobility in chronic forced-swim-stressed rats.

    Science.gov (United States)

    Kitamura, Yoshihisa; Araki, Hiroaki; Nagatani, Tadashi; Takao, Katsuyuki; Shibata, Kazuhiko; Gomita, Yutaka

    2004-12-01

    We studied the influence of imipramine on the duration of immobility in chronic forced-swim-stressed rats. Both single and chronic administration of imipramine potently shortened immobility in naive rats during forced-swim testing. However, chronic, 14-day forced-swim stress testing blocked the immobility-decreasing effect induced by a single administration of imipramine. When imipramine was administered for 14 days concurrently with forced-swim stress testing, immobility was shortened significantly. From the viewpoint of imipramine's effect, these findings suggest that chronic forced-swim stress testing in rats may be an effective animal model for depression.

  19. Influence of imipramine on the duration of immobility in chronic forced-swim-stressed rats.

    Directory of Open Access Journals (Sweden)

    Kitamura,Yoshihisa

    2004-12-01

    Full Text Available

    We studied the influence of imipramine on the duration of immobility in chronic forced-swim-stressed rats. Both single and chronic administration of imipramine potently shortened immobility in naive rats during forced-swim testing. However, chronic, 14-day forced-swim stress testing blocked the immobility-decreasing effect induced by a single administration of imipramine. When imipramine was administered for 14 days concurrently with forced-swim stress testing, immobility was shortened significantly. From the viewpoint of imipramine's effect, these findings suggest that chronic forced-swim stress testing in rats may be an effective animal model for depression.

  20. Oxidative Stress in Children with Chronic Spontaneous Urticaria

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    Fatih Dilek

    2016-01-01

    Full Text Available The pathogenesis of chronic spontaneous urticaria (CSU has not been fully understood; nevertheless, significant progress has been achieved in recent years. The aim of this study was to investigate the possible role of reactive oxygen species (ROS in the pathogenesis of CSU. Sixty-two children with CSU and 41 healthy control subjects were enrolled in the study. An extensive evaluation of demographic and clinical features was done, and serum oxidative stress was evaluated by plasma total oxidant status (TOS and total antioxidant status (TAS measurements. The median value of plasma TOS was found to be 10.49 μmol H2O2 equiv./L (interquartile range, 7.29–17.65 in CSU patients and 7.68 μmol H2O2 equiv./L (5.95–10.39 in the control group. The difference between the groups was statistically significant (p=0.003. Likewise, the median plasma TAS level in the CSU group was decreased significantly compared to that of the control group (2.64 [2.30–2.74] versus 2.76 [2.65–2.86] mmol Trolox equiv./L, resp., p = 0,001. Our results indicated that plasma oxidative stress is increased in children with CSU when compared to healthy subjects, and plasma oxidative stress markers are positively correlated with disease activity.

  1. 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

  2. Comparison of the effects of acute and chronic psychological stress on metabolic features in rats

    Institute of Scientific and Technical Information of China (English)

    Fatemeh ROSTAMKHANI; Homeira ZARDOOZ; Saleh ZAHEDIASL; Babak FARROKHI

    2012-01-01

    This study was aimed to compare the effects of acute and chronic psychological stress on metabolic factors.Forty-two male Wistar rats were divided into control and stressed groups.Stress was applied by a communication box acutely (1 d) and chronically (15 and 30 d).Blood sampling was carried out by retro-orbital-puncture method.The plasma levels of glucose,cholesterol,triglyceride,insulin,and corticosterone were measured.In addition,feed and water intake,latency to eat and drink,adrenal and body weights were determined.Acute and chronic psychological stress did not significantly change basal plasma corticosterone levels.However,immediately (1 min) after acute exposure to stress,plasma corticosterone level increased compared to that before stress exposure.Acute stress increased plasma insulin levels significantly.Fifteen days of stress exposure resulted in plasma glucose increase.Chronic stress significantly increased feed intake,latency to eat,and adrenal weight compared to acute stress.The body weights of both control and stressed groups increased markedly during the experiment.Homeostasis model assessment of insulin resistance (HOMA-IR) index did not change significantly in the stressed group.In conclusion,application of acute and chronic psychological stress leads to different metabolic and/or behavioral changes but the metabolic changes resulting from acute exposure to stress seem to be more pronounced.

  3. Oxidative Stress in Diabetic Nephropathy with Early Chronic Kidney Disease

    Science.gov (United States)

    Andrade-Sierra, Jorge

    2016-01-01

    The increase in the prevalence of diabetes mellitus (DM) and the secondary kidney damage produces diabetic nephropathy (DN). Early nephropathy is defined as the presence of microalbuminuria (30–300 mg/day), including normal glomerular filtration rate (GFR) or a mildly decreased GFR (60–89 mL/min/1.73 m2), with or without overt nephropathy. The earliest change caused by DN is hyperfiltration with proteinuria. The acceptable excretion rate of albumin in urine is 300 mg/day. Chronic kidney disease (CKD) is characterized by abnormalities in renal function that persist for >3 months with health implications. Alterations in the redox state in DN are caused by the persistent state of hyperglycemia and the increase in advanced glycation end products (AGEs) with ability to affect the renin-angiotensin system and the transforming growth factor-beta (TGF-β), producing chronic inflammation and glomerular and tubular hypertrophy and favoring the appearance of oxidative stress. In DN imbalance between prooxidant/antioxidant processes exists with an increase in reactive oxygen species (ROS). The overproduction of ROS diminishes expression of the antioxidant enzymes (manganese superoxide dismutase, glutathione peroxidase, and catalase). The early detection of CKD secondary to DN and the timely identification of patients would permit decreasing its impact on health. PMID:27525285

  4. Oxidative Stress in Diabetic Nephropathy with Early Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Alejandra Guillermina Miranda-Díaz

    2016-01-01

    Full Text Available The increase in the prevalence of diabetes mellitus (DM and the secondary kidney damage produces diabetic nephropathy (DN. Early nephropathy is defined as the presence of microalbuminuria (30–300 mg/day, including normal glomerular filtration rate (GFR or a mildly decreased GFR (60–89 mL/min/1.73 m2, with or without overt nephropathy. The earliest change caused by DN is hyperfiltration with proteinuria. The acceptable excretion rate of albumin in urine is 300 mg/day. Chronic kidney disease (CKD is characterized by abnormalities in renal function that persist for >3 months with health implications. Alterations in the redox state in DN are caused by the persistent state of hyperglycemia and the increase in advanced glycation end products (AGEs with ability to affect the renin-angiotensin system and the transforming growth factor-beta (TGF-β, producing chronic inflammation and glomerular and tubular hypertrophy and favoring the appearance of oxidative stress. In DN imbalance between prooxidant/antioxidant processes exists with an increase in reactive oxygen species (ROS. The overproduction of ROS diminishes expression of the antioxidant enzymes (manganese superoxide dismutase, glutathione peroxidase, and catalase. The early detection of CKD secondary to DN and the timely identification of patients would permit decreasing its impact on health.

  5. Chronic Non-Social Stress Affects Depressive Behaviors But Not Anxiety in Mice

    OpenAIRE

    Yoon, Sang Ho; Kim, Byung-Hak; Ye, Sang-Kyu; Kim, Myoung-Hwan

    2014-01-01

    The etiology of most psychiatric disorders is still incompletely understood. However, growing evidence suggests that stress is a potent environmental risk factor for depression and anxiety. In rodents, various stress paradigms have been developed, but psychosocial stress paradigms have received more attention than non-social stress paradigms because psychosocial stress is more prevalent in humans. Interestingly, some recent studies suggest that chronic psychosocial stress and social isolation...

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

    Directory of Open Access Journals (Sweden)

    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.

  7. Effect of Chronic Psychological Stress on Liver Metastasis of Colon Cancer in Mice.

    Directory of Open Access Journals (Sweden)

    Lu Zhao

    Full Text Available Metastasis to the liver is a main factor in colorectal cancer mortality. Previous studies suggest that chronic psychological stress is important in cancer progression, but its effect on liver metastasis has not been investigated. To address this, we established a liver metastasis model in BALB/c nude mice to investigate the role of chronic stress in liver metastasis. Our data suggest that chronic stress elevates catecholamine levels and promotes liver metastasis. Chronic stress was also associated with increased tumor associated macrophages infiltration into the primary tumor and increased the expression of metastatic genes. Interestingly, β-blocker treatment reversed the effects of chronic stress on liver metastasis. Our results suggest the β-adrenergic signaling pathway is involved in regulating colorectal cancer progression and liver metastasis. Additionally, we submit that adjunctive therapy with a β-blocker may complement existing colorectal cancer therapies.

  8. Effect of Chronic Psychological Stress on Liver Metastasis of Colon Cancer in Mice.

    Science.gov (United States)

    Zhao, Lu; Xu, Jianhua; Liang, Fang; Li, Ao; Zhang, Yong; Sun, Jue

    2015-01-01

    Metastasis to the liver is a main factor in colorectal cancer mortality. Previous studies suggest that chronic psychological stress is important in cancer progression, but its effect on liver metastasis has not been investigated. To address this, we established a liver metastasis model in BALB/c nude mice to investigate the role of chronic stress in liver metastasis. Our data suggest that chronic stress elevates catecholamine levels and promotes liver metastasis. Chronic stress was also associated with increased tumor associated macrophages infiltration into the primary tumor and increased the expression of metastatic genes. Interestingly, β-blocker treatment reversed the effects of chronic stress on liver metastasis. Our results suggest the β-adrenergic signaling pathway is involved in regulating colorectal cancer progression and liver metastasis. Additionally, we submit that adjunctive therapy with a β-blocker may complement existing colorectal cancer therapies. PMID:26444281

  9. Chronic stress disrupts fear extinction and enhances amygdala and hippocampal Fos expression in an animal model of post-traumatic stress disorder

    OpenAIRE

    Hoffman, Ann N.; Lorson, Nickolaus G.; Sanabria, Federico; Olive, M. Foster; Conrad, Cheryl D.

    2014-01-01

    Chronic stress may impose a vulnerability to develop maladaptive fear-related behaviors after a traumatic event. Whereas previous work found that chronic stress impairs the acquisition and recall of extinguished fear, it is unknown how chronic stress impacts nonassociative fear, such as in the absence of the conditioned stimulus (CS) or in a novel context. Male rats were subjected to chronic stress (STR; wire mesh restraint 6h/d/21d) or undisturbed (CON), then tested on fear...

  10. Association between endothelial dysfunction and depression-like symptoms in chronic mild stress model of depression

    DEFF Research Database (Denmark)

    Bouzinova, Elena; Bødtkjer, Donna Marie Briggs; Kudryavtseva, Olga;

    2014-01-01

    OBJECTIVE: Cardiovascular diseases have high comorbidity with major depression. Endothelial dysfunction may explain the adverse cardiovascular outcome in depression; therefore, we analyzed it in vitro. In the chronic mild stress model, some rats develop depression-like symptoms (including...... "anhedonia"), whereas others are stress resilient. METHODS: After 8 weeks of chronic mild stress, anhedonic rats reduced their sucrose intake by 55% (7%), whereas resilient rats did not. Acetylcholine-induced endothelium-dependent relaxation of norepinephrine-preconstricted mesenteric arteries was analyzed...

  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. Gene Expression Profile of the Hippocampus of Rats Subjected to Chronic Immobilization Stress

    OpenAIRE

    Li, Xiao-Hong; Chen, Jia-Xu; Yue, Guang-Xin; Liu, Yue-Yun; Zhao, Xin; Guo, Xiao-Ling; Liu, Qun; Jiang, You-Ming; Bai, Ming-Hua

    2013-01-01

    Objective This study systematically investigated the effect of chronic stress on the hippocampus and its damage mechanism at the whole genome level. Methods The rat whole genome expression chips (Illumina) were used to detect gene expression differences in the hippocampus of rats subjected to chronic immobilization stress (daily immobilization stress for 3 h, for 7 or 21 days). The hippocampus gene expression profile was studied through gene ontology and signal pathway analyses using bioinfor...

  13. Metabolomic identification of biochemical changes induced by fluoxetine and imipramine in a chronic mild stress mouse model of depression

    Science.gov (United States)

    Zhao, Jing; Jung, Yang-Hee; Jang, Choon-Gon; Chun, Kwang-Hoon; Kwon, Sung Won; Lee, Jeongmi

    2015-03-01

    Metabolomics was applied to a C57BL/6N mouse model of chronic unpredictable mild stress (CMS). Such mice were treated with two antidepressants from different categories: fluoxetine and imipramine. Metabolic profiling of the hippocampus was performed using gas chromatography-mass spectrometry analysis on samples prepared under optimized conditions, followed by principal component analysis, partial least squares-discriminant analysis, and pair-wise orthogonal projections to latent structures discriminant analyses. Body weight measurement and behavior tests including an open field test and the forced swimming test were completed with the mice as a measure of the phenotypes of depression and antidepressive effects. As a result, 23 metabolites that had been differentially expressed among the control, CMS, and antidepressant-treated groups demonstrated that amino acid metabolism, energy metabolism, adenosine receptors, and neurotransmitters are commonly perturbed by drug treatment. Potential predictive markers for treatment effect were identified: myo-inositol for fluoxetine and lysine and oleic acid for imipramine. Collectively, the current study provides insights into the molecular mechanisms of the antidepressant effects of two widely used medications.

  14. Peripheral markers of oxidative stress in chronic mercuric chloride intoxication

    Directory of Open Access Journals (Sweden)

    Gutierrez L.L.P.

    2006-01-01

    Full Text Available The present study was designed to evaluate the time course changes in peripheral markers of oxidative stress in a chronic HgCl2 intoxication model. Twenty male adult Wistar rats were treated subcutaneously daily for 30 days and divided into two groups of 10 animals each: Hg, which received HgCl2 (0.16 mg kg-1 day-1, and control, receiving the same volume of saline solution. Blood was collected at the first, second and fourth weeks of Hg administration to evaluate lipid peroxidation (LPO, total radical trapping antioxidant potential (TRAP, and superoxide dismutase (Cu,Zn-SOD, glutathione peroxidase (GPx, glutathione-S-transferase (GST, and catalase (CAT. HgCl2 administration induced a rise (by 26% in LPO compared to control (143 ± 10 cps/mg hemoglobin in the second week and no difference was found at the end of the treatment. At that time, GST and GPx were higher (14 and 24%, respectively in the Hg group, and Cu,Zn-SOD was lower (54% compared to control. At the end of the treatment, Cu,Zn-SOD and CAT were higher (43 and 10%, respectively in the Hg group compared to control (4.6 ± 0.3 U/mg protein; 37 ± 0.9 pmol/mg protein, respectively. TRAP was lower (69% in the first week compared to control (43.8 ± 1.9 mM Trolox. These data provide evidence that HgCl2 administration is accompanied by systemic oxidative damage in the initial phase of the process, which leads to adaptive changes in the antioxidant reserve, thus decreasing the oxidative injury at the end of 30 days of HgCl2 administration. These results suggest that a preventive treatment with antioxidants would help to avoid oxidative damage in subjects with chronic intoxication.

  15. Behavioral effects of chronic adolescent stress are sustained and sexually dimorphic

    OpenAIRE

    Bourke, Chase H.; Neigh, Gretchen N

    2011-01-01

    Evidence suggests that women are more susceptible to stress-related disorders than men. Animal studies demonstrate a similar female sensitivity to stress and have been used to examine the underlying neurobiology of sex-specific effects of stress. Although our understanding of the sex-specific effects of chronic adolescent stress has grown in recent years, few studies have reported the effects of adolescent stress on depressive-like behavior. The purpose of this study was to determine if a chr...

  16. Chronic obstructive lung disease and posttraumatic stress disorder: current perspectives

    Directory of Open Access Journals (Sweden)

    Abrams TE

    2015-10-01

    Full Text Available Thad E Abrams,1,2 Amy Blevins,1,3 Mark W Vander Weg1,2,4 1Department of Internal Medicine, University of Iowa, 2Center for Comprehensive Access and Delivery Research and Evaluation, Iowa City VA Health Care System, 3Hardin Health Sciences Library, 4Department of Psychological and Brain Sciences, University of Iowa, Iowa City, IA, USA Background: Several studies have reported on the co-occurrence of chronic obstructive pulmonary disease (COPD and psychiatric conditions, with the most robust evidence base demonstrating an impact of comorbid anxiety and depression on COPD-related outcomes. In recent years, research has sought to determine if there is a co-occurrence between COPD and posttraumatic stress disorder (PTSD as well as for associations between PTSD and COPD-related outcomes. To date, there have been no published reviews summarizing this emerging literature.Objectives: The primary objective of this review was to determine if there is adequate evidence to support a co-occurrence between PTSD and COPD. Secondary objectives were to: 1 determine if there are important clinical considerations regarding the impact of PTSD on COPD management, and 2 identify targeted areas for further research.Methods: A structured review was performed using a systematic search strategy limited to studies in English, addressing adults, and to articles that examined: 1 the co-occurrence of COPD and PTSD and 2 the impact of PTSD on COPD-related outcomes. To be included, articles must have addressed some type of nonreversible obstructive lung pathology.Results: A total of 598 articles were identified for initial review. Upon applying the inclusion and exclusion criteria, n=19 articles or abstracts addressed our stated objectives. Overall, there is inconclusive evidence to support the co-occurrence between PTSD and COPD. Studies finding a significant co-occurrence generally had inferior methods of identifying COPD; in contrast, studies that utilized more robust COPD

  17. Prepubertal chronic stress and ketamine administration to rats as a neurodevelopmental model of schizophrenia symptomatology.

    Science.gov (United States)

    Ram, Edward; Raphaeli, Shani; Avital, Avi

    2013-11-01

    Increased vulnerability to psychiatric disorders, such as schizophrenia, has been associated with higher levels of stress. In the early development of the central nervous system, changes in function of glutamatergic N-Methyl-D-aspartate (NMDA) receptors can possibly result in the development of psychosis, cognitive impairment and emotional dysfunction in adulthood. Thus, in this study we examined the behavioural consequences of the exposure of male rats to chronic stress (postnatal days 30-60) and ketamine administration (postnatal days 41-45); both during a sensitive developmental time window. We found that the locomotor activity of both ketamine and ketamine+chronic stress groups was significantly higher compared with that of the control rats. In contrast, the locomotor activity of the chronic stress group was significantly lower compared with all other groups. Examining anhedonia in the sucrose preference test we found a significantly decreased sucrose intake in both ketamine+chronic stress and the chronic stress groups compared with the control rats. No significant differences were observed in sucrose intake between the control and the ketamine group. The object recognition test revealed that the attention to the novel object was significantly impaired in the ketamine+chronic stress group. Similarly, the ketamine+chronic stress group showed the poorest learning ability in the eight-arm radial maze, starting on the 8th day. Finally, throughout the different pre-pulse intensities, the ketamine+chronic stress group showed impaired PPI compared with all other groups. The results indicate that the combination of prepubertal onset of chronic stress and ketamine may serve as a valid novel animal model for schizophrenia-like symptoms.

  18. 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...

  19. The appraisal of chronic stress and the development of the metabolic syndrome

    DEFF Research Database (Denmark)

    Bergmann, N; Gyntelberg, F; Faber, J

    2014-01-01

    Chronic psychosocial stress has been proposed as a risk factor for the development of the metabolic syndrome (MES). This review gives a systematic overview of prospective cohort studies investigating chronic psychosocial stress as a risk factor for incident MES and the individual elements of MES....... Thirty-nine studies were included. An association between chronic psychosocial stress and the development of MES was generally supported. Regarding the four elements of MES: i) weight gain: the prospective studies supported etiological roles for relationship stress, perceived stress, and distress, while...... the studies on work-related stress (WS) showed conflicting results; ii) dyslipidemi: too few studies on psychosocial stress as a risk factor for dyslipidemia were available to draw a conclusion; however, a trend toward a positive association was present; iii) type 2 diabetes mellitus (DM2): prospective...

  20. Chronic Psychological Stress Enhances Nociceptive Processing in the Urinary Bladder in High-Anxiety Rats

    OpenAIRE

    Robbins, M.T.; DeBerry, J.; Ness, T. J

    2007-01-01

    This study sought to determine whether acute and/or chronic psychological stress produce changes in urinary bladder nociception. Female Sprague-Dawley (SD; low/moderate anxiety) or Wistar-Kyoto (WK; high-anxiety) rats were exposed to either an acute (1 day) or a chronic (10 days) water avoidance stress paradigm or a sham stress paradigm. Paw withdrawal thresholds to mechanical and thermal stimuli and fecal pellet output, were quantified at baseline and after the final stress or sham stress ex...

  1. 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.

  2. Chronic stress and calcium oxalate stone disease: is it a potential recurrence risk factor?

    Science.gov (United States)

    Arzoz-Fabregas, Montserrat; Ibarz-Servio, Luis; Edo-Izquierdo, Sílvia; Doladé-Botías, María; Fernandez-Castro, Jordi; Roca-Antonio, Josep

    2013-04-01

    Chronic emotional stress is associated with increased cortisol release and metabolism disorders. However, few studies have evaluated the influence of chronic stress on calcium oxalate (CaOx) stone disease and its recurrence. A total of 128 patients were enrolled in this case-control study over a period of 20 months. All patients were CaOx stone formers with a recent stone episode (stone formers (FS) and 33 recurrent stone formers (RS). Dimensions of chronic stress were evaluated with self-reported validated questionnaires measuring stressful life events, perceived stress, anxiety, depression, burnout and satisfaction with life. An ad hoc self-reporting questionnaire was designed to evaluate stress-related specifically to stone episodes. Blood and urine samples were collected to determine cortisol levels and urinary composition. In addition, epidemiological data, socioeconomic information, diet and incidences of metabolic syndrome (MS) were reported. Overall, no significant differences were observed in the scores of cases and controls on any of the questionnaires dealing with stress. The number (p incidences of MS (p = 0.07) than FS. Although no differences were observed in cases and controls among any dimension of chronic stress, the number and intensity of stressful life events were higher in RS than in FS. These differences correlate with variations in blood and urinary levels and with metabolic disorders, indicating an association between chronic stress and risk of recurrent CaOx stone formation.

  3. 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.

  4. Long-lasting antidepressant action of ketamine, but not glycogen synthase kinase-3 inhibitor SB216763, in the chronic mild stress model of mice.

    Directory of Open Access Journals (Sweden)

    Xian-Cang Ma

    Full Text Available BACKGROUND: Clinical studies demonstrate that the N-methyl-D-aspartate (NMDA receptor antagonist, ketamine, induces rapid antidepressant effects in patients with refractive major depressive disorder and bipolar depression. This rapid onset of action makes ketamine a highly attractive drug for patients, particularly those who do not typically respond to therapy. A recent study suggested that glycogen synthase kinase (GSK-3 may underlie the rapid antidepressant action of ketamine, although the precise mechanisms are unclear. In this study, we examined the effects of ketamine and GSK-3 inhibitor SB216763 in the unpredictable, chronic mild stress (CMS mouse model of mice. METHODOLOGY/PRINCIPAL FINDINGS: Adult C57/B6 male mice were divided into 2 groups, a non-stressed control group and the unpredictable CMS (35 days group. Then, either vehicle, ketamine (10 mg/kg, or the established GSK-3 inhibitor, SB216763 (10 mg/kg, were administered into mice in the CMS group, while vehicle was administered to controls. In the open field test, there was no difference between the four groups (control+vehicle, CMS+vehicle, CMS+ketamine, CMS+SB216763. In the sucrose intake test, a 1% sucrose intake drop, seen in CMS mice, was significantly attenuated after a single dose of ketamine, but not SB216763. In the tail suspension test (TST and forced swimming test (FST, the increased immobility time seen in CMS mice was significantly attenuated by a single dose of ketamine, but not SB216763. Interestingly, the ketamine-induced increase in the sucrose intake test persisted for 8 days after a single dose of ketamine. Furthermore, a single administration of ketamine, but not SB216763, significantly attenuated the immobility time of the TST and FST in the control (non-stressed mice. CONCLUSIONS/SIGNIFICANCE: These findings suggest that a single administration of ketamine, but not GSK-3 inhibitor SB216763, produces a long-lasting antidepressant action in CMS model mice.

  5. L-tyrosine improves neuroendocrine function in a mouse model of chronic stress

    Institute of Scientific and Technical Information of China (English)

    Zhihua Wang; Jinghua Li; Zhiming Wang; Lingyan Xue; Yi Zhang; Yingjie Chen; Jun Su; Zhongming Li

    2012-01-01

    Adult BALB/c mice, individually housed, were stimulated with nine different stressors, arranged randomly, for 4 continuous weeks to generate an animal model of chronic stress. In chronically stressed mice, spontaneous locomotor activity was significantly decreased, escape latency in the Morris water maze test was prolonged, serum levels of total thyrotropin and total triiodothyronine were significantly decreased, and dopamine and norepinephrine content in the pallium, hippocampus and hypothalamus were significantly reduced. All of these changes were suppressed, to varying degrees, by L-tyrosine supplementation. These findings indicate that the neuroendocrine network plays an important role in chronic stress, and that L-tyrosine supplementation has therapeutic effects.

  6. Chronic Stress is Prospectively Associated with Sleep in Midlife Women: The SWAN Sleep Study

    Science.gov (United States)

    Hall, Martica H.; Casement, Melynda D.; Troxel, Wendy M.; Matthews, Karen A.; Bromberger, Joyce T.; Kravitz, Howard M.; Krafty, Robert T.; Buysse, Daniel J.

    2015-01-01

    Study Objectives: Evaluate whether levels of upsetting life events measured over a 9-y period prospectively predict subjective and objective sleep outcomes in midlife women. Design: Prospective cohort study. Setting: Four sites across the United States. Participants: 330 women (46–57 y of age) enrolled in the Study of Women's Health Across the Nation (SWAN) Sleep Study. Interventions: N/A. Measurements and Results: Upsetting life events were assessed annually for up to 9 y. Trajectory analysis applied to life events data quantitatively identified three distinct chronic stress groups: low stress, moderate stress, and high stress. Sleep was assessed by self-report and in-home polysomnography (PSG) during the ninth year of the study. Multivariate analyses tested the prospective association between chronic stress group and sleep, adjusting for race, baseline sleep complaints, marital status, body mass index, symptoms of depression, and acute life events at the time of the Sleep Study. Women characterized by high chronic stress had lower subjective sleep quality, were more likely to report insomnia, and exhibited increased PSG-assessed wake after sleep onset (WASO) relative to women with low to moderate chronic stress profiles. The effect of chronic stress group on WASO persisted in the subsample of participants without baseline sleep complaints. Conclusions: Chronic stress is prospectively associated with sleep disturbance in midlife women, even after adjusting for acute stressors at the time of the sleep study and other factors known to disrupt sleep. These results are consistent with current models of stress that emphasize the cumulative effect of stressors on health over time. Citation: Hall MH, Casement MD, Troxel WM, Matthews KA, Bromberger JT, Kravitz HM, Krafty RT, Buysse DJ. Chronic stress is prospectively associated with sleep in midlife women: the SWAN Sleep Study. SLEEP 2015;38(10):1645–1654. PMID:26039965

  7. Stress and sleep duration predict headache severity in chronic headache sufferers.

    Science.gov (United States)

    Houle, Timothy T; Butschek, Ross A; Turner, Dana P; Smitherman, Todd A; Rains, Jeanetta C; Penzien, Donald B

    2012-12-01

    The objective of this study was to evaluate the time-series relationships between stress, sleep duration, and headache pain among patients with chronic headaches. Sleep and stress have long been recognized as potential triggers of episodic headache (headache days/month), though prospective evidence is inconsistent and absent in patients diagnosed with chronic headaches (≥15 days/month). We reanalyzed data from a 28-day observational study of chronic migraine (n=33) and chronic tension-type headache (n=22) sufferers. Patients completed the Daily Stress Inventory and recorded headache and sleep variables using a daily sleep/headache diary. Stress ratings, duration of previous nights' sleep, and headache severity were modeled using a series of linear mixed models with random effects to account for individual differences in observed associations. Models were displayed using contour plots. Two consecutive days of either high stress or low sleep were strongly predictive of headache, whereas 2 days of low stress or adequate sleep were protective. When patterns of stress or sleep were divergent across days, headache risk was increased only when the earlier day was characterized by high stress or poor sleep. As predicted, headache activity in the combined model was highest when high stress and low sleep occurred concurrently during the prior 2 days, denoting an additive effect. Future research is needed to expand on current findings among chronic headache patients and to develop individualized models that account for multiple simultaneous influences of headache trigger factors.

  8. The effects of chronic social defeat stress on mouse self-grooming behavior and its patterning.

    Science.gov (United States)

    Denmark, Ashley; Tien, David; Wong, Keith; Chung, Amanda; Cachat, Jonathan; Goodspeed, Jason; Grimes, Chelsea; Elegante, Marco; Suciu, Christopher; Elkhayat, Salem; Bartels, Brett; Jackson, Andrew; Rosenberg, Michael; Chung, Kyung Min; Badani, Hussain; Kadri, Ferdous; Roy, Sudipta; Tan, Julia; Gaikwad, Siddharth; Stewart, Adam; Zapolsky, Ivan; Gilder, Thomas; Kalueff, Allan V

    2010-04-01

    Stress induced by social defeat is a strong modifier of animal anxiety and depression-like phenotypes. Self-grooming is a common rodent behavior, and has an ordered cephalo-caudal progression from licking of the paws to head, body, genitals and tail. Acute stress is known to alter grooming activity levels and disrupt its patterning. Following 15-17 days of chronic social defeat stress, grooming behavior was analyzed in adult male C57BL/6J mice exhibiting either dominant or subordinate behavior. Our study showed that subordinate mice experience higher levels of anxiety and display disorganized patterning of their grooming behaviors, which emerges as a behavioral marker of chronic social stress. These findings indicate that chronic social stress modulates grooming behavior in mice, thus illustrating the importance of grooming phenotypes for neurobehavioral stress research.

  9. Diffusion-weighted MRI and quantitative biophysical modeling of hippocampal neurite loss in chronic stress.

    Directory of Open Access Journals (Sweden)

    Peter Vestergaard-Poulsen

    Full Text Available Chronic stress has detrimental effects on physiology, learning and memory and is involved in the development of anxiety and depressive disorders. Besides changes in synaptic formation and neurogenesis, chronic stress also induces dendritic remodeling in the hippocampus, amygdala and the prefrontal cortex. Investigations of dendritic remodeling during development and treatment of stress are currently limited by the invasive nature of histological and stereological methods. Here we show that high field diffusion-weighted MRI combined with quantitative biophysical modeling of the hippocampal dendritic loss in 21 day restraint stressed rats highly correlates with former histological findings. Our study strongly indicates that diffusion-weighted MRI is sensitive to regional dendritic loss and thus a promising candidate for non-invasive studies of dendritic plasticity in chronic stress and stress-related disorders.

  10. Depressive symptoms and perceived chronic stress predict test anxiety in nursing students

    Directory of Open Access Journals (Sweden)

    Christoph Augner

    2015-09-01

    Full Text Available Aim: The aim of this study is to identify predictors of test anxiety in nursing students. Design: Cross sectional pilot study. Methods: A questionnaire was administered to 112 students of an Austrian nursing school (mean age = 21.42, SD = 5.21. Test anxiety (measured by the standardized PAF Test Anxiety Questionnaire, perceived chronic stress, depressive symptoms, pathological eating and further psychological and health parameters were measured. Results: We found highly significant correlations between test anxiety and working hours (0.25, depression score (0.52, emotional stability (-0.31, and perceived chronic stress (0.65 (p < 0.01, for all. Regression analysis revealed chronic stress and emotional instability as best predictors for test anxiety. Furthermore, path analysis revealed that past negative academic performance outcomes contribute to test anxiety via depressive symptoms and perceived chronic stress. Conclusion: Depressive symptoms and perceived chronic stress are strongly related to test anxiety. Therefore therapy and training methods that address depressive symptoms and perceived chronic stress, and thereby aim to modify appraisal of potential stressful situations, may be successful in addressing test anxiety.

  11. [Coping with chronic somatic disease according to the concept of psychological stress].

    Science.gov (United States)

    Miniszewska, Joanna; Chodkiewicz, Jan

    2013-01-01

    The article presents the problem of coping with chronic disease according to the concept of psychological stress. The Lazarus and Folkman theory in which stress is regarded as a relational concept, the importance of cognitive assessment and functions of coping with disease are described. The attention is paid to the illness perception and its impact on the behavioral and emotional processes. The most known tools for stress assessment and coping with stress and current research directions are shown.

  12. Role of stressful life events in induction or exacerbation of psoriasis and chronic urticaria

    Directory of Open Access Journals (Sweden)

    Malhotra S

    2008-01-01

    Full Text Available Background: The possibility of a causal influence of emotional stress, especially of stressful life events, on the course of various skin diseases has long been postulated. Previous reports addressing its influence on skin psoriasis and chronic urticaria have been mainly anecdotal. Objective: The aim of this study was to evaluate the stressful events of life within 1 year preceding onset or exacerbation of skin disease in patients of psoriasis vulgaris and chronic urticaria. Method: Fifty consecutive clinically diagnosed psoriasis patients and 50 consecutive clinically diagnosed chronic urticaria patients were examined clinically and administered Gurmeet Singh′s presumptive stressful life events scale. Results: Stressful life events were seen in 26% of the patients in the psoriasis vulgaris group and 16% of the patients in the chronic urticaria group within 1 year preceding onset or exacerbation of skin disease. In the psoriasis vulgaris group, the most common stressful life event seen was financial loss or problems (8%, followed by death of close family member (4%, sexual problems (4%, family conflict (2%, major personal illness or injury (2%,and transfer or change in working conditions (2%, failure in examinations (2%, family member unemployed (2%, illness of family member (2%, getting married or engaged (2%, miscellaneous (2%. In the chronic urticaria group, the most common stressful life event seen was death of a close family member (6%, followed by family conflict (2%, financial loss or problems (2%, sexual problems (2%, illness of family member (2%, getting married or engaged (2%, trouble at work with colleagues, superiors, or subordinates (2%, going on a pleasure trip (2% and extramarital relations (2%. Conclusion: Psychological stress plays a significant role in triggering or exacerbating dermatological diseases. Our study indicates the role of relaxation therapies and stress management programs in chronic diseases such as psoriasis

  13. Variable impact of chronic stress on spatial learning and memory in BXD mice.

    Science.gov (United States)

    Shea, Chloe J A; Carhuatanta, Kimberly A K; Wagner, Jessica; Bechmann, Naomi; Moore, Raquel; Herman, James P; Jankord, Ryan

    2015-10-15

    The effects of chronic stress on learning are highly variable across individuals. This variability stems from gene-environment interactions. However, the mechanisms by which stress affects genetic predictors of learning are unclear. Thus, we aim to determine whether the genetic pathways that predict spatial memory performance are altered by previous exposure to chronic stress. Sixty-two BXD recombinant inbred strains of mice, as well as parent strains C57BL/6J and DBA/2J, were randomly assigned as behavioral control or to a chronic variable stress paradigm and then underwent behavioral testing to assess spatial memory and learning performance using the Morris water maze. Quantitative trait loci (QTL) mapping was completed for average escape latency times for both control and stress animals. Loci on chromosomes 5 and 10 were found in both control and stress environmental populations; eight additional loci were found to be unique to either the control or stress environment. In sum, results indicate that certain genetic loci predict spatial memory performance regardless of prior stress exposure, while exposure to stress also reveals unique genetic predictors of training during the memory task. Thus, we find that genetic predictors contributing to spatial learning and memory are susceptible to the presence of chronic stress.

  14. Influence of Chronic Stress and Oclusal Interference on Masseter Muscle Pain in Rat

    OpenAIRE

    Simonić-Kocijan, Sunčana; Uhač, Ivone; Braut, Vedrana; Kovač, Zoran; Kovačević Pavičić, Daniela; Fugošić, Vesna; Muhvić Urek, Miranda

    2009-01-01

    This study aimed to investigate the individual effects of chronic stress and occlusal interference, as well as their combined influence on masseter muscle pain. Experiments were performed on 28 male Wistar rats. Animals were submitted to chronic stress procedure, exposed to occlusal interference, or exposed to both mantioned procedures. At the end of the procedure animals were submitted to orofacial formalin test, and nociceptive behavioral response was evaluated. Statisticaly significant dif...

  15. L-tyrosine improves neuroendocrine function in a mouse model of chronic stress

    OpenAIRE

    Wang, Zhihua; Li, Jinghua; Wang, Zhiming; Xue, Lingyan; Zhang, Yi; Chen, Yingjie; Su, Jun; Li, Zhongming

    2012-01-01

    Adult BALB/c mice, individually housed, were stimulated with nine different stressors, arranged randomly, for 4 continuous weeks to generate an animal model of chronic stress. In chronically stressed mice, spontaneous locomotor activity was significantly decreased, escape latency in the Morris water maze test was prolonged, serum levels of total thyrotropin and total triiodothyronine were significantly decreased, and dopamine and norepinephrine content in the pallium, hippocampus and hypothal...

  16. Multicomponent Behavioral Treatment for Chronic Combat-Related Posttraumatic Stress Disorder: Trauma Management Therapy

    Science.gov (United States)

    Turner, Samuel M.; Beidel, Deborah C.; Frueh, B. Christopher

    2005-01-01

    Posttraumatic stress disorder (PTSD) is a severe and chronic mental disorder that is highly prevalent within Veterans Affairs (VA) Medical Centers. A severe psychiatric disorder, combat-related PTSD is typically accompanied by multiple comorbid psychiatric disorders, symptom chronicity, and extreme social maladjustment. Thus, PTSD is a complex…

  17. The Emerging Role of Metabotropic Glutamate Receptors in the Pathophysiology of Chronic Stress-Related Disorders.

    Science.gov (United States)

    Peterlik, Daniel; Flor, Peter J; Uschold-Schmidt, Nicole

    2016-01-01

    Chronic stress-related psychiatric conditions such as anxiety, depression, and alcohol abuse are an enormous public health concern. The etiology of these pathologies is complex, with psychosocial stressors being among the most frequently discussed risk factors. The brain glutamatergic neurotransmitter system has often been found involved in behaviors and pathophysiologies resulting from acute stress and fear. Despite this, relatively little is known about the role of glutamatergic system components in chronic psychosocial stress, neither in rodents nor in humans. Recently, drug discovery efforts at the metabotropic receptor subtypes of the glutamatergic system (mGlu1-8 receptors) led to the identification of pharmacological tools with emerging potential in psychiatric conditions. But again, the contribution of individual mGlu subtypes to the manifestation of physiological, molecular, and behavioral consequences of chronic psychosocial stress remains still largely unaddressed. The current review will describe animal models typically used to analyze acute and particularly chronic stress conditions, including models of psychosocial stress, and there we will discuss the emerging roles for mGlu receptor subtypes. Indeed, accumulating evidence indicates relevance and potential therapeutic usefulness of mGlu2/3 ligands and mGlu5 receptor antagonists in chronic stress-related disorders. In addition, a role for further mechanisms, e.g. mGlu7-selective compounds, is beginning to emerge. These mechanisms are important to be analyzed in chronic psychosocial stress paradigms, e.g. in the chronic subordinate colony housing (CSC) model. We summarize the early results and discuss necessary future investigations, especially for mGlu5 and mGlu7 receptor blockers, which might serve to suggest improved therapeutic strategies to treat stress-related disorders. PMID:27296643

  18. Gene expression patterns in the hippocampus and amygdala of endogenous depression and chronic stress models.

    Science.gov (United States)

    Andrus, B M; Blizinsky, K; Vedell, P T; Dennis, K; Shukla, P K; Schaffer, D J; Radulovic, J; Churchill, G A; Redei, E E

    2012-01-01

    The etiology of depression is still poorly understood, but two major causative hypotheses have been put forth: the monoamine deficiency and the stress hypotheses of depression. We evaluate these hypotheses using animal models of endogenous depression and chronic stress. The endogenously depressed rat and its control strain were developed by bidirectional selective breeding from the Wistar-Kyoto (WKY) rat, an accepted model of major depressive disorder (MDD). The WKY More Immobile (WMI) substrain shows high immobility/despair-like behavior in the forced swim test (FST), while the control substrain, WKY Less Immobile (WLI), shows no depressive behavior in the FST. Chronic stress responses were investigated by using Brown Norway, Fischer 344, Lewis and WKY, genetically and behaviorally distinct strains of rats. Animals were either not stressed (NS) or exposed to chronic restraint stress (CRS). Genome-wide microarray analyses identified differentially expressed genes in hippocampi and amygdalae of the endogenous depression and the chronic stress models. No significant difference was observed in the expression of monoaminergic transmission-related genes in either model. Furthermore, very few genes showed overlapping changes in the WMI vs WLI and CRS vs NS comparisons, strongly suggesting divergence between endogenous depressive behavior- and chronic stress-related molecular mechanisms. Taken together, these results posit that although chronic stress may induce depressive behavior, its molecular underpinnings differ from those of endogenous depression in animals and possibly in humans, suggesting the need for different treatments. The identification of novel endogenous depression-related and chronic stress response genes suggests that unexplored molecular mechanisms could be targeted for the development of novel therapeutic agents.

  19. Stress

    Science.gov (United States)

    ... Some people experience digestive symptoms. Others may have headaches, sleeplessness, depressed mood, anger, and irritability. People under chronic stress get more frequent and severe viral infections, such ...

  20. Basic fibroblast growth factor improves learning and memory functions in chronic stress mice

    Institute of Scientific and Technical Information of China (English)

    Xian Qu; Chunying Li; Hongchang Liu; Chang Su

    2011-01-01

    Four weeks of uncertain stress was used to establish an animal model of chronic stress.Basic fibroblast growth factor was injected daily for 15 days following stress induction.Cell morphology in the hippocampal CA3 region of chronic stress mice revealed cell damage.Nitric oxide content and calcium concentration were significantly increased in the hippocampus,and learning and memory functions were significantly decreased.After basic fibroblast growth factor intervention,Ca2+ overload was decreased and neuronal damage was relieved in hippocampal neurons,which improved learning and memory functions in chronic stress mice.Latency was prolonged and the number of errors was decreased in a passive avoidance test.

  1. [Effect of chronic social stress on lipid metabolism in golden Syrian hamsters].

    Science.gov (United States)

    Zahaĭko, A L; Voronina, L M; Kaliman, P A; Strel'chenko, K V

    2008-01-01

    The changes of total lipids, lipoproteins and their fractions, free fatty acids, triacylglyceroles, free and esterified cholesterol levels and parameters of its metabolism in the blood serum and liver, glucose-6-phosphate dehydrogenase and lysosomal lipase activity in the liver, and also post-heparin lipases activity in blood of hamsters with chronic social stress are investigated. Is has been shown, that in stressed animals the prevalence in early terms of chronic stress lipolysis above lipogenesis is observed. In later terms of chronic stress the lipogenesis activation is also observed which, alongside with active lipolysis, can cause hyperlipidemia in blood. The latter phenomenon is obviously more characteristic of males, while in females the main source of fatty acids in blood is probably lipolysis in the liver. Proatherogenic redistribution of lipoprotein fractions, which was observed at chronic stress, becomes complicated by changes of their transformations processes under blood lipases action, in particular, lipases disbalance: by increasing of hepatic lipase activity without lipoprotein lipase activity increase. The increase of CETP activity in HDL, which is observed at stress, can be accompanied by atherogenic LDLB accumulation in the blood plasma. The chronic social stress is proatherogenic owing to lipid and lipoprotein metabolism changes, which lead to the shift of balance during lipids transport and their use by tissues. PMID:19140458

  2. Treadmill exercise does not change gene expression of adrenal catecholamine biosynthetic enzymes in chronically stressed rats

    Directory of Open Access Journals (Sweden)

    LJUBICA GAVRILOVIC

    2013-09-01

    Full Text Available ABSTRACT Chronic isolation of adult animals represents a form of psychological stress that produces sympatho-adrenomedullar activation. Exercise training acts as an important modulator of sympatho-adrenomedullary system. This study aimed to investigate physical exercise-related changes in gene expression of catecholamine biosynthetic enzymes (tyrosine hydroxylase, dopamine-ß-hydroxylase and phenylethanolamine N-methyltransferase and cyclic adenosine monophosphate response element-binding (CREB in the adrenal medulla, concentrations of catecholamines and corticosterone (CORT in the plasma and the weight of adrenal glands of chronically psychosocially stressed adult rats exposed daily to 20 min treadmill running for 12 weeks. Also, we examined how additional acute immobilization stress changes the mentioned parameters. Treadmill running did not result in modulation of gene expression of catecholamine synthesizing enzymes and it decreased the level of CREB mRNA in the adrenal medulla of chronically psychosocially stressed adult rats. The potentially negative physiological adaptations after treadmill running were recorded as increased concentrations of catecholamines and decreased morning CORT concentration in the plasma, as well as the adrenal gland hypertrophy of chronically psychosocially stressed rats. The additional acute immobilization stress increases gene expression of catecholamine biosynthetic enzymes in the adrenal medulla, as well as catecholamines and CORT levels in the plasma. Treadmill exercise does not change the activity of sympatho-adrenomedullary system of chronically psychosocially stressed rats.

  3. Chronic and episodic interpersonal stress as statistically unique predictors of depression in two samples of emerging adults.

    Science.gov (United States)

    Vrshek-Schallhorn, Suzanne; Stroud, Catherine B; Mineka, Susan; Hammen, Constance; Zinbarg, Richard E; Wolitzky-Taylor, Kate; Craske, Michelle G

    2015-11-01

    Few studies comprehensively evaluate which types of life stress are most strongly associated with depressive episode onsets, over and above other forms of stress, and comparisons between acute and chronic stress are particularly lacking. Past research implicates major (moderate to severe) stressful life events (SLEs), and to a lesser extent, interpersonal forms of stress; research conflicts on whether dependent or independent SLEs are more potent, but theory favors dependent SLEs. The present study used 5 years of annual diagnostic and life stress interviews of chronic stress and SLEs from 2 separate samples (Sample 1 N = 432; Sample 2 N = 146) transitioning into emerging adulthood; 1 sample also collected early adversity interviews. Multivariate analyses simultaneously examined multiple forms of life stress to test hypotheses that all major SLEs, then particularly interpersonal forms of stress, and then dependent SLEs would contribute unique variance to major depressive episode (MDE) onsets. Person-month survival analysis consistently implicated chronic interpersonal stress and major interpersonal SLEs as statistically unique predictors of risk for MDE onset. In addition, follow-up analyses demonstrated temporal precedence for chronic stress; tested differences by gender; showed that recent chronic stress mediates the relationship between adolescent adversity and later MDE onsets; and revealed interactions of several forms of stress with socioeconomic status (SES). Specifically, as SES declined, there was an increasing role for noninterpersonal chronic stress and noninterpersonal major SLEs, coupled with a decreasing role for interpersonal chronic stress. Implications for future etiological research were discussed.

  4. Chronic and episodic interpersonal stress as statistically unique predictors of depression in two samples of emerging adults.

    Science.gov (United States)

    Vrshek-Schallhorn, Suzanne; Stroud, Catherine B; Mineka, Susan; Hammen, Constance; Zinbarg, Richard E; Wolitzky-Taylor, Kate; Craske, Michelle G

    2015-11-01

    Few studies comprehensively evaluate which types of life stress are most strongly associated with depressive episode onsets, over and above other forms of stress, and comparisons between acute and chronic stress are particularly lacking. Past research implicates major (moderate to severe) stressful life events (SLEs), and to a lesser extent, interpersonal forms of stress; research conflicts on whether dependent or independent SLEs are more potent, but theory favors dependent SLEs. The present study used 5 years of annual diagnostic and life stress interviews of chronic stress and SLEs from 2 separate samples (Sample 1 N = 432; Sample 2 N = 146) transitioning into emerging adulthood; 1 sample also collected early adversity interviews. Multivariate analyses simultaneously examined multiple forms of life stress to test hypotheses that all major SLEs, then particularly interpersonal forms of stress, and then dependent SLEs would contribute unique variance to major depressive episode (MDE) onsets. Person-month survival analysis consistently implicated chronic interpersonal stress and major interpersonal SLEs as statistically unique predictors of risk for MDE onset. In addition, follow-up analyses demonstrated temporal precedence for chronic stress; tested differences by gender; showed that recent chronic stress mediates the relationship between adolescent adversity and later MDE onsets; and revealed interactions of several forms of stress with socioeconomic status (SES). Specifically, as SES declined, there was an increasing role for noninterpersonal chronic stress and noninterpersonal major SLEs, coupled with a decreasing role for interpersonal chronic stress. Implications for future etiological research were discussed. PMID:26301973

  5. New Pathogenic Concepts and Therapeutic Approaches to Oxidative Stress in Chronic Kidney Disease

    DEFF Research Database (Denmark)

    Pedraza-Chaverri, José; Sánchez-Lozada, Laura G; Osorio-Alonso, Horacio;

    2016-01-01

    In chronic kidney disease inflammatory processes and stimulation of immune cells result in overproduction of free radicals. In combination with a reduced antioxidant capacity this causes oxidative stress. This review focuses on current pathogenic concepts of oxidative stress for the decline of ki...

  6. Caring for People with Chronic Fatigue Syndrome: Perceived Stress Versus Satisfaction.

    Science.gov (United States)

    Ferrari, Joseph R.; Jason, Leonard A.

    1997-01-01

    Examined adult caregivers (N=96) caring for persons with Chronic Fatigue Syndrome (CFS) on a long-term basis. Results indicate no significant sex difference regarding caregiver stress and satisfaction. The more life satisfaction caregivers reported, the less stress and more satisfaction they experienced in caring for a person with CFS. (RJM)

  7. Chronic Stress Improves NO- and Ca2+ Flux-Dependent Vascular Function: A Pharmacological Study

    Directory of Open Access Journals (Sweden)

    Thiago Bruder-Nascimento

    2015-03-01

    Full Text Available Background: Stress is associated with cardiovascular diseases. Objective: This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO and Ca2+ dependent. Methods: Wistar rats, 30 days of age, were separated into 2 groups: control (C and Stress (St. Chronic stress consisted of immobilization for 1 hour/day, 5 days/week, 15 weeks. Systolic blood pressure was assessed. Vascular studies on aortic rings were performed. Concentration-effect curves were built for noradrenaline, in the presence of L-NAME or prazosin, acetylcholine, sodium nitroprusside and KCl. In addition, Ca2+ flux was also evaluated. Results: Chronic stress induced hypertension, decreased the vascular response to KCl and to noradrenaline, and increased the vascular response to acetylcholine. L-NAME blunted the difference observed in noradrenaline curves. Furthermore, contractile response to Ca2+ was decreased in the aorta of stressed rats. Conclusion: Our data suggest that the vascular response to chronic stress is an adaptation to its deleterious effects, such as hypertension. In addition, this adaptation is NO- and Ca2+-dependent. These data help to clarify the contribution of stress to cardiovascular abnormalities. However, further studies are necessary to better elucidate the mechanisms involved in the cardiovascular dysfunction associated with stressors. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0

  8. Chronic stress and social housing differentially affect neurogenesis in male and female rats

    NARCIS (Netherlands)

    Westenbroek, Christel; Boer, Johan A. den; Veenhuis, Maarten; Horst, Gert J. ter

    2004-01-01

    Stress plays an important role in the development of affective disorders. Women show a higher prevalence for these disorders than men. The course of a depression is thought to be positively influenced by social support. We have used a chronic stress model in which rats received foot-shocks daily for

  9. Chronic Stress, Depression and Immunity in Spouses of Metastatic Breast Cancer Patients

    Science.gov (United States)

    Mortimer, Jane S. Blake; Sephton, Sandra E.; Kimerling, Rachel; Butler, Lisa; Bernstein, Aaron S.; Spiegel, David

    2005-01-01

    Objective: The objective of this study was to examine how the chronicity of stress affects psychological stress-responses, depressive symptoms, and "in vivo" immunocompetence in spouses of women with metastatic breast cancer. Methods: Participants were 34 spouses of breast cancer patients. Their wives had been living with a diagnosis of recurrence…

  10. Chronic Stress Improves NO- and Ca2+ Flux-Dependent Vascular Function: A Pharmacological Study

    Energy Technology Data Exchange (ETDEWEB)

    Bruder-Nascimento, Thiago, E-mail: bruderthiago@usp.br [Departamento de Farmacologia - Instituto de Biociências de Botucatu - Universidade do Estado de São Paulo (UNESP), Botucatu, São Paulo (Brazil); Departamento de Clínica Médica - Faculdade de Medicina de Botucatu - Universidade do Estado de São Paulo (UNESP), Botucatu, São Paulo (Brazil); Campos, Dijon Henrique Salome [Departamento de Clínica Médica - Faculdade de Medicina de Botucatu - Universidade do Estado de São Paulo (UNESP), Botucatu, São Paulo (Brazil)

    2015-03-15

    Stress is associated with cardiovascular diseases. This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO) and Ca2+ dependent. Wistar rats, 30 days of age, were separated into 2 groups: control (C) and Stress (St). Chronic stress consisted of immobilization for 1 hour/day, 5 days/week, 15 weeks. Systolic blood pressure was assessed. Vascular studies on aortic rings were performed. Concentration-effect curves were built for noradrenaline, in the presence of L-NAME or prazosin, acetylcholine, sodium nitroprusside and KCl. In addition, Ca{sup 2+} flux was also evaluated. Chronic stress induced hypertension, decreased the vascular response to KCl and to noradrenaline, and increased the vascular response to acetylcholine. L-NAME blunted the difference observed in noradrenaline curves. Furthermore, contractile response to Ca{sup 2+} was decreased in the aorta of stressed rats. Our data suggest that the vascular response to chronic stress is an adaptation to its deleterious effects, such as hypertension. In addition, this adaptation is NO- and Ca{sup 2+}-dependent. These data help to clarify the contribution of stress to cardiovascular abnormalities. However, further studies are necessary to better elucidate the mechanisms involved in the cardiovascular dysfunction associated with stressors. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0)

  11. 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

  12. Unique Hippocampal Changes and Allodynia in a Model of Chronic Stress

    OpenAIRE

    Kim, Seong-Ho; Moon, Il Soo; Park, In-Sick

    2013-01-01

    Sustained stress can have numerous pathologic effects. There have been several animal models for chronic stress. We tried to identify the changes of pain threshold and hippocampus in a model of chronic stress. Male Sprague-Dawley rats were kept in a cage filled with 23℃ water to a height of 2.2 cm for 7 days. Nociceptive thresholds, expressed in grams, were measured with a Dynamic Plantar Aesthesiometer. Golgi staining was used to identify hippocampal changes. To demonstrate how long allodyni...

  13. Chronicity of depressive problems and the cortisol response to psychosocial stress in adolescents: the TRAILS study.

    Science.gov (United States)

    Booij, Sanne H; Bouma, Esther M C; de Jonge, Peter; Ormel, Johan; Oldehinkel, Albertine J

    2013-05-01

    Clinical and epidemiological studies, further supported by meta-analytic studies, indicate a possible association between chronicity (i.e., persistence or recurrence) of depression and hypothalamic-pituitary-adrenal (HPA) axis responsiveness to psychosocial stress. In the present study, we examined whether and how chronicity of depressive problems predicts cortisol responses to a standardized social stress test in adolescents. Data were collected in a high-risk focus sample (n=351) of the Tracking Adolescents' Individual Lives Survey (TRAILS) cohort, a large prospective population study with bi- to triennial measurements. Depressive problems were assessed around age 11, 13.5, and 16. Cortisol levels were measured in saliva, sampled before, during, and after the Groningen Social Stress Test (GSST), to determine the cortisol response to psychosocial stress. The area under the curve with respect to the increase (AUCi) (i.e., change from baseline) of the cortisol response was used as a measure of HPA axis response. By means of linear regression analysis and repeated-measures analysis of variance, it was examined whether chronicity of depressive problems predicted the cortisol response to the GSST around the age of 16. Chronicity of depressive problems was significantly associated with cortisol stress responses. The relationship was curvilinear, with recent-onset depressive problems predicting an increased cortisol response, and more chronic depressive problems a blunted response. The results of this study suggest that depressive problems initially increase cortisol responses to stress, but that this pattern reverses when depressive problems persist over prolonged periods of time. PMID:22963816

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Individual differences in early adolescents' latent trait cortisol (LTC): Relation to recent acute and chronic stress.

    Science.gov (United States)

    Stroud, Catherine B; Chen, Frances R; Doane, Leah D; Granger, Douglas A

    2016-08-01

    Research suggests that environmental stress contributes to health by altering the regulation of the hypothalamic pituitary adrenal (HPA) axis. Recent evidence indicates that early life stress alters trait indicators of HPA axis activity, but whether recent stress alters such indicators is unknown. Using objective contextual stress interviews with adolescent girls and their mothers, we examined the impact of recent acute and chronic stress occurring during the past year on early adolescent girls' latent trait cortisol (LTC) level. We also examined whether associations between recent stress and LTC level: a) varied according to the interpersonal nature and controllability of the stress; and b) remained after accounting for the effect of early life stress. Adolescents (n=117;M age=12.39years) provided salivary cortisol samples three times a day (waking, 30min post-waking and bedtime) over 3days. Results indicated that greater recent interpersonal acute stress and greater recent independent (i.e., uncontrollable) acute stress were each associated with a higher LTC level, over and above the effect of early adversity. In contrast, greater recent chronic stress was associated with a lower LTC level. Findings were similar in the overall sample and a subsample of participants who strictly adhered to the timed schedule of saliva sample collection. Implications for understanding the impact of recent stress on trait-like individual differences in HPA axis activity are discussed. PMID:27155256

  16. Overgeneral autobiographical memory and chronic interpersonal stress as predictors of the course of depression in adolescents.

    Science.gov (United States)

    Sumner, Jennifer A; Griffith, James W; Mineka, Susan; Rekart, Kathleen Newcomb; Zinbarg, Richard E; Craske, Michelle G

    2011-01-01

    This study investigated whether overgeneral autobiographical memory (OGM) predicts the course of depression in adolescents. As part of a larger longitudinal study of risk for emotional disorders, 55 adolescents with a past history of major depressive disorder or minor depressive disorder completed the Autobiographical Memory Test. Fewer specific memories predicted the subsequent onset of a major depressive episode (MDE) over a 16-month follow-up period, even when covarying baseline depressive symptoms. This main effect was qualified by an interaction between specific memories and chronic interpersonal stress: Fewer specific memories predicted greater risk of MDE onset over follow-up at high (but not low) levels of chronic interpersonal stress. Thus, our findings suggest that OGM, in interaction with chronic interpersonal stress, predicts the course of depression among adolescents, and highlight the importance of measuring interpersonal stress in OGM research.

  17. Molecular Signatures of Psychosocial Stress and Cognition Are Modulated by Chronic Lithium Treatment.

    Science.gov (United States)

    Brzózka, Magdalena M; Havemann-Reinecke, Ursula; Wichert, Sven P; Falkai, Peter; Rossner, Moritz J

    2016-07-01

    Chronic psychosocial stress is an important environmental risk factor of psychiatric diseases such as schizophrenia. Social defeat in rodents has been shown to be associated with maladaptive cellular and behavioral consequences including cognitive impairments. Although gene expression changes upon psychosocial stress have been described, a comprehensive transcriptome profiling study at the global level in precisely defined hippocampal subregions which are associated with learning has been lacking. In this study, we exposed adult C57Bl/6N mice for 3 weeks to "resident-intruder" paradigm and combined laser capture microdissection with microarray analyses to identify transcriptomic signatures of chronic psychosocial stress in dentate gyrus and CA3 subregion of the dorsal hippocampus. At the individual transcript level, we detected subregion specific stress responses whereas gene set enrichment analyses (GSEA) identified several common pathways upregulated upon chronic psychosocial stress related to proteasomal function and energy supply. Behavioral profiling revealed stress-associated impairments most prominent in fear memory formation which was prevented by chronic lithium treatment. Thus, we again microdissected the CA3 region and performed global transcriptome analysis to search for molecular signatures altered by lithium treatment in stressed animals. By combining GSEA with unsupervised clustering, we detected pathways that are regulated by stress and lithium in the CA3 region of the hippocampus including proteasomal components, oxidative phosphorylation, and anti-oxidative mechanisms. Our study thus provides insight into hidden molecular phenotypes of chronic psychosocial stress and lithium treatment and proves a beneficial role for lithium treatment as an agent attenuating negative effects of psychosocial stress on cognition. PMID:26714764

  18. Molecular Signatures of Psychosocial Stress and Cognition Are Modulated by Chronic Lithium Treatment.

    Science.gov (United States)

    Brzózka, Magdalena M; Havemann-Reinecke, Ursula; Wichert, Sven P; Falkai, Peter; Rossner, Moritz J

    2016-07-01

    Chronic psychosocial stress is an important environmental risk factor of psychiatric diseases such as schizophrenia. Social defeat in rodents has been shown to be associated with maladaptive cellular and behavioral consequences including cognitive impairments. Although gene expression changes upon psychosocial stress have been described, a comprehensive transcriptome profiling study at the global level in precisely defined hippocampal subregions which are associated with learning has been lacking. In this study, we exposed adult C57Bl/6N mice for 3 weeks to "resident-intruder" paradigm and combined laser capture microdissection with microarray analyses to identify transcriptomic signatures of chronic psychosocial stress in dentate gyrus and CA3 subregion of the dorsal hippocampus. At the individual transcript level, we detected subregion specific stress responses whereas gene set enrichment analyses (GSEA) identified several common pathways upregulated upon chronic psychosocial stress related to proteasomal function and energy supply. Behavioral profiling revealed stress-associated impairments most prominent in fear memory formation which was prevented by chronic lithium treatment. Thus, we again microdissected the CA3 region and performed global transcriptome analysis to search for molecular signatures altered by lithium treatment in stressed animals. By combining GSEA with unsupervised clustering, we detected pathways that are regulated by stress and lithium in the CA3 region of the hippocampus including proteasomal components, oxidative phosphorylation, and anti-oxidative mechanisms. Our study thus provides insight into hidden molecular phenotypes of chronic psychosocial stress and lithium treatment and proves a beneficial role for lithium treatment as an agent attenuating negative effects of psychosocial stress on cognition.

  19. Lymphocytes from Chronically Stressed Mice Confer Antidepressant-Like Effects to Naive Mice

    OpenAIRE

    Brachman, Rebecca A.; Lehmann, Michael L.; Maric, Dragan; Herkenham, Miles

    2015-01-01

    We examined whether cells of the adaptive immune system retain the memory of psychosocial stress and thereby alter mood states and CNS function in the host. Lymphocytes from mice undergoing chronic social defeat stress or from unstressed control mice were isolated and adoptively transferred into naive lymphopenic Rag2−/− mice. Changes in affective behavior, hippocampal cell proliferation, microglial activation states, and blood cytokine levels were examined in reconstituted stress-naive mice....

  20. Pain experience of Iraq and Afghanistan Veterans with comorbid chronic pain and posttraumatic stress

    Directory of Open Access Journals (Sweden)

    Samantha D. Outcalt, PhD

    2014-07-01

    Full Text Available Chronic pain and posttraumatic stress disorder (PTSD co-occur at high rates, and Veterans from recent wars in Iraq and Afghanistan may be particularly vulnerable to both conditions. The objective of this study was to identify key aspects of chronic pain, cognitions, and psychological distress associated with comorbid PTSD among this sample of Veterans. Baseline data were analyzed from a randomized controlled trial testing a stepped-care intervention for chronic musculoskeletal pain. Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF Veterans with chronic pain only (n = 173 were compared with those with chronic pain and clinically significant posttraumatic stress symptoms (n = 68. Group differences on pain characteristics, pain cognitions, and psychological distress were evaluated. Results demonstrated that OIF/OEF Veterans with comorbid chronic musculoskeletal pain and PTSD experienced higher pain severity, greater pain-related disability and increased pain interference, more maladaptive pain cognitions (e.g., catastrophizing, self-efficacy, pain centrality, and higher affective distress than those with chronic pain alone. Veterans of recent military conflicts in Iraq and Afghanistan may be particularly vulnerable to the compounded adverse effects of chronic pain and PTSD. These results highlight a more intense and disabling pain and psychological experience for those with chronic pain and PTSD than for those without PTSD.

  1. Chronic Stress, Drug Use, and Vulnerability to Addiction

    OpenAIRE

    Sinha, Rajita

    2008-01-01

    Stress is a well-known risk factor in the development of addiction and in addiction relapse vulnerability. A series of population-based and epidemiological studies have identified specific stressors and individual-level variables that are predictive of substance use and abuse. Preclinical research also shows that stress exposure enhances drug self-administration and reinstates drug seeking in drug-experienced animals. The deleterious effects of early life stress, child maltreatment, and accum...

  2. Rumination as a Mediator of Chronic Stress Effects on Hypertension: A Causal Model

    Directory of Open Access Journals (Sweden)

    William Gerin

    2012-01-01

    Full Text Available Chronic stress has been linked to hypertension, but the underlying mechanisms remain poorly specified. We suggest that chronic stress poses a risk for hypertension through repeated occurrence of acute stressors (often stemming from the chronic stress context that cause activation of stress-mediating physiological systems. Previous models have often focused on the magnitude of the acute physiological response as a risk factor; we attempt to extend this to address the issue of duration of exposure. Key to our model is the notion that these acute stressors can emerge not only in response to stressors present in the environment, but also to mental representations of those (or other stressors. Consequently, although the experience of any given stressor may be brief, a stressor often results in a constellation of negative cognitions and emotions that form a mental representation of the stressor. Ruminating about this mental representation of the stressful event can cause autonomic activation similar to that observed in response to the original incident, and may occur and persist long after the event itself has ended. Thus, rumination helps explain how chronic stress causes repeated (acute activation of one’s stress-mediating physiological systems, the effects of which accumulate over time, resulting in hypertension risk.

  3. 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.

  4. Some physiological and biochemical methods for acute and chronic stress evaluation in dairy cows

    Directory of Open Access Journals (Sweden)

    Giuseppe Bertoni

    2010-01-01

    Full Text Available Stress factors are so numerous and so diverse in their strength and duration that the consequences on animal welfare can be quite varied. The first important distinction concerns the characterization of acute and chronic stress conditions. Acute stress is a short-lived negative situation that allows a quick and quite complete recovery of the physiological balance (adaptation, while chronic stress is a long lasting condition from which the subject cannot fully recover (maladaptation. In the latter case, the direct effects of the stress factors (heat, low energy, anxiety, suffering etc., as well as the indirect ones (changes occurring at endocrinological, immune system or function level can be responsible for pre-pathological or pathological consequences which reduce animal welfare. To evaluate the possible chronic stress conditions in single animals or on a farm (in particular a farm of dairy cows, some parameters of the direct or indirect effects can be utilised. They are physiological (mainly hormone changes: cortisol, β-endorphin, behavioural (depression, biochemical (metabolites, acute phase proteins, glycated proteins etc., as well as performance parameters (growing rate, milk yield, fertility, etc.. Special attention has been paid to the interpretation of cortisol levels and to its changes after an ACTH challenge. Despite fervent efforts, well established and accepted indices of chronic stress (distress are currently lacking; but without this objective evaluation, the assessment of animal welfare and, therefore, the optimization of the livestock production, could prove more difficult.

  5. Plasma omega 3 polyunsaturated fatty acid status and monounsaturated fatty acids are altered by chronic social stress and predict endocrine responses to acute stress in titi monkeys

    Science.gov (United States)

    Disturbances in fatty acid (FA) metabolism may link chronic psychological stress, endocrine responsiveness, and psychopathology. Therefore, lipid metabolome-wide responses and their relationships with endocrine (cortisol; insulin; adiponectin) responsiveness to acute stress (AS) were assessed in a ...

  6. Environmental enrichment reduces behavioural alterations induced by chronic stress in Japanese quail.

    Science.gov (United States)

    Laurence, A; Houdelier, C; Calandreau, L; Arnould, C; Favreau-Peigné, A; Leterrier, C; Boissy, A; Lumineau, S

    2015-02-01

    Animals perceiving repeated aversive events can become chronically stressed. Chronic activation of the hypothalamic-pituitary-adrenal (HPA) axis can have deleterious consequences on physiological parameters (e.g. BW, blood chemistry) and behaviour (e.g. emotional reactivity, stereotypies, cognition). Environmental enrichment (EE) can be a mean to reduce animal stress and to improve welfare. The aim of this study was first, to assess the effects of EE in battery cages on the behaviour of young Japanese quail and second, to evaluate the impact of EE on quail exposed to chronic stress. The experiment involved quail housed in EE cages and submitted or not to a chronic stress procedure (CSP) (EE cages, control quail: n=16, CSP quail: n=14) and quail housed in standard cages and exposed or not to the CSP (standard non-EE cages, control quail: n=12, CSP quail: n=16). Our procedure consisted of repeated aversive events (e.g. ventilators, delaying access to food, physical restraint, noise) presented two to five times per 24 h, randomly, for 15 days. During CSP, EE improved quail's welfare as their stereotypic pacing decreased and they rested more. CSP decreased exploration in all quail. After the end of CSP, quail presented increased emotional reactivity in emergence test. However, the effect of EE varied with test. Finally, chronic stress effects on comfort behaviours in the emergence test were alleviated by EE. These results indicate that EE can alleviate some aspects of behavioural alterations induced by CSP. PMID:25354525

  7. The appraisal of chronic stress and the development of the metabolic syndrome: a systematic review of prospective cohort studies

    OpenAIRE

    Bergmann, N; Gyntelberg, F; Faber, J

    2014-01-01

    Chronic psychosocial stress has been proposed as a risk factor for the development of the metabolic syndrome (MES). This review gives a systematic overview of prospective cohort studies investigating chronic psychosocial stress as a risk factor for incident MES and the individual elements of MES. Thirty-nine studies were included. An association between chronic psychosocial stress and the development of MES was generally supported. Regarding the four elements of MES: i) weight gain: the prosp...

  8. Unique genetic loci identified for emotional behavior in control and chronic stress conditions.

    Directory of Open Access Journals (Sweden)

    Kimberly AK Carhuatanta

    2014-10-01

    Full Text Available An individual’s genetic background affects their emotional behavior and response to stress. Although studies have been conducted to identify genetic predictors for emotional behavior or stress response, it remains unknown how prior stress history alters the interaction between an individual’s genome and their emotional behavior. Therefore, the purpose of this study is to identify chromosomal regions that affect emotional behavior and are sensitive to stress exposure. We utilized the BXD behavioral genetics mouse model to identify chromosomal regions that predict fear learning and emotional behavior following exposure to a control or chronic stress environment. 62 BXD recombinant inbred strains and C57BL/6 and DBA/2 parental strains underwent behavioral testing including a classical fear conditioning paradigm and the elevated plus maze. Distinct quantitative trait loci (QTLs were identified for emotional learning, anxiety and locomotion in control and chronic stress populations. Candidate genes, including those with already known functions in learning and stress were found to reside within the identified QTLs. Our data suggest that chronic stress history reveals novel genetic predictors of emotional behavior.

  9. Effects of chronic and acute stress on rat behaviour in the forced-swim test.

    Science.gov (United States)

    Suvrathan, Aparna; Tomar, Anupratap; Chattarji, Sumantra

    2010-11-01

    Stress and depression may share common neural plasticity mechanisms. Importantly, the development and reversal of stress-induced plasticity requires time. These temporal aspects, however, are not captured fully in the forced-swim test (FST), a behavioural model for testing antidepressant efficacy, used originally in naïve animals. The present study probed whether and how a rodent model of stress affects behaviour in the FST over time. We found that the intensity and duration of stress are critical in the development of depressive symptoms in male Wistar rats (n = 37) as tested in the FST. Chronic immobilization stress (2 h/day for 10 days) elicited a range of responses, from low to high values of immobility in the FST on day 1, and subsequent immobility on day 2 was inversely related to individual day 1 values. As a whole, chronically stressed rats did not exhibit any significant change in immobility either on day 1 or day 2 compared to control rats. However, climbing behaviour was reduced uniformly from day 1 to day 2, despite the differences in immobility. In contrast, a separate group of rats (n = 30) subjected to the same chronic stressor displayed a significant reduction in open-arm exploration in the elevated plus maze, indicative of a robust increase in anxiety-like behaviour. Furthermore, when the 10-day chronic stress paradigm was reduced to a single 2-h episode of immobilization stress, it triggered a uniform day 1 to day 2 increase in immobility, which was not persistent 10 days later. These results highlight a need for closer examination of the ways in which stress-induced modulation of behaviour in the FST may be used and interpreted in future studies aimed at exploring connections between stress and depression.

  10. Stress sensitivity and resilience in the chronic mild stress rat model of depression; an in situ hybridization study

    DEFF Research Database (Denmark)

    Bergström, A; Jayatissa, M N; Mørk, A;

    2008-01-01

    We used the validated chronic mild stress (CMS) paradigm to induce anhedonia, a core symptom of major depression, in rats. Thirty percent of animals exposed to CMS are resistant to the development of anhedonia, whereas the remaining are responsive, CMS resilient and CMS sensitive, respectively. We...... in stress. Moreover, in the CA3 we found downregulation of vascular endothelial growth factor (VEGF) mRNA in the CMS sensitive group. Downregulation of VEGF suggests impaired hippocampal function, caused by loss of trophic factor neuroprotective support, as part of a previously uncharacterized mechanism...... vasopressin (AVP) in the paraventricular nucleus of the hypothalamus. In particular, HPA axis seems to be activated in the CMS resilient group suggesting other pathways protecting against stress sensitivity. We applied the restraint stress procedure to compare effects of a faster and simpler form of stress...

  11. Chronic stimulation of alpha-2A-adrenoceptors with guanfacine protects rodent prefrontal cortex dendritic spines and cognition from the effects of chronic stress

    OpenAIRE

    Hains, Avis Brennan; Yabe, Yoko; Arnsten, Amy F.T.

    2015-01-01

    The prefrontal cortex (PFC) provides top-down regulation of behavior, cognition, and emotion, including spatial working memory. However, these PFC abilities are greatly impaired by exposure to acute or chronic stress. Chronic stress exposure in rats induces atrophy of PFC dendrites and spines that correlates with working memory impairment. As similar PFC grey matter loss appears to occur in mental illness, the mechanisms underlying these changes need to be better understood. Acute stress expo...

  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. 慢性应激与动脉粥样硬化%Chronic Stress and Atherosclerosis

    Institute of Scientific and Technical Information of China (English)

    李金平; 胡厚源

    2009-01-01

    Research suggests that chronic stress is a risk factor for the development of several diseases. Chronic stress can influence blood pressure, platelet function, blood fat, endothelial function, macrophage activation, and more. In this paper we review the relation between chronic stress and atherosclerosis.%研究表明慢性应激是许多疾病发生的危险因素,慢性应激对血压、血小板功能、血脂、内皮功能、巨噬细胞活化和炎症因子等与动脉硬化有关的因素均可产生影响,现将综述慢性应激与动脉粥样硬化之间的关系.

  14. Neuropeptide Y and leptin receptor expression in the hypothalamus of rats with chronic immobilization stress

    Institute of Scientific and Technical Information of China (English)

    Shaoxian Wang; Jiaxu Chen; Guangxin Yue; Minghua Bai; Meijing Kou; Zhongye Jin

    2013-01-01

    In this study, Sprague-Dawley rats were immobilized to a frame for 3 hours a day for 21 days to establish a model of chronic immobilization stress. The body weight and food intake of rats subjected to chronic immobilization stress were significantly decreased compared with the control group. Dual-labeling immunofluorescence revealed that the expression of leptin receptor and the co-localization coeffient in these leptic receptor neurons in the arcuate nucleus of the hypothalamus were both upregulated, while the number of neuropeptide Y neurons was decreased. Chronic immobilization stress induced high expression of leptin receptor in the arcuate nucleus and suppressed the synthesis and secretion of neuropeptide Y, thereby disrupting the pathways in the arcuate nucleus that regulate feeding behavior, resulting in diminished food intake and reduced body weight.

  15. Efficacy of subantimicrobial-dose doxycycline against nitrosative stress in chronic periodontitis

    OpenAIRE

    PÂRVU, ALINA ELENA; ALB, SANDU FLORIN; Crăciun, Alexandra; Taulescu, Marian Aurel

    2012-01-01

    Aim: To evaluate the effectiveness of subantimicrobial-dose doxycycline (SDD) as an adjunct to scaling and root planing (SRP) treatment against the nitrosative stress of moderate to advanced chronic periodontitis. Methods: Adults with untreated chronic periodontitis (n=174) were randomly administered SRP+SDD (n=87) (20 mg of doxycycline twice daily) or SRP+placebo (n=87) treatment for 3 months. At baseline and after 3 months, the probing depths (PD), bleeding on probing (BOP) and clinical att...

  16. Morphology of Pyramidal Neurons in the Rat Prefrontal Cortex: Lateralized Dendritic Remodeling by Chronic Stress

    Directory of Open Access Journals (Sweden)

    Claudia Perez-Cruz

    2007-01-01

    Full Text Available The prefrontal cortex (PFC plays an important role in the stress response. We filled pyramidal neurons in PFC layer III with neurobiotin and analyzed dendrites in rats submitted to chronic restraint stress and in controls. In the right prelimbic cortex (PL of controls, apical and distal dendrites were longer than in the left PL. Stress reduced the total length of apical dendrites in right PL and abolished the hemispheric difference. In right infralimbic cortex (IL of controls, proximal apical dendrites were longer than in left IL, and stress eliminated this hemispheric difference. No hemispheric difference was detected in anterior cingulate cortex (ACx of controls, but stress reduced apical dendritic length in left ACx. These data demonstrate interhemispheric differences in the morphology of pyramidal neurons in PL and IL of control rats and selective effects of stress on the right hemisphere. In contrast, stress reduced dendritic length in the left ACx.

  17. Chronic stress differentially affects antioxidant enzymes and modifies the acute stress response in liver of Wistar rats.

    Science.gov (United States)

    Djordjevic, J; Djordjevic, A; Adzic, M; Niciforovic, A; Radojcic, M B

    2010-01-01

    Clinical reports suggest close interactions between stressors, particularly those of long duration, and liver diseases, such as hepatic inflammation, that is proposed to occur via reactive oxygen species. In the present study we have used 21-day social isolation of male Wistar rats as a model of chronic stress to investigate protein expression/activity of liver antioxidant enzymes: superoxide dismutases (SODs), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GLR), and protein expression of their upstream regulators: glucocorticoid receptor (GR) and nuclear factor kappa B (NFkB). We have also characterized these parameters in either naive or chronically stressed animals that were challenged by 30-min acute immobilization. We found that chronic isolation caused decrease in serum corticosterone (CORT) and blood glucose (GLU), increase in NFkB signaling, and disproportion between CuZnSOD, peroxidases (CAT, GPx) and GLR, thus promoting H2O2 accumulation and prooxidative state in liver. The overall results suggested that chronic stress exaggerated responsiveness to subsequent stressor at the level of CORT and GLU, and potentiated GLR response, but compromised the restoration of oxido-reductive balance due to irreversible alterations in MnSOD and GPx. PMID:20406049

  18. EVALUATION OF OXIDATIVE STRESS MARKERS IN CHRONIC KIDNEY FAILURES OF SOUTH INDIAN POPULATION

    Directory of Open Access Journals (Sweden)

    Kemidi Ilaiah

    2013-01-01

    Full Text Available Oxidative stress defines an imbalance between the formation of reactive oxygen species and antioxidants. The existence of oxidative stress and higher incidence of cardiovascular diseases (CVD in association with uraemia is proven from studies on Chronic Kidney Disease (CKD patients. Non traditional risk factors like oxidative stress are being given special emphasis to explain high incidence and identification of new therapeutic interventions. Excess Reactive oxygen Species levels have been implicated to damage DNA, lipids, proteins etc., It may also affect the cells of host, particularly at the inflammation site contributing to proteinuria observed in Chronic Kidney Disease patients. The uremic status, oxidant and antioxidant levels were assessed in the present study. This prospective observational study was conducted for nine months. Patients meeting the study criteria were included. Malonyldialdehyde (MDA, glutathione-S-transferase (GST, Protein thiols, Total proteins, Serum urea, creatinine, albumin and Haemoglobin levels were estimated using suitable methods. Study recruited 108 Chronic Kidney Disease patients, divided into three groups namely, patients without haemodialysis (54, patients with haemodialysis (54 and control population (50. Serum urea, creatinine, MDA and GST levels were found to be significantly increased (P<0.0001, and total proteins, albumin, proteinthiols, and Haemoglobin levels were found to be significantly decreased in Chronic Renal Failure patients compared to normal controls (P<0.0001. Our study confirms the presence of oxidative stress in Chronic Kidney Disease patient population. Our study also emphasises the need for anti-oxidant therapy in CKD patients.

  19. Role of anuloma viloma pranayama in reducing stress in chronic alcoholics

    International Nuclear Information System (INIS)

    Despite improved clinical care, heightened public awareness and wide spread use of health innovations, alcoholism remains a leading cause of death in many parts of the world. Chronic alcoholics suffer from stress and multitude of symptoms. The progressive addiction to alcohol will gradually nullify all other interests in the patient's life so that a deterioration of the physical, psychological, social, cultural and religious values takes place. The role of yoga in healing asthma, arthritis and other disorders has been known. Methods: Breathing technique (Anuloma Viloma Pranayama) was taught to chronic alcoholics. Using galvanic skin resistance, stress levels were measured before and after anuloma viloma yoga in controls and chronic alcoholics. Results: Reduced stress levels were noted using the galvanic skin resistance in both controls and chronic alcoholics after yogic breathing. Conclusion: There is a promising effect of simple yoga techniques in organising effective rehabilitation and treatment programmes to reduce stress in chronic alcoholics. This study would help to chart out a better management programme for enhancing relapse and alleviate the symptoms. (author)

  20. Strain Differences in the Chronic Mild Stress Animal Model of Depression and Anxiety in Mice

    OpenAIRE

    Jung, Yang-Hee; Hong, Sa-Ik; Ma, Shi-Xun; Hwang, Ji-Young; Kim, Jun-Sup; lee, Ju-hyun; Seo, Jee-Yeon; Lee, Seok-Yong; Jang, Choon-Gon

    2014-01-01

    Chronic mild stress (CMS) has been reported to induce an anhedonic-like state in mice that resembles some of the symptoms of human depression. In the present study, we used a chronic mild stress animal model of depression and anxiety to examine the responses of two strains of mice that have different behavioral responsiveness. An outbred ICR and an inbred C57BL/6 strain of mice were selected because they are widely used strains in behavioral tests. The results showed that the inbred C57BL/6 a...

  1. 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.

  2. Chronic Bilateral Tibial Stress Fractures with Valgus Treated with Bilateral Intramedullary Nailing: A Case Report

    Directory of Open Access Journals (Sweden)

    Steven K Dailey

    2014-01-01

    Full Text Available Introduction: Stress fractures are overuse injuries most commonly seen in athletes, military recruits, and individuals with endocrine abnormalities. It has been demonstrated that chronic cases of anterior tibial stress fractures refractory to conservative management respond well to intramedullary nailing. To our knowledge, only one report has been published concerning patients with bilateral tibial stress fractures treated with bilateral intramedullary nailing. All patients in the series were high-level athletes. We present the case of a non-athletic patient with chronic bilateral tibial stress fractures and associated deformity successfully treated with bilateral intramedullary nails. Case Report: A 23-year-old Caucasian female full-time student presented with chronic bilateral shin pain for approximately five years. She had failed an extensive regimen of conservative management. She was diagnosed with chronic bilateral tibial stress fractures based on history, physical examination, and radiologic findings. She subsequently underwent sequential intramedullary nailing of her tibiae. Both tibiae were in valgus alignment; however, this did not preclude nail placement. The nails deformed upon insertion into the sclerotic canals to conform to the deformation. Post operatively the tibiae united and patient was relieved of her symptoms. Conclusion: Bilateral intramedullary nailing of chronic bilateral tibial stress fractures should be considered as a treatment option for all patients, not just high-level athletes, who fail a trial of conservative management. Additionally, mild to moderate tibial malalignment does not necessarily preclude tibial nailing as the smaller nails placed in sclerotic canals will likely deform on insertion and conform to the canal. Keywords: Bilateral intramedullary nailing, bilateral tibial stress fractures, valgus

  3. Update in the methodology of the chronic stress paradigm: internal control matters.

    Science.gov (United States)

    Strekalova, Tatyana; Couch, Yvonne; Kholod, Natalia; Boyks, Marco; Malin, Dmitry; Leprince, Pierre; Steinbusch, Harry Mw

    2011-04-27

    To date, the reliability of induction of a depressive-like state using chronic stress models is confronted by many methodological limitations. We believe that the modifications to the stress paradigm in mice proposed herein allow some of these limitations to be overcome. Here, we discuss a variant of the standard stress paradigm, which results in anhedonia. This anhedonic state was defined by a decrease in sucrose preference that was not exhibited by all animals. As such, we propose the use of non-anhedonic, stressed mice as an internal control in experimental mouse models of depression. The application of an internal control for the effects of stress, along with optimized behavioural testing, can enable the analysis of biological correlates of stress-induced anhedonia versus the consequences of stress alone in a chronic-stress depression model. This is illustrated, for instance, by distinct physiological and molecular profiles in anhedonic and non-anhedonic groups subjected to stress. These results argue for the use of a subgroup of individuals who are negative for the induction of a depressive phenotype during experimental paradigms of depression as an internal control, for more refined modeling of this disorder in animals.

  4. Update in the methodology of the chronic stress paradigm: internal control matters

    Directory of Open Access Journals (Sweden)

    Boyks Marco

    2011-04-01

    Full Text Available Abstract To date, the reliability of induction of a depressive-like state using chronic stress models is confronted by many methodological limitations. We believe that the modifications to the stress paradigm in mice proposed herein allow some of these limitations to be overcome. Here, we discuss a variant of the standard stress paradigm, which results in anhedonia. This anhedonic state was defined by a decrease in sucrose preference that was not exhibited by all animals. As such, we propose the use of non-anhedonic, stressed mice as an internal control in experimental mouse models of depression. The application of an internal control for the effects of stress, along with optimized behavioural testing, can enable the analysis of biological correlates of stress-induced anhedonia versus the consequences of stress alone in a chronic-stress depression model. This is illustrated, for instance, by distinct physiological and molecular profiles in anhedonic and non-anhedonic groups subjected to stress. These results argue for the use of a subgroup of individuals who are negative for the induction of a depressive phenotype during experimental paradigms of depression as an internal control, for more refined modeling of this disorder in animals.

  5. Attenuation of the cytotoxic T lymphocyte response to lymphocytic choriomeningitis virus in mice subjected to chronic social stress

    OpenAIRE

    Sommershof, Annette; Basler, Michael; Riether, Carsten; Engler, Harald; Gröttrup, Marcus

    2011-01-01

    Chronic stress is suspected to increase the susceptibility to infections but experimental evidence from physiological stress models is scarce. We examined the effects of chronic social stress on virus-specific CTL responses in mice after infection with lymphocytic choriomeningitis virus (LCMV). Mice subjected to social stress on six consecutive days prior to infection showed a significant reduction of IFN-γ producing TCD8+ splenocytes and markedly lowered plasma concentrations of IFN-γ. In co...

  6. Systematic review of the association between chronic social stress and telomere length: A life course perspective.

    Science.gov (United States)

    Oliveira, Bruna Silva; Zunzunegui, Maria Victoria; Quinlan, Jacklyn; Fahmi, Hassan; Tu, Mai Thanh; Guerra, Ricardo Oliveira

    2016-03-01

    Our aim was to examine whether chronic social stress is associated with telomere length throughout the life course, following our protocol published in 2014. Structured searches were conducted in MEDLINE (PubMed interface), EMBASE (OVID interface), Cochrane Central (OVID interface) and grey from their start date onwards. Reference lists of retrieved citations were hand searched for relevant studies. Eighteen studies published until May 1, 2015 investigating the association between chronic social stress (as defined by poverty, exposure to violence, or family caregiving) and telomere length in healthy or diseased adults and children were independently selected by 2 reviewers. Sixteen of those studies were cross-sectional and two had a longitudinal design. Studies differed in type of stress exposure, method to measure telomere length and cell type. As meta-analysis could not be conducted, the data were synthesized as a narrative review. Based on this comprehensive review, chronic social stress accompanies telomere shortening in both early and adult exposures, with most eligible studies showing a significant relationship. We discuss the significance of chronic stress of social origin and the potential for social interventions through public policies and we recommend methodological improvements that would allow for future meta-analysis. PMID:26732034

  7. Euthanasia, moral stress, and chronic illness in veterinary medicine.

    Science.gov (United States)

    Rollin, Bernard E

    2011-05-01

    Euthanasia is a double-edged sword in veterinary medicine. It is a powerful and ultimately the most powerful tool for ending the pain and suffering. Demand for its use for client convenience is morally reprehensible and creates major moral stress for ethically conscious practitioners. But equally reprehensible and stressful to veterinarians is the failure to use it when an animal faces only misery, pain, distress, and suffering. Finding the correct path through this minefield may well be the most important ethical task facing the conscientious veterinarian. PMID:21601753

  8. Family Stress, Resources, and Family Types: Chronic Illness in Children.

    Science.gov (United States)

    McCubbin, Marilyn A.

    1988-01-01

    Measured family stress, resources, parental coping, and family types in families who had a child with myelomeningocele. Determined the relationships between the family characteristics, the child's health status, and number of active health problems based on level of impairment. Demonstrated an increasing level of family system involvement…

  9. Chronic stress and brain plasticity: Mechanisms underlying adaptive and maladaptive changes and implications for stress-related CNS disorders.

    Science.gov (United States)

    Radley, Jason; Morilak, David; Viau, Victor; Campeau, Serge

    2015-11-01

    Stress responses entail neuroendocrine, autonomic, and behavioral changes to promote effective coping with real or perceived threats to one's safety. While these responses are critical for the survival of the individual, adverse effects of repeated exposure to stress are widely known to have deleterious effects on health. Thus, a considerable effort in the search for treatments to stress-related CNS disorders necessitates unraveling the brain mechanisms responsible for adaptation under acute conditions and their perturbations following chronic stress exposure. This paper is based upon a symposium from the 2014 International Behavioral Neuroscience Meeting, summarizing some recent advances in understanding the effects of stress on adaptive and maladaptive responses subserved by limbic forebrain networks. An important theme highlighted in this review is that the same networks mediating neuroendocrine, autonomic, and behavioral processes during adaptive coping also comprise targets of the effects of repeated stress exposure in the development of maladaptive states. Where possible, reference is made to the similarity of neurobiological substrates and effects observed following repeated exposure to stress in laboratory animals and the clinical features of stress-related disorders in humans. PMID:26116544

  10. Could stress contribute to pain-related fear in chronic pain?

    Directory of Open Access Journals (Sweden)

    Sigrid eElsenbruch

    2015-12-01

    Full Text Available Learning to predict pain based on internal or external cues constitutes a fundamental and highly adaptive process aimed at self-protection. Pain-related fear is an essential component of this response, which is formed by associative and instrumental learning processes. In chronic pain, pain-related fear may become maladaptive, drive avoidance behaviors and contribute to symptom chronicity. Pavlovian fear conditioning has proven fruitful to elucidate associative learning and extinction involving aversive stimuli, including pain, but studies in chronic pain remain scarce. Stress demonstrably exerts differential effects on emotional learning and memory processes, but this has not been transferred to pain-related fear. Within this perspective, we propose that stress could contribute to impaired pain-related associative learning and extinction processes and call for interdisciplinary research. Specifically, we suggest to test the hypotheses that (1 extinction-related phenomena inducing a re-activation of maladaptive pain-related fear (e.g., reinstatement, renewal likely occur in everyday life of chronic pain patients and may alter pain processing, impair perceptual discrimination and favour overgeneralization; (2 acute stress prior to or during acquisition of pain-related fear may facilitate the formation and/or consolidation of pain-related fear memories, (3 stress during or after extinction may impair extinction efficacy resulting in greater reinstatement or context-dependent renewal of pain-related fear; and (4 these effects could be amplified by chronic stress due to early adversity and/or psychiatric comorbidity such as depression or anxiety in patients with chronic pain.

  11. 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...

  12. 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...

  13. Environmental enrichment and cafeteria diet attenuate the response to chronic variable stress in rats.

    Science.gov (United States)

    Zeeni, N; Bassil, M; Fromentin, G; Chaumontet, C; Darcel, N; Tome, D; Daher, C F

    2015-02-01

    Exposure to an enriched environment (EE) or the intake of a highly palatable diet may reduce the response to chronic stress in rodents. To further explore the relationships between EE, dietary intake and stress, male Sprague-Dawley rats were fed one of two diets for 5 weeks: high carbohydrate (HC) or "cafeteria" (CAF) (Standard HC plus a choice of highly palatable cafeteria foods: chocolate, biscuits, and peanut butter). In addition, they were either housed in empty cages or cages with EE. After the first two weeks, half of the animals from each group were stressed daily using a chronic variable stress (CVS) paradigm, while the other half were kept undisturbed. Rats were sacrificed at the end of the 5-week period. The effects of stress, enrichment and dietary intake on animal adiposity, serum lipids, and stress hormones were analyzed. Results showed an increase in intra-abdominal fat associated with the CAF diet and an increase in body weight gain associated with both the CAF diet and EE. Furthermore, the increase in ACTH associated with CVS was attenuated in the presence of EE and the CAF diet independently while the stress-induced increase in corticosterone was reduced by the combination of EE and CAF feeding. The present study provides evidence that the availability of a positive environment combined to a highly palatable diet increases resilience to the effects of CVS in rats. These results highlight the important place of palatable food and supportive environments in reducing central stress responses.

  14. Comparison of the Adulthood Chronic Stress Effect on Hippocampal BDNF Signaling in Male and Female Rats.

    Science.gov (United States)

    Niknazar, Somayeh; Nahavandi, Arezo; Peyvandi, Ali Asghar; Peyvandi, Hassan; Akhtari, Amin Shams; Karimi, Mohsen

    2016-08-01

    Studies show that gender plays an important role in stress-related disorders, and women are more vulnerable to its effect. The present study was undertaken to investigate differences in the change in expression of brain-derived neurotrophic factor (BDNF), and its tyrosine intracellular kinase-activating receptor (TrkB) genes in the male and female rats' hippocampus (HPC) under chronic mild repeated stress (CMRS) conditions. In this experiment, male and female Wistar rats were randomly divided into two groups: the CMRS and the control group. To induce stress, a repeated forced swimming paradigm was employed daily for adult male and female rats for 21 days. At the end of the stress phase, elevated plus maze (EPM) was used for measuring the stress behavioral effects. Serum corticosterone level was measured by ELISA. BDNF and TrkB gene methylation and protein expression in the HPC were detected using real-time PCR and Western blotting. Chronic stress in the adolescence had more effects on anxiety-like behavior and serum corticosterone concentration in female rats than males. Furthermore, stressed female rats had higher methylation levels and following reduced protein expression of BDNF but not TrkB compared to stressed male rats. These findings suggest that in exposure to a stressor, sex differences in BDNF methylation may be root cause of decreased BDNF levels in females and may underlie susceptibility to pathology development. PMID:26189832

  15. If It Goes up, Must It Come Down? Chronic Stress and the Hypothalamic-Pituitary Adrenocortical Axis in Humans

    Science.gov (United States)

    Miller, Gregory E.; Chen, Edith; Zhou, Eric S.

    2007-01-01

    The notion that chronic stress fosters disease by activating the hypothalamic-pituitary adrenocortical (HPA) axis is featured prominently in many theories. The research linking chronic stress and HPA function is contradictory, however, with some studies reporting increased activation, and others reporting the opposite. This meta-analysis showed…

  16. Childhood Poverty, Chronic Stress, and Young Adult Working Memory: The Protective Role of Self-Regulatory Capacity

    Science.gov (United States)

    Evans, Gary W.; Fuller-Rowell, Thomas E.

    2013-01-01

    Prior research shows that childhood poverty as well as chronic stress can damage children's executive functioning (EF) capacities, including working memory. However, it is also clear that not all children suffer the same degree of adverse consequences from risk exposure. We show that chronic stress early in life (ages 9-13) links childhood…

  17. The effect of Brazilian propolis on serum thyroid hormones in broilers reared under chronic heat stress

    Science.gov (United States)

    This experiment evaluated the effect of dietary supplement with green Brazilian propolis on serum thyroxin (T4) and tri-iodothyronine (T3) levels in broiler chickens exposed to chronic heat stress for 4 wks (from 15 to 42 d of age). Five hundred and four 15-d-old, male broiler chickens (Ross 708) w...

  18. Stress in adolescents with a chronically ill parent: inspiration from Rolland's Family Systems-Illness model

    NARCIS (Netherlands)

    D.S. Sieh; A.L.C. Dikkers; J.M.A. Visser-Meily; A.M. Meijer

    2012-01-01

    This article was inspired by Rolland’s Family Systems-Illness (FSI) model, aiming to predict adolescent stress as a function of parental illness type. Ninety-nine parents with a chronic medical condition, 82 partners, and 158 adolescent children (51 % girls; mean age = 15.1 years) participated in th

  19. Chronic light reduction reduces overall resilience to additional shading stress in the seagrass

    NARCIS (Netherlands)

    Yaakub, S.M.; Chen, E.; Bouma, T.; Erftemeijer, P.L.A.; Todd, P.A.

    2014-01-01

    Seagrasses have substantial capacity to survive long periods of light reduction, but how acclimation to chronic low light environments may influence their ability to cope with additional stress is poorly understood. This study examines the effect of temporal light reduction by adding two levels of s

  20. Effects of prenatal exposure to chronic mild stress and toluene in rats

    DEFF Research Database (Denmark)

    Hougaard, Karin; Andersen, Maibritt B; Hansen, Ase M;

    2005-01-01

    The aim of the present study was to elucidate whether prenatal chronic stress, in combination with exposure to a developmental neurotoxicant, would increase effects in the offspring compared with the effects of either exposure alone. Development and neurobehavioral effects were investigated in fe...

  1. Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder : A randomized clinical trial

    NARCIS (Netherlands)

    Feder, Adriana; Parides, Michael K.; Murrough, James W.; Perez, Andrew M.; Morgan, Julia E.; Saxena, Shireen; Kirkwood, Katherine; Aan Het Rot, Marije; Lapidus, Kyle A.B.; Wan, Le-Ben; Iosifescu, Dan; Charney, Dennis S.

    2014-01-01

    IMPORTANCE Few pharmacotherapies have demonstrated sufficient efficacy in the treatment of posttraumatic stress disorder (PTSD), a chronic and disabling condition. OBJECTIVE To test the efficacy and safety of a single intravenous subanesthetic dose of ketamine for the treatment of PTSD and associate

  2. Perceived stress and severity of chronic rhinosinusitis in allergic and nonallergic patients.

    Science.gov (United States)

    Tomljenovic, Dejan; Pinter, Darko; Kalogjera, Livije

    2014-01-01

    Chronic stress exposure carries greater risk of onset of atopic respiratory disorders such as rhinitis and asthma. The interaction between depression, anxiety, and severity of chronic rhinosinusitis (CRS) has been suggested. We aimed to access the relationship between psychological stress, severity of CRS, and atopy. Sixty-three consecutive patients referred with CRS were asked to score the severity of rhinosinusitis symptoms on a visual analog scale and to fill in questionnaires on the disease-specific quality of life and perceived stress-22-item Sino-Nasal Outcome Test (SNOT-22) and measure of perceived stress (MPS) scale, respectively. Inclusion criteria for the study were a reliable allergy evaluation and a recent computerized tomography (CT) scan of the sinuses. Patients with nasal polyps (NPs), asthma, and previous surgery were excluded. The study group consisted of 14 allergic and 18 nonallergic patients with CRS without NPs (CRSsNPs). Correlation between MPS and SNOT-22 scores in the study group was highly significant (Pearson r = 0.61; p = 0.001). Patients with higher stress scores had significantly stronger postnasal discharge, thick discharge, cough, disturbed sleep, fatigue, and sadness. Postnasal drip was significantly stronger in patients with allergy. The correlation between SNOT-22 and CT scores was insignificant. The correlation between MPS and SNOT-22 scores suggests an interaction between severity of CRS and chronic stress, but not with the extent of the disease on CT in CRSsNPs. Chronic psychological stress might be one of the factors that modifies the disease severity and may lead to uncontrolled disease in CRS patients. PMID:25295807

  3. Review of posttraumatic stress disorder and chronic pain: The path to integrated care

    Directory of Open Access Journals (Sweden)

    Carri-Ann Gibson, MD, DAAPM

    2012-06-01

    Full Text Available With the large number of Veterans experiencing posttraumatic stress disorder (PTSD and chronic pain, the purpose of this article is to review the prevalence of PTSD and chronic pain, the theoretical models that explain the maintenance of both conditions, and the challenges faced by providers and families who care for these patients. The Department of Veterans Affairs (VA/Department of Defense (DOD VA/DOD Clinical Practice Guideline for Management of Post-Traumatic Stress with special attention to chronic pain is presented. Limited scientific evidence supports specific care and treatment of PTSD and chronic pain, and this challenges providers to investigate and research potential treatment options. Integrated care models designed for working with these patients are reviewed, including a focus on the techniques and strategies to address not only PTSD and chronic pain, but other conditions, including substance dependence and depression. A specific focus on headaches, back pain, and neuropathic pain follows, including treatment recommendations such as pharmacological, psychotherapeutic, and complementary approaches, given the high rates of these pain complaints for Veterans in PTSD clinical programs. Integrated care is presented as a viable solution and approach that challenges clinicians and researchers to develop innovative, scientifically based therapeutics and treatments to enhance the recovery and quality of life for Veterans with PTSD and chronic pain.

  4. Chronic stress is associated with pain precipitation and elevation in DeltaFosb expression

    Directory of Open Access Journals (Sweden)

    Hang eWang

    2016-05-01

    Full Text Available A number of acute or repeated stimuli can induce expression of DeltaFosB (ΔFosB, a transcription factor derived from the fosB gene (an osteosarcoma viral oncogene via alternative splicing. ΔFosB protein is currently viewed as a 'molecular switch' to repeated stimuli that gradually converts acute responses into relatively stable adaptations underlying long-term neural and behavioral plasticity. ΔFosB has received extensive attention in drug addition, depression and stress adaptation, but changes in ΔFosB protein expression during pain is not fully understood. In this study we explored ΔFosB expression in the medial prefrontal cortex (mPFC of rats experiencing chronic or acute stress-induced pain. Our data reveal that chronic pain induced by neonatal colorectal distension, chronic constriction injury of the sciatic nerve, or maternal separation was associated with an increase in ΔfosB protein expression in mPFC, but acute application of acetic acid or zymosan did not alter the ΔFosB protein expression. ΔFosB expression in the rat visual cortex, a non pain-related brain region, did not change in response to chronic constriction injury of the sciatic nerve and acetic acid treatment. In conclusion, our results indicate that ΔFosB protein expression is significantly elevated in rats that have experienced chronic pain and stress, but not acute pain. The ΔFosB protein may serve as an important transcription factor for chronic stress-induced pain. Further research is needed to improve the understanding of both the upstream signaling leading to ΔFosB protein expression as well as the regulation of ΔFosB gene expression in cortical neurons.

  5. The power of exercise: buffering the effect of chronic stress on telomere length.

    Directory of Open Access Journals (Sweden)

    Eli Puterman

    Full Text Available BACKGROUND: Chronic psychological stress is associated with detrimental effects on physical health, and may operate in part through accelerated cell aging, as indexed by shorter telomeres at the ends of chromosomes. However, not all people under stress have distinctly short telomeres, and we examined whether exercise can serve a stress-buffering function. We predicted that chronic stress would be related to short telomere length (TL in sedentary individuals, whereas in those who exercise, stress would not have measurable effects on telomere shortening. METHODOLOGY AND PRINCIPAL FINDINGS: 63 healthy post-menopausal women underwent a fasting morning blood draw for whole blood TL analysis by a quantitative polymerase chain reaction method. Participants completed the Perceived Stress Scale (Cohen et al., 1983, and for three successive days reported daily minutes of vigorous activity. Participants were categorized into two groups-sedentary and active (those getting Centers for Disease Control-recommended daily amount of activity. The likelihood of having short versus long telomeres was calculated as a function of stress and exercise group, covarying age, BMI and education. Logistic regression analyses revealed a significant moderating effect of exercise. As predicted, among non-exercisers a one unit increase in the Perceived Stress Scale was related to a 15-fold increase in the odds of having short telomeres (p<.05, whereas in exercisers, perceived stress appears to be unrelated to TL (B = -.59, SE = .78, p = .45. DISCUSSION: Vigorous physical activity appears to protect those experiencing high stress by buffering its relationship with TL. We propose pathways through which physical activity acts to buffer stress effects.

  6. Oxidative stress in cases of chronic fluoride intoxication

    OpenAIRE

    Ailani, Vinita; R. C. Gupta; Gupta, Sunil Kumar; Gupta, Kapil

    2009-01-01

    This study was conducted to find out the level of oxidative stress and effect of supplementation of vitamin C, D and Calcium on levels of SOD, serum and urinary fluoride in children residing in endemic fluorosis area. For this the fluoride belt of Jaipur district was selected. The parameters selected were Super oxide dismutase, serum fluoride and urinary fluoride. The study was conducted on one hundred children, selected from four areas (25 from each area) consuming water containing 1.2, 2.4,...

  7. 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.

  8. Electroconvulsive stimulation reverses anhedonia and cognitive impairments in rats exposed to chronic mild stress

    DEFF Research Database (Denmark)

    Henningsen, K; Woldbye, D P D; Wiborg, O

    2013-01-01

    Electroconvulsive therapy remains the most effective treatment for depression including a fast onset of action. However, this therapeutic approach suffers from some potential drawbacks. In the acute phase this includes amnesia. Electroconvulsive stimulation (ECS) has previously been shown...... to reverse a depression-like state in the chronic mild stress model of depression (CMS), but the effect of ECS on cognition has not previously been investigated. In this study the CMS model was used to induce a depressive-like condition in rats. The study was designed to investigate the acute effect of ECS...... treatment on working memory and the chronic effect of repeated ECS treatments on depression-like behavior and working memory. The results indicated that, in the acute phase, ECS treatment induced a working memory deficit in healthy controls unexposed to stress, while repeated treatments reversed stress...

  9. 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...

  10. 逍遥散抗慢性心理应激海马神经元凋亡的机理研究%Mechanism of Xiaoyao Powder in Counteracting Apoptosis of Hippocampus Neurons Caused by Chronic Psychological Stress

    Institute of Scientific and Technical Information of China (English)

    王文竹; 杨忠华; 徐志伟; 苏俊芳

    2011-01-01

    Objective To investigate the effect of Xiaoyao Powder(XP) on apoptosis of hippocampus neurons and glucocorticoid receptor(GR) mRNA expression caused by chronic psychological stress. Methods Wistar rats were randomized to 3 groups: normal group(without any stimulation,gastric gavage of 2 mL normal saline per day), model group( chronic mild unpredictable stress, gastric gavage of 2 mL normal saline per day) and XP group(gastric gavage of 2 mL XP one hour before stress). The changes of body weight and sucrose preference were observed. The apoptotic rate of hippocampal neurons were detected by PI staining method and GR mRNA expression by in-situ hybridization.Results After treatment with chronic mild unpredictable stress for 21 days, the body weight as well as the weight gain was lower in the model group and XP group than that in the normal group(P < 0.01 ), and the sucrose preference was decreased in the model group (P < 0.01 ). In the model group, the apoptotic rate of hippocampal neurons was increased(P < 0.05), and GR mRNA expression was decreased(P < 0.01 ). XP decreased the apoptotic rate (P < 0.05) and increased GR mRNA expression(P < 0.01 ). Conclusion Chronic mild unpredictable stress can significantly decrease sucrose preference. XP can counteract the decrease of sucrose preference and significantly improve the apoptosis of hippocampus neurons caused by chronic psychological stress, which mechanism maybe related to the regulation of GR mRNA expression.%目的 观察逍遥散抗慢性心理应激海马神经元凋亡及糖皮质激素受体(GR)表达的影响.方法 Wistar 大鼠按体重分为正常组、模型组、逍遥散组.正常组及模型组灌胃等量生理盐水,逍遥散组给予逍遥散7.02g/kg.观察实验前后大鼠体重及糖水偏爱度的变化,采用PI法检测大鼠海马神经元凋亡,原位杂交法检测GR mrRNA表达.结果 经过21 d慢性轻度不可预计应激(CMUS)造模后,模型组、逍遥散组体重及

  11. Assessing Cumulative Thermal Stress in Fish During Chronic Exposure to High Temperature

    Energy Technology Data Exchange (ETDEWEB)

    Bevelhimer, M.S.; Bennett, W.R.

    1999-11-14

    As environmental laws become increasingly protective, and with possible future changes in global climate, thermal effects on aquatic resources are likely to receive increasing attention. Lethal temperatures for a variety of species have been determined for situations where temperatures rise rapidly resulting in lethal effects. However, less is known about the effects of chronic exposure to high (but not immediately lethal) temperatures and even less about stress accumulation during periods of fluctuating temperatures. In this paper we present a modeling framework for assessing cumulative thermal stress in fish. The model assumes that stress accumulation occurs above a threshold temperature at a rate depending on the degree to which the threshold is exceeded. The model also includes stress recovery (or alleviation) when temperatures drop below the threshold temperature as in systems with large daily variation. In addition to non-specific physiological stress, the model also simulates thermal effects on growth.

  12. Integration of animal behaviors under stresses with different time courses

    Institute of Scientific and Technical Information of China (English)

    Lun Zheng; Xigeng Zheng

    2014-01-01

    We used animal models of“forced swim stress”and“chronic unpredictable stress”, and tried to reveal whether a passive coping style of high lfotation behavior in forced swim stress predicts an-hedonia behavior after chronic unpredictable stress, and whether the dopamine system regulates lfoating and anhedonia behaviors. Our results conifrmed that depression-prone rats use“lfoating behavior”as a coping strategy in forced swim stress and more readily suffer from anhedonia during chronic unpredictable stress. Intraperitoneal injection or nucleus accumbens microin-jection of the dopamine 2/3 receptor subtype agonist ropinirole reduced lfoating behaviors in depression-prone animals, but increased sucrose preference in rats showing anhedonia. These data indicate that lfoating behavior is a defensive mode that is preferred by susceptible individ-uals under conditions of acute stress. Simultaneously, these animals more readily experienced anhedonia under long-term stress;that is, they were more readily affected by depression. Our results suggest that dopamine 2/3 receptor subtypes in the nucleus accumbens play an important role in lfoating behaviors and anhedonia.

  13. Chronic mild stress alters circadian expressions of molecular clock genes in the liver.

    Science.gov (United States)

    Takahashi, Kei; Yamada, Tetsuya; Tsukita, Sohei; Kaneko, Keizo; Shirai, Yuta; Munakata, Yuichiro; Ishigaki, Yasushi; Imai, Junta; Uno, Kenji; Hasegawa, Yutaka; Sawada, Shojiro; Oka, Yoshitomo; Katagiri, Hideki

    2013-02-01

    Chronic stress is well known to affect metabolic regulation. However, molecular mechanisms interconnecting stress response systems and metabolic regulations have yet to be elucidated. Various physiological processes, including glucose/lipid metabolism, are regulated by the circadian clock, and core clock gene dysregulation reportedly leads to metabolic disorders. Glucocorticoids, acting as end-effectors of the hypothalamus-pituitary-adrenal (HPA) axis, entrain the circadian rhythms of peripheral organs, including the liver, by phase-shifting core clock gene expressions. Therefore, we examined whether chronic stress affects circadian expressions of core clock genes and metabolism-related genes in the liver using the chronic mild stress (CMS) procedure. In BALB/c mice, CMS elevated and phase-shifted serum corticosterone levels, indicating overactivation of the HPA axis. The rhythmic expressions of core clock genes, e.g., Clock, Npas2, Bmal1, Per1, and Cry1, were altered in the liver while being completely preserved in the hypothalamic suprachiasmatic nuculeus (SCN), suggesting that the SCN is not involved in alterations in hepatic core clock gene expressions. In addition, circadian patterns of glucose and lipid metabolism-related genes, e.g., peroxisome proliferator activated receptor (Ppar) α, Pparγ-1, Pparγ-coactivator-1α, and phosphoenolepyruvate carboxykinase, were also disturbed by CMS. In contrast, in C57BL/6 mice, the same CMS procedure altered neither serum corticosterone levels nor rhythmic expressions of hepatic core clock genes and metabolism-related genes. Thus, chronic stress can interfere with the circadian expressions of both core clock genes and metabolism-related genes in the liver possibly involving HPA axis overactivation. This mechanism might contribute to metabolic disorders in stressful modern societies.

  14. Gene expression profile of the hippocampus of rats subjected to chronic immobilization stress.

    Directory of Open Access Journals (Sweden)

    Xiao-Hong Li

    Full Text Available OBJECTIVE: This study systematically investigated the effect of chronic stress on the hippocampus and its damage mechanism at the whole genome level. METHODS: The rat whole genome expression chips (Illumina were used to detect gene expression differences in the hippocampus of rats subjected to chronic immobilization stress (daily immobilization stress for 3 h, for 7 or 21 days. The hippocampus gene expression profile was studied through gene ontology and signal pathway analyses using bioinformatics. A differentially expressed transcription regulation network was also established. Real-time quantitative polymerase chain reaction (RT-PCR was used to verify the microarray results and determine expression of the Gabra1, Fadd, Crhr2, and Cdk6 genes in the hippocampal tissues. RESULTS: Compared to the control group, 602 differentially expressed genes were detected in the hippocampus of rats subjected to stress for 7 days, while 566 differentially expressed genes were expressed in the animals experiencing stress for 21 days. The stress significantly inhibited the primary immune system functions of the hippocampus in animals subjected to stress for both 7 and 21 days. Immobilization activated the extracellular matrix receptor interaction pathway after 7 day exposure to stress and the cytokine-cytokine receptor interaction pathway. The enhanced collagen synthesis capacity of the hippocampal tissue was the core molecular event of the stress regulation network in the 7-day group, while the inhibition of hippocampal cell growth was the core molecular event in the 21-day group. For the Gabra1, Fadd, Crhr2, and Cdk6 genes, RT-PCR results were nearly in line with gene chip assay results. CONCLUSION: During the 7-day and 21-day stress processes, the combined action of polygenic, multilevel, and multi-signal pathways leads to the disorder of the immunologic functions of the hippocampus, hippocampal apoptosis, and proliferation disequilibrium.

  15. The Influence of Work-Related Chronic Stress on the Regulation of Emotion and on Functional Connectivity in the Brain

    OpenAIRE

    Armita Golkar; Emilia Johansson; Maki Kasahara; Walter Osika; Aleksander Perski; Ivanka Savic

    2014-01-01

    Despite mounting reports about the negative effects of chronic occupational stress on cognitive and emotional functions, the underlying mechanisms are unknown. Recent findings from structural MRI raise the question whether this condition could be associated with a functional uncoupling of the limbic networks and an impaired modulation of emotional stress. To address this, 40 subjects suffering from burnout symptoms attributed to chronic occupational stress and 70 controls were investigated us...

  16. Hippocampal dysfunction and cognitive impairments provoked by chronic early-life stress involve excessive activation of CRH receptors

    OpenAIRE

    Ivy, Autumn S.; Rex, Christopher S.; Chen, Yuncai; Dubé, Céline; Maras, Pamela M.; Grigoriadis, Dimitri E.; Christine M Gall; Lynch, Gary; Baram, Tallie Z.

    2010-01-01

    Chronic stress impairs learning and memory in humans and rodents and disrupts long-term potentiation (LTP) in animal models. These effects are associated with structural changes in hippocampal neurons, including reduced dendritic arborization. Unlike the generally reversible effects of chronic stress on adult rat hippocampus, we have previously found that the effects of early-life stress endure and worsen during adulthood, yet the mechanisms for these clinically important sequelae are poorly ...

  17. May Chronic Childhood Constipation Cause Oxidative Stress and Potential Free Radical Damage to Children?

    Institute of Scientific and Technical Information of China (English)

    JI-YUE WANG; YE-LING WANG; SHENG-LI ZHOU; JUN-FU ZHOU

    2004-01-01

    To investigate whether chronic childhood constipation (CCC) may cause oxidative stress and potential free radical damage to children, and to explore the mechanisms by which CCC may cause oxidative stress and potential free radical damage to chronic constipation patients (CCPs). Methods Sixty CCPs and sixty healthy child volunteers (HCVs) whose ages, gender and others were matched for the CCPs were enrolled in a randomized controlled study, in which levels of vitamin C (VC) and vitamin E (VE) in plasma as well as activities of superoxide dismutase (SOD) and catalase (CAT) in erythrocytes were determined by spectrophotometric analytical methods. Results Compared with average values of the above biochemical parameters in the HCVs group, the average values of VC and VE in plasma as well as those of SOD and CAT in erythrocytes in the CCPs group were significantly decreased (P<0.0001). Linear regression and bivariate correlation analysis showed that with prolonged course of the CCPs, the levels of VC and VE in plasma as well as the activities of SOD and CAT in erythrocytes in the CCPs were decreased gradually (P<0.0001). Conclusion The findings in the present study suggest that chronic childhood constipation causes oxidative stress and potential free radical damage to children with chronic constipation.

  18. Chronic bladder ischemia and oxidative stress: new pharmacotherapeutic targets for lower urinary tract symptoms.

    Science.gov (United States)

    Nomiya, Masanori; Andersson, Karl-Erik; Yamaguchi, Osamu

    2015-01-01

    Chronic bladder ischemia is potentially a common cause of lower urinary tract symptoms in the elderly. Epidemiological studies have shown a close association between lower urinary tract symptoms and vascular risk factors for atherosclerosis, and investigations using transrectal color Doppler ultrasonography have shown a negative correlation between decreased lower urinary tract perfusion and International Prostate Symptom Score in elderly patients with lower urinary tract symptoms. Bladder blood flow is also known to decrease in men with bladder outlet obstruction as a result of benign prostatic hyperplasia. Studies in animal models suggest that chronic bladder ischemia and repeated ischemia/reperfusion during a micturition cycle might produce oxidative stress, leading to denervation of the bladder and the expression of tissue-damaging molecules in the bladder wall, which could be responsible for the development of bladder hyperactivity progressing to bladder underactivity. The effects of drugs with different mechanisms of action; for example, α1-adrenoceptor antagonists, phosphodiesterase type 5 inhibitors, free radical scavengers and β3-adrenoceptor agonist, have been studied in animal models of chronic bladder ischemia. The drugs, representing different treatment principles for increasing blood flow and decreasing oxidative stress, showed protective effects not only on urodynamic parameters, but also on negative effects on muscle contractility and on detrimental structural bladder wall changes. Improvement of lower urinary tract perfusion and control of oxidative stress can be considered new therapeutic strategies for treatment of bladder dysfunction induced by chronic ischemia. PMID:25339506

  19. INFLUENCE OF ACUTE EXERCISE ON OXIDATIVE STRESS IN CHRONIC SMOKERS

    Directory of Open Access Journals (Sweden)

    Zehra Serdar

    2003-09-01

    Full Text Available The relative oxidative insult caused by exercise and smoking on biological systems are well documented, however, their cumulative influence needs to be clarified. In order to examine the collective effects of exercise and smoking on oxidant and antioxidant parameters, young male smokers (n=10 and non-smokers (n=10 made to perform a negative slope (10% cycling exercise for 30 minutes at individual load equivalent to 60% maximal oxygen consumption (VO2max. Pre- and post-exercise (post-ex haematocrit, haemoglobin, white blood cells, plasma malondialdehyde (MDA levels, protein carbonyl formation and non-HDL oxidation, erythrocyte superoxide dismutase (SOD and glutathione peroxidase (GPX activities, serum ceruloplasmin (CER and urinary cotinine concentrations were evaluated. Pre-ex CER and urinary cotinine concentrations of smokers were significantly higher (p<0.05 and p<0.01, respectively compared to that of non-smokers and pre-ex CER concentrations were significantly correlated with cotinine levels in all subjects (p<0.05. Significant (p<0.01 increases were observed in non-HDL oxidation following the exercise in both groups and the elevations were more pronounced in smokers. Pre-ex SOD and GPX activities were not different between the two groups, however post-ex enzyme activities were significantly reduced in smokers (p<0.05. MDA and protein carbonyl concentrations were not different between the two groups and there were not any significant changes due to exercise.In conclusion, according to the results of the present study, we suggest that erythrocyte antioxidants SOD and GPX and plasma non-HDL are more prone to the possible oxidant damage of acute physical exercise in chronic smokers.

  20. Mindfulness-based stress reduction: a non-pharmacological approach for chronic illnesses

    Directory of Open Access Journals (Sweden)

    Asfandyar Khan Niazi

    2011-01-01

    Full Text Available Background: Mindfulness Based Stress Reduction (MBSR therapy is a meditation therapy, though originally designed for stress management, it is being used for treating a variety of illnesses such as depression, anxiety, chronic pain, cancer, diabetes mellitus, hypertension, skin and immune disorders. Aim: The aim of this systematic review is to determine the efficacy of MBSR in the treatment of chronic illnesses; it’s mechanism of action and adverse effects. It describes an alternative method of treatment for physicians and patients that may help patients cope with their diseases in a more effective way. Materials and Methods: COCHRANE, EMBASE and MEDLINE were systematically searched for data on outcome of treatment with MBSR used alone or in conjunction with other treatments. The data available on prevention of diseases through MBSR was also analyzed. Results: All the 18 studies included in this systematic review showed improvement in the condition of patients after MBSR therapy. These studies were focused on patients with chronic diseases like cancer, hypertension, diabetes, HIV/AIDS, chronic pain and skin disorders, before and after MBSR therapy. Conclusions: Although the research on MBSR is sparse, the results of these researches indicate that MBSR improves the condition of patients suffering from chronic illnesses and helps them cope with a wide variety of clinical problems.

  1. Mindfulness-based stress reduction: A non-pharmacological approach for chronic illnesses

    Directory of Open Access Journals (Sweden)

    Asfandyar Khan Niazi

    2011-01-01

    Full Text Available Background: Mindfulness Based Stress Reduction (MBSR therapy is a meditation therapy, though originally designed for stress management, it is being used for treating a variety of illnesses such as depression, anxiety, chronic pain, cancer, diabetes mellitus, hypertension, skin and immune disorders. Aim: The aim of this systematic review is to determine the efficacy of MBSR in the treatment of chronic illnesses; it′s mechanism of action and adverse effects. It describes an alternative method of treatment for physicians and patients that may help patients cope with their diseases in a more effective way. Materials and Methods: COCHRANE, EMBASE and MEDLINE were systematically searched for data on outcome of treatment with MBSR used alone or in conjunction with other treatments. The data available on prevention of diseases through MBSR was also analyzed. Results: All the 18 studies included in this systematic review showed improvement in the condition of patients after MBSR therapy. These studies were focused on patients with chronic diseases like cancer, hypertension, diabetes, HIV/AIDS, chronic pain and skin disorders, before and after MBSR therapy. Conclusions: Although the research on MBSR is sparse, the results of these researches indicate that MBSR improves the condition of patients suffering from chronic illnesses and helps them cope with a wide variety of clinical problems.

  2. STRESS AS PREDISPOSING FACTOR OF SOME CHRONIC DISEASES INCLUDING PERIODONTAL DISEASE

    Directory of Open Access Journals (Sweden)

    Dewi-Nurul M Dewi-Nurul

    2006-04-01

    Full Text Available Stress is hypothesized as a common pathway for several related chronic diseases of man. Psychosocial stress as modified by perceptions and coping by patients can lead to physical processes. Psychoneuroimmunologic (PNI studies have suggested that psychosocial stress can alter immune function and increase vulnerability to illnesses. The patients also have high sensitivity to periodontal disease (PD. This article describes the association of stress as a physiological response to diseases such as PD, rheumatoid arthritis (RA, and inflammatory bowel disease. The psychosocial stress can lead to physiological processes through 1 the hypothalamic-pituitary-adrenal (HPA axis leading to glucocortico-steroid secretion; 2 the autonomic nervous system, resulting in the release of catecholamine; or 3 the hypothalamic-pituitary-gonadal axis, resulting in the release of sex hormones. These processes may affect chronic diseases. It can be concluded that psychosocial stress in periodontal disease patients must be considered and social support must be provided in order to achieve an optimum periodontal therapy result.

  3. The evolution of the painful sensitivity in acute and chronic stress.

    Science.gov (United States)

    Cristea, A; Ciobanu, A; Stoenescu, M; Rusei, I

    1994-01-01

    The clinical research was made on two groups of young volunteer students. We considered stress consisting in chronic informational overexposure during the examination session and the acute stress from their emotions before a hard examination. The painful sensitivity was analysed by measuring the retraction time of the finger from water at 55 degrees C. The experimental research was made on a group of 100 male mice. The acute stress was performed by subjecting each mouse to swim (behavioral despair test). Painful sensitivity was determined by the test of the hot plate heated at 50 degrees C. Individuals with hyper (H) and hypo (h) painful sensitivity were selected for the tests. In chronic stress, the results proved increased painful sensitivity (hyperalgia) more important at "h" compared to "H" (p behaviors with opposite mechanisms involved in stress analgesia. This hypothesis is related with studies which demonstrate the involvement in stress analgesia of non-opioid monoaminergic mechanisms together with the opioid mechanisms (Lewis, 1980). PMID:8640371

  4. Housing in Pyramid Counteracts Neuroendocrine and Oxidative Stress Caused by Chronic Restraint in Rats

    Directory of Open Access Journals (Sweden)

    M. Surekha Bhat

    2007-01-01

    Full Text Available The space within the great pyramid and its smaller replicas is believed to have an antistress effect. Research has shown that the energy field within the pyramid can protect the hippocampal neurons of mice from stress-induced atrophy and also reduce neuroendocrine stress, oxidative stress and increase antioxidant defence in rats. In this study, we have, for the first time, attempted to study the antistress effects of pyramid exposure on the status of cortisol level, oxidative damage and antioxidant status in rats during chronic restraint stress. Adult female Wistar rats were divided into four groups as follows: normal controls (NC housed in home cage and left in the laboratory; restrained rats (with three subgroups subject to chronic restraint stress by placing in a wire mesh restrainer for 6 h per day for 14 days, the restrained controls (RC having their restrainers kept in the laboratory; restrained pyramid rats (RP being kept in the pyramid; and restrained square box rats (RS in the square box during the period of restraint stress everyday. Erythrocyte malondialdehyde (MDA and plasma cortisol levels were significantly increased and erythrocyte-reduced glutathione (GSH levels, erythrocyte glutathione peroxidase (GSH-Px and superoxide dismutase (SOD activities were significantly decreased in RC and RS rats as compared to NC. However, these parameters were maintained to near normal levels in RP rats which showed significantly decreased erythrocyte MDA and plasma cortisol and significantly increased erythrocyte GSH levels, erythrocyte GSH-Px and SOD activities when compared with RS rats. The results showed that housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats.

  5. Chronic intermittent psychological stress promotes macrophage reverse cholesterol transport by impairing bile acid absorption in mice.

    Science.gov (United States)

    Silvennoinen, Reija; Quesada, Helena; Kareinen, Ilona; Julve, Josep; Kaipiainen, Leena; Gylling, Helena; Blanco-Vaca, Francisco; Escola-Gil, Joan Carles; Kovanen, Petri T; Lee-Rueckert, Miriam

    2015-05-11

    Psychological stress is a risk factor for atherosclerosis, yet the pathophysiological mechanisms involved remain elusive. The transfer of cholesterol from macrophage foam cells to liver and feces (the macrophage-specific reverse cholesterol transport, m-RCT) is an important antiatherogenic pathway. Because exposure of mice to physical restraint, a model of psychological stress, increases serum levels of corticosterone, and as bile acid homeostasis is disrupted in glucocorticoid-treated animals, we investigated if chronic intermittent restraint stress would modify m-RCT by altering the enterohepatic circulation of bile acids. C57Bl/6J mice exposed to intermittent stress for 5 days exhibited increased transit through the large intestine and enhanced fecal bile acid excretion. Of the transcription factors and transporters that regulate bile acid homeostasis, the mRNA expression levels of the hepatic farnesoid X receptor (FXR), the bile salt export pump (BSEP), and the intestinal fibroblast growth factor 15 (FGF15) were reduced, whereas those of the ileal apical sodium-dependent bile acid transporter (ASBT), responsible for active bile acid absorption, remained unchanged. Neither did the hepatic expression of cholesterol 7α-hydroxylase (CYP7A1), the key enzyme regulating bile acid synthesis, change in the stressed mice. Evaluation of the functionality of the m-RCT pathway revealed increased fecal excretion of bile acids that had been synthesized from macrophage-derived cholesterol. Overall, our study reveals that chronic intermittent stress in mice accelerates m-RCT specifically by increasing fecal excretion of bile acids. This novel mechanism of m-RCT induction could have antiatherogenic potential under conditions of chronic stress. PMID:25969465

  6. Efficacy of subantimicrobial-dose doxycycline against nitrosative stress in chronic periodontitis

    Institute of Scientific and Technical Information of China (English)

    Alina Elena P(A)RVU; Sandu Florin ALB; Alexandra CR(A)CIUN; Marian Aurel TAULESCU

    2013-01-01

    Aim: To evaluate the effectiveness of subantimicrobial-dose doxycycline (SDD) as an adjunct to scaling and root planing (SRP) treatment against the nitrosative stress of moderate to advanced chronic periodontitis.Methods: Adults with untreated chronic periodontitis (n=174) were randomly administered SRP+SDD (n=87) (20 mg of doxycycline twice daily) or SRP+placebo (n=87) treatment for 3 months.At baseline and after 3 months,the probing depths (PD),bleeding on probing (BOP) and clinical attachment level (CAL) were measured,and a gingivomucosal biopsy was collected to assay the induction of nitric oxide synthase (iNOS) and 3-nitrotyrosine (3NT),and blood was collected to assay for total nitrites and nitrates (NOx) and 3NT.Results: Compared to baseline,at the completion of treatment,significant decreases in the levels of tissue iNOS and 3NT and serum NOx and 3NT were observed in both groups.SRP+SDD yielded a greater reduction in the gingivomucosal and serum nitrosative stress markers than did SRP+placebo.PD,BOP,and CAL reduction were correlated with the nitrosative stress parameters.Conclusion: On a short-term basis,SDD therapy may be used as an adjunct to SRP treatment against nitrosative stress in moderate to advanced chronic periodontitis.

  7. A cafeteria diet modifies the response to chronic variable stress in rats.

    Science.gov (United States)

    Zeeni, N; Daher, C; Fromentin, G; Tome, D; Darcel, N; Chaumontet, C

    2013-03-01

    Stress is known to lead to metabolic and behavioral changes. To study the possible relationships between stress and dietary intake, male Sprague-Dawley rats were fed one of three diets for 6 weeks: high carbohydrate (HC), high fat (HF), or "Cafeteria" (CAF) (Standard HC plus a choice of highly palatable cafeteria foods: chocolate, biscuits, and peanut butter). After the first 3 weeks, half of the animals from each group (experimental groups) were stressed daily using a chronic variable stress (CVS) paradigm, while the other half of the animals (control groups) were kept undisturbed. Rats were sacrificed at the end of the 6-week period. The effects of stress and dietary intake on animal adiposity, serum lipids, and corticosterone were analyzed. Results showed that both chronic stress and CAF diet resulted in elevated total cholesterol, increased low-density lipoprotein (LDL), and lower high-density lipoprotein (HDL). In addition, increases in body weight, food intake, and intra-abdominal fat were observed in the CAF group compared with the other dietary groups. In addition, there was a significant interaction between stress and diet on serum corticosterone levels, which manifest as an increase in corticosterone levels in stressed rats relative to non-stressed controls in the HC and HF groups but not in the CAF group. These results show that a highly palatable diet, offering a choice of food items, is associated with a reduction in the response to CVS and could validate a stressor-induced preference for comfort food that in turn could increase body weight.

  8. 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...

  9. Impaired Hippocampal Neuroligin-2 Function by Chronic Stress or Synthetic Peptide Treatment is Linked to Social Deficits and Increased Aggression

    DEFF Research Database (Denmark)

    van der Kooij, Michael A; Fantin, Martina; Kraev, Igor;

    2014-01-01

    display reduced sociability and increased aggression. This occurs along with a reduction of NLGN-2, but not NLGN-1 expression (as shown with Western blot, immunohistochemistry and electron microscopy analyses), throughout the hippocampus and detectable in different layers of the CA1, CA3 and DG subfields...... and are related to similar abnormalities in animal models. Chronic stress increases the likelihood for affective disorders and has been shown to induce changes in neural structure and function in different brain regions, with the hippocampus being highly vulnerable to stress. Previous studies have shown evidence...... of chronic stress-induced changes in the neural E/I balance in the hippocampus. Therefore, we hypothesized that chronic restraint stress would lead to reduced hippocampal NLGN-2 levels, in association with alterations in social behavior. We found that rats submitted to chronic restraint stress in adulthood...

  10. Tracking CNS and systemic sources of oxidative stress during the course of chronic neuroinflammation.

    Science.gov (United States)

    Mossakowski, Agata A; Pohlan, Julian; Bremer, Daniel; Lindquist, Randall; Millward, Jason M; Bock, Markus; Pollok, Karolin; Mothes, Ronja; Viohl, Leonard; Radbruch, Moritz; Gerhard, Jenny; Bellmann-Strobl, Judith; Behrens, Janina; Infante-Duarte, Carmen; Mähler, Anja; Boschmann, Michael; Rinnenthal, Jan Leo; Füchtemeier, Martina; Herz, Josephine; Pache, Florence C; Bardua, Markus; Priller, Josef; Hauser, Anja E; Paul, Friedemann; Niesner, Raluca; Radbruch, Helena

    2015-12-01

    The functional dynamics and cellular sources of oxidative stress are central to understanding MS pathogenesis but remain elusive, due to the lack of appropriate detection methods. Here we employ NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX enzymes) in vivo to identify inflammatory monocytes, activated microglia, and astrocytes expressing NOX1 as major cellular sources of oxidative stress in the central nervous system of mice affected by experimental autoimmune encephalomyelitis (EAE). This directly affects neuronal function in vivo, indicated by sustained elevated neuronal calcium. The systemic involvement of oxidative stress is mirrored by overactivation of NOX enzymes in peripheral CD11b(+) cells in later phases of both MS and EAE. This effect is antagonized by systemic intake of the NOX inhibitor and anti-oxidant epigallocatechin-3-gallate. Together, this persistent hyper-activation of oxidative enzymes suggests an "oxidative stress memory" both in the periphery and CNS compartments, in chronic neuroinflammation. PMID:26521072

  11. Influence of omega-3 fatty acid status on the way rats adapt to chronic restraint stress.

    Directory of Open Access Journals (Sweden)

    Marie Hennebelle

    Full Text Available Omega-3 fatty acids are important for several neuronal and cognitive functions. Altered omega-3 fatty acid status has been implicated in reduced resistance to stress and mood disorders. We therefore evaluated the effects of repeated restraint stress (6 h/day for 21 days on adult rats fed omega-3 deficient, control or omega-3 enriched diets from conception. We measured body weight, plasma corticosterone and hippocampus glucocorticoid receptors and correlated these data with emotional and depression-like behaviour assessed by their open-field (OF activity, anxiety in the elevated-plus maze (EPM, the sucrose preference test and the startle response. We also determined their plasma and brain membrane lipid profiles by gas chromatography. Repeated restraint stress caused rats fed a control diet to lose weight. Their plasma corticosterone increased and they showed moderate behavioural changes, with increases only in grooming (OF test and entries into the open arms (EPM. Rats fed the omega-3 enriched diet had a lower stress-induced weight loss and plasma corticosterone peak, and reduced grooming. Rats chronically lacking omega-3 fatty acid exhibited an increased startle response, a stress-induced decrease in locomotor activity and exaggerated grooming. The brain omega-3 fatty acids increased as the dietary omega-3 fatty acids increased; diets containing preformed long-chain omega-3 fatty acid were better than diets containing the precursor alpha-linolenic acid. However, the restraint stress reduced the amounts of omega-3 incorporated. These data showed that the response to chronic restraint stress was modulated by the omega-3 fatty acid supply, a dietary deficiency was deleterious while enrichment protecting against stress.

  12. Effects of chronic variable stress on cognition and Bace1 expression among wild-type mice.

    Science.gov (United States)

    Cordner, Z A; Tamashiro, K L K

    2016-01-01

    Stressful life events, activation of the hypothalamic-pituitary-adrenal (HPA) axis and glucocorticoids are now thought to have a role in the development of several neurodegenerative and psychiatric disorders including Alzheimer's disease (AD) through mechanisms that may include exacerbation of cognitive impairment, neuronal loss, and beta-amyloid (Aβ) and tau neuropathology. In the current study, we use a wild-type mouse model to demonstrate that chronic variable stress impairs cognitive function and that aged mice are particularly susceptible. We also find that stress exposure is associated with a 1.5- to 2-fold increase in the expression of Bace1 in the hippocampus of young adult mice and the hippocampus, prefrontal cortex and amygdala of aged mice. Further, the increased expression of Bace1 was associated with decreased methylation of several CpGs in the Bace1 promoter region. In a second series of experiments, exposure to environmental enrichment (EE) prevented the stress-related changes in cognition, gene expression and DNA methylation. Together, these findings re-affirm the adverse effects of stress on cognition and further suggest that aged individuals are especially susceptible. In addition, demonstrating that chronic stress results in decreased DNA methylation and increased expression of Bace1 in the brain may provide a novel link between stress, Aβ pathology and AD. Finally, understanding the mechanisms by which EE prevented the effects of stress on cognition and Bace1 expression will be an important area of future study that may provide insights into novel approaches to the treatment of AD. PMID:27404286

  13. Studies on protein turnover and energy expenditure in chronically undernourished adults during stress of infection

    International Nuclear Information System (INIS)

    Chronic undernutrition in man leads to adaptive responses which could reduce the requirements for dietary energy and protein. It is also possible that these adaptive responses, which are economical in nature, could lead to a decreased capacity for combating stress. Undernourished people are more susceptible to infections, and during these stresses, show different patterns of protein and energy metabolism from well-nourished subjects. Animal models have clearly shown a diminished response to tissue injury, in terms of the anabolic acute phase response. It is proposed to study the effect of prior nutritional status on the degree to which an infective stress stimulates the acute phase protein synthesis by the liver. In addition, the supply of amino acids to the liver in conditions of stress could come from the breakdown of body tissue proteins, particularly muscle. It is intended to study muscle protein turnover by the use of 13C-leucine in undernourished subjects under conditions of stress. Since whole body protein turnover can be measured by two methods, using 15N-glycine and 13C-leucine, a comparison of these two methods will initially be made in chronically undernourished subjects. It is also intended to study daily energy expenditure in the subject by an isotopic method, i.e. the appearance of 13CO2 in the breath after the administration of 13C-bicarbonate. (author). 8 refs

  14. Chronic restraint stress inhibits hair growth via substance P mediated by reactive oxygen species in mice.

    Directory of Open Access Journals (Sweden)

    Nan Liu

    Full Text Available BACKGROUNDS: Solid evidence has demonstrated that psychoemotional stress induced alteration of hair cycle through neuropeptide substance P (SP mediated immune response, the role of reactive oxygen species (ROS in brain-skin-axis regulation system remains unknown. OBJECTIVES: The present study aims to investigate possible mechanisms of ROS in regulation of SP-mast cell signal pathway in chronic restraint stress (CRS, a model of chronic psychoemotional stress which induced abnormal of hair cycle. METHODS AND RESULTS: Our results have demonstrated that CRS actually altered hair cycle by inhibiting hair follicle growth in vivo, prolonging the telogen stage and delaying subsequent anagen and catagen stage. Up-regulation of SP protein expression in cutaneous peripheral nerve fibers and activation of mast cell were observed accompanied with increase of lipid peroxidation levels and reduction of the activities of superoxide dismutase (SOD and glutathione peroxidase (GSH-Px in CRS mice skin. In addition, SP receptor antagonist (RP67580 reduced mast cell activations and lipid peroxidation levels as well as increased GSH-Px activity and normalized hair cycle. Furthermore, antioxidant Tempol (a free radical scavenger also restored hair cycle, reduced SP protein expression and mast cell activation. CONCLUSIONS: Our study provides the first solid evidence for how ROS play a role in regulation of psychoemotional stress induced SP-Mast cell pathway which may provide a convincing rationale for antioxidant application in clinical treatment with psychological stress induced hair loss.

  15. An intestinal microRNA modulates the homeostatic adaptation to chronic oxidative stress in C. elegans

    Science.gov (United States)

    Kato, Masaomi; Kashem, Mohammed Abul; Cheng, Chao

    2016-01-01

    Adaptation to an environmental or metabolic perturbation is a feature of the evolutionary process. Recent insights into microRNA function suggest that microRNAs serve as key players in a robust adaptive response against stress in animals through their capacity to fine-tune gene expression. However, it remains largely unclear how a microRNA-modulated downstream mechanism contributes to the process of homeostatic adaptation. Here we show that loss of an intestinally expressed microRNA gene, mir-60, in the nematode C. elegans promotes an adaptive response to chronic – a mild and long-term – oxidative stress exposure. The pathway involved appears to be unique since the canonical stress-responsive factors, such as DAF-16/FOXO, are dispensable for mir-60 loss to enhance oxidative stress resistance. Gene expression profiles revealed that genes encoding lysosomal proteases and those involved in xenobiotic metabolism and pathogen defense responses are up-regulated by the loss of mir-60. Detailed genetic studies and computational microRNA target prediction suggest that endocytosis components and a bZip transcription factor gene zip-10, which functions in innate immune response, are directly modulated by miR-60 in the intestine. Our findings suggest that the mir-60 loss facilitates adaptive response against chronic oxidative stress by ensuring the maintenance of cellular homeostasis. PMID:27623524

  16. Chronic vitamin C deficiency does not accelerate oxidative stress in ageing brains of guinea pigs

    DEFF Research Database (Denmark)

    Tveden-Nyborg, Pernille; Andersen, Stine Hasselholt; Miyashita, Namiyo;

    2012-01-01

    , a lack of vitamin C could be associated with an increase in redox imbalance in the ageing brain. The present study compared oxidative stress of ageing to that of a long-term non-scorbutic vitamin C deficiency in guinea pigs. Adults (3-9 months old) were compared to old (36-42 months old) animals during...... a six-month dietary intervention by assessing vitamin C transport and redox homeostasis in the brain. In contrast to our hypothesis, chronic vitamin C deficiency did not affect the measured markers of oxidative stress in the brains of adult and aged animals. However, aged animals generally showed...

  17. [Coagulation hemostasis and fibrinolytic potential of blood in conditions of chronic stress and terahertz therapy].

    Science.gov (United States)

    Kirichuk, V F; Tsymbal, A A; Antipova, O N; Tupikin, V D; Maĭborodin, A V; Krenitskiĭ, A P; Betskiĭ, O V

    2007-01-01

    The effects of electromagnetic rays of maximum high frequencies of radiation molecular spectrum and absorption of nitrogen oxide 150, 176-150, 664 GHz on blood coagulation properties of white laboratory rats subjected to chronic immobilization stress have been studied. It is shown that preventive course of electromagnetic irradiation with terahertz range at the frequencies of molecular spectrum of radiation and absorption of nitrogen oxide 150, 176-150, 664 GHz warns about development of stress disturbances of coagulation component of the hemostasis system and fibrinolysis in animals. PMID:17465273

  18. Effects of Chronic Mild Stress in Female Bax Inhibitor-1-Gene Knockout Mice

    OpenAIRE

    Sui, Zhi-Yan; Chae, Han-Jung; Huang, Guang-Biao; Zhao, Tong; Shrestha Muna, Sushma; Chung, Young-Chul

    2012-01-01

    Objective The anti-apoptotic protein Bax inhibitor-1 (BI-1) is a regulator of apoptosis linked to endoplasmic reticulum (ER) stress, and BI-1-/- mice exhibit increased sensitivity to tissue damage. The purpose of this study was to investigate the role of BI-1 in the pathogenesis of chronic mild stress (CMS)-induced depression-like behaviors in BI-1-/- mice. Methods We delivered CMS for 2 or 6 weeks in BI-1-knockout and wild-type mice. Control groups of BI-1-knockout and wild-type mice were le...

  19. Baicalin influences the dendritic morphology of newborn neurons in the hippocampus of chronically stressed rats

    Institute of Scientific and Technical Information of China (English)

    Xinghua Jiang; Junmei Xu; Dingquan Zou; Lin Yang; Yaping Wang

    2013-01-01

    Chronic stress models, established in adult Sprague-Dawley rats through a 14-day subcutaneous injection of 40 mg/kg corticosterone, once per day, were given a daily oral feeding of 50 mg/kg baicalin. The study was an attempt to observe the effect of baicalin on neurogenesis in chronically stressed rats. Results showed that subcutaneous injection of corticosterone significantly decreased the total number of doublecortin-positive neurons in the hippocampus. The reduced cell number caused by corticosterone was mainly due to the decrease of class II doublecortin-positive neurons, but the class I doublecortin-positive neurons were unaffected. Baicalin treatment increased the number of both class I and class II doublecortin-positive neurons. In addition, doublecortin-positive neurons showed less complexity in dendritic morphology after corticosterone injection, and this change was totally reversed by baicalin treatment. These findings suggest that baicalin exhibits a beneficial effect on adult neurogenesis.

  20. Gender differences in response of hippocampus to chronic glucocorticoid stress: role of glutamate receptors.

    Science.gov (United States)

    Liu, Howard H; Payne, H Ross; Wang, Bin; Brady, Scott T

    2006-04-01

    Glucocorticoids (GC) play critical roles in the pathophysiological reactions to environmental stress. In brain, morphological changes were examined in hippocampal CA3 neurons with 2 weeks of chronic elevation of GC in male and female mice. Molecular correlates and underlying mechanisms paralleling these morphologic changes in hippocampus were investigated. Although the hippocampal neurons in the CA3 area in male mice atrophy with chronically elevated GC, female mice show minimal morphological changes with comparable GC regimens. These sexual morphological differences correlate with differences in the postsynaptic dense protein (PSD95) as well as the spectrum of glutamate receptors induced by GC treatment in male and female mice, including NMDA, AMPA, and KA receptors. These findings suggest that synaptic receptor composition is adapted to the unique physiological requirements of males and females and illuminate underlying mechanisms of GC/stress responses in the brain.

  1. Proteomic changes of the porcine small intestine in response to chronic heat stress.

    Science.gov (United States)

    Cui, Yanjun; Gu, Xianhong

    2015-12-01

    Acute heat stress (HS) negatively affects intestinal integrity and barrier function. In contrast, chronic mild HS poses a distinct challenge to animals. Therefore, this study integrates biochemical, histological and proteomic approaches to investigate the effects of chronic HS on the intestine in finishing pigs. Castrated male crossbreeds (79.00 ± 1.50 kg BW) were subjected to either thermal neutral (TN, 21 °C; 55% ± 5% humidity; n=8) or HS conditions (30 °C; 55% ± 5% humidity; n=8) for 3 weeks. The pigs were sacrificed after 3 weeks of high environmental exposure and the plasma hormones, the intestinal morphology, integrity, and protein profiles of the jejunum mucosa were determined. Chronic HS reduced the free triiodothyronine (FT3) and GH levels. HS damaged intestinal morphology, increased plasma d-lactate concentrations and decreased alkaline phosphatase activity of intestinal mucosa. Proteome analysis of the jejunum mucosa was conducted by 2D gel electrophoresis and mass spectrometry. Fifty-three intestinal proteins were found to be differentially abundant, 18 of which were related to cell structure and motility, and their changes in abundance could comprise intestinal integrity and function. The down-regulation of proteins involved in tricarboxylic acid cycle (TCA cycle), electron transport chain (ETC), and oxidative phosphorylation suggested that chronic HS impaired energy metabolism and thus induced oxidative stress. Moreover, the changes of ten proteins in abundance related to stress response and defense indicated pigs mediated long-term heat exposure and counteracted its negative effects of heat exposure. These findings have important implications for understanding the effect of chronic HS on intestines.

  2. Pre-stress performance in an instrumental training predict post-stress behavioral alterations in chronically stressed rats

    OpenAIRE

    Shigenobu Toda

    2015-01-01

    Stress is a major factor in the development of major depressive disorder (MDD), but few studies have assessed individual risk based on pre-stress traits. In this study, we employed appetitive instrumental lever pressing with a progressive ratio schedule to assess the individual pre-stress behavioral and cognitive traits in experimentally naïve Sprague–Dawley rats. Based on the behavioral data, the animals were classified into four subgroups (Low Motivation, Quick Learner, Slow Learner, and Hy...

  3. Sleep-disordered breathing and oxidative stress in preclinical chronic mountain sickness (excessive erythrocytosis)

    OpenAIRE

    Julian, Colleen Glyde; Vargas, Enrique; Gonzales, Marcelino; Dávila, R. Daniela; Ladenburger, Anne; Reardon, Lindsay; Schoo, Caroline; Powers, Robert W.; Lee-Chiong, Teofilo; Moore, Lorna G.

    2013-01-01

    Chronic mountain sickness (CMS) is considered to be a loss of ventilatory acclimatization to high altitude (>2500 m) resulting in marked arterial hypoxemia and polycythemia. This case-control study explores the possibility that sleep-disordered breathing (SBD) and associated oxidative stress contribute to the etiology of CMS. Nocturnal respiratory and SaO2 patterns were measured using standard polysomnography techniques and compared between male high-altitude residents (aged 18–25) with precl...

  4. The ecology of suffering: developmental disorders of structured stress, emotion, and chronic inflammation

    OpenAIRE

    Wallace, Rodrick

    2003-01-01

    'Punctuated equilibrium' models of cognitive process, adapted from the Large Deviations Program of probability theory, are applied to the interaction between immune function and emotion in the context of culturally structured psychosocial stress. The analysis suggests: (1) Chronic inflammatory diseases should be comorbid and synergistic with characteristic emotional dysfunction, and may form a collection of joint disorders most effectively treated at the individual level using multifa...

  5. IMPACT OF CHRONIC POSTTRAUMATIC STRESS DISORDER ON THE QUALITY OF LIFE OF WAR SURVIVORS

    OpenAIRE

    Bravo-Mehmedbašić, Alma; Kučukalić, Abdulah; Džubur Kulenović, Alma; Suljić, Enra

    2010-01-01

    Background: Research data from studies of functional neuroanatomy and neurochemistry indicate various dysfunctions in certain areas of the brain in individuals who suffer from chronic Posttraumatic Stress Disorder. These abnormalities are involved in the evolution of symptoms of PTSD, deterioration of cognitive functions and decreased quality of life of the survivors. The intensity of these symptoms is in direct correlation with the degree of dysfunction in the central nervous system...

  6. Ovariectomy-induced chronic abdominal hypernociception in rats: Relation with brain oxidative stress

    OpenAIRE

    Bárbara B. Garrido-Suárez; Gabino Garrido-Garrido; Marian Castro Labrada; Addis Bellma Menéndez; Roberto Menéndez Soto del Valle; René Delgado-Hernández

    2015-01-01

    Context: Ovarian hormone deficiency observed in menopausal women increases the production of reactive oxygen species, which could be implicated in central sensitization subjacent in chronic functional pain syndromes. Aims: To examine the hyperalgesic state induced by ovariectomy in adult rats and its relation to some oxidative stress outcomes. Methods: The female Wistar rats were divided into normal, sham ovariectomized (OVX) and OVX groups, which were tested for mechanical and therma...

  7. Comorbidity Factors and Brain Mechanisms Linking Chronic Stress and Systemic Illness

    OpenAIRE

    Vanja Duric; Sarah Clayton; Mai Lan Leong; Li-Lian Yuan

    2016-01-01

    Neuropsychiatric symptoms and mental illness are commonly present in patients with chronic systemic diseases. Mood disorders, such as depression, are present in up to 50% of these patients, resulting in impaired physical recovery and more intricate treatment regimen. Stress associated with both physical and emotional aspects of systemic illness is thought to elicit detrimental effects to initiate comorbid mental disorders. However, clinical reports also indicate that the relationship between ...

  8. Stressful Life Events, Chronic Difficulties, and the Symptoms of Clinical Depression

    OpenAIRE

    Muscatell, Keely A.; Slavich, George M.; Monroe, Scott M.; Gotlib, Ian H.

    2009-01-01

    Major life events and chronic difficulties have been found to be associated with the onset of depression. Little is known, however, about how exposure to such stressors is related to the clinical presentation of this disorder. We addressed this issue by administering an interview-based measure of life stress, the Beck Depression Inventory, and the Global Assessment of Functioning scale to 100 adults diagnosed with major depressive disorder. Participants who experienced a preonset severe life ...

  9. Depressive symptoms and perceived chronic stress predict test anxiety in nursing students

    OpenAIRE

    Christoph Augner

    2015-01-01

    Aim: The aim of this study is to identify predictors of test anxiety in nursing students. Design: Cross sectional pilot study. Methods: A questionnaire was administered to 112 students of an Austrian nursing school (mean age = 21.42, SD = 5.21). Test anxiety (measured by the standardized PAF Test Anxiety Questionnaire), perceived chronic stress, depressive symptoms, pathological eating and further psychological and health parameters were measured. Results: We found highly significant correlat...

  10. Redrawing Papez' circuit: a theory about how acute stress becomes chronic and causes disease.

    Science.gov (United States)

    Eggers, Arnold E

    2007-01-01

    The diseases of chronic stress include migraine, essential hypertension, depression, and the metabolic syndrome. A theory is presented to explain how acute stress becomes chronic and causes these inter-related conditions. The theory is based on a new "circuit of emotion", which is derived from Papez' famous theory of emotion. The hypothesis is as follows: There is a basic circuit of emotion which runs from the hippocampus (defined as the dentate gyrus plus the CA regions), where emotion arises, to the amygdala and from there to serotonergic pacemaker cells in the dorsal raphe nucleus (DRN). The DRN projects back to the dentate gyrus in two ways: a direct route without a stop and an indirect route via pacemaker cells in the entorhinal cortex. The purpose of the direct route is to promote neurogenesis in the subgranular zone of the dentate; the indirect route has two purposes: to imprint ongoing moments of consciousness onto new dentate cells for retention as memory and to provide a negative feedback loop for regulation of the whole process. The hippocampus, the amygdala, and the DRN all project to the hypothalamus, which are branches off the basic loop that subserve the autonomic expression of emotion. Pathologic overdrive of the DRN causes overdrive of the entorhinal cortex, which leads to excitotoxic cell death of neurons in the hippocampus involved in the negative feedback loop. The disinhibited amygdala and DRN are then free to orchestrate the syndromes of chronic stress. Recovery from chronic stress requires repopulation of the dentate gyrus and restoration of the feedback loop. Excitotoxic cell death in the hippocampus results from either extraordinary acute stress or increased susceptibility to DRN overdrive, as might be caused, for example, by genetic factors, age, high cortisol levels, or incomplete recovery from previous damage. Three goals for therapeutic intervention are identified: inhibition of pacemaker cells in the DRN (which can be targeted by

  11. 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.

  12. 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.

  13. 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

  14. Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats

    Indian Academy of Sciences (India)

    Ashok Iyyaswamy; Sheeladevi Rathinasamy

    2012-09-01

    This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

  15. Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats.

    Science.gov (United States)

    Iyyaswamy, Ashok; Rathinasamy, Sheeladevi

    2012-09-01

    This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

  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. The Effect of Chronic Mild Stress and Imipramine on the Markers of Oxidative Stress and Antioxidant System in Rat Liver.

    Science.gov (United States)

    Duda, Weronika; Curzytek, Katarzyna; Kubera, Marta; Iciek, Małgorzata; Kowalczyk-Pachel, Danuta; Bilska-Wilkosz, Anna; Lorenc-Koci, Elżbieta; Leśkiewicz, Monika; Basta-Kaim, Agnieszka; Budziszewska, Bogusława; Regulska, Magdalena; Ślusarczyk, Joanna; Gruca, Piotr; Papp, Mariusz; Maes, Michael; Lasoń, Władysław; Antkiewicz-Michaluk, Lucyna

    2016-08-01

    Liver abnormalities have been reported to occur in up to 20 % of patients on a long-term therapy with the tricyclic antidepressant drug imipramine (IMI). The mechanism involved in this IMI-induced process is unknown but a contribution of oxidative stress is highly likely. Chronic mild stress (CMS) is widely used for modeling depressive-like behavior in rats. In the present study, we examined the effects of CMS and chronic IMI treatment, applied alone or in combination, on the levels of oxidative stress markers, such as reactive oxygen species (ROS), malondialdehyde (MDA), non-protein sulfhydryl groups, and sulfane sulfur as well as on activities of key antioxidant enzymes: catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase in the rat liver. Administration of IMI for 5 weeks to rats subjected to CMS resulted in a gradual significant reduction of anhedonia measured by sucrose intake, in a majority of animals (CMS IMI-reactive, CMS IMI-R), although about 20 % of rats did not respond to the IMI treatment (CMS IMI non-reactive, CMS IMI-NR). CMS-induced hepatic oxidative stress, estimated by increased ROS and MDA concentrations, was not prevented by the IMI administration, moreover, in CMS IMI-NR animals, the level of the marker of lipid peroxidation, i.e., MDA was increased in comparison to CMS-subjected rats and activity of antioxidant enzymes (GPx and CAT) was decreased compared to IMI-treated rats. The clinical significance of this observation remains to be established. PMID:26961706

  18. Possible antidepressant effects of vanillin against experimentally induced chronic mild stress in rats

    Directory of Open Access Journals (Sweden)

    Amira M. Abo-youssef

    2016-06-01

    Full Text Available Vanillin is a flavoring agent widely used in food and beverages such as chocolates and dairy products and it is also used to mask unpleasant tastes in medicine. It has been reported to have antioxidant, anti-inflammatory and antiapoptotic properties. The current study was designed to investigate the protective effects of vanillin against experimentally induced stress in rats. Briefly rats were subdivided into four groups. Three groups were subjected to chronic mild stress and the fourth group served as normal control group. One week before induction of stress drugs or saline was administered daily and continued for another nine weeks. At the end of the experimental period behavioral tests including sucrose preference test, forced swim test and elevated plus maze test were assessed. In addition, brain biochemical parameters including MDA, GSH, NO and serotonin were determined. Vanillin succeeded to restore the behavioral and biochemical changes associated with stress. It significantly increased sucrose consumption in sucrose preference test and time spent in open arm in elevated plus maze test as compared to stress control group. It also reduced immobility time in forced swim test and time spent in closed arm in elevated plus maze test. Additionally, it significantly decreased brain MDA and NO levels and significantly increased brain GSH and Serotonin levels compared to stress control group. It could be concluded that vanillin showed beneficial protective effects against experimentally induced stress in rats.

  19. Absent effect of zinc deficiency on the oxidative stress of erythrocytes in chronic uremic rats.

    Science.gov (United States)

    Chen, Shu-Ming; Wang, Ching-Chu; Lin, Fanny; Young, Tze-Kong

    2002-03-31

    Both anemia and zinc deficiency are commonly observed in patients with chronic uremia. Oxidative stress of red blood cells (RBC) has been suggested to participate in the development of anemia in these patients with chronic uremia due to reduced life span of RBC. Whether zinc deficiency aggravates the effect of oxidative stress on RBC of chronic uremia is still not understood. We thus performed the study to determine the influence of zinc deficiency on the oxidative stress of RBC in uremic rats. Zinc deficiency was induced by long-term dietary zinc deficiency. Five-sixth nephrectomy (5/6 Nx) was used to produce chronic uremia. Experiment was carried out in the following five groups: normal control (NL), chronic uremia (Nx), chronic uremia + dietary zinc deficiency (Nx-D), Nx-D + zinc supplement (Nx-DZ) and Chronic uremia + pair-fed (Nx-PF). Osmotic fragility and lipid peroxidation of RBC were used to evaluate the oxidative stress of RBC. Five weeks after 5/6 nephrectomy (Nx), 5/6 Nx rats present a syndrome of uremia to elevate the levels of plasma creatinine and urea, and reduce the level of plasma zinc (1.12 +/- 0.08 vs 1.35 +/- 0.05 ug/ml). But they does not find to produce anemia and to increase osmotic fragility and lipid peroxidation in RBC. Dietary zinc deficiency in Nx-D group produced severe anorexia and reduced plasma zinc and selenium levels and the activity of RBC-GPX. Yet in Nx-D rats, osmotic fragility and susceptibility of lipid peroxidation in red cells did not increase, because of the increase of plasma copper level (1.85 +/- 0.3 vs 1.41 +/- 0.05 microg/ml) and RBC-SOD activity (1.95 +/- 0.27 vs 0.78 +/- 0.05 unit/g Hb). Zinc supplement in Nx-D rats (Nx-DZ group) recovered the appetite and normalized the levels of plasma zinc, copper and selenium. Food restriction in 5/6 Nx rats (Nx-PF group) decreased plasma copper level and increased osmotic fragility of RBC and elevated the susceptibility of lipid peroxidation after stressing RBC with H2O2 Because

  20. Heart Rate Variability as an Indicator of Chronic Stress Caused by Lameness in Dairy Cows.

    Directory of Open Access Journals (Sweden)

    Levente Kovács

    Full Text Available Most experimental studies on animal stress physiology have focused on acute stress, while chronic stress, which is also encountered in intensive dairy cattle farming--e.g. in case of lameness--, has received little attention. We investigated heart rate (HR and heart rate variability (HRV as indicators of the autonomic nervous system activity and fecal glucocorticoid concentrations as the indicator of the hypothalamic-pituitary-adrenal axis activity in lame (with locomotion scores 4 and 5; n = 51 and non-lame (with locomotion scores 1 and 2; n = 52 Holstein-Friesian cows. Data recorded during the periods of undisturbed lying--representing baseline cardiac activity--were involved in the analysis. Besides linear analysis methods of the cardiac inter-beat interval (time-domain geometric, frequency domain and Poincaré analyses non-linear HRV parameters were also evaluated. With the exception of standard deviation 1 (SD1, all HRV indices were affected by lameness. Heart rate was lower in lame cows than in non-lame ones. Vagal tone parameters were higher in lame cows than in non-lame animals, while indices of the sympathovagal balance reflected on a decreased sympathetic activity in lame cows. All geometric and non-linear HRV measures were lower in lame cows compared to non-lame ones suggesting that chronic stress influenced linear and non-linear characteristics of cardiac function. Lameness had no effect on fecal glucocorticoid concentrations. Our results demonstrate that HRV analysis is a reliable method in the assessment of chronic stress, however, it requires further studies to fully understand the elevated parasympathetic and decreased sympathetic tone in lame animals.

  1. 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

  2. The effect of chronic peripheral nesfatin-1 application on blood pressure in normal and chronic restraint stressed rats: related with circulating level of blood pressure regulators.

    Science.gov (United States)

    Ayada, Ceylan; Turgut, Günfer; Turgut, Sebahat; Güçlü, Zuhal

    2015-01-01

    Nesfatin is a peptide secreted by peripheral tissues, central and peripheral nervous system. It is involved in the regulation of homeostasis. Although the effects of nesfatin-1 on nutrition have been studied widely in the literature, the mechanisms of nesfatin-1 action and also relations with other physiological parameters are still not clarified well. We aimed to investigate the effect of peripheral chronic nesfatin-1 application on blood pressure regulation in normal and in rats exposed to restraint immobilization stress. In our study, three month-old male Wistar rats were used. Rats were divided into 4 groups as Control, Stress, Control+Nesfatin-1, Nesfatin-1+Stress. Angiotensinogen, angiotensin converting enzyme 2, angiotensin II, endothelin-1, endothelial nitric oxide synthase, aldosterone, cortisol, nesfatin-1 levels were determined in plasma samples by ELISA. Our results have shown that chronic peripheral nesfatin-1 administration increases blood pressure in normal and in rats exposed to chronic restraint stress. Effect of nesfatin-1 on circulating level of angiotensinogen, angiotensin converting enzyme 2, angiotensin II, endothelin-1, endothelial nitric oxide synthase, aldosterone and cortisol has been identified. We can conclude that elevated high blood pressure after chronic peripheral nesfatin-1 administration in rats exposed to chronic restraint stress may be related to decreased plasma level of endothelial nitric oxide synthase concentration. PMID:25504061

  3. Validation and use of hair cortisol as a measure of chronic stress in eastern chipmunks (Tamias striatus)

    OpenAIRE

    Mastromonaco, Gabriela F; Gunn, Kelsey; McCurdy-Adams, H.; Edwards, D. B.; Schulte-Hostedde, Albrecht I.

    2014-01-01

    Stress levels of individuals are documented using glucocorticoid concentrations (including cortisol) in blood, saliva, urine or faeces, which provide information about stress hormones during a short period of time (minutes to days). In mammals, use of hair cortisol analysis allows for the assessment of prolonged stress over weeks and months and provides information on chronic stress levels without bias associated with handling. Here, we validate hair cortisol analysis in wild rodents using ex...

  4. 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

  5. The protective role of Bax Inhibitor-1 against chronic mild stress through the inhibition of monoamine oxidase A

    OpenAIRE

    Hwa-Young Lee; Geum-Hwa Lee; Anu Marahatta; Shun-Mei Lin; Mi-Rin Lee; Kyu Yun Jang; Kyung Min Kim; Hee Jae Lee; Jae-Won Lee; Tarique Rajasaheb Bagalkot; Young-Chul Chung; Yong-Chul Lee; Hyung-Ryong Kim; Han-Jung Chae

    2013-01-01

    The anti-apoptotic protein Bax inhibitor-1 (BI-1) is a regulator of apoptosis linked to endoplasmic reticulum (ER) stress. It has been hypothesized that BI-1 protects against neuron degenerative diseases. In this study, BI-1−/− mice showed increased vulnerability to chronic mild stress accompanied by alterations in the size and morphology of the hippocampi, enhanced ROS accumulation and an ER stress response compared with BI-1+/+ mice. BI-1−/− mice exposed to chronic mild stress showed signif...

  6. Chronic Stress and Adolescents' Mental Health : Modifying Effects of Basal Cortisol and Parental Psychiatric History. The TRAILS Study

    NARCIS (Netherlands)

    Zandstra, Anna Roos E.; Hartman, Catharina A.; Nederhof, Esther; van den Heuvel, Edwin R.; Dietrich, Andrea; Hoekstra, Pieter J.; Ormel, Johan

    2015-01-01

    Large individual differences in adolescent mental health following chronic psychosocial stress suggest moderating factors. We examined two established moderators, basal cortisol and parental psychiatric history, simultaneously. We hypothesized that individuals with high basal cortisol, assumed to in

  7. The effect of chronic stress on prenatal development of the central nervous system.

    Science.gov (United States)

    Giordana, L N; Bozzo, A A; Cots, D S; Monedero Cobeta, I; Rolando, A; Borghi, D; Diaz, T; Gauna, H F; Romanini, M C

    2015-02-01

    The survival of developing embryos depends on the control and maintenance of homeostasis. Stress caused by chronic immobilization during pregnancy in rats may alter the normal development of the nervous system and increase susceptibility to psychiatric disorders. We investigated the effects of chronic stress on cell proliferation in the forebrains of embryos at 12 days of gestation, and in the hippocampus, dentate gyrus and cortex in embryos at 17 and 21 days of gestation. We examined serial sections of the embryonic brains of control and stressed rats at days 12, 17 and 21 of gestation. Brain sections were immunolabeled with anti-PCNA and stereological analysis was performed on 540 images. The results showed no statistical differences on days 12 and 17 of gestation in the proliferation area of the structures studied, whereas on day 21 of gestation, proliferation decreased in the cortex and dentate gyrus of embryos of the stressed group. These changes were related to decreased prolactin and increased corticosterone concentrations in the plasma.

  8. Effects of administration of oral n-acetylcysteine on oxidative stress in chronic obstructive pulmonary disease patients in rural population

    OpenAIRE

    Kale SB; AB Patil; Anita Kale

    2016-01-01

    Background: Chronic obstructive pulmonary disease (COPD) is a common pulmonary disease and the fourth leading cause of death globally. Oxidative stress is an important attribute in the pathogenesis of COPD. Targeting oxidative stress would be a logical therapeutic approach for COPD and glutathione precursors like N-acetylcysteine (NAC) have shown therapeutic promise in the treatment of this chronic pathology. This study attempts to determine the dose related effects of NAC on the oxidative s...

  9. Chronic psycho-social stress & colitis: Physiological, neuroendocrine, and immunological studies with male C57BL/6 mice

    OpenAIRE

    Reber, Stefan Oskar

    2007-01-01

    The experiments of the present thesis were designed to investigate the effects of two different models of chronic psycho-social stress (SD/OC; CSC) on the severity of and the regeneration after an experimentally induced colitis and the development of spontaneous colonic inflammation in male mice. In addition, underlying mechanisms were investigated, thereby mainly focusing on the HPA axis as a possible mediator of chronic psycho-social stress effects on colonic inflammation. Further knowledge...

  10. Gestational chronic mild stress: Effects on acoustic startle in male offspring of rats

    DEFF Research Database (Denmark)

    Hougaard, K.S.; Mandrup, Karen; Kjaer, S.L.;

    2011-01-01

    from dams exposed to chronic mild stress (CMS) during gestation. In humans, decreased PPI has been reported to be associated with anxiety. Because of its potential translational value across species, the modulation of startle reactivity may be a useful tool in examining altered emotional reactivity...... following prenatal insults. The present study aimed at investigating whether prenatally stressed male offspring would display altered startle phenotype. Stress was induced by maternal gestational exposure to alternating procedures, i.e. CMS. At the age of 3 months, half of the offspring were blood sampled...... under restraint. At the age of 6 months, i.e. three months later, all animals were tested in the acoustic startle and the light enhanced startle (LES) paradigm. Control and CMS male offspring showed similar basal startle and LES levels. Maternal gestational exposure to the relatively mild, variable...

  11. Chronic psychosocial stress increases the risk for inflammation-related colon carcinogenesis in male mice.

    Science.gov (United States)

    Peters, Sebastian; Grunwald, Nicole; Rümmele, Petra; Endlicher, Esther; Lechner, Anja; Neumann, Inga D; Obermeier, Florian; Reber, Stefan O

    2012-07-01

    Patients with inflammatory bowel diseases (IBDs) have a higher risk of developing colorectal cancer (CRC) than the general population. Furthermore, chronic psychosocial stress increases the likelihood of developing IBD and multiple types of malignant neoplasms, including CRC. Here, for the first time, we investigate the effects of chronic psychosocial stress in male mice on an artificially induced CRC, by employing the chronic subordinate colony (CSC) housing paradigm in combination with the reliable azoxymethane (AOM)/dextran sodium sulfate (DSS) CRC model. Colonoscopy revealed that CSC mice showed accelerated macroscopic suspect lesions. In addition, more CSC mice developed low-grade dysplasia (LGD) and/or high-grade dysplasia (HGD) in the colonic tissue compared to the single-housed control mice (SHC). CSC mice showed an increased number of Ki67+ and a decreased number of terminal deoxynucleotidyl transferase dUTP nick end labeling epithelial cells in colonic tissue. Colonic liver receptor homolog-1 (LRH-1), cyclooxygenase II (COXII), tumor necrosis factor, forkhead box P3 (FoxP3) mRNA as well as colonic ß-catenin, COXII, and LRH-1 protein expression were also increased in CSC compared with SHC mice. Although the number of CD4+ Th cells was increased, a tendency toward a decreased colonic interferon-γ (IFN-γ) mRNA expression was observed. Furthermore, despite an increased percentage of CD3+ cells and CD3+/FoxP3+ double-positive cells within mesenteric lymph node cells of CSC mice, IFN-γ secretion from these cells was unaffected. Altogether, our results suggest that chronic psychosocial stress increases the risk for AOM/DSS-induced and, thus, inflammation-related CRC. Finally, assessment of additional time points may test whether the shift from tumor-protective Th1 cell to regulatory T-cell immunity represents a consequence of increased carcinogenesis or a causal factor involved in its development.

  12. Adolescent chronic mild stress alters hippocampal CB1 receptor-mediated excitatory neurotransmission and plasticity.

    Science.gov (United States)

    Reich, C G; Mihalik, G R; Iskander, A N; Seckler, J C; Weiss, M S

    2013-12-01

    Endocannabinoids (eCBs) are involved in the stress response and alterations in eCB signaling may contribute to the etiology of mood disorders. Exposure to chronic mild stress (CMS), a model of depression, produces downregulation of the cannabinoid 1 (CB1) receptor in the hippocampus of male rats. However, it is unknown how this stress-induced change in CB1 levels affects eCB-mediated neurotransmission. In vitro, field potential recordings from CMS-exposed (21-days) rats were performed to assess the effects of stress on eCB-regulated glutamatergic neurotransmission in/on hippocampal area CA1. We observed that application of the CB1 agonist, WIN 55,212-5 (1 μM), in stress animals resulted in a ∼135% increase in excitatory neurotransmission, whereas CB1 activation in non-stress animals leads to a ∼30% decrease. However, during blockade of GABA(A) neurotransmission with picrotoxin, CB1 activation yielded a ∼35% decrease in stress animals. These findings indicate that CMS does not directly affect glutamatergic neurotransmission. Rather, CMS sensitizes CB1 function on GABAergic terminals, leading to less inhibition and an increase in excitatory neurotransmission. This finding is reinforced in that induction of weak long-term-potentiation (LTP) is enhanced in CMS-exposed animals compared to controls and this enhancement is CB1-dependent. Lastly, we observed that the LTP-blocking property of WIN 55,212-5 shifts from being glutamate-dependent in non-stress animals to being GABA-dependent in stress animals. These results effectively demonstrate that CMS significantly alters hippocampal eCB-mediated neurotransmission and synaptic plasticity.

  13. 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

  14. Chronic idiopathic urticaria, psychological co-morbidity and posttraumatic stress: the impact of alexithymia and repression.

    Science.gov (United States)

    Hunkin, Victoria; Chung, Man Cheung

    2012-12-01

    The objective of this study was to investigate the interrelationship between chronic idiopathic urticaria (CIU), psychological co-morbidity, posttraumatic stress, repression and alexithymia. 89 participants with CIU and 105 without CIU responded to an online questionnaire. Both groups completed the general health questionnaire-12, the perceived stress scale, the posttraumatic stress diagnostic scale and the Toronto alexithymia scale-20 and were categorised into four defence mechanism groups (repressive, defensive, high-anxious, low-anxious). CIU participants also completed the Skindex-17 and a self-report severity measure. CIU participants reported higher levels of alexithymia than the control group and their defence mechanism was most likely to be categorised as defensive, with conscious self-image management reported alongside high manifest anxiety. Partial least squares analysis revealed significant paths between posttraumatic stress and CIU severity and psychological co-morbidity. Posttraumatic stress was associated with alexithymia and type of defence mechanism. Only being in the high-anxious group partially mediated the relationship between posttraumatic stress and CIU severity. In conclusion, there is evidence for a relationship between CIU and trauma. The severity of posttraumatic symptoms varies depending upon alexithymic traits and defence mechanisms used. Disease severity and psychological co-morbidity are differentially influenced by the relationships between trauma, alexithymic traits and defence mechanisms. PMID:22362490

  15. Rats with high or low sociability are differently affected by chronic variable stress.

    Science.gov (United States)

    Tõnissaar, M; Herm, L; Eller, M; Kõiv, K; Rinken, A; Harro, J

    2008-04-01

    Depression is strongly related to social behavior. We have previously shown that social behavior of rats is individually stable. The purpose of the present study was to compare the sensitivity of animals with different sociability to chronic variable stress (CVS). Four social interaction tests were performed with 60 single-housed male Sprague-Dawley rats. Twenty rats with the lowest and 20 with the highest average social activity time were selected as low sociability (LS) and high sociability (HS) rats, respectively. Both groups were further divided into control and stress groups with equal average body weight. The CVS procedure lasted for 3 weeks. The stressors applied were cold water and wet bedding, imitation of injection, stroboscopic light, movement restriction in a small cage, tail pinch with a clothespin, and strong illumination during the predicted dark phase. In HS-rats, but not in LS-rats, CVS reduced sucrose intake compared with baseline after 3 weeks, suggesting that HS-rats are more vulnerable to anhedonia elicited by CVS. LS-animals were more anxious in the social interaction and open field tests, but stress eliminated differences with HS-animals in the social interaction test and increased their activity in the forced swimming test. In LS-rats stress increased ex vivo dopamine levels and reduced 5-HT levels in the frontal cortex, suggesting that the increased behavioral activity after stress may be related to increased impulsivity. This study thus revealed that animals with high sociability trait are more vulnerable to anhedonia elicited by chronic stress in conditions of single housing. PMID:18343596

  16. Increased anxiety, voluntary alcohol consumption and ethanol-induced place preference in mice following chronic psychosocial stress.

    Science.gov (United States)

    Bahi, Amine

    2013-07-01

    Stress exposure is known to be a risk factor for alcohol use and anxiety disorders. Comorbid chronic stress and alcohol dependence may lead to a complicated and potentially severe treatment profile. To gain an understanding of the interaction between chronic psychosocial stress and drug exposure, we studied the effects of concomitant chronic stress exposure on alcohol reward using two-bottle choice and ethanol-conditioned place preference (CPP). The study consisted of exposure of the chronic subordinate colony (CSC) mice "intruders" to an aggressive "resident" mouse for 19 consecutive days. Control mice were single housed (SHC). Ethanol consumption using two-bottle choice paradigm and ethanol CPP acquisition was assessed at the end of this time period. As expected, CSC exposure increased anxiety-like behavior and reduced weight gain as compared to SHC controls. Importantly, in the two-bottle choice procedure, CSC mice showed higher alcohol intake than SHC. When testing their response to ethanol-induced CPP, CSC mice achieved higher preference for the ethanol-paired chamber. In fact, CSC exposure increased ethanol-CPP acquisition. Taken together, these data demonstrate the long-term consequences of chronic psychosocial stress on alcohol intake in male mice, suggesting chronic stress as a risk factor for developing alcohol consumption and/or anxiety disorders.

  17. Chronic family stress moderates the association between a TOMM40 variant and triglyceride levels in two independent Caucasian samples

    DEFF Research Database (Denmark)

    Jiang, Rong; Brummett, Beverly H; Hauser, Elizabeth R;

    2013-01-01

    TOMM40 SNP rs157580 has been associated with triglyceride levels in genome-wide association studies (GWAS). Chronic caregiving stress moderates the association between triglyceride levels and a nearby SNP rs439401 that is associated with triglyceride levels in GWAS. Here, we report data from two...... independent Caucasian samples (242 U.S. women and men; 466 Danish men) testing the hypothesis that chronic family stress also moderates the association between rs157580 and triglyceride levels. The interaction of rs157580 and family stress in predicting triglyceride levels was statistically significant...... in the U.S. sample (p=0.004) and marginally significant (p=0.075) in the Danish sample. The G allele of rs157580 was associated with increased triglyceride levels among family stressed cases in both samples compared with A/A cases, but not among controls. Chronic family stress moderates the association...

  18. Neuroprotective mechanism of losartan and its interaction with nimesulide against chronic fatigue stress.

    Science.gov (United States)

    Kumar, Anil; Singh, Barinder; Mishra, Jitendriya; Sah, Sangeeta Pilkhwal; Pottabathini, Raghavender

    2015-12-01

    Potential role of angiotensin-II and cyclooxygenase have been suggested in the pathophysiology of chronic fatigue stress. The present study has been designed to evaluate the neuroprotective effect of losartan and its interaction with nimesulide against chronic fatigue stress and related complications in mice. In the present study, male Laca mice (20-30 g) were subjected to running wheel activity test session (RWATS) for 6 min daily for 21 days. Losartan, nimesulide and their combinations were administered daily for 21 days, 45 min before being subjected to RWATS. Various behavioral and biochemical and neuroinflammatory mediators were assessed subsequently. 21 days RWATS treatment significantly decreased number of wheel rotations/6 min indicating fatigue stress like behaviors as compared to naive group. 21 days treatment with losartan (10 and 20 mg/kg, ip), nimesulide (5 and 10 mg/kg, po) and their combinations significantly improved behavior [increased number of wheel rotations, reversal of post-exercise fatigue, locomotor activity, antianxiety-like behavior (number of entries, latency to enter and time spent in mirror chamber), and memory performance (transfer latency in plus-maze performance task)], biochemical parameters (reduced serum corticosterone, brain lipid peroxidation, nitrite concentration, acetylcholinesterase activity, restored reduced glutathione levels and catalase activity) as compared to RWATS control. Besides, TNF-α, CRP levels were significantly attenuated by these drugs and their combinations as compared to control. The present study highlights the role of cyclooxygenase modulation in the neuroprotective effect of losartan against chronic fatigue stress-induced behavioral, biochemical and cellular alterations in mice.

  19. Administration of Lactobacillus helveticus NS8 improves behavioral, cognitive, and biochemical aberrations caused by chronic restraint stress.

    Science.gov (United States)

    Liang, S; Wang, T; Hu, X; Luo, J; Li, W; Wu, X; Duan, Y; Jin, F

    2015-12-01

    Increasing numbers of studies have suggested that the gut microbiota is involved in the pathophysiology of stress-related disorders. Chronic stress can cause behavioral, cognitive, biochemical, and gut microbiota aberrations. Gut bacteria can communicate with the host through the microbiota-gut-brain axis (which mainly includes the immune, neuroendocrine, and neural pathways) to influence brain and behavior. It is hypothesized that administration of probiotics can improve chronic-stress-induced depression. In order to examine this hypothesis, the chronic restraint stress depression model was established in this study. Adult specific pathogen free (SPF) Sprague-Dawley rats were subjected to 21 days of restraint stress followed by behavioral testing (including the sucrose preference test (SPT), elevated-plus maze test, open-field test (OFT), object recognition test (ORT), and object placement test (OPT)) and biochemical analysis. Supplemental Lactobacillus helveticus NS8 was provided every day during stress until the end of experiment, and selective serotonin reuptake inhibitor (SSRI) citalopram (CIT) served as a positive control. Results showed that L. helveticus NS8 improved chronic restraint stress-induced behavioral (anxiety and depression) and cognitive dysfunction, showing an effect similar to and better than that of CIT. L. helveticus NS8 also resulted in lower plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, higher plasma interleukin-10 (IL-10) levels, restored hippocampal serotonin (5-HT) and norepinephrine (NE) levels, and more hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression than in chronic stress rats. Taken together, these results indicate an anti-depressant effect of L. helveticus NS8 in rats subjected to chronic restraint stress depression and that this effect could be due to the microbiota-gut-brain axis. They also suggest the therapeutic potential of L. helveticus NS8 in stress-related and possibly other

  20. Administration of Lactobacillus helveticus NS8 improves behavioral, cognitive, and biochemical aberrations caused by chronic restraint stress.

    Science.gov (United States)

    Liang, S; Wang, T; Hu, X; Luo, J; Li, W; Wu, X; Duan, Y; Jin, F

    2015-12-01

    Increasing numbers of studies have suggested that the gut microbiota is involved in the pathophysiology of stress-related disorders. Chronic stress can cause behavioral, cognitive, biochemical, and gut microbiota aberrations. Gut bacteria can communicate with the host through the microbiota-gut-brain axis (which mainly includes the immune, neuroendocrine, and neural pathways) to influence brain and behavior. It is hypothesized that administration of probiotics can improve chronic-stress-induced depression. In order to examine this hypothesis, the chronic restraint stress depression model was established in this study. Adult specific pathogen free (SPF) Sprague-Dawley rats were subjected to 21 days of restraint stress followed by behavioral testing (including the sucrose preference test (SPT), elevated-plus maze test, open-field test (OFT), object recognition test (ORT), and object placement test (OPT)) and biochemical analysis. Supplemental Lactobacillus helveticus NS8 was provided every day during stress until the end of experiment, and selective serotonin reuptake inhibitor (SSRI) citalopram (CIT) served as a positive control. Results showed that L. helveticus NS8 improved chronic restraint stress-induced behavioral (anxiety and depression) and cognitive dysfunction, showing an effect similar to and better than that of CIT. L. helveticus NS8 also resulted in lower plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, higher plasma interleukin-10 (IL-10) levels, restored hippocampal serotonin (5-HT) and norepinephrine (NE) levels, and more hippocampal brain-derived neurotrophic factor (BDNF) mRNA expression than in chronic stress rats. Taken together, these results indicate an anti-depressant effect of L. helveticus NS8 in rats subjected to chronic restraint stress depression and that this effect could be due to the microbiota-gut-brain axis. They also suggest the therapeutic potential of L. helveticus NS8 in stress-related and possibly other

  1. Lipid peroxidation and total radical-trapping potential of the lungs of rats submitted to chronic and sub-chronic stress

    Directory of Open Access Journals (Sweden)

    Torres R.L.

    2004-01-01

    Full Text Available Exposure to stress induces a cluster of physiological and behavioral changes in an effort to maintain the homeostasis of the organism. Long-term exposure to stress, however, has detrimental effects on several cell functions such as the impairment of antioxidant defenses leading to oxidative damage. Oxidative stress is a central feature of many diseases. The lungs are particularly susceptible to lesions by free radicals and pulmonary antioxidant defenses are extensively distributed and include both enzymatic and non-enzymatic systems. The aim of the present study was to determine lipid peroxidation and total radical-trapping potential (TRAP changes in lungs of rats submitted to different models of chronic stress. Adult male Wistar rats weighing 180-230 g were submitted to different stressors (variable stress, N = 7 or repeated restraint stress for 15 (N = 10 or 40 days (N = 6 and compared to control groups (N = 10 each. Lipid peroxidation levels were assessed by thiobarbituric acid reactive substances (TBARS, and TRAP was measured by the decrease in luminescence using the 2-2'-azo-bis(2-amidinopropane-luminol system. Chronic variable stress induced a 51% increase in oxidative stress in lungs (control group: 0.037 ± 0.002; variable stress: 0.056 ± 0.007, P < 0.01. No difference in TBARS was observed after chronic restraint stress, but a significant 57% increase in TRAP was presented by the group repeatedly restrained for 15 days (control group: 2.48 ± 0.42; stressed: 3.65 ± 0.16, P < 0.05. We conclude that different stressors induce different effects on the oxidative status of the organism.

  2. Chronic hypoxia during gestation enhances uterine arterial myogenic tone via heightened oxidative stress.

    Directory of Open Access Journals (Sweden)

    Daliao Xiao

    Full Text Available Chronic hypoxia during gestation has profound adverse effects on the adaptation of uteroplacental circulation in pregnancy. Yet, the underlying mechanisms are not fully understood. The present study tested the hypothesis that enhanced production of reactive oxygen species (ROS in uterine arteries plays a critical role in the maladaptation of uterine circulation associated with chronic hypoxia. Uterine arteries were isolated from nonpregnant and near-term pregnant sheep maintained at sea level (~300 m or exposed to high-altitude (3801 m hypoxia for 110 days. Hypoxia significantly increased ROS production in uterine arteries of pregnant, but not nonpregnant, sheep. This was associated with a significant increase in NADPH oxidase (Nox 2, but not Nox1 or Nox4, protein abundance and total Nox activity in uterine arteries of pregnant animals. Chronic hypoxia significantly increased pressure-dependent uterine arterial myogenic tone in pregnant sheep, which was abrogated by a Nox inhibitor apocynin. Additionally, the hypoxia-induced increase in myogenic reactivity of uterine arteries to phorbol 12,13-dibutyrate in pregnant sheep was blocked by apocynin and tempol. In consistence with the myogenic responses, the hypoxia-mediated down-regulation of BKCa channel activity in uterine arteries of pregnant animals was reversed by apocynin. The findings suggest that heightened oxidative stress in uterine arteries plays a key role in suppressing the BKCa channel activity, resulting in increased myogenic reactivity and maladaptation of uteroplacental circulation caused by chronic hypoxia during gestation.

  3. Effects of childhood poverty and chronic stress on emotion regulatory brain function in adulthood.

    Science.gov (United States)

    Kim, Pilyoung; Evans, Gary W; Angstadt, Michael; Ho, S Shaun; Sripada, Chandra S; Swain, James E; Liberzon, Israel; Phan, K Luan

    2013-11-12

    Childhood poverty has pervasive negative physical and psychological health sequelae in adulthood. Exposure to chronic stressors may be one underlying mechanism for childhood poverty-health relations by influencing emotion regulatory systems. Animal work and human cross-sectional studies both suggest that chronic stressor exposure is associated with amygdala and prefrontal cortex regions important for emotion regulation. In this longitudinal functional magnetic resonance imaging study of 49 participants, we examined associations between childhood poverty at age 9 and adult neural circuitry activation during emotion regulation at age 24. To test developmental timing, concurrent, adult income was included as a covariate. Adults with lower family income at age 9 exhibited reduced ventrolateral and dorsolateral prefrontal cortex activity and failure to suppress amygdala activation during effortful regulation of negative emotion at age 24. In contrast to childhood income, concurrent adult income was not associated with neural activity during emotion regulation. Furthermore, chronic stressor exposure across childhood (at age 9, 13, and 17) mediated the relations between family income at age 9 and ventrolateral and dorsolateral prefrontal cortex activity at age 24. The findings demonstrate the significance of childhood chronic stress exposures in predicting neural outcomes during emotion regulation in adults who grew up in poverty.

  4. 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

  5. Chronic Kidney Disease Induced Intestinal Mucosal Barrier Damage Associated with Intestinal Oxidative Stress Injury

    Science.gov (United States)

    Yu, Chao; Wang, Qiang; Zhou, Chunyu; Kang, Xin; Zhao, Shuang; Liu, Shuai; Fu, Huijun; Yu, Zhen; Peng, Ai

    2016-01-01

    Background. To investigate whether intestinal mucosal barrier was damaged or not in chronic kidney disease progression and the status of oxidative stress. Methods. Rats were randomized into two groups: a control group and a uremia group. The uremia rat model was induced by 5/6 kidney resection. In postoperative weeks (POW) 4, 6, 8, and 10, eight rats were randomly selected from each group to prepare samples for assessing systemic inflammation, intestinal mucosal barrier changes, and the status of intestinal oxidative stress. Results. The uremia group presented an increase trend over time in the serum tumor necrosis factor-alpha, interleukin-6 (IL-6) and IL-10, serum D-lactate and diamine oxidase, and intestinal permeability, and these biomarkers were significantly higher than those in control group in POW 8 and/or 10. Chiu's scores in uremia group were also increased over time, especially in POW 8 and 10. Furthermore, the intestinal malondialdehyde, superoxide dismutase, and glutathione peroxidase levels were significantly higher in uremia group when compared with those in control group in POW 8 and/or 10. Conclusions. The advanced chronic kidney disease could induce intestinal mucosal barrier damage and further lead to systemic inflammation. The underlying mechanism may be associated with the intestinal oxidative stress injury. PMID:27493661

  6. Chronic Arsenic Exposure-Induced Oxidative Stress is Mediated by Decreased Mitochondrial Biogenesis in Rat Liver.

    Science.gov (United States)

    Prakash, Chandra; Kumar, Vijay

    2016-09-01

    The present study was executed to study the effect of chronic arsenic exposure on generation of mitochondrial oxidative stress and biogenesis in rat liver. Chronic sodium arsenite treatment (25 ppm for 12 weeks) decreased mitochondrial complexes activity in rat liver. There was a decrease in mitochondrial superoxide dismutase (MnSOD) activity in arsenic-treated rats that might be responsible for increased protein and lipid oxidation as observed in our study. The messenger RNA (mRNA) expression of mitochondrial and nuclear-encoded subunits of complexes I (ND1 and ND2) and IV (COX I and COX IV) was downregulated in arsenic-treated rats only. The protein and mRNA expression of MnSOD was reduced suggesting increased mitochondrial oxidative damage after arsenic treatment. There was activation of Bax and caspase-3 followed by release of cytochrome c from mitochondria suggesting induction of apoptotic pathway under oxidative stress. The entire phenomenon was associated with decrease in mitochondrial biogenesis as evident by decreased protein and mRNA expression of nuclear respiratory factor 1 (NRF-1), nuclear respiratory factor 2 (NRF-2), peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), and mitochondrial transcription factor A (Tfam) in arsenic-treated rat liver. The results of the present study indicate that arsenic-induced mitochondrial oxidative stress is associated with decreased mitochondrial biogenesis in rat liver that may present one of the mechanisms for arsenic-induced hepatotoxicity. PMID:26767369

  7. Quantifying Chronic Stress Exposure for Cumulative Risk Assessment: Lessons Learned from a Case Study of Allostatic Load

    Science.gov (United States)

    Although multiple methods of quantifying environmental chemical exposures have been validated for use in human health risk assessment, quantifying chronic stress exposure is more challenging. Stress is a consequence of perceiving an “exposure” (e.g., violence, poverty) as more th...

  8. Chronic and Acute Stress, Gender, and Serotonin Transporter Gene-Environment Interactions Predicting Depression Symptoms in Youth

    Science.gov (United States)

    Hammen, Constance; Brennan, Patricia A.; Keenan-Miller, Danielle; Hazel, Nicholas A.; Najman, Jake M.

    2010-01-01

    Background: Many recent studies of serotonin transporter gene by environment effects predicting depression have used stress assessments with undefined or poor psychometric methods, possibly contributing to wide variation in findings. The present study attempted to distinguish between effects of acute and chronic stress to predict depressive…

  9. Oxidative stress and nucleic acid oxidation in patients with chronic kidney disease.

    Science.gov (United States)

    Sung, Chih-Chien; Hsu, Yu-Chuan; Chen, Chun-Chi; Lin, Yuh-Feng; Wu, Chia-Chao

    2013-01-01

    Patients with chronic kidney disease (CKD) have high cardiovascular mortality and morbidity and a high risk for developing malignancy. Excessive oxidative stress is thought to play a major role in elevating these risks by increasing oxidative nucleic acid damage. Oxidative stress results from an imbalance between reactive oxygen/nitrogen species (RONS) production and antioxidant defense mechanisms and can cause vascular and tissue injuries as well as nucleic acid damage in CKD patients. The increased production of RONS, impaired nonenzymatic or enzymatic antioxidant defense mechanisms, and other risk factors including gene polymorphisms, uremic toxins (indoxyl sulfate), deficiency of arylesterase/paraoxonase, hyperhomocysteinemia, dialysis-associated membrane bioincompatibility, and endotoxin in patients with CKD can inhibit normal cell function by damaging cell lipids, arachidonic acid derivatives, carbohydrates, proteins, amino acids, and nucleic acids. Several clinical biomarkers and techniques have been used to detect the antioxidant status and oxidative stress/oxidative nucleic acid damage associated with long-term complications such as inflammation, atherosclerosis, amyloidosis, and malignancy in CKD patients. Antioxidant therapies have been studied to reduce the oxidative stress and nucleic acid oxidation in patients with CKD, including alpha-tocopherol, N-acetylcysteine, ascorbic acid, glutathione, folic acid, bardoxolone methyl, angiotensin-converting enzyme inhibitor, and providing better dialysis strategies. This paper provides an overview of radical production, antioxidant defence, pathogenesis and biomarkers of oxidative stress in patients with CKD, and possible antioxidant therapies.

  10. Oxidative Stress and Nucleic Acid Oxidation in Patients with Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    Chih-Chien Sung

    2013-01-01

    Full Text Available Patients with chronic kidney disease (CKD have high cardiovascular mortality and morbidity and a high risk for developing malignancy. Excessive oxidative stress is thought to play a major role in elevating these risks by increasing oxidative nucleic acid damage. Oxidative stress results from an imbalance between reactive oxygen/nitrogen species (RONS production and antioxidant defense mechanisms and can cause vascular and tissue injuries as well as nucleic acid damage in CKD patients. The increased production of RONS, impaired nonenzymatic or enzymatic antioxidant defense mechanisms, and other risk factors including gene polymorphisms, uremic toxins (indoxyl sulfate, deficiency of arylesterase/paraoxonase, hyperhomocysteinemia, dialysis-associated membrane bioincompatibility, and endotoxin in patients with CKD can inhibit normal cell function by damaging cell lipids, arachidonic acid derivatives, carbohydrates, proteins, amino acids, and nucleic acids. Several clinical biomarkers and techniques have been used to detect the antioxidant status and oxidative stress/oxidative nucleic acid damage associated with long-term complications such as inflammation, atherosclerosis, amyloidosis, and malignancy in CKD patients. Antioxidant therapies have been studied to reduce the oxidative stress and nucleic acid oxidation in patients with CKD, including alpha-tocopherol, N-acetylcysteine, ascorbic acid, glutathione, folic acid, bardoxolone methyl, angiotensin-converting enzyme inhibitor, and providing better dialysis strategies. This paper provides an overview of radical production, antioxidant defence, pathogenesis and biomarkers of oxidative stress in patients with CKD, and possible antioxidant therapies.

  11. Prolactin mediates effects of chronic psychological stress on induction of fibrofatty cells in the heart.

    Science.gov (United States)

    Song, Jiangping; Wang, Mangyuan; Chen, Xiao; Liu, Li; Chen, Liang; Song, Zhizhao; Teng, Xiao; Xing, Yong; Chen, Kai; Zhao, Kun; Hou, Jianfeng; Yang, Pingchang

    2016-01-01

    Cardiocyte apoptosis plays an important role in the pathogenesis of heart diseases. The mechanism is unclear. It is reported that prolactin (PRL) is involved in cardiac disorders. This study aims to investigate the role of PRL in mediating the psychological stress-induced fibrofatty cell differentiation in the heart. In this study, BALB/c mice were treated with a 30-day restraint stress. The heart tissue was processed by paraffin embedding and hematoxylin and eosin. The expression of Sca1 in NIH3T3 cells was assessed by cell culture, flow cytometry and Western blotting. The results showed that chronic stress induced fibrofatty cells in the mouse heart and high serum PRL levels. The induction of fibrofatty cell was mimicked by administration with recombinant PRL. The stress also induced the expression of Sca1 in the mouse heart. Exposure of NIH3T3 cells (a fibroblast cell line) to PRL in the culture enhanced the expression of stem cell antigen-1 (Sca1), phosphorylation of signal transducer and activator of transcription 3 (STAT3) and expression of adipocyte-related protein molecules, including adiponectin, fatty acid binding protein (aP2), peroxisome proliferator activated receptor-g (PPARg) and CCAAT/enhancer binding protein (C/EBP)α, in the cells. We conclude that psychological stress-derived PRL induces fibroblasts to differentiate into fibrofatty cells in the heart.

  12. Role of Tyrosine Isomers in Acute and Chronic Diseases Leading to Oxidative Stress - A Review.

    Science.gov (United States)

    Molnár, Gergő A; Kun, Szilárd; Sélley, Eszter; Kertész, Melinda; Szélig, Lívia; Csontos, Csaba; Böddi, Katalin; Bogár, Lajos; Miseta, Attila; Wittmann, István

    2016-01-01

    Oxidative stress plays a major role in the pathogenesis of a variety of acute and chronic diseases. Measurement of the oxidative stress-related end products may be performed, e.g. that of structural isomers of the physiological para-tyrosine, namely meta- and ortho-tyrosine, that are oxidized derivatives of phenylalanine. Recent data suggest that in sepsis, serum level of meta-tyrosine increases, which peaks on the 2(nd) and 3(rd) days (pglucose product in non-diabetic septic cases (pRats were fed a standard high cholesterol-diet, and were given para-tyrosine or vehicle orally. High-cholesterol feeding lead to a significant increase in aortic wall meta-tyrosine content and a decreased vasorelaxation of the aorta to insulin and the glucagon-like peptide-1 analogue, liraglutide, that both could be prevented by administration of para-tyrosine. Concluding, these data suggest that meta- and ortho-tyrosine are potential markers of oxidative stress in acute diseases related to oxidative stress, and may also interfere with insulin action in septic humans. Competition of meta- and ortho-tyrosine by supplementation of para-tyrosine may exert a protective role in oxidative stress-related diseases. PMID:26785996

  13. 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.

  14. Differential oxidative stress and DNA damage in rat brain regions and blood following chronic arsenic exposure.

    Science.gov (United States)

    Mishra, D; Flora, S J S

    2008-05-01

    Chronic arsenic poisoning caused by contaminated drinking water is a wide spread and worldwide problem particularly in India and Bangladesh. One of the possible mechanisms suggested for arsenic toxicity is the generation of reactive oxygen species (ROS). The present study was planned 1) to evaluate if chronic exposure to arsenic leads to oxidative stress in blood and brain - parts of male Wistar rats and 2) to evaluate which brain region of the exposed animals was more sensitive to oxidative injury. Male Wistar rats were exposed to arsenic (50A ppm sodium arsenite in drinking water) for 10A months. The brain was dissected into five major parts, pons medulla, corpus striatum, cortex, hippocampus, and cerebellum. A number of biochemical variables indicative of oxidative stress were studied in blood and different brain regions. Single-strand DNA damage using comet assay was also assessed in lymphocytes. We observed a significant increase in blood and brain ROS levels accompanied by the depletion of GSH/GSSG ratio and glucose-6-phosphate dehydrogenase (G6PD) activity in different brain regions of arsenic-exposed rats. Chronic arsenic exposure also caused significant single-strand DNA damage in lymphocytes as depicted by comet with a tail in arsenic-exposed cells compared with the control cells. On the basis of results, we concluded that the cortex region of the brain was more sensitive to oxidative injury compared with the other regions studied. The present study, thus, leads us to suggest that arsenic induces differential oxidative stress in brain regions with cortex followed by hippocampus and causes single-strand DNA damage in lymphocytes.

  15. Mental strain and chronic stress among a communit sample of university students with irritable bowel syndrome symptoms

    OpenAIRE

    Gulewitsch, Marco D.; Paul Enck; Juliane Schwille-Kiuntke; Katja Weimer; Schlarb, Angelika A.

    2013-01-01

    Aim. To investigate the degree of mental strain and chronic stress in a German community sample of students with IBS-like symptoms. Methods and Materials. Following an internet-based survey about stress, this study recruited 176 German university students (23.45 ± 2.48 years; 48.3% males) with IBS-like symptoms according to Rome III and 181 students without IBS (23.55 ± 2.82 years; 50.3% males) and compared them regarding current mental strain (SCL-90-R) and the extend of chronic stress. Beyo...

  16. Influence of chronic stress and terahertz radiation at nitric oxide frequency on functional activity of thyroid gland

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    Tsymbal А.А.

    2010-12-01

    Full Text Available In the chronic stress conditions oppression of functional activity of thyroid gland is revealed. Influence of terahertz radiation at the nitric oxide frequency of 150,176-150,664 GHz on functional activity of thyroid gland in the conditions of chronic experimental stress was studied. It was shown that during 15 minutes of influence of terahertz waves at nitric oxide frequency partial restoration of studied indicators of activity of thyroid gland was observed in stressed animals. At 30 minute mode of influence of specified waves a complete recovery of broken indicators of functional condition of thyroid gland was determined

  17. 3xTgAD mice exhibit altered behavior and elevated Aβ after chronic mild social stress

    OpenAIRE

    Rothman, Sarah M.; Herdener, Nathan; Camandola, Simonetta; Texel, Sarah J.; Mughal, Mohamed R.; Cong, Wei-na; Martin, Bronwen; Mattson, Mark P.

    2011-01-01

    Chronic stress may be a risk factor for developing Alzheimer’s disease (AD), but most studies of the effects of stress in models of AD utilize acute adverse stressors of questionable clinical relevance. The goal of this work was to determine how chronic psychosocial stress affects behavioral and pathological outcomes in an animal model of AD, and to elucidate underlying mechanisms. A triple-transgenic mouse model of AD (3xTgAD mice) and nontransgenic control mice were used to test for an affe...

  18. 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

  19. The model of rat lipid metabolism disorder induced by chronic stress accompanying high-fat-diet

    OpenAIRE

    Shaodong Chen; Jing Li; Haihong Zhou; Manting Lin; Yihua Liu

    2011-01-01

    Abstract Objective To develop an animal model of Lipid Metabolism Disorder, which conforms to human clinical characteristic. Methods: There were 24 male Wistar rats that were randomly divided into 3 groups with 8 rats in each. They were group A (normal diet), group B (high-fat-diet), group C (chronic stress+ high-fat-diet). Group A was fed with normal diet, while group B and C were fed with high-fat-diet, going on for 55 days. From the 35th day, group B and C received one time of daily chroni...

  20. Quantitative evaluation of integrated neuroendocrine and immune responses to chronic stress in rats male

    OpenAIRE

    Polovynko, Іlona S; Zajats, Lyubomyr М; Zukow, Walery; Yanchij, Roman I; Popovych, Іgor L

    2016-01-01

    Polovynko Іlona S, Zajats Lyubomyr М, Zukow Walery, Yanchij Roman I, Popovych Іgor L. Quantitative evaluation of integrated neuroendocrine and immune responses to chronic stress in rats male. Journal of Education, Health and Sport. 2016;6(8):154-166. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.60023 http://ojs.ukw.edu.pl/index.php/johs/article/view/3745       The journal has had 7 points in Ministry of Science and Higher Education parametric evalua...

  1. The Effect of Synchronized Running Activity with Chronic Stress on Passive Avoidance Learning and Body Weight in Rats

    OpenAIRE

    Maryam Radahmadi; Hojjatallah Alaei; Mohammad R Sharifi; Nasrin Hosseini

    2013-01-01

    Background: Different stressors induce learning and memory impairment and physical activity influence learning and memory enhancement. In this research, we investigated the effect of synchronized running activity with stress on acquisition and retention time of passive avoidance test. Methods: Male Wistar rats were randomly divided into five groups as follows: Control (Co), Sham (Sh), Exercise (Ex), Stress (St), synchronized exercise with stress (St and Ex) groups. Chronic restraint stres...

  2. Social stress exacerbates the aversion to painful experiences in rats exposed to chronic pain: The role of the locus coeruleus

    OpenAIRE

    Bravo, Lidia; Alba-Delgado, Cristina; Torres-Sanchez, Sonia; Micó, Juan Antonio; Neto, Fani L; Berrocoso, Esther

    2013-01-01

    Stressful experiences seem to negatively influence pain perception through as yet unknown mechanisms. As the noradrenergic locus coeruleus (LC) nucleus coordinates many components of the stress response, as well as nociceptive transmission, we evaluated whether the sensory and affective dimension of chronic neuropathic pain worsens in situations of stress due to adaptive changes of LC neurons. Accordingly, male rats were socially isolated for 5 weeks, and in the last 2 weeks, neuropathic pain...

  3. 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

  4. Hypericum perforatum treatment: effect on behaviour and neurogenesis in a chronic stress model in mice

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    Cuzzocrea Salvatore

    2011-01-01

    Full Text Available Abstract Background Extracts of Hypericum perforatum (St. John's wort have been traditionally recommended for a wide range of medical conditions, in particular mild-to-moderate depression. The present study was designed to investigate the effect of Hypericum perforatum treatment in a mouse model of anxiety/depressive-like behavior, induced by chronic corticosterone administration. Methods CD1 mice were submitted to 7 weeks corticosterone administration and then behavioral tests as Open Field (OF, Novelty-Suppressed Feeding (NSF, Forced Swim Test (FST were performed. Cell proliferation in hippocampal dentate gyrus (DG was investigated by both 5-bromo-2'-deoxyuridine (BrdU and doublecortin (DCX immunohistochemistry techniques and stereological procedure was used to quantify labeled cells. Golgi-impregnation method was used to evaluate changes in dendritic spines in DG. Hypericum perforatum (30 mg/Kg has been administered for 3 weeks and then neural development in the adult hippocampus and behavioral changes have been examined. Results The anxiety/depressive-like state due to chronic corticosterone treatment was reversed by exogenous administration of Hypericum perforatum; the proliferation of progenitor cells in mice hippocampus was significantly reduced under chronic corticosterone treatment, whereas a long term treatment with Hypericum perforatum prevented the corticosterone-induced decrease in hippocampal cell proliferation. Corticosterone-treated mice exhibited a reduced spine density that was ameliorated by Hypericum perforatum administration. Conclusion These results provide evidence of morphological adaptations occurring in mature hippocampal neurons that might underlie resilient responses to chronic stress and contribute to the therapeutic effects of chronic Hypericum perforatum treatment.

  5. New Pathogenic Concepts and Therapeutic Approaches to Oxidative Stress in Chronic Kidney Disease

    Science.gov (United States)

    Sánchez-Lozada, Laura G.; Osorio-Alonso, Horacio

    2016-01-01

    In chronic kidney disease inflammatory processes and stimulation of immune cells result in overproduction of free radicals. In combination with a reduced antioxidant capacity this causes oxidative stress. This review focuses on current pathogenic concepts of oxidative stress for the decline of kidney function and development of cardiovascular complications. We discuss the impact of mitochondrial alterations and dysfunction, a pathogenic role for hyperuricemia, and disturbances of vitamin D metabolism and signal transduction. Recent antioxidant therapy options including the use of vitamin D and pharmacologic therapies for hyperuricemia are discussed. Finally, we review some new therapy options in diabetic nephropathy including antidiabetic agents (noninsulin dependent), plant antioxidants, and food components as alternative antioxidant therapies. PMID:27429711

  6. New Pathogenic Concepts and Therapeutic Approaches to Oxidative Stress in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    José Pedraza-Chaverri

    2016-01-01

    Full Text Available In chronic kidney disease inflammatory processes and stimulation of immune cells result in overproduction of free radicals. In combination with a reduced antioxidant capacity this causes oxidative stress. This review focuses on current pathogenic concepts of oxidative stress for the decline of kidney function and development of cardiovascular complications. We discuss the impact of mitochondrial alterations and dysfunction, a pathogenic role for hyperuricemia, and disturbances of vitamin D metabolism and signal transduction. Recent antioxidant therapy options including the use of vitamin D and pharmacologic therapies for hyperuricemia are discussed. Finally, we review some new therapy options in diabetic nephropathy including antidiabetic agents (noninsulin dependent, plant antioxidants, and food components as alternative antioxidant therapies.

  7. Personality dysfunction and complex posttraumatic stress disorder among chronically traumatized Bosnian refugees.

    Science.gov (United States)

    Palić, Sabina; Elklit, Ask

    2014-02-01

    A proposal for the inclusion of complex posttraumatic stress disorder (CPTSD) in the upcoming ICD-11 has been put forward. Using self-report, we investigated the resemblance between disorders of extreme stress not otherwise specified (DESNOS) and both axis I and II syndromes among 116 treatment-seeking Bosnian refugees. In this sample, the prevalence of DESNOS overlapped to a large degree with the prevalence of schizotypal and paranoid personality disorders (PDs). There was, however, also a large prevalence of axis I syndromes in the group. Thus, DESNOS in the refugees can be categorized as an axis I or II disorder depending on the chronicity and the severity of functional impairment. DESNOS and PD-like states were even observed among the refugees with no history of childhood maltreatment. No large differences were observed between DESNOS and PD regarding sex. The symptom constellation of CPTSD in the ICD-11 is partially supported. However, CPTSD might resemble PD to a considerable degree.

  8. Effects of Chronic Forced Swim Stress with Different Session on the Interphase and Termination of Phase 2 in the Formalin Test

    OpenAIRE

    Sina Pozesh; Elaheh Erami; Hassan Azhdari Zarmehri; Nima Heidari; Elmira Ghasemi

    2014-01-01

    Introduction: Stress have bidirectional effects on pain threshold and behaviours. Whereas acute stress often results in analgesia, chronic stress can trigger hyperalgesia/allodynia. The formalin test as an inflammation model, consist of three phases and the effects of repeated forced swim stress with different session numbers on these phases have not been investigated. Therefore, in this study the effects of chronic forced swim stress with different intensities evaluated in formalin test were...

  9. Emotional Stress and Cardiovascular Complications in Animal Models: A Review of the Influence of Stress Type

    Science.gov (United States)

    Crestani, Carlos C.

    2016-01-01

    Emotional stress has been recognized as a modifiable risk factor for cardiovascular diseases. The impact of stress on physiological and psychological processes is determined by characteristics of the stress stimulus. For example, distinct responses are induced by acute vs. chronic aversive stimuli. Additionally, the magnitude of stress responses has been reported to be inversely related to the degree of predictability of the aversive stimulus. Therefore, the purpose of the present review was to discuss experimental research in animal models describing the influence of stressor stimulus characteristics, such as chronicity and predictability, in cardiovascular dysfunctions induced by emotional stress. Regarding chronicity, the importance of cardiovascular and autonomic adjustments during acute stress sessions and cardiovascular consequences of frequent stress response activation during repeated exposure to aversive threats (i.e., chronic stress) is discussed. Evidence of the cardiovascular and autonomic changes induced by chronic stressors involving daily exposure to the same stressor (predictable) vs. different stressors (unpredictable) is reviewed and discussed in terms of the impact of predictability in cardiovascular dysfunctions induced by stress.

  10. Effects of chronic stress on the onset and progression of Huntington's disease in transgenic mice.

    Science.gov (United States)

    Mo, Christina; Renoir, Thibault; Hannan, Anthony J

    2014-11-01

    Huntington's disease (HD) is a neurodegenerative disease caused by a tandem repeat mutation encoding an expanded polyglutamine tract. Our previous work showed that memory deficits in HD transgenic mice could be accelerated by increased levels of stress hormone, while memory in WT mice remained unaffected. HD patients experience higher levels of stress compared to the general population and symptoms of HD also include motor, cognitive, psychiatric, sexual and olfactory abnormalities, and an associated decline in activities of daily living. Therefore we investigated the impact of a robust stressor (i.e. restraint) on the onset and progression of a range of behavioral phenotypes in R6/1 transgenic HD mice. Restraint was administered for 1h daily from 6weeks of age and continued until R6/1 mice were clearly motor symptomatic at 14weeks of age. Serum corticosterone levels in both R6/1 and WT littermates were elevated immediately after the last restraint session and weight gain was suppressed in restrained animals throughout the treatment period. Motor coordination and locomotor activity were enhanced by chronic restraint in males, regardless of genotype. However, there was no effect of restraint on motor performances in female animals. At 8weeks of age, olfactory sensitivity was impaired by restraint in R6/1 HD female mice, but not in WT mice. In male R6/1 mice, the olfactory deficit was exacerbated by restraint and olfaction was also impaired in male WT mice. The development of deficits in saccharin preference, Y-maze memory, nest-building and sexually-motivated vocalizations was unaffected by chronic restraint in R6/1 and had little impact on such behavioral performances in WT animals. We provide evidence that chronic stress can negatively modulate specific endophenotypes in HD mice, while the same functions were affected to a lesser extent in WT mice. This vulnerability in HD animals seems to be sex-specific depending on the stress paradigm used. It is hoped that our

  11. Chronic Stress and Limbic-Hypothalamopituitary-Adrenal Axis (LHPA Response in Female Reproductive system

    Directory of Open Access Journals (Sweden)

    Farideh Zafari Zangeneh

    2009-12-01

    Full Text Available The hypothalamo-pituitary-adrenocortical (HPA axis is a critical adaptive system that maximizes survival potential in the face of physical or psychological challenge. The principal end products of the HPA axis, glucocorticoid hormones, act on multiple organ systems, including the brain, to maintain homeostatic balance. The brain is a target of stress, and the hippocampus is the first brain region, besides the hypothalamus, to be recognized as a target of glucocorticoids. These anatomical areas in brain are limbic system, and in particular the hippocampus, medial prefrontal cortex (mPFC and amigdal that have multiple control points in regulation of the hypothalamic–pituitary–adrenal (HPA axis. The studies show the prefrontal cortex (PFC plays an important role in the regulation of stress-induced hypothalamic–pituitary–adrenal (HPA activity and regulation of gonadal function in men and women is under the control of the HPA. This regulation is complex and sex steroids are important regulators of GnRH and gonadotropin release through classic feedback mechanisms in the hypothalamus and pituitary gland. Chronic stress can have a deleterious effect on the reproductive axis that, for females, is manifested in reduced pulsatile gonadotropin secretion and increased incidence of ovulatory abnormalities and infertility. The limbic–hypothalamic–pituitary–adrenal (LHPA axis suggests a functional role for gonadal steroids in the regulation of a female’s response to stress.

  12. 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

  13. The effect of synchronized running activity with chronic stress on passive avoidance learning and body weight in rats

    Directory of Open Access Journals (Sweden)

    Maryam Radahmadi

    2013-01-01

    Results: Our results showed that: (1 Exercise under no stress provides beneficial effects on memory acquisition and retention time compared to Control group; especially retention time had significantly (P < 0.05 increased in exercised group. (2 Chronic stress with and without synchronized exercise significantly (P < 0.01, P < 0.05, respectively impaired acquisition and retention time. (3 Body weight differences were significantly (P < 0.01, P < 0.001 and P < 0.001 lower than Control group in exercise, stress and synchronized exercise with stress groups, respectively. (4 Adverse effects of restraint stress (psychical stress were probably greater than physical activity effects on learning, memory and weight loss. Conclusions: The data confirmed that synchronized exercise with stress had not significantly protective role in improvement of passive avoidance acquisition and retention time; hence it did not significantly improve learning and memory deficit in stressed rats; whereas exercise alone could improve memory deficit in rats.

  14. Chronic inflammatory diseases are stimulated by current lifestyle: how diet, stress levels and medication prevent our body from recovering

    Directory of Open Access Journals (Sweden)

    Bosma-den Boer Margarethe M

    2012-04-01

    Full Text Available Abstract Serhan and colleagues introduced the term "Resoleomics" in 1996 as the process of inflammation resolution. The major discovery of Serhan's work is that onset to conclusion of an inflammation is a controlled process of the immune system (IS and not simply the consequence of an extinguished or "exhausted" immune reaction. Resoleomics can be considered as the evolutionary mechanism of restoring homeostatic balances after injury, inflammation and infection. Under normal circumstances, Resoleomics should be able to conclude inflammatory responses. Considering the modern pandemic increase of chronic medical and psychiatric illnesses involving chronic inflammation, it has become apparent that Resoleomics is not fulfilling its potential resolving capacity. We suggest that recent drastic changes in lifestyle, including diet and psycho-emotional stress, are responsible for inflammation and for disturbances in Resoleomics. In addition, current interventions, like chronic use of anti-inflammatory medication, suppress Resoleomics. These new lifestyle factors, including the use of medication, should be considered health hazards, as they are capable of long-term or chronic activation of the central stress axes. The IS is designed to produce solutions for fast, intensive hazards, not to cope with long-term, chronic stimulation. The never-ending stress factors of recent lifestyle changes have pushed the IS and the central stress system into a constant state of activity, leading to chronically unresolved inflammation and increased vulnerability for chronic disease. Our hypothesis is that modern diet, increased psycho-emotional stress and chronic use of anti-inflammatory medication disrupt the natural process of inflammation resolution ie Resoleomics.

  15. 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

  16. [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.

  17. Protective Effects of Lentinan against T Lymphocytes Injury in Mice under Chronic Radiation Stress

    Institute of Scientific and Technical Information of China (English)

    WANG Yong; LI Ming-chun; FU Qing-jie

    2013-01-01

    Objective To study the effects of lentinan (LTN) on mice exposed to chronic radiation.Methods Animals were divided into three groups (n =10),they were animals exposed to radiation (Rad),normal control animals (Ctr),and irradiated animals treated with LTN (Rad + LTN).Animal model of chronic radiation stress injury was induced by irradiating mice with 60Co γ-ray for 6 weeks from Monday to Friday consecutively.Before radiation,the mice in Rad + LTN group were ip injected with 0.5 mL LTN (0.01 mg/mL),whereas mice in other groups were injected with 0.9% physiological saline.The effects of LTN treatment on irradiated mice were examined by histological analysis on the spleen.The cell numbers and viability of T lymphocytes,which were isolated from the spleen,were determined by Trypan blue staining.Nitric oxide (NO) production and interleukin-2 (IL-2) secretion in T lymphocytes were also measured.Results Chronic radiation significantly reduced the body weights and the spleen and thymus indexes,associated with reduced T lymphocytes viability and functions,and elevated NO production.Treatment with LTN significantly normalized the elevated NO production,and attenuated the negative outcomes resulting from radiation mentioned above.Conclusion The results suggest that radioprotective effect of LTN may be contributed by improved T lymphocytes viability and functions via regulating the NO and IL-2 production in T lymphocytes.

  18. Protective Effects of Lentinan against T Lymphocytes Injury in Mice under Chronic Radiation Stress

    Institute of Scientific and Technical Information of China (English)

    WANG; Yong; LI; Ming-chun; FU; Qing-jie

    2013-01-01

    Objective To study the effects of lentinan (LTN) on mice exposed to chronic radiation. Methods Animals were divided into three groups (n = 10), they were animals exposed to radiation (Rad), normal control animals (Ctr), and irradiated animals treated with LTN (Rad + LTN). Animal model of chronic radiation stress injury was induced by irradiating mice with 60 Co γ-ray for 6 weeks from Monday to Friday consecutively. Before radiation, the mice in Rad + LTN group were ip injected with 0.5 mL LTN (0.01 mg/mL), whereas mice in other groups were injected with 0.9% physiological saline. The effects of LTN treatment on irradiated mice were examined by histological analysis on the spleen. The cell numbers and viability of T lymphocytes, which were isolated from the spleen, were determined by Trypan blue staining. Nitric oxide (NO) production and interleukin-2 (IL-2) secretion in T lymphocytes were also measured. Results Chronic radiation significantly reduced the body weights and the spleen and thymus indexes, associated with reduced T lymphocytes viability and functions, and elevated NO production. Treatment with LTN significantly normalized the elevated NO production, and attenuated the negative outcomes resulting from radiation mentioned above. Conclusion The results suggest that radioprotective effect of LTN may be contributed by improved T lymphocytes viability and functions via regulating the NO and IL-2 production in T lymphocytes.

  19. The number of granule cells in rat hippocampus is reduced after chronic mild stress and re-established after chronic escitalopram treatment

    DEFF Research Database (Denmark)

    Jayatissa, Magdalena N; Bisgaard, Christina; West, Mark J;

    2008-01-01

    Stress and depression cause structural changes in the hippocampal formation. Some of these can be reversed by chronic antidepressant treatment. In the present study, we examined the changes in the total number of granule cells and the volume of the granule cell layer after exposing rats to chronic...... changes, indicating a decrease in sensitivity to a reward, were assessed in terms of sucrose consumption. We found a significant 22.4% decrease in the total number of granule cells in the stressed rats. This decrease was reversed in the stressed escitalopram treated rats that responded to the treatment...... shows that the anhedonia-like state in the CMS rats is associated with a reduced number of granule cells. We conclude that escitalopram acts on specific cellular targets during neuronal differentiation and that recovery from anhedonia-like behavior in rats may be the consequence of an escitalopram...

  20. Voluntary exercise and increased food intake after mild chronic stress improve social avoidance behavior in mice.

    Science.gov (United States)

    Otsuka, Airi; Shiuchi, Tetsuya; Chikahisa, Sachiko; Shimizu, Noriyuki; Séi, Hiroyoshi

    2015-11-01

    It is well-established that exercise can influence psychological conditions, cognitive function, and energy metabolism in peripheral tissues including the skeletal muscle. However, it is not clear whether exercise can influence social interaction with others and alleviate defeat stress. This study investigated the effect of voluntary wheel running on impaired social interaction induced by chronic social defeat stress (SDS) using the resident-intruder social defeat model. Mice were divided into three groups: control, stress alone, and stress+exercise. SDS was performed by exposing C57BL/6 mice to retired ICR mice for 2.5 min. The C57BL/6 mice were continuously defeated by these resident (aggressor) mice and, following 5 days of SDS, experienced 2 days of rest with no SDS. Mice in the stress+exercise group were allowed to voluntarily run on a wheel for 2h after every SDS exposure. Two weeks later, compared to the control group, the stress group showed a higher ratio of time spent in the corner zone of a social interaction paradigm even though SDS did not elicit depressive- and anxiety-like behaviors. We also observed that voluntary exercise, which did not affect muscle weight and gene expression, decreased social avoidance behavior of stressed mice without clear changes in brain monoamine levels. Interestingly, food intake in the stress+exercise group was the greatest among the three groups. To test the effect of the exercise-induced increase in food intake on social behavior, we set up a pair-fed group where food intake was restricted. We then compared these mice to mice in the stress alone group. We found that the ratio of time spent in the corner zone of the social interaction test was not different between ad libitum- and pair-fed groups, although pair-fed mice spent more time in the corner zone when an aggressor mouse was present than when it was absent. In addition, pair-feeding did not show exercise-induced reductions of adrenal gland weight and enhanced the

  1. 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

  2. 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...

  3. Chronic stress and moderate physical exercise prompt widespread common activation and limited differential activation in specific brain regions.

    Science.gov (United States)

    Kim, Tae-Kyung; Han, Pyung-Lim

    2016-10-01

    Chronic stress in rodents produces depressive behaviors, whereas moderate physical exercise counteracts stress-induced depressive behaviors. Chronic stress and physical exercise appear to produce such opposing effects by changing the neural activity of specific brain regions. However, the detailed mechanisms through which the two different types of stimuli regulate brain function in opposite directions are not clearly understood. In the present study, we attempted to explore the neuroanatomical substrates mediating stress-induced behavioral changes and anti-depressant effects of exercise by examining stimulus-dependent c-Fos induction in the brains of mice that were exposed to repeated stress or exercise in a scheduled manner. Systematic and integrated analyses of c-Fos expression profiles indicated that various brain areas, including the prelimbic cortex, lateral septal area, and paraventricular nuclei of hypothalamus were commonly and strongly activated by both stress and exercise, while the lateral habenula and hippocampus were identified as being preferentially activated by stress and exercise, respectively. Exercise-dependent c-Fos expression in all regions examined in the brain occurred in both glutamatergic and GABAergic neurons. These results suggest that chronic stress and moderate exercise produce counteractive effects on mood behaviors, along with prompting widespread common activation and limited differential activation in specific brain regions. PMID:27539656

  4. Chronic activation of NPFFR2 stimulates the stress-related depressive behaviors through HPA axis modulation.

    Science.gov (United States)

    Lin, Ya-Tin; Liu, Tzu-Yu; Yang, Ching-Yao; Yu, Yu-Lian; Chen, Ting-Chun; Day, Yuan-Ji; Chang, Che-Chien; Huang, Guo-Jen; Chen, Jin-Chung

    2016-09-01

    Neuropeptide FF (NPFF) is a morphine-modulating peptide that regulates the analgesic effect of opioids, and also controls food consumption and cardiovascular function through its interaction with two cognate receptors, NPFFR1 and NPFFR2. In the present study, we explore a novel modulatory role for NPFF-NPFFR2 in stress-related depressive behaviors. In a mouse model of chronic mild stress (CMS)-induced depression, the expression of NPFF significantly increased in the hypothalamus, hippocampus, medial prefrontal cortex (mPFC) and amygdala. In addition, transgenic (Tg) mice over-expressing NPFFR2 displayed clear depression and anxiety-like behaviors with hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis, reduced expression of glucocorticoid receptor (GR) and neurogenesis in the hippocampus. Furthermore, acute treatment of NPFFR2 agonists in wild-type (WT) mice enhanced the activity of the HPA axis, and chronic administration resulted in depressive and anxiety-like behaviors. Chronic stimulation of NPFFR2 also decreased the expression of hippocampal GR and led to persistent activation of the HPA axis. Strikingly, bilateral intra-paraventricular nucleus (PVN) injection of NPFFR2 shRNA predominately inhibits the depressive-like behavior in CMS-exposed mice. Antidepressants, fluoxetine and ketamine, effectively relieved the depressive behaviors of NPFFR2-Tg mice. We speculate that persistent NPFFR2 activation, in particular in the hypothalamus, up-regulates the HPA axis and results in long-lasting increases in circulating corticosterone (CORT), consequently damaging hippocampal function. This novel role of NPFFR2 in regulating the HPA axis and hippocampal function provides a new avenue for combating depression and anxiety-like disorder. PMID:27243477

  5. Chronic activation of NPFFR2 stimulates the stress-related depressive behaviors through HPA axis modulation.

    Science.gov (United States)

    Lin, Ya-Tin; Liu, Tzu-Yu; Yang, Ching-Yao; Yu, Yu-Lian; Chen, Ting-Chun; Day, Yuan-Ji; Chang, Che-Chien; Huang, Guo-Jen; Chen, Jin-Chung

    2016-09-01

    Neuropeptide FF (NPFF) is a morphine-modulating peptide that regulates the analgesic effect of opioids, and also controls food consumption and cardiovascular function through its interaction with two cognate receptors, NPFFR1 and NPFFR2. In the present study, we explore a novel modulatory role for NPFF-NPFFR2 in stress-related depressive behaviors. In a mouse model of chronic mild stress (CMS)-induced depression, the expression of NPFF significantly increased in the hypothalamus, hippocampus, medial prefrontal cortex (mPFC) and amygdala. In addition, transgenic (Tg) mice over-expressing NPFFR2 displayed clear depression and anxiety-like behaviors with hyperactivity in the hypothalamic-pituitary-adrenal (HPA) axis, reduced expression of glucocorticoid receptor (GR) and neurogenesis in the hippocampus. Furthermore, acute treatment of NPFFR2 agonists in wild-type (WT) mice enhanced the activity of the HPA axis, and chronic administration resulted in depressive and anxiety-like behaviors. Chronic stimulation of NPFFR2 also decreased the expression of hippocampal GR and led to persistent activation of the HPA axis. Strikingly, bilateral intra-paraventricular nucleus (PVN) injection of NPFFR2 shRNA predominately inhibits the depressive-like behavior in CMS-exposed mice. Antidepressants, fluoxetine and ketamine, effectively relieved the depressive behaviors of NPFFR2-Tg mice. We speculate that persistent NPFFR2 activation, in particular in the hypothalamus, up-regulates the HPA axis and results in long-lasting increases in circulating corticosterone (CORT), consequently damaging hippocampal function. This novel role of NPFFR2 in regulating the HPA axis and hippocampal function provides a new avenue for combating depression and anxiety-like disorder.

  6. The bio-distribution of the antidepressant clomipramine is modulated by chronic stress in mice: Effects on behavior

    Directory of Open Access Journals (Sweden)

    Georgia eBalsevich

    2015-01-01

    Full Text Available Major depression is one of the most common psychiatric disorders, severely affecting the quality of life of millions of people worldwide. Despite the availability of several classes of antidepressants, treatment efficacy is still very variable and many patients do not respond to the treatment. Clomipramine (CMI, a classical and widely used antidepressant, shows widespread interindividual variability of efficacy, while the environmental factors contributing to such variability remain unclear. We investigated whether chronic stress modulates the bio-distribution of CMI, and as a result the behavioral response to CMI treatment in a mouse model of chronic social defeat stress. Our results show that stress exposure increased anxiety-like and depressive-like behaviors and altered the stress response. Chronic defeat stress furthermore significantly altered CMI bio-distribution. Interestingly, CMI bio-distribution highly correlated with anxiety-like and depressive-like behaviors only under basal conditions. Taken together, we provide first evidence demonstrating that chronic stress exposure modulates CMI bio-distribution and behavioral responses. This may contribute to CMI’s broad interindividual variability, and is especially relevant in clinical practice.

  7. Study of C57 mice depression model induced by chronic stress and separation%慢性应激联合孤养C57小鼠抑郁模型的研究

    Institute of Scientific and Technical Information of China (English)

    姚丽华; 陈建新; 王晓萍; 王惠玲; 王高华; 刘忠纯

    2014-01-01

    目的 探讨C57小鼠慢性不可预见性温和应激(chronic unpredictable mild stress,GUMS)联合孤养建立抑郁模型的可行性和有效性.方法 将30只雄性C57小鼠随机分为CUMS+孤养组、CUMS+孤养+氟西汀组、对照组各10只,前两组CUMS+孤养致抑郁模型3周,3周后对CUMS+孤养+氟西汀组进行氟西汀干预,观察小鼠应激前、应激后及干预后的摄食量/体质量、旷场实验和液体消耗实验变化.结果 与对照组比较,建模21d后CUMS+孤养组和CUMS+孤养+氟西汀组小鼠摄食量/体质量、糖水偏好、旷场总行程显著下降(P<0.05);经氟西汀干预14 d后摄食量/体质量、旷场总行程与对照组比较无明显差异(P>0.05),但糖水消耗量明显提高(P<0.05),与CUMS+孤养组比较也有明显改善(P<0.05).结论 C57小鼠CUMS联合孤养制作抑郁模型的效果肯定,是研究抑郁症较为理想的动物模型.%Objective To investigate the feasibility and effectiveness of C57 mice depression model established by chronic unpredictable mild stress (CUMS) and separation.Methods 30 male C57 mice were randomly divided into three groups:CUMS + separation group (group CS),CUMS + separation + fluoxetine group (group CSF),and control group (group C).The mice of group CS and group CSF were fed with chronic unpredictable mild stress (CUMS) and separation for 3 weeks.Then,the mice of group CSF were given fluoxetine.To record the food intake/body weight,liquid consumption and field test of the mice at relevant time point.Results Compared with control group,the food intake/body weight,total route in the field test,and the sucrose solution consumption in liquid consumption test of group CS and group CSF decreased significantly (P<0.05) at the 21th days.But after giving fluoxetine for 14 days,group CSF had no significant differences with group C except sucrose solution consumption.Although the difference of sucrose solution preferences was significant compared with

  8. Ethanol metabolism, oxidative stress, and endoplasmic reticulum stress responses in the lungs of hepatic alcohol dehydrogenase deficient deer mice after chronic ethanol feeding

    OpenAIRE

    Kaphalia, Lata; Boroumand, Nahal; Ju, Hyunsu; Kaphalia, Bhupendra S.; Calhoun, William J

    2014-01-01

    Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal c...

  9. Post-traumatic stress, depression, and anxiety in patients with injury-related chronic pain: A pilot study

    OpenAIRE

    Sofia Åhman; Britt-Marie Stålnacke

    2008-01-01

    Sofia Åhman, Britt-Marie StålnackeDepartment of Community Medicine and Rehabilitation, Umeå University, SwedenAim: To investigate, in patients with injury-related chronic pain, pain intensity, levels of post-traumatic stress, anxiety and depressions.Methods: One hundred and sixty patients aged 17–62 years, admitted for assessment to the Pain Rehabilitation Clinic at the Umeå University Hospital, Umeå Sweden, for chronic pain caused b...

  10. Skeletal Muscle Regeneration and Oxidative Stress Are Altered in Chronic Kidney Disease.

    Science.gov (United States)

    Avin, Keith G; Chen, Neal X; Organ, Jason M; Zarse, Chad; O'Neill, Kalisha; Conway, Richard G; Konrad, Robert J; Bacallao, Robert L; Allen, Matthew R; Moe, Sharon M

    2016-01-01

    Skeletal muscle atrophy and impaired muscle function are associated with lower health-related quality of life, and greater disability and mortality risk in those with chronic kidney disease (CKD). However, the pathogenesis of skeletal dysfunction in CKD is unknown. We used a slow progressing, naturally occurring, CKD rat model (Cy/+ rat) with hormonal abnormalities consistent with clinical presentations of CKD to study skeletal muscle signaling. The CKD rats demonstrated augmented skeletal muscle regeneration with higher activation and differentiation signals in muscle cells (i.e. lower Pax-7; higher MyoD and myogenin RNA expression). However, there was also higher expression of proteolytic markers (Atrogin-1 and MuRF-1) in CKD muscle relative to normal. CKD animals had higher indices of oxidative stress compared to normal, evident by elevated plasma levels of an oxidative stress marker, 8-hydroxy-2' -deoxyguanosine (8-OHdG), increased muscle expression of succinate dehydrogenase (SDH) and Nox4 and altered mitochondria morphology. Furthermore, we show significantly higher serum levels of myostatin and expression of myostatin in skeletal muscle of CKD animals compared to normal. Taken together, these data show aberrant regeneration and proteolytic signaling that is associated with oxidative stress and high levels of myostatin in the setting of CKD. These changes likely play a role in the compromised skeletal muscle function that exists in CKD. PMID:27486747

  11. Hyperglycemia Aggravates Hepatic Ischemia Reperfusion Injury by Inducing Chronic Oxidative Stress and Inflammation

    Directory of Open Access Journals (Sweden)

    Yihan Zhang

    2016-01-01

    Full Text Available Aim. To investigate whether hyperglycemia will aggravate hepatic ischemia reperfusion injury (HIRI and the underlying mechanisms. Methods. Control and streptozotocin-induced diabetic Sprague-Dawley rats were subjected to partial hepatic ischemia reperfusion. Liver histology, transferase, inflammatory cytokines, and oxidative stress were assessed accordingly. Similarly, BRL-3A hepatocytes were subjected to hypoxia/reoxygenation (H/R after high (25 mM or low (5.5 mM glucose culture. Cell viability, reactive oxygen species (ROS, and activation of nuclear factor-erythroid 2-related factor 2 (Nrf2 and nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB were determined. Results. Compared with control, diabetic rats presented more severe hepatic injury and increased hepatic inflammatory cytokines and oxidative stress. HIRI in diabetic rats could be ameliorated by pretreatment of N-acetyl-L-cysteine (NAC or apocynin. Excessive ROS generation and consequent Nrf2 and NF-κB translocation were determined after high glucose exposure. NF-κB translocation and its downstream cytokines were further increased in high glucose cultured group after H/R. While proper regulation of Nrf2 to its downstream antioxidases was observed in low glucose cultured group, no further induction of Nrf2 pathway by H/R after high glucose culture was identified. Conclusion. Hyperglycemia aggravates HIRI, which might be attributed to chronic oxidative stress and inflammation and potential malfunction of antioxidative system.

  12. Post-traumatic stress, depression, and anxiety in patients with injury-related chronic pain: A pilot study

    Directory of Open Access Journals (Sweden)

    Sofia Åhman

    2008-10-01

    Full Text Available Sofia Åhman, Britt-Marie StålnackeDepartment of Community Medicine and Rehabilitation, Umeå University, SwedenAim: To investigate, in patients with injury-related chronic pain, pain intensity, levels of post-traumatic stress, anxiety and depressions.Methods: One hundred and sixty patients aged 17–62 years, admitted for assessment to the Pain Rehabilitation Clinic at the Umeå University Hospital, Umeå Sweden, for chronic pain caused by an injury, answered a set of questionnaires to assess post-traumatic stress (Impact of Event Scale [IES], pain intensity (VAS, depression, and anxiety (Hospital Anxiety and Depression Scale [HAD].Results: Moderate to severe post-traumatic stress was reported by 48.1% of the patients. Possible–probable anxiety on the HAD was scored by 44.5% and possible–probable depression by 45.2%. Pain intensity (VAS was significantly correlated to post-traumatic stress (r = 0.183, p = 0.022, the HAD-scores anxiety (r = 0.186, p = 0.0021, and depression (r = 0.252, p = 0.002. No statistically significant differences were found between genders for post-traumatic stress, pain intensity, anxiety, or depression. Participants with moderate to severe stress reaction reported statistically significant higher anxiety scores on the HAD (p = 0.030 in comparison with patients with mild stress.Conclusion: The findings of relationships between pain intensity, post-traumatic stress, depression, and anxiety may have implications for clinicians and underline the importance of considering all these factors when managing patients with injury-related chronic pain.Keywords: post-traumatic stress disorder, anxiety, chronic pain

  13. GDNF在慢性应激和老化致小鼠行为与认知损伤中的作用%Role of GDNF in the behavior and cognitive impairment of mice induced by chronic stress and aging

    Institute of Scientific and Technical Information of China (English)

    李亚; 张亚楠; 陈亚静; 张冠雄; 史建勋

    2013-01-01

    Objective: To investigate the effects of chronic stress on the spatial learning-memory and the role of glial cell line-derived neurotrophic factor (GDNF) of prefrontal cortex (PFC) and hippocampus (HP) in different age mice. Methods: The chronic stress model mice in 21 days with multiple chronic unpredictable stressors were applied. The spontaneous behavior and spatial learning-memory ability of mice were tested, using Open field and Morris water maze task, and the expression of GDNF in HP and PFC were detected by immunohistoche-mical method. Results: Compared with young mice, the spontaneous behaviors were significantly decreased and the spatial learning-memory function were significantly decreased (P<0.05, P<0.01) in aged mice. The GDNF expression in the CA3, DG of HP and PFC were significantly reduced in aged mice (P<0.05, P<0.01). After chronic stress, the spontaneous behaviors were remarkably decreased and the ability of spatial learning-memory of the stress group mice were significantly decreased (P< 0.05, P<0.01) compared with those of the control group mice. The expression of GDNF in HP and PFC were remarkably reduced (P<0.05, P<0.01) in stress group mice. The aged stress mice had more serious changes after chronic stress. Conclusion: The brain aging and chronic stress in mice causes behavioral changes and the damage of spatial learning-memory function, and which may be nearly related to the expression of GDNF in HP and PFC.%目的:探讨慢性应激对不同月龄小鼠空间学习记忆功能的影响,以及小鼠前脑皮层和海马胶质细胞源性神经营养因子(GDNF)的作用.方法:采用多因素慢性应激动物模型,通过旷场试验和Morris水迷宫试验,检测不同月龄小鼠行为及空间学习记忆能力,并检测GDNF在小鼠脑海马和前脑皮层的表达.结果:与青年(2月龄)小鼠比较,老年(15月龄)小鼠的自发活动和探究行为明显减少,空间学习记忆能力明显降低(P<0.05,P<0.01),且海马CA3

  14. 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.

  15. Increasing orthostatic stress impairs neurocognitive functioning in chronic fatigue syndrome with postural tachycardia syndrome.

    Science.gov (United States)

    Ocon, Anthony J; Messer, Zachary R; Medow, Marvin S; Stewart, Julian M

    2012-03-01

    CFS (chronic fatigue syndrome) is commonly co-morbid with POTS (postural tachycardia syndrome). Individuals with CFS/POTS experience unrelenting fatigue, tachycardia during orthostatic stress and ill-defined neurocognitive impairment, often described as 'mental fog'. We hypothesized that orthostatic stress causes neurocognitive impairment in CFS/POTS related to decreased CBFV (cerebral blood flow velocity). A total of 16 CFS/POTS and 20 control subjects underwent graded tilt table testing (at 0, 15, 30, 45, 60 and 75°) with continuous cardiovascular, cerebrovascular, and respiratory monitoring and neurocognitive testing using an n-back task at each angle. The n-back task tests working memory, concentration, attention and information processing. The n-back task imposes increasing cognitive challenge with escalating (0-, 1-, 2-, 3- and 4-back) difficulty levels. Subject dropout due to orthostatic presyncope at each angle was similar between groups. There were no n-back accuracy or RT (reaction time) differences between groups while supine. CFS/POTS subjects responded less correctly during the n-back task test and had greater nRT (normalized RT) at 45, 60 and 75°. Furthermore, at 75° CFS/POTS subjects responded less correctly and had greater nRT than controls during the 2-, 3- and 4-back tests. Changes in CBFV were not different between the groups and were not associated with n-back task test scores. Thus we conclude that increasing orthostatic stress combined with a cognitive challenge impairs the neurocognitive abilities of working memory, accuracy and information processing in CFS/POTS, but that this is not related to changes in CBFV. Individuals with CFS/POTS should be aware that orthostatic stress may impair their neurocognitive abilities.

  16. Chronic mild stress (CMS in mice: of anhedonia, 'anomalous anxiolysis' and activity.

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    Martin C Schweizer

    Full Text Available BACKGROUND: In a substantial proportion of depressed patients, stressful life events play a role in triggering the evolution of the illness. Exposure to stress has effects on different levels in laboratory animals as well and for the rat it has been shown that chronic mild stress (CMS can cause antidepressant-reversible depressive-like effects. The adoption of the model to the mouse seems to be problematic, depending on the strain used and behavioural endpoint defined. Our aim was to evaluate the applicability of CMS to mice in order to induce behavioural alterations suggested to reflect depression-like symptoms. METHODOLOGY/PRINCIPAL FINDINGS: A weekly CMS protocol was applied to male mice of different mouse strains (D2Ola, BL/6J and BL/6N and its impact on stress-sensitive behavioural measures (anhedonia-, anxiety- and depression-related parameters and body weight was assessed. Overnight illumination as commonly used stressor in CMS protocols was particularly investigated in terms of its effect on general activity and subsequently derived saccharin intake. CMS application yielded strain-dependent behavioural and physiological responses including 'paradox' anxiolytic-like effects. Overnight illumination was found to be sufficient to mimic anhedonic-like behaviour in BL/6J mice when being applied as sole stressor. CONCLUSIONS/SIGNIFICANCE: The CMS procedure induced some behavioural changes that are compatible with the common expectations, i.e. 'anhedonic' behaviour, but in parallel behavioural alterations were observed which would be described as 'anomalous' (e.g. decreased anxiety. The results suggest that a shift in the pattern of circadian activity has a particular high impact on the anhedonic profile. Changes in activity in response to novelty seem to drive the 'anomalous' behavioural alterations as well.

  17. Stress management skills, cortisol awakening response, and post-exertional malaise in Chronic Fatigue Syndrome.

    Science.gov (United States)

    Hall, Daniel L; Lattie, Emily G; Antoni, Michael H; Fletcher, Mary Ann; Czaja, Sara; Perdomo, Dolores; Klimas, Nancy G

    2014-11-01

    Chronic Fatigue Syndrome (CFS) is characterized in part by debilitating fatigue typically exacerbated by cognitive and/or physical exertion, referred to as post-exertional malaise (PEM). In a variety of populations, the cortisol awakening response (CAR) has stood out as a marker of endocrine dysregulation relevant to the experience of fatigue, and may therefore be particularly relevant in CFS. This is the first study to examine PEM and the CAR in a sample of individuals with CFS. The CAR has also been established as a stress-sensitive measure of HPA axis functioning. It follows that better management of stress could modulate the CAR, and in turn PEM. In this cross-sectional study, we hypothesized that greater Perceived Stress Management Skills (PSMS) would relate to lower reports of PEM, via the impact of PSMS on the CAR. A total of 117 adults (72% female) with a CFS diagnosis completed self-report measures of PSMS and PEM symptomatology and a two-day protocol of saliva collection. Cortisol values from awakening and 30 min post-awakening were used to compute the CAR. Regression analyses revealed that greater PSMS related to greater CAR and greater CAR related to less PEM severity. Bootstrapped analyses revealed an indirect effect of PSMS on PEM via the CAR, such that greater PSMS related to less PEM, via a greater CAR. Future research should examine these trends longitudinally and whether interventions directed at improving stress management skills are accompanied by improved cortisol regulation and less PEM in individuals with CFS. PMID:25049069

  18. Chronic stress disrupts fear extinction and enhances amygdala and hippocampal Fos expression in an animal model of post-traumatic stress disorder.

    Science.gov (United States)

    Hoffman, Ann N; Lorson, Nickolaus G; Sanabria, Federico; Foster Olive, M; Conrad, Cheryl D

    2014-07-01

    Chronic stress may impose a vulnerability to develop maladaptive fear-related behaviors after a traumatic event. Whereas previous work found that chronic stress impairs the acquisition and recall of extinguished fear, it is unknown how chronic stress impacts nonassociative fear, such as in the absence of the conditioned stimulus (CS) or in a novel context. Male rats were subjected to chronic stress (STR; wire mesh restraint 6 h/d/21d) or undisturbed (CON), then tested on fear acquisition (3 tone-footshock pairings), and two extinction sessions (15 tones/session) within the same context. Then each group was tested (6 tones) in the same context (SAME) or a novel context (NOVEL), and brains were processed for functional activation using Fos immunohistochemistry. Compared to CON, STR showed facilitated fear acquisition, resistance to CS extinction on the first extinction day, and robust recovery of fear responses on the second extinction day. STR also showed robust freezing to the context alone during the first extinction day compared to CON. When tested in the same or a novel context, STR exhibited higher freezing to context than did CON, suggesting that STR-induced fear was independent of context. In support of this, STR showed increased Fos-like expression in the basolateral amygdala and CA1 region of the hippocampus in both the SAME and NOVEL contexts. Increased Fos-like expression was also observed in the central amygdala in STR-NOVEL vs. CON-NOVEL. These data demonstrate that chronic stress enhances fear learning and impairs extinction, and affects nonassociative processes as demonstrated by enhanced fear in a novel context. PMID:24508064

  19. Chronic stress disrupts fear extinction and enhances amygdala and hippocampal Fos expression in an animal model of post-traumatic stress disorder.

    Science.gov (United States)

    Hoffman, Ann N; Lorson, Nickolaus G; Sanabria, Federico; Foster Olive, M; Conrad, Cheryl D

    2014-07-01

    Chronic stress may impose a vulnerability to develop maladaptive fear-related behaviors after a traumatic event. Whereas previous work found that chronic stress impairs the acquisition and recall of extinguished fear, it is unknown how chronic stress impacts nonassociative fear, such as in the absence of the conditioned stimulus (CS) or in a novel context. Male rats were subjected to chronic stress (STR; wire mesh restraint 6 h/d/21d) or undisturbed (CON), then tested on fear acquisition (3 tone-footshock pairings), and two extinction sessions (15 tones/session) within the same context. Then each group was tested (6 tones) in the same context (SAME) or a novel context (NOVEL), and brains were processed for functional activation using Fos immunohistochemistry. Compared to CON, STR showed facilitated fear acquisition, resistance to CS extinction on the first extinction day, and robust recovery of fear responses on the second extinction day. STR also showed robust freezing to the context alone during the first extinction day compared to CON. When tested in the same or a novel context, STR exhibited higher freezing to context than did CON, suggesting that STR-induced fear was independent of context. In support of this, STR showed increased Fos-like expression in the basolateral amygdala and CA1 region of the hippocampus in both the SAME and NOVEL contexts. Increased Fos-like expression was also observed in the central amygdala in STR-NOVEL vs. CON-NOVEL. These data demonstrate that chronic stress enhances fear learning and impairs extinction, and affects nonassociative processes as demonstrated by enhanced fear in a novel context.

  20. DIFFERENTIAL REGULATION OF THE 5-HT1A TRANSCRIPTIONAL MODULATORS FREUD-1 AND NUDR BY CHRONIC STRESS

    OpenAIRE

    Iyo, Abiye H.; Kieran, Niamh; Chandran, Agata; Albert, Paul R.; WICKS, IVY; Bissette, Garth; Austin, Mark C.

    2009-01-01

    Chronic stress is known to affect brain areas involved in learning and emotional responses. These changes, thought to be related to the development of cognitive deficits are evident in major depressive disorder (MDD) and other stress related pathophysiologies. The serotoninrelated transcription factors ((Freud-1/CC2D1A; five prime repressor element under dual repression/coiled-coil C2 domain-1A and NUDR/Deaf-1; nuclear deformed epidermal autoregulatory factor) are two important regulators of ...

  1. Psychosocial predictors of chronic Post-Traumatic Stress Disorder in Sri Lankan tsunami survivors.

    Science.gov (United States)

    Lommen, Miriam J J; Sanders, Angelique J M L; Buck, Nicole; Arntz, Arnoud

    2009-01-01

    This study aimed to determine whether psychological factors associated with Post-Traumatic Stress Disorder (PTSD) identified in Western samples generalize to low Social-Economical-Status (SES) populations in an underdeveloped Asian country. The study included 113 survivors of the 2004-tsunami on the south coast of Sri Lanka, recruited from 4 preschools and 10 villages for displaced persons. With logistic regressions the relations between interview-based PTSD diagnosis and psychological factors were assessed, controlling for putative confounders. Fifteen months post-trauma the prevalence of PTSD was 52.2%. Multivariate analyses indicated that negative interpretation of tsunami-memories was significantly (PPTSD. Of the putative confounders, gender and (non-replaced) lost work equipment were related to current PTSD (PPTSD is quite universal, suggesting that interventions focusing on this factor may be important in treatment of tsunami survivors who are suffering from chronic PTSD.

  2. Chronic Psychosocial Factors and Acute Physiological Responses to Laboratory-Induced Stress in Healthy Populations: A Quantitative Review of 30 Years of Investigations

    Science.gov (United States)

    Chida, Yoichi; Hamer, Mark

    2008-01-01

    This meta-analysis included 729 studies from 161 articles investigating how acute stress responsivity (including stress reactivity and recovery of hypothalamic-pituitary-adrenal [HPA] axis, autonomic, and cardiovascular systems) changes with various chronic psychosocial exposures (job stress; general life stress; depression or hopelessness;…

  3. Sub-chronic iron overload triggers oxidative stress development in rat brain: implications for cell protection.

    Science.gov (United States)

    Piloni, Natacha E; Perazzo, Juan C; Fernandez, Virginia; Videla, Luis A; Puntarulo, Susana

    2016-02-01

    This work was aimed to test the hypothesis that sub-chronic administration of iron-dextran (Fe-dextran) (six doses of 50 mg Fe-dextran/kg) to rats triggers a transient oxidative stress in brain and mechanisms of cellular antioxidant defence. After 2 h of administration of the 6th dose, a significant increase of total Fe, the labile Fe pool (LIP), the lipid radical (LR(•))/α-tocopherol (α-T) content ratio were observed, as compared to values in control brain homogenates. The ascorbyl radical (A(•))/ascorbate (AH(-)) content ratio and the oxidation rate of 2',7'-dichlorodihidrofluorescein (DCFH-DA) were significantly higher in Fe-dextran treated rats, as compared to values in brain from control rats after 4 h treatment. An increase in both catalase (CAT) and superoxide dismutase (SOD) activity was observed at 8 and 1-2 h, respectively. No significant changes were detected in the nuclear factor-κB (NF-κB) levels in nuclear extracts from rat brains after 1-8 h of Fe-dextran administration. After 2 h of Fe administration Fe concentration in cortex, striatum and hippocampus was significantly increased as compared to the same areas from control animals. Both, CAT and SOD activities were significantly increased in cortex after Fe administration over control values, without changes in striatum and hippocampus. Taken as a whole, sub-chronic Fe administration enhances the steady state concentration of Fe in the brain LIP that favors the settlement of an initial oxidative stress condition, both at hydrophilic and lipophilic compartments, resulting in cellular protection evidenced by antioxidant enzyme upregulation. PMID:26677163

  4. Nitrosative stress in human skeletal muscle attenuated by exercise countermeasure after chronic disuse

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    Michele Salanova

    2013-01-01

    Full Text Available Activity-induced nitric oxide (NO imbalance and “nitrosative stress” are proposed mechanisms of disrupted Ca2+ homeostasis in atrophic skeletal muscle. We thus mapped S-nitrosylated (SNO functional muscle proteins in healthy male subjects in a long-term bed rest study (BBR2-2 Study without and with exercise as countermeasure in order to assess (i the negative effects of chronic muscle disuse by nitrosative stress, (ii to test for possible attenuation by exercise countermeasure in bed rest and (iii to identify new NO target proteins. Muscle biopsies from calf soleus and hip vastus lateralis were harvested at start (Pre and at end (End from a bed rest disuse control group (CTR, n=9 and two bed rest resistive exercise groups either without (RE, n=7 or with superimposed vibration stimuli (RVE, n=7. At subcellular compartments, strong anti-SNO-Cys immunofluorescence patterns in control muscle fibers after bed rest returned to baseline following vibration exercise. Total SNO-protein levels, Nrf-2 gene expression and nucleocytoplasmic shuttling were changed to varying degrees in all groups. Excess SNO-protein levels of specific calcium release/uptake proteins (SNO-RyR1, –SERCA1 and –PMCA and of contractile myosin heavy chains seen in biopsy samples of chronically disused skeletal muscle were largely reduced by vibration exercise. We also identified NOS1 as a novel NO target in human skeletal muscle controlled by activity driven auto-nitrosylation mechanisms. Our findings suggest that aberrant levels of functional SNO-proteins represent signatures of uncontrolled nitrosative stress management in disused human skeletal muscle that can be offset by exercise as countermeasure.

  5. Plasma protein thiols: an early marker of oxidative stress in asthma and chronic obstructive pulmonary disease.

    Science.gov (United States)

    Zinellu, Angelo; Fois, Alessandro Giuseppe; Sotgia, Salvatore; Zinellu, Elisabetta; Bifulco, Fabiana; Pintus, Gianfranco; Mangoni, Arduino A; Carru, Ciriaco; Pirina, Pietro

    2016-02-01

    Chronic obstructive pulmonary disease (COPD) and asthma are both characterized by heterogeneous chronic airway inflammation and obstruction as well as oxidative stress (OS). However, it is unknown whether OS occurs in early disease and how to best assess its presence. Plasma OS markers (TBARS, PSH, taurine, GSH, ergothioneine and paraoxonase 1 activity) and lung function tests were measured in patients with mild stable asthma (n = 24) and mild stable COPD (n = 29) and in age- and sex-matched controls. Forced expiratory volume in 1 s (FEV1 ) was associated with age both in patients and control groups. By contrast, FEV1 was positively correlated with PSH only in COPD (ρ = 0·49, P = 0·007). In multiple logistic regression analysis, lower PSH was the only OS marker independently associated with increased odds of both asthma (OR = 0·32, 95% CI 0·13-0·78, P = 0·01) and COPD (OR = 0·50, 95% CI 0·26-0·95, P = 0·03). These findings suggest that proteins -SH are a sensitive OS marker in early COPD and asthma.

  6. Moclobemide up-regulates proliferation of hippocampal progenitor cells in chronically stressed mice

    Institute of Scientific and Technical Information of China (English)

    Yun-feng LI; You-zhi ZHANG; Yan-qin LIU; Heng-lin WANG; Li YUAN; Zhi-pu LUO

    2004-01-01

    AIM: To explore the action mechanism of antidepressants. METHODS: The PC12 cell proliferation was detected by flow cytometry,. The proliferation of hippocampal progenitor cells and level of brain-derived neurotrophic factor (BDNF) were measured by immunohistochemistry. RESULTS: Treatment with N-methylaspartate (NMDA)600 μmol/L for 3 d significantly decreased the percentage of S-phase in PC12 cells, while in the presence of classical antidepressant, moclobemide (MOC) 2 and 10 μmol/L, the percentage in S-phase increased. Furthermore,the proliferation of progenitor cells in hippocampal dentate gyrus (subgranular zone), as well as the level of BDNF in hippocampus significantly decreased in chronically stressed mice, while chronic administration with MOC 40mg/kg (ip) up-regulated the progenitor cell proliferation and BDNF level in the same time course. CONLUSION:Up-regulation of the proliferation of hippocampal progenitor cells is one of the action mechanisms for MOC, which may be closely related to the elevation of BDNF level at the same time. These results also extend evidence for our hypothesis that up-regulation of the hippocampal neurogenesis is one of the common mechanisms for antidepressants.

  7. Moclobemide up-regulates proliferation of hippocampal progenitor cells in chronically stressed mice

    Institute of Scientific and Technical Information of China (English)

    Yun-fengLI; You-zhiZHANG; Yan-qinLIU; Heng-linWANG; LiYUAN; Zhi-puLUO

    2004-01-01

    AIM: To explore the action mechanism of antidepressants. METHODS: The PC 12 cell proliferation was detected by flow cytometry,. The proliferation of hippocampal progenitor cells and level of brain-derived neurotrophic factor (BDNF) were measured by immunohistochemistry. RESULTS: Treatment with N-methylaspartate (NMDA)600 μmol/L for 3 d significantly decreased the percentage of S-phase in PC12 cells, while in the presence of classical antidepressant, moclobemide (MOC) 2 and 10 μnol/L, the percentage in S-phase increased. Furthermore,the proliferation of progenitor cells in hippocampal dentate gyrus (subgranular zone), as well as the level of BDNF in hippocampus significantly decreased in chronically stressed mice, while chronic administration with MOC 40 mg/kg (ip) up-regulated the progenitor cell proliferation and BDNF level in the same time course. CONLUSION:Up-regulation of the proliferation of hippocampal progenitor cells is one of the action mechanisms for MOC, which may be closely related to the elevation of BDNF level at the same time. These results also extend evidence for our hypothesis that up-regulation of the hippocampal neurogenesis is one of the common mechanisms for antidepressants.

  8. Heavy metals and its relationships with biomarkers of oxidative stress in chronic smokers

    Directory of Open Access Journals (Sweden)

    Raquel Salazar-Lugo

    2015-12-01

    Full Text Available Concentrations of metals Fe, Zn, Cu, Cr, Cd and Ni and their relationship with oxidative stress biomarkers were evaluated in 50 chronic smokers, both females and males (30 to 84 years. Smokers were divided into two groups (1-5 cigarettes/day, 25, and smokers of more than 6 cigarettes/day, 25. Metal concentrations in whole blood and urine were determined by atomic absorption spectrophotometry with inductively coupled (ICP; hematological and biochemical assays were performed to determine total proteins, fractionated proteins and total thiols. Smokers had higher concentrations of Fe regardless of the number of cigarettes smoked and lower concentrations of Zn, Cr and Ni, No di erences were observed in Cu blood concentrations. Smokers show Cd concentrations between 5.0-10.0 μg/L and non-smokers between 0,0-5,0 μg/L. No signi cant di erences were observed in of Hb, Hct and MCHC concentrations, neither albumin and globulins concentrations; an increased in leukocytes and total thiol was observed in smokers. Blood Fe concentrations were correlated with leucocytes and with Cd. Also, it was showed correlation between albumin and thiols. Zn and Cu concentrations were increased in urine of smokers. According to these results, in chronic smokers, the distribution of Fein the body plays a central role in the possible progression and development of diseases related to smoking.

  9. Stress transiently affects pavlovian-to-instrumental transfer

    Directory of Open Access Journals (Sweden)

    Pedro eMorgado

    2012-06-01

    Full Text Available Stress bias decision-making processes by favoring the shift to habits as a result of changes in corticostriatal circuits. Given that these same circuits are implicated in action control and outcome encoding implicated in adaptive responses we herein assessed the impact of chronic stress in a pavlovian-to-instrumental transfer (PIT paradigm. Data reveals that rats submitted to a chronic unpredictable stress model did not display deficits in pavlovian conditioning nor on the learning of instrumental task, but were impaired in PIT; importantly, after a stress-free period the PIT deficits were no longer observed. These results are relevant to understand how stress bias multiple incentive processes that contribute to instrumental performance.

  10. Stress and Withdrawal from Chronic Ethanol Induce Selective Changes in Neuroimmune mRNAs in Differing Brain Sites.

    Science.gov (United States)

    Knapp, Darin J; Harper, Kathryn M; Whitman, Buddy A; Zimomra, Zachary; Breese, George R

    2016-01-01

    Stress is a strong risk factor in alcoholic relapse and may exert effects that mimic aspects of chronic alcohol exposure on neurobiological systems. With the neuroimmune system becoming a prominent focus in the study of the neurobiological consequences of stress, as well as chronic alcohol exposure proving to be a valuable focus in this regard, the present study sought to compare the effects of stress and chronic ethanol exposure on induction of components of the neuroimmune system. Rats were exposed to either 1 h exposure to a mild stressor (restraint) or exposure to withdrawal from 15 days of chronic alcohol exposure (i.e., withdrawal from chronic ethanol, WCE) and assessed for neuroimmune mRNAs in brain. Restraint stress alone elevated chemokine (C-C motif) ligand 2 (CCL2), interleukin-1-beta (IL-1β), tumor necrosis factor alpha (TNFα) and toll-like receptor 4 (TLR4) mRNAs in the cerebral cortex within 4 h with a return to a control level by 24 h. These increases were not accompanied by an increase in corresponding proteins. Withdrawal from WCE also elevated cytokines, but did so to varying degrees across different cytokines and brain regions. In the cortex, stress and WCE induced CCL2, TNFα, IL-1β, and TLR4 mRNAs. In the hypothalamus, only WCE induced cytokines (CCL2 and IL-1β) while in the hippocampus, WCE strongly induced CCL2 while stress and WCE induced IL-1β. In the amygdala, only WCE induced CCL2. Finally-based on the previously demonstrated role of corticotropin-releasing factor 1 (CRF1) receptor inhibition in blocking WCE-induced cytokine mRNAs-the CRF1 receptor antagonist CP154,526 was administered to a subgroup of stressed rats and found to be inactive against induction of CCL2, TNFα, or IL-1β mRNAs. These differential results suggest that stress and WCE manifest broad neuroimmune effects in brain depending on the cytokine and brain region, and that CRF inhibition may not be a relevant mechanism in non-alcohol exposed animals. Overall, these

  11. 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

  12. 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

  13. 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.

  14. Examining SLV-323, a novel NK1 receptor antagonist, in a chronic psychosocial stress model for depression

    NARCIS (Netherlands)

    Czeh, B; Pudovkina, O; van der Hart, MGC; Simon, M; Heilbronner, U; Michaelis, T; Watanabe, T; Frahm, J; Fuchs, E

    2005-01-01

    Rationale: Substance P antagonists have been proposed as candidates for a new class of antidepressant compounds. Objectives: We examined the effects of SLV-323, a novel neurokinin 1 receptor (NK1R) antagonist, in the chronic psychosocial stress paradigm of adult male tree shrews. Methods: Animals we

  15. Mechanical stress as the common denominator between chronic inflammation, cancer and Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Marcel eLevy Nogueira

    2015-09-01

    Full Text Available The pathogenesis of common diseases such as Alzheimer’s disease (AD and cancer are currently poorly understood. Inflammation is a common risk factor for cancer and AD. Recent data, provided by our group and from others, demonstrate that increased pressure and inflammation are synonymous. There is a continuous increase in pressure from inflammation to fibrosis and then cancer. This in line with the numerous papers reporting high interstitial pressure in cancer. But most authors focus on the role of pressure in the lack of delivery of chemotherapy in the center of the tumor. Pressure may also be a key factor in carcinogenesis. Increased pressure is responsible for oncogene activation and cytokine secretion. Accumulation of mechanical stress plays a key role in the development of diseases of old age such as cardiomyopathy, atherosclerosis and osteoarthritis. Growing evidence suggest also a possible link between mechanical stress in the pathogenesis of AD. The aim of this review is to describe environmental and endogenous mechanical factors possibly playing a pivotal role in the mechanism of chronic inflammation, AD and cancer.

  16. Role of oxidative stress & transient receptor potential in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Protiti Bose

    2015-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD affect millions of people worldwide and is known to be one of the leading causes of death. The highly sensitive airways protect themselves from irritants by cough and sneeze which propel endogenous and exogenous substances to minimize airway noxious effects. One noxious effect of these substances is a